Exhibit 10.15

 

CONFIDENTIAL

 

LICENSE AGREEMENT*

 

BETWEEN

 

SCRAS S.A.S.

 

AND

 

NUVIOS

 

27 September 2005

 

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* Confidential Treatment Requested by the Registrant. Redacted Portion Filed
Separately with the Commission.

 

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TABLE OF CONTENTS

 

 

 

Page

 

 

 

ARTICLE 1

INTERPRETATION — DEFINITIONS

1

 

 

 

ARTICLE 2

GRANT OF RIGHTS

9

 

 

 

ARTICLE 3

MILESTONE PAYMENTS

13

 

 

 

ARTICLE 4

PAYMENTS BASED ON SALES OF LICENSED PRODUCT

15

 

 

 

ARTICLE 5

PAYMENT, REPORTING, AUDITING

17

 

 

 

ARTICLE 6

DEVELOPMENT GOVERNANCE

19

 

 

 

ARTICLE 7

DEVELOPMENT PLAN AND CONDUCT OF DEVELOPMENT ACTIVITIES

21

 

 

 

ARTICLE 8

DEVELOPMENT — REGULATORY AND SAFETY

24

 

 

 

ARTICLE 9

MANUFACTURE AND SUPPLY

26

 

 

 

ARTICLE 10

COMMERCIALIZATION

28

 

 

 

ARTICLE 11

INTELLECTUAL PROPERTY

31

 

 

 

ARTICLE 12

CONFIDENTIAL INFORMATION

38

 

 

 

ARTICLE 13

PUBLICATION AND PRESS RELEASE

39

 

 

 

ARTICLE 14

REPRESENTATIONS, WARRANTIES AND COVENANTS

41

 

 

 

ARTICLE 15

TERM AND TERMINATION

44

 

 

 

ARTICLE 16

INDEMNIFICATION

48

 

 

 

ARTICLE 17

DISPUTE RESOLUTIONS AND GOVERNING LAW

49

 

 

 

ARTICLE 18

MISCELLANEOUS

50

 

 

 

APPENDIX A - CHEMICAL STRUCTURE OF BIM-44058

54

 

 

APPENDIX B - IPSEN PATENT RIGHTS

55

 

 

APPENDIX C — NUVIOS DEVELOPMENT PLAN

57

 

 

APPENDIX D —

 

 

 

APPENDIX E — IPSEN INDS AND OTHER APPLICATIONS FOR REGULATORY APPROVAL

85

 

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CONFIDENTIAL

 

LICENSE AGREEMENT

 

This License Agreement (“Agreement”) is entered into on September 27, 2005 by
and between, on the one hand, SCRAS S.A.S., a French corporation, with its
principal office at 42, Rue du Docteur Blanche, 75016 Paris, France, on behalf
of itself and its Affiliates (collectively, “Ipsen”), and, on the other hand,
Nuvios, Inc., a United States corporation, with its principal office at 300
Technology Square — 5th floor, Cambridge, MA 02139, on behalf of themselves and
their Affiliates (collectively, “Nuvios”).

 

Recitals

 

1.                                      Ipsen has developed and owns
intellectual property rights related to proprietary compounds known as BIM 44058
and analogs and possesses know-how including know-how related to formulation
technology including sustained release formulations.

 

2.                                      The management of Nuvios has expertise
in the development of pharmaceutical products for the treatment of osteoporosis.

 

3.                                      Nuvios has interest in having access to
BIM-44058 and analogs claimed under the Ipsen Patent Rights (as defined below),
to pursue a worldwide development program, and thereafter, to commercialize the
resulting products.

 

4.                                      The Parties have prepared this Agreement
to govern the development and commercialization of products resulting from this
Agreement.

 

Now, therefore, in consideration of the premises and the mutual covenants and
agreements contained in this Agreement, the Parties, intending to be legally
bound, do hereby agree as follows:

 

ARTICLE 1   INTERPRETATION — DEFINITIONS

 

1.1.                            In this Agreement, unless the context otherwise
requires, all references to a particular Article, Section, or Appendix, shall be
a reference to that Article, Section or Appendix, in or to this Agreement, as it
may be amended from time to time pursuant to this Agreement.

 

1.1.1.                                     Headings are inserted for convenience
only and shall not affect the meaning or interpretation of any provision of this
Agreement.

 

1.1.2.                                     This Agreement incorporates all
Appendices as a part of this Agreement by reference.

 

1.1.3.                                     The term “including” (or any
variation thereof such as “include”) shall be without limitation to the
generality of the preceding words.

 

1.1.4.                                     Unless the contrary intention
appears, words in the singular shall include the plural and vice versa.

 

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1.1.5.                                     Unless the contrary intention
appears, words denoting persons shall include any individual, partnership,
company, corporation, joint venture, trust, association, organization or other
entity.

 

1.1.6.                                     Reference to any statute or
regulation includes any modification or re-enactment of that statute or
regulation.

 

The following capitalized terms, whether used in the singular or the plural,
shall have the following meanings as used in this Agreement unless otherwise
specifically indicated:

 

1.2.                            Accounting Period shall mean each calendar
quarter commencing respectively on January 1, April 1, July 1 and October 1,
each being the first day of an Accounting Period, and finishing respectively on
March 31, June 30, September 30 and December 31, each being the last day of an
Accounting Period.

 

1.3.                            Affiliate shall mean (a) an entity which owns,
directly or indirectly, a controlling interest in a Party, by stock ownership or
otherwise, (b) any entity in which a. Party owns a controlling interest, by
stock ownership or otherwise; or (c) any entity, under direct or indirect common
control with a Party. For purposes of this paragraph, “controlling interest” and
“control” mean ownership of fifty percent (50%) or more of the voting stock
permitted to vote for the election of the board of directors or any other
arrangement resulting in control or the right to control the management and the
affairs of the Party.

 

1.4.                            BIM-44058 shall mean the compound the chemical
structure of which is set forth on Appendix A.

 

1.5.                            Bundled Product shall mean Licensed
Product(s) sold to a third party with one or more other products or services in
circumstances where either (i) the price of the Licensed Product(s) is not shown
separately on the invoice or (ii) the Licensed Product(s) (or a portion of the
units of Licensed Product(s)) are detailed on a separate invoice where the price
is shown as nil (free of charge) for the Licensed Product(s) (or for those units
of the Licensed Product(s)).

 

1.6.                            Confidential Information shall have the meaning
set forth in Article 12.

 

1.7.                            Contractor shall mean any third party with whom
Nuvios enters into an agreement pursuant to which Nuvios grants to such third
party the right to commercialize (including, without limitation, the right to
promote, market and/or sell) Licensed Product in any country of the Territory.
Notwithstanding the foregoing, the term “Contractor” shall in no event include
(i) any Affiliate of Nuvios or (ii) any such third party which whom Nuvios
enters into an agreement if the relationship established between Nuvios and such
third party pursuant to such agreement is for such third party to be a
wholesaler of Licensed Product in any country of the Territory.

 

1.8.                            Cover (as an adjective or as a verb including
conjugations and variations such as “Covered,” “Coverage” or “Covering”) shall
mean that the developing, making, using, offering for sale, promoting, selling
or importing of a given compound, formulation or product would infringe a Valid
Claim of an issued patent in the absence of a license under such Valid Claim.

 

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The determination of whether a compound, formulation or product is covered by a
particular Valid Claim shall be made on a country-by-country basis.

 

1.9.                            Development shall mean the Pre-clinical Studies,
Phase I, II & III Clinical Trials, filing of NDAs, and other activities,
including pharmaceutical and manufacturing development as well as regulatory
work, necessary to obtain Regulatory Approval of a Licensed Product.

 

1.10.                     Development Plan shall mean any version and variations
of a document prepared for the Development of a Licensed Product in the
Territory, that outlines the Development activities including regulatory
strategies, to be performed by Nuvios under this Agreement. Such a document
shall contain targeted timelines of the Development phases and clinical
endpoints.

 

1.11.                     Effective Date shall mean the latest of the dates of
signature by each Party as shown on the signature page of this Agreement.

 

1.12.                     EMEA shall mean the European Medicines Agency or any
successor agency.

 

1.13.                     FDA shall mean the United States of America Food and
Drug Administration or any successor agency.

 

1.14.                     First Commercial Sale shall mean, in each country of
the Territory, each first invoiced sale to a third party of Licensed Product in
the country after obtaining Regulatory Approval in such country.

 

1.15.                     FTE shall mean a period equivalent to the number of
hours that an employee in the full time employment of either Party would be
obliged to spend at work in any twelve (12) month period of continuous
employment.

 

1.16.                     Gross Sales shall mean the gross amount invoiced by
Nuvios, its Affiliates or Contractors for sales of a Licensed Product to third
parties in the Territory. For purposes of clarification, the gross amount
invoiced among Nuvios, its Affiliates or Contractors with respect to sales of
Licensed Product shall not be considered as Gross Sales. Notwithstanding the
foregoing provisions of this definition, sales of Licensed Product for use in
clinical or pre-clinical trials or other research or development activities or
free of charge dispositions of Licensed Product for purposes of a commercially
reasonable sampling program shall not give rise to any Gross Sales for purposes
of this Agreement.

 

1.17.                     Health Agency shall mean a governmental or official
body in a given country of the Territory, including FDA and EMEA, as well as any
national or international or local regulatory agency, department, bureau or
other governmental entity, which reviews, validates and/or delivers Regulatory
Approvals.

 

1.18.                     IND shall mean an application to the FDA, the filing
of which is necessary for the first administration to humans of Licensed
Product, or the equivalent application to the equivalent agency in any other
country or group of countries.

 

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1.19.                     Infringe (as a noun, adjective or verb including
conjugations and variations such as “Infringed,” “Infringes”, “Infringing” and
“Infringement”) shall mean infringement, misappropriation, unauthorized use,
misuse or other violation of the Patent Rights, know-how, inventions, trade
secrets or other intellectual property (except trademarks) of any person or
entity, whether such person or entity owns such Patent Rights, Know-How,
inventions, trade secrets or other intellectual property (except trademarks) or
otherwise has the valid right of use thereof, including, without limitation,
pursuant to a license.

 

1.20.                     Invention shall mean any invention or discovery,
whether or not patentable, made as a result of the research or Development
activities of a Party or the Parties pursuant to, or in connection with, this
Agreement and which relates to Licensed Product or to Licensed Compound. An
“Invention” may be made by employees of Ipsen solely or jointly with a third
party (an “Ipsen Invention”), by employees of Nuvios solely or jointly with a
third party (a “Nuvios Invention”), or jointly by employees of Ipsen and Nuvios
with or without a third party (a “Joint Invention”), in each instance as
determined by U.S. laws of inventorship.

 

1.21.                     Ipsen Compound Know How shall mean all Ipsen Know-How
other than Ipsen Formulation Know-How.

 

1.22.                     Ipsen Compound Patent Rights shall mean all Ipsen
Patent Rights other than Ipsen Formulation Patent Rights. The Ipsen Compound
Patent Rights on the Effective Date are listed in Appendix B1 to this Agreement.

 

1.23.                     Ipsen Compound Technology shall mean all Ipsen
Compound Know-How and Ipsen Compound Patent Rights.

 

1.24.                     Ipsen Formulation Know How shall mean all Ipsen
Know-How that is related to the delivery or formulation of peptides (including
Ipsen Solid Technology).

 

1.25.                     Ipsen Formulation Patent Rights shall mean all Ipsen
Patent Rights that are related to the delivery or formulation of peptides
(including Ipsen Solid Technology) The Ipsen Formulation Patent Rights on the
Effective Date are listed in Appendix B2 to this Agreement.

 

1.26.                     Ipsen Formulation Technology shall mean all Ipsen
Formulation Know-How and Ipsen Formulation Patent Rights.

 

1.27.                     Ipsen Joint Technology Rights shall mean all of
Ipsen’s right, title and interest in the Joint Patent Rights and the Joint
Inventions.

 

1.28.                     Ipsen Know-How shall mean all Know-How that (A) Ipsen
owns, or otherwise under which Ipsen has right to grant licenses or to give
access to use, as of the Effective Date or at any time during the Term and
(B) is necessary or useful to the research, Development, manufacture, marketing,
promotion, use, sale, import or export of Licensed Compound or Licensed Product,
including, without limitation, all data and information regarding the safety and
efficacy of Licensed Compound or Licensed Product. The term “Ipsen Know-How”
shall also include all Know-How in connection with Ipsen Inventions, but shall
not include any Joint Inventions.

 

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1.29.                     Ipsen Patent Rights means all Patent Rights that
(A) Ipsen owns, or otherwise under which Ipsen has the right to grant licenses,
as of the Effective Date or at any time during the Term and (B) is necessary or
useful to the research, Development, manufacture, marketing, promotion, use,
sale, import or export of Licensed Compound or Licensed Product. The term “Ipsen
Patent Rights” shall also include all Patent Rights claiming Ipsen Inventions,
but shall not include any Joint Patent Rights. Appendix B lists all Ipsen Patent
Rights as of the Effective Date.

 

1.30.                     Japanese Development Plan shall mean the then current
version of a document that details the development activities and other
activities, including pharmaceutical and manufacturing as well as regulatory
work to be performed by Teijin in Japan that are necessary or useful to obtain
Regulatory Approval and commercialize Licensed Product in Japan.

 

1.31.                     Joint Patent Rights means Patent Rights that claim
Joint Inventions.

 

1.32.                     JSC shall mean the Joint Steering Committee referred
to in Article 6.

 

1.33.                     Know-How shall mean technical and other information,
including information comprising or relating to concepts, discoveries, data,
designs, formulae, ideas, inventions, methods, models, assays, research plans,
procedures, designs for experiments and tests and results of experimentation and
testing (including results of research or Development or other developments),
formulations, processes (including manufacturing processes, specifications and
techniques), laboratory records, chemical, pharmacological, toxicological,
clinical, analytical and quality control data, trial data, case report forms,
data analyses, reports, manufacturing data, pre-clinical data and summaries and
information contained in submissions to, and information from, ethical
committees and Health Agencies, including documents containing any of the above.

 

1.34.                     Licensed Compound means (i) BIM-44058 or (ii) any
analog of BIM-44058.

 

1.35.                     Licensed Product Claim means, for a given Licensed
Product in a given country of the Territory, a Valid Claim of Ipsen Compound
Patent Rights, Ipsen Formulation Patent Rights or Joint Patent Rights that
Covers such Licensed Product in such country.

 

1.36.                     Licensed Product shall mean all formulations, dosage
forms, and presentations (including vials and pre-filled syringes) of a product
or pharmaceutical composition containing a Licensed Compound as a
pharmaceutically active agent. Licensed Product may be formulated under the
Ipsen Formulation Technology or under the formulation of a third party.

 

1.37.                     Manufacturing Cost shall mean, the internal
(calculated with reference to FTE where applicable) and external costs and
expenses determined in accordance with generally accepted accounting principles
as consistently applied by a Party in the ordinary course of its business, in
relation to the manufacture of Licensed Compound and Licensed Product, which
costs shall include, but not be limited to the sum of (a) the cost of goods
produced, including, but not limited to, direct labor, material, depreciation,
energy, quality control, waste disposal and production management, payments to
third parties for costs incurred and product testing, as well as allocable
overhead, (b) any value

 

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added tax or other applicable tax (but not income tax) paid or payable by a
Party in connection with the manufacture or supply of Licensed Compound or
Licensed Product, and (c) any other costs borne by a Party for the packaging,
transport, customs clearance, and storage of Product (e.g., containers, freight,
duties, insurance and warehousing).

 

1.38.                     NDA Filing shall mean a New Drug Application filed as
a result of activities under this Agreement with the FDA, or the equivalent
application to the equivalent agency in any other country of the Territory, the
filing of which is necessary to market and sell a Licensed Product, including
all amendments and supplements to any of the foregoing.

 

1.39.                     Net Sales shall mean shall mean Gross Sales less
deductions (not otherwise taken into account) for the (a) transportation charges
including insurance, if included in the invoiced price, (b) sales taxes, excise
taxes, value added taxes, customs duties and any use or turnover taxes imposed
by any governmental authority upon the production, importation, use or sale of
Licensed Products, that are required to be paid to the government by the seller
and included in the invoiced price, (c) normal and customary trade, quantity and
cash discounts (including prompt pay discounts) allowed and taken,
(d) allowances or credits to customers on account of actual rejection or return
of Licensed Products or on account of discounts, retroactive price reductions,
rebates or administrative fees affecting Licensed Products and (e) amounts
written off as uncollectible as actually incurred (and specifically identified)
as bad debt in accordance with the seller’s normal accounting procedures,
consistently applied.

 

In the event that a Licensed Product is sold as a component of a Bundled
Product, then Net Sales shall be determined by multiplying the Net Sales of the
Bundled Product by the fraction A/(A+B) where A equals the average selling price
of such Licensed Product sold separately in finished form and B equals the
aggregate average selling price of the relevant other product(s) included in
such Bundled Product sold separately in finished form, in each case in the
relevant country in which sales of such Bundled Product were made, during the
same Accounting Period and in similar volumes. In the event that no separate
sale of such Licensed Product is made during the applicable Accounting Period in
similar volumes and in the relevant country in which the sale of such Bundled
Product was made and that there are separate sales of the relevant other
product(s) included in such Bundled Product in similar volumes and in the
relevant country in which the sale of such Bundled Product was made, then Net
Sales shall be determined by multiplying the Net Sales of the Bundled Product by
the fraction (E — B)/E, where E equals the average selling price of the Bundled
Product for the country in which sales were made. In the event that no separate
sale of either such Licensed Product or the relevant other product(s) is made
during the applicable Accounting Period in similar volumes and in the relevant
country in which the sale of such Bundled Product was made, then Net Sales shall
be determined by multiplying the Net Sales of the Bundled Product by the
fraction C/(C+D), where C equals the fully absorbed cost of manufacturing such
Licensed Product and D equals the fully absorbed cost of manufacturing the
relevant other product(s).

 

1.40.                     Nuvios Joint Technology Rights shall mean all of
Nuvios’ right, title and interest in the Joint Patent Rights and the Joint
Inventions.

 

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1.41.                     Nuvios Know-How shall mean all Know-How (A) that is
obtained by Nuvios as a result of works performed by Nuvios, or by third parties
appointed by Nuvios, pursuant to or in connection with the Development Plan and
(B) that is necessary or useful to the research, Development, manufacture,
marketing, promotion, use, sale, import or export of Licensed Compound or
Licensed Product. The term “Nuvios Know-How” shall also include (i) all INDs and
NDAs filed by Nuvios with respect to Licensed Product and all related data and
files in connection with such INDs and NDAs and (ii) all Know-How in connection
with Nuvios Inventions. Notwithstanding anything express or implied in the
foregoing provisions of this definition, the term “Nuvios Know-How” shall not
include any Joint Inventions or any invention or Know-How claimed in the Joint
Patent Rights.

 

1.42.                     Nuvios Patent Rights means all Patent Rights (A) that
are obtained by Nuvios as a result of works performed by Nuvios, or by third
parties appointed by Nuvios, pursuant to or in connection with the Development
Plan and (B) that are necessary or useful to the research, Development,
manufacture, marketing, promotion, use, sale, import or export of Licensed
Compound or Licensed Product. Nuvios Patent Rights include (i) any Patent Rights
claiming any improvement, invention or discovery obtained or made by Nuvios with
respect to Licensed Compounds and/or Licensed Product and (ii) all Patent Rights
claiming Nuvios Inventions. Notwithstanding anything express or implied in the
foregoing provisions of this definition, the term “Nuvios Patent Rights” shall
not include any or all Joint Patent Rights.

 

1.43.                     Nuvios Trademark shall have the meaning attributed to
it under Section 11.1.

 

1.44.                     Party shall mean, individually, SCRAS S.A.S. or
Nuvios, Inc., and “Parties” shall mean collectively, SCRAS S.A.S. and
Nuvios, Inc.

 

1.45.                     Patent Rights shall mean all rights under any patent
or patent application in any country of the world, including any substitution,
extension or supplementary protection certificate, reissue, re-examination,
renewal, division, continuation or continuation-in-part thereof.

 

1.46.                     Phase I Clinical Trial shall mean a human clinical
trial normally conducted in healthy volunteers with the aim of establishing the
pharmacokinetic, pharmacodynamic and early safety profile.

 

1.47.                     Phase Ib Clinical Trial shall mean a human clinical
trial normally conducted in healthy volunteers but in certain circumstances in
patients, with the aim of establishing the pharmacokinetic, pharmacodynamic and
early safety profile.

 

1.48.                     Phase I Initiation shall mean the date when a Licensed
Product is first administered to human subjects for a Phase I Clinical Trial in
the Territory.

 

1.49.                     Phase II Clinical Trial shall mean a human clinical
trial that is required for Regulatory Approval where a product is tested in a
limited number of patients for the purpose of establishing dose ranging and/or
first indication of efficacy of product for a therapeutic or prophylactic use.

 

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1.50.                     Phase II Initiation shall mean the date when a
Licensed Product is first administered to patient for a Phase II Clinical Trial
in the Territory.

 

1.51.                     Phase III Clinical Trial shall mean a pivotal
multi-center human clinical trial in a large number of patients to establish
safety or efficacy in the particular claim and indication tested and required to
obtain Regulatory Approval.

 

1.52.                     Phase III Initiation shall mean the date when a
Licensed Product is first administered to a patient for a Phase III Clinical
Trial in the Territory.

 

1.53.                     Pre-Clinical Package shall mean a package containing
available research and pre-clinical data with respect to Licensed Compound or
Licensed Product.

 

1.54.                     Pre-Clinical Study shall mean those laboratory tests
and studies on animals which are conducted to gather evidence justifying a Phase
I Clinical Trial.

 

1.55.                     Regulatory Approval shall mean any and all approvals,
licenses, registrations or authorizations (including pricing and reimbursement
approvals) whether or not conditional, that are granted by FDA, EMEA or other
Health Agency and are necessary for the commercial sale of Licensed Product in a
regulatory jurisdiction in the Territory and obtained as a result of activities
under this Agreement.

 

1.56.                     Related Agreement shall mean any agreement entered or
to be entered into between the Parties pursuant to, and in accordance with,
Section 7.3, 8.4, 9.1, Section 9.3 or Section 10.2.

 

1.57.                     Research Agreement shall mean the agreement referred
to Article 7.3 whereby Ipsen should carry out research work on the Ipsen
Formulation Technology with Licensed Compound and/or Licensed Product.

 

1.58.                     ROW shall mean all countries of the Territory except
the United States of America.

 

1.59.                     Royalty Term shall mean for each Licensed Product and
each country of the Territory, the later of (a) expiration of the last to expire
Licensed Product Claim in such country with respect to such Licensed Product and
(b) ten (10) years from the First Commercial Sale in such country of such
Licensed Product. With regards to the calculation of the ten-year period, the EU
shall be considered as one country. Notwithstanding anything express or implied
in the foregoing provisions of this definition, if, with respect to any Licensed
Product in any country of the Territory, on the date that is ten (10) years from
the First Commercial Sale in such country of such Licensed Product, there is no
Valid Claim of an issued patent within the Ipsen Patent Rights or the Joint
Patent Rights that Covers such Licensed Product in such country, then the
Royalty Term for such Licensed Product in such country shall automatically
expire and terminate on such date.

 

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1.60.                     Teijin means Teijin Pharma Ltd, Iino Building, 1-1,
Uchisaiwaicho 2-chome, Chiyoda-ku, Tokyo 100-8585, Japan, Ipsen’s current third
party licensee in Japan licensed under Ipsen Patent Rights and Ipsen Know-How to
develop, market, distribute, offer for sale, sell, and/or import, Licensed
Product in Japan. In the event that any other person or entity becomes licensed
under Ipsen Patent Rights and Ipsen Know-How to research, develop, market,
distribute, offer for sale, sell and/or import Licensed Product in Japan or in
the event that Ipsen develops, markets, distributes, offer for sale, sells
and/or imports Licensed Product in Japan, then, for purposes of this Agreement,
the term “Teijin” shall mean such other person or entity, or Ipsen, as the case
may be.

 

1.61.                     Teijin Agreement means that certain agreement between
Teijin and Ipsen, as in effect from time to time, pursuant to which, among other
things, Ipsen has licensed Teijin under the Ipsen Patent Rights and Ipsen
Know-How to research, develop, market, distribute, offer for sale, sell and/or
import Licensed Product in Japan.

 

1.62.                     Term shall have the meaning set forth in Section 15.1.

 

1.63.                     Territory shall mean all countries of the world,
except Japan, and subject to co-marketing and co-promotion rights reserved to
Ipsen in France pursuant to this Agreement.

 

1.64.                     Unlicensed Product shall mean, with respect to any
Licensed Product in any given country within the Territory, any product or
pharmaceutical composition that (A) consists of or contains the same active
pharmaceutical ingredient as such Licensed Product, and (B) is commercially
available in such country other than as a result of the licenses granted by
Ipsen to Nuvios pursuant to this Agreement.

 

1.65.                     Valid Claim shall mean a claim in any (a) unexpired
and issued Patent Right that has not been dedicated to the public, disclaimed,
revoked or held invalid by a final unappealable decision or unappealed decision
of a court of competent jurisdiction after the period for filing an appeal has
expired or (b) pending patent application which patent application has been on
file with the application patent office for no more than fifteen (15) years from
the earliest date from which the patent application was filed or claims earliest
priority, provided in case the patent application concerned is a Nuvios Patent
Right or Ipsen Patent Right, Nuvios or Ipsen (as applicable) has undertaken good
faith, consistent and reasonable commercial efforts to advance to issuance of a
Patent Right.

 

ARTICLE 2   GRANT OF RIGHTS

 

2.1.                            License to Nuvios.

 

Subject to the terms of this Agreement, Ipsen grants to Nuvios:

 

·                                          an exclusive (even as to Ipsen )
right and license in all countries of the Territory, under the Ipsen Compound
Technology and the Ipsen Joint Technology Rights, to research, develop,
register, use, make, have made, import, export, market,

 

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distribute, offer for sale and sell Licensed Compound and/or Licensed Product in
the Territory (it being understood and agreed that, notwithstanding the
foregoing exclusive grant to Nuvios, Nuvios hereby authorizes and consents to
the exercise by Ipsen of any and all rights under the Ipsen Compound Technology
if and to the extent necessary for the sole purpose of Ipsen performing its
obligations under Section 9.1 of this Agreement or under the Research
Agreement),

 

·                                          an exclusive (even as to Ipsen and
Teijin) right and license under the Ipsen Compound Technology and the Ipsen
Joint Technology Rights, to make and have made Licensed Compound and/or Licensed
Product in Japan (it being understood that the foregoing exclusive grant to
Nuvios shall not limit or diminish the obligations of Nuvios pursuant to
Article 9 hereof), and

 

·                                          an exclusive (even as to Ipsen)
license in all countries of the Territory, under Ipsen Formulation Technology,
for use thereof only and solely to develop, register, use, make, have made,
import, export, market, distribute, offer for sale and sell Licensed Compound
and/or Licensed Product in the Territory, to the exclusion of any use of the
Ipsen Formulation Technology for research purposes. Notwithstanding the
foregoing exclusive license rights granted to Nuvios in this paragraph with
respect to the Ipsen Formulation Technology, Nuvios shall not exercise any or
all of such exclusive license rights with respect to any formulation for
Licensed Compound and/or Licensed Product that is different from the current
formulation therefore as of the Effective Date unless and until Nuvios and Ipsen
enter into the Research Agreement. During the Term, (i) Ipsen shall not, except
pursuant to the Research Agreement, use all or any portion of the Ipsen
Formulation Technology for research purposes related to, or in connection with,
Licensed Compound and/or Licensed Product, and (ii) Ipsen shall not grant to any
third party the right to use all or any portion of the Ipsen Formulation
Technology for research purposes related to, or in connection with, Licensed
Compound and/or Licensed Product. During the Term, (x) Ipsen shall not use all
or any portion of the Ipsen Formulation Technology for any purpose or use
(including, without limitation, research, development and commercial purpose or
use) related to, or in connection with, Parathyroid Hormone (“PTH”), PTH related
protein (“PTHrP”) or analogs of PTH or PTHrP, and (y) Ipsen shall not grant to
any third party the right to use all or any portion of the Ipsen Formulation
Technology for any purpose or use (including, without limitation, research,
development and commercial purpose or use) related to, or in connection with,
PTH, PTHrP or analogs of PTH or PTHrP.

 

2.2.                            Rights retained by Ipsen:

 

For the avoidance of doubt, Ipsen retains all rights to and under the Ipsen
Formulation Technology (i) in relation to any compounds, or products containing
any compound, other than Licensed Compound, Licensed Product, PTH, PTHrP or
analogs of PTH or PTHrP, and (ii) to perform Ipsen’s obligations under the
Research Agreement.

 

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In respect of Licensed Compound and Licensed Product in France: Ipsen may elect
to co-promote or co-market Licensed Product in France under the conditions set
forth in Article 10.2 hereof, in which case Ipsen shall co-promote or co-market,
as the case may be, Licensed Product in France pursuant to, and in accordance
with, the provisions of Article 10.2.

 

All rights in and to the Ipsen Compound Technology and Ipsen Formulation
Technology not expressly granted to Nuvios under this Agreement are reserved
exclusively to Ipsen.

 

2.3.                            Sublicenses

 

The rights and licenses granted to Nuvios under Section 2.1 shall include the
right to grant sublicenses to a third party under such rights and licenses, in
whole or in part, and shall also include the right to grant to any direct or
indirect third party sublicensee of such rights and licenses granted to Nuvios
under Section 2.1 the right of such direct or indirect third party sublicensee
to further sublicense such rights and licenses to Nuvios under Section 2.1 to
another third party. If Nuvios grants a sublicense pursuant to this Section 2.3,
Nuvios shall ensure that all of the applicable terms and conditions of this
Agreement shall apply to the third party sublicensee to the same extent as they
apply to Nuvios with respect to, and to the extent, of the rights sublicensed.
Nuvios shall assume full responsibility for the performance of all obligations
so imposed by Nuvios on such third party sublicensee and will itself account to
Ipsen for all payments due under this Agreement by reason of such sublicense.

 

2.4.                            Contractors

 

The rights and licenses granted to Nuvios under Section 2.1 shall include the
right to grant rights to Contractors under such rights and licenses, in whole or
in part, and shall also include the right to grant to any direct or indirect
third party Contractors the right of such direct or indirect Contractors to
further subcontract such rights to another third party. If Nuvios enter into an
agreement with a Contractor pursuant to this Section 2.4, Nuvios shall ensure
that all of the applicable terms and conditions of this Agreement shall apply to
the Contractor to the same extent as they apply to Nuvios with respect to, and
to the extent, of the rights granted. Nuvios shall assume full responsibility
for the performance of all obligations so imposed by Nuvios on Contractor and
will itself account to Ipsen for all payments due under this Agreement by reason
of such subcontract.

 

2.5.                            Licenses to Ipsen

 

Subject to the terms of this Agreement, Nuvios shall grant to Ipsen an exclusive
(even as to Nuvios) royalty free license under Nuvios Inventions, Nuvios Joint
Technology Rights, Nuvios Know-How and Nuvios Patent Rights, to research,
develop, register, use, import, export, market, distribute, offer for sale and
sell Licensed Compound and/or Licensed Product in Japan; provided, however, that
(i) such Licensed Compound and/or Licensed Product is Covered by a Valid Claim
of Ipsen Patent Rights in the United States, Canada and the European Union and
(ii) such Licensed Compound and/or Licensed Product is the same compound or
product as Licensed Compound and/or Licensed Product Developed or being
Developed by Nuvios pursuant to the Development Plan. Nuvios shall make and
implement any such grant of exclusive license rights

 

11

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to Ipsen at such time as Ipsen shall have presented evidence reasonably
satisfactory to Nuvios that all inventions, know-how or patent rights owned or
controlled by Teijin that are necessary or useful to research, develop,
register, use, import, export, market, distribute, offer for sale and sell
Licensed Compound and/or Licensed Product in the Territory are included within
Ipsen Compound Technology. Such evidence may include a written agreement
executed by Teijin acknowledging and agreeing that, for purposes of this
Agreement, all inventions, know-how or patent rights owned or controlled by
Teijin that are necessary or useful to research, develop, register, use, import,
export, market, distribute, offer for sale and sell Licensed Compound and/or
Licensed Product in the Territory are included within Ipsen Compound Technology.
Ipsen shall have the right to sublicense to Teijin any or all of the exclusive
license rights that Nuvios shall grant to Ipsen in the manner contemplated under
this paragraph, and otherwise Ipsen shall not have the right to sublicense,
assign or otherwise transfer to any person or entity any or all of such
exclusive license rights. Subject to the terms of this Agreement, Nuvios shall
grant to Ipsen a non-exclusive license under Nuvios Inventions, Nuvios Know-How
and Nuvios Patent Rights, to co-promote or co-market Licensed Compound and/or
Licensed Product in France pursuant to, and in accordance with, the provisions
of Article 10.2. Nuvios shall make and implement any such grant of non-exclusive
license rights to Ipsen in the co-promotion agreement or co-marketing agreement
to be entered into by the Parties pursuant to, and in accordance with, the
provisions of Article 10.2. Ipsen shall not have the right to sublicense, assign
or otherwise transfer to any person or entity any or all of the non-exclusive
license rights that Nuvios shall grant to Ipsen in the manner contemplated under
this paragraph.

 

2.6.                            Prohibited Uses and Activities

 

2.6.1.                                     Ipsen shall not use any Ipsen
Compound Technology, Ipsen Formulation Technology or any Ipsen Joint Technology
Rights in contravention or violation of the exclusive license rights granted to
Nuvios pursuant to Section 2.1. Ipsen shall not grant licenses or otherwise
transfer any rights to any person or entity (other than Nuvios) if and to the
extent that any such grant or other transfer would violate, contravene, conflict
with, or be inconsistent with the exclusive license rights granted to Nuvios
pursuant to Section 2.1.

 

2.6.2.                                     In addition, at any time from and
after the Effective Date and for as long as Ipsen receives royalties pursuant to
Article 4 of this Agreement with respect to any country of the Territory and
there is no Unlicensed Product being sold in such country of the Territory by
persons other than Ipsen or any of its Affiliates, (i) none of Ipsen and its
Affiliates, shall register, use, make, import, export, market, distribute, offer
for sale and sell any Unlicensed Product in such country of the Territory, and
(ii) none of Ipsen and its Affiliates shall enter into any agreement with any
person or entity (other than Nuvios) pursuant to which such person or entity
other than Nuvios shall research, develop, register, use, make, have made,
import, export, market, distribute, offer for sale and sell Licensed Compound,
Licensed Product and/or Unlicensed Product in such country of the Territory.

 

12

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ARTICLE 3   MILESTONE PAYMENTS

 

3.1.                            Subject to the provisions of Sections 3.2 and
3.3 below, Nuvios shall pay to Ipsen the following non-refundable and
non-creditable amounts upon the occurrence of the following events:

 

13

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Events

 

Amount

 

 

 

 

 

Concurrently with the execution of this Agreement

 

USD

250,000

 

 

 

 

 

Within 60 days of the first of (i) completion of the first Phase Ib final study
report where the clinical endpoints set forth in the Development Plan are
reached or (ii) Phase II Initiation by Nuvios

 

USD

250,000

 

 

 

 

 

Within 60 days of completion of the first Phase II final study report where the
clinical endpoints set forth in the Development Plan are reached

 

USD

500,000

 

 

 

 

 

Within 15 days of initiation of the first Phase III study (at the election of
Nuvios, up to 50% payable in Nuvios stock provided stock price has been agreed
within a 60-day negotiation period)

 

EUR

1 million

 

 

 

 

 

Within 15 days of the submission of the NDA to the FDA, and the acceptance by
the FDA of such submission for review

 

EUR

[*]

 

 

 

 

 

Within 15 days of approval of the NDA by the FDA

 

EUR

[*]

 

 

 

 

 

Within 15 days of Regulatory Approval by the EMEA or first Regulatory Approval
by any European Union Member State.

 

EUR

[*]

 

 

 

 

 

Within 90 days of end of first calendar year in which Net Sales of Licensed
Product in such calendar year are equal to or greater than USD 250 m

 

EUR

 [*]

 

 

 

 

 

Within 90 days of end first calendar year in which Net Sales of Licensed Product
in such calendar year exceed USD 300 m

 

EUR

 [*]

 

 

Each milestone payment by Nuvios to Ipsen pursuant to the foregoing provisions
of this Section 3.1 shall be paid only once, regardless of how many times a
particular milestone is achieved and notwithstanding that more than one Licensed
Product achieves a given milestone. Without limiting the generality of the
foregoing sentence, in no event shall the aggregate amount of milestone payments
made by Nuvios to Ipsen pursuant to this Section 3.1 under any circumstances
exceed (i) one million (1,000,000) USD and thirty six million (36,000,000) EUR.

 

3.2.                            Subject to the provisions of Section 3.3 below,
should Nuvios sublicense or otherwise grant or transfer, whole or part of this
Agreement to a third party sublicensee or Contractor, Nuvios shall make payment
to Ipsen of the Share (defined below) of all upfront fees and all milestone
payments received by Nuvios from such sublicensees or Contractors in direct or
indirect consideration for such grant of rights.

 

--------------------------------------------------------------------------------

* Confidential Treatment Requested by the Registrant. Redacted Portion Filed
Separately with the Commission.

 

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3.3.                            The Share shall depend on when the agreement
referred to in article 3.2 above with such sublicensee or Contractor is executed
by Nuvios:

 

Date of execution of the agreement

 

Share payable within
thirty (30) days following
execution of the agreement

 

Before Phase Ib is completed

 

[*]

%

 

 

 

 

After Phase Ib is completed and before first NDA filing

 

[*]

%

 

 

 

 

After first NDA filing

 

[*]

%

 

provided however that:

 

3.3.1.                                     in the event that Nuvios grants
rights to a sublicensee or Contractor with respect to all countries in the
Territory, then the payments that Nuvios is required to make to Ipsen pursuant
to Section 3.2 hereof and this Section 3.3 shall be in lieu of remaining
Milestone Payments that Nuvios would otherwise be required to pay to Ipsen
pursuant to Section 3.1 above, and

 

3.3.2.                                     in the event that Nuvios grants
rights to a sublicensee or Contractor with respect to only some of the countries
in the Territory, then all remaining Milestone Payments owed by Nuvios to Ipsen
pursuant to Section 3.1 shall be appropriately and equitably reduced to reflect
and account for the market size that is accounted for by those countries in the
Territory in respect of which Nuvios has granted such rights relative to the
market size that is accounted for by all countries in the Territory.

 

ARTICLE 4   PAYMENTS BASED ON SALES OF LICENSED PRODUCT

 

4.1.                            Royalties.

 

(a)                                 In consideration for the rights and license
granted under Section 2.1. and regardless of the fact that Ipsen Formulation
Technology is, or is not an element of Licensed Product, Nuvios shall, subject
to the provisions of Sections 4.2 and 4.3 below, pay royalties to Ipsen based
upon Net Sales of any given Licensed Product in any given country in the
Territory during the Royalty Term applicable to sales of such Licensed Product
in such country, which royalties shall be equal to 5% of such Net Sales. For
purposes of clarification, the determination of the amount of royalties due
Ipsen pursuant to this Section 4.1(a) shall be made on a Licensed
Product-by-Licensed Product basis and on a country-by-country basis. Payment of
royalties due to Ipsen pursuant to this Section 4.1(a) shall be made in
accordance with the provisions of Article 5 hereof.

 

--------------------------------------------------------------------------------

* Confidential Treatment Requested by the Registrant. Redacted Portion Filed
Separately with the Commission.

 

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(b)                                 In consideration for the rights and license
under Ipsen Know-How granted to Nuvios pursuant to this Agreement, Nuvios shall
pay royalties to Ipsen based upon net sales by Nuvios, its Affiliates,
sublicensees or other commercialization contractors of any pharmaceutical
product (other than Licensed Compound or Licensed Product) that is a Nuvios
Invention and that was derived from or based on Ipsen Know-How that is
Confidential Information of Ipsen, which royalties shall be equal to [*] percent
([*]%) of such net sales. For the purpose of calculating the royalties due to
Ipsen pursuant to this Section 4.1(b), the provisions of Section 4.1(a) (other
than the royalty rate specified therein), Section 4.2, Section 4.3 and Article 5
hereof and the definition of Net Sales shall apply “mutatis mutandis”. Nuvios
shall have the unilateral right to terminate Ipsen’s rights under this
Section 4.1(b), upon written notice to Ipsen with immediate effect, if Ipsen in
any country of the world brings an action or proceeding seeking to have a Nuvios
Patent Right or Joint Patent Right declared invalid or unenforceable

 

(c)                                  Notwithstanding the foregoing provisions of
Section 4.1(a) and Section 4.1(b) or any other provisions of this Agreement to
the contrary, in the event that Ipsen or its Affiliates, has committed a
material breach of article 2.1 or article 2.6 as a result of any actions or
activities of Ipsen or its Affiliates in a country of the Territory, then all
obligations of Nuvios, its Affiliates, sublicensees or Contractors under this
Section 4.1 to pay royalties in such country shall terminate effective
immediately upon Nuvios giving written notice of termination to Ipsen.

 

4.2.                            Adjustments related to Unlicensed Products.

 

Notwithstanding anything express or implied in Section 4.1 to the contrary, if,
in a given country of the Territory, (i) there is no Valid Claim of an issued
patent within Ipsen Patent Rights or Joint Patent Rights that Covers the
composition of matter of a Licensed Product, the methods of use thereof and/or
manufacturing or formulation processes thereof in such country, and (ii) either:

 

(A) aggregate unit sales in such country of Unlicensed Products constitute more
than [*]% of the market share on a per unit basis with respect to all unit sales
of such Unlicensed Products and such Licensed Product in such country THEN
Nuvios, its Affiliates, sublicensees or Contractors shall have the right to
calculate royalty payments by including only [*]% of the amount of Net Sales
Nuvios, its Affiliates, sublicensees or Contractors would have otherwise
included for such country to calculate royalty payments, or constitute more than
[*]% of the market share on a per unit basis with respect to all unit sales of
such Unlicensed Products and such Licensed Product in such country THEN the
obligation of Nuvios, its Affiliates, sublicensees or Contractors to pay
royalties to Ipsen pursuant to Section 4.1(a) with respect to sales of such
Licensed Product in such country shall terminate and be of no further force or
effect.

 

--------------------------------------------------------------------------------

* Confidential Treatment Requested by the Registrant. Redacted Portion Filed
Separately with the Commission.

 

16

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OR (B) Unlicensed Products are commercially available in such country and the
per unit retail price of such Licensed Product has suffered a decline of more
than [*]% from the per unit price at which such Licensed Product was being sold
in such country immediately prior to the commercial entry of such Unlicensed
Products in such country, THEN Nuvios, its Affiliates, sublicensees or
Contractors shall have the right to calculate royalty payments by including only
[*]% of the amount of Net Sales Nuvios, its Affiliates, sublicensees or
Contractors would have otherwise included for such country to calculate royalty
payments, or has suffered a decline of more than [*]% from the per unit price at
which such Licensed Product was being sold in such country immediately prior to
the commercial entry of such Unlicensed Products in such country, THEN the
obligation of Nuvios, its Affiliates, sublicensees or Contractors to pay
royalties to Ipsen pursuant to Section 4.1(a) with respect to sales of such
Licensed Product in such country shall terminate and be of no further force or
effect.

 

4.3.                            Adjustments Related to third party Payments.

 

If, in connection with any Licensed Compound or Licensed Product, Nuvios is
obligated to remit payments to third parties in relation to intellectual
property rights owned by such third parties, including, without limitation, when
Nuvios licenses in formulation technology from third party for use with Licensed
Compound or Licensed Product and/or as determined pursuant to Article 11.7 of
this Agreement, Nuvios shall be permitted to offset against payments due to
Ipsen under this Agreement up to fifty percent (50%) of any payments due to such
third parties during any calendar year, provided however that this offset does
not result in a reduction of more than [*]% of the royalty payments that would
otherwise have been due to Ipsen in any calendar year. In case Nuvios has not
been able to offset any allowed amount during any relevant calendar year, no
resulting payment shall be due from Ipsen to Nuvios as a result of such
shortfall, but Nuvios shall be entitled to carry over such shortfall to one or
more subsequent calendar years and seek to offset the full amount of such
shortfall against payments otherwise due to Ipsen in such subsequent calendar
year or calendar years (subject always to the limitation set forth in this
Section 4.3 that in no event shall royalty payments that would otherwise have
been due to Ipsen during in any calendar year be reduced by more than [*]%).

 

ARTICLE 5   PAYMENT, REPORTING, AUDITING

 

5.1.                            Currency and Conversion.

 

All payments under this Agreement shall be in Euros except the milestone
payments indicated in 3.1 to be in US Dollars as well as royalty payments
referred to in this Article 5.1 with respect to Net Sales in the USA.

 

Calculation of Net Sales and royalties by Nuvios:

 

With respect to the USA: For the purpose of the royalty calculation for the USA,
Nuvios shall calculate Net Sales and calculate and pay corresponding royalties
in USD.

 

--------------------------------------------------------------------------------

* Confidential Treatment Requested by the Registrant. Redacted Portion Filed
Separately with the Commission.

 

17

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With respect to ROW: For the purpose of the royalty calculation for the ROW,
Nuvios shall calculate Net Sales and corresponding royalties in Euros. For this
purpose, whenever calculations of Net Sales or royalties require conversion from
any currency (other than Net Sales achieved in the Euro zone), Nuvios shall
convert into EUROS the amount of Gross Sales and Net Sales, using the middle
market spots exchange rates (as published in the Wall Street Journal European
Edition or if no longer available any other sources mutually-agreed by the
Parties) of the last working day of each applicable Accounting Period.

 

5.2.                            Payments and Reporting.

 

After the First Commercial Sale of Licensed Product in the Territory, Nuvios
shall calculate royalties quarterly at the end of each Accounting Period (i.e.,
March 31, June 30, September 30 and December 31) and shall pay royalties on Net
Sales quarterly within sixty (60) days after the end of each Accounting Period.

 

With each such payment, Nuvios shall provide in writing to Ipsen for the
relevant Accounting Period at least the following information split by United
States of America, EU, and any other countries of the Territory:

 

·                                          Gross Sales (expressed in the
currency in which the sale of Licensed Product is made, and for Gross Sales
achieved in the ROW, the applicable conversion rates and the resulting amount in
Euros);

 

·                                          Net Sales (expressed in the currency
in which the sale of Licensed Product is made, and for Net Sales achieved in the
ROW, the applicable conversion rates and the resulting amount in Euros);

 

·                                          Total royalty payable (expressed in
USD for the Net Sales achieved in the USA and in Euros with respect to ROW).

 

5.3.                            Late payments. Any payment under Articles 3 and
4 that is not timely paid shall bear interest, to the extent permitted by
applicable law, at the average one month European Interbank Offered Rate
(EURIBOR) as reported by Datastream (or a successor or similar organization)
from time to time, calculated on the number of days such a payment is overdue,
plus two (2) percentage points.

 

5.4.                            Taxes

 

Each Party shall pay all sales, turnover, income, revenue, value added, and
other taxes levied on account of payments accruing or made to it under this
Agreement. Nothing in the foregoing sentence shall be deemed to affect the
definition of Manufacturing Cost and/or any right that either Party specifically
is provided or granted under this Agreement to charge and collect from the other
Party the Manufacturing Cost incurred by such Party in connection with Licensed
Product supplied by such Party to the other Party.

 

18

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If provision is made in law or regulation of any country for withholding of
taxes of any type, levies or other charges with respect to any amounts payable
under this Agreement to a Party, the other Party (“Withholding Party”) shall
promptly pay such tax, levy or charge for and on behalf of the Party to the
proper governmental authority, and shall promptly furnish the Party with a
signed original certificate of such tax deduction. The Withholding Party shall
have the right to deduct any such tax, levy or charge actually paid from payment
due by the Party or be promptly reimbursed by the Party if no further payments
are due by the Party. Each Party agrees to assist the other Party in claiming
exemption from such deductions or withholdings under double taxation or similar
agreement or treaty from time to time in force and in minimizing the amount
required to be so withheld or deducted.

 

5.5.                            Blocked Countries. If by reason of law Nuvios is
unable to convert to Euros a portion of the amount due by it under this
Agreement, then Nuvios shall notify Ipsen in writing and Nuvios shall pay to
Ipsen such portion in the currency of any other country designated by Ipsen and
legally available to Nuvios.

 

5.6.                            Accounting.

 

Nuvios shall maintain and shall cause its Affiliates and Contractors to maintain
full, true and accurate books of account containing all particulars that may be
necessary for the purpose of calculating all royalties payable under this
Agreement. Such books of account shall be kept at their principal place of
business. Nuvios shall permit Ipsen, by independent qualified public accountants
selected by Ipsen and reasonably acceptable to Nuvios, to examine such books and
records at any reasonable time, but not later than three (3) years following the
rendering of any corresponding reports, accountings and payments pursuant to
this Agreement. The foregoing right of review may be exercised only once during
each twelve (12) month period. Such accountants may be required by Nuvios to
enter into a reasonably acceptable confidentiality agreement, and in no event
shall such accountants disclose to Ipsen any information other than such as
relates to the accuracy of reports and payments made or due hereunder. The
opinion of said independent accountants regarding such reports, accountings and
payments shall be binding on the parties other than in the case of manifest
error. Ipsen shall bear the cost of any such examination and review; provided
that if the inspection and audit shows an underpayment of royalty of more than
five percent (5%) of the amount due for the applicable Accounting Period, then
Nuvios shall promptly reimburse Ipsen for all costs incurred in connection with
such examination and review. Nuvios shall promptly pay to Ipsen the amount of
any such underpayment revealed by an examination and review together with late
payment interest pursuant to Article 5.3.

 

ARTICLE 6   DEVELOPMENT GOVERNANCE

 

6.1.                            Joint Steering Committee:

 

The Parties shall establish a Joint Steering Committee (JSC) which shall act as
a consultative body for the purpose of monitoring the design and implementation
of the Development Plan and generally as the forum for information sharing with
respect to the

 

19

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Development Plan. The JSC will consist of an equal number of representatives
from each Party (one or more). Each Party shall, within forty five (45) days
after the Effective Date, select its initial representatives and set a date
shortly thereafter (no later than 45 days) for the first meeting of such JSC.
Each Party may replace its representatives at any time on prior written notice
to the other Party. The Chairperson of the JSC shall be from Nuvios. The
Chairperson shall be responsible for providing an agenda for each meeting at
least ten (10) business days in advance of such meeting.

 

The JSC shall be responsible for:

 

·                                          Monitoring the Development activities
carried out by Nuvios under the Development Plan

 

·                                          co-ordinating the Development Plan
and Japanese Development Plan and activities thereunder, including scheduling
and prioritization thereof;

 

·                                          deciding on changes to Development
Plan;

 

6.2.                            Japanese Development Committee: Development
works to be undertaken in Japan shall be set forth in the Japanese Development
Plan which shall be (i) consistent with the Development Plan, (ii) consistent
with the determinations made by the JSC with respect to development activities
to be pursued, continued, discontinued or modified in Japan for the purposes of
optimizing the global development of Licensed Compound or Licensed Product in
both the Territory and Japan or for purposes of reducing the risk of global
development of Licensed Compound or Licensed Product in both the Territory and
Japan and (iii) determined in collaboration with Teijin within the framework of
a committee made of representatives of Ipsen and Teijin (Japanese Development
Committee). The chairman of the Japanese Development Committee shall at all
times be a member appointed by Ipsen. Ipsen shall represent Nuvios’ interest on
the basis of Nuvios’ instructions to Ipsen in the Japanese Development Committee
and shall not take without prior approval from Nuvios any decision with regards
to the clinical and the regulatory strategy in Japan. Nuvios shall provide Ipsen
with detailed written instructions related to the Japanese Development Plan and
its performance in a timely manner so as to enable Ipsen to comply with its
obligations under this article 6.2.

 

6.3.                            Meetings of the Joint Steering Committee:

 

The JSC shall meet at least twice (2) per year, with at least one (1) meeting
during each year in person (the location of each meeting in person to alternate
between the offices of each Party), for so long as the Development Plan
contemplates clinical development of a Licensed Product. The JSC may appoint
working sub-groups to communicate frequently and outside formal meetings.

 

The Party hosting a meeting shall prepare written draft minutes of the meeting
in reasonable detail and distribute such draft minutes to all members of the JSC
for comment and review within ten (10) business days after the relevant meeting.
The JSC members shall have seven

 

20

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(7) business days to provide comments. The Party preparing the minutes shall
incorporate timely received comments and distribute finalized minutes to all
members of the JSC within twenty four (24) business days of the relevant
meeting.

 

6.4.                            Meetings of the Japanese Development Committee:

 

The Japanese Development Committee shall first meet no later than sixty days
following signature of the first Development Plan. Thereafter the Japanese
Development Committee shall meet no less than every four (4) months as decided
by the chairman of the Japanese Development Committee. Additional meetings can
be convened by Ipsen or Teijin with no less than thirty (30) days prior written
notice which shall include the agenda for such extraordinary meeting. The agenda
of the meetings shall be prepared by the chairman of the Japanese Development
Committee and shall include any matter raised by Ipsen or Teijin for discussion
within the Japanese Development Committee.

 

Meetings of the Japanese Development Committee shall take place alternatively in
Teijin’s or Ipsen premises, in person or by video or teleconference. Ipsen shall
invite and Nuvios shall be entitled to attend and participate in all meetings of
the Japanese Development Committee, but shall have no voting right. Minutes of
the meetings shall be prepared and sent to all members of the Japanese
Development Committee by the chairman of the Japanese Development Committee.
Ipsen shall, without delay, supply Nuvios with a copy thereof for Nuvios’
comments as appropriate.

 

6.5.                            Decision-making authority:

 

Decisions of the JSC shall generally be taken by consensus. In the event of a
disagreement or a deadlock, Nuvios shall have the right to cast a tie-breaking
vote. It is understood and agreed that the exercise by Nuvios of a tie-breaking
vote so as to resolve a disagreement or deadlock at the Joint Steering Committee
shall in no way result in the elimination or reduction of Nuvios’ obligation to
use reasonable commercial efforts to develop and commercialize Licensed Product
in those countries within the Territory where it is commercially reasonable to
do so in accordance with the applicable provisions of Article 7.

 

ARTICLE 7   DEVELOPMENT PLAN AND CONDUCT OF DEVELOPMENT ACTIVITIES

 

7.1.                            Development Plan

 

The Parties have agreed upon the first Development Plan in the form attached as
Appendix C.

 

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7.2.                            Conduct of Development activities

 

Subject to the provisions set forth below in this Section 7.2, Nuvios shall use
reasonable commercial efforts to develop the Licensed Product for registration
and commercialization in those countries within the Territory where it is
commercially reasonable to do so.

 

Subject to the provisions set forth below in this Section 7.2, Nuvios shall use
reasonable commercial efforts to complete the Development Plan in order to
obtain FDA, EMEA and any other Regulatory Approvals for one Licensed Product in
those countries within the Territory where it is commercially reasonable to do
so. Nuvios shall use reasonable commercial efforts to conduct its tasks and
obligations under the Development Plan:

 

·                                          in accordance with Good Laboratory,
Good Clinical and Good Manufacturing Practices, to the extent these are
applicable;

 

·                                          in accordance with all relevant legal
requirements and shall be responsible for obtaining all necessary approvals
therefore from any Health Agency or applicable competent authority; and,

 

·                                          keeping or causing to be kept written
laboratory notebooks and other records and reports of the results and progress
of the works to be performed in sufficient detail for to accomplish its
obligations under this Agreement.

 

Nuvios shall have ultimate responsibility for all aspects of Development of
Licensed Product in the Territory, and shall bear all related costs. Nuvios
shall have no responsibility for development and costs of Licensed Product in
Japan.

 

The Parties acknowledge that time shall be of the essence in this Agreement and
thus that the time deadlines defined in any Development Plan should be complied
with and, as a matter of principle, not be postponed. However, the Parties agree
that the time deadlines defined in any Development Plan may be reasonably
modified by the JSC.

 

Notwithstanding the provisions of the immediately preceding paragraph or the
other provisions of this Agreement (including, without limitation, this
Article 7) to the contrary, Nuvios reserves the right to cause the JSC at any
time to change or modify the Development Plan or any of the preclinical studies
or clinical trials described in the Development Plan (and the time deadlines
defined in the Development Plan), or to abandon any portion of the Development
Plan or discontinue any such preclinical studies or clinical trials, in response
to (i) regulatory requirements, (ii) scientific constraints, (iii) significant
increases in the anticipated costs of Development, (iv) any significant adverse
event or condition relating to the safety or efficacy of a Licensed Product,
(v) significant changes in the anticipated costs of manufacturing,
(vi) significant adverse changes in market conditions or in market potential of
a drug candidate, or (viii) any reasonable determination made by Nuvios in good
faith that such change, modification, abandonment or discontinuation is designed
ultimately to improve the probability of obtaining Regulatory Approval of
Licensed Product in the Territory.

 

Nuvios shall communicate to Ipsen in a timely manner all Nuvios Know How, and
Ipsen shall be authorized to communicate to Teijin all of such Nuvios Know How,
free of charge,

 

22

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provided that Ipsen takes appropriate steps (including, without limitation,
entering into appropriate confidentiality agreements) to ensure that all of such
Nuvios Know How disclosed by Ipsen to Teijin is only considered, evaluated and
(to the extent permitted pursuant to Section 2.5 hereof) used by Teijin for
purposes related only and exclusively to the development and further
commercialization of License Product in Japan. At the request of Nuvios, Ipsen
shall cause Teijin to enter into a confidentiality agreement with Nuvios in form
and substance reasonably satisfactory to Nuvios and Teijin. Nuvios’ agreement
and obligations under this paragraph are subject to compliance by Ipsen with all
of its agreements and obligations set forth in the next paragraph.

 

Ipsen shall communicate, or shall cause Teijin to communicate to Ipsen or
Nuvios, free of charge and in a timely manner all Know-How, intellectual
property rights and data resulting from the performance of the Japanese
Development Plan provided that all of such Know-How, intellectual property
rights and data disclosed by Ipsen to Nuvios is only considered, evaluated and
used by Nuvios for purposes related only and exclusively to the development and
commercialization of Licensed Product in the Territory. At the request of
Teijin, Nuvios shall enter into confidentiality with Teijin in form and
substance reasonably satisfactory to Nuvios and Teijin. Ipsen’s agreement and
obligations under this paragraph are subject to compliance by Nuvios with all of
its agreements and obligations set forth in the immediately preceding paragraph.

 

Ipsen shall ensure that the Japanese Development Plan is consistent in all
material respects with the Development Plan, and Ipsen shall cause Teijin and
the Japanese Development Committee to make such changes to the Japanese
Development Plan to ensure that it is consistent in all material respects to the
Development Plan. In addition, in the event that the Development Committee
determines that changing or modifying the Japanese Development Plan or any of
the preclinical studies or clinical trials described in the Japanese Development
Plan (or the time deadlines defined in the Japanese Development Plan), or the
abandonment of any portion of the Japanese Development Plan or discontinuation
of any preclinical studies or clinical trials described in the Japanese
Development Plan, is in the best interests of the global development and
commercialization of Licensed Product in both the Territory and Japan, then
Ipsen shall use reasonable commercial efforts (including, without limitation,
enforcing Ipsen’s rights under the Teijin Agreement) to cause Teijin and the
Japanese Development Committee to make and/or implement such changes,
modifications, abandonment or discontinuation.

 

It is understood that Teijin shall have responsibility for day to day operations
under the Japanese Development Plan.

 

7.3.                            Research programme on Ipsen Formulation
Technology

 

In the event Nuvios intends to develop a formulation of the Licensed Product
with the Ipsen Formulation Technology, Nuvios and Ipsen shall agree and enter
into a separate research agreement containing a research work program and budget
under which Ipsen shall use reasonable commercial efforts to carry out research
activities to provide Nuvios with a Licensed Product formulated with Ipsen
Formulation Technology. All research activities carried out by Ipsen pursuant to
this Section 7.3 will be charged by Ipsen to Nuvios at the following rates:

 

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·                                          Internal costs: USD [*] per FTE

 

·                                          External costs: at cost.

 

Any such costs shall be invoiced by Ipsen to Nuvios quarterly in advance (with
respect to internal costs) and shall be payable within thirty (30) days of the
date of each invoice which shall also set forth those third party invoices
received during the preceding quarter. Invoice shall include the addition of
value added tax or any similar tax which may be applicable. In no event shall
Ipsen invoice Nuvios, and Nuvios be required to pay, for amounts in excess of
the amounts set forth in the budget agreed upon by the Parties, unless otherwise
agreed between the Parties.

 

Ipsen provides no guarantee of success that its research activities under such
research agreement will be successful and will result in a Licensed Compound
formulated with Ipsen Formulation Technology that is eligible for further
development activities.

 

The Parties acknowledge that time shall be of the essence in this Agreement and
thus that the time deadlines defined in any research work program agreed by both
Parties pursuant to this Section 7.3 should be complied with and, as a matter of
principle, not be postponed. However, the Parties agree that the time deadlines
defined in any such research work program may be reasonably modified by the
Parties.

 

Ipsen may not transfer, delegate or assign any of its obligations under this
Section 7.3 to any person or entity without the prior written consent of Nuvios,
which shall not be unreasonably withheld or delayed.

 

ARTICLE 8   DEVELOPMENT — REGULATORY AND SAFETY

 

8.1.                            Transfer of Ipsen Know-How and Documentation to
Nuvios. The Parties agree that, promptly following the Effective Date, at the
reasonable request from Nuvios, Ipsen shall transfer:

 

·                                          Any historical Serious Adverse Events
reports - Research and development reports

 

·                                          Any copies of any correspondence in
its possession or under its control with any regulatory agencies related to
Licensed Compound

 

·                                          Copies of all documents in its
possession or under its control relating to any Ipsen Know-How pertaining to the
research, Development or manufacture of Licensed Compound or Licensed Product

 

·                                          Copies of all patents and patent
applications included within Ipsen Patent Rights pertaining to Licensed Compound
or Licensed Product

 

--------------------------------------------------------------------------------

* Confidential Treatment Requested by the Registrant. Redacted Portion Filed
Separately with the Commission.

 

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Upon the reasonable request from Nuvios made at any time or from time to time
during the Term, Ipsen shall transfer to Nuvios all of the items listed above to
the extent that such items have not previously been transferred to Nuvios.

 

In addition, from time to time during the Term, at the reasonable request of
Nuvios, Ipsen agrees to make available to Nuvios those of Ipsen’s employees and
consultants that have knowledge and expertise in connection with researching,
developing, manufacturing, obtaining regulatory approval for, or creating and
prosecuting intellectual property with respect to, any of the Licensed Compounds
or Licensed Products for purposes of facilitating the transfer of all Ipsen
Know-How to Nuvios in connection with any such Licensed Compound or Licensed
Product. The performance by Ipsen of its obligations under this paragraph shall
be at no cost to Nuvios.

 

8.2.                            Responsibility for Regulatory Affairs. Nuvios
shall be responsible for all regulatory affairs in the Territory related to
Licensed Compound and Licensed Product, including the preparation and filing of
applications for Regulatory Approval, as well as any or all governmental
approvals required to manufacture, or have manufactured, Licensed Compound or
Licensed Product. Nuvios shall file all such applications in its own name, or
that of its Affiliate. Nuvios shall provide Ipsen with copies of all
correspondence and final filings (including, without limitation, IND filings and
NDA Filings) related to Licensed Product with regulatory authorities for Ipsen
and/or Teijin’, provided that Ipsen has complied with all of its obligations in
the next sentence. Ipsen shall provide, or cause Teijin to provide, Nuvios with
copies of all correspondence and final filings (including, without
limitation, IND filings and NDA Filings) made by Teijin related to Licensed
Product with regulatory authorities in Japan.

 

8.3.                            Ownership of Regulatory Approvals: Nuvios shall
own all Regulatory Approval files and Regulatory Approvals in the Territory,
provided that with respect to France, if Ipsen has elected to co-market the
Licensed Product in France pursuant to, and in accordance with, the provisions
of Section 10.2, Nuvios shall apply for two NDAs to allow co-marketing in
France. One NDA shall be in the name of Nuvios and the other NDA shall be in the
name of Ipsen.

 

8.4.                            Drug Safety Database and pharmaco-vigilance
responsibility. Nuvios shall be the holder of the reference global safety
database. With respect to Japan and France, as the case may be, the Parties
further agree that Nuvios will execute with Ipsen or Teijin (as Ipsen shall
indicate) and when deemed appropriate by the Parties before Nuvios initiates any
clinical trial, a separate pharmaco-vigilance agreement (the “Pharmacoviligance
Agreement”) in form and substance reasonably satisfactory to Nuvios and the
other party or parties thereto that will include the mutually agreed process to
be used for the exchange of pharmaco-vigilance data. The Pharmacovigilance
Agreement shall include the following: Upon identification of any potential
safety issue, Nuvios’ Drug Safety group will contact all Parties’ members of the
joint Drug Safety Committee (as defined in the Pharmacovigilance Agreement) if
an urgent need requires such a committee to meet. The joint Drug Safety
Committee will at its meeting agree on appropriate measures to deal with the
relevant safety issue and all Parties shall fully implement such measures. The
joint Drug Safety Committee shall operate by consensus with the exception that,
if there is disagreement or deadlock at the joint Drug Safety Committee, Nuvios
shall have

 

25

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the final say as holder of the main regulatory responsibilities to the extent
permitted by applicable laws and regulations. Ipsen shall cause Teijin to comply
with the provisions of this Section 8.4.

 

ARTICLE 9   MANUFACTURE AND SUPPLY

 

9.1.                            Clinical Supply for the Phase I and Phase II
Clinical Trials. Except as otherwise agreed by the JSC, Ipsen shall make and
supply, or cause to be made and supplied, all necessary clinical supply of the
injection formulation of the Licensed Compound and/or Licensed Product
(described in Appendix D hereto) that is available to Ipsen on the Effective
Date for use by Nuvios for the performance of Phase I and first Phase II
Clinical Trials under the Development Plan. Clinical supply of Licensed Compound
or Licensed Product to Nuvios under this Section 9.1 shall be provided at
Ipsen’s Manufacturing Cost. The Parties shall enter into a clinical supply
agreement and a technical agreement with respect to such clinical supplies by
Ipsen to Nuvios. Such supply agreement and technical agreement are appended
hereto in Appendix D. Ipsen shall not be obligated to manufacture clinical
supply of Licensed Compound and/or Licensed Product for any Phase III clinical
study or for commercial supply.

 

9.2.                            Transition.

 

At the request of Nuvios, Ipsen shall provide to Nuvios a manufacturing transfer
package no later than sixty (60) days from the date of request by Nuvios, and
Ipsen shall use reasonable commercial efforts to transfer to Nuvios all Ipsen
Know-How and methods pertaining to the manufacture of Licensed Compound and/or
Licensed Product and Nuvios shall use commercial reasonable efforts to
understand and implement such Ipsen Know How and methods pertaining to the
manufacture of Licensed Compound and/or Licensed Product. The timing and the
steps to be followed by the Parties in connection with any such transfer shall
be set out in more detail in the clinical supply and technical agreement
contemplated under Section 9.1 above. Nuvios shall request that Ipsen proceed to
the transfer contemplated by this Section 9.2 in a timely manner so that the
timing set forth in the clinical supply and technical agreement contemplated
under Section 9.1 above is complied with. Prior to the commencement of a Phase
III Clinical Trial with respect to Licensed Compound or Licensed Product by
Nuvios, Nuvios shall use reasonable commercial efforts to review and implement
and scale-up the manufacturing processes in a timely manner so as to be capable
of supplying adequate quantities of conforming Licensed Compound and Licensed
Product for a Phase III Clinical Trial in compliance with the targeted timelines
of the Development Plan and the Japanese Development Plan. Clinical supply of
Licensed Product to Ipsen for onward supply to Teijin under this Article 9.2
shall be provided at Nuvios’ Manufacturing Cost for such clinical supply at the
time of the manufacture thereof. At such time as Nuvios shall have successfully
implemented and scaled-up the manufacturing processes so as to be capable of
supplying adequate quantities of conforming Licensed Compound and Licensed
Product for such Phase III Clinical Trial, Ipsen shall cease all manufacturing
activities with respect to Licensed Compound and Licensed Product.

 

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9.3.                            Commercial Supply.

 

Nuvios shall be solely and exclusively responsible for the manufacture, in
accordance with good manufacturing practice, and supply of commercial quantities
of Licensed Product in the Territory (including France) and Japan after receipt
of Regulatory Approval therefore in the applicable jurisdiction or
jurisdictions.

 

With respect to Japan: Nuvios shall supply commercial quantities of finished and
fully labeled Licensed Product (and shall provide any clinical supplies that may
be required after obtaining Regulatory Approval) to Ipsen for Teijin in Japan at
a supply price equal to 10% of net sales in Japan. Should the manufacturing
costs be anticipated to exceed 10% of net sales in Japan, as evidenced by
Nuvios, then the Parties shall discuss in good faith to define a new supply
price which shall be no less than a supply price equal to such manufacturing
costs plus a reasonable markup (not to exceed [*] percent of such manufacturing
costs).

 

With respect to France if Ipsen has elected to co-market Licensed Product in
France: Nuvios shall supply commercial quantities of finished and fully labeled
Licensed Product (and shall provide any clinical supplies that may be required
after obtaining Regulatory Approval) to Ipsen for France at a supply price equal
to (i) for commercial supplies, Nuvios’ Manufacturing Cost plus a [*] percent
([*] %) margin, and (ii) for clinical supplies, Nuvious Manufacturing Cost.

 

The Parties, with respect to the supply of Licensed Product for France and for
Japan contemplated pursuant to this Section 9.3, shall agree on the terms of a
commercial supply agreement and a technical agreement no later than the date of
first NDA filing for Licensed Product in the corresponding country. It shall be
a condition precedent to Nuvios’ supply obligations under this Section 9.3 that
the Parties shall have agreed upon the terms of, and executed and delivered to
each other, such supply agreement and such technical agreement. Without limiting
the foregoing provisions of this paragraph, such agreements should provide
standard provisions commonly used in the industry, including:

 

·                                          that Ipsen or Teijin shall provide
binding forecasts of the clinical and commercial quantities of Licensed Product
required for Japan,

 

·                                          that Nuvios or its contractor shall
manufacture in accordance with good manufacturing practice and supply Licensed
Product compliant to specifications,

 

·                                          that disruption of supply shall be
remedied by equitable sharing of available stock,

 

·                                          that Ipsen or Teijin shall bear the
costs (including, without limitation, capital costs) associated with
establishing any special manufacturing process or changing any established
manufacturing process, in either case that may be required in Japan for the
manufacture of Licensed Product but is not required in the Territory,

 

·                                          audit of the manufacturing facility
and the manufacturing process implemented in the manufacture of Licensed
Compound and Licensed Product so as to ensure that Nuvios or its contractor
manufactures in accordance with good manufacturing

 

--------------------------------------------------------------------------------

* Confidential Treatment Requested by the Registrant. Redacted Portion Filed
Separately with the Commission.

 

27

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practice and the Regulatory Approvals, including the Japanese Regulatory
Approvals;

 

·                                          audit of Nuvios’ or its contractor’s
Manufacturing Cost and that upon request from Ipsen, Nuvios will provide to
Ipsen a certificate from the Nuvios auditors confirming the determination of
Manufacturing Cost in accordance with IAS as consistently applied by Nuvios or
its contractor in determining the cost of goods.

 

ARTICLE 10   COMMERCIALIZATION

 

10.1.                     Nuvios, at its own expense, shall have sole
responsibility and decision-making authority for the marketing, promotion, sale
and distribution of Licensed Product in the Territory under Nuvios’s Regulatory
Approvals. Subject to obtaining any required Regulatory Approvals and subject
also to the provisions set forth below in Section 10.4, Nuvios shall use
reasonable commercial efforts to market, promote, sell and distribute the
Licensed Product in those countries within the Territory where it is
commercially reasonable to do so.

 

10.2.                     Ipsen may, at any time during the term of this
Agreement, elect to co-market or co-promote a Licensed Product in France, free
of charge, provided that (i) at the time of such election Nuvios has either
elected to file for Regulatory Approval to sell such Licensed Product in France
or is selling such Licensed Product in France, (ii) at the time of such election
such Licensed Product is Covered by a Valid Claim of Ipsen Patent Rights in
France and (iii) at the time of such election Ipsen is not in material breach of
this Agreement or any of the Related Agreements. In the event that Ipsen makes
any such election, the Parties shall, within thirty days following the
notification of such election to Nuvios, enter into either a co-promotion
agreement or co-marketing agreement containing standard provisions as usual in
the pharmaceutical industry and the following particular conditions:

 

10.2.1.                              Nuvios will be responsible for ensuring
that the requisite Regulatory Approvals are submitted and, if necessary, varied
or transferred and shall use reasonable commercial efforts to obtain the same in
order to permit such co-marketing or co-promotion in France.

 

10.2.2.                              Co-promotion particular provisions:

 

·                                          All revenues from sales of Licensed
Product in France will be booked by Nuvios.

 

·                                          Nuvios shall have final say as to the
identity of the accounts to be called on by the respective sales forces of
Nuvios and Ipsen, as to the number, frequency and priority of sales calls, and
as to the allocation of sales call responsibilities among the respective sales
forces of Nuvios and Ipsen.

 

·                                          Ipsen shall elect the percentage (not
to exceed [*]%) of the revenues from sales of Licensed Product in France to
which Ipsen shall be entitled, Ipsen shall be allocated such percentage of such
revenues, and Ipsen shall be allocated that same

 

--------------------------------------------------------------------------------

* Confidential Treatment Requested by the Registrant. Redacted Portion Filed
Separately with the Commission.

 

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percentage of the aggregate amount (the “Co-Promotion Expenses Amount”) of those
costs and expenses incurred by both Nuvios and Ipsen in connection with such
co-promotion efforts that would be customarily shared costs and expenses in a
typical drug co-promotion arrangement in the pharmaceutical industry.

 

·                                          The Parties shall make payments to
each other on a quarterly basis to the extent necessary so that each Party is
allocated its proper percentage of the revenues from sales of Licensed Product
in France during the applicable calendar quarter and its proper percentage of
the Co-promotion Expenses Amount during the applicable calendar quarter.

 

·                                          Ipsen will pay Nuvios on a quarterly
basis a [*]% royalty on Ipsen’s allocable portion of the net revenues from sales
of Licensed Product in France during the applicable calendar quarter.

 

10.2.3.                              Co-marketing provisions:

 

·                                          Each of Nuvios and Ipsen will be a
Regulatory Approval holder, unless dual Regulatory Approval holders are not
permitted under the applicable law, in which case Nuvios shall be the Regulatory
Approval holder. Nuvios shall have responsibility for all pricing/ reimbursement
approvals. Each Party will market and distribute Licensed Product in France
under such Party’s own brand. For purposes of this Section 10.2.3, Licensed
Product co-marketed by Ipsen in France shall be referred to as “Ipsen Licensed
Product”.

 

·                                          Ipsen will purchase finished Ipsen
Licensed Product from Nuvios at Nuvios Manufacturing Cost plus a [*]% markup.
Ipsen Licensed Product shall be packaged and labeled in such manner so as to
clearly distinguish Ipsen Licensed Product from Licensed Product commercialized
by Nuvios in France or elsewhere in the Territory.

 

·                                          Ipsen will pay Nuvios on a quarterly
basis a [*]% royalty on Ipsen’s net sales from the sale of Ipsen Licensed
Product in France during the applicable calendar quarter, and Nuvios will pay
Ipsen on a quarterly basis a [*]% royalty on Net Sales from the sale of Licensed
Product in France by Nuvios, its Affiliates or Contractors during the applicable
calendar quarter.

 

·                                          In the event that either Party
becomes aware that units of Ipsen Licensed Product sold or intended for sale in
France by Ipsen are being exported from France and imported into and sold in
another country in the Territory, such Party shall provide written notice to the
other Party and Ipsen shall have a period of ninety (90) days to remedy the
situation. If, within such ninety (90) day period, Ipsen is unable to cause the
export of Licensed Product from France and sale in any other country or
countries to stop, then Nuvios may require that an independent qualified public

 

--------------------------------------------------------------------------------

* Confidential Treatment Requested by the Registrant. Redacted Portion Filed
Separately with the Commission.

 

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accountant selected by Nuvios and reasonably acceptable to Ipsen examine, at the
expense of Nuvios, the books and accounts of Ipsen with respect to the sales of
Ipsen Licensed Product with a view to determine whether a material quantity of
such Ipsen Licensed Product have been exported from France. If and when it is
determined that a material quantity of such Ipsen Licensed Product have been
exported from France, the cost of such examination incurred by Nuvios shall be
reimbursed by Ipsen and Ipsen shall be required to make payment to Nuvios of an
amount equal to [*] percent ([*]%) of the net sales of Ipsen in France with
respect to any units of Ipsen Licensed Product that have been determined to have
been exported from France.

 

10.2.4.                              Assignment and sub license:

 

Ipsen’s rights under this Section 10.2 may not be assigned, sublicensed or
transferred to any person or entity.

 

10.2.5.                              Condition Precedent:

 

The respective rights and obligations of the Parties under this Section 10.2 are
subject to the condition precedent that the Parties shall have mutually agreed
upon, and executed and delivered to each other, a co-promotion agreement or
co-marketing agreement, as the case may be, with respect to sales and
commercialization of Licensed Product in France that incorporates the provisions
of this Section 10.2.

 

10.3.                     In the event that either Party becomes aware that
units of Licensed Product sold or intended for sale in Japan by Teijin, its
Affiliates or sublicensees are being exported from Japan and imported into and
sold in any country or countries in the Territory, such Party shall provide
written notice to the other Party and Teijin and, thereafter, Ipsen or Teijin
shall have a period of ninety (90) days to remedy the situation. If, within such
ninety (90) day period, neither Ipsen nor Teijin is able to cause the export of
Licensed Product from Japan and sale in any other country or countries to stop,
then Nuvios may require that an independent qualified public accountant selected
by Nuvios and reasonably acceptable to Teijin examine, at the expense of Nuvios,
the books and accounts of Teijin with respect to the sales of Licensed Product
with a view to determine whether a material quantity of such Licensed Product
has been exported from Japan. If and when it is determined that a material
quantity of such Licensed Product has been exported from Japan, the cost of such
examination incurred by Nuvios shall be reimbursed by Ipsen or Teijin and Ipsen
shall be required to make payment, or to cause Teijin to make payment, to Nuvios
of an amount equal to [*] percent ([*]%) of the net sales of Teijin in Japan
with respect to any units of Licensed Product that have been determined to have
been exported from Japan.

 

--------------------------------------------------------------------------------

* Confidential Treatment Requested by the Registrant. Redacted Portion Filed
Separately with the Commission.

 

30

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ARTICLE 11   INTELLECTUAL PROPERTY

 

11.1.                     Trademarks

 

Nuvios shall identify and select one or more trademarks to be used to register,
distribute and promote Licensed Product in the Territory (collectively, “Nuvios
Trademarks” and each individually a “Nuvios Trademark”). Unless otherwise agreed
between the Parties, Ipsen shall not avail itself of any license on any Nuvios
Trademark, shall not register or use any Nuvios Trademark and shall not license,
register or use any other trademark or trade name which is the same as, or
confusingly similar to, any Nuvios Trademark in any country, except Japan where
Ipsen or Teijin may use the Nuvios Trademark and in such event, Nuvios shall
grant appropriate license free of charge to Ipsen or Teijin for use of such
Nuvios Trademark in Japan (except to the extent provided in the next sentence).
Nuvios shall own and, at its cost, shall be responsible for procurement,
registration, maintenance and enforcement of all Nuvios Trademarks used or
registered in connection with any Licensed Product, except that Ipsen or Teijin
shall pay for all of the costs and expenses of Nuvios in connection with
procuring, registering, maintaining and enforcing Nuvios Trademarks in Japan.

 

Ipsen shall identify and select one or more trademarks to be used to register,
distribute and promote such Licensed Product under Ipsen Regulatory Approvals in
France (collectively, “Ipsen Trademarks” and each individually an “Ipsen
Trademark”), provided that, in identifying, selecting, registering and/or using
any such Ipsen Trademark, Ipsen complies with all of the provisions of the first
paragraph of this Section 11.1 that are applicable to Ipsen. Unless otherwise
agreed between the Parties, Nuvios shall not avail itself of any license on any
Ipsen Trademark, shall not register or use any Ipsen Trademark and shall not
license, register or use any other trademark or trade name which is the same as,
or confusingly similar to, any Ipsen Trademark in France. Ipsen shall own and,
at its cost, shall be responsible for procurement, maintenance and enforcement
of all Ipsen Trademarks used or registered in connection with any Licensed
Product.

 

11.2.                     Infringements of Trademarks

 

Nuvios and Ipsen shall give prompt written notice to the other Party of any
suspected or actual infringement by any person of Nuvios’ rights in the Nuvios
Trademarks, or any potential or actual infringement of any person’s rights which
might result from use of any Nuvios Trademark, that comes to the attention of
the Parties during the term of this Agreement. Nuvios shall have the right but
not the obligation to initiate proceedings against, or defend claims made by,
any person in connection with any Nuvios Trademark. The commencement,
strategies, termination, settlement or defense of any action relating to the
validity or infringement of Nuvios Trademarks shall be decided by Nuvios. Any
such proceedings shall be at the expense of Nuvios. Any damages or costs
recovered by Nuvios as a result of any such proceedings or claims, shall be for
the sole benefit and account of Nuvios.

 

Nuvios and Ipsen shall give prompt written notice to the other Party of any
suspected or actual infringement by any person of Ipsen’s rights in the Ipsen
Trademarks, or any potential or actual infringement of any person’s rights which
might result from use of any Ipsen Trademark, that comes to the attention of the
Parties during the term of this Agreement. Ipsen shall have the right but not
the obligation to initiate proceedings against, or defend claims made by, any
person in connection with any Ipsen Trademark. The commencement, strategies,
termination, settlement or defense of any action relating to the validity or
infringement of Ipsen Trademarks shall be

 

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decided by Ipsen. Any such proceedings shall be at the expense of Ipsen. Any
damages or costs recovered by Ipsen as a result of any such proceedings or
claims, shall be for the sole benefit and account of Ipsen.

 

11.3.                     Patent Right and Know-How Ownership

 

11.3.1.                              Ipsen shall own all Ipsen Inventions,
Nuvios shall own all Nuvios Inventions, and Ipsen and Nuvios shall jointly own
all Joint Inventions. Each Party promptly will notify the other Party in writing
of (i) any Inventions that the notifying Party believes is a Joint Invention and
(ii) any Inventions for which the notifying Party intends to file a patent
application. Each Party shall require all of its employees and contractors to
assign all Inventions made by them to such Party.

 

11.3.2.                              As between Ipsen and Nuvios, any and all
Ipsen Know-How, Ipsen Patent Rights and Ipsen Formulation Technology are and
shall remain vested in and owned by Ipsen, subject only to the exclusive
licenses granted by Ipsen to Nuvios pursuant to Section 2.1.

 

11.3.3.                              As between Ipsen and Nuvios, any and all
Nuvios Know-How and Nuvios Patent Rights are and shall remain vested in and
owned by Nuvios.

 

11.3.4.                              Any and all Joint Inventions and Joint
Patent Rights shall be owned by the Parties in equal undivided shares. Except to
the extent otherwise provided elsewhere in this Agreement to the contrary
(including, without limitation, the provisions of Section 2.1 pursuant to which
Ipsen granted to Nuvios an exclusive license to all of Ipsen’s right, title and
interest in and to all of the Joint Inventions and Joint Patent Rights for
certain uses specified therein), each Party shall be free to use its undivided
share of any and all Joint Inventions or any and all Joint Patent Rights without
having to obtain the agreement or consent of the other Party, without having to
provide notice of such use to the other Party and without having to make any
accounting to the other Party for such use or any revenues or profits derived
from such use. In addition, except to the extent otherwise provided elsewhere in
this Agreement to the contrary, each Party shall be free to sell, assign,
license and otherwise transfer or dispose of all or any portion of such Party’s
undivided share in any and all Joint Inventions or any and all Joint Patent
Rights without having to obtain the agreement or consent of the other Party,
without having to provide notice of such sale, assignment, license or other
transfer or disposition to the other Party and without having to make any
accounting to the other Party for such sale, assignment, license or other
transfer or disposition or any revenues or profits derived from such sale,
assignment, license or other transfer or disposition; provided, however, that
(x) any buyer, assignee, licensee or other transferee of all or any portion of
the Joint Inventions and Joint Patent Rights shall take all or the portion of
the Joint Inventions and/or Joint Patent Rights so transferred subject to all of
the agreements and obligations under this Agreement of the transferring Party
(including, without limitation, the exclusive licenses granted by Ipsen to
Nuvios pursuant to Section 2.1 hereof with respect to certain uses of Ipsen’s
right, title and interest to the Joint Inventions and Joint Patent Rights),
(y) such buyer, assignee, licensee or other transferee shall, as a condition
precedent to the

 

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effectiveness of any such sale, assignment, license or other transfer or
disposition, execute an instrument in writing agreeing to assume all of the
agreements and obligations under this Agreement of the transferring Party to the
extent applicable to the Joint Inventions or Joint Patent Rights, or the portion
thereof, transferred to such buyer, assignee, licensee or other transferee, and
(z) any such sale, assignment, license or other transfer or disposition shall
not operate to release the transferring Party from any of its agreements or
obligations under this Agreement.

 

Nuvios may use during the Term any and all Joint Inventions and Joint Patent
Rights for the purposes contemplated in this Agreement.

 

11.4.                     Filing — Prosecution and Maintenance of Ipsen Patent
Rights and Nuvios Patent Rights

 

Ipsen shall at its own cost and expense be solely responsible for the filing,
prosecution and maintenance of the Ipsen Patent Rights in the Territory,
including the conduct and defense of any claims or proceedings relating to the
Ipsen Patent Rights in the Territory (including but not limited to any
interference, reissue or re-examination or opposition proceedings); provided,
however, that Ipsen shall (i) provide Nuvios with all material documentation and
correspondence from, sent to or filed with patent offices in the Territory
regarding the Ipsen Patent Rights, (ii) provide Nuvios with a reasonable
opportunity to review and comment upon all filings with such patent offices in
advance of submissions to such patent offices, and (iii) shall consider, in good
faith, incorporating any reasonable comments provided by Nuvios with respect to
any such filings. Without limiting the generality of the foregoing provisions of
this Section 11.4, Ipsen shall at its own cost and expense file, prosecute and
maintain Ipsen Patent Rights in any country in the Territory as reasonably
requested by Nuvios acting in a reasonable commercial manner with regards the
market potential of such country, including the conduct and defense of any
claims or proceedings relating to the Ipsen Patent Rights in such country
(including but not limited to any interference, reissue or re-examination or
opposition proceedings). If Ipsen determines in its sole discretion to abandon
or not to file, prosecute or maintain any claim, patent or patent application
within the Ipsen Patent Rights in any country in the Territory, including the
conduct and defense of any claims or proceedings relating to such claim, patent
or patent application (including but not limited to any interference, reissue or
re-examination or opposition proceedings), then Ipsen shall provide Nuvios with
thirty (30) days prior written notice of such determination, and shall provide
Nuvios with the opportunity to file, prosecute and maintain such claim, patent
or patent application in such country in the name of Nuvios (or an Affiliate of
Nuvios) as assignee, including the conduct and defense of any claims or
proceedings relating to such claim, patent or patent application in such country
(including but not limited to any interference, reissue or re-examination or
opposition proceedings), and Ipsen shall assign to Nuvios its entire right in
such claim, patent or patent application in such country, and thereafter Nuvios
shall be responsible for all costs and expenses in connection with the filing,
prosecution or maintenance of any such claim, patent or patent application
assigned by Ipsen to Nuvios pursuant to this Section 11.4(a). Ipsen shall also
pay for all costs and expenses in connection with any assignment by Ipsen to
Nuvios of any claim, patent or patent application pursuant to

 

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this Section 11.4(a). Nuvios shall upon first request from Ipsen deliver to
Ipsen the original of any Regulatory Approval for the purpose of applying for
any supplementary protection certificates of any Ipsen Patent Rights.

 

11.4.1.                              Nuvios shall at its own cost and expense be
solely responsible for the filing, prosecution and maintenance of the Nuvios
Patent Rights, including the conduct and defense of any claims or proceedings
relating to the Nuvios Patent Rights in the Territory (including but not limited
to any interference, reissue or re-examination or opposition proceedings).

 

11.4.2.                              Each Party will take account of the other
Party’s interest in the performance of its obligations under this Section 11.4.
Each Party shall provide to the other all assistance reasonably requested by the
other Party on all such matters (at the expense of such other Party), including
agreeing to and taking all steps and executing all documents necessary to be
joined as claimant or defendant in any proceedings in any country.

 

11.5.                     Filing — Prosecution and Maintenance of Joint Patent
Rights. Unless the Parties otherwise mutually agree in writing, Nuvios shall
have the first right to file, prosecute and maintain the Joint Patent Rights in
any and all countries of the world, including the conduct and defense of any
claims or proceedings relating to the Joint Patent Rights in any and all
countries of the world (including but not limited to any interference, reissue
or re-examination or opposition proceedings), provided however, in the event
that Nuvios determines in its sole discretion to abandon or not to file,
prosecute or maintain any claim, patent or patent application within the Joint
Patent Rights in any country of the world, including the conduct and defense of
any claims or proceedings relating to such claim, patent or patent application
(including but not limited to any interference, reissue or re-examination or
opposition proceedings), then Nuvios shall provide Ipsen with thirty (30) days
prior written notice of such determination, and Ipsen shall have such right and
upon exercise of such right, Ipsen shall have the right to file, prosecute and
maintain such claim, patent or patent application in such country, including the
conduct and defense of any claims or proceedings relating to such claim, patent
or patent application in such country (including but not limited to any
interference, reissue or re-examination or opposition proceedings). In each case
under this Section 11.5, the filing Party (A) shall give the non-filing Party a
reasonable opportunity to review the text of the application or submission
before filing, (B) shall consult with the non-filing Party with respect thereto,
(C) shall, prior to filing any application or submission, incorporate any
reasonable comments that the non-filing Party shall make on a timely basis to
such application or submission and (D) shall supply the non-filing Party with a
copy of the application or submission as filed, together with notice of its
filing date and serial number and all substantive prosecution. Each Party shall
keep the other advised of the status of the actual and prospective patent
filings described above in this Section 11.5 and, upon the request of the other,
provide advance copies of any papers related to the filing, prosecution and
maintenance of such patent filings. Nuvios shall promptly give notice to Ipsen
of the grant, lapse, revocation, surrender, invalidation or abandonment in the
Territory or outside the Territory of any Joint Patent Rights being prosecuted
by Nuvios. Ipsen shall promptly give notice to

 

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Nuvios of the grant, lapse, revocation, surrender, invalidation or abandonment
in the Territory or outside the Territory of any Joint Patent Rights being
prosecuted by Ipsen. With respect to all filings under this Section 11.5, the
filing Party shall be responsible for payment of all costs and expenses related
to such filings (including, without limitation, fees and disbursements of
outside legal counsel in connection with such filings), subject to prompt
reimbursement from the non-filing Party for fifty percent (50%) of all of such
costs and expenses. Either Party may disclaim its interest in any particular
patent or patent application included in the Joint Patent Rights, in which case
(X) the disclaiming Party shall assign its ownership interest in such patent or
patent application to the other Party for no additional consideration, (Y) the
Party which is then the sole owner shall be solely responsible for all future
costs of such patent or patent application and (Z) the disclaiming Party shall
hold no further rights thereunder.

 

11.6.                     Infringement

 

Each Party shall give prompt written notice to the other of any suspected or
actual Infringement by a third party of all or any portion of the Ipsen Compound
Technology, Ipsen Formulation Technology, Nuvios Patent Rights, Nuvios Know-How,
Nuvios Inventions, Joint Inventions or Joint Patent Rights (the Infringed
Rights) that comes to the attention of that Party during the Royalty Term with
respect to any and all countries in the Territory. Nuvios shall have the first
right but not the obligation to initiate and pursue proceedings against such
third party in connection with any such suspected or actual Infringement of all
or any portion of the Ipsen Compound Technology, Ipsen Formulation Technology,
Joint Inventions or Joint Patent Rights„ and Nuvios shall have the sole right
but not the obligation to initiate and pursue proceedings against such third
party in connection with any such suspected or actual Infringement of all or any
portion of Nuvios Patent Rights, Nuvios Know-How or Nuvios Inventions. The
commencement, strategies, termination, and settlement of any action or
proceedings relating to the validity or suspected or actual Infringement of the
Ipsen Compound Technology, Ipsen Formulation Technology, Joint Inventions or
Joint Patent Rights, or any portion thereof shall be decided by Nuvios in
consultation with Ipsen. The commencement, strategies, termination, and
settlement of any action or proceedings relating to the validity or suspected or
actual Infringement of Nuvios Patent Rights, Nuvios Know-How or Nuvios
Inventions, or any portion thereof, shall be decided solely by Nuvios without
any requirement that Nuvios consult with Ipsen. Any proceedings initiated and
pursued by Nuvios pursuant to this Section 11.6 shall be at the expense of
Nuvios. Nothing in this Agreement, however, shall be deemed to require Nuvios to
enforce all or any portion of the Ipsen Compound Technology, Ipsen Formulation
Technology, Joint Inventions or Joint Patent Rights„ Nuvios Patent Rights,
Nuvios Know-How or Nuvios Inventions against others; provided, however, that if
Nuvios does not enforce all or any portion of the Ipsen Compound
Technology, Ipsen Formulation Technology, Joint Inventions or Joint Patent
Rights„ Ipsen may do so at its expense and, if necessary under the relevant law
of the concerned jurisdiction, in the name of Nuvios as a plaintiff, unless
Nuvios reasonably believes that pursuit by Ipsen of any such enforcement action
jeopardizes all or any portion of the Ipsen Compound Technology, Ipsen
Formulation Technology, Joint Inventions or Joint Patent Rights„ including the
validity thereof, and sends written notice to Ipsen stating that Ipsen should
not pursue any such enforcement action for this reason, in which case Ipsen
shall

 

35

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not pursue any such enforcement action. Ipsen may not settle any proceedings or
other enforcement action without the prior written consent of Nuvios, which
consent shall not be unreasonably withheld or delayed. At the request of the
Party bringing such enforcement action or proceeding under this Section 11.6,
the other Party shall cooperate reasonably with such Party, including without
limitation by having such other Party agree to be named as a party if necessary
to such enforcement action or proceeding, and any such reasonable cooperation by
such other Party shall be at the sole cost and expense of such Party that
requested such cooperation. The Party not bringing an enforcement action or
proceeding under this Section 11.6 shall be entitled to separate representation
in such matter by counsel of its own choice and at its own expense. Any damages,
costs or other amounts recovered in connection with any action or proceeding
initiated and pursued by Nuvios or Ipsen pursuant to this Section 11.6,
including, without limitation, any settlement thereof, shall be allocated first
to the reimbursement of any reasonable expenses incurred by the Party that
initiated and pursued such action or proceeding pursuant to this Section 11.6,
and any remaining amounts shall be allocated as follows: (i) in the case of any
action or proceeding initiated and pursued by Nuvios, such remaining amounts
shall be treated as Net Sales and the royalty on such sums shall be payable to
Ipsen pursuant to Article 4, and (ii) in the case of any action or proceeding
initiated and pursued by Ipsen, such remaining amounts shall be split fifty
percent (50%) to Nuvios and fifty percent (50%) to Ipsen.

 

11.7.                     third party intellectual property rights

 

11.7.1.                              Each Party shall give prompt written notice
to the other of any intellectual property rights of any third party which could
reasonably be considered as constituting impediment on the use of the Ipsen
Compound Technology, Ipsen Formulation Technology, Joint Inventions or Joint
Patent Rights in accordance with the provisions of this Agreement or on the
research, development, manufacture, use, marketing, promotion, distribution,
sale, import or export of Licensed Compound or Licensed Product, in which event
the Parties shall agree on the strategy and procedural steps to be taken in
respect of opposing and/or settling such potential impediment.

 

11.7.2.                              Each Party shall give prompt written notice
to the other of claims or suits arising out of actual or alleged Infringement of
Patent Rights, Know-How or other intellectual property owned by a third party,
as a result of any use of the Ipsen Compound Technology, Ipsen Formulation
Technology, Joint Inventions or Joint Patent Rights in accordance with the
provisions of this Agreement or on the research, development, manufacture, use,
marketing, promotion, distribution, sale, import or export of Licensed Compound
or Licensed Product, in which event Nuvios shall have up to ninety (90) days
from receipt of such written notice to contest or defend such claim or suit on
behalf of itself and on behalf of Ipsen. If Nuvios elects to contest or defend
such claim or suit, Nuvios shall notify Ipsen of such election, and shall keep
Ipsen fully informed of any development in such claim or suit, including by
transmitting copies of all documents in such claim or suit. If Nuvios contests
or defends a claim or suit pursuant to this Section 11.7.2, then (a) Nuvios
shall control of the defense of such claim or suit, (b) Ipsen shall provide
assistance in the defense of such claim or suit in a reasonable and timely
manner

 

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upon reasonable request of Nuvios and at Nuvios’ sole cost and expense; and
(c) Nuvios shall have the right to compromise or settle such claim or suit;
provided, however, that such compromise or settlement shall be subject to
Ipsen’s prior written approval, which shall not be unreasonably withheld.
Notwithstanding Nuvios’ control of the defense of any such claim or
proceeding, Ipsen shall have the right to participate in such defense using
counsel of its own choice and at its own expense.

 

11.7.3.                              If, within such ninety (90) day period,
Nuvios elects not to contest or defend, or fails to notify Ipsen of its intent
to contest to or defend, such claim or suit, then Ipsen shall have the right to
contest or defend such claim or suit on behalf of itself and Nuvios and shall
keep Nuvios fully informed of any development in such claim or suit, including
by transmitting copies of all documents submitted in such claim or suit. If
Ipsen contests or defends a claim or suit pursuant to this Section 11.7.3, then
(a) Ipsen shall control the defense of such claim or suit, (b) Nuvios shall
provide assistance in the defense of such claim or suit in a reasonable and
timely manner upon reasonable request of Ipsen and at Ipsen’s sole cost and
expense and (c) Ipsen shall have the right to compromise or settle such claim or
suit; provided, however, that such compromise or settlement shall be subject to
Nuvios’s prior written approval, which shall not be unreasonably withheld.
Notwithstanding Ipsen’s control of the defense of any such claim or proceeding,
Nuvios shall have the right to participate in such defense using counsel of its
own choice and at its own expense.

 

11.7.4.                              The defending Party shall bear its own
costs and expenses (including, without limitation, attorneys fees and court
costs) in connection with the defense of any claim or suit pursuant to
Section 11.7.2 or Section 11.7.3, and the defending Party shall also bear the
costs and expenses of the other Party if and to the extent that such costs and
expenses were incurred by such other Party in connection with reasonable
assistance provided by such other Party in connection with such defense at the
request of the defending Party.

 

11.7.5.                              In the event that, in connection with the
defense of any claim or suit pursuant to this Section 11.7 or any settlement
thereof, the defending Party shall receive damages, costs or other amounts, such
damages, costs or other amounts shall be treated in the manner contemplated
under Section 11.6 as if they had been received by the defending Party in
connection with any action or proceeding initiated and pursued by the defending
Party pursuant to Section 11.6 above.

 

11.7.6.                              The provisions of this Section 11.7 and the
respective rights and obligations of the Parties under this Section 11.7 shall
be without prejudice to any of the provisions of Article 16 or any of the
respective rights and obligations of the Parties under Article 16.

 

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11.8.                     Patent Notices.

 

All notices provided under this Article 11 to Nuvios shall be given to:

 

Nuvios, Inc.

300 Technology Square — 5th floor

Cambridge, MA 02139

Attn: Bart Henderson, Chief Business Officer

 

with a copy to:

 

Hamilton Brook Smith & Reynolds, P.C.

530 Virginia Road

P.O. Box 9133

Concord, MA 01742

Attn: David Brook, Esq.

 

All notices provided under this Article 11 to Ipsen shall be given to:

 

SCRAS S.A.S.

24, Rue Erlanger

75016 Paris, France

Attn: Head, Patent Law

 

ARTICLE 12   CONFIDENTIAL INFORMATION

 

12.1.                     Non-Disclosure and Non-Use. In performing under this
Agreement, the Parties will share proprietary information (“Confidential
Information”) with each other. A Party receiving Confidential Information under
this Agreement (“Receiver”) from the other disclosing Party (“Discloser”) shall
maintain such Confidential Information as follows:

 

The Receiver of a given item of Confidential Information agrees:

 

not to use such Confidential Information for any purpose other than in
connection with the purpose of carrying out this Agreement;

 

to treat such Confidential Information as it would for its own confidential
information of the same nature and importance; and

 

to take all reasonable precautions to prevent the disclosure of such
Confidential Information to any third party without the prior written consent of
the Discloser, except to the extent otherwise permitted pursuant to Section 12.3
below.

 

12.2.                     Exceptions. A Receiver shall be relieved of any and
all obligations under Section 12.1 regarding Confidential Information which:

 

was known to the Receiver or its Affiliates prior to receipt hereunder or under
any confidentiality agreements signed prior to the Effective Date between the
Parties; or

 

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as demonstrated by the Receiver by competent written proof, is independently
generated by the Receiver or its Affiliates by persons who have not had access
to or knowledge of the Confidential Information disclosed hereunder; or

 

at the time of disclosure by the Discloser to the Receiver, was generally
available to the public, or which after disclosure hereunder becomes generally
available to the public through no fault attributable to the Receiver, or its
Affiliates or sublicensees; or

 

is hereafter made available to the Receiver or its Affiliates for use and
unrestricted disclosure by the Receiver from any third party having a right to
do so.

 

12.3.                     Authorized Disclosure.

 

12.3.1.                              Nothing in this Agreement shall prohibit
disclosure by a Receiver of Confidential Information to its Affiliates,
employees, consultants, potential sublicensees or assignees, sublicensees,
assignees, advisors, clinical investigators, contract manufacturers, potential
lenders, lenders, potential investors, investors, or other third parties, if
any, but only on a strict need to know basis for purposes of (i) carrying out,
or causing to be carried out, any of the provisions of this Agreement, (ii) the
exercise by such Receiver of any of its rights under this Agreement, and
(iii) providing for the delegation of any of the obligations of such Receiver
under this Agreement; provided, however, that, except in the case of any such
disclosure to Receiver’s Affiliates, such disclosure occurs in the context of a
written confidentiality agreement containing provisions substantially as
protective as those of this Article.

 

12.3.2.                              The restrictions set forth in this
Article 12 shall not prevent either Party from disclosing any Confidential
Information related to Licensed Compound or Licensed Product to government
agencies to the extent reasonably necessary to secure government approval for
the development, manufacture or commercialization of a Licensed Compound or a
Licensed Product.

 

The restrictions set forth in this Article shall not prevent disclosure to the
extent required by law or pursuant to a judicial or governmental order, provided
that the Receiver makes reasonable efforts to minimize the extent of any
required disclosure and gives the Discloser sufficient notice to permit the
Discloser to seek a protective order or other similar order with respect to such
Confidential Information, with Receiver’s reasonable assistance therefore.

 

12.4.                     Survival. This Article 12 shall survive any
termination or expiration of this Agreement for a period of ten (10) years.

 

ARTICLE 13   PUBLICATION AND PRESS RELEASE

 

13.1.                     Publications.

 

Neither Party shall publish or publicly present the results of studies carried
out under this Agreement without the opportunity for prior review by the other
Party in accordance with the provisions set forth below in this Section 13.1,
and Ipsen shall not publish or publicly present the

 

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results of studies carried out under this Agreement by Nuvios, its Affiliates,
sublicensees or contractors. For purposes of this Section 13.1, the term
“Publication Eligible Material” shall mean any proposed abstracts, manuscripts
or presentations (including verbal presentations) that relate to any Licensed
Compound or Licensed Product and that are eligible for publication or public
presentation by a given Party under this Section 13.1 upon compliance with all
of the procedures set forth in this Section 13.1 for publication. Each Party
agrees to provide the other Party the opportunity to review any Publication
Eligible Material that such Party proposes to publish or publicly present at
least sixty (60) days prior to their intended submission for publication and
agrees, upon request, not to submit or publicly present any such Publication
Eligible Material until the other Party is given a reasonable period of time
(not to exceed sixty (60) days) to secure patent protection for any material in
such publication or presentation that is owned by the non-publishing Party
(either individually or jointly with the publishing Party) and which the
non-publishing Party believes to be patentable. Neither Party shall have the
right to publish or publicly present Confidential Information of the other
Party, and each Party shall remove the Confidential Information of the other
Party from any proposed publication or presentation upon request by such other
Party. Nothing contained in this Section 13.1 shall prohibit the inclusion of
information necessary to file a patent application with a government authority,
except for Confidential Information of the non-filing Party, provided the
non-filing Party is given a reasonable opportunity to review the information to
be included prior to submission of such patent application. Notwithstanding the
foregoing, the Parties recognize that independent investigators have been
engaged, and will be engaged in the future, to conduct clinical trials of
Licensed Products. Such independent investigators are understood to operate in
an academic environment and shall be allowed to release information regarding
such studies in a manner consistent with academic standards. In the event that
either Party submits any manuscript or other publication relating to any
Licensed Compound or Licensed Product, it will consider and acknowledge the
contributions of the other Party, including, as appropriate, co-authorship.

 

13.2.                     Press Release; Public Disclosure of Agreement. The
Parties shall issue a mutually agreed upon joint press release at an agreed date
promptly following the execution of this Agreement. Ipsen and Nuvios will
jointly discuss and agree in writing on any statement to the public regarding
this Agreement or any aspect of this Agreement, subject in each case to
disclosure otherwise required by law or regulation as determined in good faith
by each Party. When a Party elects to make any such statement it will give the
other Party at least ten (10) day’s notice to the other Party to review and
comment on such statement.

 

13.3.                     Non-Disclosure of Termination Event. In the event of a
termination of this Agreement by Nuvios under Section 15.4, Nuvios will not
disclose or cause to be disclosed to any third party the facts or circumstances
regarding such termination, except for any such disclosure which is required by
law (including if requested by any regulatory agency, taxing authority or
commission of competent jurisdiction). As part of its obligation under this
Section 13.3, except as is required by law (including if requested by any
regulatory agency, taxing authority or commission of competent jurisdiction),
Nuvios will not (i) issue any press release with respect to the facts or
circumstances regarding termination of this Agreement under Section 15.4 or
(ii) respond to press inquiries with respect to the facts or circumstances
regarding such termination, other than responses which are materially consistent
with public disclosure regarding the same by Ipsen. For purposes of clarity,
nothing in this Section 13.3 shall prevent or

 

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restrict Nuvios from disclosing or causing to be disclosed publicly or to any
third party the fact that Nuvios has terminated this Agreement for any reason or
no reason if and when such termination has in fact occurred. In addition,
notwithstanding anything express or implied in this Section 13.3 to the
contrary, Nuvios shall be free to disclose the facts or circumstances regarding
any termination of this Agreement by Nuvios under Section 15.4 to any third
party to whom Nuvios is entitled to disclose Confidential Information of Ipsen
pursuant to Section 12.3 (it being understood that, for purposes of this
sentence and the provisions of Section 12.3, such facts and circumstances shall
be treated as Confidential Information of Ipsen).

 

ARTICLE 14   REPRESENTATIONS, WARRANTIES AND COVENANTS

 

14.1.                     Mutual Representations and Warranties. Each Party
hereby represents and warrants as follows:

 

(a)                                 It is a corporation duly organized, validly
existing and in good standing under the laws of the jurisdiction in which it is
incorporated, and has full corporate power and authority and the legal right to
own and operate its property and assets and to carry on its business as it is
now being conducted and as contemplated in this Agreement, including, without
limitation, the right to grant the licenses it is granting hereunder.

 

(b)                                 On the Effective Date, (i) it has the full
right and authority to enter into this Agreement and perform its obligations
hereunder, (ii) it is not aware of any impediment that would prevent it from
entering into the Agreement or that would inhibit its ability to perform its
obligations under this Agreement, (iii) it has taken all necessary corporate
action on its part required to authorize the execution and delivery of this
Agreement and the performance of its obligations hereunder, and (iv) this
Agreement has been duly executed and delivered on behalf of such Party, and
constitutes a legal, valid and binding obligation of such Party that is
enforceable against it in accordance with its terms.

 

(c)                                  It has not entered into any agreement with
any third party that is in conflict with the rights granted to the other Party
under this Agreement, and has not taken any action that would in any way prevent
it from granting the rights granted to the other Party under this Agreement, or
that would otherwise materially conflict with or materially adversely affect the
rights granted to the other Party under this Agreement. Its performance and
execution of this Agreement will not result in a breach of any other contract to
which it is a party.

 

(d)                                 On the Effective Date, it is not aware of
any action, suit, inquiry or investigation instituted by any third party which
questions or threatens the validity of this Agreement.

 

(e)                                  All necessary consents, approvals and
authorizations of all governmental authorities and other persons or entities
required to be obtained by such Party in

 

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connection with the execution, delivery and performance of this Agreement have
been obtained.

 

(f)                                   To the best of its knowledge, each Party
has, on the Effective Date, the right to grant to the other Party the rights and
licenses granted by such Party to the other Party pursuant to this Agreement.

 

(g)                                  Each Party has, on the Effective Date, the
necessary qualified personnel, equipment, technical know-how and other means to
perform its duties under this Agreement in a timely manner in accordance with
the terms hereof.

 

14.2.                     Ipsen Representations and Warranties.

 

Ipsen warrants and represents that:

 

(a)                                 Ipsen is the owner of the Ipsen Patent
Rights and the Ipsen Know-How that exist on the Effective Date, free and clear
(on the Effective Date) of all liens or security interests. On the Effective
Date, Ipsen is not aware of any right or license of any third party that is
required to permit Ipsen to perform its obligations under this Agreement in
accordance with the terms of this Agreement or to permit Nuvios to exercise its
rights hereunder in accordance with the terms of this Agreement.

 

(b)                                 On the Effective Date, Ipsen does not own,
control or otherwise have the right to use or practice any rights under any
patent or patent application that are not included in the Ipsen Patent Rights on
the Effective Date and that would be necessary or useful to the research,
Development, manufacture, marketing, promotion, use, sale, import or export of
Licensed Compound or Licensed Product.

 

(c)                                  On the Effective Date and to Ipsen’s
knowledge, there are no claims against Ipsen asserting that the Ipsen Compound
Technology or the Ipsen Formulation Technology Infringes the rights of any third
party. On the Effective Date and to Ipsen’s knowledge (after conducting a
reasonable investigation), there are no patents or patent applications of any
third party that have published prior to the Effective Date or that are
otherwise publicly available prior to the Effective Date and that would be
Infringed by the use, practice or exploitation of all or any portion of Ipsen
Compound Technology.

 

(d)                                 On or prior to the Effective Date, Ipsen has
not given any notice to any third party asserting Infringement by such third
party of all or any portion of the Ipsen Compound Technology or the Ipsen
Formulation Technology and to Ipsen’s knowledge, Ipsen is not aware of any such
Infringement.

 

(e)                                  On the Effective Date, Ipsen is not a party
to any contract or agreement with a third party pursuant to which Ipsen
licensed-in or otherwise acquired or has the right to use the Ipsen Compound
Technology or Ipsen Formulation Technology or pursuant to which Ipsen or Nuvios
(or any of Nuvios’ sublicensees or

 

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Contractors) is or will be required to make payments on account of the use,
practice or exploitation of all or any portion of the Ipsen Compound Technology
or Ipsen Formulation Technology.

 

(f)                                   Appendix E sets forth an accurate and
complete list of all INDs and other applications for Regulatory Approval with
respect to Licensed Compound and/or Licensed Product filed by Ipsen anywhere in
the world on or prior to the Effective Date. Ipsen is on the Effective Date the
owner of all INDs and other applications for Regulatory Approval set forth on
Appendix E, free and clear (as of the Effective Date) of all liens, encumbrances
or security interests in favor of third parties. On and prior to the Effective
Date and to Ipsen’s knowledge, Ipsen has complied in all material respects with
all laws applicable to all INDs and other applications for Regulatory Approval
set forth on Appendix E.

 

(g)                                  Ipsen has disclosed to Nuvios (i) the
results of all preclinical and clinical testing in its possession or control or
that are known to Ipsen on the Effective Date; and (ii) all information in its
possession or control or that are known to Ipsen on the Effective Date
concerning side effects, injury, toxicity or sensitivity reaction and incidents
or severity thereof with respect to Licensed Compound and/or Licensed Product.
Ipsen has not withheld any information which, in Ipsen’s reasonable judgment, is
material to this transaction. All information and data disclosed by Ipsen to
Nuvios are complete and accurate in all material respects.

 

(h)                                 On the Effective Date, there is no
litigation against Ipsen with respect to all or any portion of the Ipsen
Compound Technology or Ipsen Formulation Technology.

 

(i)                                     On or prior to the Effective Date, Ipsen
has not entered into any agreement with a third party pursuant to which Ipsen
shall have agreed not to enforce any right of Ipsen to preclude such third party
from using or practicing any or all of the Ipsen Compound Technology or the
Ipsen Formulation Technology.

 

(j)                                    On the Effective Date, Ipsen is not aware
that it is in breach of all or any portion of the Teijin Agreement. On or prior
to the Effective Date, Ipsen has not been notified by Teijin that Teijin
believes that Ipsen is in breach of all or any portion of the Teijin Agreement.

 

(k)                                 In the event of a deadlock or disagreement
in the Japanese Development Committee, Ipsen has the right to cast a
tie-breaking vote and that the Teijin Agreement provides that (i) the ultimate
decision-making power and authority with respect to all matters concerning the
development of Licensed Compound or Licensed Product in Japan is with the
Japanese Development Committee and (ii) Teijin is required to abide by any
decision made by the Japanese Development Committee with respect to the
development of Licensed Compound or Licensed Product in Japan.

 

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(l)                                     During the course of negotiation of this
Agreement prior to the Effective Date, Nuvios, or representatives of Nuvios,
have had the opportunity to ask questions of and receive answers from
representatives of Ipsen concerning, and to obtain information, documents,
records and books relative to, Ipsen, its business, Licensed Compound, Licensed
Product, and Ipsen represents and warrants that it did not knowingly withhold
any material information from Nuvios in response to Nuvios’s inquiries or
otherwise in connection with the subject matter of this Agreement.

 

(m)                             Appendix B sets forth an accurate and complete
list of all Ipsen Patent Rights on the Effective Date. Appendix B1 sets forth an
accurate and complete list of all Ipsen Compound Patent Rights on the Effective
Date. Appendix B2 sets forth an accurate and complete list of all Ipsen
Formulation Patent Rights on the Effective Date.

 

14.3.                     Nuvios Representations and Warranties. Nuvios warrants
and represents that as of the Effective Date, Nuvios did not knowingly withhold
any material information related to the Ipsen Patent Rights with regards to
third party intellectual property rights.

 

14.4.                     No Other Representations or Warranties. EXCEPT AS
EXPRESSLY PROVIDED IN THIS AGREEMENT OR IN ANY OTHER WRITTEN AGREEMENT BETWEEN
THE PARTIES, THE FOREGOING REPRESENTATIONS AND WARRANTIES ARE IN LIEU OF, AND
EACH PARTY EXPRESSLY DISCLAIMS, ANY AND ALL REPRESENTATIONS AND WARRANTIES OF
ANY KIND, EXPRESS OR IMPLIED, INCLUDING, WITHOUT LIMITATION, WARRANTIES OF
DESIGN, MERCHANTABILITY, AND FITNESS FOR A PARTICULAR PURPOSE.

 

14.5.                     Mutual Covenants. Each Party covenants the following:

 

That it shall comply in all material respects with all federal, state,
provincial, territorial, governmental and local laws, rules and regulations
applicable to the development, manufacture and commercialization of Licensed
Product by such Party.

 

That it shall disclose immediately to the other Party all information in its
possession or control and as to which it becomes aware concerning side effects,
injury, toxicity or sensitivity reaction and incidents or severity thereof with
respect to Licensed Product.

 

ARTICLE 15   TERM AND TERMINATION

 

15.1.                     Term. The Term of this Agreement shall commence upon
the Effective Date. This Agreement is entered into for a period commencing on
the Effective Date and, unless this Agreement is terminated sooner as provided
in this Article 15, ending on the date when no payment obligations under this
Agreement are or will become due pursuant to Article 4.1 under any and all
countries in the Territory. Upon expiration of the Term of this Agreement, the
licenses granted by Ipsen to Nuvios pursuant to Section 2.1 hereof, to the
extent they remain in full force and effect at the time of such expiration,
shall thereafter become irrevocable, perpetual

 

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and fully paid-up exclusive licenses and shall survive such expiration of the
Term of this Agreement.

 

In any event of early termination of this Agreement (other than due to early
termination by Nuvios on account of material breach by Ipsen of any of its
obligations under this Agreement), all licenses granted by Ipsen to Nuvios
pursuant to Section 2.1 hereof shall terminate and Ipsen Know-How and Ipsen
Patent Rights shall revert back to Ipsen at no cost. In any event of early
termination of this Agreement (other than due to early termination by Nuvios on
account of material breach by Ipsen of any of its obligations under this
Agreement), Nuvios preclinical, clinical and manufacturing data and improvements
with respect to Licensed Product shall be transferred to Ipsen or its designee,
at no cost to Ipsen.

 

In any event of early termination of this Agreement (other than due to early
termination by Nuvios on account of material breach by Ipsen of any of its
obligations under this Agreement), Nuvios shall in accordance with Section 15.5
of this Agreement (i) transfer to Ipsen or a third party appointed by Ipsen, at
no cost to Ipsen, all of the then ongoing development activities and the
manufacturing Know-How with respect to Licensed Product, and (ii) use reasonable
commercial efforts to effect such transfer so as to avoid or minimize
disruptions in the ongoing development or supply of Licensed Product.

 

15.2.                     Breach. A Party (“Non-Breaching Party”) shall have the
right, in addition to any other rights and remedies, to terminate this Agreement
in the event the other Party (“Breaching Party”) is in breach of any of its
material obligations under this Agreement. The Non-Breaching Party shall provide
written notice to the Breaching Party, which notice shall identify the breach.
The Breaching Party shall have a period of sixty (60) days after such written
notice is provided to cure such breach. If such breach is not cured within the
relevant period, this Agreement shall terminate.

 

The waiver by either Party of any breach of any term or condition of this
Agreement shall not be deemed a waiver as to any subsequent or similar breach.

 

The right to terminate this Agreement under this Section 15.2 is in addition to
any other right and protection that may otherwise be available as a result of a
breach, including, without limitation, the right to damages.

 

15.3.                     Voluntary Termination.

 

Nuvios may terminate the Agreement for any reason, any time after the final
study report Phase Ib has been delivered to Ipsen.

 

15.4.                     Ipsen Right to Voluntarily Terminate.

 

Ipsen shall have the unilateral right to terminate this Agreement in its
entirety, upon written notice to Nuvios with immediate effect, if Nuvios in any
country of the world brings an action or proceeding seeking to have an Ipsen
Patent Right declared invalid or unenforceable.

 

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Ipsen may terminate this Agreement pursuant to, and in accordance with, the
provisions of Section 15.2 in the event that Nuvios fails to use reasonable
commercial efforts to develop the Licensed Product for sale and
commercialization in those countries within the Territory where it is
commercially reasonable to do so subject to, and in accordance with, the
provisions of Section 7.2 hereof, or fails to use reasonable commercial efforts
to perform its obligations under the latest revised version of the Development
Plan approved by the JSC subject to, and in accordance with, the provisions of
Section 7.2 hereof, or fails to use reasonable commercial efforts to launch and
sell one Licensed Product in those countries within the Territory where it is
commercially reasonable to do so subject to, and in accordance with, the
provisions of Sections 10.1 and 10.4 hereof.

 

Ipsen may terminate this Agreement pursuant to, and in accordance with, the
provisions of Section 15.2 in the event that this Agreement is assigned or
sublicensed or in the event that a third party acquires Nuvios or in the event
that Nuvios acquires control over a PTH or a PTHrP compound that is in clinical
development or is commercially available in the Territory and that, following
such assignment, sublicense, acquisition, or acquisition of control by Nuvios,
such assignee, sublicensee, acquirer or Nuvios fails to meet the timetable under
the latest revised version of the Development Plan approved by the JSC. Any
failure to meet such timetable under the circumstances contemplated in this
paragraph shall be deemed, for purposes of this paragraph and Section 15.2, a
material breach of Nuvios’ obligations under this Agreement.

 

15.5.                     Consequences of Early Termination by Nuvios without
Cause or by Ipsen for Cause. Upon termination of this Agreement by Nuvios
pursuant to Section 15.3 or upon termination of this Agreement by Ipsen pursuant
to Section 15.2 or Section 15.4:

 

15.5.1.                              Nuvios shall:

 

15.5.2.1 make its personnel reasonably available to Ipsen as necessary to effect
an orderly transition of development and commercial responsibilities, with the
reasonable cost of such personnel to be borne by Nuvios for such services; and

 

15.5.2.2 assign and transfer to Ipsen and execute all such documents as may be
reasonably required, therefore, at no expense to Ipsen, all of Nuvios’s right,
title and interest in the following to the extent they pertain to Licensed
Product:

 

·                                          all regulatory filings (such as INDs
and drug master files), Regulatory Approvals, clinical trial agreements (to the
extent assignable and not cancelled); and

 

·                                          all data, including formulation data,
results, clinical trial data, support documentation having arisen out of the
materials and other information, in Nuvios’s possession and control related to
Licensed Product in the Territory; and

 

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·                                          all customer lists, marketing and
promotional material, and all other documentation related to marketing, sale,
and promotion of the Licensed Product in the Territory, and

 

·                                          all trademarks used for Licensed
Product, provided however that the responsibility of preparing and filing of the
documents for the recordation of the assignments with the competent authorities
in each applicable country and any action required ancillary, shall be borne by
Ipsen and that each Party shall bear its expenses caused by its activities in
connection with the assignments and transfer of the trademarks.

 

15.5.2.                              Nuvios shall initiate transfer (and
complete the same in a timely manner), to Ipsen of all technical and industrial
know how related to the manufacturing of Licensed Product for use by Ipsen and
shall provide reasonable assistance and support (up to a reasonable number of
person-days of qualified personnel) as may be reasonably required by Ipsen to be
in a position to make Licensed Compound and Licensed Product itself. Any such
transfer under this Section 15.5.3 shall be at Nuvios expense during the
termination notice period and at Ipsen’s expense thereafter.

 

15.5.3.                              All licenses granted by Ipsen to Nuvios
under this Agreement, and all licenses granted by Nuvios to Ipsen or Teijin
under this Agreement, shall terminate on the effective date of termination.
Notwithstanding anything in this Section 15.5.4 or elsewhere in this Agreement
to the contrary, Nuvios may for a period not exceeding six months continue
making, marketing, promoting and selling Licensed Compound and Licensed Product
in the Territory after the termination of such licenses.

 

15.5.4.                              No compensation or refund shall be due by
either Party to the other Party, otherwise than damages as determined by a court
of competent jurisdiction:

 

15.5.5.                              Nuvios shall agree to take such actions and
execute such instruments, agreements and documents as are necessary to effect
the foregoing.

 

15.5.6.                              Unless otherwise agreed by the Parties, the
termination of this Agreement shall cause the automatic termination of all
ancillary agreements related hereto, including, but not limited to, the supply
agreements and technical agreements referred to in Article 9.

 

15.6.                     Accrued Rights; Surviving Rights and Obligations.

 

Expiration or termination of this Agreement, for any reason, will not relieve
either Party of any obligation accruing prior to such expiration or termination.
Articles and Sections 1, 5.6, 12, 13, 14, 15, 16, 17 and 18 shall survive
expiration or termination of this Agreement. In addition, the obligations and
rights of any other provisions of this Agreement, which by their nature of the
provision and the nature of the termination or expiration, are intended to
survive, shall survive and continue to be enforceable.

 

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ARTICLE 16   INDEMNIFICATION

 

16.1.                     Indemnification by Ipsen. Ipsen agrees to indemnify,
hold harmless and defend Nuvios and its Affiliates and their respective
directors, officers, employees and agents (collectively, the “Nuvios
Indemnitees”) from and against any and all suits, claims, actions, demands,
liabilities, expenses and/or loss, cost of defense (including without limitation
reasonable attorneys’ fees, court costs, witness fees, damages, judgments, fines
and amounts paid in settlement) and any other amounts (collectively, “Losses”)
that any Nuvios Indemnitee becomes legally obligated to pay to a third party,
because of any claim or claims against such Nuvios Indemnitee to the extent that
such claim or claims arise out of or resulted from (i) a breach of a
representation or warranty or covenant by Ipsen under Article 14; (ii) a breach
by Ipsen of any other provision of this Agreement or of any representation,
warranty, covenant or other provision in any Related Agreement; (iii) the
manufacture by or on behalf of Ipsen under Article 9; (iv) the use, development,
handling or commercialization of any Licensed Compound, any Licensed Product or
the Ipsen Formulation Technology by or on behalf of Ipsen or any of its
Affiliates, licensees, sublicensees, distributors or contractors, or any of
their respective employees or agents; or (iv) the gross negligence or willful
misconduct of Ipsen, its Affiliates, licensees, sublicensees, distributors or
contractors, or any of their respective employees or agents; provided, however,
that Ipsen shall not be required to indemnify the Nuvios Indemnitees for any
Losses pursuant to this Section 16.1 to the extent that (1) such Losses arise
from Nuvios’ breach of any of the provisions of this Agreement or any Related
Agreement, (2) such Losses arise or result from the gross negligence or willful
misconduct of Nuvios or any of its Affiliates, licensees, sublicensees,
contractors or distributors, or any of their respective agents or employees, or
(3) Ipsen’s liability for such Losses is limited pursuant to Section 16.4.

 

16.2.                     Indemnification by Nuvios. Nuvios agrees to indemnify,
hold harmless and defend Ipsen and its Affiliates and their respective
directors, officers, employees and agents (collectively, the “Ipsen
Indemnitees”) from and against any and all Losses that any Ipsen Indemnitee
becomes legally obligated to pay to a third party, because of any claim or
claims against such Ipsen Indemnitee to the extent that such claim or claims
arise out of or resulted from (i) a breach of a representation or warranty or
covenant by Nuvios under Article 14, (ii) a breach by Nuvios of any other
provision of this Agreement or of any representation, warranty, covenant or
other provision in any Related Agreement, (iii) the manufacture by or on behalf
of Nuvios under Article 9; (iv) the making, use, development, handling or
commercialization of any Licensed Compound or any Licensed Product by or on
behalf of Nuvios or any of its Affiliates, licensees, sublicensees or
Contractors, or any of their respective employees or agents or (v) the gross
negligence or willful misconduct of Nuvios, its Affiliates, licensees,
sublicensees or Contractors, or any of their respective employees or agents;
provided, however, that Nuvios shall not be required to indemnify the Ipsen
Indemnitees for any Losses pursuant to this Section 16.2 to the extent that
(1) such Losses arise from Ipsen’s breach of any of the provisions of this
Agreement or any Related Agreement, (2) such Losses arise or result from the
gross negligence or willful misconduct of Ipsen or any of its Affiliates,
licensees, sublicensees, contractors or distributors, or any of their respective
agents or employees, (3) such Losses arise or result from any Infringement of
the patent rights or other intellectual property rights of any third party by
all or any portion of the Ipsen Patent Rights, Ipsen Know-How or Ipsen
Formulation Technology or (4) Nuvios’ liability for such Losses is limited
pursuant to Section 16.4.

 

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16.3.                     Procedure. In the event of a claim by a third party
against any person entitled to indemnification under this Agreement
(“Indemnified Person”), the Indemnified Person shall promptly notify the Party
having the indemnification obligation under this Agreement with respect to such
claim (such Party, the “Indemnifying Party”) in writing of the claim. The
indemnifying Party shall have the right to assume the defense of any such third
party claim for which it is obligated to indemnify the Indemnified Person under
this Article XVI. The Indemnified Person shall cooperate with the Indemnifying
Party (and its insurer) as the Indemnifying Party may reasonably request, and at
the Indemnifying Party’s sole cost and expense. The Indemnified Person shall
have the right to participate, at its own expense and with counsel of its
choice, in the defense of any claim or suit that has been assumed by the
Indemnifying Party. The Indemnifying Party shall have no obligation to indemnify
an Indemnified Person in connection with any settlement made without the
Indemnifying Party’s prior written consent. If the Parties cannot agree as to
the application of this Article XVI to any third party claim, the Parties may
conduct separate defenses of such claims, with each Party retaining the right to
claim indemnification from the other in accordance with this Article XVI upon
resolution of the underlying claim.

 

16.4.                     NOTWITHSTANDING ANYTHING EXPRESS OR IMPLIED IN THIS
AGREEMENT TO THE CONTRARY, IN NO EVENT SHALL EITHER PARTY BE LIABLE TO THE OTHER
PARTY FOR LOSS OF PROFITS, SPECIAL, INDIRECT, INCIDENTAL, PUNITIVE OR
CONSEQUENTIAL DAMAGES ARISING OUT OF THIS AGREEMENT.

 

ARTICLE 17   DISPUTE RESOLUTIONS AND GOVERNING LAW

 

17.1.                     Disputes. Unless otherwise set forth in this
Agreement, in the event of a dispute arising under this Agreement between the
Parties, the Parties shall remain bound by the terms of this Agreement and each
Party shall refer such dispute to one executive officer, and such executive
officer shall attempt in good faith to resolve such dispute.

 

17.2.                     Arbitration. If the Parties are unable resolve a given
dispute pursuant to Section 17.1 within sixty (60) days of referring such
dispute to the executive officers, the Parties shall remain bound by the terms
of this Agreement and either Party may have the given dispute settled by binding
arbitration in the manner described below:

 

17.3.                     Arbitration Request. If a Party intends to begin an
arbitration to resolve a dispute arising under this Agreement, such Party shall
provide written notice (the “Arbitration Request”) to the other Party of such
intention and the issues for resolution.

 

17.4.                     Additional Issues. Within thirty (30) business days
after the receipt of the Arbitration Request, the other Party may, by written
notice, add additional issues for resolution.

 

17.5.                     Arbitration Procedure. Any arbitration to resolve a
dispute arising under this Agreement shall be a final and binding arbitration
pursuant to the then-current Rules of Arbitration of the International Chamber
of Commerce as hereinafter provided:

 

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17.5.1.                              The Arbitration Tribunal shall consist of
three (3) arbitrators. Each party shall nominate in the Arbitration Request and
the answer thereto one (1) arbitrator and the two (2) arbitrators so named will
then jointly appoint the third arbitrator as chairman of the Arbitration
Tribunal. If one Party fails to nominate its arbitrator or, if the parties’
arbitrators cannot agree on the person to be named as chairman within sixty (60)
days, the International Chamber of Commerce shall make the necessary
appointments for arbitrator or chairman in accordance with the Rules of
Arbitration of the International Chamber of Commerce.

 

17.5.2.                              The place of arbitration shall be in
London, England, and the arbitration proceedings shall be held in English. The
procedural law of the place of arbitration shall apply where the said Rules are
silent.

 

17.5.3.                              The award of the Arbitration Tribunal shall
be final and judgment upon such an award may be entered in any competent court
or application may be made to any competent court for juridical acceptance of
such an award and order of enforcement.

 

17.5.4.                              Notwithstanding the referral of any
dispute, controversy or claim arising out of or in connection with this
Agreement to arbitration pursuant to this Section 17.5, both Parties shall
remain free to seek interim, injunctive or conservatory relief, provided that
the order of the relevant judicial authority shall not in any way prejudice the
above tribunals’ power to settle the dispute referred to them in accordance with
the Rules of Arbitration of the International Chamber of Commerce.

 

17.6.                     Governing Law. This Agreement shall be governed by and
construed in accordance with the laws of the State of New York, U.S.A., without
reference to its conflict of laws principles, and shall not be governed by the
United Nations Convention of International Contracts on the Sale of Goods (the
Vienna Convention).

 

ARTICLE 18   MISCELLANEOUS

 

18.1.                     Agency - Independent Contractor. Neither Party is an
employee, agent or representative of the other Party for any purpose, and nor
shall this Agreement create or establish an employment, agency or any other
relationship. Except as may be specifically provided herein, neither Party shall
have any right, power, or authority, nor shall they represent themselves as
having authority to assume, create or incur any expense, liability or
obligation, express or implied, on behalf of the other Party, or otherwise act
as an agent for the other Party for any purpose.

 

18.1.1.                              The Parties agree that the relationship of
Ipsen and Nuvios established by this Agreement is that of independent licensee
and licensor. This Agreement does not, is not intended to, and shall not be
construed to; establish a partnership or joint venture.

 

18.2.                     Entire Agreement. This Agreement, including all
appendices, schedules and attachments, embodies the entire understanding of the
Parties with respect to the subject matter

 

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hereof and supersedes all previous communications, representations or
understandings, and agreements, whether oral or written, between the Parties
relating to the subject matter hereof.

 

18.3.                     Assignment. Except to the extent otherwise expressly
provided elsewhere in this Agreement, either Party may assign this Agreement or
any of such Party’s rights and obligations under this Agreement to any of its
Affiliates or any third party, provided that the rights and obligations of the
Parties under this Agreement shall be binding upon and inure to the benefit of
the successors and assigns of the Parties and that an assignment or delegation
of this Agreement by a Party or of any of a Party’s obligations under this
Agreement shall not operate to release such Party from any of its obligations
under this Agreement or from the specific obligation assigned or delegated by
such Party. Any assignment not in accordance with this Agreement shall be void.

 

18.4.                     Notices. Any notice or other communication under this
Agreement, unless otherwise specified, shall be in writing and provided when
delivered to the addressee at the address listed below (a) on the date of
delivery if delivered in person or (b) three (3) days after mailing to the other
Party by express mail or overnight delivery service, which obtains a signed
receipt:

 

In the case of Ipsen:

 

SCRAS S.A.S.

42, Rue du Docteur Blanche

75016 Paris

Attn.: General Counsel

 

In the case of Nuvios:

 

Nuvios Inc.

300 Technology Square — 5th Floor

Cambridge, MA 02139

Attn: M. Bart Hendersson — Chief Business Officer

 

Either Party may change its address for communications by a notice in writing to
the other Party in accordance with this Section.

 

18.5.                     Force Majeure. Any prevention, delay or interruption
of performance (collectively “Delay”) by any Party under this Agreement shall
not be a breach of this Agreement if and to the extent caused by occurrences
beyond the reasonable control of the Party affected by the force majeure,
including but not limited to acts of God, embargoes, governmental restrictions,
terrorism, general strike, fire, flood, earthquake, explosion, riots, wars
(declared or undeclared), civil disorder, rebellion or sabotage. The affected
Party shall immediately notify the other Party upon the commencement and end of
the Delay. During the Delay, any time for performance hereunder by either Party
shall be extended by the actual time of Delay. If the Delay resulting from the
force majeure exceeds six (6) months, the other Party, upon written

 

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notice to the affected Party, may elect to (a) treat such Delay as a material
breach solely for purposes of exercising the right to terminate this Agreement
for material breach pursuant to, and in accordance with, Section 15.2, or (b)
extend the term of this Agreement for an amount of time equal to the Delay.

 

18.6.                     Severability. If any of the provisions of this
Agreement are held to be void or unenforceable by a court of competent
jurisdiction, then such void or unenforceable provisions shall be replaced by
valid and enforceable provisions which will achieve as far as possible the
economic business intentions of the Parties. However the remainder of this
Agreement will remain in full force and effect, provided that the material
interests of the Parties are not affected, i.e. the Parties would presumably
have concluded this Agreement without the unenforceable provisions.

 

18.7.                     No Right to Use Names. Except as otherwise expressly
provided herein, this Agreement provides no grant of right to a Party, express
or implied, to use in any manner the housemarks or trademarks of the other Party
or its Affiliates.

 

18.8.                     Bankruptcy. All rights and licenses granted under or
pursuant to this Agreement by Nuvios or Ipsen are, and will otherwise be deemed
to be, for purposes of Section 365(n) of the U.S. Bankruptcy Code (or the
equivalent provisions, if any, in the bankruptcy laws of the applicable
jurisdiction) licenses of right to “intellectual property” as defined under
Section 101 of the U.S. Bankruptcy Code. The Parties agree that the Parties, as
licensees of such rights under this Agreement, will retain and may fully
exercise all of their rights and elections under the U.S. Bankruptcy Code. The
Parties further agree that, in the event of the commencement of a bankruptcy
proceeding by or against either Party under the U.S. Bankruptcy Code, the Party
hereto that is not a party to such proceeding will be entitled to a complete
duplicate of (or complete access to, as appropriate) any such intellectual
property and all embodiments of such intellectual property, and same, if not
already in their possession, will be promptly delivered to them (a) upon any
such commencement of a bankruptcy proceeding upon their written request
therefore, unless the Party subject to such proceeding elects to continue to
perform all of its obligations under this Agreement, or (b) if not delivered
under (a) above, following the rejection of this Agreement by or on behalf of
the Party subject to such proceeding upon written request therefore by the
non-subject Party.

 

18.9.                     Performance by Affiliates. Each of Nuvios and Ipsen
acknowledge that obligations under this Agreement may be performed by Affiliates
of Nuvios and Ipsen. Each of Nuvios and Ipsen guarantee and warrant any
performance of this Agreement by its Affiliates. Wherever in this Agreement the
Parties delegate responsibility to Affiliates, the Parties agree that such
entities may not make decisions inconsistent with this Agreement, amend the
terms of this Agreement or act contrary to its terms in any way.

 

18.10.              Counterparts. The Parties may execute this Agreement in
counterparts, each of which the Parties shall deem an original, but all of which
together shall constitute one and the same instrument.

 

52

--------------------------------------------------------------------------------

 

18.11.              Waiver. A waiver of any default, breach or non-compliance
under this Agreement is not effective unless signed by the Party to be bound by
the waiver. No waiver will be inferred from or implied by any failure to act or
delay in acting by a Party in respect of any default, breach, non-observance or
by anything done or omitted to be done by the other Party. The waiver by a Party
of any default, breach or non-compliance under this Agreement will not operate
as a waiver of that Party’s rights under this Agreement in respect of any
continuing or subsequent default, breach or non-compliance (whether of the same
or any other nature).

 

In Witness Whereof, the Parties have executed this Agreement in two originals by
their proper officers as of the date and year first above written.

 

 

SCRAS S.A.S.

 

 

Nuvios Inc

 

 

 

 

 

By:

/s/ C. Giraut

 

By:

/s/ C. R. Lyttle

 

 

 

 

 

Name:

C. Giraut

 

Name:

C. Richard Lyttle

 

 

 

 

 

Title:

President

 

Title:

President & CEO

 

53

--------------------------------------------------------------------------------

 

APPENDIX A - CHEMICAL STRUCTURE OF BIM-44058

 

Description of the Product

 

Denomination/Code Number

 

Laboratory code: BIM444058 (free base)/ BIM44058 (acetate salt)

 

Chemical Formula

 

[Glu22.23, Leu23.28.31, Aib29, Lys26.30] hPTHrP (1-34) NH2

 

This peptide is available as an acetate salt designated BIM44058

 

Molecular Formula and Weight

 

Molecular formula (base): C174 H300 N56 O49.

 

Molecular weight (base): 3960.7.

 

Molecular Structure:

 

[g17732li11i001.jpg]

 

54

--------------------------------------------------------------------------------

 

APPENDIX B - IPSEN PATENT RIGHTS

 

APPENDIX B 1 - IPSEN COMPOUND PATENT RIGHTS

 

Patent Family In Which BIM-44058 Is Claimed

 

Biomeasure
Reference No.

 

Application
Country

 

Serial No.

 

Application File
Date

 

Patent Number

 

Patent Issue Date

 

Patent Expiry

 

 

 

 

 

 

 

 

 

 

 

 

 

038/US2

 

United States

 

08/779,768

 

01-07-97

 

5,969,095

 

10-19-1999

 

03-29-2016

038/US/PCT2

 

PCT

 

PCT/US96/11292

 

07-03-96

 

 

 

 

 

 

038/US/PCT2/EP

 

Europe

 

96924355.9

 

01-30-98

 

0 847 278

 

09-24-2003

 

07-03-2016

Registration: AT, BE, CH, DE, DK, ES, FI, FR, GB, GR, IE, IT, LI, LU, MC, NL,
PT, SE; Ext: AL, LT, LV, SI

038/US/PCT2/EP-A

 

Europe

 

03077383.2

 

07-30-2003

 

Pending

 

 

 

 

038/US/PCT2/JP

 

Japan

 

9-505897

 

01-12-98

 

Pending

 

 

 

 

038/US/PCT2/JP-A

 

Japan

 

2003-008027

 

01-16-2003

 

Pending

 

 

 

 

038/US/PCT2/AU

 

Australia

 

64834/96

 

07-03-96

 

707094

 

07-01-1999

 

07-03-2016

038/US/PCT2/CA

 

Canada

 

2,226,177

 

12-19-97

 

Pending

 

 

 

 

038/US/PCT2/CN

 

China

 

96196926.1

 

07-03-96

 

Pending

 

 

 

 

038/US/PCT2/CN-A

 

China

 

200410005427.7

 

07-03-96

 

Pending

 

 

 

 

038/US/PCT2/CN/HK

 

Hong Kong

 

99100132.1

 

01-13-99

 

Pending

 

 

 

 

038/US/PCT2/HU

 

Hungary

 

P9901718

 

07-03-96

 

Pending

 

 

 

 

038/US/PCT2/IL

 

Israel

 

122837

 

07-03-96

 

122837

 

02-11-2003

 

07-03-2016

038/US/PCT2/KR

 

Korea

 

1998-0700249

 

01-13-98

 

0500853

 

07-04-2005

 

07-03-2016

038/US/PCT2/KR-A

 

Korea

 

2004-706338

 

04-28-2004

 

Pending

 

 

 

 

038/US/PCT2/KR-B

 

Korea

 

2004-706339

 

04-28-2004

 

Pending

 

 

 

 

038/US/PCT2/KR-C

 

Korea

 

2004-706340

 

04-28-2004

 

Pending

 

 

 

 

038/US/PCT2/KR-D

 

Korea

 

2004-706341

 

04-28-2004

 

Pending

 

 

 

 

038/US/PCT2/MX

 

Mexico

 

PA/a/1998/000418

 

07-03-96

 

222317

 

08-26-2004

 

07-03-2016

038/US/PCT2/NZ

 

New Zealand

 

312899

 

01-20-98

 

312899

 

02-08-2000

 

07-03-2016

038/US/PCT2/PL

 

Poland

 

P.325905

 

01-12-98

 

186710

 

08-07-2003

 

07-03-

2016038/US/PCT2/RU

 

Russia

 

98102406

 

07-03-96

 

2,157,699

 

10-20-2000

 

07-03-2016

038/US/PCT2/SG

 

Singapore

 

9706046-1

 

07-03-96

 

51260

 

10-16-2001

 

07-03-2016

038/US/TW

 

Taiwan

 

85108390

 

07-11-96

 

153897

 

08-07-2002

 

07-11-2016

 

 

 

 

 

 

 

 

 

 

 

 

 

Closely Related Patent Cases

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

038/US

 

United States

 

08/626,186

 

03-29-96

 

5,723,577

 

03-03-1998

 

03-29-2016

 

55

--------------------------------------------------------------------------------

 

038/US3

 

United States

 

08/813,534

 

03-07-97

 

5,955,574

 

09-21-1999

 

03-29-2016

03B/US3/PCT2

 

PCT

 

PCT/US97/22498

 

12-08-97

 

 

 

 

 

 

038/US3/PCT2/US2

 

United States

 

09/399,499

 

09-20-99

 

6,544,949

 

04-08-2003

 

03-29-2016

038/US3/PCT2/US2-A

 

United States

 

10/289,519

 

11-06-2002

 

6,921,750

 

07-26-2005

 

03-29-2016

038/US3/PCT2/US2-B

 

United States

 

11/094,662

 

03-30-2005

 

Pending

 

 

 

 

038/US3/PCT2/EP

 

Europe

 

97951595.4

 

07-08-99

 

Allowed

 

 

 

 

038/US3/PCT2/JP

 

Japan

 

10-530865

 

12-08-97

 

Pending

 

 

 

 

038/US3/PCT2/AU

 

Australia

 

55199/98

 

12-08-97

 

741584

 

03-21-2002

 

12-08-2017

038/US3/PCT2/CA

 

Canada

 

2,276,614

 

07-02-99

 

2,276,614

 

06-11-2002

 

12-08-2017

038/US3/PCT2/CN

 

China

 

97181915.7

 

12-08-97

 

ZL97181915.7

 

02-11-2004

 

12-08-2017

038/US3/PCT2/CN-HK

 

Hong Kong

 

00105467.3

 

12-08-2000

 

1026215

 

07-09-2004

 

12-08-2017

038/US3/PCT2/CZ

 

Czech Republic

 

PV 1999-2398

 

07-02-99

 

Pending

 

 

 

 

038/US3/PCT2/HU

 

Hungary

 

P9904596

 

12-08-97

 

Pending

 

 

 

 

038/US3/PCT2/IL

 

Israel

 

130794

 

07-06-2000

 

Pending

 

 

 

 

038/US3/PCT2/IN

 

India

 

7/MAS/98

 

01-01-98

 

Pending

 

 

 

 

038/US3/PCT2/KR

 

Korea

 

1999-7006165

 

07-07-99

 

0497709

 

06-17-2005

 

12-08-2017

038/US3/PCT2/MX

 

Mexico

 

PA/a/1999/006387

 

07-07-99

 

222316

 

08-26-2004

 

12-08-2017

038/US3/PCT2/NO

 

Norway

 

1999 3341

 

12-08-97

 

Pending

 

 

 

 

038/US3/PCT2/NZ

 

New Zealand

 

336610

 

07-06-99

 

336610

 

11-09-2001

 

12-08-2017

038/US3/PCT2/PL

 

Poland

 

P.334438

 

07-15-99

 

Pending

 

 

 

 

038/US3/PCT2/PL-A

 

Poland

 

P.370525

 

10-04-2004

 

Pending

 

 

 

 

038/US3/PCT2/RU

 

Russia

 

99117145

 

08-06-99

 

2,198,182

 

02-10-2003

 

12-08-2017

038/US3/PCT2/SG

 

Singapore

 

9903165-0

 

07-05-99

 

66567

 

07-18-2000

 

12-08-2017

038/US3/AR2

 

Argentina

 

P 98 01 00058

 

01-06-98

 

Pending

 

 

 

 

038/US3/AR2-A

 

Argentina

 

P 03 01 00515

 

02-17-2003

 

Pending

 

 

 

 

038/US2/US3/TW

 

Taiwan

 

87100028

 

01-02-98

 

156542

 

06-01-2002

 

01-02-2018

 

APPENDIX B 2 — IPSEN FORMULATION PATENT RIGHTS

 

·                                          Solid drugs (minicylinders) also
referred to as “IRE”: WO 96/07397 = EP 778,767

·                                          Needle-less: WO 96/08289= EP 782,465
= US 5,542,920

·                                          Vac: WO 97/46202

·                                          Micro-VAC 2” (WO 01/26718).

 

56

--------------------------------------------------------------------------------

 

APPENDIX C — NUVIOS DEVELOPMENT PLAN

 

[g17732li13i001.jpg]

 

BA058 Development Plan

 

Version:

1.0

 

 

Date:

September 20, 2005

 

Nuvios, Inc.

300 Technology Square, 5th Floor

Cambridge, MA 02139

Tel: 617.551.4700

 

Disclosure Statement

 

This document contains information that is confidential and proprietary to
Nuvios, Incorporated. Any unauthorized use or disclosure of such information
without the prior written authorization of Nuvios, Incorporated is expressly
prohibited.

 

57

--------------------------------------------------------------------------------

 

TABLE OF CONTENTS

 

1.0

Executive Summary

59

 

 

 

2.0

CLINICAL PROGRAM

61

 

 

 

 

2.1

Phase 1 Program

61

 

2.2

Phase 2 Clinical Program

63

 

2.3

Phase 3 Clinical Program

66

 

2.4

Other Clinical Studies

68

 

 

 

3.

FORMULATION STUDIES

70

 

 

 

4.

NON-CLINICAL PROGRAM

70

 

 

 

 

4.1

Toxicology/Pharmacology

70

 

 

 

5.

REGULATORY STRATEGY

70

 

 

 

6.

TIMELINES

71

 

58

--------------------------------------------------------------------------------

 

1.0                               EXECUTIVE SUMMARY

 

BA058 is an analogue of the first 34 amino acids of human parathyroid
hormone-related peptide [hPTHrP(1-34)]. BA058 was originally discovered and
developed by the Beaufour-Ipsen Pharma Group under the name BIM44058. Nuvios,
Inc. plans to develop BA058 for the treatment of osteoporosis in postmenopausal
women and men at risk of fracture.

 

This development plan for BA058 is premised upon a strategy of demonstrating a
substantial improvement in dosing regimen over Forteo® teriparatide (rDNA
origin) injection [rhPTH(1-34)] for the treatment of patients with osteoporosis,
improving convenience for patients with severe osteoporosis for whom the current
18 month regimen of daily Forteo® injections is inconvenient.

 

Pre-clinical data suggest that BA058 has a better therapeutic index compared to
Forteo® which should enable an improved dosing regimen cycle that is shorter in
total duration, or requires less frequent injections, or which can be delivered
in novel formulations. Specifically, the preclinical data support the ability to
give higher doses of BA058 than Forteo® without inducing resorption or
hypercalcemia.

 

Based on the commercial strategy for BA058 and the current regulatory climate
(refer to the FDA guidance document for the “Development of Parathyroid Hormone
for the Prevention and Treatment of Osteoporosis,” [1]), the first step is to
conduct a one week, multiple ascending dose study in healthy postmenopausal
women with the following goals:

 

·                  To demonstrate that BA058 has the potential for an improved
therapeutic index, enabling the delivery of a more effective anabolic dose
without inducing hypercalcemia in comparison to Forteo®.

 

·                  To evaluate PK, pharmacodynamics and safety after multiple
doses.

 

The results from the Phase IB study will be used to select two doses of BA058
for use in a 3-month proof-of-concept (POC) study to be conducted in
postmenopausal women with osteoporosis. This study would be a comparative trial
vs. Forteo® and is designed to answer the following questions:

 

·                  Does BA058 induce resorption to any significant degree (when
compared to measures of bone formation and the corresponding changes in bone
markers of the comparator )?

 

·                  What is the effect of 3 months of BA058 treatment on BMD and
how does this compare to the Forteo® arm in the study? How does BA058’s effect
on BMD compare to changes observed when Forteo® is given for 12-18 months (i.e.,
historical controls)?

 

·                  Does BA058 induce hypercalcemia and is it less than Forteo®?

 

59

--------------------------------------------------------------------------------

 

·                  Does BA058 have acceptable tolerability, patient
satisfaction, and an acceptable safety, PK and pharmacodynamic profile?

 

Target Product Profile - osteoporosis

 

Indication:

 

BA058 is indicated for the treatment of postmenopausal women with osteoporosis
who are at high risk of fracture.

 

BA058 is indicated to increase bone mass in men with primary or hypogonadal
osteoporosis who are at high risk of fracture.

 

 

 

Efficacy:

 

Statistically equivalent or superior effect on BMD relative to Forteo®.

 

 

 

Dosing:

 

Significantly shortened dosing cycle to restore BMD (vs. 12+ months for Forteo®)
when administered QD via subcutaneous administration.

 

Alternatively, significantly shortened dosing schedule than once-daily (e.g. 3
times/week).

 

Improved formulations that allow a significant advance in dosing convenience
along with reduced pain.

 

 

 

Safety:

 

Absence of significant hypercalcemia with BA058 treatment.

 

60

--------------------------------------------------------------------------------

 

2.0 CLINICAL PROGRAM

 

2.1                               Phase 1 Program

 

The overall objective of the Phase 1 program is to characterize the safety,
tolerability, and pharmacokinetic profile of BA058 following single and multiple
dosing.

 

Phase 1a: Single ascending dose study

 

This study was completed in March 2005 and the full clinical study report is
being prepared by Ipsen. Full study results are required for the pre-IND meeting
with FDA and subsequent IND filing.

 

 

Title:

 

A Phase I Single-Center study in two parts assessing the safety,
pharmacokinetics, pharmacodynamics and absolute bioavailability of BIM44058, a
hPTHrP(1-34) analogue, administered as single doses to healthy elderly
volunteers of both genders: Part A, randomized, double-blind, dose-escalating,
parallel groups, placebo-controlled design; Part B, randomized, open-label,
two-period, cross-over design

 

 

 

Protocol Number:

 

2-52-52127-001

 

Phase 1b:  Multiple ascending dose study

 

The strategic goals for this study are...

 

1)                                     To demonstrate that BA058 has the
potential for an improved therapeutic index, enabling the delivery of higher
doses than Forteo® without inducing hypercalcemia.

 

2)                                     To evaluate PK, pharmacodynamics and
safety after multiple doses.

 

These goals will be met if the compound achieves clinical endpoints that suggest
no clinically meaningful incidence of hypercalcemia, and the ability to deliver
a more effective anabolic dose of BA058 with good safety and tolerability than
is possible with Forteo®.

 

The study will be a randomized, double-blind, placebo-controlled, ascending
multiple-dose safety, tolerability, and pharmacokinetic study of subcutaneously
administered BA058 in healthy postmenopausal women.

 

61

--------------------------------------------------------------------------------

 

Title:

 

A Randomized, Double-Blind, Placebo-Controlled, Ascending Multiple-Dose Safety,
Tolerability, Pharmacokinetic and Pharmacodynamic Study of BA058 in Healthy
Postmenopausal Women ( Pending FDA Approval)

 

 

 

Protocol Number:

 

BA058-05-001

 

The study will be designed to:

 

·                  Determine the safety and tolerability of multiple
subcutaneous doses of BA058 in healthy postmenopausal women.

 

·                  Determine the effect of BA058 on serum calcium levels.

 

·                  Determine the pharmacokinetics and pharmacodynamics of
multiple subcutaneous doses of BA058 in healthy postmenopausal women.

 

A total of 40 eligible subjects will be sequentially enrolled into one of four
study groups consisting of 10 subjects each. Within each study group of 10
subjects, 8 will be randomly assigned to receive BA058 and 2 will be randomly
assigned to receive placebo. All subjects at each dosage level will start dosing
on the same day and receive a total of 7 doses of study medication. After a dose
level has been determined to be well tolerated, different subjects will be
entered into the next study group. The proposed dosages and number of subjects
that will receive study medication are shown below.

 

 

 

 

 

 

 

Number of Subjects Randomized

 

Study Group

 

Proposed
Doses

 

Days of
Dosing

 

Total Number
of Subjects

 

BA058

 

Placebo

 

 

 

 

 

 

 

 

 

 

 

 

 

1

 

5 µg

 

7

 

10

 

8

 

2

 

 

 

 

 

 

 

 

 

 

 

 

 

2

 

20 µg

 

7

 

10

 

8

 

2

 

 

 

 

 

 

 

 

 

 

 

 

 

3

 

40 µg

 

7

 

10

 

8

 

2

 

 

 

 

 

 

 

 

 

 

 

 

 

4

 

80 µg

 

7

 

10

 

8

 

2

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Total

 

40

 

32

 

8

 

 

62

--------------------------------------------------------------------------------

 

Assumptions for Phase 1 Study:

 

1.                                      Study will be conducted in healthy,
postmenopausal women meeting stated inclusion/exclusion criteria. [Note:
requires FDA agreement to proceed in this population of subjects.]

 

2.                                      All subjects will receive a subcutaneous
dose of study medication (BA058 or placebo) once daily for 7 days.

 

3.                                      Study assessments:

 

·                  Physical examinations, vital signs, ECGs, clinical labs
(hematology, chemistry, urinalysis), adverse events, and local tolerability.

 

·                  Pharmacokinetics: full PK profile on Days 1 and 7 and trough
samples on other study days.

 

·                  Pharmacodynamics: serum total and ionized calcium,
phosphorus, cAMP, procollagen 1 carboxy terminal propeptide (PICP), and bone
specific alkaline phosphatase. Urine calcium, phosphorus, cAMP, and creatinine
execretion

 

·                  Presence of Anti-BA058 antibodies.

 

Timing:

 

1.                                      Total time involvement = 9 months from
first patient in (FPI) to draft clinical study report.

 

2.                                      FPI in 1Q06 and draft clinical study
report available 4Q06.

 

2.2                               Phase 2 Clinical Program

 

The Phase 2 study will be a proof-of-concept (POC) study assessing the effects
of several doses of BA058 on markers of bone turnover and BMD. The primary
objectives of this study are to assess the dose response of BA058, compare BA058
to Forteo®, and to select the BA058 doses that will be used in subsequent
efficacy studies. The strategic goal for this trial will be to confirm the
ability to deliver more effective anabolic doses of BA058 with good safety and
tolerability than is possible with Forteo, with clinical endpoints that
demonstrate a wider anabolic window for BA058 (i.e. greater effects on BMD at 3
months, and a higher ratio of bone formation vs. resorption) compared to Forteo.

 

Phase 2: 3-month treatment study

 

The Phase 2 study will be a randomized, double-blind, parallel group study in
which study medications will be administered for a total of 3 months. The study
will compare two doses of BA058 to Forteo® (20 µg) and placebo. Postmenopausal
women with BMD T scores below -2.5 will potentially be eligible for the study.

 

63

--------------------------------------------------------------------------------

 

Title:

 

A Randomized, Double-Blind, Parallel-Group Study to Evaluate the Safety and
Effectiveness of BA058 on Bone Mineral Density in Postmenopausal Women with
Moderate to Severe Osteoporosis

 

 

 

Protocol Number:

 

BA058-05-002

 

The objectives of this study follow:

 

·                  Determine the safety and tolerability of BA058 after 3 months
of dosing in postmenopausal women with osteoporosis.

 

·                  Determine the pharmacokinetics of BA058 after 3 months of
dosing in postmenopausal women with osteoporosis.

 

·                  Determine pharmacodynamic effects (i.e., effects on mineral
metabolism and biochemical markers of bone formation and resorption) after 3
months of treatment with BA058.

 

·                  Determine effects on BMD after 3 months of treatment with
BA058.

 

A total of 300 eligible patients will be enrolled and randomized to one of the
four treatments below:

 

Study Group

 

Study Medication

 

Dose (sc)

 

Number of Patients

 

 

 

 

 

 

 

 

 

1

 

BA058

 

To be determined

 

75

 

 

 

 

 

 

 

 

 

2

 

BA058

 

To be determined

 

75

 

 

 

 

 

 

 

 

 

3

 

Forteo®

 

20 µg

 

75

 

 

 

 

 

 

 

 

 

4

 

Placebo

 

—

 

75

 

 

 

 

 

 

 

 

 

 

 

 

 

Total

 

300

 

 

Assumptions for Phase 2 Study:

 

1.                                      The study will be conducted in
postmenopausal women with osteoporosis defined as a BMD T score below -2.5.

 

64

--------------------------------------------------------------------------------

 

2.                                      The study consists of a (minimum) 1
month Screening Period, 3-month Treatment Period, and a one-month Follow-up
Period (no study medications). Therefore, each patient is in the trial for a
total of 4 months.

 

3.                                      All subjects will receive a subcutaneous
dose of study medication (BA058, Forteo® 20 µg, or placebo) once daily for 3
months.

 

4.                                      All subjects to receive calcium
supplements and vitamin D.

 

5.                                      Study assessments:

 

·                  Physical examinations, vital signs, ECGs, clinical labs
(hematology, chemistry, urinalysis), serum total and ionized calcium,
phosphorus, thyroid hormones, adverse events, and local tolerability.

 

·                  Pharmacokinetics: serial PK samples taken on a subgroup of
patients.

 

·                  Pharmacodynamics (i.e., biochemical markers of bone
metabolism and resorption): procollagen 1 carboxy terminal propeptide (PICP),
bone specific alkaline phosphatase (BSAP) osteocalcin, cathepsin K, urine N
telopeptide (NTX), urinary free deoxypyridinoline, nephrogenic cAMP level,
urinary calcium excretion, creatinine clearance vitamin D intact PTH (1-84)

 

·                  Efficacy: measure changes in BMD (lumbar spine, hip,
forearm).

 

·                  Anti-BA058 antibody.

 

6.                                      With 75 patients in each dosing arm,
this study would be powered to detect a difference of 4% increase in lumbar BMD,
(i.e. from a 1% difference for placebo to 5% for BA058, or from a 4% difference
for Forteo® to an 8% increase for Tharp). However, anticipated differences in
markers of bone formation and resorption have to be examined before final
determination on the number of patients required.

 

7.                                      Sufficient BA058 is available and
packaged in time to start the study.

 

We will compare BA058’s effects on markers of bone formation, resorption and on
BMD with Forteo®. Also important would be the comparison of BA058’s effects on
BMD to the historical effects on BMD previously reported with longer term
treatment with Forteo®. If the data from this POC study shows that BA058 effect
on BMD or bone formation and resorption markers is statistically better than
Forteo®, then the next step would be to proceed to a Phase 3 study to evaluate
long-term treatment with BA058 to assess effects on BMD and reduction of
fractures.

 

Timing:

 

1.                                      Total time involvement = 24 months from
first patient in (FPI) to preliminary clinical results.

 

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2.                                      FPI in 1Q07, LPI 2Q08,LPO 4Q08 and draft
clinical study report available 1Q09.

 

Estimated Study Metrics:

 

Number of sites:

 

15-18

 

 

 

Number of site visits:

 

15-18 qualification and initiation visits

8 interim visits per site / per site

1 close-out visit / per site

 

 

 

Investigator’s Meeting:

 

For all study sites

 

 

 

Number of subjects screened:

 

750-900

(assumes 2.5-3.1 ratio of screened: enrolled)

 

 

 

Number of subjects enrolled:

 

300 (75 per treatment group)

 

 

 

Screening rate:

 

7-9 / site / month

 

 

 

Enrollment rate:

 

2-3 patients / site / month

 

2.3                               Phase 3 Clinical Program

 

The Phase 3 study will be a non-inferiority trial versus Forteo® to be conducted
in postmenopausal women with osteoporosis at risk of fracture.

 

Phase 3: 4-6 month BA058 treatment versus 12-month Forteo® treatment.

 

The Phase 3 study will be a randomized, double-blind study with a primary
endpoint of proportion of patients with one or more new vertebral fractures. The
tentative plan for this study is to assess a more convenient dosing regimen of
BA058 (e.g. 4-6 months of daily SC injections) versus a 12-month treatment
regimen with Forteo®. After completion of the study, an observational
post-treatment follow up study will be conducted to assess whether patients
continue to benefit from prior treatment with study medication.

 

Title:

 

Effects of BA058 in the Treatment of Postmenopausal Women with Osteoporosis

 

 

 

Protocol Number:

 

BA058-05-003

 

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Title:

 

Extended Follow-Up of Patients in BA058 Clinical Trials

 

 

 

Protocol Number:

 

BA058-05-004

 

The primary objective of the study is to:

 

·                  Demonstrate a reduction in the proportion of patients with
new vertebral fractures following treatment with study medication.

 

The secondary objectives of the study are to:

 

·                  Establish the safety of chronic administration of BA058 in
postmenopausal women with osteoporosis.

 

·                  Compare the effects of chronic administration of BA058 with
calcium and vitamin D versus Forteo® with calcium and vitamin D on lumbar spine
and hip BMD in postmenopausal women with osteoporosis.

 

·                  Assess the effects of chronic administration of BA058 on
biochemical markers of bone formation and resorption.

 

·                  Assess the durability of response by following patients in a
long-term post-study observational period.

 

A total of 3200 eligible patients will be enrolled and randomized to one of the
two treatments below:

 

Study Group

 

Study Medication

 

Dose (sc)

 

Number of Patients

1

 

BA058

 

To be determined

 

1,600*

2

 

Forteo®

 

20µg

 

1,600*

 

 

 

 

Total

 

3,200

 

--------------------------------------------------------------------------------

*Assumes a ratio of BA058: Forteo of 1:1.

 

Assumptions for Phase 3 Study:

 

1.                                      New formulation will be available for
patients to self-administer study medications.

 

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2.                                      The study will be conducted in
postmenopausal women with BMD T scores below -2.5 and meeting all other stated
inclusion/exclusion criteria.

 

3.                                      The Phase 3 study consists of a
(minimum) one-month Screening Period, 12-month Treatment Period, and a one-month
Follow-Up Period (no study medication). Each patient is in the trial for a total
of 14 months.

 

4.                                      The extended follow-up part of the study
starts once a patient completes the Phase 3 study.

 

5.                                      All subjects to receive calcium
supplements and vitamin D.

 

6.                                      Study assessments.

 

·                  Physical examinations, vital signs, ECGs, clinical labs
(hematology, chemistry, urinalysis), serum total and ionized calcium,
phosphorus, thyroid hormones, adverse events, and local tolerability.

 

·                  Pharmacokinetics: serial PK samples taken on a subgroup of
patients.

 

·                  Pharmacodynamics (i.e., biochemical markers of bone
metabolism and resorption): procollagen 1 carboxy terminal propeptide (PICP)
bone specific alkaline phosphatase (BSAP), osteocalcin, cathepsin K, urine N
telopeptide (NTX) urinary free deoxypyridinoline, nephrogenic cAMP level,
urinary calcium excretion, creatinine clearance, vitamin D, intact PTH (1-84).

 

·                  Efficacy: measure a reduction in the proportion of patients
with new vertebral fractures following treatment. Other assessments changes in
BMD (lumbar spine, hip, forearm).

 

·                  Anti-BA058 antibody.

 

Timing:

 

It’s assumed that 12 months of treatment and an additional 12-month post-study
observational period would be required. Thus, the Phase 3 program from the start
of the trial to completion of the long-term follow-up period, will take ~56
months.

 

Estimated Study Metrics:

 

To be determined.

 

2.4          Other Clinical Studies

 

New Formulations

 

Upon the availability of alternative formulations or delivery systems,
bioavailability studies will have to be conducted to compare the old/new
formulations.

 

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Alternative Dosing Schedules

 

Exploring various dosing frequencies or dosing cycles (i.e., less frequently
than once-daily) may need additional clinical studies to prove efficacy and
safety and/or additional study arms in the currently planned studies.

 

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3. FORMULATION STUDIES

 

BA058 is currently supplied for clinical use as a freeze dried lyophilizate
(i.e., freebase) in glass vials which are reconstituted with sterile 0.9% sodium
chloride for subcutaneous injection. A liquid/aqueous form was also developed
and used for intravenous dosing in the initial clinical study.

 

The plan is to continue with the same freeze dried lyophilizate formulation for
the scheduled Phase lb study in which BA058 will be administered once daily by
subcutaneous injection in a controlled environment. However, prior to conducting
longer term studies (i.e. the Phase II study) with BA058, another formulation
(auto injector?) will have to be developed so that the product can be used by
out patients with osteoporosis who will participate in these studies. Prior to
use of any new formulation (or delivery system), a bioavailability study when
have to be conducted to demonstrate bioequivalence with the previously used
formulation.

 

4. NON-CLINICAL PROGRAM

 

4.1          Toxicology/Pharmacology

 

The currently available toxicology package includes both a 3-month rat and a
3-month monkey study. In order to proceed with longer term clinical studies, we
anticipate conducting the following studies:

 

·                  12-month rat study

 

·                  12-month monkey study

 

In addition, prior to NDA submission, we need to plan and conduct a 24 month rat
carcinogenicity study.

 

Studies will have to be conducted to quantitate anti-BA058 antibody production
and development of neutralizing antibodies.

 

5. REGULATORY STRATEGY

 

The current plan is to have a pre-IND meeting with FDA in 4Q05 followed by
filing of the full IND to FDA within one month of the meeting. This will enable
start of the proposed Phase lb program in 1Q06 (estimated first patient in is
January 7, 2006).

 

Other meetings with FDA would occur after results from the Phase lb study are
available (Pre-Phase 2 meeting) and after results from the Phase 2 study are
available (End-of-Phase 2 or Pre-Phase 3 meeting).

 

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6. TIMELINES

 

Tentative timelines for each the IND filing and individual studies are provided
below:

 

Pre-IND and IND

 

Pre-IND meeting request to FDA:

 

01 Sep 05

Pre-IND package to FDA*:

 

Oct 17

Pre-IND meeting:

 

Nov 19

IND filing:

 

Dec 05/Jan 06

 

--------------------------------------------------------------------------------

*Requires full results from Phase la clinical study.

 

Phase 1b study

 

First Patient In (FPI):

 

1Q06

Last Patient Out (LPO):

 

2Q06

Enrollment rate:

 

Full cohort of 10 subjects at the same time

Subsequent cohorts:

 

3 week intervals

Study close out:

 

2Q06 (1 month)

Queries and data base lock:

 

3Q06 (1.5 months)

Analysis and draft clinical study report (includes PK, ECG, and biomarker
reports):

 

4Q06 (2.5 months)

 

Phase 2 study

 

IND Amendment:

 

4Q06 (submission of Phase 2 protocol and any other required documents)

First Patient In (FPI):

 

1Q07

Last Patient Out (LPO):

 

4Q08

Enrollment rate:

 

2-3 patients / per site / per month

 

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Study close out:

 

4Q08

Queries and data base lock:

 

1Q09

Analysis and draft clinical study report (includes PK, ECG, and biomarker
reports):

 

1Q09

 

Phase 3 study

 

End-of-Phase 2 meeting:

 

2Q09

IND Amendment:

 

2Q09 (submission of Phase 3 protocol and any other required documents)

First Patient In (FPI):

 

3Q09

Last Patient In (LPI):

 

4Q10

Last Patient Out (LPO):

 

4Q11

Enrollment rate:

 

2-3 patients / per site / per month

Study close out:

 

1Q11

Queries and data base lock:

 

1Q12

Analysis and draft clinical study report (includes PK, ECG, and biomarker
reports):

 

2Q12

Post-Study Observational Period - LPO:

 

2Q13

 

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APPENDIX D — CLINICAL SUPPLY AND TECHNICAL TRANSFER AGREEMENT

BIM 44058 INJECTION CLINICAL SUPPLIES AND TECHNOLGY TRANSFER

 

BETWEEN

 

Beaufour Ipsen Industrie S.A.S, rue d’Ethe Virton, 28100, France, duly
represented by Mike Dey, Vice-President, Pharmaceutical Development

 

Hereinafter referred to as IPSEN, on the one hand,

 

AND

 

NUVIOS Inc, a United States Corporation , having its registered office at 300
Technology Square-5th Floor, Cambridge, MA, USA duly represented by Richard
Lyttle, Chief Execuive Officer

 

hereinafter referred to as NUVIOS, , on the other hand,

 

WHEREAS :

 

NUVIOS and [SCRAS S.A.S. (a company organised and existing under the laws of
France, having its registered office at 42 rue du Dr. Blanche, 75016 Paris,
France)] (to be confirmed) have entered into an agreement named “License
Agreement between [SCRAS] and Nuvios” for BIM 44058,  dated XX September, 2005,
which is hereinafter referred to as the BIM 44058 Agreement.

 

IPSEN is SCRAS S.A.S.’ Affiliate (as defined in the BIM 44058 Agreement)
designated by SCRAS S.A.S. to manufacture for NUVIOS , the Compound and
Formulated Compound as defined in the BIM 44058 Agreement.

 

NUVIOS and IPSEN wish to enter into this agreement contemplated under
Section 9.1 of the BIM 44058 Agreement in relation to the manufacturing of
Product for use thereof by NUVIOS as part of the Development of the Compound
under the BIM 44058 Agreement.

 

NOW, THEREFORE THE PARTIES HERETO AGREE AS FOLLOWS:

 

DEFINITIONS

 

All capitalised terms used in this Agreement and which are not specifically
defined herein shall have the meaning attributed to them under the BIM 44058 
Agreement.

 

1.2          Compound shall mean the Licensed Compound as defined in the BIM
44058 Agreement.

 

1.3                     Formulated Compound shall mean the Compound, formulated
as a freeze dried injection, contained in a glass vial as described in Table 1
below.

 

1.4          cGMP shall mean current Good Manufacturing Practices in effect in
European Union and USA for clinical studies.

 

1.5          Manufacturing & Analytical Procedure shall mean the procedure
governing the manufacturing and analysis operations of the Compound and
Formulated Compound which may be specifically required in US or EU.  This
procedure is established when necessary by mutual agreement of the Parties, and
is signed by the Responsible Persons appointed by each Party.

 

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Table 1 Composition of BIM 44058 Injection

 

Material

 

Supplier

 

Unitary Formula
(per vial)

BIM44058C
Dextran 70
Citric acid 0.25% (w/v)
Water for injections**

 

Kinerton
Interchemical
Prolabo meram

 

0.1 mg (free base)
50 mg
qs pH 4.5*
qs 1 g

Type I clear glass vial, 11-13 ml
Grey chlorobutyl PTFE stopper, 20 mm
Flip-off metal crimp

 

Verretubex
Djikyo
West
Pharma

 

1
1
1

 

--------------------------------------------------------------------------------

* to get pH5 5.5 after lyophilisation ** removed after freeze-drying step.

 

1.6          Responsible Person shall mean: - For Ipsen, the Vice President
,Pharmaceutical Development, who is responsible for manufacturing clinical
supplies of Compound and Formulated Compound, as well as for Quality Control
thereof, ensuring procedures are performed as required by cGMP and that records
and samples are maintained as required under this Agreement, and for ensuring
correct release for despatch of Compound and Formulated Compound for clinical
use by NUVIOS under this Agreement.  These activities can be delegated to
appropriate individuals described in Ipsen SOPs for clinical supplies. - For
NUVIOS ,

 

1.7          Safety Agreement shall mean the document referred to in Section 8.4
of the BIM44058 Agreement as the “Pharmacovigilance Agreement”, covering
operational aspects of the conduct of clinical trials under the BIM 44058
Agreement regarding pharmacovigilance, including but not limited to withdrawal
proceedings, complaints handling, definitions of adverse events format of the
different reports and reporting procedures between the Parties and vis-à-vis
third parties.

 

1.8          Technical Specifications shall mean the technical documents that
consist of investigational drug supply request signed by Responsible Person of
NUVIOS and investigational drug supply acceptance signed by Responsible Person
of IPSEN to be agreed and signed for each clinical trial, covering all
technical, quality and logistical aspects of the manufacturing, control and
delivery to NUVIOS of the Formulated Compound manufactured by IPSEN for NUVIOS
for the purpose of this Agreement.
Each Technical Specifications sets out the specifications of the Compound / or
Formulated Compound as well as the manufacturing, control, storage and delivery
procedures for the Compound or Formulated Compound as well as instruction on
reserve samples. Each Technical Specifications shall be signed by the
Responsible Persons appointed by each Party.

 

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PURPOSE

 

The purpose of this Agreement is to establish the terms and conditions governing

 

(i) the manufacturing and delivery by IPSEN (or by IPSEN’s designated
manufacturer) for NUVIOS of the Compound for the purposes of the conduct by
NUVIOS of Phase I and first Phase II Clinical Trials under the Development Plan
as provided in the BIM 44058 Agreement;

 

(ii) the manufacturing and delivery by IPSEN (or by IPSEN’s designated
manufacturer) for NUVIOS of the Formulated Compound for the purposes of the
conduct by NUVIOS of Phase I and Phase II Clinical Trials under the Development
Plan as provided in the BIM 44058 Agreement ;

 

(iii) the provision by IPSEN (or by IPSEN’s designated manufacturer) of the
following services to NUVIOS: release, intermediate labeling and bulk packing
using packaging and labelling materials of Ipsen’s specification or using
packaging and labelling materials laid-out and supplied by NUVIOS to IPSEN when
appropriate, as well as delivery of Compound and Formulated Compound to NUVIOS
and retainment of reserve samples and reanalysis of appropriate samples ;

 

(iv) support activities for transfer of process and analytical technology to the
NUVIOS selected contractor.  The costings and estimated timescales shown in
Appendix 2, assume a single contractor for each of drug substance and drug
product.  Packaging and labeling of primary containers of Compound and
Formulated Compound eitherNUVIOS shall use the Compound or Formulated Compound
supplied to NUVIOS by IPSEN under this Agreement solely in accordance with and
for the purposes of the performance of Phase I and Phase II Clinical Trials
under the Development Plan of the Compound and Formulated Compound as provided
under the terms and conditions of the BIM 44058 Agreement.

 

For the avoidance of doubt, IPSEN shall not be required to supply NUVIOS with
Compound or Formulated Compound for Phase III Clinical Trial.

 

All relevant terms and conditions of the BIM 44058 Agreement shall fully apply
to and govern this Agreement.

 

MANUFACTURING - ORDERS — DELIVERY - REANALYSIS

 

IPSEN certifies that it possesses or that IPSEN’s designated manufacturer for
the purposes herein possesses, adequate premises and equipment, and sufficient
experience and knowledge as well as a competent personnel in order to carry out
the operations contemplated under Clause 2.1 of this Agreement, in a
satisfactory manner and in accordance with regulations governing medicine for
human use, cGMP (if and to the extent applicable), the Technical Specifications
and the Manufacturing & Analytical Procedure.

 

IPSEN declares that it or that IPSEN’s designated manufacturer for the purposes
herein holds, the authorisations required in their respective countries in order
to manufacture, store, and deliver the Compound and Formulated Compound.

 

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The Technical Specifications for Clinical Trials and the Manufacturing &
Analytical Procedure are the subject of a document drawn up and signed by the
Parties separately from the present Agreement for each Clinical Trial to be
conducted by NUVIOS under the BIM 44058 Agreement.  The Technical Specifications
for Clinical Trials shall cover the aspects relevant to this Agreement and
listed in the procedure GCP004 - “Investigational Product Order for Clinical
Studies” and GCP026 - “Clinical Investigational Product Handling Procedure”,
copies of which shall be made available by IPSEN to NUVIOS and are appended to
this Agreement,Appendices 3 and 4 respectively.

 

The rules and systems governing orders placed by NUVIOS for NUVIOS’s required
quantities of Compound and Formulated Compound shall be described in the
Technical Specifications.

 

Interpretation and summary of cGMP covering the manufacture of the Compound and
Formulated Compound, requirements for quality control and responsibilities of
both Parties is attached as Appendix 1 hereto.

 

IPSEN undertakes to manufacture each Compound and Formulated Compound in
accordance with the manufacturing, analysis and control methods stipulated in
the corresponding Technical Specifications and Manufacturing & Analytical
Procedure.  In particular, after required quality control checks, and
verification of the appropriate manufacture under cGMP, IPSEN shall supply the
primary containers of Compound and Formulated Compounds to NUVIOS, packed and
labelled either using packaging and labelling materials of Ipsen’s specfication
or using the packaging and labelling materials laid-out and supplied by NUVIOS
when appropriate.  Compound and Formulated Compound shall be supplied to NUVIOS
for final labelling and packaing operations, and quality assurance release by
NUVIOS

 

IPSEN may entrust other pharmaceutical ingredients or products manufacturers
with all or part of the operations contemplated under this Agreement.  IPSEN
shall inform NUVIOS of the identity of any such third-party manufacturers and
the operations entrusted by IPSEN thereto.

 

NUVIOS undertakes that all the administrative prerequisites relating to each
Clinical Trial shall be obtained for each Clinical Trial centre prior to
delivery of Compound or Formulated Compound thereto.

 

IPSEN shall, with each delivery of Compound or Formulated Compound to NUVIOS,
supply or procure the supply of a certificate of analysis related to each
delivered batch showing that such batch conforms with the then current
specifications and quality standards of Compound or Formulated Compound as shown
in the applicable Technical Specifications or Manufacturing & Analytical
Procedure.

 

Each delivery of Compound to the persons and places indicated by NUVIOS shall be
accompanied by (i) the documents referred to in the procedures GCP004 -
“Investigational Product Order for Clinical Studies” and GCP026 - “ Clinical
Investigational Product Handling Procedure”, including a delivery slip
mentioning the name of the Compound , the batch number, the use-by date, the
storage conditions, and the quantities delivered. and, (ii) the documents which
might be required by NUVIOS for the purpose of complying with relevant
regulations in EU or US applicable to the Compound or Formulated Compound.

 

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NUVIOS shall ensure and inform IPSEN in writing that the delivery thus carried
out was made to the correct addressee and that the latter took proper delivery.

 

Upon receipt of the Compound or Formulated Compound NUVIOS shall perform
necessary labelling, packaging and quality checking thereof as shall be
determined in the Technical Specifications or in the Manufacturing & Analytical
Procedure before releasing the Compound or Formulated Compound for use in
clinical studies.

 

Unused quantities of Compound or Formulated Compound shall at NUVIOS option
either be returned to NUVIOS or with IPSEN prior written consent,  locally
destroy unused quantities of Compound or Formulated Compound.  In such case,
NUVIOS shall send to IPSEN the corresponding certificates of destruction.

 

IPSEN shall retain reserve samples as specified in the Technical Specification
for duration stated in clinical GMP.  IPSEN shall perform reanalysis of reserve
samples when required under Ipsen SOPs, or when agreed with NUVIOS.

 

NON-COMPLIANCE OF BATCHES

 

NUVIOS shall notify IPSEN of any deficiency in quantity or any defect which was
immediately discoverable - in writing within 10 working days after the delivery
to NUVIOS of the Compound or Formulated Compound.  NUVIOS shall promptly notify
IPSEN in writing of any latent defect that was not immediately discoverable in
the quality checking but found before the expiry date of the Compound or
Formulated Compound.  NUVIOS shall not use any quantity of the Compound or
Formulated Compound that NUVIOS has discovered is defective.

 

In case of notification of a defect of the delivered quantities of Compound or
Formulated Compound, within the time period mentioned hereabove, IPSEN shall at
IPSEN option, take back or have NUVIOS destroy, the relevant quantities of
Compound or Formulated Compound, at IPSEN’s expenses and IPSEN shall replace
them as soon as practicable so as to avoid any disruption of supply to NUVIOS.

 

In case of discrepancies of the results of the analysis performed by NUVIOS and
IPSEN on the delivered quantities of the Compound or Formulated Compound, and in
case of any dispute between the Parties regarding the quality of the Compound or
Formulated Compound, NUVIOS or IPSEN shall appoint an independent expert to whom
the other Party may not unreasonably object and who shall assess whether the
delivered quantities are defective or not.  In case the delivered quantities of
the Compound or Formulated Compound are found to be defective, IPSEN shall pay
for the costs of appointment of such expert.  In case the delivered quantities
of Compound are found not to be defective, NUVIOS shall pay for the costs of
appointment of such expert.

 

FINANCIAL CONDITIONS — REPORTING OBLIGATIONS

 

In consideration for the provision by IPSEN to NUVIOS of the manufacturing,
delivery, release, packaging, and labelling services under this Agreement,
before delivery of each

 

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subject batch or lot of Formulated Compound or BIM44058 Compound, NUVIOS shall
make the following payment to IPSEN:

 

First batch of approximately 1600 vials manufactured;

 

€

65,000

 

 

 

 

 

Subsequent lots if 1600 vials of the same Product

 

€

55,000

 

 

 

 

 

Raw Materials , sufficient for 150g Compound

 

€

50,000

 

 

 

 

 

Delivery of agreed amount of peptide; 150g

 

€

400,000

 

 

If quantitities of Compound less than 150g are agreed for supply then the costs
will be agreed prior to manufacture and the remaining raw materials purchased
would be provided to NUVIOS at no further cost, other than transportation and
any importation cost which would be charged at cost.

 

The sum stipulated in Article 5.1 shall be paid by NUVIOS to IPSEN following
receipt by NUVIOS of the corresponding invoice and before delivery.

 

PHARMACOVIGILANCE -CLAIMS - LIABILITY - WITHDRAWAL

 

The Parties will carry out their obligation with respect to safety data
exchanging of the Compound or Formulated Compound in accordance with the
procedures defined in BIM 44058 Agreement.  However, that nothing contained
herein shall be construed as restricting either Party’s right to make a timely
report of such matter to any government agency or take other action that it
deems to be appropriate or required by applicable law or regulations in the
territory.

 

In relation with Clinical Trials only, conducted by NUVIOS under the BIM 44058
Agreement, NUVIOS shall, if required under NUVIOS procedures,  implement the
Formulated Compound batch recall or withdrawal in accordance with NUVIOS
relevant standard operating procedure.  Such withdrawal will be notified to the
Responsible Persons under this Agreement, immediately such formal decision is
reached within NUVIOS.

 

Liabilities and indemnification of the Parties in connection with the operations
contemplated under this Agreement, shall be governed by the terms and conditions
of the BIM 44058 Agreement.

 

CONFIDENTIALITY

 

In addition to the Parties’ respective obligations under Article 12  of the BIM
44058 Agreement, NUVIOS undertakes to keep strictly confidential and to use
exclusively in accordance with the terms and conditions of the BIM 44058
Agreement, in particular in accordance with Article 12 of the BIM 44058
Agreement, all information in relation to the operations contemplated under this
Agreement, of whatever nature, form or media, including without limitation, the
processes and methods of manufacturing the Compound and Formulated Compound,
including if deemed appropriate by IPSEN,

 

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Chemistry, Manufacturing and Control data in relation thereto, communicated or
developed by IPSEN or its third-party designated manufacturer.  For the
avoidance of doubt, all information made available to NUVIOS under this
Agreement shall be deemed to be Ipsen Development Information under the BIM
44058 Agreement.

 

ENTRY INTO EFFECT AND TERM

 

This Agreement enters into effect on the day of its signature by the Parties.
This Agreement shall expire upon completion of the Phase II Clinical Trials
contemplated under this Agreement, unless extended by mutual agreement of the
Parties.

 

Either Party may terminate this Agreement at any time with immediate effect upon
notice to the other Party, in case of termination of (i) the Development of the
Compound or Formulated Compound under the BIM 44058 Agreement, (ii) the Detailed
Development Plan under the BIM 44058 Agreement, or (iii) the BIM 44058
Agreement.

 

Either Party may terminate this Agreement for those other applicable causes
identified in Article 15 of the BIM 44058 Agreement.

 

Notwithstanding early termination of this Agreement, this Agreement shall remain
applicable to any ongoing Clinical Trial identified in the Technical
Specifications until signature of the final report of the last Clinical Trial,
unless the corresponding Technical Specifications is earlier terminated by
mutual agreement of the Parties.

 

MISCELLANEOUS

 

In case one of the provisions of this Agreement would be considered null and
void, it shall be considered to be unwritten but shall not lead to the nullity
of the Agreement.

 

The Technical Specifications, the Manufacturing & Analytical Procedure, the
Safety Agreement, form an integral part of this Agreement.

 

Articles 17 and 18 of the License Agreement shall apply to this Agreement
mutatis mutandis.

 

Signed in two copies, one for each Party

 

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CLINICAL SUPPLY AGREEMENT APPENDIX 1 — Interpretation and summary of cGMP
Responsibilities for specific stages of the manufacture and supply of Compound
or Formulated Compound are described in Table 1 below.

 

Definitions of the terms used in the table are stated in clinical Good
Manufacturing Practices.

 

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TABLE 2   Responsibility for Clinical Supplies

 

Content

 

Summary

 

Responsibility

Study Co-ordination

 

Assign Clinical Project Manager

Obtain all Ethical and regulatory approvals for study

Order required numbers of Clinical Supplies

 

Nuvios

 

 

 

 

 

Protocol

 

Prepare protocol including all details of centers, study blinding, randomization
requirements

 

Nuvios

 

 

 

 

 

Technical Specifications

 

Prepare Technical Specifications documentation

Approval for all clinical protocol requirements being met

Approval for all regulatory requirements being met

Approval for all Technical and Product Quality requirements being met at
manufacture

 

Nuvios

Nuvios

Nuvios

Ipsen

 

 

 

 

 

Manufacture and Quality Control

 

Procure, store, perform lot analysis of raw materials, and manage retain samples

 

Manufacture, perform lot analysis of BIM 44058 Injection, and manage retain
samples.

Provide Certificate of Analysis in required format

 

Ipsen

 

Ipsen

 

Ipsen

 

 

 

 

 

Shipment of Formulated Compound

 

Packing of bulk product in suitable protective packaging to ensure correct
storage and shipment to Paris airport.

Receipt, interim storage and arrangements for transatlantic shipment to Nuvios
contracted Clinical Research Organisation.

Receipt, customs clearance and transportation to Nuvios CRO

 

Ipsen

 

Nuvios

 

Nuvios

 

 

 

 

 

Packaging and labeling

 

Receipt, acceptance tests (if required) and all labeling and Packaging for
clinical supplies

Provision of all labeling and packaging components and materials labeling,
including translation sand verification of translated text.

 

Nuvios

 

Nuvios

 

 

 

 

 

Release of investigational product

 

Quality Assurance release of investigational product based on Ipsen provided
Certificate of Analysis for formulated product and upon successful review of
packaging & labeling batch records.

 

Nuvios

 

 

 

 

 

Ongoing Stability

 

If required, periodic testing of stored samples to verify ongoing stability

 

Nuvios

 

81

--------------------------------------------------------------------------------

 

Testing

 

and compliance with specifications, of formulated compound

 

 

 

 

 

 

 

Complaint & recall

 

Perform complaint managing, recall actions

 

Nuvios

 

 

 

 

 

Manufactuing Document retention

 

Retain all manufacturing and product testing documents for at least 10 years
after expiry of the Compound or Formulated compound lot.

Retain all Packaging and Labelling documentation as required

 

Ipsen

 

Nuvios

 

82

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CLINICAL SUPPLY AGREEMENT APPENDIX 2; Outline Program Timings and Costs for
Manufacture of BIM 44058 Compound Clinical Supplies and Process Transfers to
NUVIOS Contractor

 

Phasing of Costs for BIM 44058 for Transfer to Nuvios

 

 

 

Total

 

2005

 

2006

 

Item

 

€000s

 

3Q

 

4Q

 

Total 05

 

1Q

 

2Q

 

3Q

 

4Q

 

Total 06

 

Active Ingredient

 

492

 

42

 

50

 

92

 

0

 

400

 

0

 

0

 

400

 

Testing GMP Lot for CT supply

 

12

 

12

 

 

 

12

 

 

 

 

 

 

 

 

 

0

 

Starting materials for API supply for 150g

 

50

 

 

 

50

 

50

 

 

 

 

 

 

 

 

 

0

 

Manufacture API Lot 150g

 

400

 

 

 

 

 

0

 

 

 

400

 

 

 

 

 

400

 

Stock of API existing Lot

 

24

 

24

 

 

 

24

 

 

 

 

 

 

 

 

 

0

 

Working Ref Std vials ; c 900 vials + 0.9g

 

6

 

6

 

 

 

6

 

 

 

 

 

 

 

 

 

0

 

Technology Transfer Support for API

 

139

 

33

 

54

 

87

 

40

 

12

 

0

 

0

 

52

 

Process transfer (@€1000 per day; 240k/FTE)

 

62

 

18

 

26

 

44

 

12

 

6

 

 

 

 

 

18

 

Analytical transfer (@€1000 per day; 240k/FTE)

 

57

 

15

 

18

 

33

 

18

 

6

 

 

 

 

 

24

 

Travel to US 2 trips x 2 scientists

 

20

 

 

 

10

 

10

 

10

 

 

 

 

 

 

 

10

 

Drug Product Clinical Supplies

 

190

 

0

 

130

 

130

 

0

 

60

 

0

 

0

 

60

 

Placebo Lot x nominal 1600 vials Fill c 19 Sep

 

65

 

 

 

65

 

65

 

 

 

 

 

 

 

 

 

0

 

Active Lot x nominal 1600 vials Fill c 26 Sep

 

65

 

 

 

65

 

65

 

 

 

 

 

 

 

 

 

0

 

Additional Active Lot Fill c April 2006

 

60

 

 

 

 

 

0

 

 

 

60

 

 

 

 

 

60

 

Technology Transfer Support for Drug Product

 

108

 

31

 

38

 

69

 

33

 

6

 

0

 

0

 

39

 

Process transfer (@€1000 per day; 240k/FTE)

 

28

 

13

 

10

 

23

 

5

 

6

 

 

 

 

 

5

 

Analytical transfer (@€1000 per day; 240k/FTE)

 

60

 

18

 

18

 

36

 

18

 

 

 

 

 

 

 

24

 

Travel to US 2 trips x 2 scientists

 

20

 

 

 

10

 

10

 

10

 

 

 

 

 

 

 

10

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

GRAND TOTAL

 

929

 

106

 

272

 

378

 

73

 

478

 

0

 

0

 

551

 

 

83

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CLINICAL SUPPLY AGREEMENT APPENDIX 3  GCP004 - “Investigational Product Order
for Clinical Studies”

 

Ipsen Group

 

R&D Standard Operating Procedure

Effective: 10 March 2005

 

Number: GCP004.05

 

--------------------------------------------------------------------------------

 

INVESTIGATIONAL MEDICINAL PRODUCT ORDER
FOR CLINICAL STUDIES

 

--------------------------------------------------------------------------------

 

R&D SOP AUTHOR:

 

L. EGGINK

Clinical Research Manager

Clinical Operations, R&D

 

PRIMARY REVIEWER:

 

C. MARTIN

On behalf of the R&D SOP Committee

 

R&D STEERING COMMITTEE SOP AUTHORISATION

 

P. MERAT

Senior Vice-president, Clinical Development,

R&D, Ipsen Group

 

 

SIGN:

/s/ Patrick Merat

 

DATE:

February 15, 2005

 

Copy No. 67

 

 

 

CONFIDENTIAL

The contents of this document are confidential and proprietary to the Ipsen
group.
Unauthorised use, disclosure or reproduction is strictly prohibited

 

84

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TABLE OF CONTENTS

 

 

 

Page

 

 

 

1.

INTRODUCTION

86

 

 

 

 

1.1

Objective

86

 

1.2

Scope

86

 

1.3

Roles and Responsibilities

86

 

 

 

2.

PROCEDURE

87

 

 

 

 

2.1

Processing the Investigational Medicinal Product Orders

87

 

 

2.1.1

Forecasting of Investigational Medicinal Products requirements

87

 

 

2.1.2

Ordering of Bulk Formulated Product

87

 

 

2.1.3

Technical Specification

87

 

 

2.1.4

Packaging Order

88

 

2.2

Labelling Instructions

88

 

2.3

Release of Investigational Medicinal Product

89

 

2.4

Use of Clinical Supplies Tracking Workflow application

89

 

2.5

Archiving

89

 

 

2.5.1

At Sponsor

89

 

 

2.5.2

At Manufacturer and/or CTSU

89

 

2.6

Flowchart: Ordering Investigational Medicinal Products for Clinical Trials

90

 

 

 

3.

CONTINGENCIES

91

 

 

 

4.

R&D SOP FORMS AND TEMPLATES

91

 

 

 

5.

BIBLIOGRAPHIC REFERENCES

91

 

85

--------------------------------------------------------------------------------

 

1.                                      INTRODUCTION

 

1.1                               Objective

 

This procedure defines the different stages and documentation required to plan,
prepare and order Investigational Medicinal Products (IMP) for clinical studies
from the Clinical Trials Supplies Unit (CTSU).

 

1.2                               Scope

 

This procedure must be followed for IMP orders and any compassionate use
supplies within the Ipsen group.

 

This procedure should also be enforced for clinical studies sponsored by
industrial partners but where Ipsen is only responsible for the IMP supply.

 

1.3                               Roles and Responsibilities

 

·                                          CTSU must ensure that a technical and
quality agreement exists between the sponsor and the manufacturing site
specifying assigned responsibilities of each party in accordance with current
Good Manufacturing Practice (GMP) requirements.

 

·                                          The Clinical Study Coordinator (CSC)
is responsible for submitting to the CTSU (or CTSU contact) forecasts of
intended IMP requirements and updating the amount at least quarterly.

 

·                                          The CSC is responsible for the
coordination of all IMP ordering activities for each of his/her delegated
studies.

 

·                                          The CTSU is responsible for providing
the Technical Specification for the CSC and the Regulatory Affairs
representative to approve and, to provide the final approved and signed
Technical Specification to the CSC.

 

·                                          The CTSU is responsible for supplying
IMP in accordance with GMP and Good Clinical Practice (GCP) and to the
specifications (outlined in the Technical Specification and any registered
Investigational Medicinal Product Dossier (IMPD) or Investigational New Drug
(IND)) agreed between the CSC, CTSU, Pharmaceutical Development, QA and
Regulatory Affairs.

 

·                                          The CSC and the Regulatory Affairs
representative are responsible for approving master labels for the study.  There
should exist a representative for labeling in each participating Ipsen or
Contract Research Organisation (CRO) office, who will verify and document
compliance with local regulations.  Responsibilities for the local
representative for labeling are:

 

86

--------------------------------------------------------------------------------

 

·                                          Providing translations of core labels
text, when necessary, to the CSC and CTSU, which are compliant with local legal
requirements.  This is done through liaison with Regulatory Affairs, where
available.

 

·                                          Checking Master Labels

 

2.                                      PROCEDURE

 

2.1                               Processing the Investigational Medicinal
Product Orders

 

2.1.1                     Forecasting of Investigational Medicinal Products
requirements

 

At least quarterly, the CTSU sends an IMP forecast sheet to the CSC for
completion and return back to the CTSU.

 

The CSC will complete forecasts of supplies up to one year in advance taking
into account IMP manufacturing lead time and shelf life, treatment duration and
recruitment period.

 

2.1.2                     Ordering of Bulk Formulated Product

 

A request for the manufacture of Bulk Formulated Product will be placed by the
CSC as soon as possible after the Ipsen Study Approval is obtained.  The request
for Bulk Formulated Product manufacture should be made using the Bulk Formulated
Product Manufacturing Order (Ref. GCP004-A).

 

The request for manufacturing Bulk Formulated Product must contain the
requirements for all countries participating in the study for a 12-month
period.  If the study duration is expected to exceed significantly beyond 12
months, an additional order must be submitted before the 12-month period covered
if the first order has finished.

 

A copy of the approved protocol synopsis must be attached to the Bulk Formulated
Product Manufacturing Order (GCP004-A).

 

2.1.3                     Technical Specification

 

The CTSU will provide a first draft of the Technical Specification to the CSC
for review.  The Technical Specification contains information valid for the
study including:

 

·                                          Study design

 

·                                          Randomisation numbers and their
syntax, strata label and period (if applicable)

 

·                                          Estimated Times Frames

 

·                                          Participating Countries

 

·                                          Description of Packs and Labelling

 

87

--------------------------------------------------------------------------------

 

·                                          Calculation of IMP Requirements

 

·                                          Despatch Requirements

 

·                                          Return & Product destruction
requirements

 

·                                          Approval of master and translated
labels by Ipsen local affiliates or by central regulatory affairs.

 

The CSC completes, reviews and returns the Technical Specification to the CTSU
for finalisation.  Both CSC and CTSU agree on packaging design, presentation of
the IMP and on timelines for setting up the IMP.

 

The CSC and CTSU representative must ensure and document that the Technical
Specification is consistent with the final approved protocol.

 

The Technical Specification represents the official agreement between the CTSU
and the CSC on IMP specifications.

 

2.1.4                     Packaging Order

 

The CSC/designee must submit a Packaging Order (GCP004-B) to the CTSU once the
protocol has been approved. This form is used to order a specific amount of IMP
and must be used for the first supplies as well as re-supplies or additional
supplies.

 

The signed and completed Packaging Order (GCP004-B) is sent back to the CSC and
filed in the Trial Master File (TMF).  A copy is kept at the CTSU.

 

2.2                               Labelling Instructions

 

Labelling text must be in local language and complaint with national laws in
force.  The core label texts for all packaging units are created by the CTSU in
collaboration with the CSC.  They will be defined in the Technical Specification
and are compliant with the requirements of Annex 13 of The Rules Governing
Medicinal Products in the European Union and US FDA 21 CFR 312.6 Labelling of an
Investigational New Drug.

 

When applicable, a “local law complaint” translation (or adjustment) of the core
label text must be requested by the CSC to the local responsible person for
labeling.  Label translations (or adjustments) are included as part of the
Technical Specification.

 

The CTSU is responsible for preparing master labels and translations provided in
the Technical Specification.

 

Written approval of the master labels and translated labels must be given by the
CSC and the Regulatory Affairs representative.

 

88

--------------------------------------------------------------------------------

 

The CTSU is responsible for production and quality control of the labels
produced and maintaining copies of those labels for reference.

 

2.3                               Release of Investigational Medicinal Product

 

The CTSU’s issue of the Certificate of Analysis (CofA) for the Bulk Formulated
Product and the Pack Batch Release Certificate of the finished drug product, is
considered the “Technical Green Light” for the IMP to be released.

 

These certificates are sent by the CTSU to the CSC to the CSC for archiving in
the TMF.

 

The CSC authorises the release of IMP for delivery to a clinical trial site
following the requirements of the IMP Release Form (Ref. GCP088-B).

 

IMP supply to a clinical trial site will be done just prior to or during the
site initiation visit after the CSC has completed the IMP Despatch
Form (GCP026-A) and sent it to the CTSU or an interim storage facility.  IMP may
only be supplied to clinical trial sites when all required documentation, as
specified in SOP GCP088, has been obtained.

 

2.4                               Use of Clinical Supplies Tracking Workflow
application

 

In case the Clinical Supplies Tracking Workflow (CSTW) application is used for a
clinical study, the procedure described in this SOP will still apply but the
forms GCP004-A and GCP004-B are replaced by their equivalent electronic form
within the CSTW.

 

When filing is required, a paper copy of the electronically approved form will
be accepted.

 

2.5                               Archiving

 

2.5.1                     At Sponsor

 

All the documents must be archived in the TMF in compliance with Ipsen R&D SOPs
(Ref. GEN031, GCP092) and GCP.

 

2.5.2                     At Manufacturer and/or CTSU

 

All the documents must be archived according to manufacturer’s and/or CTSU SOPs
and current GMP.

 

89

--------------------------------------------------------------------------------

 

2.6                               Flowchart:  Ordering Investigational Medicinal
Products for Clinical Trials

 

[g17732li17ai001.jpg]

 

90

--------------------------------------------------------------------------------

 

3.                                      CONTINGENCIES

 

None

 

4.                                      R&D SOP FORMS AND TEMPLATES

 

Title

 

Reference

 

Status

Bulk Formulated Product Manufacturing Order

 

GCP004-A

 

Compulsory

Packaging Order (for Beaufour Ipsen Industrie, Dreux)

 

GCP004-B

 

Compulsory

 

5.                                      BIBLIOGRAPHIC REFERENCES

 

1.                                      Directive 2003/94/EC on GMP for
Medicinal Products for Human Use.

2.                                      “Manufacture of Investigational
Medicinal Products” Most current version of Annex 13 of the EU guide to GMP.

3.                                      US FDA 21 CFR part 210: Current GMP in
manufacturing, processing, packing, or holding of drugs; general.

4.                                      US FDA 21 CFR part 211: Current GMP for
finished pharmaceuticals.

5.                                      Ipsen Group R&D SOP GCP088 Initiation of
Clinical Trial Sites.

6.                                      Ipsen Group R&D SOP GCP026 Clinical
Investigation Product Handling Procedures.

7.                                      Ipsen Group R&D SOP GCP092 Management of
the Trial Master File & Investigator Site File.

8.                                      Ipsen Group R&D SOP GEN031: R&D Records,
Archiving and Retention.

 

91

--------------------------------------------------------------------------------

 

 

CLINICAL SUPPLY AGREEMENT APPENDIX 4 GCP026 - “Clinical Investigational Product
Handling Procedure”

 

Ipsen Group

 

R&D Standard Operating Procedure

Effective: 10 March 2005

 

Number: GCP026.04

 

--------------------------------------------------------------------------------

 

CLINICAL INVESTIGATIONAL MEDICINAL

PRODUCT HANDLING PROCEDURES

 

--------------------------------------------------------------------------------

 

R&D SOP AUTHOR:

 

FRANCIS SÉGUY

Clinical Research Manager

Clinical Operations, R&D

 

PRIMARY REVIEWER:

 

LIZ COXON

On behalf of the R&D SOP Committee

 

R&D STEERING COMMITTEE SOP AUTHORISATION

 

P. MERAT

Senior Vice-President, Clinical Development,

R&D, Ipsen Group

 

SIGN:

/s/Patrick Merat

 

DATE:

February 15, 2005

 

92

--------------------------------------------------------------------------------

 

TABLE OF CONTENTS

 

 

 

Page

 

 

 

1.

INTRODUCTION

94

 

 

 

 

1.1.

Objective

94

 

1.2.

Scope

94

 

1.3.

Roles and Responsibilities

94

 

 

 

2.

PROCEDURE

95

 

 

 

 

2.1.

IMP Despatch

95

 

 

2.1.1.

Despatch request

95

 

 

2.1.2.

Packaging and despatch specifications

95

 

 

2.1.3.

Despatch confirmation

96

 

2.2.

IMP accountability

96

 

2.3.

IMP Storage / Shipment Incidence

96

 

2.4.

Expired IMP and relabelling procedures

96

 

2.5.

Returned investigational product

97

 

2.6.

Destruction of an investigational product

97

 

 

 

3.

CLINICAL SUPPLIES TRACKING WORKFLOW APPLICATION

98

 

 

 

4.

CONTINGENCIES

98

 

 

 

5.

R&D SOP FORMS AND TEMPLATES

98

 

 

 

6.

BIBLIOGRAPHIC REFERENCES

98

 

93

--------------------------------------------------------------------------------

 

1.                                      INTRODUCTION

 

1.1.                            Objective

 

To describe the procedures to be followed for handling clinical Investigational
Medicinal Products (IMP) in order to comply with applicable regulations and
guidelines for Good Clinical Practice (GCP) and Good Manufacturing Practice
(GMP).

 

1.2.                            Scope

 

This Research & Development (R&D) Standard Operating Procedure (SOP) applies to
Ipsen R&D, Ipsen affiliates and any staff delegated the responsibility for the
handling and documenting of IMP movements. Any consultants or Contract Research
Organisations (CRO) required to handle IMP on behalf of Ipsen are included
within the requirements of this SOP. This procedure covers the mechanisms for
storage, transfer and documentation of IMP for outward despatch to
investigational and other sites and their complete accountability, retrieval and
destruction.

 

1.3.                            Roles and Responsibilities

 

·                                          The Clinical Trial Supplies Unit
(CTSU) is responsible for ensuring that validated packaging and appropriate
shipping conditions are used when an IMP is despatched directly to either an
Interim Storage Facility or an investigational site.

 

·                                          The CTSU must ensure that all IMPs
sent to the investigational site or Interim Storage Facility can be tracked at
any time.

 

·                                          If an Interim Storage Facility is
used, it is the CTSU’s responsibility to ensure that the facility has adequate
controls for storage of IMP and that the packaging used is in compliance with
the Technical Specification.

 

·                                          The Clinical Study Coordinator (CSC),
in consultation with regulatory affairs and CTSU representatives, should ensure
that correct IMP import/export documentation is in place prior to IMP despatch.

 

·                                          The CSC or designee is responsible,
in association with the CTSU, for ensuring that the shelf-life of the IMP
available at the investigational site is adequate in the context of their
intended use.

 

·                                          The CSC or designee is responsible
for requesting the despatch of an IMP to investigational (or other) sites from
the CTSU and where appropriate from any Interim Storage Facility or labelling
and packaging facility that may be used.

 

·                                          The CSC or designee is responsible,
if applicable, for providing the block randomisation information to the CTSU and
for ensuring that the study IMP are distributed by blocks to the centres.

 

94

--------------------------------------------------------------------------------

 

·                                          The CSC or designee is responsible
for ensuring adequate accountability of all IMP sent to the investigational site
or Interim Storage Facility, during the clinical trial, and in particular before
any retrieval of IMP from the investigational site for destruction.

 

·                                          Monitors are responsible for
reviewing, checking any IMP accountability documentation at the investigational
sites and for ensuring the accountability is adequate and for requesting the
return or destruction of used (when applicable) and unused IMP, to or at the
appropriate facility.

 

·                                          The CSC is responsible for
authorising the destruction of the IMP.

 

·                                          The CTSU is responsible for providing
storage for returned IMP, destroying IMP upon request and ensuring proper
labelling in the event of reallocating or extending the expiry date.

 

2.                                      PROCEDURE

 

2.1.                            IMP Despatch

 

2.1.1.                  Despatch request

 

IMPs can be despatched either directly from the CTSU to an investigational site
or to an Interim Storage Facility, or from an Interim Storage Facility to an
investigational site. The CSC or designee must request all transfers of IMPs on
the IMP Despatch Form (GCP026-A). The CSC must provide the CTSU with a list of
designees, with their signatures, who are authorised to sign the IMP Despatch
Form. A copy of this form must also be filed in the Trial Master File (TMF).

 

The CTSU out source, manufacture and pack the IMP in accordance with current
GMP. The CTSU must also provide the CSC or designee with Certificate of Analysis
(CofA) and the Pack Batch Release Certificate for each batch of an IMP supplied
which is considered the technical green light.

 

The IMP Despatch Form must be sent by the CSC or designee to the despatch office
(CTSU or Interim Storage Facility).

 

Additional supporting documentation can be attached to the IMP Despatch
Form where appropriate (e.g., a letter of approval from the doctor for
compassionate/named patient supplies, import licence).

 

IMP Despatch Forms must be filed in the TMF.

 

2.1.2.                  Packaging and despatch specifications

 

Supplies will be despatched to the recipient named on the IMP Despatch Form. The
Monitor must check that the required delivery date specified on the form takes
into account the range of acceptable delivery dates.

 

95

--------------------------------------------------------------------------------

 

The packaging used for the shipment must be clearly and distinctly labelled with
warnings and handling instructions, according to the requirements detailed in
the approved Technical Specification document for this clinical study.

 

Each package will include a Shipment Note and Acknowledgement of Receipt
(GCP026-B) partly completed by the despatch office, CofA and/or Pack Batch
Release Certificate, if required. The IMP must be dispatched as per the
Technical Specification document.

 

2.1.3.                  Despatch confirmation

 

The CTSU or Interim Storage Facility must complete the despatch details at the
bottom of the IMP Despatch Form and send it to the requestor and recipient to
confirm despatch and the expected date of arrival. If applicable, the requestor
should specify in the comments section of the IMP Despatch Form whether other
people/entities have to be notified of the IMP despatch. The completed IMP
Despatch Form and associated documentation is filed in the TMF.

 

Once the IMP has been delivered, the recipient at the investigational site or
Interim Storage Facility must complete the relevant sections of the Shipment
Note and Acknowledgement of Receipt, with date and condition of IMP on arrival
and forward it to the CTSU/Interim Storage Facility. The CTSU/Interim Storage
Facility will transmit the Shipment Note and Acknowledgement of Receipt to the
CSC for filing in the TMF. If the Shipment Note and Acknowledgement of Receipt
are not returned from the recipient, the CTSU/Interim Storage Facility must
either contact the intended recipient or inform the monitor to ensure delivery
has occurred and to request the Shipment Note and Acknowledgement of Receipt.

 

2.2.                            IMP accountability

 

All IMP accountability checks at site must be documented on the IMP
Accountability Log (GCP026-C) and in the monitoring report (R&D SOPs GCP030 and
GCP089). All IMP accountability at the Interim Storage Facility must be
documented, and copies filed in the TMF.

 

2.3.                            IMP Storage / Shipment Incidence

 

Any deviations/problems in either storage or shipping conditions must be
notified to the CSC via the IMP Incident Form (GCP026-F) who should then report
details of the incident to the CTSU. The Quality Assurance of the Pharmaceutical
Development Dpt. will decide whether the affected IMPs can still be authorised
for use. The decision must be documented and filed in the TMF.

 

2.4.                            Expired IMP and relabelling procedures

 

If IMP is due to expire within the next three months, the CSC or designee must
liaise with the CTSU, to assess if the expiry date of the IMPs can be extended
or if they must be replaced. Depending on the outcome, the CTSU is required to
organise replacement supplies or relabelling in case of expiry date extension.

 

96

--------------------------------------------------------------------------------

 

When an extension of expiry date has been agreed and has been documented by the
CTSU, the CSC or designee has to request additional labels from the CTSU. The
CSC or designee confirms with the CTSU the batch number, box/pack numbers,
centre numbers and quantity of labels required.

 

The CTSU provides the CSC or designee with documentation confirming the expiry
date extension and additional labels. The additional labels must be affixed to
the IMP and should state the new expiry date and repeat the batch number. The
additional labels may be superimposed on the old expiry date, but not on the
original batch number.

 

The relabelling should be performed at an appropriately authorised manufacturing
site. If agreed by the CTSU and the CSC, this may be performed at the
investigational site by or under the supervision of the clinical trial site
pharmacist, or designee in accordance with national regulations. Where this is
not possible, it may be performed by the clinical trial monitor(s). The
operation should be performed in accordance with GMP principles, and should be
checked by a second person. This operation must be documented on the IMP
Relabelling Form (GCP026-E). This form should be duly signed and dated by the
person performing the operation and the second person checking this activity, on
the day of completion and filed in the batch records at the CTSU and a copy
filed in the TMF.

 

2.5.                            Returned investigational product

 

When used or unused IMPs are being retrieved from the investigational site, an
IMP Return/Destruction Form must be completed (GCP026-D), and approved (signed
and dated) by both a representative at the investigational site and the monitor
before despatching the IMPs. The original must be sent with the returned IMPs, a
copy must be sent to the CSC for filing in the TMF and a copy must remain at
site.

 

Used and unused IMPs can either be destroyed on the investigational site or
returned to the CTSU or Interim Storage Facility as defined in the protocol.
Used or unused IMPs returned from investigational sites must be stored at either
the Interim Storage Facility or at the original CTSU with labels on the
containers to describe the contents. This storage must be maintained until IMP
destruction has been agreed between the CSC and storage facility (refer to
section 2.6).

 

If IMPs cannot be returned, the monitor should instruct the site that supplies
must not be destroyed until the monitor has performed an IMP accountability
check and has ensured the accountability is adequate.

 

2.6.                            Destruction of an investigational product

 

The IMP can be destroyed during and after the clinical trial, either at the
investigational site, the Interim Storage Facility or at the CTSU facility, only
upon formal CSC or designee’s request. The CSC is responsible for informing the
CTSU or local Interim Storage Facility (as appropriate) when destruction of an
IMP is requested through the IMP Return/Destruction Form (GCP026-D).

 

97

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The delivered, used and recovered quantities of IMP should be recorded,
reconciled and verified by the monitor for each trial site and each trial
period. Destruction of unused IMPs should be carried out for a given trial site
or a given trial period only after any discrepancies have been investigated and
satisfactorily explained and the reconciliation has been accepted.

 

In case of long-lasting clinical studies, it is advisable to proceed with
ongoing destruction of IMP s.

 

Records of IMP destruction (including batch numbers, box/pack numbers if
applicable, method of destruction and quantity destroyed) should be signed and
dated by the relevant person performing the destruction and the approval of a
second person. Records of IMP destruction and corresponding documentation must
be collected by the monitor and filed in the TMF (R&D SOP GCP090).

 

3.                                      CLINICAL SUPPLIES TRACKING WORKFLOW
APPLICATION

 

In case the Clinical Supplies Tracking Workflow (CSTW) application is used for a
clinical study, the procedure described in this SOP will still apply but the
forms GCP026-A and GCP026-B are replaced by their equivalent electronic form
within the CSTW. When filing is required, a paper copy of the electronically
approved form will be accepted.

 

4.                                      CONTINGENCIES

 

None.

 

5.                                      R&D SOP FORMS AND TEMPLATES

 

Title

 

Reference

 

Status

IMP Despatch Form

 

GCP026-A

 

Compulsory

Shipment Note and Acknowledgement of Receipt

 

GCP026-B

 

Example

IMP Accountability Log

 

GCP026-C

 

Example

IMP Return/Destruction Form

 

GCP026-D

 

Compulsory

IMP Relabelling Form

 

GCP026-E

 

Compulsory

IMP Incident Form

 

GCP026-F

 

Compulsory

 

6.                                      BIBLIOGRAPHIC REFERENCES

 

1.                                      EU Clinical Trial Directive 2001 / 20 /
EC

 

2.                                      ICH Harmonised Tripartite Guidelines: E6
Guideline for Good Clinical Practice

 

3.                                      Ipsen Group R&D SOP GCP030 Management of
Study Manuals

 

98

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4.                                      Ipsen Group R&D SOP GCP089 Monitoring of
Clinical Trial Sites

 

5.                                      Ipsen Group R&D SOP GCP090 Close-out of
Clinical Trial Sites

 

99

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APPENDIX E — IPSEN INDs AND OTHER APPLICATIONS FOR REGULATORY APPROVAL

 

US INDs —None

 

Other EU CTAs — No EU CTAs.

 

A deposition (notification) for the phase 1 study conducted in 2004 by Ipsen was
submitted in Germany January 23 2004 (see attached). The registration number
received from the BfArM acknowledging receipt of this deposition was 4021410
(see attached original and English translation).

 

Subsequent correspondence February 26 2004 (see attached) from MDS Pharma
Services to the BfArM notified the Authority of BIM44058 Toxicology and Safety
Pharmacology studies completed and sponsored by Ipsen

 

Regulatory (market) approvals - None

 

100

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[g17732li19i001.jpg]

 

[ILLEGIBLE]

 

 

 

 

Postanschrift:

 

EINGEGANGEN

Kurt-Georg-Kiesinger-Allee 3

MDS Pharma Services

 

D-53175 Bonn

z.Hd. Herrn Steffen Hoppe

26. Jan. 2004

Telefon: (0228) 207 - 30

Arnikastr. 4

 

Telefax: (0228) 207 - 5207

 

 

IVBB: 01888 - 307 -

85635 Hohenkirchen

 

e-mail: poststelle@bfarm.de

 

Ihre Zeichen und Nachricht vom

Gesch.Z.: [ILLEGIBLE]

Telefon: (0228) 207-

Bonn

 

 

7140-00-37/Z 172.10/12

5845

23.01.2004

 

Eingangsbestätigung

 

Klinische Prūfung § 40 Abs. 1 Nr. 6 AMG

 

Ihre Unterlagen vom 15.01.2004 sind am 19.01.2004 bei uns eingegangen:

 

Voriagenummer:

4021410

 

 

Name der Studie:

2-52-52127-001

 

Wir bitten, bei weiteren Einreichungen zu diesem prüfplan sowie bei allen
Anzeigen von Verdachtsfällen auf schwerwiegende unerwünschte
Arzneimittelwirkungen gemäß § 29 (1) AMG stets die Vorlagenummer anzugèben.

 

Mit freundlichen Grüssen

 

Im Auftrag

[ILLEGIBLE]

 

[g17732li19i002.jpg]

 

101

--------------------------------------------------------------------------------

 

[Illegible]

 

 

 

 

Postanschrift:

MDS Pharma Services

EINGEGANCEN

Kurt-Georg-Kiesinger-Allee 3

Germany GmbH

 

D-53175 Bonn

Herrn Steffen Hoppe

02. Feb. 2004

Telefon:

(01888) - 307 - 0

Arnikastraße 4

 

 

(0228) 207 - 30

 

 

Telefax:

(01888) - 307 - 5207

 

 

 

(0228) 207 - 5207

85635 Höhenkirchen/Siegertsbrunn

Nachrichtlich

e-mail:

poststelle@bfarm.de

 

Landesbehörden Bayern / Hamburg

 

vorab per Fax: 08102/4007

Ihre Zelchen and Nachricht vorn

Gesch.Z: [Illegible]

 

Telefon: (01888) 307-

Bonn

15.01.2004

B VP2. A-7140-00-37/

 

4320

29. JAN. 2004

 

4021410

 

 

 

 

Betr.:

Klinische Prüfung §40 Abs. 1 Satz 1 Nr. 6 AMG.

 

Eingangsdatum BfArm

:

19. Januar 2004

 

Vorlage der Unterlagen

:

vollständig

 

Votum der zuständigen EK

:

zustimmend mit Auflagen, Auflagen wurden erfüllt

 

Vorlagenummer

:

4021410

 

Klinische Prüfung                      :      A phase I single-centre study in
two parts assessing the safety, pharmacokinetics, pharmacodynamics and absolute
bioavailability of BIM44058, a hPTHrP (1-34) analogue, administered as single
doses to healthy elderly volunteers of both genders: Part A, randomised,
double-blind, dose-escalating, parallel groups, placebo-controlled design;
Part B, randomised, open-label, two-period, cross-over design (Protokoll
einschl. Amendment 1 v. 05.12.2003)

 

Code

:

2-52-52127-001

 

Leiter der Klinischen Prüfung gemäß § 40 Abs. 1 Satz 1 Nr.4 und 7 AMG: Werner
Weber, Hamburg

 

Vorlage Unterlagen zur pharmakologisch-toxikologischen Prüfung: Investigator’s
Brochure für BIM44058, Version 2 (23.10.2003) wurde vorgelegt

 

Sehr geehrte Damen und Herren,

 

es wird bestätigt, dass zur o.g. klinischen Prüfung Ihre Unterlagen zum Zweck
der Vorlage gemäß § 40 Abs. 1 Satz 1 Nr. 6 AMG beim BfArM eingegangen sind. Die
Unterlagen sind nach formaler Prüfung und unter Berūcksichtigung des vorgelegten
Prüfplanes Vollständig. Es liegt ein zustimmendes Votum der für den Leiter der
Klinischen Prüfung Zuständigen Ethik-Kommission vor. Mit Eingang der bisherigen
Unterlagen beim BfArM wurden die Voraussetzungen für den Beginn einer Klinischen
Prüfung gemäß § 40 Abs. 1 Satz 1 Nr. 6 und Satz 2 AMG erfüllt.

 

Die Unterlagen werden unter der o.g. Vorlagenummer verwahrt. Bitte geben Sie die
Vorlage-Nr. und den Code des Prüfplans stets im weiteren Schriftverkehr zur o.g.
klinischen Prüfung an und verwenden Sie als Postanschrift:

 

Bundesinstitut für Arzneimittel und Medizinprodukte, Fachregistratur Z 172.22,

Kurt-Georg-Kiesinger-Allee 3, D-53175 Bonn,

Tel. +49 (0)228-207-5854, Fax +49 (0)228-207-5207

 

Hinweis: Die nach § 2 Abs. 9 der verordnung zur Ǎnderung der Kostenverordnung
für die Zulassung von Arzneimitteln durch das Bundesinstitut für Arzneimittel
und Medizinprodukte und das Bundesinstitut für gesundheitlichen
Verbraucherschutz und Veterinärmedizin vom 19. Mārz 2002 (BGBI. 2002 Teil I vom
22.

 

102

--------------------------------------------------------------------------------

 

März 2002) fūr die Bearbeitung von Unterlagen nach § 40 Abs. 1 des AMG zu
erhebenden Gebühren werden Ihnen mit einem gesonderten Kostenbescheld von der
Kostenstelle des BfArM mitgeteilt.

 

Mit freundlichen Grūßen

im Auftrag

 

[ILLEGIBLE]

 

 

Dr. med. F. Hackenberger

 

103

--------------------------------------------------------------------------------

 

Bf ArM, Bonn

to MDS Pharma Services

 

Copy to

Land authorities of Bavaria / Hamburg

 

29 January 2004

 

Ref.:

Clinical study § 40 section 1 sentence 1 no. 6 AMG

 

Date of receipt by BfArM

:

19 January 2004

 

Presentation of documents

:

complete

 

Vote by the responsible ethics committee

:

approved with conditions, conditions have been fulfilled

 

Submission number

:

4021410

 

Clinical study

:

A phase 1 single-centre study in two parts assessing the safety,

 

pharmacokinetics, pharmacodynamics and absolute bioavailablity of BIM44058, a
hPTHrP(1-34) analogue, administered as single doses to healthy elderly
volunteers of both genders: Part A, randomised, double-blind, does-escalating,
parallel groups, placcbo-controlled design; Part B, randomised, open-label,
two-period, cross-over design (Protocol including amendment 1 of 05.12.2003)

 

Code

:

2-52-52127-001

 

Director of the clinical study pursuant to § 40 section 1 sentence no. 4 and 7
AMG:  Werner Weber, Hamburg

 

Documents submitted concerning pharmacological-toxi cological studies: 
Investigator’s brochure for BIM44058, version 2 (23.10.2003) has been presented

 

Dear Sir or Madam,

 

herewith we confirm that the BfArM has received the documents you submitted
pursuant to § 40 section 1 sentence 1 no. 6 AMG for the clinical study mentioned
above. After a formal review and taking into account the protocol submitted the
documents are complete. The ethics committee responsible for the director of the
clinical study has voted to approve the study. With the receipt of the said
document by the BfArM the conditions pursuant to § 40 section 1 sentence 1 no. 6
and sentence 2 AMG for initiating a clinical study have been met.

 

The documents will be filed under the submission number mentioned above. Please
always quote the submission number and the code of the protocol in any further
correspondence on the clinical study mentioned above and use the following
postal address:

 

Bundesinstitut für Arzneimittel und Medizinprodukte, Fachregistratur Z 172.22,

Kurt-Georg-Kiesinger-Allee 3, D-53175 Bonn,

Phone +49(0)228-207-5845, Fax +49 (0)228-207-5207

 

104

--------------------------------------------------------------------------------

 

Note: You will be informed by the cost centre of the BfArM about the fee to be
paid according to § 2 section 9 of the Official Regulation Concerning the Change
of the Fee Schedule for the Licensing of Drugs by the Federal Institute for
Drugs and Medical Devices and the Federal Institute for Consumer Health Care and
Veterinary Medicine of 19 March 2002 (BGBI. 2002 part I of 22 March 2002) for
reviewing documents pursuant to § 40 para 1 AMG.

 

Yours sincerely

by order

 

 

signature

Dr. med. F. Hackenberger

 

105

--------------------------------------------------------------------------------

 

 

Arnikastrasse 4

 

D-85635 Höhenkirchen/Siegertsbrunn, Gern

 

www.mdsps.com

 

email: mds.munich@mdsps.com

 

Tel: +49 81 02 808 0 Fax : +49 8102 400 7

 

[g17732li27i001.jpg]

 

Bundesinstitut für

 

Arzneimittel und Medizinprodukte

26.02.2004

Fachregistratur Z 172.10

 

Kurt-Georg-Kissinger-Allee 3

 

 

53175 Bonn

 

MDS Studie Nr. AA15328

Vorlage-Nummer: 402 1410

Titel:

A Phase I single-centre study in two parts assessing the safety,
pharmacokinetics, pharmacodynamics and absolute bioavailability of BIM44058, a
hPTHrP(1-34) analogue, administered as single doses to healthy elderly
volunteers of both genders: Part A, randomised, double-blind, dose-escalating,
parallel groups, placebo-controlled design; Part B, randomised, open-label,
two-period, cross-over design

 

Sehr geehrte Damen und Herren,

 

der Sponsor der Studie hats uns gebeten, Safety Pharmacology Reports und
Toxicology Reports über die Studienmedikation BIM44058 an Sie weiterzuleiten.

 

Nachfolgend sende ich Ihnen eine Aufstellung über die Reports sowie jeweils ein
Exemplar der Reports zu.

 

Mit freundlichen Grüβen

 

 

[ILLEGIBLE]

 

Steffen Hoppe

Clinical Study Manager

 

 

MDS Pharma Services Germany GmbH

 

[ILLEGIBLE]:

 

[ILLEGIBLE] Hamburg HRB 28 004

 

[ILLEGIBLE] Bank 24

 

[ILLEGIBLE]

 

[ILLEGIBLE]

 

106

--------------------------------------------------------------------------------

 

MDS to BfArM

 

26.02.2004

 

MDS Study no. AA15328

 

Dear Sir or Madam,

 

The sponsor of the study has asked us to forward Safety Pharmacology Reports and
Toxicology Reports concerning study medication BIM44058 to you.

 

Enclosed I will send you a list of the reports and one copy each of the reports.

 

107

--------------------------------------------------------------------------------

 

[g17732li31i001.jpg]

 

BIM44058 - Safety Pharmacology reports

 

[ILLEGIBLE]

 

[ILLEGIBLE]

 

 

 

D01.377/1

 

Safety pharmacology study of neurobehavioral effects (irwin test) after
subcutaneous or intravenous administration in the rat

 

 

 

D01.378/1

 

Safety pharmacology study of effects on sodium barbital sleeping time after
subcutaneous administration in the rat

 

 

 

D01.379/1

 

Safety pharmacology study of effects on Electroconvulsive Shock Treshold after
subcutaneous administration in the rat

 

 

 

D01.380/1

 

Safety pharmacology study effects on Pentylenetetrazole Seizure after
subcutaneous administration in the rat

 

 

 

D01.381/1

 

Safety pharmacology study of hemodynamic effects after intravenous
administration in the anesthetized dog

 

 

 

D01.382/1

 

Safety pharmacology study of assessment of cardiovascular risk after
subcutaneous administration in the conscious dog monitored by telemetry

 

 

 

D01.383/3

 

Evaluation of arrhythmogenic risk in an in vitro model (Purkinje fiber) in the
rabbit

 

 

 

D01.384/1

 

in vitro effect on HERG recorded in Human Embryonic Kidney (HEK) 293 Cells

 

 

 

D01.385/1

 

Safety pharmacology study of effects on respiration after subcutaneous
administration in the conscious rat

 

 

 

D01.386/1

 

Safety pharmacology study of effects on gastrointestinal transit after
subcutaneous administration in the rat

 

 

 

D01.387/1

 

Safety pharmacology study of ulcerogenic effects after subcutaneous
administration in the rat

 

 

 

D01.388/1

 

Safety pharmacology study of effects on Gastric Acid Secretion after
subcutaneous administration in the rat

 

 

 

D01.389/1

 

Safety pharmacology study of effects on diuresis and urinary excretion after
subcutaneous administration in the rat

 

 

 

D01.390/1

 

Safety pharmacology study of effects on bleeding time after subcutaneous
administration in the anesthetized rat

 

 

 

D02.031/1

 

Safety pharmacology study of effects on Activity Meter after subcutaneous or
intravenous administration in the rat

 

108

--------------------------------------------------------------------------------

 

BIM44058 - Toxicology reports

 

[ILLEGIBLE]

 

[ILLEGIBLE]

 

 

 

17458 TAS

 

BIM-44058 Acute intravenous toxicity in mice

 

 

 

17459 TAS

 

BIM-44058 Acute subcutaneous toxicity in mice

 

 

 

18431 TAR

 

BIM-44058 Acute intravenous toxicity in rats

 

 

 

18432 TAR

 

BIM-44058 Acute subcutaneous toxicity in rats

 

 

 

434/89

 

BIM-44058 Reverse mutation in four histidine-requiring strains of salmonella
typhimurium and one tryptophan-requiring strain of Escherichia coli

 

 

 

434/90

 

BIM-44048 Induction of chromosome aberrations in cultured human peripheral blood
lymphocytes

 

 

 

18455 TSP

 

BIM-44058 Four week toxicity study by subcutaneous administration to cynomolgus
monkeys

 

 

 

19022 TCP

 

BIM-44058 13-week toxicity study by subcutaneous injection in cynomolgus monkeys
followed by a ‘-week treatement free period

 

109

--------------------------------------------------------------------------------

 

CONFIDENTIAL— Execution Copy

 

LICENSE AGREEMENT AMENDMENT NO. 1

 

This Amendment No.°1 (the “Amendment No. 1”) is entered into on September 12,
2007 (the “Amendment Date”) by and between Radius Health Inc., a Delaware
Corporation, formerly known as Nuvios, Inc. with its principal office at 300
Technology Square — 5th floor, Cambridge, MA 02139, United States of America, on
behalf of itself and its Affiliates (“Radius”), and SCRAS S.A.S., a French
corporation, with its principal office at 42 rue du Docteur Blanche, 75016
Paris, France on behalf of itself and its Affiliates (“Ipsen”).

 

RECITALS

 

1.                          Ipsen and Radius (the “Parties”) entered into the
certain license agreement as of September 27, 2005 (the “Agreement”).

 

2.                          The Parties wish to enter into this Amendment No. 1
to amend certain provisions of the Agreement in connection with the grant by
Radius to Novartis International Pharmaceutical Ltd. (“Novartis”) of certain
option rights to take a sublicense from Radius.

 

NOW THEREFORE, in consideration of the mutual covenants and promises contained
in this Amendment No. 1, the Parties agree as follows:

 

ARTICLE 1  —  CONDITIONS PRECEDENT

 

This Amendment No. 1 shall enter into force upon the completion of the following
cumulative conditions precedent:

 

1.1          Radius and Novartis enter into an option agreement whereby Novartis
will have an option to license certain intellectual property rights from Radius
under terms and conditions to be agreed (the “Option Agreement”); and

 

1.2          Radius and Novartis agree on the terms of a fully-fledged license
agreement which will be attached to the Option Agreement (the “Radius-Novartis
Agreement”) as set forth in the Option Agreement; and

 

1.3          Novartis exercises its option under the Option Agreement within six
(6) months after Novartis has received the Study Report (as defined in the
Option Agreement) and Radius and Novartis execute the Radius-Novartis Agreement.

 

In the event the condition precedent in paragraph 1.1 is not completed by 31
December 2007, or the condition precedent in paragraph 1.2 is not completed by
31 March 2008 or the condition precedent in paragraph 1.3 is not completed as
set forth above, this Amendment No. 1 shall be deemed null and void at the later
date relating to the completion of these three conditions precedent as set forth
above.

 

ARTICLE 2  —  AMENDMENTS TO CERTAIN PROVISIONS OF THE AGREEMENT

 

2.1          Third Party Payments. Section 4.3 of the Agreement is amended to
read in full as follows:

 

--------------------------------------------------------------------------------

 

“4.3 Adjustments Related to Third Party Payments. If, in connection with any
Licensed Compound or Licensed Product, Nuvios is obligated to remit payments to
third parties in relation to intellectual property rights owned by such third
parties including when Nuvios is obliged to license in formulation technology
from third party for use with the Licensed Product and/or as determined pursuant
to Article 11.7 of this Agreement Nuvios shall be permitted to offset against
payments due to Ipsen under this Agreement up to fifty percent (50%) of any
payments due to such third parties during any calendar year, provided however
that this offset does not result in a reduction of more than 50% of the royalty
payments that would otherwise have been due to Ipsen in any calendar year.

 

If (i) in connection with any Licensed Compound or Licensed Product, Novartis is
obligated to remit payment to third parties in relation to intellectual property
rights owned by such third parties including when Novartis is obliged to license
in formulation technology from third party for use with the Licensed Product
and/or as determined pursuant to Article 11.7 of this Agreement (the “NVS Third
Party Payments”) and (ii) pursuant to the Radius-Novartis Agreement, Novartis is
entitled to deduct part or all of NVS Third Party Payments from the payments due
by Novartis to Nuvios (the “Novartis Deduction”), Nuvios shall be permitted to
offset against royalty payments due to Ipsen under this Agreement up to fifty
percent (50%) of the Novartis Deduction during any calendar year, provided
however that (a) this offset does not result in a reduction of more than 50% of
the royalty payments that would otherwise have been due to Ipsen in any calendar
year and (b) this offset is not superior to 25% of the NVS Third Party Payments.

 

In no event shall the provisions of the two (2) above paragraphs be applied
cumulatively and in no event shall any offset(s) pursuant to this Section 4.3
result in a reduction of more than 50% of the royalty payments that would
otherwise have been due to Ipsen in any calendar year.”

 

2.2          Royalty Term. Section 1.59 of the Agreement is amended to read in
full as follows:

 

“1.59 Royalty Term shall mean for each Licensed Product and each country of the
Territory, the later of (a) expiration of the last to expire Licensed Product
Claim in such country with respect to such Licensed Product and (b) ten (10)
years from the First Commercial Sale in such country of such Licensed Product.
Notwithstanding anything express or implied in the foregoing provisions of this
definition, if, with respect to any Licensed Product in any country of the
Territory, on the date that is ten (10) years from the First Commercial Sale in
such country of such Licensed Product, there is no Valid Claim of an issued
patent within the Ipsen Patent Rights or the Joint Patent Rights that Covers
such Licensed Product in such country, then the Royalty Term for such Licensed
Product in such country shall automatically expire and terminate on such date.”

 

2.3          Payment of Share of Sublicense. Section 3.3 is revised to include
the following text in the header to the right hand column of the table:

 

“Share payable within seven (7) days following receipt of payments from Novartis
under the Radius-Novartis Agreement. Nuvios shall issue the invoice to Novartis
promptly upon the occurrence of the event triggering the payments and shall
inform Ipsen promptly upon receipt of the corresponding payments from Novartis.
In case of a failure of Novartis to pay the due sums to Nuvios within the delay
as set forth in the Radius-Novartis Agreement, Nuvios shall pay the

 

2

--------------------------------------------------------------------------------

 

Share due to Ipsen within seven (7) days upon expiry of the delay granted to
Novartis for the payment due to Nuvios as set forth in the Radius-Novartis
Agreement.”

 

2.4          Treatment of Sublicensee on Termination. A new Section 15.7 is
added to the Agreement to read in full as follows:

 

“15.7 Sublicenses. Notwithstanding any provision of this Agreement to the
contrary, in the event this Agreement is terminated by Ipsen pursuant to
Section 15.2 and in the event such termination does not result from a material
breach of Nuvios’ obligations which results from the performance or the lack of
performance by Novartis of its obligations under the Radius-Novartis Agreement,
Radius-Novartis Agreement shall be novated from Nuvios to Ipsen and shall become
a direct license between Ipsen and Novartis under the following conditions:
(i) Novartis agrees to such novation in a writing pursuant to which it
acknowledges each of the statements in the following clauses (ii)-(iv),
(ii) Ipsen shall have all Nuvios’ rights as provided in the Radius-Novartis
Agreement; (iii) Ipsen shall not be bound by obligations towards Novartis in
excess of its obligations as set forth in this Agreement including in particular
but without limitation Ipsen shall not assume, and shall not be responsible to
Novartis for any representations and warranties other than the ones stated in
this Agreement, and (iv) Novartis shall remain bound by the terms and conditions
of the Radius-Novartis Agreement as if the Radius-Novartis Agreement had been
entered into by Ipsen and Novartis.”

 

2.5          Payments and Financial Reporting.

 

(a) Section 1.39 of the Agreement is amended to read in full as follows:

 

“Net Sales” means the net sales made by Nuvios, Novartis and any of their
Affiliates or sublicensees (the “Selling Party”) of the Licensed Product sold to
Third Parties other than sublicensees in bona fide, arm’s-length transactions,
as determined in accordance with the Selling Party’s usual and customary
accounting methods, which are in accordance with its Accounting Standards as
consistently applied by such Selling Party: (a) in the case of any sale or other
disposal of a Licensed Product between or among Novartis and its Affiliates or
sublicensees, for resale, Net Sales shall be calculated only on the value
charged or invoiced on the first arm’s length sale thereafter to a Third Party;
(b) in the case of any sale which is not invoiced or is delivered before
invoice, Net Sales shall be calculated at the time of shipment or when the
Licensed Product is paid for, if paid for before shipment or invoice; (c) in the
case of any sale or other disposal for value, such as barter or counter-trade,
of any Licensed Product, or part thereof other than in an arm’s-length
transaction exclusively for money, Net Sales shall be calculated on the value of
non-cash consideration received or the fair market price (if higher) of the
Licensed Product in the country of sale or disposal; and (d) in the event the
Licensed Product is sold as a Bundled Licensed Product, the Net Sales of the
Licensed Product, for the purposes of determining royalty payments, shall be
determined by multiplying the Net Sales of the Bundled Licensed Product by the
fraction, A/(A+B) where A is the weighted (by sales volume) average sale price
in a particular country of the Licensed Product when sold separately in finished
form and B is the weighted average sale price in that country of the other
Licensed Product(s) sold separately in finished form. In the event that such
average sale price cannot be determined for both the Licensed Product and the
other Licensed Product(s) in Bundled Licensed Product, Net Sales for purposes of
determining royalty payments shall be agreed by the Parties based on the
relative value contributed by each component, such agreement not to be
unreasonably withheld. For the avoidance of doubt, sales between Novartis, its
Affiliates, sublicensees and designees shall not be considered Net Sales (unless
such Person is the end user of the Licensed Product), which shall be calculated
on Net Sales of Novartis, its Affiliates, sublicensees and designees to
independent third party customers.”

 

3

--------------------------------------------------------------------------------

 

(b) Section 5.4 of the Agreement is revised to include the following text at the
end of Section 5.4:

 

“Ipsen will pay any and all taxes levied on account of any payments made to it
under this Agreement. If any taxes are required to be withheld by Nuvios, Nuvios
will: (a) deduct such taxes from the payment made to Ipsen; (b) timely pay the
taxes to the proper taxing authority; (c) promptly send proof of payment to
Ipsen; and (d) promptly and reasonably assist Ipsen in its efforts to obtain a
credit for such tax payment. Each Party agrees to reasonably assist the other
Party in lawfully claiming exemptions from and/or minimizing such deductions or
withholdings under double taxation laws or similar circumstances.”

 

(c) The first sentence of Section 5.2 of the Agreement is revised to read in
full as follows:

 

“5.2 Payments and Reporting. After the First Commercial Sale of Licensed Product
in the Territory, Nuvios shall calculate royalties quarterly at the end of each
Accounting Period (i.e., March 31, June 30, September 30 and December 31) and
shall pay royalties on Net Sales quarterly within sixty (60) days after the end
of each Accounting Period. Nuvios may delay the payment of royalties on Net
Sales until a maximum of ninety (90) days after the end of each Accounting
Period provided that Nuvios shall pay to Ipsen interest on such late payment
between the 60th and the effective date of payment of the royalties, at the rate
of EURIBOR 1 month plus 0.50% on sales in EURO and LIBOR 1 month USD plus 0.5%
on sales in USD.”

 

2.6          No other changes. Except to the extent expressly amended by this
Amendment No. 1, all of the terms, provisions and conditions of the Agreement
remain unchanged and in full force and effect. The term “Agreement”, as used in
the Agreement, shall henceforth be deemed to be a reference to the Agreement as
amended by this Amendment No. 1.

 

ARTICLE 3  —  MISCELLANEOUS

 

3.1          Duration. This Amendment No.1 shall enter into force as set forth
in Article 1 and shall remain in full force and effect until the Agreement is
terminated, provided however that Articles 2.4 and 3.3 of this Amendment No. 1
shall survive any expiry or termination of the Agreement.

 

3.2          Definitions. Capitalized terms used in this Amendment No. 1 and not
defined herein are used with the meanings ascribed to them in the Agreement.

 

3.3          Execution Copy. This Amendment No. 1 may be executed in
counterparts, each of which will be deemed an original with all such
counterparts together constituting one instrument.

 

IN WITNESS WHEREOF, the Parties hereto have caused this Amendment No. 1 to be
executed by their respective duly authorized officers, and have duly delivered
and executed this Amendment No. 1 as of the Amendment Date.

 

RADIUS HEALTH INC.

SCRAS S.A.S

 

 

 

 

 

By:

/s/ C. R. Lyttle

 

By:

/s/ Claire Giraut

Name:

C. Richard Lyttle

 

Name:

Claire Giraut

Title:

President & CEO

 

Title:

Director General

 

4

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Execution Copy

 

LICENSE AGREEMENT AMENDMENT NO. 2

 

Radius Health Inc., a Delaware Corporation, formerly known as Nuvios, Inc.
(“Radius”), and Ipsen Pharma SAS, a French corporation formerly known as SCRAS
S.A.S., on behalf of itself and its Affiliates (Ipsen) (the “Parties”) entered
into the certain License Agreement as of September 27, 2005 (“Effective Date”),
as amended by that certain License Agreement Amendment No. effective as of
September 12, 2007 (as amended, the “Agreement”).  The Parties wish to enter
into this License Agreement Amendment No. 2 (“Amendment No. 2”) effective as of
May 11, 2011 (“Amendment Date”) to amend certain provisions of the Agreement.

 

NOW THEREFORE, in consideration of the mutual covenants and promises contained
in this Amendment No. 2, the Parties agree as follows:

 

1.  Phase III Clinical Trial Milestone Payment.  The provision of the fifth
table cell of Section 3.1 of the Agreement concerning payment by Radius to Ipsen
of EUR 1 million in connection with initiation of a first Phase III study is
revised to read in full as follows:

 

Events

 

Amount

(a)  Within 15 days of the initiation of the first Phase III study ( as such
period may be extended with interest in accordance with Section 2 below), Nuvios
shall pay Ipsen EUR 1 million. Ipsen shall in lieu of payment of such amount in
cash accept payment in the form of the of having Nuvios issue shares of Nuvios
Series A-1 Preferred Stock, provided that (i) the issuance of the Series A-1
Preferred Stock to Ipsen shall be made pursuant to a Series A-1 Convertible
Preferred Stock Issuance Agreement in the form of Attachment 1 to this Amendment
No. 2, executed concurrently herewith (“Series A-1 SPA”); and (ii) Ipsen shall
not have terminated such agreement due to the failure of the conditions to be
satisfied prior to June 30, 2011. If Ipsen does terminate the agreement, the
milestone payment shall be immediately due and payable in cash, along with any
interest accrued pursuant to paragraph 2 below.

 

EUR 1 million

 

2.  Payment Mechanics for Phase III Clinical Trial Milestone.  The shares of
Series A-1 Preferred Stock issuable to Ipsen will be issued in connection with
the Stage-1 closing of the Series A-1 SPA. As such financing is not scheduled to
close until after the 15-day period set forth in the fifth table cell of
Section 3.1 of the Agreement, Radius may defer payment pending Closing of the
Series A-1 SPA (or termination of the Series A-1 SPA), and Radius shall pay
Ipsen interest on such milestone payment at the rate specified in Section 5.3 of
the Agreement during the period between the 15th day following the initiation of
the Phase III study and the date that Radius issues the shares of Series A-1
Preferred Stock to Ipsen.  Such interest shall be paid in cash at the time the
shares of Series A-1 Preferred Stock are issued to Ipsen.

 

1

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3.  Other Terms Related to the A-1 Financing.  Radius represents and warrants
that it has provided to Ipsen the agreements containing the terms of other
investors in the Series A-1 financing and that such agreements and schedules
thereto are current and accurate.  Radius also agrees to notify Ipsen should
Radius waive the transfer restrictions of any Series A-1 Preferred stockholder,
and agrees to provide Ipsen with the opportunity to transfer a pro-rata portion
of Ipsen’s Series A-1 Preferred Stock on the same terms.

 

4.  Confidentiality.  Notwithstanding Article 12 of the Agreement, neither Party
shall disclose any Confidential Information, or the terms of the Agreement,
including Amendment No. 1 or this Amendment No. 2 except to the extent required
by a court or other governmental authority (and specifically including necessary
disclosures pursuant to requirements of the Securities Exchange Commission
(“SEC”) or any securities exchange upon which such Party’s securities are
listed), provided that the disclosing Party (a) gives the other Party advance
written notice of the disclosure, (b) uses reasonable efforts to resist
disclosing such information, (c) cooperates with the other Party on request to
obtain a confidential treatment or otherwise limit the disclosure (including the
redaction of information reasonably requested by such other Party), and (d) as
soon as reasonably possible, provides a letter from its counsel confirming that
such information is, in fact, required to be disclosed by such governmental
authority.

 

5.  Change of Radius Notice Address.  Section 18.4 of the Agreement is revised
to replace the current notice address for Nuvios with the following notice
address:

 

“Radius Health, Inc.

201 Broadway, 6th Floor

Cambridge, MA 02139, USA

Attn: President.”

 

6.  Ratification. Except to the extent expressly amended by this Amendment
No. 2, all of the terms, provisions and conditions of the Agreement are hereby
ratified and confirmed and shall remain in full force and effect. The term
“Agreement”, as used in the Agreement, shall henceforth be deemed to be a
reference to the Agreement as amended by this Amendment No. 2.

 

7.  General.

 

(a)  Capitalized terms used in this Amendment No. 2 and not defined herein are
used with the meanings ascribed to them in the Agreement.

 

(b)  This Amendment No. 2 may be executed in counterparts, each of which will be
deemed an original with all such counterparts together constituting one
instrument.

 

(c)  This Amendment No. 2 shall take effect as of the Amendment Date and shall
remain in effect in accordance with the terms and provisions of the Agreement.

 

IN WITNESS WHEREOF, the Parties hereto have caused this Amendment No. 2 to be
executed by their respective duly authorized officers, and have duly delivered
and executed this Amendment No. 2 under seal as of the Amendment Date.

 

RADIUS HEALTH INC.

IPSEN PHARMA SAS

 

 

BY:

/s/ C. Richard Lyttle

 

BY:

/s/ Marc de Garidel

NAME:

/s/ C. Richard Lyttle

 

NAME:

Marc de Garidel

TITLE:

President & CEO

 

TITLE:

Chairman and CEO

 

2

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Execution Copy

 

Attachment 1

 

FORM OF

SERIES A-1 CONVERTIBLE PREFERRED

STOCK ISSUANCE AGREEMENT

 

THIS SERIES A-1 CONVERTIBLE PREFERRED STOCK ISSUANCE AGREEMENT, dated this 11th
day of May, 2011 (“Agreement”) is entered into by and among Radius Health, Inc.,
a Delaware corporation (the “Corporation”), and Ipsen Pharma SAS, a French
corporation formerly known as SCRAS S.A.S. (“Investor”).

 

WHEREAS, the Corporation and the Investor are parties to that certain License
Agreement dated as of September 27, 2005, as amended by that certain License
Agreement Amendment No. 1 effective as of September 12, 2007 and that certain
License Agreement Amendment No. 2 effective as of May 11, 2011 (the “License
Agreement”) and pursuant to Amendment No. 2 have agreed that the Corporation
shall issue shares of Series A-1 Convertible Preferred Stock (as hereinafter
defined) to the Investor in satisfaction of the €1,000,000 milestone due
Investor by the Corporation upon the initiation of the first Phase III study as
provided in the fifth table cell of Section 3.1 of the License Agreement.

 

WHEREAS, the Corporation has entered into a Series A-1 Convertible Preferred
Stock Purchase Agreement dated April 25, 2011 with several other investors
providing for the issuance to such investors of an aggregate US $60,000,000 of
Series A-1 Convertible Preferred Stock (as hereinafter defined), as more
specifically set forth therein (the “April 25 Agreement”).

 

NOW, THEREFORE, in consideration of the mutual covenants and agreements herein
contained, the parties hereto, intending to be legally bound, hereby agree as
follows:

 

SECTION 1.                            Filing of Restated Certificate of
Incorporation.

 

1.1                               Recapitalization.

 

(a)                                 Prior to the Stage I Closing (as defined in
Section 4(a) hereof), the Corporation shall have filed the Fourth Amended and
Restated Certificate of Incorporation of the Corporation, in the form attached
hereto as Exhibit A (the “Restated Certificate”).  Pursuant to the Restated
Certificate, among other things:

 

(i)                                     simultaneously with the effective date
of the filing of the Restated Certificate (the “Split Effective Date”), a
reverse split (the “Reverse Split”) of the Corporation’s outstanding capital
stock shall occur as follows: (A) each share of the Corporation’s Common Stock,
par value $.01 per share (“Common Stock”), issued and outstanding or held as
treasury shares immediately prior to the Split Effective Date shall
automatically without any action on the part of the holder thereof, be
reclassified and changed into 0.06666667 of one share of Common Stock from and
after the Split Effective Date, (B) each share of the Corporation’s Series A
Junior Convertible Preferred Stock, par value $.01 per share (“Series A Stock”),
issued and outstanding or held as treasury shares immediately prior to the Split
Effective Date shall automatically without any action on the part of the holder
thereof, be

 

3

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reclassified and changed into 0.06666667 of one share of Series A Stock from and
after the Split Effective Date, (C) each share of the Corporation’s Series B
Convertible Redeemable Preferred Stock, par value $.01 per share (“Series B
Stock”), issued and outstanding or held as treasury shares immediately prior to
the Split Effective Date shall automatically without any action on the part of
the holder thereof, be reclassified and changed into 0.06666667 of one share of
Series B Stock from and after the Split Effective Date and (D) each share of the
Corporation’s Series C Convertible Redeemable Preferred Stock, par value $.01
per share (“Series C Stock” and together with the Series A Stock and the
Series B Stock, the “Existing Preferred Stock”), issued and outstanding or held
as treasury shares immediately prior to the Split Effective Date shall
automatically without any action on the part of the holder thereof, be
reclassified and changed into 0.06666667 of one share of Series C Stock from and
after the Split Effective Date;

 

(ii)                                  in the event that a current stockholder of
the Corporation does not participate in the financing contemplated hereby at
least at the level of its Pro Rata Share (as defined below), by committing to
purchase and purchasing (or securing an investor who commits to purchase and
purchases) at least at the level of its Pro Rata Share, a percentage of each
series of such holder’s Existing Preferred Stock equal to such holder’s
Applicable Portion (as defined in the Restated Certificate) shall automatically
convert into shares of Common Stock (all such shares of Common Stock being
referred to herein, collectively, as the “Forced Conversion Shares”), at a rate
of 1 share of Common Stock for every 5 shares of Existing Preferred Stock to be
so converted, such automatic conversion (hereinafter, the “Forced Conversion”)
to occur and become effective immediately prior to the consummation of the Stage
I Closing (the “Effective Time”);

 

(iii)                               each share of Series C Stock remaining
outstanding after the Forced Conversion shall, immediately following the Forced
Conversion, automatically be reclassified and converted into one (1) share of
Series A-2 Preferred Stock (as defined in Section 1.2 hereof), and all accrued
dividends on such reclassified share of Series C Stock shall be forfeited;

 

(iv)                              each share of Series B Stock remaining
outstanding after the Forced Conversion shall, immediately following the Forced
Conversion, automatically be reclassified and converted into one (1) share of
Series A-3 Preferred Stock (as defined in Section 1.2 hereof), and all accrued
dividends on such reclassified share of Series B Stock shall be forfeited; and

 

(v)                                 each share of Series A Stock remaining
outstanding after the Forced Conversion shall, immediately following the Forced
Conversion, automatically be reclassified and converted into one (1) share of
Series A-4 Preferred Stock (as defined in Section 1.2 hereof) (the automatic
reclassification and conversion of the Existing Preferred Stock pursuant to the
Restated Certificate into shares of Series A-2 Preferred Stock, Series A-3
Preferred Stock and Series A-4 Preferred Stock, as applicable, as described in
the provisions set forth above, is hereinafter referred to as the “Automatic
Reclassification”). The Reverse Split, the Forced Conversion and the Automatic
Reclassification are hereinafter referred to, collectively, as the
“Recapitalization”.

 

(b)                                 As used in this Agreement, the term “Pro
Rata Share” means, with

 

4

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respect to any holder of Existing Preferred Shares (an “Existing Preferred
Holder”), that amount equal to $35,000,000 multiplied by the quotient obtained
by dividing (A) the number of shares of issued and outstanding Common Stock
owned by such Existing Preferred Holder as of March 31, 2011 (or, in the case of
a holder of Existing Preferred Stock who received all of its shares of Existing
Preferred Stock in a transfer from a former holder of Existing Preferred Stock
occurring after March 31, 2011, the number shares of issued and outstanding
Common Stock owned by such former holder of Existing Preferred Stock as of
March 31, 2011) by (B) the aggregate number of shares of issued and outstanding
Common Stock owned as of such date by all Existing Preferred Holders.  For
purposes of the computation set forth in clauses (i) and (ii) above, all issued
and outstanding securities held by Existing Preferred Holders that are
convertible into or exercisable or exchangeable for shares of Common Stock
(including any issued and issuable shares of Existing Preferred Stock) or for
any such convertible, exercisable or exchangeable securities, shall be treated
as having been so converted, exercised or exchanged at the rate or price at
which such securities are convertible, exercisable or exchangeable for shares of
Common Stock in effect at the time in question, whether or not such securities
are at such time immediately convertible, exercisable or exchangeable.

 

(c)                                  The procedures for implementing the
Recapitalization are more specifically set forth in the Restated Certificate.

 

(d)                                 All stock numbers and prices set forth in
this Agreement give effect to the Reverse Split and no further adjustments are
necessary with respect thereto.

 

1.2                               Rights and Preferences of the Authorized
Stock.  In addition to setting forth the Recapitalization, the Restated
Certificate also sets forth, among other things, the terms, designations,
powers, preferences, and relative, participating, optional, and other special
rights, and the qualifications, limitations and restrictions of the Series A-1
Preferred Stock, Series A-2 Preferred Stock, Series A-3 Preferred Stock,
Series A-4 Preferred Stock, Series A-5 Preferred Stock and Series A-6 Preferred
Stock (as such terms are hereinafter defined).  Pursuant to the Restated
Certificate, the Corporation shall be authorized to issue up to (i) 34,859,964
shares of Common Stock, par value $.01 per share (“Common Stock”), and
(ii) 29,364,436 shares of Preferred Stock (the “Preferred Stock”), 10,000,000 of
which shall have been designated as Series A-1 Convertible Preferred Stock, par
value $.01 per share (“Series A-1 Preferred Stock”), 9,832,133 of which shall
have been designated as Series A-2 Convertible Preferred Stock, par value $.01
per share (“Series A-2 Preferred Stock”), 1,422,300 of which shall have been
designated as Series A-3 Convertible Preferred Stock, par value $.01 per share
(“Series A-3 Preferred Stock”), 40,003 of which shall have been designated as
Series A-4 Convertible Preferred Stock, par value $.01 per share (“Series A-4
Preferred Stock”), 70,000 of which shall have been designated as Series A-5
Convertible Preferred Stock, par value $.01 per share (“Series A-5 Preferred
Stock”), and 8,000,000 of which shall have been designated as Series A-6
Convertible Preferred Stock, par value $.01 per share (“Series A-6 Preferred
Stock”).  The Common Stock and the Preferred Stock shall have the respective
terms as set forth in the Restated Certificate.

 

5

--------------------------------------------------------------------------------

 

SECTION 2.                            Authorization of Issuance and Sale of
Series A-1 Preferred Stock; Reservation of Reserved Common Shares.

 

Subject to the terms and conditions of the April 25 Agreement, the Corporation
has authorized the following:

 

(a)                                 the issuance on the Stage I Closing Date (as
defined in Section 4(a) hereof) of an aggregate of 2,631,845 shares of
Series A-1 Preferred Stock (subject to adjustment to reflect stock splits, stock
dividends, stock combinations, recapitalizations and like occurrences other than
the Reverse Split) (such shares of Series A-1 Preferred Stock being sometimes
hereinafter referred to as the “Stage I Preferred Shares”), and the reservation
of an equal number of shares of Common Stock for issuance upon conversion of the
Stage I Preferred Shares (such reserved Common Stock being sometimes hereinafter
collectively referred to as the “Stage I Reserved Common Shares”).

 

(b)                                 the issuance on the Stage II Closing Date
(as defined in the April 25 Agreement) of an aggregate of 2,631,845 shares of
Series A-1 Preferred Stock (subject to adjustment to reflect stock splits, stock
dividends, stock combinations, recapitalizations and like occurrences other than
the Reverse Split) (such shares of Series A-1 Preferred Stock being sometimes
hereinafter referred to as the “Stage II Preferred Shares”), and the reservation
of an equal number of shares of Common Stock for issuance upon conversion of the
Stage II Preferred Shares (such reserved Common Stock being sometimes
hereinafter collectively referred to as the “Stage II Reserved Common Shares”).

 

(c)                                  the issuance on the Stage III Closing Date
(as defined in the April 25 Agreement) of an aggregate of 2,631,845 shares of
Series A-1 Preferred Stock (subject to adjustment to reflect stock splits, stock
dividends, stock combinations, recapitalizations and like occurrences other than
the Reverse Split) (such shares of Series A-1 Preferred Stock being sometimes
hereinafter referred to as the “Stage III Preferred Shares”), and the
reservation of an equal number of shares of Common Stock for issuance upon
conversion of the Stage III Preferred Shares (such reserved Common Stock being
sometimes hereinafter collectively referred to as the “Stage III Reserved Common
Shares” and together with the Stage I Reserved Common Shares and the Stage II
Reserved Common Shares, the “Reserved Common Shares”).

 

SECTION 3.                            Issuance of Series A-1 Preferred Stock.

 

3.1                               Agreement to Issue the Series A-1 Preferred
Stock. Subject to the terms and conditions hereof, the Corporation is selling to
the Investor and the Investor is purchasing from the Corporation the number of
shares of Series A-1 Preferred Stock set forth next to such Investor’s name of
Schedule 1 hereto under the caption “Stage 1 Preferred Shares” for the
consideration set forth in Section 3.3.

 

3.2                               Delivery of Series A-1 Preferred Stock. At the
Closing (as defined in Section 4), the Corporation shall deliver to the Investor
a certificate, registered in the name of the Investor, representing that number
of shares of Series A-1 Preferred Stock equal to the quotient (rounded up to the
nearest whole number) obtained by dividing (x) the U.S. Dollar equivalent
(determined in accordance with the provisions of the next sentence) of
€1,000,000 by (y) US$8.142 per share.  The Corporation shall determine the U.S.
Dollar equivalent of such €1,000,000 using the

 

6

--------------------------------------------------------------------------------

 

exchange rate for buying U.S. Dollars with EUROS set forth in The Wall Street
Journal (Online Edition) Market Data Center at
http://online.wsj.com/mdc/public/page/marketsdata.html on the Business Day that
is two (2) Business Days preceding the date of the Closing.  Delivery of
certificate representing Series A-1 Preferred Stock to the Investor shall be
made in satisfaction of the milestone due Investor by the Corporation pursuant
to fifth table cell of Section 3.1 of the of the License Agreement upon the
initiation of the first Phase III study.

 

SECTION 4.                            The Closing.

 

The closing (the “Stage I Closing” or the “Closing”) hereunder with respect to
the transactions contemplated by Sections 2(a) and 3.1 hereof will take place by
facsimile transmission of executed copies of the documents contemplated hereby
delivered on either (i) May 17, 2011 or (ii) if on such date the conditions
precedent set forth in Section 7.1 and 7.2 hereof have not been satisfied or
waived, no later than the third (3d) business day after the conditions set forth
in Sections 7.1 and 7.2 hereof have been satisfied or waived in writing by the
Majority Investors, such Stage I Closing to be held at the offices of Bingham
McCutchen LLP, One Federal Street, Boston, MA 02110 (such date sometimes being
referred to herein as the “Stage I Closing Date”).

 

SECTION 5.                            Representations and Warranties of the
Corporation to the Investor.

 

Except as set forth in the Corporation’s disclosure schedule dated as of
April 25, 2011 and delivered herewith (the “Corporation’s Disclosure Schedule”),
which shall be arranged to correspond to the representations and warranties in
this Section 5, or, in each case, as applicable to the relevant other Sections
of this Agreement, and the disclosure in any portion of the Corporation’s
Disclosure Schedule shall qualify the corresponding provision in this Section 5
and any other provision of this Agreement, including but not limited to the
provisions of this Section 5, to which it is reasonably apparent on its face
that such disclosure relates notwithstanding the lack of any explicit
cross-reference, the Corporation hereby represents and warrants to the Investors
as of the date of this Agreement and as of the Effective Time as follows:

 

5.1                               Organization. The Corporation is a corporation
duly organized, validly existing and in good standing under the laws of the
State of Delaware and has all requisite corporate power and authority to own and
lease its property and to carry on its Business (as defined in Section 5.6) as
presently conducted and as proposed to be conducted as described in the
Executive Summary (as defined in Section 5.6).  The Corporation is duly
qualified to do business as a foreign corporation in the states set forth on
Schedule 5.1 of the Corporation’s Disclosure Schedule.  The Corporation does not
own or lease property or engage in any activity in any other jurisdiction which
would require its qualification in such jurisdiction and in which the failure to
be so qualified would have a material adverse effect on the Business,
properties, assets, liabilities, condition (financial or otherwise) or prospects
of the Corporation (a “Corporation Material Adverse Effect”).

 

5.2                               Capitalization.

 

(a)                                 The authorized capital stock of the
Corporation immediately prior

 

7

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to the Stage I Closing shall consist of:

 

(i)                                     34,859,964 shares of Common Stock, of
which:

 

(1)                                 522,506 shall be validly issued and
outstanding, fully paid and nonassessable (including 266 shares issuable upon
exercise of warrants to purchase Common Stock);

 

(2)                                 29,364,436 shares shall have been duly
reserved for issuance upon conversion of the Series A-1 Preferred Stock,
Series A-2 Preferred Stock, Series A-3 Preferred Stock, Series A-4 Preferred
Stock, Series A-5 Preferred Stock and Series A-6 Preferred Stock (including
147,384 shares of Series A-1 Preferred Stock issuable upon exercise of warrants
to purchase Series A-1 Preferred Stock); and

 

(3)                                 2,015,666 shares shall have been duly
reserved for issuance in connection with options available under the
Corporation’s 2003 Long-Term Incentive Plan, as amended (the “2003 Plan Option
Shares”).

 

(ii)                                  29,364,436 shares of Preferred Stock of
which:

 

(1)                                 63,000 shall have been designated the
Series A Stock, 61,664 of which shall be issued and outstanding, fully paid and
nonassessable;

 

(2)                                 1,600,000 shall have been designated the
Series B Stock, 1,599,997 of which shall be issued and outstanding, fully paid
and nonassessable;

 

(3)                                 10,146,629 shall have been designated the
Series C Preferred Stock, all of which shall be issued and outstanding, fully
paid and nonassessable;

 

(4)                                 10,000,000 shall have been designated the
Series A-1 Preferred Stock, none of which shall be issued and outstanding;

 

(5)                                 9,832,133 shall have been designated the
Series A-2 Preferred Stock, none of which shall be issued and outstanding;

 

(6)                                 1,422,300 shall have been designated the
Series A-3 Preferred Stock, none of which shall be issued and outstanding;

 

(7)                                 40,003 shall have been designated the
Series A-4 Preferred Stock, none of which shall be issued and outstanding;

 

(8)                                 70,000 shall have been designated the
Series A-5 Preferred Stock, none of which shall be issued and outstanding;

 

(9)                                 8,000,000 shall have been designated the
Series A-6 Preferred Stock, none of which shall be issued and outstanding.

 

(b)                                 The authorized capital stock of the
Corporation immediately

 

8

--------------------------------------------------------------------------------

 

following the Stage I Closing, assuming compliance with all of the provisions of
this Agreement by each of the Investors, shall consist of:

 

(i)                                     34,859,964 shares of Common Stock, of
which:

 

(1)                                 522,506 shall be validly issued and
outstanding, fully paid and nonassessable (including 266 shares issuable upon
exercise of warrants to purchase Common Stock);

 

(2)                                 29,364,436 shares shall have been duly
reserved for issuance upon conversion of the Series A-1 Preferred Stock,
Series A-2 Preferred Stock, Series A-3 Preferred Stock, Series A-4 Preferred
Stock, Series A-5 Preferred Stock and Series A-6 Preferred Stock (including
147,384 shares of Series A-1 Preferred Stock issuable upon exercise of warrants
to purchase Series A-1 Preferred Stock); and

 

(3)                                 2,015,666 shares shall have been duly
reserved for issuance in connection with options available under the
Corporation’s 2003 Long-Term Incentive Plan, as amended;

 

(ii)                                  29,364,436 shares of Preferred Stock of
which:

 

(1)                                 63,000 shall have been designated the
Series A Preferred Stock, none of which shall be issued and outstanding;

 

(2)                                 1,600,000 shall have been designated the
Series B Preferred Stock, none of which shall be issued and outstanding;

 

(3)                                 10,146,629 shall have been designated the
Series C Preferred Stock, none of which shall be issued and outstanding;

 

(4)                                 10,000,000 shall have been designated the
Series A-1 Preferred Stock, of which 4,136,912 shall be validly issued and
outstanding, fully paid and nonassessable;

 

(5)                                 9,832,133 shall have been designated the
Series A-2 Preferred Stock, all of which shall be validly issued and
outstanding, fully paid and nonassessable;

 

(6)                                 1,422,300 shall have been designated the
Series A-3 Preferred Stock, all of which shall be validly issued and
outstanding, fully paid and nonassessable;

 

(7)                                 40,003 shall have been designated the
Series A-4 Preferred Stock, all of which shall be validly issued and
outstanding, fully paid and nonassessable;

 

(8)                                 70,000 shall have been designated the
Series A-5 Preferred Stock, of which 66,028 shall be validly issued and
outstanding, fully paid and nonassessable; and

 

(9)                                 8,000,000 shall have been designated the
Series A-6 Preferred

 

9

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Stock, none of which shall be issued and outstanding.

 

(c)                                  Except (i) pursuant to the terms of this
Agreement, (ii) at any time prior to the Stage I Closing, pursuant to the terms
of the Amended and Restated Stockholders’ Agreement, dated as of December 15,
2006, by and among the Corporation and the stockholders named therein, as
amended to date (the “Existing Stockholders’ Agreement”), (iii) as of and at all
times following the Stage I Closing, pursuant to the terms of that certain
Amended and Restated Stockholders’ Agreement to be entered into in connection
with the Stage I Closing, as contemplated by Section 7.2(b), in the form
attached hereto as Exhibit B (the “Stockholders’ Agreement”), and (iv) as set
forth in Schedule 5.2 attached hereto, there are and, immediately following the
Stage I Closing, there will be: (1) no outstanding warrants, options, rights,
agreements, convertible securities or other commitments or instruments pursuant
to which the Corporation is or may become obligated to issue, sell, repurchase
or redeem any shares of capital stock or other securities of the Corporation
(other than the 2003 Plan Option Shares); (2) no preemptive, contractual or
similar rights to purchase or otherwise acquire shares of capital stock of the
Corporation pursuant to any provision of law, the Restated Certificate, the
by-laws of the Corporation (the “by-laws”) or any agreement to which the
Corporation is a party or may otherwise be bound; (3) no restrictions on the
transfer of capital stock of the Corporation imposed by the Restated Certificate
or by-laws of the Corporation, any agreement to which the Corporation is a
party, any order of any court or any governmental agency to which the
Corporation is subject, or any statute other than those imposed by relevant
state and federal securities laws; (4) no cumulative voting rights for any of
the Corporation’s capital stock; (5) no registration rights under the Securities
Act of 1933, as amended (the “Securities Act”), with respect to shares of the
Corporation’s capital stock; (6) to the Corporation’s Knowledge, no options or
other rights to purchase shares of capital stock from stockholders of the
Corporation granted by such stockholders; and (7) no agreements, written or
oral, between the Corporation and any holder of its securities, or, to the
Corporation’s Knowledge, among holders of its securities, relating to the
acquisition, disposition or voting of the securities of the Corporation.

 

5.3                               Authorization of this Agreement and the
Stockholders’ Agreement. The execution, delivery and performance by the
Corporation of this Agreement and the Stockholders’ Agreement and the
consummation of the transactions contemplated hereby and thereby, including the
Recapitalization and the Merger, have been duly authorized by all requisite
action on the part of the Corporation. Each of this Agreement and the
Stockholders’ Agreement has been duly executed and delivered by the Corporation
and constitutes a valid and binding obligation of the Corporation, enforceable
in accordance with its respective terms. The execution, delivery and performance
of this Agreement and the Stockholders’ Agreement, the filing of the Restated
Certificate and the compliance with the provisions hereof and thereof by the
Corporation, will not:

 

(a)                                 violate any provision of law, statute,
ordinance, rule or regulation or any ruling, writ, injunction, order, judgment
or decree of any court, administrative agency or other governmental body;

 

(b)                                 conflict with or result in any breach of any
of the terms, conditions or provisions of, or constitute (with due notice or
lapse of time, or both) a default (or give rise to any right of termination,
cancellation or acceleration) under (i) any agreement, document,

 

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instrument, contract, understanding, arrangement, note, indenture, mortgage or
lease to which the Corporation is a party or under which the Corporation or any
of its assets is bound, which conflict, breach or default would have a
Corporation Material Adverse Effect, (ii) the Restated Certificate, or (iii) the
by-laws;

 

(c)                                  result in the creation of any lien,
security interest, charge or encumbrance upon any of the properties or assets of
the Corporation; or

 

(d)                                 conflict with any stockholder’s rights to
participate in the transactions contemplated hereby, including but not limited
to any rights to purchase Series A-1 Preferred Stock hereunder.

 

5.4                               Authorization of Series A-1 Preferred Stock
and Reserved Common Shares.

 

(a)                                 The issuance, sale and delivery of the
Series A-1 Preferred Stock pursuant to the terms hereof and the issuance sale
and deliver of the Series A-2 Preferred Stock, the Series A-3 Preferred Stock
and the Series A-4 Preferred Stock pursuant to the Recapitalization, have been
duly authorized by all requisite action of the Corporation, and, when issued,
sold and delivered in accordance with this Agreement or the Recapitalization,
the shares of Series A-1 Preferred Stock, Series A-2 Preferred Stock, Series A-3
Preferred Stock and Series A-4 Preferred Stock will be validly issued and
outstanding, fully paid and nonassessable, with no personal liability attaching
to the ownership thereof, and, except as may be set forth in the Stockholders’
Agreement (with respect to which the Corporation is in compliance with its
obligations thereunder), not subject to preemptive or any other similar rights
of the stockholders of the Corporation or others.

 

(b)                                 The reservation, issuance, sale and delivery
by the Corporation of the Reserved Common Shares and of all shares of Common
Stock issuable upon conversion of shares of Series A-2 Preferred Stock,
Series A-3 Preferred Stock and Series A-4 Preferred Stock have been duly
authorized by all requisite action of the Corporation, and the Reserved Common
Shares have been duly reserved in accordance with Section 2 of this Agreement.
Upon the issuance and delivery of the Reserved Common Shares in accordance with
the terms of this Agreement, the Reserved Common Shares will be validly issued
and outstanding, fully paid and nonassessable and not subject to preemptive or
any other similar rights of the stockholders of the Corporation or others.

 

5.5                               Consents and Approvals. No authorization,
consent, approval or other order of, or declaration to or filing with, any
governmental agency or body (other than filings required to be made under
applicable federal and state securities laws) or any other person, entity or
association is required for: (a) the valid authorization, execution, delivery
and performance by the Corporation of this Agreement and the Stockholders’
Agreement; (b) the valid authorization, issuance, sale and delivery of the
Series A-1 Preferred Stock; (c) the valid authorization, reservation, issuance,
sale and delivery of the Reserved Common Shares; or (d) the filing of the
Restated Certificate.  The Corporation has obtained all other consents that are
necessary to permit the consummation of the transactions contemplated hereby and
thereby, other than the Merger.

 

11

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5.6                               Business of the Corporation.

 

(a)                                 Except as set forth in Schedule 5.6(a) of
the Corporation’s Disclosure Schedule, the business of the Corporation (the
“Business”) is described in the executive summary of the Corporation, a copy of
which is attached hereto as Exhibit C (the “Executive Summary”).

 

(b)                                 Schedule 5.6 of the Corporation’s Disclosure
Schedule sets forth a list of all agreements or commitments to which the
Corporation is a party or by which the Corporation or the Corporation’s assets
and properties are bound that are material to the business of the Corporation as
currently conducted, and, without limitation, of the foregoing, all of the types
of agreements or commitments set forth below (each, a “Material Agreement”):

 

(i)                                     agreements which require future
expenditures by the Corporation in excess of $100,000 or which might result in
payments to the Corporation in excess of $100,000;

 

(ii)                                  employment and consulting agreements,
employee benefit, bonus, pension, profit-sharing, stock option, stock purchase
and similar plans and arrangements;

 

(iii)                               agreements involving research, development,
or the license of Intellectual Property (as defined in Section 5.12) (other than
research, development, or license agreements which require future expenditures
by the Corporation in amounts less than $100,000 or which might result in
payments to the Corporation in amounts less than $100,000 in each case that do
not grant to a third party or to the Corporation any rights in connection with
the commercialization of any products), the granting of any right of first
refusal, or right of first offer or comparable right with respect to any
Intellectual Property or payment or receipt by the Corporation of milestone
payments or royalties;

 

(iv)                              agreements relating to a joint venture,
partnership, collaboration or other arrangement involving a sharing of profits,
losses, costs or liabilities with another person or entity;

 

(v)                                 distributor, sales representative or similar
agreements;

 

(vi)                              agreements with any current or former
stockholder, officer or director of the Corporation or any “affiliate” or
“associate” of such persons (as such terms are defined in the rules and
regulations promulgated under the Securities Act), including without limitation
agreements or other arrangements providing for the furnishing of services by,
rental of real or personal property from, or otherwise requiring payments to,
any such person or entity;

 

(vii)                           agreements under which the Corporation is
restricted from carrying on any business, or competing in any line of business,
anywhere in the world;

 

(viii)                        indentures, trust agreements, loan agreements or
notes that involve or evidence outstanding indebtedness, obligations or
liabilities for borrowed money;

 

(ix)                              agreements for the disposition of a material
portion of the

 

12

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Corporation’s assets (other than for the sale of inventory in the ordinary
course of business);

 

(x)                                 agreements of surety, guarantee or
indemnification;

 

(xi)                              interest rate, equity or other swap or
derivative instruments;

 

(xii)                           agreements obligating Corporation to register
securities under the Securities Act; and

 

(xiii)                        agreements for the acquisition of any of the
assets, properties, securities or other ownership interests of the Corporation
or another person or the grant to any person of any options, rights of first
refusal, or preferential or similar rights to purchase any of such assets,
properties, securities or other ownership interests.

 

(c)                                  The Corporation has no present expectation
or intention of not fully performing all of its obligations under each Material
Agreement and, to the Corporation’s Knowledge, there is no breach or anticipated
breach by any other party or parties to any Material Agreements.

 

(d)                                 All of the Material Agreements are valid, in
full force and effect and binding against the Corporation and to the
Corporation’s Knowledge, binding against the other parties thereto in accordance
with their respective terms.  Neither the Corporation, nor, to the Corporation’s
Knowledge, any other party thereto, is in default of any of its obligations
under any of the agreements or contracts listed on the Schedule 5.6 of the
Corporation’s Disclosure Schedule, nor, to the Corporation’s Knowledge, does any
condition exist that with notice or lapse of time or both would constitute a
default thereunder.  The Corporation has delivered to each Investor or its
representative true and complete copies of all of the foregoing Material
Agreements or an accurate summary of any oral Material Agreements (and all
written amendments or other modifications thereto).

 

(e)                                  Except as provided in Schedule 5.6(e) of
the Corporation’s Disclosure Schedule: (i) there are no actions, suits,
arbitrations, claims, investigations or legal or administrative proceedings
pending or, to the Corporation’s Knowledge, threatened, against the Corporation,
whether at law or in equity; (ii) there are no judgments, decrees, injunctions
or orders of any court, government department, commission, agency,
instrumentality or arbitrator entered or existing against the Corporation or any
of its assets or properties for any of the foregoing or otherwise; and (iii) the
Corporation has not admitted in writing its inability to pay its debts generally
as they become due, filed or consented to the filing against it of a petition in
bankruptcy or a petition to take advantage of any insolvency act, made an
assignment for the benefit of creditors, consented to the appointment of a
receiver for itself or for the whole or any substantial part of its property, or
had a petition in bankruptcy filed against it, been adjudicated a bankrupt, or
filed a petition or answer seeking reorganization or arrangement under the
federal bankruptcy laws or any other laws of the United States or any other
jurisdiction.

 

(f)                                   Except as set forth in Schedule 5.6(f) of
the Corporation’s Disclosure Schedule, the Corporation is in compliance with all
obligations, agreements and conditions contained in any evidence of indebtedness
or any loan agreement or other contract or agreement (whether or not relating to
indebtedness) to which the Corporation is a party or is

 

13

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subject (collectively, the “Obligations”), the lack of compliance with which
could afford to any person the right to accelerate any indebtedness or terminate
any right of or agreement with the Corporation. To the Corporation’s Knowledge
all other parties to such Obligations are in compliance with the terms and
conditions of such Obligations.

 

(g)                                  Except for employment and consulting
agreements set forth on Schedule 5.6 attached hereto and for agreements and
arrangements relating to the 2003 Plan Option Shares and except as provided in
Schedule 5.6(g) of the Corporation’s Disclosure Schedule, this Agreement and the
Stockholders’ Agreement, there are no agreements, understandings or proposed
transactions between the Corporation and any of its officers, directors or other
“affiliates” (as defined in Rule 405 promulgated under the Securities Act).

 

(h)                                 To the Corporation’s Knowledge, no employee
of or consultant to the Corporation is in violation of any term of any
employment contract, patent disclosure agreement or any other contract or
agreement, including, but not limited to, those matters relating (i) to the
relationship of any such employee with the Corporation or to any other party as
a result of the nature of the Corporation’s Business as currently conducted, or
(ii) to unfair competition, trade secrets or proprietary or confidential
information.

 

(i)                                     Each employee and director of or
consultant to the Corporation, and each other person who has been issued shares
of the Corporation’s Common Stock or options to purchase shares of the
Corporation’s Common Stock is a signatory to, and is bound by, the Stockholders’
Agreement and, in the case of Common Stock issued to employees, directors and
consultants, a stock restriction agreement, all with stock transfer restrictions
and rights of first offer in favor of the Corporation in a form previously
approved by the Board of Directors of the Corporation (the “Board of
Directors”). In addition, each such stock restriction agreement contains a
vesting schedule previously approved by the Board of Directors.

 

(j)                                    The Corporation does not have any
collective bargaining agreements covering any of its employees or any employee
benefit plans.

 

(k)                                 The Corporation has at all times complied
with all provisions of its by-laws and Restated Certificate, and is not in
violation of or default under any provision thereof, any contract, instrument,
judgment, order, writ or decree to which it is a party or by which it or any of
its properties are bound, and the Corporation is not in violation of any
material provision of any federal or state statute, rule or regulation
applicable to the Corporation.

 

5.7                               Disclosure.  None of this Agreement, the
Stockholders’ Agreement or the Executive Summary, nor any document, certificate
or instrument furnished to any of the Investors or their counsel in connection
with the transactions contemplated by this Agreement, contains or will contain
any untrue statement of a material fact or omits or will omit to state a
material fact necessary in order to make the statements contained herein or
therein, in light of the circumstances under which they were made, not
misleading.  To the Corporation’s Knowledge, there is no fact which the
Corporation has not disclosed to the Investors or their counsel which would
reasonably be expected to result in a Corporation Material Adverse Effect.

 

5.8                               Financial Statements.  The Corporation has
furnished to each of the

 

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Investors a complete and accurate copy of (i) the unaudited balance sheet of the
Corporation at December 31, 2010 and the related unaudited statements of
operations and cash flows for the fiscal year then ended, and (ii) the unaudited
balance sheet of the Corporation (the “Balance Sheet”) at February 28, 2011 (the
“Balance Sheet Date”) and the related unaudited statements of operations and
cash flows for the two month period then ended (collectively, the “Financial
Statements”).  The Financial Statements are in accordance with the books and
records of the Corporation, present fairly the financial condition and results
of operations of the Corporation at the dates and for the periods indicated, and
have been prepared in accordance with generally accepted accounting principles
(“GAAP”) consistently applied, except, in the case of any unaudited Financial
Statements, for the absence of footnotes normally contained therein and subject
to normal and recurring year-end audit adjustments that are substantially
consistent with prior year-end audit adjustments.

 

5.9                               Absence of Undisclosed Liabilities.  The
Corporation has no liabilities of any nature (whether known or unknown and
whether absolute or contingent), except for (a) liabilities shown on the Balance
Sheet and (b) contractual and other liabilities incurred in the ordinary course
of business which are not required by GAAP to be reflected on a balance sheet
and which would not, either individually or in the aggregate, have or result in
a Corporation Material Adverse Effect.  The Corporation does not have any
liabilities (and there is no basis for any present or, to the Corporation’s
Knowledge, future proceeding against the Corporation giving rise to any
liability) arising out of any personal injury and/or death or damage to property
relating to or arising in connection with any clinical trials conducted by or on
behalf of the Corporation.

 

5.10                        Absence of Changes.  Since the Balance Sheet Date
and except as contemplated by this Agreement, there has been (i) no event or
fact that individually or in the aggregate has had a Corporation Material
Adverse Effect, (ii) no declaration, setting aside or payment of any dividend or
other distribution with respect to, or any direct or indirect redemption or
acquisition of, any of the capital stock of the Corporation, (iii) no waiver of
any valuable right of the Corporation or cancellation of any debt or claim held
by the Corporation, (iv) no loan by the Corporation to any officer, director,
employee or stockholder of the Corporation, or any agreement or commitment
therefor, (v) no increase, direct or indirect, in the compensation paid or
payable to any officer, director, employee or agent Corporation and no change in
the executive management of the Corporation or the terms of their employment,
(vi) no material loss, destruction or damage to any property of the Corporation,
whether or not insured, (vii) no labor disputes involving the Corporation, or
(viii) no acquisition or disposition of any assets (or any contract or
arrangement therefor), nor any transaction by the Corporation otherwise than for
fair value in the ordinary course of business.

 

5.11                        Payment of Taxes. The Corporation has prepared and
filed within the time prescribed by, and in material compliance with, applicable
law and regulations, all federal, state and local income, excise or franchise
tax returns, real estate and personal property tax returns, sales and use tax
returns, payroll tax returns and other tax returns required to be filed by it,
and has paid or made provision for the payment of all accrued and paid taxes and
other charges to which the Corporation is subject and which are not currently
due and payable. The federal income tax returns of the Corporation have never
been audited by the Internal Revenue Service. Neither the Internal Revenue
Service nor any other taxing authority is now asserting nor is

 

15

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threatening to assert against the Corporation any deficiency or claim for
additional taxes or interest thereon or penalties in connection therewith, and
the Corporation does not know of any such deficiency or basis for such
deficiency or claim.

 

5.12                        Intellectual Property.

 

(a)                                 Schedule 5.12(a) lists each patent, patent
application, copyright registration or application therefor, mask work
registration or application therefor, and trademark, trademark application,
trade name, service mark and domain name registration or application therefor
owned by the Corporation, licensed by the Corporation or otherwise used by the
Corporation (collectively, the “Listed Rights”). For each of the Listed Rights
set forth on Schedule 5.12(a), an assignment to the Corporation of all right,
title and interest in the Listed Right (or license to practice the Listed Right
if owned by others) has been executed. All employees of and consultants to the
Corporation have executed an agreement providing for the assignment to the
Corporation of all right, title and interest in any and all inventions,
creations, works and ideas made or conceived or reduced to practice wholly or in
part during the period of their employment or consultancy with the Corporation,
including all Listed Rights, to the extent described in any such agreement and
providing for customary provisions relating to confidentiality and
non-competition.

 

(b)                                 Except as set forth on Schedule 5.12(b), the
Listed Rights comprise all of the patents, patent applications, registered
trademarks and service marks, trademark applications, trade names, registered
copyrights and all licenses that have been obtained by the Corporation, and
which, to the Corporation’s Knowledge, are necessary for the conduct of the
Business of the Corporation as now being conducted and as proposed to be
conducted in the Executive Summary. Except as set forth on Schedule 5.12(b), the
Corporation owns all of the Listed Rights and Intellectual Property, as
hereinafter defined, free and clear of any valid and enforceable rights, claims,
liens, preferences of any party against such Intellectual Property. To the
Corporation’s Knowledge, except as set forth in Schedule 5.12(b), the Listed
Rights and Intellectual Property are valid and enforceable rights and the
practice of such rights does not infringe or conflict with the rights of any
third party.

 

(c)                                  To the Corporation’s Knowledge, the
Corporation owns or has the right to use all Intellectual Property necessary
(i) to use, manufacture, market and distribute the Customer Deliverables (as
defined below) and (ii) to operate the Internal Systems (as defined below). The
Corporation has taken all reasonable measures to protect the proprietary nature
of each item of Corporation Intellectual Property (as defined below), and to
maintain in confidence all trade secrets and confidential information that it
owns or uses. To the Corporation’s Knowledge no other person or entity has any
valid and enforceable rights to any of the Corporation Intellectual Property
owned by the Corporation (except as set forth in Schedule 5.12(c)), and no other
person or entity is infringing, violating or misappropriating any of the
Corporation Intellectual Property.

 

(d)                                 To the Corporation’s Knowledge, none of the
Customer Deliverables, or the manufacture, marketing, sale, distribution,
importation, provision or use thereof, infringes or violates, or constitutes a
misappropriation of, any valid and enforceable Intellectual Property rights of
any person or entity; and, to the Corporation’s Knowledge neither

 

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the marketing, distribution, provision or use of any Customer Deliverables
currently under development by the Corporation will, when such Customer
Deliverables are commercially released by the Corporation, infringe or violate,
or constitute a misappropriation of, any valid and enforceable Intellectual
Property rights of any person or entity that exist today. To the Corporation’s
Knowledge, none of the Internal Systems, or the use thereof, infringes or
violates, or constitutes a misappropriation of, any valid and enforceable
Intellectual Property rights of any person or entity.

 

(e)                                  There is neither pending nor overtly
threatened, or, to the Corporation’s Knowledge, any basis for, any claim or
litigation against the Corporation contesting the validity or right to use any
of the Listed Rights or Intellectual Property, and the Corporation has not
received any notice of infringement upon or conflict with any asserted right of
others nor, to the Corporation’s Knowledge, is there a basis for such a notice.
To the Corporation’s Knowledge, no person, corporation or other entity is
infringing the Corporation’s rights to the Listed Rights or Intellectual
Property. Schedule 5.12(e) lists any complaint, claim or notice, or written
threat thereof, received by the Corporation alleging any such infringement,
violation or misappropriation, and the Corporation has provided to the Investors
complete and accurate copies of all written documentation in the possession of
the Corporation relating to any such complaint, claim, notice or threat. The
Corporation has provided to the Investors complete and accurate copies of all
written documentation in the Corporation’s possession relating to claims or
disputes known to each of the Corporation concerning any Corporation
Intellectual Property.

 

(f)                                   Except as otherwise provided in Schedule
5.12(f), the Corporation, to the Corporation’s Knowledge has no obligation to
compensate others for the use of any Listed Right or any Intellectual Property,
nor has the Corporation granted any license or other right to use, in any
manner, any of the Listed Rights or Intellectual Property, whether or not
requiring the payment of royalties. Schedule 5.12(f) identities each license or
other agreement pursuant to which the Corporation has licensed, distributed or
otherwise granted any rights to any third party with respect to any Corporation
Intellectual Property. Except as described in Schedule 5.12(f), the Corporation
has not agreed to indemnify any person or entity against any infringement,
violation or misappropriation of any Intellectual Property rights with respect
to any Corporation Intellectual Property.

 

(g)                                  Schedule 5.12(g) identifies each item of
Corporation Intellectual Property that is owned by a party other than the
Corporation, and the license or agreement pursuant to which the Corporation uses
it (excluding off-the-shelf software programs licensed by the Corporation
pursuant to “shrink wrap” licenses).

 

(h)                                 The Corporation has not disclosed the source
code for any software developed by it, or other confidential information
constituting, embodied in or pertaining to such software, to any person or
entity, except pursuant to the agreements listed in Schedule 5.12(h), and the
Corporation has taken reasonable measures to prevent disclosure of any such
source code.

 

(i)                                     All of the copyrightable materials
incorporated in or bundled with the Customer Deliverables have been created by
employees of the Corporation within the scope

 

17

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of their employment by the Corporation or by independent contractors of the
Corporation who have executed agreements expressly assigning all right, title
and interest in such copyrightable materials to the Corporation. Except as
listed in Schedule 5.12(i), no portion of such copyrightable materials was
jointly developed with any third party.

 

(j)                                    To the Corporation’s Knowledge, the
Customer Deliverables and the Internal Systems are free from significant defects
or programming errors and conform in all material respects to the written
documentation and specifications therefor.

 

(k)                                 For purposes of this Agreement, the
following terms shall have the following meanings:

 

(i)                                     “Customer Deliverables” shall mean
(a) the products that the Corporation (i) currently manufactures, markets, sells
or licenses or (ii) currently plans to manufacture, market, sell or license in
the future and (b) the services that the Corporation (i) currently provides or
(ii) currently plans to provide in the future.

 

(ii)                                  “Internal Systems” shall mean the internal
systems of each of the Corporation that are presently used in its Business or
operations, including, computer hardware systems, software applications and
embedded systems.

 

(iii)                               “Intellectual Property” shall mean all:
(A) patents, patent applications, patent disclosures and all related
continuation, continuation-in-part, divisional, reissue, reexamination, utility
model, certificate of invention and design patents, design patent applications,
registrations and applications for registrations, including Listed Rights;
(B) trademarks, service marks, trade dress, internet domain names, logos, trade
names and corporate names and registrations and applications for registration
thereof; (C) copyrights and registrations and applications for registration
thereof; (D) mask works and registrations and applications for registration
thereof; (E) computer software, data and documentation; (F) inventions, trade
secrets and confidential business information, whether patentable or
nonpatentable and whether or not reduced to practice, know-how, manufacturing
and product processes and techniques, research and development information,
copyrightable works, financial, marketing and business data, pricing and cost
information, business and marketing plans and customer and supplier lists and
information; (G) other proprietary rights relating to any of the foregoing
(including remedies against infringements thereof and rights of protection of
interest therein under the laws of all jurisdictions); and (H) copies and
tangible embodiments thereof.

 

(iv)                              “Corporation Intellectual Property” shall mean
the Intellectual Property owned by or licensed to the Corporation and
incorporated in, underlying or used in connection with the Customer Deliverables
or the Internal Systems.

 

(v)                                 “Corporation’s Knowledge” shall mean
(a) with respect to matters relating directly to the Corporation and its
operations, the knowledge of Richard Lyttle, Nicholas Harvey, Louis O’Dea and
Gary Hattersley (the “Officers”) as well as other knowledge which such Officers
would have possessed had they made diligent inquiry of appropriate employees and
agents of the Corporation with respect to the matter in question; provided, that
such Officers shall not be obligated to inquire further with respect to any list
herein or in any

 

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schedule hereto, and (b) with respect to external events or conditions, the
actual knowledge of the Officers.

 

5.13                        Securities Laws. Neither the Corporation nor anyone
acting on its behalf has offered securities of the Corporation for sale to, or
solicited any offers to buy the same from, or sold securities of the Corporation
to, any person or organization, in any case so as to subject the Corporation,
its promoters, directors and/or officers to any Liability under the Securities
Act, the Securities and Exchange Act of 1934, as amended, or any state
securities or “blue sky” law (collectively, the “Securities Laws”).  The offer,
grant, sale and/or issuance of the following were not, are not, or, as the case
may be, will not be, in violation of the Securities Laws when offered, sold and
issued in accordance with this Agreement and the 2003 Long-Term Incentive Plan,
as amended:

 

(a)                                 the Series A-1 Preferred Stock, as
contemplated by this Agreement and the Exhibits and Schedules hereto, and in
partial reliance upon the representations and warranties of the Investors set
forth in Section 6 hereof;

 

(b)                                 the Series A-2 Preferred Stock, the
Series A-3 Preferred Stock and the Series A-4 Preferred Stock in the
Recapitalization;

 

(c)                                  the Common Stock issuable upon the
conversion of Existing Preferred Stock in the Forced Conversion and the
conversion of the Series A-1 Preferred Stock, Series A-2 Preferred Stock,
Series A-3 Preferred Stock or Series A-4 Preferred Stock and in partial reliance
upon the representations and warranties of the Investors set forth in Section 6
hereof; and

 

(d)                                 the 2003 Plan Option Shares and stock
options covering such shares.

 

5.14                        Title to Properties.

 

(a)                                 The Corporation has valid title to, or in
the case of leased properties and assets, valid leasehold interests in, all of
its properties and assets, necessary to conduct the Business in the manner in
which it is currently conducted (in each case, free and clear of all liens,
security interests, charges and other encumbrances of any kind, except liens for
taxes not yet due and payable), including without limitation, all rights under
any investigational drug application of the Corporation filed in the United
States and in foreign countries, all rights pursuant to the authority of the FDA
and any foreign counterparts to conduct clinical trials with respect to any
investigational drug application filed with such agency relating to biologics or
drugs relating to the Business and all rights, if any, to apply for approval to
commercially market and sell biologics or drugs and none of such properties or
assets is subject to any lien, security interest, charge or other encumbrance of
any kind, other than those the material terms of which are described in Schedule
5.14(a).

 

(b)                                 The Corporation does not own any real
property or any buildings or other structures, nor have options or any
contractual obligations to purchase or acquire any interest in real property. 
Schedule 5.14(b) lists all real property leases to which the Corporation is a
party and each amendment thereto.  All such current leases are in full force and
effect, are

 

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valid and effective in accordance with their respective terms, and there is not,
under any of such leases, any existing default or event of default (or event
that with notice or lapse of time, or both, would constitute a default).  The
Corporation, in its capacity as lessee, is not in violation of any zoning,
building or safety ordinance, regulation or requirement or other law or
regulation applicable to the operation of its leased properties, nor has it
received any notice of violation with which it has not complied.

 

(c)                                  The equipment, furniture, leasehold
improvements, fixtures, vehicles, any related capitalized items and other
tangible property material to the Business are in good operating condition and
repair, ordinary wear and tear excepted.

 

5.15                        Investments in Other Persons. Except as indicated in
Schedule 5.15 attached hereto, (a) the Corporation has not made any loan or
advance to any person or entity which is outstanding on the date hereof nor is
it committed or obligated to make any such loan or advance, and (b) the
Corporation has never owned or controlled and does not currently own or control,
directly or indirectly, any subsidiaries and has never owned or controlled and
does not currently own or control any capital stock or other ownership interest,
directly or indirectly, in any corporation, association, partnership, trust,
joint venture or other entity.

 

5.16                        ERISA. Except as set forth in Schedule 5.16, neither
the Corporation nor any entity required to be aggregated with the Corporation
under Sections 414(b), (c), (m) or (n) of the Code (as hereinafter defined),
sponsors, maintains, has any obligation to contribute to, has any liability
under, or is otherwise a party to, any Benefit Plan.  For purposes of this
Agreement, “Benefit Plan” shall mean any plan, fund, program, policy,
arrangement or contract, whether formal or informal, which is in the nature of
(i) any qualified or non-qualified employee pension benefit plan (as defined in
Section 3(2) of the Employee Retirement Income Security Act of 1974, as amended
(“ERISA”)) or (ii) an employee welfare benefit plan (as defined in section
3(1) of ERISA).  With respect to each Benefit Plan listed in Schedule 5.16, to
the extent applicable:

 

(a)                                 Each such Benefit Plan has been maintained
and operated in all material respects in compliance with its terms and with all
applicable provisions of ERISA, the Internal Revenue Code of 1986, as amended
(the “Code”), and all statutes, orders, rules, regulations, and other authority
which are applicable to such Benefit Plan;

 

(b)                                 All contributions required by law to have
been made under each such Benefit Plan (without regard to any waivers granted
under Section 412 of the Code) to any fund or trust established thereunder in
connection therewith have been made by the due date thereof:

 

(c)                                  Each such Benefit Plan intended to qualify
under Section 401(a) of the Code is the subject of a favorable unrevoked
determination letter issued by the Internal Revenue Service as to its qualified
status under the Code, which determination letter may still be relied upon as to
such tax qualified status, and no circumstances have occurred that would
adversely affect the tax qualified status of any such Benefit Plan;

 

(d)                                 The actuarial present value of all accrued
benefits under each such

 

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Benefit Plan subject to Title IV of ERISA did not, as of the latest valuation
date of such Benefit Plan, exceed the then current value of the assets of such
Benefit Plan allocable to such accrued benefits, all as based upon the actuarial
assumptions and methods currently used for such Benefit Plan;

 

(e)                                  None of such Benefit Plans that are
“employee welfare benefit plans” as defined in Section 3(1) of ERISA provides
for continuing benefits or coverage for any participant or beneficiary of any
participant after such participant’s termination of employment, except as
required by applicable law; and

 

(f)                                   Neither the Corporation nor any trade or
business (whether or not incorporated) under common control with the Corporation
within the meaning of Section 4001 of ERISA has, or at any time has had, any
obligation to contribute to any “multiemployer plan” as defined in Section 3(37)
of ERISA.

 

5.17                        Use of Proceeds. The net proceeds received by the
Corporation from the sale of the Series A-1 Preferred Stock shall be used by the
Corporation generally for the purposes set forth in Schedule 5.17 attached
hereto.

 

5.18                        Permits and Other Rights; Compliance with Laws.  The
Corporation has all permits, licenses, registrations, certificates,
accreditations, orders, authorizations or approvals from any Governmental Entity
(“Permits”) issued to or held by the Corporation.  Other than the Permits listed
on Schedule 5.18, there are no Permits, the loss or revocation of which would
result in a Corporation Material Adverse Effect.  The Corporation has all
Permits necessary to permit it to own its properties and to conduct its Business
as presently conducted and as proposed to be conducted.  Each such Permit is in
full force and effect and, to the Corporation’s Knowledge, no suspension or
cancellation of such Permit is threatened and there is no basis for believing
that such Permit will not be renewable upon expiration.  The Corporation is in
compliance in all material respects under each such Permit, and the transactions
contemplated by this Agreement will not cause a violation under any of such
Permits.  The Corporation is in compliance in all material respects with all
provisions of the laws and governmental rules and regulations applicable to its
Business, properties and assets, and to the products and services sold by it,
including, without limitation, all such rules, laws and regulations relating to
fair employment practices and public or employee safety. The Corporation is in
compliance with the Clinical Laboratories Improvement Act of 1967, as amended.

 

5.19                        Insurance. Schedule 5.19 sets forth a true and
complete list of all policies or binders of fire, theft, liability, product
liability, workmen’s compensation, vehicular, directors’ and officers’ and other
insurance held by or on behalf of the Corporation.  Such policies and binders
are in full force and effect, are in the amounts not less than is customarily
obtained by corporations of established reputation engaged in the same or
similar business and similarly situated and are in conformity with the
requirements of all leases or other agreements to which the Corporation is a
party and are valid and enforceable in accordance with their terms.  The
Corporation’s product liability insurance covers its clinical trials.  The
Corporation is not in default with respect to any provision contained in such
policy or binder nor has the Corporation failed to give any notice or present
any claim under any such policy or binder in due and timely fashion.  There are
no outstanding unpaid claims under any such policy or binder.  The

 

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Corporation has not received notice of cancellation or non-renewal of any such
policy or binder.

 

5.20                        Board of Directors. Except as provided in Schedule
5.20 attached hereto, the Corporation has not extended any offer or promise or
entered into any agreement, arrangement, understanding or otherwise, whether
written or oral, with any person or entity by which the Corporation has agreed
to allow such person or entity to participate, in any way, in the affairs of the
Board of Directors, including without limitation, appointment or nomination as a
member, or right to appear at, or receive the minutes of a meeting of the Board
of Directors.

 

5.21                        Books and Records.  The minute books of the
Corporation contain complete and accurate records of all meetings and other
corporate actions of the stockholders and Boards of Directors and committees
thereof.  The stock ledger of the Corporation is complete and accurate and
reflects all issuances, transfers, repurchases and cancellations of shares of
capital stock of the Corporation.

 

5.22                        Environmental Matters.

 

(a)                                 The Corporation has not used, generated,
manufactured, refined, treated, transported, stored, handled, disposed,
transferred, produced, processed or released (together defined as “Release”) any
Hazardous Materials (as hereinafter defined) in any manner or by any means in
violation of any Environmental Laws (as hereinafter defined). To the
Corporation’s Knowledge, neither the Corporation nor any prior owner or tenant
of the Property (as hereinafter defined) has Released any Hazardous Material or
other pollutant or effluent into, on or from the Property in a way which can
pose a risk to human health or the environment, nor is there a threat of such
Release. As used herein, the term “Property” shall include, without limitation,
land, buildings and laboratory facilities owned or leased by the Corporation or
as to which the Corporation now has any duties, responsibilities (for clean-up,
remedy or otherwise) or liabilities under any Environmental Laws, or as to which
the Corporation or any subsidiary of the Corporation may have such duties,
responsibilities or liabilities because of past acts or omissions of the
Corporation or any such subsidiary or their predecessors, or because the
Corporation or any such subsidiary or their predecessors in the past was such an
owner or operator of, or some other relationship with, such land, buildings
and/or laboratory facilities, all as more fully described in Schedule 5.22(a) of
the Corporation’s Disclosure Schedule. The term “Hazardous Materials” shall mean
(A) any chemicals, materials or substances defined as or included in the
definition of “hazardous substances,” “hazardous wastes,” “hazardous materials,”
“extremely hazardous wastes,” “restricted hazardous wastes,” “toxic substances,”
“toxic pollutants,” “hazardous air pollutants,” “contaminants,” “toxic
chemicals,” “toxins,” “hazardous chemicals,” “extremely hazardous substances,”
“pesticides,” “oil” or related materials as defined in any applicable
Environmental Law, or (B) any petroleum or petroleum products, oil, natural or
synthetic gas, radioactive materials, asbestos-containing materials, urea
formaldehyde foam insulation, radon, and any other substance defined or
designated as hazardous, toxic or harmful to human health, safety or the
environment under any Environmental Law.

 

(b)                                 No notice of lien under any Environmental
Laws has been filed against any Property of the Corporation.

 

(c)                                  The use of the Property complies with
lawful, permitted and

 

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conforming uses in all material respects under all applicable building, tire,
safety, subdivision, zoning, sewer, environmental, health, insurance and other
such laws, ordinances, rules, regulations and plan approval conditions of any
governmental or public body or authority relating to the use of the Property.

 

(d)                                 Except as described in Schedule 5.22(d) of
the Corporation’s Disclosure Schedule, to the Corporation’s Knowledge, the
Property does not contain: (i) asbestos in any form; (ii) urea formaldehyde foam
insulation; (iii) transformers or other equipment which contain dialectic fluid
containing levels of polychlorinated biphenyls; (iv) radon; or (v) any other
chemical, material or substance, the exposure to which is prohibited, limited or
regulated by a federal, state or local government agency, authority or body, or
which, even if not so regulated, to the Corporation’s Knowledge after reasonable
investigation, may or could pose a hazard to the health and safety of the
occupants of the Property or the owners or occupants of property adjacent to or
in the vicinity of the Property.

 

(e)                                  The Corporation has not received written
notice that the Corporation is a potentially responsible party for costs
incurred at a cleanup site or corrective action under any Environmental Laws. 
The Corporation has not received any written requests for information in
connection with any inquiry by any Governmental Authority (as defined
hereinafter) concerning disposal sites or other environmental matters. As used
herein, “Governmental Authority” shall mean any nation or government, any
federal, state, municipal, local, provincial, regional or other political
subdivision thereof and any entity or person exercising executive, legislative,
judicial, regulatory or administrative functions of, or pertaining to,
government, Schedule 5.22(e) of the Corporation’s Disclosure Schedule identifies
all locations where Hazardous Materials used in whole or in part by the Business
of the Corporation or resulting from the Business, facilities or Property of the
Corporation have been stored or disposed of by or on behalf of the Corporation.
As used herein, “Environmental Laws” shall mean all applicable federal, state
and local laws, ordinances, rules and regulations that regulate, fix liability
for, or otherwise relate to, the handling, use (including use in industrial
processes, in construction, as building materials, or otherwise), storage and
disposal of hazardous and toxic wastes and substances, and to the discharge,
leakage, presence, migration, threatened Release or Release (whether by
disposal, a discharge into any water source or system or into the air, or
otherwise) of any pollutant or effluent. Without limiting the preceding
sentence, the term “Environmental Laws” shall specifically include the following
federal and state laws, as amended:

 

FEDERAL

 

Comprehensive Environmental Response Compensation and Liability Act of 1980, as
amended by the Superfund Amendments and Reauthorization Act of 1986, 42 U.S.C. §
9601 et seq.; the Emergency Planning and Community Right-to-Know Act, 42 U.S.C.
§ 11001 et seq.; the Resource Conservation and Recovery Act, 42 U.S.C. § 6901 et
seq.; the Federal Water Pollution Control Act, 33 U.S.C. § 1251 et seq.; the
Federal Insecticide, Fungicide and Rodenticide Act, 7 U.S.C. § 136 et seq.; the
Toxic Substance Control Act, 15 U.S.C. § 2601 et seq.; the Oil Pollution Act of
1990, 33 U.S.C. § 1001 et seq.; the Hazardous Materials

 

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Transportation Act, as amended, 49 U.S.C. § 1801 et seq.; the Atomic Energy Act,
as amended 42 U.S.C. § 2011 et seq.; the Occupational Safety and Health Act, as
amended, 29 U.S.C. § 651 et seq.; the Federal Food, Drug and Cosmetic Act, as
amended 21 U.S.C. § 301 et seq. (insofar as it regulates employee exposure to
Hazardous Substances); the Clean Air Act, 42 U.S.C. 7401 et. seq.

 

STATE

 

MASSACHUSETTS ENVIRONMENTAL STATUTES

 

Massachusetts Clean Waters Act, Mass. Gen. L. Ch. 21, Section 26, et. seq., and
regulations thereto; Massachusetts Solid Waste Disposal Laws. Mass. Gen. L. Ch.
16, Section 18, et. seq., and Ch. 111, Section 1 05A, and regulations thereto;
Massachusetts Oil and Hazardous Materials Release Prevention and Response Act,
Mass. Gen. L., Ch. 21 E, Section 1, et. seq., and regulations thereto;
Massachusetts Solid Waste Facilities Law, Mass. Gen. L., Ch. 21H, Section 1, et.
seq., and regulations thereto; Massachusetts Toxic Use Reduction Act, Mass. Gen.
L., Ch. 211, Section 1, et. seq., and regulations thereto; Massachusetts Litter
Control Laws, Mass. Gen. L. Ch. 111. Section 1 50A, et. seq., and regulations
thereto; Massachusetts Wetlands Protection Laws, Mass. Gen. L., Ch. 130,
Section 105, et. seq., and regulations thereto; Massachusetts Environmental Air
Pollution Control Law, Mass. Gen. L.. Ch. 101, Section 2B, et. seq., and
regulations thereto; Massachusetts Environmental Policy Act, Mass. Gen. L. Ch.
30, Section 61, et. seq., and regulations thereto; and Massachusetts Hazardous
Waste Laws, Mass. Gen. L. Ch. 21C, Section 1, et. seq., and regulations thereto.

 

(f)                                   The Corporation has maintained all
environmental and operating documents and records substantially in the manner
and for the time periods required by the Environmental Laws and any other laws,
regulations or orders and has never conducted an environmental audit except as
disclosed in Schedule 5.22(f) of the Corporation’s Disclosure Schedule. For
purposes of this Section 5.22(f), an environmental audit shall mean any
evaluation, assessment, study or test performed at the request of or on behalf
of a Governmental Authority, including, but not limited to, a public liaison
committee, but does not include normal or routine inspections, evaluations or
assessments which do not relate to a threatened or pending charge, restraining
order or revocation of any permit, license, certificate, approval,
authorization, registration or the like issued pursuant to the Environmental
Laws and any other law, regulation or order.

 

(g)                                  To the Corporation’s Knowledge, no part of
the Property of the Corporation is (i) located within any wetlands area,
(ii) subject to any wetlands regulations, or (iii) included in or is proposed
for inclusion in, or abuts any property included in or proposed for inclusion
in, the National Priority List or any similar state lists.

 

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5.23                        FDA Matters.

 

(a)                                 The Corporation has (i) complied in all
material respects with all applicable laws, regulations and specifications with
respect to the manufacture, design, sale, storing, labeling, testing,
distribution, inspection, promotion and marketing of all of the Corporation’s
products and product candidates and the operation of manufacturing facilities
promulgated by the U.S. Food and Drug Administration (the “FDA”) or any
corollary entity in any other jurisdiction and (ii) conducted, and in the case
of any clinical trials conducted on its behalf, caused to be conducted, all of
its clinical trials with reasonable care and in compliance in all material
respects with all applicable laws and the stated protocols for such clinical
trials.

 

(b)                                 All of the Corporation’s submissions to the
FDA and any corollary entity in any other jurisdiction, whether oral, written or
electronically delivered, were true, accurate and complete in all material
respects as of the date made, and remain true, accurate and complete in all
material respects and do not misstate any of the statements or information
included therein, or omit to state a fact necessary to make the statements
therein not materially misleading.

 

(c)                                  The Corporation has not committed any act,
made any statement or failed to make any statement that would breach the FDA’s
policy with respect to “Fraud, Untrue Statements of Material Facts, Bribery, and
Illegal Gratuities” set forth in 56 Fed. Reg. 46191 (September 10, 1991) or any
similar laws, rules or regulations, whether under the jurisdiction of the FDA or
a corollary entity in any other jurisdiction, and any amendments or other
modifications thereto.  Neither the Corporation nor, to the Corporation’s
Knowledge, any officer, employee or agent of the Corporation has been convicted
of any crime or engaged in any conduct that would reasonably be expected to
result in (i) debarment under 21 U.S.C. Section 335a or any similar state or
foreign law or regulation or (ii) exclusion under 42 U.S.C. Section 1320a 7 or
any similar state or foreign law or regulation, and neither the Corporation nor,
to the Corporation’s Knowledge, any such person has been so debarred or
excluded.

 

(d)                                 The Corporation has not sold or marketed any
products prior to receiving any required or necessary approvals or consents from
any federal or state governmental authority, including but not limited to the
FDA under the Food, Drug & Cosmetics Act of 1976, as amended, and the
regulations promulgated thereunder, or any corollary entity in any
jurisdiction.  The Corporation has not received any notice of, nor is the
Corporation aware of any, actions, citations, warning letters or Section 305
notices from the FDA or any corollary entity.

 

5.24                        Compliance with Privacy Laws

 

(a)                                 For purposes of this Agreement:

 

(i)                                     “Foreign Privacy Laws” shall mean
(a) the Directive 95/46/EC of the Parliament and of the Council of the European
Union of 24 October 1995 on the protection of individuals with regard to the
collection, use, disclosure, and processing of personal data and on the free
movement of such data, (b) the corresponding national rules, regulations, codes,
orders, decrees and rulings thereunder of the member states of the European
Union and (c) any rules, regulations, codes, orders, decree, and rulings
thereunder related to privacy, data protection or data transfer issues
implemented in other countries.

 

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(ii)                                  “US Privacy Laws” shall mean any rules,
regulations, codes, orders, decrees, and rulings thereunder of any federal,
state, regional, county, city, municipal or local government of the United
States or any department, agency, bureau or other administrative or regulatory
body obtaining authority from any of the foregoing that relate to privacy, data
protection or data transfer issues, including all implementing laws, ordinances
or regulations, including, without limitation, the Health Insurance Portability
and Accountability Act of 1996, as amended; the Children’s Online Privacy
Protection Act (COPPA) of 1998, as amended; the Financial Modernization Act
(Graham-Leach-Bliley Act) of 2000, as amended; the Fair Credit Reporting Act of
1970, as amended; the Privacy Act of 1974, as amended; the Family Education
Rights and Privacy Act of 1974, as amended; the Right to Financial Privacy Act
of 1978, as amended; the Privacy Protection Act of 1980, as amended; the Cable
Communications Policy Act of 1984, as amended; the Electronic Communications
Privacy Act of 1986, as amended; the Video Privacy Protection Act of 1988, as
amended; the Telephone Consumer Protection Act of 1991, as amended; the Driver’s
Privacy Protection Act of 1994, as amended; the Communications Assistance for
Law Enforcement Act of 1994, as amended; the Telecommunications Act of 1996, as
amended; and any implementing regulations related thereto;

 

(b)                                 The Corporation is currently and has been at
all times in compliance in all material respects with all Foreign Privacy Laws
and US Privacy Laws; and the Corporation has not received notice (in writing or
otherwise) regarding violation of such Foreign Privacy Laws or US Privacy Laws.

 

(c)                                  No action, suit, proceeding, investigation,
charge, complaint, claim, demand, or notice has been filed or commenced against
the Corporation, nor to the Corporation’s Knowledge threatened against the
Corporation, relating to Foreign Privacy Laws and US Privacy Laws; nor has the
Corporation incurred any material liabilities (whether accrued, absolute,
contingent or otherwise) under any Foreign Privacy Laws or US Privacy Laws.

 

(d)                                 Health Insurance Portability and
Accountability Act of 1996.  The Corporation (i) has assessed the applicability
of the Health Insurance Portability and Accountability Act of 1996 and its
implementing regulations (collectively, “HIPAA”) to the Corporation, including
the fully insured and self-insured health plans that the Corporation sponsors or
has sponsored or contributes to or has contributed to and health care provider
activities, if any, in which the Corporation engages, (ii) has complied in all
relevant respects with HIPAA, including 45 C.F.R. Part 160 and Subparts A and E
of Part 164 (the “HIPAA Privacy Rule”), including but not limited to HIPAA
Privacy Rule requirements relating to health information use and disclosure,
notices of privacy rights, appointment of a Privacy Officer, adoption of a
privacy policy, amendment of plan documents, and implementation of employee
training as to the handling of protected health information, and (iii) if
required under the HIPAA Privacy Rule, has entered into business associate
agreements on behalf of the Corporation’s health plans covering the handling of
protected health information with vendors and others categorized under HIPAA as
business associates of the Corporation’s health plans.

 

(e)                                  Other Health Information Laws.  Without
limiting the generality of Section 5.24(a) through Section 5.24(d),

 

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(i)                                     the Corporation is currently, and has
been at all times since its incorporation, in compliance in all material
respects with all applicable health insurance, health information security,
health information privacy, and health information transaction format Laws (each
a “Health Information Law”), including, without limitation, any rules,
regulations, codes, orders, decrees, and rulings thereunder of any federal,
state, regional, county, city, municipal or local government, whether foreign or
domestic, or any department, agency, bureau or other administrative or
regulatory body obtaining authority from any of the foregoing; and

 

(ii)                                  no action, suit, proceeding,
investigation, charge, complaint, claim, demand, or notice has been filed or
commenced against the Corporation nor to the Corporation’s Knowledge threatened
against the Corporation, alleging any failure to comply with any Health
Information Law; nor has the Corporation incurred any material liabilities
(whether accrued, absolute, contingent or otherwise) under any Health
Information Law.

 

5.25                        Health Care and Affiliated Transactions; Stark and
Anti-Kickback Laws.

 

(a)                                 For purposes of the Stark II law and
implementing regulations, if applicable, none of the directors or officers of
the Corporation, or physicians employed by the Corporation, any other affiliates
of the Corporation, or any of their respective immediate family members is
(i) to the Corporation’s Knowledge, a partner or stockholder or has any other
economic interest in any customer or supplier of the Corporation; (ii) a party
to any transaction or contract with the Corporation; or (iii) indebted to the
Corporation.  The Corporation has not paid, or incurred any obligation to pay,
any fees, commissions or other amounts to and is not a party to any agreement,
business arrangement or course of dealing with any firm of or in which any of
directors, officers or affiliates of the Corporation, or any of their respective
immediate family members, is a partner or stockholder or has any other economic
interest, other than ownership of less than one percent (1%) of a publicly
traded corporation.  No physician or family member of a physician has a
financial relationship with the Corporation in violation of Section 1877 of the
Social Security Act.  The Corporation has made all filings required by
Section 1877 of the Social Security Act.

 

(b)                                 The Corporation has complied with all
applicable state and federal “anti-kickback,” fraud and abuse, false claims and
related statutes and regulations.  The Corporation has received no notice of nor
is otherwise aware of any inquiries, audits, subpoenas or other investigations
involving Corporation by the U.S. Department of Health and Human Services, the
U.S. Office of Inspector General, any U.S. Attorney’s Office or any other
federal or state agency with jurisdiction over such statutes or regulations.

 

SECTION 6.                            Representations and Warranties of the
Investor to the Corporation.

 

The Investor represents and warrants to the Corporation as follows:

 

(a)                                 It is acquiring the Series A-1 Preferred
Stock and, in the event it should acquire Reserved Common Shares upon conversion
of the Series A-1 Preferred Stock, it will be acquiring such Reserved Common
Shares, for its own account, for investment and not with a view to the
distribution thereof within the meaning of the Securities Act.

 

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(b)                                 It is an “accredited investor” as such term
is defined in Rule 501(a) promulgated under the Securities Act.

 

(c)                                  It agrees that the Corporation may place a
legend on the certificates delivered hereunder stating that the Series A-1
Preferred Stock and any Reserved Common Shares have not been registered under
the Securities Act, and, therefore, cannot be offered, sold or transferred
unless they are registered under the Securities Act or an exemption from such
registration is available and that the offer, sale or transfer of the Series A-1
Preferred Stock and any Reserved Common Shares is further subject to any
restrictions imposed by this Agreement and the Stockholders’ Agreement.

 

(d)                                 The execution, delivery and performance by
it of this Agreement have been duly authorized by all requisite action of it.

 

(e)                                  It further understands that the exemptions
from registration afforded by Rule 144 and Rule 144A (the provisions of which
are known to it) promulgated under the Securities Act depend on the satisfaction
of various conditions, and that, if applicable, Rule 144 may afford the basis
for sales only in limited amounts.

 

(f)                                   It has such knowledge and experience in
business and financial matters and with respect to investments in securities of
privately-held companies so as to enable it to understand and evaluate the risks
of its investment in the Series A-1 Preferred Stock and form an investment
decision with respect thereto.  It has been afforded the opportunity during the
course of negotiating the transactions contemplated by this Agreement to ask
questions of, and to secure such information from, the Corporation and its
officers and directors as it deems necessary to evaluate the merits of entering
into such transactions.

 

(g)                                  It is duly organized and validly existing
and has the power and authority to enter into this Agreement and it has not been
organized, reorganized or recapitalized specifically for the purpose of
acquiring the securities of the Corporation.

 

(h)                                 It has adequate net worth and means of
providing for its current needs and personal contingencies to sustain a complete
loss of its investment in the Corporation.  The Investors understand that the
foregoing representations and warranties shall be deemed material and to have
been relied upon by the Corporation.

 

SECTION 7.                            Closing Conditions.

 

(a)                                 It shall be a condition precedent to the
obligations of the Corporation hereunder to be performed at the Stage I Closing,
as to the Investor that the representations and warranties contained herein of
the Investor hereunder shall be true and correct as of the date of such Closing
with the same force and effect as though such representations and warranties had
been made on and as of such date.

 

(b)                                 The Stage I Closing pursuant to the April 25
Agreement shall have occurred or, if the Closing takes place on May 17, 2011,
shall occur concurrently with the Closing hereunder, and in each case the sale
of stock under such Agreement shall be at a per

 

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share purchase price equal to that hereunder and aggregate proceeds to the
Company shall not be at less $20 million.

 

(c)                                  Ipsen has become a party to the Amended and
Restated Stockholders’ Agreement dated April 25, 2011 among the Company and the
other parties named therein.

 

SECTION 8.                            Acknowledgement Regarding the Merger.

 

The Investor hereby, in its capacity as a future stockholder of the Corporation,
(a) acknowledges that such Investor is aware that the Corporation has, prior to
the execution and delivery of this Agreement, entered into an Agreement and Plan
of Merger with MPMAC and Merger Sub with respect to the proposed Merger, an
executed copy of which is attached hereto as Exhibit F (the “Merger Agreement”),
and (b) acknowledges that such Investor has received and reviewed the Merger
Agreement.

 

SECTION 9.                            Expenses and Fees.

 

The Corporation shall pay, and hold the Investor harmless against all liability
for the payment of all costs and other expenses incurred by the Investor in
connection with the Corporation’s performance of and compliance with all
agreements and conditions contained herein or contemplated hereby on its part to
be performed or complied with.  The Corporation further agrees that it will pay,
and hold the Investor harmless from, any and all liability with respect to any
stamp or similar taxes which may be determined to be payable in connection with
the execution and delivery of this Agreement or any modification, amendment or
alteration of the terms or provisions of this Agreement and that it will
similarly pay, and hold the Investor harmless from, all issue taxes in respect
of the issuance of the Series A-1 Preferred Stock to the Investor.  the

 

SECTION 10.                     Certain Covenants.

 

Without the prior written consent of the holders of a majority of the shares of
Series A-1 Preferred Stock issued and outstanding at the time (the “Majority
Investors”), the Corporation shall not issue any shares of Series A-1 Preferred
Stock or any securities convertible into shares of Series A-1 Preferred Stock
other than (i) Excluded Stock (as defined in the Certificate of Incorporation of
the Corporation), (ii) pursuant to the terms of this Agreement or (iii) pursuant
to agreements, warrants or arrangements described on Schedule 10 hereof.

 

SECTION 11.                     Brokers or Finders.

 

The Corporation represents and warrants to the Investor, and the Investor
represents and warrants to the Corporation, that, other than Leerink Swann LLC,
which has acted as advisor to the Corporation in connection with the
transactions contemplated by this Agreement, no person or entity has or will
have, as a result of the transactions contemplated by this Agreement, any right,
interest or valid claim against or upon the Corporation or the Investors for any
commission, fee or other compensation as a finder or broker because of any act
or omission by the Corporation or the Investor or by any agent of the
Corporation or the Investors.

 

29

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SECTION 12.                     Exchanges Lost. Stolen or Mutilated
Certificates.

 

Upon surrender by the Investor to the Corporation of shares of Series A-1
Preferred Stock or Reserved Common Shares acquired by such Investor hereunder,
the Corporation, at its expense, will issue in exchange therefor, and deliver to
such Investor, a new certificate or certificates representing such shares in
such denominations as may be requested by such Investor. Upon receipt of
evidence satisfactory to the Corporation of the loss, theft, destruction or
mutilation of any certificate representing any shares of Common Stock or
Preferred Stock purchased or acquired by any Investor hereunder and, in case of
any such loss, theft or destruction, upon delivery of any indemnity agreement
satisfactory to the Corporation, or in case of any such mutilation, upon
surrender and cancellation of such certificate, the Corporation, at its expense,
will issue and deliver to such Investor a new certificate for such shares of
Common Stock or Preferred Stock, as applicable, of like tenor, in lieu of such
lost, stolen or mutilated certificate.

 

SECTION 13.                     Survival of Representations and Warranties.

 

The representations and warranties set forth in Sections 5 and 6 hereof shall
survive the Closings indefinitely.

 

SECTION 14.                     Indemnification.

 

The Corporation shall indemnify, defend and hold the Investor harmless against
any and all liabilities, loss, cost or damage, together with all reasonable
costs and expenses related thereto (including legal and accounting fees and
expenses), arising from, relating to, or connected with the untruth, inaccuracy
or breach of any statements, representations, warranties or covenants of the
Corporation contained herein, including, but not limited to, all statements,
representations, warranties or covenants concerning environmental matters.

 

SECTION 15.                     Remedies.

 

In case any one or more of the representations, warranties, covenants and/or
agreements set forth in this Agreement shall have been breached by any party
hereto, the party or parties entitled to the benefit of such representations,
warranties, covenants or agreements may proceed to protect and enforce its or
their rights either by suit in equity and/or action at law, including, but not
limited to, an action for damages as a result of any such breach and/or an
action for specific performance of any such covenant or agreement contained in
this Agreement.  The rights, powers and remedies of the parties under this
Agreement are cumulative and not exclusive of any other right, power or remedy
which such parties may have under any other agreement or law.  No single or
partial assertion or exercise of any right, power or remedy of a party hereunder
shall preclude any other or further assertion or exercise thereof.

 

SECTION 16.                     Successors and Assigns.

 

Except as otherwise expressly provided herein, this Agreement shall bind and
inure to the benefit of the Corporation and the Investor and the respective
permitted successors and assigns of the Investor and the permitted successors
and assigns of the Corporation. Subject to the provisions of Sections 3.1, 3.2,
3.3 and 3.10 of the Stockholders’ Agreement, this Agreement and

 

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the rights and duties of the Investor set forth herein may be freely assigned,
in whole or in part, by the Investor.  Neither this Agreement nor any of the
rights or duties of the Corporation set forth herein shall be assigned by the
Corporation, in whole or in part, without having first received the written
consent of the Majority Investors.  Notwithstanding the foregoing, upon the
consummation of the Merger and with respect to all times following the
consummation of the Merger, (i) the Corporation shall, and hereby does, assign
all of its rights, duties and obligations under this Agreement to MPMAC and
(ii) all references to the “Corporation” in this Agreement and to its capital
stock or any other aspects of the Corporation shall be deemed to be references
to MPMAC and its capital stock and other applicable aspects of MPMAC.  MPMAC, by
executing this Agreement as an anticipated successor and assign to the
Corporation, does hereby assume, effective upon the consummation of the Merger,
all of the Corporation’s rights, duties and obligations under this Agreement and
Radius will be released from its duties and obligations under this Agreement. 
All parties to this Agreement hereby consent to the assignment and assumption
contemplated between the Corporation and MPMAC set forth in this paragraph.

 

SECTION 17.                     Entire Agreement.

 

This Agreement, together with the other writings referred to herein, including
the Restated Charter and the Stockholders’ Agreement, or delivered hereunder and
which form a part hereof, contains the entire agreement among the parties with
respect to the subject matter hereof and amends, restates and supersedes all
prior and contemporaneous arrangements or understandings, whether written or
oral, with respect thereto.

 

SECTION 18.                     Notices.

 

All notices, requests, consents and other communications hereunder to any party
shall be deemed to be sufficient if contained in a written instrument delivered
in person or duly sent by first class registered, certified or overnight mail,
postage prepaid, or telecopied or e-mailed with a confirmation copy by regular
mail, addressed, telecopied or e-mailed, as the case may be, to such party at
the address, telecopier number or e-mail address, as the case may be, set forth
below or such other address, telecopier number or e-mail address, as the case
may be, as may hereafter be designated in writing by the addressee to the
addressor listing all parties:

 

(i)                                     if to the Corporation. to:

 

Radius Health, Inc.

201 Broadway

Sixth Floor

Cambridge, MA 02139

Attention: B. Nicholas Harvey

Telecopier: (617) 444-1834
E-mail: bnharvey@radiuspharm.com

 

with a copy to:

 

Bingham McCutchen

One Federal Street

Boston. MA 02110-1726

 

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Attention: Julio E. Vega, Esq.

Telecopier: (617) 951-8736
E-mail:  Julio.vega@bingham.com

 

(ii)                                  if to Investor, as set forth on Schedule
1.

 

All such notices, requests, consents and other communications shall be deemed to
have been received: (a) in the case of personal delivery, on the date of such
delivery; (b) in the case of mailing, on the third business day following the
date of such mailing; (c) in the case of overnight mail, on the first business
day following the date of such mailing; (d) in the case of facsimile
transmission, when confirmed by facsimile machine report; or (e) in the case of
e-mail delivery, when confirmed by the sender’s e-mail system.

 

SECTION 19.                     Changes.

 

The terms and provisions of this Agreement may not be modified or amended, or
any of the provisions hereof waived, temporarily or permanently, except pursuant
to a writing executed by a duly authorized representative of the Corporation,
MPMAC and the Investor..

 

SECTION 20.                     Counterparts.

 

This Agreement may be executed in any number of counterparts, and each such
counterpart shall be deemed to be an original instrument, but all such
counterparts together shall constitute but one agreement.

 

SECTION 21.                     Headings.

 

The headings of the various sections of this Agreement have been inserted for
convenience of reference only and shall not be deemed to be a part of this
Agreement.

 

SECTION 22.                     Nouns and Pronouns.

 

Whenever the context may require, any pronouns used herein shall include the
corresponding masculine, feminine or neuter forms, and the singular form of
names and pronouns shall include the plural and vice-versa.

 

SECTION 23.                     Severability.

 

Any provision of this Agreement that is prohibited or unenforceable in any
jurisdiction shall, as to such jurisdiction, be ineffective to the extent of
such prohibition or unenforceability without invalidating the remaining
provisions hereof and any such prohibition or unenforceability in any
jurisdiction shall not invalidate or render unenforceable such provision in any
other jurisdiction.

 

SECTION 24.                     Further Assurances.

 

The parties shall cooperate reasonably with each other in connection with any
steps

 

32

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required to be taken as part of their respective obligations under this
Agreement, and shall furnish upon request to each other such further
information, execute and deliver to each other such other documents, and do such
other acts and things, all as the other party may reasonably request for
purposes of carrying out the intend of this Agreement and consummating the
transactions contemplated hereby.

 

SECTION 25.                     Governing Law.

 

This Agreement shall be governed by and construed in accordance with the laws of
the State of Delaware, excluding choice of laws rules thereof.

 

(Remainder of Page Left Intentionally Blank.)

 

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(Signature Page to Stock Purchase Agreement)

 

IN WITNESS WHEREOF, the parties hereto have executed this Agreement as of the
date first above written.

 

 

THE CORPORATION:

 

 

 

RADIUS HEALTH, INC.

 

 

 

 

 

By:

 

 

Name:

C. Richard Edmund Lyttle

 

Title:

President

 

 

 

 

 

As an anticipated successor and assign to the Corporation under Section 16
hereof:

 

 

 

MPM ACQUISITION CORP.

 

 

 

 

 

By:

 

 

Name:

C. Richard Edmund Lyttle

 

Title:

President

 

 

 

 

 

INVESTOR:

 

 

 

IPSEN PHARMA SAS

 

 

 

 

 

By:

 

 

Name:

Marc de Garidel

 

Title:

Chairman and CEO

 

34

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Schedule I

 

Name of Investors

 

Address of Record

 

Stage I
Preferred
Shares

Ipsen Pharma SAS

 

Attn: Ipsen Pharma SAS 42 Rue du Docteur Blanche 75016 Paris, France

 

See calculation in Section 3.2

TOTAL:

 

 

 

 

 

35

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Exhibit A

 

Form of Restated Certificate

 

36

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FOURTH AMENDED AND RESTATED

 

CERTIFICATE OF INCORPORATION

 

OF

 

RADIUS HEALTH, INC.

 

(Pursuant to Section 242 and 245 of the

General Corporation Law of the State of Delaware)

 

Radius Health, Inc., a Delaware corporation hereby certifies as follows:

 

1.              The name of the corporation is Radius Health, Inc. (the
“Corporation”). The Corporation filed its original Certificate of Incorporation
with the Secretary of State of the State of Delaware on October 3, 2003 and the
name under which it was originally incorporated was NuVios, Inc.

 

2.              This Fourth Amended and Restated Certificate of Incorporation
(the “Certificate”) amends, restates and integrates the provisions of the Third
Amended and Restated Certificate of Incorporation as heretofore in effect (the
“Prior Certificate”), has been duly adopted in accordance with the provisions of
Sections 242 and 245 of the General Corporation Law of the State of Delaware
(“DGCL”), and has been approved by written consent of the stockholders of the
Corporation in accordance with the provisions of Section 228 of the DGCL (prompt
notice of such action having been given to those stockholders who did not
consent in writing).

 

3.              Effective immediately at the effective date of the filing of
this Certificate (the “Effective Time”), the Prior Certificate, as heretofore
amended, is hereby further amended and restated to read in its entirety as
follows:

 

ARTICLE I
Name

 

The name of the corporation is Radius Health, Inc.

 

ARTICLE II
Purpose

 

The Corporation is organized to engage in any lawful act or activity for which a
corporation may be organized under the DGCL.

 

ARTICLE IIA
Reverse Split

 

Simultaneously with the Effective Time (the “Split Effective Date”), a reverse
split (the “Reverse Split”) of the Corporation’s outstanding capital stock shall
occur as follows: (a) each share of Common Stock issued and outstanding or held
as treasury shares immediately prior to the Split Effective Date (the “Old
Common Stock”) shall automatically without any action on the part of the holder
thereof, be reclassified and changed into 0.06666667 of one share of Common
Stock from and after the Split Effective Date (the “New Common Stock”), (b) each
share of Series A Stock issued and outstanding or held as treasury shares
immediately prior to the Split Effective Date (the “Old Series A Stock”) shall
automatically without any action on the part of the holder thereof, be
reclassified and changed into

 

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0.06666667 of one share of Series A Stock from and after the Split Effective
Date (the “New Series A Stock”), (c) each share of Series B Stock issued and
outstanding or held as treasury shares immediately prior to the Split Effective
Date (the “Old Series B Stock”) shall automatically without any action on the
part of the holder thereof, be reclassified and changed into 0.06666667 of one
share of Series B Stock from and after the Split Effective Date (the “New
Series B Stock”) and (d) each share of Series C Stock issued and outstanding or
held as treasury shares immediately prior to the Split Effective Date (the “Old
Series C Stock”) shall automatically without any action on the part of the
holder thereof, be reclassified and changed into 0.06666667 of one share of
Series C Stock from and after the Split Effective Date (the “New Series C
Stock”).  No fractional shares of Common Stock or Preferred Stock shall be
issued upon such reclassification effected by the Reverse Split.  Rather, if
such reclassification would result in the issuance of any fractional share to
any stockholder after aggregating all fractional shares of any class or series
of stock otherwise issuable to such stockholder, the Corporation shall, in lieu
of issuing any fractional share to such stockholder, pay a cash amount to such
stockholder equal to the sum of (A) the product of any fractional share of New
Common Stock pertaining to such stockholder multiplied by $8.142, (B) the
product of any fractional share of New Series A Stock pertaining to such
stockholder multiplied by $8.142, (C) the product of any fractional share of New
Series B Stock pertaining to such stockholder multiplied by $8.142 and (D) the
product of any fractional share of New Series C Stock pertaining to such
stockholder multiplied by $8.142.  Subject to the rest of the provisions of this
Certificate, each holder of a certificate or certificates, which immediately
prior to the Split Effective Date represented outstanding shares of Old Common
Stock, Old Series A Stock, Old Series B Stock and Old Series C Stock, as
applicable (the “Old Certificates”), shall, from and after the Split Effective
Date, be entitled to receive upon surrender of such Old Certificates to the
Corporation’s transfer agent for cancellation, a certificate or certificates
(the “New Certificates”) representing the shares of New Common Stock, New
Series A Stock, New Series B Stock and New Series C Stock, as applicable, into
which the shares of Old Common Stock, Old Series A Stock, Old Series B Stock and
Old Series C Preferred Stock formerly represented by such Old Certificates so
surrendered are reclassified under the terms hereof.  All stock numbers and
prices set forth in this Certificate (including, without limitation, those share
numbers set forth in Article III) give effect to the Reverse Split and no
further adjustments are necessary with respect thereto.

 

ARTICLE III
Capital Stock

 

Authorization. The total number of shares of all classes of stock which the
Corporation shall have authority to issue is Seventy-six Million Thirty-four
Thousand Twenty-nine (76,034,029) shares, consisting of Sixty Three Thousand
(63,000) shares of Series A Junior Convertible Preferred Stock, par value $.01
per share (the “Series A Stock”), One Million Six Hundred Thousand (1,600,000)
shares of Series B Convertible Redeemable Preferred Stock, par value $.01 per
share (the “Series B Stock”), Ten Million One Hundred Forty-six Thousand Six
Hundred Twenty-nine (10,146,629) shares of Series C Convertible Preferred Stock,
par value $.01 per share, (the “Series C Stock”, and together with the Series B
Stock, the “Existing Senior Preferred Stock”, and collectively with the Series A
Stock and Series B Stock, the “Existing Preferred Stock”), Ten Million
(10,000,000) shares of Series A-1 Convertible Preferred Stock, par value $.01
per share (the “Series A-1 Stock”), Nine Million Eight Hundred Thirty-two
Thousand One Hundred Thirty-three (9,832,133) shares of Series A-2 Convertible
Preferred Stock, par value $.01 per share (the “Series A-2 Stock”), One Million
Four Hundred Twenty-two Thousand Three Hundred (1,422,300) shares of Series A-3
Convertible Preferred Stock, par value $.01 per share, (the “Series A-3 Stock”
and together with the Series A-1 Stock and Series A-2 Stock, the “Participating
Preferred Stock”), Forty Thousand and Three (40,003) shares of Series A-4
Convertible Preferred Stock, par value $.01 per share (the “Series A-4 Stock”),
Seventy Thousand (70,000) shares of Series A-5 Convertible Preferred Stock, par
value $.01 per share (the “Series A-5 Stock”) and Eight Million (8,000,000)
shares of Series A-6 Convertible Preferred Stock, par value $.01 per share (the
“Series A-6

 

38

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Stock”, and together with the Series A-1 Stock, the Series A-2 Stock, the
Series A-3 Stock, the Series A-4 Stock and the Series A-5 Stock, the “New
Preferred Stock”), and Thirty-four Million Eight Hundred Fifty-nine Thousand
Nine Hundred Sixty-four (34,859,964) shares of Common Stock, par value $.01 per
share (the “Common Stock”).

 

SPECIAL NOTE:  The terms, conditions, designations, preferences and privileges
of the Existing Preferred Stock are set forth below in Part A of this
Article III, however, it is expected that upon the Stage I Closing (as defined
in the Series A-1 Purchase Agreement) of the Qualified Financing (as defined
herein), all shares of Existing Preferred Stock will be converted into shares of
New Preferred Stock or Common Stock, the terms, conditions, designations,
preferences and privileges of which are set forth in Part B and Part C of this
Article III, respectively.

 

PART A. EXISTING PREFERRED STOCK

 

1.              Designation and Amount.  The number of shares, powers, terms,
conditions, designations, preferences and privileges, relative, participating,
optional and other special rights, and qualifications, limitations and
restrictions, if any, of the Existing Preferred Stock shall be as set forth in
this Part A. The number of authorized shares of the Series A Stock is Sixty
Three Thousand (63,000), the number of authorized shares of the Series B Stock
is One Million Six Hundred Thousand (1,600,000), and the number of authorized
shares of the Series C Stock is Ten Million One Hundred Forty-six Thousand Six
Hundred Twenty-nine (10,146,629).

 

2.              Ranking.  The Corporation’s shares of Series C Stock shall rank,
as to dividends and upon Liquidation (as defined in Section A.4(b) hereof) and
Event of Sale (as defined in Section A.4(h) hereof), equally with each other and
senior and prior to the Corporation’s shares of  Series B Stock and Series A
Stock.  The Corporation’s shares of Series B Stock shall rank, as to dividends
and upon Liquidation and Event of Sale, equally with each other and senior and
prior to the Corporation’s shares of Series A Stock.  With respect to dividends,
Liquidation and Event of Sale prior, the Series A Stock, Series B Stock and
Series C Stock shall rank senior and prior to the Corporation’s Common Stock and
to all other classes or series of stock issued by the Corporation, except as
otherwise approved by the affirmative vote or consent of the holders shares of
Existing Senior Preferred Stock representing at least a majority of the shares
of the voting power of the Existing Senior Preferred Stock then outstanding
(determined as set forth in the second sentence of Section A.6(a) hereof) (the
“Existing Senior Majority”).

 

3.              Dividend Provisions.

 

(a)                                 Series C Stock.  The holders of shares of
the Series C Stock shall be entitled to receive dividends at the rate of 8% of
the Series C Original Purchase Price (as defined in Section A.8 hereof) per
annum, compounding annually, and which will accrue on a quarterly basis
commencing on the applicable date of issuance of each of such shares of Series C
Stock.  The holders of Series C Stock shall be entitled to receive dividends
prior in right to the payment of dividends and other distributions (whether in
cash, property or securities of the Corporation, including subscription or other
rights to acquire securities of the Corporation) on the Series B Stock, Series A
Stock and Common Stock.  Dividends hereunder shall be payable in cash, when, as
and if declared or paid by the Board of Directors and, as accrued, on any
Liquidation (as defined in Section A.4(b) hereof) or Event of Sale (as defined
in Section A.4(h)(vii) hereof), or upon any Redemption Date (as defined in
Section A.5(c) hereof).  Dividends hereunder shall be payable in shares of
Common Stock (calculated based upon the then effective Series C Conversion
Price), as accrued, upon the conversion of the Series C Stock into Common
Stock.  Whenever any dividend may be declared or paid on any shares of Series C
Stock, the Board of Directors shall also declare and pay a dividend on the same
terms, at the same rate and in like kind upon each other share of the Series C
Stock then outstanding, so that all outstanding shares of Series C Stock

 

39

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will participate equally with each other and ratably per share (calculated as
provided in Section A.3(d) hereof).  Whenever any dividend or other
distribution, whether in cash or property or in securities of the Corporation
(or subscription or other rights to purchase or acquire securities of the
Corporation), may be declared or paid on: (i) any shares of the Common Stock,
the Board of Directors shall also declare and pay a dividend on the same terms,
at the same rate and in like kind upon each share of the Series C Stock then
outstanding so that all outstanding shares of Series C Stock will participate in
such dividend ratably with such shares of Common Stock (calculated as provided
in Section A.3(d) hereof); or (ii) any shares of any other series of Preferred
Stock, the Board of Directors shall also declare and pay a dividend on the same
terms, at the same or equivalent rate upon each share of the Series C Stock then
outstanding so that all outstanding shares of Series C Stock will participate in
such dividend ratably with such shares of such other series of Preferred Stock
(based on the number of shares of Common Stock into which each share Series C
Stock and each share of such other series of Preferred Stock is then
convertible, if applicable, or, otherwise, the relative liquidation preference
per share, of such other series of Preferred Stock as compared with the Series C
Stock then outstanding).

 

(b)                                 Series B Stock.  Following payment in full
of required dividends to the holders of Series C Stock in accordance with
Section A.3(a) above, the holders of shares of the Series B Stock shall be
entitled to receive dividends at the rate of 8% of the Series B Original
Purchase Price (as defined in Section A.8 hereof) per annum, compounding
annually, and which will accrue on a quarterly basis commencing on the
applicable date of issuance of each of such shares of Series B Stock.  The
holders of Series B Stock shall be entitled to receive dividends prior in right
to the payment of dividends and other distributions (whether in cash, property
or securities of the Corporation, including subscription or other rights to
acquire securities of the Corporation) on the Series A Stock and Common Stock. 
Dividends hereunder shall be payable in cash, when, as and if declared or paid
by the Board of Directors and, as accrued, on any Liquidation (as defined in
Section A.4(b) hereof) or Event of Sale (as defined in Section A.4(h) hereof),
or upon any Redemption Date (as defined in Section A.5(c) hereof).  Dividends
hereunder shall be payable in shares of Common Stock (calculated based upon the
then effective Series B Conversion Price), as accrued, upon the conversion of
the Series B Stock into Common Stock.  Whenever any dividend may be declared or
paid on any shares of Series B Stock, the Board of Directors shall also declare
and pay a dividend on the same terms, at the same rate and in like kind upon
each other share of the Series B Stock then outstanding, so that all outstanding
shares of Series B Stock will participate equally with each other and ratably
per share (calculated as provided in Section A.3(d) hereof).  Whenever any
dividend, whether in cash or property or in securities of the Corporation (or
subscription or other rights to purchase or acquire securities of the
Corporation), may be declared or paid on: (i) any shares of the Common Stock,
the Board of Directors shall also declare and pay a dividend on the same terms,
at the same rate and in like kind upon each share of the Series B Stock then
outstanding so that all outstanding shares of Series B Stock will participate in
such dividend ratably with such shares of Common Stock (calculated as provided
in Section A.3(d) hereof); or (ii) any shares of Series A Stock, the Board of
Directors shall also declare and pay a dividend on the same terms, at the same
or equivalent rate upon each share of the Series B Stock then outstanding so
that all outstanding shares of Series B Stock will participate in such dividend
ratably with such shares of Series A Stock (based on the number of shares of
Common Stock into which each share of Series B Stock and each share of Series A
Stock is then convertible, if applicable, or, otherwise, the relative
liquidation preference per share, of Series A Stock as compared with the
Series B Stock then outstanding).

 

(c)                                  Series A Stock.  Following payment in full
of required dividends to the holders of Series C Stock and Series B Stock in
accordance with Sections A.3(a) and (b) above, the holders of shares of the
Series A Stock shall be entitled to receive, when, if and as declared by the
Board of Directors, dividends on any shares of Series A Stock, out of funds
legally available for that purpose, at a rate to be determined by the Board of
Directors if and when they may so declare any dividend on the Series A Stock.

 

40

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(d)                                 In connection with any dividend declared or
paid hereunder, each share of Existing Preferred Stock shall be deemed to be
that number of shares (including fractional shares) of Common Stock into which
it is then convertible, rounded up to the nearest one-tenth of a share.  No
fractional shares of capital stock shall be issued as a dividend hereunder. The
Corporation shall pay a cash adjustment for any such fractional interest in an
amount equal to the fair market value thereof on the last Business Day (as
defined in Section A.8 hereof) immediately preceding the date for payment of
dividends as determined by the Board of Directors in good faith.

 

4.              Liquidation Rights.

 

(a)                                 With respect to rights on Liquidation (as
defined in Section A.4(b) hereof): (i) the shares of Series C Stock shall rank
equally with each other and senior and prior to the shares of Series B Stock,
Series A Stock and the Common Stock and to all other classes or series of stock
issued by the Corporation, except as otherwise approved by the affirmative vote
or consent of the Existing Senior Majority; (ii) the shares of Series B Stock
shall rank equally with each other and senior and prior to the shares of
Series A Stock and the shares of Common Stock and to all other junior classes or
series of stock issued by the Corporation, and junior to the Series C Stock; and
(iii) the Series A Stock shall rank senior and prior to the Corporation’s Common
Stock and to all other junior classes or series of stock issued by the
Corporation, and junior to the Existing Senior Preferred Stock.

 

(b)                                 In the event of any liquidation, dissolution
or winding-up of the affairs of the Corporation (collectively, a “Liquidation”):
(i) the holders of shares of Series C Stock then outstanding (the “Series C
Stockholders”) shall be entitled to receive out of the assets of the Corporation
legally available for distribution to its stockholders, whether from capital,
surplus or earnings, before any payment shall be made to the holders of Series B
Stock then outstanding (the “Series B Stockholders”), the holders of Series A
Stock then outstanding (the “Series A Stockholders,” and collectively with the
Series C Stockholders and the Series B Stockholders, the “Existing Preferred
Stockholders”), or the holders of Common Stock or any other class or series of
stock ranking on Liquidation junior to such Series C Stock, an amount per share
equal to the Series C Original Purchase Price (as defined in Section A.8
hereof), plus an amount equal to any declared or accrued but unpaid dividends
thereon, calculated pursuant to Section A.3(a) hereof; (ii) after the
distribution to the Series C Stockholders of the full amount to which they are
entitled to receive pursuant to this Section A.4(b), the Series B Stockholders
shall be entitled to receive out of the assets of the Corporation legally
available for distribution to its stockholders, whether from capital, surplus or
earnings, before any payment shall be made to the Series A Stockholders or the
holders of Common Stock or any other class or series of stock ranking on
Liquidation junior to such Series B Stock, an amount per share equal to the
Series B Original Purchase Price (as defined in Section A.8 hereof), plus an
amount equal to any declared or accrued but unpaid dividends thereon, calculated
pursuant to Section A.3(b) hereof; and (iii) after the distribution to the
Series B Stockholders of the full amount to which they are entitled to receive
pursuant to this Section A.4(b), the Series A Stockholders shall be entitled to
receive out of the assets of the Corporation legally available for distribution
to its stockholders, whether from capital, surplus or earnings, before any
payment shall be made to the holders of Common Stock or any other class or
series of stock ranking on Liquidation junior to such Series A Stock, an amount
per share equal to the Series A Original Purchase Price (as defined in
Section A.8 hereof), plus an amount equal to any declared but unpaid dividends
thereon, calculated pursuant to Section A.3(c) hereof. Notwithstanding the
foregoing or anything else expressed or implied herein, the transactions
contemplated by that certain Agreement and Plan of Merger dated as of April 25,
2011 by and among the Corporation, MPM Acquisition Corp. and RHI Merger Corp.
(the “Merger Agreement”) shall not be a “Liquidation” for purposes of this
Certificate.

 

(c)                                  If, upon any Liquidation the assets of the
Corporation available for distribution to its stockholders shall be insufficient
to pay the Series C Stockholders the full amount to which each of

 

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them shall be entitled pursuant to Section A.4(b) above, then the Series C
Stockholders shall share ratably in any distribution of assets according to the
respective amounts which would be payable to them in respect of the shares of
Series C Stock held upon such distribution if all amounts payable on or with
respect to such shares were paid in full.

 

(d)                                 If, upon any Liquidation the assets of the
Corporation available for distribution to its stockholders shall be insufficient
to pay the Series B Stockholders the full amount to which each of them shall be
entitled pursuant to Section A.4(b) above, then after payment to the Series C
Stockholders of the full amount to which such stockholders are entitled pursuant
to Section A.4(b) above, the Series B Stockholders shall share ratably in any
remaining distribution of assets according to the respective amounts which would
be payable to them in respect of the shares of Series B Stock held upon such
distribution if all amounts payable on or with respect to such shares were paid
in full.

 

(e)                                  If, upon any Liquidation the assets of the
Corporation available for distribution to its stockholders shall be insufficient
to pay the Series A Stockholders the full amount to which each of them shall be
entitled pursuant to Section A.4(b) above, then after payment to the Series C
Stockholders and Series B Stockholders of the full amount to which such
stockholders are entitled pursuant to Section A.4(b) above, the Series A
Stockholders shall share ratably in any remaining distribution of assets
according to the respective amounts which would be payable to them in respect of
the shares of Series A Stock held upon such distribution if all amounts payable
on or with respect to such shares were paid in full.

 

(f)                                   In the event of any Liquidation, after
payment shall have been made to the Existing Preferred Stockholders of the full
amount to which they shall be entitled pursuant to Section A.4(b), the holders
of each other class or series of capital stock (other than Common Stock) ranking
on Liquidation junior to such Series C Stock, Series B Stock and Series A Stock
(in descending order of seniority), but senior to the Common Stock, as a class,
shall be entitled to receive an amount equal (and in like kind) to the aggregate
preferential amount fixed for each such junior class or series of capital
stock.  If, upon any Liquidation prior to the Initial Closing of the Qualified
Financing, after payment shall have been made to the Existing Preferred
Stockholders of the full amount to which they shall be entitled pursuant to
Section A.4(b), the assets of the Corporation available for distribution to its
stockholders shall be insufficient to pay a class or series of capital stock
(other than the Common Stock) junior to the Series C Stock, Series B Stock and
Series A Stock the full amount to which they shall be entitled pursuant to the
preceding sentence, the holders of such other class or series of capital stock
shall share ratably, based upon the number of then outstanding shares of such
other class or series of capital stock, in any remaining distribution of assets
according to the respective preferential amounts fixed for such junior class or
series of capital stock or which would be payable to them in respect of the
shares held by them upon such distribution if all amounts payable on or with
respect to such shares were paid in full.

 

(g)                                  In the event of any Liquidation prior,
after payments shall have been made first to the Existing Preferred Stockholders
and then to the holders of each junior class or series of capital stock (other
than Common Stock) which is junior to the Series C Stock, Series B Stock and the
Series A Stock but senior to the Common Stock, of the full amount to which they
each shall be entitled as aforesaid, the holders of Common Stock, as a class,
shall be entitled to share ratably with the Series C Stockholders and Series B
Stockholders (calculated with respect to such Series C Stock and Series B Stock
as provided in the last sentence in this Section A.4(g)) in all remaining assets
of the Corporation legally available for distribution to its stockholders.  For
purposes of calculating the amount of any payment to be paid upon any such
Liquidation pursuant to the participation feature described in this
Section A.4(g), each share of such Existing Senior Preferred Stock shall be
deemed to be that number of shares (including fractional shares and any shares
attributable to the payment of accrued and unpaid

 

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dividends upon conversion of such Preferred Stock pursuant to Section A.7(b)) of
Common Stock into which it is then convertible, rounded to the nearest one-tenth
of a share.

 

(h)                                 (i) In the event of and simultaneously with
the closing of an Event of Sale (as hereinafter defined), the Corporation shall,
unless waived by the Existing Senior Majority or otherwise prevented by law,
redeem all of the shares of Series C Stock, Series B Stock and Series A Stock
then outstanding for a cash amount per share determined as set forth below in
this Section A.4(h) hereof (the “Special Liquidation Price,” said redemption
being referred to herein as a “Special Liquidation”).  In the event the Event of
Sale involves consideration that does not consist of cash, then the Special
Liquidation Price may be paid with such consideration having a value equal to
the Special Liquidation Price.  To the extent there is any cash consideration in
connection with an Event of Sale, at the option of the holders of a majority of
the Series C Stock, the cash consideration will first (i) be applied to satisfy
the Special Liquidation Price payable to the Series C Stockholders (in relative
proportion to the full liquidation preference the Series C Stockholders would
have received had there been sufficient cash consideration to have paid their
liquidation preference in full); then (ii) be applied to satisfy the Special
Liquidation Price payable to the holders of Series B Stock (in relative
proportion to the full liquidation preference the Series B Stockholders would
have received had there been sufficient cash consideration to have paid their
liquidation preference in full), prior to the payment thereof to any other
stockholders of the Corporation; and (iii) then be applied to satisfy the
Special Liquidation Price payable to the holders of Series A Stock (in relative
proportion to the full liquidation preference the Series A Stockholders would
have received had there been sufficient cash consideration to have paid their
liquidation preference in full), prior to the payment thereof to any other
stockholders of the Corporation.  For all purposes of this Section A.4(h), the
Special Liquidation Price shall be equal to that amount per share which would be
received by each Existing Preferred Stockholder if, in connection with an Event
of Sale, all the consideration paid in exchange for the assets or the shares of
capital stock (as the case may be) of the Corporation were actually paid to and
received by the Corporation and the Corporation were immediately thereafter
liquidated and its assets distributed pursuant to Sections A.4(a) through
(h) hereof.  To the extent that one or more redemptions (as described in
Section A.5 hereof) and/or Special Liquidations are occurring concurrently, the
Special Liquidation under this Section A.4(h) shall be deemed to occur first. 
The date upon which the Special Liquidation shall occur is sometimes referred to
herein as the “Special Liquidation Date”.

 

(ii)                                  In the absence of an applicable waiver
pursuant to Section A.4(h)(i) above, at any time on or after the Special
Liquidation Date, an Exisiting Preferred Stockholder shall be entitled to
receive the Special Liquidation Price for each such share of Series C Stock,
Series B Stock or Series A Stock owned by such holder.  Subject to the
provisions of Section A.4(h)(iii) hereof, payment of the Special Liquidation
Price will be made to each such holder upon actual delivery to the Corporation
or its transfer agent of the certificate of such holder representing such shares
of Series A Stock, Series B Stock or Series C Stock, as the case may be, or an
affidavit of loss as to the same.

 

(iii)                               If on the Special Liquidation Date less than
all the shares of either Series C Stock, Series B Stock or Series A Stock then
outstanding may be legally redeemed by the Corporation, the Special Liquidation
shall be made first as to the Series C Stock pro rata with respect to such
Series C Stock based upon the number of outstanding shares of Series C Stock
then owned by each such holder thereof until such holders are satisfied in full,
then to the holders of the Series B Stock pro rata with respect to such Series B
Stock based upon the number of outstanding shares of Series B Stock then owned
by each holder thereof, and then to the holders of the Series A Stock pro rata
with respect to such Series A Stock based upon the number of outstanding shares
of Series A Stock then owned by each holder thereof.

 

(iv)                              On and after any Special Liquidation Date, all
rights in respect of the shares of Existing Preferred Stock to be redeemed shall
cease and terminate except the right to receive the applicable Special
Liquidation Price as provided herein, and such shares of Existing Preferred
Stock shall

 

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no longer be deemed to be outstanding, whether or not the certificates
representing such shares of Existing Preferred Stock have been received by the
Corporation; provided, however, that, if the Corporation defaults in the payment
of the Special Liquidation Price with respect to any Existing Preferred Stock,
the rights of the holder(s) thereof with respect to such shares of Existing
Preferred Stock shall continue until the Corporation cures such default.

 

(v)                                 Anything contained herein to the contrary
notwithstanding, all or any of the provisions of this Section A.4(h) may be
waived by the Existing Senior Majority, by delivery of written notice of waiver
to the Corporation prior to the closing of any Event of Sale.

 

(vi)                              Any notice required to be given to the holders
of shares of Preferred Stock pursuant to Section A.7(g) hereof in connection
with an Event of Sale shall include a statement by the Corporation of (A) the
Special Liquidation Price which each Preferred Stockholder shall be entitled to
receive upon the occurrence of a Special Liquidation under this
Section A.4(h) and (B) the extent to which the Corporation will, if at all, be
legally prohibited from paying each holder of Preferred Stock the Special
Liquidation Price.

 

(vii)                           For purposes of this Section A.4(h), an “Event
of Sale” shall mean: (A) the sale by the stockholders of voting control of the
Corporation, (B) the merger, consolidation or reorganization with or into any
other corporation, entity or person or any other corporate reorganization, in
which (I) the capital stock of the Corporation immediately prior to such merger,
consolidation or reorganization represents less than 50% of the voting power of
the surviving entity (or, if the surviving entity is a wholly owned subsidiary,
its parent) immediately after such merger, consolidation or reorganization or
(II) the surviving entity (or, if the surviving entity is a wholly owned
subsidiary, its parent) has a class of securities that is (or has been within 90
days prior to such transaction) tradeable on any public market or exchange or
(C) the sale, exclusive license or other disposition of all or substantially all
of the assets or intellectual property of the Corporation in a single
transaction or series of related transactions. Notwithstanding the foregoing or
anything else expressed or implied herein, the transactions contemplated by the
Merger Agreement shall not be an “Event of Sale” for purposes of this
Certificate.

 

5.              Redemption.

 

(a)                                 At the request of the Existing Senior
Majority (the “Requesting Holders”) made at any time on or after December 15,
2011, the Corporation shall redeem on the Redemption Date, unless otherwise
prevented by law, at a redemption price per share equal to the Series C Original
Purchase Price for each share of Series C Stock and Series B Original Purchase
Price for each share of Series B Stock, plus in each case an amount equal to any
declared or accrued but unpaid dividends thereon, all of the Existing Senior
Preferred Stock outstanding at the time that such request is made.  The total
sum payable per share of Existing Senior Preferred Stock on the Redemption Date
is hereinafter referred to as the “Redemption Price,” and the payment to be made
on the Redemption Date is hereinafter referred to as the “Redemption Payment.” 
Notwithstanding any limitations specified in this Section A.5, in the event that
the Corporation at any time breaches any of the provisions in the this
Certificate or any of its representations, warranties, covenants and/or
agreements set forth in (i) that certain Stockholders’ Agreement among the
Corporation and the parties set forth therein (as amended, the “Stockholders’
Agreement”) or that certain Series C Convertible Redeemable Preferred Stock
Purchase Agreement among the Corporation and the signatories thereto (the “Stock
Purchase Agreement”), each as entered into contemporaneously with the filing of
the Prior Certificate, or (ii) that certain Series B Convertible Redeemable
Preferred Stock Purchase Agreement dated as of November 14, 2003 among the
Corporation and the signatories thereto (as amended, the “Series B Stock
Purchase Agreement”), then upon any such breach the Senior Majority may elect,
at their sole discretion, if any such breach is not cured by the 60th day after
receipt by the Corporation of notice of such breach from a holder, to accelerate
the maturity of

 

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the rights of all of the holders under this Section A.5(a) and cause the
immediate redemption of all of the shares of Existing Senior Preferred Stock
held by them (less any shares that the Corporation is prevented by law from
redeeming, which shall be redeemed by the Corporation as soon as permitted under
law).  With respect to a breach of which the Corporation is aware or reasonably
should be aware, such 60 day period within which the Corporation shall have the
right to cure such breach shall be deemed to have commenced on the tenth day
after the occurrence of such breach, irrespective of notice of such breach from
any holder, if the Corporation shall not have notified the holders of such
breach by such date.

 

(b)                                 On and after the Redemption Date, all rights
of any Requesting Holder with respect to those shares of Existing Senior
Preferred Stock being redeemed by the Corporation pursuant to Section A.5(a),
except the right to receive the applicable Redemption Price per share, shall
cease and terminate, and such shares of Existing Senior Preferred Stock shall no
longer be deemed to be outstanding, whether or not the certificates representing
such shares have been received by the Corporation; provided, however, that,
notwithstanding anything to the contrary set forth herein, (A) if the
Corporation defaults in the payment of the Redemption Payment, the rights of the
Requesting Holder with respect to its shares of Existing Senior Preferred Stock
shall continue until the Corporation cures such default, and (B) without
limiting any other rights of a Requesting Holder, upon the occurrence of a
subsequent Liquidation, with respect to the shares of Existing Senior Preferred
Stock in respect of which no Redemption Payment has been received by a
Requesting Holder, such Requesting Holder shall be accorded the rights and
benefits set forth in Section A.4 hereof in respect of such remaining shares, as
if no prior redemption request had been made.

 

(c)                                  If the Requesting Holders elect to exercise
redemption rights hereunder, such Requesting Holders shall send notice of such
election (the “Redemption Notice”) by first-class, certified mail, return
receipt requested, postage prepaid, to the Corporation at its principal place of
business or to any transfer agent of the Corporation.  Within five (5) Business
Days after receipt of the Redemption Notice, the Corporation shall notify in
writing all other Existing Senior Preferred Stockholders of the request by a
Requesting Holder for the redemption of Existing Senior Preferred Stock (the
“Corporation Notice”).  On the twentieth (20th) Business Day following the date
upon which the Corporation received the Redemption Notice, the Corporation shall
pay each holder of Existing Senior Preferred Stock the applicable Redemption
Price pursuant to the terms of Section A.5(a), provided that the Corporation or
its transfer agent has received the certificate(s) representing the shares of
Existing Senior Preferred Stock to be redeemed.  Such payment date shall be
referred to herein as the “Redemption Date.”  If, on the Redemption Date, less
than all the shares of Existing Senior Preferred Stock may be legally redeemed
by the Corporation, the redemption of Existing Senior Preferred Stock shall be
pro rata according to the respective amounts which would be payable to the
Existing Senior Preferred Stockholders in respect of their shares of Existing
Senior Preferred Stock if the Redemption Price were paid in full for all such
shares, and any shares of Existing Senior Preferred Stock not redeemed shall be
redeemed on the first date following such Redemption Date on which the
Corporation may lawfully redeem such shares (pro rata according to the
respective amounts which would be payable to the Existing Senior Preferred
Stockholders in respect of the remaining shares of Existing Senior Preferred
Stock if the Redemption Price were paid in full for all such shares).  The
Corporation shall redeem (to the extent permitted by law) the shares of Existing
Senior Preferred Stock on the Redemption Date and the Corporation shall promptly
advise each holder of Existing Senior Preferred Stock of the Redemption Date or
of the relevant facts applicable thereto preventing such redemption.  Upon
redemption of only a portion of the number of shares covered by a Existing
Senior Preferred Stock certificate, the Corporation shall issue and deliver to
or upon the written order of the holder of such Existing Senior Preferred Stock
certificate, at the expense of the Corporation, a new certificate covering the
number of shares of the Existing Senior Preferred Stock representing the
unredeemed portion of the Existing Senior Preferred Stock certificate, which new
certificate shall entitle the holder thereof to all the rights, powers and
privileges of a holder of such shares.

 

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(d)                                 Shares of the Existing Senior Preferred
Stock are not subject to or entitled to the benefit of any sinking fund.

 

6.              Voting.

 

(a)                                 Subject to any separate voting rights
provided for herein or otherwise required by law, for so long as Existing Senior
Preferred Stock remains outstanding, the holders of Existing Preferred Stock
shall be entitled to vote, together with the holders of Common Stock as one
class, on all matters as to which holders of Common Stock shall be entitled to
vote, in the same manner and with the same effect as such holders of Common
Stock.  In any such vote, each share of Existing Preferred Stock shall entitle
the holder thereof to the number of votes per share that equals the number of
shares of Common Stock (including fractional shares) into which each such share
of Preferred Stock is then convertible, rounded up to the nearest one-tenth of a
share, but not including any shares of Common Stock issuable upon conversion of
any dividends accrued on such Existing Preferred Stock.

 

(b)                                 In addition to the rights specified in
Section A.6(a), for so long as any shares of Existing Senior Preferred Stock are
outstanding, the holders of the Existing Senior Preferred Stock, voting as a
separate class, shall have the right to elect six (6) members of the Board of
Directors of the Corporation (such directors, the “Existing Preferred
Directors”).  In any election of Existing Preferred Directors pursuant to this
Section A.6(b), each holder of Existing Senior Preferred Stock shall be entitled
to one vote for each share of Common Stock (including fractional shares) into
which each such share of Existing Senior Preferred Stock is then convertible,
rounded up to the nearest one-tenth of a share (determined as set forth in the
second sentence of Section A.6(a) hereof), and no holder of Existing Senior
Preferred Stock shall be entitled to cumulate its votes by giving one candidate
more than one vote per share.  The voting right of the holders of Existing
Senior Preferred Stock, contained in this Section A.6(b), may be exercised at a
special meeting of the holders of Existing Senior Preferred Stock called as
provided in accordance with the by-laws of the Corporation, at any annual or
special meeting of the stockholders of the Corporation, or by written consent of
such holders of Existing Senior Preferred Stock in lieu of a meeting.  The
Existing Preferred Directors elected pursuant to this Section A.6(b) shall serve
from the date of their election and qualification until their successors have
been duly elected and qualified.

 

(c)                                  A vacancy in the directorships elected by
the holders of Existing Senior Preferred Stock pursuant to Section A.6(b), may
be filled by a vote at a meeting called in accordance with the by-laws of the
Corporation or written consent in lieu of such meeting of the holders of such
Existing Senior Preferred Stock.

 

(d)                                 For so long as Existing Preferred Stock
remains outstanding, the holders of capital stock of the Corporation, voting as
a single class, shall elect the remaining member or members of the Board of
Directors of the Corporation.  In any election of directors pursuant to this
Section A.6(d), each stockholder shall be entitled to one vote for each share of
Common Stock held or, if Existing Preferred Stock, into which each such share of
Existing Preferred Stock is then convertible (determined in accordance with
Section A.6(a) hereof), and no stockholder shall be entitled to cumulate its
votes by giving one candidate more than one vote per share.  The voting right of
the stockholders contained in this Section A.6(d) apply only so long as shares
of Existing Preferred Stock remains and outstanding and may be exercised at a
special meeting of the stockholders called as provided in accordance with the
by-laws of the Corporation, at any annual or special meeting of the stockholders
of the Corporation, or by written consent of the stockholder in lieu of a
meeting.  The director or directors elected pursuant to this
Section A.6(d) shall serve from the date of their election and qualification
until their successors have been duly elected and qualified.

 

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(e)                                  A vacancy in the directorship or
directorships elected by the stockholders pursuant to Section A.6(d), may be
filled by a vote at a meeting called in accordance with the by-laws of the
Corporation or written consent in lieu of such meeting of the stockholders of
the Corporation.

 

(f)                                   For so long as shares of Existing
Preferred Stock are outstanding, the Corporation shall not, directly or
indirectly, through a merger, consolidation, reorganization or otherwise,
without the affirmative approval of the Existing Senior Majority, acting
separately from the holders of Common Stock or any other securities of the
Corporation, given by written consent in lieu of a meeting or by vote at a
meeting called for such purpose, for which meeting or approval by written
consent timely and specific notice in the manner provided in the by-laws of the
Corporation (“Notice”) shall have been given to each holder of such Existing
Senior Preferred Stock, do the following:

 

(i)                                     sell, abandon, transfer, lease or
otherwise dispose of all or substantially all of its or any subsidiary’s
properties or assets;

 

(ii)                                  sell, abandon, transfer, exclusively
license or otherwise dispose of or encumber any of its material intellectual
property;

 

(iii)                               purchase, lease or otherwise acquire all or
substantially all of the assets of another entity or acquire the securities of
any other entity;

 

(iv)                              except as otherwise required by this
Certificate or as contemplated in the Series A-1 Purchase Agreement, alter the
rights, preferences or privileges of or reclassify any of its or its
subsidiaries’ securities or declare or pay any dividend or make any distribution
with respect to shares of its capital stock (whether in cash, shares of capital
stock or other securities or property);

 

(v)                                 except as otherwise required by this
Certificate or as contemplated in the Series A-1 Purchase Agreement, make any
payment on account of the purchase, redemption, or other retirement of any share
of capital stock of the Corporation or any subsidiary, or distribute to holders
of Series B Stock, Series A Stock or Common Stock shares of the Corporation’s
capital stock (other than Common Stock in connection with a stock split by way
of stock dividend) or other securities of other entities, evidences of
indebtedness issued by the Corporation or other entities, or other assets or
options or rights other than the repurchase of shares of Common Stock issued
pursuant to the Corporation’s 2003 Long-Term Incentive Plan, as amended, for
employees or consultants;

 

(vi)                              except as contemplated by the Merger Agreement
(as defined herein) merge, consolidate or reorganize with or into, or permit any
subsidiary to merge, consolidate or reorganize with or into, any other
corporation or corporations or other entity or entities;

 

(vii)                           voluntarily dissolve, liquidate or wind-up or
carry out any partial liquidation or distribution or transaction in the nature
of a partial liquidation or distribution;

 

(viii)                        except as otherwise required by this Certificate
or as contemplated in the Series A-1 Purchase Agreement, in any manner alter or
change the designations, powers, preferences, rights, qualifications,
limitations or restrictions of the Series C Stock or Series B Stock;

 

(ix)                              take any action to cause any amendment,
alteration or repeal of any of the provisions of this Certificate or the by-laws
of the Corporation or the organizational documents of the Corporation’s
subsidiaries if any;

 

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(x)                                 except as otherwise required by this
Certificate or as contemplated in the Series A-1 Purchase Agreement and except
for the issuance of capital stock or other securities constituting shares of
Excluded Stock (as defined in Section A.7(e)(ii) below), authorize, designate,
create, increase or decrease the authorized number of, reclassify, or issue or
agree to issue any equity or debt security of the Corporation or any subsidiary
or any security, right, option or warrant convertible into, or exercisable or
exchangeable for, shares of the capital stock of the Corporation or any
capitalized lease with an equity feature with respect to the capital stock of
the Corporation;

 

(xi)                              adopt, approve, amend or modify any stock
option plan of the Corporation or adopt, approve amend or modify the form of any
stock option agreement or restricted stock purchase agreement, or amend or
modify any stock option agreement or restricted stock purchase agreement entered
into between the Corporation and its employees, directors or consultants except
for immaterial changes made thereto from time to time by officers of the
Corporation;

 

(xii)                           accelerate the vesting schedule or exercise date
or dates of any such options or in any stock option agreement or restricted
stock purchase agreement entered into between the Corporation and its directors,
officers, employees, consultants or independent contractors, or waive or modify
the Corporation’s repurchase rights with respect to any shares of the
Corporation’s stock issuable pursuant to any restricted stock purchase agreement
entered into between the Corporation and its directors, officers, employees,
consultants or independent contractors;

 

(xiii)                        grant any stock options with an exercise price per
share that is less than the fair market value of such share on the date of such
grant (as determined by the Board of Directors of the Corporation) or issue or
sell capital stock of the Corporation pursuant to restricted stock awards or
restricted stock purchase agreements at a price per share less than the fair
market value of such share on the date of such issuance or sale (as determined
by the Board of Directors of the Corporation);

 

(xiv)                       increase the number of shares of Common Stock
authorized for issuance under the Corporation’s 2003 Long-Term Incentive Plan,
as amended;

 

(xv)                          except as otherwise required by this Certificate
or as contemplated in the Series A-1 Purchase Agreement, increase or decrease
the authorized number of the members of the Board of Directors;

 

(xvi)                       participate or allow any subsidiary to participate
in any business other than which it is engaged as of the date of this
Certificate or subsequent to the date of this Certificate as approved by the
Board of Directors; or

 

(xvii)                    incur any indebtedness by the Corporation or any
subsidiary above and beyond the amounts set forth herein, in the Series A-1
Purchaser Agreement or in the Stockholders’ Agreement.

 

The foregoing approval shall be obtained in addition to any approval required by
law.

 

(g)                                  The Corporation shall obtain the consent of
the Board of Directors before it may authorize or issue any additional shares of
capital stock of the Corporation, other than the issuance of any shares of New
Preferred Stock as contemplated by this Certificate or the Series A-1 Purchase
Agreement, or any of its subsidiaries.

 

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7.              Conversion.

 

(a)                                 Any Existing Preferred Stockholder shall
have the right, at any time or from time to time, to convert any or all of its
shares of Existing Preferred Stock into that number of fully paid and
nonassessable shares of Common Stock for each share of Existing Preferred Stock
so converted equal to the quotient of the Series A Original Purchase Price,
Series B Original Purchase Price or Series C Original Purchase Price, as
applicable, for such share divided by the Series A Conversion Price, the
Series B Conversion Price or the Series C Conversion Price (each as defined in
Section A.7(e) hereof), as applicable, for such share of Existing Preferred
Stock, as last adjusted and then in effect, rounded up to the nearest one-tenth
of a share; provided, however, that cash shall be paid in lieu of the issuance
of fractional shares of Common Stock, as provided in Section A.7(d) hereof.

 

(b)                                 (i) Any Existing Preferred Stockholder who
exercises the right to convert shares of Existing Preferred Stock into shares of
Common Stock, pursuant to this Section A.7 shall be entitled to payment of all
accrued dividends, whether or not declared and all declared but unpaid dividends
payable with respect to such Existing Preferred Stock pursuant to Section A.3
herein, up to and including the Conversion Date (as defined in
Section A.7(b)(iii) hereof).

 

(ii)                                  Any Existing Preferred Stockholder may
exercise the right to convert such shares into Common Stock pursuant to this
Section A.7 by delivering to the Corporation during regular business hours, at
the office of the Corporation or any transfer agent of the Corporation or at
such other place as may be designated by the Corporation, the certificate or
certificates for the shares to be converted (the “Existing Preferred
Certificate”), duly endorsed or assigned in blank to the Corporation (if
required by it) or an affidavit of loss as to the same.

 

(iii)                               Each Existing Preferred Certificate shall be
accompanied by written notice stating that such holder elects to convert such
shares and stating the name or names (with address) in which the certificate or
certificates for the shares of Common Stock (the “Common Certificate”) are to be
issued.  Such conversion shall be deemed to have been effected on the date when
such delivery is made, and such date is referred to herein as the “Conversion
Date.”

 

(iv)                              As promptly as practicable thereafter, the
Corporation shall issue and deliver to or upon the written order of such holder,
at the place designated by such holder, (A) a Common Certificate for the number
of full shares of Common Stock to which such holder is entitled and (B) a check
or cash in respect of any fractional interest in shares of Common Stock to which
such holder is entitled, as provided in Section A.7(d) hereof, payable with
respect to the shares so converted up to and including the Conversion Date.

 

(v)                                 The person in whose name the Common
Certificate or Certificates are to be issued shall be deemed to have become a
holder of record of Common Stock on the applicable Conversion Date, unless the
transfer books of the Corporation are closed on such Conversion Date, in which
event the holder shall be deemed to have become the stockholder of record on the
next succeeding date on which the transfer books are open, provided that the
Series A Conversion Price, Series B Conversion Price or Series C Conversion
Price, as applicable, upon which the conversion shall be executed shall be that
in effect on the Conversion Date.

 

(vi)                              Upon conversion of only a portion of the
number of shares covered by an Existing Preferred Certificate, the Corporation
shall issue and deliver to or upon the written order of the holder of such
Existing Preferred Certificate, at the expense of the Corporation, a new
certificate covering the number of shares of Existing Preferred Stock
representing the unconverted portion of the Existing Preferred Certificate,
which new certificate shall entitle the holder thereof to all the rights, powers
and privileges of a holder of such Existing Preferred Stock.

 

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(c)                                  If an Existing Preferred Stockholder shall
surrender more than one share of the same class of Existing Preferred Stock for
conversion at any one time, then the number of full shares of Common Stock
issuable upon conversion thereof shall be computed on the basis of the aggregate
number of shares of Existing Preferred Stock so surrendered.

 

(d)                                 No fractional shares of Common Stock shall
be issued upon conversion of Existing Preferred Stock. The Corporation shall
instead pay a cash adjustment for any such fractional interest in an amount
equal to the Current Market Price thereof on the Conversion Date, as determined
in accordance with Section A.7(e)(vii) hereof.

 

(e)                                  For all purposes of this Article III,
Part A, the initial conversion price of the Series A Stock shall be the Series A
Original Purchase Price, the initial conversion price of the Series B Stock
shall be the Series B Original Purchase Price and the initial conversion price
of the Series C Stock shall be the Series C Original Purchase Price, in each
case subject to adjustment from time to time as follows (the conversion price of
any or each of the Series A Stock, Series B Stock and the Series C Stock, as
adjusted from time to time, is sometimes referred to generically in this
Section A.7 as the “Conversion Price”):

 

(i)                                     Subject to Section A.7(e)(ii) and
A.7(e)(x) below, if the Corporation shall, at any time or from time to time
after the Effective Time, issue or sell any shares of Common Stock (which term,
for purposes of this Section A.7(e)(i), including all subsections thereof, shall
be deemed to include all other securities convertible into, or exchangeable or
exercisable for, shares of Common Stock (including, but not limited to, Existing
Preferred Stock) or options to purchase or other rights to subscribe for such
convertible or exchangeable securities, in each case other than Excluded Stock
(as defined in Section A.7(e)(ii) below), for a consideration per share less
than the Series C Conversion Price in effect immediately prior to the issuance
of such Common Stock or other securities (a “Dilutive Issuance”), then (X) the
Conversion Price for the Series A Stock (the “Series A Conversion Price”) in
effect immediately prior to each such Dilutive Issuance shall automatically be
reduced to a price equal to the product obtained by multiplying such Series A
Conversion Price by a fraction, the numerator of which shall be the number of
shares of Common Stock outstanding immediately prior to such issuance
(including, without limitation, shares of Common Stock issued or issuable upon
conversion of the outstanding Existing Preferred Stock, upon exercise of
outstanding stock options and warrants or otherwise under Section A.7(e)(i)(d))
plus the number of shares of Common Stock that the aggregate consideration
received by the Corporation for the additional stock so issued would purchase at
such Series C Conversion Price as in effect immediately prior to such issuance,
and the denominator of which shall be the number of shares of Common Stock
outstanding immediately prior to such issuance (including, without limitation,
shares of Common Stock issued or issuable upon conversion of the outstanding
Existing Preferred Stock, upon exercise of outstanding stock options or
otherwise under Section A.7(e)(i)(d)) plus the number of shares of additional
stock so issued, (Y) the Conversion Price for the Series B Stock (the “Series B
Conversion Price”) in effect immediately prior to each such Dilutive Issuance
shall automatically be reduced to a price equal to the product obtained by
multiplying such Series B Conversion Price by a fraction, the numerator of which
shall be the number of shares of Common Stock outstanding immediately prior to
such issuance (including, without limitation, shares of Common Stock issued or
issuable upon conversion of the outstanding Existing Preferred Stock, but
excluding shares of Common Stock issuable upon conversion of any dividends
accrued on such Existing Preferred Stock) plus the number of shares of Common
Stock that the aggregate consideration received by the Corporation for the
additional stock so issued would purchase at such Series C Conversion Price as
in effect immediately prior to such issuance, and the denominator of which shall
be the number of shares of Common Stock outstanding immediately prior to such
issuance (including, without limitation, shares of Common Stock issued or
issuable upon conversion of the outstanding Existing Preferred Stock, but
excluding shares of Common Stock issuable upon conversion of any dividends
accrued on such Preferred Stock) plus the number of shares of

 

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additional stock so issued, and (Z) the Conversion Price for the Series C Stock
(the “Series C Conversion Price”) in effect immediately prior to each such
Dilutive Issuance shall automatically be reduced to a price equal to the product
obtained by multiplying such Series C Conversion Price by a fraction, the
numerator of which shall be the number of shares of Common Stock outstanding
immediately prior to such issuance (including, without limitation, shares of
Common Stock issued or issuable upon conversion of the outstanding Existing
Preferred Stock, but excluding shares of Common Stock issuable upon conversion
of any dividends accrued on such Existing Preferred Stock) plus the number of
shares of Common Stock that the aggregate consideration received by the
Corporation for the additional stock so issued would purchase at such Series C
Conversion Price as in effect immediately prior to such issuance, and the
denominator of which shall be the number of shares of Common Stock outstanding
immediately prior to such issuance (including, without limitation, shares of
Common Stock issued or issuable upon conversion of the outstanding Existing
Preferred Stock, but excluding shares of Common Stock issuable upon conversion
of any dividends accrued on such Existing Preferred Stock) plus the number of
shares of additional stock so issued.  For purposes of this Section A.7(e)(i),
the number of shares of Common Stock deemed issuable upon conversion of such
outstanding shares of Existing Preferred Stock shall be determined without
giving effect to any adjustments to the applicable Conversion Price resulting
from the Dilutive Issuance that is the subject of this calculation.  For the
purposes of any adjustment of the Conversion Price pursuant to this
Section A.7(e)(i), the following provisions shall be applicable.

 

a.                                      In the case of the issuance of Common
Stock in whole or in part for cash, the consideration shall be deemed to be the
amount of cash paid therefor after deducting therefrom any discounts,
commissions or other expenses allowed, paid or incurred by the Corporation for
any underwriting or otherwise in connection with the issuance and sale thereof,
plus the value of any property other than cash received by the Corporation,
determined as provided in Section A.7(e)(i)(b) hereof, plus the value of any
other consideration received by the Corporation determined as set forth in
Section A.7(e)(i)(c) hereof.

 

b.                                      In the case of the issuance of Common
Stock for a consideration in whole or in part in property other than cash, the
value of such property other than cash shall be deemed to be the fair market
value of such property as determined in good faith by the Board of Directors,
irrespective of any accounting treatment; provided, however, that such fair
market value of such property as determined by the Board of Directors shall not
exceed the aggregate Current Market Price (as defined in
Section A.7(e)(viii) hereof) of the shares of Common Stock or such other
securities being issued, less any cash consideration paid for such shares,
determined as provided in Section A.7(e)(i)(a) hereof and less any other
consideration received by the Corporation for such shares, determined as set
forth in Section A.7(e)(i)(c) hereof.

 

c.                                       In the case of the issuance of Common
Stock for consideration in whole or in part other than cash or property, the
value of such other consideration shall be deemed to be the aggregate par value
of such Common Stock (or the aggregate stated value if such Common Stock has no
par value).

 

d.                                      In the case of the issuance of options
or other rights to purchase or subscribe for Common Stock or the issuance of
securities by their terms convertible into or exchangeable or exercisable for
Common Stock or options to purchase or other rights to subscribe for such
convertible or exchangeable or exercisable securities:

 

i.                                          the aggregate maximum number of
shares of Common Stock deliverable upon exercise of such options to purchase or
rights to subscribe for Common Stock shall be deemed to have been issued at the
time such options or rights were issued and for a consideration equal to the
consideration (determined in the manner provided in Sections A.7(e)(i)(a), (b)

 

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and (c) hereof), if any, received by the Corporation upon the issuance of such
options or rights plus the minimum purchase price provided in such options or
rights for the Common Stock covered thereby (the consideration in each case to
be determined in the manner provided in Sections A.7(e)(i)(a), (b) and
(c) hereof);

 

ii.                                       the aggregate maximum number of shares
of Common Stock deliverable upon conversion of, or in exchange for, any such
convertible or exchangeable securities or upon the exercise of options to
purchase or rights to subscribe for such convertible or exchangeable securities
and subsequent conversion or exchange thereof shall be deemed to have been
issued at the time such securities were issued or such options or rights were
issued and for a consideration equal to the consideration received by the
Corporation for any such securities and related options or rights (excluding any
cash received on account of accrued interest or accrued dividends), plus the
minimum additional consideration, if any, to be received by the Corporation upon
the conversion or exchange of such securities or the exercise of any related
options or rights (the consideration in each case to be determined in the manner
provided in Sections A.7(e)(i)(a), (b) and (c) hereof);

 

iii.                                    if there is any change (whether
automatic pursuant to the terms contained therein or as a result of the
amendment of such terms) in the exercise price of, or number of shares
deliverable upon exercise of, any such options or rights or upon the conversion
or exchange of any such convertible or exchangeable securities (other than a
change resulting from the original antidilution provisions thereof in place at
the time of issuance of such security), then the applicable Conversion Price
shall automatically be readjusted in proportion to such change (notwithstanding
the foregoing, no adjustment pursuant to this clause shall have the effect of
increasing the applicable Conversion Price to an amount which exceeds the lower
of (i) the applicable Conversion Price on the original adjustment date, or
(ii) the applicable Conversion Price that would have resulted from any Dilutive
Issuances between the original adjustment date and such readjustment date);

 

iv.                                   upon the expiration of any such options or
rights or the termination of any such rights to convert or exchange such
convertible or exchangeable securities (or in the event that the change that
precipitated an adjustment pursuant to Section A.7(e)(i)(d)(iii) hereof is
reversed or terminated, or expires), then the applicable Conversion Price shall
be automatically readjusted to the applicable Conversion Price that would have
been obtained had such options, rights or convertible or exchangeable securities
not been issued; and

 

v.                                      if the terms of any option or
convertible security (excluding options or convertible securities which, upon
exercise, conversion or exchange thereof, would entitle the holder thereof to
receive shares of Common Stock which are Excluded Stock), the issuance of which
was not a Dilutive Issuance, are revised after the Original Issuance Date
(either automatically pursuant the provisions contained therein or as a result
of an amendment to such terms) to provide for either (1) any increase in the
number of shares of Common Stock issuable upon the exercise, conversion or
exchange of any such option or convertible security or (2) any decrease in the
consideration payable to the Corporation upon such exercise, conversion or
exchange, then such option or convertible security, as so amended, and the
shares of Common Stock subject thereto shall be deemed to have been issued
effective upon such increase or decrease becoming effective.

 

(ii)                                  “Excluded Stock” shall mean:

 

a.                                      Common Stock issued upon conversion of
any shares of Existing Preferred Stock, including any shares of Common Stock
issuable upon conversion of any dividends accrued on such Existing Preferred
Stock;

 

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b.                                      Common Stock issued or issuable to
officers, directors or employees of or consultants or independent contractors to
the Corporation, pursuant to any written agreement, plan or arrangement to
purchase, or rights to subscribe for, such Common Stock, including Common Stock
issued under the Corporation’s 2003 Long-Term Incentive Plan, as amended, or
other equity incentive plan or other agreements that have been approved in form
and in substance by the Existing Senior Majority, calculated in accordance with
Section A.6(a) of Article III herein (including, in such calculation, any
outstanding restricted stock awards held by such holders), and which, as a
condition precedent to the issuance of such shares, provide for the vesting of
such shares and subject such shares to restrictions on transfer and rights of
first offer in favor of the Corporation, and restricted stock grants to
directors, employees or consultants as approved by the Board of Directors of the
Corporation; provided, however, that the maximum number of shares of Common
Stock heretofore or hereafter issuable pursuant to the Corporation’s 2003
Long-Term Incentive Plan, as amended, and all such agreements, plans and
arrangements shall not exceed 2,015,666 shares of Common Stock;

 

c.                                       Common Stock issued as a stock dividend
or distribution on the Existing Preferred Stock payable in shares of Common
Stock, or capital stock of any other class issuable upon any subdivision,
recombination, split-up or reverse stock split of all the outstanding shares of
such class of capital stock;

 

d.                                      Common Stock or other securities issued
or issuable to banks, lenders or landlords, provided that each such issuance is
approved by the Board of Directors, including, but not limited to, warrants to
acquire Common Stock held by Silicon Valley Bank (or its affiliates, successors
and assignees), warrants to purchase Preferred Stock issued or to be issued to
GE Healthcare Financial Services, Inc. (“GEHFS”) and Oxford Finance Corporation
(“OFC”) pursuant to a proposed debt financing approved by the Board of Directors
(the “GE Financing”), shares of Preferred Stock issued or issuable to GE in
connection with the GE Financing or upon exercise by GEHFS or OFC of warrants
issued in the GE Financing and shares of common stock issuable upon conversion
of any such shares of Preferred Stock issued to GEHFS or OFC pursuant to the GE
Financing;

 

e.                                       Common Stock or other securities issued
or issuable to third parties in connection with strategic partnerships or
alliances, corporate partnerships, joint ventures or other licensing
transactions, provided that each such transaction and related issuance is
approved by the Board of Directors, including, but not limited to, (A) any
shares of Preferred Stock or Common Stock issued or issuable to Ipsen Pharma SAS
(“Ipsen”), pursuant to the terms of that certain License Agreement, as amended
and may be amended with the approval of the Board of Directors of the
Corporation and in effect from time to time, by and between the Corporation and
Ipsen as payment milestones in lieu of cash payments and (B) hares of Series A-5
Stock issued or issuable pursuant to that certain Stock Issuance Agreement as of
March 29, 2011 by and between the Corporation and Nordic Bioscience and the
letter agreement as of March 29, 2011 by and between the Corporation and Nordic
Bioscience, pursuant to which the Corporation will issue shares of the
Corporation’s Series A-5 Convertible Preferred Stock, $0.01 par value per share
and the issuance of Series A-6 Stock issued or to be issued as dividends on such
Series A-5 Stock, and shares of Common Stock issuable upon conversion of any
such shares of Series A-5 Stock and Series A-6 Stock;

 

f.                                        Common Stock or other securities
issued or issuable pursuant to the acquisition by the Corporation of any other
corporation, partnership, joint venture, trust or other entity by any merger,
stock acquisition, reorganization, or purchase of substantially all assets or
otherwise in which the Corporation or its stockholders of record immediately
prior to the effective date of such transaction, directly or indirectly, own at
least a majority of the voting power of the acquired entity or the resulting
entity after such transaction, in each case so long as approved by the Board of
Directors;

 

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g.                                       Common Stock or other securities, the
issuance of which is approved by the Existing Senior Majority, with such
approval expressly waiving the application of the anti-dilution provisions of
this Section A.7 as a result of such issuance;

 

h.                                      Preferred Stock (and Common Stock
issuable upon conversion of such Preferred Stock) or Common Stock issued or
issuable pursuant to any warrant outstanding as of the date hereof or any
warrant and any shares of Preferred Stock or common stock, or common stock
issued upon exercise of any Preferred Stock, issued in connection with the
Qualified Financing, including, but not limited to a warrant for shares of
Series A-1 Preferred Stock issued or issuable to Leerink Swan, any shares of
Preferred Stock or Common Stock upon exercise thereof and any Common Stock
issuable upon conversion of such Preferred Stock issued upon exercise thereof;

 

j.                                         All shares of Preferred Stock issued
in connection with the Qualified Financing as provided in this Certificate and
the Series A-1 Purchase Agreement, and all shares of Common Stock issued or
issuable upon conversion of any such shares of Preferred Stock.

 

(iii)                               If the number of shares of Common Stock
outstanding at any time after the Effective Time is increased by a stock
dividend payable in shares of Common Stock or by a subdivision or split-up of
shares of Common Stock, then, following the record date fixed for the
determination of holders of Common Stock entitled to receive such stock
dividend, subdivision or split-up, the applicable Conversion Price shall be
appropriately decreased in the form of a Proportional Adjustment (as defined in
Section A.8) so that the number of shares of Common Stock issuable on conversion
of each share of Existing Preferred Stock shall be increased in proportion to
such increase in outstanding shares.

 

(iv)                              If the number of shares of Common Stock
outstanding at any time after the Effective Time is decreased by a combination
of the outstanding shares of Common Stock (other than pursuant to the Reverse
Split), then, following the record date for such combination, the applicable
Conversion Price shall be appropriately increased in the form of a Proportional
Adjustment so that the number of shares of Common Stock issuable on conversion
of each share of Existing Preferred Stock shall be decreased in proportion to
such decrease in outstanding shares.

 

(v)                                 Except as contemplated in Certificate and
the Series A-1 Purchaser Agreement, if at any time after the Effective Time, the
Corporation shall make or issue, or fix a record date for the determination of
holders of Common Stock entitled to receive, a dividend or other distribution
payable in securities of the Corporation (other than shares of Common Stock) or
in cash or other property, then and in each such event provision shall be made
so that the holders of the Existing Preferred Stock shall receive upon
conversion thereof in addition to the number of shares of Common Stock
receivable thereupon, the kind and amount of securities of the Corporation, cash
or other property which they would have been entitled to receive had the
Existing Preferred Stock been converted into Common Stock on the date of such
event and had they thereafter, during the period from the date of such event to
and including the conversion date, retained such securities receivable by them
as aforesaid during such period, giving application to all adjustments called
for during such period under this paragraph with respect to the rights of the
holders of the Existing Preferred Stock; and provided further, however, that no
such adjustment shall be made if the holders of Existing Preferred Stock
simultaneously receive a dividend or other distribution of such securities,
cash, or other property in an amount equal to the amount of such securities,
cash, or other property as they would have received if all outstanding shares of
Existing Preferred Stock had been converted into Common Stock on the date of
such event.

 

(vi)                              Subject to the provisions of
Section A.4(h) above, in the event, at any time after the Effective Time, of any
capital reorganization, or any reclassification of the capital stock of the

 

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Corporation (other than pursuant to the Reverse Split, other than as
contemplated under this Certificate and the Series A-1 Purchase Agreement and
other than a change in par value or from par value to no par value or from no
par value to par value or as a result of a stock dividend or subdivision,
split-up or combination of shares), or the consolidation or merger of the
Corporation with or into another person (other than pursuant to the Merger
Agreement and other than any consolidation or merger in which the Corporation is
the continuing corporation and which does not result in any change in the
powers, designations, preferences and rights, or the qualifications, limitations
or restrictions, if any, of the capital stock of the Corporation) or of the sale
or other disposition of all or substantially all the properties and assets of
the Corporation in their entirety to any other person (any such transaction, an
“Extraordinary Transaction”), then the Corporation shall provide appropriate
adjustment in the form of a Proportional Adjustment to the applicable Conversion
Price with respect to each share of Existing Preferred Stock outstanding after
the effectiveness of such Extraordinary Transaction (excluding any Existing
Preferred Stock redeemed pursuant to Section A.5 hereof in connection therewith)
such that each share of Existing Preferred Stock outstanding immediately prior
to the effectiveness of the Extraordinary Transaction (other than shares
redeemed pursuant to Section A.5 hereof) shall be convertible into the kind and
number of shares of stock or other securities or property of the Corporation, or
of the corporation resulting from or surviving such Extraordinary Transaction,
that a holder of the number of shares of Common Stock deliverable (immediately
prior to the effectiveness of the Extraordinary Transaction) upon conversion of
such share of Existing Preferred Stock would have been entitled to receive upon
such Extraordinary Transaction. The provisions of this Section A.7(e)(v) shall
similarly apply to successive Extraordinary Transactions.

 

(vii)                           All calculations under this Section A.7(e) shall
be made to the nearest one-tenth of a cent ($.001) or to the nearest one-tenth
of a share, as the case may be.

 

(viii)                        For the purpose of any computation pursuant to
Section A.7(d) hereof or this Section A.7(e), the Current Market Price at any
date of one share of Common Stock shall be defined as the average of the daily
closing prices for the 30 consecutive Business Days ending on the fifth (5th)
Business Day before the day in question (as adjusted for any stock dividend,
split-up, combination or reclassification that took effect during such 30
Business Day period), determined as follows:

 

a.                                      If the Common Stock is listed or
admitted for trading on a national securities exchange, then the closing price
for each day shall be the last reported sales price regular way or, in case no
such reported sales took place on such day, the average of the last reported bid
and asked prices regular way, in either case on the principal national
securities exchange on which the Common Stock is listed or admitted to trading.

 

b.                                      If the Common Stock is not at the time
listed or admitted for trading on any such exchange, then such price shall be
equal to the last reported bid and asked prices on such day as reported by the
NASD OTCBB or the National Quotation Bureau, Inc., or any similar reputable
quotation and reporting service if such quotation is not reported by the NASD
OTCBB or the National Quotation Bureau, Inc.

 

c.                                       If the Common Stock is not traded in
such manner that the quotations referred to in this Section A.7(d)(viii) are
available for the period required hereunder, then the Current Market Price shall
be the fair market value of such share, as determined in good faith by a
majority of the entire Board of Directors.

 

(ix)                              In any case in which the provisions of this
Section A.7(e) shall require that an adjustment shall become effective
immediately after a record date for an event, the Corporation may defer until
the occurrence of such event (A) issuing to the holder of any shares of Existing
Preferred Stock

 

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converted after such record date and before the occurrence of such event the
additional shares of capital stock issuable upon such conversion by reason of
the adjustment required by such event over and above the shares of capital stock
issuable upon such conversion before giving effect to such adjustment, and
(B) paying to such holder any cash amounts in lieu of fractional shares pursuant
to Section A.7(d) hereof; provided, however, that the Corporation shall deliver
to such holder a due bill or other appropriate instrument evidencing such
holder’s right to receive such additional shares and such cash upon the
occurrence of the event requiring such adjustment.

 

(x)                                 If a state of facts shall occur that,
without being specifically controlled by the provisions of this Section A.7,
would not fairly protect the conversion rights of the holders of the Existing
Preferred Stock in accordance with the essential intent and principles of such
provisions, then the Board of Directors shall make an adjustment in the
application of such provisions, in accordance with such essential intent and
principles, so as to protect such conversion rights.

 

(xi)                              Notwithstanding the foregoing, there shall be
no adjustment to the Conversion Price for any issuance or deemed issuance of any
shares of Common Stock (which term, for purposes of this Section A.7(e)(x),
including all subsections thereof, shall be deemed to include all securities
convertible into, or exchangeable or exercisable for, whether directly or
indirectly, shares of Common Stock) for a consideration per share greater than
the Series C Original Purchase Price.

 

(f)                                   Whenever the applicable Conversion Price
shall be adjusted as provided in Section A.7(e) hereof, the Corporation shall
forthwith file and keep on record at the office of the Secretary of the
Corporation and at the office of its transfer agent or at such other place as
may be designated by the Corporation, a statement, signed by both its President
or Chief Executive Officer and its Treasurer or Chief Financial Officer, showing
in detail the facts requiring such adjustment and the applicable Conversion
Price that shall be in effect after such adjustment. The Corporation shall also
cause a copy of such statement to be sent by first-class, certified mail, return
receipt requested, postage prepaid, to each Existing Preferred Stockholder at
such holder’s address appearing on the Corporation’s records. Where appropriate,
such copy shall be given in advance of any such adjustment and shall be included
as part of a notice required to be mailed under the provisions of
Section A.7(g) hereof.

 

(g)                                  In the event the Corporation shall propose
to take any action of the types described in Section A.7(e)(i), (iii), (iv) or
(v) hereof, or any other Event of Sale, the Corporation shall give notice to
each Existing Preferred Stockholder in the manner set forth in
Section A.7(f) hereof, which notice shall specify the record date, if any, with
respect to any such action and the date on which such action is to take place.
Such notice shall also set forth such facts with respect thereto as shall be
reasonably necessary to indicate the effect of such action (to the extent such
effect may be known at the date of such notice) on the applicable Conversion
Price with respect to the Existing Preferred Stock, and the number, kind or
class of shares or other securities or property which shall be deliverable or
purchasable upon each conversion of Preferred Stock. In the case of any action
that would require the fixing of a record date, such notice shall be given at
least 20 days prior to the record date so fixed, and in the case of any other
action, such notice shall be given at least 30 days prior to the taking of such
proposed action.

 

(h)                                 The Corporation shall pay all documentary,
stamp or other transactional taxes attributable to the issuance or delivery of
shares of capital stock of the Corporation upon conversion of any shares of
Existing Preferred Stock; provided, however, that the Corporation shall not be
required to pay any taxes which may be payable in respect of any transfer
involved in the issuance or delivery of any certificate for such shares in a
name other than that of the Existing Preferred Stockholder in respect of which
such shares of Existing Preferred Stock are being issued.

 

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(i)                                     The Corporation shall reserve out of its
authorized but unissued shares of Common Stock, solely for the purpose of
effecting the conversion of the Existing Preferred Stock, sufficient shares of
Common Stock to provide for the conversion of all outstanding shares of Existing
Preferred Stock.

 

(j)                                    All shares of Common Stock which may be
issued in connection with the conversion provisions set forth herein will, upon
issuance by the Corporation, be validly issued, fully paid and nonassessable,
not subject to any preemptive or similar rights, and free from all taxes, liens
or charges with respect thereto created or imposed by the Corporation.

 

(k)                                 Upon the consummation of a qualified firm
commitment underwritten public offering of Common Stock of the Corporation
registered under the Securities Act of 1933, as amended, pursuant to which
(i) the Company valuation prior to the offering is equal to or greater than $200
million and (ii) the aggregate gross proceeds to the Corporation (before
deduction of underwriters commissions and expenses) are at least $40 million (a
“Qualified Public Offering”), each share of Existing Preferred Stock then
outstanding shall, by virtue of and immediately prior to the closing of such
qualified firm commitment public offering and without any action on the part of
the holder thereof, be deemed automatically converted into that number of shares
of Common Stock of which the Existing Preferred Stock would be convertible if
such conversion were to occur immediately prior to closing of the Qualified
Public Offering. The holder of any shares of Existing Preferred Stock converted
into Common Stock pursuant to this Section A.7(k) shall be entitled to payment
of all declared or accrued but unpaid dividends, if any, payable on or with
respect to such shares up to and including the date of the closing of such
Qualified Public Offering which shall be deemed the Conversion Date for purposes
of this Section A.7(k).

 

8.              Definitions.  As used in this Part A of Article III of this
Certificate, the following terms shall have the corresponding meanings:

 

“Business Day” shall mean any day other than a Saturday, Sunday or day on which
banks are closed in the city and state where the principal executive office of
the Corporation is located.

 

“Series A Original Purchase Price” shall mean, with respect to the Series A
Stock and after giving effect to the Reverse Split, $15.00 per share, subject,
for all purposes other than Section A.7 hereof (which provisions shall be
applied in accordance with their own terms), to Proportional Adjustment.

 

“Series B Original Purchase Price” shall mean, with respect to the Series B
Stock and after giving effect to the Reverse Split, $15.00 per share, subject,
for all purposes other than Section A.7 hereof (which provisions shall be
applied in accordance with their own terms), to Proportional Adjustment.

 

“Series C Original Purchase Price” shall mean, with respect to the Series C
Stock and after giving effect to the Reverse Split, $8.142 per share, subject,
for all purposes other than Section A.7 hereof (which provisions shall be
applied in accordance with their own terms), to Proportional Adjustment.

 

“Proportional Adjustment” shall mean an adjustment made to the price of the
Preferred Stock upon the occurrence of a stock split, reverse stock split, stock
dividend, stock combination reclassification or other similar change with
respect to such security, such that the price of one share of the Preferred
Stock before the occurrence of any such

 

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change shall equal the aggregate price of the share (or shares or fractional
share) of such security (or any other security) received by the holder of the
Preferred Stock with respect thereto upon the effectiveness of such change.
Notwithstanding the foregoing, the Reverse Split shall not rigger or give rise
to any Proportional Adjustment.

 

9.              Forced Conversion in the Qualified Financing.

 

(a)                                 Definitions.  For purposes of this
Section A.9 of Article III, the following definitions shall apply:

 

(i)                                     “Applicable Portion” shall mean that
percentage of a holder of Existing Preferred Stock’s Pro Rata Portion not
committed to be purchased by such holder in the Qualified Financing.

 

(ii)                                  “Offered Securities” shall mean the
Series A-1 Stock offered for sale in the Qualified Financing.

 

(iii)                               “Pro Rata Portion” shall mean, with respect
to any holder of Existing Preferred Stock, that percentage figure which
expresses the ratio that (A) the number of shares of issued and outstanding
Common Stock owned by such holder of Existing Preferred Stock as of March 31,
2011 (or, in the case of a holder of Existing Preferred Stock who received all
of its shares of Existing Preferred Stock in a transfer from a former holder of
Existing Preferred Stock occurring after March 31, 2011, the number shares of
issued and outstanding Common Stock owned by such former holder of Existing
Preferred Stock as of March 31, 2011) bears to (B) the aggregate number of
shares of issued and outstanding Common Stock owned as of such date by all
holders of Existing Preferred Stock.  For purposes of the computation set forth
in clauses (A) and (B) above, all issued and outstanding securities held by
holders of Existing Preferred Stock (or former holders of Existing Preferred
Stock, as applicable, under clause (A) above) that are convertible into or
exercisable or exchangeable for shares of Common Stock (including any issued and
issuable shares of Existing Preferred Stock) or for any such convertible,
exercisable or exchangeable securities, shall be treated as having been so
converted, exercised or exchanged at the rate or price at which such securities
are convertible, exercisable or exchangeable for shares of Common Stock in
effect at the time in question, whether or not such securities are at such time
immediately convertible, exercisable or exchangeable.

 

(iv)                              “Qualified Financing” shall mean the
transaction involving the issuance of shares of Series A-1 Stock pursuant to the
terms of the Series A-1 Purchase Agreement.

 

(v)                                 “Series A-1 Offering Existing Investor
Available Amount” means Thirty Five Million Dollars ($35,000,000) of the total
amount of Offered Securities in the Qualified Financing.

 

(vi)                              “Series A-1 Purchase Agreement” shall mean
that certain Series A-1 Convertible Preferred Stock Purchase Agreement dated as
of April 25, 2011 by and among the Corporation and the “Investors” party
thereto.

 

(b)                                 Conversion of Existing Preferred Stock to
Common Stock in Connection with the Qualified Financing.  In the event that an
Existing Preferred Stockholder does not participate in the Qualified Financing
by committing to purchase and purchasing (or securing an investor who commits to
purchase and purchases), pursuant to the terms of the Series A-1 Purchase
Agreement, in the Qualified Financing in the aggregate and within the time
period specified in the Series A-1 Purchase Agreement such holder’s Pro Rata
Portion of the Series A-1 Offering Existing Investor Available Amount, then the
Applicable Portion of each series of Existing Preferred Stock held by such
holder shall automatically, and without any further action on the part of such
holder, be converted into shares of Common Stock at a rate

 

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of 1 share of Common Stock for every 5 shares of Existing Preferred Stock to be
so converted and all accrued dividends on such shares of Existing Preferred
Stock shall be forfeited. The conversion set forth in this paragraph (b) is
referred to as the “Forced Conversion”. The Forced Conversion shall become
effective immediately prior to, but subject to the consummation of, the Stage I
Closing (as defined in the Series A-1 Purchase Agreement).

 

(c)                                  Conversion of Series C Stock to Series A-2
Stock in the Qualified Financing.  Each share of Series C Stock that remains
outstanding after the Forced Conversion shall, immediately following the Forced
Conversion and upon the consummation of the Stage I Closing, automatically, and
without any further action by any holder thereof, be reclassified and converted
into one (1) share of Series A-2 Stock and all accrued dividends on such
reclassified shares of Series C Stock shall be forfeited.

 

(d)                                 Conversion of Series B Stock to Series A-3
Stock in the Qualified Financing.  Each share of Series B Stock that remains
outstanding after the Forced Conversion shall, immediately following the Forced
Conversion and upon the consummation of the Stage I Closing, automatically, and
without any further action by any holder thereof, be reclassified and converted
into one (1) share of Series A-3 Stock and all accrued dividends on such
reclassified shares of Series B Stock shall be forfeited.

 

(e)                                  Conversion of Series A Stock to Series A-4
Stock in the Qualified Financing.  Each share of Series A Stock that remains
outstanding after the Forced Conversion shall, immediately following the Forced
Conversion and upon the consummation of the Stage I Closing, automatically, and
without any further action by any holder thereof, be reclassified and converted
into one (1) share of Series A-4 Stock.

 

(f)                                  
Procedure.                                       Immediately following the Stage
I Closing, all stock certificates representing shares of Existing Preferred
Stock shall be deemed cancelled and shall thereafter be deemed to evidence only
(i) the number of shares of Common Stock into which such shares of Existing
Preferred Stock were converted as a result of the Forced Conversion or (ii) the
number of shares of Series A-2 Stock, Series A-3 or Series A-4 Stock into which
such shares of Existing Preferred Stock were reclassified and converted pursuant
to the foregoing provisions of this Section A.9 of Article III.  Each holder of
a certificate or certificates that, immediately before the Stage I Closing,
represented shares of Existing Preferred Stock shall, as soon as practicable
after the Stage I Closing, surrender such certificate or certificates, duly
endorsed for transfer or with duly executed stock transfer powers sufficient to
permit transfers attached, at the office of the Corporation or any transfer
agent for such shares of Existing Preferred Stock (or such holder shall notify
the Corporation or any transfer agent that such certificate or certificates have
been lost, stolen or destroyed and shall execute an agreement reasonably
satisfactory to the Corporation to indemnify the Corporation from any loss
incurred by it in connection therewith).  The Corporation shall, as soon as
practicable thereafter, issue and deliver at such office to such holder, or to
such holder’s nominee or nominees, a certificate or certificates for the number
of shares of Common Stock into which such holder’s shares of Existing Preferred
Stock were converted pursuant to the Forced Conversion or shares of Series A-2
Stock, Series A-3 or Series A-4 Stock, as applicable, to which such holder shall
be entitled as aforesaid.  From and after the Stage I Closing, each stock
certificate that, prior to the Stage I Closing, represented shares of Existing
Preferred Stock that were converted into Common Stock pursuant to the Forced
Conversion or reclassified and converted into shares of Series A-2 Stock,
Series A-3 or Series A-4 Stock as provided above shall, until its surrender, be
deemed to represent the number of shares of Common Stock, Series A-2 Stock,
Series A-3 or Series A-4 Stock, as applicable, into which such shares of
Existing Preferred Stock were converted or reclassified.

 

(g)                                  No Reissue of Converted Existing Preferred
Stock. No share of Existing Preferred Stock that is converted pursuant to any of
the provisions of this Section A.9 shall be reissued, and the

 

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Corporation shall not hold such share of Existing Preferred Stock so converted
in treasury but, instead, shall retire and cancel such share immediately upon
the conversion thereof pursuant to this Section A.9.

 

PART B. NEW PREFERRED STOCK

 

1.              Designation and Amount.  The number of shares, powers, terms,
conditions, designations, preferences and privileges, relative, participating,
optional and other special rights, and qualifications, limitations and
restrictions, if any, of the New Preferred Stock shall be as set forth in this
Part B. The number of authorized shares of the Series A-1 Stock is Ten Million
(10,000,000), the number of authorized shares of the Series A-2 Stock is Nine
Million Eight Hundred Thirty-two Thousand One Hundred Thirty-three (9,832,133),
the number of authorized shares of the Series A-3 Stock is One Million Four
Hundred Twenty-two Thousand Three Hundred (1,422,300), the number of authorized
shares of the Series A-4 Stock is Forty Thousand and Three (40,003), the number
of authorized shares of the Series A-5 Stock is Seventy Thousand (70,000) and
the number of authorized shares of the Series A-6 Stock is Eight Million
(8,000,000).

 

2.              Ranking.  As to dividends (other than with respect to the
payment of the Series A-5 Accruing Dividend which shall rank senior in payment
to any other dividends payable on any and all series of New Preferred Stock) and
upon Liquidation (as defined in Section B.4(b) hereof) or an Event of Sale (as
defined in Section B.5 hereof), each share of Series A-1 Stock shall rank
equally with each other share of Series A-1 Stock and senior to all shares of
Series A-2 Stock, Series A-3 Stock, Series A-4 Stock, Series A-5 Stock,
Series A-6 Stock and shares of Common Stock and all other classes or series of
stock not authorized by this Certificate as of the Effective Time; each share of
Series A-2 Stock shall rank equally with each other share of Series A-2 Stock
and senior to all shares of Series A-3 Stock, Series A-4 Stock, Series A-5
Stock, Series A-6 Stock and shares of Common Stock and all other classes or
series of stock not authorized by this Certificate as of the Effective Time;
each share of Series A-3 Stock, Series A-5 Stock and Series A-6 Stock shall rank
equally with each other share of Series A-3 Stock, Series A-5 and Series A-6
Stock and senior to all shares of Series A-4 Stock and shares of Common Stock
and all other classes or series of stock not authorized by this Certificate as
of the Effective Time; except, in all cases, as otherwise approved by the
affirmative vote or consent of holders of shares of Series A-1 Stock, Series A-2
Stock and/or Series A-3 Stock representing at least 70% of the voting power of
the shares of Series A-1 Stock, Series A-2 Stock and Series A-3 Stock then
outstanding (determined as set forth in the second sentence of
Section A.6(a) hereof) (the “New Senior Majority”). Each share of Series A-4
Stock, shall rank equally with each other share of Series A-4 Stock and senior
to all shares of Common Stock and all other classes or series of stock not
authorized by this Certificate as of the Effective Time, except as otherwise
approved by the affirmative vote or consent of the New Senior Majority.

 

3.              Dividend Provisions.

 

(a)                     Series A-1 Stock.  The holders of shares of Series A-1
Stock shall be entitled to receive a per share dividend at the rate of 8% of the
Series A-1 Original Purchase Price (as defined in Section B.8 hereof) per annum,
compounding annually (the “Series A-1 Accruing Dividend”), and which will accrue
on a quarterly basis commencing on the date of issuance of such share of
Series A-1 Stock. The holders of Series A-1 Stock shall be entitled to receive
dividends prior in right to the payment of dividends and other distributions
(whether in cash, property or securities of the Corporation, including
subscription or other rights to acquire securities of the Corporation) on the
Series A-2 Stock, Series A-3 Stock, Series A-4 Stock, Series A-5 Stock,
Series A-6 Stock and Common Stock, but not with respect to the payment of the
Series A-5 Special Accruing Dividend, as set forth in Section B.3(d) below,
which shall rank senior in payment to any dividends payable with respect to the
Series A-1 Stock.  Any dividends with respect to the Series A-1 Stock shall be
payable, at the sole discretion of the Board of Directors, in cash or the
issuance of that number of shares of Common Stock equal to the quotient obtained
by dividing (x) the amount of such

 

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accrued and unpaid dividends thereon by (y) the Current Market Price of a share
of Common Stock, when, as and if declared or paid by the Board of Directors and,
as accrued, on any Liquidation or Event of Sale.  Dividends with respect to the
Series A-1 Stock shall be payable in shares of Common Stock (calculated based
upon the then effective Series A-1 Conversion Price), as accrued, upon the
conversion of the Series A-1 Stock into Common Stock.  Whenever any dividend may
be declared or paid on any share of Series A-1 Stock, the Board of Directors
shall also declare and pay a dividend on the same terms, at the same rate and in
like kind upon each other share of the Series A-1 Stock then outstanding, so
that all outstanding shares of Series A-1 Stock will participate equally with
each other and ratably per share (calculated as provided in
Section B.3(f) hereof).  Whenever any dividend or other distribution, whether in
cash or property or in securities of the Corporation (or subscription or other
rights to purchase or acquire securities of the Corporation), may be declared or
paid on: (i) any shares of the Common Stock, the Board of Directors shall also
declare and pay a dividend on the same terms, at the same rate and in like kind
upon each share of the Series A-1 Stock then outstanding so that all outstanding
shares of Series A-1 Stock will participate in such dividend ratably with such
shares of Common Stock (calculated as provided in Section B.3(e) hereof); or
(ii) any shares of any other series of Preferred Stock (other than the
Series A-2 Accruing Dividend, the Series A-3 Accruing Dividend and the
Series A-5 Special Accruing Dividend), the Board of Directors shall also declare
and pay a dividend on the same terms, at the same or equivalent rate upon each
share of the Series A-1 Stock then outstanding so that all outstanding shares of
Series A-1 Stock will participate in such dividend ratably with such shares of
such other series of Preferred Stock (based on the number of shares of Common
Stock into which each share of Series A-1 Stock and each share of such other
series of Preferred Stock is then convertible, if applicable, or, otherwise, the
relative liquidation preference per share, of such other series of Preferred
Stock as compared with the Series A-1 Stock then outstanding).

 

(b)                     Series A-2 Stock.  The holders of shares of Series A-2
Stock shall be entitled to receive a per share dividend at the rate of 8% of the
Series A-2 Original Purchase Price (as defined in Section B.8 hereof) per annum,
compounding annually (the “Series A-2 Accruing Dividend”), and which will accrue
on a quarterly basis commencing on the date of issuance of such share of
Series A-2 Stock. The holders of Series A-2 Stock shall be entitled to receive
dividends prior in right to the payment of dividends and other distributions
(whether in cash, property or securities of the Corporation, including
subscription or other rights to acquire securities of the Corporation) on the
Series A-3 Stock, Series A-4 Stock, Series A-5 Stock, Series A-6 Stock and
Common Stock, but not with respect to the payment of the Series A-5 Special
Accruing Dividend, as set forth below in Section B.3(d) below, which shall rank
senior in payment to any dividends payable with respect to the Series A-2
Stock.  Any dividends with respect to the Series A-2 Stock shall be payable, at
the sole discretion of the Board of Directors, in cash or the issuance of that
number of shares of Common Stock equal to the quotient obtained by dividing
(x) the amount of such accrued and unpaid dividends thereon by (y) the then fair
market value of a share of Common Stock, when, as and if declared or paid by the
Board of Directors and, as accrued, on any Liquidation or Event of Sale.
Dividends with respect to the Series A-2 Stock shall be payable in shares of
Common Stock (calculated based upon the then effective Series A-2 Conversion
Price), as accrued, upon the conversion of the Series A-2 Stock into Common
Stock.  Whenever any dividend may be declared or paid on any share of Series A-2
Stock, the Board of Directors shall also declare and pay a dividend on the same
terms, at the same rate and in like kind upon each other share of the Series A-2
Stock then outstanding, so that all outstanding shares of Series A-2 Stock will
participate equally with each other and ratably per share (calculated as
provided in Section B.3(f) hereof).  Whenever any dividend or other
distribution, whether in cash or property or in securities of the Corporation
(or subscription or other rights to purchase or acquire securities of the
Corporation), may be declared or paid on: (i) any shares of the Common Stock,
the Board of Directors shall also declare and pay a dividend on the same terms,
at the same rate and in like kind upon each share of the Series A-2 Stock then
outstanding so that all outstanding shares of Series A-2 Stock will participate
in such dividend ratably with such shares of Common Stock (calculated as
provided in Section B.3(f) hereof); or (ii) any shares of any other series of
Preferred Stock (other than the Series A-1 Accruing Dividend, the Series A-3
Accruing Dividend and the Series A-5 Special Accruing Dividend), the Board of
Directors shall also declare and pay

 

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a dividend on the same terms, at the same or equivalent rate upon each share of
the Series A-2 Stock then outstanding so that all outstanding shares of
Series A-2 Stock will participate in such dividend ratably with such shares of
such other series of Preferred Stock (based on the number of shares of Common
Stock into which each share of Series A-2 Stock and each share of such other
series of Preferred Stock is then convertible, if applicable, or, otherwise, the
relative liquidation preference per share, of such other series of Preferred
Stock as compared with the Series A-2 Stock then outstanding).

 

(c)                      Series A-3 Stock.  The holders of shares of Series A-3
Stock shall be entitled to receive a per share dividend at the rate of 8% of the
Series A-3 Original Purchase Price (as defined in Section B.8 hereof) per annum,
compounding annually (the “Series A-3 Accruing Dividend”), and which will accrue
on a quarterly basis commencing on the date of issuance of such share of
Series A-3 Stock. The holders of Series A-3 Stock shall be entitled to receive
dividends prior in right to the payment of dividends and other distributions
(whether in cash, property or securities of the Corporation, including
subscription or other rights to acquire securities of the Corporation) on the
Series A-4 Stock, Series A-5 Stock, Series A-6 Stock and Common Stock, but not
with respect to the payment of the Series A-5 Special Accruing Dividend, as set
forth below in Section B.3(d) below, which shall rank senior in payment to any
dividends payable with respect to the Series A-3 Stock.  Any dividends with
respect to the Series A-3 Stock shall be payable, at the sole discretion of the
Board of Directors, in cash or the issuance of that number of shares of Common
Stock equal to the quotient obtained by dividing (x) amount of such accrued and
unpaid dividends thereon by (y) the then fair market value of a share of Common
Stock, when, as and if declared or paid by the Board of Directors and, as
accrued, on any Liquidation or Event of Sale. Dividends with respect to the
Series A-3 Stock shall be payable in shares of Common Stock (calculated based
upon the then effective Series A-3 Conversion Price), as accrued, upon the
conversion of the Series A-3 Stock into Common Stock.  Whenever any dividend may
be declared or paid on any share of Series A-3 Stock, the Board of Directors
shall also declare and pay a dividend on the same terms, at the same rate and in
like kind upon each other share of the Series A-3 Stock then outstanding, so
that all outstanding shares of Series A-3 Stock will participate equally with
each other and ratably per share (calculated as provided in
Section B.3(f) hereof).  Whenever any dividend or other distribution, whether in
cash or property or in securities of the Corporation (or subscription or other
rights to purchase or acquire securities of the Corporation), may be declared or
paid on: (i) any shares of the Common Stock, the Board of Directors shall also
declare and pay a dividend on the same terms, at the same rate and in like kind
upon each share of the Series A-3 Stock then outstanding so that all outstanding
shares of Series A-3 Stock will participate in such dividend ratably with such
shares of Common Stock (calculated as provided in Section B.3(f) hereof); or
(ii) any shares of any other series of Preferred Stock (other than the
Series A-1 Accruing Dividend, the Series A-2 Accruing Dividend and the
Series A-5 Special Accruing Dividend), the Board of Directors shall also declare
and pay a dividend on the same terms, at the same or equivalent rate upon each
share of the Series A-3 Stock then outstanding so that all outstanding shares of
Series A-3 Stock will participate in such dividend ratably with such shares of
such other series of Preferred Stock (based on the number of shares of Common
Stock into which each share of Series A-3 Stock and each share of such other
series of Preferred Stock is then convertible, if applicable, or, otherwise, the
relative liquidation preference per share, of such other series of Preferred
Stock as compared with the Series A-3 Stock then outstanding).

 

(d)                     Series A-5 Stock.  Without regard to the payment of the
required dividends to the holders of Series A-1 Stock, Series A-2 Stock and
Series A-3 Stock in accordance with Section B.3(a), (b) and (c), respectively,
above, the holders of shares of the Series A-5 Stock shall be entitled to
receive a per share dividend (the “Series A-5 Special Accruing Dividend”) that
shall accrue and be paid in the form of Series A-6 Stock or other securities
subject to and in accordance with the provisions of that certain Stock Issuance
Agreement to which the Corporation and Nordic Bioscience Clinical Development
VII A/S are party dated March 29, 2011 (the “Stock Issuance Agreement”).
Whenever any dividend may be declared or paid on any shares of Series A-5 Stock,
the Board of Directors shall also declare and pay a dividend on the same terms,
at the same rate and in like kind upon each other share of the Series A-5 Stock
then

 

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outstanding, so that all outstanding shares of Series A-5 Stock will participate
equally with each other and ratably per share (calculated as provided in
Section B.3(f) hereof).  Whenever any dividend or other distribution, whether in
cash or property or in securities of the Corporation (or subscription or other
rights to purchase or acquire securities of the Corporation), may be declared or
paid on: (i) any shares of the Common Stock, the Board of Directors shall also
declare and pay a dividend on the same terms, at the same rate and in like kind
upon each share of the Series A-5 Stock then outstanding so that all outstanding
shares of Series A-5 Stock will participate in such dividend ratably with such
shares of Common Stock (calculated as provided in Section B.3(f) hereof); or
(ii) any shares of any other series of Preferred Stock (other than the
Series A-1 Accruing Dividend, the Series A-2 Accruing Dividend and the
Series A-3 Accruing Dividend), the Board of Directors shall also declare and pay
a dividend on the same terms, at the same or equivalent rate upon each share of
the Series A-5 Stock then outstanding so that all outstanding shares of
Series A-5 Stock will participate in such dividend ratably with such shares of
such other series of Preferred Stock (based on the number of shares of Common
Stock into which each share of Series A-5 Stock and each share of such other
series of Preferred Stock is then convertible, if applicable, or, otherwise, the
relative liquidation preference per share, of such other series of Preferred
Stock as compared with the Series A-5 Stock then outstanding).

 

(e)                      Series A-4 Stock and Series A-6 Stock.  Following
payment in full of required dividends to the holders of Series A-1 Stock,
Series A-2 Stock, Series A-3 and Series A-5 Stock or any other class or series
of capital stock that is senior to or on parity with the any such series of
Preferred Stock as to dividends, in accordance with Sections B.3(a), (b), (c) or
(d) above or any other section of this Certificate as in effect from time to
time, the holders of shares of the Series A-4 Stock and Series A-6 Stock shall
be entitled to receive, when, if and as declared by the Board of Directors,
dividends on any shares of Series A-4 Stock or Series A-6 Stock, as the case may
be, out of funds legally available for that purpose, at a rate to be determined
by the Board of Directors if and when they may so declare any dividend on the
Series A-4 Stock or A-6 Stock, as the case may be.  Whenever any dividend may be
declared or paid on any shares of Series A-4 Stock or Series A-6 Stock, as
applicable, the Board of Directors shall also declare and pay a dividend on the
same terms, at the same rate and in like kind upon each other share of the
Series A-4 Stock or the Series A-6 Stock, as applicable, then outstanding, so
that all outstanding shares of Series A-4 Stock or Series A-6 Stock, as
applicable, will participate equally with each other and ratably per share
(calculated as provided in Section B.3(f) hereof).  Whenever any dividend or
other distribution, whether in cash or property or in securities of the
Corporation (or subscription or other rights to purchase or acquire securities
of the Corporation), may be declared or paid on: (i) any shares of the Common
Stock, the Board of Directors shall also declare and pay a dividend on the same
terms, at the same rate and in like kind upon each share of the Series A-4 Stock
and Series A-6 Stock then outstanding so that all outstanding shares of
Series A-4 Stock and Series A-6 Stock will participate in such dividend ratably
with such shares of Common Stock (calculated as provided in
Section B.3(f) hereof); or (ii) any shares of any other series of Preferred
Stock (other than the Series A-1 Accruing Dividend, the Series A-2 Accruing
Dividend, the Series A-3 Accruing Dividend and the Series A-5 Special Accruing
Dividend), the Board of Directors shall also declare and pay a dividend on the
same terms, at the same or equivalent rate upon each share of the Series A-4
Stock and Series A-6 Stock then outstanding so that all outstanding shares of
Series A-4 Stock and Series A-6 Stock will participate in such dividend ratably
with such shares of such other series of Preferred Stock (based on the number of
shares of Common Stock into which each share of Series A-4 Stock and Series A-6
Stock and each share of such other series of Preferred Stock is then
convertible, if applicable, or, otherwise, the relative liquidation preference
per share, of such other series of Preferred Stock as compared with the
Series A-4 Stock and Series A-6 Stock then outstanding).

 

(f)                       In connection with any dividend declared or paid
hereunder, each share of Preferred Stock shall be deemed to be that number of
shares (including fractional shares) of Common Stock into which it is then
convertible, rounded up to the nearest one-tenth of a share.  No fractional
shares of capital stock shall be issued as a dividend hereunder. The Corporation
shall pay a cash adjustment for any

 

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such fractional interest in an amount equal to the fair market value thereof on
the last Business Day (as defined in Section B.8 hereof) immediately preceding
the date for payment of dividends as determined by the Board of Directors in
good faith.

 

4.              Liquidation Rights.

 

(a)                     As to rights upon any Liquidation or an Event of Sale,
each share of Series A-1 Stock shall rank equally with each other share of
Series A-1 Stock and senior to all shares of Series A-2 Stock, Series A-3 Stock,
Series A-4 Stock, Series A-5 Stock and Series A-6 Stock; each share of
Series A-2 Stock shall rank equally with each other share of Series A-2 Stock
and senior to all shares of Series A-3 Stock, Series A-4 Stock, Series A-5 Stock
and Series A-6 Stock; each share of Series A-3 Stock, Series A-5 Stock and
Series A-6 Stock shall rank equally with each other share of Series A-3 Stock,
Series A-5 and Series A-6 Stock and senior to all shares of Series A-4 Stock and
shares of Common Stock and all other classes or series of stock not authorized
by this Certificate as of the Effective Time, except as otherwise approved by
the affirmative vote or consent of the New Senior Majority. Each share of
Series A-4 Stock, shall rank equally with each other share of Series A-4 Stock
and senior to all shares of Common Stock and all other classes or series of
stock not authorized by this Certificate as of the Effective Time, except as
otherwise approved by the affirmative vote or consent of the New Senior
Majority.

 

(b)                     In the event of any liquidation, dissolution or
winding-up of the affairs of the Corporation (collectively, a “Liquidation”):
(i) the holders of shares of Series A-1 Stock then outstanding (the “Series A-1
Stockholders”) shall be entitled to receive, ratably with each other, out of the
assets of the Corporation legally available for distribution to its
stockholders, whether from capital, surplus or earnings, before any payment
shall be made to the holders of Series A-2 Stock then outstanding (the
“Series A-2 Stockholders”), Series A-3 Stock then outstanding (the “Series A-3
Stockholders”), Series A-4 Stock then outstanding (the “Series A-4
Stockholders”), Series A-5 Stock then outstanding (the “Series A-5
Stockholders”)  or Series A-6 Stock then outstanding (the “Series A-6
Stockholders” and collectively with the Series A-1 Stockholders, Series A-2
Stockholders, Series A-3 Stockholders, Series A-4 Stockholders and the
Series A-5 Stockholders, the “New Preferred Stockholders”), or the holders of
Common Stock or any other class or series of stock ranking on Liquidation junior
to such Series A-1 Stock, an amount per share equal to the Series A-1 Original
Purchase Price (as defined in Section B.8 hereof), plus an amount equal to any
declared or accrued but unpaid dividends thereon, calculated pursuant to
Section B.3(a) hereof; and (ii) after the distribution to the Series A-1
Stockholders, and any other class or series of capital stock that is senior to
the Series A-2 Stock as to Liquidation, of the full amount to which they are
entitled to receive pursuant to this Section B.4(b) or any other section of this
Certificate as in effect from time to time, the Series A-2 Stockholders, shall
be entitled to receive, ratably with each other, out of the assets of the
Corporation legally available for distribution to its stockholders, whether from
capital, surplus or earnings, before any payment shall be made to the Series A-3
Stockholders, the Series A-4 Stockholders, the Series A-5 Stockholders or the
Series A-6 Stockholders, or the holders of Common Stock or any other class or
series of stock ranking on Liquidation junior to such Series A-2 Stock, an
amount per share equal to the Series A-2 Original Purchase Price (as defined in
Section B.8 hereof), plus an amount equal to any declared or accrued but unpaid
dividends thereon, calculated pursuant to Section B.3(b) hereof; (iii) after the
distribution to the Series A-1 Stockholders, the Series A-2 Stockholders and
holders of any other class or series of capital stock that is senior the
Series A-3 Stock as to Liquidation, of the full amount to which they are
entitled to receive pursuant to this Section B.4(b) or any other section of this
Certificate as in effect from time to time, the Series A-3 Stockholders, the
Series A-5 Stockholders, and the Series A-6 Stockholders shall be entitled to
receive out of the assets of the Corporation legally available for distribution
to its stockholders, whether from capital, surplus or earnings, before any
payment shall be made to the Series A-4 Stockholders or the holders of Common
Stock or any other class or series of stock ranking

 

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on Liquidation junior to such Series A-3 Stock, Series A-5, or Series A-6 Stock
an amount per share equal to the Series A-3 Original Purchase Price (as defined
in Section B.8 hereof), Series A-5 Original Purchase Price (as defined in
Section B.8 hereof) or Series A-6 Original Purchase Price (as defined in
Section B.8 hereof), respectively, plus an amount equal to any declared or
accrued but unpaid dividends thereon, calculated pursuant to Section B.3 hereof;
and (iv) after the distribution to the Series A-1 Stockholders, the Series A-2
Stockholders, the Series A-3 Stockholders, the Series A-5 Stockholders, the
Series A-6 Stockholders and holders of any other class or series of capital
stock that is senior to the Series A-4 Stock as to Liquidation, of the full
amount to which they are entitled to receive pursuant to this Section B.4(b) or
any other section of this Certificate as in effect from time to time, the
Series A-4 Stockholders shall be entitled to receive out of the assets of the
Corporation legally available for distribution to its stockholders, whether from
capital, surplus or earnings, before any payment shall be made to the holders of
Common Stock or any other class or series of stock ranking on Liquidation junior
to such Series A-4 Stock an amount per share equal to the Series A-4 Original
Purchase Price (as defined in Section B.8 hereof), plus an amount equal to any
declared but unpaid dividends thereon, calculated pursuant to Section B.3
hereof.

 

(c)                      If, upon any Liquidation, the assets of the Corporation
available for distribution to its stockholders shall be insufficient to pay the
Series A-1 Stockholders the full amount to which each of them shall be entitled
pursuant to Section A.4(b) above, then the Series A-1 Stockholders shall share
ratably in any distribution of assets according to the respective amounts which
would be payable to them in respect of the shares of Series A-1 Stock held upon
such distribution if all amounts payable on or with respect to such shares were
paid in full.

 

(d)                     If, upon any Liquidation, the assets of the Corporation
available for distribution to its stockholders shall be insufficient to pay the
Series A-2 Stockholders the full amount to which each of them shall be entitled
pursuant to Section B.4(b) above and to pay to the holders of any other class or
series of capital stock that is on a parity with the Series A-2 Stock upon
Liquidation the full amount to which each of such holders shall be entitled
pursuant to Section B.4(b) or any other section of this Certificate as in effect
from time to time, then the Series A-2 Stockholders and such holders shall share
ratably in any distribution of assets according to the respective amounts which
would be payable to them in respect of the shares of Series A-2 Stock and the
shares of such other class or series of capital stock held upon such
distribution if all amounts payable on or with respect to all of such shares
were paid in full.

 

(e)                      If, upon any Liquidation, the assets of the Corporation
available for distribution to its stockholders shall be insufficient to pay the
Series A-3 Stockholders, the Series A-5 Stockholders and the Series A-6
Stockholders the full amount to which each of them shall be entitled pursuant to
Section B.4(b) above and to pay to the holders of any other class or series of
capital stock that is on a parity with the Series A-3, Series A-5 Stock and the
Series A-6 Stock upon Liquidation the full amount to which each of such holders
shall be entitled pursuant to Section B.4(b) or any other section of this
Certificate as in effect from time to time, then the Series A-3 Stockholders,
the Series A-5 Stockholders, the Series A-6 Stockholders and such holders shall
share ratably in any distribution of assets according to the respective amounts
which would be payable to them in respect of the shares of Series A-3 Stock,
Series A-5 Stock and Series A-6 Stock and the shares of such other class or
series of capital stock, as the case may be, held upon such distribution if all
amounts payable on or with respect to all of such shares were paid in full.

 

(f)                       If, upon any Liquidation, the assets of the
Corporation available for distribution to its stockholders shall be insufficient
to pay the Series A-4 Stockholders the full amount to which each of them shall
be entitled pursuant to Section B.4(b) above and to pay to the holders of any
other class or series of capital stock that is on a parity with the Series A-4
Stock upon Liquidation the full amount to which each of such holders shall be
entitled pursuant to Section B.4(b) or any other section of this Certificate as
in effect from time to time, then the Series A-4 Stockholders and such holders
shall share ratably in any distribution of assets according to the respective
amounts which would be payable to them in respect of the

 

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shares of Series A-4 Stock and the shares of such other class or series of
capital stock held upon such distribution if all amounts payable on or with
respect to all of such shares were paid in full.

 

(g)                      In the event of any Liquidation, after payment shall
have been made to the New Preferred Stockholders of the full amount to which
they shall be entitled pursuant to Section B.4(b) and to the holders of any
class or series of capital stock that is senior to or on parity with the New
Preferred Stock, or any series, thereof, as in effect from time to time, the
holders of each other class or series of capital stock (other than Common Stock)
ranking on Liquidation junior to the New Preferred Stock, but senior to the
Common Stock, as a class, shall be entitled to receive an amount equal (and in
like kind) to the aggregate preferential amount fixed for each such junior class
or series of capital stock.  If, upon any Liquidation, after payment shall have
been made to the New Preferred Stockholders of the full amount to which they
shall be entitled pursuant to Section B.4(b), the assets of the Corporation
available for distribution to its stockholders shall be insufficient to pay a
class or series of capital stock (other than the Common Stock) junior to the New
Preferred Stock the full amount to which they shall be entitled pursuant to the
preceding sentence, the holders of such other class or series of capital stock
shall share ratably, based upon the number of then outstanding shares of such
other class or series of capital stock, in any remaining distribution of assets
according to the respective preferential amounts fixed for such junior class or
series of capital stock or which would be payable to them in respect of the
shares held by them upon such distribution if all amounts payable on or with
respect to such shares were paid in full.

 

(h)                     In the event of any Liquidation, after payments shall
have been made first to the New Preferred Stockholders and to the holders of any
class or series of capital stock that is senior to or on parity with the New
Preferred Stock, or any series thereof, as in effect from time to time, and to
the holders of class or series of capital stock that is junior to or on parity
with the New Preferred Stock but senior to the Common Stock, of the full amount
to which they each shall be entitled as aforesaid, the holders of Common Stock,
as a class, shall be entitled to share ratably with the holders of Participating
Preferred Stock as provided in the last sentence in this Section B.4(h)) in all
remaining assets of the Corporation legally available for distribution to its
stockholders.  For purposes of calculating the amount of any payment to be paid
upon any such Liquidation pursuant to the participation feature described in
this Section B.4(h), each share of such Participating Preferred Stock shall be
deemed to be that number of shares (including fractional shares and any shares
attributable to the payment of accrued and unpaid dividends upon conversion of
such Participating Preferred Stock pursuant to Section B.7(b)) of Common Stock
into which it is then convertible, rounded to the nearest one-tenth of a share.

 

(i)                         (i) In the event of and simultaneously with the
closing of an Event of Sale, the Corporation shall, unless waived by the New
Senior Majority or otherwise prevented by law, redeem all of the shares of New
Preferred Stock then outstanding for a cash amount per share determined as set
forth in Sections B.4(a) through (h) hereof (the “Special Liquidation Price,”
said redemption being referred to herein as a “Special Liquidation”).  In the
event the Event of Sale involves consideration that does not consist of cash,
then the Special Liquidation Price may be paid with such consideration having a
value equal to the Special Liquidation Price.  To the extent there is any cash
consideration in connection with an Event of Sale, at the option of the New
Senior Majority, the cash consideration will first (i) be applied to satisfy the
Special Liquidation Price payable to the Series A-1 Stockholders and to the
holders of any other class or series of capital stock that is senior to or on
parity with the Series A-1 Stock as to Liquidation; and then (ii) be applied to
satisfy the Special Liquidation Price payable to the holders of Series A-2 Stock
and to the holders of any other class or series of capital stock that is junior
to the Series A-1 Stock but senior to or on parity with the Series A-2 Stock as
to Liquidation; and then (iii) be applied to satisfy the Special Liquidation
Price payable to holders of Series A-3 Stock, Series A-5 Stock, Series A-6 Stock
and any other class or series of capital stock that is junior to the Series A-2
Stock but senior to or on parity with the Series A-3 Stock, Series A-5 Stock and
Series A-6 Stock as to Liquidation (in relative proportion to the full
liquidation preference the Series A-3 Stockholders, Series A-5 Stockholders,
Series A-6 Stockholders and

 

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the holders of such other class or series of capital stock would have received
had there been sufficient cash consideration to have paid their liquidation
preference in full) and then (iv) be applied to satisfy the Special Liquidation
Price payable to the holders of Series A-4 Stock and to the holders of any other
class or series of capital stock that is junior to the Series A-3 Stock,
Series A-5 Stock and Series A-6 Stock but senior to or on parity with the
Series A-4 Stock, in all cases, prior to the payment thereof to any other
stockholders of the Corporation.  For all purposes of this Section B.4(i), the
Special Liquidation Price shall be equal to that amount per share which would be
received by each New Preferred Stockholder if, in connection with an Event of
Sale, all the consideration paid in exchange for the assets or the shares of
capital stock (as the case may be) of the Corporation were actually paid to and
received by the Corporation and the Corporation were immediately thereafter
liquidated and its assets distributed pursuant to Sections B.4(a) through
(h) hereof.  To the extent that one or more redemptions (as described in
Section B.5 hereof) and/or Special Liquidations are occurring concurrently, the
Special Liquidation under this Section B.4(i) shall be deemed to occur first. 
The date upon which the Special Liquidation shall occur is sometimes referred to
herein as the “Special Liquidation Date”.

 

(ii)                                  In the absence of an applicable waiver
pursuant to Section B.4(i) above, at any time on or after the Special
Liquidation Date, a New Preferred Stockholder shall be entitled to receive the
Special Liquidation Price for each such share of New Preferred Stock owned by
such holder.  Subject to the provisions of Section B.4(i)(iii) hereof, payment
of the Special Liquidation Price will be made to each such holder upon actual
delivery to the Corporation or its transfer agent of the certificate of such
holder representing such shares of New Preferred Stock, as the case may be, or
an affidavit of loss as to the same.

 

(iii)                               If on the Special Liquidation Date less than
all the shares of New Preferred Stock then outstanding may be legally redeemed
by the Corporation, the Special Liquidation shall be made first as to the
Series A-1 Stock (and any other class or series of capital stock that is senior
to or on parity with the Series A-1 Stock as to Liquidation), pro rata with
respect to such Series A-1 Stock  (or such other class or series of capital
stock that is senior to or on parity with the Series A-1 Stock as to
Liquidation) based upon the number of outstanding shares of Series A-1 Stock (or
such other class or series of capital stock that is senior to or on parity with
the Series A-1 Stock as to Liquidation) then owned by each such holder thereof
until such holders are satisfied in full, and then to the Series A-2 Stock (and
any other class or series of capital stock that is junior to the Series A-1
Stock but senior to or on parity with the Series A-2 Stock as to Liquidation),
pro rata with respect to such Series A-2 Stock (or such other class or series of
capital stock that is junior to the Series A-1 Stock but senior to or on parity
with the Series A-2 Stock as to Liquidation) based upon the number of
outstanding shares of Series A-2 Stock (or such other class or series of capital
stock that is junior to the Series A-1 Stock but senior to or on parity with the
Series A-2 Stock as to Liquidation) then owned by each such holder thereof until
such holders are satisfied in full, and then to the holders of the Series A-3
Stock, Series A-5 Stock and Series A-6 Stock (and any other class or series of
capital stock that is junior to the Series A-2 Stock but senior to or on parity
with the Series A-3 Stock, Series A-5 Stock and Series A-6 Stock as to
Liquidation), pro rata with respect to such Series A-3, Stock Series A-5 Stock
and Series A-6 Stock (or such other class or series of capital stock that is
junior to the Series A-2 Stock but senior to or on parity with the Series A-3
Stock, Series A-5 Stock and Series A-6 Stock as to Liquidation) based upon the
number of outstanding shares of Series A-3 Stock, Series A-5 Stock and
Series A-6 Stock (or such other class or series of capital stock that is junior
to the Series A-2 Stock but senior to or on parity with the Series A-3 Stock,
Series A-5 Stock and Series A-6 Stock as to Liquidation) then owned by each
holder thereof, and then to the Series A-4 Stock (and any other class or series
of capital stock that is junior to the Series A-3 Stock, Series A-5 Stock and
Series A-6 Stock but senior to or on parity with the Series A-4 Stock as to
Liquidation), pro rata with respect to such Series A-4 Stock (or such other
class or series of capital stock that is junior to the Series A-3 Stock,
Series A-5 Stock and Series A-6 Stock but senior to or on parity with the
Series A-4 Stock as to Liquidation) based upon the number of outstanding shares
of Series A-4 Stock (or such other

 

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class or series of capital stock that is junior to the Series A-3 Stock,
Series A-5 Stock and Series A-6 Stock but senior to or on parity with the
Series A-4 Stock as to Liquidation) then owned by each such holder thereof until
such holders are satisfied in full.

 

(iv)                              On and after any Special Liquidation Date, all
rights in respect of the shares of New Preferred Stock to be redeemed shall
cease and terminate except the right to receive the applicable Special
Liquidation Price as provided herein, and such shares of New Preferred Stock
shall no longer be deemed to be outstanding, whether or not the certificates
representing such shares of New Preferred Stock have been received by the
Corporation; provided, however, that, if the Corporation defaults in the payment
of the Special Liquidation Price with respect to any New Preferred Stock, the
rights of the holder(s) thereof with respect to such shares of New Preferred
Stock shall continue until the Corporation cures such default.

 

(v)                                 Anything contained herein to the contrary
notwithstanding, all or any of the provisions of this Section B.4(i) may be
waived by the New Senior Majority, by delivery of written notice of waiver to
the Corporation prior to the closing of any Event of Sale.

 

(vi)                              Any notice required to be given to the holders
of shares of New Preferred Stock pursuant to Section B.7(g) hereof in connection
with an Event of Sale shall include a statement by the Corporation of (A) the
Special Liquidation Price which each New Preferred Stockholder shall be entitled
to receive upon the occurrence of a Special Liquidation under this
Section B.4(i) and (B) the extent to which the Corporation will, if at all, be
legally prohibited from paying each holder of New Preferred Stock the Special
Liquidation Price.

 

5.              Definition of “Event of Sale” and “Shell Company Successor”. 
For purposes of this Part B of Article III, an “Event of Sale” shall mean:
(A) the sale by the stockholders of voting control of the Corporation, (B) the
merger, consolidation or reorganization with or into any other corporation,
entity or person or any other corporate reorganization, in which (I) the capital
stock of the Corporation immediately prior to such merger, consolidation or
reorganization represents less than 50% of the voting power of the surviving
entity (or, if the surviving entity is a wholly owned subsidiary, its parent)
immediately after such merger, consolidation or reorganization or (II) the
surviving entity (or, if the surviving entity is a wholly owned subsidiary, its
parent) has a class of securities that is (or has been within 90 days prior to
such transaction) tradeable on any public market or exchange or (C) the sale,
exclusive license or other disposition of all or substantially all of the assets
or intellectual property of the Corporation in a single transaction or series of
related transactions. Notwithstanding the foregoing and for purposes of
clarification, the term “Event of Sale” shall not include any transaction
involving the Corporation and the Shell Company Successor that is described in
clause (iii) of the Shell Company Successor definition set forth below. “Shell
Company Successor” means a shell company that (i) has securities registered
under the Securities Exchange Act of 1934, as amended, (ii) has nominal
operations and nominal assets (prior to any of the transactions described in
clause (iii)) and (iii) directly or indirectly through one or more direct or
indirect subsidiaries acquires the Corporation and/or all or substantially all
of its assets or business (whether pursuant to a stock purchase, an asset
purchase, a merger or any other similar transaction), and in consideration for
such acquisition issues to the former stockholders of the Corporation shares of
capital stock of such shell company.

 

6.              Voting.

 

(a)                     Subject to any separate voting rights provided for
herein or otherwise required by law, the holders of New Preferred Stock shall be
entitled to vote, together with the holders of Common Stock as one class, on all
matters as to which holders of Common Stock shall be entitled to vote, in the
same manner and with the same effect as such holders of Common Stock.  In any
such vote, each share of

 

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New Preferred Stock shall entitle the holder thereof to the number of votes per
share that equals the number of shares of Common Stock (including fractional
shares) into which each such share of New Preferred Stock is then convertible,
rounded up to the nearest one-tenth of a share, but not including any shares of
Common Stock issuable upon conversion of any dividends accrued on such New
Preferred Stock.

 

(b)                     In addition to the rights specified in Section B.6(a):

 

(i)                           for so long as any shares of Series A-1 Stock are
outstanding, the holders of a majority of the shares of Series A-1 Stock
outstanding, voting as a separate class, shall have the right to elect two
(2) members of the Board of Directors of the Corporation; and

 

(ii)                        Oxford Bioscience Partners IV L.P. (including for
this purpose, members of the Oxford/Saints Group (as defined in the
Stockholders’ Agreement), HealthCare Ventures or Wellcome Trust (collectively,
the “G3 Holders”) voting as a separate class shall have the right to elect one
(1) member of the Board of Directors of the Corporation by majority vote of the
shares of Series A-1 Stock held by them; provided, however, that in order to be
eligible to vote or consent with respect to the election of such member of the
Board of Directors, a G3 Holder together with members of such G3 Holders’ Group
(as defined in the Stockholders’ Agreement) must hold greater than twenty
percent (20%) of the shares of Series A-1 Stock purchased under the Series A-1
Stock Purchase Agreement by such G3 Holder and the members of such G3 Holders’
Group; and

 

(iii)                     MPM Capital L.P., voting as a separate class, shall
have the right to elect one (1) member of the Board of Directors of the
Corporation by majority vote of the shares of Series A-1 Stock held by MPM
Capital L.P.; provided that such member of the Board of Directors shall be an
individual with particular expertise in the development of pharmaceutical
products; and, provided, further, that in order to be eligible to vote or
consent with respect to the election of such member of the Board of Directors,
MPM Capital L.P. together with members of the MPM Group (as defined in the
Stockholders’ Agreement) must hold greater than twenty percent (20%) of the
shares of Series A-1 Stock purchased under the Series A-1 Stock Purchase
Agreement by MPM Capital L.P. and the members of the MPM Group.

 

(iv)                    The members of the Board of Directors elected by the
Series A-1 Stockholders, the G3 Holders and MPM Capital L.P. pursuant to this
Section B.6(b) are referred to herein as the “New Preferred Directors”.

 

(c)                      In any election of New Preferred Directors pursuant to
Section B.6(b), each holder of New Preferred Stock eligible to participate in
the election of New Preferred Directors shall be entitled to one vote for each
share of Common Stock (including fractional shares) into which each such share
of New Preferred Stock held by such holder is then convertible, rounded up to
the nearest one-tenth of a share (determined as set forth in the second sentence
of Section B.6(a) hereof), and no holder of New Preferred Stock shall be
entitled to cumulate its votes by giving one candidate more than one vote per
share.  The voting right of the Series A-1 Stockholders, the G3 Holders and the
MPM Holder contained in Section B.6(b), may be exercised at a special meeting of
the applicable holders of New Preferred Stock called as provided in accordance
with the by-laws of the Corporation, at any annual or special meeting of the
stockholders of the Corporation, or by written consent of such applicable
holders of New Preferred Stock in lieu of a meeting.  The New Preferred
Directors elected pursuant to Section B.6(b) shall serve from the date of their
election and qualification until their successors have been duly elected and
qualified.  The number of directors constituting the entire membership of the
Board of Directors of the Corporation shall be set by the Board of Directors
pursuant to the By-Laws of the Corporation.

 

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(d)                     A vacancy in the directorships elected by the Series A-1
Stockholders, the G3 Holders or the MPM Holder pursuant to Section B.6(b), may
be filled by a vote at a meeting called in accordance with the by-laws of the
Corporation or written consent in lieu of such meeting of the applicable holders
of New Preferred Stock, respectively or by the remaining directors as provided
in the by-laws of the Corporation.

 

(e)                      The holders of capital stock of the corporation, voting
as a single class, shall elect the remaining member or members of the Board of
Directors of the Corporation.  In any election of directors pursuant to this
Section B.6(e), each stockholder shall be entitled to one vote for each share of
Common Stock held or, if New Preferred Stock, into which each such share of New
Preferred Stock is then convertible (determined in accordance with
Section B.6(a) hereof), and no stockholder shall be entitled to cumulate its
votes by giving one candidate more than one vote per share.  The voting right of
the stockholders contained in this Section B.6(e) may be exercised at a special
meeting of the stockholders called as provided in accordance with the by-laws of
the Corporation, at any annual or special meeting of the stockholders of the
Corporation, or by written consent of the stockholder in lieu of a meeting.  The
director or directors elected pursuant to this Section B.6(e) shall serve from
the date of their election and qualification until their successors have been
duly elected and qualified.

 

(f)                       A vacancy in the directorship or directorships elected
by the stockholders pursuant to Section B.6(e), may be filled by a vote at a
meeting called in accordance with the by-laws of the Corporation or written
consent in lieu of such meeting of the stockholders of the Corporation or by the
remaining directors as provided in the by-laws of the Corporation.

 

(g)                      Except as otherwise expressed, implied or contemplated
in this Certificate, the Series A-1 Purchase Agreement or the Merger Agreement,
the Corporation shall not, directly or indirectly, through a merger,
consolidation, reorganization or otherwise, without the affirmative approval of
the New Senior Majority acting separately from the holders of Common Stock or
any other securities of the Corporation, given by written consent in lieu of a
meeting or by vote at a meeting called for such purpose, for which meeting or
approval by written consent timely and specific notice in the manner provided in
the by-laws of the Corporation shall have been given to each Series A-1
Stockholder, Series A-2 Stockholder and Series A-3 Stockholder to do the
following:

 

(i)                                     authorize, create, designate, issue or
sell any class or series of capital stock (including any shares of treasury
stock) or rights, options, warrants or other securities convertible into or
exercisable or exchangeable for capital stock which by its terms is convertible
into or exchangeable for any equity security, other then Excluded Stock, which,
as to the payment of dividends or distribution of assets, including without
limitation distributions to be made upon a Liquidation, is senior to or on a
parity with the Series A-1 Stock; or

 

(ii)                                                amend, alter or repeal any
provision of this Certificate; or

 

(iii)                                             permit, approve or agree to
any Liquidation, Event of Sale, dissolution or winding up of the Corporation.

 

The foregoing approval shall be obtained in addition to any approval required by
law.

 

(h)                     Except as otherwise expressed, implied or contemplated
in this Certificate, the Series A-1 Purchase Agreement or the Merger Agreement,
the Corporation shall not, directly or indirectly, through a merger,
consolidation, reorganization or otherwise, without the affirmative approval of
holders of a majority of the then outstanding shares of Series A-1 Stock, acting
separately from the holders of Common Stock or any other securities of the
Corporation, given by written consent in lieu of a meeting or

 

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by vote at a meeting called for such purpose, for which meeting or approval by
written consent timely and specific notice in the manner provided in the by-laws
of the Corporation shall have been given to each holder of such Series A-1
Stock, amend, alter or repeal any provision of this Certificate if such
amendment, alteration or repeal would (i) alter or change the rights,
preferences or privileges of the Series A-1 Stock in a manner that materially
adversely affects the Series A-1 Stock and such amendment does not change or
alter the comparable rights, preferences or privileges of any other series of
New Preferred Stock in a manner that materially adversely affects such other
series of New Preferred Stock or (ii) increases or decreases the authorized
number of shares of Series A-1 Stock. The foregoing approval shall be obtained
in addition to any approval required by law. For purposes of clarification, the
creation, authorization or issuance of any new class or series of capital stock
of the Corporation having rights, preferences or privileges senior to or on a
parity with the Series A-1 Stock (and any amendment to the certificate of
incorporation of the Company for purposes of creating or authorizing such new
class or series of capital stock) shall not be deemed or treated as materially
adversely affecting the Series A-1 Stock.

 

(i)                         Except as otherwise expressed, implied or
contemplated in this Certificate, the Series A-1 Purchase Agreement or the
Merger Agreement, the Corporation shall not, directly or indirectly, through a
merger, consolidation, reorganization or otherwise, without the affirmative
approval of holders of a majority of the then outstanding shares of Series A-2
Stock, acting separately from the holders of Common Stock or any other
securities of the Corporation, given by written consent in lieu of a meeting or
by vote at a meeting called for such purpose, for which meeting or approval by
written consent timely and specific notice in the manner provided in the by-laws
of the Corporation shall have been given to each holder of such Series A-2
Stock, amend, alter or repeal any provision of this Certificate if such
amendment, alteration or repeal would (i) alter or change the rights,
preferences or privileges of the Series A-2 Stock in a manner that materially
adversely affects the Series A-2 Stock and such amendment does not change or
alter the comparable rights, preferences or privileges of any other series of
New Preferred Stock in a manner that materially adversely affects such other
series of New Preferred Stock or (ii) increases or decreases the authorized
number of shares of Series A-2 Stock. The foregoing approval shall be obtained
in addition to any approval required by law. For purposes of clarification, the
creation, authorization or issuance of any new class or series of capital stock
of the Corporation having rights, preferences or privileges senior to or on a
parity with the Series A-2 Stock (and any amendment to the certificate of
incorporation of the Company for purposes of creating or authorizing such new
class or series of capital stock) shall not be deemed or treated as materially
adversely affecting the Series A-2 Stock.

 

(j)                        Except as otherwise expressed, implied or
contemplated in this Certificate, the Series A-1 Purchase Agreement or the
Merger Agreement, the Corporation shall not, directly or indirectly, through a
merger, consolidation, reorganization or otherwise, without the affirmative
approval of holders of a majority of the then outstanding shares of Series A-3
Stock, acting separately from the holders of Common Stock or any other
securities of the Corporation, given by written consent in lieu of a meeting or
by vote at a meeting called for such purpose, for which meeting or approval by
written consent timely and specific notice in the manner provided in the by-laws
of the Corporation shall have been given to each holder of such Series A-3
Stock, amend, alter or repeal any provision of this Certificate if such
amendment, alteration or repeal would (i) alter or change the rights,
preferences or privileges of the Series A-3 Stock in a manner that materially
adversely affects the Series A-3 Stock and such amendment does not change or
alter the comparable rights, preferences or privileges of any other series of
New Preferred Stock in a manner that materially adversely affects such other
series of New Preferred Stock or (ii) increases or decreases the authorized
number of shares of Series A-3 Stock. The foregoing approval shall be obtained
in addition to any approval required by law. For purposes of clarification, the
creation, authorization or issuance of any new class or series of capital stock
of the Corporation having rights, preferences or privileges senior to or on a
parity with the Series A-3 Stock (and any amendment to the certificate of
incorporation of the Company for purposes of creating or authorizing such new
class or series of capital stock) shall not be deemed or treated as materially
adversely affecting the Series A-3 Stock.

 

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(k)                     Except as otherwise expressed, implied or contemplated
in this Certificate, the Series A-1 Purchase Agreement or the Merger Agreement,
the Corporation shall not, directly or indirectly, through a merger,
consolidation, reorganization or otherwise, without the affirmative approval of
holders of a majority of the then outstanding shares of Series A-4 Stock, acting
separately from the holders of Common Stock or any other securities of the
Corporation, given by written consent in lieu of a meeting or by vote at a
meeting called for such purpose, for which meeting or approval by written
consent timely and specific notice in the manner provided in the by-laws of the
Corporation shall have been given to each holder of such Series A-4 Stock,
amend, alter or repeal any provision of this Certificate if such amendment,
alteration or repeal would (i) alter or change the rights, preferences or
privileges of the Series A-4 Stock in a manner that materially adversely affects
the Series A-4 Stock and such amendment does not change or alter the comparable
rights, preferences or privileges of any other series of New Preferred Stock in
a manner that materially adversely affects such other series of New Preferred
Stock or (ii) increases or decreases the authorized number of shares of
Series A-4 Stock. The foregoing approval shall be obtained in addition to any
approval required by law. For purposes of clarification, the creation,
authorization or issuance of any new class or series of capital stock of the
Corporation having rights, preferences or privileges senior to or on a parity
with the Series A-4 Stock (and any amendment to the certificate of incorporation
of the Company for purposes of creating or authorizing such new class or series
of capital stock) shall not be deemed or treated as materially adversely
affecting the Series A-4 Stock.

 

(l)                         Except as otherwise expressed, implied or
contemplated in this Certificate, the Series A-1 Purchase Agreement or the
Merger Agreement, the Corporation shall not, directly or indirectly, through a
merger, consolidation, reorganization or otherwise, without the affirmative
approval of holders of a majority of the then outstanding shares of Series A-5
Stock, acting separately from the holders of Common Stock or any other
securities of the Corporation, given by written consent in lieu of a meeting or
by vote at a meeting called for such purpose, for which meeting or approval by
written consent timely and specific notice in the manner provided in the by-laws
of the Corporation shall have been given to each holder of such Series A-5
Stock, amend, alter or repeal any provision of this Certificate if such
amendment, alteration or repeal would (i) alter or change the rights,
preferences or privileges of the Series A-5 Stock in a manner that materially
adversely affects the Series A-5 Stock and such amendment does not change or
alter the comparable rights, preferences or privileges of any other series of
New Preferred Stock in a manner that materially adversely affects such other
series of New Preferred Stock or (ii) increases or decreases the authorized
number of shares of Series A-5 Stock. The foregoing approval shall be obtained
in addition to any approval required by law. For purposes of clarification, the
creation, authorization or issuance of any new class or series of capital stock
of the Corporation having rights, preferences or privileges senior to or on a
parity with the Series A-5 Stock (and any amendment to the certificate of
incorporation of the Company for purposes of creating or authorizing such new
class or series of capital stock) shall not be deemed or treated as materially
adversely affecting the Series A-5 Stock.

 

(m)                 Except as otherwise expressed, implied or contemplated in
this Certificate, the Series A-1 Purchase Agreement or the Merger Agreement, the
Corporation shall not, directly or indirectly, through a merger, consolidation,
reorganization or otherwise, without the affirmative approval of holders of a
majority of the then outstanding shares of Series A-6 Stock, acting separately
from the holders of Common Stock or any other securities of the Corporation,
given by written consent in lieu of a meeting or by vote at a meeting called for
such purpose, for which meeting or approval by written consent timely and
specific notice in the manner provided in the by-laws of the Corporation shall
have been given to each holder of such Series A-6 Stock, amend, alter or repeal
any provision of this Certificate if such amendment, alteration or repeal would
(i) alter or change the rights, preferences or privileges of the Series A-6
Stock in a manner that materially adversely affects the Series A-6 Stock and
such amendment does not change or alter the comparable rights, preferences or
privileges of any other series of New Preferred Stock in a manner that
materially adversely affects such other series of New Preferred Stock or
(ii) increases or decreases the authorized number of shares of Series A-6 Stock.
The foregoing approval shall be obtained in

 

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addition to any approval required by law. For purposes of clarification, the
creation, authorization or issuance of any new class or series of capital stock
of the Corporation having rights, preferences or privileges senior to or on a
parity with the Series A-6 Stock (and any amendment to the certificate of
incorporation of the Company for purposes of creating or authorizing such new
class or series of capital stock) shall not be deemed or treated as materially
adversely affecting the Series A-6 Stock.

 

(n)                     The Corporation shall obtain the consent of the Board of
Directors before it may authorize or issue any additional shares of capital
stock of the Corporation or any of its subsidiaries.

 

7.              Conversion.

 

(a)                     Any New Preferred Stockholder shall have the right, at
any time or from time to time, to convert any or all of its shares of New
Preferred Stock into that number of fully paid and nonassessable shares of
Common Stock for each share of New Preferred Stock so converted equal to the
quotient of the Series A-1 Original Purchase Price, Series A-2 Original Purchase
Price, Series A-3 Original Purchase Price, Series A-4 Original Purchase Price,
Series A-6 Original Purchase Price or Series A-6 Original Purchase Price, as
applicable, for such share divided by the Series A-1 Conversion Price, the
Series A-2 Conversion Price, Series A-3 Conversion Price, Series A-4 Conversion
Price, Series A-5 Conversion Price or the Series A-6 Conversion Price (each as
defined in Section B.7(e)(i) hereof), as applicable, for such share of New
Preferred Stock, as last adjusted and then in effect, rounded up to the nearest
one-tenth of a share; provided, however, that cash shall be paid in lieu of the
issuance of fractional shares of Common Stock, as provided in
Section B.7(d) hereof.

 

(b)                     (i) Any New Preferred Stockholder who exercises the
right to convert shares of New Preferred Stock into shares of Common Stock
pursuant to this Section B.7 shall be entitled to payment of all accrued
dividends, whether or not declared and all declared but unpaid dividends payable
with respect to such New Preferred Stock pursuant to Section B.3 herein, up to
and including the Conversion Date (as defined in Section B.7(b)(iii) hereof).

 

(ii)                                  Any New Preferred Stockholder may exercise
the right to convert such shares into Common Stock pursuant to this Section B.7
by delivering to the Corporation during regular business hours, at the office of
the Corporation or any transfer agent of the Corporation or at such other place
as may be designated by the Corporation, the certificate or certificates for the
shares to be converted (the “New Preferred Certificate”), duly endorsed or
assigned in blank to the Corporation (if required by it) or an affidavit of loss
as to the same.

 

(iii)                               Each New Preferred Certificate shall be
accompanied by written notice stating that such holder elects to convert such
shares and stating the name or names (with address) in which the certificate or
certificates for the shares of Common Stock (the “Common Certificate”) are to be
issued.  Such conversion shall be deemed to have been effected on the date when
such delivery is made, and such date is referred to herein as the “Conversion
Date.”

 

(iv)                              As promptly as practicable thereafter, the
Corporation shall issue and deliver to or upon the written order of such holder,
at the place designated by such holder, (A) a Common Certificate for the number
of full shares of Common Stock to which such holder is entitled and (B) a check
or cash in respect of any fractional interest in shares of Common Stock to which
such holder is entitled, as provided in Section B.7(d) hereof, payable with
respect to the shares so converted up to and including the Conversion Date.

 

(v)                                 The person in whose name the Common
Certificate or Certificates are to be issued shall be deemed to have become a
holder of record of Common Stock on the applicable

 

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Conversion Date, unless the transfer books of the Corporation are closed on such
Conversion Date, in which event the holder shall be deemed to have become the
stockholder of record on the next succeeding date on which the transfer books
are open, provided that the Series A-1 Conversion Price, the Series A-2
Conversion Price, Series A-3 Conversion Price, Series A-4 Conversion Price, the
Series A-5 Conversion Price or the Series A-6 Conversion Price, as applicable,
upon which the conversion shall be executed shall be that in effect on the
Conversion Date.

 

(vi)                              Upon conversion of only a portion of the
number of shares covered by a New Preferred Certificate, the Corporation shall
issue and deliver to or upon the written order of the holder of such New
Preferred Certificate, at the expense of the Corporation, a new certificate
covering the number of shares of New Preferred Stock representing the
unconverted portion of the New Preferred Certificate, which new certificate
shall entitle the holder thereof to all the rights, powers and privileges of a
holder of such New Preferred Stock.

 

(c)                      If a New Preferred Stockholder shall surrender more
than one share of the same class of New Preferred Stock for conversion at any
one time, then the number of full shares of Common Stock issuable upon
conversion thereof shall be computed on the basis of the aggregate number of
shares of New Preferred Stock so surrendered.

 

(d)                     No fractional shares of Common Stock shall be issued
upon conversion of New Preferred Stock. The Corporation shall instead pay a cash
adjustment for any such fractional interest in an amount equal to the Current
Market Price thereof on the Conversion Date, as determined in accordance with
Section B.7(e)(vi) hereof.

 

(e)                      For all purposes of this Article III, Part B, the
initial conversion price of the Series A-1 Stock shall be the Series A-1
Original Purchase Price, the initial conversion price of the Series A-2 Stock
shall be the Series A-2 Original Purchase Price,  the initial conversion price
of the Series A-3 Stock shall be the Series A-3 Original Purchase Price, the
initial conversion price of the Series A-4 Stock shall be the Series A-4
Original Purchase Price, the initial conversion price of the Series A-5 Stock
shall be the Series A-5 Original Purchase Price, and the initial conversion
price of the Series A-6 Stock shall be the Series A-6 Original Purchase Price,
in each case subject to adjustment from time to time as follows (the conversion
price of any or each of the Series A-1 Stock, the Series A-2 Stock, the
Series A-3 Stock, the Series A-4 Stock, the Series A-5 Stock and the Series A-6
Stock is sometimes referred to generically in this Section B.7 as the
“Conversion Price”):

 

(i)                                     Subject to Section B.7(e)(ii) and
B.7(e)(x) below, if the Corporation shall, at any time or from time to time
after the Series A-1 Original Issuance Date, issue or sell any shares of Common
Stock (which term, for purposes of this Section B.7(e)(i), including all
subsections thereof, shall be deemed to include all other securities convertible
into, or exchangeable or exercisable for, shares of Common Stock (including, but
not limited to, Preferred Stock) or options to purchase or other rights to
subscribe for such convertible or exchangeable securities, in each case other
than Excluded Stock (as defined in Section B.7(e)(ii) below), for a
consideration per share less than the Series A-1 Conversion Price in effect
immediately prior to the issuance of such Common Stock or other securities (a
“New Dilutive Issuance”), then (X) the Conversion Price of the Series A-1 Stock
(the “Series A-1 Conversion Price”) in effect immediately prior to each such New
Dilutive Issuance shall automatically be reduced to a price equal to the product
obtained by multiplying such Series A-1 Conversion Price by a fraction, the
numerator of which shall be the number of shares of Common Stock outstanding
immediately prior to such issuance (including, without limitation, shares of
Common Stock issued or issuable upon conversion of the outstanding Preferred
Stock, but excluding shares of Common Stock issuable upon conversion of any
dividends accrued on such Preferred Stock) plus the number of shares of Common
Stock that the aggregate consideration received by the Corporation for the
additional stock so issued would purchase at

 

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such Series A-1 Conversion Price as in effect immediately prior to such
issuance, and the denominator of which shall be the number of shares of Common
Stock outstanding immediately prior to such issuance (including, without
limitation, shares of Common Stock issued or issuable upon conversion of the
outstanding Preferred Stock, but excluding shares of Common Stock issuable upon
conversion of any dividends accrued on such Preferred Stock) plus the number of
shares of additional stock so issued, (Y) the Conversion Price for the
Series A-2 Stock (the “Series A-2 Conversion Price”) in effect immediately prior
to each such New Dilutive Issuance shall automatically be reduced to a price
equal to the product obtained by multiplying such Series A-2 Conversion Price by
a fraction, the numerator of which shall be the number of shares of Common Stock
outstanding immediately prior to such issuance (including, without limitation,
shares of Common Stock issued or issuable upon conversion of the outstanding
Preferred Stock, but excluding shares of Common Stock issuable upon conversion
of any dividends accrued on such Preferred Stock) plus the number of shares of
Common Stock that the aggregate consideration received by the Corporation for
the additional stock so issued would purchase at such Series A-2 Conversion
Price as in effect immediately prior to such issuance, and the denominator of
which shall be the number of shares of Common Stock outstanding immediately
prior to such issuance (including, without limitation, shares of Common Stock
issued or issuable upon conversion of the outstanding Preferred Stock, but
excluding shares of Common Stock issuable upon conversion of any dividends
accrued on such Preferred Stock) plus the number of shares of additional stock
so issued, and (Z) the Conversion Price for the Series A-3 Stock (the
“Series A-3 Conversion Price”) in effect immediately prior to each such New
Dilutive Issuance shall automatically be reduced to a price equal to the product
obtained by multiplying such Series A-3 Conversion Price by a fraction, the
numerator of which shall be the number of shares of Common Stock outstanding
immediately prior to such issuance (including, without limitation, shares of
Common Stock issued or issuable upon conversion of the outstanding Preferred
Stock, but excluding shares of Common Stock issuable upon conversion of any
dividends accrued on such Preferred Stock) plus the number of shares of Common
Stock that the aggregate consideration received by the Corporation for the
additional stock so issued would purchase at such Series A-3 Conversion Price as
in effect immediately prior to such issuance, and the denominator of which shall
be the number of shares of Common Stock outstanding immediately prior to such
issuance (including, without limitation, shares of Common Stock issued or
issuable upon conversion of the outstanding Preferred Stock, but excluding
shares of Common Stock issuable upon conversion of any dividends accrued on such
Preferred Stock) plus the number of shares of additional stock so issued.  For
purposes of this Section B.7(e)(i), the number of shares of Common Stock deemed
issuable upon conversion of such outstanding shares of Existing Preferred Stock
shall be determined without giving effect to any adjustments to the applicable
Conversion Price resulting from the New Dilutive Issuance that is the subject of
this calculation.  For purposes of Part B of this Certificate, the term
“Series A-4 Conversion Price” shall mean the Conversion Price of the Series A-4
Stock, the term “Series A-5 Conversion Price” shall mean the Conversion Price of
the Series A-5 Stock and the term “Series A-6 Conversion Price” shall mean the
Conversion Price of the Series A-6 Stock.  For the purposes of any adjustment of
the Conversion Price pursuant to this Section B.7(e)(i), the following
provisions shall be applicable.

 

a.                                      In the case of the issuance of Common
Stock in whole or in part for cash, the consideration shall be deemed to be the
amount of cash paid therefor after deducting therefrom any discounts,
commissions or other expenses allowed, paid or incurred by the Corporation for
any underwriting or otherwise in connection with the issuance and sale thereof,
plus the value of any property other than cash received by the Corporation,
determined as provided in Section B.7(e)(i)(b) hereof, plus the value of any
other consideration received by the Corporation determined as set forth in
Section B.7(e)(i)(c) hereof.

 

b.                                      In the case of the issuance of Common
Stock for a consideration in whole or in part in property other than cash, the
value of such property other than cash shall be deemed to be the fair market
value of such property as determined in good faith by the Board of

 

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Directors, irrespective of any accounting treatment; provided, however, that
such fair market value of such property as determined by the Board of Directors
shall not exceed the aggregate Current Market Price (as defined in
Section B.7(e)(viii) hereof) of the shares of Common Stock or such other
securities being issued, less any cash consideration paid for such shares,
determined as provided in Section B.7(e)(i)(a) hereof and less any other
consideration received by the Corporation for such shares, determined as set
forth in Section B.7(e)(i)(c) hereof.

 

c.                                       In the case of the issuance of Common
Stock for consideration in whole or in part other than cash or property, the
value of such other consideration shall be deemed to be the aggregate par value
of such Common Stock (or the aggregate stated value if such Common Stock has no
par value).

 

d.                                      In the case of the issuance of options
or other rights to purchase or subscribe for Common Stock or the issuance of
securities by their terms convertible into or exchangeable or exercisable for
Common Stock or options to purchase or other rights to subscribe for such
convertible or exchangeable or exercisable securities:

 

i.                                          the aggregate maximum number of
shares of Common Stock deliverable upon exercise of such options to purchase or
rights to subscribe for Common Stock shall be deemed to have been issued at the
time such options or rights were issued and for a consideration equal to the
consideration (determined in the manner provided in Sections B.7(e)(i)(a),
(b) and (c) hereof), if any, received by the Corporation upon the issuance of
such options or rights plus the minimum purchase price provided in such options
or rights for the Common Stock covered thereby (the consideration in each case
to be determined in the manner provided in Sections B.7(e)(i)(a), (b) and
(c) hereof);

 

ii.                                       the aggregate maximum number of shares
of Common Stock deliverable upon conversion of, or in exchange for, any such
convertible or exchangeable securities or upon the exercise of options to
purchase or rights to subscribe for such convertible or exchangeable securities
and subsequent conversion or exchange thereof shall be deemed to have been
issued at the time such securities were issued or such options or rights were
issued and for a consideration equal to the consideration received by the
Corporation for any such securities and related options or rights (excluding any
cash received on account of accrued interest or accrued dividends), plus the
minimum additional consideration, if any, to be received by the Corporation upon
the conversion or exchange of such securities or the exercise of any related
options or rights (the consideration in each case to be determined in the manner
provided in Sections B.7(e)(i)(a), (b) and (c) hereof);

 

iii.                                    if there is any change (whether
automatic pursuant to the terms contained therein or as a result of the
amendment of such terms) in the exercise price of, or number of shares
deliverable upon exercise of, any such options or rights or upon the conversion
or exchange of any such convertible or exchangeable securities (other than a
change resulting from the original antidilution provisions thereof in place at
the time of issuance of such security), then the applicable Conversion Price
shall automatically be readjusted in proportion to such change (notwithstanding
the foregoing, no adjustment pursuant to this clause shall have the effect of
increasing the applicable Conversion Price to an amount which exceeds the lower
of (i) the applicable Conversion Price on the original adjustment date, or
(ii) the applicable Conversion Price that would have resulted from any Dilutive
Issuances between the original adjustment date and such readjustment date);

 

iv.                                   upon the expiration of any such options or
rights or the termination of any such rights to convert or exchange such
convertible or exchangeable securities (or in the event that the change that
precipitated an adjustment pursuant to Section

 

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B.7(e)(i)(d)(iii) hereof is reversed or terminated, or expires), then the
applicable Conversion Price shall be automatically readjusted to the applicable
Conversion Price that would have been obtained had such options, rights or
convertible or exchangeable securities not been issued; and

 

v.                                      if the terms of any option or
convertible security (excluding options or convertible securities which, upon
exercise, conversion or exchange thereof, would entitle the holder thereof to
receive shares of Common Stock which are Excluded Stock), the issuance of which
was not a New Dilutive Issuance, are revised after the Series A-1 Original
Issuance Date (either automatically pursuant the provisions contained therein or
as a result of an amendment to such terms) to provide for either (1) any
increase in the number of shares of Common Stock issuable upon the exercise,
conversion or exchange of any such option or convertible security or (2) any
decrease in the consideration payable to the Corporation upon such exercise,
conversion or exchange, then such option or convertible security, as so amended,
and the shares of Common Stock subject thereto shall be deemed to have been
issued effective upon such increase or decrease becoming effective.

 

(ii)                                  “Excluded Stock” shall mean:

 

a.                                      Common Stock issued upon conversion of
any shares of Preferred Stock, including any shares of Common Stock issuable
upon conversion of any dividends accrued on such Preferred Stock;

 

b.                                      Common Stock issued or issuable to
officers, directors or employees of or consultants or independent contractors to
the Corporation, pursuant to any written agreement, plan or arrangement to
purchase, or rights to subscribe for, such Common Stock, including Common Stock
issued under the Corporation’s 2003 Long-Term Incentive Plan, as amended, or
other equity incentive plan or other agreements that have been approved in form
and in substance by the New Senior Majority, calculated in accordance with
Section B.6(a) of Article III herein (including, in such calculation, any
outstanding restricted stock awards held by such holders), and which, as a
condition precedent to the issuance of such shares, provide for the vesting of
such shares and subject such shares to restrictions on transfer and rights of
first offer in favor of the Corporation, and restricted stock grants to
directors, employees or consultants as approved by the Board of Directors of the
Corporation; provided, however, that the maximum number of shares of Common
Stock heretofore or hereafter issuable pursuant to the Corporation’s 2003
Long-Term Incentive Plan, as amended, and all such agreements, plans and
arrangements shall not exceed 2,015,666 shares of Common Stock;

 

c.                                       Common Stock issued as a stock dividend
or distribution on the Preferred Stock payable in shares of Common Stock, or
capital stock of any other class issuable upon any subdivision, recombination,
split-up or reverse stock split of all the outstanding shares of such class of
capital stock;

 

d.                                      Common Stock or other securities issued
or issuable to banks, lenders or landlords, provided that each such issuance is
approved by the Board of Directors, including, but not limited to, warrants to
acquire Common Stock held by Silicon Valley Bank (or its affiliates, successors
and assignees), warrants to purchase Preferred Stock issued or to be issued to
GE Healthcare Financial Services, Inc. (“GEHFS”) and Oxford Finance Corporation
(“OFC”) pursuant to a proposed debt financing approved by the Board of Directors
(the “GE Financing”), shares of Preferred Stock issued or issuable to GE in
connection with the GE Financing or upon exercise by GEHFS or OFC of warrants
issued in the GE Financing and shares of common stock issuable upon conversion
of any such shares of Preferred Stock issued to GEHFS or OFC pursuant to the GE
Financing;

 

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e.                                       Common Stock or other securities issued
or issuable to third parties in connection with strategic partnerships or
alliances, corporate partnerships, joint ventures or other licensing
transactions, provided that each such transaction and related issuance is
approved by the Board of Directors, including, but not limited to, (A) any
shares of Preferred Stock or Common Stock issued or issuable to Ipsen Pharma SAS
(“Ipsen”), pursuant to the terms of that certain License Agreement, as amended
and may be amended with the approval of the Board of Directors of the
Corporation and in effect from time to time, by and between the Corporation and
Ipsen as payment for milestones in lieu of cash payments and (B) shares of
Series A-5 Stock issued or issuable pursuant to that certain Stock Issuance
Agreement as of March 29, 2011 by and between the Corporation and Nordic
Bioscience and the letter agreement as of March 29, 2011 by and between the
Corporation and Nordic Bioscience, pursuant to which the Corporation will issue
shares of the Corporation’s Series A-5 Convertible Preferred Stock, $0.01 par
value per share and the issuance of Series A-6 Stock issued or to be issued as
dividends on such Series A-5 Stock, and shares of Common Stock issuable upon
conversion of any such shares of Series A-5 Stock and Series A-6 Stock;

 

f.                                        Common Stock or other securities
issued or issuable pursuant to the acquisition by the Corporation of any other
corporation, partnership, joint venture, trust or other entity by any merger,
stock acquisition, reorganization, or purchase of substantially all assets or
otherwise in which the Corporation or its stockholders of record immediately
prior to the effective date of such transaction, directly or indirectly, own at
least a majority of the voting power of the acquired entity or the resulting
entity after such transaction, in each case so long as approved by the Board of
Directors;

 

g.                                       Common Stock or other securities, the
issuance of which is approved by the New Senior Majority, with such approval
expressly waiving the application of the anti-dilution provisions of this
Section B.7 as a result of such issuance;

 

h.                                      Preferred Stock or Common Stock issued
or issuable pursuant to any warrant outstanding as of the date hereof or any
warrant and any shares of Preferred Stock or common stock, or common stock
issued upon exercise of any Preferred Stock, issued in connection with the
Qualified Financing, including, but not limited to a warrant for shares of
Series A-1 Preferred Stock issued or issuable to Leerink Swan, any shares of
Preferred Stock or Common Stock upon exercise thereof and any Common Stock
issuable upon conversion of such Preferred Stock issued upon exercise thereof;
and

 

i.                                          All shares of New Preferred Stock
and Common stock issued in connection with the Qualified Financing as provided
in this Certificate and the Series A-1 Purchaser Agreement, and all shares of
Common Stock issued or issuable upon conversion of any such shares of New
Preferred Stock.

 

(iii)                               If the number of shares of Common Stock
outstanding at any time after the Series A-1 Original Issuance Date (as defined
in Section B.8) is increased by a stock dividend payable in shares of Common
Stock or by a subdivision or split-up of shares of Common Stock, then, following
the record date fixed for the determination of holders of Common Stock entitled
to receive such stock dividend, subdivision or split-up, the applicable
Conversion Price shall be appropriately decreased in the form of a Proportional
Adjustment (as defined in Section B.8) so that the number of shares of Common
Stock issuable on conversion of each share of New Preferred Stock shall be
increased in proportion to such increase in outstanding shares.

 

(iv)                              If the number of shares of Common Stock
outstanding at any time after the Series A-1 Original Issuance Date is decreased
by a combination of the outstanding shares of Common Stock

 

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(other than pursuant to the Reverse Split), then, following the record date for
such combination, the applicable Conversion Price shall be appropriately
increased in the form of a Proportional Adjustment so that the number of shares
of Common Stock issuable on conversion of each share of New Preferred Stock
shall be decreased in proportion to such decrease in outstanding shares.

 

(v)                                 Except as otherwise contemplated in the
Series A-1 Purchase Agreement, if at any time after the Series A-1 Original
Issuance Date, the Corporation shall make or issue, or fix a record date for the
determination of holders of Common Stock entitled to receive, a dividend or
other distribution payable in securities of the Corporation (other than shares
of Common Stock) or in cash or other property, then and in each such event
provision shall be made so that the holders of the New Preferred Stock shall
receive upon conversion thereof in addition to the number of shares of Common
Stock receivable thereupon, the kind and amount of securities of the
Corporation, cash or other property which they would have been entitled to
receive had the New Preferred Stock been converted into Common Stock on the date
of such event and had they thereafter, during the period from the date of such
event to and including the conversion date, retained such securities receivable
by them as aforesaid during such period, giving application to all adjustments
called for during such period under this paragraph with respect to the rights of
the holders of the New Preferred Stock; and provided further, however, that no
such adjustment shall be made if the holders of New Preferred Stock
simultaneously receive a dividend or other distribution of such securities,
cash, or other property in an amount equal to the amount of such securities,
cash, or other property as they would have received if all outstanding shares of
New Preferred Stock had been converted into Common Stock on the date of such
event.

 

(vi)                              Subject to the provisions of
Section B.4(i) above, in the event, at any time after the Series A-1 Original
Issuance Date, of any capital reorganization, or any reclassification of the
capital stock of the Corporation (other than pursuant to the Reverse Split,
other than as contemplated under this Certificate and the Series A-1 Purchase
Agreement and other than a change in par value or from par value to no par value
or from no par value to par value or as a result of a stock dividend or
subdivision, split-up or combination of shares), or the consolidation or merger
of the Corporation with or into another person (other than pursuant to the
Merger Agreement and other than a consolidation or merger in which the
Corporation is the continuing corporation and which does not result in any
change in the powers, designations, preferences and rights, or the
qualifications, limitations or restrictions, if any, of the capital stock of the
Corporation) or of the sale or other disposition of all or substantially all the
properties and assets of the Corporation in their entirety to any other person
(any such transaction, an “Extraordinary Transaction”), then the Corporation
shall provide appropriate adjustment in the form of a Proportional Adjustment to
the applicable Conversion Price with respect to each share of New Preferred
Stock outstanding after the effectiveness of such Extraordinary Transaction such
that each share of New Preferred Stock outstanding immediately prior to the
effectiveness of the Extraordinary Transaction shall be convertible into the
kind and number of shares of stock or other securities or property of the
Corporation, or of the corporation resulting from or surviving such
Extraordinary Transaction, that a holder of the number of shares of Common Stock
deliverable (immediately prior to the effectiveness of the Extraordinary
Transaction) upon conversion of such share of New Preferred Stock would have
been entitled to receive upon such Extraordinary Transaction. The provisions of
this Section B.7(e)(vi) shall similarly apply to successive Extraordinary
Transactions.

 

(vii)                           All calculations under this Section B.7(e) shall
be made to the nearest one-tenth of a cent ($.001) or to the nearest one-tenth
of a share, as the case may be.

 

(viii)                        For the purpose of any computation pursuant to
Section B.7(d), Section B.3(a) hereof or this Section B.7(e), the “Current
Market Price” at any date of one share of Common Stock shall be defined as the
average of the daily closing prices for the 20 consecutive Business Days ending
on the fifth (5th) Business Day before the day in question (as adjusted for any
stock dividend, split-up,

 

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combination or reclassification that took effect during such 20 Business Day
period), determined as follows:

 

a.                                      If the Common Stock is listed or
admitted for trading on a national securities exchange, then the closing price
for each day shall be the last reported sales price regular way or, in case no
such reported sales took place on such day, the average of the last reported bid
and asked prices regular way, in either case on the principal national
securities exchange on which the Common Stock is listed or admitted to trading.

 

b.                                      If the Common Stock is not at the time
listed or admitted for trading on any such exchange, then such price shall be
equal to the last reported bid and asked prices on such day as reported by the
NASD OTCBB or the National Quotation Bureau, Inc., or any similar reputable
quotation and reporting service if such quotation is not reported by the NASD
OTCBB or the National Quotation Bureau, Inc.

 

c.                                       If the Common Stock is not traded in
such manner that the quotations referred to in this Section B.7(d)(viii) are
available for the period required hereunder, then the Current Market Price shall
be the fair market value of such share, as determined in good faith by a
majority of the entire Board of Directors.

 

(ix)                              In any case in which the provisions of this
Section B.7(e) shall require that an adjustment shall become effective
immediately after a record date for an event, the Corporation may defer until
the occurrence of such event (A) issuing to the holder of any shares of New
Preferred Stock converted after such record date and before the occurrence of
such event the additional shares of capital stock issuable upon such conversion
by reason of the adjustment required by such event over and above the shares of
capital stock issuable upon such conversion before giving effect to such
adjustment, and (B) paying to such holder any cash amounts in lieu of fractional
shares pursuant to Section B.7(d) hereof; provided, however, that the
Corporation shall deliver to such holder a due bill or other appropriate
instrument evidencing such holder’s right to receive such additional shares and
such cash upon the occurrence of the event requiring such adjustment.

 

(x)                                 If a state of facts shall occur that,
without being specifically controlled by the provisions of this Section B.7,
would not fairly protect the conversion rights of the holders of the New
Preferred Stock in accordance with the essential intent and principles of such
provisions, then the Board of Directors shall make an adjustment in the
application of such provisions, in accordance with such essential intent and
principles, so as to protect such conversion rights.

 

(f)                       Whenever the applicable Conversion Price shall be
adjusted as provided in Section B.7(e) hereof, the Corporation shall forthwith
file and keep on record at the office of the Secretary of the Corporation and at
the office of its transfer agent or at such other place as may be designated by
the Corporation, a statement, signed by both its President or Chief Executive
Officer and its Treasurer or Chief Financial Officer, showing in detail the
facts requiring such adjustment and the applicable Conversion Price that shall
be in effect after such adjustment. The Corporation shall also cause a copy of
such statement to be sent by first-class, certified mail, return receipt
requested, postage prepaid, to each New Preferred Stockholder at such holder’s
address appearing on the Corporation’s records. Where appropriate, such copy
shall be given in advance of any such adjustment and shall be included as part
of a notice required to be mailed under the provisions of Section B.7(g) hereof.

 

(g)                      In the event the Corporation shall propose to take any
action of the types described in Section B.7(e)(i), (iii), (iv) or (v) hereof,
or any other Event of Sale, other then the transactions contemplated by the
Series A-1 Purchase Agreement and the Merger Agreement, the Corporation shall
give

 

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notice to each New Preferred Stockholder in the manner set forth in
Section B.7(f) hereof, which notice shall specify the record date, if any, with
respect to any such action and the date on which such action is to take place.
Such notice shall also set forth such facts with respect thereto as shall be
reasonably necessary to indicate the effect of such action (to the extent such
effect may be known at the date of such notice) on the applicable Conversion
Price with respect to the New Preferred Stock, and the number, kind or class of
shares or other securities or property which shall be deliverable or purchasable
upon each conversion of New Preferred Stock. In the case of any action (other
than any action contemplated or required by the Series A-1 Purchase Agreement or
Merger Agreement) that would require the fixing of a record date, such notice
shall be given at least 20 days prior to the record date so fixed, and in the
case of any other action, such notice shall be given at least 30 days prior to
the taking of such proposed action.

 

(h)                     The Corporation shall pay all documentary, stamp or
other transactional taxes attributable to the issuance or delivery of shares of
capital stock of the Corporation upon conversion of any shares of New Preferred
Stock; provided, however, that the Corporation shall not be required to pay any
taxes which may be payable in respect of any transfer involved in the issuance
or delivery of any certificate for such shares in a name other than that of the
New Preferred Stockholder in respect of which such shares of New Preferred Stock
are being issued.

 

(i)                         The Corporation shall reserve out of its authorized
but unissued shares of Common Stock, solely for the purpose of effecting the
conversion of the New Preferred Stock, sufficient shares of Common Stock to
provide for the conversion of all outstanding shares of New Preferred Stock.

 

(j)                        All shares of Common Stock which may be issued in
connection with the conversion provisions set forth herein will, upon issuance
by the Corporation, be validly issued, fully paid and nonassessable, not subject
to any preemptive or similar rights, and free from all taxes, liens or charges
with respect thereto created or imposed by the Corporation.

 

8.              Definitions.  As used in this Part B of Article III of this
Certificate, the following terms shall have the corresponding meanings:

 

“Business Day” shall mean any day other than a Saturday, Sunday or day on which
banks are closed in the city and state where the principal executive office of
the Corporation is located.

 

“Series A-1 Original Issuance Date” shall mean the date of issuance by the
Corporation of the first share of Series A-1 Stock to be issued by the
Corporation.

 

“Series A-1 Original Purchase Price” shall mean, with respect to the Series A-1
Stock and after giving effect to the Reverse Split, $8.142 per share, subject,
for all purposes other than Section B.7 hereof (which provisions shall be
applied in accordance with their own terms), to Proportional Adjustment.

 

“Series A-2 Original Purchase Price” shall mean, with respect to the Series A-2
Stock and after giving effect to the Reverse Split, $8.142 per share, subject,
for all purposes other than Section B.7 hereof (which provisions shall be
applied in accordance with their own terms), to Proportional Adjustment.

 

“Series A-3 Original Purchase Price” shall mean, with respect to the Series A-3
Stock and after giving effect to the Reverse Split, $8.142 per share, subject,
for all purposes other than Section B.7 hereof (which provisions shall be
applied in accordance with their own terms), to Proportional Adjustment.

 

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“Series A-4 Original Purchase Price” shall mean, with respect to the Series A-4
Stock and after giving effect to the Reverse Split, $8.142 per share, subject,
for all purposes other than Section B.7 hereof (which provisions shall be
applied in accordance with their own terms), to Proportional Adjustment.

 

“Series A-5 Original Purchase Price” shall mean, with respect to the Series A-5
Stock and after giving effect to the Reverse Split, $8.142 per share, subject,
for all purposes other than Section B.7 hereof (which provisions shall be
applied in accordance with their own terms), to Proportional Adjustment.

 

“Series A-6 Original Purchase Price” shall mean, with respect to the Series A-6
Stock and after giving effect to the Reverse Split, $8.142 per share, subject,
for all purposes other than Section B.7 hereof (which provisions shall be
applied in accordance with their own terms), to Proportional Adjustment.

 

“Proportional Adjustment” shall mean an adjustment made to the price of the
Preferred Stock upon the occurrence of a stock split, reverse stock split, stock
dividend, stock combination reclassification or other similar change with
respect to such security, such that the price of one share of the New Preferred
Stock before the occurrence of any such change shall equal the aggregate price
of the share (or shares or fractional share) of such security (or any other
security) received by the holder of the New Preferred Stock with respect thereto
upon the effectiveness of such change.  Notwithstanding the foregoing, the
Reverse Split shall not trigger or give rise to any Proportional Adjustment.

 

9.              Forced Conversion and Forfeiture Upon Failure to Perform Future
Funding Obligations Pursuant to the Series A-1 Purchase Agreement.

 

(a)                     Trigger Event.  In the event that an Investor (as
defined in the Series A-1 Purchase Agreement) does not timely and completely
fulfill his, her or its Future Funding Obligations (as defined in the Series A-1
Purchase Agreement) in the Qualified Financing pursuant to the terms of
Series A-1 Purchase Agreement, then (i) all shares of New Preferred Stock then
held by such Investor shall automatically, and without any further action on the
part of such Investor, be converted into shares of Common Stock at a rate of 1
share of Common Stock for every 10 shares of New Preferred Stock to be so
converted and (ii) the Corporation shall have the right to repurchase and such
holders shall be required to sell all shares of Common Stock issued upon
conversion (either pursuant to the foregoing clause (i) or otherwise) of all
Additional A-1 Preferred Stock (as defined in the Series A-1 Purchase
Agreement), all Series A-2 Stock, all Series A-3 Stock and all Series A-4 Stock
issued to such Investor pursuant to the Automatic Reclassification (as defined
in the Series A-1 Purchase Agreement) (the “Repurchased Shares”) for a per share
purchase price equal to the par value of such Repurchased Share and all such
Repurchased Shares shall thereafter be cancelled by the Corporation and no
longer be issued and outstanding shares of capital stock of the Corporation, in
accordance with Section 4(e) of the Series A-1 Purchase Agreement and
Section 9.(b) below. The conversion and repurchase of shares to the Corporation
set forth in this Section 9.(a) is referred to as a “Subsequent Closing
Adjustment”.

 

(b)                     Procedural Requirements.  Upon a Subsequent Closing
Adjustment, each holder of shares of New Preferred Stock converted pursuant to
Section B.9(a) shall be sent written notice of such Subsequent Closing
Adjustment and the place designated for mandatory conversion of all such shares
of New Preferred Stock and the repurchase of all Repurchased Shares.  Upon
receipt of such notice, each holder of such shares of New Preferred Stock and
Repurchased Shares shall surrender his, her or its certificate or certificates
for all such shares (or, if such holder alleges that such certificate has been
lost, stolen or destroyed, a lost certificate affidavit and agreement reasonably
acceptable to the Corporation to

 

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indemnify the Corporation against any claim that may be made against the
Corporation on account of the alleged loss, theft or destruction of such
certificate) to the Corporation at the place designated in such notice. If so
required by the Corporation, certificates surrendered for conversion or
repurchase shall be endorsed or accompanied by written instrument or instruments
of transfer, in form satisfactory to the Corporation, duly executed by the
registered holder or by his, her or its attorney duly authorized in writing. 
All rights with respect to the New Preferred Stock so converted or such
Repurchased Shares to be repurchased, including the rights, if any, to receive
notices and vote (other than as a holder of shares of Common Stock that are not
Repurchased Shares), will terminate at the time of the failure to fulfill the
obligations of any Closing (as defined in the Series A-1 Purchase Agreement)
(notwithstanding the failure of the holder or holders thereof to surrender the
certificates for such shares at or prior to such time), except only the rights
of the holders thereof, upon surrender of their certificate or certificates
therefor (or lost certificate affidavit and agreement), to receive the items
provided for in the next sentence of this Section B.9(b).  As soon as
practicable after the surrender of the certificate or certificates (or lost
certificate affidavit and agreement) for New Preferred Stock so converted that
is not included among the Repurchased Shares, the Corporation shall issue and
deliver to such holder, or to his, her or its nominees, a certificate or
certificates for the number of full shares of Common Stock issuable on such
conversion in accordance with the provisions hereof, together with cash as
provided in B.7(d) in lieu of any fraction of a share of Common Stock otherwise
issuable upon such conversion and the payment of any declared but unpaid
dividends on the shares of New Preferred Stock converted.  Such converted New
Preferred Stock, together with all Repurchased Shares pursuant to
B.9(a)(ii) shall be retired and cancelled and may not be reissued as shares of
such series, and the Corporation may thereafter take such appropriate action
(without the need for stockholder action) as may be necessary to reduce the
authorized number of shares of New Preferred Stock and Common Stock accordingly.

 

10.                   Special Mandatory Conversion.

 

(a)                     Trigger Events.  Each share of New Preferred Stock shall
be automatically converted into fully paid and non-assessable shares of Common
Stock at the then-effective applicable Conversion Price in the event that
(i) the New Senior Majority shall have elected to convert all shares of New
Preferred Stock or (2) the Common Stock of the Corporation becomes listed for
trading on a national securities exchange. Each of the conversions set forth in
this Section B.10(a) is referred to as a “Special Mandatory Conversion.”  All
accrued but unpaid dividends on shares New Preferred Stock shall be paid, in
cash or additional shares at the discretion of the Board of Directors, in
connection with any Special Mandatory Conversion.

 

(b)                     Procedural Requirements.  Upon a Special Mandatory
Conversion, each holder of shares of New Preferred Stock converted pursuant to
Section B.10(a) shall be sent written notice of such Special Mandatory
Conversion and the place designated for mandatory conversion of all shares of
New Preferred Stock.  Upon receipt of such notice, each holder of such shares of
New Preferred Stock shall surrender his, her or its certificate or certificates
for all such shares (or, if such holder alleges that such certificate has been
lost, stolen or destroyed, a lost certificate affidavit and agreement reasonably
acceptable to the Corporation to indemnify the Corporation against any claim
that may be made against the Corporation on account of the alleged loss, theft
or destruction of such certificate) to the Corporation at the place designated
in such notice. If so required by the Corporation, certificates surrendered for
conversion shall be endorsed or accompanied by written instrument or instruments
of transfer, in form satisfactory to the Corporation, duly executed by the
registered holder or by his, her or its attorney duly authorized in writing. 
All rights with respect to the New Preferred Stock so converted, including the
rights, if any, to receive notices and vote (other than as a holder of Common
Stock), will terminate at the time of the Special Mandatory Conversion
(notwithstanding the failure of the holder or holders thereof to surrender the
certificates for such shares at or prior to such time), except only the rights
of the holders thereof, upon surrender of their certificate or certificates
therefor (or lost certificate affidavit and agreement), to receive

 

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the items provided for in the next sentence of this Section B.10(b).  As soon as
practicable after the Special Mandatory Conversion and the surrender of the
certificate or certificates (or lost certificate affidavit and agreement) for
New Preferred Stock so converted, the Corporation shall issue and deliver to
such holder, or to his, her or its nominees, a certificate or certificates for
the number of full shares of Common Stock issuable on such conversion in
accordance with the provisions hereof, together with cash as provided in
B.7(d) in lieu of any fraction of a share of Common Stock otherwise issuable
upon such conversion and the payment of any declared but unpaid dividends on the
shares of New Preferred Stock converted, and a new certificate for the number of
shares, if any, of New Preferred Stock represented by such surrendered
certificate and not converted pursuant to B.10(a).  Such converted New Preferred
Stock shall be retired and cancelled and may not be reissued as shares of such
series, and the Corporation may thereafter take such appropriate action (without
the need for stockholder action) as may be necessary to reduce the authorized
number of shares of New Preferred Stock accordingly.

 

(c)                      Duration of Section. This Section B.10 and the rights
and obligations of the parties hereunder shall automatically terminate on the
consummation of a Liquidation or an Event of Sale.

 

PART C. COMMON STOCK

 

1.              Designation and Amount.  The number of shares, powers, terms,
conditions, designations, preferences and privileges, relative, participating,
optional and other special rights, and qualifications, limitations and
restrictions of the Common Stock shall be as set forth in this Part C of
Article III of this Certificate.  The number of authorized shares of Common
Stock shall initially be Thirty-four Million Eight Hundred Fifty-nine Thousand
Nine Hundred Sixty-four (34,859,964) shares. Such authorized shares of Common
Stock may be increased or decreased (but not below the combined number of shares
thereof then outstanding and those reserved for issuance upon conversion of the
Preferred Stock) by the affirmative vote of the holders of the majority of the
stock of the Corporation entitled to vote, irrespective of the provisions of
Section 242(b)(2) of the Delaware General Corporation Law.  The affirmative vote
of the holders of shares of Common Stock, voting alone as a class, will not be
required in connection therewith.

 

2.              Voting.  Except as provided in this Certificate or by applicable
law, each Common Stockholder shall be entitled to one vote only for each share
of Common Stock held of record on all matters as to which holders of Common
Stock shall be entitled to vote, which voting rights shall not be cumulative.

 

3.              Other Rights.  Each share of Common Stock issued and outstanding
shall be identical in all respects with each other such share, and no dividends
shall be paid on any shares of Common Stock unless the same dividend is paid on
all shares of Common Stock outstanding at the time of such payment. Except for
and subject to those rights expressly granted to the holders of Preferred Stock
and except as may be provided by the laws of the State of Delaware, the holders
of Common Stock shall have all other rights of stockholders, including, without
limitation, (a) the right to receive dividends, when and as declared by the
Board of Directors, out of assets lawfully available therefor, and (b) in the
event of any distribution of assets upon a Liquidation or Liquidation, after and
subject to distribution to the holders of Preferred Stock and any other class or
series of capital stock (other than the Common Stock) ranking senior to Common
Stock of all amounts such class is entitled to receive pursuant to this
Certificate, the right to receive ratably and equally, together with the holders
of the Series A-1 Stock, Series A-2 Stock and Series A-3 Stock pursuant to this
Certificate, all the remaining assets and funds of the Corporation.

 

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ARTICLE IV
Registered Agent

 

The address of its registered office in the State of Delaware is 2711
Centerville Road, Suite 400, Wilmington, Delaware 19808, New Castle County. The
name of its registered agent at such address is: Corporation Service Company.

 

ARTICLE V
Board of Directors

 

The entire Board of Directors of the Corporation shall consist of seven
(7) persons.  Unless and except to the extent that the by-laws of the
Corporation otherwise require, the election of directors of the Corporation need
not be by written ballot.

 

ARTICLE VI
By-laws

 

In furtherance and not in limitation of the powers conferred by the laws of the
State of Delaware, the Board of Directors is expressly authorized to adopt,
amend or repeal the by-laws of the Corporation subject to the provisions of
Section A.6(f)(ix) of Article III hereof.

 

ARTICLE VII
Perpetual Existence

 

The Corporation is to have perpetual existence.

 

ARTICLE VIII
Amendments and Repeal

 

Except as otherwise specifically provided in this Certificate, the Corporation
reserves the right at any time, and from time to time, to amend, alter, change
or repeal any provision contained in this Certificate, and to add or insert
other provisions authorized at such time by the laws of the State of Delaware,
in the manner now or hereafter prescribed by law; and all rights, preferences
and privileges of whatsoever nature conferred upon stockholders, directors or
any other persons whomsoever by and pursuant to this Certificate in its present
form or as hereafter amended are granted subject to the rights reserved in this
Article VIII.

 

ARTICLE IX
Compromises and Arrangements

 

Whenever a compromise or arrangement is proposed between this Corporation and
its creditors or any class of them and/or between this Corporation and its
stockholders or any class of them, any court of equitable jurisdiction within
the State of Delaware may, on the application in a summary way of this
Corporation or of any creditor or stockholder thereof or on the application of
any receiver or receivers appointed for this Corporation under the provisions of
Section 291 of Title 8 of the DGCL or on the application of trustees in
dissolution or of any receiver or receivers appointed for this Corporation under
the provisions of Section 279 of Title 8 of the DGCL, order a meeting of the
creditors or class of creditors, and/or of the stockholders or class of
stockholders of this Corporation, as the case may be, which parties are to be
summoned in such manner as the court directs.  If a majority in number
representing three-fourths (3/4) in value of either the creditors or a class of
creditors and/or of the stockholders or a class of stockholders of this
Corporation, as the case may be, agree to any compromise

 

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or arrangement and to any reorganization of this Corporation as a consequence of
such compromise or arrangement, said compromise or arrangement and said
reorganization shall, if sanctioned by the court to which said application has
been made, be binding on all the creditors or class of creditors and/or on all
the stockholders or class of stockholders of this Corporation, as the case may
be, and also on this Corporation.

 

ARTICLE X
Limitation of Liability

 

1.              The Corporation shall, to the fullest extent permitted by
Section 145 of the DGCL, as the same may be amended and supplemented from time
to time, indemnify and advance expenses to (i) its directors (including
observers to the Board of Directors) and officers, and (ii) any person who at
the request of the Corporation is or was serving as a director (including
observers to the Board of Directors), officer, employee or agent of another
corporation, partnership, joint venture, trust or other enterprise, from and
against any and all of the expenses, liabilities, or other matters referred to
in or covered by said section as amended or supplemented (or any successor
thereto), provided, however, that except with respect to proceedings to enforce
rights to indemnification, the by-laws of the Corporation may provide that the
Corporation shall indemnify any director (including observers to the Board of
Directors), officer or such person in connection with a proceeding (or part
thereof) initiated by such director (including observers to the Board of
Directors), officer or such person only if such proceeding (or part thereof) was
authorized by the Board of Directors of the Corporation.  The Corporation, by
action of its Board of Directors, may provide indemnification or advance
expenses to employees and agents of the Corporation or other persons only on
such terms and conditions and to the extent determined by the Board of Directors
in its sole and absolute discretion.  The indemnification provided for herein
shall not be deemed exclusive of any other rights to which those indemnified may
be entitled under any by-law, agreement, vote of stockholders or disinterested
directors or otherwise, both as to action in their official capacity and as to
action in another capacity while holding such office.  The indemnification
provided for herein shall continue as to a person who has ceased to be a
director, officer, employee, or agent of the Corporation and shall inure to the
benefit of the heirs, executors and administrators of such a person.

 

2.              No director (including observers to the Board of Directors) of
this Corporation shall be personally liable to the Corporation or its
stockholders for monetary damages for breach of fiduciary duty as a director,
except to the extent that exemption from liability or limitation thereof is not
permitted under the DGCL as in effect at the time such liability or limitation
thereof is determined.  No amendment, modification or repeal of this Article X
shall apply to or have any effect on the liability or alleged liability of any
director of the Corporation for or with respect to any acts or omissions of such
director occurring prior to such amendment, modification or repeal. If the DGCL
is amended after approval by the stockholders of this Article to authorize
corporate action further eliminating or limiting the personal liability of
directors, then the liability of a director of the Corporation shall be
eliminated or limited to the fullest extent permitted by the DGCL.

 

3.              The Corporation hereby renounces, to the fullest extent
permitted by Section 122(17) of the DGCL, any interest or expectancy of the
Corporation in, or in being offered an opportunity to participate in, any
business opportunities that are presented to any of its directors who are not
otherwise employed by the Corporation, other than business opportunities that
are presented to any director acting solely and specifically in his or her
capacity as a director of the Corporation.  No amendment or repeal of this
Article shall apply to or have any effect on the liability or alleged liability
of any such director for or with respect to any opportunities of which such
director become aware prior to such amendment or repeal.

 

(remainder of this page intentionally left blank.)

 

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IN WITNESS WHEREOF, the undersigned has caused this Certificate to be duly
executed on behalf of the Corporation on
                                          , 2011.

 

 

RADIUS HEALTH, INC.

 

 

 

 

By:

 

 

Name: C. Richard Edmund Lyttle

 

Title:  Chief Executive Officer and President

 

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Exhibit B

 

Form of Stockholders’ Agreement

 

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FORM OF
AMENDED AND RESTATED
STOCKHOLDERS’ AGREEMENT

 

THIS AMENDED AND RESTATED STOCKHOLDERS’ AGREEMENT, dated this       day of May,
2011, is entered into by and among (i) Radius Health, Inc., a Delaware
corporation (the “Corporation”), (ii) those common stockholders of the
Corporation listed on Schedule 1 hereto (hereinafter referred to collectively as
the “Common Stockholders”), (iii) those stockholders of the Corporation who hold
Series A-1 Convertible Preferred Stock, par value $.01 per share (“Series A-1
Preferred Stock”), listed on Schedule 2 hereto (hereinafter referred to
collectively as the “Series A-1 Stockholders”), (iv) those stockholders of the
Corporation who hold Series A-2 Convertible Preferred Stock, par value $.01 per
share (“Series A-2 Preferred Stock”), listed on Schedule 3 hereto (hereinafter
referred to collectively as the “Series A-2 Stockholders”), (v) those
stockholders of the Corporation who hold Series A-3 Convertible Preferred Stock,
par value $.01 per share (“Series A-3 Preferred Stock”), listed on Schedule 4
hereto (hereinafter referred to collectively as the “Series A-3 Stockholders”),
(vi) those stockholders of the Corporation who hold Series A-4 Convertible
Preferred Stock, par value $.01 per share (“Series A-4 Preferred Stock”), listed
on Schedule 5 hereto (hereinafter referred to collectively as the “Series A-4
Stockholders”), (vii) that certain stockholder of the Corporation who holds
Series A-5 Convertible Preferred Stock, par value $.01 per share (“Series A-5
Preferred Stock”), listed on Schedule 6 hereto (hereinafter referred to as the
“Series A-5 Stockholder”) and (viii) any person or entity that becomes a party
hereto pursuant to Section 17 hereof or otherwise (the “Additional
Stockholders”).

 

WITNESSETH:

 

WHEREAS, the Corporation and the Series A-1 Stockholders have entered into a
Series A-1 Convertible Preferred Stock Purchase Agreement, dated the date hereof
(the “Stock Purchase Agreement”), in connection with which the Corporation has
agreed to sell shares Series A-1 Preferred Stock, and the Corporation desires to
grant to the Series A-1 Stockholders certain registration and other rights with
respect to such shares;

 

WHEREAS, the Corporation and certain of the other parties hereto entered into an
Amended and Restated Stockholders’ Agreement, dated December 15, 2006, as
amended by Amendment No. 1 to Amended and Restated Stockholders’ Agreement,
dated February 22, 2007, Amendment No. 2 to Amended and Restated Stockholders’
Agreement, dated August 17, 2007, and Amendment No. 3 to Amended and Restated
Stockholders’ Agreement, dated October 18, 2008 (as so amended, the “Prior
Agreement”), which Prior Agreement the requisite persons desire to amend and
restate in its entirety as set forth herein; and

 

WHEREAS, as a condition to Series A-1 Stockholders entering into the Stock
Purchase Agreement, the Common Stockholders, Series A-2 Stockholders, Series A-3
Stockholders, Series A-4 Stockholders, Series A-5 Stockholder and Series A-6
Stockholder (as hereinafter defined) have agreed to certain restrictions on
their rights to dispose of their shares of Common Stock (as hereinafter defined)
and Preferred Stock (as hereinafter defined) as contained in this Agreement;

 

NOW, THEREFORE, in consideration of the foregoing and of the respective
covenants and undertakings of the Corporation and the Stockholders hereunder and
under the Stock Purchase Agreement, the parties hereto do hereby agree as
follows:

 

SECTION 1.  Definitions. As used herein, the following terms shall have the
following respective meanings:

 

Board shall mean the Board of Directors of the Corporation.

 

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BB Bio shall mean BB Biotech Ventures II, L.P. including any successor thereto
or any assignee of the interest, in whole or in part, of BB Bio under this
Agreement

 

BB Bio Group shall mean: (i) BB Bio; (ii) BB BIOTECH AG, (iii) any investment
fund limited partnership now existing or hereafter formed which is affiliated
with or under common control with one or more general partners of any general
partner of any of the foregoing (a “BB Bio Fund”); (iv) any limited partners or
affiliates of BB Bio or any other BB Bio Fund; and (v) any successors or assigns
of any of the foregoing.

 

Brookside shall mean Brookside Capital Partners Fund L.P., a Delaware limited
partnership, including any successor thereto or any assignee of the interest, in
whole or in part, of Brookside Capital Partners Fund L.P. under this Agreement.

 

Brookside Group shall mean: (i) Brookside; (ii) any investment fund limited
partnership now existing or hereafter formed which is affiliated with or under
common control with one or more general partners of any general partner of
Brookside (a “Brookside Fund”); (iii) any limited partners or affiliates of
Brookside or any other Brookside Fund; and (iv) any successors or assigns of any
of the foregoing.

 

Certificate shall mean the Fourth Amended and Restated Certificate of
Incorporation of the Corporation and the certificate of incorporation of the
Corporation’s successors and assigns, each as amended from time to time.

 

Commission shall mean the U.S. Securities and Exchange Commission.

 

Common Stock shall mean the Common Stock, par value $.01 per share, of the
Corporation.

 

Effectiveness Date means, with respect to the Registration Statement required to
be filed under Section 3.4(a), the 90th calendar day following the Closing Date;
provided, however, that, if the Commission reviews and has written comments to
the filed Registration Statement, then the Effectiveness Date shall be the 180th
calendar day following the Closing Date; provided further, however, that in the
event the Corporation is notified by the Commission that the Registration
Statement will not be reviewed or is no longer subject to further review and
comments, the Effectiveness Date shall be the fifth Trading Day following the
date on which the Corporation is so notified if such date precedes the dates
required above; provided further, however, that if the Effectiveness Date falls
on a Saturday, Sunday or other day on which the Commission is not open for
business, then the Effectiveness Date shall be extended to the next day on which
the Commission is open for business.

 

Effectiveness Period shall have the meaning set forth in Section 3.4(a) hereof.

 

Equity Percentage shall mean, as to any Series A-1 Stockholder or Other
Preferred Stockholder, as applicable, that percentage figure which expresses the
ratio that (a) the number of shares of issued and outstanding Common Stock then
owned by such Series A-1 Stockholder or Other Preferred Stockholder bears to
(b) the aggregate number of shares of issued and outstanding Common Stock then
owned by all Series A-1 Stockholders and Other Preferred Stockholders. For
purposes solely of the computation set forth in clauses (a) and (b) above and
the right of oversubscription (as set forth in Section 2.3(d)), all issued and
outstanding securities held by the Series A-1 Stockholders and Other Preferred
Stockholders that are convertible into or exercisable or exchangeable for shares
of Common Stock (including any issued and issuable shares of Preferred Stock) or
for any such convertible, exercisable or exchangeable securities, shall be
treated as having been so converted, exercised or exchanged at the rate

 

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or price at which such securities are convertible, exercisable or exchangeable
for shares of Common Stock in effect at the time in question (which, for
purposes of Section 2.3 of this Agreement, shall be at the time of delivery by
the Corporation of the notice of the Offer contemplated by Section 2.3(b)),
whether or not such securities are at such time immediately convertible,
exercisable or exchangeable.

 

Event shall have the meaning set forth in Section 3.4(b) hereof.

 

Event Date shall have the meaning set forth in Section 3.4(b) hereof.

 

Exchange Act shall mean the Securities Exchange Act of 1934, as amended.

 

Exchange Act Registration Statement shall have the meaning set forth in
Section 2.5 hereof.

 

Excess Securities shall have the meaning set forth in Section 2.3(d) hereof.

 

Excess Securities Notice shall have the meaning set forth in
Section 2.3(d) hereof.

 

Excess Securities Period shall have the meaning set forth in
Section 2.3(d) hereof.

 

Excluded Forms shall have the meaning given such term in Section 3.5 hereof.

 

Excluded Securities shall mean, collectively:

 

(i)            the Reserved Shares:

 

(ii)           Common Stock issued or issuable to officers, directors or
employees of or consultants or independent contractors to the Corporation,
pursuant to any written agreement, plan or arrangement, including pursuant to
any options granted under the 2003 Long-Term Incentive Plan, as amended, of the
Corporation, to purchase, or rights to subscribe for, such Common Stock, that
has been approved in form and in substance by the holders of a majority of the
voting power of the Series A-1 Preferred Stock then outstanding, calculated in
accordance with Section A.6(a) of Article III of the Certificate, and which, as
a condition precedent to the issuance of such shares, provides for the vesting
of such shares and subjects such shares to restrictions on Transfers and rights
of first offer in favor of the Corporation; provided, however, that the maximum
number of shares of Common Stock heretofore or hereafter issuable pursuant to
the 2003 Long-Term Incentive Plan, as amended, and all such agreements, plans
and arrangements shall not exceed 2,015,666 shares of Common Stock;

 

(iii)          Common Stock issued as a stock dividend payable in shares of
Common Stock, or capital stock of any class issuable upon any subdivision,
recombination, split-up or reverse stock split of all the outstanding shares of
such class of capital stock of the Corporation;

 

(iv)          Common Stock or other securities issued or issuable pursuant to
the acquisition by the Corporation of any other corporation, partnership, joint
venture, trust or other entity by any merger, stock acquisition, reorganization,
purchase of substantially all assets or otherwise in which the Corporation, or
its stockholders of record immediately prior to the effective date of such
transaction, directly or indirectly, own at least a majority of the voting power
of the acquired entity or the resulting entity after such transaction, in each
case so long as such transaction is approved by the Board of Directors;

 

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(v)           Common Stock or other securities issued or issuable to banks,
lenders or landlords, provided that each such issuance is approved by the Board
of Directors, including, but not limited to, warrants to acquire Common Stock
held by Silicon Valley Bank (or its affiliates, successors and assignees),
warrants to purchase Preferred Stock issued or to be issued to GE Healthcare
Financial Services, Inc. (“GEHFS”) and Oxford Finance Corporation (“OFC”)
pursuant to a proposed debt financing approved by the Board of Directors (the
“GE Financing”), shares of Preferred Stock issued or issuable to GE in
connection with the GE Financing or upon exercise by GEHFS or OFC of warrants
issued in the GE Financing and shares of common stock issuable upon conversion
of any such shares of Preferred Stock issued to GEHFS or OFC pursuant to the GE
Financing;

 

(vi)          Common Stock or other securities issued or issuable to third
parties in connection with strategic partnerships or alliances, corporate
partnerships, joint ventures or other licensing transactions, provided that each
such transaction and related issuance is approved by the Board of Directors,
including, but not limited to, (A) any shares of Preferred Stock or Common Stock
issued or issuable to Ipsen Pharma SAS (“Ipsen”), pursuant to the terms of that
certain License Agreement, as amended and may be amended with the approval of
the Board of Directors of the Corporation and in effect from time to time, by
and between the Corporation and Ipsen as payment milestones in lieu of cash
payments and (B) shares of Series A-5 Stock issued or issuable pursuant to that
certain Stock Issuance Agreement as of March 29, 2011 by and between the
Corporation and Nordic Bioscience and the letter agreement as of March 29, 2011
by and between the Corporation and Nordic Bioscience, pursuant to which the
Corporation will issue shares of the Corporation’s Series A-5 Convertible
Preferred Stock, $0.01 par value per share and the issuance of Series A-6 Stock
issued or to be issued as dividends on such Series A-5 Stock, and shares of
Common Stock issuable upon conversion of any such shares of Series A-5 Stock and
Series A-6 Stock;

 

(vii)         Common Stock or other securities, the issuance of which is
approved by the Majority Investors, with such approval expressly waiving the
application of the anti-dilution or right of first refusal provisions of the
Agreement as a result of such issuance;

 

(viii)        Preferred Stock or Common Stock issued or issuable pursuant to any
warrant outstanding as of the date hereof or any warrant and any shares of
Preferred Stock or common stock, or common stock issued upon exercise of any
Preferred Stock, issued in connection with the Qualified Financing, including,
but not limited to a warrant for shares of Series A-1 Preferred Stock issued or
issuable to Leerink Swan, any shares of Preferred Stock or Common Stock upon
exercise thereof and any Common Stock issuable upon conversion of such Preferred
Stock issued upon exercise thereof; and

 

(ix)          All shares of Preferred Stock and Common Stock issued pursuant to
the Stock Purchase Agreement and related recapitalization, as the same may be
amended from time to time by the parties thereto in accordance with its terms,
and all shares of Common Stock issued or issuable upon conversion of any such
shares of Preferred Stock.

 

Filing Date means, with respect to the Registration Statement required to be
filed under Section 3.4, the 60th calendar day following the date of
consummation of the Merger; provided, however, that if the Filing Date falls on
a Saturday, Sunday or other day on which the Commission is not open for
business, then the Filing Date shall be extended to the next day on which the
Commission is open for business.

 

FINRA shall have the meaning set forth in Section 3.4(b)(viii) hereof.

 

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Group shall mean: (i) as to any Stockholder that is a corporation or other
entity, any and all of the venture capital limited partnerships or corporations
now existing or hereafter formed that are affiliated with or under common
control with one or more of the controlling stockholders of such Stockholder and
any predecessor or successor thereto; (ii) in the case of any member of the HCV
Group, any other member of the HCV Group; (iii) in the case of any member of the
MPM Group, any other member of the MPM Group; (iv) in the case of any member of
the Brookside Group, any other member of the Brookside Group; (v) in the case of
any member of the Oxford/Saints Group, any other member of the Oxford/Saints
Group; (vi) in the case of any member of the BB Bio, any other member of the BB
Bio Group and (vi) in the case of Wellcome, any successor trustee of the
Wellcome Trust or additional trustee or trustees of the Wellcome Trust from time
to time, or any company whose shares are all held directly or indirectly by the
Wellcome Trust, or any nominee or custodian of any such person.

 

HCV Group shall mean: (i) HCV VII; (ii) any venture capital limited partnership
now existing or hereafter formed which is affiliated with or under common
control with one or more general partners of any general partner of HCV VII (an
“HCV Fund”); (iii) any limited partners or affiliates of HCV VII or any other
HCV Fund; and (iv) any successors or assigns of any of the foregoing.

 

HCV VII shall mean HealthCare Ventures VII, L.P. a Delaware limited partnership,
including any successor thereto or any assignee of the interest, in whole or in
part, of HCV VII under this Agreement.

 

Holder or Holders means the holder or holders, as the case may be, from time to
time of Registrable Securities.

 

Independent Directors shall have the meaning set forth in Section 4.1(b) hereof.

 

Industry Expert Director shall have the meaning set forth in
Section 4.1(b) hereof.

 

Investor Directors shall have the meaning set forth in Section 4.1(b) hereof.

 

Investors shall mean each of the persons listed on Schedule 2 hereto, severally,
but not jointly and severally.

 

Issuer Filing shall have the meaning set forth in Section 3.4(g) hereof.

 

Majority Investors shall mean the holders of a majority of the voting power of
the Series A-1 Preferred Stock, Series A-2 Preferred Stock and Series A-3
Preferred Stock then outstanding, voting together as a single class, calculated
in accordance with Section A.6 of Article III of the Certificate (including, in
such calculation, any shares issued upon conversion of such Series A-1 Preferred
Stock, Series A-2 Preferred Stock and Series A-3 Preferred Stock then
outstanding).

 

Merger shall have the meaning ascribed thereto in the Stock Purchase Agreement.

 

MPM shall mean MPM Capital L.P.

 

MPM Group shall mean (i) MPM BioVentures III, L.P., (ii) MPM BioVentures III QP.
L.P., (iii) MPM BioVentures III GmbH & Co. Beteiligungs KG, (iv) MPM BioVentures
III Parallel Fund, L.P., (v) MPM Asset Management Investors 2003 VIII LLC,
(vi) MPM Bio IV NVS Strategic Fund, L.P., (vii) any other venture capital
limited partnership now existing or hereafter formed which is affiliated with or
under common control with the foregoing or one or more general partners of the
foregoing, and (viii) any successors or assigns of the foregoing.

 

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Notice of Acceptance shall have the meaning set forth in Section 2.3(c) hereof.

 

Offer shall have the meaning set forth in Section 2.3(b) hereof.

 

Offered Securities shall mean, except for Excluded Securities, (i) any shares of
Common Stock, Preferred Stock or any other equity security of the Corporation,
(ii) any debt security, (iii) any capitalized lease with any equity feature with
respect to the Corporation, or (iv) any option, warrant or other right to
subscribe for, purchase or otherwise acquire any such equity security, debt
security or capitalized lease.

 

Option Shares shall mean the 2003 Plan Option Shares as defined in
Section 5.2(a)(i)(3) of the Stock Purchase Agreement.

 

Other Preferred Stockholder shall mean any holder of shares of Series A-2
Preferred Stock, Series A-3 Preferred Stock, Series A-4 Preferred Stock,
Series A-5 Preferred Stock or Series A-6 Preferred Stock.

 

Other Shares shall have the meaning set forth in Section 3.5(e) hereof.

 

Oxford shall mean Oxford Bioscience Partners IV L.P., until such time as such
entity shall have transferred all of its Common Stock and Preferred Stock to OBP
IV — Holdings LLC, at which time “Oxford” shall mean OBP IV — Holdings LLC.

 

Oxford/Saints Group shall mean (i) Oxford Bioscience Partners IV L.P., (ii) mRNA
Fund II L.P., (iii) OBP IV — Holdings LLC, (iv) mRNA II — Holdings LLC,
(v) Saints Capital VI, L.P., (vi) any other venture capital limited partnership
now existing or hereafter formed which is affiliated with or under common
control with the foregoing or one or more general partners of the foregoing, and
(vii) any successors or assigns of the foregoing.

 

Person (whether or not capitalized) means an individual, corporation,
partnership, limited partnership, limited liability company, syndicate, trust,
association or entity or government, political subdivision, agency or
instrumentality of a government.

 

Plan of Distribution shall have the meaning set forth in Section 3.4(a) hereof.

 

Preferred Shares shall mean shares of Series A-1 Preferred Stock, Series A-2
Preferred Stock, Series A-3 Preferred Stock, Series A-4 Preferred Stock,
Series A-5 Preferred Stock and shares of the Corporation’s Series A-6
Convertible Preferred Stock, par value $0.01 per share (the “Series A-6
Preferred Stock”, with any holder of Series A-6 Preferred Stock being referred
to herein as a “Series A-6 Stockholder”).

 

Preferred Stock shall mean the Preferred Stock, par value $.01 per share, of the
Corporation.

 

Preferred Stockholders shall mean, collectively, all holders of shares of
Preferred Stock of the Corporation.

 

Prospectus means the prospectus included in a Registration Statement (including,
without limitation, a prospectus that includes any information previously
omitted from a prospectus filed as part of an effective registration statement
in reliance upon Rule 430A promulgated under the Securities Act), as amended or
supplemented by any prospectus supplement, with respect to the terms of the
offering of

 

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any portion of the Registrable Securities covered by a Registration Statement,
and all other amendments and supplements to the Prospectus, including
post-effective amendments, and all material incorporated by reference or deemed
to be incorporated by reference in such Prospectus.

 

Qualified Public Offering shall have the same meaning as that set forth in the
Certificate.

 

Refused Securities shall have the meaning set forth in Section 2.3(f) hereof.

 

Registrable Securities shall mean all of the Preferred Shares, the Common Stock
issued or issuable upon the conversion of the Preferred Shares, all shares of
Common Stock issued or issuable in respect thereof by way of stock splits, stock
dividends, stock combinations, recapitalizations or like occurrences, and any
other shares of Common Stock or other securities of the Corporation which may be
issued hereafter to any of the Investors or any member of their Group which are
convertible into or exercisable for shares of Common Stock (including, without
limitation, other classes or series of convertible Preferred Stock, warrants,
options or other rights to purchase Common Stock or convertible debentures or
other convertible debt securities) and the Common Stock issued or issuable upon
such conversion or exercise of such other securities, which have not been sold
(a) in connection with an effective registration statement filed pursuant to the
Securities Act or (b) pursuant to Rule 144 or Rule 144A promulgated by the
Commission under the Securities Act.

 

Registrable Shares shall mean the shares of Common Stock issued or issuable upon
the conversion or exchange of the Registrable Securities or otherwise
constituting a portion of the Registrable Securities.

 

Registration Statement means any registration statement required to be filed by
the Corporation under Section 3.4 and any additional registration statement
contemplated by Section 3.4(b)(iii), including (in each case) the Prospectus,
amendments and supplements to such registration statement or Prospectus,
including pre- and post-effective amendments, all exhibits thereto, and all
material incorporated by reference or deemed to be incorporated by reference in
such registration statement.

 

Reserved Shares shall mean the shares of Common Stock issued or issuable by the
Corporation upon the conversion of the Preferred Shares.

 

Restricted Stock shall mean all shares of capital stock of the Corporation,
excluding the Series A-1 Registrable Securities, Series A-2 Registrable
Securities and Series A-3 Registrable Securities, including (i) all shares of
Common Stock, (ii) all shares of Series A-4 Preferred Stock, (iii) all shares of
Series A-5 Preferred Stock, (iv) all shares of Series A-6 Preferred Stock,
(v) all additional shares of capital stock of the Corporation hereafter issued
and outstanding, (vi) all shares of capital stock of the Corporation into which
such shares may be converted or for which they may be exchanged or exercised and
(vii) all other shares of capital stock issued or issuable by way of stock
splits, stock dividends, stock combinations, recapitalizations or like
occurrences on such shares.

 

Rule 415 means Rule 415 promulgated by the Commission pursuant to the Securities
Act, as such Rule may be amended from time to time, or any similar rule or
regulation hereafter adopted by the Commission having substantially the same
purpose and effect as such Rule.

 

Rule 424 means Rule 424 promulgated by the Commission pursuant to the Securities
Act, as such Rule may be amended from time to time, or any similar rule or
regulation hereafter adopted by the Commission having substantially the same
purpose and effect as such Rule.

 

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Securities Act shall mean the Securities Act of 1933, as amended.

 

Selling Stockholder Questionnaire shall have the meaning set forth in
Section 3.4(a) hereof.

 

Sell shall mean as to any Restricted Stock, to sell, or in any other way
directly or indirectly, transfer, assign, distribute, encumber or otherwise
dispose of either voluntarily or involuntarily; provided, however, that the term
“Sell” shall not include the transfer, by gift or otherwise without
consideration, of any Restricted Stock (a) by a Common Stockholder, Series A-4
Stockholder, Series A-5 Stockholder or Series A-6 Stockholder to any or all
members of a class of persons consisting of his or her spouse, other members of
his or her immediate family and/or his, her or their descendants, or to a trust
of which all of the beneficiaries are members of such class, or (b) by a Common
Stockholder, Series A-4 Stockholder, Series A-5 Stockholder or Series A-6
Stockholder that is a trust, employee benefit plan or individual retirement
account, to the beneficiary or beneficiaries of such trust, employee benefit
plan or individual retirement account, as applicable (each, a “Related
Transferee”); provided, that any such transfer to a Related Transferee shall be
permitted only on, and subject to, the express conditions that:

 

(i)            such Related Transferee shall be deemed to be a Common
Stockholder, Series A-4 Stockholder, Series A-5 Stockholder or Series A-6
Stockholder, as applicable, hereunder and shall hold the Restricted Stock
subject to the provisions of this Agreement; and

 

(ii)           such Related Transferee executes all documents necessary or
desirable, in the reasonable judgment of the Corporation and the Investors, to
become a party to, and be bound by the terms of this Agreement, including but
not limited to an Instrument of Adherence pursuant to Section 17 hereof.

 

Series A-1 Directors shall have the meaning set forth in Section 4.1(b) hereof.

 

Series A-1 Preferred Stock shall have the meaning set forth in the second
paragraph of this Agreement.

 

Series A-2 Preferred Stock shall have the meaning set forth in the first
paragraph of this Agreement.

 

Series A-3 Preferred Stock shall have the meaning set forth in the first
paragraph of this Agreement.

 

Series A-4 Preferred Stock shall have the meaning set forth in the first
paragraph of this Agreement.

 

Series A-5 Preferred Stock shall have the meaning set forth in the first
paragraph of this Agreement.

 

Series A-6 Preferred Stock shall have the meaning set forth in the definition of
“Preferred Shares” above.

 

Series A-1 Registrable Shares shall mean the shares of Common Stock issued or
issuable upon the conversion or exchange of the Series A-1 Registrable
Securities or otherwise constituting a portion of the Series A-1 Registrable
Securities.

 

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Series A-1 Registrable Securities shall mean any of the Series A-1 Preferred
Stock, the Common Stock issued or issuable upon the conversion of the Series A-1
Preferred Stock, all shares of Common Stock issued or issuable in respect
thereof by way of stock splits, stock dividends, stock combinations,
recapitalizations or like occurrences, and any other shares of Common Stock or
other securities of the Corporation which may be issued hereafter to any of the
Series A-1 Stockholders or any member of their Group which are convertible into
or exercisable for shares of Common Stock (including, without limitation, other
classes or series of convertible Preferred Stock, warrants, options or other
rights to purchase Common Stock or convertible debentures or other convertible
debt securities) and the Common Stock issued or issuable upon such conversion or
exercise of such other securities, which have not been sold (a) in connection
with an effective registration statement tiled pursuant to the Securities Act or
(b) pursuant to Rule 144 or Rule 144A promulgated by the Commission under the
Securities Act.

 

Series A-2 Registrable Shares shall mean the shares of Common Stock issued or
issuable upon the conversion or exchange of the Series A-2 Registrable
Securities or otherwise constituting a portion of the Series A-2 Registrable
Securities.

 

Series A-2 Registrable Securities shall mean any of the Series A-2 Preferred
Stock, the Common Stock issued or issuable upon the conversion of the Series A-2
Preferred Stock, all shares of Common Stock issued or issuable in respect
thereof by way of stock splits, stock dividends, stock combinations,
recapitalizations or like occurrences, and any other shares of Common Stock or
other securities of the Corporation which may be issued hereafter to any of the
Investors or any member of their Group which are convertible into or exercisable
for shares of Common Stock (including, without limitation, other classes or
series of convertible Preferred Stock, warrants, options or other rights to
purchase Common Stock or convertible debentures or other convertible debt
securities) and the Common Stock issued or issuable upon such conversion or
exercise of such other securities, which have not been sold (a) in connection
with an effective registration statement tiled pursuant to the Securities Act or
(b) pursuant to Rule 144 or Rule 144A promulgated by the Commission under the
Securities Act.

 

Series A-3 Registrable Shares shall mean the shares of Common Stock issued or
issuable upon the conversion or exchange of the Series A-3 Registrable
Securities or otherwise constituting a portion of the Series A-3 Registrable
Securities.

 

Series A-3 Registrable Securities shall mean any of the Series A-3 Preferred
Stock, the Common Stock issued or issuable upon the conversion of the Series A-3
Preferred Stock, all shares of Common Stock issued or issuable in respect
thereof by way of stock splits, stock dividends, stock combinations,
recapitalizations or like occurrences, and any other shares of Common Stock or
other securities of the Corporation which may be issued hereafter to any of the
Investors or any member of their Group which are convertible into or exercisable
for shares of Common Stock (including, without limitation, other classes or
series of convertible Preferred Stock, warrants, options or other rights to
purchase Common Stock or convertible debentures or other convertible debt
securities) and the Common Stock issued or issuable upon such conversion or
exercise of such other securities, which have not been sold (a) in connection
with an effective registration statement tiled pursuant to the Securities Act or
(b) pursuant to Rule 144 or Rule 144A promulgated by the Commission under the
Securities Act.

 

Series A-1 Stockholder shall have the meaning set forth in the second paragraph
of this Agreement.

 

Series A-2 Stockholders shall have the meaning set forth in the first paragraph
of this Agreement.

 

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Series A-3 Stockholders shall have the meaning set forth in the first paragraph
of this Agreement.

 

Series A-4 Stockholder shall have the meaning set forth in the first paragraph
of this Agreement.

 

Series A-5 Stockholder shall have the meaning set forth in the first paragraph
of this Agreement.

 

Series A-6 Stockholder shall have the meaning set forth in the definition of
“Preferred Shares” above.

 

Specified Preferred Director shall have the meaning set forth in
Section 4.1(b) hereof.

 

Specified Preferred Holder shall mean each of Oxford, Wellcome and HCV VII.

 

Stock Purchase Agreement shall mean the Series A-1 Convertible Preferred Stock
Purchase Agreement, dated as of the date hereof, among the Corporation and the
Investors listed on Schedule I thereto.

 

Stockholders shall mean all holders of capital stock of the Corporation.

 

Trading Day shall have the meaning set forth in Section 3.4(a) hereof.

 

30-Day Period shall have the meaning set forth in Section 2.3(b) hereof.

 

Transfer shall include any disposition of any Restricted Stock, Series A-1
Preferred Stock, Series A-2 Preferred Stock or Series A-3 Preferred Stock or of
any interest therein which would constitute a sale thereof within the meaning of
the Securities Act.

 

Wellcome shall mean The Wellcome Trust Limited, as trustee of the Wellcome
Trust.

 

SECTION 2.  Certain Covenants of the Corporation.

 

2.1          Meetings of the Board of Directors.  The Corporation shall call,
and use its best efforts to have, regular meetings of the Board not less often
than quarterly. The Corporation shall promptly pay all reasonable and
appropriately documented travel expenses and other out-of-pocket expenses
incurred by directors who are not employed by the Corporation in connection with
attendance at meetings to transact the business of the Corporation or attendance
at meetings of the Board or any committee thereof.

 

2.2          Reservation of Shares of Common Stock and Preferred Stock, Etc. 
The Corporation shall at all times have authorized and reserved out of its
authorized but unissued shares of Common Stock a sufficient number of shares of
Common Stock to provide for the conversion of the Preferred Shares. Neither the
issuance of the Preferred Shares nor the shares of Common Stock issuable upon
the conversion of the Preferred Shares shall be subject to a preemptive right of
any other Stockholder.

 

2.3          Right of First Refusal.

 

(a)           The Corporation shall not issue, sell or exchange, agree to issue,
sell or exchange, or reserve or set aside for issuance, sale or exchange, any
Offered Securities, unless in each

 

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case the Corporation shall have first offered to sell to the Series A-1
Stockholders, Series A-2 Stockholders and the Series A-3 Stockholders
(collectively, the “ROFR Stockholders”) all of such Offered Securities on the
terms set forth herein. Each ROFR Stockholder shall be entitled to purchase up
to its Equity Percentage of the Offered Securities. Each ROFR Stockholder may
delegate its rights and obligations with respect to such Offer to one or more
members of its Group, which members shall thereafter be deemed to be “ROFR
Stockholders” for the purpose of applying this Section 2.3 to such Offer.

 

(b)           The Corporation shall deliver to each ROFR Stockholder written
notice of the offer to sell the Offered Securities, specifying the price and
terms and conditions of the offer (the “Offer”). The Offer by its terms shall
remain open and irrevocable for a period of 30 days from the date of its
delivery to such ROFR Stockholders (the “30-Day Period”), subject to extension
to include the Excess Securities Period (as such term is hereinafter defined).

 

(c)           Each ROFR Stockholder shall evidence its intention to accept the
Offer by delivering a written notice signed by such ROFR Stockholder, as
applicable, setting forth the number of shares that such ROFR Stockholder elects
to purchase (the “Notice of Acceptance”). The Notice of Acceptance must be
delivered to the Corporation prior to the end of the 30-Day Period. The failure
by a ROFR Stockholder to exercise its rights hereunder shall not constitute a
waiver of any other rights or of the right to receive notice of and participate
in any subsequent Offer.

 

(d)           If any ROFR Stockholder fails to exercise its right hereunder to
purchase its Equity Percentage of the Offered Securities, the Corporation shall
so notify the other ROFR Stockholders in a written notice (the “Excess
Securities Notice”). The Excess Securities Notice shall be given by the
Corporation promptly after it learns of the intention of any ROFR Stockholder
not to purchase all of its Equity Percentage of the Offered Securities, but in
no event later than ten (10) business days after the expiration of the 30-Day
Period. The ROFR who or which have agreed to purchase their Equity Percentage of
the Offered Securities shall have the right to purchase the portion not
purchased by such ROFR Stockholders (the “Excess Securities”), on a pro rata
basis, by giving notice within ten (10) business days after receipt of the
Excess Securities Notice from the Corporation. The twenty (20) business day
period during which (i) the Corporation must give the Excess Securities Notice
to the applicable ROFR Stockholders, and (ii) each of them must then give the
Corporation notice of their intention to purchase all or any portion of their
pro rata share of the its Excess Securities, is hereinafter referred to as the
“Excess Securities Period.”

 

(e)           If the ROFR Stockholders tender their Notice of Acceptance prior
to the end of the 30-Day Period, indicating their intention to purchase all of
the Offered Securities, or, if prior to the termination of the Excess Securities
Period the ROFR Stockholders tender Excess Securities Notices to purchase all of
the Excess Securities, the Corporation shall schedule a closing of the sale of
all such Offered Securities. Upon the closing of the sale of the Offered
Securities to be purchased by the ROFR Stockholders and the Excess Securities to
be purchased by ROFR Stockholders, each ROFR Stockholder shall (i) purchase from
the Corporation that portion of the Offered Securities and Excess Securities, as
applicable, for which it tendered a Notice of Acceptance and an Excess
Securities Notice, as applicable, upon the terms specified in the Offer, and
(ii) execute and deliver an agreement further restricting transfer of such
Offered Securities substantially as set forth in Section 3.1, 3.2 and 3.3 of
this Agreement. In addition, with respect to the Offered Securities and Excess
Securities being purchased by the ROFR Stockholders, the Corporation shall
provide each such ROFR Stockholder with the rights and benefits set forth in
this Agreement. The obligation of the ROFR Stockholders to purchase such Offered
Securities and Excess Securities, as applicable, is further conditioned upon the
preparation of a purchase agreement embodying the terms of the Offer, which
shall be reasonably satisfactory in form and substance to such ROFR Stockholder
and each of their respective counsels.

 

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(f)            The Corporation shall have ninety (90) days from the expiration
of the 30-Day Period, or the Excess Securities Period, if applicable, to sell
the Offered Securities (including the Excess Securities) refused by the ROFR
Stockholders (the “Refused Securities”) to any other person or persons, but only
upon terms and conditions which are in all material respects (including, without
limitation, price and interest rate) no more favorable to such other person or
persons, and no less favorable to the Corporation, than those set forth in the
Offer. Upon and subject to the closing of the sale of all of the Refused
Securities (which shall include full payment to the Corporation), each ROFR
Stockholder shall (i) purchase from the Corporation those Offered Securities and
Excess Securities, as applicable, for which it tendered a Notice of Acceptance
and an Excess Securities Notice, if applicable, upon the terms specified in the
Offer, and (ii) execute and deliver an agreement restricting transfer of such
Offered Securities and Excess Securities, as applicable, substantially as set
forth in Sections 3.1, 3.2 and 3.3 of this Agreement. In addition, with respect
to the Offered Securities or Excess Securities being purchased by the ROFR
Stockholders, the Corporation shall provide each such ROFR Stockholder with the
rights and benefits set forth in this Agreement. The Corporation agrees, as a
condition precedent to accepting payment for and making delivery of any Refused
Securities to any executive officer, employee, consultant or independent
contractor of or to the Corporation, or to any other person, to have each and
every such person execute and deliver this Agreement, as may be modified or
amended from time to time pursuant to Section 11 hereof, to the extent such
purchaser has not already executed this Agreement. The obligation of the ROFR
Stockholders to purchase such Offered Securities and Excess Securities, as
applicable, is further conditioned upon the preparation of a purchase agreement
embodying the terms of the Offer, which shall be reasonably satisfactory in form
and substance to such ROFR Stockholder and each of their respective counsels.

 

(g)           In each case, any Offered Securities not purchased either by the
ROFR Stockholders or by any other person in accordance with this Section 2.3 may
not be sold or otherwise disposed of until they are again offered to the ROFR
Stockholders under the procedures specified in Paragraphs (a), (b), (c), (d),
(e) and (f) hereof.

 

(h)           Each ROFR Stockholder may, by prior written consent, waive its
rights under this Section 2.3. Such a waiver shall be deemed a limited waiver
and shall only apply to the extent specifically set forth in the written consent
of such ROFRR Stockholder.

 

(i)            This Section 2.3 and the rights and obligations of the parties
hereunder shall automatically terminate on the consummation of a Qualified
Public Offering.

 

2.4          Filing of Reports Under the Exchange Act.

 

(a)           The Corporation shall give prompt notice to the holders of
Preferred Stock of (i) the filing of any registration statement (an “Exchange
Act Registration Statement”) pursuant to the Exchange Act, relating to any class
of equity securities of the Corporation, (ii) the effectiveness of such Exchange
Act Registration Statement, and (iii) the number of shares of such class of
equity securities outstanding, as reported in such Exchange Act Registration
Statement, in order to enable the Stockholders to comply with any reporting
requirements under the Exchange Act or the Securities Act. Upon the written
request of the Majority Investors, the Corporation shall, at any time after the
Corporation has already registered shares of Common Stock under the Securities
Act file an Exchange Act Registration Statement relating to any class of equity
securities of the Corporation or issuable upon conversion or exercise of any
class of debt or equity securities or warrants or options of the Corporation
then held by the Series A-1 Stockholders, whether or not the class of equity
securities with respect to which such request is made shall be held by the
number of persons which would require the filing of a registration statement
under Section 12(g)(I) of the Exchange Act.

 

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(b)           If the Corporation shall have filed an Exchange Act Registration
Statement or a registration statement (including an offering circular under
Regulation A promulgated under the Securities Act) pursuant to the requirements
of the Securities Act, which shall have become effective (and in any event, at
all times following the initial public offering of any of the securities of the
Corporation), then the Corporation shall comply with all other reporting
requirements of the Exchange Act (whether or not it shall be required to do so)
and shall comply with all other public information reporting requirements of the
Commission as a condition to the availability of an exemption from the
Securities Act for the sale of any of the Restricted Stock by any holder of
Restricted Stock or the sale of any of the Series A-1 Stock by any holder of
Series A-1 Stock (including any such exemption pursuant to Rule 144 or Rule 144A
thereof, as amended from time to time, or any successor rule thereto or
otherwise). The Corporation shall cooperate with each holder of Registrable
Securities in supplying such information as may be necessary for such holder to
complete and file any information reporting forms presently or hereafter
required by the Commission as a condition to the availability of an exemption
from the Securities Act (under Rule 144 or Rule 144A thereunder or otherwise)
for the sale of any Registrable Securities.

 

2.5          Directors’ & Officers’ Insurance.  The Corporation shall continue
to maintain a directors’ and officers’ liability insurance policy covering all
directors, observers and executive officers of the Corporation.

 

2.6          Properties and Business Insurance.  The Corporation shall continue
to maintain from responsible and reputable insurance companies or associations
valid policies of insurance against such casualties, contingencies and other
risks and hazards and of such types and in such amounts as is customary for
similarly situated businesses.

 

2.7          Preservation of Corporate Existence.  The Corporation shall
preserve and maintain its corporate existence, rights, franchises and privileges
in the jurisdiction of its incorporation, and qualify and remain qualified as a
foreign corporation in each jurisdiction in which (i) such qualification is
necessary or desirable in view of its business and operations or the ownership
or lease of its properties or (ii) the failure to so qualify would have a
material adverse effect on the business, properties, assets or condition
(financial or otherwise) of the Corporation.

 

2.8          Compliance with Laws.  The Corporation shall comply with all
applicable laws, rules, regulations, requirements and orders of the United
States or any applicable foreign jurisdiction in the conduct of its business
including, without limitation, all labor, employment, wage and hour, health and
safety, environmental, health insurance, health information security, privacy,
data protection and data transfer laws, and shall adopt and monitor policies and
procedures designed to comply with all such applicable laws, rules, regulations
and orders, except where noncompliance would not have a material adverse effect
on the business, properties, assets or condition (financial or otherwise) of the
Corporation.

 

2.9          Payment of Taxes.  The Corporation will pay and discharge all
lawful Taxes (as defined below) before such Taxes shall become in default and
all lawful claims for labor, materials and supplies which, if not paid when due,
might become a lien or charge upon its property or any part thereof; provided,
however, that the Corporation shall not be required to pay and discharge any
such Tax, assessment, charge, levy or claim so long as the validity thereof is
being contested by or for the Corporation in good faith by appropriate
proceedings and an adequate reserve therefore has been established on its books.
The term “Tax” (and, with correlative meaning, “Taxes”) means all United States
federal, state and local, and all foreign, income, profits, franchise, gross
receipts, payroll, transfer, sales, employment, use, property, excise, value
added, ad valorem, estimated, stamp, alternative or add-on minimum, recapture,
environmental, withholding and any other taxes, charges, duties, impositions or

 

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assessments, together with all interest, penalties, and additions imposed on or
with respect to such amounts, or levied, assessed or imposed against the
Corporation.

 

2.10        Management Compensation.  The Board of Directors (upon the
recommendation of the Compensation Committee or otherwise) shall determine the
compensation to be paid by the Corporation to its management. Any grants of
capital stock or options to employees, officers, directors or consultants of the
Corporation and its Subsidiaries shall be made pursuant to the Plan.

 

2.11        No Further Pay-to-Play Provisions.  The Corporation hereby covenants
and agrees that at no time after the date of this Agreement, without the prior
written consent of each of Wellcome, one member of the HCV Group, one member of
the MPM Group, one member of the Brookside Group, one member of the BB Bio
Group, and one member of the Oxford/Saints Group, shall it enter into any
agreement or amend the Certificate to implement terms that would automatically
convert Preferred Shares into shares of Common Stock, or impose any other
penalty on the holder of Preferred Shares, solely because the holders of such
Preferred Shares fail to participate at any level in a transaction pursuant to
which the Corporation raises funds through the issuance of debt or equity
securities (other than any Closing contemplated by the Stock Purchase
Agreement).

 

2.12        Confidentiality, Assignment of Inventions and Non-Competition
Agreements for Key Employees.  The Corporation shall cause each person who
becomes an employee of or a consultant to the Corporation subsequent to the date
hereof, and who shall have or be proposed to have access to confidential or
proprietary information of the Corporation, to execute a confidentiality,
assignment of inventions, and non-competition agreement in form and substance
attached hereto as Exhibit A or otherwise approved by the Board prior to the
commencement of such person’s employment by the Corporation in such capacity.

 

2.13        Duration of Section.  Sections 2.5 through 2.12 and the rights and
obligations of the parties hereunder shall automatically terminate on the
earlier of (i) the consummation of an Event of Sale (as defined in the
Certificate) or (ii) the automatic conversion of all of the Preferred Stock of
the Corporation pursuant to the terms and conditions of the Certificate upon 
the listing, or the admitting for trading, of the Common Stock on a national
securities exchange.

 

SECTION 3.  Transfer of Securities.

 

3.1          Restriction on Transfer.  The Series A-1 Preferred Stock,
Series A-2 Preferred Stock, the Series A-3 Preferred Stock and the Restricted
Stock shall not be transferable, except upon the conditions specified in this
Section 3, which conditions are intended solely to ensure compliance with the
provisions of the Securities Act in respect of the Transfer thereof.  In
addition, no Series A-1 Preferred Stock, Series A-2 Preferred Stock, the
Series A-3 Preferred Stock or Restricted Stock shall be transferred unless, as
conditions precedent to such transfer, the transferee thereof agrees in writing
to be bound by the obligations of the transferring Stockholder hereunder.

 

3.2          Restrictive Legend.  Each certificate evidencing any Series A-1
Preferred Stock, Series A-2 Preferred Stock, Series A-3 Preferred Stock and
Restricted Stock and each certificate evidencing any such securities issued to
subsequent transferees of any Series A-1 Preferred Stock, Series A-2 Preferred
Stock, Series A-3 Preferred Stock and Restricted Stock shall (unless otherwise
permitted by the provisions of Section 3.3 or 3.10 hereof) be stamped or
otherwise imprinted with a legend in substantially the following form:

 

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THE SECURITIES REPRESENTED BY THIS CERTIFICATE HAVE BEEN ACQUIRED FOR INVESTMENT
AND HAVE NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933, AS AMENDED (THE
“SECURITIES ACT”), OR ANY STATE SECURITIES LAW. THE SECURITIES MAY NOT BE
PLEDGED, HYPOTHECATED, SOLD OR TRANSFERRED IN THE ABSENCE OF AN EFFECTIVE
REGISTRATION STATEMENT FOR THE SECURITIES UNDER THE SECURITIES ACT OR ANY
APPLICABLE STATE SECURITIES LAW OR AN EXEMPTION THEREFROM UNDER SUCH ACT OR LAW.

 

3.3          Notice of Transfer.  By acceptance of any Restricted Stock,
Series A-1 Preferred Stock, Series A-2 Preferred Stock or Series A-3 Preferred
Stock, the holder thereof agrees to give prior written notice to the Corporation
of such holder’s intention to effect any Transfer and to comply in all other
respects with the provisions of this Section 3.3. Each such notice shall
describe the manner and circumstances of the proposed Transfer and shall be
accompanied by: (a) the written opinion of counsel for the holder of such
Restricted Stock, Series A-1 Preferred Stock, Series A-2 Preferred Stock or
Series A-3 Preferred Stock, or, at such holder’s option, a representation letter
of such holder, addressed to the Corporation (which opinion and counsel, or
representation letter, as the case may be, shall be reasonably acceptable to the
Corporation), as to whether, in the case of a written opinion, in the opinion of
such counsel such proposed Transfer involves a transaction requiring
registration of such Restricted Stock, Series A-1 Preferred Stock, Series A-2
Preferred Stock or Series A-3 Preferred Stock under the Securities Act and
applicable state securities laws or an exemption thereunder is available, or, in
the case of a representation letter, such letter sets forth a factual basis for
concluding that such proposed transfer involves a transaction requiring
registration of such Restricted Stock, Series A-1 Preferred Stock, Series A-2
Preferred Stock or Series A-3 Preferred Stock under the Securities Act and
applicable state securities laws or that an exemption thereunder is available,
or (b) if such registration is required and if the provisions of Section 3.4
hereof are applicable, a written request addressed to the Corporation by the
holder of such Restricted Stock, Series A-1 Preferred Stock, Series A-2
Preferred Stock or Series A-3 Preferred Stock, describing in detail the proposed
method of disposition and requesting the Corporation to effect the registration
of such Registrable Shares pursuant to the terms and provisions of Section 3.4
hereof; provided, however, that (y) in the case of a Transfer by a holder to a
member of such holder’s Group, no such opinion of counsel or representation
letter of the holder shall be necessary, provided that the transferee agrees in
writing to be subject to Sections 3.1, 3.2, 3.3, 3.10 hereof to the same extent
as if such transferee were originally a signatory to this Agreement, and (z) in
the case of any holder of Restricted Stock, Series A-1 Preferred Stock,
Series A-2 Preferred Stock or Series A-3 Preferred Stock that is a partnership,
no such opinion of counsel or representation letter of the holder shall be
necessary for a Transfer by such holder to a partner of such holder, or a
retired partner of such holder who retires after the date hereof, or the estate
of any such partner or retired partner if, with respect to such Transfer by a
partnership, (i) such Transfer is made in accordance with the partnership
agreement of such partnership, and (ii) the transferee agrees in writing to be
subject to the terms of Sections 3.1, 3.2, 3.3, 3.10 hereof to the same extent
as if such transferee were originally a signatory to this Agreement. If in an
opinion of counsel or as reasonably concluded from the facts set forth in the
representation letter of the holder (which opinion and counsel or representation
letter, as the case may be, shall be reasonably acceptable to the Corporation),
the proposed Transfer may be effected without registration under the Securities
Act and any applicable state securities laws or “blue sky” laws, then the holder
of Restricted Stock, Series A-1 Preferred Stock, Series A-2 Preferred Stock or
Series A-3 Preferred Stock shall thereupon be entitled to effect such Transfer
in accordance with the terms of the notice delivered by it to the Corporation.
Each certificate or other instrument evidencing the securities issued upon such
Transfer (and each certificate or other instrument evidencing any such
securities not Transferred) shall bear the legend set forth in Section 3.2
hereof unless: (a) in such opinion of such counsel or as can be concluded from
the representation letter of such holder (which opinion and counsel or
representation letter shall be reasonably acceptable to the

 

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Corporation) the registration of future Transfers is not required by the
applicable provisions of the Securities Act and state securities laws, or
(b) the Corporation shall have waived the requirement of such legend; provided,
however, that such legend shall not be required on any certificate or other
instrument evidencing the securities issued upon such Transfer in the event such
transfer shall be made in compliance with the requirements of Rule 144 (as
amended from time to time or any similar or successor rule) promulgated under
the Securities Act. The holder of Restricted Stock, Series A-1 Preferred Stock,
Series A-2 Preferred Stock or Series A-3 Preferred Stock shall not effect any
Transfer until such opinion of counsel or representation letter of such holder
has been given to and accepted by the Corporation (unless waived by the
Corporation) or, if applicable, until registration of the Registrable Shares
involved in the above-mentioned request has become effective under the
Securities Act. In the event that an opinion of counsel is required by the
registrar or transfer agent of the Corporation to effect a transfer of
Restricted Stock, Series A-1 Preferred Stock, Series A-2 Preferred Stock or
Series A-3 Preferred Stock in the future, the Corporation shall seek and obtain
such opinion from its counsel, and the holder of such Restricted Stock,
Series A-1 Preferred Stock, Series A-2 Preferred Stock or Series A-3 Preferred
Stock shall provide such reasonable assistance as is requested by the
Corporation (other than the furnishing of an opinion of counsel) to satisfy the
requirements of the registrar or transfer agent to effectuate such transfer. 
Notwithstanding anything to the contrary herein, the provisions of this
Section 3.3 and of Sections 3.1 and 3.2 shall not apply, and shall be deemed of
no force or effect, with respect to shares of capital stock of the Corporation
that are subject to a re-sale registration statement under the Securities Act,
provided that such registration statement has been declared, and continues to
remain, effective by the Commission.

 

3.4          Registration Rights.

 

(a)           Shelf Registration.

 

(i)            On or prior to the Filing Date, the Corporation shall prepare and
file with the Commission a Registration Statement covering the resale of all of
the Registrable Shares for an offering to be made on a continuous basis pursuant
to Rule 415. The Registration Statement shall be on Form S-1 or another
appropriate form in accordance herewith and shall contain (unless otherwise
directed by Holders of at least 85% of the then outstanding Registrable Shares)
substantially the “Plan of Distribution” attached hereto as Annex A. Subject to
the terms of this Agreement, the Corporation shall use its reasonable best
efforts to cause such Registration Statement to be declared effective under the
Securities Act as promptly as possible after the filing thereof, but in any
event on or prior to the Effectiveness Date, and shall use its reasonable best
efforts to keep the Registration Statement continuously effective (whether on
Form S-1 or amended to Form S-3 or another appropriate form in accordance
herewith) under the Securities Act until all Registrable Shares have been sold,
or may be sold without volume restrictions pursuant to Rule 144, as determined
by the counsel to the Corporation pursuant to a written opinion letter to such
effect, addressed and acceptable to the transfer agent of the Corporation and
the affected Holders (the “Effectiveness Period”). The Corporation shall
telephonically request effectiveness of the Registration Statement as of
5:00 p.m. New York City time on a day during which the public markets are open
for trading stocks (a “Trading Day”). The Corporation shall immediately notify
the Holders via facsimile or by e-mail delivery of a “.pdf” format data file of
the effectiveness of the Registration Statement on the same Trading Day that the
Corporation telephonically confirms effectiveness with the Commission, which
shall be the date requested for effectiveness of the Registration Statement. The
Corporation shall, by 9:30 a.m. New York City time on the Trading Day after the
Effective Date, file a final Prospectus with the Commission as required by
Rule 424. Failure to so notify the Holder within 1 Trading Day of such
notification of effectiveness or failure to file a final Prospectus as foresaid
shall be deemed an Event under Section 3.4(b).

 

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(ii)           If: (A) the Registration Statement is not filed on or prior to
the Filing Date or has not been declared effective by the Commission by the
Effectiveness Date, or (B) the Corporation fails to file with the Commission a
request for acceleration in accordance with Rule 461 promulgated under the
Securities Act, within 5 Trading Days of the date that the Corporation is
notified (orally or in writing, whichever is earlier) by the Commission that a
Registration Statement will not be “reviewed” or not be subject to further
review, or (C) prior to the Effectiveness Date of a Registration Statement, the
Corporation fails to file a pre-effective amendment and otherwise respond in
writing to comments made by the Commission in respect of such Registration
Statement within 14 calendar days after the receipt of comments by or notice
from the Commission that such amendment is required in order for such
Registration Statement to be declared effective, or (D) after the Effectiveness
Date of a Registration Statement, such Registration Statement ceases for any
reason to remain continuously effective as to all Registrable Securities
included in such Registration Statement, or the Holders are otherwise not
permitted to utilize the Prospectus therein to resell such Registrable
Securities, for more than 20 consecutive calendar days or more than an aggregate
of 40 calendar days during any 12-month period (which need not be consecutive
calendar days) (any such failure or breach being referred to as an “Event”, and
for purposes of clause (A) the date on which such Event occurs, or for purposes
of clause (B) the date on which such 5 Trading Day period is exceeded, or for
purposes of clause (C) the date which such 14 calendar day period is exceeded,
or for purposes of clause (D) the date on which such 20 or 40 calendar day
period, as applicable, is exceeded being referred to as an “Event Date”), then,
in addition to any other rights the Holders may have hereunder or under
applicable law, on each such Event Date and on each monthly anniversary of each
such Event Date (if the applicable Event shall not have been cured by such date)
until the applicable Event is cured, the Corporation shall pay to each Holder an
amount in cash, as partial liquidated damages and not as a penalty, equal to 1%
of the aggregate purchase price paid by such Holder pursuant to the Stock
Purchase Agreement for any Registrable Securities then held by such Holder.  The
parties agree that the maximum aggregate liquidated damages payable to a Holder
under this Agreement shall be sixteen percent (16%) of the aggregate Purchase
Price (as defined in the Stock Purchase Agreement) paid by such Holder pursuant
to the Stock Purchase Agreement.  If the Corporation fails to pay any partial
liquidated damages pursuant to this Section 3.4(b) in full within seven days
after the date payable, the Corporation will pay interest thereon at a rate of
ten percent (10%) per annum (or such lesser maximum amount that is permitted to
be paid by applicable law) to the Holder, accruing daily from the date such
partial liquidated damages are due until such amounts, plus all such interest
thereon, are paid in full. The partial liquidated damages pursuant to the terms
hereof shall apply on a daily pro-rata basis for any portion of a month prior to
the cure of an Event.

 

(iii)          In the event that the Corporation is unable for any reason to
include in the Registration Statement required to be filed under
Section 3.4(a)(i) all of the Registrable Securities, then the Corporation shall
use its reasonable best efforts to file and cause to be declared effective
additional Registration Statements, in order to uphold its obligations under
Section 3.4(a)(i), as promptly as practicable. If not all Registrable Securities
may be included in any one Registration Statement, then the Registrable
Securities to be included shall be allocated among Holders of such Registrable
Securities on a pro rata basis based on the total number of Registrable
Securities held by all Holders that have not been included in a Registration
Statement.

 

(b)           Registration Procedures. In connection with the Corporation’s
registration obligations hereunder, the Corporation shall:

 

(i)            Not less than seven Trading Days prior to the filing of any
Registration Statement and not less than two Trading Days prior to the filing of
any related Prospectus or any amendment or supplement thereto, (A) furnish to
each Holder copies of all such documents proposed to be filed, which documents
(other than those incorporated or deemed to be incorporated by reference) will
be subject to the review of such Holders, and (B) cause its officers and
directors, counsel and

 

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independent certified public accountants to respond to such inquiries as shall
be necessary, in the reasonable opinion of respective counsel to each Holder, to
conduct a reasonable investigation within the meaning of the Securities Act; and
not file a Registration Statement or any such Prospectus or any amendments or
supplements thereto to which the Holders of 67% of the Registrable Securities
shall reasonably object in good faith, provided that the Corporation is notified
of such objection in writing no later than 5 Trading Days after the Holders have
been so furnished copies of a Registration Statement or 1 Trading Day after the
Holders have been so furnished copies of any related Prospectus or amendments or
supplements thereto. Each Holder agrees to furnish to the Corporation a
completed questionnaire in the form attached to this Agreement as Annex B or
other form reasonably acceptable to the Corporation (a “Selling Stockholder
Questionnaire”) not less than 2 Trading Days prior to the Filing Date or by the
end of the 4th Trading Day following the date on which such Holder receives
draft materials in accordance with this Section. During any periods that the
Corporation is unable to meet its obligations hereunder with respect to the
registration of the Registrable Securities because the Holders of 67% of the
Registrable Securities exercise their rights under this section to object to the
filing of a Registration Statement, any liquidated damages that are accruing, at
such time shall be tolled and any Event that may otherwise occur because of the
exercise of such rights or such delay shall be suspended, until the Holders of
67% of the Registrable Securities no longer object to the filing of such
Registration Statement (provided that such tolling shall only occur if the
Corporation uses commercially reasonable efforts to resolve such objection). If
any Holder fails to furnish its Selling Stockholder Questionnaire related to a
particular Registration Statement not less than 2 Trading Days prior to the
Filing Date or by the end of the 4th Trading Day following the date on which
such Holder receives draft materials in accordance with this Section, any
liquidated damages that are accruing, as well as any other rights of such Holder
under this Agreement with regard to such Registration Statement, including
without limitation, the right to include such Holder’s Registrable Securities in
such Registration Statement, shall be tolled as to such Holder until such
information is received by the Corporation; provided, however, that the
Corporation shall use commercially reasonable efforts to include such
Registrable Securities in such Registration Statement or the next most available
Registration Statement as soon as possible after such information is furnished
to the Corporation.

 

(ii)           (A) Prepare and file with the Commission such amendments,
including post-effective amendments, to a Registration Statement and the
Prospectus used in connection therewith as may be necessary to keep a
Registration Statement continuously effective as to the applicable Registrable
Securities for the Effectiveness Period and prepare and file with the Commission
such additional Registration Statements in order to register for resale under
the Securities Act all of the Registrable Securities; (B) cause the related
Prospectus to be amended or supplemented by any required Prospectus supplement
(subject to the terms of this Agreement), and as so supplemented or amended to
be filed pursuant to Rule 424; (C) respond as promptly as reasonably possible to
any comments received from the Commission with respect to a Registration
Statement or any amendment thereto and provide as promptly as reasonably
possible to the Holders true and complete copies of all correspondence from and
to the Commission relating to a Registration Statement (provided that the
Corporation may excise any information contained therein which would constitute
material non-public information as to any Holder which has not executed a
confidentiality agreement with the Corporation); and (D) comply in all material
respects with the provisions of the Securities Act and the Exchange Act with
respect to the disposition of all Registrable Securities covered by a
Registration Statement during the applicable period in accordance (subject to
the terms of this Agreement) with the intended methods of disposition by the
Holders thereof set forth in such Registration Statement as so amended or in
such Prospectus as so supplemented.

 

(iii)          If during the Effectiveness Period, the number of Registrable
Securities at any time exceeds 100% of the number of shares of Common Stock then
registered in a Registration Statement, file as soon as reasonably practicable
an additional Registration Statement covering the resale by the Holders of not
less than the number of such Registrable Securities.

 

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(iv)          Notify the Holders of Registrable Securities to be sold (which
notice shall, pursuant to clauses (C) through (F) hereof, be accompanied by an
instruction to suspend the use of the Prospectus until the requisite changes
have been made) as promptly as reasonably possible (and, in the case of
(A)(1) below, not less than 1 Trading Day prior to such filing, in the case of
(C) and (D) below, not more than 1 Trading Day after such issuance or receipt
and, in the case of (E) below, not less than 3 Trading Days prior to the
financial statements in any Registration Statement becoming ineligible for
inclusion therein) and (if requested by any such Person) confirm such notice in
writing no later than 1 Trading Day following the day (A)(1) when a Prospectus
or any Prospectus supplement or post-effective amendment to a Registration
Statement is proposed to be filed; (2) when the Commission notifies the
Corporation whether there will be a “review” of such Registration Statement and
whenever the Commission comments in writing on such Registration Statement (in
which case the Corporation shall provide true and complete copies thereof and
all written responses thereto to each of the Holders that pertain to the Holders
as a selling stockholder or to the Plan of Distribution, but not information
which the Corporation believes would constitute material and non-public
information); and (3) with respect to a Registration Statement or any
post-effective amendment, when the same has become effective; (B) of any request
by the Commission or any other federal or state governmental authority for
amendments or supplements to a Registration Statement or Prospectus or for
additional information; (C) of the issuance by the Commission or any other
federal or state governmental authority of any stop order suspending the
effectiveness of a Registration Statement covering any or all of the Registrable
Securities or the initiation of any Proceedings for that purpose; (D) of the
receipt by the Corporation of any notification with respect to the suspension of
the qualification or exemption from qualification of any of the Registrable
Securities for sale in any jurisdiction, or the initiation or threatening of any
Proceeding for such purpose; (E) of the occurrence of any event or passage of
time that makes the financial statements included in a Registration Statement
ineligible for inclusion therein or any statement made in a Registration
Statement or Prospectus or any document incorporated or deemed to be
incorporated therein by reference untrue in any material respect or that
requires any revisions to a Registration Statement, Prospectus or other
documents so that, in the case of a Registration Statement or the Prospectus, as
the case may be, it will not contain any untrue statement of a material fact or
omit to state any material fact required to be stated therein or necessary to
make the statements therein, in light of the circumstances under which they were
made, not misleading; and (F) the occurrence or existence of any pending
corporate development with respect to the Corporation that the Corporation
believes may be material and that, in the good faith determination of the
Corporation, based on the advice of counsel, makes it not in the best interest
of the Corporation to allow continued availability of a Registration Statement
or Prospectus, provided that any and all of such information shall remain
confidential to each Holder until such information otherwise becomes public,
unless disclosure by a Holder is required by law; provided, further, that
notwithstanding each Holder’s agreement to keep such information confidential,
the Holders make no acknowledgement that any such information is material,
non-public information.

 

(v)           Use its reasonable best efforts to avoid the issuance of, or, if
issued, obtain the withdrawal of (A) any order suspending the effectiveness of a
Registration Statement, or (B) any suspension of the qualification (or exemption
from qualification) of any of the Registrable Securities for sale in any
jurisdiction, at the earliest practicable moment.

 

(vi)          If requested by a Holder, furnish to such Holder, without charge
(A) at least one conformed copy of each such Registration Statement and each
amendment thereto, including financial statements and schedules, all documents
incorporated or deemed to be incorporated therein by reference to the extent
requested by such Person, and all exhibits to the extent requested by such
Person (including those previously furnished or incorporated by reference)
promptly after the filing of such documents with the Commission, and (B) during
the Effectiveness Period, as many copies of the Prospectus included in the
Registration Statement and any amendment or supplement thereto as such

 

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Holder may reasonably request; provided, however, that the Corporation shall
have no obligation to provide any document pursuant to this clause that is
available on the Commission’s EDGAR system.

 

(vii)         Subject to the terms of this Agreement, consent to the use of each
Prospectus and each amendment or supplement thereto by each of the selling
Holders in connection with the offering and sale of the Registrable Securities
covered by such Prospectus and any amendment or supplement thereto, except after
the giving of any notice pursuant to Section 3.4(b)(iv).

 

(viii)        Effect a filing with respect to the public offering contemplated
by the Registration Statement (an “Issuer Filing”) with the Financial Industry
Regulatory Authority (“FINRA”) Corporate Financing Department pursuant to FINRA
Rule 5110 within 1 Trading Day of the date that the Registration Statement is
first filed with the Commission and pay the filing fee required by such Issuer
Filing; and use commercially reasonable efforts to pursue the Issuer Filing
until FINRA issues a letter confirming that it does not object to the terms of
the offering contemplated by the Registration Statement.

 

(ix)          Prior to any resale of Registrable Securities by a Holder, use its
reasonable best efforts to register or qualify or cooperate with the selling
Holders in connection with the registration or qualification (or exemption from
the registration or qualification) of such Registrable Securities for the resale
by the Holder under the securities or blue sky laws of such jurisdictions within
the United States as any Holder reasonably requests in writing, to keep each
registration or qualification (or exemption therefrom) effective during the
Effectiveness Period and to do any and all other acts or things reasonably
necessary to enable the disposition in such jurisdictions of the Registrable
Securities covered by a Registration Statement; provided, that the Corporation
shall not be required to qualify generally to do business in any jurisdiction
where it is not then so qualified, subject the Corporation to any material tax
in any such jurisdiction where it is not then so subject or file a general
consent to service of process in any such jurisdiction.

 

(x)           If requested by the Holders, cooperate with the Holders to
facilitate the timely preparation and delivery of certificates representing
Registrable Securities to be delivered to a transferee pursuant to a
Registration Statement, which certificates shall be free, to the extent
permitted by the Stock Purchase Agreement, of all restrictive legends, and to
enable such Registrable Securities to be in such denominations and registered in
such names as any such Holders may request. In connection therewith, if required
by the Corporation’s transfer agent, the Corporation shall promptly after the
effectiveness of a Registration Statement cause an opinion of counsel as to the
effectiveness of the Registration Statement to be delivered to and maintained
with the transfer agent, together with any other authorizations, certificates
and directions required by the transfer agent, which authorize and direct the
transfer agent to issue such Registrable Securities without legend upon sale by
the holder of such shares of Registrable Securities under the Registration
Statement.

 

(xi)          Upon the occurrence of any event contemplated by this
Section 3.4(b), as promptly as reasonably possible under the circumstances
taking into account the Corporation’s good faith assessment of any adverse
consequences to the Corporation and its stockholders of the premature disclosure
of such event, prepare a supplement or amendment, including a post-effective
amendment, to a Registration Statement or a supplement to the related Prospectus
or any document incorporated or deemed to be incorporated therein by reference,
and file any other required document so that, as thereafter delivered, neither a
Registration Statement nor Prospectus will contain an untrue statement of a
material fact or omit to state a material fact required to be stated therein or
necessary to make the statements therein, in light of the circumstances under
which they were made, not misleading. If the Corporation notifies and instructs
the Holders in accordance with clauses (iii) through (vi) of
Section 3.4(b)(iv) above to suspend the use of any Prospectus until the
requisite changes to such

 

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Prospectus have been made, then the Holders shall suspend use of such
Prospectus; use its reasonable best efforts to ensure that the use of the
Prospectus may be resumed as promptly as is practicable; and be entitled to
exercise its right under this Section 3.4(b)(xi) to suspend the availability of
a Registration Statement and Prospectus, subject to the payment of partial
liquidated damages pursuant to Section 3.4(a)(ii), for a period not to exceed 40
calendar days (which need not be consecutive days) in any 12 month period.

 

(xii)         Comply with all applicable rules and regulations of the
Commission.

 

(c)           The Corporation may require each selling Holder to furnish to the
Corporation a certified statement as to the number of shares of Common Stock
beneficially owned by such Holder and any affiliate thereof and as to any FINRA
affiliations and, if required by the Commission, of any natural persons that
have voting and dispositive control over the Registrable Securities. During any
periods that the Corporation is unable to meet its obligations hereunder with
respect to the registration of the Registrable Securities solely because any
Holder fails to furnish such information within 3 Trading Days of the
Corporation’s request, any liquidated damages that are accruing at such time as
to such Holder only, as well as any other rights of such Holder under this
Agreement, including without limitation, the right to include such Holder’s
Registrable Securities in a Registration Statement shall be tolled and any Event
that may otherwise occur solely because of such delay shall be suspended as to
such Holder only, until such information is delivered to the Corporation;
provided, however, that the Corporation shall use commercially reasonable
efforts to include such Registrable Securities in such Registration Statement or
the next most available Registration Statement as soon as possible after such
information is furnished to the Corporation.

 

3.5          Piggyback Registration.

 

(a)           Each time that the Corporation proposes for any reason to register
any of its securities under the Securities Act, other than pursuant to a
registration statement on Form S-4, Form S-8 or Form S-1 or similar or successor
forms, but in regard to Form S-1 only in connection with the initial public
offering of the Corporation’s Common Stock (collectively, “Excluded Forms”), the
Corporation shall promptly give written notice of such proposed registration to
all holders of Registrable Securities, which notice shall also constitute an
offer to such holders to request inclusion of any Registrable Shares in the
proposed registration.

 

(b)           Each holder of Registrable Securities shall have 30 days from the
receipt of such notice to deliver to the Corporation a written request
specifying the number of Registrable Shares such holder intends to sell and the
holder’s intended method of disposition.

 

(c)           In the event that the proposed registration by the Corporation is,
in whole or in part, an underwritten public offering of securities of the
Corporation, any request under Section 3.5(b) may specify that the Registrable
Shares be included in the underwriting (i) on the same terms and conditions as
the shares of Common Stock, if any, otherwise being sold through underwriters
under such registration, or (ii) on terms and conditions comparable to those
normally applicable to offerings of common stock in reasonably similar
circumstances in the event that no shares of Common Stock other than Registrable
Shares are being sold through underwriters under such registration.

 

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(d)           Upon receipt of a written request pursuant to Section 3.5(b), the
Corporation shall promptly use its best efforts to cause all such Registrable
Shares to be registered under the Securities Act, to the extent required to
permit sale or disposition as set forth in the written request.

 

(e)           Notwithstanding the foregoing, if the managing underwriter of any
such proposed registration determines and advises in writing that the inclusion
of all Registrable Shares proposed to be included in the underwritten public
offering, together with any other issued and outstanding shares of Common Stock
proposed to be included therein by holders other than the holders of Registrable
Securities (such other shares hereinafter collectively referred to as the “Other
Shares”) would interfere with the successful marketing of the Corporation’s
securities, then the total number of such securities proposed to be included in
such underwritten public offering shall be reduced, (i) first by the shares
requested to be included in such registration by the holders of Other Shares,
(ii) second, if necessary by all Registrable Securities which are not Series A-2
Registrable Securities, Series A-3 Registrable Securities or Series A-1
Registrable Securities, and (iii) third, if necessary, (A) one-half (1/2) by the
securities proposed to be issued by the Corporation, and (B) one-half (1/2) by
the holders of Series A-2 Registrable Shares, Series A-3 Registrable Shares
and/or Series A-1 Registrable Shares proposed to be included in such
registration by the holders thereof, on a pro rata basis calculated based upon
the number of Registrable Shares, Series A-2 Registrable Shares, Series A-3
Registrable Shares or Series A-1 Registrable Shares sought to be registered by
each such holder; provided, that the aggregate number of securities proposed to
be included in such registration by the holders of Series A-2 Registrable
Shares, Series A-3 Registrable Shares and/or Series A-1 Registrable Shares shall
only be reduced hereunder if and to the extent that such securities exceed
twenty-five percent (25%) of the aggregate number of securities included in such
registration. The shares of Common Stock that are excluded from the underwritten
public offering pursuant to the preceding sentence shall be withheld from the
market by the holders thereof for a period, not to exceed 90 days from the
closing of such underwritten public offering, that the managing underwriter
reasonably determines as necessary in order to effect such underwritten public
offering.

 

3.6          Registrations on Form S-3.  At such time as the Registration
Statement contemplated by Section 3.4 shall no longer be effective, each holder
of Registrable Securities shall have the right to request in writing an
unlimited number of registrations on Form S-3. Each such request by a holder
shall: (a) specify the number of Registrable Shares which the holder intends to
sell or dispose of, (b) state the intended method by which the holder intends to
sell or dispose of such Registrable Shares, and (c) request registration of
Registrable Shares having a proposed aggregate offering price of at least
$1,000,000. Upon receipt of an adequate request pursuant to this Section 3.6,
the Corporation shall use its best efforts to effect such registration or
registrations on Form S-3.

 

3.7          Preparation and Filing.  If and whenever the Corporation is under
an obligation pursuant to the provisions of Sections 3.5 and/or 3.6 to use its
best efforts to effect the registration of any Registrable Shares, the
Corporation shall, as expeditiously as practicable:

 

(a)           prepare and file with the Commission a registration statement with
respect to such securities and use its best efforts to cause such registration
statement to become and remain effective in accordance with
Section 3.7(b) hereof;

 

(b)           prepare and file with the Commission such amendments and
supplements to such registration statement and the prospectus used in connection
therewith as may be necessary to keep such registration statement effective
until the earlier of (i) the sale of all Registrable Shares covered thereby or
(ii) nine months from the date such registration statement first becomes
effective, and to comply with the provisions of the Securities Act with respect
to the sale or other disposition of all Registrable Shares covered by such
registration statement;

 

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(c)           furnish to each holder whose Registrable Shares are being
registered pursuant to this Section 3 such number of copies of any summary
prospectus or other prospectus, including a preliminary prospectus, in
conformity with the requirements of the Securities Act, and such other documents
as such holder may reasonably request in order to facilitate the public sale or
other disposition of such Registrable Shares;

 

(d)           use its best efforts to register or qualify the Registrable Shares
covered by such registration statement under the securities or blue sky laws of
such jurisdictions as each holder whose Registrable Shares are being registered
pursuant to this Section 3 shall reasonably request, and do any and all other
acts or things which may be necessary or advisable to enable such holder to
consummate the public sale or other disposition in such jurisdictions of such
Registrable Shares; provided, however, that the Corporation shall not be
required to consent to general service of process for all purposes in any
jurisdiction where it is not then subject to process, qualify to do business as
a foreign corporation where it would not be otherwise required to qualify or
submit to liability for state or local taxes where it is not otherwise liable
for such taxes;

 

(e)           at any time when a prospectus covered by such registration
statement and relating thereto is required to be delivered under the Securities
Act within the appropriate period mentioned in Section 3.7(b) hereof, notify
each holder whose Registrable Shares are being registered pursuant to this
Section 3 of the happening of any event as a result of which the prospectus
included in such registration, as then in effect, includes an untrue statement
of a material fact or omits to state a material fact required to be stated
therein or necessary to make the statements therein not misleading in the light
of the circumstances then existing and, at the request of such holder, prepare,
file and furnish to such holder a reasonable number of copies of a supplement to
or an amendment of such prospectus as may be necessary so that, as thereafter
delivered to the purchasers of such shares, such prospectus shall not include an
untrue statement of a material fact or omit to state a material fact required to
be stated therein or necessary to make the statements therein not misleading in
the light of the circumstances then existing;

 

(f)            if the Corporation has delivered preliminary or final
prospectuses to the holders of Registrable Shares that are being registered
pursuant to this Section 3 and after having done so the prospectus is amended to
comply with the requirements of the Securities Act, the Corporation shall
promptly notify such holders and, if requested, such holders shall immediately
cease making offers of Registrable Shares and return all prospectuses to the
Corporation. The Corporation shall promptly provide such holders with revised
prospectuses and, following receipt of the revised prospectuses, such holders
shall be free to resume making offers of the Registrable Shares; and

 

(g)           furnish, at the request of any holder whose Registrable Shares are
being registered pursuant to this Section 3, on the date that such Registrable
Shares are delivered to the underwriters for sale in connection with a
registration pursuant to this Section 3 if such securities are being sold
through underwriters, or on the date that the registration statement with
respect to such securities becomes effective if such securities are not being
sold through underwriters, (i) an opinion, dated such date, of the counsel
representing the Corporation for the purposes of such registration, in form and
substance as is customarily given to underwriters in an underwritten public
offering, addressed to the underwriters, if any, and to the holder or holders
making such request, and (ii) a letter dated such date, from the independent
certified public accountants of the Corporation, in form and substance as is
customarily given by independent certified public accountants to underwriters in
an underwritten public offering, addressed to the underwriters, if any, and to
the holder or holders making such request.

 

3.8          Expenses.  The Corporation shall pay all expenses incurred by the
Corporation in complying with this Section 3, including, without limitation, all
registration and filing fees (including

 

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all expenses incident to filing with the FINRA), fees and expenses of complying
with the securities and blue sky laws of all such jurisdictions in which the
Registrable Shares are proposed to be offered and sold, printing expenses and
fees and disbursements of counsel (including with respect to each registration
effected pursuant to Sections 3.4, 3.5 and 3.6, the reasonable fees and
disbursements of a counsel for the holders of Registrable Shares that are being
registered pursuant to this Section 3, such counsel for the holders of
Registrable Shares shall be designated by a vote of a majority of the holders of
Registrable Shares to be included in such registration, determined in accordance
with Article III, Section A.6(a) of the Certificate); provided, however, that
all underwriting discounts and selling commissions applicable to the Registrable
Shares covered by registrations effected pursuant to Section 3.4, 3.5 or 3.6
hereof shall be borne by the seller or sellers thereof, in proportion to the
number of Registrable Shares sold by each such seller or sellers.

 

3.9          Indemnification.

 

(a)           In the event of any registration of any Registrable Shares under
the Securities Act pursuant to this Section 3 or registration or qualification
of any Registrable Shares pursuant to Section 3.7(d) hereof, the Corporation
shall indemnify and hold harmless the seller of such shares, each underwriter of
such shares, if any, each broker or any other person acting on behalf of such
seller and each other person, if any, who controls any of the foregoing persons,
within the meaning of the Securities Act, against any losses, claims, damages or
liabilities, joint or several, to which any of the foregoing persons may become
subject under the Securities Act or otherwise, insofar as such losses, claims,
damages or liabilities (or actions in respect thereof) arise out of or are based
upon an untrue statement or alleged untrue statement of a material fact
contained in any registration statement under which such Registrable Shares were
registered under the Securities Act, any preliminary prospectus or final
prospectus contained therein, or any amendment or supplement thereto, or any
document incident to registration or qualification of any Registrable Shares
pursuant to Section 3.7(d) hereof or arise out of or are based upon the omission
or alleged omission to state therein a material fact required to be stated
therein or necessary to make the statements therein not misleading or, with
respect to any prospectus, necessary to make the statements therein, in light of
the circumstances under which they were made, not misleading, or any violation
by the Corporation of the Securities Act or any state securities or blue sky
laws applicable to the Corporation and relating to action or inaction required
of the Corporation in connection with such registration or qualification under
the Securities Act or such state securities or blue sky laws. The Corporation
shall reimburse on demand such seller, underwriter, broker or other person
acting on behalf of such seller and each such controlling person for any legal
or any other expenses reasonably incurred by any of them in connection with
investigating or defending any such loss, claim, damage, liability or action;
provided, however, that the Corporation shall not be liable in any such case to
the extent that any such loss, claim, damage or liability arises out of or is
based upon an untrue statement or alleged untrue statement or omission or
alleged omission made in said registration statement, preliminary or final
prospectus or amendment or supplement thereto or any document incident to
registration or qualification of any Registrable Shares pursuant to
Section 3.7(d) hereof, in reliance upon and in conformity with written
information furnished to the Corporation by such seller, underwriter, broker,
other person or controlling person specifically for use in the preparation
hereof.

 

(b)           Before Registrable Shares held by any prospective seller shall be
included in any registration pursuant to this Section 3, such prospective seller
and any underwriter acting on its behalf shall have agreed to indemnify and hold
harmless (in the same manner and to the same extent as set forth in paragraph
(a)) the Corporation, each director of the Corporation, each officer of the
Corporation who signs such registration statement and any person who controls
the Corporation within the meaning of the Securities Act, with respect to any
untrue statement or omission from such registration statement, any preliminary
prospectus or final prospectus contained therein, or any amendment or supplement
thereto, if such untrue statement or omission was made in reliance upon and in
conformity

 

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with written information furnished to the Corporation through an instrument duly
executed by such seller or such underwriter specifically for use in the
preparation of such registration statement, preliminary prospectus, final
prospectus or amendment or supplement; provided, however, that the maximum
amount of liability in respect of such indemnification shall be limited, in the
case of each prospective seller, to an amount equal to the net proceeds actually
received by such prospective seller from the sale of Registrable Shares effected
pursuant to such registration.

 

(c)           Promptly after receipt by an indemnified party of notice of the
commencement of any action involving a claim referred to in Section 3.9(a) or
(b) hereof, such indemnified party will, if a claim in respect thereof is to be
made against the indemnifying party under this Section 3.9, give written notice
to the latter of the commencement of such action. In case any such action is
brought against an indemnified party, the indemnifying party will be entitled to
participate in and to assume the defense thereof jointly with any other
indemnifying party similarly notified to the extent that it may wish, with
counsel reasonably satisfactory to such indemnified party, and, after notice to
such indemnified party from the indemnifying party of its election to assume the
defense thereof, the indemnifying party shall be responsible for any legal or
other expenses subsequently incurred by such indemnifying party in connection
with the defense thereof; provided, however, that, if any indemnified party
shall have reasonably concluded that there may be one or more legal defenses
available to such indemnified party which are different from or additional to
those available to the indemnifying party, or that such claim or litigation
involves or could have an effect upon matters beyond the scope of the indemnity
agreement provided in this Section 3.9, the indemnifying party shall not have
the right to assume the defense of such action on behalf of such indemnified
party, and such indemnifying party shall reimburse such indemnified party and
any person controlling such indemnified party for the fees and expenses of
counsel retained by the indemnified party which are reasonably related to the
matters covered by the indemnity agreement provided in this Section 3.9. The
indemnifying party shall not make any settlement of any claims in respect of
which it is obligated to indemnify an indemnified party or parties hereunder,
without the written consent of the indemnified party or parties, which consent
shall not be unreasonably withheld.

 

(d)           In order to provide for just and equitable contribution to joint
liability under the Securities Act, in any case in which either (i) any holder
of Registrable Shares exercising rights under this Agreement, or any controlling
person of any such holder, makes a claim for indemnification pursuant to this
Section 3.9, but it is judicially determined (by the entry of a final judgment
or decree by a court of competent jurisdiction and the expiration of time to
appeal or the denial of the last right of appeal) that such indemnification may
not be enforced in such case notwithstanding the fact that this Section 3.9
provides for indemnification in such case, or (ii) contribution under the
Securities Act may be required on the part of any such holder or any such
controlling person in circumstances for which indemnification is provided under
this Section 3.9; then, in each such case, the Corporation and such holder will
contribute to the aggregate losses, claims, damages or liabilities to which they
may be subject as is appropriate to reflect the relative fault of the
Corporation and such holder in connection with the statements or omissions which
resulted in such losses, claims, damages or liabilities, it being understood
that the parties acknowledge that the overriding equitable consideration to be
given effect in connection with this provision is the ability of one party or
the other to correct the statement or omission which resulted in such losses,
claims, damages or liabilities, and that it would not be just and equitable if
contribution pursuant hereto were to be determined by pro rata allocation or by
any other method of allocation which does not take into consideration the
foregoing equitable considerations. Notwithstanding the foregoing, (i) no such
holder will be required to contribute any amount in excess of the proceeds to it
of all Registrable Shares sold by it pursuant to such registration statement,
and (ii) no person or entity guilty of fraudulent misrepresentation, within the
meaning of Section 11(f) of the Securities Act, shall be entitled to
contribution from any person or entity who is not guilty of such fraudulent
misrepresentation.

 

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(e)           Notwithstanding any of the foregoing, if, in connection with an
underwritten public offering of any Registrable Shares, the Corporation, the
holders of such Registrable Shares and the underwriters enter into an
underwriting or purchase agreement relating to such offering which contains
provisions covering indemnification among the parties, then the indemnification
provision of this Section 3.9 shall be deemed inoperative for purposes of such
offering.

 

3.10        Removal of Legends, Etc.  Notwithstanding the foregoing provisions
of this Section 3, the restrictions imposed by this Section 3 upon the
transferability of any Restricted Stock, Series A-1 Preferred Stock, Series A-2
Preferred Stock or Series A-3 Preferred Stock shall cease and terminate when
(a) any such Restricted Stock, Series A-1 Preferred Stock, Series A-2 Preferred
Stock or Series A-3 Preferred Stock are sold or otherwise disposed of in
accordance with the intended method of disposition by the seller or sellers
thereof set forth in a registration statement or such other method contemplated
by Section 3.3 hereof that does not require that the securities transferred bear
the legend set forth in Section 3.2 hereof, including a Transfer pursuant to
Rule 144 or a successor rule thereof (as amended from time to lime), or (b) the
holder of Restricted Stock, Series A-1 Preferred Stock, Series A-2 Preferred
Stock or Series A-3 Preferred Stock has met the requirements for transfer of
such Restricted Stock, Series A-1 Preferred Stock, Series A-2 Preferred Stock or
Series A-3 Preferred Stock pursuant to subparagraph (b)(1) of Rule 144 or a
successor rule thereof (as amended from time to time) promulgated by the
Commission under the Securities Act. Whenever the restrictions imposed by this
Section 3 have terminated, a holder of a certificate for Restricted Stock,
Series A-1 Preferred Stock, Series A-2 Preferred Stock or Series A-3 Preferred
Stock as to which such restrictions have terminated shall be entitled to receive
from the Corporation, without expense, a new certificate not bearing the
restrictive legend set forth in Section 3.2 hereof and not containing any other
reference to the restrictions imposed by this Section 3. Notwithstanding the
above, nothing herein shall limit the restrictions imposed upon transfer of the
Restricted Securities pursuant to Section 8 hereof nor the imposition of the
legend provided for therein.

 

3.11        Lock-up Agreement.

 

(a)           Each Stockholder agrees that, during the 180-day period following
the date hereof, such Stockholder will not, without the prior written consent of
the Company, sell, assign, transfer, make a short sale of, loan, grant any
option for the purchase of, or exercise registration rights with respect to any
shares of Common Stock or shares of capital stock or other securities of the
Corporation convertible into or exercisable for, whether directly or indirectly,
shares of Common Stock, other than to a member of such Stockholder’s Group;
provided, however, that notwithstanding the foregoing but subject to the
provisions of Section 3.11(b) below, (i) on or at any time after each of the
dates listed in the table below under the caption “Initial Lock-up Release
Date”, such Stockholder shall be permitted to sell, assign, transfer, make a
short sale of, loan, or grant any option for the purchase of, with respect to
that number of shares of Common Stock issued or issuable upon conversion of
shares of Series A-1 Conversion Shares (the “Series A-1 Conversion Shares”) held
or issuable to such Stockholder that corresponds to a percentage of the total
number of Series A-1 Conversion Shares held or issuable to such Stockholder at
such time, which percentage is set forth in the table below under the caption
“Initial Lock-up Release Percentage”.

 

Initial Lock-up Release Date

 

Initial Lock-up Release Percentage

 

 

 

 

 

30th day after the date of this Agreement

 

5

%

 

 

 

 

60th day after the date of this Agreement

 

15

%

 

 

 

 

90th day after the date of this Agreement

 

30

%

 

 

 

 

120th day after the date of this Agreement

 

50

%

 

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(b)           Notwithstanding the foregoing, (A) subject to clause (C) below,
the restriction on transfer set forth in Section 3.11(a) above shall not apply
to block trades of 10,000 shares or more of the Series A-1 Conversion Shares,
(B) subject to clause (C) below, if, on or at any time after any date listed in
the table set forth in Section 3.11(a) above, the average of the closing bid and
ask price of the Company’s Common Stock if quoted on any electronic quotation
system, including but not limited to the OTC:BB for the five (5) trading days
ending on such date, or the average last-sale price of the Company’s Common
Stock if listed on a national securities exchange for the five (5) trading days
ending on such date, is greater than $16.29 per share (subject to proportionate
and equitable adjustment upon any stock split, stock dividend, reverse stock
split or similar event that becomes effective after the date of this Agreement),
the percentage in the table set forth in Section 3.11(a) above that corresponds
to such date shall be doubled and (C) in no event shall any Stockholder be
permitted, during the period commencing on the date hereof and ending on the
date of the listing of the Company’s Common Stock on a national securities
exchange, to sell, assign, transfer, make a short sale of, loan, grant any
option for the purchase of, or exercise registration rights with respect to any
Series A-1 Conversion Shares for a price less than $8.142 (subject to
proportionate and equitable adjustment upon any stock split, stock dividend,
reverse stock split or similar event that becomes effective after the date of
this Agreement), except (x) with the prior written consent of the Company or
(y) to a member of such Stockholder’s Group.

 

(c)           Each Stockholder agrees further that, if the Company or a managing
underwriter so requests of such Stockholder in connection with a registered
public offering of securities of the Company, such Stockholder will not, without
the prior written consent of the Company or such underwriters, sell, assign,
transfer, make a short sale of, loan, grant any option for the purchase of, or
exercise registration rights with respect to any shares of Common Stock or
shares of capital stock or other securities of the Corporation convertible into
or exercisable for, whether directly or indirectly, shares of Common Stock,
other than to a member of such Stockholder’s Group, during the period of (i)180
days following the closing of the first public offering of securities offered
and sold for the account of the Corporation that is registered under the
Securities Act, or (ii) 90 days following the closing of any other public
offering of securities offered and sold for the account of the Corporation that
is registered under the Securities Act ; provided that such request is made of
all officers, directors and 1% and greater Stockholders and each such person
shall be similarly bound; and, provided, further, that nothing in this
Section 3.11(c) shall prevent any Stockholder from participating in any
registered public offering of the Corporation as a selling stockholder or
security holder.

 

(d)           In the event that the Corporation releases or causes to be
released any Stockholder from any restrictions on transfer set forth in the
foregoing provisions of this Section 3.11, the Corporation shall release or
cause to be released all other Stockholders in similar fashion and any such
release of all Stockholders shall be implemented on a pro rata basis.

 

3.12        Duration of Section.  With respect to each holder of Registrable
Shares, Sections 3.4, 3.5 and 3.6 shall automatically terminate for that holder
on the fourth anniversary of the Filing Date.

 

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SECTION 4.  Election of Directors.

 

4.1          Voting for Directors.  At the first annual meeting of the
Stockholders of the Corporation after the Stage I Closing, and thereafter at
each annual meeting and each special meeting of the Stockholders of the
Corporation called for the purposes of electing directors of the Corporation,
and at any time at which Stockholders of the Corporation shall have the right
to, or shall, vote or consent to the election of directors, then, in each such
event, each Stockholder shall vote all shares of Preferred Stock, Common Stock
and any other shares of voting stock of the Corporation then owned (or
controlled as to voting rights) by it, him or her, whether by purchase, exercise
of rights, warrants or options, stock dividends or otherwise:

 

(a)           to fix and maintain the number of directors on the Board at seven
(7);

 

(b)           to the extent entitled under the Certificate as in effect as of
the date of this Agreement, to elect as Directors of the Corporation on the date
hereof and in any subsequent election of Directors the following individuals:

 

(i)            in the case of the two (2) directors to be elected by the holders
of Series A-1 Preferred Stock under the Certificate, two (2) individuals to be
designated by the affirmative vote or written consent of the holders of a
majority of the outstanding shares of Series A-1 Preferred Stock (the
“Series A-1 Directors”), who shall initially be Ansbert Gadicke and Martin
Muenchbach.

 

(ii)           in the case of the one (1) director to be elected by the G3
Holders (as defined in the Certificate), one (1) director to be designated by
the affirmative vote or written consent of those G3 Holders holding a majority
of the shares held by the G3 Holders (the “Specified Preferred Director”), who
shall initially be Jonathan Fleming, provided, however, that in order to be
eligible to vote or consent with respect to the designation of an individual as
a nominee for election as the Specified Preferred Director, a G3 Holder together
with members of such G3 Holders’ Group must hold greater than twenty percent
(20%) of the Preferred Stock purchased under the Series A-1 Stock Purchase
Agreement by such G3 Holder and members of such G3 Holders’ Group;

 

(iii)          in the case of the one (1) director to be elected by MPM, one
(1) director to be designated by the affirmative vote or written consent of MPM,
provided that such director be an individual with particular expertise in the
development of pharmaceutical products, as reasonably determined by MPM, if any
(the “Industry Expert Director” and together with the Series A-1 Directors and
the Specified Preferred Director, the “Investor Directors”), who shall initially
be Elizabeth Stoner, provided, further, however, that in order to be eligible to
vote or consent with respect to the designation of an individual as a nominee
for election as the Industry Expert Preferred Director, MPM together with
members of the MPM Group must hold greater than twenty percent (20%) of the
Preferred Stock purchased under the Series A-1 Stock Purchase Agreement by MPM
and members of the MPM Group.

 

(iv)          in the case of the remaining directors to be elected by the
holders of Preferred Stock and Common Stock, voting together as a single class,
under the Certificate, three (3) individuals as follows:

 

a.             two industry or market experts, each of whom shall be designated
by a majority of the other members of the Board, including a majority of the
Investor Directors (the “Independent Directors”), and who shall initially be
Alan Auerbach and Kurt Graves; and

 

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b.             the Chief Executive Officer of the Corporation, who shall
initially be Richard Lyttle.

 

4.2          Observer Rights.

 

(a)           HCV VII shall have the right to appoint an observer to the Board
(the “HCV Observer”) as long as HCV VII, together with members of the HCV Group,
holds greater than seventy five percent (75%) of the Series A-1 Preferred Stock
originally purchased by HCV VII and members of the HCV Group pursuant to the
Purchase Agreement. The HCV Observer shall have the right to attend all meetings
of the Board in a non-voting observer capacity, and the Corporation shall
provide to the HCV Observer all materials provided to the members of the Board
and notice of such meetings, all in the manner and at the time provided to the
members of the Board; provided, however, that the Corporation reserves the right
to exclude such representatives from access to any material or meeting or
portion thereof if the Corporation believes upon advice of counsel that such
exclusion is necessary to preserve the attorney-client privilege or to protect
highly confidential information, the disclosure of which should not be made to
any person who does not have a fiduciary or other similar duty to the
Corporation. The decision of the Board with respect to the privileged or
confidential nature of such information shall be final and binding. HCV VII’s
rights under this Section 4.2(a) may only be assigned in connection with the
transfer of all of the Preferred Stock held by HCV VII to the assignee. In
addition and without limiting the foregoing, in the event that HCV VII appoints
any person to be the HCV Observer under this Section 4.2(a) who, in the good
faith determination of the Board, has conflicting interests with the
Corporation, then the Corporation shall have the right, at any time and from
time to time, to exclude the HCV Observer from access to any meeting, or any
portion thereof, and/or deny the HCV Observer access to any information and
documents, or any portions thereof.

 

(b)           Saints Capital IV, L.P. (“Saints”) shall have the right to appoint
an observer to the Board (the “Saints Observer”) as long as Saints, together
with other members of the Saints/Oxford Group, holds greater than seventy-five
percent (75%) of the Series A-1 Preferred Stock originally purchased by Saints
and the other member of the Saints/Oxford Group pursuant to the Purchase
Agreement. The Saints Observer shall have the right to attend all meetings of
the Board in a non-voting observer capacity, and the Corporation shall provide
to the Saints Observer all materials provided to the members of the Board and
notice of such meetings, all in the manner and at the time provided to the
members of the Board; provided, however, that the Corporation reserves the right
to exclude such representatives from access to any material or meeting or
portion thereof if the Corporation believes upon advice of counsel that such
exclusion is necessary to preserve the attorney-client privilege or to protect
highly confidential information, the disclosure of which should not be made to
any person who does not have a fiduciary or other similar duty to the
Corporation. The decision of the Board with respect to the privileged or
confidential nature of such information shall be final and binding. Saints’
rights under this Section 4.2(b) may only be assigned in connection with the
transfer of all of the Preferred Stock held by Saints to the assignee. In
addition and without limiting the foregoing, in the event that Saints appoints
any person to be the Saints Observer under this Section 4.2(b) who, in the good
faith determination of the Board, has conflicting interests with the
Corporation, then the Corporation shall have the right, at any time and from
time to time, to exclude the Saints Observer from access to any meeting, or any
portion thereof, and/or deny the Saints Observer access to any information and
documents, or any portions thereof.

 

(c)           Brookside shall have the right to appoint an observer to the Board
(the “Brookside Observer”) as long as Brookside, together with other members of
the Brookside Group, holds greater than seventy-five percent (75%) of the
Series A-1 Preferred Stock originally purchased by Brookside and the other
member of the Brookside Group pursuant to the Purchase Agreement. The Brookside
Observer shall have the right to attend all meetings of the Board in a
non-voting observer

 

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capacity, and the Corporation shall provide to the Brookside Observer all
materials provided to the members of the Board and notice of such meetings, all
in the manner and at the time provided to the members of the Board; provided,
however, that the Corporation reserves the right to exclude such representatives
from access to any material or meeting or portion thereof if the Corporation
believes upon advice of counsel that such exclusion is necessary to preserve the
attorney-client privilege or to protect highly confidential information, the
disclosure of which should not be made to any person who does not have a
fiduciary or other similar duty to the Corporation. The decision of the Board
with respect to the privileged or confidential nature of such information shall
be final and binding. Brookside’s rights under this Section 4.2(c) may only be
assigned in connection with the transfer of all of the Preferred Stock held by
Brookside to the assignee. In addition and without limiting the foregoing, in
the event that Brookside appoints any person to be the Brookside Observer under
this Section 4.2(c) who, in the good faith determination of the Board, has
conflicting interests with the Corporation, then the Corporation shall have the
right, at any time and from time to time, to exclude the Brookside Observer from
access to any meeting, or any portion thereof, and/or deny the Brookside
Observer access to any information and documents, or any portions thereof.

 

(d)           Wellcome shall have the right to appoint an observer to the Board
(the “Wellcome Observer”) as long as Wellcome holds greater than seventy five
percent (75%) of the Series A-1 Preferred Stock originally purchased by Wellcome
pursuant to the Purchase Agreement. The Wellcome Observer shall have the right
to attend all meetings of the Board in a non-voting observer capacity, and the
Corporation shall provide to the Wellcome Observer all materials provided to the
members of the Board and notice of such meetings, all in the manner and at the
time provided to the members of the Board; provided, however, that the
Corporation reserves the right to exclude such representatives from access to
any material or meeting or portion thereof if the Corporation believes upon
advice of counsel that such exclusion is necessary to preserve the
attorney-client privilege or to protect highly confidential information, the
disclosure of which should not be made to any person who does not have a
fiduciary or other similar duty to the Corporation. The decision of the Board
with respect to the privileged or confidential nature of such information shall
be final and binding. Wellcome’s rights under this Section 4.2(a) may only be
assigned in connection with the transfer of all of the Preferred Stock held by
Wellcome to the assignee. In addition and without limiting the foregoing, in the
event that Wellcome appoints any person to be the Wellcome Observer under this
Section 4.2(a) who, in the good faith determination of the Board, has
conflicting interests with the Corporation, then the Corporation shall have the
right, at any time and from time to time, to exclude the Wellcome Observer from
access to any meeting, or any portion thereof, and/or deny the Wellcome Observer
access to any information and documents, or any portions thereof.

 

4.3          Cooperation of the Corporation.  The Corporation shall use its best
efforts to effectuate the purposes of this Section 4, including (i) taking such
actions as are necessary to convene annual and/or special meetings of the
Stockholders for the election of directors and (ii) promoting the adoption of
any necessary amendment of the by-laws of the Corporation and the Certificate.

 

4.4          Notices. The Corporation shall provide the Series A-1 Stockholders,
MPM and the Specified Preferred Holders with at least twenty (20) days’ prior
notice in writing of any intended mailing of notice to the Stockholders of a
meeting at which directors are to be elected, and such notice shall include the
names of the persons designated by the Corporation pursuant to this Section 4. 
The Series A-1 Stockholders, MPM and the Specified Preferred Holders shall
notify the Corporation in writing at least three (3) days prior to such mailing
of the persons designated by them respectively pursuant to Section 4.1 above as
nominees for election to the Board.  In the absence of any notice from the
Series A-1 Stockholders, MPM and the Specified Preferred Holders, the
director(s) then serving and previously designated by the Series A-1
Stockholders, MPM and the Specified Preferred Holders, as applicable, shall be
renominated.

 

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4.5                               Removal.  Except as otherwise provided in this
Section 5, no Stockholder shall vote to remove any member of the Board
designated in accordance with the foregoing provisions of this Section 4 unless
the party or group of stockholders, as applicable, who designated such director
(the “Designating Party”) shall so vote or otherwise consent, and, if the
Designating Party shall so vote or otherwise consent, then the non-designating
Stockholders shall likewise so vote. Any vacancy on the Board created by the
resignation, removal, incapacity or death of any person designated under the
foregoing provisions of this Section 4 may be filled by another person
designated by the original Designating Party. Each Stockholder shall vote all
shares of voting stock of the Corporation owned or controlled by such
Stockholder in accordance with each such new designation.

 

4.6                               Quorum.  A quorum for any meeting of the Board
of Directors shall consist of a majority of all directors; provided, that at
least a majority of the Investor Directors is in attendance at such meeting. If,
at any meeting, a quorum is not present for any reason, then another Board of
Directors meeting may be convened within no less than two (2) and no more than
ten (10) business days and, at such meeting, a majority of all directors shall
constitute a quorum for all purposes.

 

4.7                               Committees.  Each of the Investor Directors
shall have the right to sit on any committee of the Board of Directors.

 

4.8                               Duration of Section.  This Section 4 and the
rights and obligations of the parties hereunder shall automatically terminate on
the earlier of (i) the consummation of an Event of Sale (as defined in the
Certificate) or (ii) the automatic conversion of all of the Preferred Stock of
the Corporation pursuant to the Certificate as a result of the listing, or the
admitting for trading, of the Common Stock on a national securities exchange.
Prior to such termination, the rights and obligations of any Preferred
Stockholder under this Section 4 shall terminate upon the date on which such
Preferred Stockholder or its Group no longer owns any Preferred Stock, whereupon
the obligations of the remaining Stockholders to vote in favor of the designee
of such Preferred Stockholder shall also terminate.

 

SECTION 5.  Indemnification.

 

5.1                               Indemnification of Investors.  In the event
that any Series A-1 Preferred Stockholder, Series A-2 Preferred Stockholder,
Series A-3 Preferred Stockholder, Series A-5 Preferred Stockholder, Series A-6
Preferred Stockholder or any director, officer, employee, affiliate or agent
thereof (the “Indemnitees”), become involved in any capacity in any action,
proceeding, investigation or inquiry in connection with or arising out of any
matter related to the Corporation or any Indemnitee’s role or position with the
Corporation, the Corporation shall reimburse each Indemnitee for its legal and
other expenses (including the cost of any investigation and preparation) as they
are incurred by such Indemnitee in connection therewith. The Corporation also
agrees to indemnify each Indemnitee, pay on demand and protect, defend, save and
hold harmless from and against any and all liabilities, damages, losses,
settlements, claims, actions, suits, penalties, fines, costs or expenses
(including, without limitation, attorneys’ fees) (any of the foregoing, a
“Claim”) incurred by or asserted against any Indemnitee of whatever kind or
nature, arising from, in connection with or occurring as a result of this
Agreement or the matters contemplated by this Agreement; provided, however, that
the Corporation shall not be required to indemnify any Indemnitee hereunder in
connection with any matter as to which a court of competent jurisdiction has
made a final non-appealable determination that such Indemnitee has acted with
gross negligence or willful or intentional misconduct in connection therewith.
The foregoing agreement shall be in addition to any rights that any Indemnitee
may have at common law or otherwise.

 

5.2                               Advancement of Expenses.  The Corporation
shall advance all expenses reasonably incurred by or on behalf of the
Indemnitees in connection with any Claim or potential Claim

 

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within twenty (20) days after the receipt by the Corporation of a statement or
statements from the Indemnitee requesting such advance payment or payments from
time to time.

 

SECTION 6.  Remedies.  In case any one or more of the covenants and/or
agreements set forth in this Agreement shall have been breached by any party
hereto, the party or parties entitled to the benefit of such covenants or
agreements may proceed to protect and enforce its or their rights, either by
suit in equity and/or action at law, including, but not limited to, an action
for damages as a result of any such breach and/or an action for specific
performance of any such covenant or agreement contained in this Agreement.  The
rights, powers and remedies of the parties under this Agreement are cumulative
and not exclusive of any other right, power or remedy which such parties may
have under any other agreement or law. No single or partial assertion or
exercise of any right, power or remedy of a party hereunder shall preclude any
other or further assertion or exercise thereof.

 

SECTION 7.  Successors and Assigns.

 

7.1                               Series A-1, A-2 and A-3 Stockholders.  Except
as otherwise expressly provided herein, this Agreement shall bind and inure to
the benefit of the Corporation and each of the Series A-1 Stockholder,
Series A-2 Stockholder and Series A-3 Stockholder parties hereto and the
respective successors and permitted assigns of the Corporation and each of the
Series A-1 Stockholder, Series A-2 Stockholder and Series A-3 Stockholder
parties hereto (including any member of a Stockholder’s Group). Subject to the
requirements of Section 3 hereof, this Agreement and the rights and duties of
the Series A-1 Stockholder, Series A-2 Stockholder and Series A-3 Stockholder
set forth herein may be freely assigned, in whole or in part, by each Series A-1
Stockholder, Series A-2 Stockholder and Series A-3 Stockholder to any member of
their respective Group, provided such transferee is an “affiliate” of such
Series A-1 Stockholder, Series A-2 Stockholder or Series A-3 Stockholder, as the
case may be, as such term is defined under Rule 501 of the Securities Act (it
being recognized and agreed that each member of the Oxford/Saints Group shall be
deemed to be “affiliates” of each other for this purpose). Any transferee from a
Series A-1 Stockholder, Series A-2 Stockholder or Series A-3 Stockholder, as the
case may be, to whom rights under Section 3 are transferred shall, as a
condition to such transfer, deliver to the Corporation a written instrument by
which such transferee identifies itself, gives the Corporation notice of the
transfer of such rights, identities the securities of the Corporation owned or
acquired by it and agrees to be bound by the obligations imposed hereunder to
the same extent as if such transferee were a Series A-1 Stockholder, Series A-2
Stockholder or Series A-3 Stockholder, as applicable, hereunder. A transferee to
whom rights are transferred pursuant to this Section 7.1 will be thereafter
deemed to be a Series A-1 Stockholder, Series A-2 Stockholder or Series A-3
Stockholder, as applicable, for the purpose of the execution of such transferred
rights and may not again transfer such rights to any other person or entity,
other than as provided in this Section 7.1.  Upon the consummation of the
Merger: (i) all of the rights and obligations of this Agreement pertaining to
the Series A-1 Stockholders and the shares of Series A-1 Preferred Stock of the
Corporation held by them shall be deemed to apply in the same manner to the
holders of Series A-1 Preferred Stock, par value $0.0001 per share of MPM
Acquisition Corp., a Delaware corporation (“MPMAC”), and the shares of such
MPMAC Series A-1 Preferred Stock held by them, respectively, as if such shares
of MPMAC stock were shares of Series A-1 Preferred Stock for all purposes of
this Agreement; (ii) all of the rights and obligations of this Agreement
pertaining to the Series A-2 Stockholders and the shares of Series A-2 Preferred
Stock of the Corporation held by them shall be deemed to apply in the same
manner to the holders of Series A-2 Preferred Stock, par value $0.0001 per share
of MPMAC, and the shares of such MPMAC Series A-2 Preferred Stock held by them,
respectively, as if such shares of MPMAC stock were shares of Series A-2
Preferred Stock for all purposes of this Agreement; and (iii) all of the rights
and obligations of this Agreement pertaining to the Series A-3 Stockholders and
the shares of Series A-3 Preferred Stock of the Corporation held by them shall
be deemed to apply in the same manner to the holders of Series A-3 Preferred
Stock, par value $0.0001 per share of MPMAC, and the shares of such MPMAC
Series A-3

 

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Preferred Stock held by them, respectively, as if such shares of MPMAC stock
were shares of Series A-3 Preferred Stock for all purposes of this Agreement.

 

7.2                               Other Stockholders.  Except as otherwise
expressly provided herein, this Agreement shall bind and inure to the benefit of
the Corporation and each of the Common Stockholders and the Series A-4
Stockholders, Series A-5 Stockholders and Series A-6 Stockholders (collectively,
the “Other Stockholders”) and the respective successors and permitted assigns of
the Corporation and each of the Other Stockholders. Subject to the requirements
of Section 3 hereof, this Agreement and the rights and duties of the Other
Stockholders set forth herein may be assigned, in whole or in part, by any Other
Stockholder to a Related Transferee or to any member of their respective Group,
provided such transferee is an “affiliate” of such Other Stockholder, as such
term is defined under Rule 501 of the Securities Act (it being recognized and
agreed that each Member of the Oxford/Saints Group shall be deemed to be
“affiliates” of each other for this purpose). Any transferee from an Other
Stockholder to whom rights under Section 3 are transferred shall, as a condition
to such transfer, deliver to the Corporation a written instrument by which such
transferee identifies itself, gives the Corporation notice of the transfer of
such rights, identifies the securities of the Corporation owned or acquired by
it and agrees to be bound by the obligations imposed hereunder to the same
extent as if such transferee were an Other Stockholder hereunder. A transferee
to whom rights are transferred pursuant to this Section 7.2 will be thereafter
deemed to be an Other Stockholder for the purpose of the execution of such
transferred rights and may not again transfer such rights to any other person or
entity, other than as provided in this Section 7.2.  Upon the consummation of
the Merger: (i) all of the rights and obligations of this Agreement pertaining
to the holders of Common Stock and the shares of Common Stock of the Corporation
held by them shall be deemed to apply in the same manner to the holders of
Common Stock, par value $0.0001 per share of MPMAC, and the shares of such MPMAC
Common Stock held by them, respectively, as if such shares of MPMAC stock were
shares of Common Stock for all purposes of this Agreement; (ii) all of the
rights and obligations of this Agreement pertaining to the Series A-4
Stockholders and the shares of Series A-4 Preferred Stock of the Corporation
held by them shall be deemed to apply in the same manner to the holders of
Series A-4 Preferred Stock, par value $0.0001 per share of MPMAC, and the shares
of such MPMAC Series A-4 Preferred Stock held by them, respectively, as if such
shares of MPMAC stock were shares of Series A-4 Preferred Stock for all purposes
of this Agreement; (iii) all of the rights and obligations of this Agreement
pertaining to the Series A-5 Stockholders and the shares of Series A-5 Preferred
Stock of the Corporation held by them shall be deemed to apply in the same
manner to the holders of Series A-5 Preferred Stock, par value $0.0001 per share
of MPMAC, and the shares of such MPMAC Series A-5 Preferred Stock held by them,
respectively, as if such shares of MPMAC stock were shares of Series A-5
Preferred Stock for all purposes of this Agreement; and (iv) all of the rights
and obligations of this Agreement pertaining to the Series A-2 Stockholders and
the shares of Series A-6 Preferred Stock of the Corporation held by them shall
be deemed to apply in the same manner to the holders of Series A-6 Preferred
Stock, par value $0.0001 per share of MPMAC, and the shares of such MPMAC
Series A-6 Preferred Stock held by them, respectively, as if such shares of
MPMAC stock were shares of Series A-6 Preferred Stock for all purposes of this
Agreement.

 

7.3                               The Corporation.  Neither this Agreement nor
any of the rights or duties of the Corporation set forth herein shall be
assigned by the Corporation, in whole or in part, without having first received
the written consent of the Majority Investors.  Notwithstanding the foregoing,
upon the consummation of the Merger with respect to all times after the
consummation of the Merger, (i) the Corporation shall, and hereby does, assign
all of its rights, duties and obligations under this Agreement to MPMAC and
(ii) all references to the “Corporation” in this Agreement and to its capital
stock or any other aspects of the Corporation shall be deemed to be references
to MPMAC and its capital stock and other applicable aspects of MPMAC.  MPMAC, by
executing this Agreement as an anticipated successor and assign to the
Corporation, does hereby assume, effective upon the consummation of the

 

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Merger, all of the Corporation’s rights, duties and obligations under this
Agreement.  All parties to this Agreement hereby consent to the assignment and
assumption contemplated between the Corporation and MPMAC set forth in this
paragraph.

 

SECTION 8.  Duration of Agreement.  The rights and obligations of the
Corporation and each Stockholder set forth herein shall survive indefinitely,
unless and until, by the respective terms of this Agreement, they are no longer
applicable.

 

SECTION 9.  Entire Agreement.  This Agreement, together with the other writings
referred to herein or delivered pursuant hereto which form a part hereof,
contains the entire agreement among the parties with respect to the subject
matter hereof and amends, restates and supersedes all prior and contemporaneous
arrangements or understandings with respect thereto.

 

SECTION 10.  Notices.  All notices, requests, consents and other communications
hereunder to any party shall be deemed to be sufficient if contained in a
written instrument delivered in person or duly sent by first class registered,
certified or overnight mail, postage prepaid, or telecopied with a confirmation
copy by regular mail, addressed or telecopied, as the case may be, to such party
at the address or telecopier number, as the case may be, set forth below or such
other address or telecopier number, as the case may be, as may hereafter be
designated in writing by the addressee to the addressor listing all parties:

 

(i)                                     if to the Corporation, to:

 

Radius Health, Inc.

201 Broadway

Sixth Floor

Cambridge, MA 02139

Attention: Chief Executive Officer

 

Telecopier: (617) 551-4701

 

with a copy to:

 

Bingham McCutchen LLP

One Federal Street

Boston, MA 02110-1726

Attention: Julio E. Vega, Esq.

Telecopier: (617) 951-8736

 

(ii)                                  if to the Investors, as set forth on
Schedule 2; to the Common Stockholders, as set forth on Schedule 1; to the
holders of Series A-2 Preferred Stock, as set forth on Schedule 3; to the
holders of Series A-3 Preferred Stock, as set forth on Schedule 4; to the
holders of Series A-4 Preferred Stock, as set forth on Schedule 5; to the holder
of Series A-5 Preferred Stock and/or Series A-6 Preferred Stock, as set forth on
Schedule 6,

 

All such notices, requests, consents and communications shall be deemed to have
been received (a) in the case of personal delivery, on the date of such
delivery, (b) in the case of mailing, on the third business day following the
date of such mailing, (c) in the case of overnight mail, on the first business
day following the date of such mailing, and (d) in the case of facsimile
transmission, when confirmed by facsimile machine report.

 

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SECTION 11.  Changes.  The terms and provisions of this Agreement may not be
modified or amended, or any of the provisions hereof waived, temporarily or
permanently, except pursuant to the written consent of the Corporation and the
Majority Investors, and to the extent that there is a material adverse effect of
any such modification or amendment on the rights and obligations of the holders
of shares of Series A-4 Preferred Stock, Series A-5 Preferred Stock or
Series A-6 Preferred Stock in a manner more adverse than such effect on the
holders of Series A-1 Preferred Stock, Series A-2 Preferred Stock or Series A-3
Preferred Stock, respectively, a majority in combined voting power of the such
more affected series then outstanding, determined in accordance with
Section A.6(a) of Article III of the Certificate. Additional parties who become
Common Stockholders or Series A-4 Stockholders, Series A-5 Stockholders or
Series A-6 Stockholders pursuant to an instrument of adherence will not
constitute a change under this Section 11. Notwithstanding the foregoing,
(a) any modification or amendment to this Agreement that would adversely affect
one Series A-1 Stockholder, Series A-2 Stockholder or Series A-3 Stockholder in
a manner that is directed specifically to such Series A-1 Stockholder,
Series A-2 Stockholder or Series A-3 Stockholder, rather than to all Series A-1
Stockholders, Series A-2 Stockholders and Series A-3 Stockholders, shall be
subject to the approval of each such Series A-1 Stockholder, Series A-2
Stockholder or Series A-3 Stockholder, as applicable, (b) any modification or
amendment to Section 2.11 hereof shall be subject to the further approval of
Wellcome, at least one member of HCV Group, one member of the MPM Group, one
member of the Brookside Group, one member of the BB Bio Group, and the
Oxford/Saints Group, (c) any modification to Section 4.1(b)(i) shall be subject
to the further approval of Stockholders holding at least a majority of the
outstanding shares of Series A-1 Preferred Stock, (d) any modification to
Section 4.1(b)(ii) shall be subject to the further approval of at least two of
the Specified Preferred Holders, (e) any modification to
Section 4.1(b)(iii) shall be subject to the further approval of at least one
member of the MPM Group, (f) any modification to Section 4.2(a) shall be subject
to the further approval of at least one member of the HCV Group, (g) any
modification to Section 4.2(b) shall be subject to the further approval of
Saints, (h) any modification to Section 4.2(c) shall be subject to the further
approval of at least one member of the Brookside Group and (i) any modification
to Section 4.2(d) shall be subject to the further approval of Wellcome. It is
understood that this separate consent would not be required if any such adverse
effect results from the application of criteria uniformly to all Stockholders
even if such application may affect Stockholders differently.

 

SECTION 12.  Counterparts.  This Agreement may he executed in any number of
counterparts, each such counterpart shall be deemed to he an original instrument
and all such counterparts together shall constitute but one agreement.

 

SECTION 13.  Headings.  The headings of the various sections of this Agreement
have been inserted for convenience of reference only, and shall not be deemed to
be a part of this Agreement.

 

SECTION 14.  Nouns and Pronouns.  Whenever the context may require, any pronouns
used herein shall include the corresponding masculine, feminine or neuter forms,
and the singular form of names and pronouns shall include the plural and
vice-versa.

 

SECTION 15.  Severability.  Any provision of this Agreement that is prohibited
or unenforceable in any jurisdiction shall, as to such jurisdiction, be
ineffective to the extent of such prohibition or unenforceability without
invalidating the remaining provisions hereof, and any such prohibition or
unenforceability in any jurisdiction shall not invalidate or render
unenforceable such provision in any other jurisdiction.

 

SECTION 16.  Governing Law.  This Agreement shall be governed by and construed
in accordance with the laws of the Commonwealth of Massachusetts, excluding
choice of law rules thereof.

 

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SECTION 17.                     Additional Parties.  Notwithstanding anything to
the contrary contained herein, any Stockholder may become a party to this
Agreement following the delivery to, and written acceptance by, the Corporation
of an execute and Instrument of Adherence to this Agreement in the Form attached
hereto as Annex C.  No action or consent by Stockholder parties hereto shall be
required for such joinder to this Agreement by such additional Stockholder, so
long as such additional Stockholder has agreed in writing to be bound by all of
the obligations as Stockholder party hereunder as indicated in the Instrument of
Adherence and the Instrument of Adherence has been accepted in writing by the
Corporation.

 

[remainder of page intentionally left blank]

 

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(Signature Page to Stockholders’ Agreement)

 

IN WITNESS WHEREOF the parties hereto have executed this Agreement on the date
first above written.

 

 

THE CORPORATION:

 

 

 

RADIUS HEALTH, INC.

 

 

 

By:

 

 

 

Name: C. Richard Edmund Lyttle

 

 

Title: President

 

 

 

 

 

 

 

As an anticipated successor and assign to the Corporation under Section 7.3
hereof:

 

 

 

 

MPM ACQUISITION CORP.

 

 

 

 

 

By:

 

 

 

Name: C. Richard Edmund Lyttle

 

 

Title: President

 

 

 

 

 

 

 

INVESTORS:

 

 

 

BB BIOTECH VENTURES II, L.P.

 

By:

 

 

 

Its:

 

 

 

 

 

 

 

By:

 

 

 

Name:

Ben Morgan

 

 

Title:

Director

 

 

 

 

 

 

 

BB BIOTECH GROWTH N.V.

 

By:

 

 

 

Its:

 

 

 

 

 

 

 

By:

 

 

 

Name:

H. J. Van Neutegem

 

 

Title:

Managing Director

 

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HEALTHCARE VENTURES VII, LP,

 

By:

HealthCare Partners VII, L.P.

 

 

Its General Partner

 

 

 

 

 

 

 

By:

 

 

 

Name: Jeffrey Steinberg

 

 

Title: Administrative Partner of HealthCare Partners VII, L.P.

 

 

The General Partner of HealthCare Ventures VII, L.P.

 

 

 

 

 

 

 

MPM BIOVENTURES III, L.P.

 

 

 

By:

MPM BioVentures III GP, L.P.,

 

 

its General Partner

 

By:

MPM BioVentures III LLC,

 

 

its General Partner

 

 

 

 

By:

 

 

 

Name: Ansbert Gadicke

 

 

Title: Series A Member

 

 

 

 

 

 

 

MPM BIOVENTURES III-QP, L.P.

 

 

 

By:

MPM BioVentures III GP, L.P.,

 

 

its General Partner

 

By:

MPM BioVentures III LLC,

 

 

its General Partner

 

 

 

 

By:

 

 

 

Name: Ansbert Gadicke

 

 

Title: Series A Member

 

 

 

 

 

 

 

MPM BIOVENTURES III GMBH & CO. BETEILIGUNGS KG

 

 

 

By:

MPM BioVentures III GP, L.P.,

 

 

in its capacity as the Managing Limited Partner

 

By:

MPM BioVentures III LLC,

 

 

its General Partner

 

 

 

 

By:

 

 

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Name: Ansbert Gadicke

 

 

Title: Series A Member

 

 

 

 

 

 

 

MPM BIOVENTURES III PARALLEL FUND, L.P.

 

 

 

 

By:

MPM BioVentures III GP, L.P.,

 

 

its General Partner

 

By:

MPM BioVentures III LLC,

 

 

its General Partner

 

 

 

 

By:

 

 

 

Name: Ansbert Gadicke

 

 

Title: Series A Member

 

 

 

 

 

 

 

MPM ASSET MANAGEMENT INVESTORS 2003 BVIII LLC

 

 

 

By:

 

 

 

Name: Ansbert Gadicke

 

 

Title: Manager

 

 

 

 

 

 

 

MPM BIO IV NVS STRATEGIC FUND, L.P.

 

 

 

 

By:

MPM BioVentures IV GP LLC,

 

 

its General Partner

 

By:

MPM BioVentures IV LLC,

 

 

its Managing Member

 

 

 

 

By:

 

 

 

Name: Ansbert Gadicke

 

 

Title:

 

 

 

 

 

 

 

HEALTHCARE PRIVATE EQUITY LIMITED PARTNERSHIP

 

By:

Waverley Healthcare Private Equity

 

 

Limited, its general partner

 

 

 

 

 

 

 

By:

 

 

 

Name: Andrew November

 

 

Title: Director

 

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THE WELLCOME TRUST LIMITED, AS TRUSTEE OF THE WELLCOME TRUST

 

 

 

 

 

By:

 

 

 

Name: Peter Percisa Gray

 

 

Title: Managing Director

 

 

 

 

 

 

 

 

 

Dr. Raymond F. Schinazi

 

 

 

 

 

 

 

OXFORD BIOSCIENCE PARTNERS IV L.P.

 

By:

OBP Management IV L.P.

 

 

 

 

 

 

 

By:

 

 

 

Name: Jonathan Fleming

 

 

Title: General Partner

 

 

 

 

 

 

 

MRNA Fund II L.P.

 

By:

OBP Management IV L.P.

 

 

 

 

 

 

 

By:

 

 

 

Name: Jonathan Fleming

 

 

Title: General Partner

 

 

 

 

 

 

 

SAINTS CAPITAL VI, L.P.,

 

a limited partnership

 

 

 

By:

Saints Capital VI LLC,

 

a limited liability company

 

 

 

 

 

By:

 

 

 

Name: David P. Quinlivan

 

 

Title: Managing Member

 

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EXPLANATORY NOTE

 

The following Plan of Distribution was not attached as Annex A to this
Stockholders Agreement at the time this Stockholders Agreement was executed and
it is not part of the executed agreement.  The Plan of Distribution was
subsequently distributed to the stockholders of the Company separate from the
Stockholders Agreement and is being include here for informational purposes
only.

 

Annex A

 

PLAN OF DISTRIBUTION

 

We are registering the shares offered by this prospectus on behalf of the
selling stockholders. The selling stockholders, which as used herein includes
donees, pledgees, transferees or other successors-in-interest selling shares of
common stock or interests in shares of common stock received after the date of
this prospectus from a selling stockholder as a gift, pledge, partnership
distribution or other transfer, may, from time to time, sell, transfer or
otherwise dispose of any or all of their shares of common stock or interests in
shares of common stock on any stock exchange, market or trading facility on
which the shares are traded or in private transactions. These dispositions may
be at fixed prices, at prevailing market prices at the time of sale, at prices
related to the prevailing market price, at varying prices determined at the time
of sale, or at negotiated prices.

 

The selling stockholders may use any one or more of the following methods when
disposing of shares or interests therein:

 

·                                         ordinary brokerage transactions and
transactions in which the broker-dealer solicits purchasers;

 

·                                         block trades in which the
broker-dealer will attempt to sell the shares as agent, but may position and
resell a portion of the block as principal to facilitate the transaction;

 

·                                         purchases by a broker-dealer as
principal and resale by the broker-dealer for its account;

 

·                                         an exchange distribution in accordance
with the rules of the applicable exchange;

 

·                                         privately negotiated transactions;

 

·                                         short sales;

 

·                                         through the writing or settlement of
options or other hedging transactions, whether through an options exchange or
otherwise;

 

·                                         broker-dealers may agree with the
selling stockholders to sell a specified number of such shares at a stipulated
price per share;

 

·                                         a combination of any such methods of
sale; and

 

·                                         any other method permitted pursuant to
applicable law.

 

The selling stockholders may, from time to time, pledge or grant a security
interest in some or all of the shares of common stock owned by them and, if they
default in the performance of their secured obligations, the pledgees or secured
parties may offer and sell the shares of common stock, from time to time, under
this prospectus, or under an amendment to this prospectus under
Rule 424(b)(3) or other applicable provision of the Securities Act amending the
list of selling stockholders to include the pledgee, transferee or other
successors in interest as selling stockholders under this prospectus. The
selling stockholders also may transfer the shares of common stock in other
circumstances, in which case the transferees, pledgees or other successors in
interest will be the selling beneficial owners for purposes of this prospectus.

 

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In connection with the sale of our common stock or interests therein, the
selling stockholders may enter into hedging transactions with broker-dealers or
other financial institutions, which may in turn engage in short sales of the
common stock in the course of hedging the positions they assume. The selling
stockholders may also sell shares of our common stock short and deliver these
securities to close out their short positions, or loan or pledge the common
stock to broker-dealers that in turn may sell these securities. The selling
stockholders may also enter into option or other transactions with
broker-dealers or other financial institutions or the creation of one or more
derivative securities which require the delivery to such broker-dealer or other
financial institution of shares offered by this prospectus, which shares such
broker-dealer or other financial institution may resell pursuant to this
prospectus (as supplemented or amended to reflect such transaction).

 

The aggregate proceeds to the selling stockholders from the sale of the common
stock offered by them will be the purchase price of the common stock less
discounts or commissions, if any. Each of the selling stockholders reserves the
right to accept and, together with their agents from time to time, to reject, in
whole or in part, any proposed purchase of common stock to be made directly or
through agents. We will not receive any of the proceeds from this offering. Upon
any exercise of the warrants by payment of cash, however, we will receive the
exercise price of the warrants.

 

The selling stockholders also may resell all or a portion of the shares in open
market transactions in reliance upon Rule 144 under the Securities Act of 1933,
provided that they meet the criteria and conform to the requirements of that
rule.

 

The selling stockholders and any broker-dealers that act in connection with the
sale of the shares offered hereby might be deemed to be “underwriters” within
the meaning of Section 2(11) of the Securities Act, and any commissions received
by such broker-dealers and any profit on the resale of the securities sold by
them while acting as principals might be deemed to be underwriting discounts or
commissions under the Securities Act.

 

To the extent required, the shares of our common stock to be sold, the names of
the selling stockholders, the respective purchase prices and public offering
prices, the names of any agents, dealer or underwriter, any applicable
commissions or discounts with respect to a particular offer will be set forth in
an accompanying prospectus supplement or, if appropriate, a post-effective
amendment to the registration statement that includes this prospectus.

 

In order to comply with the securities laws of some states, if applicable, the
common stock may be sold in these jurisdictions only through registered or
licensed brokers or dealers. In addition, in some states the common stock may
not be sold unless it has been registered or qualified for sale or an exemption
from registration or qualification requirements is available and is complied
with.

 

The anti-manipulation rules of Regulation M under the Exchange Act may apply to
sales of shares in the market and to the activities of the selling stockholders
and their affiliates. In addition, we will make copies of this prospectus (as it
may be supplemented or amended from time to time) available to the selling
stockholders for the purpose of satisfying the prospectus delivery requirements
of the Securities Act. The selling stockholders may indemnify any broker-dealer
that participates in transactions involving the sale of the shares against
certain liabilities, including liabilities arising under the Securities Act.

 

We have agreed to indemnify the selling stockholders against liabilities,
including liabilities under the Securities Act and state securities laws,
relating to the registration of the shares offered by this prospectus.

 

We have agreed with the selling stockholders to keep the registration statement
of which this prospectus constitutes a part effective until the earlier of
(1) such time as all of the shares covered by this prospectus have been disposed
of pursuant to and in accordance with the registration statement or (2) the date
on which the shares may be sold pursuant to Rule 144 of the Securities Act.

 

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EXPLANATORY NOTE

 

The following Questionnaire for Selling Stockholders was not attached as Annex B
to this Stockholders Agreement at the time this Stockholders Agreement was
executed and it is not part of the executed agreement.  The Questionnaire for
Selling Stockholders was subsequently distributed to the stockholders of the
Company separate from the Stockholders Agreement and is being include here for
informational purposes only.

 

 

Annex B

 

Radius Health, Inc.

 

Questionnaire for Selling Stockholders

 

All questions should be answered as of the date you sign this Questionnaire,
unless otherwise specified.  Please return the completed Questionnaire by fax or
other electronic transmission (with the originally signed copy to follow by
mail) to:

 

 

Kathryn Ostman, Esq.

Bingham McCutchen LLP

One Federal Street

Boston, MA 02110

617-951-8637

With a copy to:

Nicholas Harvey

Chief Financial Officer

Radius Health, Inc.

201 Broadway, Sixth Floor

Cambridge, MA 02139

 

 

Please state the Selling Stockholder’s

name and mailing address:

 

 

 

Please answer the following questions:

 

(a)                                Within the past three years, have you held
any position or office or (other than as a securityholder) had any relationship
with the Company or affiliates(1)?

 

Yes o          No o

 

If yes, please describe.

 

--------------------------------------------------------------------------------

(1)  Please refer to the definition of affiliate in Appendix A hereto.

 

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(b)                                 Set forth below the number of shares of
Common Stock of the Company owned beneficially(2) by you after the Merger (the
“Shares”).  For each holding, please state under the column entitled “Statements
Concerning Beneficial Ownership” (a) the name in which the securities are held,
(b) if issuable upon conversion of preferred stock held, indicate the type and
number of preferred shares held, (c) if issuable upon exercise of common or
preferred share purchase warrants, indicate the type of warrant and exercise
price, (d) the number of securities with respect to which you have sole voting
power,(3) (e) the number of securities with respect to which you have shared
voting power,(4) (f) the amount and/or number of securities with respect to
which you have sole investment power,(5) (g) the amount and/or number of
securities with respect to which you have shared investment power,(6) and
(h) the amount and/or number of securities with respect to which you have the
right to acquire beneficial(7) ownership by AUGUST 22, 2011.

 

Shares Beneficially Owned

 

Number of Shares

 

Statements Concerning
Beneficial Ownership

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

(c)           Number of Shares to be Offered Pursuant to the Registration
Statement:

 

ALL                 If less than ALL, number of Shares to be Offered:

 

(d)                                Attached as Appendix B hereto is a draft of
the “Plan of Distribution” section of the Registration Statement.  Do you
propose to offer or sell any securities of the Company by means other than those
described in Appendix B?

 

Yes o              No o

 

If yes, please describe.

 

--------------------------------------------------------------------------------

(2)  Please refer to the definition of affiliate in Appendix A hereto.

(3)  Please refer to the discussion on voting power in the definition of
beneficial ownership in Appendix A.

(4)  Please refer to the discussion on voting power in the definition of
beneficial ownership in Appendix A.

(5)  Please refer to the discussion on investment power in the definition of
beneficial ownership in Appendix A.

(6)  Please refer to the discussion on investment power in the definition of
beneficial ownership in Appendix A.

(7)  Please refer to the definition of affiliate in Appendix A hereto.

 

132

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(e)                                 Do you currently have specific plans to
offer any securities of the Company through the selling efforts of brokers or
dealers?

 

Yes o              No o

 

If yes, briefly describe the terms of any agreement, arrangement or
understanding, entered into or proposed to be entered into with any broker or
dealer, including any discounts or commissions to be paid to dealers.

 

(f)                                  Are any of the securities of the Company to
be offered otherwise than for cash?

 

Yes o              No o

 

If yes, please describe.

 

(g)                                 Are any finders to be involved in the
offering or sale of any of the securities of the Company?

 

Yes o              No o

 

If yes, please describe.

 

The undersigned hereby represents that all the information supplied herein is
true, correct and complete as of the date hereof. The undersigned understands
that the foregoing information will be use in connection with a proposed filing
of a Registration Statement, and that the answers to the questions submitted
will be relied on by the Company and its officers and directors in preparing the
Registration Statement. The undersigned agrees to notify Radius Health, Inc.
immediately of any material change in the forgoing answers.  In connection with
his, her or its purchase of securities, the

 

 

Dated:

 

 

(Name of Holder)

 

 

 

 

 

By:

 

 

Name:

 

 

Title:

 

 

133

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APPENDIX A

 

DEFINITIONS

 

(1)           Affiliate of a specified person (as defined below), means a person
who directly or indirectly through one or more intermediaries, controls (as
defined below), or is controlled by, or is under common control with, the person
specified.

 

(2)           Beneficial, or beneficially, as applied to the ownership of
securities, has been defined by the Securities and Exchange Commission to mean
the following:

 

A beneficial owner of a security includes any person (as defined below) who,
directly or indirectly, through any contract, arrangement, understanding,
relationship, or otherwise has or shares “voting power” and/or “investment
power”.  Voting power includes the power to vote, or to direct the voting of,
such security; investment power includes the power to dispose, or to direct the
disposition, of such security.

 

Note that more than one person may have a beneficial interest in the same
securities; one may have voting power and the other may have investment power.

 

Even if a person, directly or indirectly, creates or uses a trust, proxy, power
of attorney, pooling arrangement or any other contract, arrangement or device
with the purpose or effect of divesting such person of beneficial ownership of a
security or preventing the vesting of such beneficial ownership to avoid the
reporting requirements of section 13(d) of the Securities Exchange Act, he will
still be deemed to be the beneficial owner of such security.

 

A person is deemed to be the beneficial owner of a security if that person has
the right to acquire beneficial ownership of such security at any time within 60
days, including but not limited to any right to acquire:  (i) through the
exercise of any option, warrant or right; (ii) through the conversion of a
security; (iii) pursuant to the power to revoke a trust, discretionary account,
or similar arrangement; or (iv) pursuant to the automatic termination of a
trust, discretionary account or similar arrangement.

 

A member of a national securities exchange is not deemed to be a beneficial
owner of securities held directly or indirectly by it on behalf of another
person solely because such member is the record holder of such securities and,
pursuant to the rules of such exchange, may direct the vote of such securities,
without instruction, on other than contested matters or matters that may affect
substantially the rights or privileges of the holders of the securities to be
voted, but is otherwise precluded by the rules of such exchange from voting
without instruction.

 

A person who in the ordinary course of business is a pledgee of securities
pursuant to a bona fide pledge agreement will not be deemed to be the beneficial
owner of such pledged securities merely because there has been a default under
such an agreement, except during such time as the event of default shall remain
uncured for more than 30 days or at any time before a default is cured if the
power acquired by the pledgee pursuant to the default enables him to change or
influence control of the issuer.

 

A person may also be regarded as the beneficial owner of securities held in the
name of his spouse, his minor children or other relatives of his or her spouse
sharing his home, or held in a trust of which he is a beneficiary or trustee, if
the relationships are such that he has voting power and/or investment power with
respect to such securities.

 

134

--------------------------------------------------------------------------------

 

If you have any reason to believe that any interest you have, however remote,
might be described as a beneficial interest, describe such interest.

 

(3)           Control means the possession, directly or indirectly, of the power
to direct or cause the direction of the management and policies of a person,
whether through the ownership of voting securities, by contract, or otherwise.

 

(4)           Person includes two or more persons acting as a partnership,
limited partnership, syndicate or other group for the purpose of acquiring,
holding, or disposing of securities of an issuer.

 

135

--------------------------------------------------------------------------------

 

APPENDIX B

 

PLAN OF DISTRIBUTION

 

We are registering the shares offered by this prospectus on behalf of the
selling stockholders. The selling stockholders, which as used herein includes
donees, pledgees, transferees or other successors-in-interest selling shares of
common stock or interests in shares of common stock received after the date of
this prospectus from a selling stockholder as a gift, pledge, partnership
distribution or other transfer, may, from time to time, sell, transfer or
otherwise dispose of any or all of their shares of common stock or interests in
shares of common stock on any stock exchange, market or trading facility on
which the shares are traded or in private transactions. These dispositions may
be at fixed prices, at prevailing market prices at the time of sale, at prices
related to the prevailing market price, at varying prices determined at the time
of sale, or at negotiated prices.

 

The selling stockholders may use any one or more of the following methods when
disposing of shares or interests therein:

 

·                                         ordinary brokerage transactions and
transactions in which the broker-dealer solicits purchasers;

 

·                                         block trades in which the
broker-dealer will attempt to sell the shares as agent, but may position and
resell a portion of the block as principal to facilitate the transaction;

 

·                                         purchases by a broker-dealer as
principal and resale by the broker-dealer for its account;

 

·                                         an exchange distribution in accordance
with the rules of the applicable exchange;

 

·                                         privately negotiated transactions;

 

·                                         short sales;

 

·                                         through the writing or settlement of
options or other hedging transactions, whether through an options exchange or
otherwise;

 

·                                         broker-dealers may agree with the
selling stockholders to sell a specified number of such shares at a stipulated
price per share;

 

·                                         a combination of any such methods of
sale; and

 

·                                         any other method permitted pursuant to
applicable law.

 

The selling stockholders may, from time to time, pledge or grant a security
interest in some or all of the shares of common stock owned by them and, if they
default in the performance of their secured obligations, the pledgees or secured
parties may offer and sell the shares of common stock, from time to time, under
this prospectus, or under an amendment to this prospectus under
Rule 424(b)(3) or other applicable provision of the Securities Act amending the
list of selling stockholders to include the pledgee, transferee or other
successors in interest as selling stockholders under this prospectus. The
selling stockholders also may transfer the shares of common stock in other
circumstances, in which case the transferees, pledgees or other successors in
interest will be the selling beneficial owners for purposes of this prospectus.

 

In connection with the sale of our common stock or interests therein, the
selling stockholders may enter into hedging transactions with broker-dealers or
other financial institutions, which may in turn engage in short sales of the
common stock in the course of hedging the positions they assume. The selling
stockholders may also sell shares of our common stock short and deliver these
securities to close out their short positions, or loan or pledge the common
stock to broker-dealers that in turn may sell these securities. The selling
stockholders may also enter into option or other transactions with
broker-dealers or other financial institutions or the creation of one or more

 

136

--------------------------------------------------------------------------------

 

derivative securities which require the delivery to such broker-dealer or other
financial institution of shares offered by this prospectus, which shares such
broker-dealer or other financial institution may resell pursuant to this
prospectus (as supplemented or amended to reflect such transaction).

 

The aggregate proceeds to the selling stockholders from the sale of the common
stock offered by them will be the purchase price of the common stock less
discounts or commissions, if any. Each of the selling stockholders reserves the
right to accept and, together with their agents from time to time, to reject, in
whole or in part, any proposed purchase of common stock to be made directly or
through agents. We will not receive any of the proceeds from this offering. Upon
any exercise of the warrants by payment of cash, however, we will receive the
exercise price of the warrants.

 

The selling stockholders also may resell all or a portion of the shares in open
market transactions in reliance upon Rule 144 under the Securities Act of 1933,
provided that they meet the criteria and conform to the requirements of that
rule.

 

The selling stockholders and any broker-dealers that act in connection with the
sale of the shares offered hereby might be deemed to be “underwriters” within
the meaning of Section 2(11) of the Securities Act, and any commissions received
by such broker-dealers and any profit on the resale of the securities sold by
them while acting as principals might be deemed to be underwriting discounts or
commissions under the Securities Act.

 

To the extent required, the shares of our common stock to be sold, the names of
the selling stockholders, the respective purchase prices and public offering
prices, the names of any agents, dealer or underwriter, any applicable
commissions or discounts with respect to a particular offer will be set forth in
an accompanying prospectus supplement or, if appropriate, a post-effective
amendment to the registration statement that includes this prospectus.

 

In order to comply with the securities laws of some states, if applicable, the
common stock may be sold in these jurisdictions only through registered or
licensed brokers or dealers. In addition, in some states the common stock may
not be sold unless it has been registered or qualified for sale or an exemption
from registration or qualification requirements is available and is complied
with.

 

The anti-manipulation rules of Regulation M under the Exchange Act may apply to
sales of shares in the market and to the activities of the selling stockholders
and their affiliates. In addition, we will make copies of this prospectus (as it
may be supplemented or amended from time to time) available to the selling
stockholders for the purpose of satisfying the prospectus delivery requirements
of the Securities Act. The selling stockholders may indemnify any broker-dealer
that participates in transactions involving the sale of the shares against
certain liabilities, including liabilities arising under the Securities Act.

 

We have agreed to indemnify the selling stockholders against liabilities,
including liabilities under the Securities Act and state securities laws,
relating to the registration of the shares offered by this prospectus.

 

We have agreed with the selling stockholders to keep the registration statement
of which this prospectus constitutes a part effective until the earlier of
(1) such time as all of the shares covered by this prospectus have been disposed
of pursuant to and in accordance with the registration statement or (2) the date
on which the shares may be sold pursuant to Rule 144 of the Securities Act.

 

137

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Annex C

 

Instrument of Adherence
to
Amended and Restated
Stockholders’ Agreement
dated             , 2011

 

Reference is hereby made to that certain THIS AMENDED AND RESTATED STOCKHOLDERS’
AGREEMENT (the “Agreement”), dated the          day of
                            , 2011, entered into by and among (i) Radius
Health, Inc., a Delaware corporation (the “Corporation”) and the Stockholder
parties thereto. Capitalized terms used herein without definition shall have the
respective meanings ascribed thereto in the Agreement.

 

The undersigned (the “New Stockholder Party”), in order to become the owner or
holder of                                    shares of
                                                                             and
all other shares of the Corporation’s capital stock hereinafter acquired, of the
Company (the “Acquired Shares”), hereby agrees that, from and after the date
hereof, the undersigned has become a party to the Agreement in the capacity of a
                                                                 party to the
Agreement, and is entitled to all of the benefits under, and is subject to all
of the obligations, restrictions and limitations set forth in, the Agreement
that are applicable to such Stockholder parties and shall be deemed to have made
all of the representations and warranties made by such Stockholder parties
thereunder.  This Instrument of Adherence shall take effect and shall become a
part of the Agreement on the latest date of execution by both the New
Stockholder Party and the Corporation.

 

Executed under seal as of the date set forth below under the laws of the
Commonwealth of Massachusetts.

 

 

Print Name:

 

 

 

 

 

 

 

 

Signature:

 

 

 

Name:

 

 

Title:

 

 

 

 

Accepted:

RADIUS HEALTH, INC.

 

 

By:

 

 

 

Name:

 

 

Title:

 

 

 

 

Date:

 

 

 

138

--------------------------------------------------------------------------------

 

Exhibit F

 

Executed Agreement and Plan of Merger

 

Filed as Exhibit 10.1 to the Form 8-K/A filed on October 24, 2011

 

139

--------------------------------------------------------------------------------

 

Disclosure Schedules

 

140

--------------------------------------------------------------------------------

 

RADIUS HEALTH, INC.

 

Disclosure Schedule (“Schedule”) to the Series A-1 Convertible Preferred Stock
Purchase Agreement, dated April 25, 2011 (the “Purchase Agreement”)

 

The following Schedule is delivered by Radius Health, Inc., a Delaware
corporation (the “Corporation”) in connection with the Stage I Closing under the
Purchase Agreement.  This Schedule sets forth exceptions to the representations
and warranties of the Corporation to be given at the Stage I Closing (which
exceptions shall be deemed to be representations and warranties as if made under
the Purchase Agreement).  The information in this Schedule is provided as of the
Stage I Closing Date.

 

The disclosure of any item or information in this Schedule shall not be
construed as an admission that such item or information is material to the
Corporation, and any inclusion in the Schedule shall expressly not be deemed to
constitute an admission, or otherwise imply, that any such item or information
is material or creates measures of materiality for the purposes of the Purchase
Agreement.  Nothing in this Schedule constitutes an admission of any liability
or obligation of the Corporation to any third party, nor an admission to any
third party against the Corporation’s interests.

 

With respect to any matter that is clearly disclosed in any Section of this
Schedule in such a way as to make its relevance to the information called for by
another Section of this Schedule readily apparent, such matter shall be deemed
to have been included in the Schedule in response to such other Section,
notwithstanding the omission of any appropriate cross-reference thereto. The
Section numbers referred to in this Schedule correspond to the Section numbers
in the Purchase Agreement.  Capitalized terms not otherwise defined in this
Schedule shall have the meanings set forth in the Purchase Agreement.

 

141

--------------------------------------------------------------------------------

 

Schedule 5.1

 

Organization

 

1.              The Corporation is qualified to do business as a foreign
corporation in the Commonwealth of Massachusetts.

 

142

--------------------------------------------------------------------------------

 

Schedule 5.2

 

Capitalization

 

1.              Capitalization of the Corporation Immediately Following the
Stage I Closing:

 

RADIUS

 

 

 

CAPITALIZATION AFTER 1ST SERIES A-1, A-5 and IPSEN CLOSING

 

 

 

%

 

Post

 

%

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Series A-1

 

Common

 

Common

 

Post

 

Shares

 

Fully Diluted

 

Fully

 

 

 

Series A-1

 

Series A-2

 

Series A-3

 

Series A-4

 

Series A-5

 

Common

 

Warrants

 

Warrants

 

Options

 

Shares

 

Out

 

Shares

 

Diluted

 

Preferred Holders

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

MPM Bioventures III Funds

 

82,225

 

121,944

 

29,850

 

 

 

 

 

—

 

 

 

 

 

 

 

234,019

 

1.46

%

234,019

 

1.32

%

MPM Bioventures III-QP, L.P.

 

1,222,905

 

1,813,643

 

443,959

 

 

 

 

 

—

 

 

 

 

 

 

 

3,480,507

 

21.69

%

3,480,507

 

19.67

%

MPM Bioventures III GMBH & Co.

 

103,351

 

153,275

 

37,520

 

 

 

 

 

—

 

 

 

 

 

 

 

294,146

 

1.83

%

294,146

 

1.66

%

MPM Bioventures III Parallel Fund, L.P.

 

36,932

 

54,773

 

13,408

 

 

 

 

 

—

 

 

 

 

 

 

 

105,113

 

0.66

%

105,113

 

0.59

%

MPM Asset Management Investors 2003

 

23,681

 

35,114

 

8,595

 

 

 

 

 

—

 

 

 

 

 

 

 

67,390

 

0.42

%

67,390

 

0.38

%

MPM Bio IV NVS Strategic Fund

 

540,013

 

1,842,426

 

—

 

 

 

 

 

—

 

 

 

 

 

 

 

2,382,439

 

14.85

%

2,382,439

 

13.47

%

Wellcome Trust

 

255,223

 

2,103,250

 

—

 

 

 

 

 

—

 

 

 

 

 

 

 

2,358,473

 

14.70

%

2,358,473

 

13.33

%

HealthCare Ventures VII

 

196,512

 

982,789

 

636,632

 

 

 

 

 

83,113

 

 

 

 

 

 

 

1,899,046

 

11.83

%

1,899,046

 

10.73

%

Saints Capital (OBP IV Holdings)

 

162,133

 

1,086,285

 

249,830

 

 

 

 

 

15,173

 

 

 

 

 

 

 

1,513,421

 

9.43

%

1,513,421

 

8.56

%

Saints Capital (mRNA Fund II Holdings)

 

1,627

 

10,900

 

2,506

 

 

 

 

 

151

 

 

 

 

 

 

 

15,184

 

0.09

%

15,184

 

0.09

%

BB Biotech Ventures II

 

435,965

 

1,051,625

 

—

 

 

 

 

 

—

 

 

 

 

 

 

 

1,487,590

 

9.27

%

1,487,590

 

8.41

%

Scottish Widows

 

68,059

 

560,866

 

—

 

 

 

 

 

—

 

 

 

 

 

 

 

628,925

 

3.92

%

628,925

 

3.56

%

Raymond F. Schinazi

 

7,575

 

15,243

 

—

 

4,142

 

 

 

—

 

 

 

 

 

 

 

26,960

 

0.17

%

26,960

 

0.15

%

David E. Thompson Revocable Trust

 

1,964

 

 

 

 

 

16,190

 

 

 

—

 

 

 

 

 

 

 

18,154

 

0.11

%

18,154

 

0.10

%

Hostetler Family Trust

 

—

 

 

 

 

 

—

 

 

 

3,071

 

 

 

 

 

 

 

3,071

 

0.02

%

3,071

 

0.02

%

H.Watt Gregory, III

 

1,329

 

 

 

 

 

10,957

 

 

 

—

 

 

 

 

 

 

 

12,286

 

0.08

%

12,286

 

0.07

%

The Richman Trust

 

650

 

 

 

 

 

5,357

 

 

 

—

 

 

 

 

 

 

 

6,007

 

0.04

%

6,007

 

0.03

%

Breining Family Trust

 

407

 

 

 

 

 

3,357

 

 

 

—

 

 

 

 

 

 

 

3,764

 

0.02

%

3,764

 

0.02

%

Dr. Dennis A. Carson

 

—

 

 

 

 

 

—

 

 

 

533

 

 

 

 

 

 

 

533

 

0.00

%

533

 

0.00

%

B Van Wyck

 

—

 

 

 

 

 

—

 

 

 

363

 

 

 

 

 

 

 

363

 

0.00

%

363

 

0.00

%

Jonnie K. Westbrook

 

—

 

 

 

 

 

—

 

 

 

363

 

 

 

 

 

 

 

363

 

0.00

%

363

 

0.00

%

Nordic Bioscience

 

 

 

 

 

 

 

 

 

64,430

 

 

 

 

 

 

 

 

 

64,430

 

0.40

%

64,430

 

0.36

%

Brookside

 

409,400

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

409,400

 

2.55

%

409,400

 

2.31

%

BB Biotech AG

 

409,400

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

409,400

 

2.55

%

409,400

 

2.31

%

Ipsen

 

173,263

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

173,263

 

1.08

%

173,263

 

0.98

%

Leerink

 

 

 

 

 

 

 

 

 

 

 

 

 

8,188

 

 

 

 

 

—

 

0.00

%

8,188

 

0.05

%

 

143

--------------------------------------------------------------------------------

 

RADIUS

 

 

 

CAPITALIZATION AFTER 1ST SERIES A-1, A-5 and IPSEN CLOSING

 

 

 

%

 

Post

 

%

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Series A-1

 

Common

 

Common

 

Post

 

Shares

 

Fully Diluted

 

Fully

 

 

 

Series A-1

 

Series A-2

 

Series A-3

 

Series A-4

 

Series A-5

 

Common

 

Warrants

 

Warrants

 

Options

  

Shares

  

Out

 

Shares

 

Diluted

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Common Holders

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Alan Auerbach

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

256,666

 

—

 

0.00

%

256,666

 

1.45

%

Stavros C. Manolagas

 

 

 

 

 

 

 

 

 

 

 

91,040

 

 

 

 

 

—

 

91,040

 

0.57

%

91,040

 

0.51

%

Michael Rosenblatt

 

 

 

 

 

 

 

 

 

 

 

46,664

 

 

 

 

 

41,168

 

46,664

 

0.29

%

87,832

 

0.50

%

John Thomas Potts Trust

 

 

 

 

 

 

 

 

 

 

 

20,291

 

 

 

 

 

—

 

20,291

 

0.13

%

20,291

 

0.11

%

John Thomas Potts, Jr.

 

 

 

 

 

 

 

 

 

 

 

4,496

 

 

 

 

 

47,245

 

4,496

 

0.03

%

51,741

 

0.29

%

John Katzenellenbogen Trust

 

 

 

 

 

 

 

 

 

 

 

40,438

 

 

 

 

 

—

 

40,438

 

0.25

%

40,438

 

0.23

%

John Katzenellenbogen

 

 

 

 

 

 

 

 

 

 

 

8,961

 

 

 

 

 

6,666

 

8,961

 

0.06

%

15,627

 

0.09

%

Bart Henderson

 

 

 

 

 

 

 

 

 

 

 

30,468

 

 

 

 

 

—

 

30,468

 

0.19

%

30,468

 

0.17

%

Board of Trustees of the Uni of Arkansas

 

 

 

 

 

 

 

 

 

 

 

17,333

 

 

 

 

 

—

 

17,333

 

0.11

%

17,333

 

0.10

%

Sillicon Valley Bank

 

 

 

 

 

 

 

 

 

 

 

—

 

 

 

266

 

—

 

—

 

0.00

%

266

 

0.00

%

Ben Lane

 

 

 

 

 

 

 

 

 

 

 

8,125

 

 

 

 

 

—

 

8,125

 

0.05

%

8,125

 

0.05

%

Ruff Trust

 

 

 

 

 

 

 

 

 

 

 

5,124

 

 

 

 

 

—

 

5,124

 

0.03

%

5,124

 

0.03

%

H2 Enterprises, LLC

 

 

 

 

 

 

 

 

 

 

 

5,124

 

 

 

 

 

—

 

5,124

 

0.03

%

5,124

 

0.03

%

Dr. Karl Y. Hostetler

 

 

 

 

 

 

 

 

 

 

 

5,124

 

 

 

 

 

—

 

5,124

 

0.03

%

5,124

 

0.03

%

Czerepak, Elizabeth

 

 

 

 

 

 

 

 

 

 

 

—

 

 

 

 

 

11,666

 

—

 

0.00

%

11,666

 

0.07

%

Stavroula Kousteni, Ph.D.

 

 

 

 

 

 

 

 

 

 

 

421

 

 

 

 

 

—

 

421

 

0.00

%

421

 

0.00

%

Robert L. Jilka, Ph.D.

 

 

 

 

 

 

 

 

 

 

 

572

 

 

 

 

 

—

 

572

 

0.00

%

572

 

0.00

%

Robert S. Weinstein, M.D.

 

 

 

 

 

 

 

 

 

 

 

421

 

 

 

 

 

—

 

421

 

0.00

%

421

 

0.00

%

Teresita M. Bellido, Ph.D.

 

 

 

 

 

 

 

 

 

 

 

234

 

 

 

 

 

—

 

234

 

0.00

%

234

 

0.00

%

Chris Glass

 

 

 

 

 

 

 

 

 

 

 

—

 

 

 

 

 

1,333

 

—

 

0.00

%

1,333

 

0.01

%

Dotty McIntyre, RA

 

 

 

 

 

 

 

 

 

 

 

891

 

 

 

 

 

—

 

891

 

0.01

%

891

 

0.01

%

Thomas E. Sparks, Jr.

 

 

 

 

 

 

 

 

 

 

 

883

 

 

 

 

 

—

 

883

 

0.01

%

883

 

0.00

%

Sam Ho

 

 

 

 

 

 

 

 

 

 

 

833

 

 

 

 

 

—

 

833

 

0.01

%

833

 

0.00

%

Charles O’Brien, Ph.D.

 

 

 

 

 

 

 

 

 

 

 

140

 

 

 

 

 

—

 

140

 

0.00

%

140

 

0.00

%

Alwyn Michael Parfitt, M.D.

 

 

 

 

 

 

 

 

 

 

 

280

 

 

 

 

 

—

 

280

 

0.00

%

280

 

0.00

%

Barry Pitzele

 

 

 

 

 

 

 

 

 

 

 

266

 

 

 

 

 

—

 

266

 

0.00

%

266

 

0.00

%

Benita S. Katzenellenbogen, Ph.D.

 

 

 

 

 

 

 

 

 

 

 

187

 

 

 

 

 

—

 

187

 

0.00

%

187

 

0.00

%

Kelly Colbourn

 

 

 

 

 

 

 

 

 

 

 

102

 

 

 

 

 

—

 

102

 

0.00

%

102

 

0.00

%

Julie Glowacki, Ph.D.

 

 

 

 

 

 

 

 

 

 

 

93

 

 

 

 

 

—

 

93

 

0.00

%

93

 

0.00

%

Socrates E. Papapoulos, M.D.

 

 

 

 

 

 

 

 

 

 

 

93

 

 

 

 

 

—

 

93

 

0.00

%

93

 

0.00

%

Tonya D. Smith

 

 

 

 

 

 

 

 

 

 

 

66

 

 

 

 

 

—

 

66

 

0.00

%

66

 

0.00

%

Kent Westbrook, M.D.

 

 

 

 

 

 

 

 

 

 

 

46

 

 

 

 

 

—

 

46

 

0.00

%

46

 

0.00

%

Edie Estabrook

 

 

 

 

 

 

 

 

 

 

 

—

 

 

 

 

 

4,266

 

—

 

0.00

%

4,266

 

0.02

%

Maysoun Shomali

 

 

 

 

 

 

 

 

 

 

 

2,383

 

 

 

 

 

—

 

2,383

 

0.01

%

2,383

 

0.01

%

Lumpkins, Mary

 

 

 

 

 

 

 

 

 

 

 

—

 

 

 

 

 

400

 

—

 

0.00

%

400

 

0.00

%

Guerriero, Jonathan

 

 

 

 

 

 

 

 

 

 

 

2,500

 

 

 

 

 

12,166

 

2,500

 

0.02

%

14,666

 

0.08

%

Grunwald, Maria

 

 

 

 

 

 

 

 

 

 

 

—

 

 

 

 

 

14,666

 

—

 

0.00

%

14,666

 

0.08

%

McCarthy, Daniel F.

 

 

 

 

 

 

 

 

 

 

 

—

 

 

 

 

 

3,200

 

—

 

0.00

%

3,200

 

0.02

%

Sullivan, Kelly

 

 

 

 

 

 

 

 

 

 

 

—

 

 

 

 

 

1,666

 

—

 

0.00

%

1,666

 

0.01

%

Welch, Kathy

 

 

 

 

 

 

 

 

 

 

 

—

 

 

 

 

 

6,400

 

—

 

0.00

%

6,400

 

0.04

%

Richard Lyttle

 

 

 

 

 

 

 

 

 

 

 

66,666

 

 

 

 

 

489,227

 

66,666

 

0.42

%

555,893

 

3.14

%

Louis O’Dea

 

 

 

 

 

 

 

 

 

 

 

29,207

 

 

 

 

 

165,355

 

29,207

 

0.18

%

194,562

 

1.10

%

Nick Harvey

 

 

 

 

 

 

 

 

 

 

 

30,000

 

 

 

 

 

143,716

 

30,000

 

0.19

%

173,716

 

0.98

%

Gary Hattersley

 

 

 

 

 

 

 

 

 

 

 

—

 

 

 

 

 

83,384

 

—

 

0.00

%

83,384

 

0.47

%

Chris Miller

 

 

 

 

 

 

 

 

 

 

 

33,355

 

 

 

 

 

30,498

 

33,355

 

0.21

%

63,853

 

0.36

%

ESOP Remaining

 

 

 

 

 

 

 

 

 

 

 

—

 

 

 

 

 

315,172

 

—

 

0.00

%

315,172

 

1.78

%

Additions to Option Plan

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

—

 

—

 

0.00

%

—

 

0.00

%

Total

 

4,132,614

 

9,832,133

 

1,422,300

 

40,003

 

64,430

 

555,594

 

8,188

 

266

 

1,634,860

 

16,047,074

 

100.00

%

17,690,388

 

100.00

%

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Per Share

 

$

8.1420

 

 

 

$

8.1420

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Post-money $

 

$

130,655,277

 

 

 

$

144,035,139

 

 

 

 

144

--------------------------------------------------------------------------------

 

2.     In connection with that certain Loan and Security Agreement, dated as of
August 6, 2004, by and between the Corporation and Silicon Valley Bank (“SVB”),
as amended, the Corporation issued to SVB a warrant exercisable for the purchase
of an aggregate of up to 20,000 shares of Series A Junior Convertible Preferred
Stock at $1.00 per share (as amended, the “SVB Warrant”).  The warrant, which
expires in August 2014, will be amended and restated as of the Stage I Closing
Date to purchase shares of the Corporation’s common stock.  The warrant was 100%
vested as of the grant date.

 

3.     Series A Convertible Redeemable Preferred Stock Purchase Agreement, dated
November 14, 2003, by and among the Corporation and the stockholders listed on
the schedules thereto.

 

4.     Series B Convertible Redeemable Preferred Stock Purchase Agreement, dated
November 14, 2003, by and among the Corporation and the stockholders listed on
the schedules thereto.

 

5.     Series C Convertible Redeemable Preferred Stock Purchase Agreement, dated
December 15, 2006, by and among the Corporation and the Investors referenced
therein, as amended by Amendment No. 1 thereto, dated February 12, 2007,
Amendment No. 2 thereto, dated February 22, 2007, Amendment No. 3 thereto, dated
August 17, 2007, and Amendment No. 4 thereto, dated November 14, 2008.

 

6.     Fourth Amended and Restated Certificate of Incorporation of the
Corporation filed with the Secretary of State of the State of Delaware on
May 17, 2011.

 

7.     Growth Capital Loan Proposal Letter by and among the Corporation, GE
Healthcare Financial Services, Inc., and Oxford Finance Corporation, dated
December 21, 2010.  The proposed loan documents would include an obligation of
the Corporation to issue a warrant to purchase Series A-1 Convertible Preferred
Stock for 4% of the principal as drawn, equaling $1,000,000 (4% of $25 million).

 

8.     In connection with that certain Letter Agreement by and between the
Corporation and Leerink Swann LLC (“Leerink”), dated September 24, 2010, the
Corporation is obligated to issue a warrant to purchase Series A-1 Convertible
Preferred Stock of the Corporation (the “Leerink Warrant”).

 

9.     Stock Issuance Agreement by and between the Corporation and Nordic
Bioscience Clinical Development VII A/S (“Nordic”), dated March 29, 2011.

 

10.  In connection with that certain License Agreement, dated September 27,
2005, by and between SCRAS S.A.S., a French corporation, with its principal
office at 42, Rue du Docteur Blanche, 75016 Paris, France, on behalf of itself
and its Affiliates (collectively, “Ipsen”), and the Corporation, as amended on
September 12, 2007, and assigned by SCRAS S.A.S. to successor Ipsen Pharma SAS
on January 1, 2009 (the “Ipsen License Agreement”), the Corporation is currently
in discussions with Ipsen to make its payment milestones to Ipsen pursuant to
the Ipsen License Agreement with shares of Series A-1 Preferred Stock at $8.142
per share.

 

11.  2007 Amended and Restated Management and Employee Bonus Plan approved at a
meeting of the Board of Directors of the Corporation held on October 1, 2009 and
approved by the Stockholders by written consent on November 11, 2009, which
shall be terminated by written agreement of the participants effective upon the
Closing.

 

145

--------------------------------------------------------------------------------

 

Schedule 5.6(a)

 

Business of the Corporation

 

None.

 

146

--------------------------------------------------------------------------------

 

Schedule 5.6

 

Business of the Corporation

 

A.    Loan Agreements

 

1.     Growth Capital Loan Proposal Letter by and among the Corporation, GE
Healthcare Financial Services, Inc., and Oxford Finance Corporation, dated
December 21, 2010.

 

2.     Demand Promissory Note issued by MPM Acquisition Corp. to the
Corporation, dated November 22, 2010.

 

B.    License Agreements

 

1.     Ipsen License Agreement.

 

2.     Pharmaceutical Development Agreement by and between the Corporation and
Ipsen, dated January 2, 2006, as amended by Amendment No. 1, dated January 1,
2007, Amendment No. 2, dated January 1, 2009, and Amendment No. 3, dated
June 16, 2010.

 

3.     License Agreement, dated June 29, 2006, by and between Eisai Co. and the
Corporation.

 

C.    Research, Development and/or Service Agreements

 

1.         Development and Clinical Supplies Agreement by and between the
Corporation, 3M Company and 3M Innovative Properties (3M Company and 3M
Innovative Properties, collectively, “3M”), dated June 19, 2009, as amended on
each of May 5, 2009, December 31, 2009, March 3, 2010, September 16, 2010,
September 29, 2010, February 4, 2011, and March 2, 2011.

 

2.         Letter of Payment Authorization for Study No. 670364 by and between
the Corporation and Charles River Laboratories (“CRL”), dated November 20, 2010.

 

3.         Letter of Payment Authorization for Dawley Rat - Rat Bone Quality
Study by and between the Corporation and CRL, dated February 7, 2011.

 

4.         Work Order No. 2 by and between the Corporation and LONZA Sales Ltd.
(“Lonza”), dated January 15, 2010, as amended April 27, 2010, and as further
amended December 15, 2010.

 

5.         Letter Agreement by and between the Corporation and Leerink , dated
February 4, 2010.

 

6.         Letter Agreement by and between the Corporation and Leerink, dated
September 24, 2010.

 

7.         Stock Issuance Agreement by and between the Corporation and Nordic,
dated March 29, 2011.

 

8.         Amendment Letter by and between the Corporation and Nordic, dated
February 1, 2011.

 

147

--------------------------------------------------------------------------------

 

9.         Clinical Trial Services Agreement and Work Statement NB-1 by and
between the Corporation and Nordic, dated March 29, 2011.

 

10.      Side Letter by and between the Corporation and Nordic, dated March 29,
2011.

 

11.      Engagement Letter by and between the Corporation and Ernst & Young LLP,
dated October 5, 2010.

 

12.      Master Clinical Services Agreement by and between the Corporation and
Celerion, Inc., dated November 2, 2010, as amended by Work Order No. 1, dated
November 3, 2010.

 

13.      Change Order No. 2 to Statement of Work by and between the Corporation
and INC Research, Inc., dated September 3, 2010.

 

14.      Letter of Payment Authorization for Chronic Dermal Toxicity Study by
and between the Corporation and CRL, dated April 29, 2011.

 

D.    Real Property

 

1.     Sublease by and between the Corporation and Sonos, Inc., dated
January 14, 2011, for the property located at 201 Broadway, Cambridge,
Massachusetts.

 

E.    ERISA

 

1.     Radius Health, Inc. 401(k) Plan

 

2.     Radius Health, Inc. Flexible Spending Account Plan

 

F.     Indemnification Agreements

 

1.     Please see Schedule 5.6(g).

 

2.     Please see general commercial agreement indemnification provisions
included in the material license agreements listed above.

 

G.    Other Agreements

 

1.     Pursuant to an engagement with Leerink Swann LLC (“Leerink”) for services
in connection with the Series A-1 Financing, the Corporation has agreed to issue
to Leerink a Warrant to purchase 24,564 shares of Series A-1 Convertible
Preferred Stock at the Stage I Closing.

 

2.     Amended and Restated Stockholders’ Agreement, dated as of December 15,
2006, by and between the Corporation, the Investors, the Original Stockholders,
the Series A Stockholders and the Series B Stockholders (each as defined
therein), as amended by Amendment No. 1 thereto, dated as of February 22, 2007,
Amendment No. 2 thereto, dated as of August 17, 2007, and Amendment No. 3
thereto, dated as of October    , 2008.

 

3.     The Corporation has granted Alan Auerbach registration rights with
respect to shares issuable upon exercise of granted options.

 

148

--------------------------------------------------------------------------------

 

4.     The Corporation has granted registration rights to SVB pursuant to the
terms of the SVB Warrant.

 

5.     The Corporation has granted board observation rights to BB Biotech
Ventures II, L.P. pursuant to a Letter Agreement dated as of February 22, 2007,
by and between the Corporation and BB Biotech Ventures II, L.P.

 

H.    Stock Option Plans

 

1.     2003 Long Term Incentive Plan

 

2.     2007 Management and Employee Bonus Plan approved at a meeting of the
Board of Directors of the Corporation held on December 6, 2007 and approved by
the Stockholders by written consent on February 14, 2008, which shall be
terminated by written agreement of the participants effective upon the Closing.

 

149

--------------------------------------------------------------------------------

 

I.     Stock Option Agreements

 

The Corporation has entered into Stock Option Agreements with the following
individuals:

 

Option
Number

 

Name

 

# Options

 

Grant
Date

 

Options
Canceled

 

Options
Outstanding

04-051

 

Ho, Sam

 

10,000

 

5/4/2004

 

 

 

—

03-002

 

Lane, Ben

 

325,000

 

12/16/2003

 

203,125

 

—

03-003

 

Henderson, Bart

 

650,000

 

12/16/2003

 

192,969

 

—

03-001

 

Hattersley, Gary

 

162,500

 

12/16/2003

 

 

 

162,500

04-003

 

O’Brien, Charles

 

8,000

 

2/5/2004

 

 

 

8,000

04-005

 

Kousteni, Stavroula

 

30,000

 

2/5/2004

 

 

 

30,000

03-005

 

Manolagas, Stavros

 

1,108,812

 

11/14/2003

 

 

 

—

03-008

 

Rosenblatt, Michael

 

370,241

 

11/14/2003

 

 

 

—

03-007

 

Potts, John Thomas

 

304,374

 

11/14/2003

 

 

 

—

03-006

 

Katsenellenbogen, John

 

606,573

 

11/14/2003

 

 

 

—

03-004

 

Pitzele, Barnett

 

5,000

 

12/16/2003

 

1,000

 

—

04-001

 

Bellido, Teresita

 

17,000

 

2/4/2004

 

 

 

17,000

04-002

 

Jilka, Robert

 

28,000

 

2/4/2004

 

 

 

25,725

04-004

 

Weinstien, Robert

 

17,000

 

2/4/2004

 

 

 

17,000

04-072

 

Glass, Chris

 

10,000

 

8/12/2004

 

 

 

10,000

04-052

 

Estabrook, Edith

 

24,000

 

5/4/2004

 

 

 

24,000

04-071

 

Colbourn, Kelly

 

1,000

 

8/12/2004

 

 

 

—

04-103

 

Lyttle, Richard

 

1,625,000

 

10/28/2004

 

 

 

1,625,000

04-101

 

Guy, Keisha

 

8,000

 

10/28/2004

 

8,000

 

—

04-102

 

McIntyre, Dotty

 

8,000

 

10/28/2004

 

2,000

 

—

04-100

 

Shomali, Maysoun

 

15,000

 

12/28/2004

 

15,000

 

—

05-01

 

Glass, Chris

 

10,000

 

12/6/2005

 

 

 

10,000

06-02

 

Hattersley, Gary

 

81,250

 

2/15/2006

 

 

 

81,250

06-04

 

Guy, Keisha

 

8,000

 

2/15/2006

 

8,000

 

—

06-05

 

McIntyre, Dotty

 

8,000

 

2/15/2006

 

4,000

 

—

06-06

 

Shomali, Maysoun

 

15,000

 

2/15/2006

 

15,000

 

—

06-01

 

Ho, Sam

 

10,000

 

2/15/2006

 

7,500

 

—

06-03

 

Colbourn, Kelly

 

3,000

 

2/15/2006

 

2,469

 

—

06-07

 

O’Dea, Louis

 

570,000

 

2/15/2006

 

 

 

339,625

07-01

 

McIntyre, Dotty

 

27,000

 

7/12/2007

 

23,625

 

—

07-08

 

Lyttle, Richard

 

2,377,688

 

7/12/2007

 

 

 

2,377,688

07-07

 

O’Dea, Louis

 

830,941

 

7/12/2007

 

 

 

623,206

07-09

 

Harvey, B. Nicholas

 

1,250,840

 

7/12/2007

 

 

 

1,250,840

07-06

 

Hattersley, Gary

 

356,653

 

7/12/2007

 

 

 

356,653

07-10

 

Miller, Chris

 

500,336

 

7/12/2007

 

 

 

—

07-11

 

Katsenellenbogen, John

 

100,000

 

7/12/2007

 

 

 

100,000

07-12

 

Potts, John Thomas

 

540,790

 

7/12/2007

 

 

 

540,790

07-13

 

Rosenblatt, Michael

 

660,491

 

7/12/2007

 

 

 

412,805

07-02

 

Shomali, Maysoun

 

44,000

 

7/12/2007

 

8,250

 

—

07-03

 

Estabrook, Edith

 

16,000

 

7/12/2007

 

 

 

16,000

07-05

 

Lumpkins, Mary

 

3,000

 

7/12/2007

 

 

 

3,000

 

150

--------------------------------------------------------------------------------

 

07-04

 

Guerriero, Jonathan

 

100,000

 

7/12/2007

 

 

 

62,500

07-14

 

Grunwald, Maria

 

137,500

 

12/6/2007

 

 

 

137,500

07-15

 

Herendeen, Hillary

 

8,000

 

12/6/2007

 

8,000

 

—

07-16

 

Downall, Julie

 

8,000

 

12/6/2007

 

8,000

 

—

08-01

 

Welch, Kathy

 

60,000

 

2/7/2008

 

 

 

60,000

08-09

 

Lyttle, Richard

 

3,040,081

 

5/8/2008

 

 

 

3,040,081

08-05

 

O’Dea, Louis

 

1,064,028

 

5/8/2008

 

 

 

1,064,028

08-06

 

Harvey, B. Nicholas

 

950,025

 

5/8/2008

 

 

 

950,025

08-08

 

Hattersley, Gary

 

456,012

 

5/8/2008

 

 

 

456,012

08-07

 

Miller, Chris

 

380,010

 

5/8/2008

 

23,751

 

356,259

08-02

 

McCarthy, Daniel F.

 

30,000

 

5/8/2008

 

 

 

30,000

08-03

 

Zielstorff, Mark

 

10,000

 

5/8/2008

 

10,000

 

—

08-04

 

Gallacher, Kyla

 

10,000

 

5/8/2008

 

10,000

 

—

08-14

 

Lyttle, Richard

 

1,295,640

 

12/3/2008

 

 

 

1,295,640

08-10

 

O’Dea, Louis

 

453,474

 

12/3/2008

 

 

 

453,474

08-11

 

Harvey, B. Nicholas

 

404,888

 

12/3/2008

 

 

 

404,888

08-13

 

Hattersley, Gary

 

194,346

 

12/3/2008

 

 

 

194,346

08-12

 

Miller, Chris

 

161,955

 

12/3/2008

 

60,734

 

101,221

08-26

 

Potts, John Thomas

 

167,891

 

12/3/2008

 

 

 

167,891

08-25

 

Rosenblatt, Michael

 

204,715

 

12/3/2008

 

 

 

204,715

08-16

 

Grunwald, Maria

 

82,500

 

12/3/2008

 

 

 

82,500

08-15

 

Guerriero, Jonathan

 

120,000

 

12/3/2008

 

 

 

120,000

08-17

 

Shomali, Maysoun

 

50,000

 

12/3/2008

 

50,000

 

—

08-18

 

Welch, Kathy

 

36,000

 

12/3/2008

 

 

 

36,000

08-19

 

Estabrook, Edie

 

24,000

 

12/3/2008

 

 

 

24,000

08-20

 

McCarthy, Daniel F.

 

18,000

 

12/3/2008

 

 

 

18,000

08-21

 

Gallacher, Kyla

 

6,000

 

12/3/2008

 

6,000

 

—

08-22

 

Zielstorff, Mark

 

6,000

 

12/3/2008

 

6,000

 

—

08-23

 

Downall, Julie

 

4,800

 

12/3/2008

 

4,800

 

—

08-24

 

Lumpkins, Mary

 

3,000

 

12/3/2008

 

 

 

3,000

09-01

 

Sullivan, Kelly

 

25,000

 

4/9/2009

 

 

 

25,000

09-02

 

McKay, Kathleen

 

45,000

 

4/9/2009

 

45,000

 

—

09-03

 

Czerepak, Elizabeth

 

75,000

 

4/9/2009

 

 

 

75,000

09-04

 

Czerepak, Elizabeth

 

75,000

 

12/2/2009

 

 

 

75,000

10-01

 

Auerbach, Alan

 

2,084,602

 

10/12/2010

 

 

 

2,084,602

10-02

 

Auerbach, Alan

 

1,765,398

 

10/12/2010

 

 

 

1,765,398

10-03

 

Czerepak, Elizabeth

 

25,000

 

11/30/2010

 

 

 

25,000

 

151

--------------------------------------------------------------------------------

 

Option
Number

 

Name

 

# Options

 

Grant
Date

 

Options
Canceled

 

Options
Outstanding

04-051

 

Ho, Sam

 

10,000

 

5/4/2004

 

 

 

—

03-002

 

Lane, Ben

 

325,000

 

12/16/2003

 

203,125

 

—

03-003

 

Henderson, Bart

 

650,000

 

12/16/2003

 

192,969

 

—

03-001

 

Hattersley, Gary

 

162,500

 

12/16/2003

 

 

 

162,500

03-005

 

Manolagas, Stavros

 

1,108,812

 

11/14/2003

 

 

 

—

03-008

 

Rosenblatt, Michael

 

370,241

 

11/14/2003

 

 

 

—

03-007

 

Potts, John Thomas

 

304,374

 

11/14/2003

 

 

 

—

03-006

 

Katsenellenbogen, John

 

606,573

 

11/14/2003

 

 

 

—

03-004

 

Pitzele, Barnett

 

5,000

 

12/16/2003

 

1,000

 

—

04-072

 

Glass, Chris

 

10,000

 

8/12/2004

 

 

 

10,000

04-052

 

Estabrook, Edith

 

24,000

 

5/4/2004

 

 

 

24,000

04-071

 

Colbourn, Kelly

 

1,000

 

8/12/2004

 

 

 

—

04-103

 

Lyttle, Richard

 

1,625,000

 

10/28/2004

 

 

 

1,625,000

04-101

 

Guy, Keisha

 

8,000

 

10/28/2004

 

8,000

 

—

04-102

 

McIntyre, Dotty

 

8,000

 

10/28/2004

 

2,000

 

—

04-100

 

Shomali, Maysoun

 

15,000

 

12/28/2004

 

15,000

 

—

05-01

 

Glass, Chris

 

10,000

 

12/6/2005

 

 

 

10,000

06-02

 

Hattersley, Gary

 

81,250

 

2/15/2006

 

 

 

81,250

06-04

 

Guy, Keisha

 

8,000

 

2/15/2006

 

8,000

 

—

06-05

 

McIntyre, Dotty

 

8,000

 

2/15/2006

 

4,000

 

—

06-06

 

Shomali, Maysoun

 

15,000

 

2/15/2006

 

15,000

 

—

06-01

 

Ho, Sam

 

10,000

 

2/15/2006

 

7,500

 

—

06-03

 

Colbourn, Kelly

 

3,000

 

2/15/2006

 

2,469

 

—

06-07

 

O’Dea, Louis

 

570,000

 

2/15/2006

 

 

 

339,625

07-01

 

McIntyre, Dotty

 

27,000

 

7/12/2007

 

23,625

 

—

07-08

 

Lyttle, Richard

 

2,377,688

 

7/12/2007

 

 

 

2,377,688

07-07

 

O’Dea, Louis

 

830,941

 

7/12/2007

 

 

 

623,206

07-09

 

Harvey, B. Nicholas

 

1,250,840

 

7/12/2007

 

 

 

1,250,840

07-06

 

Hattersley, Gary

 

356,653

 

7/12/2007

 

 

 

356,653

07-11

 

Katsenellenbogen, John

 

100,000

 

7/12/2007

 

 

 

100,000

07-12

 

Potts, John Thomas

 

540,790

 

7/12/2007

 

 

 

540,790

07-13

 

Rosenblatt, Michael

 

660,491

 

7/12/2007

 

 

 

412,805

07-02

 

Shomali, Maysoun

 

44,000

 

7/12/2007

 

8,250

 

—

07-03

 

Estabrook, Edith

 

16,000

 

7/12/2007

 

 

 

16,000

07-05

 

Lumpkins, Mary

 

3,000

 

7/12/2007

 

 

 

3,000

07-04

 

Guerriero, Jonathan

 

100,000

 

7/12/2007

 

 

 

62,500

07-14

 

Grunwald, Maria

 

137,500

 

12/6/2007

 

 

 

137,500

07-15

 

Herendeen, Hillary

 

8,000

 

12/6/2007

 

8,000

 

—

07-16

 

Downall, Julie

 

8,000

 

12/6/2007

 

8,000

 

—

08-01

 

Welch, Kathy

 

60,000

 

2/7/2008

 

 

 

60,000

08-09

 

Lyttle, Richard

 

3,040,081

 

5/8/2008

 

 

 

3,040,081

08-05

 

O’Dea, Louis

 

1,064,028

 

5/8/2008

 

 

 

1,064,028

08-06

 

Harvey, B. Nicholas

 

950,025

 

5/8/2008

 

 

 

950,025

08-08

 

Hattersley, Gary

 

456,012

 

5/8/2008

 

 

 

456,012

08-02

 

McCarthy, Daniel F.

 

30,000

 

5/8/2008

 

 

 

30,000

 

152

--------------------------------------------------------------------------------

 

08-03

 

Zielstorff, Mark

 

10,000

 

5/8/2008

 

10,000

 

—

08-04

 

Gallacher, Kyla

 

10,000

 

5/8/2008

 

10,000

 

—

08-14

 

Lyttle, Richard

 

1,295,640

 

12/3/2008

 

 

 

1,295,640

08-10

 

O’Dea, Louis

 

453,474

 

12/3/2008

 

 

 

453,474

08-11

 

Harvey, B. Nicholas

 

404,888

 

12/3/2008

 

 

 

404,888

08-13

 

Hattersley, Gary

 

194,346

 

12/3/2008

 

 

 

194,346

08-26

 

Potts, John Thomas

 

167,891

 

12/3/2008

 

 

 

167,891

08-25

 

Rosenblatt, Michael

 

204,715

 

12/3/2008

 

 

 

204,715

08-16

 

Grunwald, Maria

 

82,500

 

12/3/2008

 

 

 

82,500

08-15

 

Guerriero, Jonathan

 

120,000

 

12/3/2008

 

 

 

120,000

08-17

 

Shomali, Maysoun

 

50,000

 

12/3/2008

 

50,000

 

—

08-18

 

Welch, Kathy

 

36,000

 

12/3/2008

 

 

 

36,000

08-19

 

Estabrook, Edie

 

24,000

 

12/3/2008

 

 

 

24,000

08-20

 

McCarthy, Daniel F.

 

18,000

 

12/3/2008

 

 

 

18,000

08-21

 

Gallacher, Kyla

 

6,000

 

12/3/2008

 

6,000

 

—

08-22

 

Zielstorff, Mark

 

6,000

 

12/3/2008

 

6,000

 

—

08-23

 

Downall, Julie

 

4,800

 

12/3/2008

 

4,800

 

—

08-24

 

Lumpkins, Mary

 

3,000

 

12/3/2008

 

 

 

3,000

09-01

 

Sullivan, Kelly

 

25,000

 

4/9/2009

 

 

 

25,000

09-02

 

McKay, Kathleen

 

45,000

 

4/9/2009

 

45,000

 

—

09-03

 

Czerepak, Elizabeth

 

75,000

 

4/9/2009

 

 

 

75,000

09-04

 

Czerepak, Elizabeth

 

75,000

 

12/2/2009

 

 

 

75,000

10-01

 

Auerbach, Alan

 

2,084,602

 

10/12/2010

 

 

 

2,084,602

10-02

 

Auerbach, Alan

 

1,765,398

 

10/12/2010

 

 

 

1,765,398

10-03

 

Czerepak, Elizabeth

 

25,000

 

11/30/2010

 

 

 

25,000

 

153

--------------------------------------------------------------------------------

 

J.     Consulting Agreements

 

The Corporation has entered into consulting agreements with the following
parties:

 

Party

 

Effective Date

1.   Dr. John Bilezidian

 

9/14/2005

2.   Dr. David Archer

 

10/24/2005

3.   Beckloff Associates, Inc

 

6/18/2004

4.   Terisita Bellido

 

6/24/2004

5.   Dr. M. Shalender Bashin

 

1/3/2006

6.   IntaPro LLC

 

3/22/2005

7.   Access BIO, LC

 

7/8/2005

8.   Dr. John C. Chabala

 

5/3/2004

9.   SVC Associates, Inc

 

10/25/2005

10. Burton G Christensen

 

7/23/2004

11. Dr. Mitchell Creinin

 

10/17/2005

12. Frame and Spence Consulting LLP

 

7/21/2005

13. Dr. Christopher Glass

 

9/1/2004

14. Dr. Frances J. Hayes

 

4/21/2005

15. TLG Consulting Inc

 

7/1/2005

16. Robert A. Jassmond

 

4/18/2006

17. Robert Jilka

 

6/24/2004

18. Dr. John Katzenellenbogen

 

11/14/2003

19. Cathy Kerzner

 

11/18/2005

20. Stavroula Kousteni

 

6/24/2004

21. Richard Labaudiniere

 

1/1/2004

22. Robert Lindsay

 

07/26/2004

23. Willis Maddrey

 

07/23/2004

24. Dr. Stavros C. Manolagas

 

11/14/2003

25. Dr. Stavros C. Manolagas

 

12/14/2005

26. Musso and Associates LLC

 

06/24/2005

27. Musso and Associates LLC

 

03/08/2006

28. Robert M. Neer

 

11/22/2005

29. Anthony Norman

 

6/4/2004

30. Charles O’Brien

 

06/24/2004

31. Skokie Valley Consulting Agrmt

 

12/01/2003

32. PK Noonan & Associates LLC

 

07/08/2005

33. Dr. John Thomas Potts, Jr

 

11/14/2003

34. Dr. Cliff Rosen

 

07/22/2005

35. Dr. Michael Rosenblatt

 

11/14/2003

36. Joseph S. Simon

 

07/08/2005

37. Ian Smith

 

07/13/2004

38. Gilbert Stork

 

07/13/2004

39. KellySci Consulting Inc.

 

11/16/2007

40. Robert J. Szot

 

06/22/2005

41. Robert Weinstein

 

06/24/2004

42. ChanTest Inc

 

11/08/2005

43. Diamond BioPharm Ltd

 

10/26/2007

44. Diamond BioPharm Ltd

 

8/15/2007

 

154

--------------------------------------------------------------------------------

 

45. Diamond BioPharm Ltd

 

8/15/2007

46. Team Consulting Ltd

 

8/18/2007

47. Joel Morganroth

 

10/23/2007

48. Joel Morganroth

 

10/10/2006

49. INTAPRO LLC

 

3/22/2005

50. Roy Swaringen

 

3/6/2008

51. Skokie Valley Consulting Corp.

 

12/1/2003

52. Target Health Inc.

 

4/14/2006

53. LGL Consulting LLC

 

4/28/2008

54. David Archer

 

3/26/2008

55. Osheroff Consulting Services LLC

 

8/15/2008

56. Dylan J. Callahan a.k.a. d/b/a Organized Minds

 

6/1/2008

57. PK Noonan & Associates LLC

 

9/15/2008

58. Matrix BioAnalytical Laboratories Inc

 

4/11/2008

59. Prof David Handelsman

 

2/9/2009

60. David Goltzman

 

3/4/2009

61. Professor Dennis Black

 

4/14/2009

62. Dr. Radha Iyengar

 

7/20/2009

63. Frame and Spence Consulting LLP

 

5/5/2009

64. Access Bio LC

 

8/20/2009

65. David Archer, MD

 

3/27/2009

66. Jean-Francois Sibi

 

11/2/2009

67. Diamond Biopharm Ltd

 

11/9/2009

68. Harry Genant, MD

 

12/12/2009

69. Radha Iyengar

 

1/19/2010

70. Safety Partners, Inc.

 

06/03/2004

71. Joel Morganroth

 

10/10/2006

72. Joel Morganroth

 

10/23/2007

73. Robert Schenken

 

07/24/2004

74. Kathleen Banks

 

11/13/2009

75. Goldmann Consulting LLC

 

7/5/2010

76. Duck Flats Pharma LLC

 

8/2/2010

77. Dennis Black

 

11/29/2010

78. Welsh Consulting

 

1/20/2011

79. Michael Gross

 

5/3/2011

 

K.    Employment Agreements

 

1.     Letter Agreement by and between the Corporation and C. Richard Edmund
Lyttle, dated July 2, 2004.

 

2.     Letter Agreement by and between the Corporation and B. Nicholas Harvey,
dated November 15, 2006.

 

3.     Letter Agreement by and between the Corporation and Louis St. Laurence
O’Dea, dated January 30, 2006, as amended by Letter Agreement dated July 21,
2008.

 

4.     Letter Agreement by and between the Corporation and Gary Hattersley,
dated November 21, 2003, as amended by Letter Agreement dated July 21, 2008.

 

155

--------------------------------------------------------------------------------

 

5.     See also Attachment A to this Schedule 5.6 for the Form of Letter
Agreement entered into by and between the Corporation and its at-will employees.

 

156

--------------------------------------------------------------------------------

 

Attachment A to

Schedule 5.6

 

Form of Employee Letter Agreement

 

                              ,2007

 

Dear               :

 

It is my pleasure to offer you the position of
                                           at Radius Health, Inc. (the
“Company”).  As you know, I am excited about the contributions that I expect you
will make to the success of the Company.  Accordingly, if you accept this
offer, I would like us to agree that you could start at Radius on or before
                               (the “Start Date”).  This offer may be accepted
by you by countersigning where indicated at the end of this letter.

 

DUTIES AND EXTENT OF SERVICE

 

As                                           , you will report to
                                           and you will have responsibility for
performing those duties as are customary for, and are consistent with, such
position, as well as those duties that may be designated to you from time to
time.  As you know, your employment will be contingent upon your agreeing to
abide by the rules, regulations, instructions, personnel practices, and policies
of the Company and any changes therein that the Company may adopt from time to
time, and your execution of the Company’s standard Nondisclosure, Developments,
and Non-Competition Agreement.

 

COMPENSATION AND BENEFITS

 

Your salary will be $                       per semi-monthly pay period, minus
applicable taxes and withholdings.  Such salary may be adjusted from time to
time in accordance with normal business practice and in the sole discretion of
the Company.

 

You will be entitled to three weeks paid vacation annually.  You will also be
entitled to participate in such employee benefit plans and fringe benefits as
may be offered or made available by the Company to its employees.

 

STOCK OPTIONS

 

At the first meeting of the Company’s Board of Directors following your Start
Date, it is my intention that the Company will recommend to the Board of
Directors that you receive a common stock option grant of               
shares.  This offer is contingent upon approval by the Board of Directors of
your option grant specifically.  Promptly after the Grant Date, the Company and
you will execute and deliver to each other the Company’s then standard form of
stock option agreement, evidencing the Option and the terms thereof.  As you
know, the Option shall be subject to, and governed by, the terms and provisions
of the Plan and your stock option agreement.

 

NONDISCLOSURE, DEVELOPMENTS AND NON-COMPETITION

 

As you know, prior to commencing, and as a condition to your employment with the
Company, all employees are required to agree to sign a copy of the Company’s
standard Nondisclosure, Developments, and Non-Competition Agreement.  The
Company will ask you to sign this agreement after you have signed and returned
this letter and prior to or on your Start Date.

 

157

--------------------------------------------------------------------------------

 

At-Will Employment

 

This letter shall not be construed as an agreement, either expressed or implied,
to employ you for any stated term, and shall in no way alter the Company’s
policy of employment at-will, under which both you and the Company remain free
to terminate the employment relationship, with or without cause, at any time,
with or without notice.  Similarly, nothing in this letter shall be construed as
an agreement, either express or implied, to pay you any compensation or grant
you any benefit beyond the end of your employment with the Company.   In
addition, nothing in any documents published by the Company shall in any way
modify the above terms and these terms cannot be modified in any way by any oral
or written representations made by anyone employed by the Company, except by
written document signed by C. Richard Lyttle.

 

NO CONFLICTING OBLIGATION AND OBLIGATIONS

 

You represent and warrant that the performance by you of any or all of the terms
of this letter agreement and the performance by you of your duties as an
employee of the Company do not and will not breach or contravene (i) any
agreement or contract (including, without limitation, any employment or
consulting agreement, any agreement not to compete or any confidentiality or
nondisclosure agreement) to which you are or may become a party on or at an time
after the Start Date or (ii) any obligation you may otherwise have under
applicable law to any former employer or to any person to whom you have
provided, provide or will provide consulting services.

 

I am pleased on behalf of Radius to extend this offer to have you join us.  This
is an exciting time for Radius and we would be delighted to have you as part of
our organization.

 

Please acknowledge your acceptance of this offer and the terms of this letter
agreement by signing below and returning a copy to me.

 

Sincerely,

 

I hereby acknowledge that I have had a full and adequate opportunity to read,
understand and discuss the terms and conditions contained in this letter
agreement prior to signing hereunder.

 

Date this          day of                             , 20

 

158

--------------------------------------------------------------------------------

 

Schedule 5.6(e)

 

Business of the Corporation

 

None.

 

159

--------------------------------------------------------------------------------

 

Schedule 5.6(f)

 

Business of the Corporation

 

None.

 

160

--------------------------------------------------------------------------------

 

Schedule 5.6(g)

 

Business of the Corporation

 

1.              Indemnification Agreement, dated November 14, 2003, by and
between the Corporation and Michael Rosenblatt, M.D.

 

2.              Indemnification Agreement, dated November 14, 2003, by and
between the Corporation and Christopher Mirabelli.

 

3.              Indemnification Agreement, dated November 14, 2003, by and
between the Corporation and Augustine Lawlor.

 

4.              Indemnification Agreement, dated November 14, 2003, by and
between the Corporation and Ansbert K. Gadicke.

 

5.              Indemnification Agreement, dated November 14, 2003, by and
between the Corporation and Edward Mascioli, M.D.

 

6.              Indemnification Agreement, dated October 12, 2010, by and
between the Corporation and Alan Auerbach.

 

161

--------------------------------------------------------------------------------

 

Schedule 5.12(a)

 

Intellectual Property

 

1.              The Corporation has filed for registration of its trademark
rights in the following marks:

 

·                  N (Design), Application No. 78/391,239, Filing Date:
26-Mar-2004

 

·                  RADIUS, Application No. 78/707,397, Filing Date: 06-Sep-2005

 

·                  RADIUS, Application No. 78/707,419, Filing Date: 06-Sep-2005

 

·                  RADIUS (& Design), Application No. 78/797,031, Filing Date:
23-Jan-2006

 

·                  RADIUS (& Design), Application No. 78/797,016), Filing Date:
23-Jan-2006

 

2.              Domain name:  www.radiuspharm.com

 

3.              See also Attachment A to this Schedule 5.12(a).

 

162

--------------------------------------------------------------------------------

 

Attachment A to

Schedule 5.12(a)

 

RADIUS PATENT AND PATENT APPLICATION SUMMARY

 

RAD-1901

 

A.            Owned by Radius

 

HBSR Docket No.

 

Application Number
and
Filing Date

 

Inventors

 

Status

 

Title

3803.1016-000
(US)

 

61/127,025
(5/09/08)

 

Richard C. Lyttle,
Gary Hattersley, Louis O’Dea

 

Expired

 

Pharmaceutical Combinations and Methods of Using Same

3803.1016-001
(PCT)

 

PCT/US2009/002885
(5/07/09)

 

Richard C. Lyttle,
Gary Hattersley, Louis O’Dea

 

Pending

 

Pharmaceutical Combinations and Methods of Using Same

3803.1016-002
(US)

 

12/991,791
(5/7/09)

 

Richard C. Lyttle,
Gary Hattersley, Louis O’Dea

 

Pending

 

Pharmaceutical Combinations and Methods of Using Same

3803.1022-000
(US)

 

61/334,095
(5/12/10)

 

Richard C. Lyttle,
Gary Hattersley, Louis O’Dea

 

Pending
(Provisional)

 

Therapeutic Regimens

 

B.            Jointly Owned by Radius and Eisai

 

HBSR Docket No.

 

Application Number
(Pub. Number-Date)
and
Filing Date

 

Inventors

 

Status

 

Title

3803.1001-000
(US)

 

60/816,191
(6/23/06)

 

Richard C. Lyttle, Bart Henderson, Gary Hattersley

 

U.S. Provisional;
(Expired 06/23/07)

 

Treatment of Vasomotor Symptoms With Selective Estrogen Receptor Modulators

3803.1001-002
(PCT)

 

PCT/US2007/014598
(WO2008/002490-1/3/08)
6/22/07

 

Richard C. Lyttle, Bart Henderson, Gary Hattersley

 

Expired

 

Treatment of Vasomotor Symptoms With Selective Estrogen Receptor Modulators

 

163

--------------------------------------------------------------------------------

 

C.            Solely Owned by Radius

 

HBSR Docket No.

 

Application Number
(Pub. Number-Date)
and
Filing Date

 

Inventors

 

Status

 

Short Description

3803.1001-003
(US)

 

12/308,640
 (6/22/07)

 

(US 2010/0105733 A1-4/29/2010)

 

Richard C. Lyttle, Bart Henderson, Gary Hattersley

 

U.S. National Stage of PCT
Pending

 

Treatment of Vasomotor Symptoms With Selective Estrogen Receptor Modulators

3803.1001-004
(Europe)

 

07796378.3
(6/22/07)

 

(EP2037905-3/25/09)

 

Richard C. Lyttle, Bart Henderson, Gary Hattersley

 

EP Regional Phase
Pending

 

Treatment of Vasomotor Symptoms With Selective Estrogen Receptor Modulators

3803.1001-005
(Canada)

 

2656067
 (6/22/07)

 

Richard C. Lyttle, Bart Henderson, Gary Hattersley

 

Canadian National Stage of PCT
Pending

 

Treatment of Vasomotor Symptoms With Selective Estrogen Receptor Modulators

 

D.            Licensed to Radius by Eisai

 

HBSR Reference
No.

 

Country

 

App.and/or Patent Number
(Pub. Number-Date) and
Filing Date

 

Status

 

Short Description

3803.0020-003

 

Australia

 

2003292625 B2
(2003292625 A1-7/22/2004)
12/25/03

 

Granted
11/6/2008
Australian National Stage of PCT

 

Selective Estrogen Receptor Modulators

3803.0020-004

 

Canada

 

2512000
12/25/03

 

Pending
Canadian National Stage of PCT

 

Selective Estrogen Receptor Modulators

3803.0020-002

 

Europe

 

EP 2003782904
 (1577288 A1-9/21/05)
12/25/03

 

Pending
European Regional Stage of PCT

 

Selective Estrogen Receptor Modulators

3803.0020-001

 

USA

 

US. Patent No. 7,612,114
11/158,245
(2006/0116364-6/1/06)
6/22/05

 

Granted
Continuation-in-Part of U.S. Designation of PCT

 

Selective Estrogen Receptor Modulators

 

164

--------------------------------------------------------------------------------

 

HBSR Reference
No.

 

Country

 

App.and/or Patent Number
(Pub. Number-Date) and
Filing Date

 

Status

 

Short Description

3803.0020-000

 

PCT

 

PCT/JP2003/016808
(12/25/03)
Publication No. WO 2004/058682
(7/15/04)

 

Expired

 

Selective Estrogen Receptor Modulators

3803.0020-005

 

India

 

2829/DELNP/2005
(12/25/2003)

 

Pending
Indian National Stage of PCT

 

Selective Estrogen Receptor Modulators

3803.0020-006

 

Australia

 

Div. of 2003292625 B2

 

Pending

 

Selective Estrogen Receptor Modulators

3803.0020-007

 

United States

 

Application No. 12/544,965
8/20/2009
Publication No. US2009/0325930
12/31/2009

 

Pending

 

Selective Estrogen Receptor Modulators

 

SARMS

 

A.            Owned by Radius

 

HBSR Docket No.

 

Application Number
and
Filing Date

 

Inventors

 

Status

 

Short Description

3803.1015-000
(US)

 

61/066,697
(02/22/08)

 

Chris P. Miller

 

Expired

 

Selective Androgen Receptor Modulators

3803.1015-001
(US)

 

61/132,353
(6/18/08)

 

Chris P. Miller

 

Expired

 

Selective Androgen Receptor Modulators

3803.1015-002
(US)

 

61/205,727
(1/21/09)

 

Chris P. Miller

 

Expired

 

Selective Androgen Receptor Modulators

3803.1015-003
(PCT)

 

PCT/US2009/001035
(2/19/09)

 

Chris P. Miller

 

Expired

 

Selective Androgen Receptor Modulators

3803.1015-004
(US)

 

12/378,812
(2/19/09)

 

Chris P. Miller

 

Pending

 

Selective Androgen Receptor Modulators

3803.1015-005
(US)

 

12/541,489
(8/14/09)

 

Chris P. Miller

 

Pending

 

Selective Androgen Receptor Modulators

 

165

--------------------------------------------------------------------------------

 

HBSR Docket No.

 

Application Number
and
Filing Date

 

Inventors

 

Status

 

Short Description

3803.1015-006
(US)

 

12/806,636
(8/17/10)

 

Chris P. Miller

 

Pending

 

Selective Androgen Receptor Modulators

3803.1015-007
(Australia)

 

2009215843
(2/19/09)

 

Chris P. Miller

 

Pending

 

Selective Androgen Receptor Modulators

3803.1015-008
(Brazil)

 

PI09078444
(2/19/09)

 

Chris P. Miller

 

Pending

 

Selective Androgen Receptor Modulators

3803.1015-009
(Canada)

 

2716320
(2/19/09)

 

Chris P. Miller

 

Pending

 

Selective Androgen Receptor Modulators

3803.1015-010
(Europe)

 

09712082.8
(2/19/09)

 

Chris P. Miller

 

Pending

 

Selective Androgen Receptor Modulators

3803.1015-011
(India)

 

6324DELNP2010
(2/19/09)

 

Chris P. Miller

 

Pending

 

Selective Androgen Receptor Modulators

3803.1015-012
(Japan)

 

2010547633
(2/19/09)

 

Chris P. Miller

 

Pending

 

Selective Androgen Receptor Modulators

3803.1015-013
(Mexico)

 

MXA2010009162
(2/19/09)

 

Chris P. Miller

 

Pending

 

Selective Androgen Receptor Modulators

 

HBSR Docket No.

 

Application Number
and
Filing Date

 

Inventors

 

Status

 

Short Description

3803.1019-000
(US)

 

61/212,399
(4/10/99)

 

Chris P. Miller

 

Expired

 

Selective Androgen Receptor Modulators

3803.1019-001
(PCT)

 

PCT/US2010/030480 (4/9/10)

 

Chris P. Miller

 

Pending

 

Published as
WO2010/118287 (10/14/10)

 

Selective Androgen Receptor Modulators

 

HBSR Docket No.

 

Application Number
and
Filing Date

 

Inventors

 

Status

 

Short Description

3803.1021-000
(US)

 

61/301,492
(2/4/10)

 

Chris P. Miller

 

Expired

 

Selective Androgen Receptor Modulators

3803.1021-001
(PCT)

 

PCT/US2011/023768 (2/4/11)

 

Chris P. Miller

 

Pending

 

Selective Androgen Receptor Modulators

 

166

--------------------------------------------------------------------------------

 

HBSR Docket No.

 

Application
Number and
Filing Date

 

Inventors

 

Status

 

Short Description

3803.1023-000
(US)

 

61/361,168
(7/2/10)

 

Chris P. Miller

 

Pending

 

Selective Androgen Receptor Modulators

 

HBSR Docket No.

 

Application
Number and
Filing Date

 

Inventors

 

Status

 

Short Description

3803.1024-000
(US)

 

61/387,440
(9/28/10)

 

Chris P. Miller

 

Pending

 

Selective Androgen Receptor Modulators

 

BaO58

 

A.            Jointly Owned by Radius and Ipsen

 

HBSR Docket No.

 

Application Number
and
Filing Date

 

Inventors

 

Status

 

Short Description

3803.1004-000
(US)

 

60/848,960
(10/3/06)

 

Michael J. Dey, Nathalie Mondoly, Benedice Rigaud, Bart Henderson and
Richard C. Lyttle

 

Expired

 

PTHrP Formulation

3803.1004-002
(PCT)

 

PCT/US2007/021216
(10/3/07)

 

Michael J. Dey, Nathalie Mondoly, Benedice Rigaud, Bart Henderson and
Richard C. Lyttle

 

Expired

 

PTHrP Formulation

3803.1004-003
(US)

 

12/151,975
(5/9/08)

 

Michael J. Dey, Nathalie Mondoly, Benedice Rigaud, Bart Henderson and
Richard C. Lyttle

 

Granted
US Patent No. 7,803,770
(9/28/10)

 

PTHrP Formulation

3803.1004-004
(Australia)

 

2007322334
(10/3/07)

 

Michael J. Dey, Nathalie Mondoly, Benedice Rigaud, Bart Henderson and
Richard C. Lyttle

 

Pending

 

PTHrP Formulation

 

167

--------------------------------------------------------------------------------

 

HBSR Docket No.

 

Application Number
and
Filing Date

 

Inventors

 

Status

 

Short Description

3803.1004-005
(Brazil)

 

PU07198213
(10/3/07)

 

Michael J. Dey, Nathalie Mondoly, Benedice Rigaud, Bart Henderson and
Richard C. Lyttle

 

Pending

 

PTHrP Formulation

3803.1004-006
(Canada)

 

2664734
(10/3/07)

 

Michael J. Dey, Nathalie Mondoly, Benedice Rigaud, Bart Henderson and
Richard C. Lyttle

 

Pending

 

PTHrP Formulation

3803.1004-007
(China)

 

200780037021.9
(10/3/07)

 

Michael J. Dey, Nathalie Mondoly, Benedice Rigaud, Bart Henderson and
Richard C. Lyttle

 

Pending

 

PTHrP Formulation

3803.1004-008
(Europe)

 

07870768.4
(10/3/07)

 

Michael J. Dey, Nathalie Mondoly, Benedice Rigaud, Bart Henderson and
Richard C. Lyttle

 

Pending

 

PTHrP Formulation

3803.1004-009
(India)

 

2340DELNP2009
(10/3/07)

 

Michael J. Dey, Nathalie Mondoly, Benedice Rigaud, Bart Henderson and
Richard C. Lyttle

 

Pending

 

PTHrP Formulation

3803.1004-010
(Israel)

 

197926
(10/3/07)

 

Michael J. Dey, Nathalie Mondoly, Benedice Rigaud, Bart Henderson and
Richard C. Lyttle

 

Pending

 

PTHrP Formulation

3803.1004-011
(Japan)

 

2009531434
(10/3/07)

 

Michael J. Dey, Nathalie Mondoly, Benedice Rigaud, Bart Henderson and
Richard C. Lyttle

 

Pending

 

PTHrP Formulation

3803.1004-012
(Korea)

 

1020097008736
(10/3/07)

 

Michael J. Dey, Nathalie Mondoly, Benedice Rigaud, Bart Henderson and
Richard C. Lyttle

 

Pending

 

PTHrP Formulation

3803.1004-013
(Mexico)

 

MXA2009003569
(10/3/07)

 

Michael J. Dey, Nathalie Mondoly, Benedice Rigaud, Bart Henderson and
Richard C. Lyttle

 

Pending

 

PTHrP Formulation

 

168

--------------------------------------------------------------------------------

 

HBSR Docket No.

 

Application Number
and
Filing Date

 

Inventors

 

Status

 

Short Description

3803.1004-014
(New Zealand)

 

576682
(10/3/07)

 

Michael J. Dey, Nathalie Mondoly, Benedice Rigaud, Bart Henderson and
Richard C. Lyttle

 

Pending

 

PTHrP Formulation

3803.1004-015
(Norway)

 

20091545
(10/3/07)

 

Michael J. Dey, Nathalie Mondoly, Benedice Rigaud, Bart Henderson and
Richard C. Lyttle

 

Pending

 

PTHrP Formulation

3803.1004-016
(Russian Federation)

 

2009116531
(10/3/07)

 

Michael J. Dey, Nathalie Mondoly, Benedice Rigaud, Bart Henderson and
Richard C. Lyttle

 

Pending

 

PTHrP Formulation

3803.1004-017
(Singapore)

 

2009922401
(10/3/07)

 

Michael J. Dey, Nathalie Mondoly, Benedice Rigaud, Bart Henderson and
Richard C. Lyttle

 

Pending

 

PTHrP Formulation

3803.1004-018
(Ukraine)

 

200904264
(10/3/07)

 

Michael J. Dey, Nathalie Mondoly, Benedice Rigaud, Bart Henderson and
Richard C. Lyttle

 

Pending

 

PTHrP Formulation

3803.1004-019
(US)

 

12/311,418
(10/3/07)

 

Michael J. Dey, Nathalie Mondoly, Benedice Rigaud, Bart Henderson and
Richard C. Lyttle

 

Pending

 

PTHrP Formulation

3803.1004-020
(PCT)

 

PCT/US2009/002868
(5/8/09)

 

Michael J. Dey, Nathalie Mondoly, Benedice Rigaud, Bart Henderson and
Richard C. Lyttle

 

Abandoned

 

PTHrP Formulation

3803.1004-021
(Hong Kong)

 

09109160.6
(10/2/09)

 

Michael J. Dey, Nathalie Mondoly, Benedice Rigaud, Bart Henderson and
Richard C. Lyttle

 

Pending

 

PTHrP Formulation

3803.1004-022
(US)

 

12/855,458
(8/12/10)

 

Michael J. Dey, Nathalie Mondoly, Benedice Rigaud, Bart Henderson and
Richard C. Lyttle

 

Pending

 

PTHrP Formulation

 

169

--------------------------------------------------------------------------------

 

B.            Licensed to Radius by Ipsen (BaO58)

 

Ipsen Reference No.

 

Country

 

Application Number
Filing Date and
Priority

 

Status

 

Short Description

038/US

 

USA

 

08/626,186
(03/29/96)

 

U.S. Patent 5,723,577
(03/03/98)
Expires 03/29/16

 

Analogs of PTH

038/US2

 

USA

 

08/779,768
(01/07/97)

 

U.S. Patent 5,969,095 (10/19/99)
Expires 3/29/16

 

Claims BA058

038/US/PCT2

 

PCT

 

PCT/US96/11292
(07/03/96)

 

Expired

 

Analogs of PTH

038/US/PCT2/EP

 

Europe

 

96924355.9
(01/30/98)

 

Regional Phase entry of
PCT/US96/11292

 

European Patent 0 847 278
(09/24/03)
Expires 07/03/16
Activation in AT, BE, CH, DE, DK, ES, FI, FR, Gb, GR, IE, IT, LI, LU, MC, NL,
PT, SE; Ext: AL, LT, LV, SI
Now Abandoned in AL, LT, LU, MC, SI, LV

 

Analogs of PTH

038/US/PCT2/EP-A

 

Europe

 

03077383.2
(07/30/03)

 

Divisional of
96924355.9

 

European Patent No.:1405861
Expires 7/3/2016

 

Activation in AT, BE, CH, DE, DK, ES, FI, FR, Gb, GR, IE, IT, LI, LU, MC, NL,
PT, SE

 

Analogs of PTH

038-EP-EPD[3]

 

Europe

 

10156965.5
(3/18/2010)

 

Pending

 

Analogs of PTH

038/US/PCT2/JP

 

Japan

 

9-505897
(07/03/96)

 

Regional Phase entry of
PCT/US96/11292

 

Pending
Published 8/17/1999

 

Analogs of PTH

 

170

--------------------------------------------------------------------------------

 

Ipsen Reference No.

 

Country

 

Application Number
Filing Date and
Priority

 

Status

 

Short Description

038/US/PCT2/JP-A

 

Japan

 

008027/03
(01/16/03)
Divisional of 9-505897

 

Patent No. 4008825
Granted 08/23/07
Expires 7/3/2016

 

Analogs of PTH

038/US/PCT2/AU

 

Australia

 

64834/96
(07/03/96)

 

Regional Phase entry of
PCT/US96/11292

 

Patent No. 707094
(07/01/99)
Expires 07/03/16

 

Analogs of PTH

038/US/PCT2/CA

 

Canada

 

2,226,177
(07/03/96)

 

Regional Phase entry of
PCT/US96/11292

 

Patent No.:2,226,177

 

Expires 7/3/2016

 

Analogs of PTH

038/US/PCT2/CN

 

China

 

96196926.1
(07/03/96)

 

Regional Phase entry of
PCT/US96/11292

 

Patent No. ZL96 196926.1
(2/25/06)
Expires 07/03/16

 

Analogs of PTH

038/US/PCT2/CN-A

 

China

 

200410005427.2
(07/03/96)

 

Divisional of
96196926.1

 

Patent No.. ZL200410005427.7
(8/20/02)
Expires 07/03/16

 

Analogs of PTH

038/US/PCT2/CN-C

 

China

 

2006 10100113.4
(7/21/06)

 

Divisional of
2004 10005427.7

 

Patent No.: ZL200610100113

 

Expires 7/3/2016

 

Analogs of PTH

038-CN-DIV[4]

 

China

 

20100150544.8

 

Pending

 

Analogs of PTH

038/US/PCT2/CN-HK

 

Hong Kong

 

99100132.1
(01/13/99)
Registration in Hong Kong of 961 96926.1

 

Patent No. 1 014 876
Expires 07/03/16

 

Analogs of PTH

 

171

--------------------------------------------------------------------------------

 

Ipsen Reference No.

 

Country

 

Application Number
Filing Date and
Priority

 

Status

 

Short Description

038/US/PCT2/HU

 

Hungary

 

P9901718
(07/03/96)

 

Regional Phase entry of
PCT/US96/11292

 

Patent No.: 226935

 

Expires 7/3/2016

 

Analogs of PTH

038/US/PCT2/IL

 

Israel

 

122837
(07/03/96

 

Regional Phase entry of
PCT/US96/11292

 

Patent No. 122837
(02/11/03)
Expires 07/03/16

 

Analogs of PTH

038/US/PCT2/KR

 

Korea

 

1998-0700249
(07/03/96)

 

Regional Phase entry of
PCT/US96/11292

 

Patent No. 0500853
(07/04/05)
Expires 07/03/16

 

Analogs of PTH

038/US/PCT2/KR-A

 

Korea

 

2004-706338
(04/28/04)
Divisional of 1998-0700249

 

Patent No. 0563600
(3/16/06)
Expires 07/03/16

 

Analogs of PTH

038/US/PCT2/KR-B

 

Korea

 

2004-706339
(04/28/04)
Divisional of 1998-0700249

 

Patent No. 0563601
(3/16/06)
Expires 07/03/16

 

Analogs of PTH

038/US/PCT2/KR-C

 

Korea

 

2004-706340
(04/28/04)
Divisional of 1998-0700249

 

Patent No. 0563602
(3/16/06)
Expires 07/03/16

 

Analogs of PTH

038/US/PCT2/KR-D

 

Korea

 

2004-706341
(04/28/04)
Divisional of 1998-0700249

 

Patent No. 0563112
(3/15/06)
Expires 07/03/16

 

Analogs of PTH

038/US/PCT2/MX

 

Mexico

 

PA/a/1998/000418
(07/03/96)

 

Regional Phase entry of
PCT/US96/11292

 

Patent No. 222317
(08/26/04)
Expires 07/03/16

 

Analogs of PTH

 

172

--------------------------------------------------------------------------------

 

Ipsen Reference No.

 

Country

 

Application Number
Filing Date and
Priority

 

Status

 

Short Description

038/US/PCT2/NZ

 

New Zealand

 

312899
(01/20/98)

 

Regional Phase entry of
PCT/US96/11292

 

Patent No. 312899
(02/08/00)
Expires 07/03/16

 

Analogs of PTH

038/US/PCT2/PL

 

Poland

 

P.325905
(01/12/98)

 

Regional Phase entry of
PCT/US96/11292

 

Patent No. 186710
(08/07/03)
Expires 07/03/16

 

Analogs of PTH

*038/US/PCT2/RU

 

Russia

 

98/102406
(7/3/96)

 

Patent No. 2,157,699
(10/20/00)

 

Analogs of PTH

*038/US/PCT2/SG

 

Singapore

 

9706046.1
(7/3/96)

 

Patent No. P-51260
(10/16/01)

 

Analogs of PTH

*038/US/TW

 

Taiwan

 

85108390
(07/11/96)

 

Patent No. 153897
(08/07/02)

 

Analogs of PTH

038/US3

 

USA

 

08/813,534
(03/07/97)

 

Patent No. 5,955,574
(09/21/99)
Expires 03/29/16

 

Analogs of PTH

038/US3/PCT2

 

PCT

 

PCT/US97/22498
(12/08/97)

 

Expired

 

Analogs of PTH

038/US3/PCT2/US2

 

USA

 

09/399,499
(09/20/99)

 

Patent No. 6,544,949
(04/08/03)
Expires 03/29/16

 

Claims a method of treating osteoporosis with BA058 and a pharmaceutical
composition including BA058

038/US3/PCT2/US2-A

 

USA

 

10/289,519
(11/06/02)

 

Patent No. 6,921,750
(07/26/05)
Expires 03/29/16
Reissue Application filed 9/16/06
Application No. 11/523,812

 

Analogs of PTH

 

173

--------------------------------------------------------------------------------

 

Ipsen Reference No.

 

Country

 

Application Number
Filing Date and
Priority

 

Status

 

Short Description

038/US3/PCT2/US2-B

 

USA

 

11/094,662
(03/30/05)

 

Patent No. 7632811

 

Expires 9/6/2019

 

Analogs of PTH

038/US3/PCT2/EP

 

Europe

 

97951595.4
(12/08/97)
National Stage of PCT/US97/22498
(12/08/97)

 

Patent No. EP0948541
(03/29/06)
Expires 12/08/17

 

Activation in: AT, BE, CH, LI, DE, DK, ES, FI, FR, GB, GR, IE, IT, LU, MC, NL,
PT, SE;
Extension States: AL, LT, LV, MK, RO and SI
Now Abandoned in AL, LT, LU, MK, MC, RO, SI

 

Analogs of PTH

038/US3/PCT2/EP-A

 

Europe

 

05026436.5
(12/12/05)

 

Divisional of EP 97951595.4

 

European Patent No. 1645566

 

Expires 12/8/2017

 

Activation in: AT, BE, CH, DE, DK, ES, FI, FR, GB, GR, IE, IT, NL, PT, SE

 

Analogs of PTH

038/US3/PCT2/JP

 

Japan

 

10-530865
(12/08/97)
National Stage of PCT/US97/22498
(12/08/97)

 

Patent No. 3963482
06/01/07
Expires 12/08/17

 

Analogs of PTH

038/US3/PCT2/AU

 

Australia

 

55199/98
(12/08/97)
National Stage of PCT/US97/22498
(12/08/97)

 

Patent No. 741584
(03/21/02)
Expires 12/08/17

 

Analogs of PTH

038/US3/PCT2/CA

 

Canada

 

2,276,614
(12/08/97)
National Stage of PCT/US97/22498
(12/08/97)

 

Patent No. 2,276,614
(06/11/02)
Expires 12/08/17

 

Analogs of PTH

 

174

--------------------------------------------------------------------------------

 

Ipsen Reference No.

 

Country

 

Application Number
Filing Date and
Priority

 

Status

 

Short Description

038/US3/PCT2/CN

 

China

 

97181915.7
(12/08/97)
National Stage of PCT/US97/22498
(12/08/97)

 

Patent No. ZL97181915.7
(02/11/04)
Expires 12/08/17

 

Analogs of PTH

038/US3/PCT2/CN-HK

 

Hong Kong

 

00105467.3
(12/08/00)
Registration of 97181915.7

 

1026215
(07/09/04)
Expires 12/08/17

 

Analogs of PTH

038/US3/PCT2/CZ

 

Czech Republic

 

PV 1999-2398
(12/08/97)
National Stage of PCT/US97/22498
(12/08/97)

 

Patent No.298937
(02/06/08)
Expires 12/08/17

 

Analogs of PTH

038/US3/PCT2/CZ-A

 

Czech Republic

 

PV2005-594
(9/16/05)

 

Divisional of
PV 2398-99

 

Pending

 

Analogs of PTH

038/US3/PCT2/HU

 

Hungary

 

P9904596
(12/08/97)
National Stage of PCT/US97/22498
(12/08/97)

 

Pending
Published
6/28/2000

 

Analogs of PTH

038/US3/PCT2/HU-A

 

Hungary

 

P0600009
(1/11/06)

 

Divisional of
HU P 99 04596

 

Pending
Published 01/26/2006

 

Analogs of PTH

038/US3/PCT2/IL

 

Israel

 

130794
(12/08/07)
National Stage of PCT/US97/22498
(12/08/97)

 

Patent No.130794
(07/03/06)
Expires 12/08/17

 

Analogs of PTH

 

175

--------------------------------------------------------------------------------

 

Ipsen Reference No.

 

Country

 

Application Number
Filing Date and
Priority

 

Status

 

Short Description

038/US3/PCT2/IN

 

India

 

7/MAS/98
(12/08/97)
National Stage of PCT/US97/22498
(12/08/97)

 

Patent No. 228906

 

Expires 1/1/2018

 

Analogs of PTH

038/US3/PCT2/IN-A

 

India

 

63/CHE/2008
 (01/08/08)
Divisional of 7/MAS/98

 

Pending

 

Analogs of PTH

038/US3/PCT2/IN-B

 

India

 

456/CHE/2008
(02/22/08)
Divisional of 7/MAS/98

 

Pending

 

Analogs of PTH

038/US3/PCT2/KR

 

Korea

 

1999-7006165
(12/08/97)
National Stage of PCT/US97/22498
(12/08/97)

 

Patent No. 0497709
(06/17/05)
Expires 12/08/17

 

Analogs of PTH

038/US3/PCT2/KR-A

 

Korea

 

2005-7003295
(2/25/05)

 

Divisional of
KR 1999-7006165

 

Patent No. 0699422
(3/19/07)
Expires 12/08/17

 

Analogs of PTH

038/US3/PCT2/MX

 

Mexico

 

Pa/a/1999/006387
(12/08/97)

 

Patent No. 222316
(08/26/04)
Expires 12/08/17

 

Analogs of PTH

038/US3/PCT2/NZ

 

New Zealand

 

336610
(12/08/97)
National Stage of PCT/US97/22498
(12/08/97)

 

Patent No. 336610
(11/09/01)
Expires 12/08/17

 

Analogs of PTH

038/US3/PCT2/PL

 

Poland

 

P-334438
(12/08/97)
National Stage of PCT/US97/22498
(12/08/97)

 

Patent No. 191898
(2/15/06)
Expires 12/08/17

 

Analogs of PTH

 

176

--------------------------------------------------------------------------------

 

Ipsen Reference No.

 

Country

 

Application Number
Filing Date and
Priority

 

Status

 

Short Description

038/US3/PCT2/PL-A

 

Poland

 

P.370525
(10/04/04)
Divisional of P.33438

 

Patent No. 191239
(09/03/07)
Expires 12/08/17

 

Analogs of PTH

038/US3/PCT2/RU

 

Russia

 

99117145
(12/08/97)
National Stage of PCT/US97/22498
(12/08/97)

 

Patent No. 2,198,182
(02/10/03)
Expires 12/08/17

 

Analogs of PTH

038/US3/PCT2/SG

 

Singapore

 

9903165.0
(12/08/97)
National Stage of PCT/US97/22498
(12/08/97)

 

Patent No. 66567
(07/18/00)
Expires 12/08/17

 

Analogs of PTH

038/US2/US3/TW

 

Taiwan

 

87100028
(01/02/98)

 

Patent No. 156542
(06/01/02)
Expires 01/02/18

 

Analogs of PTH

038/US/PCT2/CN-C/HK

 

HK

 

Filing 07103960.3
4/16/2007

 

Patent No. HK1096976
Expires 7/3/2016

 

Analogs of PTH

038/US3/PCT2/US2-C

 

US

 

Filing 11/684,383
3/09/2007

 

Patent No. 7,410,948
(8/12/08)
Expires 03/29/16

 

Analogs of PTH

 

B.            Jointly Owned by Radius and 3M

 

HBSR Docket No.

 

Application Number
and
Filing Date

 

Inventors

 

Status

 

Short Description

3803.1025-000
(US)

 

61/478,466
(4/22/2011)

 

Gary Hattersley, Kris J. Hansen, Amy S. Determan

 

Pending

 

Method of drug delivery for PTH, PTHrP, and related peptides.

 

177

--------------------------------------------------------------------------------

 

Schedule 5.12(b)

 

Intellectual Property

 

1.              See items listed as “Jointly Owned” or “Licensed to Radius” in
Item 3 of Schedule 5.12(a).

 

2.              Certain rights licensed to 3M pursuant to that certain
Development and Clinical Supplies Agreement with 3M dated June 19, 2009.

 

178

--------------------------------------------------------------------------------

 

Schedule 5.12(c)

 

Intellectual Property

 

1.              See items listed as “Jointly Owned” or “Licensed to Radius” in
Item 3 of Schedule 5.12(a).

 

2.              Certain rights licensed to 3M pursuant to that certain
Development and Clinical Supplies Agreement with 3M dated June 19, 2009.

 

179

--------------------------------------------------------------------------------

 

Schedule 5.12(e)

 

Intellectual Property

 

None.

 

180

--------------------------------------------------------------------------------

 

Schedule 5.12(f)

 

Intellectual Property

 

1.              See items listed as “Jointly Owned” or “Licensed to Radius” in
Item 3 of Schedule 5.12(a).

 

2.              Certain rights licensed to 3M pursuant to that certain
Development and Clinical Supplies Agreement with 3M dated June 19, 2009.

 

181

--------------------------------------------------------------------------------

 

Schedule 5.12(g)

 

Intellectual Property

 

1.              See items listed as “Jointly Owned” or “Licensed to Radius” in
Item 3 of Schedule 5.12(a).

 

2.              Certain rights licensed to the Corporation pursuant to that
certain Development and Clinical Supplies Agreement with 3M dated June 19, 2009.

 

182

--------------------------------------------------------------------------------

 

Schedule 5.12(h)

 

Intellectual Property

 

None.

 

183

--------------------------------------------------------------------------------

 

Schedule 5.12(i)

 

Intellectual Property

 

None.

 

184

--------------------------------------------------------------------------------

 

Schedule 5.14(a)

 

Title to Properties

 

None.

 

185

--------------------------------------------------------------------------------

 

Schedule 5.14(b)

 

Title to Properties

 

1.              Sublease by and between the Corporation and Sonos, Inc., dated
January 14, 2011, for the property located at 201 Broadway, Cambridge,
Massachusetts.

 

186

--------------------------------------------------------------------------------

 

Schedule 5.15

 

Investments in Other Persons

 

1.              Demand Promissory Note issued by MPM Acquisition Corp. to the
Corporation, dated November 22, 2010.

 

187

--------------------------------------------------------------------------------

 

Schedule 5.16

 

ERISA

 

1.              Radius Health, Inc. 401(k) Plan

 

2.              Radius Health, Inc. Flexible Spending Account Plan

 

188

--------------------------------------------------------------------------------

 

Schedule 5.17

 

Use of Proceeds

 

1.              The Corporation anticipates using the net proceeds from the sale
of the Series A-1 Preferred Stock to complete enrollment of the Phase 3 study of
the subcutaneous form of the Corporation’s product candidate BA058 (PTHrP
analog), complete the Phase 1b study of the transdermal form of BA058, bolster
the Corporation’s balance sheet to improve negotiation leverage with  potential
partners, and to complete a reverse merger with a publicly reporting Form 10
shell enabling the Corporation to eventually become publicly traded and listed
on a national securities exchange such as Nasdaq.  The amounts actually expended
by the Corporation for the above purposes may vary significantly depending on
numerous factors, including future revenue growth, if any, the progress of the
Corporation’s research and development efforts and technological advances and
hence, the Corporation’s management will retain broad discretion in the
allocation of the net proceeds from the Series A-1 Preferred Stock.

 

189

--------------------------------------------------------------------------------

 

Schedule 5.18

 

Permits and Other Rights; Compliance with Laws

 

None.

 

190

--------------------------------------------------------------------------------

 

Schedule 5.19

 

Insurance

 

COVERAGE AND LIMITS

 

INSURANCE COMPANY

 

POLICY NUMBER

 

TERM

 

PREMIUM

COMMERCIAL PACKAGE

 

Travelers Property Casualty Co. of AME

 

6305876P819

 

01/30/2011 - 01/30/2012

 

$5,598.00

 

 

 

 

 

 

 

 

 

PROPERTY

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Replacement Cost Valuation on Personal Property

 

 

 

 

 

 

 

 

Special Form Causes of Loss including Equipment Breakdown

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Scheduled Location

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

201 Broadway

 

 

 

 

 

 

 

 

Cambridge , MA 02139

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Limits

 

 

 

 

 

 

 

 

 

Business Personal Property

$1,050,000

 

 

 

 

 

 

 

 

Business Income/Extra Expense

$250,000

 

 

 

 

 

 

 

 

Property at Unscheduled Location

$50,000

 

 

 

 

 

 

 

 

Property in Transit

$50,000

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Deductibles

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Property

$2,500

 

 

 

 

 

 

 

 

Business Income Waiting Period

24 Hours

 

 

 

 

 

 

 

 

 

191

--------------------------------------------------------------------------------

 

COVERAGE AND LIMITS

 

INSURANCE COMPANY

 

POLICY NUMBER

 

TERM

 

PREMIUM

COMMERCIAL PACKAGE

 

Travelers Property Casualty Co. of AME

 

6305876P819

 

01/30/2011 - 01/30/2012

 

$5,598.00

 

 

 

 

 

 

 

 

 

GENERAL LIABILITY

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

General Aggregate Limit

$2,000,000

 

 

 

 

 

 

 

 

Products/Completed Operations Aggregate

Excluded

 

 

 

 

 

 

 

 

Each Occurrence Limit

$1,000,000

 

 

 

 

 

 

 

 

Advertising Injury and Personal Injury Limit

$1,000,000

 

 

 

 

 

 

 

 

Premises Damage

$300,000

 

 

 

 

 

 

 

 

Medical Expense

$10,000

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

EMPLOYEE BENEFITS LIABILITY (CLAIMS-MADE)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Each Claim Limit

$1,000,000

 

 

 

 

 

 

 

 

Aggregate Limit

$3,000,000

 

 

 

 

 

 

 

 

Deductible

$0

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

COVERAGE AND LIMITS

 

INSURANCE COMPANY

 

POLICY NUMBER

 

TERM

 

PREMIUM

FOREIGN PACKAGE

 

Travelers Property Casualty Co. of AME

 

TE06904263

 

01/30/2011 - 01/30/2012

 

$2,500.00

 

 

 

 

 

 

 

 

 

INTERNATIONAL GENERAL LIABILITY

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

General Aggregate Limit

$2,000,000

 

 

 

 

 

 

 

 

Products/Completed Operations Aggregate

Excluded

 

 

 

 

 

 

 

 

Each Occurrence Limit

$1,000,000

 

 

 

 

 

 

 

 

Advertising Injury and Personal Injury Limit

$1,000,000

 

 

 

 

 

 

 

 

Premises Damage

$300,000

 

 

 

 

 

 

 

 

Medical Expense

$10,000

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

INTERNATIONAL AUTOMBOBILE

 

HIRED & NON-OWNED AUTO LIABILITY – EXCESS/DIC

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Combined Single Limit for Bodily Injury and/or Property Damage

$1,000,000

 

 

 

 

 

 

 

 

 

192

--------------------------------------------------------------------------------

 

 

COVERAGE AND LIMITS

 

INSURANCE COMPANY

 

POLICY NUMBER

 

TERM

 

PREMIUM

FOREIGN PACKAGE

 

 

Travelers Property Casualty Co. of AME

 

TE06904263

 

01/30/2011  - 01/30/2012

 

$2,500.00

 

 

 

 

 

 

 

 

 

 

Medical Payments

$10,000

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

COVERAGE AND LIMITS

 

INSURANCE COMPANY

 

POLICY NUMBER

 

TERM

 

PREMIUM

FOREIGN PACKAGE

 

Travelers Property Casualty Co. of AME

 

TE06904263

 

01/30/2011  - 01/30/2012

 

$2,500.00

 

 

 

 

 

 

 

 

 

 

FOREIGN VOLUNTARY WORKERS’ COMPENSATION

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Description of Covered Employees

 

 

 

 

 

 

 

 

 

International Executive Employees -

State of Hire Benefits

 

 

 

 

 

 

 

 

Other International Employees -

Country of Origin Benefits

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

EMPLOYER’S LIABILITY

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Limits of Liability

 

 

 

 

 

 

 

 

 

Bodily Injury by Accident (Each Accident)

$1,000,000

 

 

 

 

 

 

 

 

Bodily Injury by Disease (Aggregate)

$1,000,000

 

 

 

 

 

 

 

 

Bodily Injury by Disease (Each Employee)

$1,000,000

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Coverage Extensions

 

 

 

 

 

 

 

 

 

Repatriation/Transportation - Each Person

$25,000

 

 

 

 

 

 

 

 

Repatriation/Transportation - Aggregate

$50,000

 

 

 

 

 

 

 

 

 

193

--------------------------------------------------------------------------------

 

 

COVERAGE AND LIMITS

 

INSURANCE COMPANY

 

POLICY NUMBER

 

TERM

 

PREMIUM

COMMERCIAL AUTOMOBILE

 

Charter Oak Fire Ins. Co.

 

BA5881P281

 

01/30/2011  - 01/30/2012

 

$683.00

 

 

 

 

 

 

 

 

 

HIRED & NON-OWNED AUTO LIABILITY

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Combined Single Limit for Bodily Injury and/or Property Damage

$1,000,000

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

HIRED CAR PHYSICAL DAMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Limit

Actual Cash Value

 

 

 

 

 

 

 

 

Comprehensive Deductible

$0

 

 

 

 

 

 

 

 

Collision Deductible

$500

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

COVERAGE AND LIMITS

 

INSURANCE COMPANY

 

POLICY NUMBER

 

TERM

 

PREMIUM

WORKERS’ COMPENSATION

 

Charter Oak Fire Ins. Co.

 

UB9485C327

 

01/30/2011  - 01/30/2012

 

$4,040.00

Subject to Audit

COVERAGE A –

WORKERS’ COMPENSATION

 

 

 

 

 

 

 

 

 

Statutory in MA

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

COVERAGE B –

EMPLOYER’S LIABILITY

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Bodily Injury by Accident (Each Accident)

$500,000

 

 

 

 

 

 

 

 

Bodily Injury by Disease (Aggregate)

$500,000

 

 

 

 

 

 

 

 

Bodily Injury by Disease (Each Employee)

$500,000

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

COVERAGE C –

OTHER STATES except

 

 

 

 

 

 

 

 

 

ND, OH, WA, WY & those listed in Coverage A

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Note:

Coverage C has limitations.  Please contact WGA if you begin operations in any
state not listed under Coverage A.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Based on estimated payroll as follows:

 

 

 

 

 

 

 

 

 

194

--------------------------------------------------------------------------------

 

 

COVERAGE AND LIMITS

 

INSURANCE COMPANY

 

POLICY NUMBER

 

TERM

 

PREMIUM

WORKERS’ COMPENSATION

 

Charter Oak Fire Ins. Co.

 

UB9485C327

 

01/30/2011  - 01/30/2012

 

$4,040.00

Subject to Audit

MA

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Class Code

Class Description

Payroll

 

 

 

 

 

 

 

 

8810

Clerical Office Employees NOC

$1,300,000

 

 

 

 

 

 

 

 

4512

Biomedical Research Laboratories

$1,400,000

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

COVERAGE AND LIMITS

 

INSURANCE COMPANY

 

POLICY NUMBER

 

TERM

 

PREMIUM

COMMERCIAL UMBRELLA

 

St. Paul Fire & Marine Insurance Co.

 

TE06904241

 

01/30/2011  - 01/30/2012

 

$4,004.00

 

 

 

 

 

 

 

 

 

 

LIMITS OF LIABILITY

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Per Occurrence

$5,000,000

 

 

 

 

 

 

 

 

General Aggregate

$5,000,000

 

 

 

 

 

 

 

 

Self-Insured Retention

$10,000

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Underlying Coverages

Domestic General Liability

Domestic Employee Benefits Liability

Domestic Employer’s Liability

Domestic Automobile Liability

Foreign General Liability

Foreign Employer’s Liability

Foreign Automobile Liability

 

 

 

 

 

 

 

 

 

 

195

--------------------------------------------------------------------------------

 

 

COVERAGE AND LIMITS

 

INSURANCE COMPANY

 

POLICY NUMBER

 

TERM

 

PREMIUM

PRODUCTS LIABILITY

 

Federal Insurance Company

 

35854927

 

01/30/2011  - 01/30/2012

 

$55,500.00

 

 

 

 

 

 

 

 

 

 

LIMITS OF LIABILITY

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Aggregate Limit

$10,000,000

 

 

 

 

 

 

 

 

Each Occurrence Limit

$10,000,000

 

 

 

 

 

 

 

 

Deductible – Each Event

$25,000

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Retroactive Dates:

 

 

 

 

 

 

 

 

 

$5,000,000

1/20/2006

 

 

 

 

 

 

 

 

$5,000,000 excess of $5,000,000

7/17/2008

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Rated on Number of Participant

2,448

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Claims-Made Coverage

Defense Costs included in Limit of Liability

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

COVERAGE AND LIMITS

 

INSURANCE COMPANY

 

POLICY NUMBER

 

TERM

 

PREMIUM

WORLD WIDE TRANSIT

 

Allianz Global Corporate Specialty-AGCS

 

OC91225900

 

03/25/2011  - 03/25/2012

 

$16,600.00

 

 

 

 

 

 

 

 

 

 

Transit Limits

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Any One Vessel/Connecting Conveyance

$1,200,000

 

 

 

 

 

 

 

 

Any One Aircraft/Connecting Conveyance

$1,200,000

 

 

 

 

 

 

 

 

Any One Inland Conveyance

$1,200,000

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Deductible

$2,500

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Storage Limits

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Aptuit

$8,500,000

 

 

 

 

 

 

 

 

12 Clinical Sites

$3,200,000

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Deductible

$5,000

 

 

 

 

 

 

 

 

 

--------------------------------------------------------------------------------

* No Single Location to exceed $1,100,000

 

196

--------------------------------------------------------------------------------

 

 

COVERAGE AND LIMITS

 

INSURANCE COMPANY

 

POLICY NUMBER

 

TERM

 

PREMIUM

MANAGEMENT LIABILITY

 

Federal Insurance Company

 

82108432

 

10/08/2010  - 10/08/2011

 

$23,445.00

 

 

 

 

 

 

 

 

 

 

DIRECTORS’ & OFFICERS’ LIABILITY

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Maximum Aggregate Limit

$5,000,000

 

 

 

 

 

 

 

 

Dedicated Limit for Executives

$500,000

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Deductibles:

 

 

 

 

 

 

 

 

 

Non-Indemnified Loss

$0

 

 

 

 

 

 

 

 

Indemnified Loss

$25,000

 

 

 

 

 

 

 

 

Company Loss

$25,000

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Prior & Pending Litigation Date

4/29/2005

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Claims-Made Coverage

Defense Costs included in Limit of Liability

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

COVERAGE AND LIMITS

 

INSURANCE COMPANY

 

POLICY NUMBER

 

TERM

 

PREMIUM

MANAGEMENT LIABILITY

 

Federal Insurance Company

 

82108432

 

10/08/2010  - 10/08/2011

 

$23,445.00

 

 

 

 

 

 

 

 

 

 

EMPLOYMENT PRACTICES LIABILITY

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Maximum Aggregate Limit

$5,000,000

 

 

 

 

 

 

 

 

Third Party Liability Limit

$5,000,000

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Deductibles:

 

 

 

 

 

 

 

 

 

EPL

$5,000

 

 

 

 

 

 

 

 

 

197

--------------------------------------------------------------------------------

 

COVERAGE AND LIMITS

 

INSURANCE COMPANY

 

POLICY NUMBER

 

TERM

 

PREMIUM

MANAGEMENT LIABILITY

 

Federal Insurance Company

 

82108432

 

10/08/2010  - 10/08/2011

 

$23,445.00

 

 

 

 

 

 

 

 

 

 

Third Party

$5,000

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

  Prior & Pending Litigation Date

4/29/2005

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Claims-Made Coverage

Defense Costs included in Limit of Liability

 

FIDUCIARY LIABILITY

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Maximum Aggregate Limit

$1,000,000

 

 

 

 

 

 

 

 

Deductible

$0

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Prior & Pending Litigation Date

4/29/2005

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Claims-Made Coverage

Defense Costs included in Limit of Liability

 

KIDNAP & RANSOM COVERAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Kidnapping and Extortion Threat

$1,000,000

 

 

 

 

 

 

 

 

Custody

$1,000,000

 

 

 

 

 

 

 

 

Expense

$1,000,000

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Accidental Loss

$1,000,000

 

 

 

 

 

 

 

 

(i) Loss of Life

$1,000,000

 

 

 

 

 

 

 

 

(ii) Mutilation

25%

 

 

 

 

 

 

 

 

(iii) All other

100%

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Legal Liability Costs

$1,000,000

 

 

 

 

 

 

 

 

Emergency Political Repatriation

$500,000

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

COVERAGE AND LIMITS

 

INSURANCE COMPANY

 

POLICY NUMBER

 

TERM

 

PREMIUM

DENMARK – FOREIGN CLINICAL TRIAL

 

Newline

 

59001710A188

 

10/14/2010 - 10/14/2013

 

$45,000

(plus 14% tax)

Policy Limit

€5,000,000

 

 

 

 

 

 

 

 

Deductible

€1,500

 

 

 

 

 

 

 

 

 

198

--------------------------------------------------------------------------------

 

COVERAGE AND LIMITS

 

INSURANCE COMPANY

 

POLICY NUMBER

 

TERM

 

PREMIUM

DENMARK – FOREIGN CLINICAL TRIAL

 

Newline

 

59001710A188

 

10/14/2010 – 10/14/2013

 

$45,000

(plus 14% tax)

Number of Subjects

750

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

COVERAGE AND LIMITS

 

INSURANCE COMPANY

 

POLICY NUMBER

 

TERM

 

PREMIUM

CZECH REPUBLIC – FOREIGN CLINICAL TRIAL

 

Newline

 

59001710A187

 

10/19/2010 – 10/19/2013

 

$21,375

 

 

 

 

 

 

 

 

 

 

Policy Limit

€2,500,000

 

 

 

 

 

 

 

 

Policy Sublimit

€250,000

 

 

 

 

 

 

 

 

Deductible

€0

 

 

 

 

 

 

 

 

Number of Subjects

225

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

COVERAGE AND LIMITS

 

INSURANCE COMPANY

 

POLICY NUMBER

 

TERM

 

PREMIUM

ESTONIA – FOREIGN CLINICAL TRIAL

 

QBE Syndicate 1886

 

10ME222515KA076

 

10/19/2010 – 10/19/2013

 

$17,750

 

 

 

 

 

 

 

 

 

 

Policy Limit

€5,000,000

 

 

 

 

 

 

 

 

Deductible

€1,500

 

 

 

 

 

 

 

 

Number of Subjects

175

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

COVERAGE AND LIMITS

 

INSURANCE COMPANY

 

POLICY NUMBER

 

TERM

 

PREMIUM

LITHUANIA – FOREIGN CLINICAL TRIAL

 

QBE Syndicate 1886

 

10ME222515KA077

 

10/19/2010 – 10/19/2013

 

$17,750

 

 

 

 

 

 

 

 

 

 

Policy Limit

17,500,000 LTL

 

 

 

 

 

 

 

 

Policy Sublimit

100,000 LTL

 

 

 

 

 

 

 

 

Deductible

€1,500

 

 

 

 

 

 

 

 

Number of Subjects

175

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

COVERAGE AND LIMITS

 

INSURANCE COMPANY

 

POLICY NUMBER

 

TERM

 

PREMIUM

POLAND – FOREIGN CLINICAL TRIAL

 

QBE Syndicate 1886

 

10ME222515KA078

 

10/19/2010 – 10/19/2013

 

$17,750

 

 

 

 

 

 

 

 

 

 

Policy Limit

€5,000,000

 

 

 

 

 

 

 

 

Deductible

€0

 

 

 

 

 

 

 

 

Number of Subjects

150

 

 

 

 

 

 

 

 

 

199

--------------------------------------------------------------------------------

 

COVERAGE AND LIMITS

 

INSURANCE COMPANY

 

POLICY NUMBER

 

TERM

 

PREMIUM

LITHUANIA – FOREIGN CLINICAL TRIAL

 

QBE Syndicate 1886

 

10ME222515KA077

 

10/19/2010 – 10/19/2013

 

$17,750

 

 

 

 

 

 

 

 

 

COVERAGE AND LIMITS

 

INSURANCE COMPANY

 

POLICY NUMBER

 

TERM

 

PREMIUM

ROMANIA – FOREIGN CLINICAL TRIAL

 

Newline

 

59001710A189

 

10/19/2010 – 10/19/2013

 

$14,000

 

 

 

 

 

 

 

 

 

 

Policy Limit

€5,000,000

 

 

 

 

 

 

 

 

Deductible

€1,500

 

 

 

 

 

 

 

 

Number of Subjects

125

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

COVERAGE AND LIMITS

 

INSURANCE COMPANY

 

POLICY NUMBER

 

TERM

 

PREMIUM

BRAZIL – FOREIGN CLINICAL TRIAL

 

HDI-Gerling

 

39001162602140

 

10/20/2010 – 10/20/2013

 

$33,000

 

 

 

 

 

 

 

 

 

 

Policy Limit

$1,000,000

 

 

 

 

 

 

 

 

Deductible

$10,000

 

 

 

 

 

 

 

 

Number of Subjects

400

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

COVERAGE AND LIMITS

 

INSURANCE COMPANY

 

POLICY NUMBER

 

TERM

 

PREMIUM

HONG KONG – FOREIGN CLINICAL TRIAL

 

HDI-Gerling

 

16000000245983

 

10/20/2010 – 10/20/2013

 

297,400 HKD

 

 

 

 

 

 

 

 

 

 

Policy Limit

20,000,000 HKD

 

 

 

 

 

 

 

 

Policy Sublimit

10,000,000 HKD

 

 

 

 

 

 

 

 

Deductible

50,000 HKD

 

 

 

 

 

 

 

 

Number of Subjects

400

 

 

 

 

 

 

 

 

 

--------------------------------------------------------------------------------

* All Foreign Clinical Trial premiums are subject to audit at expiration.

 

200

--------------------------------------------------------------------------------

 

 

Schedule 5.20

 

Board of Directors

 

1.              The Corporation has agreed pursuant to that certain Term Sheet
dated March 31, 2011, to allocate four of the seven seats on the Board of
Directors to certain of the Investors listed in Schedule I to the Purchase
Agreement.

 

2.              The Corporation has agreed, in Article III, Section A.6(b) of
its Fourth Amended and Restated Certificate of Incorporation, filed with the
Secretary of State of the State of Delaware on May 17, 2011, to allocate four of
the seven seats on the Board of Directors to certain of the Investors listed in
Schedule I to the Purchase Agreement.

 

201

--------------------------------------------------------------------------------

 

Schedule 5.22(a)

 

Environmental Matters

 

None.

 

202

--------------------------------------------------------------------------------

 

Schedule 5.22(d)

 

Environmental Matters

 

1.         The following chemicals, radioactive materials, or other potentially
harmful materials or substances were present or used on the Property at 300
Technology Square, Cambridge, Massachusetts 02139, which is no longer occupied
by the Corporation:

 

Less than 10 liters

 

Less than 1 liter

 

Less than 1 kg

 

Less than 10g

Acetone

 

acetic acid

 

4-C2-Hydroxyethyl-1- piperazineethanesulfonic acid

 

Adenoslne 5’ Triposphate Disodium

Ethanol

 

acetonitrile

 

acrylamide

 

All Gel Dydrazide

Isopentyl alcohol

 

Benzyl alcohol

 

agarose

 

abendonate

Methanol

 

butanol

 

albumin

 

Bromopherol blue

Wescodyne

 

chloroform

 

aromoblum acetate

 

Cholecalciferol

Xylene

 

Citric Acid

 

beta-cyclodextrin

 

Dihydroxytestosterone

bleach

 

Coomassie Blue Stain

 

Calcium Chloride

 

estradiol

 

 

DEPC water

 

Carbamychofine Chloride

 

Ethldium Bromide

 

 

diethyl pyrocarbonate

 

Chloramidopropyl (Dimethylammonio)-2 Hydroxy-1-Propoanesultonate

 

Forskolin

 

 

dimethylacetamide

 

Chloramphenicol

 

Geneticin

 

 

dimethylformamide

 

dextran sulfate

 

Heparin Sodium

 

 

dimethylsuloxide

 

dithothrepl

 

ketamine

 

 

Ethyl Acetate

 

ettylepadiamine tetraacetic acid

 

Lipopolysaccharide

 

 

Ethyl Alcohol

 

Gelatin

 

nandrolone

 

 

Ethylene Glycol

 

Glucose

 

Phorbal – 12-myristate 13 acetate

 

 

formic acid

 

glycine

 

raloxfene

 

 

glycerol

 

Guanldine thcyanate

 

streptavicin

 

 

heptane

 

hemaloxylin

 

tamoxlene

 

 

Hexane

 

Hepes Free Acid

 

testosterone

 

 

hydrochloric acid

 

Hexamine cobalt trichloride

 

tetracycline hydrochloride

 

 

hydrogen peroxide

 

Histopaque 1077

 

toluidine blue

 

 

isoflurane

 

magnesium chloride

 

xyazine

 

 

isopropyl alcohol

 

Magnesium Sulfate

 

xylene canole

 

 

mercapioethanol

 

melthycellulose

 

 

 

 

octane

 

methylmethacrylate

 

 

 

 

pH calibration buffers 4, 7, 10

 

paraffin wax

 

 

 

 

phenol

 

Paraformaldehyde

 

 

 

 

phenopthalein

 

Phosphate buffered saline

 

 

 

 

phosphate buffered saline

 

polyvinlypyrolidone

 

 

 

 

phosphoric acid

 

Potassium Acetate

 

 

 

 

polyoxyethylene

 

potassium chloride

 

 

 

 

potassium hydroxide

 

Potassium Hydroxide

 

 

 

 

Propanol

 

sodium Acetate

 

 

 

 

propylene glycol

 

sodium Azide

 

 

 

 

sulphuric acid

 

sodium bicarbonate

 

 

 

 

Tetramethylbenzidine

 

Sodium Carbonate

 

 

 

 

trichioroacatic acid

 

Sodium chloride

 

 

 

 

triethanplamine

 

Sodium hydroxide

 

 

 

 

Tritton X-100

 

Sodium phosphate

 

 

 

 

 

 

Sucrose

 

 

 

 

 

 

Tetraethylammonium chloride

 

 

 

 

 

 

Thioglycolic acid

 

 

 

 

 

 

trishydorchloride

 

 

 

203

--------------------------------------------------------------------------------

 

Human Cell Line

 

Murine Cell Line

 

Other Cell Lines

 

 

 

 

 

HeLa

 

C2C12

 

HEK293

HOB

 

ST2

 

COS

SaOs2

 

MC3T3E1

 

 

MG63

 

U32

 

 

U2OS

 

OB6

 

 

 

 

UMR106

 

 

 

 

MLOY4

 

 

 

 

 

 

 

Radioactive Material

 

Chemical/Physical Form

 

Maximum Possession Limit

 

 

 

 

 

A.

Hydrogen-3

A.

Any

A

20 millicuries

 

B.

Carbon-14

B.

Any

B.

5 millicuries

 

C.

Phosphorus-32

C.

Any

C.

20 millicuries

 

D.

Phosphorus-33

D.

Any

D.

20 millicuries

 

E.

Sulfur-35

E.

Any

E.

20 millicuries

 

F.

Iodine-125

G.

Bound

G.

5 millicuries

 

 

204

--------------------------------------------------------------------------------

 

Schedule 5.22(e)

 

Environmental Matters

 

1.              The premises previously subleased by the Corporation and located
at 300 Technology Square, Cambridge, Massachusetts 02139.

 

205

--------------------------------------------------------------------------------

 

Schedule 5.22(f)

 

Environmental Matters

 

None.

 

206

--------------------------------------------------------------------------------

 

Schedule 10

 

Certain Covenants

 

1.              Pursuant to an engagement with Leerink Swann LLC (“Leerink”) for
services in connection with the Series A-1 Financing, the Corporation has agreed
to issue to Leerink a Warrant to purchase 24,564 shares of Series A-1
Convertible Preferred Stock at the Stage I Closing.

 

2.              On December 21, 2010, the Corporation Accepted and Agreed to a
Proposal from GE Healthcare Financial Services, Inc. (“GEHFS”) and Oxford
Finance Corporation (“Oxford Finance”) which forth the terms on which GEHFS and
Oxford Finance Corporation would provide debt financing to the Corporation in an
aggregate amount of $25m in tree tranched term loans.  As part of the Proposal,
the Corporation would be required to issue to GEHFS and Oxford Finance warrants
to purchase, in the aggregate, 122,820 shares of Series A-1 Convertible
Preferred Stock and to grant to GEHFS the right to purchase up to an additional
122,820 shares on terms substantially the same as those on which MPM is making
their investment in the Corporation in the Series A-1 Financing. It is expected
that operative documents pertaining to such debt financing will be finalized on
or about the Stage I Closing Date.

 

3.              Pursuant to the terms of that certain License Agreement by and
between the Corporation and Ipsen Pharma SAS (“Ipsen”), as amended, the
Corporation may issue shares of Series A-1 Preferred Stock to Ipsen as payment
milestones, in lieu of cash payments, at $8.142 per share.

 

207

--------------------------------------------------------------------------------