Exhibit 10.100

CERTAIN MATERIAL (INDICATED BY AN ASTERISK) HAS BEEN OMITTED FROM THIS DOCUMENT
PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT. THE OMITTED MATERIAL HAS BEEN
FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.

CAPTISOL® SUPPLY AGREEMENT

BY AND BETWEEN

CYDEX, INC.

AND

THE HOVIONE GROUP

Dated as of December 20, 2002

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CAPTISOL® SUPPLY AGREEMENT

THIS CAPTISOL SUPPLY AGREEMENT (the “AGREEMENT”) is entered into as of
December 20, 2002 by and between:

 

  (1) CYDEX, INC., a Delaware corporation with an office at 12980 Metcalf
Avenue, Suite 470, Overland Park, Kansas, 66213 (“CYDEX”); and

 

  (2) HOVIONE LLC, a New Jersey limited liability company with an office at 40
Lake Drive, East Windsor, New Jersey 08250 (“AGENT”), acting as exclusive sales
agent for the USA for the manufacturers, HOVIONE FARMACIENCIA S.A., a Portuguese
corporation (“HOVIONE SA”), and HOVIONE PHARMASCIENCE LIMITED, a Macau
corporation (“HOVIONE LIMITED”), and acting as exclusive sales agent for the
project manager HOVIONE INTERNATIONAL LIMITED, a Hong Kong corporation with an
office at 172 Gloucester Road, Wanchai, Hong Kong (“HOVIONE INTERNATIONAL”),
jointly and severally. AGENT, HOVIONE SA, HOVIONE LIMITED and HOVIONE
INTERNATIONAL are collectively referred to herein as “HOVIONE”).

BACKGROUND

CYDEX desires to purchase from HOVIONE, and HOVIONE desires to supply to CYDEX,
CAPTISOL in accordance with the terms and conditions of this AGREEMENT.

AGREEMENTS

NOW, THEREFORE, in consideration of the mutual promises hereinafter made and the
mutual benefits to be derived from this AGREEMENT, and other good and valuable
consideration, the receipt and sufficiency of which is acknowledged, the parties
hereto, intending to be legally bound, hereby agree as follows:

ARTICLE I.

DEFINITIONS

Capitalized terms shall have the meanings ascribed to them in this Article I or
as otherwise set forth in this AGREEMENT.

“AAA” has the meaning set forth in Section 10.4(b) hereof.

“ACT” means the United States Federal Food, Drug and Cosmetic Act, as amended.

“AFFILIATE” means any individual, corporation or other legal entity which a
party directly or indirectly through one or more intermediaries controls or
which is controlled by or under common control with such party. For the purpose
of this AGREEMENT, “control” means the possession, direct or indirect, of the
power to direct or cause the direction of the management

 

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and policies of an individual, corporation or other legal entity, whether
through the ownership of voting securities, by contract, or otherwise.

“AGREEMENT” means this Captisol Supply Agreement between HOVIONE and CYDEX.

“ALTERNATE SUPPLIER” has the meaning set forth in Section 3.10(b) hereof.

“APPLICABLE LAWS” means all applicable laws, statutes, rules, regulations,
ordinances, orders, decrees, writs, judicial or administrative decisions and the
like of any nation or government, any state or other political subdivision
thereof, any entity exercising executive, judicial, regulatory or administrative
functions of or pertaining to government (including, without limitation, any
governmental authority, agency, department, board, commission or instrumentality
of any governmental unit or any political subdivision thereof), any tribunal or
arbitrator of competent jurisdiction, and any self-regulatory organization.

“CAPTISOL” means ß-cyclodextrin sulfobutyl ether, sodium salt, as manufactured
pursuant to the process set forth in Exhibit B hereto and meeting the
SPECIFICATIONS.

“cGMP” means the then-current Good Manufacturing Practices as promulgated under
the ACT at 21 CFR (chapters 210 and 211), as the same may be amended or
re-enacted from time to time and as interpreted in accordance with then-current
industry standards and FDA policies.

“CLAIM” has the meaning set forth in Section 10.4(a) hereof.

“COMMERCIAL PRODUCTION DATE” has the meaning set forth in Section 2.2 hereof.

“CONFIDENTIAL INFORMATION” means all information, data, know-how and all other
business, technical and financial data disclosed pursuant to the terms of the
Confidential Disclosure Agreement between the parties dated August 8, 2002 or
hereunder by one party or any of its AFFILIATES to the other party or any of its
AFFILIATES, except any portion thereof which:

 

  (i) at the time of disclosure, is in the public knowledge;

 

  (ii) after disclosure, becomes part of the public knowledge by publication or
otherwise, except by breach of this AGREEMENT by the recipient;

 

  (iii) the recipient can demonstrate by its written records was in the
recipient’s possession at the time of such disclosure, and which was not
acquired, directly or indirectly, from the disclosing party;

 

  (iv) is lawfully disclosed to the recipient on a non-confidential basis by a
third party who is not obligated to the disclosing party or any other third
party to retain it in confidence;

 

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  (v) results from research and development by the recipient independent of such
disclosure and can be so documented in writing; or

 

  (vi) is required to be disclosed by legal process; provided that in each such
case the party so disclosing information timely informs the other party and uses
its best efforts to limit the disclosure and maintain confidentiality to the
extent possible and permits the other party to attempt by appropriate legal
means to limit such disclosure.

“CONTRACT YEAR” means the twelve (12) month period commencing on the COMMERCIAL
PRODUCTION DATE and ending on the first anniversary of the COMMERCIAL PRODUCTION
DATE and each consecutive twelve (12) month period thereafter during the TERM.

“CYDEX” has the meaning set forth in the first paragraph hereof.

“CYDEX INDEMNIFIED PARTY” has the meaning set forth in Section 9.2 hereof.

“DATE OF MANUFACTURE” means the date on the certificate of analysis of each
batch of CAPTISOL that evidences the release approval of the batch by HOVIONE.

“EFFECTIVE DATE” means January 1, 2003.

“FDA” means the United States Food and Drug Administration or any successor
entity thereto.

“FORCE MAJEURE” has the meaning set forth in Section 10.1 hereof.

“FORECAST” has the meaning set forth in Section 3.5 hereof.

“HOVIONE” has the meaning set forth in the first paragraph hereof.

“HOVIONE INDEMNIFIED PARTY” has the meaning set forth in Section 9.1 hereof.

“HOVIONE QUALITY SYSTEM” means the procedures, methods and controls that are in
force at HOVIONE manufacturing sites and that evidence compliance with the
requirements of the FDA, other health authorities and the requirements of this
AGREEMENT.

“ICH GUIDELINES” means all relevant guidelines promulgated from time to time by
the International Conference on Harmonisation of Technical Requirements for
Registration of Pharmaceuticals for Human Use.

“INITIAL TERM” means the period commencing upon the EFFECTIVE DATE and ending on
December 31, 2010.

“IPEC GMPs” means Good Manufacturing Practices as promulgated from time to time
by the International Pharmaceutical Excipients Council.

 

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“INVENTION” means information relating to any innovation, improvement,
development, discovery, computer program, device, trade secret, method,
know-how, process, technique or the like, whether or not written or otherwise
fixed in any form or medium, regardless of the media on which contained and
whether or not patentable or copyrightable.

“LIABILITY” means any and all liabilities, losses, damages, penalties, fines,
assessments, expenses and costs of any kind or nature required to be paid by a
party hereunder (or its AFFILIATE) to any third party (which shall not include
any AFFILIATE of such paying party), primary or secondary, direct or indirect,
absolute or contingent, known or unknown, including without limitation costs of
settlement, reasonable attorneys’ fees and related costs and expenses and any
liabilities for claims of personal injury or death, suffered or incurred by an
indemnified party hereunder.

“PORTUGUESE CPI” has the meaning set forth in Section 4.2(e) hereof.

“PORTUGUESE CPI INCREASE” has the meaning set forth in Section 4.2(e) hereof.

“RULES” has the meaning set forth in Section 10.4(b) hereof.

“SPECIFICATIONS” means the written specifications for the CAPTISOL attached as
Exhibit A hereto, as the same may be amended from time to time by CYDEX pursuant
to the provisions of Section 6.3 herein.

“SUPPLY INTERRUPTION” has the meaning set forth in Section 3.10 hereof.

“TERM” has the meaning set forth in Section 5.1 hereof.

“UNIT PRICES” has the meaning set forth in Section 4.1 hereof.

Unless the context clearly indicates otherwise, the use herein of the singular
shall include the plural, and the use of the masculine shall include the
feminine.

ARTICLE II.

ENGINEERING AND VALIDATION

2.1 General. HOVIONE at its sole cost and expense, subject to the compensation
payable by CYDEX pursuant to Section 2.5 hereof, shall perform all necessary
engineering work, equipment acquisition and commissioning, training, validation
activities and other work required for HOVIONE’s Loures site to manufacture and
supply CAPTISOL in accordance with the provisions of this AGREEMENT, including
without limitation the manufacture and supply of CAPTISOL meeting the
SPECIFICATIONS in accordance with the manufacturing process description attached
hereto as Exhibit B. For clarity, HOVIONE at its sole cost and expense shall
allocate or procure all necessary facilities and equipment (including without
limitation spray dryers and analytical equipment) to manufacture and supply
CAPTISOL. HOVIONE shall submit its protocols for engineering and validation
batches to CYDEX for its approval prior to commencing any such batch, such
approval not to be unreasonably withheld or delayed. CYDEX shall not
unreasonably withhold or delay its approval of any matter described as requiring
the approval of CYDEX in this Article II, provided that it shall be deemed
reasonable

 

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for CYDEX to withhold such approval if protocols, reports or any other matter
fail to meet industry standards or if HOVIONE’s equipment or process will not
reasonably deliver CAPTISOL that would meet the warranties specified in
Article VIII hereof. Protocols, reports and other documents to be provided by
HOVIONE to CYDEX under this AGREEMENT, whether for approval or for information,
shall be provided in English.

2.2 Timing. HOVIONE shall use its reasonable best efforts to accomplish the work
and services required by this Article II for HOVIONE’s Loures site in accordance
with the Gantt chart timelines attached hereto as Exhibit C to achieve a date
for its capability to commercially produce CAPTISOL in accordance with the
provisions of this AGREEMENT. The actual date for such capability shall be
referred to herein as the “COMMERCIAL PRODUCTION DATE”, which shall be on or
before May 31, 2004. In the event that HOVIONE fails to complete the work and
services required by this Article II for HOVIONE’s Loures site on or before
[***], then CYDEX shall have the right in its discretion to terminate this
AGREEMENT upon [***] days notice to HOVIONE, whereupon HOVIONE shall refund all
amounts paid by CYDEX to HOVIONE to date hereunder within [***] days of such
notice, and CYDEX shall have no further liability to make payments to HOVIONE
hereunder.

2.3 Engineering Batches. HOVIONE shall successfully complete [***] full-scale
engineering batches of CAPTISOL prior to [***]. Each such batch shall yield a
minimum of [***] Kg of CAPTISOL to be an acceptable engineering batch. HOVIONE
shall not commence engineering batches until CYDEX has approved, with respect to
the equipment necessary for the manufacture of CAPTISOL, (i) HOVIONE’s
installation of such equipment (by inspection), (ii) the design qualification
report for such equipment, (iii) the installation qualification report for such
equipment, and (iv) the operational qualification report for such equipment.
Engineering batches shall be manufactured in accordance with cGMP but shall not
be required to meet the SPECIFICATIONS. The sole purpose of engineering batches
is to detect deficiencies in the production line and to adjust the process
parameters.

2.4 Validation Batches. HOVIONE shall successfully complete [***] full-scale
validation batches of CAPTISOL prior to [***]. Each such batch shall yield a
minimum of [***] Kg of CAPTISOL to be an acceptable validation batch. HOVIONE
shall not commence validation batches until CYDEX has approved the results of
the engineering batches.

2.5 Compensation for Engineering and Validation Work. As full compensation for
the obligations of HOVIONE pursuant to this Article II, including without
limitation the manufacture and supply of engineering and validation batches,
CYDEX shall compensate HOVIONE as follows:

(a) Purchase of Engineering and Validation Batches. The purchase price for the
engineering and validation batches referred to in Sections 2.3 and 2.4 hereof
(and, for clarity, compensation to HOVIONE for any other batches that may be
required if any validation batch fails; provided however that CYDEX shall have
no responsibility to pay for any failed validation batch) shall be an amount
equal to [***] Dollars US$[***], payable as follows:

 

 

*** Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to the
omitted portions.

 

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  (i) An advance payment of [***] Dollars US$[***] %, together with CYDEX’s
first purchase order pursuant to Section 2.3 or 2.4 hereof, on or before [***];

 

  (ii) A payment of [***] Dollars US$[***] % within [***] days after HOVIONE
notifies CYDEX that HOVIONE has actually begun production of the first
engineering batch, subject to CYDEX’s approval of HOVIONE’s protocol for such
engineering batch and, with respect the equipment necessary for the manufacture
of CAPTISOL, (A) the installation of such equipment (by inspection), (B) the
design qualification report for such equipment, (C) the installation
qualification report for such equipment, and (D) the operational qualification
report for such equipment; and

 

  (iii) A payment of [***] Dollars US$[***] % within [***] days after CYDEX
approves HOVIONE’s (A) certificates of analysis evidencing quality control
release of all validation batches as to quality and intended purpose, and
(B) process validation campaign report.

(b) Payment for HOVIONE Engineering Services. On or before [***] CYDEX shall
issue a purchase order to HOVIONE for all engineering services required for the
matters contemplated by this Article II, pursuant to which CYDEX shall pay
HOVIONE a fee in the amount of [***] Dollars (US$[***], payable as follows:

 

  (i) [***] Dollars (US$[***] % upon issuance of such purchase order;

 

  (ii) [***] Dollars (US$[***] % on or before [***]

 

  (iii) [***] Dollars (US$[***] % [***] days after CYDEX approves, with respect
to the equipment necessary for the manufacture of CAPTISOL, (A) HOVIONE’s
installation of such equipment (by inspection), (B) the design qualification
report for such equipment, (C) the installation qualification report for such
equipment, and (D) the operational qualification report for such equipment; and

 

  (iv) [***] Dollars (US$[***] % at the successful conclusion of the validation
campaign, which for purposes of this clause shall be upon the parties’ mutual
approval of the final quality control release of the third consecutive
validation batch that conforms with the warranties specified in Article VIII
hereof with no significant process deviations.

HOVIONE shall reimburse CYDEX for such engineering fees in accordance with
Section 4.2(h) and 5.3 (vii) hereof.

2.6 Available Capacity. From and after the COMMERCIAL PRODUCTION DATE during the
TERM, HOVIONE shall at all times maintain an annual manufacturing capacity at
its Loures site suitable to meet CYDEX’s expected requirements of CAPTISOL as
long as its

 

 

*** Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to the
omitted portions.

 

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FORECASTS do not exceed [***], provided that CYDEX shall provide FORECASTS
pursuant to Section 3.5 hereof to permit HOVIONE to efficiently schedule the use
of such capacity.

2.7 Macau Site. At such time as (i) the forecasted requirements by CYDEX for
CAPTISOL pursuant to its FORECASTS equal or exceed [***] for any CONTRACT YEAR,
or (ii) HOVIONE determines to be necessary or advisable and CYDEX does not
unreasonably withhold approval, HOVIONE at its sole expense shall establish a
second manufacturing facility for CAPTISOL at its Macau site capable of
producing [***] of CAPTISOL per year and shall validate such site to permit the
manufacture and supply of CAPTISOL at such site in accordance with the terms and
conditions of this AGREEMENT, all on a timely basis for delivery of all
quantities of CAPTISOL ordered by CYDEX hereunder. For the avoidance of doubt,
there will be no reimbursement by CYDEX to HOVIONE for the costs and expenses of
HOVIONE related to the Macau site, including without limitation engineering
fees. Prior to use of the Macau facility for the production of CAPTISOL, such
facility shall have passed inspection and audit by CYDEX for compliance with
IPEC GMPs, FDA cGMPs, ICH GUIDELINES and other relevant guidance documents
issued by IPEC, FDA and ICH. In consideration for HOVIONE having established a
second facility to manufacture CAPTISOL, HOVIONE shall be free to choose to
manufacture CAPTISOL in either facility as long as all quality and compliance
requirements are met. From and after such time as HOVIONE begins to use its
Macau site for the manufacture of CAPTISOL, HOVIONE shall at all times maintain
an annual manufacturing capacity suitable to meet CYDEX’s expected requirements
of CAPTISOL up to [***].

2.8 Additional Engineering Services. At the reasonable request of CYDEX, but
subject to advance notice and availability, HOVIONE shall provide additional
engineering and process development services related to CAPTISOL at rates to be
negotiated in good faith by the parties.

ARTICLE III.

MANUFACTURE AND DELIVERY OF CAPTISOL

3.1 Purchase and Sale. Pursuant and subject to the terms and conditions of this
AGREEMENT, from and after the COMMERCIAL PRODUCTION DATE, HOVIONE agrees to
manufacture CAPTISOL at its Loures and Macau facilities for CYDEX, and CYDEX
agrees to purchase CAPTISOL from HOVIONE. All quantities of CAPTISOL
manufactured or supplied by HOVIONE and its AFFILIATES shall be exclusively for
CYDEX, and HOVIONE shall not manufacture or supply quantities of CAPTISOL for
any third parties (whether or not such third parties have the legal right to
license HOVIONE to do so) without the express written consent of CYDEX, which
CYDEX may provide or withhold in its sole discretion.

3.2 CYDEX Purchase Requirements. CYDEX shall make the following purchases of
CAPTISOL from HOVIONE, and HOVIONE shall supply to CYDEX such purchases:

 

 

*** Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to the
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(a) First CONTRACT YEAR Commitment. CYDEX shall issue purchase orders for at
least [***] but no more than [***] of CAPTISOL for deliveries in the first
CONTRACT YEAR and shall issue said purchase order within [***] days after the
EFFECTIVE DATE of this AGREEMENT. CYDEX may increase quantities of CAPTISOL
ordered for delivery in the first CONTRACT YEAR and HOVIONE shall supply such
quantifies on a best efforts basis, provided that CYDEX provides notice to
HOVIONE of such change at least [***] months prior to the COMMERCIAL PRODUCTION
DATE if the COMMERCIAL PRODUCTION DATE has been generally anticipated by the
parties for at least [***] months.

(b) Requirements. From and after the COMMERCIAL PRODUCTION DATE, during the
TERM, except as provided herein, CYDEX shall purchase its requirements of
CAPTISOL exclusively from HOVIONE. Notwithstanding the foregoing, (i) such
commitment shall not apply to customers or licensees of CYDEX who may have been
or may be granted the legal right to independently source CAPTISOL, (ii) such
commitment shall not apply if CYDEX’s requirements for CAPTISOL exceed HOVIONE’s
ability to meet such requirements, (iii) such commitment is subject to Sections
10.1 (for FORCE MAJEURE) and 3.10 (for SUPPLY INTERRUPTION) hereof, and
(iv) such commitment shall cease to apply if the average UNIT PRICE (estimated
or actual) for a CONTRACT YEAR exceeds US$[***].

(c) US$[***] Minimum. During the TERM, CYDEX shall purchase from HOVIONE at
least [***] Dollars US$[***] in purchase price value of CAPTISOL, at such times
as CYDEX may determine in its discretion (subject to the forecasting and
purchase order provisions of Sections 3.5 and 3.6 hereof). For clarity, the
compensation paid by CYDEX to HOVIONE for engineering and validation batches
pursuant to Section 2.5(a) hereof shall be counted and included within such
aggregate requirement.

3.3 Supply Restrictions. All quantities of CAPTISOL manufactured or supplied by
HOVIONE and its AFFILIATES shall be exclusively for CYDEX. Given the financial
subsidies and technology transfer provided by CYDEX hereunder, during the TERM
and for a period of [***] years following the TERM, HOVIONE and its AFFILIATES
shall not (1) manufacture or supply quantities of CAPTISOL for any third parties
(whether or not such third parties have the legal right to license HOVIONE to do
so) without the express written consent of CYDEX, which CYDEX may provide or
withhold in its sole discretion, and (ii) manufacture or supply any product
similar to or competitive with CAPTISOL which would (A) infringe the proprietary
rights owned by or licensed to CYDEX, or (B) utilize any information or
technology provided by CYDEX to HOVIONE.

3.4 Labeling and Packaging. HOVIONE shall package and label CAPTISOL as directed
from time to time by CYDEX at least [***] days prior to the relevant delivery of
CAPTISOL. CYDEX shall be responsible for paying all out-of-pocket costs of the
design of any new packaging and labeling of HOVIONE or CYDEX for CAPTISOL and
shall provide to HOVIONE (which shall actually prepare such packaging and
labeling) CYDEX’s logo, color codes, designs, information, graphics and art work
to be applied to CAPTISOL. HOVIONE

 

 

*** Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to the
omitted portions.

 

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acknowledges and agrees that the costs of all standard packaging and standard
labeling for CAPTISOL are included in the UNIT PRICES for CAPTISOL. Any changes
thereto shall be charged separately.

3.5 FORECASTS, Purchase Orders and Minimum Quantities. Within [***]) days after
the commencement of any CONTRACT YEAR, CYDEX shall provide HOVIONE with a
written [***] month forecast of its anticipated purchase order for commercial
quantities of CAPTISOL for the subsequent CONTRACT YEAR (“FORECAST”), specifying
quantities and delivery dates. Not later than [***] months in advance of such
CONTRACT YEAR, CYDEX shall be required to place its irrevocable purchase order
for [***] percent [***]% of the aggregate quantities of CAPTISOL specified in
its FORECAST, provided that CYDEX shall have the right, with respect to not more
than [***] percent [***]%of FORECASTED quantities, to (i) increase or decrease
such FORECASTED quantities, and/or (ii) change the allocation of such quantities
among deliveries scheduled and new delivery dates, provided in aggregate the
changed amounts are not disproportionately concentrated in time thereby causing
HOVIONE to produce and deliver in that period in excess of the [***] its
obligations. CYDEX’s irrevocable purchase order shall be for at least[***].
HOVIONE shall confirm acceptance of such annual irrevocable purchase order
within [***]days of receipt. Should CYDEX desire to make additional changes in
quantities and/or delivery dates, CYDEX shall notify HOVIONE and HOVIONE will
use its best efforts to accommodate CYDEX’s requests.

3.6 Supply. HOVIONE shall accept all such purchase orders for quantities up to
[***] percent [***]% of the quantities specified in CYDEX’s FORECASTS and shall
supply all quantities of CAPTISOL so ordered to CYDEX within [***] days of the
delivery date(s) specified in each such purchase order, unless otherwise agreed.
HOVIONE shall advise and maintain regular communication with CYDEX regarding
delays and progress on issued orders. No purchase order, shipping document,
confirmation or waybill shall be deemed to modify, supplement or substitute for
the terms and conditions of this AGREEMENT, except upon the mutual written
agreement of the parties. All such documents shall be subject to, and shall be
deemed to incorporate, the teens and conditions of this AGREEMENT.

3.7 Additional Inventory. HOVIONE shall manufacture and hold in inventory an
additional quantity of CAPTISOL equal to [***] percent [***]% of the quantities
specified by CYDEX in each of its purchase orders. CYDEX shall not be required
to purchase or pay for such additional inventory until the earlier of (i) the
date on which CYDEX requests that such additional inventory be delivered to
CYDEX to meet unforeseen demand or replace interrupted manufacturing capacity,
or (ii) [***] from the DATE OF MANUFACTURE.

3.8 Delivery. CAPTISOL shall be shipped by HOVIONE DDP (INCOTERMS 2000) by air
to any destination (or multiple destinations) designated by CYDEX, provided said
duties on CAPTISOL for said destination have been suspended. If duties cease to
be suspended or if any other impositions, import duty or otherwise, cause
additional delivery costs to HOVIONE beyond CIF costs, then HOVIONE shall be
free to add such extra costs to the sales price of

 

 

*** Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to the
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CAPTISOL. All deliveries of confirmed CYDEX orders shall be available for
shipment to CYDEX on or before the date specified in the relevant purchase
order. CYDEX may also direct HOVIONE to deliver CAPTISOL into CYDEX’s inventory,
stored at HOVIONE’s site. HOVIONE warrants that such CAPTISOL shall be stored
and preserved in accordance with mutually agreed conditions, and shall be
labeled as inventory owned by CYDEX. HOVIONE shall maintain insurance for such
CYDEX inventory with CYDEX named as an insured, and shall provide a certificate
of such insurance to CYDEX upon its request from time to time. Such storage and
insurance shall be provided without charge to CYDEX for a period of not more
than [***] days counted as from DATE OF MANUFACTURE, and shall be provided to
CYDEX by HOVIONE at HOVIONE’s monthly storage rate thereafter, for the relevant
quantity of CAPTISOL. At such times as CYDEX may direct to HOVIONE in writing,
quantities of CAPTISOL from such inventory shall be further shipped by HOVIONE
at its cost DDP (INCOTERMS 2000) by air to any destination (or multiple
destinations) designated by CYDEX in quantities of no less than one batch. For
smaller batches additional packing and freight charges shall apply.

3.9 Shortages/Damaged Goods/Rejected Goods.

(a) Shortages/Damaged Goods. CYDEX shall notify HOVIONE in writing of any
obvious visible damage or obvious shortage in quantity of any shipment of
CAPTISOL within its possession within [***] days after receipt by CYDEX. In the
event of (i) any shortage in quantity of any shipment of CAPTISOL that is not
within CYDEX’s possession, (ii) any non-obvious shortage in quantity of any
shipment of CAPTISOL within CYDEX’s possession, or (iii) any non-obvious damage
to any CAPTISOL, CYDEX shall notify HOVIONE in writing within [***] days after
discovery of such shortage or damage. In the event of any shortage or damage as
described in this Section 3.9(a), HOVIONE shall make up the shortage or replace
the damaged shipment within [***] days after notification by CYDEX, if
replacement CAPTISOL stock is available, or if no such replacement stock is
available, CYDEX shall deduct the invoiced amount relating to any shortage of
CAPTISOL or damaged CAPTISOL from payment of the HOVIONE invoice or invoices for
such CAPTISOL.

(b) Rejected Goods. CYDEX shall notify HOVIONE in writing by issuing a complaint
of any claim relating to any shipment of CAPTISOL failing to meet the
SPECIFICATIONS or packaging requirements to be agreed upon (other than due
solely to storage, handling or shipping by CYDEX, its AFFILIATES or customers)
within [***] business days after delivery. Such notification shall specify the
packaging size and lot number of such CAPTISOL. HOVIONE shall replace any such
CAPTISOL that is rejected within [***] business days after notification by
CYDEX, if replacement CAPTISOL stock is available. CYDEX shall not be
responsible, and shall receive a credit from HOVIONE, for any additional costs
of shipping and freight required to be paid as a result of any replacement of
CAPTISOL under this Section 3.9(b). The provisions of this Section 3.9(b) shall
not apply to CAPTISOL which fails to meet the SPECIFICATIONS or packaging
requirements due solely to storage, handling or shipping by CYDEX, its
AFFILIATES or customers. After CYDEX returns the

 

 

*** Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to the
omitted portions.

 

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non-compliant product to HOVIONE and if HOVIONE is unable to replace the
returned product with an equal amount of compliant product, CYDEX may deduct the
invoiced amount for any CAPTISOL which is rejected (other than due solely to
storage, handling or shipping by CYDEX, its AFFILIATES or customers) from
payment of the HOVIONE invoice or invoices for such CAPTISOL.

(c) Disputes. In the event of a dispute regarding whether any CAPTISOL fails to
meet the SPECIFICATIONS which HOVIONE and CYDEX are unable to resolve, a sample
of such CAPTISOL shall be submitted by one of the parties to an independent
laboratory reasonably acceptable to both parties for testing and the test
results obtained by such laboratory shall be final and controlling. The fees and
expenses of such laboratory testing and all additional shipping and
transportation costs incurred as a result of the dispute shall be borne entirely
by the party against whom such laboratory’s findings are made. In the event the
test results indicate that the CAPTISOL in question fails to meet the
SPECIFICATIONS, HOVIONE shall replace such CAPTISOL within [***] days after
receipt of such results if replacement CAPTISOL stock is available. The
party-not-at-fault shall not be responsible, and shall receive a credit from the
party-at-fault, for any additional costs of shipping and freight required to be
paid as a result of any replacement of CAPTISOL under this Section 3.9(c). After
CYDEX returns the non-compliant product to HOVIONE and if HOVIONE is unable to
replace the returned product with an equal amount of compliant product, CYDEX
shall deduct the invoice amount for any CAPTISOL which is so determined to fail
to meet the SPECIFICATIONS from payment of the HOVIONE invoice or invoices for
such CAPTISOL.

(d) Time Limit. HOVIONE shall have no liability for any claim with regard to
quality or compliance issues, shortage or damaged goods, or any other kind of
complaint related to CAPTISOL, if HOVIONE is not notified thereof in writing
within [***] of the date of invoice.

3.10 SUPPLY INTERRUPTION. For purposes of this AGREEMENT, a “SUPPLY
INTERRUPTION” shall be deemed to occur: (i) if HOVIONE’s ability to supply
adequate quantities of CAPTISOL in saleable form in a timely manner to CYDEX is
adversely affected or inhibited as reasonably determined by both parties,
(ii) if HOVIONE notifies CYDEX of an event of FORCE MAJEURE pursuant to
Section 10.1 hereof, or (iii) if in any [***] day period covered by a FORECAST,
HOVIONE fails to deliver, in saleable form in accordance with the terms of this
AGREEMENT, at least [***]% by quantity or by value of CAPTISOL ordered by CYDEX
in accordance with its FORECASTS (for whatever cause or no cause). For purposes
of this AGREEMENT, a SUPPLY INTERRUPTION shall be deemed to have been fully
cured [***]. In the event of any SUPPLY INTERRUPTION, the following terms and
conditions shall apply, which shall be cumulative and not in the alternative:

(a) Pro Rata Entitlement. In the event of a SUPPLY INTERRUPTION, CYDEX shall be
entitled to a pro rata (in unit quantity) share of the manufacturing capacity of

 

 

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HOVIONE and its AFFILIATES for the manufacture of CAPTISOL as compared to the
manufacture of other products, to the extent operationally relevant.

(b) ALTERNATE SUPPLIER. In the event of a SUPPLY INTERRUPTION, CYDEX shall have
the right to designate and qualify one or more alternate suppliers for CAPTISOL,
which selection need not be approved by HOVIONE (each an “ALTERNATE SUPPLIER”).
HOVIONE, at CYDEX’s expense, shall promptly provide at such times and locations
as may reasonably be requested by CYDEX, reasonable cooperation to CYDEX in
qualifying any ALTERNATE SUPPLIER. From the time that any SUPPLY INTERRUPTION
begins until such SUPPLY INTERRUPTION is fully cured, and for a commercially
reasonable period of time thereafter, CYDEX may obtain quantities of CAPTISOL
from one or more ALTERNATE SUPPLIERS. [***].

(c) Termination of AGREEMENT. CYDEX may terminate this AGREEMENT if the SUPPLY
INTERRUPTION is not fully cured within [***] days after the date on which the
SUPPLY INTERRUPTION began as described in this Section 3.10.

3.11 Compliance with APPLICABLE LAWS. HOVIONE and its AFFILIATES shall comply
fully with APPLICABLE LAWS in the performance of this AGREEMENT.

3.12 License. CYDEX grants to HOVIONE a royalty-free, non-exclusive license
during the TERM to use the intellectual property rights of CYDEX solely to make
CAPTISOL for sale to CYDEX under and pursuant to this AGREEMENT.

ARTICLE IV.

PRICES AND PAYMENT

4.1 Initial UNIT PRICES. As full compensation for the performance of HOVIONE
hereunder for the manufacture and supply of CAPTISOL from its Loures site from
and after the COMMERCIAL PRODUCTION DATE, CYDEX shall pay HOIVONE the following
supply prices (“UNIT PRICES”) for CAPTISOL:

 

Quantities of CAPTISOL Supplied in a CONTRACT YEAR

   UNIT PRICES
(US$)  

Engineering Batches

 

(in addition to those provided for under Section 2.3)

   US$ [***]   

Validation Batches

 

(in addition to those provided for under Section 2.4)

   US$ [***]   

[***]

   US$ [***]   

 

 

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[***]    US$ [*** ]  [***]    US$ [*** ] 

Such UNIT PRICES shall be adjusted only as provided in Section 4.2 hereof. An
estimated UNIT PRICE for deliveries of CAPTISOL to be used for all invoices in a
given CONTRACT YEAR shall be based on the purchase order for such CONTRACT YEAR.
Within [***] days following the end of each CONTRACT YEAR, CYDEX shall submit to
HOVIONE a reconciliation of the total amount that should have been paid by CYDEX
for all quantities of CAPTISOL purchased during such CONTRACT YEAR in accordance
with the actual UNIT PRICE against the total amounts actually billed by HOVIONE
and paid for by CYDEX for such quantities based on the estimated UNIT PRICE for
such year. If such reconciliation shows that CYDEX has overpaid for such
purchases, then HOVIONE shall, upon [***] days’ notice, at CYDEX’s election,
either refund such overpayment or credit such overpayment against future
purchases of CAPTISOL. If such reconciliation shows that CYDEX has underpaid for
such purchases, then CYDEX shall remit the balance so determined to be due to
HOVIONE within [***] days of its submission of such reconciliation. Such UNIT
PRICES include all raw materials, conversion costs and delivery costs (other
than customs duties, if any, in the country where CAPTISOL is to be delivered as
directed by CYDEX).

4.2 Adjustments to UNIT PRICES. The initial UNIT PRICES specified in Section 4.1
hereof shall be adjusted only as follows:

(a) Variance from Engineering Information. The initial UNIT PRICES specified in
Section 4.1 represent the parties’ best estimate as of the EFFECTIVE DATE for
the cost of [***] for CAPTISOL and were based on the manufacturing efficiency
set forth in Exhibit E and the information contained in Exhibit B. If and to the
extent that HOVIONE can demonstrate by clear and precise evidence that the
manufacturing efficiency set forth in Exhibit E is not achievable (any such
evidence to be based on the first [***], then the initial UNIT PRICES (for the
first CONTRACT YEAR, which shall also be the base reference point for future
CONTRACT YEARS for which such revised UNIT PRICES will be adjusted pursuant to
this and other clauses of this Section 4.2) as set out in Section 4.1 shall be
[***] required to manufacture in accordance with the manufacturing efficiency
set forth in Exhibit E, provided that no increase shall exceed [***] percent
[***]% in the aggregate (i.e., the initial UNIT PRICE for quantities of CAPTISOL
below [***] cannot be more than US$[***], subject to the other adjustments
permitted by this Section 4.2).

(b) Currency Exchange Rates. UNIT PRICES for each CONTRACT YEAR shall be
adjusted (after all other adjustments are made pursuant to this Section 4.2) for
certain currency exchange rate changes as specified in Exhibit D hereto.

(c) Reduction in Raw Materials Usage. As of the [***] of the COMMERCIAL
PRODUCTION DATE in 2006 and 2008, and if relevant each even-numbered year
thereafter (i.e., 2010, 2012, etc.), the UNIT PRICES shall be increased or
decreased, as the

 

 

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case may be, in an amount equal to [***] percent [***]% of the actual increase
or decrease in the average cost of raw materials achieved (on the basis of the
average per kilogram of raw materials used to the per kilogram of CAPTISOL
manufactured) in the previous [***] CONTRACT YEARS related to greater
efficiencies in the manufacturing process set forth in Exhibit B.

(d) Changes in Raw Materials Prices. UNIT PRICES for each CONTRACT YEAR shall be
adjusted in an amount equal to [***]% of any increase or decrease in the costs
of raw materials (on a per kilogram of raw materials basis) as compared to the
previous CONTRACT YEAR.

(e) Changes in PORTUGUESE CPI. As of the anniversary of the COMMERCIAL
PRODUCTION DATE in 2006 and 2008, and if relevant each even-numbered year
thereafter (i.e., 2010, 2012, etc.), with sole respect to the conversion cost
component (and not raw materials cost component) of each UNIT PRICE, each UNIT
PRICE shall be increased or decreased [***](the “PORTUGUESE CPI”), using 118.2
on October 2002 (using the Base 100: 1997 series) as the base reference point
(the “PORTUGUESE CPI INCREASE”). For purposes of this Section 4.2(e), the
conversion cost component of a UNIT PRICE for purposes of computing the
PORTUGUESE CPI INCREASE shall be the UNIT PRICE less [***]of CAPTISOL multiplied
by the [***] on the said date divided by 118.2.

(f) Use of Macau Site. The UNIT PRICES for CAPTISOL manufactured and supplied
from HOVIONE’s Macau site shall not exceed the UNIT PRICES for CAPTISOL
manufactured and supplied from HOVIONE’s Loures site, as determined pursuant to
this Article IV.

(g) Changes to SPECIFICATIONS or Process. In the event that CYDEX initiates a
change to the SPECIFICATIONS or the testing or manufacturing process for
CAPTISOL pursuant to Section 6.3 hereof, the UNIT PRICES shall be adjusted as
provided in such Section 6.3.

(h) Reimbursement for Loures Engineering Services. At such time as CYDEX has
completed payment of [***] Dollars (US$[***] to HOVIONE for CAPTISOL (including
without limitation payments made by CYDEX pursuant to Section 2.5(a) hereof for
engineering and validation batches), the UNIT PRICES for quantities of CAPTISOL
shall be reduced for the next [***] Dollars (US$[***] worth of CAPTISOL ordered
by CYDEX so that the [***] Dollar (US$[***] engineering fee paid by CYDEX
pursuant to Section 2.5(b) hereof shall be reimbursed to CYDEX on a pro rata
basis for such quantities of CAPTISOL.

4.3 Payment. All payments required by this AGREEMENT shall be made in United
States Dollars. All invoices shall be paid by CYDEX not later than [***] days
after the date of HOVIONE’s invoice, which shall not be dated earlier than the
delivery date specified in CYDEX’s purchase order related to such invoice.
Notwithstanding the foregoing, HOVIONE may invoice CYDEX for all CAPTISOL
manufactured per CYDEX’s purchase order within [***] days of the DATE OF
MANUFACTURE of such CAPTISOL. Unless CYDEX notifies

 

 

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HOVIONE in writing of a good faith dispute, with respect to payments not
received within [***] days after the date due, interest shall accrue on any
amount overdue at the rate of one and [***] percent [***]%per month, such
interest to begin accruing on a daily basis from the date due, and shall accrue
both before and after judgment. Should CYDEX repeatedly delay payment of a
HOVIONE invoice, or if HOVIONE should reasonably consider that a credit risk
exists, HOVIONE shall be free to require that each purchase order be accompanied
by an irrevocable and confirmed letter of credit issued by a USA bank.

4.4 Marketing. CYDEX shall be responsible for all advertising, marketing and
sales costs associated with the distribution of CAPTISOL, and shall have
complete authority for all resale pricing decisions for CAPTISOL.

4.5 Continuous Improvement. The parties, through specifically designated
personnel of each party, shall collaborate on a regular basis during the TERM to
identify, track and review specific cost-saving opportunities relating to the
supply of CAPTISOL hereunder (including, without limitation, increasing
manufacturing efficiencies and reducing raw materials and manufacturing costs).

ARTICLE V.

TERM AND TERMINATION

5.1 TERM of this AGREEMENT. The term of this AGREEMENT (the “TERM”) shall be the
INITIAL TERM together with any renewal terms pursuant to Section 5.2 hereof,
unless this AGREEMENT is earlier terminated in accordance with the provisions of
Section 5.3 hereof.

5.2 Renewal Periods. This AGREEMENT shall automatically continue after the
INITIAL TERM for successive renewal terms of two (2) years each unless either
party gives written notice to the other party of its intention to terminate this
AGREEMENT at least [***] prior to the end of the INITIAL TERM or any renewal
term.

5.3 Early Termination. Either CYDEX or HOVIONE, as the case may be, may
terminate this AGREEMENT forthwith by notice in writing to the other party as
follows:

 

  (i) either party may terminate this AGREEMENT if the other party commits a
material breach of this AGREEMENT, which in the case of a breach capable of
remedy shall not have been remedied within [***] days of the receipt by the
other party of a notice identifying the breach and requiring its remedy or such
longer time as the party in breach may demonstrate to the other party is
necessary to remedy the breach using its reasonable efforts to do so; or

 

  (ii) either party may terminate this AGREEMENT without prior advance notice to
the other party in the event that (i) the other party is declared insolvent or
bankrupt by

 

 

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a court of competent jurisdiction; (ii) the other party files a voluntary
petition of bankruptcy or insolvency or for reorganization or for an arrangement
or for the appointment of a receiver or trustee of the party or of its assets,
in any court of competent jurisdiction; or (iii) this AGREEMENT is assigned by
such other party for the benefit of creditors; or

 

  (iii) CYDEX may terminate this AGREEMENT upon [***] days’ written notice in
the event that the FDA or any other regulatory authority takes any action, or
raises any objection, that prevents CYDEX from importing, exporting, purchasing
or selling CAPTISOL; or

 

  (iv) CYDEX may terminate this AGREEMENT effective immediately upon notice if
at any time during the TERM HOVIONE or an AFFILIATE becomes debarred or receives
notice of action or threat of action with respect to its debarment by the FDA or
any other regulatory authority having jurisdiction over CAPTISOL. HOVIONE shall
notify CYDEX immediately if at any time during the TERM HOVIONE or any of its
AFFILIATES or their officers or employees becomes so debarred, or receives
notice of action or threat of action with respect to any such debarment; or

 

  (v) CYDEX may terminate this AGREEMENT in accordance with Section 2.2 or
Section 3.10(c) hereof; or

 

  (vi) either party may terminate this AGREEMENT in accordance with Section 10.1
hereof.

 

  (vii) If prior to the end of the first CONTRACT YEAR HOVIONE is unable to meet
the manufacturing efficiency set forth in Exhibit E, and an increase of [***]
percent [***]% in UNIT PRICES as provided for in Section 4.2(a) is inadequate to
compensate HOVIONE for its increased costs to manufacture CAPTISOL, and if other
commercial arrangements cannot be agreed to between HOVIONE and CYDEX, HOVIONE
shall be free to terminate this AGREEMENT by giving [***] prior written notice
to CYDEX and by returning to CYDEX [***] percent [***]% of the amounts received
from CYDEX under 2.5 (b) as well as those amounts received by HOVIONE from CYDEX
under 2.5 (a) for which HOVIONE did not manufacture and supply the corresponding
two (2) engineering batches and the [***] validation batches. During the [***]
year period following HOVIONE’s notice of termination, (i) CYDEX shall not be
required to purchase CAPTISOL exclusively from HOVIONE, (ii) HOVIONE shall
provide reasonable cooperation to CYDEX in qualifying any new supplier on
reasonable terms to be negotiated, and (iii) HOVIONE shall manufacture and
supply CAPTISOL to CYDEX on the terms and conditions of this AGREEMENT, provided
however that the purchase price of CAPTISOL shall be determined as follows: UNIT
PRICE (as set forth in Section 4.1 hereof) minus

 

 

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(raw material costs and delivery costs) minus [***] percent [***]% of UNIT
PRICE) multiplied by the dividend of [***] plus [***] percent [***]% of UNIT
PRICE).

Adjusted Unit Price=

[***]

Example:         [***]

AUP = [***]

5.4 Consequences of Termination and Survival. Termination of this AGREEMENT for
whatever reason shall not affect the accrued rights and obligations of HOVIONE
or CYDEX arising under or out of this AGREEMENT. The provisions of Articles I,
VII and X and of Sections 6.1, 6.6, 6.7, 6.8, 6.9, 9.1, 9.2, 9.3, 9.4, 9.6 and
9.7 of this AGREEMENT and this Section 5.4 shall survive the expiration or
termination of this AGREEMENT or of any extensions thereof. In addition, any
other provisions which are required to interpret and enforce the parties’ rights
and obligations under this AGREEMENT shall also survive such expiration or
termination to the extent required for the full observation and performance of
this AGREEMENT by the parties hereto.

ARTICLE VI.

MANUFACTURING COMPLIANCE,

ACCESS AND REGULATORY MATTERS

6.1 Tests; Retained Samples; Documentation. HOVIONE shall perform, or cause to
be performed, tests on each lot or batch of CAPTISOL manufactured pursuant to
this AGREEMENT before delivery to CYDEX. Such tests shall include those
referenced in Exhibit A and shall be used to determine compliance with the
SPECIFICATIONS. Samples of CAPTISOL and the results of all such testing,
certificates of analysis, release documents and similar documents shall be
retained by HOVIONE in accordance with prudent industry standards and APPLICABLE
LAWS and made available by HOVIONE to CYDEX upon its request for a period of
[***] from the date of delivery to CYDEX pursuant to Section 3.8 hereof, or such
longer period if any required by APPLICABLE LAWS.

6.2 Manufacturing Compliance. CAPTISOL shall be manufactured in accordance with
IPEC GMPs, FDA cGMPs, ICH GUIDELINES, the manufacturing process description
attached hereto as Exhibit B, and all APPLICABLE LAWS, and shall be manufactured
and supplied from HOVIONE’s Loures and Macau sites only.

6.3 Change Control. Any changes in SPECIFICATIONS or the test methods referenced
in Exhibit A or manufacturing processes described in Exhibit B shall not be made
by HOVIONE without CYDEX’s prior substantive involvement and written approval,
which

 

 

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approval may be withheld in CYDEX’s sole discretion. CYDEX may make changes to
such SPECIFICATIONS, test methods or manufacturing processes, provided that
(i) CYDEX shall consult with HOVIONE prior to any such change to confirm that
HOVIONE’s manufacturing processes will permit such change, and (ii) in the event
that raw materials costs or conversion costs are increased or decreased by any
such change initiated by CYDEX, then the UNIT PRICES for CAPTISOL shall be
increased or decreased, as the case may be, in an amount equal to such increase
or decrease in costs. HOVIONE and CYDEX shall negotiate in good faith an
equitable means of financing any costs associated with implementation of such a
change request on commercially reasonable terms. If additional material capital
equipment is required to implement any such change, the parties shall negotiate
in good faith an equitable means of financing the costs of such equipment on
commercially reasonable terms.

6.4 Access to Facilities. Upon the reasonable prior written request of CYDEX,
CYDEX and/or customers of CYDEX shall have the right to inspect those portions
of HOVIONE’s manufacturing and testing facilities where CAPTISOL is being
manufactured, tested or stored, as the case may be, during regular business
hours, to ascertain compliance with the provisions of this AGREEMENT. The
charges, if any, to be paid by CYDEX to HOVIONE for such purposes are specified
in Exhibit E hereto.

6.5 Regulatory Correspondence. HOVIONE shall promptly (and in any event within
[***] days after receipt by HOVIONE) provide to CYDEX copies of all
correspondence to or from the FDA or any other governmental authority received
by HOVIONE relating to CAPTISOL and all other correspondence received by HOVIONE
bearing on the safety of CAPTISOL.

6.6 Inquiries and Complaints relating to CAPTISOL. Except for technical product
complaints relating to the manufacture of CAPTISOL or as otherwise required by
law or governmental regulation, CYDEX shall be responsible for investigating and
responding to all inquiries, complaints and adverse events regarding CAPTISOL.
It shall be CYDEX’s right and responsibility to comply with all reporting
requirements regarding adverse events and quality matters relating to the
CAPTISOL.

6.7 Response to Complaints and/or Adverse Events. Pursuant to any reported
complaint and/or adverse event, if the nature of the reported complaint and/or
adverse or event requires testing, HOVIONE shall, at CYDEX’s reasonable request
and expense, perform, or cause to be performed, analytical testing of
corresponding retention samples and provide the results thereof to CYDEX as soon
as reasonably practicable; provided, however, that HOVIONE shall be responsible
for the reasonable costs of such testing and reporting to the FDA or any other
governmental regulatory agency if it is determined that HOVIONE is responsible
for such reported complaint and/or adverse event. Such testing shall be
performed using approved testing procedures.

6.8 Additional Information. HOVIONE shall provide to CYDEX in a timely manner,
but in no event less than [***] days prior to the due date of CYDEX’s annual
update to its Drug

 

 

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Master File with respect to CAPTISOL, all information (in written form) which
CYDEX reasonably requests regarding CAPTISOL in order to comply with APPLICABLE
LAWS.

6.9 Recalls. In the event (i) the FDA or any other governmental or regulatory
authority issues a directive, order or, following the issuance of a safety
warning or alert with respect to CAPTISOL, a written request that CAPTISOL or
any product containing CAPTISOL be recalled or retrieved, (ii) a court of
competent jurisdiction orders such a recall or retrieval, or (iii) CYDEX
determines that any CAPTISOL should be recalled or retrieved or that a “dear
doctor” letter is required relating to restrictions on the use of CAPTISOL or
any product containing CAPTISOL, the parties shall take all appropriate
corrective actions, and shall cooperate in the investigations surrounding the
recall, retrieval or letter. In the event that CYDEX reasonably determines that
any CAPTISOL should be recalled, CYDEX shall consult with HOVIONE prior to
taking any corrective actions. In the event that such recall results from any
cause or event other than that arising from the defective manufacture, storage
or handling which would constitute a breach by HOVIONE of this AGREEMENT, CYDEX
shall be responsible for all documented out-of-pocket expenses of such recall
consistent with directions received from the appropriate governmental or
regulatory authority. In the event that such recall results from any cause or
event arising from the defective manufacture, storage or handling which would
constitute a breach by HOVIONE of this AGREEMENT, HOVIONE shall be responsible
for all such documented out-of-pocket expenses. For purposes of this AGREEMENT,
HOVIONE’s expenses shall be limited to the expenses of notification and
destruction or return of the recalled CAPTISOL and product containing CAPTISOL,
all other documented out-of-pocket costs incurred in connection with such recall
and the replacement of the recalled CAPTISOL and the product containing
CAPTISOL, not to exceed the limit set forth in Section 9.7.

6.10 Compliance. HOVIONE ensures compliance with all the health authority
requirements as well as client requirements through ensuring that all
manufacturing and control operations meet the requirements of the HOVIONE
QUALITY SYSTEM. This has been established in order to record and evidence
compliance with all requirements. It is the responsibility of HOVIONE to ensure
that the HOVIONE QUALITY SYSTEM is being constantly updated in a diligent manner
and that it enables HOVIONE to meet the requirements set forth herein. It is the
responsibility of CYDEX to audit HOVIONE a minimum of [***], such [***] and any
follow up audit to be at no cost to CYDEX, to a level of detail that CYDEX
considers appropriate in order to assure itself that the quality system in place
at HOVIONE is adequate for HOVIONE to meet the requirements that CYDEX has
requested of HOVIONE. Should CYDEX identify any system weakness, any event of
non-compliance with any of the requirements, or any non-conformity, it shall
notify HOVIONE within [***] by means of an audit report or by means of a
complaint. HOVIONE shall respond in writing within [***]. Any audits in excess
of the [***] by CYDEX or a CYDEX customer will be charged to CYDEX at a rate to
be negotiated in good faith by the parties.

 

 

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6.11 Relationship Management. The parties hereto hereby agree to create a
Technical Committee and a Management Committee.

The Technical Committee shall be composed of one representative of each party.
Initially, such representatives shall be:

 

•    for CYDEX:

     Mr. Doug Hecker

•    for HOVIONE:

     Mr. Jorge Pastilha

Each party may designate a replacement representative to the Technical Committee
at any time during the TERM upon written notice to the other party. The
Technical Committee shall be in charge of resolving all technical issues
relating to the installation and qualification of the manufacturing facilities
of CAPTISOL, change control and all documentation issues, and determining
mutually agreeable performance indicators in terms of compliance, quality,
supply, service, hygiene, safety and environment and costs and cost reductions,
as set out in this AGREEMENT, in the spirit of continuous improvement.

The Management Committee shall be composed of one representative of each Party.
Initially, such representatives shall be

 

•    for CYDEX:

     Dr. Joseph Lacz

•    for HOVIONE:

     Mr. David Hoffman

Each party may designate a replacement representative to the Management
Committee at any time during the TERM upon written notice to the other party.
Such Management Committee shall be in charge of reviewing the performance
indicators as defined by the Technical Committee, confirming the UNIT PRICES
applicable for each CONTRACT YEAR, managing the relationship between the parties
with the aim of continuous improvement and, if necessary, resolving amicably any
potential dispute between the parties.

Meetings of both Committees shall be held as often as necessary upon request of
one of its members and at least every [***] months. Decisions of both Committees
shall be taken unanimously by their members. In the event a Committee is unable
to reach a unanimous decision, such issue shall constitute a CLAIM and shall be
resolved in accordance with the provisions of Section 10.4 of this AGREEMENT.
For each meeting of both Committees, written minutes shall be established and
signed by each member.

The teams shall operate according to sound principles of project management
which include:

 

  •  

Regular meetings face-to-face, by telephone or video-conference with a
well-defined agenda and meeting minutes.

 

  •  

Well-defined tasks with a defined responsible party and a deadline. All such
tasks shall be well-identified in an overall Gantt chart describing the calendar
of the project.

 

 

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Meetings of both Committees shall be held either:t i) alternatively, at
HOVIONE’s premises in Loures and at CYDEX’s premises in Kansas City or ii) at
HOVIONE’s Technology Transfer Center in East Windsor, New Jersey. The inviting
party shall take care of the organization of the meeting, the preparation of the
agenda, the drafting and distribution of the minutes.

ARTICLE VII.

CONFIDENTIALITY AND PROPRIETARY RIGHTS

7.1 Confidentiality. Except as otherwise provided in this Section 7.1:

 

  (i) HOVIONE and its AFFILIATES will retain in confidence and use only for the
purposes contemplated hereby any CONFIDENTIAL INFORMATION disclosed to it by or
on behalf of CYDEX in connection with the performance of this AGREEMENT; and

 

  (ii) CYDEX and its AFFILIATES will retain in confidence and use only for the
purposes contemplated hereby any CONFIDENTIAL INFORMATION disclosed to it by or
on behalf of HOVIONE in connection with the performance of this AGREEMENT.

To the extent it is reasonably necessary or appropriate to fulfill its
obligations or exercise its rights under this AGREEMENT or any rights which
survive termination or expiration hereof, each party may disclose CONFIDENTIAL
INFORMATION to its AFFILIATES (and with respect to CYDEX, its
customers/licensees) on condition that such entities or persons agree (a) to
keep the CONFIDENTIAL INFORMATION confidential to the same extent as each party
is required to keep the CONFIDENTIAL INFORMATION confidential and (b) to use the
CONFIDENTIAL INFORMATION only for such purposes as such party is entitled to use
the CONFIDENTIAL INFORMATION.

7.2 Proprietary Rights.

(a) CYDEX Information. CYDEX shall own and retain all right, title and interest
in and to all information, documents and tangible and intangible materials which
CYDEX provides to HOVIONE in connection with this AGREEMENT.

(b) Work Product. CYDEX shall own and shall have all rights to use all
information, documents and tangible and intangible materials which result from
the performance by HOVIONE of the services contemplated by this AGREEMENT
(including, without limitation, data, test results, measurements, quantitative
and qualitative analyses, processes, samples, and inventions and technology
relating to CAPTISOL).

(c) INVENTIONS. All INVENTIONS relating to CAPTISOL which are conceived or
created by HOVIONE and/or its AFFILIATES or their agents or jointly by CYDEX and
HOVIONE and/or its AFFILIATES or their agents in contemplation of or in the
course of performing services under this AGREEMENT shall be owned by CYDEX,
provided that CYDEX shall and hereby does grant to HOVIONE a perpetual,
royalty-free, non-exclusive, world-wide, irrevocable license (without the right
to sublicense) to use and/or practice all such

 

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INVENTIONS to (i) manufacture CAPTISOL pursuant to this AGREEMENT, and
(ii) manufacture and sell any other product not similar to or competitive with
CAPTISOL or any other product being developed or commercialized by CYDEX or its
AFFILIATES from time to time. For a period [***] from the EFFECTIVE DATE, CYDEX
shall provide HOVIONE with the preferred opportunity to obtain additional
manufacturing business from CYDEX to the extent that INVENTIONS which are
conceived or created by HOVIONE and/or its AFFILIATES or their agents or jointly
by CYDEX and HOVIONE and/or its AFFILIATES or their agents (i) provide CYDEX an
additional period of exclusivity, or (ii) relate to the synthesis or isolation
of CAPTISOL and are required for the performance of the subject manufacturing
services. CYDEX shall award such manufacturing business to HOVIONE if
(y) HOVIONE has the capability to provide equivalent service quality as other
bidding parties, and (z) HOVIONE’s bid to provide such manufacturing services is
not more than [***] percent [***]% of the lowest third party bid.

(d) Trademarks. CYDEX shall retain all right, title and interest arising under
all APPLICABLE LAWS in the trademark “CAPTISOL®” and all other trademarks and
trade names related to or associated with CYDEX or CAPTISOL and in all other
trademarks and trade names which may be adopted with respect to CAPTISOL.

(e) Further Assurances. Upon the reasonable request of CYDEX, HOVIONE and its
AFFILIATES shall without additional consideration execute and deliver such
assignments and other documents as may be necessary to give effect to the
provisions of this Section 7.2.

7.3 Patents. If during the TERM HOVIONE authors one or more patents that become
instrumental at extending the commercial life of CAPTISOL, then at CYDEX’s sole
discretion, HOVIONE may be awarded a fee of no less than [***] Dollars ($[***]
net per each US patent that issues and is assigned to CYDEX.

ARTICLE VIII.

WARRANTIES

8.1 Quality of CAPTISOL. HOVIONE warrants to CYDEX that all CAPTISOL
manufactured and supplied to CYDEX pursuant to this AGREEMENT shall, at the time
of delivery pursuant to Section 3.8 hereof:

 

  (i) meet the SPECIFICATIONS for CAPTISOL in effect at the time of such
delivery;

 

 

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  (ii) not be adulterated within the meaning of the ACT and shall not be an
article which may not, under the provisions of the ACT, be introduced into
interstate commerce; and

 

  (iii) be free and clear of all liens, security interests and other
encumbrances.

8.2 Quality of Performance. HOVIONE warrants to CYDEX that the performance of
the obligations of HOVIONE hereunder, including without limitation the
manufacture and supply of CAPTISOL, shall in all respects be in accordance with:

 

  (i) IPEC GMPs;

 

  (ii) FDA cGMPs;

 

  (iii) ICH GUIDELINES; and

 

  (iv) APPLICABLE LAWS.

8.3 Mutual Representations and Warranties. Each party represents and warrants to
the other as follows:

(a) Power and Authorization. It has all requisite power and authority (corporate
and otherwise) to enter into this AGREEMENT and has duly authorized by all
necessary action the execution and delivery hereof by the officer or individual
whose name is signed on its behalf below.

(b) No Conflict. Its execution and delivery of this AGREEMENT and the
performance of its obligations hereunder do not and will not conflict with or
result in a breach of or a default under its organizational instruments or any
other agreement, instrument, order, law or regulation applicable to it or by
which it may be bound.

(c) Enforceability. This AGREEMENT has been duly and validly executed and
delivered by it and constitutes its valid and legally binding obligation,
enforceable in accordance with its terms, except as enforcement may be limited
by bankruptcy, insolvency or other laws of general application relating to or
affecting the enforcement of creditors’ rights and except as enforcement is
subject to general equitable principles.

8.4 Exclusion of Other Warranties. EXCEPT AS EXPRESSLY SET FORTH IN THIS
AGREEMENT, EACH PARTY DISCLAIMS ALL WARRANTIES IN RESPECT OF CAPTISOL AND THIS
AGREEMENT, WHETHER EXPRESS OR IMPLIED, INCLUDING WITHOUT LIMITATION ANY IMPLIED
WARRANTY AS TO MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE.

 

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ARTICLE IX.

INDEMNIFICATION, LIMITATION OF LIABILITY AND INSURANCE

9.1 Indemnification by CYDEX. CYDEX shall indemnify, defend and hold harmless
HOVIONE and its AFFILIATES, and their employees, officers and directors, and
their successors and assigns (each, an “HOVIONE INDEMNIFIED PARTY”), from and
against any and all LIABILITIES which the HOVIONE INDEMNIFIED PARTY may incur,
suffer or be required to pay resulting from or arising in connection with the
breach of this AGREEMENT by CYDEX or its AFFILIATES, except to the extent that
any such LIABILITY is due to the negligence or wrongful act(s) of a HOVIONE
INDEMNIFIED PARTY.

9.2 Indemnification by HOVIONE. HOVIONE shall indemnify, defend and hold
harmless CYDEX and its AFFILIATES, employees, officers and directors and its
successors and assigns (each, a “CYDEX INDEMNIFIED PARTY”), from and against any
and all LIABILITIES which the CYDEX INDEMNIFIED PARTY may incur, suffer or be
required to pay resulting from or arising in connection with the breach of this
AGREEMENT by HOVIONE or its AFFILIATES, except to the extent that any such
LIABILITY is due to the negligence or wrongful act(s) of a CYDEX INDEMNIFIED
PARTY.

9.3 Process of Indemnification. Promptly after an indemnified party becomes
aware of any potential LIABILITY hereunder, such party shall deliver written
notice to the indemnifying party, stating the nature of the potential LIABILITY;
provided, however, that the delay in giving or the failure to give such
notification shall not affect the indemnification provided hereunder except to
the extent the indemnifying party shall have been actually prejudiced as a
result of such delay or failure. The indemnified party shall give the
indemnifying party such information with respect to the potential LIABILITY as
the indemnifying party may from time to time reasonably request. The
indemnifying party shall have the right to conduct the defense of any suit,
claim or other proceeding related to the LIABILITY if it has assumed
responsibility for the suit, claim or other proceeding in writing; provided,
however, if in the reasonable judgment of the indemnified party, such suit,
claim or proceeding involves an issue or matter which could have a material
adverse effect on the business, operations or assets of the indemnified party,
the indemnified party may elect, at its own expense, to conduct a separate
defense thereof, but in no event shall any such election be construed as a
waiver of any indemnification rights such indemnified party may have under this
Article VIII, at law or in equity, or otherwise. If the indemnifying party
defends the suit or claim, the indemnified party may participate in (but not
control) the defense thereof at its sole cost and expense; provided, however,
that the indemnifying party shall pay the reasonable fees and costs of any
separate counsel to the extent such representation is due to a conflict of
interest between the parties.

9.4 Settlements. Neither party may settle a claim or action related to a
LIABILITY without the consent of the other party, which consent shall not be
unreasonably withheld, if such settlement would impose any monetary obligation
on the other party or require the other party to submit to an injunction or
otherwise limit the other party’s rights under this AGREEMENT, and any payment
made by a party in such a settlement without obtaining such consent shall be at
its own cost and expense. Notwithstanding the foregoing, the indemnifying party
will be liable under this Article VIII for any settlement effected without its
consent if the indemnifying party has refused to acknowledge liability for
indemnification hereunder and/or declines to defend the

 

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indemnified party in any such claim, action or proceeding and it is determined
by arbitration pursuant to Section 10.4 hereof that the indemnifying party was
liable to the indemnified party for indemnification related to such settlement.

9.5 General Liability Insurance. HOVIONE shall obtain and maintain in effect for
the term of this AGREEMENT general liability insurance or indemnity policies
with an insurer reasonably satisfactory to CYDEX, in an amount not less than
US$[***], which policies shall name CYDEX as an additional insured.

9.6 CAPTISOL Liability Claims. As soon as it becomes aware, each party shall
give the other party prompt written notice of any claim involving CAPTISOL, any
injury alleged to have occurred as a result of the use or application of
CAPTISOL, and any circumstances that may give rise to litigation or recall of
CAPTISOL or regulatory action that may affect the sale of manufacture of
CAPTISOL, specifying, to the extent the party has such information, the time,
place and circumstances thereof and the names and addresses of the persons
involved. Each party shall also furnish promptly to the other party copies of
all papers received in respect of any claim, action or suit arising out of such
alleged defect or, injury or regulatory action. HOVIONE shall have no
responsibility for any CAPTISOL liability claim except to the extent such claim
results from the defective manufacture, storage or handling of CAPTISOL which
would constitute a breach by HOVIONE of this AGREEMENT.

9.7 Limitation of Liability. With the exception of cases of gross negligence or
willful misconduct, HOVIONE’s maximum aggregate liability under this AGREEMENT
to CYDEX in all other cases shall not exceed [***].

ARTICLE X.

GENERAL PROVISIONS

10.1 FORCE MAJEURE. Neither party shall be held liable or responsible for
failure or delay in fulfilling or performing any of its obligations under this
AGREEMENT (other than the payment of money owed hereunder) to the extent that
such failure or delay results from any cause to the extent beyond its reasonable
control, including, without limitation, fire, flood, typhoon, earthquake,
natural disaster, explosion, war, strike, labor unrest, riot, embargo, acts of
terrorism, acts or omissions of carriers, act of God or enactment or revision of
any law, rule, regulation or regulatory advisory opinion or order applicable to
the manufacturing, marketing, sale, reimbursement and/or pricing of CAPTISOL
(“FORCE MAJEURE”). The supply prices of raw materials and changes in conversion
costs shall not be considered to be FORCE MAJEURE. Such excuse shall continue as
long as the FORCE MAJEURE event continues, following which such party shall
promptly resume performance hereunder. The party affected by a FORCE MAJEURE
event shall notify the other party thereof as promptly as practicable after its

 

 

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the Commission. Confidential treatment has been requested with respect to the
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occurrence. Such notice shall describe the nature of such FORCE MAJEURE event
and the extent and expected duration of the affected party’s inability fully to
perform its obligations hereunder. The affected party shall use due diligence,
where practicable, to minimize the effects of or end any such event so as to
facilitate the resumption of full performance hereunder and shall notify the
other party when it is again fully able to perform such obligations. Should the
delay resulting from a FORCE MAJEURE event exceed [***], the non-invoking party
shall then have the right to terminate this AGREEMENT upon [***] days notice.
From the time that any FORCE MAJEURE begins until such FORCE MAJEURE is fully
cured, and for a commercially reasonable period of time thereafter, CYDEX may
obtain quantities of CAPTISOL from one or more third parties. CYDEX shall not be
obligated to purchase FORECASTED quantities of CAPTISOL if CYDEX has entered
into a contract to purchase CAPTISOL from an ALTERNATE SUPPLIER.

10.2 Governing Law. This AGREEMENT shall be construed in accordance with the
laws of the State of Delaware in the United States of America, without giving
effect to the principles of conflicts of law thereof.

10.3 Headings and References. All section headings contained in this AGREEMENT
are for convenience of reference only and shall not affect the meaning or
interpretation of this AGREEMENT.

10.4 Dispute Resolution.

(a) Negotiation. Any dispute, controversy or claim arising out of or relating to
this AGREEMENT, the validity of this AGREEMENT or the breach or termination of
this AGREEMENT or the rights of either party for indemnification hereunder
(each, a “CLAIM”), shall be submitted in the first instance to the Chief
Executive Officer of HOVIONE for HOVIONE and the Chief Executive Officer of
CYDEX for CYDEX.

(b) Arbitration. If any CLAIM cannot be resolved by the individuals designated
in Section 10.4 (a) within [***] days after being submitted to them, and except
for the right of either party to apply to a court of competent jurisdiction for
a temporary restraining order to preserve the status quo or to prevent
irreparable harm pending the selection and confirmation of a panel of
arbitrators in accordance herewith, such CLAIM shall be exclusively and finally
resolved by arbitration in accordance with the Commercial Arbitration Rules (the
“RULES”) of the American Arbitration Association (the “AAA”) in effect on the
day the arbitration is commenced in accordance with this AGREEMENT, except as
modified by this Section 10.4. After expiration of the [***] day period pursuant
to Section 10.4(a) hereof, either party may commence arbitration by serving upon
the other party a written demand for arbitration sent by a courier service of
internationally recognized reputation, in accordance with this AGREEMENT, with a
copy of the same delivered by a courier service of internationally recognized
reputation, to the AAA regional office in which either party is then located.
The number of arbitrators shall be three (3), one (1) of whom is selected by
CYDEX, one (1) of whom is selected by HOVIONE and one (1) of whom is selected by
HOVIONE and CYDEX (or by the other two arbitrators if

 

 

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the parties cannot, within [***] after the commencement of the arbitration
proceeding, agree on the third arbitrator). In the event that either party shall
fail to appoint an arbitrator within [***] days after the commencement of the
arbitration proceeding, such arbitrator and the third arbitrator shall be
appointed by the AAA in accordance with the RULES. The arbitration award shall
be in English rendered by a majority of the members of the board of arbitration.
The panel shall not be entitled to modify this AGREEMENT or the transactions
contemplated herein. The arbitration proceeding shall be conducted in the
English language and shall be brought in New York, New York, USA unless the
parties agree in writing to conduct the arbitration in another location. The AAA
shall have jurisdiction over all parties to this AGREEMENT for purposes of the
arbitration and the parties hereby expressly consent to such jurisdiction.

(c) Arbitral Award. The arbitration decision shall be final and binding. The
prevailing party may enter such decision in any court having competent
jurisdiction. Each party hereby expressly waives any right to object to such
jurisdiction on the basis of venue or forum non conveniens. Each party waives
any right it may have by statute, treaty or law to contest the jurisdiction or
venue of any court or service made pursuant to Section 10.8 (Notices) hereof in
an action or proceeding to enforce an arbitral award, including without
limitation any right under the Hague Convention on the Service Abroad of
Judicial and Extrajudicial Documents in Civil or Commercial Matters and the
Hague Convention on the Taking of Evidence Abroad in Civil or Commercial
Matters, and each party agrees that the validity of arbitral awards shall only
be challenged in accordance with Article V of the United Nations Convention on
the Recognition and Enforcement of Foreign Arbitral Awards. Each party consents
to the jurisdiction and administration of the AAA for purposes of the
arbitration proceedings contemplated herein.

(d) Remedies. Notwithstanding any other provision of this AGREEMENT, any party
may apply to a court of competent jurisdiction for an order in the nature of a
temporary restraining order or preliminary injunction for purposes of
maintaining the status quo pending the final resolution of any dispute pursuant
to the arbitration provisions hereof. The parties shall have all rights and
remedies provided under Delaware law related to the enforcement of this
AGREEMENT.

(e) Expenses. The expenses of any arbitration including the reasonable attorney
fees of the prevailing party, shall be borne by the party deemed to be at fault
or on a pro-rata basis should the arbitration conclude in a finding of mutual
fault.

10.5 Severability, If any provision of this AGREEMENT is held by a court of
competent jurisdiction to be invalid or unenforceable, it shall be modified to
the minimum extent necessary to make it valid and enforceable.

10.6 Entire Agreement. The Confidential Disclosure Agreement between the parties
dated August 8, 2002, this AGREEMENT and the Exhibits hereto constitute the
entire AGREEMENT between the parties relating to the subject matter hereof and
supersede all previous writings and understandings, whether oral or written,
relating to the subject matter of this AGREEMENT.

 

 

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10.7 Amendment. This AGREEMENT may not be amended, supplemented or otherwise
modified except by an instrument in writing signed by the parties that
specifically refers to this AGREEMENT.

10.8 Notices. Any notice required or permitted under this AGREEMENT shall be in
writing and sent by a courier service of internationally recognized reputation,
charges prepaid, or by facsimile transmission with confirmation by reputable
courier service, to the address or facsimile number specified below. Such
notices shall be deemed given three [***] days following deposit with such
courier service or [***] following such facsimile transmission.

 

If to HOVIONE:      Hovione LLC      40 Lake Drive      East Windsor, New Jersey
08250 USA      Attention: President, US Operations      Facsimile: 609-918-2420
With a copy to:      Hovione FarmaCiencia      Sete Casas, Loures      Portugal
     Attention: Chief Executive Officer      Facsimile: 01-351-21-982-9498 If to
CYDEX:      CyDex, Inc.      Suite 470      12980 Metcalf Avenue      Overland
Park, Kansas, 66213 USA      Attention: Chief Executive Officer      Facsimile:
+1-913-685-8856 With a copy to:      CyDex, Inc.      Suite 470      12980
Metcalf Avenue      Overland Park, Kansas, 66213 USA      Attention: General
Counsel      Facsimile: +1-913-685-8856

10.9 Assignment and Binding Effect. Neither party shall assign its rights or
delegate or subcontract its duties in whole or in part under this AGREEMENT
without the other party’s prior written consent, which consent shall not be
unreasonably withheld or delayed, provided that the assigning party shall
guarantee to the other party all of such party’s obligations hereunder and the
assignee shall undertake in writing to observe and perform such obligations.
Notwithstanding the foregoing, CYDEX may assign its rights and/or delegate its
duties hereunder without the consent of HOVIONE to (i) the purchaser of
substantially all of the assets

 

 

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of CYDEX related to its CAPTISOL business, or (ii) an AFFILIATE of CYDEX. In the
event that CYDEX assigns its rights and/or delegates its duties hereunder
without the consent of HOVIONE, then all terms and conditions of this AGREEMENT
shall survive and the assignee of such CYDEX rights, or whomsoever CYDEX
delegates its right to, shall also enjoy the rights and obligations set out in
this AGREEMENT. As a result of such assignment or delegation, or whatever
transfer, HOVIONE’s rights hereunder may not be hurt, reduced or affected. CYDEX
acknowledges that HOVIONE may determine which HOVIONE party hereto (i.e., AGENT,
HOVIONE SA, HOVIONE LIMITED or HOVIONE INTERNATIONAL) shall perform particular
obligations hereunder. Any other assignment shall be void. Any other delegation
or subcontracting shall be a breach of this AGREEMENT.

10.10 No Agency. It is understood and agreed that each party shall have the
status of an independent contractor under this AGREEMENT and that nothing in
this AGREEMENT shall be construed as authorization for either party (as between
CYDEX and HOVIONE) to act as agent for the other, provided that HOVIONE
represents and warrants to CYDEX that AGENT is duly authorized to act for and
legally bind all of the HOVIONE parties related to this AGREEMENT.

10.11 No Strict Construction. This AGREEMENT has been prepared jointly and shall
not be strictly construed against any party.

10.12 Counterparts. This AGREEMENT may be executed in multiple counterparts,
each of which shall be an original as against any party whose signature appears
thereon but both of which together shall constitute one and the same instrument.

Remainder of this page left blank intentionally.

 

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IN WITNESS WHEREOF, the parties, through their authorized representatives, have
duly executed this AGREEMENT as of the date first written above.

 

CYDEX, INC.     HOVIONE LLC By:  

/s/ Edward W. Mehrer

    By:  

/s/ David Hoffman

Name:  

EDWARD W. MEHRER

    Name:  

DAVID HOFFMAN

Title:  

Chief Executive and Pres.

    Title:  

PRESIDENT US OPERATIONS

Date:  

1/10/03

    Date:  

7 JAN. 2003

By:  

/s/ Susan M. Gardner

    By:  

/s/ Lavinia Emery

Name:  

Susan M. Gardner

    Name:  

Lavinia Emery

Title:  

VP & General Counsel

    Title:  

Office Manager

Date:  

1/10/03

    Date:  

7 Jan. 2003

Accepted and agreed:       HOVIONE FARMACIENCIA S.A.     HOVIONE PHARMASCIENCE
LIMITED By:  

/s/ Noé Carreira

    By:  

/s/ G. Villax

Name:  

NOÉ CARREIRA

    Name:  

G. Villax

Title:  

S.TE GENERAL MANAGER - DIRECTOR

    Title:  

Chief Executive & Director

Date:  

20 DEC 2002 in LOURES

    Date:  

23 DEC 2002 in Montella

By:  

/s/ Jorge Pasticha

    By:  

/s/ Christina Bismarck

Name:  

JORGE PASTICHA

    Name:  

CHRISTINA BISMARCK

Title:  

DIRECTOR – CONTROL AND LOGISTICS

    Title:  

—

Date:  

20 December 2002

    Date:  

Montella, 23 December 2002

HOVIONE INTERNATIONAL LIMITED       By:  

/s/ G. Villax

      Name:  

G. Villax

      Title:  

Chief Executive & Director

      Date:  

23 DEC 2002 in Montella

      By:  

/s/ Christina Bismarck

      Name:  

CHRISTINA BISMARCK

      Title:  

—

      Date:  

Montella, 23 December 2002

     

 

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EXHIBIT A

Initial CAPTISOL SPECIFICATIONS

[***]

 

 

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Exhibit B

MANUFACTURING PROCESS DESCRIPTION

[***]

 

 

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the Commission. Confidential treatment has been requested with respect to the
omitted portions.

 

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Exhibit C

Engineering and Validation Process [***]

[***].

 

 

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the Commission. Confidential treatment has been requested with respect to the
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EXHIBIT D

CALCULATION OF ADJUSTED UNIT PRICES

FOR CERTAIN CURRENCY EXCHANGE RATE DEVIATIONS

[***]

 

 

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EXHIBIT E

MANUFACTURING EFFICIENCY

[***]

 

 

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the Commission. Confidential treatment has been requested with respect to the
omitted portions.

 

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