Exhibit 10.8

 

STRICTLY CONFIDENTIAL

 

AMENDMENT N°2 TO PHARMACEUTICAL DEVELOPMENT*

AGREEMENT

 

BETWEEN

 

BEAUFOUR IPSEN INDUSTRIE S.A.S., a French corporation incorporated under the
laws of France, located at rue d’Ethe Virton, 28100, France, duly represented by
Jean-Pierre Dubuc, President,

 

hereinafter referred to as “Ipsen”, on the one hand,

 

AND

 

RADIUS HEALTH Inc., a United States corporation incorporated under the laws of
the State of Delaware, United States, with its principal office at 300
Technology Square-5th Floor, Cambridge, MA, USA and formerly known as
Nuvios, Inc., duly represented by Richard Lyttle, Chief Executive Officer,

 

hereinafter referred to as “Radius”, on the other hand.

 

WHEREAS

 

A.                                   Ipsen and Radius are parties to that
certain License Agreement dated September 27, 2005 (the “License Agreement”).

 

B.                                     Within the framework of the License
Agreement, Ipsen and Radius have entered into a pharmaceutical development
agreement to develop a multidose injection for BIM 44058 dated as of January 2,
2006 (the “Pharmaceutical Development Agreement”) pursuant to which Ipsen
performs certain research and development tasks and activities in view of
developing a new formulation of Licensed Compound and/or Licensed Product.

 

C.                                     Ipsen and Radius have decided to further
extend the duration and the scope of the Work Plan and to provide for the
consideration relating to such an extension under an amendment to the
Pharmaceutical Development Agreement ( “Amendment n°1”).

 

D.                                    Radius has requested, and Ipsen had agreed
to manufacture some further stability batches and therefore to further extend
the duration and the scope of the Work Plan under a second amendment to the
Pharmaceutical Development Agreement (this “Amendment n°2”).

 

NOW, THEREFORE, in consideration of the premises and the performance of the
covenants herein contained, IT IS AGREED AS FOLLOWS:

 

1.                                      In this Amendment n°2, unless otherwise
expressly provided herein, the capitalized words and phrases shall have the same
meaning as in the Pharmaceutical Development Agreement and in Amendment n°1.

 

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

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

 

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

 

2.                                      The May 31, 2007 deadline agreed upon
for the performance by Ipsen or its subcontractors of all the work set out in
the Extended Work Plan further to Amendment n°1 and its payment by Radius, is
extended to December 31, 2012.

 

For sake of clarity, any reference to the date of December 31, 2006 in
Article 10 of the Pharmaceutical Development Agreement and May 31, 2007 in the
Amendment n°1 which relates to the performance of the Original Work Plan and the
Extended Work Plan shall be replaced by and extended to December 31, 2012. The
budget agreed upon in respect to all the work described in the Original Work
Plan and the Extended Work Plan shall remain unchanged, except for the over
overrun of €[*] approved by Radius in Q4, 2006.

 

3.                                      The Work Plan is amended so as to
include the work described in Appendix A to this Amendment n°2 (the “Second
Extended Work Plan”). For clarity, all references to the Work Plan in the
Pharmaceutical Development Agreement shall be deemed to include all work
described in the Extended Work Plan, the Second Extended Work Plan as well as
the work described in the Original Work Plan. Should Radius wish Ipsen to
perform any other work in addition to the activities described in the Second
Extended Work Plan, Radius and Ipsen shall enter into a new agreement or
amendment.

 

4.                                      Timelines described in Appendix A are
subject to the execution by Ipsen of an amendment to its existing agreement with
Vetter.

 

5.                                      Activities related to the manufacture of
Phase III clinical batches by Vetter and tested by Ipsen in the Second Extended
Work Plan as identified in paragraphs 2, 4, 5 of Appendix A shall not be
commenced by Ipsen unless authorized in writing by Nick Harvey, Chief Financial
Officer of Radius or other representative designated in writing by Radius.

 

6.                                      Payments:

 

(a)                                  Subject to any modification of the budget
included in the Second Extended Work Plan to be prior agreed in writing by the
parties by Mike Dey, Vice-President, Pharmaceutical Development for Ipsen and by
Nick Harvey, Chief Financial Officer to Radius or by any other representative
designated by the relevant Party, the total amount to be paid by Radius to Ipsen
in connection with the research activities and tasks pursuant to the Second
Extended Work Plan and this Amendment n°2 shall be as specified in the here
aftached Appendix A. Such total amount includes all costs in connection with
such research activities, including costs of materials, supplies, services,
personnel, subcontractors and overhead, regardless of whether such research
activities are performed by Ipsen or by a subcontractor or both. The budget
included in the Second Extended Work Plan as described in Appendix A to this
Amendment n°2 shows the breakdown by calendar quarter of such total amounts in
Euros.

 

(b)                                 Ipsen shall invoice Radius no later than [*]
([*]) days after the end of each calendar quarter for the amount corresponding
to actual FTE time spent as per

 

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

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

 

2

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

 

timesheets incurred plus actual external cost bills received and approved by
Ipsen during the elapsed quarter, as shall in each case be reported in
reasonable detail on the invoice annex. Radius shall make payment of each
invoice within [*] ([*]) days after receipt thereof in Euros.

 

(c)                                  Without the prior written consent of
Radius, in no event shall Ipsen invoice Radius for an amount due in respect of
any calendar year that is greater than the amount budgeted for such calendar
year in the Second Extended Work Plan plus the [*] percent ([*]%) limit defined
in article 4(d) of this Amendment n°2. In addition, and notwithstanding anything
expressed or implied in this Amendment n°2 to the contrary (including without
limitation, the Second Extended Work Plan), in no event shall Radius have any
obligation to make payments to Ipsen pursuant to this Amendment n°2 for any work
done by Ipsen at any time after December 31, 2012 unless Radius shall have
authorized in writing any such work.

 

Radius shall pay for all work in respect of which Ipsen has entered into legally
binding commitments with subcontractors and which occurs before December 31,
2012, that may not be cancelled by Ipsen without incurring penalties, provided
that all of such work is within the framework of the Second Extended Work Plan
and the cost of such work is within the budget included in the Second Extended
Work Plan.

 

The remaining samples from stability studies will be made available for Radius
to ship to Radius nominated contract laboratory by December 31, 2012. Should
Radius request in writing that Ipsen conduct work on Radius behalf, Ipsen will
be under no obligation to conduct such work.

 

(d)                                 Should external costs incurred by Ipsen in
relation to the performance of the activities described in the Second Extended
Work Plan be more than as specified in Appendix A hereby attached for such
activities, Radius shall reimburse Ipsen such additional costs up to a maximum
of [*] percent ([*]%) of the relevant annual amount described in Appendix A for
the performance of the specific tasks that resulted in such additional costs. In
addition, should internal costs incurred by Ipsen in relation to performance of
the Second Extended Work Plan be more than as specified in Appendix A due to an
increase in the number of FTE’s required (but not the cost per FTE), Radius
shall reimburse Ipsen such additional costs up to a maximum of [*] percent
([*]%) of the relevant annual amount described in Appendix A for the performance
of the specific tasks that resulted in such additional costs. In either case,
any reimbursement of costs in excess of such percentage will have to be prior
agreed by Radius and, in the absence of any such prior agreement by Radius,
shall be the responsibility of Ipsen. Ipsen shall use all reasonable efforts to
avoid any such cost overruns.

 

7.                                      This Amendment n°2 shall enter into
force retroactively upon its signature as of January 1st, 2009 and shall remain
in full force and in effect until complete performance of the

 

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

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

 

3

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

 

Second Extended Work Plan or termination of the Pharmaceutical Development
Agreement in accordance with its terms.

 

8.                                      All other terms and conditions of the
Pharmaceutical Development Agreement shall remain in full force and effect and
shall apply to this Amendment n°2 which is made part of the Pharmaceutical
Development Agreement.

 

9.                                      This Amendment n°2 shall be governed by,
interpreted and construed in accordance with the laws of the State of New York,
U.S.A., without regard to the conflicts of law principles, and shall not be
governed by the United Nations Conventions of International Contracts on the
Sale of Goods (the Vienna Convention).

 

IN WITNESS WHEREOF, the Parties hereto have caused this Amendment n°2 to be duly
executed by their respective duly authorized representatives:

 

Date: January 30, 2009

 

Date: January 17, 2009

 

 

 

SIGNED by B.N. HARVEY

 

SIGNED by Jean-Pierre Dubuc

CFO

 

 

 

 

 

/s/ B.N. Harvey

 

/s/ Jean-Pierre Dubuc

on behalf of

 

as President of

RADIUS HEALTH Inc.

 

BEAUFOUR IPSEN INDUSTRIE S.A.S.

 

4

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

 

APPENDIX A

 

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

 

CMC Activities for BA058
Phase III
Radius / Ipsen

 

1 Stability Batches at Vetter

 

·                  Component Supply for [*]ml Cartridge with new crimp cap +
current bromobutyl stopper

·                  Stoppers available as standard stock item in Vetter.

·                  Standard RTS crimp caps require 12-14 weeks delivery; as
already ordered, estimated delivery date week commencing 26th Jan 2009

·                  Machinability test (cartridges fill with new crimp caps and
maximum filling volume and dimensional limits) Project work = [*]€

 

 

·                  Stability Batches Scheduled at Vetter in March 2009

·

 

BA058 placebo

 

 

·

 

BA058 [*]mg/ml solution

 

[*] cartridges / batch

·

 

BA058 [*]mg/ml solution

 

 

 

 

 

 

 

Uses same equipment as used in Ph III

 

 

Manufacturing starting date

 

March 09

Stability studies start

 

April 2009

 

·                  Costs and Timings

 

Cartridge fill volume will be increased to maximum, to increase assurance of
delivering [*] doses from each cartridge

 

Filling Stability/Technical batches

 

€ [*]

From €[*] for placebo & [*]€ for stability batches [*]&[*]mg/ml, + [*]€ project
management, microbiological validation [*]€, Closure container integrity test
[*]€.

 

2 Clinical Batches [*] ml Cartridges

 

·                  Manufacturing of 3 Clinical Batches by Vetter and Tested by
lpsen

·                  BA058 placebo

·                  BA058 [*]mg/ml solution [*] cartridges / batch

·                  BA058 [*]mg/ml solution

 

·                  Planned in May 2009 :

·                  Clinical studies start in July 2009

 

·

 

Costs

 

€ [*]

·                  From [*] per lot + [*]€ project management costs

 

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

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

 

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

 

3 Stability Testing of Phase III Preparation Lots

 

Activities

 

Duration

 

FTE*

 

FTE cost,
(k€)**

 

External cost
(k€)

Formulation and Process Development

 

 

 

 

 

 

 

 

New crimp caps Supply

 

[*] weeks

 

—

 

[*]

 

[*]

Sterile filtration validation with new API (Millipore)

 

[*] months

 

F: [*]
A: [*]

 

[*]

 

[*]

Stability Studies

 

 

 

 

 

 

 

 

Machinability test & project work

 

[*] month

 

—

 

[*]

 

[*]

[*]-month ICH stability study (2 active + 1 placebo): manufacturing + stab study
at 5°C for [*]months & 25°C for [*] months & stab-in-use + Mixing study,
filtration trials (Vetter) + µbio validation

 

[*] months (including agreement) Final time point: [*]

 

F: [*]
A: [*]
µ: [*]

 

[*]

 

[*]

 

 

TOTAL

 

 

 

[*]

 

[*]

 

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

* F: formulation - A: Analytical - µ: Microbiology

** FTE rates of €[*] per year

 

4 Testing of Ph III Supplies

 

Activities

 

Duration

 

FTE*

 

FTE cost,
(k€)**

 

External cost
(k€)

Clinical Supply

 

 

 

 

 

 

 

 

Phase III clinical batches manufacturing + release (2 active + 1 placebo)

 

[*] months (including agreement)

 

F: [*]
A: [*]
µ: [*]

 

[*]

 

[*]

Re-assay program to verify stability

 

[*]months

 

A: [*]
µ: [*]

 

[*]

 

[*]

IND

 

[*] months

 

F: [*]

 

[*]

 

[*]

Project Management

 

—

 

F: [*]

 

[*]

 

[*]

 

 

 

 

TOTAL

 

[*]

 

[*]

 

 

 

 

 

 

[*]

 

 

 

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

* F: formulation - A: Analytical - µ: Microbiology

** FTE rates of €[*] per year

 

5 Phasing of Costs for Ph III Program

 

BA058 Phase III Quarterly breakdown for work plan activities

 

Drug Substance & Drug Product Program

 

 

 

2009

 

2010

 

2011

 

2012

 

 

In €000

 

Q1

 

Q2

 

Q3

 

Q4

 

Q1

 

Q2

 

Q3

 

Q4

 

Q1

 

Q2

 

Q3

 

Q4

 

Q1

 

Q2

 

Q3

 

Q4

 

Total

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

External costs

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Internal costs

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Total costs/Quarter

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

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

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

 

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

 

Total cost/year

 

[*]

 

 

 

 

 

 

 

[*]

 

 

 

 

 

 

 

[*]

 

 

 

 

 

 

 

[*]

 

 

 

 

 

 

 

[*]

 

API costs not included; API is supplied by Radius

 

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

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

 

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

 

6 API needed for Drug Product development activities

 

·                  Estimation based on available BA058 API available in stock on
September, 2008

 

Activities

 

Units manufactured

 

API (pure)
needed

 

API batch #

Stability studies (ICH Current Formulation with new crimp caps [*]mg/ml &
[*]mg/ml

 

[*] cartridges as 1 x [*] ea of [*]mg/ml, [*]mg/ml & placebo

 

[*]g + [*]g = [*]g

 

Lonza API in final cartridge CC and stopper at Vetter at scale for Ph III

Optimize/Validate analytical Method

 

/

 

[*] g

 

M12507 (Ipsen batch)

Finalise API methods

 

/

 

[*]g

 

Lonza API

Sterile filtration validation

 

[*]mL

 

[*]g

 

Lonza API to mimic Ph III process

Clinical batches for Ph III
Made to a suitable Validation protocol & to provide stability lots for long-term
storage

 

1 x [*] cart x [*]mg/m1 + 1 x [*]cart x [*]mg/m1+1 x [*]cart x placebo

 

(GMP batch)
[*]g + [*]g
[*]g + [*]g
[*]g + [*]g

 

Two strength to be manufactured at Vetter at Ph III scale
1st lots mid 2009
2nd lots end 2009
3rd lots early 2010

 

· Total new API needed for Phase III activities = [*] g (pure peptide)

 

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

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

 

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