Exhibit 10.1

 

STRICTLY CONFIDENTIAL

 

Confidential Treatment Requested

 

Under 17 C.F.R. §§ 200.80(b)(4) and
240.24b-2

 

 

Execution Copy

 

AMENDMENT N°4 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 Sates, 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 (“Amendment n°2”).

 

E.                                      Radius has requested, and Ipsen had
agreed to manufacture Phase III batches and to upgrade analytical methods to NDA
filing levels for purity/impurities testing to meet full ICH requirements and
therefore to further extend the duration and the scope of the Work Plan under a
third amendment to the Pharmaceutical Development Agreement (“Amendment n°3”).

 

[*] Certain information in this document has been omitted and filed separately
with the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions.

 

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F.                                      Radius has requested, and Ipsen had
agreed to manufacture, test and release extra Phase III batches and run
stability studies and therefore to further extend the duration and the scope of
the Work Plan under a fourth amendment to the Pharmaceutical Development
Agreement (this “Amendment n°4”).

 

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°4, 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, Amendment n°2 and
Amendment n°3.

 

2.              The Work Plan is amended so as to include the work described in
Appendix A to this Amendment n°4 (the “Fourth 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
Reduced Second Extended Work Plan, the Third 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 Fourth Extended
Work Plan, Radius and Ipsen shall enter into a new agreement or amendment.

 

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

 

4.              Activities related to the manufacture of additional Phase III
clinical batches by Vetter and tested by Ipsen in 2011 or 2012 and any batch
Scale Up Plans in the Fourth Extended Work Plan as identified in paragraphs 2
and 3 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.

 

5.              Payments

 

(a)          Subject to any modification of the budget included in the Fourth
Extended Work Plan to be prior agreed in writing by the parties by Aidan Murphy,
Senior Vice-President, CMC and Engineering for Ipsen and by Nick Harvey, Chief
Financial Officer for 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 Fourth Extended Work Plan
and this Amendment n°4 shall be as specified in the here attached 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
Fourth Extended Work Plan as described in Appendix A to this Amendment n°4 shows
the breakdown by calendar quarter of such total amounts in Euros.

 

(b)         Ipsen shall invoice Radius no later than thirty (30) days after the
end of each calendar quarter for the amount corresponding to actual FTE time
spent as per 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 thirty (30) days after receipt thereof in Euros.

 

[*] Certain information in this document has been omitted and filed separately
with the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions.

 

2

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(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 Fourth Extended
Work Plan plus the ten percent (10%) limit defined in article 4(d) of this
Amendment n°4. In addition, and notwithstanding anything expressed or implied in
this Amendment n°4 to the contrary (including without limitation, the Fourth
Extended Work Plan), in no event shall Radius have any obligation to make
payments to Ipsen pursuant to this Amendment n°4 for any work done by Ipsen at
any time after December 31, 2014 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,
2014, that may not be cancelled by Ipsen without incurring penalties, provided
that all of such work is within the framework of the Fourth Extended Work Plan
and the cost of such work is within the budget included in the Fourth 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, 2014. 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 Fourth 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 ten percent (10%)
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 Fourth
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 ten percent (10%) 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.

 

6.              This Amendment n°4 shall enter into force retroactively upon its
signature as of January 2, 2011 and shall remain in full force and in effect
until complete performance of the Fourth Extended Work Plan or termination of
the Pharmaceutical Development Agreement in accordance with its terms.

 

7.              Section 4 of Appendix A to Amendment n°3 to the Pharmaceutical
Development Agreement is renumbered as Section 3, there being no Section 3 in
Annex A to Amendment n°3.

 

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°4 which is made part of the Pharmaceutical Development Agreement.

 

9.             This Amendment n°4 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).

 

[*] Certain information in this document has been omitted and filed separately
with the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions.

 

3

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IN WITNESS WHEREOF, the Parties hereto have caused this Amendment n°4 to be duly
executed by their respective duly authorized representatives intending it to
take effect as of January 2, 2011:

 

 

Date: December 7, 2011

 

Date: December 15, 2011

 

 

 

SIGNED by

 

SIGNED by Jean-Pierre Dubuc

 

 

 

/s/ B. Nicholas Harvey, CFO

 

/s/ Jean-Pierre Dubuc

 

 

 

 

 

 

on behalf of

 

as President of

RADIUS HEALTH Inc.

 

BEAUFOUR IPSEN INDUSTRIE S.A.S.

 

[*] Certain information in this document has been omitted and filed separately
with the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions.

 

4

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APPENDIX  A

 

Updated CMC Activities for BA058

Phase III Supply Amendment 4

28th May 2010

Version Updated 6th October 2011

 

1. Summary of Work Program from 2010

 

Requested Manufacture of Clinical Batches 1.5 ml Cartridges x 6 completed and
product supplied in late 2010, As per Proposal from 28th May

 

·                  Manufacturing of 6 Clinical Batches by Vetter and Tested by
Ipsen

·                  Gives nominally 5,000 each, placebo and 2mg/ml cartridges

·                  Provided for clinical use by end Oct, Nov and Dec

 

·                  Testing, Release and Stability Testing of Phase III Lots

 

Upgrade of analytical methods completed and full testing and release of three
lots each of active and placebo completed.

 

Stability testing of last lot made in 2010, set up in early 2011, so €[*] FTE
costs transferred to updated 2011 costs.

 

Invoiced amounts for 2010 and Q1 2011 are compared with initial budgeted amounts
for 2010.

 

Planned in 2010

 

Variance Vs
Budget 2010

 

Actual 2010

 

Moved to 2011

 

 

Cost €000s

 

FTE Cost

 

External

 

FTE Cost

 

External

 

FTE Cost

 

External

 

Comments

Stability works from amendment 2

 

[*]

 

[*]

 

[*]

 

[*]

 

 

 

 

 

 

Make and test Ph III Lots 3 x 2mg/ml and 3 x Placebo

 

[*]

 

[*]

 

[*]

 

[*]

 

 

 

 

 

Completed; FTE costs decreased for testing m

Full ICH Stability on one 2010 Lot

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

 

 

Started in early 2011; €[*] transfer to 2011

Analytical Methods Upgrade

 

[*]

 

[*]

 

[*]

 

[*]

 

 

 

 

 

Completed as planned

IND Update

 

[*]

 

[*]

 

[*]

 

[*]

 

 

 

 

 

No update required

Project Management activities

 

[*]

 

[*]

 

[*]

 

[*]

 

 

 

 

 

 

SUBTOTAL

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

 

GRAND TOTAL

 

-111

 

923

 

57

 

 

 

 

 

 

 

 

 

 

 

FTE Costs

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

 

External

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

 

Total

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

923

 

 

 

Improvement in costs by €[*], from €[*] to ~€[*] achieved by simultaneous QC
testing of multiple lots.  Stability costs (€[*]), initially planned for late
2010, now transferred to 2011, as lot was released very late 2010, and study set
up in early 2011, rather than late 2010.  Also IND update was not required.

 

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[*] Certain information in this document has been omitted and filed separately
with the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions.

 

5

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2. Updated plan for 2011-2014, for supply of Ph III lots

 

·                  Stability testing ongoing in 2011-2014 for

Lot Made in 2009 and Lot made in 2010

 

·                  Supply of additional lots from Nominal 5,000 scale cartridge
lot of BA058 2mg/ml and Placebo scheduled as

 

One lot Placebo

 

week of 23rd May 2011

 

 

One lot BA058 2mg/ml

 

week of 6th June 2011

 

 

 

 

 

 

 

One lot Placebo

 

week of 26th Sep 2011

 

 

One lot BA 058 2mg/ml

 

week of 28th Sep 2011

 

 

 

 

 

 

 

One lot Placebo

 

week of 12th Dec 2011

 

 

One lot BA 058 2mg/ml

 

week of 19th Dec 2011

 

 

 

·                  Additional stability testing

On lot to be made in Sep 2011 and on lot to be made in Dec 2011

 

Costing included here based on 5,000 cartridge scale, under this updated
schedule for Amendment 3, pending Radius decision on future scale up to larger
scale batches to be included in a next Amendment.

 

 

 

Amendment 3 Plan Updated for 2011 Planning

 

Total

 

 

 

2011

 

 

 

2012

 

 

 

2013

 

 

 

2014

 

 

 

2015

 

 

 

 

 

PROPOSED PLAN

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

#

 

Cost €000s

 

FTE Cost

 

External

 

FTE Cost

 

External

 

FTE Cost

 

External

 

FTE Cost

 

External

 

FTE Cost

 

External

 

FTE Cost

 

External

 

1

 

Stability tests ons ongoing Lots from 2009

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

 

 

 

 

 

 

 

 

 

 

 

 

2

 

Stability test Lot from Dec 2010

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

 

 

[*]

 

 

 

[*]

 

[*]

 

 

 

 

 

3

 

Stability on Lot to be made in Sep 2011

 

[*]

 

[*]

 

 

 

 

 

[*]

 

[*]

 

[*]

 

 

 

[*]

 

[*]

 

 

 

 

 

4

 

Stability on Lot to be made in Dec 2011

 

[*]

 

[*]

 

 

 

 

 

[*]

 

[*]

 

[*]

 

 

 

[*]

 

 

 

[*]

 

[*]

 

5

 

Make and test Ph III Lot (mg/ml and Placebo) - May 2011

 

[*]

 

[*]

 

[*]

 

[*]

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

6

 

Make and test Ph III Lot (mg/ml and Placebo) - Sep 2011

 

[*]

 

[*]

 

[*]

 

[*]

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

7

 

Make and test Ph III Lot (mg/ml and Placebo) - Dec 2011

 

[*]

 

[*]

 

 

 

 

 

[*]

 

[*]

 

 

 

 

 

 

 

 

 

 

 

 

 

8

 

IND update

 

[*]

 

[*]

 

[*]

 

 

 

[*]

 

 

 

[*]

 

 

 

[*]

 

 

 

[*]

 

 

 

9

 

Project Management activities

 

[*]

 

[*]

 

[*]

 

 

 

[*]

 

 

 

[*]

 

 

 

[*]

 

 

 

[*]

 

 

 

 

 

SUBTOTAL

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

[*]

 

 

 

GRAND TOTAL

 

1333

 

552

 

445

 

140

 

129

 

67

 

 

Costs based on € 250k per FTE

 

3 API needed for Manufacture and Stability Testing

 

Based on 3 x 5000 cartridge lots, each requiring [*]g API, gives [*]g pure
peptide weight, for manufacture of lots in 2011.

API should be delivered to Vetter temper evident sealed with appropriate
documentation 2 months before manufacture.

 

Updated Schedule and Budget under Amendment 4 agreed as of January 2, 2011.

 

 

/s/ B. Nicholas Harvey

 

/s/ Aidan Murphy

 

 

 

B. N Harvey, CFO

 

A. Murphy, Vice President

Radius Health

 

CMC and Engineering, Ipsen

 

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[*] Certain information in this document has been omitted and filed separately
with the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions.

 

6

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