Document:

Exhibit 10.6

 

STRICTLY CONFIDENTIAL

 

AMENDMENT N°1 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 Square5th 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.                                     Since (i) the work to be performed by Ipsen has taken longer than originally planned in the Work Plan of the Pharmaceutical Development Agreement and (ii) Radius wishes Ipsen to perform additional work to the work initially set out in the Work Plan, 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 (this “Amendment n°1”).

 

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

 

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

 

1

 

2.                                       The December 31, 2006 deadline initially agreed upon for the performance by Ipsen or its subcontractors of all the work set out in the Work Plan as it exists prior to this Amendment (the “Original Work Plan”) and its payment by Radius, is extended to May 31, 2007.

 

For sake of clarity, any reference to the date of December 31, 2006 in Article 10 of the Pharmaceutical Development Agreement which relates to the performance of the Original Work Plan shall be replaced by and extended to May 31, 2007. The budget agreed upon in respect to all the work described in the Original Work Plan shall remain unchanged, except for the over overrun of €98,000 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°1 (the “Extended Work Plan”),  some of which is to be performed in 2007 and the rest in 2008. 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, as well as the work described in the Original Work Plan. Should Radius wish Ipsen to perform any other work in addition to the 2007 and 2008 activities described in the Extended Work Plan, Radius and Ipsen shall enter into a new agreement or amendment.

 

4.                                       Payments:

 

(a) Subject to any modification of the budget included in the 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 Extended Work Plan and this Amendment n°1 shall be as specified in the here attached Appendix B, that is to say:

 

(i) The total amount to be paid by Radius to Ipsen in connection with the 2007 activities described Appendix A shall be:

 

·                                          Seventy three thousand euros (73K€) for the additional activities on Drug Substance;

 

·                                          Two hundred thirty four thousand four hundred euros (234.4K€) for additional activities on Drug Product;

 

(ii) The total amount to be paid by Radius to Ipsen in connection with the 2008 activities described in Appendix A shall be:

 

·                                          Twenty eight thousand euros (28K€) for the additional activities on Drug Substance;

 

·                                          One hundred and ninety six thousand euros (196K€) for additional activities on Drug Product;

 

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 Extended Work Plan as described in Appendix B to this Amendment shows the breakdown by calendar quarter of such total amounts in Euros.

 

2

 

(b) Ipsen shall invoice Radius no later than thirty 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 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 Extended Work Plan plus the ten percent (10%) limit defined in article 4(d) of this Amendment n°1. In addition, and notwithstanding anything expressed or implied in this Agreement to the contrary (including without limitation, the Extended Work Plan), in no event shall Radius have any obligation to make payments to Ipsen pursuant to this Amendment n°1 for any work done by Ipsen at any time after December 31, 2008 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, 2008, that may not be cancelled by Ipsen without incurring penalties, provided that all of such work is within the framework of the Extended Work Plan and the cost of such work is within the budget included in the 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, 2008. Should Radius request in writing that Ipsen conduct work on Radius behalf, Ipsen will be under no obligation to conduct such work.

 

(d)           Notwithstanding any overruns which have been approved by Radius with respect to work under the Original Work Plan, should external costs incurred by Ipsen in relation to the performance of 2007 or 2008 activities described in the Extended Work Plan be more than as specified in Appendix B 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 B 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 Work Plan be more than as specified in Exhibit B 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 B 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. For clarity, the maximum ten adjustment permitted in 2007 will be of thirty thousand seven hundred (30.7) euros and in 2008 of twenty two thousand four hundred (22.4) euros. Any reimbursement of costs in excess of such percentage will have to be prior agreed by Radius and, absent any such prior agreement by Radius, shall be the responsibility of Ipsen.

 

3

 

5.                                       This Amendment n°1 shall enter into force retroactively upon its signature as of January 1st, 2007 and shall remain in full force and in effect until complete performance of the Extended Work Plan or termination of the Pharmaceutical Development Agreement in accordance with its terms.

 

6.                                       All other terms and conditions of the Pharmaceutical Development Agreement shall remain in full force and effect and shall apply to this Amendment n°1 which is made part of the Pharmaceutical Development Agreement.

 

7.                                       This Amendment n°1 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 Agreement to be duly executed by their respective duly authorized representatives:

 

 

	
Date:   July 16,   2007
    	
 
    	
Date:   29.06.07
    
	
 
    	
 
    	
 
    
	
SIGNED   by B.N. Harvey
    	
 
    	
SIGNED   by Jean-Pierre Dubuc
    
	
 
    	
 
    	
 
    
	
/s/   B.N. Harvey
    	
 
    	
/s/   Jean-Pierre Dubuc
    
	
on   behalf of
    RADIUS HEALTH Inc.
    	
 
    	
as   President of
    BEAUFOUR IPSEN INDUSTRIE S.A.S.
    

 

4

 

APPENDIX A

 

EXTENDED WORK PLAN

 

	
 
    	
BA058:   DEVELOPMENT PLAN
    
	
 
    	
OF   READY TO USE PEN INJECTION
    
	
 
    	
FOR   PHASE II
    
	
 
    	
 
    
	
 
    	
ADDITIONAL   ACTIVITIES - 2007 & 2008
    

 

5

 

 

 

	
 

APPENDIX A

 

BA058 :   Development plan  
    of Ready to Use Pen  
    Injection for Phase II  

 

Additional   activities - 2007 & 2008
    	

    

 

6

 

Content

 

·                  Drug Substance

 

·                  Drug Product

·                  Proposed IND stability commitment

·                  Stability program

·                  Stability batches

·                  Clinical batches

·                  Stability-in-use

·                  Cost estimation for 2007 & 2008

 

7

 

 

8

 

Activities to support IND submission (API)

 

	
-   Additional test on batch 01-402:
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
(residual solvents , TFA, and optical rotation)
    	
 
    	
2007
    	
 
    	
External   cost
    	
 
    	
07k   €
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
-   Stability study of batch 01-402:
    	
 
    	
2007
    	
 
    	
[*]FTE
    	
 
    	
55k   €
    
	
 
    	
 
    	
2008
    	
 
    	
[*]FTE
    	
 
    	
28k   €
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Retest   of reference material
    	
 
    	
2007
    	
 
    	
[*]FTS
    	
 
    	
11k   €
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
TOTAL
    	
 
    	
 
    	
 
    	
73k   € in 2007
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
28k   € in 2008
    	
 
    	
 
    

 

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

 

9

 

 

10

 

 

Proposed IND Stability Commitment

 

Continue the stability study in accelerated (25°C/60%RH) and long-term (5°C) storage conditions in parallel to the clinical study.

 

Monitor periodically clinical batches in a re-assay program at the label claim storage condition (i.e. 5°C).

 

The shelf life period will be extended based on data from accelerated and long-term studies, as well as results from by this re-assay program.

 

11

 

Stability Program: 0.5 & 2 mg/ml

 

	
Time
   Point
    	
 
    	
Pull
   Date
    	
 
    	
Storage Conditions
    	
 
    	
Shelf life
   (extrapolation)
    	
 
    	
Use Date
   of clinical
   supplies *
    	
 
    	
FTE to support analytical
   work (physicochemical and
   microbiological tests - report @
   6, 12 and 24 months)
    
	
6   months
    	
 
    	
03/26/07
    	
 
    	
5°C &   25°C/60%RH (including preservative effectiveness at 25°C/60%RH)
    	
 
    	
12 months
    	
 
    	
End Oct. 07
    	
 
    	
[*]+[*] (μbio) 
   + [*]€ (external cost)**
    
	
9   months
    	
 
    	
06/26/07
    	
 
    	
5°C
    	
 
    	
18 months
    	
 
    	
End April 08
    	
 
    	
[*]
    
	
12   months
    	
 
    	
09/26/07
    	
 
    	
5°C   (including preservative effectiveness)
    	
 
    	
24 months
    	
 
    	
End Oct. 08
    	
 
    	
[*]+[*] (μbio)
    
	
18   months
    	
 
    	
March 08
    	
 
    	
5°C
    	
 
    	
24 months
    	
 
    	
End Oct. 08
    	
 
    	
[*]
    
	
24   months
    	
 
    	
Sept.   08
    	
 
    	
5°C   (including preservative effectiveness)
    	
 
    	
24 months
    	
 
    	
End Oct. 08
    	
 
    	
[*]+[*] (μbio) 
   + [*] € (external cost)**
    

 

* Use date = manufacturing date + shelf life

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

 

12

 

Stability Program: Placebo

 

	
Time
   Point
    	
 
    	
Pull
   Date
    	
 
    	
Storage Conditions
    	
 
    	
Shelf life
   (extrapolation)
    	
 
    	
Use Date
   of clinical
   supplies *
    	
 
    	
FTE to support analytical
   work (physicochemical and
   microbiological tests - report
   @ 6, 12 and 24 months)
    
	
6   months
    	
 
    	
02/16/07
    	
 
    	
5°C &   25°C/60%RH (including preservative effectiveness at 25°C/60%RH)
    	
 
    	
12 months
    	
 
    	
End Oct. 07
    	
 
    	
[*]+[*] (μbio)
    
	
9   months
    	
 
    	
05/16/07
    	
 
    	
5°C
    	
 
    	
18 months
    	
 
    	
End 08April
    	
 
    	
[*]
    
	
12   months
    	
 
    	
08/16/07
    	
 
    	
5°C   (including preservative effectiveness)
    	
 
    	
24 months
    	
 
    	
End Oct. 08
    	
 
    	
[*]+[*] (μbio)
    
	
18 months
    	
 
    	
Feb. 08
    	
 
    	
5°C
    	
 
    	
24 months
    	
 
    	
End Oct. 08
    	
 
    	
[*]
    
	
24   months
    	
 
    	
Aug. 08
    	
 
    	
5°C   (including preservative effectiveness)
    	
 
    	
24 months
    	
 
    	
End Oct. 08
    	
 
    	
[*]+[*] (μbio)
    

 

* Use date = manufacturing date + shelf life

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

 

13

 

Re-assay program: 0.5, 1, 2 mg/ml & Placebo

 

·                  To ensure the quality of the clinical supplies throughout the study :

 

It is proposed to re-test clinical batches stored at the label claim storage condition (i.e. 5°C) every 6 months until the end of the phase II clinical study

 

	
Re-Test Date
    	
 
    	
Re-Test Time Point
    	
 
    	
FTE
    
	
April 07
    	
 
    	
6 months
    	
 
    	
[*]
    
	
October 07
    	
 
    	
12 months
    	
 
    	
[*]
    
	
April 08
    	
 
    	
18 months
    	
 
    	
[*]
    
	
October 08
    	
 
    	
24 months
    	
 
    	
0.06 + 0.10 (μbio) 
   + [*] € (external cost)**
    

 

** Subcontracting of sterility test at VETTER

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

 

14

 

Stability program: stability in-use

 

·                  To simulate patient use, as far as possible

·                  Cartridge activated, inside the pen

·                  Storage at room temperature

·                  1 simulation of injection per day, during 1 month

 

	
Time point
    	
 
    	
Pull date
    	
 
    	
Storage conditions
    	
 
    	
FTE
    
	
1 month
    	
 
    	
Feb. 07
    	
 
    	
25°C/60%RH
    	
 
    	
[*]+[*] (μbio)
    
	
At shelf life
    	
 
    	
Nov. 08
    	
 
    	
25°C/60%RH
    	
 
    	
[*]+ [*] (μbio)
    

 

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

 

15

 

Drug Product: cost estimation 2007 & 2008

 

	
Year
    	
 
    	
FTE
    	
 
    	
FTE cost *
   (in k€)
    	
 
    	
External cost
   (in k€)
    	
 
    	
Total
   (in k€)
    
	
2007
    	
 
    	
[*]+ [*] (μbio)
    	
 
    	
[*]
    	
 
    	
[*]**
    	
 
    	
234.4
    
	
2008
    	
 
    	
[*]+[*] (μion)
    	
 
    	
[*]
    	
 
    	
[*] **
    	
 
    	
196.0
    

 

·FTE rates of $[*], converted at $[*]/€ to give €[*] per year

 

** Subcontracting of sterility test at VETTER + shipment

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

 

16

 

APPENDIX B

 

EXTENDED WORK PLAN

 

I.              2007 BUDGET

 

I.1           DRUG SUBSTANCE

 

	
Additional test on batch   01- 402 
   (residual solvents, TFA and optical rotation)
    	
 
    	
External cost*
    	
 
    	
07k€
    
	
Stability study of batch   01- 402
    	
 
    	
Internal cost — FTE**
   [*]
    	
 
    	
55k€
    
	
Retest of reference   material
    	
 
    	
Internal cost — FTE**
   [*]
    	
 
    	
11k€
    
	
Total
    	
 
    	
 
    	
 
    	
73k€
    

 

* Subcontracting of Additional test on batch 01- 402 at EXPANSIA + shipment 
 ** FTE rates at [*]€

 

1.2          DRUG PRODUCT

 

	
FTE
    	
 
    	
FTE cost*
    	
 
    	
External cost**
    	
 
    	
Total
    
	
[*] + [*] (μbio)
    	
 
    	
[*]€
    	
 
    	
[*]€
    	
 
    	
234.4€
    

 

* FTE rates at [*]€
 ** Subcontracting of sterility test at VETTER + shipment

 

1.3          QUARTERLY BREAKDOWN FOR EXTENDED WORK PLAN ACTIVITIES  PERFORMED IN 2007

 

	
 
    	
 
    	
2007
    	
 
    	
2007
    	
 
    
	
In K€
    	
 
    	
Q1
    	
 
    	
Q2
    	
 
    	
Q3
    	
 
    	
Q4
    	
 
    	
Total
    	
 
    
	
External Costs
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    
	
 
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    
	
Internal Costs
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    
	
 
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    
	
FTEs
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    
	
Total Costs 
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    

 

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

 

17

 

II.            2008 BUDGET

 

II. 1.        DRUG SUBSTANCE

 

	
Stability   study of batch 01- 402
    	
 
    	
Internal cost — FTE**
   [*]
    	
 
    	
[*]€
    
	
Total
    	
 
    	
 
    	
 
    	
[*]€
    

 

** FTE rates at [*]€

 

11.2        DRUG PRODUCT

 

	
FTE
    	
 
    	
FTE cost *
    	
 
    	
External cost**
    	
 
    	
Total
    
	
[*] + [*] (bio)
    	
 
    	
[*]€
    	
 
    	
[*]€
    	
 
    	
[*]€
    

 

* FTE rates at [*]€

** Subcontracting of sterility test at VETTER + shipment

 

11.3        QUARTERLY BREAKDOWN FOR EXTENDED WORK PLAN ACTIVITIES PERFORMED IN 2008

 

	
 
    	
 
    	
2008
    	
 
    	
2008
    	
 
    
	
 
    	
 
    	
Q1
    	
 
    	
Q2
    	
 
    	
Q3
    	
 
    	
Q4
    	
 
    	
Total
    	
 
    
	
External costs
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    
	
Internal costs (Drug Substance)
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    
	
Internal costs (Drug Product)
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    
	
FTEs
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    
	
Total costs
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    	
[*]
    	
 
    

 

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

 

18Exhibit 10.7

 

CONFIDENTIAL— Execution Copy

 

LICENSE AGREEMENT AMENDMENT NO. 1

 

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

 

RECITALS

 

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

 

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

 

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

 

ARTICLE 1  —  CONDITIONS PRECEDENT

 

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

 

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

 

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

 

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

 

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

 

ARTICLE 2  —  AMENDMENTS TO CERTAIN PROVISIONS OF THE AGREEMENT

 

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

 

 

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

 

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

 

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

 

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

 

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

 

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

 

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

 

2

 

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

 

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

 

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

 

2.5          Payments and Financial Reporting.

 

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

 

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

 

3

 

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

 

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

 

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

 

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

 

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

 

ARTICLE 3  —  MISCELLANEOUS

 

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

 

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

 

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

 

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

 

	
RADIUS HEALTH INC.
    	
SCRAS   S.A.S
    
	
 
    	
 
    	
 
    	
 
    	
 
    
	
By:
    	
/s/   C. R. Lyttle
    	
 
    	
By:
    	
/s/   Claire Giraut
    
	
Name:
    	
C.   Richard Lyttle
    	
 
    	
Name:
    	
Claire   Giraut
    
	
Title:
    	
President   & CEO
    	
 
    	
Title:
    	
Director   General
    

 

4

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