Document:

Exhibit 10.20

 

EXECUTION COPY

 

FOURTH AMENDMENT TO DEVELOPMENT AND CLINICAL SUPPLIES AGREEMENT*

 

This Fourth Amendment (this Amendment”) is entered into as of March 2, 2011 by and between 3M Company, and 3M Innovative Properties Company having a principal office at 3M Center, Building 275-3E-10, St. Paul, MN 55144-1000 (hereinafter “3M”), and Radius Health, Inc. having a principal office at 201 Broadway, 6th Floor, Cambridge, MA (hereinafter “Radius”) and amends the Development and Clinical Supplies Agreement dated June 19, 2009, as amended by the Amendment dated as of December 31, 2009, the Second Amendment dated as of September 16, 2010 and the Third Amendment dated as of September 29, 2010 (hereinafter, the “Agreement”). Capitalized terms used in this Amendment and not defined herein are used with the meanings ascribed to them in the Agreement.

 

RECITALS:

 

WHEREAS, the Parties wish to enter into this Amendment to address certain matters relating to the development and supply of Product to Radius by 3M for use in a Phase II clinical study.

 

NOW, THEREFORE, in consideration of the Recitals (which are incorporated herein) and other good and valuable consideration, the receipt and sufficiency of which is hereby acknowledged, the Parties agree to amend the Agreement as follows:

 

1.                                       3M shall perform the Workplan attached as Attachment 1 to this Amendment with respect to the development and supply of Product for use by Radius in a Phase II clinical study for the Product.  The Workplan may not fully disclose the detailed technical plans and protocols that 3M will follow in the performance of the Workplan, but 3M represents and warrants that it has adopted such plans and protocols and will provide them to Radius upon request. Such requests shall be submitted as Change Orders and shall be provided at Radius’ expense in the event and to the extent that 3M is required to draft such plans and non-proprietary protocols and cannot utilize plans and protocols that exist at the time that Radius makes such request.  If 3M can utilize plans and protocols that are documented at the time Radius makes such request, 3M shall provide such plans and protocols to Radius at no charge.  3M will deliver Product no later than 14 months after the effective date of this Amendment and will use commercially reasonable efforts to accomplish delivery by March 15, 2012.   The costs for development and supply of Product for the Phase II clinical study is estimated to be $5.9 million, based on the assumptions and tasks outlined in Attachment 1.The Parties shall confer regarding the estimated hours set forth in the Workplan attached as Attachment 1 and such hours may be subject to an adjustment in the event that the Parties determine that the hours required to perform the Workplan are different from the estimated hours set forth in Attachment 1.  3M will provide Radius with a list of significant tasks identified in the Workplan and the hours associated with them. 3M and Radius will meet regularly to review the progress and budget.

 

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

 

	
3M Drug Delivery Systems
    	
Confidential
    

 

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2.                                       3M will provide Radius with a copy of documentation as agreed in the Quality Agreement.  3M will also provide a development plan that addresses sterility issues and provides a strategic outline for further development activities until commercialization to Radius.  The plan and any subsequent modifications to the plan will be reviewed with Radius and Radius’ comments will be reasonably considered.   It is understood and agreed that the current plan will be a strategic document that will be subject to revision as the parties move forward.

 

3.                                       Section 2.3 of the Agreement is hereby amended to read in full as follows:

 

“2.3  Either Party may at any time propose a change to the Workplan.  If 3M reasonably believes that a proposed change will increase 3M’s costs or delay completion of the Workplan, the Parties will negotiate in good faith to accommodate such requests.  No such change will be effective unless and until set forth in a written Change Order to the Workplan with an agreed budget and timeline that is approved and signed by authorized representatives of the Parties.  ”

 

4.                                       A new Section 3.6 is hereby added to the Agreement to read in full as follows:

 

“3.6  (a)  A Steering Committee (“Steering Committee”) shall be established with the responsibilities and authority set forth in this Section 3.6.  The Steering Committee shall consist of four (4) members, two (2) members to be appointed by each of Radius and 3M.  The initial Radius members shall be Richard Lyttle and Nick Harvey and the initial 3M members shall be Steve Wick and Ann Meitz.  Each party may, with notice to the other, substitute any of its members serving on the Steering Committee.  The Parties may also, by mutual agreement, increase or decrease the number of members serving on the Steering Committee; provided that the number of members representing each party remains equal.  Radius shall have the right to appoint one of its members to be the chairperson of the Steering Committee.

 

(b)  The general purpose of the Steering Committee is to oversee the performance of the Workplan  concerning the development and supply of Product for the Phase II clinical study.  The Steering Committee shall have the responsibility and authority to: (i) monitor each of Radius’ and 3M’s implementation of their respective responsibilities under the Workplan; (ii) consider, review and approve any proposed amendments to the services or the deliverables set forth in the Workplan; (iii) report regularly to the management of both Parties upon the progress of the Workplan; (iv) provide a forum for exchange of information related to the efforts of each party with respect to the Workplan; (v) resolve disputes (if any) arising among the members of the Joint Technical Team; and (vi) conduct any other functions as Radius and 3M may agree in writing.

 

(c)  The Steering Committee shall hold meetings as mutually agreed by the Parties (but in no event less than quarterly, unless mutually agreed by the Parties).  The first meeting of the Steering Committee shall be held by April 15, 2011 and shall be held in Cambridge, Massachusetts.  After the initial meeting, meetings may be held by telephone or video

 

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conference, provided  that the Parties shall meet in person at least once per year, and such meetings shall be held in Cambridge, Massachusetts or St. Paul, Minnesota unless the Parties mutually agree to hold such meetings elsewhere.  Minutes of all meetings setting forth decisions of the Steering Committee shall be prepared by the chairperson and circulated to all Parties within thirty (30) days after each meeting, and shall not become official until approved by all Parties in writing; minutes shall be presented for approval as the first order of business at the subsequent Steering Committee meeting, or if it is necessary to approve the minutes prior to such subsequent meeting, then the Parties shall approve the minutes within thirty (30) days of receipt thereof.

 

(d)  The quorum for Steering Committee meetings shall be four (4) members, provided there is at least two (2) members from each of Radius and 3M present.  The Steering Committee will render decisions by unanimous vote.  The members of the Steering Committee shall act in good faith to cooperate with one another and to reach agreement with respect to issues to be decided by the Steering Committee.

 

(e)  Disagreements among the Steering Committee will be resolved via good-faith discussions; provided, that in the event of a disagreement that cannot be resolved within forty five (45) days after the date on which the disagreement arose, then Radius will have the right to make the final decision and such decision shall be final and binding and shall not be subject to Section 12.5; provided that the right of Radius to exercise such final decision under this Section 3.6(e) (i) shall not compel 3M to assume additional costs not agreed to under a Change Order, (ii)  shall not apply to disputes with respect to the interpretation, breach, termination or invalidity of this Agreement, (iii) shall not compel 3M to perform any activities that 3M reasonably considers to be contrary to applicable laws, regulations or ethical principles, and (iv) shall impose a duty on Radius to indemnify and hold 3M harmless from the consequences of any such Radius decision.  Any deadlock not covered by the preceding sentence shall be resolved pursuant to Section 12.5.

 

(f)  The Parties acknowledge and agree that the deliberations and decision-making of the Steering Committee shall be in accordance with the following operating principles:  (i) decisions should be made in a prompt manner; and (ii) the Parties’ mutual objective is to maximize the commercial success of the Product that is the subject of each Workplan, consistent with sound and ethical business and scientific practices.

 

(g)  The Steering Committee will have only such powers as are specifically delegated to it in this Agreement, and will have no power to amend this Agreement or waive a party’s rights or obligations under this Agreement.”

 

5.                                       5.3 will be amended as follows:

 

“5.3  3M will provide a data package to Radius in support of the Drug Product CMC section of regulatory submissions or into 3M’s DMF in support of RADIUS’ regulatory

 

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filings, such data package to include any data required by applicable regulatory authorities. It is understood and acknowledged that the Phase II clinical study that is the subject of the Workplan may be undertaken in the United States and/or in selected countries outside the United States and, accordingly, 3M will be responsible for providing Radius with all chemistry, manufacturing and control information related to the Product necessary for Radius’ regulatory filings in respect of the Product with any regulatory authority or government agency, such information may be submitted to the government agency in a DMF if this system exists in the country in which the Phase II study is undertaken.  3M shall provide such information by right of reference to a Drug Master File or in support of a Common Technical Document (CTD).  3M acknowledges and agrees that it will also be responsible for maintaining, updating, and providing all supporting chemistry, manufacturing and control information related to the Product necessary to maintain regulatory filings in respect of the product with any regulatory authority or government agency whether through a Drug Master File or in support of a Common Technical Document.”

 

6.                                       A new Section 5.7 is added to the Agreement to read in full as follows:

 

“5.7  (a)  3M shall promptly notify Radius of an impending inspection or audit by any regulatory authority of any facility(ies) where services pursuant to the Workplan are being performed as provided for in Section 5.1 of the Quality Agreement.

 

(b)  3M will notify and inform Radius with respect to the response to any inquiry or observation from any regulatory authority or government agency relating in any way to the Product or the manufacture of the Product at the 3M facility in accordance with the terms and provisions of Section 5.1 of the Quality Agreement.

 

(c)  During an inspection by the FDA or other regulatory authority concerning the services performed pursuant to the Workplan, 3M will not disclose information and materials that are not required to be disclosed to such regulatory authority, without the prior consent of Radius, which shall not unreasonably be withheld.  Such information and materials includes, and is limited to: (i) financial data and pricing data (including, but not limited to, the budget and payment sections of the applicable Workplan); (ii) sales data (other than shipment data); and, (iii) personnel data (other than data as to qualification of technical and professional persons performing functions subject to regulatory requirements).

 

7.                                       Section 6.1 and Section 11.4 of the Agreement are hereby amended to replace the $[*] per hour rate for 3M with the rate of $[*] per hour for work that is not the subject of a Change Order and the rate of $[*] per hour for work that is the subject of a Change Order.

 

8.                                       A new Section 11.3A is hereby added to the Agreement to read in full as follows:

 

“11.3A Radius may terminate within six months of February 28, 2011 with notice to 3M in the event that Radius has determined that the Phase I clinical study for the Product needs to be

 

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

 

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repeated or that additional clinical data is required with respect thereto in order to initiate the Phase II clinical study for the Product.  Radius will provide 3M upon request with certain data concerning the Phase I clinical study upon any termination pursuant to this Section 11.3A in accordance with the provisions of the Agreement concerning the provision of preclinical and clinical data.”

 

9.                                       Except to the extent expressly amended by this Amendment, all of the terms, provisions and conditions of the Agreement are hereby ratified and confirmed and shall remain in full force and effect.  The term “Agreement”, as used in the Agreement, shall henceforth be deemed to be a reference to the Agreement as amended by this Amendment.

 

10.                                 This Amendment may be executed in counterparts, each of which will be deemed an original with all such counterparts together constituting one instrument.

 

[remainder of this page intentionally left blank]

 

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IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be duly executed in duplicate as of the date set forth above

 

 

	
3M COMPANY
    	
 
    	
RADIUS HEALTH INC.
    
	
 
    	
 
    	
 
    	
 
    	
 
    
	
By
    	
/s/ Jim A. Vaughan
    	
 
    	
By
    	
/s/ B.N. Harvey
    
	
 
    	
 
    	
 
    	
 
    	
 
    
	
Print Name
    	
Jim A. Vaughan
    	
 
    	
Print Name
    	
B.N. Harvey
    
	
 
    	
 
    	
 
    	
 
    	
 
    
	
Title
    	
Division VP & GM
    	
 
    	
Title
    	
CPO
    
	
 
    	
 
    	
 
    	
 
    	
 
    
	
Date
    	
3-3-2011
    	
 
    	
Date
    	
March 2, 2011
    
	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    
	
3M INNOVATIVE PROPERTIES   COMPANY
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    
	
By
    	
/s/ Robert W. Sprague
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    
	
Print Name
    	
Robert W. Sprague
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    
	
Title
    	
Secretary
    	
 
    	
 
    	
 
    
	
Date
    	
March 3, 2011
    	
 
    	
 
    	
 
    
	
 
    	
# 201104023
    	
 
    	
 
    	
 
    

 

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Attachment 1

 

PROPOSAL TO RADIUS HEALTH INC.

 

FOR DEVELOPMENT OF A BA058-COATED MICROSTRUCTURED 

 

TRANSDERMAL SYSTEM FOR EVALUATION IN A

 

PHASE II CLINICAL STUDY

 

PRESENTED

 

BY

 

o Drug Delivery Systems

 

CONFIDENTIAL

 

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- PROPOSAL -

RADIUS BA058 SMTS PROGRAM

 

EXECUTIVE SUMMARY

 

3M Drug Delivery Systems is pleased to provide Radius Health Inc. (Radius) with this estimate for development and delivery of Phase II clinical supplies for its BA058 product delivered via 3M’s solid Microstructured Transdermal System (sMTS).

 

This estimate supports the attached work plan summary and is based on information exchanged between Radius and 3M regarding the requirements for a BA058 sMTS product.  The scope of work outlined in the summary includes all activities required for formulation development and delivery of clinical supplies to enable Radius to perform a Phase II clinical study in humans. As discussed with Radius, 3M will deliver clinical supplies no later than 14 months after the effective date of this Amendment and will use commercially reasonable efforts to accomplish delivery by March 15, 2012 if Radius approves the Phase II Workplan and initiates work on or before March 2, 2011.  If work does not commence on March 2, 2011, 3 months must be added to the time below to provide sufficient ramp up time to obtain and train resources to re-initiate the project.

 

The estimate for the activities listed in the work plan summary is provided below:

 

	
 
    	
 
    	
PROGRAM
   HOURLY
   ESTIMATE
    	
 
    	
TIMING
    
	
Scale-up Process   Optimization and Preparation of GMP Supplies for Phase II Trial
    	
 
    	
[*] hours
    	
 
    	
(as per indicated in the   above paragraph)
    
	
Direct Costs (Arrays and   Applicators based on quantities defined below arrays for each strength and 300   applicators)
    	
 
    	
$177.3k
    	
 
    	
—
    

 

Deliverables, timing and assumptions are presented in the work plan summary.

 

3M reserves the right to revise this proposal if the intended scope of work deviates from the work outlined.  Any change in this proposal shall be subject to execution of a Change Order.

 

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

 

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WORK PLAN SUMMARY

 

Objective:

 

The objective of the work plan is to optimize manufacturing and analytical activities around the production of BA058-sMTS which will be produced using a new automated process. This work plan will result in the production of BA058-sMTS patches at three different dosage strengths, and a matching placebo patch. This work plan will also support the application for and completion of a Phase 2 clinical study by Radius.

 

Deliverables:

 

·                  Delivery of up to 3 distinct GMP clinical doses of BA058 sMTS product plus 1 placebo dose for a Phase II clinical study and supporting stability work. This includes a maximum of 54,600 patches (detail for quantities is shown below.) and [*] POC applicators. Any additional patches or applicators required to support the clinical trial, stability program and the requirement for clinical retains (as per 3M’s SOP for a non-bioequivalence clinical study) will be provided under a Change Order at Radius request and expense.

 

	
Planned usage
    	
 
    	
Active patches
    	
 
    	
Placebo patches
    
	
clinical study supplies
    	
 
    	
11,250
    	
 
    	
11,250
    
	
Release testing
    	
 
    	
150
    	
 
    	
150
    
	
Retains
    	
 
    	
450
    	
 
    	
600
    
	
Stability
    	
 
    	
2100
    	
 
    	
0
    
	
3M SOP retains
    	
 
    	
250
    	
 
    	
 
    
	
Total quantity
    	
 
    	
14,200
    	
 
    	
12,000
    

 

·                  Crossed over and validated analytical methods to monitor the manufacturing process, the release activities and the stability program

·                  Stability data for each of the three active product lots, as described below.

·                  A stability program for the RTC formulation for up to 6 months as defined in this Workplan

·                  3M shall establish and maintain proprietary Drug Master Files (DMFs) including information on the components, coating and drying manufacturing processes to support regulatory filings in the U.S. and Canada. A right of reference to 3M’s DMFs will be granted to Radius to support regulatory filings in the U.S. and Canada. Outside the U.S., 3M will provide Radius with information necessary to support regulatory filing in all countries where Clinical Development of BA058-sMTS is sited.

 

This estimate does not include the time associated with execution of the Phase II clinical studies nor completion of support stability.

 

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

 

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Milestones for the Workplan:

 

All dates assume Amendment signed by March 2, 2011.  Should the Amendment be signed at a later date, then the target dates for milestones need to be adjusted accordingly.

 

1.               Start preliminary RTC optimization – March 2, 2011

2.               March API requirements delivered by Radius to 3M – March 2, 2011

3.               Methods provided to 3M for crossover – March 4, 2011

4.               April API requirements delivered by Radius to 3M – April 1, 2011

5.               May API requirements delivered by Radius to 3M – May 1, 2011

6.               Initiation of coating optimization – May 1, 2011

7.               RTC optimization concludes – June 30, 2011

8.               July API requirements delivered by Radius to 3M – July 1, 2011

9.               Equipment installation – August 1, 2011

10.         Initiation of final optimization of coating and process verification – November 28, 2011

11.         Completion of coating process verification – December 31, 2011

12.         Release phase II supplies – by March 15, 2012

 

3M assumptions of the work plan:

 

·                  Validated analytical methods exist and can be crossed over to 3M from Radius – if method development is required, a Change Order will be required at Radius expense

·                  No more than 10 analytical methods need to be crossed over

·                  Adequate GMP BA058 starting material will be provided free of charge to 3M for development and clinical supply manufacture by Radius for phase II clinical supplies.

·                  Work plan assumes the use of the POC MTS applicator system and patch design in Phase 2.

·                  Lot size is not to exceed the quantities listed above of GMP-grade BA058 sMTS arrays to best meet the needs of the Phase 2 study and stability program plans.

·                  An additional 300 units per dose will be manufactured for retains in accordance with 3M’s SOPs. Any additional supplies beyond what is shown in the above table can be provided under a Change Order at Radius’ expense.

·                  Phase II product will be manufactured as low bioburden compatible with the process for Phase 3.

·                  sMTS patches and applicators for use in the Phase II clinical study will be bulk labeled by 3M and provided to Radius for further labeling according to the requirements of the clinical protocol.

·                  Radius will be responsible for executing all elements (protocols, regulatory filings, conduct) of the Phase II trial.

·                  The clinical trial will be conducted in countries to be identified by Radius.

·                  Wear time associated with the array is 24 hours or less.

·                  Stability studies on the product in support of Phase II will be performed as indicated; the stability report will be completed within 4 months of the completion of the stability study.

 

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·                  DMFs for BA058-sMTS CCS and Coating and Drying Process will be filed at least 3 month prior to Phase 2 initiation.

 

Radius assumptions of the work plan:

 

·                  The work plan will cover the currently planned activities related to the manufacturing and support of all Phase 2 transdermal clinical trial supplies.  If additional activities are deemed necessary, such activities will be provided under a Change Order with budget and timelines agreed.

·                  This work plan also covers the currently planned CMC/Quality activities required for support of the Phase 2 program for BA058-sMTS, including the 2-year ICH stability program.  If additional activities are deemed necessary, such activities will be provided under a Change Order with budget and timelines agreed.

 

·                  This work plan also covers the currently planned Regulatory activities required for support of the Phase 2 program for BA058-sMTS in the regions and countries selected for the study.  If additional activities are deemed necessary, such activities will be provided under a Change Order with budget and timelines agreed.

 

·                  Patches will be supplied in quantities indicated in the above table to support the clinical trial, clinical retains and the stability program.  Any additional quantities required can be provided on a Change Order.

·                  Phase 2 supplies will be manufactured with a low bioburden and will be compatible with the manufacturing process planned for Phase 3.

·                  Phase 2 supplies will be manufactured with residual solvents consistent with USP 467 and its European equivalent, extractables,

·                  Each major work plan task identified below will be associated with a protocol (either existing or to be written under a Change Order) and report, both to be reviewed and agreed with Radius.  Such reports may be redacted to protect 3M proprietary information

·                  All manufacturing activities will be compliant with:

 

ICH Q1A(R2): Stability Testing of New Drug Substances and Products 3M level 2 validation of analytical procedures.  3M will provide data supporting chemistry, manufacturing and control information necessary for regulatory filings with authorities in and outside the United States

 

WORKPLAN SUMMARY OF TASKS:

BA058-sMTS Drug Product Development and

Manufacturing Process Scale-up including Phase 2 Supply Production

 

3M Environmental Health and Safety

 

Update Hazard Review

 

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Update Risk Assessment (internal)

Update Animal Use Protocols

Qualification of Suppliers

 

3M Product Development

 

Terminal sterilization study

RM Receipt and Part Manufacture

RTC Optimization/Characterization

Formulation Optimization/Characterization

Process Optimization (including drying)

Packaging Optimization

[stability program is defined elsewhere]

Supply Production for additional Bridging Tox, if required (additional charge)

 

3M Product Scale-up to Phase 2

 

RM Receipt and Part Manufacture

System Integration

Product Development/Optimization:  RTC Optimization, Process Optimization

Process/Product Verifications

 

3M Support for Execution of Phase 2 Supply Manufacture

 

Validate Analytical Methods required for the manufacturing process, release and stability programs associated with the Phase 2 clinical trial supplies

Development and Verification of Specifications for Phase 2

Development and Verification of Shipping and Storage Requirements

Update Regulatory Documentation:  Provide up-to-date Drug Product CMC data to support updated IND, File Product Specific DMFs (sMTS-BA058 CCS and sMTS-BA058 Coating and Drying Process)

 

3M Phase 2 Supply Manufacture and Stability

 

RM Receipt and Part Manufacture

RM and Component Clearance

RTC Formulation Manufacture and Clearance

Execute Clinical Tickets: Applicator Construction, estimated 300 units; 3 active doses at a maximum as indicated in the table above.

Stability of RTC at 5C/ambient RH – 1,3,6 months

Stability of RTC at 25C/60% RH – 2 days, 1 week

Stability of Phase 2 Supplies:  5C/ambient RH – 1,3,6,9,12 months; 25C/60% RH - 1,3,6,9,12 months; 40C/75% RH – 1,3,6 months; the 18 and 24 months timepoints will be added under a Change Order.

Clear, release and ship Clinical Supplies

 

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Radius Clinical Supplies Manufacturing Tasks

 

Provide GMP-grade, BA058 API, ready for formulating

Receive, label and release Phase II clinical supplies

Author Investigators Brochure and IND submission

Write clinical protocol, define safety and efficacy endpoints 

Execute or oversee the Phase II clinical study

 

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3M DRUG DELIVERY SYSTEMS CONTACT INFORMATION

 

For inquiries related to the proposal, please contact:

 

Mary Mathisen

Product Commercialization Manager

3M Drug Delivery Systems

3M Center, Bldg. 260-4N-12

St. Paul, MN 55144

Tel:  651-733-9125

Fax:  651-5751729

Cell: 651-503 0861

E-Mail: mmathisen@mmm.com

 

Mark Tomai Ph.D.

Head of Vaccine Business

3M Drug Delivery Systems

3M Center, Bldg. 275-3E-10

St. Paul, MN 55144

Tel:  651-733-5375

Cell: 651-403-0455

E-Mail: matomai@mmm.com

 

14Exhibit 10.21

 

LSCA

Nuvios, Inc.

 

LABORATORY SERVICES AND CONFIDENTIALITY AGREEMENT*

 

THIS LABORATORY SERVICES AND CONFIDENTIALITY AGREEMENT is made as of this 31st day of March, 2004 (the “Effective Date”) by and between Charles River Laboratories, Inc., a Delaware corporation with a business address at 251 Ballardvale Street, Wilmington, Massachusetts 01887, acting through the divisions and at the locations set forth on Exhibit A attached hereto and made a part hereof (“Laboratory”) and Nuvios, Inc., a Delaware corporation with a business address at 197M Boston Post Road West, Marlborough, MA 01752 (“Sponsor”).

 

BACKGROUND

 

Laboratory is a contract research organization engaged in providing product discovery and development services.  The parties desire that Laboratory provide such services (the “Services”) under the terms and conditions of this Agreement.  The Services shall consist of individual studies (each, a “Study”) defined in a Protocol/Scope of Work (as hereinafter defined) and will be performed under these terms and conditions.  In consideration of the mutual promises and covenants set forth herein and for other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the parties, intending to be legally bound, agree as follows:

 

1.  The Study.  Laboratory shall render the Services as set forth in a Protocol and/or Scope of Work, Letter of Payment Authorization and Letter of Commitment (the Protocol and/or Scope of Work, Letter of Payment Authorization and Letter of Commitment are collectively referred to here as the “Supporting Documents”).  A “Protocol” and/or “Scope of Work” shall mean an attachment to this Agreement describing the nature, design and scope of the Study and the schedule of work to be performed during the course of an individual Study conducted by Laboratory for the Sponsor.  A “Letter of Payment Authorization” shall mean an attachment to this Agreement that describes with respect to a particular Study the price, fees and payment schedule for that Study and any modifications of the terms of this Agreement as applied to a particular Study.  A “Letter of Commitment” shall mean an attachment to this Agreement that describes a commitment of space and resources by the Laboratory.  In the event of a conflict between the terms contained in the Supporting Documents and this Agreement, the terms of this Agreement shall control, unless specifically agreed upon to the contrary in the Supporting Documents.  The Supporting Documents when signed by Laboratory and Sponsor shall be incorporated into and made a part of this Agreement.

 

2.  Conduct of the Research.

 

2.1.  Laboratory will maintain industry standards of professional conduct in the performance of the Study and in the preparation of all reports.  Laboratory will adhere to all government laws and regulations applicable to the conduct of the Study.  If applicable, and as set forth in the Protocol and/or Scope of Work, Laboratory will perform the Study in compliance with the current laboratory practices of the appropriate governmental regulatory agency(ies).

 

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

 

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2.2.  Laboratory will conduct the Study in accordance with the Protocol and/or Scope of Work, which may be amended from time to time upon the mutual agreement of Laboratory and Sponsor.  If the amendment requires additional work on the part of the Laboratory, Laboratory will not conduct the additional work unless approved in writing in advance by Sponsor and if such approval is obtained, Laboratory will be paid an amount mutually agreed to by the parties.  Laboratory agrees not to intentionally change or deviate from the Protocol without Sponsor’s prior approval.  Laboratory may not make material deviations from the Protocol without the prior written approval of Sponsor.  Deviations from the Protocol that are not material may be made in an emergency without Sponsor’s approval, provided that Laboratory shall use commercially reasonable efforts to obtain Sponsor’s verbal approval, which shall be subsequently confirmed by Sponsor in writing.

 

2.3.  After the Study has been completed, Laboratory may be requested by Sponsor to provide additional consultation services concerning the Study performed by Laboratory.  Upon such a request by Sponsor, Laboratory will provide the requested services and will be paid an amount mutually agreed to by the parties.  These consultation services will be subject to the provisions on Confidentiality and Ownership set forth in Paragraphs 8 and 13, respectively.

 

3.  Study Material:  (a)  Sponsor will identify each compound, material or other substance (“Test Material”) that is to become the subject of a Study.  Sponsor will provide Laboratory with the Test Material with which to perform the Study, as well as such know-how, information and data (“Sponsor Know-How”) as Sponsor deems necessary to enable Laboratory to conduct each Study.  In addition, Sponsor shall provide Laboratory with information to apprise Laboratory of the stability of the Test Material, proper storage and safe handling requirements, including a Material Safety Data Sheet (MSDS) or equivalent documentation (“Safety Information”).  Laboratory will supply a blank MSDS to Sponsor, if necessary.

 

(b)           Subject to the provisions of this Agreement, Sponsor hereby grants to Laboratory a non-exclusive, non-transferable, royalty-free, limited license during the term of this Agreement to use the Test Materials, the Sponsor Know-How, the Safety Information and the intellectual property rights embodied in the foregoing (“Sponsor Property”) for the sole purpose of enabling Laboratory to perform the Studies (the “Permitted Purpose”).

 

(c)           Laboratory shall not use either the Sponsor Know-How or the Test Materials, nor shall it permit the same to be used, in any manner or for any purpose (including, without limitation, analysis of the Test Materials) other than for the Permitted Purpose.  Upon termination of this Agreement, Laboratory agrees promptly to return to Sponsor the Sponsor Property, including any and all unused quantity of the Test Materials.

 

4.  Personnel.  Laboratory shall use its best efforts to dedicate the same key personnel to perform each Study (each a “Study Member”) during the term of such Study.  The key Study Members will be identified in the Protocol or Scope of Work, to be approved by Sponsor prior to study initiation.  At any time during the term of this Agreement, Sponsor shall have the right to request a new Study Member be designated by Laboratory if Sponsor believes that a Study Member is not performing in a reasonably acceptable manner.  Any Study Member that no longer performs research activities hereunder for any reason shall be replaced by Laboratory

 

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with an individual that is reasonably acceptable to Sponsor and that possesses the skills, knowledge and capabilities to perform the activities required hereunder.  Laboratory represents that none of its employees who are to participate in a Study have been debarred and none of such employees are under consideration to be debarred by the Food and Drug Administration from working in or providing services to any pharmaceutical or biotechnology company under the Generic Drug Enforcement Act of 1992, as amended.

 

5.  Inspections.  Upon reasonable advance notice, Laboratory will permit Sponsor and/or its designated representatives, during normal business hours and at mutually agreeable times, to visit the Laboratory facilities where the Study is taking place to monitor Laboratory’s performance of the Study and to examine and make copies of Laboratory records relating to a Study to verify compliance by Laboratory with the terms of this Agreement.  Any such examination and copying shall be paid for by Sponsor and shall be scheduled and conducted so as to reasonably minimize the disruption of Laboratory’s research operations.

 

6.  Records and Reports.

 

6.1.  Laboratory will keep and maintain complete and accurate records of the data generated in the course of each Study and the status and progress of the Study as required by the Protocol and/or Scope of Work and/or applicable regulations, in any event, with sufficient detail for use in reports to regulatory agencies.

 

6.2.  Laboratory will furnish a report or data containing information specified in the Protocol and/or Scope of Work according to the approved time lines identified in the Protocol and/or Scope of Work.  All reports will be prepared in the standard format of the Laboratory unless otherwise specified in the Protocol and/or Scope of Work, and shall include, without limitation, the procedures used and results obtained, a description of any inventions or other intellectual property rights Laboratory believes may have been discovered or created for such Study, and any other information that Sponsor reasonably requests.  Notwithstanding the foregoing, Laboratory will inform Sponsor as soon as reasonably practicable of any inventions or other intellectual property rights Laboratory believes may have been discovered or created during the performance of the Study.

 

6.3.  All Study reports and any supporting documentation originating with Laboratory, whether written or physical (e.g., laboratory notebooks, original data, tissues, slides, photographs, etc.) are the Sponsor’s property and shall be the confidential information of Sponsor.  At Sponsor’s cost and expense, if Sponsor requests Sponsor’s property be held by Laboratory, Laboratory shall store Sponsor’s property in the manner and at a cost as agreed upon in the Supporting Documents and in accordance with Laboratory’s archiving policy attached hereto as Exhibit B.  Upon reasonable advance notice, Sponsor’s representatives shall have reasonable access to such material, and shall have the right to obtain certified, legible photocopies of the raw data and supporting documentation, at Sponsor’s expense.

 

3

 

7.  Compensation.

 

7.1.  Sponsor will pay Laboratory as set forth in the Supporting Documents (“Study Price”).  All invoices are due and payable within thirty (30) days of receipt.  Each invoice shall include a description of the services performed and the materials purchased or will reference a study landmark identified in a payment schedule defined in the Supporting Documents.  Any necessary and appropriate changes in the costs of a Study as revised by amendment to the Supporting Documents will be requested subject to written approval by authorized representatives of Laboratory and Sponsor.  All amounts not paid when due shall bear interest from the applicable due date until paid, at the lesser of one and one half percent (1.5%) per annum above the prime rate announced from time to time by Fleet Bank or its successor or the highest lawful rate of interest permitted at the time in Massachusetts.  In addition, Laboratory may elect to withhold required reports or other deliverables if the Sponsor does not make required payments within thirty (30) days.

 

8.  Confidentiality.  The parties anticipate that they will exchange proprietary and confidential information during the term of this Agreement.  The parties will identify, in writing, such information as confidential and/or proprietary.  Each party will maintain such information in confidence and will employ reasonable and appropriate procedures to prevent its unauthorized publication or disclosure.  Neither party shall use the other party’s proprietary or confidential information for any purpose other than in performance of this Agreement.  The obligations of confidentiality set forth in this paragraph will survive termination or expiration of this Agreement for a period of 5 years.

 

The confidentiality provisions of this paragraph shall not apply to any part of such information, which:

 

a)                                      is known to the receiving party at the time it was obtained from the disclosing party;

 

b)                                     is acquired by receiving party from a third party and such third party did not obtain such information directly or indirectly from the disclosing party under obligation not to disclose;

 

c)                                      is or becomes published or otherwise in the public domain other than by violation of this Agreement by the receiving party;

 

d)                                     is independently developed by the receiving party without reference to or reliance upon the information provided by the disclosing party; or

 

(e)                                  is required to be disclosed by the receiving party to comply with applicable laws or governmental regulations; provided that the receiving party provides prior written notice of such disclosure to the disclosing party and takes reasonable and lawful actions to avoid and/or minimize the extent of such disclosure.

 

4

 

9.  Use of Names.

 

Neither party will use the other party’s name or the name of any employee of the other party in any advertising, packaging, promotional material, or any other publicity relating to this Agreement, without the prior written approval of the other party.

 

10.  Warranties.

 

10.1.  Sponsor warrants that it owns or licenses all rights, title and interest in the Test Materials furnished by Sponsor to Laboratory hereunder and the intellectual property related thereto, and that Laboratory’s use of any and all such material in connection with the Study does not infringe any third party rights.

 

10.2.  Laboratory warrants that the services provided to Sponsor under this Agreement shall conform to the Protocol and/or Scope of Work specifications and the current material applicable standards, regulations and procedures of the appropriate regulatory agency(ies).

 

10.3.  THE WARRANTY BY LABORATORY SET FORTH ABOVE IS IN LIEU OF ANY AND ALL OTHER REPRESENTATIONS OR WARRANTIES, EXPRESS, IMPLIED OR STATUTORY INCLUDING, WITHOUT LIMITATION, ANY IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE OR FOR NON-INFRINGEMENT OF A PATENT, TRADEMARK OR OTHER INTELLECTUAL PROPERTY RIGHT.

 

11.  Limitation of Liability.

 

11.1.  Except for infringement of the other party’s intellectual property rights or breach of confidentiality obligations hereunder neither party will be liable for penalties or liquidated damages or for special, indirect, consequential or incidental damages of any type or kind (including, without limitation, lost profits) regardless of whether any such losses or damages are characterized as arising from breach of contract, breach of warranty, tort, strict liability or otherwise, even if such party is advised of the possibility of such losses or damages, or if such losses or damages are foreseeable.

 

11.2.  Laboratory’s liability under this Agreement, regardless of the form of action, shall not exceed the lesser of (i) the total Study Price paid for services provided under the Letter of Payment Authorization under which such liability arises or (ii) One Hundred Thousand Dollars ($100,000.00).

 

11.3.  In the event that the Laboratory commits a breach of the warranty set forth in Section 10.2 above, Laboratory’s sole liability, and Sponsor’s sole remedy shall be for Laboratory to rerun the affected work or portion of the research affected by the breach as promptly as possible at Laboratory’s cost and expense.

 

5

 

12.  Indemnities

 

12.1.  Subject to the limitation of liability contained in Section 11.2 above, Laboratory will defend, indemnify, save and hold Sponsor and its parent, subsidiaries and affiliates and their respective directors, officers, employees and agents (together, the “Sponsor Indemnitees”) harmless from and against any third party claims, demands, suits, actions, causes of action, losses, damages, fines and liabilities, including reasonable attorneys’ fees (“Claims”) arising out of or in connection with Laboratory’s negligence or willful misconduct in performance of the Study.

 

12.2.  Sponsor will defend, indemnify, save and hold Laboratory and its parent, subsidiaries and affiliates and their respective directors, officers, employees and agents (together, the “Laboratory Indemnitees”) harmless from and against any Claims arising out of or in connection with (a) the manufacture, distribution, use, sales or other disposition by Sponsor, or any distributor, customer, sublicensee or representative of Sponsor, of any of Sponsor’s product or process and/or any other substances which are produced, purified, tested or vialed by Laboratory, or (b) Sponsor’s negligence or willful misconduct in connection with this Agreement and.

 

12.3  In addition, Sponsor agrees to indemnify, release, defend and hold harmless Laboratory Indemnitees against any and all liability, loss, damage, cost or expense (including reasonable attorneys’ fees and expenses and costs of investigation) which may be incurred, suffered or required to be paid as the result of any damage suffered or alleged to be suffered, including, without limitation, death or personal injury and any direct, consequential, special and punitive damages, as the result of any contact by Sponsor or its employees with the Laboratory’s animals, tissues or specimens during visits to the Laboratory or after delivery of any samples/specimens to Sponsor.

 

13.  Ownership.

 

(a)           For purposes of this Agreement, “Study Results” shall mean all data, information, test results, laboratory notes, techniques, know-how and any other scientific and technical information that is obtained in the performance of the Studies by any Study Member.  All Study Results obtained in the testing work performed hereunder shall be the property of the Sponsor.  Subject to the provisions of this Agreement, Sponsor hereby grants to Laboratory a non-exclusive, non-transferable, royalty-free, limited license to the Study Results for its internal research purposes only.

 

(b)           No express or implied license or permission is granted hereunder to Laboratory to use the Sponsor Property, except in pursuit of the Permitted Purpose as expressly stated herein.  All of Sponsor’s rights in and to the Sponsor Property shall remain the exclusive property of Sponsor.

 

(c)           For purposes of this Agreement, “Invention” shall mean any invention, or discovery arising out of the Study that is developed, conceived, or conceived and reduced to practice during the term of this Agreement.  All Inventions will be promptly disclosed to Sponsor.  Without the prior written consent of Sponsor, Laboratory shall not at any time file,

 

6

 

cause to be filed or consent to the filing of any patent application with respect to or claiming any Sponsor Property or Invention as described in clauses (1) and (3) below.  Any Invention made which names as an inventor at least one Study Member who is an employee or affiliate of Laboratory shall be owned as follows:

 

(1)           Any Invention which involves the use of, composition of, or improvement to Sponsor Property, or a derivative or analog thereof shall be owned by the Sponsor (the “Sponsor Project Intellectual Property) and Laboratory hereby assigns to Sponsor all of Laboratory’s right, title and interest in and to any and all Sponsor Project Intellectual Property and agrees to execute such instruments of transfer, assignment, conveyance or confirmation and such other documents as Sponsor may request to evidence confirm or perfect the assignment of all Laboratory’s right, title and interest in and to any Sponsor Project Intellectual Property; and

 

(2)           Any Invention which covers a scientific process, technique, procedure, medium, device or other process that is not derived from Sponsor Property and of which an employee or agent of Sponsor is not a co-inventor shall be owned by Laboratory (the “Laboratory Project Intellectual Property); and

 

(3)           Any Invention which covers a scientific process, technique, procedure, medium, device or other process that is not derived from Sponsor Property and of which at least one employee or agent of Sponsor is a co-inventor shall be jointly owned by Laboratory and Sponsor (the “Joint Project Intellectual Property”).

 

(d)           For any Laboratory Project Intellectual Property and any Joint Project Intellectual Property, Sponsor shall be given the first option to obtain a worldwide, exclusive and perpetual, subject to customary termination provisions, license to research, develop, make, have made, sell, have sold and use (including for commercial purposes) such property.  Upon Laboratory’s receipt of such written notice, the parties shall commence exclusive, good faith negotiations for a twelve (12) month period for the purpose of executing a fair and equitable definitive license agreement.  If after 12 months, Laboratory and Sponsor are unable to reach an agreement, Laboratory shall be free to license Laboratory Project Intellectual Property or its rights in any Joint Invention to any other party.

 

14.  Insurance.  Laboratory shall carry insurance sufficient to cover its interest or liabilities hereunder including, but not limited to worker’s compensation and comprehensive general liability.

 

15.  Force Majeure.  Except with respect to the payment of monies due hereunder, neither party shall be considered in default of the performance of any obligation hereunder to the extent that the performance of such obligation is prevented or delayed by fire, flood, earthquake, explosion, strike, acts of terrorism, war, insurrection, embargo, government requirement, civil or military authority, act of God, or any other event, occurrence or condition which is not caused, in whole or in part, by that party, and which is beyond the reasonable control of that party.

 

7

 

16.  Term and Termination.

 

16.1.  This Agreement will commence on the Effective Date and will continue for five (5) years from the Effective Date or until terminated by the parties as set forth below.

 

16.2  Sponsor shall have the right to terminate an on-going Study at any time without cause upon fifteen (15) business days prior written notice to Laboratory.  In the event a Study is terminated without cause, Laboratory shall be paid for all services rendered prior to receipt of notification of termination but which have not yet been invoiced, together with any additional expenses actually incurred in connection with commitments existing at the time notice of termination is received which cannot be canceled.

 

16.3  Either party may terminate this Agreement upon sixty (60) days notice to the other party, provided that Laboratory completes all Studies in progress, and Sponsor makes all payments due to Laboratory thorough the termination date as set forth in Section 16.2.

 

16.4  Either party may terminate this agreement at any time upon thirty (30) days prior written notice to the other party, for material breach of this Agreement by the other party where such breach is not remedied to the non-breaching party’s reasonable satisfaction within the thirty (30) day notice period.

 

16.5  Upon termination, neither party will have any further obligations under this Agreement, except that (i) the liabilities accrued through the date of termination and (ii) the obligations which by their terms survive termination, including the applicable confidentiality, record keeping, regulatory compliance, intellectual property and indemnification provisions of this Agreement, shall survive termination.

 

17.  Employee Solicitation.  Laboratory and Sponsor agree that, during the term of a Study and for a period of one hundred eighty (180) days thereafter, Sponsor will not knowingly hire, and will not knowingly engage as an independent contractor, any person who has been directly involved in rendering or receiving services on the Study as an employee of Sponsor, without written consent of Laboratory.

 

18.  Dispute Resolution.  The parties shall attempt, in good faith, to resolve through negotiations any controversy, claim, or dispute arising out of this Agreement.  In the event that negotiations are not successful, the controversy, claim, or dispute shall be submitted to third party mediation upon terms reasonably acceptable to the parties.  If such claim, controversy or dispute is not resolved through mediation, upon written demand of either party, the claim, controversy or dispute shall be submitted to arbitration before three (3) arbitrators.  Such arbitration shall take place in Boston, Massachusetts, and shall proceed in accordance with the Commercial Arbitration Rules of the American Arbitration Association and the laws of the Commonwealth of Massachusetts.  Within seven (7) calendar days after either party makes a written demand on the other for arbitration, each party shall select one (1) arbitrator.  A third arbitrator shall be chosen by the arbitrators selected by the parties within thirty (30) days of the demand for arbitration, and

 

8

 

shall act as chairman.  In the event that any arbitrator is not appointed in the prescribed time period, either party may apply to the American Arbitration Association for the appointment of such arbitrator.  A record and transcript of the proceedings shall be maintained.  Any award shall be made in writing and in reasonable detail, setting forth the findings of fact and conclusion of law supporting the award.  The determination of a majority of the panel of arbitrators shall be the decision of the arbitrators, which shall be binding regardless of whether one of the parties fails or refuses to participate in the arbitration.  The decision shall be enforceable by a court of law, provided that the decision is supported by substantial fact and is without material error of law.  All costs of such arbitration, except expert fees and attorneys’ fees, shall be shared equally by the parties.

 

19.  Miscellaneous.

 

19.1  Notices.  All notices from one party to the other will be in writing and will be given by addressing the same, if to Laboratory, to the applicable address set forth on Exhibit A and, if to Sponsor, to the address set forth below, or at such other address as either may specify in writing to the other.  Notices shall be sent by overnight courier, certified mail, return receipt requested, or by other means of delivery requiring an acknowledged receipt.  All notices shall be effective upon receipt.

 

Sponsor Address:

 

Nuvios, Inc.

197M Boston Post Road West

Marlborough, MA  01752

Attn:  Bart Henderson

 

19.2  Independent Contractor.  The business relationship of the Laboratory to the Sponsor is that of an independent contractor and not of a partner, joint venturer, employer, employee or any other kind of relationship.  Laboratory will be solely responsible for expenses and liabilities associated with the employment of its employees.

 

19.3  Assignment.  This Agreement, and the rights and obligations hereunder, may not be assigned or transferred by either party without the prior written consent of the other party, except that either party may assign this Agreement in connection with the merger, consolidation or sale of substantially all assets related to the Study.

 

19.4  Entire Agreement.  This Agreement, together with the Supporting Documents, constitutes the entire agreement of the parties, superseding any and all previous agreements and understandings, whether oral or written, as to the same subject matter.  No modification or waiver of the provisions of this Agreement shall be valid or binding on either party unless in writing and signed by both parties.  No waiver of any term, right or condition under this Agreement on any one occasion shall be construed or deemed to be a waiver or continuing waiver of any such term, right or condition on any subsequent occasion or a waiver of any other term, right or condition hereunder.

 

9

 

19.5  Severability.  In the event that any one or more of the provisions contained in this Agreement will, for any reason, be held to be invalid, illegal or unenforceable in any respect, that invalidity, illegality or unenforceability will not affect any other provisions of this Agreement, and all other provisions will remain in full force and effect.  If any provision of this Agreement is held to be excessively broad, it will be reformed and construed by limiting and reducing it so as to be enforceable to the maximum extent permitted by law.

 

19.6  Applicable Law.  This Agreement will in all events and for all purposes be governed by, and construed in accordance with, the laws of The Commonwealth of Massachusetts without regard to any choice of law principle that would dictate the application of the law of another jurisdiction.

 

IN WITNESS WHEREOF, duly authorized representatives of the parties have signed this Agreement as of the Effective Date.

 

	
Charles River Laboratories, Inc.
    	
 
    	
Nuvios, Inc.
    
	
 
    	
 
    	
 
    
	
By:
    	
/s/ Mark D. Seefeld
    	
 
    	
By:
    	
/s/ Bart Henderson
    
	
 
    	
duly authorized
    	
 
    	
 
    	
duly authorized
    
	
Print Name:
    	
Mark D. Seefeld, Ph.D., DABT
    	
 
    	
Print Name:
    	
Bart Henderson
    
	
Title: General Manager, General Toxicology
    	
 
    	
Title: Chief Bus. Officer
    
	
Date: April 16, 2004
    	
 
    	
Date: 4/29/04
    
							

 

10

 

Exhibit A

 

Work may be conducted at any of the following Charles River Laboratories divisions:

 

	
Argus Division

905 Sheehy Drive, Building A

Horsham, PA 19044
    	
Navigators Regulatory and Scientific Consulting

587 Dunn Circle

Sparks, NV 89431
    
	
Arkansas Division

100 East Boone Street

Redfield, AR 72132
    	
Ohio Division

640 N. Elizabeth Street

Spencerville, OH 45887
    
	
Biopharmaceutical Services

358 Technology Drive

Malvern, PA 19355
    	
Pathology Associates Division

15 Worman’s Mill Court, Suite 1

Frederick, MD 21701
    
	
Interventional Surgical Services

Southbridge

236 Blackmer Road

Southbridge, MA 01550-3114
    	
Sierra Division

587 Dunn Circle

Sparks, NV 89431
    
	
Interventional Surgical Services

River Valley Farms

803 Prospect Avenue

Osceola, WI 54020
    	
Worcester Division

57 Union Street

Worcester, MA 01608
    
	
Milestone Biomedical Associates

15 Worman’s Mill Court, Suite 1

Frederick, MD 21701
    	
 
    

 

	
A COPY OF ALL NOTICES   SHALL BE SENT TO:
    

 

	
Charles River Laboratories, Inc.
   251 Ballardvale Street
   Wilmington, MA 01887
   Attn: General Counsel
    	
Charles River Laboratories, Inc.
   587 Dunn Circle
   Sparks, NV 89431
   Attn: Contracts Administrator
    

 

11

 

LSCA

Sponsor Name

 

Exhibit B

 

Archive Terms and Conditions

 

1.                                       All Study reports and any supporting documentation originating with Laboratory, whether written or physical (e.g., laboratory notebooks, original data, tissues, slides, photographs, etc.) are the Sponsor’s property (“Materials”).  All Materials shall remain the property of Sponsor.  Laboratory agrees to maintain industry standards in connection with the storage of the Materials and adhere to all government laws and regulations applicable to the storage of the Materials.

 

2.                                       Laboratory shall store the Materials at its current storage rates.  Laboratory may increase the rates on an annual basis upon notice to Sponsor.  If the Materials require additional and/or special storage requirements, additional charges for storage shall be assessed and invoiced to Sponsor.  Invoices shall be issued annually in advance and are due and payable upon receipt and Sponsor agrees to pay all invoices submitted.  All amounts not paid when due shall bear interest from the applicable due date until paid, at the lesser of four percent (4%) per annum above the base rate announced from time to time by Fleet Bank or its successor or the highest lawful rate of interest permitted at the time in Massachusetts.

 

3.                                       Laboratory’s liability for archival services under this Agreement, regardless of the form of action, shall not exceed the lesser of the fee paid for one year’s storage of the Materials or one thousand dollars ($1,000.00).  In no event shall Laboratory be liable for penalties or liquidated damages or for special, indirect, consequential or incidental damages of any type or kind (including, without limitation, lost profits).

 

4.                                       The term of this Agreement for archival services shall be one year and shall automatically renew unless terminated by either Laboratory or Sponsor.  Upon the termination of this Agreement, Laboratory shall contact Sponsor to determine disposition of the Materials as follows: (a) extended storage of the Materials or (b) return of the Materials to Sponsor at Sponsor’s expense.  If Sponsor requests Laboratory to continue storage of the Materials, and Laboratory agrees, the cost for storage of the Materials shall continue to be invoiced to Sponsor at Laboratory’s then current rates.  If Sponsor fails to give said instructions, Laboratory shall so notify Sponsor, and if said instructions are still not forthcoming within thirty (30) days of said notification, then Laboratory shall have the option of continuing storage of the Materials, which will be deemed to have been authorized for an additional period of not less than one (1) year or Laboratory may return the Materials to Sponsor at Sponsor’s expense.  Sponsor shall be liable for storage charges until the Materials are returned to Sponsor.  While the Materials are in transit to Sponsor, all risk of loss or exposure to the Materials shall be borne by Sponsor.

 

5.                                       Sponsor will defend, indemnify, save and hold Laboratory and its parent, subsidiaries and affiliates and their respective directors, officers, employees and agents harmless from and

 

12

 

against any claims arising out of or in connection with (a) the presence of or exposure to the Materials or (b) Sponsor’s negligence or willful misconduct in connection with this Agreement and will pay any costs and damages which may be assessed against them.

 

6.                                       Laboratory will not release the Materials to any third party, without Sponsor’s written permission unless such disclosure is compelled by valid subpoena or any applicable law.  If such disclosure is requested, Laboratory shall use its commercially reasonable efforts to provide Sponsor with written notice prior to such release.

 

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Supporting Documents

 

 

[CHARLES RIVER LETTERHEAD]

 

LETTER OF PAYMENT AUTHORIZATION

 

March 31, 2004

 

Ben Lane
 NuVios
 197M Boston Post Road - West
 #337
 Marlborough, MA 01752
 Telephone:
 Fax: 847-680-5023
 ben.c.lane@sbcglobal.net

 

Re: SSU00002:P-03 Pharmacokinetics Of Two Test Articles Following Subcutaneous Administration To Ovariectomized Swiss Webster Mice
 Estimated Study Start: 3/29/04

 

This communication is to serve as a Letter of Payment Authorization (LOPA) for the above referenced study, which will be performed at Charles River Discovery Development Services (CR-DDS-Worcester Division) as set forth below.  CR-DDS-Worcester Division shall perform these services in accordance with the existing Service Agreement executed between CR-DDS and NuVios.  Once fully executed, this LOPA shall be incorporated into and made part of the existing Service Agreement.

 

The payment schedule and price of this study are as follows:

 

·                  (50%) $11,160 upon Advance Payments Completed.

 

·                  (35%) $7,812 upon In-Life Complete Completed.

 

·                  (15%) $3,348 upon Data Summary Report Completed.

 

Total Price of Study: $22,320.00

 

In the event the study design is altered, or the study is postponed or cancelled, payments will be amended as follows:

 

The price impact (if any) of the protocol amendment/change order will be submitted in writing.  If study prices increase, the difference will be invoiced and payable upon acceptance by the Sponsor.  If study prices decrease, the Sponsor will be credited for the difference.

 

Upon receipt of a verbal and/or written request Charles River Discovery and Development Services will order or assign animals and allocate resources for your study.  If the study is dosed on or before the agreed upon date no cancellation fees are necessary.  If the study is cancelled or rescheduled more than 7 days prior to dosing there will be no cancellation charges.  Any cancellation or delay less than 7 business days by Sponsor, through no fault of CR-DDS-Worcester Division, prior to dosing will result in a charge of 25% of the total study cost.  If the Sponsor requests delay of a study start, CR-DDS-Worcester Division will make every effort to accommodate the requested change.

 

CRL-DDS-Worcester Division will store residual study samples, test articles and formulations (“samples”) free of charge for up to 6 months following issuance of the draft report/data summary.  After this 6-month period CRL-DDS-Worcester Division will return, dispose or archive samples at the rates attached.  Please authorize one of the three options listed in the attachment.  In the absence of this authorization CRL-DDS-Worcester Division will assume that samples will be shipped back to NuVios.

 

 

As acceptance of this agreement, please sign this Letter of Payment Authorization and return to Mr. Leigh Peirce at the letterhead address (or fax to Leigh Peirce at (508) 890-0192).

 

 

	
 
    	
 
    	
 
    
	
/s/   Bart Henderson
    	
 
    	
/s/   Leigh Pierce
    
	
Sponsor   Representative
    	
 
    	
Leigh   Peirce
    
	
 
    	
 
    	
 
    
	
Bart   Henderson, CBO
    	
 
    	
3/31/04
    
	
Print   (Name and Title)
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
4/2/04
    	
 
    	
 
    
	
Date
    	
 
    	
 
    

 

2

 

Attachment A

 

Sample Disposition

 

Charles River will store residual study samples, test articles and formulations (“samples”) free of charge for months following issuance of the draft report/data submission.  After this 6-month period Charles River will r dispose or archive samples at the following rates.  Please authorize one of the following three options:

 

Study Number: SSU00002

 

	
o
    	
Dispose:   Continued sample storage is unnecessary. Please dispose of samples properly.
    
	
 
    	
 
    
	
x
    	
Ship:   Please return samples to the address provided below at a fee of $350/study.
    
	
 
    	
 
    
	
 
    	
Name
    	
Gary   Hattersley, Ph.D.
    
	
 
    	
 
    	
 
    
	
 
    	
Address
    	
To   be provided
    
	
 
    	
 
    	
 
    
	
 
    	
City,   State, Zip
    	
 
    
	
 
    	
 
    	
 
    
	
 
    	
Phone
    	
617-551-4703
    
	
 
    	
 
    	
 
    
	
o
    	
Archive:   Please continue storage at CR-DDS-Worcester Division until notified. I   understand the following fees will apply and will be invoiced on a quarterly   basis.
    
	
 
    	
 
    	
 
    
	
 
    	
·
    	
$500 initial archive setup
    
	
 
    	
 
    	
 
    
	
 
    	
·
    	
$100/ bin (~1.5 ft3)
    
					

 

 

	
Authorized   Signature
    	
/s/   Ben Lane
    	
 
    	
Date
    	
April   2, 2004
    

 

3

 

[CHARLES RIVER LETTERHEAD]

 

Letter of Payment Authorization – Revision 2

 

October 2 2009

 

Gary Hattersley, Ph.D.
 VP, Biology
 RADIUS
 300 Technology Square, 5th Floor
 Cambridge, MA 02139
 Telephone: 617.551.4703
 Email: ghattersley@radiuspharm.com

 

Re:                             Charles River Study Number SSU00067

 

Dear Dr. Hattersley,

 

We thank you for your interest in Charles River and hope the attached proposal meets with your approval.  For your convenience, we have provided the following summary of the titles and prices of the studies and/or study components under discussion.  If you would like us to proceed with animal orders resource allocation, sign and date the authorization line below.  (If all studies and/or components are not being authorized at this time, please initial the studies and components you wish to authorize and sign and date the authorization line below.  If all studies are being authorized at this time, merely sign and date the authorization line below, leaving the studies and component boxes empty).  These prices are valid for 60 days, but may be modified by mutual agreement if changes to the scope of work are made.

 

	
Authorization
   Initials
    	
 
    	
Study   Number and Title
    	
 
    	
Price
    
	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
SSU00066

A   Dermal Sensitization Study in Guinea Pigs (Standard Buehler)
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
(Reference Scope of work dated: 02-Oct-2009)

Original Study Price:

Less [*] % [*] discount:

Total Study Price:
    	
 
    	
 

 

-
    	
 

[*]

[*]

$ 26,900
    
	
 
    	
 
    	
SSU00067

A   14-Day Local Tolerance Study in Rabbits with a 7-Day Recovery Period
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
(Reference Scope of work dated: 02-Oct-2009)

Original Study Price:

Less [*] % [*] discount:

Total Study Price:
    	
 
    	
 

 

-
    	
 

[*]

[*]

$ 50,000
    

 

In order to minimize the impact of study delays and cancellations for all sponsors, Charles River allocates resources at the time a signed Letter of Payment Authorization is received.  Please note that scheduling is not considered confirmed until a signed copy of this document is received.  By providing authorization via signature below, you will allow us to confirm a schedule for each authorized study.  Your signature further constitutes acceptance of the price and payment schedule.

 

Payment Schedule for Study Number SSU00066

 

The payment schedule and price of this study are as follows:

 

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

 

 

·                  25%        Due upon Authorization*

 

·                  50%        Due upon Completion of In-life

 

·                  25%        Due upon Submission of Draft Report

 

Payment Schedule for Study Number SSU00067

 

The payment schedule and price of this study are as follows:

 

·                  25%        Due upon Authorization*

 

·                  50%        Due upon Completion of In-life

 

·                  25%        Due upon Submission of Draft Report

 

*Invoice(s) will be sent no more than 60 days prior to scheduled study start.

 

In the event Charles River does not receive comments pertaining to the draft report within 60 days after submission to the Sponsor, the final invoice will be due and payable.

 

Based upon the current scope of work, we would expect to initiate these studies the week of October 26, 2009.  Prior to receipt of this signed Letter of Payment Authorization this initiation date may be lost to another study vying for the same resources.

 

We understand that occasionally you may request to delay or to cancel a study due to unforeseen circumstances.  Charles River will make every reasonable effort to accommodate requested schedule changes.  However, as significant costs are incurred related to study initiation, cancellation/delay fees will apply in proportion to the number of days’ notice given (please see attached Cancellation and Delay Policy).  Cancellation/delay fees may be assessed separately for each postponement prior to the study being cancelled or initiated.  The Cancellation and Delay Policy becomes effective upon execution of this Letter of Authorization.

 

Charles River shall perform these services in accordance with the Service Agreement (the “Agreement”) executed between Charles River and RADIUS.  Once fully executed, this Letter of Payment Authorization shall be incorporated into and made part of the Agreement.

 

STUDY MATERIAL STORAGE/ARCHIVES.  After dispatch of the draft report, all raw data, samples/specimens (except for those sent to Sponsor or Sponsor designated laboratory and resultant data which are the responsibility of Sponsor) and documents generated at Charles River during this study, together with the original copy of the protocol (including amendments) and the draft report, will be retained in the secure storage area of Charles River for one (1) year at no charge.  After this one (1) year period, Sponsor will be contacted prior.  to the end of the year to authorize continued storage or return to Sponsor, at additional cost.  At finalisation, the final report and any stored materials will be transferred to the scientific archives of Charles River.  Subsequently, storage details will be documented in the raw data.

 

Any additional storage, archiving or retention will require an Extended Archiving Agreement

 

REPEAT OF SAMPLE ANALYSIS.  If applicable, the parties agree that as of commencement of work, in some instances, repeat of sample analysis will be required.  If this arises, Charles River must notify the Sponsor as soon as possible and determine, between the parties, if these repeats are required by Sponsor.  Consequently, the price per sample analysis/occasion will apply to any additional repeats requested by the Sponsor, as well as any samples above the analytical range, which require dilution.

 

2

 

However, in the event that additional sample analysis/occasions are required, Charles River shall submit a written estimate to the Sponsor for the Sponsor’s written approval, and the Sponsor shall respond to Charles River within five (5) business days, or within the specified time period sanctioned by the Sponsor for receipt of such estimates.  Once authorization is received, Charles River will endeavor, when possible, to proceed with current batches of sample analysis.  Both parties acknowledge that Charles River will be reimbursed for any amount which relates to the repeats if the difference between the original result of the sample analysis and the repeat result of the sample analysis, is within a 30% range.

 

SHIPMENT OF TEST ARTICLES.  Sponsor and Charles River agree that all costs associated with shipping test article to Charles River shall be the responsibility of the Sponsor.  Charles River shall not be responsible for any direct or indirect damages sustained by the Sponsor resulting from any loss, destruction or damage to the test article(s).

 

In the event of a conflict between the terms set forth in this letter and the Master Service Agreement, the terms of the Master Service Agreement shall control, unless specifically agreed upon to the contrary in this letter.

 

Please sign and return this document via facsimile or email (contact information below).  Should you have any questions or require any additional information, please do not hesitate to call me.  We look forward to being of service.

 

Best regards,

 

	
/s/   Tracee D. Lyons
    	
 
    	
/s/   B.N. Harvey
    
	
Tracee   D. Lyons
    	
 
    	
Authorized   Sponsor Representative
    
	
Client   Services Representive II
    	
 
    	
 
    
	
Charles   River
    	
 
    	
B.N.   Harvey, CFO
    
	
Preclinical   Services
    	
 
    	
Print   (Name and Title)
    
	
Phone:   419.647.4196
    	
 
    	
 
    
	
Fax:   419.647.6560
    	
 
    	
Oct,   16, 2008
    
	
E-Mail: Tracee.Lyons@crl.com
    	
 
    	
Date
    

 

 

If a PO is required, please submit PO with Letter of Payment Authorization or fax to Tracee Lyons at 419.647.6560.

 

3

 

Date Created: October 2, 2009

Sponsor: Radius

 

	
Title:
    	
 
    	
A   Dermal Sensitization Study in Guinea Pigs (Standard Buehler)
    
	
 
    	
 
    	
 
    
	
Project   Number:
    	
 
    	
SSU00066
    
	
 
    	
 
    	
 
    
	
Charles   River Facility:
    	
 
    	
Ohio
    
	
 
    	
 
    	
 
    
	
Compliance:
    	
 
    	
GLP
    
	
 
    	
 
    	
 
    
	
Species/Strain:
    	
 
    	
Guinea   Pigs
    
	
 
    	
 
    	
 
    
	
Dose   Formulation Preparation:
    	
 
    	
Standard   dose formulation prepared daily; no samples obtained
    
	
 
    	
 
    	
 
    
	
Dosing   Regimen:
    	
 
    	
Phase   A: Three inductions/week to test animals on single test site (nine total   inductions)

Phase   B: Test animals challenged on new test site and challenge control animals   dosed approximately 2 weeks after Induction 9

Phase   C: Test animals rechallenged on a test site with naive rechallenge control   animals dosed (if needed).
    
	
 
    	
 
    	
 
    
	
Route   of Administration:
    	
 
    	
Dermal   (skin painting) dose administration — 6 hour exposure
    
	
 
    	
 
    	
 
    
	
Test System:
    	
 
    	
Group
    	
 
    	
Number of Animals
    
	
 
    	
Test/Placebo
    	
 
    	
10/10
    
	
 
    	
Challenge Control
    	
 
    	
10
    
	
 
    	
Rechallenge
    	
 
    	
10
    
	
 
    	
DNCB Positive Control Test
    	
 
    	
10
    
	
 
    	
Positive Control
    	
 
    	
10
    
	
 
    	
 
    	
 
    	
 
    	
 
    
	
Spares
    	
 
    	
5   animals
    
	
 
    	
 
    	
 
    
	
Total   Population
    	
 
    	
69   animals
    
	
 
    	
 
    	
 
    
	
Age
    	
 
    	
Approximately   7 weeks at receipt
    
	
 
    	
 
    	
 
    
	
Source
    	
 
    	
Charles   River Laboratories
    
	
 
    	
 
    	
 
    
	
Pretreatment   Period
    	
 
    	
At   least 5 days
    
	
 
    	
 
    	
 
    
	
Mortality/Cageside   Observations:
    	
 
    	
Mortality/viability   observations will be conducted on twice daily on all animals. Positive   clinical observations only. Dermal scoring at 24 and 48 hours.
    
	
 
    	
 
    	
 
    
	
Body   Weight/Food Consumption:
    	
 
    	
Body   weights obtained at 3 intervals.
    
	
 
    	
 
    	
 
    
	
Terminal   Procedures:
    	
 
    	
Animals   terminated without necropsy
    
	
 
    	
 
    	
 
    
	
Reporting:
    	
 
    	
Audited   draft report provided in approximately 4 weeks.
    
	
 
    	
 
    	
 
    
	
Archiving:
    	
 
    	
Archiving   materials will be maintained through final report issuance.
    

 

4

 

Date Created: October 2, 2009

Sponsor: Radius

 

	
Title:
    	
 
    	
A   14-Day Local Tolerance Study in Rabbits with a 7-Day Recovery Period
    
	
 
    	
 
    	
 
    
	
Study   Number:
    	
 
    	
SSU00067
    
	
 
    	
 
    	
 
    
	
Charles   River Facility:
    	
 
    	
Ohio
    
	
 
    	
 
    	
 
    
	
Compliance:
    	
 
    	
GLP
    
	
 
    	
 
    	
 
    
	
Species/Strain:
    	
 
    	
New   Zealand White Rabbits
    
	
 
    	
 
    	
 
    
	
Dose   Formulation Preparation (assumes basic dose   preparation):
    	
 
    	
Test   material to be dispensed as received; no samples obtained.
    
	
 
    	
 
    	
 
    
	
Dose   Formulation Analysis (assumes standard HPLC-UV method):
    	
 
    	
N/A
    
	
 
    	
 
    	
 
    
	
Dosing   Regimen:
    	
 
    	
A   single daily dose for 14-days followed by a 7-Day recovery period.
    
	
 
    	
 
    	
 
    
	
Route   of Administration:
    	
 
    	
Transdermal   patch or subcutaneous dose administration.
    
	
 
    	
 
    	
 
    
	
Test System:
    	
 
    	
 
    	
 
    	
 
    	
 
    	
Number of Animals
    
	
 
    	
Group:
    	
 
    	
Dose
    	
 
    	
Males
    	
 
    	
Females
    
	
 
    	
1
    	
 
    	
Patch - Control
    	
 
    	
3 (2)
    	
 
    	
3 (2)
    
	
 
    	
2
    	
 
    	
Patch - Low
    	
 
    	
3
    	
 
    	
3
    
	
 
    	
3
    	
 
    	
Patch - High
    	
 
    	
3 (2)
    	
 
    	
3 (2)
    
	
 
    	
 
    	
( ) animals will be held for 7-Day recovery
    
	
 
    	
 
    	
 
    
	
Spares:
    	
 
    	
4   animals
    
	
 
    	
 
    	
 
    
	
Total   Population:
    	
 
    	
30   animals
    
	
 
    	
 
    	
 
    
	
Age:
    	
 
    	
Approximately   2.5 – 3.5 kg at receipt
    
	
 
    	
 
    	
 
    
	
Source:
    	
 
    	
Charles   River
    
	
 
    	
 
    	
 
    
	
Pretreatment   Period:
    	
 
    	
Approximately   10 days.
    
	
 
    	
 
    	
 
    
	
Mortality/Cage   side Observations:
    	
 
    	
Mortality:   Twice daily on all animals.

Cage-side   Obs: Daily on all animals.
    
	
 
    	
 
    	
 
    
	
Detailed   Observations:
    	
 
    	
Weekly   and prior to termination on all animals.
    
	
 
    	
 
    	
 
    
	
Body   Weight:
    	
 
    	
Weekly   and prior to termination on all animals.
    
	
 
    	
 
    	
 
    
	
Food   Consumption:
    	
 
    	
Daily   on all animals.
    
	
 
    	
 
    	
 
    
	
Special   Assessments:
    	
 
    	
Draize   dermal scoring twice daily (pre-dose and 1-2 hours post-dose) on all animals.
    
	
 
    	
 
    	
 
    
	
Clinical   Pathology Parameters:
    	
 
    	
Coagulation   (PT and APTT), clinical chemistry and hematology on all animals at pre-test   and prior to designated termination.
    
	
 
    	
 
    	
 
    
	
Toxicokinetics   Sample Collection:
    	
 
    	
Toxicokinetic   samples will be obtained from all animals at 8 timepoints (pre-dose, 5, 15,   30, 60, 120, 180 and 240 minutes post-dose) on Days 1 and 14 (576 samples   total). Samples to be 
    

 

5

 

Date Created: October 2, 2009

Sponsor: Radius

 

	
 
    	
 
    	
shipped   to sponsor designated laboratory.
    
	
 
    	
 
    	
 
    
	
Toxicokinetic   Sample Analysis:
    	
 
    	
At   additional cost.
    
	
 
    	
 
    	
 
    
	
Toxicokinetic   Reporting:
    	
 
    	
At   additional cost.
    
	
 
    	
 
    	
 
    
	
Terminal   Procedures:
    	
 
    	
Full   gross necropsy with organ weights and tissue collection on all animals.
    
	
 
    	
 
    	
 
    
	
Histopathology:
    	
 
    	
Standard   histopathology on treated and untreated skin sites (2, sections) for all animals.   All other tissues will be retained for possible evaluation.
    
	
 
    	
 
    	
 
    
	
Audited   Draft Report:
    	
 
    	
Audited   draft report to be provided in approximately 9 weeks from the time of in-life   completion.
    

 

6

 

Date Created: October 2, 2009

 

	
Title:
    	
 
    	
A   14-Day Local Tolerance Study in Rabbits with a 7-Day Recovery Period
    
	
 
    	
 
    	
 
    
	
Study   Number:
    	
 
    	
SSU00067
    
	
 
    	
 
    	
 
    
	
Archiving:
    	
 
    	
Archiving   materials will be maintained through final report issuance.
    

 

7

 

Date Created: October 2, 2009

Sponsor: Radius

 

TOXICOLOGY: POSTPONEMENT/CANCELLATION POLICY

 

Upon receipt of the signed quote letter or correspondence from the Sponsor confirming formal authorization, Charles River Laboratories Preclinical Services, hereinafter referred to as (“Charles River”) will order or reserve animals and allocate other resources for the specified study.

 

If the study is initiated on the scheduled start date, the most current quoted price is valid (unless advised otherwise by any revised quote letter) and no postponement or cancellation charges are applicable.

 

There will be no charges if the study is rescheduled or cancelled as long as notice is provided to Charles River in advance of the defined period of time prior to the animal arrival date.

 

Should any applicable fees be charged from the animal supplier before the above-mentioned timelines, these would be the responsibility of the Sponsor.

 

If sponsor cancels study after animal arrival and before study start the following charges will apply:

 

In the event of postponement or cancellation of the study by the Sponsor, additional compensation may be requested for items procured specifically for the study (e.g., animal purchases(1), dedicated equipment, perishable or non-reusable supplies) and any non-recoverable expenses incurred by Charles River (e.g., equipment lease payments, subcontractor charges or consultant fees to which Charles is irrevocably committed).

 

In the event the Sponsor terminates an ongoing study (i.e. early termination following dosing initiation), the Sponsor will be responsible for all incurred costs.

 

Exceptions to the above terms may be made on a case-by-case basis at Charles River sole discretion, if the study cancellation or postponement has little or no financial impact on Charles River (e.g. if notice that the study is subsequently cancelled or postponed falls within the defined period of time above pre-study period but no resources have been expended or costs incurred in the preparation for the study, and the animals can be readily used in another study [or exchanged, in the case of postponement]).

 

In the event of a conflict between the terms set forth in this letter and the Master Service Agreement, the terms of the Master Service Agreement shall control, unless specifically agreed upon to the contrary in this letter.

 

(1) In order to secure animals, Charles River is required to purchase the animals upon study authorization.  Therefore, should there be a cancellation thereafter by the Sponsor, the Sponsor will incur the full cost of animals ordered.

 

8

 

[CHARLES RIVER LETTERHEAD]

 

February 19, 2009

 

Radius Health, Inc.
 300 Technology square, Fifth Floor
 Cambridge, MA 02139
 USA

 

LETTER OF AGREEMENT

 

STUDY NO.: 182253

 

STUDY TITLE:    Validation of an HPLC Method for the Determination of BA058 and PTH in Dose Formulations

 

SCOPE OF WORK DATED: To be provided

 

PRICE:  $21,850 US (as per Study Authorization dated February 9, 2009)

 

[*] % [*] discount included

 

PAYMENT TERMS:

 

	
 
    	
50%   - $10,925 US - 1st installment at commencement of laboratory work
    
	
 
    	
50%   - $10,925 US - 2nd installment at completion of laboratory work (excluding   long term stability testing, if applicable)
    

 

PROPOSED COMMENCEMENT OF WORK:  March 2009

 

PROPOSED REPORTING TIME:  Audited draft report:

 

·                  Normally generated with six weeks following the end of study

 

ACCLIMATION PERIOD:  Not applicable

 

RETENTION PERIOD:  One (1) year

 

STUDY MATERIAL STORAGE/ARCHIVES.  After dispatch of the draft report, all raw data, samples/specimens (except for those sent to Sponsor or Sponsor designated laboratory and resultant data which are the responsibility of Sponsor) and documents generated at Charles River Montreal during this study, together with the original copy of the protocol (including amendments) and the draft report, will be retained in the secure storage area of Charles River Montreal for one (1) year at no charge.  After this one (1) year period, Sponsor will be contacted prior to the end of the year to authorize continued storage or return to Sponsor, at additional cost.  At finalisation, the final report and any stored materials will be transferred to the scientific archives of Charles River Montreal.  Subsequently, storage details will be documented in the raw data.

 

Any additional storage, archiving or retention will require an Extended Archiving Agreement

 

DELAY IN PRECLINICAL WORK.  In the event that any animals are purchased by Charles River Montreal, as authorized by and on behalf of the Sponsor, for preclinical work to be performed under this Letter of Agreement, the parties hereto agree that the acclimation period (“Acclimation Period”) shall be stipulated herein.  After the completion of the Acclimation Period, should there be any delay in the commencement of the Study that is attributable to the Sponsor, in any way, then the Sponsor agrees to

 

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

 

 

Radius Health, Inc.

Letter of Agreement

Study No. 182253

 

reimburse housing fees to Charles River Montreal for the said delay at rates prevailing at the time of said delay.

 

REPEAT OF SAMPLE ANALYSIS.  If applicable for studies involving bioanalytical sample analysis, the parties agree that as of commencement of work, in some instances, repeat of sample analysis will be required.  If this arises, Charles River Montreal must notify the Sponsor as soon as possible and determine, between the parties, if these repeats are required by Sponsor.  Consequently, the price per sample analysis/occasion will apply to any additional repeats requested by the Sponsor, as well as any samples above the analytical range, which require dilution.  However, in the event that additional sample analysis/occasions are required, Charles River Montreal shall submit a written estimate to the Sponsor for the Sponsor’s written approval, and the Sponsor shall respond to Charles River Montreal within five (5) business days, or within the specified time period sanctioned by the Sponsor for receipt of such estimates.  Once authorization is received, Charles River Montreal will endeavor, when possible, to proceed with current batches of sample analysis.  Both parties acknowledge that Charles River Montreal will be reimbursed for any amount which relates to the repeats if the difference between the original result of the sample analysis and the repeat result of the sample analysis, is within a 30% range.

 

SHIPMENT OF TEST ARTICLES.  Sponsor and Charles River Montreal agree that all costs associated with shipping test article to Charles River Montreal shall be the responsibility of the Sponsor.  Charles River Montreal shall not be responsible for any direct or indirect damages sustained by the Sponsor resulting from any loss, destruction or damage to the test article(s) while in, transit.

 

This Letter of Agreement will be governed by the terms and conditions of the Laboratory Services and Confidentiality Agreement dated March 31st, 2004 as amended between Charles River Laboratories, Inc. and Radius Health, Inc. (formerly known as Nuvios, Inc.).

 

	
Radius   Health, Inc.
    	
 
    	
Charles River Laboratories
   Preclinical Services Montréal Inc.  
    
	
 
    	
 
    	
 
    
	
/s/   B.N. Harvey
    	
 
    	
/s/   Chris Perkin
    
	
B.N.   Harvey
    	
 
    	
Chris   Perkin, D.A.B. T.
   Corporate Senior Vice President &
   President, Canadian & Chinese Preclinical Services
    
	
 
    	
 
    	
 
    
	
Feb.   23, 2009
    	
 
    	
/s/   Paul Bancroft
    
	
Date
    	
 
    	
Paul   Bancroft, CMA
   Vice President Finance
    
	
 
    	
 
    	
 
    
	
 
    	
 
    	
February   19, 2009
    
	
 
    	
 
    	
Date
    

 

 

[CHARLES RIVER LETTERHEAD]

 

February 18, 2009

 

Radius Health, Inc.
 300 Technology square, Fifth Floor
 Cambridge, MA 02139

 

LETTER OF AGREEMENT

 

STUDY NO.:  182252

 

	
STUDY   TITLE:
    	
Set-Up   and Pre-Validation of an HPLC Method for the Determination of BA058 and PTH   in Dose Formulations
    

 

SCOPE OF WORK DATED:  November 14, 2008

 

PRICE:  $1,900 US/Day (as per Study Authorization dated February 9, 2009)

 

[*] % [*] discount included

 

PAYMENT TERMS:

 

·                  Monthly billing as per work performed.

 

PROPOSED COMMENCEMENT OF WORK:  February 2009

 

PROPOSED REPORTING TIME:  Not applicable

 

ACCLIMATION PERIOD:  Not applicable

 

RETENTION PERIOD:  One (1) year

 

STUDY MATERIAL STORAGE/ARCHIVES.  After dispatch of the draft report, all raw data, samples/specimens (except for those sent to Sponsor or Sponsor designated laboratory and resultant data which are the responsibility of Sponsor) and documents generated at Charles River Montreal during this study, together with the original copy of the protocol (including amendments) and the draft report, will be retained in the secure storage area of Charles River Montreal for one (1) year at no charge.  After this one (1’) year period, Sponsor will be contacted prior to the end of the year to authorize continued storage or return to Sponsor, at additional cost.  At finalisation, the final report and any stored materials will be transferred to the scientific archives of Charles River Montreal.  Subsequently, storage details will be documented in the raw data.

 

Any additional storage, archiving or retention will require an Extended Archiving Agreement

 

DELAY IN PRECLINICAL WORK.  In the event that any animals are purchased by Charles River Montreal, as authorized by and on behalf of the Sponsor, for preclinical work to be performed under this Letter of Agreement, the parties hereto agree that the acclimation period (“Acclimation Period”) shall be stipulated herein.  After the completion of the Acclimation Period, should there be any delay in the commencement of the Study that is attributable to the Sponsor, in any way, then the Sponsor agrees to reimburse housing fees to Charles River Montreal for the said delay at rates prevailing at the time of said delay.

 

REPEAT OF SAMPLE ANALYSIS.  If applicable for studies involving bioanalytical sample analysis, the parties agree that as of commencement of work, in some instances, repeat of sample analysis will be

 

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

 

 

Radius Health, Inc.

Letter of Agreement

Study No. 182252

 

required.  If this arises, Charles River Montreal must notify the Sponsor as soon as possible and determine, between the parties, if these repeats are required by Sponsor.  Consequently, the price per sample analysis/occasion will apply to any additional repeats requested by the Sponsor, as well as any samples above the analytical range, which require dilution.  However, in the event that additional sample analysis/occasions are required, Charles River Montreal shall submit a written estimate to the Sponsor for the Sponsor’s written approval, and the Sponsor shall respond to Charles River Montreal within five (5) business days, or within the specified time period sanctioned by the Sponsor for receipt of such estimates.  Once authorization is received, Charles River Montreal will endeavor, when possible, to proceed with current batches of sample analysis.  Both parties acknowledge that Charles River Montreal will be reimbursed for any amount which relates to the repeats if the difference between the original result of the sample analysis and the repeat result of the sample analysis, is within a % range.

 

SHIPMENT OF TEST ARTICLES.  Sponsor and Charles River Montreal agree that all costs associated with shipping test article to Charles River Montreal shall be the responsibility of the Sponsor.  Charles River Montreal-shall-not-be-responsible for any-direct or indirect damages sustained by the Sponsor resulting from any loss, destruction or damage to the test article(s) while in transit.

 

This Letter of Agreement will be governed by the terms and conditions of the Laboratory Services and Confidentiality Agreement dated March 31st, 2004 as amended between Charles River Laboratories, Inc. and Radius Health, Inc. (formerly known as Nuvios, Inc.).

 

	
Radius   Health, Inc.
    	
 
    	
Charles River Laboratories
   Preclinical Services Montréal Inc.
    
	
 
    	
 
    	
 
    
	
/s/   B.N. Harvey
    	
 
    	
/s/ Chris Perkin
    
	
B.N.   Harvey
    	
 
    	
Chris   Perkin, D.A.B. T.
   Corporate Senior Vice President &
   President, Canadian & Chinese Preclinical Services 
    
	
 
    	
 
    	
 
    
	
Feb.   23, 2009
    	
 
    	
/s/ Paul Bancroft
    
	
Date
    	
 
    	
Paul   Bancroft, CMA
   Vice President Finance 
    
	
 
    	
 
    	
 
    
	
 
    	
 
    	
February 19, 2009
    
	
 
    	
 
    	
Date
    

 

 

[CHARLES RIVER LETTERHEAD]

 

Letter of Payment Authorization
 Revision 2 — animal cost (at importation)

 

August 19, 2010

 

Gary Hattersley, Ph.D.
 Vice President, Biology
  RADIUS HEALTH, INC.
 5th Floor
 300 Technology Square
 Cambridge, MA 02139
 United States
 ghattersley@radiuspharm.com

 

Dear Gary,

 

We thank you for your interest in Charles River and hope the attached proposal meets with your approval.  For your convenience, we have provided the following summary of the titles and prices of the studies and/or study components under discussion.  If you would like us to proceed with animal orders resource allocation, sign and date the authorization line below.  (If all studies and/or components are not being authorized at this time, please initial the studies and components you wish to authorize and sign and date the authorization line below.  If all studies are being authorized at this time, merely sign and date the authorization line below, leaving the studies and component boxes empty).  These prices are valid for 60 days, but may be modified by mutual agreement if changes to the scope of work are made.

 

	
Authorization
   Initials
    	
 
    	
Study Number and Title
    	
 
    	
Price
    
	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
670647
    A 16-Month Osteoporosis Intervention Study in   the [*]
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
Animal cost: [*]
    Price with [*] % pre-discount:
   Total with [*] % [*] discount:
    	
 
    	
$[*]   US
    $[*] US
   $180,009 US
    

 

In order to minimize the impact of study delays and cancellations for all sponsors, Charles River allocates resources at the time a signed Letter of Payment Authorization is received.  Please note that scheduling is not considered confirmed until a signed copy of this document is received.  By providing authorization via signature below, you will allow us to confirm a schedule for each authorized study.  Your signature further constitutes acceptance of the price and payment schedule.

 

Payment Schedule for Study # 670647 — 50% of animals cost of at importation

 

	
$[*] US (50%) at importation
    

 

The screening and selection has been completed.  Animal importation will take place between weeks of August 09, 2010 to August 23.  The animal arrival at CRL will take place during week of October 4, 2010.  Prior to receipt of this signed Letter of Payment Authorization this initiation date may be lost to another study vying for the same resources.

 

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

 

 

We understand that occasionally you may request to delay or to cancel a study due to unforeseen circumstances.  Charles River will make every commercially reasonable effort to accommodate requested schedule changes.  However, the following fees would be applicable:

 

Per diem fees at a rate of $[*] US/animal per day ($[*]/day) would be invoiced in the event of a delay in the importation date planned for August 23, 2010.

 

In the event of cancellation:

 

Upon importation, Radius would be responsible for housing fees of [*] animals at a rate of $[*] US/animal per day.  The cost for animal reservation and importation ($[*]) would be applied towards the purchase of [*] animals at which point ownership of the animals would be transferred to Radius.  Radius would also have an option for the direct purchase of the remaining [*] animals reserved for this study (at a rate of $[*] US per animal).

 

Following importation, per diem fees would be invoiced for the [*] animals imported until the animals are placed elsewhere ($[*] US/animal per day).  Ownership of [*] animals would also be transferred to Radius with an option for the direct purchase of [*] animals.

 

The parties will negotiate in good faith a maximum amount of the housing charges.  The agreed amount would then be indicated in an amendment to this Letter of Payment Authorization.

 

Charles River shall perform these services in accordance with the services agreement (the “Agreement”) executed between Charles River and RADIUS HEALTH, INC. Once fully executed, this Letter of Payment Authorization shall be incorporated into and made part of the Agreement.

 

STUDY MATERIAL STORAGE/ARCHIVES.  After dispatch of the draft report, all raw data, samples/specimens (except for those sent to Sponsor or Sponsor designated laboratory and resultant data which are the responsibility of Sponsor) and documents generated at Charles River during this study, together with the original copy of the protocol (including amendments) and the draft report, will be retained in the secure storage area of Charles River for one (1) year at no charge.  After this one (1) year period, Sponsor will be contacted prior to the end of the year to authorize continued storage or return to Sponsor, at additional cost.  At finalisation, the final report and any stored materials will be transferred to the scientific archives of Charles River.  Subsequently, storage details will be documented in the raw data.

 

Any additional storage, archiving or retention will require an Extended Archiving Agreement.

 

REPEAT OF SAMPLE ANALYSIS.  If applicable for studies involving bioanalytical sample analysis, the parties agree that as of commencement of work, in some instances, repeat of sample analysis will be required.  If this arises, Charles River must notify the Sponsor as soon as possible and determine, between the parties, if these repeats are required by Sponsor.  Consequently, the price per sample analysis/occasion will apply to any additional repeats requested by the Sponsor, as well as any samples above the analytical range, which require dilution.  However, in the event that additional sample analysis/occasions are required, Charles River shall submit a written estimate to the Sponsor for the Sponsor’s written approval, and the Sponsor shall respond to Charles River within five (5) business days, or within the specified time period sanctioned by the Sponsor for receipt of such estimates.  Once authorization is received, Charles River will endeavor, when possible, to proceed with current batches of sample analysis.  Both parties acknowledge that Charles River will be reimbursed for any amount which relates to the repeats if the difference between the original result of the sample analysis and the repeat result of the sample analysis, is within a 30% range.

 

SHIPMENT OF TEST ARTICLES.  Sponsor and Charles River agree that all costs associated with shipping test article to Charles River shall be the responsibility of the Sponsor.  Charles River shall not be

 

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

 

2

 

responsible for any direct or indirect damages sustained by the Sponsor resulting from any loss, destruction or damage to the test article(s).

 

In the event of a conflict between the terms set forth in this Letter of Payment Authorization and the Agreement, the terms of the Master Service Agreement shall control, unless specifically agreed upon to the contrary in this letter.

 

Please sign and return this document via facsimile or email (contact information below).  Should you have any questions or require any additional information, please do not hesitate to call me.  We look forward to being of service.

 

Best regards,

	
/s/   Stéphane Besner
    	
 
    	
/s/   B.N. Harvey
    
	
Stéphane   Besner, B.Sc., M.B.A
   Client Manager, Sales & Marketing
   Charles River Laboratoires
   Preclinical Services Montreal Inc.
   Tel: (514) 630-2436 Fax: (514) 630-8230
   e-mail: stephane.besner@crl.com
    	
 
    	
Authorized   Sponsor Representative 
    
	
 
    	
 
    
	
 
    	
B.N.   Harvey
    
	
 
    	
Print   (Name and Title)
    
	
 
    	
 
    
	
 
    	
August   20, 2010
    
	
 
    	
Date
    

 

 

If a PO is required, please submit PO with Letter of Payment Authorization or fax to 514-630-8230.

 

	
Charles River Laboratories
   Preclinical Services Montréal Inc.
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
/s/ Michele Marcoux
    	
 
    	
 
    
	
Michele Marcoux, CMA
   Site Controller
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
Sept. 01, 2010
    	
 
    	
 
    
	
Date
    	
 
    	
 
    

 

 

A counter signed version of this document will be returned to you for your records.

 

c.c. M. Marcoux, S. Pryce, D. Trembley, S Y. Smith, Main File

 

3

 

[CHARLES RIVER LETTERHEAD]

 

AMENDED LETTER OF PAYMENT AUTHORIZATION
 AMENDMENT NUMBER 1

 

26 October 2009

 

Gary Hattersley, Ph.D.
 VP, Biology
 RADIUS
 300 Technology Square, 5th Floor
 Cambridge, MA 02139
 Telephone: 617.551.4703
 Email: ghattersley@radiuspharm.com

 

Re:          Charles River Study Number SSU00067

 

Dear Dr. Hattersley,

 

This communication is to serve as an amendment to the Letter of Payment Authorization for the above referenced study, which is being performed at Charles River.  Charles River shall perform these services in accordance with the existing Service Agreement executed between Charles River and RADIUS.  Once fully executed, this Amended LOPA shall be incorporated into and made part of the existing Service Agreement.

 

Charles River Study Number SSU00067
  A 14-Day Local Tolerance Study in Rabbits with a 7-Day Recovery Period

 

·                  Added TK Reporting at Charles River

 

·                  Added archiving for 1 year following Final Report issuance

 

The additional cost of this study change is as follows:

 

·                  $12,700.00        Due upon authorization

 

New Total Price of Study: $62,700

 

As acceptance of this agreement, please sign this Amended Letter of Payment Authorization and return to Charles River by fax at 419-647-6560.

 

 

	
/s/   B.N. Harvey
    	
 
    	
/s/   Jason W. Smedley
    
	
Sponsor   Representative
    	
 
    	
Jason   W. Smedley, B.S.
    
	
 
    	
 
    	
Study   Director
    
	
B.N.   Harvey
    	
 
    	
26   October 2009
    
	
Print   (Name and Title)
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
Date
    	
 
    	
 
    

 

 

[CHARLES RIVER LETTERHEAD]

 

AMENDED LETTER OF PAYMENT AUTHORIZATION
 AMENDMENT NUMBER 2

 

13 November 2009

 

Gary Hattersley, Ph.D.
 VP, Biology
 RADIUS
 300 Technology Square, 5th Floor
 Cambridge, MA 02139
 Telephone: 617.551.4703
 Email: ghattersley@radiuspharm.com

 

Re:          Charles River Study Number SSU00067

 

Dear Dr. Hattersley,

 

This communication is to serve as an amendment to the Letter of Payment Authorization for the above referenced study, which is being performed at Charles River.  Charles River shall perform these services in accordance with the existing Service Agreement executed between Charles River and RADIUS.  Once fully executed, this Amended LOPA shall be incorporated into and made part of the existing Service Agreement.

 

Charles River Study Number SSU00067
  A 14-Day Local Tolerance Study in Rabbits with a 7-Day Recovery Period

 

·                  Added second phase to study consisting of 5 females/group in 2 groups and 2 alternates; dose on Day 1 (24 hour exposure); mortality checks twice daily; detailed clinical observations weekly; cage-side observations daily; dermal observations twice on Day 1 and once daily thereafter; body weights weekly; clinical pathology pretest, Day 1, and Day 8; gross necropsy (save treated and untreated skin).

 

The additional cost of this study change is as follows:

 

·                  $6,300.00             Due upon authorization

 

New Total Price of Study: $69,000

 

As acceptance of this agreement, please sign this Amended Letter of Payment Authorization and return to Charles River by fax at 419-647-6560.

 

 

	
/s/   B.N. Harvey
    	
 
    	
/s/   Jason W. Smedley
    
	
Sponsor   Representative
    	
 
    	
Jason   W. Smedley, B.S.
    
	
 
    	
 
    	
Study   Director
    
	
B.N.   Harvey
    	
 
    	
13   November 2009
    
	
Print   (Name and Title)
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
16   Nov 2009
    	
 
    	
 
    
	
Date
    	
 
    	
 
    

 

 

 

[LETTERHEAD OF CHARLES RIVER]
 accelerating drug development. exactly.

 

Study Authorization

 

	
February 9, 2009
    	
 
    
	
 
    	
 
    
	
Maria Grunwald
    	
 
    
	
Radius Health, Inc.
    	
cc: Gary Hattersley
    
	
300 Technology Square, 5th Flr.
    	
 
    
	
Cambridge, MA 02139
    	
 
    
	
USA
    	
 
    

 

Dear Maria,

 

Following our recent discussions, we are pleased to attach the following revised proposal, for your approval.

 

	
Authorization
   Initials
    	
 
    	
Study Number and Title
    	
 
    	
Price
    
	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
Study   No. 182252
    Set-Up And Pre-Validation Of An HPLC Method For The Determination Of   BA058 And PTH In Dose Formulations

 

Price:
   Price: (with [*] % [*] discount)
   Estimated 7-10 days*
    	
 
    	
 

 

 

 

   US$[*]/day

US$[*]/day
    
	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
Study   No. 182253
    Validation Of An HPLC Method For The Determination Of BA058 And PTH   In Dose Formulations
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
Price:
   Price: (with [*] % [*] discount)
    	
 
    	
US$[*]

US$21,850
    

 

* Please note that the above price is based on an estimated number of days of work to be performed. Should the estimate differ from the actual number of days needed, the Sponsor will be invoiced accordingly. Please also note that the Sponsor will be updated regularly on progress.

 

Please sign and return this document via facsimile or email as soon as possible (contact information provided below). Should you have any questions or require any additional information, please do not hesitate to call me. We look forward to being of service.

 

Best regards,

 

	
/s/   Gareth Meekin
    	
 
    	
 
    
	
Gareth   Meekin, MBA
    	
 
    	
/s/   B.N. Harvey
    
	
Global   Key Account Manager, Sales & Marketing
    	
 
    	
Authorized   Sponsor Representative
    
	
Charles   River Laboratories
    	
 
    	
 
    
	
Preclinical   Services Montreal, Inc.
    	
 
    	
 
    
	
22022   Transcanadienne
    	
 
    	
B.N.   Harvey
    
	
Senneville,   Quebec, Canada, H9X 3R3
    	
 
    	
Print   (Name and Title)
    
	
Phone:   (514) 630-2381 Fax: (514) 630-8230
    	
 
    	
 
    
	
E-Mail: gareth.meekin@crl.com
    	
 
    	
Feb 11, 2009
    
	
Website:   www.criver.com
    	
 
    	
Date
    

 

Charles River

 

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

 

1

 

[LETTERHEAD OF CHARLES RIVER]
 accelerating drug development. exactly.

 

Letter of Payment Authorization — Revision 1

 

16 August 2010

 

Gary Hattersley, PhD
 VP, Biology
 RADIUS
 300 Technology Square, 5th Floor Cambridge, MA 02139
 Phone: 617.551.4703
 Email:  ghattersley@radiuspharm.com

 

Dear Dr. Hattersley,

 

We thank you for your interest in Charles River and hope the attached proposal meets with your approval. For your convenience, we have provided the following summary of the title and price of the studies and/or study components under discussion. If you would like us to proceed with animal orders resource allocation, sign and date the authorization line below. This price is valid for 60 days, but may be modified by mutual agreement if changes to the scope of work are made.

 

	
Authorization
   Initial’s
    	
 
    	
Study Number and Title
    	
 
    	
Price
    
	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
Study   # 20001926
   Title: A 7-Day Dermal Bridging Study in [*]

(Reference   scope of work dated: 06-Aug-2010)
    	
 
    	
$ 49,900
    

 

In order to minimize the impact of study delays and cancellations for all sponsors, Charles River allocates resources at the time a signed Letter of Payment Authorization is received. Please note that scheduling is not considered confirmed until a signed copy of this document is received. By providing authorization via signature below, you will allow us to confirm a schedule for each authorized study. Your signature further constitutes acceptance of the price and payment schedule.

 

Payment Schedule for Study Number 20001926

 

The payment schedule and price of this study are as follows:

 

·                  25%                        Due upon Authorization*

·                  50%                        Due upon Completion of In-life

·                  25%                        Due upon Submission of Draft Report

 

*Invoice(s) will be sent no more than 60 days prior to scheduled study start.

 

In the event Charles River does not receive comments pertaining to the draft report within 60 days after submission to the Sponsor, the final invoice will be due and payable.

 

Based upon the current scope of work, we would expect to initiate this study in late October/early November, 2010. Prior to receipt of this signed Letter of Payment Authorization this initiation date may be lost to another study vying for the same resources.

 

We understand that occasionally you may request to delay or to cancel a study due to unforeseen circumstances. Charles River will make every reasonable effort to accommodate requested

 

Charles River

 

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

 

1

 

Created on: August 16, 2010

Sponsor: RADIUS

 

schedule changes. Charles River shall perform these services in accordance with the Service Agreement (the “Agreement”) executed between Charles River and RADIUS. Once fully executed, this Letter of Payment Authorization shall be incorporated into and made part of the Agreement.

 

STUDY MATERIAL STORAGE/ARCHIVES. After dispatch of the draft report, all raw data, samples/specimens (except for those sent to Sponsor or Sponsor designated laboratory and resultant data which are the responsibility of Sponsor) and documents generated at Charles River during this study, together with the original copy of the protocol (including amendments) and the draft report, will be retained in the secure storage area of Charles River. At finalisation, the final report and any stored materials will be transferred to the scientific archives of Charles River for (1) year. Subsequently, storage details will be documented in the raw data. After this one (1) year period, Sponsor will be contacted prior to the end of the year to authorize continued storage or return to Sponsor, at additional cost.

 

Any additional storage, archiving or retention will require an Extended Archiving Agreement

 

REPEAT OF SAMPLE ANALYSIS. If applicable, the parties agree that as of commencement of work, in some instances, repeat of sample analysis will be required. If this arises, Charles River must notify the Sponsor as soon as possible and determine, between the parties, if these repeats are required by Sponsor. Consequently, the price per sample analysis/occasion will apply to any additional repeats requested by the Sponsor, as well as any samples above the analytical range, which require dilution. However, in the event that additional sample analysis/occasions are required, Charles River shall submit a written estimate to the Sponsor for the Sponsor’s written approval, and the Sponsor shall respond to Charles River within five (5) business days, or within the specified time period sanctioned by the Sponsor for receipt of such estimates. Once authorization is received, Charles River will endeavor, when possible, to proceed with current batches of sample analysis. Both parties acknowledge that Charles River will be reimbursed for any amount which relates to the repeats if the difference between the original result of the sample analysis and the repeat result of the sample analysis, is within a 30% range.

 

SHIPMENT OF TEST ARTICLES. Sponsor and Charles River agree that all costs associated with shipping test article to Charles River shall be the responsibility of the Sponsor. Charles River shall not be responsible for any direct or indirect damages sustained by the Sponsor resulting from any loss, destruction or damage to the test article(s).

 

In the event of a conflict between the terms set forth in this letter and the Master Service Agreement, the terms of the Master Service Agreement shall control, unless specifically agreed upon to the contrary in this letter.

 

2

 

Created on: August 16, 2010

Sponsor: RADIUS

 

Please sign and return this document via facsimile or email (contact information below). Should you have any questions or require any additional information, please do not hesitate to call me. We look forward to being of service.

 

Best regards,

 

	
/s/   April Jackson
    	
 
    	
 
    
	
April Jackson
    	
 
    	
/s/   B.N. Harvey
    
	
Client   Manager
    	
 
    	
Authorized   Sponsor Representative
    
	
Charles   River
    	
 
    	
 
    
	
Preclinical   Services
    	
 
    	
B.N.   Harvey, CFO
    
	
Phone:   419.647.4196
    	
 
    	
Print   (Name and Title)
    
	
Fax:   419.647.6560
    	
 
    	
 
    
	
E-Mail:   April.Jackson@crl.com
    	
 
    	
August   16, 2010
    
	
 
    	
 
    	
Date
    

 

If a PO is required, please submit PO with Letter of Payment Authorization or fax to April Jackson at 419.647.6560.

 

3

 

Created on: August 16, 2010

Sponsor: RADIUS

 

	
Title:
    	
 
    	
A   7-Day Dermal Bridging Study in [*]
    
	
 
    	
 
    	
 
    
	
Study   Number:
    	
 
    	
20001926
    
	
 
    	
 
    	
 
    
	
Charles   River Facility:
    	
 
    	
Ohio
    
	
 
    	
 
    	
 
    
	
Compliance:
    	
 
    	
GLP   
    
	
 
    	
 
    	
 
    
	
Species/Strain:
    	
 
    	
[*]
    
	
 
    	
 
    	
 
    
	
Dose   Formulation Preparation
    (assumes basic dose preparation):
    	
 
    	
Test   material to be dispensed as received; no samples obtained.
    
	
 
    	
 
    	
 
    
	
Dose   Formulation Analysis
    (assumes standard HPLC-UV method:
    	
 
    	
N/A
    
	
 
    	
 
    	
 
    
	
Dosing   Regimen:
    	
 
    	
Once   daily for 7 days.
    
	
 
    	
 
    	
 
    
	
Route   of Administration:
    	
 
    	
Transdermal   dose administration [*].
    
	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
Number of Animals
    
	
Test System:
    	
 
    	
Group
    	
 
    	
Dose
    	
 
    	
Males
    	
 
    	
Females
    
	
 
    	
 
    	
1
    	
 
    	
Control
    	
 
    	
[*]
    	
 
    	
[*]
    
	
 
    	
 
    	
2
    	
 
    	
High
    	
 
    	
[*]
    	
 
    	
[*]
    
	
 
    	
 
    	
 
    
	
Spares:
    	
 
    	
[*]   animals
    
	
 
    	
 
    	
 
    
	
Total Population:
    	
 
    	
[*]   animals
    
	
 
    	
 
    	
 
    
	
Age:
    	
 
    	
Approximately   3 - 4 months at receipt
    
	
 
    	
 
    	
 
    
	
Source:
    	
 
    	
[*]
    
	
 
    	
 
    	
 
    
	
Pretreatment Period:
    	
 
    	
Approximately   14 days
    
	
 
    	
 
    	
 
    
	
Mortality:
    	
 
    	
Mortality:   twice daily on all animals
    
	
 
    	
 
    	
 
    
	
Detailed   Observations:
    	
 
    	
Pre-dose   and daily on all animals.
    
	
 
    	
 
    	
 
    
	
Body   Weight:
    	
 
    	
Pre-dose   and Days 1, 3, 5, 7 and 8 on all animals
    
	
 
    	
 
    	
 
    
	
Special   Assessments:
    	
 
    	
Draize   dermal scoring daily on all animals.
    
	
 
    	
 
    	
 
    
	
Toxicokinetic   Samples Collection:
    	
 
    	
Toxicokinetic   samples obtained from all animals at pre-dose, 15, 30 45, 60, 120, 180, and   240 minutes on Day 1 and 7 (192 samples total). Samples to be shipped to   sponsor designated laboratory.
    
	
 
    	
 
    	
 
    
	
Toxicokinetic   Sample Analysis:
    	
 
    	
At   additional cost.
    
	
 
    	
 
    	
 
    
	
Toxicokinetic   Reporting:
    	
 
    	
At   additional cost.
    
	
 
    	
 
    	
 
    
	
Terminal   Procedures:
    	
 
    	
Full   gross necropsy with limited tissue collection (identification, skin treated   and skin untreated) on all animals.
    
	
 
    	
 
    	
 
    
	
Histopathology:
    	
 
    	
Standard   histopathology (up to 3 tissue sections) from all animals.
    
	
 
    	
 
    	
 
    
	
Audited   Draft Report:
    	
 
    	
Audited   draft report to be provided in approximately 8 weeks from the time of in-life   completion.
    
	
 
    	
 
    	
 
    
	
Archiving:
    	
 
    	
Archiving   of appropriate study related materials with Charles River for 1 year   following issuance of final report.
    

 

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

 

4

 

[CHARLES RIVER LETTERHEAD]

 

Letter of Payment Authorization
 Revision 2 – Screening portion only

 

May 26, 2010

 

Gary Hattersley, Ph.D.
 Vice President, Biology
  RADIUS HEALTH, INC.
 5th Floor
 300 Technology Square
 Cambridge, MA 02139
 United States
 ghattersley@radiuspharm.com

 

Dear Gary,

 

We thank you for your interest in Charles River and hope the attached proposal meets with your approval.  For your convenience, we have provided the following summary of the titles and prices of the studies and/or study components under discussion.  If you would like us to proceed with animal orders resource allocation, sign and date the authorization line below.  (If all studies and/or components are not being authorized at this time, please initial the studies and components you wish to authorize and sign and date the authorization line below.  If all studies are being authorized at this time, merely sign and date the authorization line below, leaving the studies and component boxes empty).  These prices are valid for 60 days, but may be modified by mutual agreement if changes to the scope of work are made.

 

	
Authorization
   Initials
    	
 
    	
Study Number and Title
    	
 
    	
Price
    
	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
670647
    A 16-Month Osteoporosis Intervention Study in   the [*]
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
Screening of [*] Animals:
    Price with [*] % pre-discount:
   Total with [*] % [*] discount:
    	
 
    	
$[*]          US
    $[*]          US
   $ 50,000 US
    

 

In order to minimize the impact of study delays and cancellations for all sponsors, Charles River allocates resources at the time a signed Letter of Payment Authorization is received.  Please note that scheduling is not considered confirmed until a signed copy of this document is received.  By providing authorization via signature below, you will allow us to confirm a schedule for each authorized study.  Your signature further constitutes acceptance of the price and payment schedule.

 

Payment Schedule for Study # 670647 — Screening of [*] Animals

 

·                  $ 50,000 US       At authorization

 

Based upon the current scope of work, we would propose to initiate the screening in May, 2010.  If animal importation is performed on or around August 11, 2010, the animal arrival at CRL would occur during week of October 4, 2010.  Prior to receipt of this signed Letter of Payment Authorization this initiation date may be lost to another study vying for the same resources.

 

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

 

 

We understand that occasionally you may request to delay or to cancel a study due to unforeseen circumstances.  Charles River will make every commercially reasonable effort to accommodate requested schedule changes.  However, the following fees would be applicable:

 

Per diem fees at a rate of $[*] US/animal per day ($[*]/day) would be invoiced in the event of a delay in the importation date planned for August 11, 2010.

 

In the event of a cancellation:

 

Before importation, the entire cost of the screening ($50,000US) and of the animal reservation ($138,807 US) would be lost.  Alternatively, Radius would have an option for the DIRECT purchase of up to [*] animals with the reservation fees paid.  Should the option be exercised, Radius would then be responsible for housing fees at a rate of $[*] US/animal per day.

 

Following importation, in addition to the screening and reservation cost, per diem fees would be invoiced until the animals are placed elsewhere ($[*] US/animal per day).  Radius would also have an option for the purchase of up to [*] animals with the reservation fees paid.  Should the option be exercised, Radius would then be responsible for housing fees at a rate of $[*] US/animal per day.

 

Charles River shall perform these services in accordance with the services agreement (the “Agreement”) executed between Charles River and RADIUS HEALTH, INC.  Once fully executed, this Letter of Payment Authorization shall be incorporated into and made part of the Agreement.

 

STUDY MATERIAL STORAGE/ARCHIVES.  After dispatch of the draft report, all raw data, samples/specimens (except for those sent to Sponsor or Sponsor designated laboratory and resultant data which are the responsibility of Sponsor) and documents generated at Charles River during this study, together with the original copy of the protocol (including amendments) and the draft report, will be retained in the secure storage area of Charles River for one (1) year at no charge.  After this one (1) year period, Sponsor will be contacted prior to the end of the year to authorize continued storage or return to Sponsor, at additional cost.  At finalisation, the final report and any stored materials will be transferred to the scientific archives of Charles River.  Subsequently, storage details will be documented in the raw data.

 

Any additional storage, archiving or retention will require an Extended Archiving Agreement.

 

REPEAT OF SAMPLE ANALYSIS.  If applicable for studies involving bioanalytical sample analysis, the parties agree that as of commencement of work, in some instances, repeat of sample analysis will be required.  If this arises, Charles River must notify the Sponsor as soon as possible and determine, between the parties, if these repeats are required by Sponsor.  Consequently, the price per sample analysis/occasion will apply to any additional repeats requested by the Sponsor, as well as any samples above the analytical range, which require dilution.  However, in the event that additional sample analysis/occasions are required, Charles River shall submit a written estimate to the Sponsor for the Sponsor’s written approval, and the Sponsor shall respond to Charles River within five (5) business days, or within the specified time period sanctioned by the Sponsor for receipt of such estimates.  Once authorization is received, Charles River will endeavor, when possible, to proceed with current batches of sample analysis.  Both parties acknowledge that Charles River will be reimbursed for any amount which relates to the repeats if the difference between the original result of the sample analysis and the repeat result of the sample analysis, is within a 30% range.

 

SHIPMENT OF TEST ARTICLES.  Sponsor and Charles River agree that all costs associated with shipping test article to Charles River shall be the responsibility of the Sponsor.  Charles River shall not be responsible for any direct or indirect damages sustained by the Sponsor resulting from any loss, destruction or damage to the test article(s).

 

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

 

2

 

In the event of a conflict between the terms set forth in this Letter of Payment Authorization and the Agreement, the terms of the Master Service Agreement shall control, unless specifically agreed upon to the contrary in this letter.

 

Please sign and return this document via facsimile or email (contact information below).  Should you have any questions or require any additional information, please do not hesitate to call me.  We look forward to being of service.

 

Best regards,

 

	
 
    	
 
    	
/s/   B.N. Harvey
    
	
/s/   Stéphane Besner
    	
 
    	
Authorized   Sponsor Representative
    
	
Stéphane   Besner, B.Sc., M.B.A
    	
 
    	
 
    
	
Client   Manager, Sales & Marketing
    	
 
    	
B.N.   Harvey
    
	
Charles   River Laboratoires
    	
 
    	
Print   (Name and Title)
    
	
Preclinical   Services Montreal Inc.
    	
 
    	
 
    
	
Tel:   (514) 630-2436 Fax: (514) 630-8230
    	
 
    	
5/26/10
    
	
e-mail: stephane.besner@crl.com
    	
 
    	
Date
    

 

 

If a PO is required, please submit PO with Letter of Payment Authorization or fax to 514-630-8230.

 

	
Charles River Laboratories
    	
 
    	
 
    
	
Preclinical Services Montréal Inc.
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
/s/ Catherine Konidas
    	
 
    	
 
    
	
Catherine   Konidas, MBA
    	
 
    	
 
    
	
Site   Director, Montreal
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
/s/   Michele Marcoux
    	
 
    	
 
    
	
Michele   Marcoux, CMA
    	
 
    	
 
    
	
Site   Controller
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
June   2, 2010
    	
 
    	
 
    
	
Date
    	
 
    	
 
    

 

A counter signed version of this document will be returned to you for your records.

 

c.c.  C. Konidas, S. Pryce, D. Trembley, S Y. Smith, Main File

 

3

 

[CHARLES RIVER LETTERHEAD]

 

Letter of Payment Authorization
 Revision 2 – Animal reservation only

 

May 26, 2010

 

Gary Hattersley, Ph.D.
 Vice President, Biology
  RADIUS HEALTH, INC.
 5th Floor
 300 Technology Square
 Cambridge, MA 02139
 United States
 ghattersley@radiuspharm.com

 

Dear Gary,

 

We thank you for your interest in Charles River and hope the attached proposal meets with your approval.  For your convenience, we have provided the following summary of the titles and prices of the studies and/or study components under discussion.  If you would like us to proceed with animal orders resource allocation, sign and date the authorization line below.  (If all studies and/or components are not being authorized at this time, please initial the studies and components you wish to authorize and sign and date the authorization line below.  If all studies are being authorized at this time, merely sign and date the authorization line below, leaving the studies and component boxes empty).  These prices are valid for 60 days, but may be modified by mutual agreement if changes to the scope of work are made.

 

	
Authorization
   Initials
    	
 
    	
Study Number and Title
    	
 
    	
Price
    
	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
670647
    A 16-Month Osteoporosis Intervention Study in   the [*]
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
Animal cost: ([*])
    Price with % pre-discount:
   Total with [*] % [*] discount:
    	
 
    	
$          [*]US
    $          [*]US
   $  138,807US
    

 

In order to minimize the impact of study delays and cancellations for all sponsors, Charles River allocates resources at the time a signed Letter of Payment Authorization is received.  Please note that scheduling is not considered confirmed until a signed copy of this document is received.  By providing authorization via signature below, you will allow us to confirm a schedule for each authorized study.  Your signature further constitutes acceptance of the price and payment schedule.

 

Payment Schedule for Study # 670647 – Reservation of [*] Animals

 

·                  $ 138,807 US     7 weeks after authorization

 

Based upon the current scope of work, we would propose to initiate the screening in May, 2010.  If animal importation is performed on or around August 11, 2010, the animal arrival at CRL would occur during week of October 4, 2010.  Prior to receipt of this signed Letter of Payment Authorization this initiation date may be lost to another study vying for the same resources.

 

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

 

 

We understand that occasionally you may request to delay or to cancel a study due to unforeseen circumstances.  Charles River will make every commercially reasonable effort to accommodate requested schedule changes.  However, the following fees would be applicable:

 

Per diem fees at a rate of $ [*] US/animal per day ([*] $/day) would be invoiced in the event of a delay in the importation date planned for August 11, 2010.

 

In the event of a cancellation:

 

Before importation, the entire cost of the screening ($50,000US) and of the animal reservation ($138,807 US) would be lost.  Alternatively, Radius would have an option for the DIRECT purchase of up to [*] animals with the reservation fees paid.  Should the option be exercised, Radius would then be responsible for housing fees at a rate of $ [*] US/animal per day.

 

Following importation, in addition to the screening and reservation cost, per diem fees would be invoiced until the animals are placed elsewhere ($[*] US/animal per day).  Radius would also have an option for the purchase of up to [*] animals with the reservation fees paid.  Should the option be exercised, Radius would then be responsible for housing fees at a rate of $ [*] US/animal per day.

 

Charles River shall perform these services in accordance with the services agreement (the “Agreement”) executed between Charles River and RADIUS HEALTH, INC.  Once fully executed, this Letter of Payment Authorization shall be incorporated into and made part of the Agreement.

 

STUDY MATERIAL STORAGE/ARCHIVES.  After dispatch of the draft report, all raw data, samples/specimens (except for those sent to Sponsor or Sponsor designated laboratory and resultant data which are the responsibility of Sponsor) and documents generated at Charles River during this study, together with the original copy of the protocol (including amendments) and the draft report, will be retained in the secure storage area of Charles River for one (1) year at no charge.  After this one (1) year period, Sponsor will be contacted prior to the end of the year to authorize continued storage or return to Sponsor, at additional cost.  At finalisation, the final report and any stored materials will be transferred to the scientific archives of Charles River.  Subsequently, storage details will be documented in the raw data.

 

Any additional storage, archiving or retention will require an Extended Archiving Agreement.

 

REPEAT OF SAMPLE ANALYSIS.  If applicable for studies involving bioanalytical sample analysis, the parties agree that as of commencement of work, in some instances, repeat of sample analysis will be required.  If this arises, Charles River must notify the Sponsor as soon as possible and determine, between the parties, if these repeats are required by Sponsor.  Consequently, the price per sample analysis/occasion will apply to any additional repeats requested by the Sponsor, as well as any samples above the analytical range, which require dilution.  However, in the event that additional sample analysis/occasions are required, Charles River shall submit a written estimate to the Sponsor for the Sponsor’s written approval, and the Sponsor shall respond to Charles River within five (5) business days, or within the specified time period sanctioned by the Sponsor for receipt of such estimates.  Once authorization is received, Charles River will endeavor, when possible, to proceed with current batches of sample analysis.  Both parties acknowledge that Charles River will be reimbursed for any amount which relates to the repeats if the difference between the original result of the sample analysis and the repeat result of the sample analysis, is within a 30% range.

 

SHIPMENT OF TEST ARTICLES.  Sponsor and Charles River agree that all costs associated with shipping test article to Charles River shall be the responsibility of the Sponsor.  Charles River shall not be responsible for any direct or indirect damages sustained by the Sponsor resulting from any loss, destruction or damage to the test article(s).

 

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

 

2

 

In the event of a conflict between the terms set forth in this Letter of Payment Authorization and the Agreement, the terms of the Master Service Agreement shall control, unless specifically agreed upon to the contrary in this letter.

 

Please sign and return this document via facsimile or email (contact information below).  Should you have any questions or require any additional information, please do not hesitate to call me.  We look forward to being of service.

 

Best regards,

 

	
 
    	
 
    	
/s/   B.N. Harvey
    
	
 
    	
 
    	
Authorized   Sponsor Representative
    
	
Stéphane   Besner, B.Sc., M.B.A
    	
 
    	
 
    
	
Client   Manager, Sales & Marketing
    	
 
    	
B.N.   Harvey
    
	
Charles   River Laboratoires
    	
 
    	
Print   (Name and Title)
    
	
Preclinical   Services Montreal Inc.
    	
 
    	
 
    
	
Tel:   (514) 630-2436 Fax: (514) 630-8230
    	
 
    	
5/26/10
    
	
e-mail:   stephane.besner@crl.com
    	
 
    	
Date
    

 

 

If a PO is required, please submit PO with Letter of Payment Authorization or fax to 514-630-8230.

 

	
Charles River Laboratories
    	
 
    	
 
    
	
Preclinical Services Montréal Inc.
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
/s/   Catherine Konidas
    	
 
    	
 
    
	
Catherine   Konidas, MBA
    	
 
    	
 
    
	
Site   Director, Montreal
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
/s/   Michele Marcoux
    	
 
    	
 
    
	
Michele   Marcoux, CMA
    	
 
    	
 
    
	
Site   Controller
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
June   2, 2010
    	
 
    	
 
    
	
Date
    	
 
    	
 
    

 

A counter signed version of this document will be returned to you for your records.

 

c.c.  C. Konidas, S. Pryce, D. Trembley, S Y. Smith, Main File

 

3

 

[CHARLES RIVER LETTERHEAD]

 

LETTER OF PAYMENT AUTHORIZATION

 

August 23, 2004

 

Ben Lane
  NuVios
 197M Boston Post Road
 Marlborough, MA 01752
 Fax: 847-680-5023
 Email: ben.c.lane@sbcglobal.net

 

Re: SSU00006: “PHARMACOKINETICS OF A TEST ARTICLE FOLLOWING SUBCUTANEOUS IMPLANT IN OVARIECTOMIZED FEMALE SWISS WEBSTER MICE.”

 

This communication serves as a Letter of Payment Authorization (LOPA) for the above referenced study, which will be performed at Charles River Discovery Development Services - Worcester Division (CR-DDS-Worcester Division) as set forth below.  CR-DDS-Worcester Division shall perform these services in accordance with the Services Agreement executed between CRL and Nuvios, Inc. Once fully executed, this LOPA shall be incorporated into and made part of the Service Agreement.

 

The payment schedule and price of this study are as follows:

 

·                  (100%)       $29,400          Due Upon In-Life Completion

 

Total Price of Study: $29,400

 

In the event the study design is altered, or the study is postponed or cancelled, payments will be amended as follows:

 

The price impact (if any) of the protocol amendment/change order will be submitted in writing.  If study prices are increased, the difference will be invoiced and payable upon acceptance by the Sponsor.  If study prices decrease, the Sponsor will be credited for the difference.

 

In the event CR-DDS- Worcester Division does not receive comments pertaining to the draft report within 60 days after submission to the Sponsor, the final invoice will be due and payable.  Authorization to finalize the report must be received within six (6) months of draft report submission (unless agreed upon differently with the Sponsor) after which CR-DDS- Worcester Division will automatically finalize the report and submit to the Sponsor.

 

As acceptancepf.this agreement, please sign this Letter of Payment Authorization and return to Jessica Metterville at the letterhead address (or fax to Jessica Metterville at 508.890.0192).

 

	
/s/   Christopher K. Mirabelli, Acting CEO
    	
 
    	
/s/   Jessica Metterville
    
	
Sponsor   Representative
    	
 
    	
Jessica   Metterville
    
	
 
    	
 
    	
Client   Services
    
	
Christopher   K. Mirabelli
    	
 
    	
August 23,   2004
    
	
Print   (Name and Title)
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
August   25, 2004
    	
 
    	
 
    
	
Date
    	
 
    	
 
    

 

 

[CHARLES RIVER LETTERHEAD]

 

Letter of Payment Authorization

 

April 8, 2010

 

Gary Hattersley, Ph.D.
 Vice President, Biology
  RADIUS HEALTH, INC.
 5th Floor
 300 Technology Square
 Cambridge, MA 02139
 United States
 ghattersley@radiuspharm.com

 

Dear Gary,

 

We thank you for your interest in Charles River and hope the attached proposal meets with your approval.  For your convenience, we have provided the following summary of the titles and prices of the studies and/or study components under discussion.  If you would like us to proceed with animal orders resource allocation, sign and date the authorization line below.  (If all studies and/or components are not being authorized at this time, please initial the studies and components you wish to authorize and sign and date the authorization line below.  If all studies are being authorized at this time, merely sign and date the authorization line below, leaving the studies and component boxes empty).  These prices are valid for 60 days, but may be modified by mutual agreement if changes to the scope of work are made.

 

	
Authorization
   Initials
    	
 
    	
Study Number and Title
    	
 
    	
Price
    
	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
670647
    A 16-Month Osteoporosis Intervention Study in   the [*]
    (Reference scope of work dated: 03/12/2010)
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
Screening   of: [*] Animals

Revised Price with [*]% [*] discount:
    	
 
    	
[*]

$ 14,960 US
    

 

In order to minimize the impact of study delays and cancellations for all sponsors, Charles River allocates resources at the time a signed Letter of Payment Authorization is received.  Please note that scheduling is not considered confirmed until a signed copy of this document is received.  By providing authorization via signature below, you will allow us to confirm a schedule for each authorized study.  Your signature further constitutes acceptance of the price and payment schedule.

 

Payment Schedule for Study # 670647 — Screening of [*] Animals

 

The payment schedule of this study is as follows:

 

·                  100%     Billing as per work performed

 

Based upon the current scope of work, we would propose to initiate these studies in Q2, 2010.  Prior to receipt of this signed Letter of Payment Authorization this initiation date may be lost to another study vying for the same resources.

 

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

 

 

We understand that occasionally you may request to delay or to cancel a study due to unforeseen circumstances.  Charles River will make every commercially reasonable effort to accommodate requested schedule changes.

 

Charles River shall perform these services in accordance with the services agreement (the “Agreement”) executed between Charles River and RADIUS HEALTH, INC.  Once fully executed, this Letter of Payment Authorization shall be incorporated into and made part of the Agreement.

 

STUDY MATERIAL STORAGE/ARCHIVES.  After dispatch of the draft report, all raw data, samples/specimens (except for those sent to Sponsor or Sponsor designated laboratory and resultant data which are the responsibility of Sponsor) and documents generated at Charles River during this study, together with the original copy of the protocol (including amendments) and the draft report, will be retained in the secure storage area of Charles River for one (1) year at no charge.  After this one (1) year period, Sponsor will be contacted prior to the end of the year to authorize continued storage or return to Sponsor, at additional cost.  At finalisation, the final report and any stored materials will be transferred to the scientific archives of Charles River.  Subsequently, storage details will be documented in the raw data.

 

Any additional storage, archiving or retention will require an Extended Archiving Agreement.

 

REPEAT OF SAMPLE ANALYSIS.  If applicable for studies involving bioanalytical sample analysis, the parties agree that as of commencement of work, in some instances, repeat of sample analysis will be required.  If this arises, Charles River must notify the Sponsor as soon as possible and determine, between the parties, if these repeats are required by Sponsor.  Consequently, the price per sample analysis/occasion will apply to any additional repeats requested by the Sponsor, as well as any samples above the analytical range, which require dilution.  However, in the event that additional sample analysis/occasions are required, Charles River shall submit a written estimate to the Sponsor for the Sponsor’s written approval, and the Sponsor shall respond to Charles River within five (5) business days, or within the specified time period sanctioned by the Sponsor for receipt of such estimates.  Once authorization is received, Charles River will endeavor, when possible, to proceed with current batches of sample analysis.  Both parties acknowledge that Charles River will be reimbursed for any amount which relates to the repeats if the difference between the original result of the sample analysis and the repeat result of the sample analysis, is within a 30% range.

 

SHIPMENT OF TEST ARTICLES.  Sponsor and Charles River agree that all costs associated with shipping test article to Charles River shall be the responsibility of the Sponsor.  Charles River shall not be responsible for any direct or indirect damages sustained by the Sponsor resulting from any loss, destruction or damage to the test article(s).

 

In the event of a conflict between the terms set forth in this Letter of Payment Authorization and the Agreement, the terms of the Master Service Agreement shall control, unless specifically agreed upon to the contrary in this letter.

 

2

 

Please sign and return this document via facsimile or email (contact information below).  Should you have any questions or require any additional information, please do not hesitate to call me.  We look forward to being of service.

 

Best regards,

 

	
 
    	
 
    	
/s/   B.N. Harvey
    
	
Stéphane Besner, B.Sc., M.B.A
    	
 
    	
Authorized   Sponsor Representative
    
	
Client Manager, Sales & Marketing
    	
 
    	
 
    
	
Charles River Laboratoires
    	
 
    	
B.N.   Harvey, CFO
    
	
Preclinical Services Montreal Inc.
    	
 
    	
Print   (Name and Title)
    
	
22022 Transcanadienne
    	
 
    	
 
    
	
Senneville, Québec, Canada H9X 3R3
    	
 
    	
April 8, 2010
    
	
Tel: (514) 630-2436 Fax: (514) 630-8230
    	
 
    	
Date
    
	
e-mail: stephane.besner@crl.com
    	
 
    	
 
    
	
Web site: www.criver.com
    	
 
    	
 
    

 

 

If a PO is required, please submit PO with Letter of Payment Authorization or fax to 514-630-8230.

 

	
Charles River Laboratories
    	
 
    	
 
    
	
Preclinical Services Montréal Inc.
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
/s/ Catherine Konidas
    	
 
    	
 
    
	
Catherine   Konidas, MBA
    	
 
    	
 
    
	
Site   Director, Montreal
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
Michele   Marcoux
    	
 
    	
 
    
	
Michele   Marcoux, CMA
    	
 
    	
 
    
	
Site   Controller
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
April   14, 2010
    	
 
    	
 
    
	
Date
    	
 
    	
 
    

 

A counter signed version of this document will be returned to you for your records.

 

c.c.  C. Konidas, S. Pryce, D. Trembley, S Y. Smith, Main File

 

3

 

 

AMENDED LETTER OF PAYMENT AUTHORIZATION

AMENDMENT NUMBER 1

 

25 May 2011

 

Gary Hattersley, PhD

VP, Biology

RADIUS

300 Technology Square, 5th Floor

Cambridge, MA 02139

Phone: 617.551.4703

Email: ghattersley@radiuspharm.com

 

Dear Dr. Hattersley,

 

This communication is to serve as an amendment to the Letter of Payment Authorization for the above referenced study, which is being performed at Charles River Laboratories.  Charles River Laboratories shall perform these services in accordance with the existing Service Agreement executed between Charles River Laboratories and RADIUS.  Once fully executed, this Amended LOPA shall be incorporated into and made part of the existing Service Agreement.

 

Charles River Laboratories Study Number 20009789

 

A 6-Month Dermal Toxicity Study in [*] with 2-Week Recovery

 

·                  ECGs collected on the recovery phase animals prior to recovery phase termination but not evaluated unless needed.

·                  TK blood tubes to be filled with aprotinin

·                  TK/Immuno Interpretation

 

The additional cost of this study change is as follows:

 

·                  $14,165                   Due upon authorization

 

New Total Price of Study:  $420,765

 

As acceptance of this agreement, please sign this Amended Letter of Payment Authorization and return to Charles River Laboratories by fax at 419-647-6560.

 

	
/s/   B.N. Harvey
    	
 
    	
/s/   April Jackson
    
	
Sponsor   Representative
    	
 
    	
April Jackson
    
	
 
    	
 
    	
Account   Manager
    
	
B.N.   Harvey, CFO
    	
 
    	
25May2011
    
	
Print   (Name and Title)
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
May   27, 2011
    	
 
    	
 
    
	
Date
    	
 
    	
 
    

 

Charles River Laboratories LOPA

 

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

 

1

 

 

AMENDED LETTER OF PAYMENT AUTHORIZATION

AMENDMENT NUMBER 2 — Revision 1

 

July 20, 2011

 

Gary Hattersley, PhD

VP, Biology

RADIUS

300 Technology Square, 5th Floor

Cambridge, MA 02139

Phone: 617.551.4703

Email: ghattersley@radiuspharm.com

 

Dear Dr. Hattersley,

 

This communication is to serve as an amendment to the Letter of Payment Authorization for the above referenced study, which is being performed at Charles River Laboratories.  Charles River Laboratories shall perform these services in accordance with the existing Service Agreement executed between Charles River Laboratories and RADIUS.  Once fully executed, this Amended LOPA shall be incorporated into and made part of the existing Service Agreement.

 

Charles River Laboratories Study Number 20009789

 

A 3-Month Dermal Toxicity Study in [*] with 2-Week Recovery

 

·                  Study duration changed from 6 months to 3 months

 

The reduced cost of this study change is as follows:

 

·                  -$ [*]

 

New Total Price of Study:  $329,265

 

Revised Payment Schedule for $329,265:

 

Payments Sent:

 

Study Authorization: $ [*]

 

Study Initiation: $ [*]

 

ALOPA#1: $ [*]

 

Payments to be invoiced:

 

Month 2: $ [*]

 

Month 3: $ [*]

 

Submission of Draft Report (5%): $16,465

 

Submission of Final Report** (5%): $16,465

 

** Final payment milestone due within 45 days of the draft report if no response from the sponsor over the draft report.

 

Charles River Laboratories ALOPA

 

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

 

1

 

As acceptance of this agreement, please sign this Amended Letter of Payment Authorization and return to Charles River Laboratories by fax at 419-647-6560.

 

	
B.N.   Harvey
    	
 
    	
/s/   April Jackson
    
	
Sponsor   Representative
    	
 
    	
April Jackson
    
	
 
    	
 
    	
Client   Manager
    
	
B.N. Harvey, CFO
    	
 
    	
20-Jul-2011
    
	
Print   (Name and Title)
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
May 27, 2011
    	
 
    	
 
    
	
Date
    	
 
    	
 
    

 

2

 

 

Letter of Payment Authorization – Revision 3

 

April 29, 2011

 

Gary Hattersley, PhD

VP, Biology

RADIUS

300 Technology Square, 5th Floor

Cambridge, MA 02139

Phone: 617.551.4703

Email: ghattersley@radiuspharm.com

 

Dear Dr. Hattersley,

 

We thank you for your interest in Charles River and hope the attached proposal meets with your approval. For your convenience, we have provided the following summary of the title and price of the studies and/or study components under discussion. If you would like us to proceed with animal orders resource allocation, sign and date the authorization line below. This price is valid for 60 days, but may be modified by mutual agreement if changes to the scope of work are made.

 

	
Authorization
   Initial’s
    	
 
    	
Study Number and Title
    	
 
    	
Price
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
Study   # 20009789 
   Title: A 6-Month Dermal Toxicity Study in [*] with   2-Week Recovery
    	
 
    	
$
    	
 406,600
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
Optional 3-Month Main Extension (dosing and observations only):
    	
 
    	
$
    	
[*]
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
Expediting Reporting (writing only)*

 

*Does not include expediting of study related parameters, only of   writing of physical report.
    	
 
    	
$
    	
[*] per week
    	
 
    

 

In order to minimize the impact of study delays and cancellations for all sponsors, Charles River allocates resources at the time a signed Letter of Payment Authorization is received.  Please note that scheduling is not considered confirmed until a signed copy of this document is received.  By providing authorization via signature below, you will allow us to confirm a schedule for each authorized study. Your signature further constitutes acceptance of the price and payment schedule.

 

Payment Schedule for Study Number 20009789

 

The payment schedule and price of this study are as follows:

	
·
    	
 
    	
15%
    	
 
    	
Due   upon Authorization*
    
	
·
    	
 
    	
12.5%
    	
 
    	
Due   upon Study Initiation (Day 1)
    
	
·
    	
 
    	
12.5%
    	
 
    	
Due   Interim – Month 2
    
	
·
    	
 
    	
12.5%
    	
 
    	
Due   Interim – Month 3
    
	
·
    	
 
    	
12.5%
    	
 
    	
Due   Interim – Month 4
    
	
·
    	
 
    	
12.5%
    	
 
    	
Due   Interim – Month 5
    
	
·
    	
 
    	
12.5%
    	
 
    	
Due   Interim – Month 6
    
	
·
    	
 
    	
5%
    	
 
    	
Due   upon Submission of Draft Report
    
	
·
    	
 
    	
5%
    	
 
    	
Due   upon Submission of Final Report**
    

 

*Invoice(s) will be sent no more than 60 days prior to scheduled study start.

** Final payment milestone due within 45 days of the draft report if no response from the sponsor over the draft report.

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

 

1

 

In the event Charles River does not receive comments pertaining to the draft report within 60 days after submission to the Sponsor, the final invoice will be due and payable.

 

Based upon the current scope of work, we would expect to initiate this study (Day 1) in early to mid July, 2011.  Prior to receipt of this signed Letter of Payment Authorization this initiation date may be lost to another study vying for the same resources.

 

We understand that occasionally you may request to delay or to cancel a study due to unforeseen circumstances.  Charles River will make every reasonable effort to accommodate requested schedule changes and will be handled in accordance with the Service Agreement.

 

Charles River shall perform these services in accordance with the Service Agreement (the “Agreement”) executed between Charles River and RADIUS.  Once fully executed, this Letter of Payment Authorization shall be incorporated into and made part of the Agreement.

 

STUDY MATERIAL STORAGE/ARCHIVES.  After dispatch of the draft report, all raw data, samples/specimens (except for those sent to Sponsor or Sponsor designated laboratory and resultant data which are the responsibility of Sponsor) and documents generated at Charles River during this study, together with the original copy of the protocol (including amendments) and the draft report, will be retained in the secure storage area of Charles River.  At finalisation, the final report and any stored materials will be transferred to the scientific archives of Charles River for (1) year.  Subsequently, storage details will be documented in the raw data.  After this one (1) year period, Sponsor will be contacted prior to the end of the year to authorize continued storage or return to Sponsor, at additional cost.

 

Any additional storage, archiving or retention will require an Extended Archiving Agreement

 

REPEAT OF SAMPLE ANALYSIS.  If applicable, the parties agree that as of commencement of work, in some instances, repeat of sample analysis will be required.  If this arises, Charles River must notify the Sponsor as soon as possible and determine, between the parties, if these repeats are required by Sponsor.  Consequently, the price per sample analysis/occasion will apply to any additional repeats requested by the Sponsor, as well as any samples above the analytical range, which require dilution.  However, in the event that additional sample analysis/occasions are required, Charles River shall submit a written estimate to the Sponsor for the Sponsor’s written approval, and the Sponsor shall respond to Charles River within five (5) business days, or within the specified time period sanctioned by the Sponsor for receipt of such estimates.  Once authorization is received, Charles River will endeavor, when possible, to proceed with current batches of sample analysis.  Both parties acknowledge that Charles River will be reimbursed for any amount which relates to the repeats if the difference between the original result of the sample analysis and the repeat result of the sample analysis, is within a 30% range.

 

SHIPMENT OF TEST ARTICLES.  Sponsor and Charles River agree that all costs associated with shipping test article to Charles River shall be the responsibility of the Sponsor.  Charles River shall not be responsible for any direct or indirect damages sustained by the Sponsor resulting from any loss, destruction or damage to the test article(s).

 

In the event of a conflict between the terms set forth in this letter and the Master Service Agreement, the terms of the Master Service Agreement shall control, unless specifically agreed upon to the contrary in this letter.

 

2

 

Please sign and return this document via facsimile or email (contact information below).  Should you have any questions or require any additional information, please do not hesitate to call me.  We look forward to being of service.

 

Best regards,

 

	
/s/   April Jackson
    	
 
    	
 
    
	
April Jackson
    	
 
    	
/s/ B.N. Harvey
    
	
Client Manager
    	
 
    	
Authorized Sponsor Representative
    
	
Charles River
    	
 
    	
 
    
	
Preclinical Services
    	
 
    	
B.N. Harvey, CFO
    
	
Phone: 419.647.4196 ext 361
    	
 
    	
Print (Name and Title)
    
	
Fax:  419.647.6560
    	
 
    	
 
    
	
E-Mail:    April.Jackson@crl.com
    	
 
    	
April 29, 2011
    
	
 
    	
 
    	
Date
    

 

If a PO is required, please submit PO with Letter of Payment Authorization or fax to April Jackson at 419.647.6560.

 

3

 

	
Title:
    	
 
    	
A   6-Month Dermal Toxicity Study in [*] with 2-Week Recovery
    
	
 
    	
 
    	
 
    
	
Study   Number:
    	
 
    	
20009789
    
	
 
    	
 
    	
 
    
	
Charles River Facility:
    	
 
    	
Ohio
    
	
 
    	
 
    	
 
    
	
Compliance:
    	
 
    	
GLP
    
	
 
    	
 
    	
 
    
	
Species/Strain:
    	
 
    	
[*]
    
	
 
    	
 
    	
 
    
	
Dose   Formulation Preparation (assumes basic dose   preparation):
    	
 
    	
Test   material to be dispensed as received; no samples obtained.
    
	
 
    	
 
    	
 
    
	
Dose   Formulation Analysis (assumes standard HPLC-UV method):
    	
 
    	
N/A
    
	
 
    	
 
    	
 
    
	
Dosing   Regimen:
    	
 
    	
Once   daily for 182 days (6 months).
    
	
 
    	
 
    	
 
    
	
Route   of Administration:
    	
 
    	
Transdermal   dose administration [*].
    
	
 
    	
 
    	
 
    
	
Test System:
    	
 
    	
 
    	
 
    	
 
    	
 
    	
Number of Animals
    
	
 
    	
 
    	
Group
    	
 
    	
Dose
    	
 
    	
Males
    	
 
    	
Females
    
	
 
    	
 
    	
1
    	
 
    	
Control
    	
 
    	
[*]
    	
 
    	
[*]
    
	
 
    	
 
    	
2
    	
 
    	
Low
    	
 
    	
[*]
    	
 
    	
[*]
    
	
 
    	
 
    	
3
    	
 
    	
High
    	
 
    	
[*]
    	
 
    	
[*]
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    

	
 
    	
 
    	
*2 animals/sex/group held   for 2-Week Recovery
    
	
 
    	
 
    	
 
    
	
Spares:
    	
 
    	
[*]   animals
    
	
 
    	
 
    	
 
    
	
Total Population:
    	
 
    	
[*]   animals
    
	
 
    	
 
    	
 
    
	
Age:
    	
 
    	
Approximately   3-4 months at receipt
    
	
 
    	
 
    	
 
    
	
Source:
    	
 
    	
[*]
    
	
 
    	
 
    	
 
    
	
Pretreatment Period:
    	
 
    	
Approximately   14 days
    
	
 
    	
 
    	
 
    
	
Mortality/Cage   side Observations:
    	
 
    	
Mortality:   twice daily on all animals
    
	
 
    	
 
    	
 
    
	
 
    	
 
    	
Cage-side   Obs: Daily (up to [*] hours post-dose) on all animals
    
	
 
    	
 
    	
 
    
	
Detailed   Observations:
    	
 
    	
Pre-test,   weekly and at termination on all animals.
    
	
 
    	
 
    	
 
    
	
Body   Weight:
    	
 
    	
Pre-test,   weekly and at termination on all animals.
    
	
 
    	
 
    	
 
    
	
Special   Assessments:
    	
 
    	
Ophthalmology   examination on all animals pre-dose and near termination on all animals.   Recovery termination at additional cost.
    
	
 
    	
 
    	
 
    
	
 
    	
 
    	
ECG   measurements at pre-test and near main termination on all animals. Recovery   termination at additional cost.
    
	
 
    	
 
    	
 
    
	
 
    	
 
    	
Draize   dermal scoring weekly on all animals.
    
	
 
    	
 
    	
 
    
	
Clinical   Pathology Parameters:
    	
 
    	
Standard   hematology, clinical chemistry, and coagulation (PT and APTT) performed   pre-test, Day 28, Day 91, and Day 182 on all animals and on Day 197 on   recovery animals.
    

 

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

 

4

 

	
Title:
    	
 
    	
A   6-Month Dermal Toxicity Study in [*] with 2-Week Recovery
    
	
 
    	
 
    	
 
    
	
Study   Number:
    	
 
    	
20009789
    
	
 
    	
 
    	
 
    
	
Toxicokinetic Samples Collection:
    	
 
    	
Toxicokinetic   samples (1.5 mL of plasma) obtained from all animals at 8 time points on Day   1 and Day 182 ([*] samples total). Samples to be shipped to sponsor   designated laboratory.
    
	
 
    	
 
    	
 
    
	
Immunogenicity Samples Collection:
    	
 
    	
1   sample collected from each animal at pre-test and 6-months ([*] samples).   Samples to be shipped to sponsor designated laboratory.
    
	
 
    	
 
    	
 
    
	
Terminal   Procedures:
    	
 
    	
Full   gross necropsy with organ weights and tissue collection on all animals ~Day   183 (main) and ~Day 197 (recovery).
    
	
 
    	
 
    	
 
    
	
Histopathology:
    	
 
    	
Standard   histopathology (up to [*] tissue sections) from all [*] animals.
    
	
 
    	
 
    	
 
    
	
Draft   Report:
    	
 
    	
Audited   draft report provided in approximately 14 weeks from the time of in-life   completion.
    
	
 
    	
 
    	
 
    
	
Archiving:
    	
 
    	
Archiving   materials will be maintained with Charles River for 1 year following the   final report issuance.
    

 

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

 

5

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