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 [*] months after the effective date of
this Amendment and will use commercially reasonable efforts to accomplish
delivery by [*].   The costs for development and supply of Product for the Phase
II clinical study is estimated to be $[*], 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.

 

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* 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 [*] and
shall be held in Cambridge, Massachusetts.  After the initial meeting, meetings
may be held by telephone or video

 

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

 

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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 [*] ([*])
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 [*] ([*]) 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 [*] ([*]) 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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* Confidential Treatment Requested by the Registrant. Redacted Portion Filed
Separately with the Commission.

 

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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 [*] months of [*] with notice to 3M in the
event that Radius has determined that the Phase I clinical study for the Product
needs to be

 

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* 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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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 [*]
months after the effective date of this Amendment and will use commercially
reasonable efforts to accomplish delivery by [*] if Radius approves the Phase II
Workplan and initiates work on or before [*].  If work does not commence on [*],
[*] 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 [*] applicators)

 

$[*]

 

—

 

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.

 

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* 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 [*] 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 [*] 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 [*] 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

 

[*]

 

[*]

Release testing

 

[*]

 

[*]

Retains

 

[*]

 

[*]

Stability

 

[*]

 

[*]

3M SOP retains

 

[*]

 

[*]

Total quantity

 

[*]

 

[*]

 

·                  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 [*]
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.

 

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* 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 [*].  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 – [*]

2.               March API requirements delivered by Radius to 3M – [*]

3.               Methods provided to 3M for crossover – [*]

4.               April API requirements delivered by Radius to 3M – [*]

5.               May API requirements delivered by Radius to 3M – [*]

6.               Initiation of coating optimization – [*]

7.               RTC optimization concludes – [*]

8.               July API requirements delivered by Radius to 3M – [*]

9.               Equipment installation – [*]

10.         Initiation of final optimization of coating and process verification
– [*]

11.         Completion of coating process verification – [*]

12.         Release phase II supplies – by [*]

 

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 [*] 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 [*] 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 [*] 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 [*]
months of the completion of the stability study.

 

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

 

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·                  DMFs for BA058-sMTS CCS and Coating and Drying Process will
be filed at least [*] 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 [*]-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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* Confidential Treatment Requested by the Registrant. Redacted Portion Filed
Separately with the Commission.

 

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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 [*] units; [*]
active doses at a maximum as indicated in the table above.

Stability of RTC at 5C/ambient RH – [*] months

Stability of RTC at 25C/60% RH – [*] days, [*] week

Stability of Phase 2 Supplies:  5C/ambient RH – [*], months; 25C/60% RH - [*]
months; 40C/75% RH – [*] months; the [*] and [*] months timepoints will be added
under a Change Order.

Clear, release and ship Clinical Supplies

 

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

 

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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

 

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