Exhibit 10.52

**Text Omitted and Filed Separately

with the Securities and Exchange Commission

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(4)

and 240.24b-2

EXECUTION COPY

SECOND AMENDED AND RESTATED

COLLABORATION AND LICENSE AGREEMENT

between

REGULUS THERAPEUTICS INC.

And

SANOFI

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SECOND AMENDED AND RESTATED

COLLABORATION AND LICENSE AGREEMENT

THIS SECOND AMENDED AND RESTATED COLLABORATION AND LICENSE AGREEMENT (the
“Agreement”) is made and entered into this February 4, 2014 (the “Second
Restatement Date”), by and between SANOFI (formerly, SANOFI-AVENTIS), a French
Corporation (“Sanofi”) having a place of business at 54, rue la Boétie, 75008,
Paris, France, registered in the Paris Trade and Company Register under
no. 395 030 844, and REGULUS THERAPEUTICS INC., a Delaware Corporation
(“Regulus”) having a place of business at 3545 John Hopkins Court, Suite 210,
San Diego, California 92121-1121. Sanofi and Regulus each may be referred to
herein individually as a “Party,” or collectively as the “Parties.”

WHEREAS, Regulus possesses certain patent rights, know-how and technology with
respect to therapeutic microRNA Compounds;

WHEREAS, Regulus and Sanofi entered into a Collaboration and License Agreement
(the “Original Agreement”) dated June 21, 2010 (the “Effective Date”), under
which the Parties agreed to conduct a Research Program to identify one or more
Licensed Compounds for a limited number of Collaboration Targets and Regulus
granted Sanofi exclusive rights to Licensed Compounds and Products arising from
the Research Program;

WHEREAS, Regulus and Sanofi amended and restated the Original Agreement pursuant
to an Amended and Restated Collaboration and License Agreement (the “First
Restated Agreement”) dated July 16, 2012 (the “First Restatement Date”), under
which the Parties agreed to expand the scope of the Research Program;

WHEREAS, Sanofi and Regulus now desire to amend and restate the Restated
Agreement with this Agreement; and

WHEREAS, in connection with the execution of this Agreement, the Parties are
entering into a Stock Purchase Agreement dated as of the Second Restatement
Date, pursuant to which Sanofi is purchasing $10 million of shares of Regulus’
common stock (the “Stock Purchase Agreement”).

NOW, THEREFORE, in consideration of the foregoing and the mutual covenants
herein contained, the Parties do hereby agree as follows.

ARTICLE 1

DEFINITIONS

The terms used in this Agreement with initial letters capitalized, whether used
in the singular or the plural, will have the meaning set forth in APPENDIX 1, or
if not listed in APPENDIX 1, the meaning designated in places throughout the
Agreement.

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ARTICLE 2

GRANT OF RIGHTS; EXCLUSIVITY

Section 2.1 Mir-21 Licenses and Options.

2.1.1 License to Mir-21 Compounds and Products. Subject to the terms and
conditions of this Agreement (including, without limitation, Section 2.1.3,
Section 2.1.4, Section 2.3, Section 3.4.3(a) and Section 9.4.1), Regulus hereby
grants to Sanofi a worldwide, royalty-bearing, exclusive license, with the right
to grant sublicenses as set forth in Section 2.4 below, under the Regulus
Know-How and Regulus Patents to Research, Develop, make, have made, use, gain
Approval, Commercialize, sell, offer for sale, have sold, export and import
Mir-21 Compounds, Mir-21 Products, and Companion Diagnostics for use with Mir-21
Products; in each case, in the Product Field (the “Mir-21 License”).

2.1.2 Mir-21 POC Program Research License. Subject to the terms and conditions
of this Agreement, Sanofi hereby grants to Regulus, (i) a worldwide,
royalty-free, co-exclusive (with Sanofi) sublicense, without the right to grant
further sublicenses (other than in connection with the use of subcontractors or
consultants in accordance with Section 3.9.4), under the Regulus Know-How and
Regulus Patents licensed to Sanofi under Section 2.1.1, and (ii) a worldwide,
royalty-free, co-exclusive (with Sanofi) license, without the right to grant
further sublicenses (other than in connection with the use of subcontractors or
consultants in accordance with Section 3.9.4), under Sanofi Inventions and
Sanofi Program Patents; in each case, solely to perform the Mir-21 POC Program
activities for which Regulus is responsible as specified in the applicable
Mir-21 POC Program Plan during the applicable Mir-21 POC Program Term. For
clarity, upon termination of a Mir-21 POC Program pursuant to Section 3.4, the
license granted by Sanofi to Regulus under this Section 2.1.2 shall terminate
and be of no further force or effect.

2.1.3 Mir-21 POC Program Options. On a Mir-21 POC Program-by Mir-21 POC Program
basis, upon expiration of the POC Program Term for a particular Mir-21 POC
Program, Regulus shall deliver to Sanofi the POC Study Report for such Mir-21
POC Program, and an invoice for both the Option Exercise Fee and POC Program
Reimbursement Amount for such POC Program (which invoices shall be payable in
accordance with Section 6.5 and Section 6.7, respectively, only in the event
Sanofi exercises the Mir-21 Option in accordance with this Section 2.1.3), and
Sanofi may elect to continue the Development of any Mir-21 POC Program Product
that is the subject of such Mir-21 POC Program, the Mir-21 Compound(s) contained
in any such Mir-21 POC Program Product, and Companion Diagnostics for use with
any such Mir-21 POC Program Product after expiration of the applicable POC
Program Term, in accordance with the terms and conditions of this Agreement
(each, a “Mir-21 Option”), by: (a) delivering written notice of such election to
Regulus prior to expiration of the Option Period for such POC Program; and
(b) paying to Regulus the applicable Option Exercise Fee and POC Program
Reimbursement Amount for such POC Program in accordance with Section 6.5 and
Section 6.7, respectively.

2.1.4 Consequences of Failure to Exercise Mir-21 Option. On a Mir-21 POC
Program-by-Mir-21 POC Program basis, in the event that Sanofi fails to exercise
its Mir-21 Option with respect to a particular Mir-21 POC Program in accordance
with Section 2.1.3 prior

 

2.

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to expiration of the applicable Option Period, then, effective as of expiration
of such Option Period:

(a) the Mir-21 Option with respect to such Mir-21 POC Program shall terminate
and be of no further force or effect;

(b) the Mir-21 License shall terminate solely with respect to any Mir-21 POC
Program Product that was the subject of such Mir-21 POC Program, the Mir-21
Compound(s) contained in any such Mir-21 POC Program Product, and Companion
Diagnostics for use with any such Mir-21 POC Program Product (collectively,
“Expired Mir-21 Program Products”), but shall otherwise continue in full force
and effect in accordance with its terms; and

(c) Sanofi shall, and it hereby does, grant to Regulus an exclusive, worldwide,
royalty-free, fully-paid, irrevocable, perpetual license, with the right to
grant sublicenses, under Sanofi’s intellectual property rights in or to the
Research Results from the Sanofi Program Activities in the POC Program Plan for
such Mir-21 POC Program and from the Sanofi Independent Activities (in each
case, including, without limitation, Sanofi Product Specific Patents and Program
Patents claiming or disclosing any such Research Results existing as of
expiration of such Option Period), solely to Research, Develop, make, have made,
use, gain Approval, Commercialize, sell, offer for sale, have sold, export and
import the applicable Expired Mir-21 Program Products in the Product Field. In
addition, Sanofi shall promptly disclose to Regulus any and all Research Results
from the Sanofi Program Activities in the POC Program Plan for such Mir-21 POC
Program, to the extent not previously disclosed to Regulus pursuant to
Section 3.8.

Notwithstanding the survival of the Mir-21 License with respect to Mir-21
Compounds, Mir-21 Products and associated Companion Diagnostics other than the
Expired Program Products as provided in the preceding paragraph, from and after
expiration of the Option Period for such Mir-21 POC Program and for as long as
Regulus (or any of its Affiliates or sublicensees) is using Commercially
Reasonable Efforts to Develop or Commercialize such Expired Program Products,
Sanofi covenants that neither it nor any of its Affiliates will, directly or
indirectly, itself or through any of its sublicensees, submit or cause to be
submitted to any Regulatory Authority any preclinical or clinical data generated
by or on behalf of Regulus (other than by Sanofi) in the performance of such
Mir-21 POC Program in support of any IND, Approval or application for Approval
of any Mir-21 Compound, Mir-21 Product or associated Companion Diagnostic;
provided, however, that Sanofi (and its Affiliates and sublicensees) shall not
be prohibited from submitting to any Regulatory Authority any safety data (but
not efficacy data) generated by or on behalf of Regulus (other than by Sanofi)
in the performance of such Mir-21 POC Program that is legally required to be
submitted to or is otherwise requested by a Regulatory Authority in connection
with any IND, Approval or application for Approval with respect to any Mir-21
Compound, Mir-21 Product or associated Companion Diagnostic that, in each case,
is not an Expired Program Product.

Section 2.2 Mir-221/222 Licenses and Option.

2.2.1 Mir-221/222 POC Program Research License. Subject to the terms and
conditions of this Agreement, Regulus hereby grants to Sanofi, a worldwide,
royalty-free,

 

3.

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co-exclusive (with Regulus) license, without the right to grant sublicenses
(other than in connection with the use of subcontractors or consultants in
accordance with Section 3.9.4), under the Regulus Know-How and Regulus Patents
solely to perform the Mir-221/222 POC Program activities for which Sanofi is
responsible as specified in the Mir-221/222 POC Program Plan during the
applicable POC Program Term. For clarity, upon termination of the Mir-221/222
POC Program pursuant to Section 3.4, the license granted by Regulus to Sanofi
under this Section 2.1.2 shall terminate and be of no further force or effect.

2.2.2 Mir-221/222 POC Program Option.

(a) Option Grant. Subject to the terms and conditions of this Agreement
(including, without limitation, Section 2.1.3, Section 3.4.3(a) or
Section 3.4.3(b), as applicable), Regulus hereby grants to Sanofi an exclusive,
non-transferable (except in connection with a permitted assignment of this
Agreement pursuant to Section 13.1) option (the “Mir-221/222 Option”),
exercisable during the Option Period in accordance with Section 2.2.2(a), to
obtain a worldwide, royalty-bearing, exclusive license, with the right to grant
sublicenses as set forth in Section 2.4 below, under the Regulus Know-How and
Regulus Patents to Research, Develop, make, have made, use, gain Approval,
Commercialize, sell, offer for sale, have sold, export and import Mir-221/222
Compounds, Mir-221/222 Products, and Companion Diagnostics for use with
Mir-221/222 Products; in each case, in the Product Field (the “Mir-221/222
License”).

(b) Option Exercise. Upon expiration of the POC Program Term for the Mir-221/222
POC Program, Regulus shall deliver to Sanofi the POC Study Report for such
Mir-21 POC Program, and an invoice for both the Option Exercise Fee and POC
Program Reimbursement Amount for such POC Program (which invoices shall be
payable in accordance with Section 6.5 and Section 6.7, respectively, only in
the event Sanofi exercises the Mir-221/222 Option in accordance with this
Section 2.2.2(b)), and Sanofi may exercise its Mir-221/222 Option by:
(i) delivering written notice of such exercise to Regulus prior to expiration of
the Option Period for the Mir-221/222 POC Program; and (ii) paying to Regulus
the applicable Option Exercise Fee and POC Program Reimbursement Amount for the
Mir-221/222 POC Program in accordance with Section 6.5 and Section 6.7,
respectively.

(c) Program License Grant Upon Option Exercise. Subject to the terms and
conditions of this Agreement (including, without limitation, Section 9.4.1 or
9.4.2, as applicable), and effective only upon exercise of the Option for the
Mir-221/222 POC Program in accordance with Section 2.2.2(a) (including timely
payment of the Option Exercise Fee and POC Program Reimbursement Amount),
Regulus hereby grants to Sanofi the Mir-221/222 License.

2.2.3 Consequences of Failure to Exercise Mir-221/222 Option. In the event that
Sanofi fails to exercise its Mir-221/222 Option in accordance with
Section 2.2.2(a) prior to expiration of the applicable Option Period, then,
effective as of expiration of such Option Period:

(a) the Mir-221/222 Option and all licenses and rights granted by Regulus to
Sanofi under this Agreement with respect to Mir-221/222 Compounds, Mir-221/222
Products and associated Companion Diagnostics shall terminate and be of no
further force or effect; and

 

4.

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(b) Sanofi shall, and it hereby does, grant to Regulus an exclusive, worldwide,
royalty-free, fully-paid, irrevocable, perpetual license, with the right to
grant sublicenses, under Sanofi’s intellectual property rights in or to the
Research Results from the Sanofi Program Activities in the Mir-221/222 POC
Program Plan (including, without limitation, Sanofi Product Specific Patents and
Program Patents claiming or disclosing any such Research Results existing as of
expiration of such Option Period), solely to Research, Develop, make, have made,
use, gain Approval, Commercialize, sell, offer for sale, have sold, export and
import Mir-221/222 Compounds, Mir-221/222 Products and associated Companion
Diagnostics; in each case, in the Product Field. In addition, Sanofi shall
promptly disclose to Regulus any and all Research Results from the Sanofi
Program Activities in the Mir-221/222 POC Program Plan, to the extent not
previously disclosed to Regulus pursuant to Section 3.8.

Section 2.3 Regulus Co-Promotion Option. Subject to the terms and conditions of
this Agreement, on a POC Program-by-POC Program basis, Sanofi hereby grants to
Regulus an exclusive, non-transferable (even in connection with a permitted
assignment of this Agreement pursuant to Section 13.1) option with respect to
each POC Program Product (each, a “Co-Promote Option”), exercisable […***…] for
such POC Program Product as set forth below, to obtain a co-exclusive (with
Sanofi), royalty-bearing right and license, without the right to sublicense,
under the Regulus Know-How, Regulus Patents, Sanofi Inventions, Sanofi Program
Patents and other necessary Patents or know-how Controlled by Sanofi, in each
case, solely to promote each POC Program Product in the U.S. in accordance with
APPENDIX 10 (such right and license, a “Co-Promote Right”). Sanofi shall deliver
written notice of its intent to file the first NDA for each POC Program Product
at least […***…] months before the date Sanofi anticipates filing such NDA.
Regulus may exercise its Co-Promote Option with respect to such POC Program
Product by delivering written notice of such exercise to Sanofi within
[…***…] months after Sanofi delivers written notice of its intent to file such
NDA. Effective upon Regulus’ exercise of its Co-Promote Option for a POC Program
Product, Sanofi hereby grants to Regulus the Co-Promote Right for such POC
Program Product, and the Parties shall negotiate in good faith and enter into a
Co-Promotion Agreement governing such co-promotion activities no later than
[…***…] months prior to Sanofi’s good faith estimate of the POC Program Product
launch date in the U.S. Such Co-Promotion Agreement shall include, without
limitation, the terms set forth in APPENDIX 10 hereto.

Section 2.4 Sublicenses. Each Program License is sublicensable only in
connection with a sublicense of a Licensed Compound, Product or Companion
Diagnostic licensed to Sanofi under such Program License to any Affiliate of
Sanofi or to any Third Party, in each case to Research, Develop, make, have
made, use, gain Approval, Commercialize, sell, offer for sale, have sold, export
and import such Licensed Compound, Product or Companion Diagnostic in the
Product Field in accordance with the terms of this Agreement; provided, however,
that Sanofi shall not have the right to sublicense a POC Program Product in the
U.S. unless and until […***…].

 

***Confidential Treatment Requested

 

5.

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Section 2.5 Exclusivity.

2.5.1 During the Term, on a Collaboration Target-by-Collaboration Target basis,
so long as any Program License or Option with respect to a Collaboration Target
is in effect, Regulus agrees that it will not […***…].

2.5.2 During the Term, on a Collaboration Target-by-Collaboration Target basis,
so long as any Program License with respect to a Collaboration Target is in
effect, Sanofi may, subject to the terms and conditions of this Agreement
(including the financial provisions set forth in Article 6), […***…], provided,
however, that, on a POC Program-by-POC Program basis, during the applicable POC
Program Term , Sanofi agrees that it will not […***…]; and (ii) with respect to
a POC Program Product that is the subject of such POC Program where the
applicable POC Program Product […***…]; in each case (both (i) and (ii) above),
only in the […***…] for which the applicable POC Program Product is being
developed and/or commercialized.

Section 2.6 License Conditions; Limitations.

2.6.1 If Sanofi fails to meet its obligations to use Commercially Reasonable
Efforts under ARTICLE 5 for a particular Licensed Compound or Product, Regulus
will have the termination rights set forth in Section 9.4.1 or 9.4.2, as
applicable.

2.6.2 Each Program License, and the exclusivity granted under Section 2.5 with
respect to the applicable Collaboration Target, are subject to and limited by
the (i) […***…], solely to the extent Regulus has, prior to the Effective Date,
provided Sanofi the provisions of such agreements in unredacted form.

2.6.3 Without limiting this Section 2.6, Regulus’ ability to conduct research
and development on […***…], and […***…]

 

***Confidential Treatment Requested

 

6.

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[…***….]. To the extent the […***…] POC Program Plan contemplates the potential
research and development of […***…], Regulus will use commercially reasonable
efforts (and will exercise its rights under the […***…]) to secure the right to
conduct research and development on […***…], and grant Sanofi a […***…] Option
under Section 2.2.1 to obtain a […***…] under Section 2.2.2(b) with respect to
[…***…], and to grant such […***…] upon exercise of such […***…], to the fullest
extent contemplated by this Agreement.

2.6.4 Pursuant to the […***…], Regulus has a non-exclusive license under certain
Patents and Know How of […***…]. Regulus has the right to request from […***…]
permission to grant a sublicense to Sanofi and its Affiliates under the […***…],
and to provide Sanofi and its Affiliates access to the […***…], in connection
with the development, manufacture and commercialization of Products that are
Development Candidates, on a Development Candidate-by-Development Candidate
basis. On a Development Candidate-by-Development Candidate basis: (a) with
respect to Development Candidates that are POC Program Products, promptly
following IND filing for such Development Candidate, Regulus shall use
commercially reasonable efforts (and will exercise its rights under the […***…])
to obtain […***…] permission (i) to grant to Sanofi and its Affiliates a
sublicense under the […***…] for such POC Program Products, and (ii) to provide
Sanofi and its Affiliates access to the […***…] pursuant to Section 4.3 for such
POC Program Products; provided, however, that, notwithstanding Regulus’ receipt
of such permission from […***…], such sublicense grant to Sanofi under the
[…***…] would not become effective, and Regulus would not be obligated to
provide such access to the […***…] to Sanofi, in each case ((i) and (ii)) unless
and until […***…]; and (b) with respect to Products that are not POC Program
Products, […***…], Regulus shall use commercially reasonable efforts (and will
exercise its rights under the […***…]) to grant to Sanofi and its Affiliates a
sublicense under the […***…], and to provide Sanofi and its Affiliates access to
the […***…].

2.6.5 Subject to Section 2.5, Regulus retains the right to grant Permitted
Licenses.

2.6.6 The […***…] granted to Sanofi under the […***…] Agreement is subject to
the terms of the […***…] Agreement (including for the avoidance of doubt the
[…***…] obligation vis-à-vis […***…] to provide reports in accordance with
[…***…]Agreement, and to keep records as set forth in Article 10 of the […***…]
Agreement, provided that Regulus agrees to directly comply with the reporting
obligations under the […***…] Agreement with respect to progress of research and
development). To the extent necessary to comply with the reporting obligations
under the […***…] Agreement, Sanofi agrees to provide Regulus with reports of
Sanofi’s progress through the JSC for so long as the

 

***Confidential Treatment Requested

 

7.

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JSC in place, and thereafter as reasonably requested by Regulus, in each case,
at intervals and with reasonable lead-times reasonably necessary for Regulus to
comply with the […***…] Agreement. Based on the information reported by Sanofi
pursuant to the preceding sentence, Regulus will prepare the necessary reports
and submit them to […***…]. However, if […***…] insists that Sanofi provide
written progress, Sanofi agrees to do so. The Parties shall cooperate in good
faith to facilitate compliance with the Existing Regulus Agreements.
Notwithstanding the foregoing, Regulus shall make a good faith effort to […***…]
that the […***…] of the […***…] the reporting obligations that Sanofi has to
Regulus under this Agreement.

ARTICLE 3

COLLABORATION

Section 3.1 Objective. During the Research Term, the Parties collaborated in
carrying out a program to discover and preclinically develop certain Licensed
Compounds (as further provided for in the R&D Plan, the “Research Program”).
Beginning as of the Second Restatement Date, Regulus will carry out, in
cooperation with Sanofi, each of the following development programs, for the
potential further clinical Development and Commercialization of Licensed
Compounds from such POC Program by Sanofi as Products.

3.1.1 a program to develop certain Mir-21 Compounds meeting the applicable
Development Candidate Criteria in one or more Indications in the Fibrosis Field
with the objective of demonstrating Proof of Concept with respect to a Mir-21
Compound Development Candidate in such Indication(s) (as further provided for in
the Mir-21 Fibrosis POC Program Plan, the “Mir-21 Fibrosis POC Program”). The
Mir-21 POC Fibrosis Program will be carried out in accordance with a written
research and development plan (the “Mir-21 Fibrosis POC Program Plan”). The
initial Mir-21 Fibrosis POC Program Plan that has been agreed to by the Parties
as of the Second Restatement Date is attached as APPENDIX 6A hereto;

3.1.2 a program to develop certain Mir-21 Compounds meeting the applicable
Development Candidate Criteria in one or more Indications in the Oncology Field
with the objective of demonstrating Proof of Concept with respect to a Mir-21
Compound Development Candidate in such Indication(s) (as further provided for in
the Mir-21 Oncology POC Program Plan, the “Mir-21 Oncology POC Program”). The
Mir-21 Oncology POC Program will be carried out in accordance with a written
research and development plan (the “Mir-21 Oncology POC Program Plan”). The
initial Mir-21 Oncology POC Program Plan that has been agreed to by the Parties
as of the Second Restatement Date is attached as APPENDIX 6B hereto; and

3.1.3 a program to develop certain Mir-221/222 Compounds meeting the applicable
Development Candidate Criteria in one or more Indications in the Oncology Field
with the objective of demonstrating Proof of Concept with respect to a
Mir-221/222 Compound Development Candidate in such Indication(s) (as further
provided for in the Mir-221/222 POC Program Plan, the “Mir-221/222 POC
Program”). The Mir-221/222 POC Program will be carried out in accordance with a
written research and development plan (the “Mir-221/222 POC

 

***Confidential Treatment Requested

 

8.

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Program Plan”). The initial Mir-221/222 POC Program Plan that has been agreed to
by the Parties as of the Second Restatement Date is attached as Appendix 6C
hereto.

Section 3.2 POC Program Plans. Each POC Program will be carried out in
accordance with a written program plan (each, a “POC Program Plan”). The initial
POC Program Plans have been agreed to by the Parties as of the Effective Date
and are attached as APPENDIX 6 hereto. The purpose of each POC Program Plan is:
(a) to detail the responsibilities and activities of Regulus with respect to
carrying out the applicable POC Program, including the Development Candidate
Criteria, POC Criteria and Target Product Profile for such POC Program; and
(b) if applicable, to detail those specific studies and/or activities under such
POC Program that are to be carried out by Sanofi (“Sanofi Program Activities”).
Regulus will be responsible for all activities under each POC Program Plan
through Achievement of Proof of Concept (except for Sanofi Program Activities,
if any), and Sanofi will be responsible for all Sanofi Program Activities (if
any) under each POC Program Plan. A POC Program Plan, including the Development
Candidate Criteria, POC Criteria, Target Product Profile and Sanofi Program
Activities for such POC Program, may be amended with the approval of the JSC,
subject to paragraph 8 of the JSC Charter. Each POC Program Plan will be updated
and amended from time to time as necessary. In addition, at such time (if ever)
as Sanofi exercises its Option with respect to a POC Program in accordance with
Section 2.2.2(a), the JSC will meet to update the applicable POC Program Plan to
implement the Manufacturing Technology transfer under Section 4.3 and to secure
supply of API to support further clinical trials after the Achievement of Proof
of Concept, the cost of which will be borne solely by Sanofi. If the Parties
cannot agree to updates or amendments to a POC Program Plan, the Parties will
first pursue the dispute resolution provisions of the JSC Charter and thereafter
follow the provisions of Section 13.4.

Section 3.3 POC Program Term. Each POC Program will be carried out during the
applicable POC Program Term, subject to the earlier termination of such POC
Program pursuant to Section 3.4.1 or Section 3.4.2.

Section 3.4 Early Termination of POC Program.

3.4.1 By Sanofi. On a POC Program-by-POC Program basis, Sanofi will have the
right to terminate a POC Program at any time upon written notice to Regulus.

3.4.2 By the Parties. On a POC Program-by-POC Program basis, the Parties may
mutually agree in writing to terminate a POC Program if they determine in good
faith, and after consultation via the JSC, that, based on the results generated
under the POC Program Plan, the further pursuit of such POC Program would be
scientifically or clinically unwarranted (e.g., due to target validation issues,
Development Candidate delivery issues, potency issues or safety issues);
provided, however, that, in the event Regulus believes, on the basis of results
generated under the POC Program Plan, that further pursuit of such POC Program
is not scientifically justifiable, but Sanofi does not agree to terminate such
POC Program, then, upon Regulus’ written request, the matter shall be submitted
to the Expert Panel as set forth in Section 13.4.5 of this Agreement for
resolution of whether or not further pursuit of such POC Program is
scientifically justifiable, and if the Expert Panel rules in favor of Regulus,
such POC Program shall be deemed terminated by such ruling.

 

9.

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3.4.3 Consequences of Early Termination of POC Program.

(a) Mir-21 POC Program. On a Mir-21 POC Program-by-Mir-21 POC Program basis, in
the event of termination of a particular Mir-21 POC Program pursuant to
Section 3.4.1 or Section 3.4.2 (such Mir-21 POC Program, the “Terminated Mir-21
POC Program”), then, effective as of termination of such Mir-21 POC Program:

(i) the Mir-21 POC Program research license granted to Regulus pursuant to
Section 2.1.2 with respect to the Terminated Mir-21 POC Program shall terminate
and be of no further force or effect;

(ii) the Mir-21 Option with respect to the Terminated Mir-21 POC Program shall
terminate and be of no further force or effect;

(iii) the Mir-21 License shall terminate solely with respect to any Mir-21 POC
Program Product that was the subject of the Terminated Mir-21 POC Program, the
Mir-21 Compound(s) contained in any such Mir-21 POC Program Product, and
Companion Diagnostics for use with any such Mir-21 POC Program Product
(collectively, “Terminated Mir-21 Program Products”), but shall otherwise
continue in full force and effect in accordance with its terms; and

(iv) Sanofi shall, and it hereby does, grant to Regulus an exclusive, worldwide,
royalty-free, fully-paid, irrevocable, perpetual license, with the right to
grant sublicenses, under Sanofi’s intellectual property rights in or to the
Research Results from the Sanofi Program Activities in the POC Program Plan for
the Terminated Mir-21 POC Program and from the Sanofi Independent Activities (in
each case, including, without limitation, Sanofi Product Specific Patents and
Program Patents claiming or disclosing any such Research Results existing as of
termination of such Mir-21 POC Program), solely to Research, Develop, make, have
made, use, gain Approval, Commercialize, sell, offer for sale, have sold, export
and import the applicable Terminated Mir-21 Program Products in the Product
Field. In addition, Sanofi shall promptly disclose to Regulus any and all
Research Results from the Sanofi Program Activities in the POC Program Plan for
such Terminated Mir-21 POC Program, to the extent not previously disclosed to
Regulus pursuant to Section 3.8.

Notwithstanding the survival of the Mir-21 License with respect to Mir-21
Compounds, Mir-21 Products and associated Companion Diagnostics other than the
Terminated Mir-21 Program Products as provided in the preceding paragraph, from
and after termination of the Terminated Mir-21 POC Program and for as long as
Regulus (or any of its Affiliates or sublicensees) is using Commercially
Reasonable Efforts to Develop or Commercialize such Terminated Mir-21 Program
Products, Sanofi covenants that neither it nor any of its Affiliates will,
directly or indirectly, itself or through any of its sublicensees, submit or
cause to be submitted to any Regulatory Authority any preclinical or clinical
data generated by or on behalf of Regulus (other than by Sanofi) in the
performance of such Terminated Mir-21 POC Program in support of any IND,
Approval or application for Approval of any Mir-21 Compound, Mir-21 Product or
associated Companion Diagnostic; provided, however, that Sanofi (and its
Affiliates and sublicensees) shall not be prohibited from submitting to any
Regulatory Authority any safety data (but not efficacy data) generated by or on
behalf of Regulus (other than by Sanofi) in the

 

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performance of such Terminated Mir-21 POC Program that is legally required to be
submitted to or is otherwise requested by a Regulatory Authority in connection
with any IND, Approval or application for Approval with respect to any Mir-21
Compound, Mir-21 Product or associated Companion Diagnostic that, in each case,
is not a Terminated Mir-21 Program Product.

(b) Mir-221/222 POC Program. In the event of termination of the Mir-221/222 POC
Program pursuant to Section 3.4.1 or Section 3.4.2, then, effective as of
termination of the Mir-221/222 POC Program:

(i) the Option with respect to the Mir-221/222 POC Program and all licenses and
rights granted by Regulus to Sanofi under this Agreement with respect to
Mir-221/222 Compounds, Mir-221/222 Products and associated Companion Diagnostics
shall terminate and be of no further force or effect; and

(ii) Sanofi shall, and it hereby does, grant to Regulus an exclusive, worldwide,
royalty-free, fully-paid, irrevocable, perpetual license, with the right to
grant sublicenses, under Sanofi’s intellectual property rights in or to the
Research Results from the Sanofi Program Activities in the POC Program Plan for
the Mir-221/222 POC Program (including, without limitation, Sanofi Product
Specific Patents and Program Patents claiming or disclosing any such Research
Results existing as of termination of such Mir-221/222 Program), solely to
Research, Develop, make, have made, use, gain Approval, Commercialize, sell,
offer for sale, have sold, export and import Mir-221/222 Compounds, Mir-221/222
Products and associated Companion Diagnostics; in each case, in the Product
Field. In addition, Sanofi shall promptly disclose to Regulus any and all
Research Results from the Sanofi Program Activities in the POC Program Plan for
the Mir-221/222 POC Program, to the extent not previously disclosed to Regulus
pursuant to Section 3.8.

3.4.4 End of POC Program Term. Upon the expiration of the POC Program Term for
such POC Program (whether as a result of termination of such POC Program or
otherwise), Regulus will not be obligated to continue to perform work under the
POC Program.

Section 3.5 Joint Steering Committee. The Parties will establish and maintain a
joint steering committee (the “JSC”) to oversee the conduct of the POC Programs,
including, but not limited to approving any changes to the POC Program Plans.
The JSC will be established, operated and governed in accordance with the
policies and procedures set forth in APPENDIX 4 attached hereto (the “JSC
Charter”). The JSC Charter may be amended with the unanimous approval of the JSC
members. As needed, the JSC will establish subcommittees and working groups that
will report to the JSC to further the objectives of the POC Programs. The JSC
and any subcommittees and working groups established by the JSC will
automatically dissolve at such time as all of the Options granted hereunder
either have been exercised, or have expired or terminated without exercise.

Section 3.6 Program Contributions.

3.6.1 Research Program. The Parties acknowledge and agree that their respective
staffing, funding and performance obligations with respect to the Research
Program have been fulfilled prior to the Second Restatement Date.

 

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3.6.2 POC Program Contributions By Regulus. During the POC Program Term for a
POC Program, Regulus will dedicate Regulus employees and/or Third Party
contractors to perform activities in support of and in accordance with the
then-current POC Program Plan. Regulus will bear all costs, including costs
related to research supplies, consumables and animals, incurred in performing
its obligations under each POC Program Plan. For clarity, during the POC Program
Term for a POC Program, Regulus will perform, and bear all costs of performing,
all IND-Enabling Studies to the extent required by the FDA to support the IND
for the Target Product Profile for such POC Program as set forth in the version
of the POC Program Plan in effect immediately prior to the start of such
IND-Enabling Studies; provided, however, that Regulus shall not be responsible
for performing, or for the costs of performing, any IND-Enabling Study that is
identified as a Sanofi Program Activity in the applicable POC Program Plan.
During the applicable POC Program Term, Regulus shall use Commercially
Reasonable Efforts to develop to Proof of Concept (i) at least one Mir-21
Compound in an Indication in the Fibrosis Field, (ii) at least one Mir-21
Compound in an Indication in the Oncology Field, and (iii) at least one
Mir-221/222 Compound in an Indication in the Oncology Field; in each case
consistent with the applicable POC Program Plan.

3.6.3 POC Program Contributions By Sanofi. During the applicable POC Program
Term, Sanofi shall use Commercially Reasonable Efforts to conduct and complete
the Sanofi Program Activities (if any) for each POC Program in accordance with
the then-current POC Program Plan. Sanofi will bear all costs, including costs
related to research supplies, consumables and animals, incurred in performing
Sanofi Program Activities under each POC Program Plan, subject to Section 4.1
and Section 6.6.

Section 3.7 Records. Each Party and its contractors will maintain complete and
accurate records of all work conducted in the performance of the Research
Program and each POC Program, and all results, data, inventions and developments
made in the performance of the Research Program and each POC Program. All such
records maintained by each Party and its contractors will be in sufficient
detail and in good scientific manner appropriate for patent and regulatory
purposes. Upon reasonable prior written notice, Regulus will provide Sanofi the
right to inspect such records, and will provide copies of all requested records,
to the extent reasonably required for the performance of Sanofi’s obligations or
the exercise of Sanofi’s rights under this Agreement. Upon reasonable prior
written notice, and solely with respect to Sanofi Program Activities and/or
Discontinued Products, Sanofi will provide Regulus the right to inspect such
records, and will provide copies of all requested records, to the extent
reasonably required for the performance of Regulus’ obligations or the exercise
of Regulus’ rights under this Agreement. In addition, Sanofi and its contractors
will maintain complete and accurate records of all work conducted by or on
behalf of Sanofi with respect to Mir-21 Compounds and Other Mir-21 Products
independently of the Mir-21 POC Programs during the applicable Option Period(s)
(“Sanofi Independent Activities”). In each case, each Party will maintain such
records and the information it receives from the other Party in confidence in
accordance with Article 7 hereof and will not use such records or information
except to the extent otherwise permitted by this Agreement.

Section 3.8 Disclosure of Results. The results of all work performed by the
Parties as part of the Research Program and each POC Program will be promptly
disclosed to the other Party in a reasonable manner as such results are
obtained. In addition, Regulus will periodically

 

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provide Sanofi with written reports of the work performed under the Research
Program and each POC Program, and the results achieved by Regulus, and Sanofi
will periodically provide Regulus with written reports of Sanofi Program
Activities performed under each POC Program, and the results achieved by Sanofi.
Regulus and Sanofi will provide reports and analyses at each JSC meeting, and
more frequently on reasonable request by the JSC, detailing the current status
of each POC Program. The results, reports, analyses and other information
regarding the Research Program and each POC Program disclosed by one Party to
the other Party pursuant hereto may be used only in accordance with the rights
granted and other terms and conditions under this Agreement. Upon reasonable
request by Sanofi, Regulus will provide Sanofi with additional data, results and
other information with respect to the work performed by Regulus in the
performance of the Research Program and each POC Program. Upon reasonable
request by Regulus, Sanofi will provide Regulus with additional data, results
and other information with respect to the work performed by Sanofi in the
performance of the Sanofi Program Activities. Any reports required, excluding
reports needed for submission to a Regulatory Agency, under this Section 3.8 may
take the form of and be recorded in minutes of the JSC that will contain copies
of any slides relating to the results and presented to the JSC. Reports needed
to support regulatory submissions and updates to a Regulatory Agency will be
provided in a timely manner and in a format as agreed upon by the JSC. During
the POC Program Term for any Mir-21 POC Program, Sanofi will provide […***…]
written summaries of the Sanofi Independent Activities performed (if any) and
the results obtained over the past […***…] with respect to Other Mir-21
Products. Sanofi will provide to Regulus such additional information regarding
such Sanofi Independent Activities and results obtained as Sanofi may determine
to be necessary or useful for the performance of the Mir-21 POC Program(s),
which information may be used by Regulus only in accordance with the rights
granted and other terms and conditions under this Agreement. Except as expressly
set forth in this Section 3.8 or as otherwise expressly provided in Section 3.11
or Section 5.2, Sanofi shall not be required to disclose to Regulus the results
of work performed by Sanofi as part of the Sanofi Independent Activities.

Section 3.9 Research Efforts; Resources, Scientific Manner. Each Party will use
Commercially Reasonable Efforts to perform each POC Program, including its
responsibilities under each POC Program Plan.

3.9.1 Throughout each POC Program Term, each Party will assign qualified and
reasonably sufficient personnel resources to the performance of such Party’s
obligations under the applicable POC Program Plan. The mixture of skills and
levels of such employees will be appropriate to the objectives of such Party’s
responsibilities under such POC Program Plan.

3.9.2 Each Party will maintain laboratories, offices, administrative support and
all other facilities at its own expense and risk necessary to carry out its
responsibilities under each POC Program Plan. Each Party agrees to make its
employees reasonably available at their respective places of employment to
consult with the other Party on issues arising during the performance of each
POC Program. Sanofi and Regulus will cooperate with each other in carrying out
each POC Program, and each Party will contribute its relevant know-how and
experience necessary to carry out each POC Program.

3.9.3 Each POC Program will be conducted by each Party in good scientific
manner, and in compliance with all applicable GCP, GLP and GMP, and applicable
legal

 

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requirements, to attempt to achieve efficiently and expeditiously the objectives
of such POC Program. Each Party will comply with all Applicable Laws, in the
performance of work under this Agreement.

3.9.4 Neither Party will perform any of its obligations under any POC Program
Plan through subcontractors or consultants, without the prior written approval
of the other Party, such approval not to be unreasonably withheld; except that
(i) Regulus may enter Permitted Licenses; and (ii) each Party may engage
consultants and subcontractors in the ordinary course that generally support
such Party’s research and development infrastructure, provided that (a) each
such consultant and subcontractor agrees in writing to assign to such Party all
Know-How and Patents conceived made or reduced to practice in performing
services for such Party, and (b) subject to Section 6.6 and Section 6.7.2, such
Party will solely bear any costs associated with such Party’s use of such
consultants and subcontractors.

Section 3.10 Materials Transfer. In order to facilitate the Programs, either
Party may provide to the other Party certain materials for use by the other
Party in furtherance of the Programs. All such materials will be used by the
receiving Party in accordance with the terms and conditions of this Agreement
solely for purposes of performing its rights and obligations under this
Agreement, and the receiving Party will not transfer such materials to any Third
Party unless expressly contemplated by this Agreement or upon the written
consent of the supplying Party.

Section 3.11 Pharmacovigilance; Safety Database. If Sanofi exercises its Option
with respect to any POC Program, then prior to IND transfer with respect to any
Product under such POC Program, designated staff from the respective Headquarter
Pharmacovigilance Department shall be requested by the Joint Steering Committee
to establish a detailed Safety Data Exchange Agreement (“SDEA”) for the Products
to be in place prior to Sanofi starting any clinical development.
Notwithstanding the foregoing, the Parties agree to the following principles:

3.11.1 If Sanofi exercises its Option with respect to a POC Program, Sanofi will
establish the global safety database for the applicable Licensed
Compounds/Products that will be used for regulatory reporting and responses to
safety queries from Regulatory Authorities. For that purpose, Regulus will
promptly transfer all safety information regarding the applicable Licensed
Compounds or Products, including, if applicable, adverse events, and drug
exposure during pregnancy data that it has regarding the Licensed Compounds or
Products to Sanofi for entry into the global safety database upon request from
Sanofi. The timelines, format and content of such transfer shall be agreed in
the SDEA.

3.11.2 Regulus maintains a database that includes information regarding the
safety and tolerability of its drug compounds, individually and as a class,
including information discovered during pre-clinical and clinical development
(the “Regulus Database”).

3.11.3 Safety Monitoring. In an effort to maximize understanding of the safety
profile and pharmacokinetics of Regulus compounds, Sanofi will cooperate with
Regulus and forward safety information to Regulus designated contact persons.
This includes transmission of serious adverse events collected from Sanofi
sponsored studies in a timely fashion as agreed in

 

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the SDEA. Vice versa Regulus shall promptly inform Sanofi on any safety issue or
class effect that may come to its attention including those from other license
partners to the extent Regulus is not precluded by written agreement with the
applicable partner from sharing such information with Sanofi. This includes also
nonclinical safety information.

3.11.4 Studies/Regulatory Documents. To the extent collected by Sanofi and in
the form in which Sanofi uses/stores such information for its own purposes,
Sanofi will provide Regulus with the results from each of the nonclinical (e.g.,
toxicology, pharmacokinetics, and safety pharmacology studies) and the clinical
studies of each Licensed Compound and Product as soon as practicable following
the date such information is available to Sanofi (but not later than
[…***…] days after Sanofi’s receipt of such information). The clinical results
will include, but will not be limited to, subject demographics and
characteristics, medical history, prior and concomitant medication usage,
adverse event reports and laboratory test results. The clinical results will be
accompanied by the clinical study protocol (original and all amendments) and an
annotated case report form (CRF) that identifies the variable names in the
transferred data associated with each of the data fields in the CRF. In
connection with any reported serious adverse event, Sanofi will provide Regulus
all serious adverse event reports (including initial, interim, follow-up,
amended, and final reports) promptly following the time these reports are
submitted to Regulatory Authorities. In addition, with respect to each Licensed
Compound and Product, Sanofi will provide Regulus with copies of annual safety
updates filed with each IND and the safety sections of any final clinical study
reports within […***…] days following the date such information is filed or is
available to Sanofi, as applicable. Furthermore, Sanofi will promptly provide
Regulus with any supporting data and answer any follow-up questions reasonably
requested by Regulus.

3.11.5 Confidentiality. All such information disclosed by Sanofi to Regulus will
be Sanofi Confidential Information; provided, however, that Regulus may disclose
any such Sanofi Confidential Information to Regulus’ other partners pursuant to
ARTICLE 7 below if such information is regarding class generic properties of
microRNA Compounds, and/or any Third Party, in each case, so long as Regulus
does not disclose the identity of the Product, or Sanofi.

3.11.6 Contacts. Sanofi will deliver all such information to Regulus for the
Regulus Database to 3545 John Hopkins Court, Suite 210, San Diego, California
92121-1121, Attention: Chief Medical Officer (or to such other address/contact
designated in writing by Regulus).

ARTICLE 4

MANUFACTURING

Section 4.1 Supply of microRNA Compound for Programs. Regulus agrees to
manufacture and supply all microRNA Compounds for use in support of each POC
Program until the exercise by Sanofi of its Option with respect to such POC
Program in accordance with Section 2.1.3 or Section 2.2.2(b), as applicable.
Regulus will bear its own costs for the manufacture of all microRNA Compound
needed for POC Program Plan activities for each POC Program until such Option
exercise, including the costs of manufacture of all microRNA

 

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Compound needed for Sanofi Program Activities. For clarity, Regulus will not be
required to manufacture and supply API or drug product for any human clinical
trial of any Licensed Compound or Product conducted by Sanofi.

4.1.1 Contract Manufacture. If Regulus intends to contract one or more Third
Parties to conduct any manufacturing activities with respect to any Licensed
Compound or Product in support of a POC Program, and prior to entering into a
definitive agreement with a Third Party with respect to the conduct of such
manufacturing activities, in each case, Regulus shall so notify Sanofi no later
than the time Regulus submits a request for quotation or proposal to any such
Third Party(ies) for those manufacturing activities, shall provide Sanofi with
the same information that Regulus provides to any such Third Party(ies) for the
purpose of such Third Party’s(ies’) preparation of such quotation or proposal,
and shall inform Sanofi of the date by which Regulus expects to select a
contract manufacturer to perform such manufacturing activities (collectively,
the “Request for Proposal”). If Sanofi is interested in performing, or having
one of its Affiliates perform, such manufacturing activities, Sanofi may, in its
sole discretion, submit a quotation or proposal to Regulus. Regulus shall
consider in good faith such quotation or proposal from Sanofi, but Regulus shall
be free to select the quotation or proposal (whether of Sanofi or of any Third
Party) that Regulus, in its sole discretion, deems to be in Regulus’ best
interests, provided, however, that Regulus shall not select any Third Party
quotation or proposal that (taken as a whole) is less favorable to Regulus than
the last quotation or proposal received from Sanofi and Regulus shall give
Sanofi the opportunity to match any Third Party quotation or proposal that
(taken as a whole) is more favorable to Regulus than the last quotation or
proposal received from Sanofi. If Regulus accepts a quotation or proposal
provided by Sanofi, the Parties shall negotiate and enter into a separate
agreement governing the performance such manufacturing activities. If Sanofi
does not submit a quotation or proposal to Regulus within […***…] days after the
Request for Proposal, or notify Regulus that it wishes to match a more favorable
Third Party quotation or proposal within […***…] days after Regulus communicates
such Third Party proposal to Sanofi, then Regulus shall be free to enter into a
definitive agreement with a Third Party with respect to the conduct of such
manufacturing activities. For clarity, this Section 4.1.1 shall not apply to any
manufacturing activities with respect to which Regulus has contracted with any
Third Party as of the Second Restatement Date, and in the case of any
manufacturing activities with respect to which Regulus is in discussions with
any Third Party as of the Second Restatement Date, Regulus shall not be
obligated to wait more than […***…] days after the Request for Proposal to
receive a quotation or proposal from Sanofi, or to consider accepting a
quotation or proposal provided by Sanofi, for such manufacturing activities if
doing so would delay Regulus’ timeline for initiation of such manufacturing
activities.

Section 4.2 Clinical and Commercial Manufacturing and Supply of Licensed
Compound and Product.

4.2.1 Product Manufacturing Responsibility. Except as otherwise provided in
Section 4.1 or elsewhere in this Agreement, the Parties acknowledge and agree
that Sanofi will be solely responsible for the manufacturing of Licensed
Compound and Product for all clinical trials and commercial supply, including
management of the overall manufacturing strategy and tactics, formulation,
internal or contract manufacturer selection for API and finished

 

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Product, associated audits, stability testing, pricing, relationship with
contract manufacturer(s) and any work proposals or contract negotiations or
contracts themselves.

4.2.2 Supply of Finished Drug Product. Except as otherwise specified in the R&D
Plan or a POC Program Plan, the Parties acknowledge and agree that Sanofi will
be solely responsible for the manufacturing, stability testing and supply of
finished drug Product.

Section 4.3 Transfer of Manufacturing Technology and Assistance. On a
Product-by-Product basis (a) with respect to POC Program Products, if Sanofi
exercises its Option with respect to a particular POC Program pursuant to
Section 2.1.3 or Section 2.2.2(b) (as applicable); and (b) with respect to
Products that are not POC Program Products, upon Sanofi’s written notice to
Regulus that such Product meets Sanofi’s internal criteria as a development
candidate, in each case ((a) or (b)), promptly after such Option exercise or
notice that a Product meets Sanofi’s internal criteria as a development
candidate, as applicable, Regulus shall disclose (and provide copies, as
applicable) to either Sanofi or a Third Party manufacturer designated by Sanofi
all Manufacturing Technology that is required for the manufacture (including the
development of the manufacturing process) of Products (including the Licensed
Compound(s) contained therein) and is reasonably necessary or useful to enable
Sanofi or such Third Party manufacturer (as appropriate) to manufacture such
Licensed Compounds and Products. The steps, planning and obligations of the
Parties regarding the transfer of the Manufacturing Technology for each Product
(including the Licensed Compound(s) contained therein) will be set forth in a
“Technology Transfer Master Plan API” to be executed between the Parties
promptly after Sanofi’s exercise of the Option for such POC Program or notice
that a Product meets Sanofi’s internal criteria as a development candidate, as
applicable. Upon request, Regulus will at all times use diligent efforts to
provide Sanofi with any additional information or on-site support as may be
required by Sanofi and its Affiliates in connection with the transfer of the
Manufacturing Technology for such Product. Sanofi shall reimburse Regulus for
any on-site support rendered at the FTE-Day Rate per FTE-day, provided further
Regulus shall in no event be obliged to provide more than […***…] in total,
unless the Parties otherwise agree in writing. For purposes of this Agreement
“Manufacturing Technology” shall mean, with respect to a particular Product, the
Know-How Controlled by Regulus that is reasonably available and reasonably
necessary for the Manufacture (including formulation, processing, filling and
packaging) of such Product (including the Licensed Compound(s) contained
therein). Sanofi and its Third Party manufacturer may use the Manufacturing
Technology only in support of the applicable Program License(s) and only for so
long as such Program License(s) are in effect, and will not use the
Manufacturing Technology in connection with any other compound or product.
Sanofi will be responsible and liable to Regulus for any practice of the
Manufacturing Technology by Sanofi’s Third Party manufacturer that breaches this
Section 4.3.

ARTICLE 5

DEVELOPMENT & COMMERCIALIZATION

Section 5.1 Development, Commercialization and Regulatory Responsibilities.
Except as otherwise specified in a POC Program Plan or a Co-Promotion Agreement,
(a) in the case of a Mir-21 POC Program Product, during such time from and after
exercise of the Option for the applicable Mir-21 POC Program as Program License
for such Mir-21 POC Program

 

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Product is in effect, and (b) in the case of any other Product for a particular
Collaboration Target, during such time as a Program License with respect to such
Collaboration Target is in effect pursuant to Section 2.1 or Section 2.2, Sanofi
will have sole responsibility, including without limitation sole responsibility
for all funding, resourcing and decision-making, for all Development and
Commercialization with respect to the Licensed Compounds and Products licensed
to Sanofi under such Program License, and Sanofi hereby assumes all regulatory
responsibilities in connection with Licensed Compounds and Products licensed to
Sanofi under such Program License, including sole responsibility for all
Regulatory Documentation and for obtaining all Approvals. Sanofi will comply
with all Applicable Laws in connection with the Development and
Commercialization of Licensed Compounds and Products. Sanofi (by itself or
through its Affiliates, sublicensees, (sub)contractors or agents, as applicable)
will use Commercially Reasonable Efforts to achieve Initiation of a Phase 2
Trial or Phase 3 Trial as soon as practicable following Sanofi’s exercise of its
Option (or at least one of its Options) for a given Collaboration Target, and
will use Commercially Reasonable Efforts to Develop and Commercialize at least
one Licensed Compound or Product for each such Collaboration Target; provided,
however, that if the Mir-21 License terminates with respect to Mir-21 POC
Program Products from both Mir-21 POC Programs, then Sanofi (by itself or
through its Affiliates, sublicensees, (sub)contractors or agents, as applicable)
will use Commercially Reasonable Efforts to identify an Other Mir-21 Product as
a candidate for Development as soon as practicable thereafter, and will use
Commercially Reasonable Efforts to Develop and Commercialize at least one Mir-21
Compound (other than a Mir-21 Compound that was the subject of a Mir-21 POC
Program) or Other Mir-21 Product. Regulus will make all IND filings for POC
Program Products in accordance with the POC Program Plans in Regulus’ name. Once
Sanofi pays Regulus the applicable Option Exercise Fee and POC Program
Reimbursement Amount under Section 6.5 and Section 6.7.2, respectively, for a
POC Program, Regulus will and hereby does assign to Sanofi, and Sanofi will own,
all INDs, NDAs, MAAs and other regulatory filings and Approvals for POC Program
Products that are the subject of such POC Program, subject to Regulus reversion
rights under ARTICLE 10. Sanofi will be solely responsible for making all IND
filings for Other Mir-21 Products licensed to Sanofi under the Mir-21 License
and will own all INDs, NDAs, MAAs and other regulatory filings and Approvals for
Other Mir-21 Products, subject to Regulus reversion rights under ARTICLE 10.

Section 5.2 Reports by Sanofi after Option Exercise. After Sanofi’s exercise of
its Option (or at least one of its Options) for a given POC Program with respect
to POC Program Products, and for as long as Sanofi is conducting Sanofi
Independent Activities with respect to Other Mir-21 Products, Sanofi will
provide a reasonably detailed […***…] report to Regulus summarizing Sanofi’s
activities over the past […***…] with respect to such Licensed Compounds and
Products and an appropriate number of representatives from each Party will meet
at least once every year to review Development activities. Sanofi will provide
to Regulus such additional information regarding such activities as Regulus may
reasonably request to allow Regulus to ascertain whether Sanofi is in compliance
with its obligations to use Commercially Reasonable Efforts under Section 5.1,
and will consider Regulus’ input regarding such activities.

Section 5.3 Product Development Plans; Integrated Product Plans. For each
Product that Sanofi is clinically developing under this Agreement, Sanofi will
prepare a development plan outlining key aspects of the clinical development of
such Product through Approval. Each development plan will contain information
customarily contained in Sanofi’s

 

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development plans for its similar products at similar stages of development
(each a “Product Development Plan”). In addition, prior to the launch of a
Product, Sanofi will prepare a global integrated Product plan outlining the key
aspects of market launch and commercialization (the “Integrated Product Plan” or
“IPP”). Sanofi will prepare each IPP at the same time and containing information
and target markets as customarily contained in Sanofi’s Commercialization plans
for its similar products at similar stages of development. Each Product
Development Plan and IPP will be updated annually by Sanofi. Sanofi will provide
to Regulus a copy of the final draft of the Product Development Plans and IPPs
(original and updates) for each of the U.S., each Major European Country and
Japan, if available. Such copies of Product Development Plans and IPPs provided
to Regulus may be redacted to the extent necessary to preserve the
confidentiality of Sanofi confidential information related to products that are
not Products. Sanofi and Regulus will meet on a yearly basis to discuss the
draft of each Product Development Plan and IPP and Sanofi will consider, in its
sole discretion, any proposals and comments made by Regulus for incorporation in
the final Product Development Plan or IPP (as the case may be).

Section 5.4 Class Generic Claims. To the extent Sanofi intends to make any
claims in a Product label that are class generic to microRNA Compounds, Sanofi
will provide such claims to Regulus in advance and will consider any proposals
and comments made by Regulus.

ARTICLE 6

FINANCIAL PROVISIONS

Section 6.1 Up-Front Payment. The Parties acknowledge that, in consideration for
the licenses and other rights granted under this Agreement, Sanofi paid to
Regulus, prior to the First Restatement Date, an irrevocable, non-creditable and
nonrefundable technology access fee equal to $25,000,000 ($[…***…] of which
Regulus allocated to the access to Mir-21 in the detailed amounts set forth on
APPENDIX 9, and $[…***…] of which Regulus allocated to the rest of the Research
Program in the detailed amounts set forth on APPENDIX 9). The Parties hereby
agree that, as of the First Restatement Date, neither Party shall owe any
obligation to the other Party under this Section 6.1.

Section 6.2 Research Program Funding. The Parties acknowledge that all Research
Program funding payments due Regulus under the Original Agreement and the First
Restated Agreement were made prior to the Second Restatement Date, and the
Parties hereby agree that, as of the Second Restatement Date, neither Party
shall owe any obligation to the other Party under this Section 6.2.

Section 6.3 No Target Designation Milestone. The Parties acknowledge that, prior
to the Second Restatement Date, no microRNA other than Mir-21 was designated as
a Collaboration Target, and the Parties hereby agree that, as of the Second
Restatement Date, neither Party shall owe any obligation to the other Party
under this Section 6.3.

Section 6.4 Stock Purchase. In partial consideration for the Options and the
performance by Regulus of the POC Program, on the Second Restatement Date,
Sanofi shall

 

***Confidential Treatment Requested

 

19.

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purchase from Regulus, and Regulus shall issue and sell to Sanofi, $10 million
of shares of Regulus’ common stock on the terms and conditions set forth in the
Stock Purchase Agreement.

Section 6.5 Option Exercise Fee. On a POC Program-by-POC Program basis, if
Sanofi exercises its Option with respect to a POC Program, then Sanofi shall pay
Regulus an irrevocable, non-creditable, and non-refundable Option exercise
payment in the applicable amount for such POC Program set forth below (the
“Option Exercise Fee”), subject to Section 6.6 (to the extent applicable), which
Option Exercise Fee must be paid to Regulus prior to expiration of the
applicable Option Period:

 

POC Program

   Option Exercise Fee  

First Mir-21 POC Program with respect to which Sanofi exercises its Option
(“First Mir-21 POC Program”)

   $ […***… ] 

Second Mir-21 POC Program with respect to which Sanofi exercises its Option
(“Second Mir-21 POC Program”)

   $ […***… ] 

Mir-221/222 POC Program

   $ […***… ] 

Section 6.6 Option Exercise Fee Credits.

(a) Option Letter Credit. Regulus hereby grants to Sanofi a one-time credit in
the amount of $1.25 million which may be applied solely to the first Option
Exercise Fee payable hereunder, and which is in full satisfaction of Regulus’
obligations to Sanofi with respect to the creditable portion of the
non-refundable fee of $2.5 million paid by Sanofi to Regulus pursuant to the
Option Letter; and

(b) Sanofi Program Cost Credit. On a POC Program-by-POC Program basis, Regulus
hereby grants to Sanofi a one-time credit in an amount equal to the reasonable
and documented internal and external costs and expenses actually incurred by
Sanofi in performing Sanofi Program Activities completed by Sanofi for a POC
Program (“Sanofi Program Costs”), which credit may be applied solely to the
Option Exercise Fee for such POC Program; provided, however, that the aggregate
amount of Sanofi Program Costs that may be credited under this Section 6.6(b)
against the aggregate Option Exercise Fees for all POC Programs is $[…***…].

(i) Ongoing Sanofi Program Cost Reporting. On a POC Program-by-POC Program
basis, within […***…] days after the end of each Calendar Quarter during which
any Sanofi Program Activities for a POC Program are performed by Sanofi, Sanofi
shall provide to Regulus an itemised statement reflecting all Sanofi Program
Costs incurred by Sanofi or for its account during such Calendar Quarter.

(ii) Sanofi Program Credit Amount. On a POC Program-by-POC Program basis, if
Sanofi elects to exercise its Option with respect to a POC Program, Sanofi’s
notice of exercise of such Option shall be accompanied by a final report of the
total Sanofi Program Costs incurred by Sanofi for such POC Program that Sanofi
is entitled to credit against the Option Exercise Fee for such POC Program
pursuant to, and subject to the limitation set forth in, the first paragraph of
this Section 6.6(b) (the “Sanofi Program Credit Amount”).

 

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20.

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(iii) Audit.

(1) Records. On a POC Program-by-POC Program basis until one year after Sanofi’s
exercise of its Option with respect to a POC Program (or, if Sanofi does not
exercise its Option with respect to a POC Program, until expiration of the
applicable Option Period), Sanofi shall keep complete and accurate records
pertaining to Sanofi Program Costs for such POC Program in sufficient detail to
permit Regulus (A) prior to exercise of such Option, to confirm the accuracy of
Sanofi’s reports delivered pursuant to Section 6.6(b)(i), and (B) after exercise
of such Option, to confirm the accuracy of the Sanofi Program Credit Amount
taken by Sanofi against the Option Exercise Fee for such POC Program pursuant to
the first paragraph of this Section 6.6(b).

(2) Sanofi Program Cost Reports. On a POC Program-by-POC Program basis, upon the
written request of Regulus and not more than once in each Calendar Year during
the applicable POC Program Term for a POC Program (but prior to Sanofi’s
delivery of notice of exercise of its Option for such POC Program), Sanofi will
permit an independent certified public accounting firm of nationally recognized
standing selected by Regulus and reasonably acceptable to Sanofi, at Regulus’
expense, to have access during normal business hours to such records of Sanofi
as may be reasonably necessary to verify the accuracy of Sanofi’s reports
delivered pursuant to Section 6.6(b)(i). Regulus will provide Sanofi with a copy
of the accounting firm’s written report within 30 days of completion of such
report. These audit rights will terminate upon Sanofi’s delivery of notice of
exercise of its Option for such POC Program, whereupon Regulus shall have the
audit rights set forth in Section 6.6(b)(iii)(3).

(3) Sanofi Program Credit Amount. On a POC Program-by-POC Program basis, upon
the written request of Regulus not more than once after Sanofi’s delivery of
notice of exercise of its Option for such POC Program, Sanofi will permit an
independent certified public accounting firm of nationally recognized standing
selected by Regulus and reasonably acceptable to Sanofi, at Regulus’ expense, to
have access during normal business hours to such records of Sanofi as may be
reasonably necessary to verify the accuracy of the Sanofi Program Credit Amount
taken by Sanofi against the Option Exercise Fee for such POC Program. These
audit rights will terminate on the first anniversary of Sanofi’s delivery of
notice of exercise of its Option for such POC Program. Regulus will provide
Sanofi with a copy of the accounting firm’s written report within […***…] days
of completion of such report. If such accounting firm concludes that the amount
credited by Sanofi against such Option Exercise Fee was higher or lower than the
actual Sanofi Program Costs that Sanofi was entitled to credit against such
Option Exercise Fee in accordance with the first paragraph of this
Section 6.6(b), then the owing Party will pay the amount due within 30 days of
the date Regulus delivers to Sanofi such accounting firm’s written report so
concluding. Regulus will bear the full cost of such audit unless such audit
discloses that the amount credited by Sanofi against such Option Exercise Fee
was equal to or greater than […***…]% of the actual Sanofi Program Costs that
Sanofi was entitled to credit against such Option Exercise Fee in accordance
with the first paragraph of this Section 6.6(b), in which case Sanofi will pay
the reasonable fees and expenses charged by the accounting firm.

(4) Confidentiality. All financial information subject to review under this
Section 6.6(b) will be the Confidential Information of Sanofi hereunder and

 

***Confidential Treatment Requested

 

21.

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will be treated in accordance with the confidentiality provisions of this
Agreement. As a condition precedent to Regulus’ audit rights under this
Section 6.6(b)(iii), Regulus’ accounting firm will enter into a confidentiality
agreement with Sanofi obligating it to treat all such financial information in
confidence pursuant to such confidentiality agreement.

Section 6.7 POC Program Costs.

6.7.1 Ongoing POC Program Cost Reporting. On a POC Program Plan-by-POC Program
Plan basis, within […***…] days after the end of each Calendar Quarter during
which any POC Program activities are performed, Regulus shall provide to Sanofi
an itemised statement reflecting all POC Program Costs incurred by Regulus or
for its account during such Calendar Quarter.

6.7.2 POC Program Cost Reimbursement. On a POC Program-by-POC Program basis,
within […***…] days after Achievement of Proof of Concept for a POC Program (or,
if earlier, within […***…] days after Sanofi’s written request in the event that
Sanofi wishes to exercise its Option for such POC Program at any time prior to
Achievement of Proof of Concept), Regulus shall deliver to Sanofi a written
invoice for an amount equal to […***…]% of Regulus’ POC Program Costs for such
POC Program (the “POC Program Reimbursement Amount”). If Sanofi does exercise
its Option with respect to such POC Program, Sanofi shall pay Regulus the
applicable POC Program Reimbursement Amount, which POC Program Reimbursement
Amount must be paid to Regulus prior to expiration of the applicable Option
Period.

6.7.3 Audit.

(a) Records. On a POC Program-by-POC Program basis until one year after Sanofi’s
exercise of its Option with respect to a POC Program (or, if Sanofi does not
exercise its Option with respect to a POC Program, until one year after
expiration of the applicable Option Period), Regulus shall keep complete and
accurate records pertaining to POC Program Costs for such POC Program in
sufficient detail to permit Sanofi (i) prior to exercise of such Option, to
confirm the accuracy of Regulus’ reports delivered pursuant to Section 6.7.1,
and (ii) after exercise of such Option, to confirm the accuracy of the POC
Program Reimbursement Amount invoiced by Regulus pursuant to Section 6.7.2.

(b) POC Program Cost Reports. On a POC Program-by-POC Program basis, upon the
written request of Sanofi and not more than once in each Calendar Year during
the applicable POC Program Term for a POC Program (but prior to Sanofi’s
delivery of notice of exercise of its Option for such POC Program), Regulus will
permit an independent certified public accounting firm of nationally recognized
standing selected by Sanofi and reasonably acceptable to Regulus, at Sanofi’s
expense, to have access during normal business hours to such records of Regulus
as may be reasonably necessary to verify the accuracy of Regulus’ reports
delivered pursuant to Section 6.7.1. Sanofi will provide Regulus with a copy of
the accounting firm’s written report within […***…] days of completion of such
report. These audit rights will terminate upon Sanofi’s delivery of notice of
exercise of its Option for such POC Program, whereupon Sanofi shall have the
audit rights set forth in Section 6.7.3(c).

 

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(c) POC Program Reimbursement Amount. On a POC Program-by-POC Program basis,
upon the written request of Sanofi not more than once after Sanofi’s delivery of
notice of exercise of its Option for such POC Program, Regulus will permit an
independent certified public accounting firm of nationally recognized standing
selected by Sanofi and reasonably acceptable to Regulus, at Sanofi’s expense, to
have access during normal business hours to such records of Regulus as may be
reasonably necessary to verify the accuracy of the POC Program Reimbursement
Amount invoiced by Regulus pursuant to Section 6.7.2. These audit rights will
terminate on the first anniversary of Sanofi’s delivery of notice of exercise of
its Option for such POC Program. Sanofi will provide Regulus with a copy of the
accounting firm’s written report within 30 days of completion of such report. If
such accounting firm concludes that the POC Program Reimbursement Amount
invoiced by Regulus was higher or lower than […***…]% of Regulus’ POC Program
Costs for such POC Program, then the owing Party will pay the amount due within
[…***…] days of the date Sanofi delivers to Regulus such accounting firm’s
written report so concluding. Sanofi will bear the full cost of such audit
unless such audit discloses that the POC Program Reimbursement Amount invoiced
by Regulus was equal to or greater than […***…]% of Regulus’ POC Program Costs
for such POC Program, in which case Regulus will pay the reasonable fees and
expenses charged by the accounting firm.

(d) Confidentiality. All financial information subject to review under this
Section 6.7.3 will be the Confidential Information of Regulus hereunder and will
be treated in accordance with the confidentiality provisions of this Agreement.
As a condition precedent to Sanofi’s audit rights under this Section 6.7.3,
Sanofi’s accounting firm will enter into a confidentiality agreement with
Regulus obligating it to treat all such financial information in confidence
pursuant to such confidentiality agreement.

Section 6.8 Milestone Payments by Sanofi.

6.8.1 Mir-21.

(a) Mir-21 POC Program Products. Sanofi will give Regulus written notice of the
first achievement (by Sanofi, its sublicensees or their respective Affiliates)
of each of the milestone events set forth below for the first Mir-21 POC Program
Product to achieve such milestone event within […***…] after such achievement.
After receiving such written notice of the achievement of any such milestone
event, Regulus shall submit an invoice to Sanofi for the amount of the milestone
payment corresponding to the applicable milestone event set forth below, and
Sanofi will pay Regulus such milestone payment amount within […***…] days after
receipt of such invoice. Subject to Section 6.8.2, each of the milestone
payments set forth below in this Section 6.8.1 shall be payable only one time,
and only for the first Mir-21 POC Program Product to achieve the applicable
milestone event (whether or not such Mir-21 POC Program Product is the same
Mir-21 POC Program Product that achieved any preceding milestone event, except
in the case of the second Approval milestone event below, which may only be
achieved by a Mir-21 POC Program Product other than the Mir-21 POC Program
Product that achieved the First Mir-21 POC Program Product Approval. Any Mir-21
POC Program Product that contains more than one Mir-21 Compound will be counted
as a single Mir-21 POC Program Product. If the first POC Program Product to
achieve NDA Filing or Approval contains both a Mir-21 Compound and a Mir-221/222
Compound, such POC Program Product shall be considered a Mir-21 POC Program
Product for purposes of this Section 6.8.1

 

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(and not a Mir-221/222 Product for purposes of Section 6.8.2), and only the
milestone payment corresponding to such milestone event under this Section 6.8.1
shall be payable with respect to achievement of such milestone by such POC
Program Product.

 

Milestone Event

   Milestone Payment  

1. […***…]

   $ […***… ] 

2. […***…]

   $ […***… ] 

3. […***…]

   $ […***… ] 

4. […***…]

   $ […***… ] 

In addition, after the first achievement of milestone event 4 in the table
above, if a Mir-21 POC Program Product (whether the same or a different Mir-21
POC Program Product that first achieved milestone 2, 3 and/or 4 in the table
above) subsequently achieves milestone event 2 and/or 3 for any Indication(s)
other than the Indication(s) for which a Mir-21 POC Program Product previously
achieved milestone event 2, 3 and/or 4 (each, an “Additional Mir-21 POC Program
Product Indication”), then Sanofi will promptly notify Regulus and will pay
Regulus an additional milestone payment in an amount equal to […***…]% of the
applicable milestone payment(s) set forth in the table above for the achievement
of milestone event 2 and/or 3 in the table above by such Mir-21 POC Program
Product for each Additional Mir-21 POC Program Product Indication. For clarity,
the milestone payment corresponding to milestone event 4 in the table above
shall be payable one time only.

(b) Other Mir-21 Products. Sanofi will give Regulus written notice of the first
achievement (by Sanofi, its sublicensees or their respective Affiliates) of each
of the milestone events set forth below for the first Mir-21 Product that is not
a Mir-21 POC Program Product (an “Other Mir-21 Product”) to achieve such
milestone event within […***…] after such achievement. After receiving such
written notice of the achievement of any such milestone event, Regulus shall
submit an invoice to Sanofi for the amount of the milestone payment
corresponding to the applicable milestone event set forth below, and Sanofi will
pay Regulus such milestone payment amount within […***…] days after receipt of
such invoice. Except as expressly set forth in the last paragraph of this
Section 6.8.1(b) with respect to milestone events 5 and 6, each of the milestone
payments set forth below in this Section 6.8.1(b) shall be payable only one
time, and only for the first Other Mir-21 Product to achieve the applicable
milestone event (whether or not such Other Mir-21 Product is the same Other
Mir-21 Product that achieved any preceding milestone event).

 

***Confidential Treatment Requested

 

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Milestone Event

   Milestone Payment  

1. […***…]

   $ […***… ] 

2. […***…]

   $ […***… ] 

3. […***…]

   $ […***… ] 

4. […***…]

   $ […***… ] 

5. […***…]

   $ […***… ] 

6. […***…]

   $ […***… ] 

In addition, after the first achievement of milestone event 5 and/or 6 in the
table above by the first Other Mir-21 Product for any Indication, if an Other
Mir-21 Product (whether the same or a different Other Mir-21 Product)
subsequently achieves such milestone event(s) for any additional Indication(s)
(each, an “Additional Other Mir-21 Indication”), then Sanofi will promptly
notify Regulus and will pay Regulus an additional milestone payment in an amount
equal to […***…]% of the applicable milestone payment(s) set forth in the table
above for the achievement of milestone event 5 and/or 6 in the table above by
such Other Mir-21 Product for each Additional Other Mir-21 Indication.

6.8.2 Mir-221/222. Sanofi will give Regulus written notice of the first
achievement (by Sanofi, its sublicensees or their respective Affiliates) of each
of the milestone events set forth below for the first Mir-221/222 Product to
achieve such milestone event within […***…] after such achievement. After
receiving such written notice of the achievement of any such milestone event,
Regulus shall submit an invoice to Sanofi for the amount of the milestone
payment corresponding to the applicable milestone event set forth below, and
Sanofi will pay Regulus such milestone payment amount within […***…] days after
receipt of such invoice. Each of the milestone payments set forth below in this
Section 6.8.1(b) shall be payable only one time, and only for the first
Mir-221/222 Product to achieve the applicable milestone event (whether or not
such Mir-221/222 Product is the same Mir-221/222 Product that achieved the
preceding milestone event). Any Mir-221/222 Product that contains more than one
Mir-221/222 Compound will be counted as a single Mir-221/222 Product.

 

Milestone Event

   Milestone Payment  

[…***…]

   $ […***… ] 

[…***…]

   $ […***… ] 

 

***Confidential Treatment Requested

 

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6.8.3 Sales Milestones. Each of the milestone payments set forth below will be
payable by Sanofi to Regulus for the first achievement of the specified
milestone events by Sanofi, its sublicensees or their Affiliates for (i) the
first Mir-21 Product to achieve the specified milestone event; and (ii) the
first Mir-221/222 Product to achieve the specified milestone event. If the first
POC Program Product to achieve an annual Net Sales milestone event set forth
below contains both a Mir-21 Compound and a Mir-221/222 Compound, the milestone
payment corresponding to such milestone event below shall be payable only one
time with respect to achievement of such milestone by such POC Program Product,
and such milestone payment would only be paid a second time if the corresponding
milestone event is subsequently achieved by a different POC Program Product
(whether such POC Program Product is a Mir-21 POC Program Product, a Mir-221/222
Product, or a combination thereof).

 

Milestone Event

   Milestone Payment  

1. Annual Net Sales […***…]

   $ […***… ] 

2. Annual Net Sales […***…]

   $ […***… ] 

Section 6.9 Royalty Payments by Sanofi.

6.9.1 U.S. Net Sales. Subject to the other provisions of this Agreement, during
the Royalty Term, Sanofi will pay to Regulus royalties on Net Sales of each POC
Program Product in the U.S., including its territories and possessions
(“U.S. Net Sales”) at the rate of […***…]%. On a POC Program Product-by- POC
Program Product basis, in the case of any POC Program Product with respect to
which Regulus exercises its Co-Promote Option, Regulus may, in its sole
discretion, elect to receive […***…]% of U.S. Profits (as defined in
APPENDIX 11) for such POC Program Product in lieu of royalties under this
Section 6.9.1; provided, however, that, unless Regulus’ notice of exercise of
such Co-Promote Option expressly states that Regulus elects to receive […***…]%
of U.S. Profits in lieu of royalties under this Section 6.9.1, Sanofi will pay
royalties to Regulus on U.S. Net Sales of such POC Program Product in accordance
with this Section 6.9.1, and APPENDIX 11 shall not apply to such POC Program
Product.

6.9.2 Ex-U.S. Net Sales. Subject to the other provisions of this Agreement,
during the Royalty Term, Sanofi will pay to Regulus royalties on worldwide Net
Sales of each POC Program Product other than U.S. Net Sales of such Product
(“Ex-U.S. Net Sales”) at the applicable rate(s) set forth below based on the
level of Ex-U.S. Net Sales of such POC Program Product in a given Calendar Year
period by Sanofi, its Affiliates and sublicensees, with the royalty rate tiered
based upon the level of such Ex-U.S. Net Sales in such Calendar Year period of
such Product as set forth in the table below.

 

Annual Ex.-U.S. Net Sales

   Royalty Rate  

For the portion of Ex-U.S. Net Sales that is […***…]

     […***… ]% 

For the portion of Ex-U.S. Net Sales that is […***…]

     […***… ]% 

For example, in the instance of a full Calendar Year, if annual Ex-U.S. Net
Sales of a POC Program Product in such Calendar Year worldwide are $[…***…], the
royalty due will be

 

***Confidential Treatment Requested

 

26.

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$[…***…] ([…***…]% of the first $[…***…] in the first increment, plus […***…]%
of the next $[…***…] in the second increment).

6.9.3 Other Mir-21 Products. Subject to the other provisions of this Agreement,
during the Royalty Term, Sanofi will pay to Regulus royalties on Net Sales of
each Other Mir-21 Product at the applicable rate(s) set forth in the table
below. The royalty rate payable with respect to each particular Other Mir-21
Product will be based on the level of annual worldwide Net Sales of such Other
Mir-21 Product in a given Calendar Year period by Sanofi, its Affiliates and
sublicensees, with the royalty rate tiered based upon the level of such
worldwide Net Sales in such Calendar Year period of such Other Mir-21 Product as
set forth in the table below.

 

Annual Worldwide Net Sales

   Royalty Rate  

For the portion that is […***…]

     […***… ]% 

For the portion that is […***…]

     […***… ]% 

For the portion that is […***…]

     […***… ]% 

For example, in the instance of a full Calendar Year, if annual worldwide Net
Sales of an Other Mir-21 Product in such Calendar Year worldwide are $[…***…],
the royalty due will be $[…***…] in the first increment, plus […***…]% of the
next $[…***…] in the second increment).

Section 6.10 Existing Third Party Payment Obligations.

6.10.1 Existing Regulus Agreements. Sanofi acknowledges that certain of the
Regulus Technology Controlled by Regulus as of the Effective Date were
in-licensed, or otherwise acquired by Regulus, from Third Parties under the
Existing Regulus Agreements, and that Regulus is obligated to pay In-License
Royalties and/or In-License Milestones to the Licensor(s) under such Existing
Regulus Agreements as a result of the Development or Commercialization of
Products by Sanofi or any of its Affiliates or sublicensees to the extent that
such Products are covered by the applicable Third Party Patents. The Parties
acknowledge and agree that Regulus will be responsible for paying […***…]% of
the In-License Royalties, In-License Milestones and Other In-License Payments
that become due to the Licensor(s) under the Existing Regulus Agreements.

6.10.2 Existing Sanofi Agreements. The Parties acknowledge and agree that, if
and to the extent that there are any Existing Sanofi Agreements, Sanofi will be
responsible for paying […***…]% of the In-License Royalties, In-License
Milestones and Other In-License Payments that become due to the Licensor(s)
under such Existing Sanofi Agreements, and […***…] of such payments will be
creditable against any payment due to Regulus hereunder.

Section 6.11 Future Third Party Agreements.

6.11.1 Identification of Necessary Patents. Subject to Section 6.11.5, if, after
the Effective Date, a Party identifies any Patent that:

 

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(a) is not Controlled by either Party;

(b) covers (i) the […***…](each, a “[…***…] Invention”), (ii) the […***…] (each,
a “[…***…] Invention”), (iii) a […***…] (each, a “[…***…] Invention”), or
(iv) […***…] that is necessary to […***…] to the […***…] in order to […***…],
excluding […***…] (each, a “[…***…] Invention”); and

(c) such Party believes in good faith is, or is likely to be, necessary for the
Development or Commercialization of a Product;

then, such Party will inform the other Party thereof, and the Parties (via the
JSC for so long as the JSC is in place) shall promptly confer with each other,
and attempt in good faith to reach consensus regarding, as to whether
in-licensing or acquiring other rights to such Patent is, or is likely to be,
necessary for the Development or Commercialization of a Product. […***…] with
respect to either or both Parties. The […***…], as well as […***…]. The Parties
will initially […***…] the […***…], provided that promptly after the […***…],
the Party whose […***…] the other Party an […***…] of the […***…] (such that the
[…***…] the other Party), and each Party […***…].

If the […***…] the Party that […***…], then such Party shall be […***…],
provided that (1) such Party shall be responsible for […***…] of the […***…],
(2) if such Party is Sanofi, none of such payments will be creditable against
any payment due to Regulus hereunder, and (3) if such Party is Regulus, then
notwithstanding any other provision of this Agreement to the contrary, such
[…***…].

 

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6.11.2 Responsible Party. If the Parties mutually agree, or […***…], that
in-licensing or acquiring other rights to a Patent meeting the criteria set
forth in Section 6.11.1 is necessary for the Development or Commercialization of
a Product (each, a “Necessary Patent”), the Party that will be responsible for
in-licensing or acquiring other rights to such Necessary Patent (the
“Responsible Party”) will be determined based on whether such Necessary Patent
covers a Target Invention, a Compound Invention, a Method Invention, or a
Formulation Invention, as follows:

Mir-21:

[…***…]

Mir-221/222:

[…***…]

Any agreement entered into by a Responsible Party pursuant to this
Section 6.11.2 shall be deemed a “Future Regulus Agreement” if Regulus is the
Responsible Party, and a “Future Sanofi Agreement” if Sanofi is the Responsible
Party.

6.11.3 Consultation; Cooperation. The Responsible Party will consult with the
other Party and consider in good faith the reasonable comments and suggestions
of the other Party regarding the financial terms of any Future Regulus Agreement
or Future Sanofi Agreement (as applicable), and in negotiating such Future
Regulus Agreement or Future Sanofi Agreement with the applicable Licensor(s)
shall use commercially reasonable efforts to minimize any In-License Royalties,
In-License Milestones and Other In-License Payments that (a) are to be borne, in
whole or in part, by the other Party pursuant to Section 6.12, (b) are
creditable against any amounts payable to Regulus hereunder in accordance with
Section 6.14.1 or Section 6.14.4, and/or (c) in the case of In-License
Royalties, are to be considered in […***…]. Except as set forth in
Section 6.11.2 or Section 6.13, Regulus will not enter any Future Regulus
Agreement that would impose any additional financial

 

***Confidential Treatment Requested

 

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obligations on Sanofi beyond those set forth in this Agreement without first
obtaining Sanofi’s prior written consent.

6.11.4 Copy of Agreement. Upon entering into any Future Regulus Agreement or
Future Sanofi Agreement that includes In-License Royalties, In-License
Milestones and/or Other In-License Payments that (a) are to be borne, in whole
or in part, by the other Party pursuant to Section 6.12, (b) where Sanofi is the
Responsible Party, are creditable against any amounts payable to Regulus
hereunder in accordance with Section 6.14.1 or Section 6.14.4, and/or (c) in the
case of In-License Royalties, are to be considered […***…], the Responsible
Party shall provide to the other Party a copy of the portion of such agreement
which sets forth the relevant In-License Royalties, In-License Milestones and/or
Other In-License Payments.

6.11.5 Sanofi Sole Responsibility for […***…] and […***…]. In the event that
after the Effective Date, Sanofi identifies any Patent not Controlled by either
Party that covers any […***…] that Sanofi determines, in its sole discretion, to
be necessary for the Development or Commercialization of a Product, Sanofi shall
have the sole responsibility for in-licensing or acquiring other rights to such
Patent, including sole responsibility for negotiation and execution of a license
or other agreement with respect thereto. Sanofi will be solely responsible for
paying 100% of the In-License Royalties, In-License Milestones and Other
In-License Payments that become due to the Licensor(s) under such agreement, and
no such payments, nor any portion thereof, will be creditable against any of
Sanofi’s payment obligations to Regulus under this Agreement.

Section 6.12 Allocation of Payments.

6.12.1 In-License Royalties. In-License Royalties payable to Licensors under any
Future Regulus Agreement or Future Sanofi Agreement shall be allocated between
the Parties based on (a) whether the applicable Third Party Patents cover a
Target Invention, a Compound Invention, a Method Invention, or a Formulation
Invention, (b) the identity of the Licensor(s), and/or (c) Indication, as
follows:

Mir-21:

[…***…]

 

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Mir-221/222:

[…***…]

6.12.2 In-License Milestones. In-License Milestones payable to Licensors under
any Future Regulus Agreement or Future Sanofi Agreement shall be allocated
between the Parties based on (a) whether the applicable Third Party Patents
cover a Target Invention, a Compound Invention, a Method Invention, or a
Formulation Invention, (b) the identity of the Licensor(s), and/or
(c) Indication, as follows:

Mir-21:

[…***…]

Mir-221/222:

[…***…]

6.12.3 Other In-License Payments. Other In-License Payments payable to Licensors
under any Future Regulus Agreement or Future Sanofi Agreement shall be allocated
between the Parties, or among the Parties and one or more Third Parties (as
applicable) based on

 

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(a) whether the applicable Third Party Patents cover a Target Invention, a
Compound Invention, a Method Invention, or a Formulation Invention, (b) the
identity of the Licensor(s), (c) Indication, and/or (d) whether the applicable
Third Party Patents are licensed to any Third Party(ies) as follows:

Mir-21:

[…***…]

Mir-221/222:

[…***…]

6.12.4 Payment Process. Sanofi will directly pay to Regulus any amounts payable
under a Future Regulus In-License in connection with a Product to the extent
such amounts are allocated to Sanofi under this Section 6.12. Sanofi will pay
directly the applicable Third Party any amounts payable under a Future Sanofi
In-License in connection with a Product; provided, to the extent any royalty
payments are allocated to Regulus under this Section 6.12, Sanofi will be
entitled to the royalty reduction as further set forth in Section 6.14.1.

Section 6.13 New Core Technology. After the Effective Date, Regulus may wish to
in-license or acquire rights to Patents from a Third Party, which Patents, if
in-licensed or acquired, would be within the scope of the definition of […***…]
Patent (“New Core Patents”), with or without associated Know-How. In such event,
Regulus shall […***…]

 

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[…***…] Sanofi’s consent, to negotiate and enter into an in-license or other
agreement with the Third Party with respect to such New Core Patents and related
Know-How, if any (collectively, “New Core Technology”). In such event (and to
the extent permitted by Regulus’ confidentiality agreement with the applicable
Third Party), Regulus will notify Sanofi regarding the nature of the […***…]
Technology and status of negotiations related to the New Core Technology through
the JSC. Once Regulus and such Third Party have executed an agreement with
respect to such New Core Technology (“New Core Technology Agreement”), Regulus
will offer such New Core Technology to Sanofi (including a description of the
upfront and other ongoing non-royalty, non-milestone payments and, except as set
forth in Section 6.13.2(b), the royalties and milestone payments paid or
potentially payable by Regulus thereunder).

6.13.1 In the case of any such New Core Technology comprising a Target
Invention, Compound Invention, Method Invention or Formulation Invention or
patent rights claiming any of the foregoing (in each case, “Section 6.9.1
Technology”), if Sanofi wishes to include such Section 6.9.1 Technology in the
Regulus Technology licensed to Sanofi under Section 2.1, Sanofi will notify
Regulus of its desire to do so within […***…] days after receipt of notice from
Regulus, whereupon such Section 6.9.1 Technology shall be included in the
Regulus Technology licensed to Sanofi under Section 2.1, and the upfront,
royalty, milestone and other ongoing payments paid or potentially payable by
Regulus under such New Core Technology Agreement shall be […***…] in accordance
with […***…], mutatis mutandis. If Sanofi […***…] such notification to Regulus
within such […***…]-day period, then notwithstanding any other provision of this
Agreement to the contrary, the applicable Section 6.9.1 Technology will […***…]
the Regulus Technology licensed to Sanofi under Section 2.1.

6.13.2 In the case of any New Core Technology other than Section 6.9.1
Technology (“Section 6.9.2 Technology”), if Sanofi wishes to include such
Section 6.9.2 Technology in the Regulus Technology licensed to Sanofi under
Section 2.1, Sanofi will notify Regulus of its desire to do so within
[…***…] days after receipt of notice from Regulus, whereupon the Parties will
negotiate in good faith regarding:

(a) a fair and commercially reasonable […***…] (and/or among the Parties and any
Regulus Third Party sublicensee(s) of such Section 6.9.2 Technology) of upfront
and other ongoing non-royalty, non-milestone payment obligations (which […***…]
of such payment obligations). As part of this […***…], Regulus will share with
Sanofi, in reasonable detail, the assumptions and methodology Regulus used to
create the […***…]; and

(b) the royalties and milestone payments to be […***…] with respect to Licensed
Compounds and Products, the Development, manufacture or Commercialization of
which is within the scope of Regulus’ in-license or other rights to the
applicable Section 6.9.2 Technology. For the avoidance of doubt, Regulus will
[…***…] to Sanofi the nature or amount of any of Regulus’ royalty and milestone
payment obligations to such Third Party.

If the Parties mutually agree in writing to the […***…] in Section 6.13.2(a) and
the royalties and milestone payments to be […***…] as described in

 

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Section 6.13.2(b), then the applicable Section 6.9.2 Technology will be included
in the Regulus Technology licensed to Sanofi under Section 2.1. If the Parties
[…***…] to the foregoing, then notwithstanding any other provision of this
Agreement to the contrary, the applicable Section 6.9.2 Technology will […***…]
the Regulus Technology licensed to Sanofi under Section 2.1. For purposes of
clarification, any payment obligations […***…] under this Section 6.13.2 will be
in addition to, and will not be creditable in whole or in part against, Sanofi’s
payment obligations set forth in this Agreement.

6.13.3 In the event of a dispute between the Parties as to whether a particular
Patent of a Third Party constitutes a New Core Patent, or whether any particular
New Core Technology constitutes Section 6.9.1 Technology or Section 6.9.2
Technology, such dispute shall be referred to an Intellectual Property Panel for
resolution in accordance with the provisions of Section 6.11.1, mutatis
mutandis.

Section 6.14 Royalty Reductions; […***…] Royalty.

6.14.1 Reduction for Third Party Royalties. Subject to Section 6.14.3, Sanofi’s
royalty obligations under Section 6.9 above with respect to a particular Product
in a particular country will be reduced by the applicable percentage (if any) of
the amount of aggregate In-License Royalties paid by Sanofi to Licensor(s) under
Future Sanofi-Agreements on sales of such Product in such country for which
Regulus is responsible, as set forth in Section 6.12; provided, however, that
the application of any such reduction shall not reduce the royalties payable by
Sanofi under this Agreement with respect to such Product in such country for any
given Calendar Quarter below the greater of (i) 50% of the applicable royalty
rates stated in Section 6.9; […***…].

6.14.2 Generic Competition. Subject to Section 6.14.3, if a Generic Product
corresponding to a Product is approved for sale by the applicable Regulatory
Authority and then sold in a particular country and the Percentage Reduction of
Net Sales is greater than […***…]% for any given Calendar Quarter in such
country, then the royalty rate applicable to such Product and such country under
Section 6.9 for such Calendar Quarter will be reduced to […***…]%; […***…]. As
used herein, the “Percentage Reduction of Net Sales” of a Product in a country
for any particular Calendar Quarter means the quotient (expressed as a
percentage) obtained by dividing (A) the difference obtained by subtracting the
[…***…] such applicable Calendar Quarter from the […***…] by (B) the […***…].
For clarity, this Section 6.14.2 will operate and will be applied on a Calendar
Quarter-by-Calendar Quarter Basis such that, for example, in the first Calendar
Quarter in a year the royalty rate set forth in Section 6.9 applicable to a
particular Product and particular country for such Calendar Quarter may be
reduced to […***…]%; but, in the second Calendar Quarter in such year the full
royalty rate set forth in Section 6.9 will be

 

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applicable to a particular Product if the […***…]% in such country for such
second Calendar Quarter. In addition, if (i) there […***…] Generic Product sold
by a Third Party, and (ii) […***…], then such Generic Product will […***…] the
royalty reduction under this Section 6.14.2.

6.14.3 […***…] Royalties. Notwithstanding any other provision of this Agreement
to the contrary (including, without limitation, Sections 6.14.1 and 6.14.2), in
no event shall the royalties payable by Sanofi to Regulus with respect to Net
Sales of a particular Product in a particular country for any Calendar Quarter
[…***…] the sum of: (a) […***…], and (b) […***…] ([…***…] Royalties”).

6.14.4 Credit for Excess Royalties Paid by Sanofi. If Sanofi’s obligation to pay
[…***…] Royalties with respect to a Product in a country under Section 6.14.3 is
triggered and, as a result, the sum of all royalties Sanofi pays to Regulus on
sales of such Product in such country (the “Supported Amount”) exceeds the
amount of royalties Sanofi would, but for the operation of Section 6.14.3,
otherwise be responsible under this ARTICLE 6 in connection with sales of such
Product in such country (the “Base Amount”), then Sanofi shall be entitled to
credit such excess amount (i.e., the Supported Amount minus the Base Amount)
against any future sales milestone payment payable by Sanofi to Regulus under
Section 6.8.3, regardless of which Product triggers such sales milestone payment
obligation.

6.14.5 No Payments to Sanofi. For purposes of clarification, and notwithstanding
any other provision of this Agreement, in no event shall the credits to which
Sanofi may be entitled under this Section 6.14 result in Regulus being obligated
to make any payment to Sanofi.

Section 6.15 Royalty Term. Royalties payable under Section 6.9 (subject to and
including any applicable reductions under Section 6.14) will be payable on a
Product-by-Product and country-by-country basis from the First Commercial Sale
of a Product in a country until the date that is the later of (i) 10 years after
the First Commercial Sale of such Product in such country or (ii) the expiration
of the last to expire Valid Claim within the Regulus Patents which would be
infringed by the sale of such Product in such country by an unauthorized party.
Such period during which royalties are payable with respect to a Product in a
country, including giving effect to any applicable reductions under
Section 6.14, is referred to herein as the “Royalty Term” for such Product in
such country. Notwithstanding expiration of the Royalty Term with respect to a
particular Product in a country, Sanofi will continue to pay to Regulus all
royalties payable by Regulus to Licensor(s) under the Existing Regulus
Agreements with respect to Net Sales of such Product in such country.

Section 6.16 Royalty Report and Payment. During the Royalty Term following the
First Commercial Sale of any Product, within […***…] days after the end of each
Calendar Quarter,

 

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Sanofi will provide Regulus with a royalty report for such Quarter showing, on a
Product-by-Product and country-by-country basis:

(a) the Net Sales of Products sold by Sanofi, its sublicensees and their
respective Affiliates during such Calendar Quarter reporting period;

(b) the royalties which will have accrued hereunder with respect to such Net
Sales;

(c) the amount of any applicable credits taken against royalties under
Section 6.14.1 and the amount of any applicable credits accrued against future
sales milestone payments under Section 6.14.4;

(d) any adjustment for Generic Products under Section 6.14.2; and

(e) any other information related to the calculation of Net Sales of Products
reasonably requested by Regulus that (i) is contained in a report and format
that is regularly generated by Sanofi’s accounting department in its normal
course of business and (ii) is reasonably necessary for Regulus to comply with
an Existing Regulus Agreement or an Additional Regulus Third Party Agreement.

Sanofi will keep, and will require its sublicensees and their respective
Affiliates to keep, complete, true and accurate books of account and records for
the purpose of determining the payments to be made under this Agreement. Upon
reasonable request by Regulus (but no more frequently than once in any
[…***…]-month period), Sanofi will report to Regulus the quantity of Product not
subject to royalties distributed by Sanofi, its Affiliates or sublicensees as
part of an expanded access program to include compassionate use, named patients
or other similar use or as part of Phase 4 Trials or as bona fide samples. All
information disclosed by Sanofi to Regulus under this Section 6.16 will be
Sanofi Confidential Information.

Section 6.17 Manner of Payment and Exchange Rate. Except as otherwise provided
in this Agreement, Regulus shall invoice Sanofi for all milestone, royalty and
other payments hereunder and Sanofi shall pay all such milestone, royalty and
other payments that are due within thirty (30) days after the receipt of the
applicable invoice. All payments to be made by Sanofi to Regulus hereunder will
be made by deposit of U.S. Dollars by wire transfer in immediately available
funds in the requisite amount to such bank account Regulus may from time to time
designate by notice to Sanofi. For sales that were made in a currency other than
U.S. Dollars, such amounts will be converted into U.S. Dollars using the average
exchange rates as calculated and utilized by Sanofi’s group reporting system and
published accounts for the applicable royalty period. All invoices to be
provided by Regulus to Sanofi under this Agreement shall include a breakdown of
the goods, services and/or activities for which payment is due, as well is
payment instructions and shall be sent by express courier service to:

Sanofi

Direction Comptable Holding

54 rue la Boétie

75008 Paris

France

 

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Section 6.18 Audits, including Audits of Royalty Reports.

6.18.1 Audits of Royalty Reports. Upon the written request of Regulus and not
more than once in each Calendar Year, Sanofi will permit an independent
certified public accounting firm of nationally recognized standing selected by
Regulus and reasonably acceptable to Sanofi, at Regulus’ expense to have access
during normal business hours to such records of Sanofi and/or its Affiliates as
may be reasonably necessary to verify the accuracy of the royalty reports
hereunder for any Calendar Year ending not more than 36 months prior to the date
of such request. These audit rights (but not any obligation to pay unpaid
royalties for such periods) with respect to any Calendar Year will terminate 3
years after the end of such Calendar Year. Regulus will provide Sanofi with a
copy of the accounting firm’s written report within 30 days of completion of
such report.

6.18.2 If such accounting firm concludes that an overpayment or underpayment was
made, then the owing Party will pay the amount due within 30 days of the date
Regulus delivers to Sanofi such accounting firm’s written report so correctly
concluding. Regulus will bear the full cost of such audit unless such audit
correctly discloses that the additional payment payable by Sanofi for the
audited period is more than […***…]% of the amount of the royalties paid for
that audited period, in which case Sanofi will pay the reasonable fees and
expenses charged by the accounting firm.

6.18.3 Sanofi will use Commercially Reasonable Efforts to include in each
sublicense granted by it to any sublicensee a provision requiring the
sublicensee to maintain records of sales made pursuant to such license and to
grant access to such records by Sanofi’s independent accountant to the same
extent and under substantially similar obligations as required of Sanofi under
this Agreement. Sanofi will advise Regulus in advance of each audit of any
sublicensee with respect to Product sales. Sanofi will provide Regulus with a
summary of the results received from the audit and, if Regulus so requests, a
copy of the audit report with respect to Product sales. Sanofi will pay the
reasonable fees and expenses charged by the accounting firm, except that Regulus
will pay for all additional services requested exclusively by Regulus from
Sanofi’s independent accountant unless the audit discloses that the additional
payments payable to Regulus for the audited period differ by more than […***…]%
from the amount of the royalties otherwise paid.

6.18.4 All financial information subject to review under this Section or under
any license agreement with a sublicensee will be Sanofi Confidential Information
and will be treated in accordance with the confidentiality provisions of this
Agreement. As a condition precedent to Regulus’ audit rights under this Section,
Regulus’ accounting firm will enter into a confidentiality agreement with Sanofi
obligating it to treat all such financial information in confidence pursuant to
such confidentiality agreement. Regulus may provide Third Parties to which
Regulus owes royalties on Products information in such audit report that are
relevant and required to comply with such Third Party’s audit rights under the
applicable license agreement between Regulus and such Third Party, provided that
such Third Party agrees in writing to keep such information confidential under
terms no less restrictive than Regulus’ obligations of confidentiality under
this Agreement.

 

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Section 6.19 Taxes.

6.19.1 Sanofi will make all payments to Regulus under this Agreement without
deduction or withholding for taxes except to the extent that any such deduction
or withholding is required by Applicable Law in effect at the time of payment.

6.19.2 Sanofi will promptly pay on behalf of Regulus any tax required to be
withheld on amounts payable under this Agreement to the appropriate governmental
authority, and Sanofi will furnish Regulus with proof of payment of such tax.
Any such tax required to be withheld will be an expense of and borne by Regulus.

6.19.3 Sanofi and Regulus will cooperate with respect to all documentation
required by any taxing authority or reasonably requested by Sanofi to secure a
reduction in the rate of applicable withholding taxes.

Section 6.20 Sublicenses. In the event Sanofi grants licenses or sublicenses to
a sublicensee to sell Products which are subject to royalties under Section 6.9,
such licenses or sublicenses will include an obligation for the sublicensee to
account for and report its sales of Products on the same basis as if such sales
were Net Sales by Sanofi.

Section 6.21 Interest. If Sanofi fails to make any payment due to Regulus under
this Agreement, then interest will accrue on a daily basis at the greater of an
annual rate equal to the […***…] (or such lower interest rate to the extent
necessary to comply with Applicable Law).

Section 6.22 Sanofi Founding Company License. Notwithstanding any other
provision in this Agreement, in the event that Sanofi is granted a license (each
such license a “Sanofi Founding Company License”) pursuant to Section 15.3 of
the Founding Company License Agreement (entitled “Effects of Termination”) from
either of the Founding Companies, then, in addition to, and not in lieu of, any
other or remedies available to Sanofi:

6.22.1 […***…] amounts payable to either of the Founding Companies pursuant to
proviso “(ii)” of the final sentence of Section 15.3, […***…]; and

6.22.2 subject to Section 6.14.3, any royalty or milestone amounts (including
both sales milestones and development milestones) payable to either of the
Founding Companies under any Sanofi Parent License, to the extent not […***…]
than were Regulus’ royalty and milestone payment obligations under the Founding
Company License Agreement, […***…] under this Agreement. If royalty or milestone
amounts payable by Sanofi to either of the Founding Companies under any Sanofi
Parent License […***…] Regulus’ royalty or milestone payment obligations under
the Founding Company License Agreement, Sanofi […***…].

 

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ARTICLE 7

CONFIDENTIALITY; PRESS RELEASES & PUBLICATIONS

Section 7.1 Confidentiality; Exceptions. Except to the extent expressly
authorized by this Agreement or otherwise agreed in writing, the Parties agree
that, during the Term and for five (5) years thereafter, the receiving Party
(the “Receiving Party”) and its Affiliates will keep confidential and will not
publish or otherwise disclose or use for any purpose other than as provided for
in this Agreement any Know-How or other confidential and proprietary information
and materials, patentable or otherwise, in any form (written, oral,
photographic, electronic, magnetic, or otherwise) which is disclosed to it by
the other Party (the “Disclosing Party”) or its Affiliates or otherwise received
or accessed by a Receiving Party in the course of performing its obligations or
exercising its rights under this Agreement, including, but not limited to, trade
secrets, Know-How, inventions or discoveries, proprietary information, formulae,
processes, techniques and information relating to the past, present and future
marketing, financial, and research and development activities of any product or
potential product or useful technology of the Disclosing Party or its Affiliates
and the pricing thereof (collectively, “Confidential Information”), except to
the extent that it can be established by the Receiving Party that such
Confidential Information:

7.1.1 was in the lawful knowledge and possession of the Receiving Party or its
Affiliates prior to the time it was disclosed to, or learned by, the Receiving
Party or its Affiliates, or was otherwise developed independently by the
Receiving Party or its Affiliates, as evidenced by written records kept in the
ordinary course of business, or other documentary proof of actual use by the
Receiving Party or its Affiliates;

7.1.2 was generally available to the public or otherwise part of the public
domain at the time of its disclosure to the Receiving Party or its Affiliates;

7.1.3 became generally available to the public or otherwise part of the public
domain after its disclosure and other than through any act or omission of the
Receiving Party or its Affiliates in breach of this Agreement; or

7.1.4 was disclosed to the Receiving Party or its Affiliates, other than under
an obligation of confidentiality, by a Third Party who had no obligation to the
Disclosing Party or its Affiliates not to disclose such information to others.

Section 7.2 Authorized Disclosure. Except as expressly provided otherwise in
this Agreement, a Receiving Party or its Affiliates may use and disclose to
Third Parties Confidential Information of the Disclosing Party as follows:
(i) with respect to any such disclosure of Confidential Information, under
confidentiality provisions no less restrictive than those in this Agreement, and
solely in connection with the performance of its obligations or exercise of its
rights granted or reserved in this Agreement (including, without limitation, the
rights to Develop and Commercialize Licensed Compounds, Products, and/or
Discontinued Products, and to grant licenses and sublicenses hereunder),
provided, that Confidential Information may be disclosed by a Receiving Party to
a governmental entity or agency without requiring such entity or agency to enter
into a confidentiality agreement with such Receiving Party if such Receiving
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used reasonable efforts to impose such requirement without success and
disclosure to such governmental entity or agency is necessary for the
performance of the Receiving Party’s obligations hereunder; (ii) to the extent
such disclosure is reasonably necessary in filing or prosecuting patent,
copyright and trademark applications (subject to Section 8.6 below) that the
Disclosing Party has the right to file or prosecute under Section 8.2; complying
with applicable governmental regulations; obtaining Approvals, conducting
clinical trials, and marketing Products, in each case, for Products that the
Disclosing Party has the right to Develop and Commercialize; or as otherwise
required by applicable law, regulation, rule or legal process (including the
rules of the SEC and any stock exchange); provided, however, that if a Receiving
Party or any of its Affiliates is required by law or regulation to make any such
disclosure of a Disclosing Party’s Confidential Information it will, except
where impracticable for necessary disclosures, for example, but without
limitation, in the event of a medical emergency, give reasonable advance notice
to the Disclosing Party of such disclosure requirement and will use its
reasonable efforts to secure confidential treatment of such Confidential
Information required to be disclosed; (iii) in communication with actual or
potential lenders, arm’s-length financial investors, merger partners, acquirers,
consultants, or professional advisors on a need-to-know basis, in each case
under confidentiality provisions no less restrictive than those of this
Agreement; (iv) to the extent and only to the extent that such disclosure is
required to comply with existing expressly stated contractual obligations owed
to such Party’s or its Affiliates’ licensor with respect to any intellectual
property licensed to the other Party under this Agreement; (v) to prosecute or
defend litigation as permitted by this Agreement; or (vi) to the extent mutually
agreed to in writing by the Parties.

Section 7.3 Press Release; Disclosure of Agreement. Sanofi agrees that Regulus
may issue a press release (which will not be a joint press release) announcing
the execution of this Agreement in substantially the form attached as
APPENDIX 12 (the “Second Restatement Press Release”). From and after the Second
Restatement Date, except for the Second Restatement Press Release, or to the
extent required to comply with applicable law, regulation, rule or legal process
or as otherwise permitted in accordance with this Section 7.3, neither Party nor
such Party’s Affiliates will make any public announcements, press releases or
other public disclosures concerning this Agreement or the terms or the subject
matter hereof without the prior written consent of the other, which will not be
unreasonably withheld. Notwithstanding the foregoing, (a) except for scientific
presentations and publications (which will be governed by Section 7.5 below)
each Party or its Affiliates may, without the other Party’s approval, make
disclosures pertaining solely to Products (as to Sanofi) licensed to Sanofi or
Discontinued Products (as to Regulus), provided, however, that Sanofi will
immediately notify (and provide as much advance notice as possible to) Regulus
of any event materially related to Products (including in such notice any
disclosure of clinical data or results, material regulatory filings or Approval)
so that the Parties may analyze the need for or desirability of publicly
disclosing or reporting such event, any press release or other similar public
communication by Sanofi related to efficacy or safety data and/or results
regarding a Licensed Compound or Product will be submitted to Regulus for review
at least five (5) Business Days (to the extent permitted by law) in advance of
such proposed public disclosure, Regulus will have the right to expeditiously
review and recommend changes to such communication and Sanofi will in good faith
consider any changes that are timely recommended by Regulus and (b) to the
extent information regarding this Agreement, a Licensed Compound or Product has
already been publicly disclosed, either Party (or its Affiliates) may
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consent of the other Party. Each Party will give the other Party a reasonable
opportunity (to the extent consistent with law) to review all material filings
with the SEC describing the terms of this Agreement prior to submission of such
filings, and will give due consideration to any reasonable comments by the
non-filing Party relating to such filing, including without limitation the
provisions of this Agreement for which confidential treatment should be sought.

Section 7.4 Remedies. Notwithstanding Section 12.4, each Party will be entitled
to seek, in addition to any other right or remedy it may have, at law or in
equity, a temporary injunction, without the posting of any bond or other
security, enjoining or restraining the other Party from any violation or
threatened violation of this Article 7.

Section 7.5 Publications.

7.5.1 Prior to Mir-221/222 Option Exercise. Prior to Sanofi’s exercise of its
Mir-221/222 Option, Regulus may, consistent with its practice with its other
compounds and products, publish and present data regarding such Collaboration
Target and Licensed Compounds and/or Products directed to such Collaboration
Target; provided, however, that Regulus will provide any such proposed
publication to Sanofi at least […***…] days prior to submission for publication
or presentation. During such […***…]-day period, Sanofi will have the right to
review and comment on any such publications and Regulus will give due
consideration to Sanofi’s requested changes. In addition, if Sanofi identifies
potentially patentable Program Inventions disclosed within such proposed
publication or presentation for which Sanofi desires that a patent application
be filed in accordance with the applicable provision of Section 8.2, then by
written notice to Regulus delivered within such […***…]-day period, Sanofi may
require Regulus to delay such publication or presentation for up to an
additional […***…] days to permit the preparation and filing of such patent
application in accordance with Section 8.2. Notwithstanding the foregoing,
Regulus may not publish or present any data or information that contains any of
Sanofi’s Confidential Information without Sanofi’s prior written consent.

7.5.2 During Term of Program License. During such time as a Program License with
respect to a particular Collaboration Target is effective, and subject to this
Section 7.5.2, Sanofi will have the right to publish summaries of results from
any human clinical trials conducted by or on behalf of Sanofi with respect to
the Licensed Compounds or Products for such Collaboration Target without
obtaining the consent of Regulus and, except as required under Law, Regulus may
not publish any of such data, without the prior consent of Sanofi; provided,
however, that, prior to Sanofi’s exercise of its Option with respect to a Mir-21
POC Program, Sanofi will not have the right to publish summaries of results from
any human clinical trial conducted by or on behalf of Sanofi with respect to a
Mir-21 Compound or Mir-21 Product that is the subject of such Mir-21 POC
Program, without obtaining the consent of Regulus (which Regulus may withhold in
its sole discretion). The Parties acknowledge that scientific lead time is a key
element of the value of the Research Program and Products under this Agreement
and further agree to use commercially reasonable efforts to control public
scientific disclosures of the results of the research and Development activities
under this Agreement (including but not limited to any such summaries of human
clinical trials data and results as required on the clinical trial registry) to
prevent any potential adverse effect of any premature public disclosure of such
results. The Parties will establish a procedure for publication review and each
Party will first submit to the other Party an early draft of all such
publications, whether

 

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they are to be presented orally or in written form, at least […***…] days prior
to submission for publication including, without limitation, to facilitate the
publication of any summaries of human clinical trials data and results as
required on the clinical trial registry of each respective Party. Each Party
will review such proposed publication in order to avoid the unauthorized
disclosure of a Party’s Confidential Information and to preserve the
patentability of inventions arising from the Research Program. If, as soon as
reasonably possible, but no longer than […***…] days following receipt of an
advance copy of a Party’s proposed publication, the other Party informs such
Party that its proposed publication contains Confidential Information of the
other Party, then such Party will delete such Confidential Information from its
proposed publication. In addition, if at any time during such […***…]-day
period, the other Party informs such Party that its proposed publication
discloses inventions made by either Party in the course of the Research Program
under this Agreement that have not yet been protected through the filing of a
patent application, or the public disclosure of such proposed publication could
be expected to have a material adverse effect on any Patents or Know-How solely
owned or Controlled by such other Party, then such Party will either (a) delay
such proposed publication, for up to […***…] days from the date the other Party
informed such Party of its objection to the proposed publication, to permit the
timely preparation and first filing of patent application(s) on the information
involved or (b) remove the identified disclosures prior to publication.

Section 7.6 Acknowledgment. Unless otherwise agreed upon in writing by the
Parties, each Party will acknowledge in any press release, public presentation
or publication regarding a Collaboration Target, Licensed Compound and/or
Product, the other Party’s role in discovering and developing the Collaboration
Target, Licensed Compound or Product, as applicable, and that such Collaboration
Targets, Licensed Compounds or Products are under license from Regulus
(including, if requested by Regulus, Regulus’ stock ticker) and otherwise
acknowledge the contributions from the other Party.

ARTICLE 8

PATENTS

The provisions of this Article 8 (excluding Section 8.1) as they relate to
Regulus Patents that are licensed to Regulus under any Existing Regulus
Agreement are subject in all respects to the terms of such Existing Regulus
Agreement. In the event of any inconsistency between Regulus’ obligations under
any Existing Regulus Agreement and the rights conferred on Sanofi by this
Article 8 (excluding Section 8.1) with respect to the Regulus Patents that are
subject to such Existing Regulus, the Existing Regulus Agreement shall control,
and the provisions of this Article 8 shall, to the extent inconsistent with the
Existing Regulus Agreement, be of no force or effect.

Section 8.1 Ownership of Inventions and Patents.

8.1.1 Title to inventions, discoveries, improvements and other technology,
whether or not patentable, conceived, made or reduced to practice in the
performance of the Research Program or the POC Programs under this Agreement
(collectively, the “Program Inventions”) and any Patents claiming such Program
Inventions (“Program Patents”), are retained by the Party that is the employer
of the inventor(s) (or, in the case of consultants and

 

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(sub)contractors, the Party for which the consultant or (sub)contractor is
providing its services). Each Party will ensure that every employee, consultant,
and (sub)contractor employed or contracted by that Party in the performance of
the Research Program and the POC Programs has a written obligation to assign all
Know-How and Patents conceived, made or reduced to practice by each such
employee, consultant, and (sub)contractor to such Party. The Parties agree that
the United States federal patent law on inventorship will determine the
inventorship of any Program Invention and the names of the inventors on any
Program Patent filings, whether sole or joint inventions, which arise in
connection with activities conducted pursuant to this Agreement. Sanofi will own
Program Inventions invented solely by employees, consultants and/or
(sub)contractors of Sanofi (the “Sanofi Inventions”) and any Patents claiming
such Program Inventions (the “Sanofi Program Patents”). Regulus will own Program
Inventions invented solely by employees, consultants and/or (sub)contractors of
Regulus (the “Regulus Inventions”) and any Patents claiming such Program
Inventions (the “Regulus Program Patents”). Regulus and Sanofi will own jointly
such Program Inventions invented jointly by employees, consultants and/or
(sub)contractors of Regulus and Sanofi (the “Joint Inventions”) and any Patents
claiming such Program Inventions (the “Joint Patents”). Regulus will promptly
disclose to Sanofi any such Regulus Invention or Joint Invention, and Sanofi
will promptly disclose to Regulus any Sanofi Invention or Joint Invention,
arising from or made in the performance of the Research Program and any patent
or patent application claiming such Program Invention. It is understood that
except as otherwise provided in this Agreement or as the Parties may otherwise
agree in writing, neither Party will have any obligation to account to the other
Party for profits, or to obtain any approval of the other Party to license,
assign, mortgage or exploit a Joint Invention by reason of joint ownership of
any such Joint Invention, and may otherwise undertake all activities a sole
owner might undertake with respect to such inventions without the consent of and
without accounting to the other joint owner, and each Party hereby waives any
right it may have under the laws of any jurisdiction to require such consent or
accounting.

8.1.2 CREATE Act. Notwithstanding anything to the contrary in this Article 8,
neither Party will have the right to make an election under the Cooperative
Research and Technology Enhancement Act of 2004, 35 U.S.C. § 103(c)(2)-(c)(3)
(the “CREATE Act”) when exercising its rights under this Article 8 without the
prior written consent of the other Party, which will not be unreasonably
withheld, conditioned or delayed. With respect to any such permitted election,
the Parties will use reasonable efforts to cooperate and coordinate their
activities with respect to any submissions, filings or other activities in
support thereof. The Parties acknowledge and agree that this Agreement is a
“joint research agreement” as defined in the CREATE Act.

Section 8.2 Filing, Prosecution and Maintenance of Patents. For purposes of this
Section 8.2, the terms “prosecute,” “prosecuting” and “prosecution,” when used
in reference to any Patent, shall be deemed to include, without limitation, the
control of any interferences, reissue proceedings, oppositions and
reexaminations with respect to such Patent.

8.2.1 Product Specific Patents.

(a) Before Option Exercise. On a Collaboration Target-by-Collaboration Target
basis, for Product Specific Patents filed prior to Sanofi’s exercise of its
Option (or at least one of its Options) for a given Collaboration Target (and
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Regulus of the applicable Option Exercise Fee and POC Program Reimbursement
Amount), Regulus will be responsible for the preparation, filing, prosecution
and maintenance of Product Specific Patents (including Product Specific Patents
that are Joint Patents) directed to such Collaboration Target or to Licensed
Compounds or Products that target or mimic (as applicable) such Collaboration
Target. Regulus will use Commercially Reasonable Efforts to prepare, file,
prosecute and maintain such Product Specific Patents in at least the countries
listed in APPENDIX 7 (each, a “Listed Country”), at Regulus’ expense; provided,
however, that if the applicable patent office in any Listed Country, other than
[…***…] and […***…], requires […***…] of patent applications […***…], Sanofi
shall reimburse Regulus for costs incurred by Regulus for […***…] of Product
Specific Patents […***…]. If Sanofi requests in writing that Regulus prepare,
file, prosecute and maintain any Product Specific Patent in any country that is
not a Listed Country (each, a “Sanofi Nominated Country”), Regulus will use
Commercially Reasonable Efforts to prepare, file, prosecute and maintain such
Product Specific Patent in such Sanofi Nominated Country, at Sanofi’s expense,
provided, however, that if Sanofi is not the sole licensee or sublicensee of
Regulus under such Product Specific Patent, Regulus will be responsible for such
expenses and Sanofi will reimburse Regulus for the amount that is equal to the
total of such expenses divided by the number of licensee(s) or sublicense(s)
under such product specific patent (such number to also include Regulus).
Regulus, or its outside counsel, will provide Sanofi with (i) a reasonably
detailed annual update of the filing, prosecution and maintenance status for
each such Product Specific Patent and (ii) any further information reasonably
requested by Sanofi from time to time regarding such Product Specific Patent;
provided, however, that if such Product Specific Patent is licensed to Regulus
by a Third Party, Regulus will not be obligated to make disclosure of
information regarding such Product Specific Patent to the extent that such
disclosure would constitute a breach of Regulus’ confidentiality obligations to
the Third Party licensor.

(b) After Option Exercise. On a Collaboration Target-by-Collaboration Target
basis, for Product Specific Patents filed after Sanofi’s exercise of its Option
(or at least one of its Options) for a given Collaboration Target (and Sanofi’s
payment to Regulus of the applicable Option Exercise Fee and POC Program
Reimbursement Amount), Sanofi will be responsible for the preparation, filing,
prosecution and maintenance of such Product Specific Patents (including Product
Specific Patents that are Joint Patents) directed to such Collaboration Target
or to Licensed Compounds or Products that target or mimic (as applicable) such
Collaboration Target, at Sanofi’s expense; provided, however, that if Sanofi is
not the sole licensee or sublicensee of Regulus under such Product Specific
Patent, Regulus will be responsible for such expenses and Sanofi will reimburse
Regulus for the amount that is equal to the total of such expenses divided by
the number of licensee(s) or sublicense(s) under such product specific patent
(such number to also include Regulus). Sanofi, or its outside counsel, will
provide Regulus with (i) a reasonably detailed monthly update of the filing,
prosecution and maintenance status for each such Product Specific Patent and
(ii) any further information reasonably requested by Regulus from time to time
regarding such Product Specific Patent.

(c) Cooperation. The Party responsible for preparing, filing, prosecuting and
maintaining any Product Specific Patent (including any Product Specific Patent
that is a Joint Patent) under Section 8.2.1(a) or Section 8.2.1(b) above (the
“Lead Party”) will consider in good faith all reasonable requests or
recommendations of the other Party regarding the preparation, filing,
prosecution and maintenance of Product Specific Patents. During such

 

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time as a Program License with respect to a particular Collaboration Target is
effective, Regulus will consider in good faith, and give effect to, all
reasonable requests or recommendations of Sanofi regarding the preparation,
filing, prosecution and maintenance of the applicable Product Specific Patents.

(d) Election Not to File, Prosecute, or Maintain Product Specific Patents. In
the event that the Lead Party decides not to pursue or continue the filing,
prosecution or maintenance of any Product Specific Patent in any country, the
Lead Party, or its outside counsel, will provide the other Party with written
notice of such decision at least 60 days in advance of any relevant filing,
prosecution or maintenance deadline, and the other Party will provide the Lead
Party with prompt notice as to whether the other Party desires to assume
responsibility and costs for such filing, prosecution or maintenance of such
Product Specific Patent. The Lead Party will not knowingly permit any such
Product Specific Patent to be abandoned in any Listed Country (or, in the case
of Regulus, any Sanofi Nominated Country for which Sanofi is bearing the expense
of preparation, filing, prosecution and maintenance of Product Specific
Patents), or elect not to file a new patent application claiming priority to a
patent application within the Product Specific Patents either before such patent
application’s issuance or within the time period required for the filing of an
international (i.e., Patent Cooperation Treaty), regional (including European
Patent Office) or national application, without the other Party’s written
consent or without the other Party otherwise first being given an opportunity to
assume full responsibility (at the other Party’s expense) for the continued
prosecution and maintenance of such Product Specific Patents, or the filing of
such new patent application. In the event that the other Party assumes
responsibility for the preparation, filing, prosecution or maintenance of any
patent or patent application as set forth above, the other Party will not be
liable to the Lead Party in any way with respect to its handling of, or the
results obtained from, the filing, prosecution, issuance, extension or
maintenance of such application or any resulting patent or any failure by it to
so file, prosecute, extend or maintain. In the event that Sanofi assumes
responsibility for the preparation, filing, prosecution or maintenance of any
such Product Specific Patent as set forth above, Regulus will assign such
Product Specific Patent to Sanofi, for no additional consideration, and such
Product Specific Patent (if later granted) will be disregarded for the purposes
of calculating the Royalty Term under Section 6.15.

8.2.2 Regulus Core Technology Patents Other Than Joint Patents. Regulus (or its
Third Party licensors of Regulus Core Technology Patents, as applicable) will be
solely responsible for the preparation, filing, prosecution and maintenance of
Regulus Core Technology Patents (other than Joint Patents that are Regulus Core
Technology Patents), at Regulus’ sole expense. At Sanofi’s reasonable request
from time to time, Regulus, or its outside counsel, will promptly provide Sanofi
with an update of the filing, prosecution and maintenance status for each of
such Regulus Core Technology Patents, including without limitation an update of
APPENDIX 3.

8.2.3 Joint Core Technology Patents. This Section 8.2.3 will apply only to:
(i) Regulus Core Technology Patents that are Joint Patents (each, a “Joint Core
Technology Patent”); and (ii) any Joint Invention that is not claimed by any
patent application in a country, provided that if a patent application claiming
such Joint Invention were filed in such country, such patent application would
be a Joint Core Technology Patent (such Joint Invention, a “Joint Core
Technology Invention”).

 

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(a) Regulus First Right to File, Prosecute and Maintain. Regulus will have the
first right to prepare, file, prosecute and maintain any new patent application
claiming a Joint Core Technology Invention, at Regulus’ expense. Regulus shall
consult with Sanofi as to the preparation, filing, prosecution and maintenance
of Joint Core Technology Patents and draft patent applications claiming Joint
Core Technology Inventions reasonably prior to any deadline or action with any
patent office, shall furnish to Sanofi copies of all relevant documents
reasonably in advance of such consultation, and shall consider in good faith the
reasonable comments and suggestions of Sanofi. Regulus, or its outside counsel,
will provide Sanofi with an update of the filing, prosecution and maintenance
status for each Joint Core Technology Patent on a periodic basis, and will
provide to Sanofi copies of any papers relating to the filing, prosecution and
maintenance of such Joint Core Technology Patents promptly upon their being
filed or received.

(b) Disclosure; Cooperation. Regulus or its outside counsel, will provide Sanofi
with (i) a reasonably detailed monthly update of the filing, prosecution and
maintenance status for such Joint Core Technology Patent and (ii) any further
information reasonably requested by Sanofi from time to time regarding such
Joint Core Technology Patent. Regulus will consider in good faith all reasonable
requests or recommendations of Sanofi regarding the preparation, filing,
prosecution and maintenance of Joint Core Technology Patents.

(c) Election Not to File, Prosecute, or Maintain Joint Core Technology Patents.
In the event that Regulus decides not to pursue or continue the filing,
prosecution or maintenance of any Joint Core Technology Patent in any country,
Regulus, or its outside counsel, will provide Sanofi with written notice of such
decision at least 60 days in advance of any relevant filing, prosecution or
maintenance deadline, and Sanofi will provide Regulus with prompt notice as to
whether Sanofi desires to assume responsibility and costs for such filing,
prosecution or maintenance of such Joint Core Technology Patent. Regulus will
not knowingly permit any such Joint Core Technology Patent to be abandoned, or
elect not to file a new patent application claiming priority to a patent
application within the Joint Core Technology Patents either before such patent
application’s issuance or within the time period required for the filing of an
international (i.e., Patent Cooperation Treaty), regional (including European
Patent Office) or national application, without Sanofi’s written consent or
without Sanofi otherwise first being given an opportunity to assume full
responsibility (at Sanofi’s expense) for the continued prosecution and
maintenance of such Joint Core Technology Patent, or the filing of such new
patent application. In the event that Sanofi assumes responsibility for the
preparation, filing, prosecution or maintenance of any Joint Core Technology
Patent as set forth above, such Joint Core Technology Patent (if later granted)
will be disregarded for the purposes of calculating the Royalty Term under
Section 6.11, provided that Regulus shall retain its joint ownership interest in
such Joint Core Technology Patent.

8.2.4 Joint Patents Other Than Joint Core Technology Patents and Product
Specific Patents. This Section 8.2.4 will apply only to: (i) Joint Patents that
are neither Joint Core Technology Patents nor Product Specific Patents (each, an
“Other Joint Patent”); and (ii) any Joint Invention that is not claimed by any
patent application in a country, provided that if a patent application claiming
such Joint Invention were filed in such country, such patent application would
be neither a Joint Core Technology Patent nor a Product Specific Patent (such
Joint Invention, an “Other Joint Invention”).

 

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(a) Sanofi First Right to File, Prosecute and Maintain. Sanofi will have the
first right to prepare, file, prosecute and maintain any new patent application
claiming an Other Joint Invention, at Sanofi’s expense. Sanofi shall consult
with Regulus as to the preparation, filing, prosecution and maintenance of Other
Joint Patents and draft patent applications claiming Other Joint Inventions
reasonably prior to any deadline or action with any patent office, shall furnish
to Regulus copies of all relevant documents reasonably in advance of such
consultation, and shall consider in good faith the reasonable comments and
suggestions of Regulus. Sanofi, or its outside counsel, will provide Regulus
with an update of the filing, prosecution and maintenance status for each Other
Joint Patent on a periodic basis, and will provide to Regulus copies of any
papers relating to the filing, prosecution and maintenance of such Other Joint
Patents promptly upon their being filed or received.

(b) Election Not to File, Prosecute, or Maintain Other Joint Patents. In the
event that Sanofi decides not to pursue or continue the filing, prosecution or
maintenance of any Other Joint Patent in any country, Sanofi, or its outside
counsel, will provide Regulus with written notice of such decision at least
60 days in advance of any relevant filing, prosecution or maintenance deadline,
and Regulus will provide Sanofi with prompt notice as to whether Regulus desires
to assume responsibility and costs for such filing, prosecution or maintenance
of such Other Joint Patent. Sanofi will not knowingly permit any such Other
Joint Patent to be abandoned, or elect not to file a new patent application
claiming priority to a patent application within the Other Joint Patents either
before such patent application’s issuance or within the time period required for
the filing of an international (i.e., Patent Cooperation Treaty), regional
(including European Patent Office) or national application, without Regulus’
written consent or without Regulus otherwise first being given an opportunity to
assume full responsibility (at Regulus’ expense) for the continued prosecution
and maintenance of such Other Joint Patent, or the filing of such new patent
application. In the event that Regulus assumes responsibility for the
preparation, filing, prosecution or maintenance of any patent or patent
application as set forth above, Regulus will not be liable to Sanofi in any way
with respect to its handling of, or the results obtained from, the filing,
prosecution, issuance, extension or maintenance of such application or any
resulting patent or any failure by it to so file, prosecute, extend or maintain.

8.2.5 Cooperation. Each Party agrees to cooperate fully in the preparation,
filing, prosecution and maintenance of Patents pursuant to this Section 8.2.
Such cooperation includes, but is not limited to: (a) executing all papers and
instruments, or requiring its employees or contractors, to execute such papers
and instruments, so as to enable the other Party to exercise its rights and
perform its obligations under this Section 8.2; and (b) promptly informing the
other Party of any matters coming to such Party’s attention that may affect the
preparation, filing, prosecution or maintenance of any such patent applications.

Section 8.3 Patent Term Extension. Regulus and Sanofi will each cooperate with
one another and will use Commercially Reasonable Efforts in obtaining patent
term restorations and/or extensions (including without limitation, any pediatric
exclusivity extensions as may be available) or supplemental protection
certificates or their equivalents in any country with respect to patent rights
covering those Products licensed by Sanofi hereunder. If elections with respect
to obtaining such patent term extensions or supplemental protection are to be
made, Sanofi will have the right to make such election, provided that (i) such
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with applicable Law so as to maximize the period of marketing exclusivity for
the Product, and (ii) Sanofi may not elect to extend a Regulus Core Technology
Patent (other than a Joint Core Technology Patent) under this Section 8.3
without Regulus’ prior written consent.

Section 8.4 Enforcement of Patents

8.4.1 Product Specific Patents.

(a) Enforcement by Sanofi. In the event that Regulus or Sanofi becomes aware of
a suspected infringement of any Product Specific Patent, or any such Product
Specific Patent is challenged in any action or proceeding (other than any
interferences, reissue proceedings, oppositions or reexaminations, which are
addressed above), such Party will notify the other Party promptly, and following
such notification, the Parties will confer and determine an appropriate course
of action in response to such suspected infringement or action or proceeding.
During such time as a Program License with respect to a particular Collaboration
Target is effective, Sanofi will have the right, but will not be obligated, to
defend any such action or proceeding or bring an infringement action with
respect to such suspected infringement at its own expense, in its own name and
entirely under its own direction and control, or settle any such action,
proceeding or dispute by license (to the extent such sublicense is permitted
under this Agreement). Regulus will reasonably assist Sanofi in any action or
proceeding being defended or prosecuted if so requested, and will lend its name
to such actions or proceedings if reasonably requested by Sanofi or required by
Applicable Law. Sanofi will reimburse Regulus for the documented out-of-pocket
costs Regulus reasonably incurs in providing such assistance as specifically
requested in writing by Sanofi. In the event Regulus is a required party to the
proceeding or action, Regulus will have the right to be represented by its own
counsel (such selection to be subject to Sanofi’s approval, such approval not to
be unreasonably withheld), and Sanofi will reimburse Regulus for the documented
external costs Regulus reasonably incurs that are reasonably related to the
proceeding or action, including attorneys fees, provided that Sanofi will retain
overall responsibility for the prosecution of such action or proceeding in such
event. In the event that Regulus is not a necessary party to the proceeding or
action, Regulus will have the right to participate and be represented in any
such suit by its own counsel at its own expense, provided that Sanofi will
retain overall responsibility for the prosecution of such action or proceedings
in such event. Sanofi may not enter any settlement of any such action or
proceeding which restricts the scope, or adversely affects the enforceability,
of a Product Specific Patent, or which could be reasonably expected to have a
material adverse financial impact on Regulus, without Regulus’ prior written
consent, which consent will not be unreasonably withheld, conditioned or
delayed.

(b) Enforcement by Regulus. If Sanofi elects not to settle, defend or bring any
action for infringement described in Section 8.4.1(a) and so notifies Regulus,
including following any request by Regulus to do so, then Regulus may defend or
bring such action at its own expense, in its own name, provided however that,
Regulus agrees not to so settle, defend or bring any action for infringement of
a Product Specific Patent Right upon Sanofi’s request based on Sanofi’s good
faith reasonable determination, the basis for which will be provided to Regulus,
that it is not in the best interest of the Parties to so settle, defend or bring
such action for infringement. In the case where Regulus proceeds to settle,
defend or bring an action for such infringement, the following will apply:
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proceeding being defended or prosecuted if so requested, and will lend its name
to such actions or proceedings if requested by Regulus or required by Applicable
Law; (ii) Regulus will reimburse Sanofi for the documented external costs Sanofi
reasonably incurs, including attorneys fees, in providing such assistance as
specifically requested in writing by Regulus; (iii) Sanofi will have the right
to participate and be represented in any such suit by its own counsel at its own
expense, provided that Regulus will retain overall responsibility for the
prosecution of such suit or proceedings in such event; and (iv) Regulus may not
enter any settlement of any action or proceeding defended or brought by Regulus
with respect to a Product Specific Patent, which restricts the scope, or
adversely affects the enforceability, of a Product Specific Patent, or which
could be reasonably expected to have a material adverse financial impact on
Sanofi without Sanofi’s prior written consent, which consent will not be
unreasonably withheld, conditioned or delayed.

(c) Withdrawal. If either Party brings an action or proceeding under this
Section 8.4.1 and subsequently ceases to pursue or withdraws from such action or
proceeding, it will promptly notify the other Party and the other Party may
substitute itself for the withdrawing Party and pursue such action or proceeding
in accordance with the terms of this Section 8.4.1 (including but not limited to
the proviso in the first sentence of Section 8.4.1(b)).

(d) Damages. In the event that either Party exercises the rights conferred above
in this Section 8.4.1 and recovers any damages or other sums in such action,
suit or proceeding or in settlement thereof, such damages or other sums
recovered will first be applied to all out-of-pocket costs and expenses incurred
by the Party which initiated such action, suit or proceeding, including, without
limitation, attorneys fees, and second to any out-of-pocket costs and expenses
incurred by the other Party and not previously reimbursed by the Party which
initiated such action, suit or proceeding according to this Section 8.4.1. Any
remaining amounts will: (i) if recovered by Sanofi, be divided as follows:
(A) as to ordinary damages based on lost sales or profit, Sanofi will retain
such funds and such funds will be treated as Net Sales and royalties will be
payable by Sanofi to Regulus with respect to such Net Sales in accordance with
Section 6.9 of this Agreement and (B) as to special or punitive damages, Sanofi
will receive […***…]% of the amount of such special or punitive damages and
Regulus will receive […***…]% of the amount of such special or punitive damages;
or (ii) if recovered by Regulus, […***…].

8.4.2 Regulus Core Technology Patents Other Than Joint Core Technology Patents.
Regulus will have the sole right to enforce Regulus Core Technology Patents
(other than Joint Core Technology Patents) and to defend Regulus Core Technology
Patents (other than Joint Core Technology Patents) against challenge in any
action or proceeding (other than any interferences, reissue proceedings,
oppositions or reexaminations, which are addressed above). In the event of
suspected infringement of a Regulus Core Technology Patent (other than a Joint
Core Technology Patent) by a Third Party in a country, wherein (a) the suspected
infringing activity competes with a Product being Commercialized by or on behalf
of Sanofi in such country, and (b) no other Patent Controlled by Sanofi (whether
by license under this Agreement or otherwise) is infringed or suspected to be
infringed by the suspected infringing activity, Section […***…] to such Product
in such country (with the suspected infringing product […***…]), unless Regulus
permits Sanofi to enforce the applicable Regulus Core Technology Patent against
such Third Party.

 

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8.4.3 Joint Core Technology Patents. In the event of suspected infringement of a
Joint Core Technology Patent by a Third Party in a country, wherein the
suspected infringing activity competes with a Product being commercialized by or
on behalf of Sanofi in such country, the Parties’ respective rights and
obligations with respect to enforcement of such Joint Core Technology Patent in
such country (including damages or settlement amounts received as a result
thereof) shall be as set forth in Section 8.4.1, mutatis mutandis. In the event
of any other suspected infringement of a Joint Core Technology Patent, the
Parties’ respective rights and obligations with respect to enforcement of such
Joint Core Technology Patent in such country will be the reverse of their
respective rights and obligations under Section 8.4.1, mutatis mutandis;
provided, however, that after reimbursement of costs, any remaining damages or
other amounts recovered will be allocated […***…]% to the Party that brought and
controlled the action, and […***…]% to the other Party.

8.4.4 Other Joint Patents. In the event of suspected infringement of an Other
Joint Patent by a Third Party in a country, wherein the suspected infringing
activity competes with a Product being commercialized by or on behalf of Sanofi
in such country, the Parties’ respective rights and obligations with respect to
enforcement of such Other Joint Patent in such country shall be as set forth in
Section 8.4.1, mutatis mutandis. In the event of any other suspected
infringement of an Other Joint Patent, the Parties shall mutually agree in good
faith on a case-by-case basis on the course of action to be taken and the
allocation of costs and recovered amounts.

8.4.5 Cooperation. The Party not enforcing a particular Patent under any of the
preceding provisions of this Section 8.4 will provide reasonable assistance to
the other Party (at such other Party’s expense), including providing access to
relevant documents and other evidence, making its employees available at
reasonable business hours, and joining the action to the extent necessary to
allow the enforcing Party to initiate or maintain the action.

Section 8.5 Determination of Certain Patent Matters. The Parties, acting in good
faith and on the advice of their respective internal or external patent counsel,
agree in good faith on: (i) the inventorship of Program Inventions under
Section 8.1.1, consistent with U.S. patent laws; (ii) whether any particular
Regulus Patent is a Regulus Core Technology Patent or a Product Specific Patent,
taking into full consideration the definitions of such terms set forth in
APPENDIX 1 and the Regulus Patents listed in APPENDIX 2 and APPENDIX 3 hereto;
and (iii) whether there exists a Product Specific Patent that is suspected to be
infringed by a suspected infringement under Section 8.4.1. If the Parties cannot
agree upon any such matter within 30 days of good faith discussions, the Parties
will refer such matter to independent patent counsel, not engaged by either
Party or any of its Affiliates for any matter in the previous three (3) years
and reasonably acceptable to both Parties. The determination of the independent
patent counsel with respect to such matter will be binding on the Parties. The
costs and expenses of the independent patent counsel will be shared equally
between the Parties.

Section 8.6 Data Exclusivity and Orange Book Listings. With respect to data
exclusivity periods (such as those periods listed in the FDA’s Orange Book
(including without limitation any available pediatric extensions) or periods
under national implementations of Article 11.1(a)(iii) of Directive 2001/EC/83,
or similar periods as may be applicable to a biologic, and all international
equivalents), Sanofi will use Commercially Reasonable Efforts

 

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consistent with its obligations under applicable law (including any applicable
consent order) to seek, maintain and enforce all such data exclusivity periods
available for the Products exclusively licensed by Sanofi hereunder. With
respect to filings in the FDA Orange Book or other similar filings or listings
as may be applicable (and foreign equivalents) for issued patents for a Product,
upon reasonable request by Sanofi, Regulus will provide reasonable cooperation
to Sanofi in filing and maintaining any such listing and filings. All listing
and filing decisions will be at the sole discretion of Sanofi; provided, however
that Sanofi will not list Regulus Core Technology Patents in the FDA Orange Book
without Regulus’ prior written consent, such consent not to be unreasonably
withheld or delayed. In no event will Regulus withhold or delay such consent
where the listing of such Regulus Core Technology Patent is required under
applicable law.

Section 8.7 Further Actions. Each Party will, upon the reasonable request of the
other Party, provide such assistance and execute such documents as are
reasonably necessary for such Party to exercise its rights and/or perform its
obligations pursuant to this Article 8; provided however, that neither Party
will be required to take any action pursuant to Article 8 that such Party
reasonably determines in its sole judgment and discretion conflicts with or
violates any applicable court or government order or decree.

Section 8.8 Infringement Claims; Oppositions. Sanofi and Regulus will promptly
inform the other in writing of any written notice to it of alleged infringement
or misappropriation, based on the research, development, making, using,
importing, exporting or selling of a Licensed Compound or Product, of a Third
Party’s intellectual property rights of which it will become aware. The Parties
will confer on the handling of such matter. Regulus will not acknowledge to a
Third Party the validity of any such allegation or admit liability without the
prior written consent of Sanofi, and Sanofi will not acknowledge to a Third
Party the validity of any such allegation or admit liability without the prior
written consent of Regulus. Sanofi and Regulus will each keep the other advised
of all material developments in the conduct of any proceedings in defending any
claim of such alleged infringement or misappropriation and will cooperate with
the other in the conduct of such defense. In no event may either Party settle
any such infringement or misappropriation claim in a manner that would limit the
rights of the other Party or impose any obligation on the other Party, without
such other Party’s prior written consent, such consent not to be unreasonably
withheld or delayed. Sanofi and Regulus will promptly inform the other in
writing of any written notice to it of actual or threatened opposition related
to the Product Specific Patents. The Parties will confer on the handling of such
matter and such matters will be handled in accordance with Section 8.2 above.

Section 8.9 Records Regarding Regulus Patents. Each Party will assign patent
counsel representatives who will be responsible for coordinating activities
between the Parties in accordance with this Article 8. Such representatives will
use commercially reasonable efforts to maintain a report listing the Regulus
Patents that are subject to the license granted to Sanofi under Section 2.1.
Such report will be used to facilitate the identification and tracking of the
Regulus Patents licensed under this Agreement, but will not, unless specifically
agreed to in a separate written agreement signed by authorized representatives
of both Parties, be considered to be a then-current complete and binding list of
the Regulus Patents licensed under this Agreement.

 

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Section 8.10 Challenge. As a material inducement for entering into this
Agreement, Sanofi acknowledges and agrees that during the term of this
Agreement, solely with respect to claims within the Regulus Patents that are
included in the license granted to Sanofi under Section 2.1, in any of the
Options or in any of the Program Licenses, in the event that Sanofi, its
Affiliates or sublicensees (a) commences or otherwise voluntarily determines to
participate in (other than as may be necessary or reasonably required to respond
to a court request or order or administrative law request or order) any action
or proceeding, challenging or denying the validity of any claim within an issued
patent or patent application within the Regulus Patents, or (b) directs,
supports or actively assists any other Person (other than as may be necessary or
reasonably required to respond to a court request or order or administrative law
request or order) in bringing or prosecuting any action or proceeding
challenging or denying the validity of any claim within an issued patent or
patent application within the Regulus Patents, then, in each case, Sanofi will
be deemed to have materially breached this Agreement, and Regulus shall be
deemed to have grounds for termination of this Agreement under Section 9.3.

Section 8.11 Amendments to Third Party Agreements. Regulus will not amend or
agree to amend any Existing Regulus Agreement, Future Regulus Agreement, or New
Core Technology Agreement for New Core Technology included in the Regulus
Technology licensed to Sanofi under Section 2.1 or under any Program License, in
any manner that would increase Sanofi’s payment obligations or reduce the scope
of Sanofi’s license under Section 2.1 or any Program License, without the prior
written consent of Sanofi.

ARTICLE 9

TERM AND TERMINATION

Section 9.1 Term. The term of this Agreement (the “Term”) commences upon the
Effective Date and, unless earlier terminated in accordance with the provisions
of this Article 9, will continue until the expiration of all payment obligations
on all Products to Regulus.

Section 9.2 Sanofi Right to Terminate. Sanofi may terminate this Agreement
(including its license rights under this Agreement) in full, or on a
Product-by-Product basis, effective upon 30 days prior written notice. For
purposes of clarification, milestone and royalty payments will be due on
milestones achieved and Products sold during the period between notice of
termination and the effective date of termination.

Section 9.3 Material Breach.

(a) If either Party believes that the other is in material breach of this
Agreement (other than with respect to a breach of Sanofi’s obligations under
Section 5.1, which is governed by Section 9.4), then the non-breaching Party may
deliver notice of such breach to the other Party. In such notice the
non-breaching Party will identify the actions or conduct that it wishes such
Party to take for an acceptable and prompt cure of such breach (or will
otherwise state its good faith belief that such breach is incurable); provided
that such identified actions or conduct will not be binding upon the other Party
with respect to the actions that it may need to take to cure such breach. If the
breach is curable, the allegedly breaching Party will have 120 days to either
cure such breach (except to the extent such breach involves the failure to make

 

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a payment when due, which breach must be cured within 30 days following such
notice) or, if a cure cannot be reasonably effected within such 120-day period,
to deliver to the non-breaching Party a plan for curing such breach which is
reasonably sufficient to effect a cure within a reasonable period. If the
breaching Party fails to (i) cure such breach within the 120-day (or 30-day, as
applicable) period or (ii) use Commercially Reasonable Efforts to carry out the
plan and cure the breach, the non-breaching Party may terminate this Agreement
on a Product-by-Product basis by providing written notice to the breaching
Party.

(b) Notwithstanding the foregoing, if the allegedly breaching Party disputes in
good faith the existence, materiality, or failure to cure of any such breach
which is not a payment breach, and provides notice to the non-breaching Party
(the “Other Party”) of such dispute within such 120-day period, the Other Party
will not have the right to terminate this Agreement in accordance with this
Section 9.3 unless and until it has been determined in accordance with
Section 12.4 that this Agreement was materially breached by the allegedly
breaching Party and that Party fails to cure such breach within 120 days
following such determination. It is understood and acknowledged that during the
pendency of such a dispute, all of the terms and conditions of this Agreement
will remain in effect and the Parties will continue to perform all of their
respective obligations hereunder.

(c) This Section 9.3 will be subject to and will not limit the provisions of
Section 9.4 and Section 9.6.

Section 9.4 Termination by Regulus For Failure of Sanofi to Use Commercially
Reasonable Efforts.

9.4.1 Subject to Sections 9.4.3 and 9.4.4, at any time after the earlier of
(a) exercise of the Option for at least one of the Mir-21 POC Programs and
(b) the expiration of the Option Periods with respect to both of the Mir-21 POC
Programs without Sanofi’s exercise of either of such Options, Regulus will have
the right to terminate the license granted under Section 2.1 and the Program
Licenses for Mir-21 (and the corresponding exclusivity obligation under
Section 2.5) on a Mir-21 Product-by-Mir-21 Product basis and country-by-country
basis, if Sanofi is in breach of its obligations to use Commercially Reasonable
Efforts as set forth in Section 5.1, provided however, that the Agreement will
not so terminate unless (i) Sanofi is given 30 days prior written notice by
Regulus of Regulus’ intent to terminate, stating the reasons and justification
for such termination and recommending steps which Sanofi should take, and
(ii) Sanofi, or its sublicensee, has not used Commercially Reasonable Efforts
during the 120-day period following such notice to pursue the Development and/or
Commercialization of at least one Mir-21 Compound or Mir-21 Product in the
applicable country. Any such termination will be limited in force and effect to
the country or countries and Products to which such breach relates.

9.4.2 Subject to Sections 9.4.3 and 9.4.4, at any time after the exercise of the
Option for the Mir-221/222 Oncology POC Program, Regulus will have the right to
terminate the Program License for Mir-221/222 (and the corresponding exclusivity
obligation under Section 2.5) on a Mir-221/222 Product-by-Mir-221/222 Product
basis and country-by-country basis, if Sanofi is in breach of its obligations to
use Commercially Reasonable Efforts as set forth in Section 5.1, provided
however, that the Agreement will not so terminate unless (i) Sanofi is

 

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given 30 days prior written notice by Regulus of Regulus’ intent to terminate,
stating the reasons and justification for such termination and recommending
steps which Sanofi should take, and (ii) Sanofi, or its sublicensee, has not
used Commercially Reasonable Efforts during the 120-day period following such
notice to pursue the Development and/or Commercialization of at least one
Mir-221/222 Compound or Mir-221/222 Product in the applicable country. Any such
termination will be limited in force and effect to the country or countries and
Products to which such breach relates.

9.4.3 It is understood and acknowledged that if Sanofi (by itself or through its
Affiliates or sublicensees) uses Commercially Reasonable Efforts to Develop and
Commercialize a Product for each Collaboration Target in each and every Major
Market Country, Sanofi will be deemed to be in compliance with its obligation
under Section 5.1 to use Commercially Reasonable Efforts to Develop and
Commercialize a Product for such Collaboration Target with respect to all
countries in the world.

9.4.4 If Sanofi disputes in good faith the existence or materiality of an
alleged breach specified in a notice provided by Regulus pursuant to
Section 9.4.1 or 9.4.2, and provides notice to Regulus of such dispute within
the 30 days following such notice provided by Regulus, Regulus will not have the
right to terminate this Agreement unless and until the existence of such
material breach or failure by Sanofi has been determined in accordance with
Section 12.4 and Sanofi fails to cure such breach within 30 days following such
determination. It is understood and acknowledged that during the pendency of
such a dispute, all of the terms and conditions of this Agreement will remain in
effect and the Parties will continue to perform all of their respective
obligations hereunder.

Section 9.5 Automatic Termination. If, at any time, (a) no Option for any POC
Program remains exercisable (whether due to expiration of the applicable Option
Period or early termination of the applicable POC Program), (b) the license
granted by Regulus to Sanofi pursuant to Section 2.1.1 has terminated in its
entirety, and (c) no Program License for any POC Program is in effect, then,
effective upon the last to occur of (a), (b) and (c), this Agreement shall
automatically terminate in its entirety.

Section 9.6 Consequences of Termination.

9.6.1 Licenses. Upon termination of this Agreement in its entirety by either
Party pursuant to this Article 9 or automatic termination of this Agreement in
its entirety pursuant to Section 9.5, the licenses granted by Regulus to Sanofi
hereunder will terminate.

9.6.2 Return of Information and Materials. Upon termination of this Agreement in
its entirety by either Party pursuant to this Article 9 or automatic termination
of this Agreement in its entirety pursuant to Section 9.5, the Parties will
return (or destroy, as directed by the other Party) all data, files, records and
other materials containing or comprising the other Party’s Confidential
Information. Notwithstanding the foregoing, the Parties will be permitted to
retain one copy of such data, files, records, and other materials for archival
purposes, and with respect to Regulus, to practice its rights under
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Section 9.7 Accrued Rights; Surviving Obligations.

9.7.1 Accrued Rights. Termination or expiration of this Agreement for any reason
will be without prejudice to any rights or financial compensation that will have
accrued to the benefit of a Party prior to such termination or expiration. Such
termination or expiration will not relieve a Party from obligations that are
expressly indicated to survive the termination or expiration of this Agreement.

9.7.2 Survival. Articles 7, 9, 10, 11 and 13; and Section 6.18, Section 6.21,
and Section 12.4 of this Agreement will survive expiration or termination of
this Agreement for any reason. Furthermore, Regulus hereby grants to Sanofi a
worldwide non-exclusive license, with the right to grant sublicenses under
Section 2.4, to Regulus Know-How existing now or in the future and disclosed to
Sanofi during the Term, solely for the further manufacture and sale of Licensed
Compounds and Products after the expiration (but not the termination) of the
Term.

Section 9.8 Rights in Bankruptcy. All rights and licenses granted under or
pursuant to this Agreement by Regulus or Sanofi are, and will otherwise be
deemed to be, for purposes of Section 365(n) of the U.S. Bankruptcy Code (i.e.,
Title 11 of the U.S. Code) or analogous provisions of Applicable Law outside the
United States, licenses of rights to “intellectual property” as defined under
Section 101 of the U.S. Bankruptcy Code or analogous provisions of Applicable
Law outside the United States. The Parties agree that each Party, as licensee of
such rights under this Agreement, will retain and may fully exercise all of its
rights and elections under the U.S. Bankruptcy Code or any other provisions of
Applicable Law outside the United States that provide similar protection for
‘intellectual property.’ The Parties further agree that, in the event of the
commencement of a bankruptcy proceeding by or against a Party under the U.S.
Bankruptcy Code or analogous provisions of Applicable Law outside the United
States, the Party that is not subject to such proceeding will be entitled to a
complete duplicate of (or complete access to, as appropriate) such intellectual
property and all embodiments of such intellectual property, which, if not
already in the non subject Party’s possession, will be promptly delivered to it
upon the non subject Party’s written request therefor. Any agreements
supplemental hereto will be deemed to be “agreements supplementary to” this
Agreement for purposes of Section 365(n) of the U.S. Bankruptcy Code.

ARTICLE 10

REGULUS REVERSION RIGHT

Section 10.1 Regulus Reversion Rights. For clarity, the Parties’ rights and
obligations under this Section 10.1 are in addition to their rights and
obligations under Sections 2.1.4, 2.2.3, 3.4.3(a) and 3.4.3(b), and this
Article 10 shall not apply to any Expired Mir-21 Program Product, Terminated
Mir-21 Program Product, or any Mir-221/222 Product that is the subject of a
license granted to Regulus pursuant to Section 2.2.3(b) or Section 3.4.3(b)(ii).
If (i) Sanofi terminates the Agreement (in full or on a Product-by-Product
basis) under Section 9.2, (ii) Sanofi’s Program License with respect to a POC
Program Product is terminated after Sanofi’s exercise of its Option with respect
to such POC Program, or (iii) Regulus terminates the Agreement under Section 9.3
or Section 9.4, Regulus may continue to Develop and Commercialize any Licensed
Compound or Product that is the subject of such termination or expiration (a
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Product”). If Regulus provides a notice in writing to Sanofi within 90 days of
such termination (an “Election Notice”) that Regulus is exercising its rights
under this Section 10.1, subject to Regulus’ payment obligations (if applicable)
under Section 10.2, Sanofi will, and it hereby does: (x) grant to Regulus a
sublicensable, worldwide license or sublicense, as the case may be, to all
Sanofi Product Specific Patents, Program Patents and Research Results Controlled
by Sanofi as of the date of the Election Notice solely as they are necessary to
make, have made, use, sell, offer for sale, have sold and import Discontinued
Products, (y) transfer to Regulus, for Regulus’ use with respect to the
Development and Commercialization of the Discontinued Products, any data,
results, regulatory information and files in the possession of Sanofi as of the
date of the Election Notice that relate to such Discontinued Products, and
(z) transfer and assign to Regulus all Regulatory Documentation with respect to
such Discontinued Product (including but not limited to identifying for Regulus,
and authorizing Regulus to reference, any Drug Master File with a Regulatory
Authority related to such Discontinued Product).

Section 10.2 Regulus Payment Obligations for Reversion Rights. If, after Sanofi
has paid the Option Exercise Fee and the POC Program Reimbursement Amount for a
POC Program, both (a) Regulus provides an Election Notice for any Discontinued
Product and (b) prior to the applicable termination under this Agreement, such
Discontinued Product had completed […***…] with respect to the applicable POC
Program, then Regulus shall pay to Sanofi (i) […***…] of any […***…] such
Discontinued Product […***…]; or (ii) if […***…] with the provisions of
Section 6.10 through Section 6.21 applying mutatis mutandis. For purposes of
this Agreement, “Licensing Revenues” will mean any payments that Regulus
receives from a Third Party in consideration of a license to further the
Development and Commercialization of a Discontinued Mir-21 Product, in each case
including, but not limited to, upfront payments, license fees, regulatory or
sales milestone payments, royalties and/or profit sharing payments, but
excluding: (i) payments made in consideration of […***…], (ii) payments to
[…***…], and (iii) payments to […***…].

ARTICLE 11

INDEMNIFICATION, INSURANCE AND LIMITATION OF LIABILITY

Section 11.1 Indemnification of Regulus. Sanofi agrees to defend Regulus, its
Affiliates and their respective directors, officers, stockholders, employees and
agents, and their respective successors, heirs and assigns (collectively, the
“Regulus Indemnitees”), and will indemnify and hold harmless the Regulus
Indemnitees, from and against any liabilities, losses, costs, damages, fees or
expenses payable to a Third Party, and reasonable attorneys’ fees and other
legal expenses with respect thereto (collectively, “Losses”) arising out of any
claim, action, lawsuit or other proceeding by a Third Party (collectively,
“Third Party Claims”) brought against any Regulus Indemnitee and resulting from
or occurring as a result of: (a) any Sanofi

 

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Program Activities conducted by a Sanofi employee, consultant or (sub)contractor
in the performance of a POC Program; (b) the Development, manufacture, use,
handling, storage, sale or other Commercialization or disposition of any
Licensed Compound or Product in the Territory by Sanofi or its Affiliates,
sublicensees or contractors, (c) any breach by Sanofi of any of its
representations, warranties or covenants pursuant to this Agreement or (d) the
negligence or willful misconduct of Sanofi or any Sanofi Affiliate or
sublicensee in connection with this Agreement; except in any such case to the
extent such Losses result from: (i) the negligence or willful misconduct of any
Regulus Indemnitee, (ii) any breach by Regulus of any of its representations,
warranties, covenants or obligations pursuant to this Agreement, or (iii) any
breach of Applicable Law by any Regulus Indemnitee.

Section 11.2 Indemnification of Sanofi. Regulus agrees to defend Sanofi, its
Affiliates and their respective directors, officers, stockholders, employees and
agents, and their respective successors, heirs and assigns (collectively, the
“Sanofi Indemnitees”), and will indemnify and hold harmless the Sanofi
Indemnitees, from and against any Losses and Third Party Claims brought against
any Sanofi Indemnitee and resulting from or occurring as a result of: (a) any
activities conducted by a Regulus employee, consultant or (sub)contractor in the
performance of the Research Program or a POC Program (unless such activities
were the subject of a dispute between Regulus’ and Sanofi’s representatives on
the JSC that was finally resolved by Sanofi’s Senior Representative, as
reflected in the minutes of JSC proceedings); (b) the Development, manufacture,
use, handling, storage, sale or other Commercialization or disposition of any
Licensed Compound or Product in the Territory by Regulus or its Affiliates,
sublicensees or contractors; (c) any breach by Regulus of any of its
representations, warranties or covenants pursuant to this Agreement or (d) the
negligence or willful misconduct of any Regulus Indemnitee or any
(sub)contractor of Sanofi in connection with this Agreement; except in any such
case to the extent such Losses result from: (i) the negligence or willful
misconduct of any Sanofi Indemnitee, (ii) any breach by Sanofi of any of its
representations, warranties, covenants or obligations pursuant to this
Agreement, or (iii) any breach of Applicable Law by any Sanofi Indemnitee.

Section 11.3 Notice of Claim. All indemnification claims provided for in
Sections 11.1 and 11.2 will be made solely by such Party to this Agreement (the
“Indemnified Party”). The Indemnified Party will give the indemnifying Party
prompt written notice (an “Indemnification Claim Notice”) of any Losses or the
discovery of any fact upon which the Indemnified Party intends to base a request
for indemnification under Section 11.1 or 11.2, but in no event will the
indemnifying Party be liable for any Losses to the extent such Losses result
from any delay in providing such notice. Each Indemnification Claim Notice must
contain a description of the claim and the nature and amount of such Loss (to
the extent that the nature and amount of such Loss is known at such time). The
Indemnified Party will furnish promptly to the indemnifying Party copies of all
papers and official documents received in respect of any Losses and Third Party
Claims.

Section 11.4 Defense, Settlement, Cooperation and Expenses.

11.4.1 Control of Defense. At its option, the indemnifying Party may assume the
defense of any Third Party Claim by giving written notice to the Indemnified
Party within 30 calendar days after the indemnifying Party’s receipt of an
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assumption of the defense of a Third Party Claim by the indemnifying Party will
not be construed as an acknowledgment that the indemnifying Party is liable to
indemnify the Indemnified Party in respect of the Third Party Claim, nor will it
constitute a waiver by the indemnifying Party of any defenses it may assert
against the Indemnified Party’s claim for indemnification. Upon assuming the
defense of a Third Party Claim, the indemnifying Party may appoint as lead
counsel in the defense of the Third Party Claim any legal counsel selected by
the indemnifying Party. In the event the indemnifying Party assumes the defense
of a Third Party Claim, the Indemnified Party will as soon as is reasonably
possible deliver to the indemnifying Party all original notices and documents
(including court papers) received by the Indemnified Party in connection with
the Third Party Claim. Should the indemnifying Party assume the defense of a
Third Party Claim, except as provided in Section 11.4.1, the Indemnified Party
will be responsible for the legal costs or expenses subsequently incurred by
such Indemnified Party in connection with the analysis, defense or settlement of
the Third Party Claim.

11.4.2 Right to Participate in Defense. Without limiting Section 11.4.1, any
Indemnified Party will be entitled to participate in, but not control, the
defense of such Third Party Claim and to employ counsel of its choice for such
purpose; provided, however, that such employment will be at the Indemnified
Party’s own cost and expense unless (i) the employment thereof has been
specifically authorized by the indemnifying Party in writing, (ii) the
indemnifying Party has failed to assume the defense and employ counsel in
accordance with Section 11.4.1 (in which case the Indemnified Party will control
the defense) or (iii) the interests of the Indemnified Party and the
indemnifying Party with respect to such Third Party Claim are sufficiently
adverse to prohibit the representation by the same counsel of both Parties under
Applicable Law, ethical rules or equitable principles in which case the
indemnifying Party will be responsible for any such costs and expenses of
counsel for the Indemnified Party.

11.4.3 Settlement. With respect to any Third Party Claims relating solely to the
payment of money damages in connection with a Third Party Claim and that will
not admit liability or violation of Law on the part of the Indemnified Party or
result in the Indemnified Party’s becoming subject to injunctive or other relief
or otherwise adversely affecting the business of the Indemnified Party in any
manner (such as granting a license or admitting the invalidity of a Patent
Controlled by an Indemnified Party), and as to which the indemnifying Party will
have acknowledged in writing the obligation to indemnify the Indemnified Party
hereunder, the indemnifying Party will have the sole right to consent to the
entry of any judgment, enter into any settlement or otherwise dispose of such
Loss, on such terms as the indemnifying Party, in its sole discretion, will deem
appropriate. With respect to all other Losses in connection with Third Party
Claims, where the indemnifying Party has assumed the defense of the Third Party
Claim in accordance with Section 11.4.1, the indemnifying Party will have
authority to consent to the entry of any judgment, enter into any settlement or
otherwise dispose of such Loss provided it obtains the prior written consent of
the Indemnified Party (which consent will not be unreasonably withheld). The
indemnifying Party will not be liable for any settlement or other disposition of
a Loss by an Indemnified Party that is reached without the written consent of
the indemnifying Party. Regardless of whether the indemnifying Party chooses to
defend or prosecute any Third Party Claim, no Indemnified Party will admit any
liability with respect to or settle, compromise or discharge, any Third Party
Claim without the prior written consent of the indemnifying Party, such consent
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11.4.4 Cooperation. Regardless of whether the indemnifying Party chooses to
defend or prosecute any Third Party Claim, the Indemnified Party will, and will
cause each other Indemnified Party to, cooperate in the defense or prosecution
thereof and will furnish such records, information and testimony, provide such
witnesses and attend such conferences, discovery proceedings, hearings, trials
and appeals as may be reasonably requested in connection therewith. Such
cooperation will include access during normal business hours afforded to
indemnifying Party to, and reasonable retention by the Indemnified Party of,
records and information that are reasonably relevant to such Third Party Claim,
and making Indemnified Parties and other employees and agents available on a
mutually convenient basis to provide additional information and explanation of
any material provided hereunder, and the indemnifying Party will reimburse the
Indemnified Party for all its reasonable out-of-pocket costs and expenses in
connection therewith.

11.4.5 Costs and Expenses. Except as provided above in this Section 11.4, the
costs and expenses, including attorneys’ fees and expenses, incurred by the
Indemnified Party in connection with any claim will be reimbursed on a Calendar
Quarter basis by the indemnifying Party, without prejudice to the indemnifying
Party’s right to contest the Indemnified Party’s right to indemnification and
subject to refund in the event the indemnifying Party is ultimately held not to
be obligated to indemnify the Indemnified Party.

Section 11.5 Insurance.

11.5.1 Regulus’ Insurance Obligations. Regulus shall maintain, at its cost,
reasonable insurance against liability and other risks associated with its
activities contemplated by this Agreement, including but not limited to its
indemnification obligations herein, in such amounts and on such terms as are
customary for prudent practices for biotech companies of similar size and with
similar resources in the pharmaceutical industry for the activities to be
conducted by it under this Agreement taking into account the scope of
development of products, provided, that, at a minimum, Regulus shall maintain,
in force at its sole cost, a general liability insurance policy providing
coverage of at least $[…***…] per claim and $[…***…] annual aggregate. In
addition to the foregoing, in the event that Regulus plans to Commercialize any
Discontinued Product, then Regulus shall increase its insurance coverage
commensurate with the additional liability and other risks associated with
Commercialization activities, and at a minimum provide that the annual aggregate
amount of such coverage is increased to at least $[…***…] at least thirty
(30) days before Regulus initiates the First Commercial Sale of any Discontinued
Product hereunder. Regulus shall furnish to Sanofi evidence of any insurance
required under this Section 11.5, upon request.

11.5.2 Sanofi’s Insurance Obligations. Sanofi hereby represents and warrants to
Regulus that it is self-insured against liability and other risks associated
with its activities and obligations under this Agreement in such amounts and on
such terms as are customary for prudent practices for large companies in the
pharmaceutical industry for the activities to be conducted by Sanofi under this
Agreement. Sanofi shall maintain such self insurance throughout the term of this
Agreement and shall furnish to Regulus evidence of such self-insurance, upon
request.

 

***Confidential Treatment Requested

 

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ARTICLE 12

REPRESENTATIONS AND WARRANTIES

Section 12.1 Representations, Warranties and Covenants. Each Party hereby
represents and warrants as of the Effective Date and covenants to the other
Party that:

12.1.1 it has the power and authority and the legal right to enter into this
Agreement and perform its obligations hereunder, and that it has taken all
necessary action on its part required to authorize the execution and delivery of
this Agreement and the performance of its obligations hereunder;

12.1.2 this Agreement has been duly executed and delivered on behalf of such
Party and constitutes a legal, valid and binding obligation of such Party and is
enforceable against it in accordance with its terms subject to the effects of
bankruptcy, insolvency or other laws of general application affecting the
enforcement of creditor rights and judicial principles affecting the
availability of specific performance and general principles of equity, whether
enforceability is considered a proceeding at law or equity;

12.1.3 all necessary consents, approvals and authorizations of all Regulatory
Authorities and other Parties required to be obtained by such Party in
connection with the execution and delivery of this Agreement and the performance
of its obligations hereunder have been obtained; and

12.1.4 the execution and delivery of this Agreement and the performance of such
Party’s obligations hereunder (i) do not conflict with or violate any
requirement of Applicable Law or any provision of the certificate of
incorporation, bylaws or any similar instrument of such Party, as applicable, in
any material way, and (ii) do not conflict with, violate, or breach or
constitute a default or require any consent not already obtained under, any
contractual obligation or court or administrative order by which such Party is
bound.

Section 12.2 Regulus Representations, Warranties, and Covenants. Regulus hereby
represents and warrants to Sanofi as of the Effective Date that:

12.2.1 Regulus is the owner of, or otherwise has the right to grant all rights
and licenses it purports to grant to Sanofi with respect to the Regulus Patents
under this Agreement for Mir-21 and Licensed Compounds identified by Regulus on
or before the Effective Date that target Mir-21;

12.2.2 To the best of its knowledge and belief, Regulus does not require any
additional licenses or other intellectual property rights in order for Regulus
to conduct its obligation under the R&D Plan with respect to Mir-21 and Licensed
Compounds identified by Regulus on or before the Effective Date that target
Mir-21;

12.2.3 Regulus has not received any written claim alleging that any of the
Regulus Patents are invalid or unenforceable;

 

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12.2.4 Regulus has not received any written claim alleging that any of Regulus’
activities relating to Mir-21 and Licensed Compounds identified by Regulus on or
before the Effective Date that target Mir-21, or any of Regulus’ activities of
the type proposed to be undertaken pursuant to the R&D Plan, infringe any
intellectual property rights of a Third Party;

12.2.5 All employees, consultants, or (sub)contractors of Regulus or Affiliates
performing Development activities hereunder on behalf of Regulus are, and
Regulus hereby covenants to Sanofi that they will be, obligated to assign all
right, title and interest in and to any inventions developed by them, whether or
not patentable, to Regulus or Affiliate, respectively, as the sole owner
thereof;

12.2.6 Regulus will, and Regulus hereby covenants to, as appropriate, hire and
maintain sufficient staff and management to support and conduct the Research
Program and each POC Program hereunder in a timely fashion;

12.2.7 If reasonably requested by Sanofi in writing, Regulus will, and Regulus
hereby covenants to, take reasonable, good faith measures and cooperate with
Sanofi to help to facilitate a good faith negotiation between Sanofi and any
Existing Regulus Agreement in the event that Sanofi desires to pursue the
Development or Commercialization of any Licensed Compound or Product and would
require a license directly from any such Third Party;

12.2.8 Regulus will not, and Regulus hereby covenants to Sanofi not to, withhold
from Sanofi any material information or correspondence, including to or from any
Regulatory Authority, that would be material and relevant to a reasonable
assessment of the scientific, commercial, safety, and regulatory liabilities or
commercial value of the Licensed Compounds;

12.2.9 Regulus will, and Regulus hereby covenants to Sanofi that it will,
perform its activities pursuant to this Agreement in compliance with good
laboratory and clinical practices and cGMP, in each case as applicable under the
laws and regulations of the country and the state and local government wherein
such activities are conducted, and with respect to the care, handling and use in
Development activities hereunder of any non-human animals by or on behalf of
Regulus, will at all times comply (and will ensure compliance by any of its
subcontractors) with all applicable federal, state and local laws, regulations
and ordinances and the guiding principles of the “3R’s”, namely, wherever
reasonably possible, reducing the number of animals used, replacing animals with
non-animal methods and refining the research techniques used for the proper
care, handling and use of animals in pharmaceutical research and development
activities; and

12.2.10 The licenses granted to Regulus under the Existing Regulus Agreements
are in full force and effect and Regulus has not received any written notice,
and is not aware, of any breach by any party to the Existing Regulus Agreements.

Section 12.3 Sanofi Covenants. Sanofi hereby covenants to Regulus that it will
perform its activities pursuant to this Agreement in compliance with good
laboratory and clinical practices and cGMP, in each case as applicable under the
laws and regulations of the country and the state and local government wherein
such activities are conducted, and with respect to the care, handling and use in
Development activities hereunder of any non-human animals by or on

 

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behalf of Sanofi, will at all times comply (and will ensure compliance by any of
its subcontractors) with all Applicable Laws and the guiding principles of the
“3R’s”, namely, wherever reasonably possible, reducing the number of animals
used, replacing animals with non-animal methods and refining the research
techniques used for the proper care, handling and use of animals in
pharmaceutical research and development activities.

Section 12.4 DISCLAIMER OF WARRANTY. EXCEPT FOR THE EXPRESS WARRANTIES SET FORTH
IN THIS ARTICLE 12, SANOFI AND REGULUS MAKE NO REPRESENTATIONS AND GRANT NO
WARRANTIES, EXPRESS OR IMPLIED, EITHER IN FACT OR BY OPERATION OF LAW, BY
STATUTE OR OTHERWISE, AND SANOFI AND REGULUS EACH SPECIFICALLY DISCLAIM ANY
WARRANTIES, WHETHER WRITTEN OR ORAL, OR EXPRESS OR IMPLIED, INCLUDING ANY
WARRANTY OF QUALITY, MERCHANTABILITY OR FITNESS FOR A PARTICULAR USE OR PURPOSE
OR ANY WARRANTY AS TO THE VALIDITY OF ANY PATENTS OR THE NON-INFRINGEMENT OF ANY
INTELLECTUAL PROPERTY RIGHTS OF THIRD PARTIES.

ARTICLE 13

MISCELLANEOUS

Section 13.1 Assignment; Sanofi Affiliates. Except as expressly set forth in
this Agreement, without the prior written consent of the other Party hereto,
neither Party will sell, transfer, assign, delegate, pledge or otherwise dispose
of, whether voluntarily, involuntarily, by operation of law or otherwise, this
Agreement or any of its rights or duties hereunder; provided, however, that:

(a) either Party may assign this Agreement and its rights and obligations
hereunder without the other Party’s consent in connection with the transfer or
sale of all or substantially all of the business of such Party to which this
Agreement relates to a Third Party, whether by merger, sale of stock, sale of
assets or otherwise, provided that in the event of such a sale or transfer
(whether this Agreement is actually assigned or is assumed by the acquiring
party by operation of law (e.g., in the context of a reverse triangular
merger)), intellectual property rights of the acquiring party in such sale or
transfer (if other than one of the Parties to this Agreement) shall not be
included in the technology licensed hereunder or otherwise subject to this
Agreement;

(b) Sanofi may, without Regulus’ consent, assign this Agreement and its rights
and obligations hereunder to an Affiliate of Sanofi, provided that such
Affiliate agrees to be bound by the terms and conditions of this Agreement and
that no such assignment to an Affiliate will relieve Sanofi of its obligations
hereunder; and

(c) Regulus may assign or transfer its rights under Article 6 (but no
liabilities) to a Third Party in connection with a royalty factoring
transaction.

The rights and obligations of the Parties under this Agreement shall be binding
upon and inure to the benefit of the successors and permitted assigns of the
Parties, and the name of a Party appearing herein will be deemed to include the
name of such Party’s successors and

 

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permitted assigns to the extent necessary to carry out the intent of this
section. Any purported assignment or transfer in violation of this Section 13.1
will be void ab initio and of no force or effect.

Section 13.2 Severability. If any provision of this Agreement is held to be
illegal, invalid or unenforceable by a court of competent jurisdiction, such
adjudication will not affect or impair, in whole or in part, the validity,
enforceability, or legality of any remaining portions of this Agreement. All
remaining portions will remain in full force and effect as if the original
Agreement had been executed without the invalidated, unenforceable or illegal
part.

Section 13.3 Governing Law; Jurisdiction. This Agreement will be governed by and
construed and enforced in accordance with the laws of the State of New York, USA
without reference to any rules of conflicts of laws. For clarification, any
dispute relating to the scope, validity, enforceability or infringement of any
Patents will be governed by and construed and enforced in accordance with the
patent laws of the applicable jurisdiction.

Section 13.4 Dispute Resolution.

13.4.1 Resolution by Senior Representatives. The Parties will seek to settle
amicably any and all disputes, controversies or claims arising out of or in
connection with this Agreement. Any dispute within the JSC’s decision-making
authority will be finally decided as set forth in APPENDIX 5. Any dispute
between the Parties which is outside the JSC’s decision-making authority and is
not subject to resolution under Section 6.11.1 or Section 13.4.5 will be
promptly presented to each Party’s respective co-chair of the JSC for
resolution, and if the co-chairs of the JSC are unable to resolve such dispute,
such dispute will then be presented to the Executive VP of R&D of Sanofi and the
Executive Vice President of Regulus (the “Senior Representatives”), or their
respective designees, for resolution. Such Senior Representatives, or their
respective designees, will meet in-person or by teleconference as soon as
reasonably possible thereafter, and use their good faith efforts to mutually
agree upon the resolution of the dispute, controversy or claim. Any dispute
within the JSC’s decision-making authority will not be subject to arbitration.

13.4.2 Request for Arbitration. If after negotiating in good faith pursuant to
Section 13.4.1, after good faith discussions undertaken within reasonable
promptness, to reach an amicable agreement within 90 days, then either Party may
upon written notice to the other submit to binding arbitration pursuant to
Section 13.4.3 below. No statements made by either Party during such discussions
will be used by the other Party or admissible in arbitration or any other
subsequent proceeding for resolving the dispute.

13.4.3 Arbitration.

(a) Any dispute, claim or controversy arising from or related in any way to this
Agreement or the interpretation, application, breach, termination or validity
thereof, including any claim of inducement of this Agreement by fraud or
otherwise, not resolved under the provisions of Section 13.4.1 will be resolved
by final and binding arbitration conducted in accordance with the terms of this
Section 13.4.3. The arbitration will be held in New York, New York, USA
according to Rules of Arbitration of the International Chamber of Commerce

 

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(“ICC”). The arbitration will be conducted by a panel of three (3) arbitrators
with significant experience in the pharmaceutical industry, unless otherwise
agreed by the Parties, appointed in accordance with applicable ICC rules. Any
arbitration herewith will be conducted in the English language to the maximum
extent possible. The arbitrators will render a written decision no later than
six (6) months following the selection of the arbitrators, including a basis for
any damages awarded and a statement of how the damages were calculated. Any
award will be promptly paid in U.S. dollars free of any tax, deduction or
offset. Each Party agrees to abide by the award rendered in any arbitration
conducted pursuant to this Section 13.4.3. With respect to money damages,
nothing contained herein will be construed to permit the arbitrator or any court
or any other forum to award punitive or exemplary damages, except in the case of
breach of Article 7. By entering into this agreement to arbitrate, the Parties
expressly waive any claim for punitive or exemplary damages, except in the case
of breach of Article 7. Each Party will pay its legal fees and costs related to
the arbitration (including witness and expert fees). Judgment on the award so
rendered will be final and may be entered in any court having jurisdiction
thereof.

(b) EACH PARTY HERETO WAIVES ITS RIGHT TO TRIAL OF ANY ISSUE BY JURY. EACH PARTY
HERETO WAIVES ANY CLAIM FOR ATTORNEYS’ FEES AND COSTS AND PREJUDGMENT INTEREST
FROM THE OTHER.

(c) EXCEPT FOR LOSSES COVERED BY THE INDEMNITIES PROVIDED UNDER ARTICLE 11, AND
ANY BREACH OF THE CONFIDENTIALITY RESTRICTIONS UNDER ARTICLE 7, EACH PARTY
HERETO WAIVES (1) ANY CLAIM TO PUNITIVE, EXEMPLARY OR MULTIPLIED DAMAGES FROM
THE OTHER; AND (2) ANY CLAIM OF CONSEQUENTIAL, INDIRECT OR INCIDENTAL DAMAGES
FROM THE OTHER.

13.4.4 Disputes Regarding Material Breach. If the Parties are in dispute as to
whether one Party is in material breach of this Agreement, then the arbitrator
will first determine if material breach has in fact occurred, and if so, will
grant the defaulting Party the cure period provided pursuant to Section 9.3 (or
9.2, as applicable). If the material breach is not cured within the time period
provided pursuant to Section 9.3 (or 9.2, as applicable), the arbitration will
continue and the arbitrator will, as part of the same arbitration, award actual
direct damages to the non-defaulting Party.

13.4.5 Certain Matters Subject to Expert Panel. If, at any time during the
Research Term, the Parties disagree on any matter arising from the a POC
Program, the Parties may elect by mutual agreement to submit such matter to a
panel of three (3) experts who are experienced in the field of
biopharmaceuticals (an “Expert Panel”). All members of the Expert Panel must be
mutually agreed by the Parties in good faith and as promptly as possible and
must be free of any conflicts of interest with respect to either or both
Parties. The Expert Panel will promptly hold a hearing to review the matter, at
which they will consider briefs submitted by each Party at least 15 days before
the hearing, as well as reasonable presentations that each Party may present.
The determination of the relevant Expert Panel as to such dispute will be
binding on both Parties. The Parties will share equally in the costs of the
Expert Panel, and each Party will bear its own costs associated with preparing
for and presenting to the Expert Panel.

 

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13.4.6 Court Actions. Nothing contained in this Agreement shall deny either
Party the right to seek injunctive or other equitable relief from a court of
competent jurisdiction in the context of a bona fide emergency or prospective
irreparable harm, and such an action may be filed and maintained notwithstanding
any ongoing dispute resolution discussions or arbitration proceeding. In
addition, either Party may bring an action in any court of competent
jurisdiction to resolve disputes pertaining to the validity, construction,
scope, enforceability, infringement or other violations of patents or other
proprietary or intellectual property rights, and no such claim shall be subject
to arbitration pursuant to Section 13.4.3.

Section 13.5 Notices. Except as otherwise provided for in this Agreement, all
notices or other communications that are required or permitted hereunder will be
in the English Language and in writing and delivered personally with
acknowledgement of receipt, sent by facsimile (and promptly confirmed by
personal delivery, registered or certified mail or overnight courier as provided
herein), sent by nationally-recognized overnight courier or sent by registered
or certified mail, postage prepaid, return receipt requested, addressed as
follows:

If to Sanofi, to:

Sanofi

54, rue la Boétie

75008 Paris, France

Attention: General Counsel

Facsimile No.: +33 1 53 77 43 03

With a copy to:

Sanofi

9 Rue du Président Allende, 94256 Gentilly Cedex, France

Attention: License Management

Facsimile No.: +33 1 53 77 48 51

If to Regulus, to:

Regulus Therapeutics Inc.

3545 John Hopkins Court, Suite 210

San Diego, California 92121-1121

USA

Attention: Chief Scientific Officer

Facsimile: +1 (858) 202-6363

With a copy to:

Attention: General Counsel

Facsimile: +1 (858) 202-6363

or to such other address as the Party to whom notice is to be given may have
furnished to the other Party in writing in accordance herewith. Any such
communication will be deemed to have been given (i) when delivered, if
personally delivered or sent by facsimile on a Business Day,

 

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(ii) on the Business Day after dispatch, if sent by nationally-recognized
overnight courier, and (iii) on the third Business Day following the date of
mailing, if sent by mail. It is understood and agreed that this Section 13.5 is
not intended to govern the day-to-day business communications necessary between
the Parties in performing their duties, in due course, under the terms of this
Agreement.

Section 13.6 Entire Agreement; Modifications. This Agreement (including the
attached Appendices and the POC Program Plans), together with the Stock Purchase
Agreement, sets forth and constitutes the entire agreement and understanding
between the Parties with respect to the subject matter hereof and thereof, and
all prior agreements, understanding, promises and representations, whether
written or oral, with respect thereto are superseded hereby. Each Party confirms
that it is not relying on any representations or warranties of the other Party
except as specifically set forth herein. No amendment, modification, release or
discharge will be binding upon the Parties unless in writing and duly executed
by authorized representatives of both Parties.

Section 13.7 Headings. The headings of Articles and Sections of this Agreement
are for ease of reference only and will not affect the meaning or interpretation
of this Agreement in any way.

Section 13.8 Relationship of the Parties. It is expressly agreed that the
Parties will be independent contractors of one another and that the relationship
between the Parties will not constitute a partnership, joint venture or agency.

Section 13.9 Waiver. Any term or condition of this Agreement may be waived at
any time by the Party that is entitled to the benefit thereof, but no such
waiver will be effective unless set forth in a written instrument duly executed
by or on behalf of the Party waiving such term or condition. Any such waiver
will not be deemed a waiver of any other right or breach hereunder.

Section 13.10 Counterparts. This Agreement may be executed in two or more
counterparts, each of which will be deemed an original, but all of which
together will constitute one and the same instrument.

Section 13.11 No Benefit to Third Parties. The representations, warranties,
covenants and agreements set forth in this Agreement are for the sole benefit of
the Parties hereto and their successors and permitted assigns, and they will not
be construed as conferring any rights on any other parties.

Section 13.12 Further Assurances. Each Party will duly execute and deliver, or
cause to be duly executed and delivered, such further instruments and do and
cause to be done such further acts and things, including the filing of such
assignments, agreements, documents and instruments, as may be necessary to carry
out the provisions and purposes of this Agreement.

Section 13.13 Force Majeure. Neither Party will be charged with any liability
for delay in performance of an obligation under this Agreement to the extent
such delay is due to a cause beyond the reasonable control of the affected
Party, such as war, riots, labor disturbances, fire, explosion, earthquake, and
compliance in good faith with any governmental Law, regulation or

 

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order. The Party affected will give prompt written notice to the other Party of
any material delay due to such causes.

Section 13.14 Interpretation.

13.14.1 Each of the Parties acknowledges and agrees that this Agreement has been
diligently reviewed by and negotiated by and between them, that in such
negotiations each of them has been represented by competent counsel and that the
final agreement contained herein, including the language whereby it has been
expressed, represents the joint efforts of the Parties hereto and their counsel.
Accordingly, in the event an ambiguity or a question of intent or interpretation
arises, this Agreement will be construed as if drafted jointly by the Parties
and no presumption or burden of proof will arise favoring or disfavoring any
Party by virtue of the authorship of any provisions of this Agreement. This
Agreement has been prepared in the English language and the English language
shall control its interpretation.

13.14.2 The definitions of the terms herein will apply equally to the singular
and plural forms of the terms defined. Whenever the context may require, any
pronoun will include the corresponding masculine, feminine and neuter forms. The
words “include”, “includes” and “including” will be deemed to be followed by the
phrase “without limitation”. The word “will” will be construed to have the same
meaning and effect as the word “will”. The word “any” will mean “any and all”
unless otherwise clearly indicated by context.

13.14.3 Unless the context requires otherwise, (i) any definition of or
reference to any agreement, instrument or other document herein will be
construed as referring to such agreement, instrument or other document as from
time to time amended, supplemented or otherwise modified (subject to any
restrictions on such amendments, supplements or modifications set forth herein
or therein), (ii) any reference to any Applicable Laws herein will be construed
as referring to such Applicable Laws as from time to time enacted, repealed or
amended, (iii) any reference herein to any person will be construed to include
the person’s successors and assigns, (iv) the words “herein”, “hereof” and
“hereunder”, and words of similar import, will be construed to refer to this
Agreement in its entirety and not to any particular provision hereof, and
(v) all references herein to Articles, Sections or Appendices, unless otherwise
specifically provided, will be construed to refer to Articles, Sections and
Appendices of this Agreement.

13.14.4 References to sections of the Code of Federal Regulations and to the
United States Code will mean the cited sections, as these may be amended from
time to time.

[SIGNATURE PAGE FOLLOWS]

 

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IN WITNESS WHEREOF, the Parties hereto have caused this Agreement to be executed
by their duly authorized representatives as of the date first above written.

REGULUS THERAPEUTICS INC.

By:  

/s/ Kleanthis G. Xanthopoulos

Name:  

Kleanthis G. Xanthopoulos, Ph.D.

Title:  

President and CEO

SANOFI By:  

/s/ Philippe Goupit

Name:  

Philippe Goupit

Title:  

Vice President, Corporate Licenses

 

SIGNATURE PAGE –SECOND AMENDED AND RESTATED COLLABORATION AND LICENSE AGREEMENT

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List of Appendices

 

Appendix 1:    Definitions Appendix 2:    Product Specific Patents Appendix 3:
   Regulus Core Technology Patents Appendix 4:    Charter of JSC Appendix 5:   
Existing Regulus Agreements Appendix 6:    Initial POC Program Plans
Appendix 6A:    Initial Mir-21 Fibrosis POC Program Plan Appendix 6B:    Initial
Mir-21 Oncology POC Program Plan Appendix 6C:    Initial Mir-221/222 Oncology
POC Program Plan Appendix 7:    Listed Countries Appendix 8:    R&D Plan
Appendix 9:    Regulus Detailed Allocation of Upfront Payments Appendix 10:   
Co-Promotion Appendix 11:    Profit-Sharing Appendix 12:    Regulus Second
Restatement Press Release

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APPENDIX 1

DEFINITIONS

“Achievement of Proof of Concept” means, with respect to a particular POC
Program, a determination by the JSC or an Expert Panel (as applicable) that a
POC Program Product that is the subject of such POC Program has demonstrated
Proof of Concept in the applicable POC Study.

“Affiliate” means any Person, whether de jure or de facto, which directly or
indirectly through one (1) or more intermediaries controls, is controlled by or
is under common control with another Person. A Person will be deemed to
“control” another Person if it (a) owns, directly or indirectly, beneficially or
legally, at least 50% of the outstanding voting securities or capital stock (or
such lesser percentage which is the maximum allowed to be owned by a Person in a
particular jurisdiction) of such other Person, or has other comparable ownership
interest with respect to any Person other than a corporation; or (b) has the
power, whether pursuant to contract, ownership of securities or otherwise, to
direct the management and policies of the Person. Notwithstanding the above,
neither of the Founding Companies of Regulus will be deemed an Affiliate of
Regulus for the purposes of this Agreement under any circumstances.

“Agreement” means this Second Amended and Restated Collaboration and License
Agreement, together with all Appendices attached hereto, and the Program Plans,
as the same may be amended or supplemented from time to time in accordance with
the terms of this Agreement.

“API” means, with respect to a Product, the bulk active pharmaceutical
ingredient for a Licensed Compound manufactured in accordance with GMP for such
Product.

“Applicable Law” or “Law” means all applicable laws, statutes, rules,
regulations and other pronouncements having the effect of law of any federal,
national, multinational, state, provincial, county, city or other political
subdivision, agency or other body, domestic or foreign, including but not
limited to any applicable rules, regulations, guidelines, or other requirements
of the Regulatory Authorities that may be in effect from time to time, but
excluding patent laws.

“Approval” means, with respect to any Product in any regulatory jurisdiction,
approval from the applicable Regulatory Authority sufficient for the
manufacture, distribution, use and sale of the Product in such jurisdiction in
accordance with Applicable Laws. In jurisdictions where the applicable
Regulatory Authority sets the pricing authorizations necessary for a Product,
Approval will not be deemed to have occurred if the final approval to market and
sell the Product is being withheld because Sanofi (or its Affiliates or
sublicensee) and the Regulatory Authority have not yet determined pricing;
provided, however, that the First Commercial Sale in such jurisdiction will be
considered Approval in such jurisdiction.

“Business Day” means a day on which banking institutions in New York, New York,
United States and Paris, France are both open for business.

“Calendar Quarter” means the respective periods of three consecutive calendar
months ending on March 31, June 30, September 30 and December 31.

 

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“Collaboration Target” means either: (i) Mir-21; or (ii) Mir-221 and/or Mir-222.

“Combination Product” means a Product that includes at least one additional
active ingredient (whether coformulated or copackaged) which is not a Licensed
Compound.

“Commercialize”, “Commercializing” and “Commercialization” means activities
directed to manufacturing, obtaining pricing and reimbursement approvals, for,
marketing, promoting, distributing, importing or selling a Product, including,
without limitation, conducting pre-and post-Approval activities, including
studies reasonably required to increase the market potential of the Product and
studies to provide improved formulation and Product delivery.

“Commercially Reasonable Efforts” means, with respect to a Licensed Compound and
Product, the carrying out of discovery, research, Development or
Commercialization activities using the efforts that the applicable Party would
reasonably devote to a compound or product of similar market potential at a
similar stage in development or product life resulting from its own research
efforts, taking into account product profile, the competitive landscape and
other relevant scientific, technical and commercial factors.

“Companion Diagnostic” means, with respect to a Product, any product or method
useful for detecting the applicable Collaboration Target as a biomarker for
identifying patient populations that are better suited to respond to the
corresponding Product in the treatment and/or prophylaxis of an approved
Indication for the Product.

“Confidential Information” has the meaning set forth in Section 7.1.

“Control” means, with respect to any Know-How, Patent or other intellectual
property right, possession by a Party (including its Affiliates) of the right
(whether by ownership, license or otherwise) to grant to the other Party
ownership, a license, sublicense and/or other right to practice under such Know
How, Patent or other intellectual property right as provided for herein without
violating the terms of any agreement or other arrangement with any Third Party.
Notwithstanding anything to the contrary under this Agreement, with respect to
any Third Party acquirer that later becomes an Affiliate of Regulus after the
Effective Date, no intellectual property of such Third Party acquirer will be
included in the licenses granted hereunder by virtue of such Third Party
acquirer becoming an Affiliate of Regulus.

“Co-Promote Option” has the meaning set forth in Section Section 2.3.

“Co-Promote Right” has the meaning set forth in Section Section 2.3.

“Cover”, “Covered” or “Covering” means, with respect to a Patent, that, but for
rights granted to a Person under such Patent, the practice by such Person of an
invention claimed in such Patent would infringe a Valid Claim included in such
Patent, or in the case of a Patent that is a patent application, would infringe
a Valid Claim in such patent application if it were to issue as a patent.

“Development” means non-clinical (such as, but not limited to, IND-enabling
toxicology and production of GMP quality Product) and clinical development
activities reasonably related to the development and submission of information
to a Regulatory Authority, including, without

 

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limitation, chemical synthesis, toxicology, pharmacology, test method
development and stability testing, manufacturing process development,
formulation development, delivery system development, quality assurance and
quality control development, manufacturing, statistical analysis, and clinical
studies. When used as a verb, “Develop” means to engage in Development.

“Development Candidate” means, on a POC Program-by-POC Program basis, a Licensed
Compound meeting the Development Candidate Criteria set forth in the applicable
POC Program Plan.

“Development Candidate Criteria” means, on a POC Program-by-POC Program basis,
with respect to the Collaboration Target that is the subject of a POC Program,
the description, as set forth in the applicable POC Program Plan, of the
characteristics that shall be used by Regulus to guide the selection of a
Licensed Compound from such POC Program as a candidate for the filing of an IND
in an Indication in the applicable Target Field.

“Disclosing Party” has the meaning set forth in Section 7.1.

“Discontinued Product” has the meaning set forth in Section 10.1.

“Dollars” or “$” means the lawful currency of the United States.

“Effective Date” has the meaning set forth in the recitals on the first page of
this Agreement.

“Election Notice” has the meaning set forth in Section 10.1.

“EMEA” means the European Regulatory Authority known as the European Medicines
Agency and any successor agency thereto.

“EU” means the European Union, as its membership may be altered from time to
time, and any successor thereto, and which, as of the Effective Date, consists
of Austria, Belgium, Czech Republic, Denmark, Estonia, Finland, France, Germany,
Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, The
Netherlands, Poland, Portugal, Slovakia, Slovenia, Spain, Sweden and the United
Kingdom, and that certain portion of Cyprus included in such organization.

“Existing Regulus Agreement” means any of the agreements listed on APPENDIX 5.

“Existing Sanofi Agreement” means any agreement to which Sanofi is a party as of
the Effective Date under which Sanofi has in-licensed or acquired rights to
Patents from a Third Party.

“Expired Mir-21 Program Product” has the meaning provided in Section 2.1.4(b).

“Ex-U.S. Net Sales” has the meaning set forth in Section 6.9.2.

 

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“FDA” means the United States Food and Drug Administration and any successor
agency thereto.

“Fibrosis” means any organ and/or tissue injury or repair encompassing multiple
biological processes and/or disorders associated with organs and/or tissues as
well as wound repair. Examples include, but are not limited to, fibrotic
disorders, dermal scarring, wound healing, burns and post-operative adhesions.

“Fibrosis Field” has the meaning set forth in subparagraph (a) of the definition
of Target Field.

“First Commercial Sale” means the first sale of a Product by Sanofi, its
Affiliates or a sublicensee to a Third Party in a particular country after
Approval of such Product has been obtained in such country.

“First Restated Agreement” has the meaning set forth in the recitals on the
first page of this Agreement.

“First Restatement Date” has the meaning set forth in the recitals on the first
page of this Agreement.

“Founding Company” means individually, either Isis Pharmaceuticals, Inc. or
Alnylam Pharmaceuticals, Inc.; and collectively, both Isis Pharmaceuticals, Inc.
and Alnylam Pharmaceuticals, Inc.

“Founding Company License Agreement” means the Amended and Restated License and
Collaboration Agreement among Regulus and the Founding Companies dated
January 1, 2009, as amended as of the Effective Date.

“FTE-Day Rate” means US $[…***…] per FTE-day, subject to adjustment on an annual
basis as of January 1 of each year beginning in 2011 by a factor which reflects
changes in the Consumer Price Index for San Diego, California as reported as of
January 1 by the U.S. Department of Labor’s Bureau of Labor Statistics in each
applicable year during the Research Term when compared to the comparable
statistic for January 1 of the preceding year. The FTE-Day Rate shall be
inclusive of all allocated overhead costs, administrative expenses and other
expenses for the employee(s) providing services under this Agreement, excluding
[…***…] costs (which Sanofi will either pay directly or reimburse to Regulus
within 30 days of invoice).

“Future Regulus Agreement” has the meaning provided in Section 6.11.2.

“Future Sanofi Agreement” has the meaning provided in Section 6.11.2.

“[…***…]” means […***…].

“[…***…] Agreement” means the License Agreement among […***…] and […***…] dated
[…***…].

 

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“Generic Product(s)” means a Third Party’s product(s) or Third Parties’
product(s) that has the same or substantially the same active pharmaceutical
ingredient as a Product and receives Approval through a regulatory approval
process in which either: (i) the applicant for, or sponsor of such Approval; or
(ii) the Regulatory Authority that granted such Approval, relied, in whole or in
part, upon […***…] submitted by, or on behalf of, Sanofi (or its Affiliate or
sublicensee), to any Regulatory Authority, to support the Approval of a Product.

“Good Clinical Practice” or “GCP” will mean the then current standards for
clinical trials for pharmaceuticals, as set forth in the United States Code of
Federal Regulations, ICH guidelines and applicable regulations, laws or rules as
promulgated thereunder, as amended from time to time, and such standards of good
clinical practice as are required by the European Union and other organizations
and governmental agencies in countries in which a Licensed Product is intended
to be sold to the extent such standards are not less stringent than United
States GCP.

“Good Laboratory Practice” or “GLP” will mean the then current standards for
laboratory activities for pharmaceuticals, as set forth in the FDA’s GLP
regulations and/or ICH guidelines and applicable regulations.

“Good Manufacturing Practice(s)” or “GMP” will mean the regulatory requirements
for current good manufacturing practices promulgated in the United States Code
of Federal Regulations including those rules promulgated by the United States
Food and Drug Administration under the U.S. Food, Drug and Cosmetic Act, 21
C.F.R. § 210 et seq., and ICH Guidelines and applicable regulations, as the same
may be amended from time to time.

“[…***…]” means the […***…] Agreement dated […***…], between […***…] and
[…***…], as amended.

“IND” means an Investigational New Drug Application (as defined in the Food,
Drug and Cosmetic Act, as amended) filed with the FDA or its foreign
counterparts.

“IND Approval” means the acceptance (or deemed acceptance) of the filing of an
IND by the applicable Regulatory Authority. For purposes of clarity, acceptance
(or deemed acceptance) of the filing of the foreign equivalent of an IND by the
applicable Regulatory Authority in such country will be an IND Approval.

“Indemnified Party” has the meaning set forth in Section 11.3.

“Indemnification Claim Notice” has the meaning set forth in Section 11.3.

“Indication” means mean any human or animal disease or condition, or sign or
symptom of a human or animal disease or condition.

“Initiation of Phase 1 Trial” means the dosing of the first human subject in a
Phase 1 Trial.

“Initiation of Phase 2 Trial” means the dosing of the first human subject in the
first Phase 2 Trial.

 

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“Initiation of Phase 3 Trial” means the dosing of the first human subject in a
Phase 3 Trial. In the case where a Phase 2b/3 Trial precedes any Phase 3 Trial
for a given Product, the first dosing of such Product in a human subject
following the review of interim data and decision to extend the period of such
Phase 2b/3 Trial in order to provide sufficient evidence of safety and efficacy
to be included as a Phase 3 Trial in filings with Regulatory Authorities will be
deemed to be the “start of Phase 3 Trial” for such Product.

“In-License Milestones” means, with respect to a particular Third Party
Agreement, all milestone payments that become payable by a Party to the
Licensor(s) under such Third Party Agreement with respect to the applicable
Third Party Patents as a result of the achievement of Development, regulatory
and/or Commercialization events by a Product. For clarity, “In-License
Milestones” shall not include any upfront payments under Third Party Agreements.

“In-License Royalties” means, with respect to a particular Third Party
Agreement, all royalties on sales of Products by Sanofi, its Affiliates and its
sublicensees that become payable by a Party to the Licensor(s) under such Third
Party Agreement with respect to the applicable Third Party Patents.

“Integrated Product Plan” or “IPP” has the meaning set forth in Section 5.3.

“Intellectual Property Panel” has the meaning set forth in Section 6.11.1.

“Joint Invention” has the meaning set forth in Section 8.1.

“Joint Patent” means any Patent that claims, and only to the extent that it
claims, a Joint Invention(s).

“JSC Charter” has the meaning set forth in 3.4.1.

“JSC” has the meaning set forth in 3.4.1.

“Know-How” means technical information and materials, including without
limitation, technology, software, instrumentation, devices, data, biological
materials, assays, constructs, compounds, inventions, practices, methods,
knowledge, know-how, trade secrets, skill and experience.

“Licensed Compound” means any Mir-21 Compound or Mir-221/222 Compound.

“Licensing Revenues” has the meaning set forth in Section 10.2.

“Licensor” means, with respect to a particular Third Party Agreement, any Third
Party that is a party to such Third Party Agreement.

“Losses” has the meaning set forth in Section 11.1.

“Major European Country” means France, Germany, Italy, Spain or the United
Kingdom.

 

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“Major Market Country” means Canada, France, Germany, Italy, Japan, Spain, the
United Kingdom, and the United States.

“Manufacturing Technology” has the meaning set forth in Section 4.3.

“microRNA” means a structurally defined functional RNA molecule usually between
21 and 25 nucleotides in length, which is derived from genetically-encoded
non-coding RNA which is predicted to be processed into a hairpin RNA structure
that is a substrate for the double-stranded RNA-specific ribonuclease Drosha and
subsequently is predicted to serve as a substrate for the enzyme Dicer, a member
of the RNase III enzyme family; including, without limitation, those microRNAs
exemplified in miRBase (http://microrna.sanger.ac.uk/). To the extent that
[…***…] for purposes of this Agreement; provided, however, that nothing
contained herein will require any Party hereto to […***…].

“microRNA Antagonist” means a single-stranded oligonucleotide (or a single
stranded analog thereof) that is designed to interfere with or inhibit a
particular microRNA. For purposes of clarity, the definition of “microRNA
Antagonist” excludes oligonucleotides that function predominantly through the
RNAi mechanism of action or the RNase H mechanism of action.

“microRNA Compound” means a compound consisting of (a) a microRNA Antagonist, or
(b) a microRNA Mimic.

“microRNA Mimic” means a double-stranded or single-stranded oligonucleotide or
analog thereof with a substantially similar base composition as a particular
microRNA and which is designed to mimic the activity of such microRNA.

“Mir-21” means the microRNA having (i) miRBase ID: hsa-miR-21; (ii) the miRBase
Accession Number MIMAT0000076, and (iii) the sequence UAGCUUAUCAGACUGAUGUUGA.

“Mir-21 Compound” means any microRNA Antagonist that modulates the expression of
Mir-21 whose primary mechanism of action is through […***…] to Mir-21.

“Mir-21 Fibrosis POC Program” has the meaning set forth in Section 3.1.1.

“Mir-21 Fibrosis POC Program Plan” has the meaning set forth in Section 3.1.1.

“Mir-21 Oncology POC Program” has the meaning set forth in Section 3.1.2.

“Mir-21 Oncology POC Program Plan” has the meaning set forth in Section 3.1.2.

“Mir-21 POC Program” means the Mir-21 Fibrosis POC Program or the Mir-21
Oncology POC Program, as applicable.

“Mir-21 POC Program Product” means, with respect to a Mir-21 POC Program, any
Mir-21 Product that is or was the subject of such Mir-21 POC Program.

 

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“Mir-21 Product” means any pharmaceutical product containing a Mir-21 Compound
(alone or with other active ingredients), in all forms, presentations,
formulations and dosage forms.

“Mir-221” means the microRNA having (i) miRBase ID: hsa-miR-221; (ii) the
miRBase Accession Number MIMAT0000278, and (iii) the sequence
AGCUACAUUGUCUGCUGGGUUUC.

“Mir-221/222 Compound” means (a) any microRNA Antagonist that modulates the
expression of Mir-221 and/or Mir-222 whose primary mechanism of action is
through its hybridization to Mir-221 and/or Mir-222, or (b) any microRNA Mimic
with a substantially similar base composition as Mir-221 and/or Mir-222 and
which is designed to mimic the activity of Mir-221 and/or Mir-222.

“Mir-221/222 POC Program” has the meaning set forth in Section 3.1.3.

“Mir-221/222 POC Program Plan” has the meaning set forth in Section 3.1.3.

“Mir-221/222 Product” means any pharmaceutical product containing a Mir-221/222
Compound (alone or with other active ingredients), in all forms, presentations,
formulations and dosage forms.

“Mir-222” means the microRNA having (i) miRBase ID: hsa-miR-222; (ii) the
miRBase Accession Number MIMAT0000279, and (iii) the sequence
AGCUACAUCUGGCUACUGGGU.

“NDA” means a New Drug Application filed with the FDA after completion of
clinical trials to obtain marketing approval for the applicable Product in the
United States.

“NDA Filing” means the acceptance by the FDA of the filing of an NDA for the
applicable Product, or the acceptance of the foreign equivalent of an NDA by the
applicable Regulatory Authority.

“Necessary Patent” has the meaning provided in Section 6.11.1.

“Net Sales” means, with respect to a Product, the gross invoice price of all
units of such Products sold by Sanofi, its Affiliates and/or their sublicensees
to any Third Party, less the following items: (a) trade discounts, credits or
allowances, (b) credits or allowances additionally granted upon returns,
rejections or recalls, (c) freight, shipping and insurance charges, (d) taxes,
duties or other governmental tariffs (other than income taxes),
(e) government-mandated rebates, and (f) a reasonable reserve for bad debts.
“Net Sales” under the following circumstances will mean the fair market value of
such Product: (i) Products which are used by Sanofi, its Affiliates or
sublicensees for any commercial purpose without charge or provision of invoice,
(ii) Products which are sold or disposed of in whole or in part for non cash
consideration, or (iii) Products which are provided to a Third Party by Sanofi,
its Affiliates or sublicensees without charge or provision of invoice and used
by such Third Party except in the cases of Products used to conduct clinical
trials, reasonable amounts of Products used as marketing samples and Product
provided without charge for compassionate or similar uses.

 

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Net Sales will not include any transfer between or among Sanofi and any of its
Affiliates or sublicensees for resale.

In the event a Product is sold as part of a Combination Product, the Net Sales
from the Combination Product, for the purposes of determining royalty payments,
will be determined by multiplying the Net Sales (as determined without reference
to this paragraph) of the Combination Product, by the fraction, A/(A+B), where A
is the average sale price of the Product when sold separately in finished form
and B is the average sale price of the other therapeutically active
pharmaceutical compound(s) included in the Combination Product when sold
separately in finished form, each during the applicable royalty period or, if
sales of all compounds did not occur in such period, then in the most recent
royalty reporting period in which sales of all occurred. In the event that such
average sale price cannot be determined for both the Product and all other
therapeutically active pharmaceutical compounds included in the Combination
Product, Net Sales for the purposes of determining royalty payments will be
calculated as above, but the average sales price in the above equation will be
replaced by a good faith estimate of the fair market value of the compound(s)
for which no such price exists.

“New Core Patents” has the meaning set forth in Section 6.9.

“New Core Technology” has the meaning set forth in Section 6.9.

“New Core Technology Agreement” has the meaning set forth in Section 6.9.

“Oncology” means any malignant neoplasm, and/or disorders associated with any
malignant neoplasm. Examples include, but are not limited to, carcinomas,
melanomas, sarcomas, lymphomas, leukemias and gliomas.

“Oncology Field” has the meaning set forth in subparagraph (b) of the definition
of Target Field.

“Option” means the Mir-21 Option or the Mir-221/222 Option.

“Option Letter” means the letter agreement between Regulus and Sanofi dated
June 21, 2013.

“Option Period” means, with respect to any POC Program, the POC Program Term
and, subject to Achievement of Proof of Concept for such POC Program, the 90-day
period beginning upon Achievement of Proof of Concept.

“Original Agreement” has the meaning set forth in the recitals on the first page
of this Agreement.

“Other In-License Payments” means, with respect to a particular Third Party
Agreement, all payments (excluding In-License Royalties and In-License
Milestones) that become payable by a Party to the applicable Licensor(s) under
such Third Party Agreement with respect to the applicable Third Party Patents.

“Other Licensor” means any Licensor that is not a Founding Company.

 

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“Other Mir-21 Product” has the meaning set forth in Section 6.8.1(b).

“Other Party” has the meaning set forth in Section 9.3.

“Party(ies)” has the meaning set forth in the opening paragraph of this
Agreement.

“Patents” means (a) patents and patent applications in any country or
jurisdiction, (b) all priority applications, divisionals, continuations, and
continuations-in-part of any of the foregoing, and (c) all patents issuing on
any of the foregoing patent applications, together with all registrations,
reissues, renewals, re-examinations, confirmations, supplementary protection
certificates, and extensions of any of (a), (b) or (c).

“Permitted License” means a license granted by Regulus to a Third Party
(i) under the Regulus Core Technology Patents (but not under the Product
Specific Patents) to […***…] (or […***…] to […***…]) solely to conduct Research,
or (ii) under the Regulus Core Technology Patents (but not under the Product
Specific Patents) to enable such Third Party to […***…] or […***…] microRNA
Compounds, where such Third Party is […***…] and is not […***…] or […***…].

“Person” means any individual, firm, corporation, partnership, limited liability
company, trust, business trust, joint venture company, governmental authority,
association or other entity.

“Phase 1 Trial” means the initial clinical testing of a Product in humans
(first-in-humans study) with the intention of gaining a preliminary assessment
of the safety of such Product.

“Phase 2 Trial” means a human clinical trial of a Product, the principal purpose
of which is a determination of preliminary short-term safety and efficacy in the
target patient population, as described in 21 C.F.R. 312.21(b) for the United
States, or a similar clinical study prescribed by the Regulatory Authorities in
a foreign country.

“Phase 2b/3 Trial” means a human clinical trial of a Product, the principal
purpose of which is a further determination of efficacy and safety, in the
target population, at the intended clinical dose or doses or range of doses, on
a sufficient number of subjects and for a sufficient period of time to confirm
the optimal manner of use of the Product (dose and dose regimen) prior to
initiation of the pivotal Phase 3 Trials, and which itself provides sufficient
evidence of safety and efficacy to be included as a Phase 3 Trial in filings
with Regulatory Authorities.

“Phase 3 Trial” means a human clinical trial of a Product on a sufficient number
of subjects that is designed to establish that a pharmaceutical product is safe
and efficacious for its intended use, and to determine warnings, precautions and
adverse reactions that are associated with such pharmaceutical product in the
dosage range to be prescribed, which trial is intended to support Approval of a
Product, as described in 21 C.F.R. 312.21(c) for the United States, or a similar
clinical study prescribed by the Regulatory Authorities in a foreign country.

“Phase 4 Trial” means a human clinical trial for a Product commenced after
receipt of Approval in the country for which such trial is being conducted and
that is conducted within the parameters of the Approval for the Product. Phase 4
Trials may include, without limitation,

 

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epidemiological studies, modeling and pharmacoeconomic studies, investigator
sponsored clinical trials of Product and post-marketing surveillance studies.

“POC Program” means any of the Mir-21 Fibrosis POC Program, the Mir-21 Oncology
POC Program and the Mir-221/222 Oncology POC Program.

“POC Program Costs” means, with respect to any POC Program, the […***…] incurred
(including […***…]) by Regulus or for its account in connection with the
performance of such POC Program during the applicable POC Program Term,
including […***…] (defined below). POC Program Costs will include, but not be
limited to the following, in each case to the extent attributable to POC Program
Plan activities: (i) costs of […***…] (collectively, “[…***…]”), […***…] and/or
having such […***…]; (ii) […***…]; (iii) costs of […***…]; (iv) […***…]; and
(v) the costs of […***…]. Notwithstanding the foregoing, POC Program Costs shall
[…***…] amounts actually paid or reimbursed by Sanofi to Regulus pursuant to
Section 3.6.3 with respect to Sanofi Program Activities that Regulus elects to
have performed by any Third Party pursuant to Section 3.6.3.

For purposes of this definition:

(a) “[…***…]” means […***…]; and

(b) “[…***…]” shall mean, with respect to any […***…], but subject to the last
sentence of this paragraph, the

 

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[…***…].

“POC Program Plan” means any of any of the Mir-21 Fibrosis POC Program Plan, the
Mir-21 Oncology POC Program Plan and the Mir-221/222 Oncology POC Program Plan.

“POC Program Product” means (i) any Mir-21 POC Program Product or (ii) any
Mir-221/222 Product, as applicable.

“POC Program Term” means, with respect to any POC Program, the period beginning
on the Second Restatement Date and, subject to earlier termination of such POC
Program pursuant to Section 3.4.1 or Section 3.4.2 or earlier termination of
this Agreement pursuant to ARTICLE 9, ending 90 days after Regulus’ delivery to
Sanofi of the POC Study Report (whether or not the results of the POC Study
demonstrate Proof of Concept).

“POC Study” means, with respect to a POC Program, the clinical trial described
in the applicable POC Program Plan that is designed to demonstrate Proof of
Concept and is identified as a “POC Study” in such POC Program Plan.

“POC Study Report” means, with respect to a POC Program, the final report from
the POC Study under such POC Program.

“Product” means any pharmaceutical product containing a Licensed Compound (alone
or with other active ingredients), in all forms, presentations, formulations and
dosage forms.

“Product Development Plan” has the meaning set forth in Section 5.3.

“Product Field” means (a) with respect to Licensed Compounds and Products, the
treatment and/or prophylaxis of any Indication and (b) with respect to Companion
Diagnostics, to the extent that Regulus Controls […***…] the applicable
Collaboration Target as […***…] for […***…] to the corresponding Product in the
treatment and/or prophylaxis of an approved Indication for the Product.

“Product Specific Patents” means all Patents (including all claims and the
entire scope of claims therein) Controlled by Regulus or its Affiliates on the
Effective Date and/or at any time thereafter, in each case claiming (a) a
Collaboration Target gene sequence or a portion thereof, (b) the specific
compositions of matter of Licensed Compounds or Products, or (c) methods of
using Licensed Compounds or Products as therapeutics; provided however, that:

(1) unless the Parties otherwise agree in writing, Patents that include claims
that are directed to subject matter and have a scope that is applicable to
microRNA Compounds in general, and not directed solely to […***…] or […***…] or
to the

 

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[…***…] thereof, will be considered to be […***…] Patents; and

(2) unless the Parties otherwise agree in writing, Patents that include claims
that are directed to the identification or isolation of microRNAs that are not
[…***…], or to the production, composition, or use of […***…] that are not
[…***…] or […***…] will be considered to be […***…] Patents.

For clarification, any Regulus Program Patent or any Joint Patent satisfying the
definition above, will be considered a Product Specific Patent. The Product
Specific Patents as of the Effective Date are listed in APPENDIX 2 attached
hereto.

“Program” means the Research Program or any POC Program.

“Program Inventions” has the meaning set forth in Section 8.1.

“Program License” means the Mir-21 License or the Mir-221/222 License.

“Program Patents” has the meaning set forth in Section 8.1.

“Program Plan” means the R&D Plan or any POC Program Plan.

“Proof of Concept” with respect to a particular POC Program has the meaning
provided in the applicable POC Program Plan.

“R&D Plan” means the written research and development plan attached as
APPENDIX 8 hereto.

“Receiving Party” has the meaning set forth in Section 7.1.

“Regulatory Authority” means any governmental authority, including without
limitation FDA, EMEA or Koseisho (i.e., the Japanese Ministry of Health, Labour
and Welfare, or any successor agency thereto), that has responsibility for
granting any licenses or approvals or granting pricing and/or reimbursement
approvals necessary for the marketing and sale of a Product in any country.

“Regulatory Documentation” means all applications, registrations, licenses,
authorizations and approvals (including all Approvals), all correspondence
submitted to or received from Regulatory Authorities (including minutes and
official contact reports relating to any communications with any Regulatory
Authority), all supporting documents and all clinical studies and tests,
including the manufacturing batch records, relating to the Product, and all data
contained in any of the foregoing, including all regulatory drug lists,
advertising and promotion documents, adverse event files and complaint files.

“Regulus Confidential Information” means any Confidential Information for which
Regulus is the Disclosing Party.

 

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“Regulus Core Technology Patents” means, subject to 6.12.3, Patents Controlled
by Regulus or its Affiliates on the Effective Date and/or at any time
thereafter, in each case that are useful or necessary for the Development and
Commercialization of Licensed Compound and Products. Regulus Core Technology
Patents will exclude the Product Specific Patents. A representative list of the
Regulus Core Technology Patents as of the Effective Date is listed in APPENDIX 3
hereto. For clarification, any Regulus Program Patent or any Joint Patent
satisfying the definition above will be considered a Regulus Core Technology
Patent.

“Regulus Database” has the meaning set forth in Section 3.11.

“Regulus Inventions” has the meaning set forth in Section 8.1.

“Regulus Know-How” means all Know-How Controlled by Regulus or its Affiliates as
of the Effective Date and/or at any time thereafter that is useful for the
Research, discovery, Development, Approval, manufacturing and Commercialization
of microRNA Compounds.

“Regulus Patents” means the Regulus Core Technology Patents and the Product
Specific Patents (including patents licensed to Regulus under an Existing
Regulus Agreement, or under a Future Regulus Agreement in accordance with
Section 6.11).

“Regulus Program Patent” has the meaning set forth in Section 8.1.

“Regulus Technology” means collectively, the Regulus Know-How and the Regulus
Patents.

“Research” means pre-clinical research including gene function, gene expression
and target validation research using cells and animals, which may include small
pilot toxicology studies but excludes IND-Enabling Studies, clinical development
and commercialization.

“Research Program” has the meaning set forth in Section 3.1.

“Research Results” means all data, information, trade secrets, inventions and
Know-How which are discovered, made, reduced to practice, identified or
developed in whole or in part by Regulus in the course of the performance of the
Research Program or any POC Program.

“Research Term” means the period that began on the Effective Date and ended on
the Second Restatement Date.

“Royalty Term” has the meaning set forth in Section 6.15.

“Sanofi Confidential Information” means any Confidential Information for which
Sanofi is the Disclosing Party.

“Sanofi Indemnitees” has the meaning set forth in Section 11.2.

“Sanofi Inventions” has the meaning set forth in Section 8.1.

 

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“Sanofi Product Specific Patent” means any Patents (including all claims and the
entire scope of claims therein) Controlled by Sanofi or its Affiliates on the
Effective Date and/or at any time thereafter, in each case claiming (a) the
sequence or a portion thereof corresponding to the Collaboration Target gene
sequence or a portion thereof, (b) the specific composition of matter of a
Product, (c) methods of using a Licensed Compound or Product as a therapeutic or
(d) methods of using a Licensed Compound as a therapeutic).

“Sanofi Independent Activities” has the meaning set forth in Section 3.7.

“Sanofi Program Activities” has the meaning set forth in Section 3.2.

“Sanofi Program Patents” has the meaning set forth in Section 8.1.

“Second Restatement Date” has the meaning set forth in the opening paragraph of
this Agreement.

“Senior Representatives” has the meaning set forth in Section 13.4.1.

“Stock Purchase Agreement” has the meaning set forth in the recitals on the
first page of this Agreement.

“Target Field” means:

(a) in the case of the Mir-21 Fibrosis POC Program, (i) the treatment and/or
prophylaxis of any or all Indications in Fibrosis and (ii) to the extent that
Regulus Controls […***…] the applicable Collaboration Target as […***…] to the
corresponding Licensed Compound in the treatment and/or prophylaxis of an
Indication in Fibrosis (collectively, the “Fibrosis Field”); or

(b) in the case of the Mir-21 Oncology POC Program or the Mir-221/222 Oncology
POC Program, (i) the treatment and/or prophylaxis of any or all Indications in
Oncology and (ii) to the extent that Regulus Controls […***…] the applicable
Collaboration Target as […***…] to the corresponding Licensed Compound in the
treatment and/or prophylaxis of an Indication in Oncology (collectively, the
“Oncology Field”).

“Target Product Profile” means, on a POC Program-by-POC Program basis, with
respect to the Collaboration Target that is the subject of a POC Program, the
description, as set forth in the applicable POC Program Plan, of the
commercially relevant range of acceptable product performance of a Licensed
Compound against key product characteristics (including but not limited to
efficacy, safety, quality, side effects, tolerability, route of administration,
contraindications and clinical endpoints), and which shall be used by Regulus to
guide and shape the progression of and development decisions for such Licensed
Compound in the applicable Target Field.

“Technology Alliance Agreement” means the Non-Exclusive Technology Alliance and
Option Agreement between the Parties dated as of the Effective Date.

 

***Confidential Treatment Requested

 

15

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“Term” has the meaning set forth in Section 9.1.

“Terminated Mir-21 Program Product” has the meaning provided in
Section 3.4.3(a)(iii).

“Territory” means all countries and jurisdictions throughout the world.

“Therapeutic Field” means any field concerning the remediation of a health
problem, including Fibrosis, Oncology, […***…], diabetes, cardiovascular,
ophthalmology, central nervous system, internal medicine, thrombosis, and
vaccines.

“Third Party” means any Person other than Regulus or Sanofi or their respective
Affiliates.

“Third Party Agreement” means an Existing Regulus Agreement, Future Regulus
Agreement, Existing Sanofi Agreement or Future Sanofi Agreement, as applicable.

“Third Party Claims” has the meaning set forth in Section 11.1.

“Third Party Patents” means, with respect to a particular Third Party Agreement,
all Necessary Patents that a Party in-licenses or acquires from the Licensor(s)
under such Third Party Agreement.

“[…***…] Patents” means all Patents licensed under the […***…] Agreement.

“U.S. Net Sales” has the meaning set forth in Section 6.9.1.

“Valid Claim” means a claim of any issued, unexpired patent that has not been
revoked or held unenforceable or invalid by a decision of a court or
governmental agency of competent jurisdiction from which no appeal can be taken,
or with respect to which an appeal is not taken within the time allowed for
appeal, and that has not been disclaimed or admitted to be invalid or
unenforceable through reissue, disclaimer or otherwise.

“[…***…]” means […***…].

“[…***…] Agreement” means the […***…] Agreement by and between the […***…],
commissioned by […***…], and […***…] dated […***…].

 

***Confidential Treatment Requested

 

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APPENDIX 2

PRODUCT-SPECIFIC PATENTS

[Attached]

 

1

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

Appendix 2

Product-Specific Patents

(as of the Second Restatement Date)

[…***…]*

 

* Pages 1 through 3 of this Appendix 2 have been redacted and omitted pursuant
to a confidential treatment request filed with the Securities and Exchange
Commission.

 

***Confidential Treatment Requested

 

1

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APPENDIX 3

REGULUS CORE TECHNOLOGY PATENTS

[Attached]

 

1

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

APPENDIX 3

REGULUS CORE TECHNOLOGY PATENTS

(as of the Second Restatement Date)

Patents and Patent Applications owned by or licensed to Regulus

[…***…]*

 

* Pages 1 through 6 of this Appendix 3 have been redacted and omitted pursuant
to a confidential treatment request filed with the Securities and Exchange
Commission.

 

***Confidential Treatment Requested

 

1

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APPENDIX 3

REGULUS CORE TECHNOLOGY PATENTS

Patents and Patent Applications Licensed to Regulus by Isis

[…***…]*

 

* Pages 1 through 48 of this Appendix 3 have been redacted and omitted pursuant
to a confidential treatment request filed with the Securities and Exchange
Commission.

 

***Confidential Treatment Requested

 

2

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APPENDIX 3

REGULUS CORE TECHNOLOGY PATENTS

Patents and Patent Applications Licensed to Regulus by Alnylam

[…***…]*

 

* Pages 1 through 19 of this Appendix 3 have been redacted and omitted pursuant
to a confidential treatment request filed with the Securities and Exchange
Commission.

 

***Confidential Treatment Requested

 

1

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APPENDIX 4

CHARTER OF THE JOINT STEERING COMMITTEE

Purpose

The Joint Steering Committee is established by Regulus and Sanofi to oversee the
POC Programs under the Agreement.

Responsibilities

1. The JSC will, using each POC Program Plan initially agreed to on the Second
Restatement Date as a basis, continue to develop and refine such POC Program
Plan, as needed, and will conduct a comprehensive review of the POC Program Plan
as needed.

2. The JSC will be responsible for oversight of the POC Program Plans. The JSC
will (i) evaluate the data generated by the Parties in the course of carrying
out the POC Program Plans, (ii) discuss and resolve any overarching issues or
significant changes in the POC Program Plans, (iii) make revisions to the POC
Program Plans as necessary, (iv) evaluate and approve additional studies to be
conducted by Sanofi (and at its sole expense) for the purpose of expanding the
applications of a Compound or Product and (v) consistent with Article 7 of the
Agreement, review and approve all public communications and disclosures,
including but not limited to data presented at external meetings and journals on
the joint Research Results. Except for amendments to the POC Program Plans (as
adopted in accordance with this charter and the Agreement), in no event will the
JSC have the power or authority to amend any provision of the Agreement.

3. The JSC will have the power to delegate its authority and duties to
sub-committees as it deems appropriate and to establish working groups to
facilitate ongoing informal exchange of information regarding progress and
results of each POC Program.

Composition

4. The JSC will at all times have an equal number of members designated by each
Party. Each Party may replace its appointed JSC representatives at any time upon
written notice to the other Party. The size and composition of the JSC provided
herein may not be changed without the consent of both Regulus and Sanofi.

5. Each JSC member will have the requisite background, experience and training
to carry out the duties and obligations of the JSC.

6. Each Party will designate one of its representatives as co-chairperson of the
JSC. Each of the co-chairpersons will be responsible, on an alternating basis
with the Sanofi co-chairperson having responsibility with respect to the initial
meeting, for scheduling meetings, preparing and circulating an agenda in advance
of each meeting, and preparing the minutes of each meeting. Each Party will
appoint an individual employee representative to serve as liaisons between the
Parties with respect to the POC Programs and to promote effective communication
between the Parties and coordination of the Parties’ activities and
responsibilities in furtherance of the POC

 

1

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Program Plans (the “Alliance Managers”). The Alliance Managers will manage and
oversee the governance of the Agreement and will serve as the primary contact
person concerning on-going interactions between the Parties under this
Agreement. The Alliance Managers shall be non-voting JSC members and will
coordinate and attend all meetings of the JSC and will be responsible for the
preparation and circulation of JSC meeting minutes for approval and will
facilitate the scheduling and conduct of JSC meetings.

Decisions

7. Each Party’s JSC members will collectively have one vote, regardless of the
number of its JSC members participating in any meeting. No votes will be taken
unless there is at least one JSC member representing each of Regulus and Sanofi
participating in such meeting. Unless otherwise specified herein, all actions
taken by the JSC as a committee will be by unanimous vote. If the JSC members
reach a deadlock on any vote, then the deadlock will be resolved in accordance
with Paragraph 8 below. Notwithstanding anything to the contrary, no decision by
the JSC will require the other Party to: (i) breach any written agreement that
such other Party may have with a Third Party (except where such agreement is
entered into in breach of any representation, warranty, covenant or obligation
of such Party under to this Agreement); (ii) perform any activities that are
outside the scope of the POC Programs; or (iii) violate any Applicable Law or
principles of scientific integrity.

8. If the JSC is unable to decide by unanimous vote on any issue within the
scope of its authority and duties, then the JSC will promptly raise such issue
to each Party’s co-chairperson on the JSC, and such co-chairs will have 10 days
to mutually agree on how to resolve such issue. If the co-chairs are unable to
resolve such issue within the 10 day period, then such issue will be brought to
each Party’s Senior Representatives, or their designees. The Senior
Representatives will have 10 days to mutually agree on how to resolve such
issue. If the Senior Representatives are unable to resolve such issue within the
10-day period, then, except as otherwise expressly set forth in the Agreement,
such issue will be finally resolved in accordance with the applicable
subparagraph below, and the resolution of such issue in accordance with the
applicable subparagraph will be binding on Sanofi and Regulus:

(a) the Parties hereby agree to submit the following matters to an Expert Panel
for final resolution in accordance with Section 13.4.5 of the Agreement: (i) any
issue relating to the Sanofi Program Activities performed or to be performed by
Sanofi that are necessary for Achievement of Proof of Concept; and (ii) any
dispute concerning the Achievement of Proof of Concept;

(b) any issue relating to Sanofi Program Activities performed or to be performed
by Sanofi that are not necessary for Achievement of Proof of Concept shall be
finally resolved by the Senior Representative of Sanofi; and

(c) any issue relating to the POC Programs other than those expressly set forth
in subparagraphs (a) and (b) above shall be finally resolved by the Senior
Representative of Regulus.

 

2

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For clarity, no study not already contemplated by the initial POC Program Plan
may be added to such POC Program Plan as a Sanofi Program Activity without the
written approval of both the Regulus and Sanofi representatives on the JSC,
which approval may be withheld at the discretion of such representatives.

Operations; Meetings

9. From the Second Restatement Date until the expiration or termination of the
last-to-expire or –terminate of the POC Program Terms, the JSC will meet twice
per year, unless otherwise agreed by the Parties’ Senior Representatives. Either
Party may request and require and ad hoc meeting of the JSC, at any time.
Meetings may be held in person or by audio or video teleconference as
appropriate. It is understood that the JSC will establish one or more working
groups which will meet for the purpose of facilitating the formal and informal
exchange of information between the Parties regarding the progress and results
of the POC Program activities on a monthly basis, unless otherwise agreed by the
JSC.

10. Meetings of the JSC will be effective only if at least one JSC
representative of each Party is present or participating. Each Party will be
responsible for all of its own expenses of participating in the JSC meetings.
The Parties will endeavor to schedule meetings of the JSC with at least 30 days
advance notice.

11. Each Party may bring additional employees to each meeting as non-voting
observers.

12. If required, the co-chair responsible for each meeting (the “Responsible
Chair”) will, in consultation with other members of the JSC, develop and set the
JSC’s agenda for each meeting. The Responsible Chair will include on such agenda
each item requested within a reasonable time in advance of such meeting by a JSC
member. The agenda and information concerning the business to be conducted at
each meeting will be communicated in writing to the members of the JSC within a
reasonable time in advance of such meeting to permit meaningful review.

13. The Responsible Chair, or such person as the Responsible Chair may
designate, will prepare, and distribute to all JSC members, draft committee
minutes within 2 weeks following each meeting and such minutes will be finalized
by the JSC promptly thereafter.

 

3

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APPENDIX 5

EXISTING REGULUS AGREEMENTS

This Appendix 5 contains a list of certain agreements in effect as of the
Effective Date between Regulus and certain Third Parties that may, as
applicable, place certain encumbrances or limitations on the licenses or
sublicenses granted to Sanofi, the exclusivity covenants, and the
representations and warranties, where specified in the Agreement.

As set forth in the Agreement, the information and disclosures contained in this
Appendix 5 are intended only to qualify and limit the licenses granted by
Regulus to Sanofi, the exclusivity covenants, and the representations and
warranties given by Regulus under the Agreement and do not expand in any way the
scope or effect of any such licenses, representations or warranties.

Nothing herein constitutes an admission of any liability or obligation of
Regulus nor an admission against any interest of Regulus. The inclusion of this
Appendix 5 or the information contained in this Appendix 5 does not indicate
that Regulus has determined that this Appendix 5 or the information contained in
this Appendix 5, when considered individually or in the aggregate, is
necessarily material to Regulus.

Existing Regulus Agreements

[…***...]

 

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APPENDIX 6

POC PROGRAM PLANS

Overview

There are two main projects being prosecuted within the ongoing collaboration
between Sanofi and Regulus Therapeutics, miR-21 and miR-221. Within the miR-21
project there are two therapeutic areas being evaluated. The first area is
focused on renal fibrosis, specifically a human condition known as Alport
Syndrome. The second therapeutic area of interest is Oncology. For the miR-221
project the sole therapeutic area of interest in Oncology. This document will
frame the ongoing activities and the planned activities within these
collaborations with a more detailed overview of the miR-21 fibrosis program
given that this is […***…]. The miR-21 and miR-221 Oncology projects are focused
on […***…] and the […***…].

The initial POC Program Plans for the miR-21 fibrosis program, the miR-21
oncology program and the miR-221/222 oncology program are attached hereto as
Appendix 6A, Appendix 6B and Appendix 6C, respectively.

 

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APPENDIX 6A

INITIAL MIR-21 FIBROSIS POC PROGRAM PLAN

miR-21 Fibrosis focusing on Alport Syndrome

[…***…] has been […***…] within the miR-21 fibrosis program. In non GLP
toxicology experiments […***…]. The […***…] by comparing the […***…] required
for efficacy with the […***…] that is achieved as adverse findings are being
observed. This […***…] is considered appropriate for a […***…].

The following activities will be performed within the miR-21 fibrosis program by
Regulus.

 

  1. […***…].

 

  2. […***…].

 

  3. […***…].

 

  4. […***…].

 

  5. […***…].

 

  6. […***…].

 

  7. […***…].

The following translational studies will be performed within the miR-21 fibrosis
program by Sanofi. Regulus will provide the compounds required for performing
these studies:

 

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  1. […***…]

 

  2. […***…]

 

  — […***…].

 

  3. […***…].

 

  4. […***…].

 

  5. […***…].

[…***…].

Definition of Proof of Concept for […***…] in patients with Alport Syndrome

Study Design: […***…]

 

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[…***…]

 

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APPENDIX 6B

INITIAL MIR-21 ONCOLOGY POC PROGRAM PLAN

miR-21 Oncology

At this time the […***…] in Oncology is […***…]. The current focus of the
project is on hepatocellular cancer although if translation results support the
pursuit of an indication other than HCC the project team may proceed in that
direction. The following activities are ongoing and/or planned by Regulus.

 

  1. […***…].

 

  2. […***…].

 

  3. […***…].

 

  4. […***…].

 

  5. […***…].

Should the studies discussed above identify a […***…] the following studies will
be performed.

 

  1. […***…].

 

  2. […***…].

 

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  3. […***…].

 

  4. […***…].

 

  5. […***…].

 

  6. […***…].

Definition of Proof of Concept for the lead clinical candidate in the miR-21
Oncology Project

The proposed proof of concept criteria that have been agreed to between Regulus
and Sanofi are described in detail below. These criteria specifically relate to
a clinical study to be performed in advanced HCC patients who have […***…].
Should the clinical plan change based on emerging findings from translational
studies a new definition of proof of concept will need to be developed by the
steering committee.

Proof of concept criteria are defined as

 

  1. […***…].

 

  a. […***…]

 

  b. […***…].

 

  2. […***…]

 

  a. […***…].

 

  3. […***…]

 

  a. […***…]

 

  b. […***…]

 

  4. […***…].

 

  5. […***…].

Postdoctoral research project ([…***…])

Following postdoc project will be performed at Sanofi, and Regulus will provide
anti-miR-21 and relevant control compounds required for these studies. The goal
of the postdoctoral project is to contribute to better understanding […***…]

 

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[…***…]. Deliverables for this project include scientific publications in
peer-reviewed journals and presentations at conferences/meetings:

Specific Aim I: […***…]:

[…***…]

Specific Aim II: […***…]:

[…***…]

 

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[…***…]

Additional studies

Additional studies, performed either internally by Sanofi or through academic
collaborators, may be proposed to the JSC in the future based on emerging data
on the target and indication of interest. Regulus and Sanofi have agreed that
anti-miR-21 efficacy will be investigated in animal models of […***…], where
upregulation of miR-21 has been documented. These studies will be performed by
external academic collaborators at […***…] and […***…]. Regulus will provide the
anti-miR-21 compounds and relevant control compounds for these studies.

None of these Sanofi activities is considered as […***…].

 

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APPENDIX 6C

INITIAL MIR-221/222 ONCOLOGY POC PROGRAM PLAN

miR-221 in Oncology

The miR-221 project will follow the plan laid out for the miR-21 project. As
both programs may focus on HCC a key set of translational studies that evaluate
the microRNA expression in HCC is necessary in order to define whether the
proposed clinical studies will be focused on two distinct segments of HCC.

Ongoing activities at Regulus include the following:

 

  1. […***…]

 

  2. […***…]

 

  3. […***…]

 

  4. […***…]

 

  5. […***…]

 

  6. […***…]

 

  7. […***…]

[…***…]:

 

  1. […***…].

 

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  2. […***…].

 

  3. […***…].

 

  4. […***…].

 

  5. […***…].

 

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APPENDIX 7

LISTED COUNTRIES

 

Patent Country Code

  

Patent Filing Country or Jurisdiction

WO   

World Intellectual Property Organization (WIPO)

EP   

European Patent Office (EPO)

EA   

Eurasian Patent Organization (EAPO)

GC   

Patent Office of the Co-operation Council for the Arab States of the Gulf (GCC)

AU   

Australia

BR   

Brazil

CA   

Canada

CN   

China

HK   

The Hong Kong Special Administrative Region of the People’s Republic of China

ID   

Indonesia

IL   

Israel

IN   

India

JP   

Japan

KR   

Korea

MX   

Mexico

MY   

Malaysia

NZ   

New Zealand

PH   

Philippines

RU   

Russian Federation

SG   

Singapore

TH   

Thailand

TW   

Taiwan

UA   

Ukraine

US   

United States of America

ZA   

South Africa

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

APPENDIX 8

INITIAL R&D PLAN

[Attached]

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

 

RESEARCH AND DEVELOPMENT PLAN

between

REGULUS THERAPEUTICS, INC.

and

SANOFI-AVENTIS

 

 

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

 

Regulus and Sanofi Collaboration on Fibrosis and […***…]

 

 

The initial research and development plan (the “R&D Plan”) described below
outlines the current research objectives under the Collaboration and License
Agreement dated June 14, 2010 between Sanofi and Regulus. Capitalized terms used
and not defined herein shall have the meanings set forth in the Agreement. In
case of any conflicts between this initial R&D Plan and the Agreement, the terms
of the Agreement shall govern. As stated in the Agreement, the Joint Steering
Committee (JSC) has the right to amend the R&D Plan at any time during the
Research Term.

Objective: Regulus and Sanofi will collaborate in the discovery and preclinical
development of microRNA therapeutics for the clinical development and
commercialization of such microRNA therapeutics by Sanofi.

Purpose of the initial R&D Plan: The purpose of this R&D Plan is to outline the
responsibilities and activities of Regulus and Sanofi with respect to carrying
out the research and preclinical development of microRNA therapeutics so as to
provide broad guidance to the scientific team in carrying out their work. The
initial R&D Plan contains a summary description of the potential specific
activities, deliverables, and projected timelines for completion of such
activities; and is subject to the modification by the JSC.

Collaboration Management: The R&D Plan will be overseen and managed by the JSC.
The R&D Plan may only be amended with the unanimous approval of the JSC (as
permitted by the JSC Charter). The R&D Plan may be amended at any time, and is
expected to be reviewed at least annually. The Parties have created and agreed
to the initial R&D Plan as a basis for the research and preclinical development
of microRNA therapeutics and it is the intent of Regulus and Sanofi to
subsequently modify the initial R&D Plan in a manner to successfully develop
microRNA therapeutics. Both Parties shall use Commercially Reasonable Efforts to
complete the activities listed in the R&D Plan as promptly and diligently as
possible.

Research Term: The R&D Plan will be carried out during the period following the
Effective Date and ending on the third anniversary of the Effective Date, unless
otherwise extended as described in the Agreement. For any extension of the
Research Term, the JSC will amend and restate the R&D Plan as necessary, subject
to the provisions of the JSC Charter.

Research Program Staffing and Resources: As described in the Agreement, Regulus
will dedicate Regulus employees during the Research Term to perform the
activities of the R&D Plan. Regulus resources will include the following:
bioinformatics, basic mechanisms, exploratory biology, in vitro and in vivo
biology, chemistry, and translational medicine. Sanofi and Regulus will
cooperate with each other in carrying out the R&D Plan and each Party will
contribute its relevant know-how and experience necessary. It is contemplated
that the Parties will work closely together and, where applicable, Sanofi will
contribute scientific expertise, assays and animal models, as defined in the
Agreement (Article 3.5.2). If appropriate, experts from Sanofi are invited to
visit the laboratories of Regulus and participate in the ongoing research
activities.

Definitions:

Program Candidates – […***…]

Research Candidates – […***…]

 

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Development Candidate – […***…]

EXECUTIVE SUMMARY:

The overall goal of the R&D Plan is to provide the framework for a microRNA
therapeutic “IND Engine” that can achieve an IND for miR-21 in […***…] followed
by several other potential INDs for microRNA therapeutics in […***…]. We have
provided a proposed timeline of these activities shown in the figure below.

[…***…]

The initial R&D Plan is organized into four sections, which may have activities
that overlap. Each section has clearly defined objectives, tasks/activities, and
deliverables to achieve the goals of selecting […***…] Collaboration Targets
(other than miR-21) and an IND for anti-miR-21 by […***…].

The initial R&D Plan has been written to reflect a flow from early stage to late
stage activities within any given program. The timeline highlights when these
activities actually occur across the programs and emphasizes that the first key
task of the Collaboration is to produce an IND for miR-21. That being said, the
four sections of the R&D Plan are:

Section I. Designating Collaboration Targets in Fibrosis;

Section II. […***…];

Section III. […***…]; and

Section IV. […***…].

Briefly, Sections I […***…] describe efforts to identify and designate
Collaboration Targets in Fibrosis and

 

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[…***…]. A detailed R&D plan for projects in […***…] will be written and
approved by the JSC by […***…].

As per the Agreement, Sanofi will designate its four Collaboration Targets
within […***…] of the Research Term (the Target Designation Period). Regulus
will be responsible for identifying and validating the Collaboration Targets
using the criteria listed below […***…]. In addition, Regulus will perform
[…***…]. Following Collaboration Target selection, Sanofi will have the right to
substitute Collaboration Targets during a period of […***…] months following
designation and in accordance with the Agreement.

Section III describes the basic workflow for […***…].

Finally, Section IV describes […***…].

DETAILS OF THE INITIAL R&D PLAN:

Section I. Designating Collaboration Targets in Fibrosis

Overview: The basic hypothesis is that microRNAs […***…]. Regulus scientists
have been working closely with a network of leading academic collaborators
[…***…].

 

REGULUS NETWORK OF ACADEMIC COLLABORATORS FOR FIBROSIS

 

Name & Institute

  

Fibrosis area focus

[…***…]

   […***…]

[…***…]

   […***…]

[…***…]

   […***…]

[…***…]

   […***…]

[…***…]

   […***…]

[…***…]

   […***…]

[…***…]

   […***…]

[…***…]

   […***…]

 

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From these collaborations […***…]. We have determined microRNA […***…]. We have
also […***…]. The […***…] offers the advantage that […***…].

[…***…].

[…***…].

[…***…].

Specific Activities:

Goal 1: Identify Collaboration Targets in Fibrosis

 

  (I) Identify potential microRNA therapeutic targets in Fibrosis

 

  a. […***…]

 

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  b. […***…]

 

  c. […***…]

Deliverable 1: […***…]

Goal 2: […***…]

Deliverable 2: […***…]

Section II. […***…]

Overview: […***…].

 

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[…***…]..

Specific Activities:

Goal 3: […***…]

Deliverable 3: […***…]

Goal 4: […***…]

[…***…]

Deliverable 4: […***…]

The basic workflow for Sections I and II is shown below:

[…***…]

Figure 1. Workflow for identification and validation of Collaboration Targets in
Fibrosis […***…]

 

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Deliverables for Sections I and II:

 

Deliverables

  

Timing

[…***…]

   […***…]

[…***…]

   […***…]

[…***…]

   […***…]

[…***…]

   […***…]

Section III. […***…]

Overview: […***…]

[…***…]

[…***…]

 

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Deliverables for Sections III: […***…]

 

Deliverables

  

Timing

[…***…]

   […***…]

[…***…]

   […***…]

[…***…]

   […***…]

[…***…]

   […***…]

Section IV. […***…]

[…***…].

 

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[…***…]

 

Deliverable

  

Criteria

  

Timing

[…***…

   […***…]    […***…]

Development Candidate Selection Criteria

If the miRNA antagonist or miRNA mimetic achieves the following profile, it will
be considered for Development Candidate status:

[…***…]

 

Criteria

  

Regulus

[…***…]

   […***…]

[…***…]

   […***…]

[…***…]

   […***…]

[…***…]

   […***…]

[…***…]

   […***…]

[…***…]

   […***…]

[…***…]

   […***…]

Table 1. Considerations for Development Candidate selection

Key IND-Enabling Activities

After a Development Candidate has been selected, Regulus will conduct
appropriate IND-enabling activities to support the miRNA antagonist for clinical
trials. The Workflow is provided below.

[…***…]

Figure 4: Workflow for key IND-enabling activities of Development Candidate
(timing: 12 months)

[…***…]

 

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[…***…]

 

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APPENDIX 8-A

R&D PLAN UPDATES

[Attached]

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

APPENDIX 8-A

R&D PLAN UPDATES

R&D Plan for miR-21 in Fibrosis

[…***…]

R&D Plan for miR-21 and miR-221 in Hepatocellular Carcinoma (HCC)

Introduction

Extensive discussions have occurred between Sanofi and Regulus with regards to
[…***…] – miR-21 and miR-221. Both of these projects will now be part of the
ongoing R&D collaboration between Sanofi and Regulus and will require additional
studies in order to achieve the next project milestones. For the miR-21 project
the next key milestone is […***…].

Summary of key R&D activities for miR-21

The key activities for miR-21 project will be as follows.

[…***…]

The aforementioned studies will be planned and executed over the next […***…]
months with the goal to […***…].

 

***Confidential Treatment Requested

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Proposed research plan and resource allocation for miR-21 ONC project up to DC
nomination

 

Task

  

Responsible

[…***…]    […***…] […***…]    […***…] […***…]    […***…] […***…]    […***…]
[…***…]    […***…] […***…]    […***…] […***…]    […***…] […***…]    […***…]
[…***…]    […***…] […***…]    […***…] […***…]    […***…] […***…]    […***…]
[…***…]    […***…] […***…]    […***…] […***…]    […***…] […***…]    […***…]
[…***…]    […***…] […***…]    […***…] […***…]    […***…] […***…]    […***…]
[…***…]    […***…]

 

***Confidential Treatment Requested

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[…***…]

Summary of key R&D activities for miR-221

The attached slide set was prepared during the earlier discussions between
Sanofi and Regulus and highlight the rational and justification for miR-221 as a
target in hepatocellular carcinoma and the detailed activities that are needed
to generate pre-clinical proof of concept for the miR-221 program. These
activities will be executed by Regulus during the next […***…] months as part of
the R&D activities associated with […***…].

[…***…]

[…***…]

Proposed validation plan for miR-221 in HCC

[…***…]

 

***Confidential Treatment Requested

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APPENDIX 9

Regulus Detailed Allocation of Upfront Payments

Mir-21 Program

Allocation of the $[…***…] payment pursuant to Section 6.1 related to Regulus’
Mir-21 Program:

 

Intellectual Property

   Percentage     Amount  

[…***…]

     […***… ]%      $[…***… ] 

[…***…]

     […***… ]%      $[…***… ] 

[…***…]

     […***… ]%      $[…***… ] 

[…***…]

     […***… ]%      $[…***… ] 

Other Programs

Allocation of the $[…***…] payment pursuant to Section 6.1 related to Other
Programs:

 

Intellectual Property

   Percentage     Amount  

[…***…]

     […***… ]%      $[…***… ] 

[…***…]

     […***… ]%      $[…***… ] 

[…***…]

     […***… ]%      $[…***… ] 

[…***…]

     […***… ]%      $[…***… ] 

 

***Confidential Treatment Requested

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APPENDIX 10

Co-Promotion

 

1. General. This Appendix sets out the principal terms under which Regulus may
co-promote, with Sanofi, a Product with respect to which Regulus has exercised
its Co-Promote Option in the U.S., subject to the negotiation and execution of a
definitive Co-Promotion Agreement as described herein.

 

2. Certain Defined Terms. Capitalized terms used but not otherwise defined
herein shall have the meanings provided in the Agreement. In addition, the
following terms, whether used in the singular or plural, shall have the
respective meanings set forth below:

 

  a. “Detail” shall mean a product presentation in a face-to-face meeting in an
individual or group practice setting between a professional sales representative
and a Target Prescriber in which one or more key product benefits are verbally
presented.

 

  b. “Detailing” shall mean the act of presenting a Detail.

 

  c. “Target Prescriber” shall mean a medical or health care professional
authorized to prescribe Products under the laws of the jurisdiction in which
such medical or health care professional is practicing, who is identified as a
member of the target audience to whom Regulus shall direct a Detail.

 

3. Co-Promotion Agreement. Upon exercise by Regulus of the Co-Promote Option,
the Parties shall enter into an agreement relating to the Detailing of Products
to Target Prescribers (the “Co-Promotion Agreement”). In conjunction with the
negotiation and execution of the Co-Promotion Agreement, and no later than
[…***…] months prior to the First Commercial Sale of a POC Program Product, the
Parties shall also negotiate and enter into an agreement setting forth mutually
acceptable guidelines and procedures for the receipt, investigation,
recordation, communication, and exchange (as between the Parties) of adverse
event reports, pregnancy reports, and any other information concerning the
safety of Products. Such guidelines and procedures will be in accordance with,
and will enable the Parties and their Affiliates to fulfill, local and
international regulatory reporting obligations to government authorities. For
purposes of clarification, notwithstanding the exercise of the Co-Promote Option
or the execution of the Co-Promotion Agreement, Sanofi shall at all times during
the Term remain obligated to pay the applicable amounts specified under
Article 6 of the Agreement with respect to each Product (whether or not such
Product is co promoted by Regulus). The Co-Promotion Agreement shall include but
not be limited to the following provisions:

 

  a.

Recruitment. The Regulus Sales Force shall be recruited by Regulus at […***…].
At the request of Regulus, Sanofi will support the recruitment of the Regulus
Sales Force. Regulus shall recruit the Regulus Sales Force with a profile to be
consistent with that of Sanofi’s sales force and reasonably agreed to by Sanofi.
The Regulus Sales Force shall have a number of representatives to be jointly
determined by Sanofi and Regulus in good faith. The

 

***Confidential Treatment Requested

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  Parties agree that the Regulus Sales Force will operate throughout the U.S.,
but the specific territories and alignment throughout the U.S. allocated to the
Regulus Sales Force shall be reasonably determined by Sanofi following good
faith consultations with Regulus. For purposes of clarification, should Regulus
exercise its Co-Promote Option with respect to a particular Product, as well as
its Co-Promote Option with respect to one or more other Products, there will be
only one Regulus sales force for all Products co-promoted by Sanofi and Regulus,
assuming the target audience for all such products is the same and that the
number of products is manageable by one sales force (2 to 3 products).

 

  b. Training. Sanofi shall provide the Regulus Sales Force with appropriate
training with respect to promotion of the Product. In addition, at Regulus’
reasonable request, Sanofi shall provide general sales training to the Regulus
Sales Force. Regulus […***…]. Sanofi […***…].

 

  c. Timing. Hiring of the Regulus Sales Force shall begin no later than […***…]
months before the then-current estimated Product launch date in the U.S., and be
completed no later than […***…] months before the then-current estimated Product
launch date in the U.S., so that Sanofi may initiate training of the Regulus
Sales Force in accordance with paragraph 3(b) above. Sanofi agrees to complete
such training within two months following initiation of such training.

 

  d. Launch Meeting. The Regulus Sales Force will attend the same launch meeting
as the Sanofi U.S. sales force for Product.

 

  e. Target Prescribers. The Target Prescribers of the Product shall be
reasonably determined by Sanofi following good faith consultations with Regulus.

 

  f. Position of Details. Details to be delivered by Regulus for the Product
shall be reasonably determined by Sanofi following good faith consultations with
Regulus.

 

  g. Content of Details. The form and content of all information communicated in
all Details or other communications to health care professionals by Regulus for
the Product shall be those developed by Sanofi at its sole expense and in use by
the corresponding Sanofi sales force in the U.S. Regulus will limit its claims
of efficacy and safety for the Product to those which are consistent with
Sanofi’s approved labeling for the applicable product and shall provide
appropriate balance in all communications regarding such products. Regulus shall
Detail the Product in strict adherence to all applicable legal, regulatory,
professional and policy requirements, including, but not limited to, all
applicable Sanofi policies that have been communicated to Regulus, as they exist
at the time of the Detail.

 

***Confidential Treatment Requested

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

  h. Compensation. Commencing upon the completion of the training of the Regulus
Sales Force on the Product, Sanofi shall […***…], provided that the Regulus
Sales Force details only Product. If there is a product other than a Product
also being detailed by the Regulus Sales Force, then Sanofi […***…] of the
Regulus Sales Force’s cost. All […***…] pursuant to this paragraph shall
[…***…].

 

  i. Schedule of Payments. Within 30 days of the end of each Calendar Quarter,
Regulus shall submit to Sanofi an invoice containing a schedule of Regulus Sales
Force activities and expenses for review and approval. Sanofi shall make the
required payments to Regulus within 30 days of receipt.

 

  j. Performance Criteria. The Parties shall agree on a minimum number of total
Details to be conducted by Regulus each year for Product based on industry
standard performance expectations of a similar specialty sales representative.
Compensation to Regulus as provided above will be subject to adjustment if the
minimum level of such Details is not achieved.

 

  k. Regulus Trademarks. All advertising and promotional material used by
Regulus and Sanofi in connection with any co-promoted Product in the U.S. shall
feature Regulus’ corporate trade name and logo if feasible under applicable U.S.
regulations (collectively, the “Regulus Marks”). Such use shall be in accordance
with a separate trademark license agreement, under which Regulus would grant to
Sanofi a non exclusive, royalty-free license to use the Regulus Marks on Product
advertising and promotional material. Regulus shall retain the ownership of the
entire right, title and interest in and to the Regulus Marks, and all goodwill
associated with or attached to the Regulus Marks arising out of the use thereof
by Sanofi shall inure to the benefit of Regulus.

 

  l. Sampling and Promotional Materials. With respect to Product, the Regulus
Sales Force shall be required to use only promotional materials provided to it
by Sanofi. Sanofi shall provide samples and promotional material to Regulus
Sales Force in a manner and quantity consistent with its provision of samples
and promotional material to its own corresponding sales force.

 

  m. Maintenance and Audit of Records. Under the Co-Promotion Agreement, Regulus
will be responsible for the maintenance of accurate records corresponding to the
invoice of the expenses and activities of the Regulus Sales Force, including,
without limitation, an accurate monthly record of the number of Details, by
position. Sanofi shall have the right to review and audit all such records.

 

***Confidential Treatment Requested

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

  n. Coordination. The Regulus Sales Force shall work in a coordinated fashion
with Sanofi’s sales force for the applicable Product.

 

  o. Joint Commercialization Committee. The Parties shall establish a joint
commercialization committee (“JCC”) with an equal number of representatives of
each party. The JCC shall meet in accordance with a schedule established by
mutual agreement of the Parties, but no less frequently than once per Calendar
Quarter, with the location for such meetings alternating between Regulus and
Sanofi facilities in the U.S. (or such other locations as may be determined by
the JCC). Alternatively, the JCC may meet by means of teleconference,
videoconference or other similar communications equipment. Each party shall bear
its own expenses related to the attendance of such meetings by its
representatives. The JCC shall be chaired by a representative of Sanofi. The JCC
will review marketing plans and coordinate implementation of field activities.
Sanofi’s representatives on the JCC shall disclose to Regulus’ representatives
on the JCC such information as is reasonably necessary for Regulus’
representatives to participate in the proceedings of the JCC.

 

  p. Term and Termination. The term of the Co-Promotion Agreement shall continue
until the last to expire Valid Claim covering the applicable Product in the
U.S., or as long as Sanofi Details such Product in the U.S., whichever occurs
later. The Co-Promotion Agreement shall be subject to termination:

 

  i. by Sanofi in the event of Regulus’ assignment of the Agreement to a Third
Party pursuant to Section 13.1(a);

 

  ii. by Sanofi at any time, if Regulus fails to meet an average of […***…]% of
the target level of Details for the Product over any […***…]-month period, or if
Regulus fails to meet […***…]% of the target level of Details for the Product
during a rolling […***…]-month period;

 

  iii. by either party upon 60 days’ prior written notice to the other party if
the other party breaches any material provision of the Co-Promotion Agreement
and has not cured such breach within the sixty (60)-day period following written
notice of termination by the non-breaching party;

 

  iv. by either party immediately in the event of termination or expiration of
the Agreement.

 

***Confidential Treatment Requested

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APPENDIX 11

Profit-Sharing

This Appendix addresses the accounting policies and procedures to be followed in
determining U.S. Profits with respect to any Product with respect to which
(a) Regulus exercises its Co-Promote Option and (b) Regulus’ notice of exercise
of such Co-Promote Option expressly states that Regulus elects to receive
[…***…]% of U.S. Profits in lieu of royalties under Section 6.9.1 of the
Agreement (such Product, an “Elected Product”). Terms not defined in this
Appendix will have the meanings set forth in the Agreement or in Appendix 1
thereto.

 

1. Calculation of U.S. Profits. “U.S. Profit” for an Elected Product means:
(i) U.S. Net Sales of such Elected Product, less (ii) Allowable Costs and
Expenses in connection with the post-marketing development, commercial
manufacturing, marketing or selling of such Elected Product in the U.S., plus or
minus (iii) Net Interest Income, all as more fully described below. All
calculations hereunder will be made using, and all defined and undefined terms
will be construed in accordance with, International Financial Reporting
Standards, consistently applied, and consistent with generally accepted methods
for activity-based project costing for similar products in similar industries.
Without limiting the foregoing, no cost item included in the calculation of U.S.
Profits for a particular Elected Product will be included more than once in
calculating U.S. Profits for such Elected Product.

U.S. Profits will be calculated on an Elected Product-by-Elected Product basis;
provided, however, that no cost item included in the calculation of U.S. Profits
for a particular Elected Product will be included in the calculation of U.S.
Profits for any other Elected Product.

 

2. Frequency of Reporting; Payments. The fiscal year for purposes of U.S.
Profits calculations will be a Calendar Year or such portion thereof as will be
applicable.

Reporting by Sanofi for revenues and expenses will be performed as follows:

 

Reporting Event

  

Frequency

  

Timing of Submission

Actuals    Quarterly   

45 days following the end of each quarter

Adjustment    Annual   

45 days following Sanofi’s fiscal year end

In addition, prior to the beginning of a financial period (i.e. a given year),
Sanofi will provide Regulus a quarterly forecast estimate of US Profits based
upon projected Net Sales and budgeted Allowable Costs and Expenses and Sanofi
will cause appropriate personnel to be available for a preliminary results
conference call with Regulus finance within 30-days of quarter-end to discuss
results and draft estimates.

 

***Confidential Treatment Requested

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Sanofi will be responsible for the preparation of reports and calculation of
U.S. Profits. Sanofi will provide to Regulus, by the submission dates shown
above, a statement showing the results for the preceding Calendar Quarter and
Calendar Year-to-date, comparing Calendar Quarter and Calendar Year-to-date
results to revenue forecasts and expense budgets, calculating the U.S. Profits
as provided in paragraph 1 above, and determining the cash payments to be made
by Sanofi to Regulus; provided, however, that until such time as U.S. Profits
are greater than $[…***…], Sanofi shall not be obligated to make any payment to
Regulus pursuant to this Appendix 11; and provided, further, that in no event
shall Regulus be obligated to make any payment to Sanofi pursuant to this
Appendix 11.

For any Calendar Quarter in which U.S. Profits are greater than $[…***…], Sanofi
shall pay to Regulus […***…]% of U.S. Profits no later than 30 days after the
date of Regulus’ invoice for such amount, which invoice shall be issued after
receipt of Sanofi’s report for such Calendar Quarter under this paragraph 2.

To the extent any year-end adjustments are determined in good faith by Sanofi to
be appropriate, an appropriate adjustment to U.S. Profits for the applicable
year will be made. In the case of an upward adjustment, Sanofi will make an
appropriate payment to Regulus within 30 days following receipt of Regulus’
invoice for such payment, which invoice shall be issued after receipt of the
report describing such upward adjustment, and in the case of a downward
adjustment, Sanofi will be entitled to an appropriate credit to be applied
against future payments to Regulus of U.S. Profits with respect to the
applicable Elected Product; provided, however, that in the event of a dispute
between the parties with respect to whether any such adjustment or any other
adjustment requested by Regulus is appropriate, such dispute will be referred to
the Senior Representatives of the Parties for resolution pursuant to Section
13.4 of the Agreement. Any such adjustment payment with respect to an upward
adjustment will: (a) be without interest if such amount is less than […***…]% of
U.S. Profits for such year; and (b) bear interest at the rate set forth in
Section 6.21 of the Agreement if such amount is greater than or equal to
[…***…]% of U.S. Profits for such year. Any such adjustment credit with respect
to a downward adjustment will be without interest.

 

3. Definitions. As used herein, the term “operating unit” will mean the standard
operating unit in which a profit and loss statement is prepared for management
accounting purposes in the party’s normal accounting procedures, consistently
applied within and across its operating units. In addition, as a supplement to
the definitions provided in the Agreement and in Appendix 1 thereto, the
following terms shall have the meanings set forth below:

 

  a. “Allowable Costs and Expenses” means those costs and expenses incurred by
the parties or for their account after the applicable Product becomes an Elected
Product that are specifically attributable or related to the post-marketing
development, commercial manufacturing, marketing or selling of an Elected
Product in the U.S., and consisting of: (i) Cost of Goods Sold,
(ii) Post-Marketing Development Expenses, (iii) Sales and Marketing Expenses and
(iv) General and Administrative Expenses.

 

***Confidential Treatment Requested

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

  b. “Cost of Goods Sold” means the actual fully-burdened cost of Elected
Products shipped in final form for commercial distribution in the U.S. As used
herein, the cost of Elected Products means (i) in the case of products and
services acquired from Third Parties, payments made to such Third Parties,
(ii) in the case of manufacturing and supply services performed by Sanofi or its
Affiliate, the actual unit costs of manufacture in bulk form or final
manufacturing, as the case may be, plus the variances and other costs
specifically provided for herein, and (iii) production costs associated with
specific packaging and labeling requirements. Actual unit costs shall consist of
direct material and direct labor costs, plus manufacturing overhead reasonably
allocable to manufacturing and supply services, of Sanofi or its Affiliate, in
each case in accordance with reasonable cost accounting methods, consistently
applied. Direct material costs shall include the costs incurred in purchasing
materials, including sales and excise taxes imposed thereon and customs duty and
charges levied by governmental authorities in the U.S., and all costs of
packaging components. Direct labor shall include the cost of employees engaged
in direct manufacturing or supply activities and direct or indirect quality
control and quality assurance activities who are directly employed in
manufacturing and packaging of Elected Products for commercial distribution in
the U.S. Manufacturing overhead allocable to manufacturing and supply services
may include indirect labor, facilities’ start-up costs, unsuccessful or low
yielding production runs, excess or idle capacity, the costs of audits,
insurance, and manufacturing and supply administrative and facilities costs,
including allocable depreciation and repairs and maintenance of existing capital
assets. Such allocations shall be in accordance with reasonable cost accounting
methods, consistently applied, of the party performing the work. Costs of Goods
Sold will also include manufacturing variances and other attributable costs not
in standard (but excluding capacity not incorporated into standard manufacturing
unit costs) such as, but not limited to, material price variances, labor hour
variances, material usage variances, excess and obsolescence, inventory reserves
and batches that do not conform to specification. Cost of Goods Sold shall
exclude Third Party royalty expenses (which are handled separately in Article 6
of the Agreement).

 

  c. “Post-Marketing Development Expenses” means the expenses incurred by a
party or for its account that are attributable to the development of an Elected
Product for the U.S. after First Commercial Sale of such Elected Product in the
U.S., calculated on a fully burdened basis. Without limiting the generality of
the foregoing, “Post-Marketing Development Expenses” will mean amounts paid by a
party to Third Parties and internal costs (calculated on a full-time equivalent
basis) incurred by a party, in each case, in support of or for extension of the
applicable Elected Product in the U.S. after the First Commercial Sale in the
U.S.: Phase 4 Trials; ongoing product development (e.g., new formulations and
routes of administration); ongoing product support; ongoing medical affairs; and
fees and expenses of outside consultants and counsel in respect of regulatory
affairs.

 

  d.

“Sales and Marketing Expenses” means the costs which are incurred by a party or
for its account attributable to the distribution, sale, promotion and marketing
of

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

  an Elected Product in the U.S., calculated on a fully burdened basis. Sales
and Marketing Expenses will mean the sum of Selling Expenses, Marketing
Management, Market and Consumer Research, Advertising, Trade Promotion, Consumer
Promotion, Education Expenses and Freight and Transportation–Out, each of which
is specified below. The costs of activities which promote a party’s business as
a whole without being product specific (such as corporate image advertising) are
specifically excluded from Sales and Marketing Expenses. To the extent multiple
products are involved and some of such products are not an Elected Product, then
such allowances will be allocated on a pro rata basis based upon net sales of
each respective product by such operating unit during the most recent quarter.

 

  i. “Advertising” will include, but not be limited to, all media costs
associated with Elected Product advertising in the U.S. as follows: production
expense/artwork including set up; design and art work for an advertisement; the
cost of securing print space, air time, etc. in newspapers, magazines, trade
journals, television, radio, billboards, etc.

 

  ii. “Consumer Promotion” will include, but not be limited to, the expenses
associated with programs to promote an Elected Product in the U.S. directly to
the prescriber or end user. This category will include, but not be limited to,
expenses associated with promoting products directly to the professional
community such as professional samples, professional literature, promotional
material costs, patient aids and detailing aids. To the extent multiple products
are involved and some of such products are not the applicable Elected Product,
then such allowances will be allocated on a pro rata basis based upon net sales
of each respective product by such operating unit during the most recent
quarter.

 

  iii. “Education” will include, but not be limited to, expenses associated with
professional education with respect to an Elected Product in the U.S. through
any means not covered above, including, but not limited to, articles appearing
in journals, newspapers, magazines or other media; seminars, scientific
exhibits, and conventions; and symposia, advisory boards and opinion leader
development activities.

 

  iv. “Freight and Transportation–Out” will include (to the extent not already
recovered in the calculation of Net Sales), but not limited to, the portion of
distribution costs relating to moving Elected Product goods in the U.S. from a
warehouse to the customer as follows: outbound transportation costs; costs of
moving goods from a manufacturing point to a warehouse at another location from
which it is ultimately to be distributed to a customer; the costs of the traffic
department where there is a separate department that has responsibility for
administration of freight costs.

 

  v.

“Market and Consumer Research” will include, but not be limited to, compensation
and departmental expenses for market and consumer

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

  research personnel and payments to Third Parties related to conducting and
monitoring professional and consumer appraisals of existing, new or proposed
Elected Products in the U.S., such as market share services (e.g., IMS data),
special research testing and focus groups.

 

  vi. “Marketing Management” will include, but not be limited to, product
management and sales promotion management compensation and departmental
expenses. This will include, but not be limited to, costs associated with
developing overall sales and marketing strategies (e.g., product line or
customer segment), as well as planning and programs for Elected Products in the
U.S. In addition, payments to Third Parties in connection with trademark
selection, filing, prosecution and enforcement in the U.S. will be included in
this category.

 

  vii. “Selling Expenses” will include, but not be limited to, the following
costs directly associated with the efforts of field sales representatives with
respect to Elected Products in the U.S.: field sales force; field sales offices;
home offices; staffs directly involved in the management of and the performance
of the selling functions; and payments to Third Parties under contract sales and
marketing agreements. The costs of detailing sales calls will be allocated on a
weighted average basis based on the proportionate time and effort given to the
detailing of Elected Products versus product other than an Elected Product at an
accounting charge rate consistently applied within and across a party’s or a
Third Party’s operating units and which is no less favorable than the internal
charge rate used by such party or such Third Party for its own internal cost
accounting purposes for products other than the Elected Product (excluding
internal profit margins and markups). Without limiting the foregoing, “Selling
Expenses” shall include all compensation paid by Sanofi to Regulus in accordance
with paragraph 3h. of Appendix 10.

 

  viii. “Trade Promotion” will include, but not be limited to, the allowances
given to retailers, brokers, distributors, hospital buying groups, etc. for
purchasing, promoting, and distribution of Elected Products in the U.S. This
will include, but not be limited to, purchasing, advertising, new distribution,
and display allowances as well as free goods, wholesale allowances and
reasonable field sales samples.

 

  e.

“General and Administrative Expenses means a party’s customary allocation, based
on direct project headcount or other generally accepted activity-based
accounting methods, of the costs of the following corporate general and
administrative functions of such party or any of its operating units incurred to
support or facilitate the post-marketing development, commercial manufacturing,
marketing or selling of Elected Products in the U.S.: finance and accounting;
purchasing and receiving; management information systems; facilities; human
resources; executive management; and legal, patent and trademark. Such costs
include, but not limited to, the costs of employees performing such functions,
the

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

  direct costs of supporting such individuals in the performance of their jobs
(e.g., travel, floor space, computers and other supplies and telephones) and the
actual cost of outside services (e.g., consulting and audit services). General
and administrative expenses of a party or operating unit that are incurred in
the development, manufacturing, marketing or selling of an Elected Product
outside the U.S. will be excluded from General and Administrative Expenses. In
view of the manner in which General and Administrative Expenses are calculated,
administration expenses will be excluded from the definition of each of the
other cost items that make up Allowable Costs and Expenses.

Notwithstanding the foregoing or any other provision of this Agreement, total
General and Administrative Expenses for an Elected Product in the U.S. shall not
exceed […***…]% of U.S. Net Sales of such Elected Product in any quarter.

 

  f. “Net Interest Income” means interest income less interest expense and
adjusted for realized gains and losses from the sale of investments.

 

  g. “U.S. Profits” will have the meaning ascribed to it in paragraph 1 above.

 

4. Foreign Exchange. The functional currency for accounting for U.S. Profits
will be U.S. Dollars. The statement of U.S. Profits will be translated into U.S.
Dollars using, for each currency, the methodology specified in Section 6.17 of
the Agreement.

 

5. Audits. Regulus will have the right to request that an independent public
accounting firm perform an audit of Sanofi’s books of accounts for the purpose
of verifying compliance with this Appendix in accordance with Sections 6.18.1
and 6.18.4, mutatis mutandis. Such audits will be conducted at the expense of
Regulus; provided, however, that if the audit results in an upward adjustment
exceeding […***…]% of U.S. Profits for such year the reasonable cost of the
audit will be borne by Sanofi. Any disputes with regard to the foregoing will be
resolved in accordance with Section 13.4 of the Agreement. Audit results will be
shared with both parties.

 

***Confidential Treatment Requested

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

APPENDIX 12

Regulus Second Restatement Press Release

 

LOGO [g652681ex10_52pg133.jpg]

DRAFT

Regulus Renews Strategic Alliance with Sanofi to Focus on Orphan Disease and
Oncology Targets and Receives Additional $10 Million Equity Investment

-Regulus to Develop microRNA-21 for Alport Syndrome,

a Life-Threatening Orphan Kidney Disease, and microRNA-21 in Oncology, to Human
Proof-of-Concept-

-Sanofi Obtains Exclusive Option to Regulus’ Program Targeting
microRNA-221/microRNA-222-

Regulus Milestones Remain with Upside in Potential Royalties

LA JOLLA, Calif., February 5, 2014 –Regulus Therapeutics Inc. (NASDAQ:RGLS)
announced today that it has renewed its strategic alliance with Sanofi to
discover, develop, and commercialize microRNA therapeutics to focus on specific
orphan disease and oncology targets. Regulus will lead development of its
fibrosis program targeting microRNA-21 (“miR-21”) for the treatment of Alport
Syndrome, an orphan, life-threatening genetic kidney disease with no approved
therapy, and for its microRNA-21 (“miR-21”) program in oncology. Sanofi has
retained its interest in these microRNA-21 programs and has gained rights to
Regulus’ preclinical program targeting microRNA-221/microRNA-222
(“miR-221/222”). Regulus is responsible for advancing the clinical candidates in
these programs to proof-of-concept. Sanofi shall have the exclusive option,
exercisable after proof-of-concept, to take over further development and
commercialization of each microRNA therapeutic program. At this stage, Regulus
will have the option to co-promote any microRNA therapeutic product in the
United States.

“The renewal of our strategic relationship with Sanofi further underscores the
commitment of both companies to realize the tremendous promise of RNA
therapeutics and the possibility to transform the field of drug discovery by
targeting microRNAs,” said Kleanthis G. Xanthopoulos, Ph.D., President and CEO
of Regulus. “We believe that Regulus’ microRNA therapeutic platform, coupled
with our focus on orphan diseases and oncology indications, combine perfectly
with Sanofi’s resources and their proven capabilities as a global-healthcare
leader to bring innovative medicines to patients in need. We look forward to
advancing our programs together and building a meaningful clinical portfolio.”

The refocused relationship allows Sanofi and Regulus to continue to collaborate
on several meaningful microRNA therapeutic programs, with a greater focus on
orphan diseases and oncology. Under the original agreement from 2010, Sanofi had
rights on up to four microRNA targets, which included Regulus’ lead fibrosis
program targeting miR-21. In 2012, the companies expanded the alliance to
collaborate on an oncology program targeting miR-21. In 2013, the companies
entered into an option letter agreement to allow for negotiation of the extended
strategic alliance announced today. Sanofi retained its interest in developing
microRNA-21 therapeutics for fibrosis and oncology indications and now has
opt-in rights to Regulus’ miR-21 and miR-221/222 program. If Sanofi chooses to
exercise its

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option on any of these programs, Sanofi will reimburse Regulus for a significant
portion of its preclinical and clinical development costs. Regulus continues to
be eligible to receive royalties on microRNA therapeutic products commercialized
by Sanofi.

Additionally, Sanofi has increased its ownership stake in Regulus through an
additional $10 million common stock investment at $7.67 per share, which
represents the volume-weighted average share price over the last 30 trading
days.

About Regulus

Regulus Therapeutics Inc. (NASDAQ:RGLS) is a biopharmaceutical company leading
the discovery and development of innovative medicines targeting
microRNAs. Regulus is uniquely positioned to leverage a mature therapeutic
platform that harnesses the oligonucleotide drug discovery and development
expertise of Alnylam Pharmaceuticals, Inc. and Isis Pharmaceuticals, Inc., which
founded the company. Regulus has a well-balanced microRNA therapeutic pipeline
entering clinical development, an emerging microRNA biomarkers platform to
support its therapeutic programs, and a rich intellectual property estate to
retain its leadership in the microRNA field. Regulus intends to focus its
proprietary efforts on developing microRNA therapeutics for oncology indications
and orphan diseases and is currently advancing several programs toward clinical
development in oncology, fibrosis and metabolic diseases. Regulus is also
developing RG-101, a GalNAc-conjugated anti-miR targeting microRNA-122, for the
treatment of chronic hepatitis C virus infection. Regulus’ commitment to
innovation and its leadership in the microRNA field have enabled the formation
of strategic alliances with AstraZeneca, GlaxoSmithKline and Sanofi. In
addition, the Company has established Regulus microMarkers™, a research and
development division focused on identifying microRNAs as biomarkers of human
disease, which is designed to support its therapeutic pipeline, collaborators
and strategic partners.

For more information, please visit http://www.regulusrx.com.

Forward-Looking Statements

Statements contained in this press release regarding matters that are not
historical facts are “forward-looking statements” within the meaning of the
Private Securities Litigation Reform Act of 1995, including statements
associated with Regulus’ expectations regarding future therapeutic and
commercial potential of Regulus’ business plans, technologies and intellectual
property related to microRNA therapeutics being discovered and developed by
Regulus. Because such statements are subject to risks and uncertainties, actual
results may differ materially from those expressed or implied by such
forward-looking statements. Words such as “believes,” “anticipates,” “plans,”
“expects,” “intends,” “will,” “goal,” “potential” and similar expressions are
intended to identify forward-looking statements. These forward-looking
statements are based upon Regulus’ current expectations and involve assumptions
that may never materialize or may prove to be incorrect. Actual results and the
timing of events could differ materially from those anticipated in such
forward-looking statements as a result of various risks and uncertainties, which
include, without limitation, risks associated with the process of discovering,
developing and commercializing drugs that are safe and effective for use as
human therapeutics, and in the endeavor of building a business around such
drugs. These and other risks concerning Regulus’ programs are described in
additional detail in Regulus’ SEC filings. All forward-looking statements
contained in this press release speak only as of the date on which they were
made. Regulus undertakes no obligation to update such statements to reflect
events that occur or circumstances that exist after the date on which they were
made.

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Contact:

Amy Conrad

Director, Investor Relations and Corporate Communications

aconrad@regulusrx.com

858-202-6321

Media:

Liz Bryan

Spectrum Science

lbryan@spectrumscience.com

202-955-6222 x2526