8-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): January 30, 2014

Regulus Therapeutics Inc.

(Exact name of registrant as specified in its charter)

Delaware	001-35670	26-4738379
(State of incorporation)	(Commission File No.)	(IRS Employer Identification No.)
3545 John Hopkins Court Suite 210 San Diego, CA		92121
(Address of principal executive offices)		(Zip Code)

Registrant’s telephone number, including area code: (858) 202-6300

N/A

(Former name or former address, if changed since last report.)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):

¨ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

¨ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

¨ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

¨ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Item 1.01 Entry into a Material Definitive Agreement.

Option Letter Amendment

On January 30, 2014, Regulus Therapeutics Inc. (the “Company”) and Sanofi entered into an amendment (the “Option Letter Amendment”) to that certain Option Letter Agreement dated June 21, 2013 (the “Option Letter Agreement”), pursuant to which the Company and Sanofi agreed to extend the exclusivity period for the Sanofi Option (as defined in the Company’s Current Report on Form 8-K filed with the Securities and Exchange Commission (“SEC”) on June 26, 2013) and the exclusivity period for the Company Option (as defined in the Company’s Current Report on Form 8-K filed with the SEC on June 26, 2013) from January 30, 2014 to February 14, 2014. A copy of the Option Letter Amendment is attached as Exhibit 99.1 hereto and is incorporated herein by reference.

Second Amended and Restated Collaboration and License Agreement

On February 4, 2014, the Company entered into a Second Amended and Restated Collaboration and License Agreement with Sanofi (the “Second Restatement”), which amends, restates and supersedes the Amended and Restated Collaboration and License Agreement entered into by the Company and Sanofi in July 2012 (which in turn amended, restated and superseded the Collaboration and License Agreement entered into by the Company and Sanofi in June 2010). The Second Restatement also supersedes the Option Letter Agreement, as amended by the Option Letter Amendment.

Under the terms of the Second Restatement, the Company and Sanofi have extended their strategic alliance to discover, develop, and commercialize microRNA therapeutics to focus on specific orphan disease and oncology targets. The Second Restatement provides that the Company will lead development of three of the Company’s therapeutic programs (each, a “Program”):

• The preclinical fibrosis program targeting microRNA-21 (“miR-21”), for the treatment of Alport Syndrome, an orphan, life-threatening genetic kidney disease with no approved therapy (the “miR-21 Fibrosis Program”);

• the preclinical program targeting miR-21 for oncology indications (the “miR-21 Oncology Program”); and

• the preclinical program targeting microRNA-221/microRNA-222 (“miR-221/222”) for oncology indications (the “miR-221/222 Oncology Program”).

The Company has agreed to use its commercially reasonable efforts to advance a clinical candidate in each of the Programs to proof of concept in a human clinical trial (“POC”) and is responsible for conducting the development and compound manufacturing activities necessary for achievement of POC, at the Company’s cost. Sanofi has the right but not the obligation to perform mutually-agreed development activities complementary to the Company’s efforts in each Program, at Sanofi’s cost. If a clinical candidate in any of the Programs achieves POC, Sanofi has the option (an “Option”), exercisable within 90 days after POC achievement in such Program (the “Option Period”), to assume all costs, responsibilities and obligations for further development and commercialization of such Program, and upon such exercise Sanofi will have an exclusive, worldwide license to develop and commercialize microRNA therapeutic products containing microRNA compounds that were the subject of such Program (“Program Products”), provided that if Sanofi exercises its Option with respect to any Program, the Company will have the option to co-promote any Program Product from such Program with Sanofi in the United States.

If Sanofi chooses to exercise its Option for any Program, Sanofi will reimburse the Company for a significant portion of the preclinical and clinical development costs incurred by the Company in performing such Program and will also pay the Company an Option exercise fee for such Program. Sanofi will be entitled to credit $1.25 million of the $2.5 million upfront option fee paid by Sanofi to the Company pursuant to the Option Letter Agreement against the Option exercise fee for the first Program with respect to which Sanofi exercises its Option. In addition, if Sanofi exercises its Option with respect to any Program, Sanofi will be entitled to credit the costs incurred by it in performing mutually-agreed activities related to such Program against the Option exercise fee for such Program, up to a maximum of $10.0 million in the aggregate for any and all Programs with respect to which Sanofi exercises its Option.

Under the Second Restatement, Sanofi retains its existing exclusive, worldwide license (the “miR-21 License”) to develop and commercialize microRNA therapeutic products targeting miR-21 (“miR-21 Products”). However, if Sanofi does not exercise its Option for an miR-21 Program within 90 days after achievement of POC in such miR-21 Program, or if an miR-21 Program is terminated before achievement of POC in such miR-21 Program, Program Products containing any of the miR-21 compounds that were the subject of such miR-21 Program (“miR-21 Program Products”) will be excluded from the miR-21 License, and the Company will have the exclusive right to develop and commercialize such miR-21 Program Products, without further obligation to Sanofi.

If Sanofi exercises its Option with respect to the miR-221/222 Program, Sanofi will receive an exclusive, worldwide license to develop and commercialize microRNA therapeutic products containing miR-221/222 compounds (“miR-221/222 Products”), subject to the Company’s option to co-promote MiR-221/222 Products from the MiR-221/222 Program with Sanofi in the United States.

If Sanofi exercises its Option with respect to at least one of the miR-21 Programs, the Company is eligible to receive clinical and regulatory milestone payments of up to $125.0 million, in the aggregate, for the first and second miR-21 Program Products to achieve the applicable clinical and regulatory milestones, as well as additional regulatory milestone payments on the subsequent achievement of regulatory milestones by any other miR-21 Program Product for a different indication. If Sanofi exercises its Option with respect to the miR-221/222 Program, the Company is eligible to receive regulatory milestone payments of up to $70.0 million for the first miR-221/222 Product to achieve such regulatory milestones.

The Company is also eligible to receive commercial milestone payments of up to an aggregate of $120.0 million if Sanofi exercises both its Option for at least one miR-21 Program and its Option for the miR-221/222 Program. In addition, the Company is entitled to receive royalties based on a percentage of net sales of miR-21 Program Products and miR-221/222 Products which, in the case of sales in the United States, will be in the middle of the 10 to 20% range, and, in the case of sales outside of the United States, will range from the low end to the middle of the 10 to 20% range, depending upon the volume of sales.

If the Company exercises its option to co-promote a Program Product, the Company will continue to be eligible to receive royalties on net sales of such Program Product in the United States at the same rate, unless the Company elects to share a portion of Sanofi’s profits from sales of such Program Product in the United States in lieu of royalties.

In the case of miR-21 Products other than miR-21 Program Products, the Company is entitled to receive preclinical, clinical and regulatory milestone payments of up to $118.0 million for the first such miR-21 Product to achieve such milestones, and additional regulatory milestone payments on subsequent achievement of regulatory milestones by any other miR-21 Product (excluding an MiR-21 Program Product) for a different indication. In addition, the Company is entitled to receive royalties on miR-21 Products other than miR-21 Program Products based on a percentage of net sales which will range from the mid-single digits to the low end of the 10 to 20% range, depending upon the volume of sales.

Sanofi may terminate the Second Restatement in full or on a product-by-product basis by giving 30 days’ prior written notice to the Company. Either party may also terminate the Second Restatement for a material breach by the other party which remains uncured after 120 days’ notice of such breach, except that (a) the Company may not exercise this termination right for an miR-21 Product until after the earlier of (i) the exercise of the Option for at least one of the mir-21 Programs and (ii) the expiration of the Option Periods with respect to both of the miR-21 Programs without Sanofi’s exercise of either of such Options, and (b) the Company may not exercise this termination right for an miR-221/222 Product until after the exercise of the Option for the miR-221/222 Program. In the event a Program or the Second Restatement is terminated by Sanofi, the rights to develop and commercialize Program Products from the terminated Program(s) (including the right to sublicense these rights to a third party) returns to the Company.

In addition, if rights to any Program Product from a Program with respect to which Sanofi exercised its Option revert to the Company after Sanofi has completed at least one Phase 2 clinical trial of such Program Product following such exercise, then, if the Company sublicenses such Program Product to a third party, the Company will be required to pay a percentage of sublicense revenues to Sanofi in the low end of the 10 to 20% range, and if the Company commercializes such Program Product on its own, the Company will be required to pay royalties to Sanofi as a percentage of net sales in the low single digits.

The foregoing description of the Second Restatement is qualified in its entirety by reference to the Second Restatement, a copy of which will be filed as an exhibit to the Company’s Annual Report on Form 10-K for the year ended December 31, 2013.

Common Stock Purchase Agreement

On February 4, 2014, in connection with the entry into the Second Restatement, the Company entered into a Common Stock Purchase Agreement (the “Purchase Agreement”) with Aventis Holdings Inc. (“Aventis”), an entity affiliated with Sanofi, pursuant to which the Company issued and sold 1,303,780 shares of the Company’s common stock (the “Shares”) to Aventis at a purchase price of $7.67 per share (representing the average of the daily volume weighted average prices per share of the Company’s common stock as reported on The Nasdaq Global Market during the 30 trading days ending on the date immediately preceding the date of the Purchase Agreement) and an aggregate purchase price of $10.0 million. A copy of the Purchase Agreement is attached as Exhibit 99.2 hereto and is incorporated herein by reference.

Registration Rights Agreement

On February 4, 2014, the Company also entered into an Registration Rights Agreement with Aventis (the “Registration Rights Agreement”), pursuant to which Aventis will have the right to require the Company to register the Shares on a Form S-3 registration statement with the SEC or to include the Shares in a registration statement filed by the Company. Aventis’ right to request a registration of the Shares will terminate on February 4, 2016. A copy of the Registration Rights Agreement is attached as Exhibit 99.3 hereto and is incorporated herein by reference.

Item 3.02 Unregistered Sales of Equity Securities.

The information relating to the issuance and sale of the Shares to Aventis in Item 1.01 of this Current Report is incorporated herein by reference. The aggregate purchase price of the Shares was $10.0 million, representing a per Share price of $7.67. The purchase price of the Shares was paid for by Aventis in immediately available funds.

The sales and issuance of the Shares were not registered under the Securities Act of the 1933, as amended (the “Securities Act”), or any state securities laws. We have relied on the exemption from the registration requirements of the Securities Act by virtue of Section 4(a)(2) thereof and Rule 506, Regulation D thereunder. In connection with Aventis’ execution of the Purchase Agreement, Aventis represented to the Company that it is an “accredited investor” as defined in Regulation D of the Securities Act and that the securities purchased by Aventis were acquired solely for its own account and for investment purposes and not with a view to the future sale or distribution by Aventis.

Item 9.01 Financial Statements and Exhibits.

(d) Exhibits.

Exhibit No.	Description
99.1	Option Letter Amendment by and between Regulus Therapeutics Inc. and Sanofi dated January 30, 2014
99.2	Common Stock Purchase Agreement by and between Regulus Therapeutics Inc. and Aventis Holdings Inc., dated February 4, 2014
99.3	Registration Rights Agreement by and between Regulus Therapeutics Inc. and Aventis Holdings Inc., dated February 4, 2014

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

	Regulus Therapeutics Inc.
Date: February 5, 2014	By:	/s/ Kleanthis G. Xanthopoulos
		Kleanthis G. Xanthopoulos, Ph.D.
		President and Chief Executive Officer

EXHIBIT INDEX

Exhibit No.	Description
99.1	Option Letter Amendment by and between Regulus Therapeutics Inc. and Sanofi dated January 30, 2014
99.2	Common Stock Purchase Agreement by and between Regulus Therapeutics Inc. and Aventis Holdings Inc., dated February 4, 2014
99.3	Registration Rights Agreement by and between Regulus Therapeutics Inc. and Aventis Holdings Inc., dated February 4, 2014

EX-99.1

Exhibit 99.1

January 30, 2014

Sanofi

54, rue La Boétie

75414 Paris, France

Attn: Philippe Goupit, Vice President, Corporate Licenses, Strategy & Development

Re: Extension of Option Periods

Dear Philippe:

Sanofi and Regulus Therapeutics Inc. (“Regulus”) are parties to that certain Option Letter, dated as of June 21, 2013 (the “Option Letter”). Capitalized terms used and not expressly defined in this letter shall have the meanings attributed to them in the Option Letter.

The parties hereto hereby acknowledge and agree that as of December 31, 2013, the parties were actively negotiating the miR-21 Co-Development Agreement and the microRNA Collaboration Agreement, and accordingly the Regulus Option Period and the Sanofi Option Period were automatically extended for an additional thirty (30) days until January 30, 2014.

The parties hereto now desire to extend the Regulus Option Period and the Sanofi Option Period as set forth herein. Accordingly, in consideration for the mutual promises set forth herein, and for other good and valuable consideration, the sufficiency of which is hereby acknowledged, the parties hereto hereby agree to amend the Option Letter as follows:

1. The third paragraph under the header “Regulus Option:” is hereby amended and restated to read in its entirety as follows: “The Regulus Option shall expire on February 14, 2014, or upon execution of the miR-21 Co-Development Agreement, whichever occurs first (“Regulus Option Period”).”

2. The second paragraph under the header “Sanofi Option:” is hereby amended and restated to read in its entirety as follows: “The Sanofi Option shall expire on February 14, 2014 or upon execution of the microRNA Collaboration Agreement, whichever occurs first (“Sanofi Option Period”).”

Except as expressly modified by this letter, all terms and conditions set forth in the Option Letter shall remain unchanged.

[Remainder of page intentionally left blank]

In order to confirm Sanofi’s agreement to this letter, please return one countersigned copy of this letter to me via email at xxxxx@regulusrx.com or by courier to my attention to 3545 John Hopkins Court, Suite 210, San Diego, California 92121, USA.

Sincerely, on behalf of Regulus,

    /s/ Kleanthis G. Xanthopoulos

Kleanthis G. Xanthopoulos, Ph.D.

President and Chief Executive Officer

Agreed on behalf of Sanofi,

  /s/ Philippe Goupit

Philippe Goupit

Vice President, Corporate Licenses

Strategy & Business Development

EX-99.2

Exhibit 99.2

EXECUTION COPY

COMMON STOCK PURCHASE AGREEMENT

This COMMON STOCK PURCHASE AGREEMENT (this “Agreement”), dated as of February 4, 2014, is made by and between REGULUS THERAPEUTICS INC., a Delaware corporation (the “Company”), and AVENTIS HOLDINGS INC., a Delaware corporation (“Purchaser”).

RECITALS:

A. The Company and Purchaser are executing and delivering this Agreement in reliance upon the exemption from securities registration afforded by Section 4(a)(2) of the Securities Act and Regulation D, Rule 506(b) thereunder.

B. Purchaser desires to purchase and the Company desires to sell, upon the terms and conditions stated in this Agreement, $10,000,000 of Common Stock of the Company.

C. The capitalized terms used herein and not otherwise defined have the meanings given them in Article 6.

AGREEMENT

In consideration of the premises and the mutual covenants contained herein and other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the Company and Purchaser hereby agree as follows:

ARTICLE 1

PURCHASE AND SALE OF COMMON STOCK

1.1 Purchase and Sale of Common Stock. At the Closing, the Company will issue and sell to Purchaser, and Purchaser will purchase from the Company, 1,303,780 shares of Common Stock (the “Securities” or the “Shares”). The purchase price for each Share shall be $7.67 (the “Purchase Price”).

1.2 Payment. At the Closing, the Company will instruct its transfer agent to credit Purchaser the Shares against delivery, within three (3) business days of the Closing Date, of the aggregate Purchase Price of $10,000,000 by wire transfer of immediately available funds in accordance with wire instructions provided by the Company to Purchaser prior to the Closing.

1.3 Closing Date. The closing of the transaction contemplated by this Agreement will take place on the date of this Agreement (the “Closing Date”) and the closing (the “Closing”) will be held at the offices of Cooley LLP, 4401 Eastgate Mall, San Diego, CA 92121 or at such other time and place as shall be agreed upon by the Company and Purchaser.

1.4 Registration Rights Agreement. In conjunction with the Closing, the parties shall enter into the Registration Rights Agreement, substantially in the form attached hereto as Exhibit A (the “Registration Rights Agreement”)

ARTICLE 2

REPRESENTATIONS AND WARRANTIES OF THE COMPANY

Except as specifically contemplated by this Agreement, the Company hereby represents and warrants to Purchaser that:

2.1 Organization and Qualification. The Company is duly incorporated, validly existing and in good standing under the laws of the State of Delaware, with full corporate power and authority to conduct its business as currently conducted as disclosed in the SEC Documents. The Company is duly qualified to do business and is in good standing in every jurisdiction in which the nature of the business conducted by it or property owned by it makes such qualification necessary, except where the failure to be so qualified or in good standing, as the case may be, would not reasonably be expected to have a Material Adverse Effect.

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2.2 Authorization; Enforcement. The Company has all requisite corporate power and authority to enter into and to perform its obligations under this Agreement and the Registration Rights Agreement, to consummate the transactions contemplated hereby and thereby and to issue the Securities in accordance with the terms hereof. The execution, delivery and performance of this Agreement and the Registration Rights Agreement by the Company and the consummation by it of the transactions contemplated hereby (including the issuance of the Securities) and thereby have been duly authorized by the Company’s Board of Directors and the Audit Committee of the Company’s Board of Directors and no further consent or authorization of the Company, its Board of Directors, or its stockholders is required. This Agreement and the Registration Rights Agreement have been duly executed by the Company and each constitutes a legal, valid and binding obligation of the Company enforceable against the Company in accordance with its terms, except as enforceability may be limited by applicable bankruptcy, insolvency, reorganization, or moratorium or similar laws affecting creditors’ and contracting parties’ rights generally and except as enforceability may be subject to general principles of equity and except as rights to indemnity and contribution may be limited by state or federal securities laws or public policy underlying such laws.

2.3 Capitalization. The authorized capital stock of the Company, as of December 31, 2013, consisted of 200,000,000 shares of Common Stock, $0.001 par value per share, of which 41,787,326 shares were issued and outstanding and 10,000,000 shares of blank check Preferred Stock, $0.001 par value per share, none of which have been designated. All of the issued and outstanding shares of Common Stock have been duly authorized, validly issued, fully paid, and nonassessable. Options to purchase an aggregate of 5,598,207 shares of Common Stock were outstanding as of December 31, 2013. Except as disclosed in or contemplated by the SEC Documents, the Company does not have outstanding any options to purchase, or any preemptive rights or other rights to subscribe for or to purchase, any securities or obligations convertible into, or any contracts or commitments to issue or sell, shares of its capital stock or any such options, rights, convertible securities or obligations other than options granted under the Company’s stock option plans and its employee stock purchase plan. The Company’s Amended and Restated Certificate of Incorporation (the “Certificate of Incorporation”), as in effect on the date hereof, and the Company’s Amended and Restated Bylaws (the “Bylaws”) as in effect on the date hereof, are each filed as exhibits to the SEC Documents.

2.4 Issuance of Securities. The Shares are duly authorized and, upon issuance in accordance with the terms of this Agreement, will be validly issued, fully paid and non-assessable and will not be subject to preemptive rights or other similar rights of stockholders of the Company.

2.5 No Conflicts; Government Consents and Permits.

(a) The execution, delivery and performance of this Agreement by the Company and the consummation by the Company of the transactions contemplated hereby (including the issuance of the Securities) will not (i) conflict with or result in a violation of any provision of its Certificate of Incorporation or Bylaws or require the approval of the Company’s stockholders, (ii) violate or conflict with, or result in a breach of any provision of, or constitute a default under, any agreement, indenture, or instrument to which the Company is a party, or (iii) result in a violation of any law, rule, regulation, order, judgment or decree (including United States federal and state securities laws and regulations and regulations of any self-regulatory organizations to which the Company or its securities are subject) applicable to the Company, except in the case of clauses (ii) and (iii) only, for such conflicts, breaches, defaults, and violations as would not reasonably be expected to have a Material Adverse Effect.

(b) The Company is not required to obtain any consent, authorization or order of, or make any filing or registration with, any court or governmental agency or any regulatory or self regulatory agency in order for it to execute, deliver or perform any of its obligations under this Agreement in accordance with the terms hereof, or to issue and sell the Securities in accordance with the terms hereof other than (i) such as have been made or obtained, (ii) any filings required to be made under federal or state securities laws, and (iii) any required filings or notifications regarding the issuance or listing of additional shares with Nasdaq.

(c) The Company has all franchises, permits, licenses, and any similar authority necessary for the conduct of its business as now being conducted by it and as currently proposed to be conducted as disclosed in the SEC Documents, except for such franchise, permit, license or similar authority, the lack of which would not reasonably be expected to have a Material Adverse Effect. The Company has not received any actual notice of any proceeding relating to revocation or modification of any such franchise, permit, license, or similar authority except where such revocation or modification would not reasonably be expected to have a Material Adverse Effect.

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2.6 SEC Documents, Financial Statements. The Company has timely filed all reports, schedules, forms, statements and other documents required to be filed by it with the SEC since January 1, 2013, pursuant to the reporting requirements of the Exchange Act (all of the foregoing filed prior to the date hereof and all exhibits included therein and financial statements and schedules thereto and documents (other than exhibits) incorporated by reference therein, being hereinafter referred to herein as the “SEC Documents”). Except as otherwise expressly stated herein, all references in this Agreement to information disclosed or described in the SEC Documents shall include the disclosure set forth on Exhibit B hereto to the extent such disclosure is filed with the SEC on a Form 8-K on or before 9:30 a.m., New York local time, on February 5, 2014. The Company is eligible to register its Common Stock for resale using Form S-1 promulgated under the Securities Act. The Company has delivered to Purchaser, or Purchaser has had access to, true and complete copies of the SEC Documents. As of their respective dates, the SEC Documents complied in all material respects with the requirements of the Exchange Act or the Securities Act, as the case may be, and the rules and regulations of the SEC promulgated thereunder applicable to the SEC Documents, and none of the SEC Documents, at the time they were filed with the SEC, contained any untrue statement of a material fact or omitted to state a material fact required to be stated therein or necessary in order to make the statements therein, in light of the circumstances under which they were made, not misleading. As of their respective dates, the Financial Statements and the related notes complied as to form in all material respects with applicable accounting requirements and the published rules and regulations of the SEC with respect thereto. The Financial Statements and the related notes have been prepared in accordance with accounting principles generally accepted in the United States, consistently applied, during the periods involved (except (i) as may be otherwise indicated in the Financial Statements or the notes thereto, or (ii) in the case of unaudited interim statements, to the extent they may not include footnotes, may be condensed or summary statements or may conform to the SEC’s rules and instructions for Reports on Form 10-Q) and fairly present in all material respects the consolidated financial position of the Company as of the dates thereof and the consolidated results of its operations and cash flows for the periods then ended (subject, in the case of unaudited statements, to normal and recurring year-end audit adjustments). All material agreements that were required to be filed as exhibits to the SEC Documents under Item 601 of Regulation S-K (collectively, the “Material Agreements”) to which the Company or any Subsidiary of the Company is a party, or the property or assets of the Company or any Subsidiary of the Company are subject, have been filed as exhibits to the SEC Documents. All Material Agreements are valid and enforceable against the Company in accordance with their respective terms, except (i) as enforceability may be limited by applicable bankruptcy, insolvency, reorganization, or moratorium or similar laws affecting creditors’ and contracting parties’ rights generally, and (ii) as enforceability may be subject to general principles of equity and except as rights to indemnity and contribution may be limited by state or federal securities laws or public policy underlying such laws. The Company is not in material breach of or default under any material provision of any of the Material Agreements, and to the Company’s knowledge, no other party to a Material Agreement is in material breach of or default under any material provision of any Material Agreements. The Company has not received a notice of termination nor is the Company otherwise aware of any threats to terminate any of the Material Agreements.

2.7 Disclosure Controls and Procedures. The Company has established and maintains disclosure controls and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) that are effective in all material respects to ensure that material information relating to the Company, including any consolidated Subsidiaries, is made known to its chief executive officer and chief financial officer by others within those entities. The Company’s certifying officers have evaluated the effectiveness of the Company’s disclosure controls and procedures as of the end of the period covered by the most recently filed quarterly or annual periodic report under the Exchange Act (such date, the “Evaluation Date”). The Company presented in its most recently filed quarterly or annual periodic report under the Exchange Act the conclusions of the certifying officers about the effectiveness of the disclosure controls and procedures based on their evaluations as of the Evaluation Date. Since the Evaluation Date, there have been no significant changes in the Company’s internal control over financial reporting (as such term is defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) or, to the Company’s knowledge, in other factors that could significantly affect the Company’s internal control over financial reporting.

2.8 Accounting Controls. The Company maintains a system of internal accounting controls sufficient to provide reasonable assurances that (i) transactions are executed in accordance with management’s general or specific authorization, (ii) transactions are recorded as necessary to permit preparation of financial statements in conformity with

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generally accepted accounting principles as applied in the United States and to maintain accountability for assets, (iii) access to assets is permitted only in accordance with management’s general or specific authorization, and (iv) the recorded accountability for assets is compared with existing assets at reasonable intervals and appropriate action is taken with respect to any differences.

2.9 Absence of Litigation. As of the date hereof, there is no action, suit, proceeding or investigation before or by any court, public board, government agency, self-regulatory organization or body pending or, to the Company’s knowledge, threatened against the Company that if determined adversely to the Company would reasonably be expected to have a Material Adverse Effect or would reasonably be expected to impair the ability of the Company to perform its obligations under this Agreement. Neither the Company, nor any director or officer thereof, is or has been the subject of any action involving a claim of violation of or liability under federal or state securities laws or a claim of breach of fiduciary duty relating to the Company. There has not been, and to the knowledge of the Company, there is not pending or contemplated, any investigation by the SEC of the Company or any current or former director or officer of the Company. The Company has not received any stop order or other order suspending the effectiveness of any registration statement filed by the Company under the Exchange Act or the Securities Act and, to the Company’s knowledge, the SEC has not issued any such order.

2.10 Intellectual Property Rights. The Company owns or possesses, or has a reasonable basis on which it believes it can obtain on reasonable terms, licenses or sufficient rights to use all patents, patent applications, patent rights, inventions, know-how, trade secrets, trademarks, trademark applications, service marks, service names, trade names and copyrights necessary to enable it to conduct its business as conducted as of the date hereof and, to its knowledge, as proposed to be conducted as described in the SEC Documents (the “Intellectual Property”). To the Company’s knowledge, the Company has not infringed the intellectual property rights of third parties and no third party, to the Company’s knowledge, is infringing the Intellectual Property of the Company, in each case, which could reasonably be expected to result in an adverse and material effect on the Company. Except as disclosed in the SEC Documents, there are no material options, licenses or agreements relating to the Intellectual Property, nor is the Company bound by or a party to any material options, licenses or agreements relating to the patents, patent applications, patent rights, inventions, know-how, trade secrets, trademarks, trademark applications, service marks, service names, trade names or copyrights of any other Person. There is no material claim or action or proceeding pending or, to the Company’s knowledge, threatened that challenges any of the rights of the Company in or to, or otherwise with respect to, any Intellectual Property.

2.11 Placement Agents. The Company has taken no action that would give rise to any claim by any Person for brokerage commissions, placement agent’s fees or similar payments relating to this Agreement or the transactions contemplated hereby.

2.12 Investment Company. The Company is not and, after giving effect to the offering and sale of the Securities, will not be an “investment company” as such term is defined in the Investment Company Act of 1940, as amended (the “Investment Company Act”). The Company shall conduct its business in a manner so that it will not become subject to the Investment Company Act.

2.13 No Material Adverse Change. Since September 30, 2013, except as described or referred to in the SEC Documents and except for cash expenditures in the ordinary course of business, there has not been any change in the assets, business, properties, financial condition or results of operations of the Company that would reasonably be expected to have a Material Adverse Effect. Since September 30, 2013, (i) there has not been any dividend or distribution of any kind declared, set aside for payment, paid or made by the Company on any class of capital stock, (ii) the Company has not sustained any material loss or interference with the Company’s business from fire, explosion, flood or other calamity, whether or not covered by insurance, or from any labor disturbance or dispute or any action, order or decree of any court or arbitrator or governmental or regulatory authority, (iii) the Company has not incurred any material liabilities except in the ordinary course of business and (iv) the Company has not issued any shares of Common Stock other than in connection with director, officer and employee compensation arrangements.

2.14 The Nasdaq Global Market. The Common Stock is listed on The Nasdaq Global Market, and, except as disclosed in the SEC Documents, to the Company’s knowledge, there are no proceedings to revoke or suspend such listing or the listing of the Shares. Except as disclosed in the SEC Documents, the Company is in compliance with the requirements of Nasdaq for continued listing of the Common Stock thereon and any other Nasdaq listing and maintenance requirements.

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2.15 Acknowledgment Regarding Purchaser’s Purchase of Securities. The Company acknowledges and agrees that Purchaser is acting solely in the capacity of an arm’s length purchaser with respect to this Agreement and the transactions contemplated hereby. The Company further acknowledges that Purchaser is not acting as a financial advisor or fiduciary of the Company (or in any similar capacity with respect to the Company) with respect to this Agreement and the transactions contemplated hereby and any advice given by Purchaser or any of its respective representatives or agents to the Company in connection with this Agreement and the transactions contemplated hereby is merely incidental to Purchaser’s purchase of the Securities. The Company further represents to Purchaser that the Company’s decision to enter into this Agreement has been based on the independent evaluation of the transactions contemplated hereby by the Company and its representatives.

2.16 Insurance. The Company is insured by insurers of recognized financial responsibility against such losses and risks and in such amounts as the Company believes are prudent and customary for a company (i) in the businesses and location in which the Company is engaged, (ii) with the resources of the Company, and (iii) at a similar stage of development as the Company. The Company has not received any written notice that the Company will not be able to renew its existing insurance coverage as and when such coverage expires. The Company believes it will be able to obtain similar coverage at reasonable cost from similar insurers as may be necessary to continue its business.

2.17 Foreign Corrupt Practices. Since January 1, 2007, neither the Company, nor to the Company’s knowledge, any director, officer, agent, employee or other Person acting on behalf of the Company has, in the course of its actions for, or on behalf of, the Company (i) used any corporate funds for any unlawful contribution, gift, entertainment or other unlawful expenses relating to political activity; (ii) made any direct or indirect unlawful payment to any foreign or domestic government official or employee from corporate funds; (iii) violated or is in violation of in any material respect any provision of the U.S. Foreign Corrupt Practices Act of 1977, as amended; or (iv) made any unlawful bribe, rebate, payoff, influence payment, kickback or other unlawful payment to any foreign or domestic government official or employee.

2.18 Private Placement. Neither the Company nor its Subsidiary or any affiliates, nor any Person acting on its or their behalf, has, directly or indirectly, made any offers or sales of any security or solicited any offers to buy any security, under any circumstances that would require registration of the Securities under the Securities Act. Assuming the accuracy of the representations and warranties of Purchaser contained in Article 3 hereof, the issuance of the Securities is exempt from registration under the Securities Act.

2.19 Registration Rights. The granting and performance of the registration rights under the Registration Rights Agreement will not violate or conflict with, or result in a breach of any provision of, or constitute a default under, any agreement, indenture, or instrument to which the Company is a party except for rights which have been properly waived.

2.20 Taxes. The Company has filed (or has obtained an extension of time within which to file) all necessary federal, state and foreign income and franchise tax returns and has paid all taxes shown as due on such tax returns, except where the failure to so file or the failure to so pay would not reasonably be expected to have a Material Adverse Effect.

2.21 Real and Personal Property. The Company has good and marketable title to, or has valid rights to lease or otherwise use, all items of real and personal property that are material to the business of the Company free and clear of all liens, encumbrances, claims and defects and imperfections of title except those that (i) do not materially interfere with the use of such property by the Company or (ii) would not reasonably be expected to have a Material Adverse Effect.

2.22 Application of Takeover Protections. The execution and delivery of this Agreement and the consummation of the transactions contemplated hereby will not impose any restriction on Purchaser, or create in any party (including any current stockholder of the Company) any rights, under any share acquisition, business combination, poison pill (including any distribution under a rights agreement), or other similar anti-takeover provisions under the Company’s charter documents or the laws of its state of incorporation.

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2.23 No Manipulation of Stock. The Company has not taken, nor will it take, directly or indirectly any action designed to stabilize or manipulate the price of the Common Stock or any security of the Company to facilitate the sale or resale of any of the Shares.

2.24 Related Party Transactions. Except with respect to the transactions (i) that are not required to be disclosed and (ii) contemplated hereby to the extent an affiliate of any director purchases Securities hereunder, all transactions that have occurred between or among the Company, on the one hand, and any of its officers or directors, or any affiliate or affiliates of any such officer or director, on the other hand, prior to the date hereof have been disclosed in the SEC Documents.

2.25 Use of Proceeds. The Company shall use the net proceeds of the sale of the Securities hereunder for research and development activities related to the Company’s preclinical and clinical development programs, working capital and general corporate purposes.

ARTICLE 3

PURCHASER’S REPRESENTATIONS AND WARRANTIES

Purchaser represents and warrants to the Company, with respect to itself and its purchase hereunder, that:

3.1 Investment Purpose. Purchaser is purchasing the Securities for its own account and not with a present view toward the public sale or distribution thereof and has no intention of selling or distributing any of such Securities or any arrangement or understanding with any other Persons regarding the sale or distribution of such Securities except as would not result in a violation of the Securities Act. Purchaser will not, directly or indirectly, offer, sell, pledge, transfer or otherwise dispose of (or solicit any offers to buy, purchase or otherwise acquire or take a pledge of) any of the Securities except pursuant to and in accordance with the Securities Act.

3.2 Reliance on Exemptions. Purchaser understands that the Securities are being offered and sold to it in reliance upon specific exemptions from the registration requirements of United States federal and state securities laws and that the Company is relying upon the truth and accuracy of, and Purchaser’s compliance with, the representations, warranties, agreements, acknowledgments and understandings of Purchaser set forth herein in order to determine the availability of such exemptions and the eligibility of Purchaser to acquire the Securities.

3.3 Information. Purchaser has had access to and the opportunity to review the SEC Documents. Neither such inquiries nor any other investigation conducted by or on behalf of Purchaser or its representatives or counsel shall modify, amend or affect Purchaser’s right to rely on the truth, accuracy and completeness of the SEC Documents and the Company’s representations and warranties contained in the Agreement.

3.4 Acknowledgement of Risk. Purchaser is able to bear the economic risk of holding the Securities for an indefinite period, and has knowledge and experience in financial and business matters such that it is capable of evaluating the risks of the investment in the Securities; and

3.5 Governmental Review. Purchaser understands that no United States federal or state agency or any other government or governmental agency has passed upon or made any recommendation or endorsement of the Securities or an investment therein.

3.6 Transfer or Resale. Purchaser understands that:

(a) the Securities have not been and are not being registered under the Securities Act or any applicable state securities laws and, consequently, Purchaser may have to bear the risk of owning the Securities for an indefinite period of time because the Securities may not be transferred unless (i) the resale of the Securities is registered pursuant to an effective registration statement under the Securities Act; (ii) Purchaser has delivered to the Company an opinion of counsel (in form, substance and scope customary for opinions of counsel in comparable transactions) to the effect that the Securities to be sold or transferred may be sold or transferred pursuant to an exemption from such registration; or (iii) the Securities are sold or transferred pursuant to Rule 144;

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(b) any sale of the Securities made in reliance on Rule 144 may be made only in accordance with the terms of Rule 144 and, if Rule 144 is not applicable, any resale of the Securities under circumstances in which the seller (or the Person through whom the sale is made) may be deemed to be an underwriter (as that term is defined in the Securities Act) may require compliance with some other exemption under the Securities Act or the rules and regulations of the SEC thereunder; and

(c) neither the Company nor any other Person is under any obligation to register the resale of the Shares under the Securities Act or any state securities laws or to comply with the terms and conditions of any exemption thereunder other than as provided in the Registration Rights Agreement.

3.7 Legends.

(a) Purchaser understands the certificates representing the Securities will bear a restrictive legend in substantially the following form (and a stop-transfer order may be placed against transfer of the certificates for such Securities):

THE SECURITIES REPRESENTED BY THIS CERTIFICATE HAVE NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933, AS AMENDED, OR THE SECURITIES LAWS OF ANY STATE OF THE UNITED STATES. THE SECURITIES MAY NOT BE SOLD, OFFERED FOR SALE, PLEDGED, HYPOTHECATED, TRANSFERRED OR ASSIGNED IN THE ABSENCE OF AN EFFECTIVE REGISTRATION STATEMENT FOR THE SECURITIES UNDER APPLICABLE SECURITIES LAWS, OR UNLESS OFFERED, SOLD, PLEDGED, HYPOTHECATED OR TRANSFERRED PURSUANT TO AN AVAILABLE EXEMPTION FROM THE REGISTRATION REQUIREMENTS OF THOSE LAWS. THE COMPANY SHALL BE ENTITLED TO REQUIRE AN OPINION OF COUNSEL REASONABLY SATISFACTORY TO THE COMPANY THAT SUCH REGISTRATION IS NOT REQUIRED TO THE EXTENT THAT SUCH OPINION IS REQUIRED PURSUANT TO THAT CERTAIN COMMON STOCK PURCHASE AGREEMENT UNDER WHICH THE SECURITIES WERE ISSUED.

(b) Purchaser may request that the Company remove, and the Company agrees to authorize the removal of any legend from the Shares (i) in connection with any sale of the Shares pursuant to Rule 144, or (ii) if such Shares are eligible for sale under Rule 144 following the expiration of the one-year holding requirement under subparagraphs (b)(1)(i) and (d) thereof.

3.8 Authorization; Enforcement. Purchaser has the requisite power and authority to enter into this Agreement and to consummate the transactions contemplated hereby. Purchaser has taken all necessary action to authorize the execution, delivery and performance of this Agreement. Upon the execution and delivery of this Agreement, this Agreement shall constitute a valid and binding obligation of Purchaser enforceable in accordance with its terms, except as enforceability may be limited by applicable bankruptcy, insolvency, reorganization, moratorium or similar laws affecting creditors’ and contracting parties’ rights generally and except as enforceability may be subject to general principles of equity and except as rights to indemnity and contribution may be limited by state or federal securities laws or public policy underlying such laws.

3.9 Residency. Purchaser is a resident of the jurisdiction set forth immediately below Purchaser’s name on the signature pages hereto.

3.10 Placement Agents. Purchaser has taken no action that would give rise to any claim by any Person for brokerage commissions, placement agent’s fees or similar payments relating to this Agreement or the transactions contemplated hereby.

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ARTICLE 4

COVENANTS

4.1 Reporting Status. The Company’s Common Stock is registered under Section 12 of the Exchange Act. During the effectiveness of the Registration Rights Agreement, the Company will timely file all documents with the SEC, and the Company will not terminate its status as an issuer required to file reports under the Exchange Act even if the Exchange Act or the rules and regulations thereunder would permit such termination.

4.2 Expenses. Each of the Company and Purchaser is liable for, and will pay, its own expenses incurred in connection with the negotiation, preparation, execution and delivery of this Agreement, including, without limitation, attorneys’ and consultants’ fees and expenses; provided, however, that the Company shall, at the Closing, pay the reasonable fees and expenses incurred by the Purchaser for reasonable legal counsel fees and disbursements incurred by such counsel in connection with preparation of the Agreement and the ancillary agreements, up to a maximum aggregate amount of $7,500.

4.3 Securities Laws Disclosure; Publicity. On or before 9:30 a.m., New York local time, on February 5, 2014 the Company shall issue a press release announcing the signing of this Agreement and describing the terms of the transactions contemplated by this Agreement. Such press release shall be approved by the parties in accordance with the procedures set forth in the Collaboration Agreement. On or before February 5, 2014, the Company shall file a Current Report on Form 8-K with the SEC describing the terms of the transactions contemplated by this Agreement and including as an exhibit to such Current Report on Form 8-K this Agreement, in the form required by the Exchange Act.

4.4 Sales by Purchaser. Purchaser will sell any Securities acquired pursuant to this Agreement in compliance with applicable prospectus delivery requirements, if any, or otherwise in compliance with the requirements for an exemption from registration under the Securities Act and the rules and regulations promulgated thereunder. Purchaser will not make any sale, transfer or other disposition of such Securities in violation of federal or state securities laws.

ARTICLE 5

CONDITIONS TO CLOSING

5.1 Conditions to Obligations of the Company. The Company’s obligation to complete the purchase and sale of the Securities to Purchaser is subject to the waiver by the Company or fulfillment as of the Closing Date of the following conditions:

(a) Representations and Warranties. The representations and warranties made by Purchaser in Article 3 shall be true and correct as of the Closing Date.

(b) Covenants. All covenants, agreements and conditions contained in this Agreement to be performed by Purchaser on or prior to the Closing Date shall have been performed or complied with.

(c) Blue Sky. The Company shall have obtained all necessary blue sky law permits and qualifications, or secured exemptions therefrom, required by any state for the offer and sale of the Securities.

(d) Nasdaq Qualification. The Shares to be issued shall be duly authorized for listing by Nasdaq, subject to official notice of issuance, to the extent required by the rules of Nasdaq.

(e) Absence of Litigation. No proceeding challenging this Agreement or the transactions contemplated hereby, or seeking to prohibit, alter, prevent or materially delay the Closing, shall have been instituted or be pending before any court, arbitrator, governmental body, agency or official.

(f) No Governmental Prohibition. The sale of the Securities by the Company shall not be prohibited by any law or governmental order or regulation.

(g) Registration Rights Agreement. Purchaser shall have executed and delivered the Registration Rights Agreement.

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5.2 Conditions to Purchaser’s Obligations at the Closing. Purchaser’s obligation to complete the purchase and sale of the Securities is subject to the waiver by Purchaser or fulfillment as of the Closing Date of the following conditions:

(a) Representations and Warranties. The representations and warranties made by the Company in Article 2 shall be true and correct as of the Closing Date.

(b) Covenants. All covenants, agreements and conditions contained in this Agreement to be performed by the Company on or prior to the Closing Date shall have been performed or complied with.

(c) Blue Sky. The Company shall have obtained all necessary blue sky law permits and qualifications, or secured exemptions therefrom, required by any state or foreign or other jurisdiction for the offer and sale of the Securities.

(d) Transfer Agent Instructions. The Company shall have delivered to its transfer agent irrevocable instructions to issue to Purchaser, or in such nominee name(s) as designated by Purchaser in writing, the Shares.

(e) Nasdaq Qualification. The Shares shall be duly authorized for listing by Nasdaq, subject to official notice of issuance, to the extent required by the rules of Nasdaq.

(f) Absence of Litigation. No proceeding challenging this Agreement or the transactions contemplated hereby, or seeking to prohibit, alter, prevent or materially delay the Closing, shall have been instituted or be pending before any court, arbitrator, governmental body, agency or official.

(g) No Governmental Prohibition. The sale of the Shares by the Company shall not be prohibited by any law or governmental order or regulation.

(h) Registration Rights Agreement. The Company shall have executed and delivered the Registration Rights Agreement.

(i) Opinion of Company Counsel. Purchaser shall have received an opinion from counsel for the Company in form and substance reasonably acceptable to Purchaser.

ARTICLE 6

DEFINITIONS

6.1 “Agreement” has the meaning set forth in the preamble.

6.2 “Bylaws” has the meaning set forth in Section 2.3.

6.3 “Certificate of Incorporation” has the meaning set forth in Section 2.3.

6.4 “Closing” has the meaning set forth in Section 1.3.

6.5 “Closing Date” has the meaning set forth in Section 1.3.

6.6 “Common Stock” means the common stock, par value $0.001 per share, of the Company.

6.7 “Company” means Regulus Therapeutics Inc.

6.8 “Evaluation Date” has the meaning set forth in Section 2.7.

6.9 “Exchange Act” means the Securities Exchange Act of 1934, as amended.

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6.10 “Financial Statements” means the financial statements of the Company included in the SEC Documents.

6.11 “Intellectual Property” has the meaning set forth in Section 2.10.

6.12 “Investment Company Act” has the meaning set forth in Section 2.12.

6.13 “Material Adverse Effect” means a material adverse effect on (a) the business, operations, assets or financial condition of the Company, taken as a whole, or (b) the ability of the Company to perform its obligations pursuant to the transactions contemplated by this Agreement.

6.14 “Material Agreements” has the meaning set forth in Section 2.6.

6.15 “Nasdaq” means The Nasdaq Stock Market LLC.

6.16 “Offering” means the private placement of the Company’s Securities contemplated by this Agreement.

6.17 “Person” means any person, individual, corporation, limited liability company, partnership, trust or other nongovernmental entity or any governmental agency, court, authority or other body (whether foreign, federal, state, local or otherwise).

6.18 “Purchaser” has the meaning set forth in the first paragraph of this Agreement.

6.19 “Purchase Price” has the meaning set forth in Section 1.1.

6.20 “Rule 144” means Rule 144 promulgated under the Securities Act, or any successor rule.

6.21 “SEC” means the United States Securities and Exchange Commission.

6.22 “SEC Documents” has the meaning set forth in Section 2.6.

6.23 “Securities” has the meaning set forth in Section 1.1.

6.24 “Securities Act” means the Securities Act of 1933, as amended, and the rules and regulations thereunder, or any similar successor statute.

6.25 “Shares” has the meaning set forth in Section 1.1.

6.26 “Subsidiary” of any Person shall mean any corporation, partnership, limited liability company, joint venture or other legal entity of which such Person (either above or through or together with any other subsidiary) owns, directly or indirectly, more than 50% of the stock or other equity interests the holders of which are generally entitled to vote for the election of the board of directors or other governing body of such corporation or other legal entity.

ARTICLE 7

GOVERNING LAW; MISCELLANEOUS

7.1 Governing Law; Jurisdiction. This Agreement will be governed by and interpreted in accordance with the laws of the State of California without regard to the principles of conflict of laws.

7.2 Counterparts; Signatures by Facsimile. This Agreement may be executed in two or more counterparts, all of which are considered one and the same agreement and will become effective when counterparts have been signed by each party and delivered to the other parties. This Agreement, once executed by a party, may be delivered to the other parties hereto by facsimile or e-mail transmission of a copy of this Agreement bearing the signature of the party so delivering this Agreement.

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7.3 Headings. The headings of this Agreement are for convenience of reference only, are not part of this Agreement and do not affect its interpretation.

7.4 Severability. If any provision of this Agreement is invalid or unenforceable under any applicable statute or rule of law, then such provision will be deemed modified in order to conform with such statute or rule of law. Any provision hereof that may prove invalid or unenforceable under any law will not affect the validity or enforceability of any other provision hereof.

7.5 Entire Agreement; Amendments. This Agreement (including all schedules and exhibits hereto) constitutes the entire agreement among the parties hereto with respect to the subject matter hereof and thereof. This Agreement supersedes all prior agreements and understandings among the parties hereto with respect to the subject matter hereof. No provision of this Agreement may be waived or amended other than by an instrument in writing signed by the party to be charged with enforcement. Any amendment or waiver by a party effected in accordance with this Section 7.5 shall be binding upon such party, including with respect to any Securities purchased under this Agreement at the time outstanding and held by such party (including securities into which such Securities are convertible and for which such Securities are exercisable) and each future holder of all such securities.

7.6 Notices. All notices required or permitted hereunder shall be in writing and shall be deemed effectively given: (a) upon personal delivery to the party to be notified, (b) when sent by confirmed email, telex or facsimile if sent during normal business hours of the recipient, if not, then on the next business day, (c) five days after having been sent by registered or certified mail, return receipt requested, postage prepaid, or (d) one business day after deposit with a nationally recognized overnight courier, specifying next day delivery, with written verification of receipt. The addresses for such communications are:

If to the Company:	Regulus Therapeutics Inc.
	3545 John Hopkins Court
	Suite 210
	San Diego, CA 92121
	Attn: Chief Executive Officer
With a copy to:	Cooley LLP
	4401 Eastgate Mall
	San Diego, CA 92121
	Attn: Thomas A. Coll, Esq.
If to Purchaser:	Aventis Holdings Inc.
	c/o Sanofi 54 rue La Boetie
	75008 Paris – France Attention: Philippe Goupit
With a copy to:	Covington & Burling LLP
	333 Twin Dolphin Drive, Ste 700 Redwood Shores, CA 94065 Attention: Scott Anthony, Esq.

Each party will provide ten days’ advance written notice to the other parties of any change in its address.

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7.7 Successors and Assigns. This Agreement is binding upon and inures to the benefit of the parties and their successors and assigns. The Company will not assign this Agreement or any rights or obligations hereunder without the prior written consent of Purchaser.

7.8 Third Party Beneficiaries. This Agreement is intended for the benefit of the parties hereto, their respective permitted successors and assigns, and is not for the benefit of, nor may any provision hereof be enforced by, any other Person.

7.9 Further Assurances. Each party will do and perform, or cause to be done and performed, all such further acts and things, and will execute and deliver all other agreements, certificates, instruments and documents, as another party may reasonably request in order to carry out the intent and accomplish the purposes of this Agreement and the consummation of the transactions contemplated hereby.

7.10 No Strict Construction. The language used in this Agreement is deemed to be the language chosen by the parties to express their mutual intent, and no rules of strict construction will be applied against any party.

7.11 Equitable Relief. The Company recognizes that, if it fails to perform or discharge any of its obligations under this Agreement, any remedy at law may prove to be inadequate relief to Purchaser. The Company therefore agrees that Purchaser is entitled to seek temporary and permanent injunctive relief in any such case. Purchaser also recognizes that, if it fails to perform or discharge any of its obligations under this Agreement, any remedy at law may prove to be inadequate relief to the Company. Purchaser therefore agrees that the Company is entitled to seek temporary and permanent injunctive relief in any such case.

7.12 Survival of Representations and Warranties. Notwithstanding any investigation made by any party to this Agreement, all representations and warranties made by the Company and Purchaser herein shall survive for a period of two (2) years following the date hereof.

[Signature Page Follows]

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IN WITNESS WHEREOF, the undersigned has caused this Common Stock Purchase Agreement to be duly executed as of the date first above written.

REGULUS THERAPEUTICS INC.
By:	/s/ Kleanthis G. Xanthopoulos
Name:	Kleanthis G. Xanthopoulos, Ph.D.
Title:	President and Chief Executive Officer

[Signature Page to Common Stock Purchase Agreement]

IN WITNESS WHEREOF, the undersigned has caused this Common Stock Purchase Agreement to be duly executed as of the date first above written.

PURCHASER: AVENTIS HOLDINGS INC.

By:	/s/ Joseph M. Palladino
Name: Joseph M. Palladino
Title: President
Address: 3711 Kennett Pike
Suite 200
Greenville, DE 19807
Facsimile: 302-777-6359

[Signature Page to Common Stock Purchase Agreement]

EXHIBIT A

REGISTRATION RIGHTS AGREEMENT

EXHIBIT B

FORM 8-K DISCLOSURE

EX-99.3

Exhibit 99.3

EXECUTION COPY

REGULUS THERAPEUTICS INC.

REGISTRATION RIGHTS AGREEMENT

THIS REGISTRATION RIGHTS AGREEMENT (this “Agreement”) is entered into as of February 4, 2014, by and between REGULUS THERAPEUTICS INC., a Delaware corporation (the “Company”), and AVENTIS HOLDINGS INC., a Delaware corporation (“Investor”). The Company and Investor may be referred to hereinafter collectively as the “Parties” and each individually as a “Party.”

RECITALS

WHEREAS, in connection with the purchase of shares of the Common Stock of the Company by Investor pursuant to that certain Common Stock Purchase Agreement dated as of the date hereof (the “Purchase Agreement”), the parties desire to enter into this Agreement in order to grant registration rights to Investor as set forth below.

NOW, THEREFORE, in consideration of these premises and for other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the parties hereto agree as follows:

SECTION 1. DEFINITIONS.

Capitalized terms used herein and not defined elsewhere herein have the meanings set forth in Exhibit A.

SECTION 2. REGISTRATION RIGHTS; MARKET STAND-OFF.

2.1 Piggyback Registrations. The Company will notify Holder in writing at least fifteen (15) days prior to the filing of any registration statement under the Securities Act for purposes of a public offering of securities of the Company (including, but not limited to, registration statements relating to secondary offerings of securities of the Company, but excluding Special Registration Statements) and will afford Holder an opportunity to include in such registration statement all or part of such Registrable Securities held by Holder. If Holder desires to include in any such registration statement all or any part of the Registrable Securities held by Holder, Holder shall within fifteen (15) days after the above-described notice from the Company, so notify the Company in writing. Such notice will state the intended method of disposition of the Registrable Securities by Holder. If Holder decides not to include all of its Registrable Securities in any registration statement thereafter filed by the Company, Holder will nevertheless continue to have the right to include any Registrable Securities in any subsequent registration statement or registration statements as may be filed by the Company with respect to offerings of its securities, all upon the terms and conditions set forth herein.

1.

(a) Underwriting. If the registration statement of which the Company gives notice under this Section 2.1 is for an underwritten offering, the Company will so advise Holder. In such event, the right of Holder to include Registrable Securities in a registration pursuant to this Section 2.1 will be conditioned upon Holder’s participation in such underwriting and the inclusion of Holder’s Registrable Securities in the underwriting to the extent provided herein. If Holder proposes to distribute its Registrable Securities through such underwriting Holder shall enter into an underwriting agreement in customary form with the underwriter or underwriters selected for such underwriting by the Company. Notwithstanding any other provision of this Agreement, if the underwriter determines in good faith that marketing factors require a limitation of the number of shares to be underwritten, the number of shares that may be included in the underwriting will be allocated, first, to the Company; second, to the “Holders” under that certain Founding Investor Rights Agreement dated January 1, 2009, as amended, by and among the Company, Isis Pharmaceuticals, Inc. and Alnylam Pharmaceuticals, Inc., and the “Holders” under that certain Investor Rights Agreement dated October 12, 2012 by and between the Company and AstraZeneca AB; and third, to Holder. If Holder disapproves of the terms of any such underwriting, Holder may elect to withdraw therefrom by written notice to the Company and the underwriter, delivered at least ten (10) business days prior to the effective date of the registration statement. Any Registrable Securities excluded or withdrawn from such underwriting will be excluded and withdrawn from the registration.

(b) Right to Terminate Registration. The Company will have the right to terminate or withdraw any registration initiated by it under this Section 2.1 whether or not Holder has elected to include securities in such registration. The Registration Expenses of such withdrawn registration will be borne by the Company in accordance with Section 2.3 hereof.

2.2 Form S-3 Registration. In case the Company receives from Holder a written request that the Company effect a registration on Form S-3 (or any successor to Form S-3) or any similar short-form registration statement, which, at the request of Holder, may be in connection with an underwritten distribution of Registrable Securities, and any related qualification or compliance with respect to all or a part of the Registrable Securities owned by Holder, the Company will:

(a) as soon as practicable, effect such registration and all such qualifications and compliances as may be so requested and as would permit or facilitate the sale and distribution of all or such portion of Holder’s Registrable Securities as are specified in such request; provided, however, that the Company will not be obligated to effect any such registration, qualification or compliance pursuant to this Section 2.2:

(i) if Form S-3 is not available for such offering by Holder;

(ii) if Holder, together with the holders of any other securities of the Company entitled to inclusion in such registration, propose to sell Registrable Securities and such other securities (if any) at an aggregate price to the public of less than three million dollars ($3,000,000);

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(iii) if within thirty (30) days of receipt of a written request from Holder pursuant to this Section 2.2, the Company gives notice to Holder of the Company’s intention to make a public offering within ninety (90) days, other than pursuant to a Special Registration Statement; provided, however, that the Company shall not utilize this right more than once in any twelve (12) month period, and provided further, that the Company shall not register any other of its shares during such 90-day period other than pursuant to a Special Registration Statement;

(iv) if the Company will furnish to Holder a certificate signed by the Chairman of the Board stating that in the good faith judgment of the Board, it would be seriously detrimental to the Company and its stockholders for such Form S-3 registration to be effected at such time, in which event the Company will have the right to defer the filing of the Form S-3 registration statement for a period of not more than one hundred twenty (120) days after receipt of the request of Holder under this Section 2.2; provided, that such right to delay a request will be exercised by the Company not more than once in any twelve (12) month period and provided that the Company shall not register any other of its shares during such 120-day period other than pursuant to a Special Registration Statement;

(v) if the Company has, within the twelve (12) month period preceding the date of such request, already effected two (2) registrations on Form S-3 for Holder pursuant to this Section 2.2, or

(vi) in any particular jurisdiction in which the Company would be required to qualify to do business or to execute a general consent to service of process in effecting such registration, qualification or compliance, unless the Company is already subject to service in such jurisdiction and except as may be required by the Securities Act.

(b) Subject to the foregoing, the Company will file a Form S-3 registration statement covering the Registrable Securities and other securities so requested to be registered as soon as practicable after receipt of the request of Holder.

2.3 Expenses of Registration. Except as specifically provided herein, all Registration Expenses incurred in connection with any registration, qualification or compliance pursuant to Section 2.1 or 2.2 herein will be borne by the Company. All Selling Expenses incurred in connection with any registrations hereunder, will be borne by the holders of the securities so registered pro rata on the basis of the number of shares so registered. The Company will not, however, be required to pay for expenses of any registration proceeding begun pursuant to Section 2.2, the request of which has been subsequently withdrawn by Holder unless (a) the withdrawal is based upon material adverse information concerning the Company of which Holder was not aware at the time of such request or (b) Holder agrees to deem such registration to have been effected as of the date of such withdrawal for purposes of determining whether the Company will be obligated pursuant to Section 2.2(a)(v), to undertake any subsequent registration, in which event such right will be forfeited by Holder). If Holder is required to pay the Registration Expenses, such expenses will be borne by the holders of securities (including Registrable Securities) requesting such registration in proportion to the

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number of shares for which registration was requested. If the Company is required to pay the Registration Expenses of a withdrawn offering pursuant to clause (a) above, then such registration will not be deemed to have been effected for purposes of determining whether the Company will be obligated pursuant to Section 2.2(a)(v) to undertake any subsequent registration.

2.4 Obligations of the Company. Whenever required to effect the registration of any Registrable Securities, the Company will, as expeditiously as reasonably possible:

(a) prepare and file with the SEC a registration statement with respect to such Registrable Securities and use all commercially reasonable efforts to cause such registration statement to become effective, and, upon the request of Holder, keep such registration statement effective for up to sixty (60) days or, if earlier, until Holder has completed the distribution related thereto; provided, however, that at any time, upon written notice to Holder and for a period not to exceed sixty (60) days thereafter (the “Suspension Period”), the Company may delay the filing or effectiveness of any registration statement or suspend the use of any registration statement (and Holder hereby agrees not to offer or sell any Registrable Securities pursuant to such registration statement during the Suspension Period) if the Company reasonably believes that there is or may be in existence material nonpublic information or events involving the Company, the failure of which to be disclosed in the prospectus included in the registration statement could result in a Violation (as defined below). In the event that the Company will exercise its right to delay the filing or effectiveness or suspend the use of a registration hereunder, the applicable time period during which the registration statement is to remain effective will be extended by a period of time equal to the duration of the Suspension Period. The Company may extend the Suspension Period for an additional consecutive sixty (60) days with the consent of Holder, which consent will not be unreasonably withheld. If so directed by the Company, Holder will (i) not offer to sell any Registrable Securities pursuant to the registration statement during the period in which the delay or suspension is in effect after receiving notice of such delay or suspension; and (ii) use its commercially reasonable efforts to deliver to the Company (at the Company’s expense) all copies, other than permanent file copies then in Holder’s possession, of the prospectus relating to such Registrable Securities current at the time of receipt of such notice. Notwithstanding the foregoing, the Company will not be required to file, cause to become effective or maintain the effectiveness of any registration statement other than a registration statement on Form S-3 that contemplates a distribution of securities on a delayed or continuous basis pursuant to Rule 415 under the Securities Act.

(b) Prepare and file with the SEC such amendments and supplements to such registration statement and the prospectus used in connection with such registration statement as may be necessary to comply with the provisions of the Securities Act with respect to the disposition of all securities covered by such registration statement for the period set forth in subsection (a) above.

(c) Furnish to Holder such number of copies of a prospectus, including a preliminary prospectus, in conformity with the requirements of the Securities Act, and such other documents as it may reasonably request in order to facilitate the disposition of Registrable Securities owned by it.

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(d) Use its commercially reasonable efforts to register and qualify the securities covered by such registration statement under such other securities or Blue Sky laws of such jurisdictions as will be reasonably requested by Holder; provided that the Company will not be required in connection therewith or as a condition thereto to qualify to do business or to file a general consent to service of process in any such states or jurisdictions, unless the Company is already subject to service in such jurisdiction and except as may be required by the Securities Act.

(e) In the event of any underwritten public offering, enter into and perform its obligations under an underwriting agreement, in usual and customary form, with the managing underwriter(s) of such offering. If Holder participates in such underwriting Holder will also enter into and perform its obligations under such an agreement.

(f) Notify Holder at any time when a prospectus relating to Holder’s Registrable Securities is required to be delivered under the Securities Act of the happening of any event as a result of which the prospectus included in such registration statement, as then in effect, includes an untrue statement of a material fact or omits to state a material fact required to be stated therein or necessary to make the statements therein not misleading in the light of the circumstances then existing. The Company will use commercially reasonable efforts to amend or supplement such prospectus in order to cause such prospectus not to include any untrue statement of a material fact or omit to state a material fact required to be stated therein or necessary to make the statements therein not misleading in the light of the circumstances then existing.

(g) Use its commercially reasonable efforts to furnish, on the date that such Registrable Securities are delivered to the underwriters for sale, if such securities are being sold through underwriters, (i) an opinion, dated as of such date, of the counsel representing the Company for the purposes of such registration, in form and substance as is customarily given to underwriters in an underwritten public offering, addressed to the underwriters, if any, and (ii) a letter, dated as of such date, from the independent certified public accountants of the Company, in form and substance as is customarily given by independent certified public accountants to underwriters in an underwritten public offering addressed to the underwriters.

2.5 Delay of Registration; Furnishing Information.

(a) Holder will not have any right to obtain or seek an injunction restraining or otherwise delaying any such registration as the result of any controversy that might arise with respect to the interpretation or implementation of this Section 2.

(b) It will be a condition precedent to the obligations of the Company to take any action pursuant to Section 2.1 or 2.2 that Holder will furnish to the Company such information regarding Holder, the Registrable Securities held by it and the intended method of disposition of such securities as will be required to effect the registration of their Registrable Securities.

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(c) The Company will have no obligation with respect to any registration requested pursuant to Section 2.2 if the number of shares or the anticipated aggregate offering price of the Registrable Securities to be included in the registration does not equal or exceed the number of shares or the anticipated aggregate offering price required to originally trigger the Company’s obligation to initiate such registration as specified in Section 2.2.

2.6 Indemnification. In the event any Registrable Securities are included in a registration statement under Section 2.1 or 2.2:

(a) To the extent permitted by law, the Company will indemnify and hold harmless Holder, the partners, members, stockholders, officers and directors of Holder, as applicable, any underwriter (as defined in the Securities Act) for Holder and each person, if any, who controls Holder or underwriter within the meaning of the Securities Act or the Exchange Act, against any losses, claims, damages, or liabilities (joint or several) to which they may become subject under the Securities Act, the Exchange Act or other federal or state law, insofar as such losses, claims, damages or liabilities (or actions in respect thereof) arise out of or are based upon any of the following statements, omissions or violations (collectively a “Violation”) by the Company: (i) any untrue statement or alleged untrue statement of a material fact contained in such registration statement or incorporated by reference therein, including any preliminary prospectus or final prospectus contained therein or any amendments or supplements thereto, (ii) the omission or alleged omission to state therein a material fact required to be stated therein, or necessary to make the statements therein not misleading, or (iii) any violation or alleged violation by the Company of the Securities Act, the Exchange Act, any state securities law or any rule or regulation promulgated under the Securities Act, the Exchange Act or any state securities law in connection with the offering covered by such registration statement; and the Company will reimburse Holder and each such partner, member, stockholder, officer, director, underwriter or controlling person for any legal or other expenses reasonably incurred by them in connection with investigating or defending any such loss, claim, damage, liability or action; provided however, that the indemnity agreement contained in this Section 2.6(a) will not apply to amounts paid in settlement of any such loss, claim, damage, liability or action if such settlement is effected without the consent of the Company, which consent will not be unreasonably withheld, nor will the Company be liable in any such case for any such loss, claim, damage, liability or action to the extent that it arises out of or is based upon a Violation which occurs in reliance upon and in conformity with written information furnished expressly for use in connection with such registration by Holder or any partner, member, officer, director, underwriter or controlling person of Holder.

(b) To the extent permitted by law, Holder will, if Registrable Securities held by Holder are included in the securities as to which such registration qualifications or compliance is being effected, indemnify and hold harmless the Company, each of its directors, its officers and each person, if any, who controls the Company within the meaning of the Securities Act, and any underwriter against any losses, claims, damages or liabilities (joint or

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several) to which the Company or any such director, officer, controlling person, underwriter, partner, director, officer or controlling person of Holder may become subject under the Securities Act, the Exchange Act or other federal or state law, insofar as such losses, claims, damages or liabilities (or actions in respect thereto) arise out of or are based upon any of the following statements: (i) any untrue statement or alleged untrue statement of a material fact contained in such registration statement or incorporated reference therein, including any preliminary prospectus or final prospectus contained therein or any amendments or supplements thereto, (ii) the omission or alleged omission to state therein a material fact required to be stated therein, or necessary to make the statements therein not misleading, or (iii) any violation or alleged violation by the Company of the Securities Act (collectively, a “Holder Violation”), in each case to the extent (and only to the extent) that such Holder Violation occurs in reliance upon and in conformity with written information furnished by Holder under an instrument duly executed by Holder and stated to be specifically for use in connection with such registration; and Holder will reimburse any legal or other expenses reasonably incurred by the Company or any such director, officer, controlling person, or underwriter in connection with investigating or defending any such loss, claim, damage, liability or action if it is judicially determined that there was such a Holder Violation; provided, however, that the indemnity agreement contained in this Section 2.6(b) will not apply to amounts paid in settlement of any such loss, claim, damage, liability or action if such settlement is effected without the consent of Holder, which consent will not be unreasonably withheld; provided further, that in no event will any indemnity under this Section 2.6 exceed the net proceeds from the offering actually received by Holder.

(c) Promptly after receipt by an indemnified party under this Section 2.6 of notice of the commencement of any action (including any governmental action), such indemnified party will, if a claim in respect thereof is to be made against any indemnifying party under this Section 2.6, deliver to the indemnifying party a written notice of the commencement thereof and the indemnifying party will have the right to participate in, and, to the extent the indemnifying party so desires, jointly with any other indemnifying party similarly noticed, to assume the defense thereof with counsel mutually satisfactory to the parties; provided, however, that an indemnified party will have the right to retain its own counsel, with the fees and expenses thereof to be paid by the indemnifying party, if representation of such indemnified party by the counsel retained by the indemnifying party would be inappropriate due to actual or potential differing interests between such indemnified party and any other party represented by such counsel in such proceeding. The failure to deliver written notice to the indemnifying party within a reasonable time of the commencement of any such action will relieve such indemnifying party of any liability to the indemnified party under this Section 2.6 to the extent, and only to the extent, prejudicial to its ability to defend such action, but the omission so to deliver written notice to the indemnifying party will not relieve it of any liability that it may have to any indemnified party otherwise than under this Section 2.6.

(d) If the indemnification provided for in this Section 2.6 is held by a court of competent jurisdiction to be unavailable to an indemnified party with respect to any losses, claims, damages or liabilities referred to herein, the indemnifying party, in lieu of indemnifying such indemnified party thereunder, will to the extent permitted by applicable law contribute to

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the amount paid or payable by such indemnified party as a result of such loss, claim, damage or liability in such proportion as is appropriate to reflect the relative fault of the indemnifying party on the one hand and of the indemnified party on the other in connection with the Violation(s) or Holder Violation(s) that resulted in such loss, claim, damage or liability, as well as any other relevant equitable considerations. The relative fault of the indemnifying party and of the indemnified party will be determined by a court of law by reference to, among other things, whether the untrue or alleged untrue statement of a material fact or the omission to state a material fact relates to information supplied by the indemnifying party or by the indemnified party and the parties’ relative intent, knowledge, access to information and opportunity to correct or prevent such statement or omission; provided, that in no event will any contribution by Holder hereunder exceed the net proceeds from the offering received by Holder.

(e) The obligations of the Company and Holder under this Section 2.6 will survive completion of any offering of Registrable Securities in a registration statement and, with respect to liability arising from an offering to which this Section 2.6 would apply that is covered by a registration filed before termination of this Agreement, such termination. No indemnifying party, in the defense of any such claim or litigation, will, except with the consent of each indemnified party, consent to entry of any judgment or enter into any settlement which does not include as an unconditional term thereof the giving by the claimant or plaintiff to such Indemnified Party of a release from all liability in respect to such claim or litigation.

2.7 “Market Stand-Off” Agreement. Holder hereby agrees that Holder will not sell, transfer, make any short sale of, grant any option for the purchase of, or enter into any hedging or similar transaction with the same economic effect as a sale of, any Shares and with respect to the Shares held by Holder (other than those included in the registration) during the 12-month period following the date of the Purchase Agreement; provided that such restrictions shall apply solely to the Shares and shall not restrict in any manner any sale, transfer, short sale of, option for the purchase of, or any hedging or similar transaction with the same economic effect as a sale of, any shares of Common Stock held by Holder that are not Shares.

2.8 Agreement to Furnish Information. Holder hereby agrees to execute and deliver such other agreements as may be reasonably requested by the Company or the underwriter that are consistent with Holder’s obligations under Section 2.7, as applicable, or that are necessary to give further effect thereto. In addition, if requested by the Company or the representative of the underwriters of Common Stock (or other securities) of the Company, Holder will provide, within ten (10) days of such request, such information as may be reasonably required by the Company or such representative in connection with the completion of any public offering of the Company’s securities pursuant to a registration statement filed under the Securities Act. The obligations described in Section 2.7 and this Section 2.8 will not apply to a Special Registration Statement. The Company may impose stop-transfer instructions with respect to the Shares subject to the foregoing restriction until the end of said day period. Holder agrees that any transferee of any shares of Registrable Securities will be bound by Sections 2.7 and 2.8. The underwriters of the Company’s stock are intended third party beneficiaries of Sections 2.7 and 2.8 and will have the right, power and authority to enforce the provisions hereof as though they were a party hereto.

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2.9 Rule 144 Reporting. With a view to making available to Holder the benefits of certain rules and regulations of the SEC which may permit the sale of the Registrable Securities to the public without registration, the Company agrees to use its best efforts to:

(a) Make and keep public information available, as those terms are understood and defined in Rule 144 or any similar or analogous rule promulgated under the Securities Act, at all times after the effective date of the first registration filed by the Company for an offering of its securities to the general public;

(b) File with the SEC, in a timely manner, all reports and other documents required of the Company under the Exchange Act; and

(c) So long as Holder owns any Registrable Securities, as applicable, furnish to Holder forthwith upon request: a written statement by the Company as to its compliance with the reporting requirements of said Rule 144, and of the Exchange Act (at any time after it has become subject to such reporting requirements); a copy of the most recent annual or quarterly report of the Company filed with the SEC; and such other reports and documents as Holder may reasonably request in connection with availing itself of any rule or regulation of the SEC allowing it to sell any such securities without registration.

2.10 Assignment of Registration Rights. The rights to cause the Company to register Registrable Securities pursuant to this Section 2 may be assigned by Holder to a transferee or assignee of Registrable Securities (for so long as such shares remain Registrable Securities) that (a) is a subsidiary, Affiliate, parent, general partner, limited partner, retired partner, member or retired member, of a Holder that is a corporation, partnership or limited liability company, or (b) is a Holder’s family member or trust for the benefit of an individual Holder; provided, however, (i) the transferor shall, within ten (10) days after such transfer, furnish to the Company written notice of the name and address of such transferee or assignee and the securities with respect to which such registration rights are being assigned and (ii) such transferee shall agree to be subject to all restrictions set forth in this Agreement

2.11 Termination of Registration Rights. The right of Holder to request registration or inclusion of Registrable Securities in any registration pursuant to Sections 2.1 or 2.2 hereof will terminate upon the date four (4) years following the date hereof. Upon such termination, such shares will cease to be “Registrable Securities” hereunder for all purposes.

SECTION 3. MISCELLANEOUS.

3.1 Governing Law. This Agreement will in all respects be governed by and construed in accordance with the substantive laws of the State of California, without regard to its choice of law rules.

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3.2 Successors and Assigns. Except as otherwise expressly provided herein, the provisions hereof will inure to the benefit of, and be binding upon, the parties hereto and their respective successors, permitted assigns, heirs, executors, and administrators and shall inure to the benefit of and be enforceable by each person who shall be a holder of Registrable Securities from time to time. Investor may directly or indirectly assign this Agreement to its parent, Affiliate or subsidiary in connection with a direct or indirect transfer of Registrable Securities to such assignee but may not otherwise assign this Agreement or, other than pursuant to Section 2.10, its rights under this Agreement without the express prior written consent of the Company. Any attempted assignment by Investor of any rights under this Agreement other than in accordance with the terms of this Agreement will be null and void.

3.3 Entire Agreement. This Agreement, including the exhibits and schedules hereto, constitutes the entire agreement between the Company and Investor with respect to the specific subject matter hereof, and supersedes all prior and contemporaneous agreements, representations, and understandings of the parties with respect to such specific subject matter. No party hereto will be liable or bound to the other in any manner by any warranties, representations or covenants with respect to the subject matter hereof except as specifically set forth herein.

3.4 Severability. If one or more provisions of this Agreement are held by a proper court or arbitral tribunal to be unenforceable under applicable law, the unenforceable portions of such provisions, or such provisions in their entirety, to the extent necessary and permitted by law, will be severed herefrom, and the balance of this Agreement will be enforceable in accordance with its terms.

3.5 Amendment and Waiver. Except as otherwise expressly provided, this Agreement may be amended or modified, and the rights and obligations under this Agreement may be waived, only upon the written consent of the Company and Investor.

3.6 Delays or Omissions. It is agreed that no delay or omission to exercise any right, power, or remedy accruing to any party, upon any breach, default or noncompliance by another party under this Agreement will impair any such right, power, or remedy, nor will it be construed to be a waiver of any such breach, default or noncompliance, or any acquiescence therein, or of any similar breach, default or noncompliance thereafter occurring. It is further agreed that any waiver, permit, consent, or approval of any kind or character on any party’s part of any breach, default or noncompliance under this Agreement or any waiver on such party’s part of any provisions or conditions of this Agreement must be in writing and will be effective only to the extent specifically set forth in such writing. All remedies, either under this Agreement, by law, or otherwise afforded to any party, will be cumulative and not alternative.

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3.7 Notices. Except where otherwise specifically provided in this Agreement, all notices, requests, consents, approvals and statements will be in writing and will be deemed to have been properly given by (i) personal delivery, (ii) electronic facsimile transmission, (iii) electronic mail, or by (iv) nationally recognized overnight courier service, addressed in each case, to the intended recipient as set forth below:

To the Company:	Regulus Therapeutics Inc. 3545 John Hopkins Court, Suite 210 San Diego, California 92121 Attention: Chief Executive Officer
With a copy to:	Cooley LLP 4401 Eastgate Mall San Diego, CA 92121 Attention: Thomas A. Coll, Esq.
To Investor:	Aventis Holdings Inc. c/o Sanofi 174 avenue de France 75635 Paris Cedex 13 – France Attention: Philippe Goupit
With a copy to:	Covington & Burling LLP 333 Twin Dolphin Drive, Ste 700 Redwood Shores, CA 94065 Attention: Scott Anthony, Esq.

Such notice, request, demand, claim or other communication will be deemed to have been duly given on (a) the date of personal delivery, (b) the date actually received if by facsimile or electronic mail; or (c) on the third business day after delivery to a nationally recognized overnight courier service, as the case may be. Either Party may change the address to which notices, requests, demands, claims, and other communications hereunder are to be delivered by giving the other Party notice in the manner herein set forth.

3.8 Fees and Expenses. Each party will pay all costs and expenses that it incurs with respect to the negotiation, execution, delivery and performance of this Agreement. If any action at law or in equity is necessary to enforce or interpret the terms of any of this Agreement, the prevailing party will be entitled to reasonable attorneys’ fees, costs and necessary disbursements in addition to any other relief to which such party may be entitled. For purposes of this Section 3.8, “prevailing party” means the net winner of a dispute, taking into account the claims pursued, the claims on which the pursuing party was successful, the amount of money sought, the amount of money awarded, and offsets or counterclaims pursued (successfully or unsuccessfully) by the other Party. If a written settlement offer is rejected and the judgment or award finally obtained is equal to or more favorable to the offeror than an offer made in writing to settle, the offeror is deemed to be the prevailing party from the date of the offer forward.

3.9 Titles and Subtitles; Form of Pronouns; Construction and Definitions. The titles of the Sections and paragraphs of this Agreement are for convenience only and are not to be considered in construing this Agreement. All pronouns used in this Agreement will be deemed to include masculine, feminine and neuter forms, the singular number includes the plural

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and the plural number includes the singular and will not be interpreted to preclude the application of any provision of this Agreement to any individual or entity. Unless the context otherwise requires, (i) each reference in this Agreement to a designated “Section,” “Schedule,” “Exhibit,” or “Appendix” is to the corresponding Section, Schedule, Exhibit, or Appendix of or to this Agreement; (ii) the word “or” will not be applied in its exclusive sense; (iii) “including” will mean “including, without limitation”; (iv) references to “$” or “dollars” will mean the lawful currency of the United States; and (v) “herein,” “hereof,” “hereunder” and other words of similar import refer to this Agreement as a whole and not to any particular Section or other subdivision. References in this Agreement to particular sections of the Securities Act or to any provisions of California law will be deemed to refer to such sections or provisions as they may be amended or succeeded after the date of this Agreement.

3.10 Counterparts. This Agreement may be executed in counterparts, each of which will be deemed an original, but all of which together will constitute one and the same instrument, and will become effective when there exist copies hereof which, when taken together, bear the authorized signatures of each of the parties hereto. Only one such counterpart signed by the party against whom enforceability is sought needs to be produced to evidence the existence of this Agreement.

3.11 Aggregation of Stock. All shares of Registrable Securities held or acquired by affiliated entities or persons or persons or entities under common management or control will be aggregated together for the purpose of determining the availability of any rights under this Agreement.

3.12 Specific Performance. The failure of either party to this Agreement to perform its agreements and covenants hereunder, including but not limited to Section 2, may cause irreparable injury to the other party to this Agreement for which monetary damages, even if available, will not be an adequate remedy. Accordingly, each of the parties hereto hereby consents to the granting of equitable relief (including specific performance and injunctive relief) by any court of competent jurisdiction to enforce any Party’s obligations hereunder. The parties further agree to waive any requirement for the securing or posting of any bond in connection with the obtaining of any such equitable relief and that this Section 3.12 is without prejudice to any other rights that the Company and Investor may have for any failure to perform this Agreement.

3.13 Termination. This Agreement will terminate and be of no further force or effect upon the termination of Holder’s registration rights hereunder pursuant to Section 2.11 above.

[THIS SPACE INTENTIONALLY LEFT BLANK]

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EXECUTION COPY

IN WITNESS WHEREOF, the parties hereto have executed this Registration Rights Agreement as of the date set forth in the first paragraph hereof.

COMPANY:
REGULUS THERAPEUTICS INC.
By:	/s/ Kleanthis G. Xanthopoulos
Name:   Kleanthis G. Xanthopoulos, Ph.D.
Title: President and Chief Executive Officer
INVESTOR:
AVENTIS HOLDINGS INC.
By:	/s/ Joseph M. Palladino
Name:   Joseph M. Palladino
Title: President

EXHIBIT A

DEFINITIONS

1.1 “Affiliate” means with respect to any specified person, any other person who or which, directly or indirectly, controls, is controlled by, or is under common control with such specified person, including, without limitation, any general partner, officer, director or manager of such person and any venture capital fund now or hereafter existing that is controlled by one or more general partners or managing members of, or is under common investment management with, such person.

1.2 “Common Stock” means the Common Stock of the Company.

1.3 “Exchange Act” means the Securities Exchange Act of 1934, as amended.

1.4 “Form S-3” means such form under the Securities Act as in effect on the date hereof or any successor or similar registration form under the Securities Act subsequently adopted by the SEC which permits inclusion or incorporation of substantial information by reference to other documents filed by the Company with the SEC.

1.5 “Holder” means Investor or transferee pursuant to Section 2.10, so long as it owns of record Registrable Securities that have not been sold to the public.

1.6 “Register,” “registered,” and “registration” refer to a registration effected by preparing and filing a registration statement in compliance with the Securities Act, and the declaration or ordering of effectiveness of such registration statement or document.

1.7 “Registrable Securities” means (a) Common Stock issued pursuant to the Purchase Agreement and (b) any Common Stock issued as (or issuable upon the conversion or exercise of any warrant, right or other security which is issued as) a dividend or other distribution with respect to, or in exchange for or in replacement of, such above-described securities. Notwithstanding the foregoing, Registrable Securities will not include any securities (i) sold by a person to the public either pursuant to a registration statement or Rule 144, or (ii) sold in a private transaction where registration rights are not transferred in accordance with Section 2.10.

1.8 “Registration Expenses” means all expenses incurred by the Company in complying with Sections 2.1 or 2.2, including, without limitation, all registration and filing fees, printing expenses, fees and disbursements of counsel for the Company, reasonable fees and disbursements not to exceed fifteen thousand dollars ($15,000) of a single special counsel for Holder, if applicable, blue sky fees and expenses and the expense of any special audits incident to or required by any such registration (but excluding the compensation of regular employees of the Company which will be paid in any event by the Company).

1.9 “Rule 144” means Rule 144 promulgated under the Securities Act, as in effect from time to time.

1.10 “SEC” means the Securities and Exchange Commission.

1.11 “Securities Act” means the Securities Act of 1933, as amended.

1.12 “Selling Expenses” means all underwriting discounts and selling commissions applicable to the sale.

1.13 “Shares” means the shares of Common Stock of the Company issued pursuant to the Purchase Agreement held from time to time by Investor and its permitted assigns.

1.14 “Special Registration Statement” means (i) a registration statement relating to any employee benefit plan or (ii) with respect to any corporate reorganization or transaction under Rule 145 of the Securities Act, any registration statements related to the issuance or resale of securities issued in such a transaction or (iii) a registration related to stock issued upon conversion of debt securities.

A-1