Limited Liability Company Agreement of Regulus Therapeutics LLC, Dated As of September 6, 20

EXECUTION COPY Exhibit 10.6Confidential Materials omitted and filed separately with the
Securities and Exchange Commission. Asterisks denote omissions. Limited Liability Company Agreement
of
Regulus Therapeutics LLC a Delaware Limited Liability Company Dated as of September 6, 2007


TABLE OF CONTENTS Page ARTICLE 1 Definitions; Representations and Warranties 1 ARTICLE 2 Organization and Description 2 2.1 Name 2 2.2 Term 2 2.3 Registered Office and Statutory Agent 2 2.4 Principal Executive Office 2 2.5 Business 2 2.6 Qualification in Other Jurisdictions 2 2.7 Filings, Reports and Formalities 2 2.8 Limited Liability 3 ARTICLE 3 Members; Voting Rights; Meetings; Withdrawal 3 3.1 Members 3 3.2 Powers of Members 3 3.3 Member Voting Rights 3 3.4 Meetings of Members 3 3.5 Action by Members Without a Meeting 5 3.6 Corporate Opportunities 5 3.7 No Priority, Etc. 6 3.8 No Withdrawal 6 3.9 Additional Members 6 ARTICLE 4 Management 6 4.1 Managing Board of Directors 6 4.2 Power and Authority of the Managing Board 7 4.3 Major Decisions 8 4.4 Meetings of the Managing Board 9 4.5 Compensation 11 4.6 Initial Designation 11 4.7 Directors Bound 11 ARTICLE 5 Employees; Operating Plan and Budget; Scientific Advisory Board 12 5.1 Employees 12

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Page 5.2 Operating Plan 14 5.3 Scientific Advisory Board 15 ARTICLE 6 Capital Contributions and Percentage Interests 16 6.1 Capital Contributions 16 6.2 Withdrawal or Reduction of Capital Contributions 17 6.3 No Interest on Capital Contributions 17 6.4 Capital Accounts 17 ARTICLE 7 Allocation of Profits and Losses; Distributions; Tax and Accounting Matters 19 7.1 Allocations 19 7.2 Distributions 21 7.3 Accounting Matters 22 7.4 Tax Status and Returns 23 7.5 754 Election 24 7.6 Tax Information 24 7.7 Tax Matters Partner 24 ARTICLE 8 Restrictions on Transfer 25 8.1 Transfer of Interests 25 8.2 Exempt Transfers 25 8.3 Substitution of Members 26 ARTICLE 9 Buy-Out 27 9.1 Right to Initiate Buy-Out 27 9.2 Negotiated Resolution 27 9.3 Non-Negotiated Resolution 28 ARTICLE 10 Dissolution 34 10.1 Dissolution 34 10.2 Liquidation 34 10.3 Liabilities 35 10.4 Settling of Accounts 35 10.5 Distribution of Proceeds 35 10.6 Certificate of Cancellation 35 10.7 Payment of Royalties 36 10.8 Treatment of Certain Assets 36

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Page ARTICLE 11 Exculpation and Indemnification 38 11.1 Duties of Directors 38 11.2 Exculpation 38 11.3 Indemnification by the Company 39 11.4 Insurance 41 11.5 Notice of Indemnification and Advancement 41 11.6 Repeal or Modification 41 11.7 Indemnification by Members 41 11.8 Limitation on Damages 42 11.9 Contractual Limitation Period 43 ARTICLE 12 Inspection of Records; Annual and Other Reports; Confidentiality 43 12.1 Records to be Kept 43 12.2 Inspection of Company Records 43 12.3 Reports 44 12.4 Confidentiality 44 ARTICLE 13 Miscellaneous 46 13.1 Governing Law 46 13.2 Amendments 46 13.3 Nature of Membership Interest; Agreement Is Binding upon Successors 47 13.4 Seal 47 13.5 Entire Agreement 47 13.6 Further Actions 47 13.7 Power of Attorney 47 13.8 No Third Party Beneficiary 48 13.9 Notice 48 13.10 Limited Liability Company 49 13.11 Fees and Expenses 49 13.12 Counterparts 50 13.13 Precedence 50 13.14 Titles and Subtitles; Form of Pronouns; Construction and Definitions 50 13.15 Severability 50 13.16 Survival of Certain Provisions 51 13.17 Survival of Warranties 51

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Page 13.18 Waiver of Partition 51 13.19 Delaware Limited Liability Company Act Prevails 51 13.20 Specific Performance 51 Schedules and Exhibits Schedule 1 - DefinitionsSchedule 2 - Representations and WarrantiesSchedule 3.1 - Names and Addresses, Initial Percentage Interests and Capital Account BalancesSchedule 4.5 - Form of Consulting AgreementSchedule 4.6 - Initial Directors of the Managing BoardSchedule 5.3 - Initial SAB Members and ChairpersonSchedule 12.4 - Press ReleaseExhibit A - Initial Approved Operating Plan

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Limited Liability Company Agreement
of
Regulus Therapeutics LLC This LIMITED LIABILITY COMPANY AGREEMENT (this " Agreement" ) of Regulus Therapeutics LLC, a Delaware limited liability company (the " Company" ), is entered into as of September 6, 2007 (the " Effective Date" ) by and among the Company, Alnylam Pharmaceuticals, Inc., a Delaware corporation (" Alnylam" ), and Isis Pharmaceuticals, Inc., a Delaware corporation (" Isis ," and together with Alnylam, the " Members" ). W I T N E S S E T H: WHEREAS , the Members desire to form a joint venture to discover, develop manufacture and commercialize miRNA Therapeutics (the " Joint Venture" ); WHEREAS , in connection therewith and on the Effective Date, the Members and the Company are entering into the following agreements, in each case as more particularly and more fully set forth therein: (a) the License Agreement; and (b) the Services Agreement; WHEREAS , a Certificate of Formation for the Company, a limited liability company organized under the laws of the State of Delaware, was filed with the Delaware Secretary of State on September 5, 2007 (the " Certificate" ); and WHEREAS , the Members desire to enter into this Agreement to provide for their respective rights, powers, duties and obligations as Members, as well as for the management, operations and activities of the Company going forward; NOW, THEREFORE, the Members by this Agreement set forth the limited liability company agreement for the Company under the Delaware Limited Liability Company Act (6 Del. C. a7 18-101 et seq. as amended from time to time, the " Act" ), upon the following terms and conditions: ARTICLE 1 Definitions; Representations and Warranties Except as otherwise defined throughout this Agreement, as used herein the capitalized terms appearing in Schedule 1 will have the meanings set forth therein. Each Member represents and warrants to the other Member and the Company that the statements set forth in Schedule 2 with respect to such Member are true and correct as of the Effective Date.

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ARTICLE 2 Organization and Description 2.1 Name . The name of the Company will be " Regulus Therapeutics LLC." The Company may from time to time do business under any other name under which it is qualified to do business. The business of the Company will be conducted in compliance with all applicable laws. 2.2 Term . The term of the Company commenced on the date of the filing of the Certificate in the office of the Secretary of State of the State of Delaware and will continue until dissolved in accordance with Article 10. 2.3 Registered Office and Statutory Agent . The registered office and statutory agent in Delaware required by the Act will be as set forth in the Certificate until such time as the registered office or statutory agent is changed in accordance with the Act. 2.4 Principal Executive Office . The principal executive office for the transaction of the Company' s business initially will be 1896 Rutherford Road, Carlsbad, California 92008. At any time, the Managing Board may change its location within the United States of America, whether within or without the State of Delaware. 2.5 Business . The Company' s business (the " Business" ) will be to (a) discover, develop, manufacture and commercialize miRNA Therapeutics and undertake all activities necessary or incidental thereto, and (b) subject to approval of the Managing Board, to conduct and carry on any other lawful business, purpose or activity which is permitted to be carried on by a limited liability company under the Act. 2.6 Qualification in Other Jurisdictions . The Company will execute, deliver and file any certificates (and any amendments or restatements thereof) necessary for the Company to qualify to do business in any jurisdiction in which the Company conducts business and in which such qualification or registration is required by law or deemed advisable by the Managing Board. 2.7 Filings, Reports and Formalities . The Company will make all filings and submit all reports required to be filed or submitted under the Act with respect to the Company. Throughout the term of the Company, the

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Company will comply with all requirements necessary to maintain the limited liability status of the Company and the limited liability status of the Members under the laws of the State of Delaware and of each other jurisdiction in which the Company does business. 2.8 Limited Liability . Except as otherwise required by the Act, the debts, obligations and liabilities of the Company, whether arising in contract, tort or otherwise, will be solely the debts, obligations and liabilities of the Company, and no Member, Director or Officer of the Company will be obligated personally for any such debt, obligation or liability of the Company solely by reason of being a member, director, manager or officer of the Company. ARTICLE 3 Members; Voting Rights; Meetings; Withdrawal 3.1 Members . Each Person who is or becomes a Member will be and remain a member of the Company until such Person ceases to be a member in accordance with the provisions of the Act, the Certificate or this Agreement. The names and addresses of the Members, and their respective Percentage Interests and Capital Accounts as of the Effective Date, are set forth on Schedule 3.1 hereto, as the same may be amended (or, with respect to the addresses of Members, noticed under Section 13.9) or adjusted from time to time pursuant to this Agreement. 3.2 Powers of Members . Except as otherwise provided herein and in the Ancillary Agreements, no Member will have any power to transact any business in the Company' s name nor have the power to sign documents, act for or on behalf of or otherwise bind the Company. Subject to the provisions of this Agreement and unless otherwise required by the Act or the Certificate, the Members hereby delegate any and all such powers to the Managing Board to carry out the business affairs of the Company on the Members' behalf. 3.3 Member Voting Rights . The Members will have no voting rights except as to those matters which, pursuant to this Agreement, the Certificate or non-waivable provisions of the Act, require the authorization or approval of the Members. Any authorization or approval required pursuant to this Agreement, the Certificate or non-waivable provisions of the Act will be effected by the unanimous affirmative vote of the Members. Such vote may be by voice vote or by ballot. 3.4 Meetings of Members . (a) Annual Meeting . The Members will convene at least one meeting every year during the fourth quarter of the Fiscal Year of the Company at the same location (or by the same remote communication) as the meeting of the Managing Board held during the fourth quarter of

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the same Fiscal Year pursuant to Section 4.2(b) and on the same day of such Managing Board meeting, or the immediately preceding or immediately following day. (b) Special Meetings . A special meeting of the Members may be called at any time by any Director or the President by written request to the Chairperson, who will consult with the Members to set a date approved by the Members (which approval will not be unreasonably withheld or delayed). (c) Notice and Minutes . (i) Written notice of all meetings of the Members will be given to each Member not less than five (5) nor more than thirty (30) days before the meeting. Such notices will state (A) the place, date and hour of the meeting and (B) those matters which, at the time of the mailing of the notice, are intended to be presented for action. Only Persons whose names are listed as Members on the records of the Company at the close of business on the Business Day immediately preceding the day on which notice of the meeting is given or, if such notice is waived, at the close of business on the Business Day immediately preceding the day on which the meeting of Members is held will be entitled to receive notice of and to vote at such meeting, and such day will be the record date for such meeting (except that the record date for Members entitled to give consent to action without a meeting will be determined in accordance with Section 3.5 hereof). (ii) The Members will appoint a representative to act as secretary for the meeting who will keep minutes of all proceedings of the meeting, which minutes will be distributed to each of the attending Members. The attending Members will consider the minutes for approval at or prior to the next meeting of the Members. The acting secretary will sign the final minutes of Member meetings and cause all such minutes and unanimous written consents of the Members executed pursuant to Section 3.5 hereof to be entered into a minute book maintained for such purpose. (d) Place of Meetings . Annual meetings of the Members will be held at a place determined in accordance with Section 3.4(a) hereof, and special meetings of the Members will be held at such place as may be designated by the Chairperson or, if not so designated, at the principal executive office of the Company. (e) Quorum . The presence at any meeting in person or by proxy of an authorized representative of both Alnylam and Isis will constitute a quorum for the transaction of business (without prejudice to the vote required for the approval of any particular action). (f) Waiver of Notice . (i) The actions of any meeting of Members, however called and noticed and wherever held, will be as valid as if taken at a meeting duly held after regular call and notice, if a quorum be present either in person or by proxy and, if notice has not been given in compliance with Section 3.4(c), each Member entitled to vote has waived notice pursuant to Section 3.4(f)(ii) or, either before or after the meeting, has signed a written waiver of notice or a written consent to a holding of the meeting, or a written approval of the minutes thereof. The waiver of notice, consent or approval need not specify either the business to be transacted or the purpose of any

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meeting. All such waivers, consents or approvals will be filed with the Company records and made a part of the minutes of the meeting. (ii) Attendance of a Member at a meeting, in person or by proxy, without protesting the lack of notice of such meeting at the beginning of such meeting, will constitute a waiver of notice by such Member, provided that such Member has been given an adequate opportunity at the meeting to protest such lack of notice. (g) Attendance by Telephone Conference, Etc . The Members may participate in a meeting of the Members by means of telephone conference or similar communications equipment by means of which all Persons participating in the meeting can hear each other, and such participation will constitute presence in person at such meeting, subject to a Member' s right to protest lack of notice pursuant to Section 3.4(f)(ii) above. 3.5 Action by Members Without a Meeting . (a) Any action that under any provision of the Act, the Certificate or this Agreement may be taken at a meeting of the Members may be taken without a meeting and without prior notice, if a consent in writing, setting forth the action so taken, is delivered to and signed by the Members necessary to authorize or take such action at a meeting at which all Members entitled to vote thereon were present and voted. (b) A telecopy, electronic mail, or other electronic transmission (each, an " electronic transmission" ) consenting to an action to be taken and transmitted by a Member or the Member' s proxyholder will be deemed to be written, signed and dated for purposes of this Section 3.5, provided that any such electronic transmission sets forth or is delivered with information from which the Company can determine (A) that the electronic transmission was transmitted by such Member or proxyholder, and (B) the date on which such Member or proxyholder transmitted such electronic transmission. The date on which such electronic transmission was transmitted will be deemed to be the date on which such consent was signed. No consent in the form of an electronic transmission will be deemed to have been delivered until its receipt by the Company at its principal executive office. (c) Unless a record date has been fixed for the determination of Members entitled to notice of and to give such written consent, the record date for such determination will be the day on which the first written consent is given. Any Member giving a written consent, or the Member' s proxyholder, may revoke the consent by a writing (including electronic transmission) received by the Company prior to the time that written consents of the Members required to authorize the proposed action have been filed with the Company, but may not do so thereafter. Such revocation is effective upon its receipt by the Company. 3.6 Corporate Opportunities . (a) Except as otherwise set forth in any Ancillary Agreement, no Director or Member or its Affiliates will be prohibited from engaging in, or carrying on, any business or activity that is similar to or in competition with another Member or the Company or any of their respective Affiliates. Except as otherwise set forth in any Ancillary Agreement, (i) neither the Company nor any other Member will have any right in or to any such businesses or activities or the income

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or profits derived therefrom as a result of entering into this Agreement, and (ii) no Director, Officer or Member or its Affiliates will have any obligation to present, or disclose the existence of, any such activities or businesses or the opportunity to participate in any of them to the Company, any of its subsidiaries or to any other Member or any other Member' s Affiliates, except as such information may be required to satisfy reporting obligations under law, including without limitation, the rules and regulations of the SEC. Notwithstanding the foregoing , the Parties acknowledge that the disclosure of such information may be required in connection with obtaining and maintaining appropriate directors' and officers' insurance. (b) Except as otherwise set forth in any Ancillary Agreement, in the event that a Member or Director acquires knowledge of a potential transaction or matter that may be a corporate opportunity for a Member and the Company, such Member or Director will have no duty to communicate or present such corporate opportunity to the Company, and the Company hereby renounces any interest or expectancy it may have in such corporate opportunity, with the result that such Member or Director will not be liable to the Company or the other Members for breach of any fiduciary duty, including for breach of any fiduciary duty as a Member or Director of the Company by reason of the fact that such Member or Director pursues or acquires such corporate opportunity for itself, directs such corporate opportunity to another Person, or does not present such corporate opportunity to the Company. 3.7 No Priority, Etc . Except as otherwise provided herein, no Member will have priority over any other Member either as to the return of the amount of its Capital Contribution to the Company, as to any distribution by the Company, or as to any other economic or other right comprising part of Membership Interests. 3.8 No Withdrawal . No Member may withdraw or resign from the Company. 3.9 Additional Members. No additional Persons may be admitted as Members, unless admitted pursuant to and in accordance with Article 8 or Section 4.3, as applicable. ARTICLE 4 Management 4.1 Managing Board of Directors . The Members will establish a Managing Board of Directors of the Company (" Managing Board" ) as of the Effective Date. (a) Directors . The Managing Board will consist of up to [**] directors (each, a " Director" ). Alnylam will have the right to designate [**] Directors who need not be Independent Directors (the " Alnylam Directors" ) and [**] Director who must be an

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Independent Director. Isis will have the right to designate [**] Directors who need not be Independent Directors (the " Isis Directors" ) and [**] Director who must be an Independent Director. The President of the Company will, at all times while in office, be a Director. Other than the President, each Director will serve at the pleasure of the designating Member until such Director' s removal by the designating Member or such Director' s resignation. If there is a vacancy on the Managing Board, the vacancy will be filled by the Member, if any, who initially designated the Director. Any Member may remove, at any time and for any reason, any or all of the Directors designated by such Member and, subject to the Independent Director requirements, designate in lieu thereof any individual(s) to serve the remainder of the relevant term. (b) Chairperson . The Chairperson of the Managing Board (" Chairperson" ) will be the President, unless otherwise designated from among the Directors by the Directors. (c) Observers . The right to attend all or particular meetings of the Managing Board (" Observer Rights" ) may be granted to any Person designated by a Member upon the approval of the other Member (such approval not to be unreasonably withheld or delayed); provided , however , that any Person granted Observer Rights, and/or any representative of such Person attending meetings of the Managing Board, will agree in writing to be subject to appropriate confidentiality obligations if requested by a Director; provided , further , that such holder of Observer Rights may be excluded from any meeting or any portion of a meeting for which any Director believes (i) such meeting or portion will involve a discussion of information that the Company or the Member designating such Director considers to be a trade secret or of a confidential or proprietary nature, (ii) exclusion of such holder of Observer Rights is desirable in order to preserve the attorney client-privilege or (iii) exclusion is otherwise merited. (d) Other Attendees . Any Director may invite a subject matter expert to attend any meeting of the Managing Board; provided , however , that any Person granted attendance rights will agree in writing to be subject to appropriate confidentiality obligations if requested by a Director and provided further that no other Director objects to such expert' s presence. Upon such objection, the expert will be excluded from any meeting or any portion of a meeting. 4.2 Power and Authority of the Managing Board . (a) The business and affairs of the Company will be managed by or under the direction of the Managing Board, except as may otherwise be provided in this Agreement. The Managing Board is hereby designated as a " manager" within the meaning of the Act and will have the power on behalf and in the name of the Company to carry out any and all objectives and purposes of the Company contemplated by this Agreement, the Act or the Certificate and to perform all acts which it may deem necessary, advisable or appropriate in connection therewith. Notwithstanding any other provision of this Agreement, the Act or the Certificate , the Managing Board will not have the power or authority to do or perform, or cause the Company or any Member to do or perform, any act with respect to a Major Decision unless such Major Decision has been approved in accordance with Section 4.3. (b) Except as otherwise provided in this Agreement, the Members agree that all determinations, decisions and actions made or taken by the Managing Board will be conclusive and absolutely binding upon the Company, the Members (but only in their capacity as such) and

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their respective successors, assigns and personal representatives; provided , however , that the foregoing will not affect the rights of the Company or any Member with respect to any matter involving a breach by a Director of Section 10.1 of this Agreement. (c) The Managing Board may establish operating committees of the Managing Board to which the Managing Board delegates various aspects of its authority. Each such operating committee will consist of an equal number of Directors designated by each Member, and vacancies in the membership of an operating committee will be filled by the Member that designated the Director whose seat is vacated. No delegation of authority to an operating committee will be to the exclusion of the authority of the Managing Board to act with respect to the matters for which authority is so delegated. All requirements with respect to meetings of the Managing Board will apply, mutatis mutandis , to meetings of operating committees thereof. 4.3 Major Decisions . (a) Notwithstanding any other provision of this Agreement, the Act or the Certificate to the contrary and in addition to any other requirement under this Agreement, the Act or the Certificate, the Company may not do or perform any of the actions set forth below (each a " Major Decision" ) without first obtaining the approval of an authorized representative of both Alnylam and Isis: (i) appoint or remove any Officer; (ii) determine the compensation of the President and Chief Scientific Officer; (iii) appoint or remove any member of the Scientific Advisory Board or remove or appoint the Chairperson of the Scientific Advisory Board (iv) amend any existing Operating Plan or approve any Proposed Operating Plan; (v) create, incur, guarantee or assume any indebtedness, except for trade payable, on behalf of the Company (including obligations in respect of capital leases), in excess of $[**]. (vi) make or obligate the Company to make any single or aggregate capital expenditure outside of the Approved Operating Budget in excess of $[**]; (vii) license, sublicense or otherwise transfer, grant a security interest in or otherwise encumber, any of the Intellectual Property owned by or licensed to the Company, other than as provided in the Ancillary Agreements; (viii) license, sublicense or otherwise obtain rights to Intellectual Property owned by a Third Party or a Member or Member' s Affiliate, except as contemplated by Sections 2.2 and 2.4 of the License Agreement;

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(ix) declare, set aside or pay any dividend or other distribution (whether in cash, stock or property or any combination thereof), other than tax distributions pursuant to Section 7.2(a) or as provided in the Ancillary Agreements; (x) enter into any partnering activities and/or collaborations; (xi) repurchase any Membership Interests of the Company; (xii) admit a new Member to the Company, except as permitted by Article 8; (xiii) Transfer any Membership Interests of the Company, except in accordance with the provisions of Article 8; (xiv) reclassify or reorganize the Membership Interests; (xv) cause or approve any (i) merger or consolidation of the Company, (ii) acquisition of any other entity or assets of any other entity, if the value of the acquisition exceeds $[**] or (iii) sale of the Company' s assets if the value of such assets exceeds $[**]; (xvi) amend, modify, waive or avoid any provision of this Agreement or the Certificate, except as expressly authorized herein or therein; (xvii) expect as provided in Article 10, liquidate, dissolve, wind up or declare the Company bankrupt; (xviii) amend any Ancillary Agreement; (xix) cause or approve the bringing of an action, suit or proceeding against a Member, an Affiliate of a Member or a Third Party; or (xx) amend this Section 4.3. 4.4 Meetings of the Managing Board . (a) Agendas . The Chairperson will prepare or direct the preparation of the agenda for, and preside over, meetings of the Managing Board. The Chairperson will deliver such agenda to each Director as soon as practicable in advance, and any Director may add items to an agenda at any time. (b) Timing; Place; Notice . (i) Regular Meetings . The Managing Board will convene at least one meeting during each quarter of each Fiscal Year of the Company, with the place of the meeting, if any, alternating between the principal offices of Alnylam and the principal offices of Isis, unless otherwise agreed to by a majority of the Directors, including at least one Alnylam Director and one Isis Director. (ii) Special Meetings . Special meetings of the Managing Board may be called by the Chairperson or at the written request of at least one (1) Director. Within three (3) days

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after determining to call or receiving a proposal for a special meeting by at least one (1) Director, the Chairperson will consult with the other Directors to determine a mutually convenient time within the following thirty (30) day period to convene such meeting; provided , however , that the decision as to time and place will be made by the Chairperson. Any special meeting of the Managing Board will not be held more than thirty (30) days from the date of the receipt of the request. (iii) Notice . Written notice of the time and place of each meeting of the Managing Board will be given by or at th ...