Document:

Investor Rights Agreement

 Exhibit 10.1 
 REGULUS THERAPEUTICS INC. 
 INVESTOR RIGHTS AGREEMENT 

 

 REGULUS THERAPEUTICS INC. 

INVESTOR RIGHTS AGREEMENT 
 THIS INVESTOR RIGHTS AGREEMENT (this “Agreement”) is entered into as of October 10, 2012 by and between
Regulus Therapeutics Inc., a Delaware corporation (the “Company”), and AstraZeneca AB, a limited liability company organized under the laws of Sweden (“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 August 14, 2012 (the “Purchase Agreement”), the parties desire to enter into this
Agreement in order to grant registration rights, information rights and other 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. RESTRICTIONS ON TRANSFER. 

Investor shall not, directly or indirectly, sell, assign, transfer, pledge, hypothecate, or otherwise deal with or encumber or dispose of in any way the
Shares or Registrable Securities, whether in whole or in part, voluntarily or involuntarily, by operation of law or otherwise (each a “Transfer”), except in accordance with the terms and conditions set forth in this
Section 2. 
 2.1 Restrictions on Transfer. Except as set forth in Section 2.2, Investor agrees not to
make any Transfer of the Shares or Registrable Securities unless and until: 
 (a) there is then in effect a registration
statement under the Securities Act covering such proposed disposition and such disposition is made in accordance with such registration statement; or 

  
 1. 

 (b) (i) The transferee has agreed in writing to be bound by the terms of this
Agreement, (ii) Investor will have notified the Company of the proposed Transfer and will have furnished the Company with a detailed statement of the circumstances surrounding the proposed Transfer, and (iii) if reasonably requested by the
Company, Investor will have furnished the Company with an opinion of counsel, reasonably satisfactory to the Company, that such disposition will not require registration of such shares under the Securities Act. It is agreed that the Company will not
require opinions of counsel for transactions made pursuant to Rule 144, except in unusual circumstances. After the consummation of its Initial Offering, the Company will not require any transferee pursuant to Rule 144 to be bound by the terms of
this Agreement if the shares so transferred do not remain Registrable Securities hereunder following such transfer. 

2.2 Exempt Transfers. Notwithstanding the provisions of Section 2.1 above, no such restriction will apply to:

 (a) a Transfer by Investor to an affiliate of Investor; provided, however, that (i) such affiliate must
have the resources, assets, experience, qualifications, permits and other rights necessary to perform under this Agreement and (ii) the transferee will agree in writing to be subject to the terms of this Agreement to the same extent as if it
were an original Party hereunder. 
 (b) a Transfer pursuant to a Change of Control of Investor. 

2.3 Stock Legends. Each certificate representing Shares or Registrable Securities will be stamped or otherwise imprinted
with legends substantially similar to the following (in addition to any legend required under applicable state securities laws): 

THE SECURITIES REPRESENTED HEREBY HAVE NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933 (THE “ACT”) AND MAY
NOT BE OFFERED, SOLD OR OTHERWISE TRANSFERRED, ASSIGNED, PLEDGED OR HYPOTHECATED UNLESS AND UNTIL REGISTERED UNDER THE ACT OR UNLESS THE COMPANY HAS RECEIVED AN OPINION OF COUNSEL SATISFACTORY TO THE COMPANY AND ITS COUNSEL THAT SUCH REGISTRATION IS
NOT REQUIRED. 
 THE SALE, PLEDGE, HYPOTHECATION OR TRANSFER OF THE SECURITIES REPRESENTED BY THIS CERTIFICATE IS SUBJECT TO THE
TERMS AND CONDITIONS OF A CERTAIN INVESTOR RIGHTS AGREEMENT BY AND BETWEEN THE STOCKHOLDER AND THE COMPANY. COPIES OF SUCH AGREEMENT MAY BE OBTAINED UPON WRITTEN REQUEST TO THE SECRETARY OF THE COMPANY. 

  
 2. 

 (a) The Company will be obligated to promptly reissue unlegended certificates at the
request of Investor if the Company has completed its Initial Offering and Investor has obtained an opinion of counsel (which counsel may be counsel to the Company) reasonably acceptable to the Company to the effect that the securities proposed to be
disposed of may lawfully be so disposed of without registration, qualification and legend, provided that the second legend listed above will be removed only at such time as Investor is no longer subject to any restrictions hereunder.

 (b) Any legend endorsed on an instrument pursuant to applicable state securities laws and the stop-transfer
instructions with respect to such securities will be removed upon receipt by the Company of an order of the appropriate blue sky authority authorizing such removal. 
 SECTION 3. COVENANTS OF THE COMPANY. 
 3.1 Financial Information and
Reporting. 
 (a) The Company will cause to be maintained complete books and records accurately reflecting the
accounts, business and transactions of the Company on a calendar-year basis and with sufficient detail and completeness customary and usual for businesses of the type engaged in by the Company. The Company’s books and records and financial
statements will be in accordance with U.S. generally accepted accounting principles. The Company’s financial statements will be audited annually by an independent nationally recognized public accounting firm approved by the Board of Directors
of the Company (the “Board”). 
 (b) As soon as practicable after the end of each fiscal year of
the Company, and in any event when first delivered to the holders of Series A Convertible Preferred Stock of the Company (the “Series A Preferred Stock”) or their designees, the Company will furnish Investor a balance sheet
of the Company, as at the end of such fiscal year, and a statement of income and a statement of cash flows of the Company, for such year, all prepared in accordance with generally accepted accounting principles consistently applied (except as noted
therein) and setting forth in each case in comparative form the figures for the previous fiscal year, all in reasonable detail. 

(c) The Company will furnish Investor, as soon as practicable after the end of the first, second and third quarterly accounting
periods in each fiscal year of the Company, and in any event when first delivered to the holders of Series A Preferred Stock or their designees, a balance sheet of the Company as of the end of each such quarterly period, and a statement of

  
 3. 

 
income and a statement of cash flows of the Company for such period and for the current fiscal year to date, prepared in accordance with generally accepted accounting principles consistently
applied (except as noted therein), with the exception that year-end audit adjustments may not have been made. 
 (d) The
Company will furnish Investor: (i) the annual budget for each fiscal year approved by the Board, promptly following the approval thereof by the Board, with competitively sensitive information redacted therefrom (and as soon as available, any
subsequent revisions thereto); and (ii) on an annual basis promptly following the end of the Company’s first fiscal quarter, an up to date capitalization table. 
 (e) The Company will provide to Investor any financial information reasonably requested by Investor, and the Company will make its management available to Investor for reasonable inquiries
regarding its financials. 
 3.2 Confidentiality of Records. Investor agrees to use the same degree of care as
Investor uses to protect its own confidential information to keep confidential and not disclose to any party any information furnished to Investor pursuant to Section 3.1 hereof that the Company identifies as being confidential or proprietary
(so long as such information is not in the public domain), except that Investor may disclose such proprietary or confidential information (i) to any affiliate, partner, subsidiary or parent of Investor as long as such affiliate, partner,
subsidiary or parent is advised of and agrees or has agreed to be bound by the confidentiality provisions of this Section 3.2 or comparable restrictions; (ii) to its attorneys, accountants, consultants and other professionals to the extent
necessary to obtain their services in connection with monitoring its investment in the Company, if such person agrees to be bound by the provisions of this Section 3.2 or comparable restrictions; (iii) at such time as it enters the public
domain through no fault of Investor; (iv) that is communicated to Investor by a third party free of any obligation of confidentiality; (v) that is developed by Investor or its agents independently of and without reference to any
confidential information communicated by the Company; or (vi) as required by applicable law. Upon request by the Company, Investor agrees to enter into a separate confidentiality agreement with the Company. Nothing in this Agreement shall
preclude or in any way restrict Investor from investing or participating in any particular enterprise, regardless of whether such enterprise has products or services that compete with those of the Company; provided, however, that Investor
shall not disclose any confidential information of the Company to any such enterprise. 
 SECTION 4. REGISTRATION RIGHTS; MARKET STAND-OFF.

 4.1 Piggyback Registrations. Other than in connection with the Initial Offering, the Company will notify all
Holders of Registrable Securities 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 

  
 4. 

 
relating to secondary offerings of securities of the Company, but excluding Special Registration Statements) and will afford each such Holder an opportunity to include in such registration
statement all or part of such Registrable Securities held by such Holder. Each Holder desiring to include in any such registration statement all or any part of the Registrable Securities held by it will, 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 such Holder. If a Holder decides not to include all of its Registrable Securities
in any registration statement thereafter filed by the Company, such 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. 
 (a)
Underwriting. If the registration statement of which the Company gives notice under this Section 4.1 is for an underwritten offering, the Company will so advise the Holders of Registrable Securities. In such event, the right of any such
Holder to include Registrable Securities in a registration pursuant to this Section 4.1 will be conditioned upon such Holder’s participation in such underwriting and the inclusion of such Holder’s Registrable Securities in the
underwriting to the extent provided herein. All Holders proposing to distribute their Registrable Securities through such underwriting will 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; and second, to the Holders on a pro rata basis based on the total number of Registrable Securities held by the Holders; provided, however, that such
reduction will not be permitted unless such registration does not include shares of any other selling stockholders. If any Holder disapproves of the terms of any such underwriting, such 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. For any Holder which is a partnership, limited liability company or corporation, the partners, retired partners, members, retired members and stockholders of such Holder, or the estates and family members of any such partners, retired
partners, members and retired members and any trusts for the benefit of any of the foregoing persons will be deemed to be a single “Holder,” and any pro rata reduction with respect to such “Holder” will be based upon the
aggregate amount of shares carrying registration rights owned by all entities and individuals included in such “Holder,” as defined in this sentence. 
 (b) Right to Terminate Registration. The Company will have the right to terminate or withdraw any registration initiated by it under this Section 4.1 whether or not any 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 4.3 hereof. 

  
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 4.2 Form S-3 Demand Registrations. In case the Company receives from any
Holder or Holders of Registrable Securities (the “Initiating Holders”) a written request or requests that the Company effect a registration on Form S-3 (or any successor to Form S-3) or any similar short-form
registration statement and any related qualification or compliance with respect to all or a part of the Registrable Securities owned by such Holder or Holders, the Company will: 

(a) promptly give written notice of the proposed registration, and any related qualification or compliance, to all other Holders of
Registrable Securities; and 
 (b) 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 such Holder’s or Holders’ Registrable Securities as are specified in such request, together with all or such portion
of the Registrable Securities of any other Holder or Holders joining in such request as are specified in a written request given within fifteen (15) days after receipt of such written notice from the Company; provided, however, that the
Company will not be obligated to effect any such registration, qualification or compliance pursuant to this Section 4.2: 

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

(ii) if the Holders, 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 fifteen million dollars ($15,000,000); 
 (iii) if within thirty (30) days of receipt of a written request from any Holder or Holders pursuant to this Section 4.2, the Company gives notice to such Holder or Holders of the
Company’s intention to make a public offering within ninety (90) days, other than pursuant to a Special Registration Statement; 
 (iv) if the Company will furnish to the Holders 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 the Holder or Holders under this Section 4.2; provided, that such right to delay a request will be exercised by the Company not more than twice in any twelve (12) month period;

  
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 (v) if the Company has, within the twelve (12) month period preceding the date
of such request, already effected one (1) registration on Form S-3 for the Holders pursuant to this Section 4.2; 

(vi) if the Company has already effected two (2) registrations on Form S-3 for the Holders pursuant to this
Section 4.2; or 
 (vii) 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. 

(c) 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 requests of the Holders. 
 4.3
Expenses of Registration. Except as specifically provided herein, all Registration Expenses incurred in connection with any registration, qualification or compliance pursuant to Section 4.1 or 4.2 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 4.2, the request of which has been subsequently withdrawn by the Initiating Holders unless (a) the withdrawal is based upon material adverse information
concerning the Company of which the Initiating Holders were not aware at the time of such request or (b) the Holders of a majority of Registrable Securities agree 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 4.2(b)(v), as applicable, to undertake any subsequent registration, in which event such right will be forfeited by all Holders). If the Holders are 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 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 4.2(b)(v) to undertake any subsequent registration. 
 4.4 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 the Holders of a majority of the 

  
 7. 

 
Registrable Securities registered thereunder, keep such registration statement effective for up to thirty (30) days or, if earlier, until the Holders have completed the distribution related
thereto; provided, however, that at any time, upon written notice to the participating Holders 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 the Holders hereby agree 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 the Holders of a majority
of the Registrable Securities registered under the applicable registration statement, which consent will not be unreasonably withheld. If so directed by the Company, all Holders registering shares under such registration statement 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 their commercially reasonable
efforts to deliver to the Company (at the Company’s expense) all copies, other than permanent file copies then in such Holders’ 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 the Holders 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 they may reasonably request in order to facilitate the disposition of Registrable Securities owned by them. 
 (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 the Holders; 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. 

  
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 (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. Each Holder participating in such underwriting will also enter into and perform its obligations under such an agreement.

 (f) Notify each Holder of Registrable Securities covered by such registration statement at any time when a prospectus
relating thereto 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. 
 4.5 Delay of Registration; Furnishing Information. 
 (a) No Holder
will 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 4. 

(b) It will be a condition precedent to the obligations of the Company to take any action pursuant to Section 4.1 or 4.2 that
the selling Holders will furnish to the Company such information regarding themselves, the Registrable Securities held by them and the intended method of disposition of such securities as will be required to effect the registration of their
Registrable Securities. 
 (c) The Company will have no obligation with respect to any registration requested pursuant to
Section 4.2 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 4.2. 

  
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 4.6 Indemnification. In the event any Registrable Securities are included in a
registration statement under Section 4.1 or 4.2: 
 (a) To the extent permitted by law, the Company will indemnify
and hold harmless each Holder, the partners, members, stockholders, officers and directors of each Holder, as applicable, any underwriter (as defined in the Securities Act) for such Holder and each person, if any, who controls such 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 each such Holder, 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 4.6(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 such Holder, partner, member, officer, director, underwriter or controlling person
of such Holder. 
 (b) To the extent permitted by law, each Holder will, if Registrable Securities held by such 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, any underwriter and any other Holder, as applicable, selling securities under such registration statement or any of such other Holder’s partners, directors or officers or any person

  
 10.

 
who controls such Holder, against any losses, claims, damages or liabilities (joint or several) to which the Company or any such director, officer, controlling person, underwriter or other such
Holder, or partner, director, officer or controlling person of such other 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 such Holder under an instrument duly executed by such Holder and stated to be specifically for use in connection with such registration; and each such Holder
will reimburse any legal or other expenses reasonably incurred by the Company or any such director, officer, controlling person, underwriter or other Holder, or partner, officer, director or controlling person of such other Holder 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 4.6(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 the Holder, which consent will not be unreasonably withheld; provided further, that in no event
will any indemnity under this Section 4.6 exceed the net proceeds from the offering actually received by such Holder, as applicable. 
 (c) Promptly after receipt by an indemnified party under this Section 4.6 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 4.6, 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 4.6 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 4.6. 

  
 11.

 (d) If the indemnification provided for in this Section 4.6 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 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 a Holder, as applicable, hereunder exceed the net proceeds from the offering received by such Holder, as applicable. 
 (e) The obligations of the Company and Holders under this Section 4.6 will survive completion of any offering of Registrable Securities, as applicable, in a registration statement and, with
respect to liability arising from an offering to which this Section 4.6 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. 
 4.7 Assignment of Registration
Rights. The rights to cause the Company to register Registrable Securities pursuant to this Section 4 may be assigned by a Holder to a transferee or assignee of Registrable Securities (for so long as such shares remain Registrable
Securities) that (a) is a subsidiary, parent, general partner, limited partner, retired partner, member or retired member, stockholder or other affiliate of a Holder that is a corporation, partnership or limited liability company,
(b) acquires all of such Holders Registrable Securities in connection with the sale of all or substantially all of such Holder’s business, or (c) acquires at least two hundred thousand (200,000) shares of Registrable Securities
(as adjusted for stock splits and combinations); or (d) is an entity affiliated by common control (or other related entity) with such Holder provided, however, (i) the transferor will, 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 will agree to be subject to all
restrictions set forth in this Agreement. 

  
 12.

 4.8 Limitation on Subsequent Registration Rights. Except as otherwise provided
herein, after the date of this Agreement, the Company will not enter into any agreement with any holder or prospective holder of any securities of the Company that would grant such holder rights to demand the registration of shares of the
Company’s capital stock, or to include such shares in a registration statement that would reduce the number of shares includable by the Holders. 
 4.9 “Market Stand-Off” Agreement. Each Holder hereby agrees that such Holder, as the case may be, 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, any Common Stock (or other securities) of the Company held by such Holder (other than those included in the registration) during the 365-day period
following the effective date of the registration statement pertaining to the Initial Offering (or such longer period, not to exceed 34 days after the expiration of the 365-day period, as the underwriters or the Company will request in order to
facilitate compliance with NASD Rule 2711 or NYSE Member Rule 472 or any successor rule); provided, that all officers, directors of the Company and all stockholders of the Company holding in the aggregate at least 1% of the Company’s equity
securities on a fully-diluted basis are bound by and have entered into similar agreements. The obligations described in this Section 4.9 will not apply to a Special Registration Statement. 

4.10 Agreement to Furnish Information. Each 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 such Holder’s obligations under Section 4.9, 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, each Holder will provide, within ten (10) days of such request, such information as may be 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 4.9 and this Section 4.10 will not apply to a Special
Registration Statement. The Company may impose stop-transfer instructions with respect to the shares of Common Stock (or other securities) subject to the foregoing restriction until the end of said day period. Each Holder agrees that any transferee
of any shares of Registrable Securities will be bound by Sections 4.9 and 4.10. The underwriters of the Company’s stock are intended third party beneficiaries of Sections 4.9 and 4.10 and will have the right, power and authority to enforce the
provisions hereof as though they were a party hereto. 
 4.11 Rule 144 Reporting. With a view to making available
to the Holders, as applicable, 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: 

  
 13.

 (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 a Holder owns any Registrable Securities, as applicable, furnish to such 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 a 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.

 4.12 Termination of Registration Rights. The right of any Holder to request registration or inclusion of
Registrable Securities in any registration pursuant to Sections 4.1 or 4.2 hereof will terminate upon the earlier of: (i) the date three (3) years following the consummation of the Initial Offering; or (ii) following the consummation
of the Initial Offering, such time as all Registrable Securities held by and issuable to such Holder (and its affiliates) may be sold pursuant to Rule 144 during any ninety (90) day period. Upon such termination, such shares will cease to be
“Registrable Securities” hereunder for all purposes. 
 SECTION 5. MISCELLANEOUS. 

5.1 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. 
 5.2 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, assigns, heirs, executors, and administrators and will inure to the benefit of and be
enforceable by each person who will be a holder of Registrable Securities from time to time; provided, however, that prior to the receipt by the Company of adequate written notice of the transfer of any Registrable Securities specifying the
full name and address of the transferee, the Company may deem and treat the person listed as the holder of such shares in its records as the absolute owner and holder of such shares for all purposes, including the payment of dividends or any
redemption price. 

  
 14.

 5.3 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. 

5.4 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. 
 5.5 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. 
 5.6 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. 
 5.7 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: President and CEO

  
 15.

			
	 With a copy to:
	  	 Cooley LLP
 4401
Eastgate Mall
 San Diego, CA 92121

Attention: Thomas A. Coll, Esq.

		
	 To Investor:
	  	 AstraZeneca AB
 SE-431 83
Mölndal
 Sweden
 Attention: Legal
Department

		
	 With a copy to:
	  	 AstraZeneca UK Limited

Strategic Planning and Business Development

Alderley House,
 Alderley Park,

Macclesfield,
 Cheshire SK10
4T

 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. 
 5.8 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 5.8, “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. 

5.9 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 and the plural
number includes the singular and will not be interpreted to preclude the 

  
 16.

 
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. 
 5.10 Counterparts. This Agreement may be executed in two or more counterparts, each of which will be deemed an original, but all of which together will constitute one and the same
instrument, 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. 
 5.11 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.

 5.12 Specific Performance. The failure of either party to this Agreement to perform its agreements and
covenants hereunder, including but not limited to Section 4, 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 5.12 is without prejudice to any other rights that the Company and Investor may have for any failure to
perform this Agreement. 
 5.13 Termination. This Agreement will terminate and be of no further force or effect
upon the earlier of (i) a Liquidation Event, Acquisition or Asset Transfer (each as defined in the Company’s Amended and Restated Certificate of Incorporation, as amended, as in effect on the date of the Purchase Agreement); or
(ii) the date three (3) years following the Closing Date (as defined in the Purchase Agreement). 
 [THIS SPACE
INTENTIONALLY LEFT BLANK] 

  
 17.

 IN WITNESS WHEREOF, the parties hereto
have executed this INVESTOR 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
CEO            

 INVESTOR: 
  

			
	ASTRAZENECA AB
		
	By:	 	/s/ Gunnar Olsson
	Name:	 	 Gunnar
Olsson            

	Title:	 	 VP & Head CVGI
iMed            

  

  
 1. 

 EXHIBIT A 
 DEFINITIONS 
 1.1 “Change of Control” means,
with respect to Investor, the earlier of (x) the public announcement of and (y) the closing of: (a) a merger, reorganization or consolidation involving Investor in which its shareholders immediately prior to such transaction would
hold less than 50% of the securities or other ownership or voting interests representing the equity of the surviving entity immediately after such merger, reorganization or consolidation, or (b) a sale to a third party of all or substantially
all of Investor’s assets or business relating to this Agreement. Investor will notify the Company within two (2) Business Days of entering into an agreement which, if consummated, would result in a Change of Control. 

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 so long as it owns of record Registrable Securities that have not been sold to
the public, or any assignee of record of such Registrable Securities in accordance with Section 4.7 hereof. 
 1.6
“Initial Offering” means the Company’s first firm commitment underwritten public offering of its Common Stock registered under the Securities Act. 
 1.7 “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. 
 1.8 “Registrable Securities” means (a) the Shares; 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, (ii) sold in a private transaction in which the transferor’s rights under Section 4 of this Agreement are not assigned or
(iii) eligible for resale pursuant to Rule 144 without volume limitations. 

 1.9 “Registration Expenses” means all expenses incurred by
the Company in complying with Sections 4.1 or 4.2, 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 ten thousand
dollars ($10,000) of a single special counsel for the Holders, 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). 
 1.10 “Rule 144” means Rule 144
promulgated under the Securities Act, as in effect from time to time. 
 1.11 “SEC” means the
Securities and Exchange Commission. 
 1.12 “Securities Act” means the Securities Act of 1933, as
amended. 
 1.13 “Selling Expenses” means all underwriting discounts and selling commissions
applicable to the sale. 
 1.14 “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. 
 1.15
“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-1Convertible Promissory Note

 Exhibit 10.2 
 THIS NOTE AND ANY SHARES ACQUIRED UPON CONVERSION OF THIS NOTE HAVE NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933, AS AMENDED, AND MAY NOT BE OFFERED, SOLD OR OTHERWISE TRANSFERRED, PLEDGED OR
HYPOTHECATED EXCEPT PURSUANT TO AN EFFECTIVE REGISTRATION STATEMENT FILED UNDER SUCH ACT OR PURSUANT TO AN OPINION OF COUNSEL SATISFACTORY TO REGULUS THERAPEUTICS INC. 
 CONVERTIBLE PROMISSORY NOTE 
  

			
	 $5,426,952.05
	 	 Issuance Date: October 10, 2012

		
		 	 No. 3

  
 FOR VALUE RECEIVED, Regulus
Therapeutics Inc., a Delaware corporation (the “Maker”), promises to pay to Glaxo Group Limited or its assigns (the “Holder”) the principal sum of $5,426,952.05, together with interest on the unpaid principal
balance of this Note from time to time outstanding at the rate per annum equal to the Interest Rate (as defined below) until paid in full. Subject to the provisions of Sections 2 and 4, all of the outstanding principal hereunder and accrued and
unpaid interest thereon (such amount, subject to any reduction pursuant to Section 3(c), the “Outstanding Amount”) shall be due and payable on October 9, 2015 (the “Maturity Date”). This Note replaces and
supersedes the Amended and Restated Convertible Promissory Note dated July 27, 2012. 
 Interest on this Note shall be
computed on the basis of a year of 360 days for the actual number of days elapsed and shall accrue and compound daily from the Issuance Date to (and including) the Maturity Date. All payments by the Maker under this Note shall be in immediately
available funds. 
 1. Definitions. For purposes of this Note: 
 (a) “Affiliates” shall mean, with respect to any Person, each Person that, directly or indirectly, controls, is controlled by or is under common control with such Person. 

(b) “Business Day” shall mean any day other than a (x) Saturday, (y) Sunday or (z) day on which state or
federally chartered banking institutions in New York, New York or London, England are not required to be open. 
 (c)
“Change of Control” shall mean (i) any “person” or “group” (as such terms are used in Sections 13(d) and 14(d) of the Exchange Act), other than Alnylam Pharmaceuticals, Inc. and Isis Pharmaceuticals,
Inc., that becomes the “beneficial owner” (as defined in Rules 13d-3 and 13d-5 under the Exchange Act) of 20% or more of the outstanding voting power of the Maker (assuming the exercise or conversion of all securities owned by such person
or group that are exercisable for or convertible into securities of the Maker with voting power), (ii) the consummation of any consolidation or merger of the Maker or similar transaction, in one or a series of transactions, involving any Person
other than one of the Maker’s subsidiaries, pursuant to which the Common Stock will be converted into, or receive a distribution of the proceeds in, cash, securities or other property, other than a transaction or series of transactions, taken
as 

 
whole, in which (A) the Persons that “beneficially own” (as defined in Rule 13d-3 under the Exchange Act), directly or indirectly, common stock of the Maker immediately prior to
such transaction beneficially own, directly or indirectly, voting shares representing a majority of the total voting power of all outstanding classes of voting shares of the continuing or surviving Person immediately after the transaction or series
of transactions and (B) the Persons that “beneficially own” (as defined in Rule 13d-3 under the Exchange Act), directly or indirectly, common stock of the Maker immediately prior to such transaction beneficially own, directly or
indirectly, the voting shares of the continuing or surviving Person necessary to elect a majority of the members of the board of directors (or their equivalent if other than a corporation) of such continuing or surviving Person immediately after the
transaction or series of transactions , (iii) the sale of all or substantially all the assets of the Maker (determined on a consolidated basis) to another Person or (iv) the approval by the stockholders of the Maker of a plan of
liquidation or dissolution or other insolvency event. 
 (d) “Collaboration Agreement” shall mean the Product
Development and Commercialization Agreement dated April 17, 2008 between Maker and Holder, as amended. 
 (e)
“Common Stock” shall mean the common stock of the Maker, par value $0.001 per share, whether or not registered. 

(f) “Conversion Price” shall mean, as of any Conversion Date or other date of determination, and subject to adjustment as
provided herein, $4.00. 
 (g) “Conversion Date” shall mean the date, which shall be prior to the Conversion
Deadline, on which this Note is converted in accordance with Section 2. 
 (h) “Convertible Securities”
shall mean any stock or securities (other than Options) directly or indirectly convertible into or exercisable or exchangeable for shares of Common Stock. 
 (i) “ERISA” shall mean the Employee Retirement Income Security Act of 1974, as amended from time to time, regulations promulgated thereunder and any successor thereto. 

(j) “Exchange Act” shall mean the Securities Exchange Act of 1934, as amended. 

(k) “Fundamental Change” shall mean a Change of Control or a Termination of Trading on or prior to the Maturity Date.

 (l) “GAAP” shall mean generally accepted accounting principles in the United States of America in effect from
time to time. 
 (m) “Indebtedness” shall mean, with respect to any Person, without duplication, (a) all
indebtedness, obligations and other liabilities (contingent or otherwise) of such Person (i) for borrowed money (including obligations of such Person in respect of overdrafts, foreign exchange contracts, currency exchange agreements, interest
rate protection agreements and any loans or advances from banks, whether or not evidenced by notes or similar instruments) or (ii) evidenced 

  
 - 2 -

 
by credit or loan agreements, bonds, debentures, notes or similar instruments (whether or not the recourse of the lender is to the whole of the assets of such Person or to only a portion thereof)
(other than any account payable or other accrued current liability or obligation incurred in the ordinary course of business in connection with the obtaining of materials or services), (b) all reimbursement obligations and other liabilities
(contingent or otherwise) of such Person with respect to letters of credit, bank guarantees or bankers’ acceptances, (c) all obligations and liabilities (contingent or otherwise) of such Person (i) in respect of leases of such Person
required, in conformity with GAAP, to be accounted for as capitalized lease obligations on the balance sheet of such Person (as determined by such Person, or the Maker in the case of any subsidiary of the Maker), or (ii) under any lease or
related document (including a purchase agreement, conditional sale or other title retention agreement) in connection with the lease of real property or improvements thereon (or any personal property included as part of any such lease) which provides
that such Person is contractually obligated to purchase or cause a third party to purchase the leased property or pay an agreed upon residual value of the leased property to the lessor (whether or not such lease transaction is characterized as an
operating lease or a capitalized lease in accordance with GAAP), (d) all obligations (contingent or otherwise) of such Person with respect to any interest rate or other swap, cap, floor or collar agreement, hedge agreement, forward contract or
other similar instrument or agreement or foreign currency hedge, exchange, purchase or similar instrument or agreement; (e) all direct or indirect guaranties, agreements to be jointly liable or similar agreements by such Person in respect of,
and obligations or liabilities of such Person to purchase or otherwise acquire or otherwise assure a creditor against loss in respect of, indebtedness, obligations or liabilities of another Person of the kind described in clauses (a) through
(d), and (f) any and all deferrals, renewals, extensions, refinancings and refundings of, or amendments, modifications or supplements to, any indebtedness, obligation or liability of the kind described in clauses (a) through (e).

 (n) “Interest Rate” shall mean 3.297%. 

(o) “Issuance Date” shall mean the Issuance Date first above written. 

(p) “Options” shall mean any rights, warrants or options to subscribe for or purchase shares of Common Stock or
Convertible Securities. 
 (q) “Person” shall mean any individual, corporation, partnership, limited liability
company, joint venture, association, joint-stock company, trust, unincorporated organization, government or any agency or political subdivision thereof or any other entity. 
 (r) “Permitted Liens” shall mean (i) any Lien for taxes not yet due or delinquent or being contested in good faith by appropriate proceedings for which adequate reserves have been
established in accordance with GAAP, (ii) any statutory Lien arising in the ordinary course of business by operation of law with respect to a liability that is not yet due or delinquent, other than any Lien imposed by ERISA, (iii) any Lien
created by operation of law, such as materialmen’s liens, mechanics’ liens and other similar liens, arising in the ordinary course of business with respect to a liability that is not yet due or delinquent and for which adequate reserves
have been established in accordance with GAAP, (iv) any Lien relating to any Purchase 

  
 - 3 -

 
Money Indebtedness upon or in any equipment acquired or held by the Maker or any of its subsidiaries to secure the purchase price of such equipment or indebtedness incurred solely for the purpose
of financing the acquisition or lease of such equipment and (v) Liens arising out of pledges or deposits under workmen’s compensation laws, unemployment insurance, old age pensions, or other social security benefits other than any Lien
imposed by ERISA. 
 (s) “Permitted Senior Indebtedness” shall mean (i) Purchase Money Indebtedness of the
Maker and (ii) any other Indebtedness of the Maker issued, assumed or otherwise incurred after the Issuance Date with respect to which the Holder has provided prior written consent to have such Indebtedness rank senior to, or pari passu with,
the obligations hereunder, which consent shall not be unreasonably withheld, conditioned or delayed. 
 (t) “Purchase
Money Indebtedness” shall mean Indebtedness (including capital lease obligations) with respect to equipment required by the Maker and used in the ordinary course of business, consisting of the deferred purchase price of such equipment,
conditional sale obligations or obligations under any title retention agreement, in each case, where the maturity of such Indebtedness does not exceed the anticipated useful life of the equipment being financed, in the ordinary course of business;
provided, however, that any lien or other encumbrance arising in connection with any such Indebtedness shall be limited to the specific equipment being financed; provided further, however, that such Indebtedness is
Incurred at the time of acquisition of such equipment. 
 (u) “Termination of Trading” shall mean the
termination or suspension for a period of more than five consecutive Business Days of trading of the Common Stock into which this Note may be converted on The Nasdaq Stock Market or any such other U.S. principal national securities exchange on which
the Common Stock is then listed. 
 2. Conversion. 
 (a) At the option of the Holder, this Note shall be convertible into shares of Common Stock of the Maker on the terms and conditions set forth in this Section 2. Notwithstanding the foregoing, if the
conversion of this Note pursuant to this Section 2 would otherwise result in the Holder, together with its Affiliates, owning more than 9.99% of the outstanding Common Stock calculated on an as-converted, fully-diluted basis (including as
outstanding shares of capital stock issuable upon exercise or conversion of all outstanding Options, Purchase Rights or other Convertible Securities of the Maker), immediately following the conversion of the Note (the “9.99%
Threshold”), the Outstanding Amount shall be converted into (i) that number of shares of Common Stock that would result in the Maker reaching, but not exceeding, the 9.99% Threshold (the “9.99% Shares”), and
(ii) an amount in cash equal to the difference between (A) the product of (1) the number of 9.99% Shares issued upon conversion, multiplied by (2) the Conversion Price and (B) the Outstanding Amount. 

(b) Subject to Sections 2(a), 2(c) and 2(d) hereof, at any time between the Issuance Date and 11:59 p.m. New York City time on the
Business Day immediately preceding the Maturity Date (the “Conversion Deadline”), the Holder shall be entitled to convert all, but not less than all, 

  
 - 4 -

 
of the then Outstanding Amount into shares of Common Stock based on the Conversion Rate described in Section 2(c) below. All shares of Common Stock issued upon conversion of this Note
(i) shall be duly issued, fully paid and non-assessable and (ii) shall not be subject to any Liens, preemptive rights or other transfer restrictions. The Maker shall pay any and all transfer, stamp and similar taxes that may be payable
with respect to the issuance and delivery of shares of Common Stock upon conversion of this Note; provided, that the Maker shall not be responsible for the payment of any income taxes that may be incurred by the Holder as a result of such
conversion. 
 (c) Conversion Rate, Adjustment to the Conversion Price. 

 

	 	(i)	The number of shares of Common Stock issuable upon conversion of this Note pursuant to this Section 2 shall be equal to (i) the Outstanding Amount as of the
Conversion Date (defined below) divided by (ii) the Conversion Price; provided that if the conversion would result in the issuance of a fraction of a share of Common Stock, the Maker shall round such fraction of a share of Common Stock up to
the nearest whole share. 

  

	 	(ii)	Adjustment of Conversion Price upon Subdivision or Combination of shares of Common Stock. If the Maker at any time on or after the Issuance Date subdivides (by
any stock split, stock dividend, recapitalization or otherwise) its outstanding shares of Common Stock into a greater number of shares, the Conversion Price in effect immediately prior to such subdivision will be proportionately reduced. If the
Maker at any time on or after the Issuance Date combines (by combination, reverse stock split or otherwise) its outstanding shares of Common Stock into a smaller number of shares, the Conversion Price in effect immediately prior to such combination
will be proportionately increased. 

  

	 	(iii)	 Rights upon a Corporate Event. In addition to and not in substitution for any other rights hereunder (but not in duplication of any adjustment
made pursuant to Section 2(c)(ii)), prior to the consummation of any transaction pursuant to which all holders of outstanding shares of Common Stock are entitled to receive securities or other assets with respect to or in exchange for shares of
Common Stock (a “Corporate Event”), the Maker shall make appropriate provision to insure that the Holder will thereafter have the right to receive upon a conversion of this Note for shares of Common Stock, (i) in addition to
the shares of Common Stock receivable upon such conversion, such securities or other assets to which the Holder would have been entitled with respect to such shares of Common Stock had such shares of Common Stock been held by the Holder upon the
consummation of such Corporate Event (without taking into account any limitations or restrictions on the convertibility of this Note) or (ii) in lieu of the shares of Common Stock otherwise receivable upon such conversion, such securities or
other assets received by the holders of shares of Common Stock in connection with the 

  
 - 5 -

	 	
consummation of such Corporate Event in such amounts as the Holder would have been entitled to receive had this Note initially been issued with conversion rights for the form of such
consideration (as opposed to shares of Common Stock) at a conversion rate for such consideration commensurate with the terms of conversion set forth in Section 2(c)(i). The provisions of this Section 2(c)(iii) shall apply similarly and
equally to successive Corporate Events and shall be applied without regard to any limitations on the conversion of this Note. 

  

	 	(iv)	Purchase Rights. If at any time the Holder grants, issues or sells any rights to purchase stock, warrants, securities or other property pro rata to all record
holders of shares of Common Stock (the “Purchase Rights”), then the Holder will be entitled to acquire, upon the terms applicable to such Purchase Rights, the aggregate Purchase Rights which the Holder could have acquired if the
Holder had held the shares of Common Stock acquirable upon complete conversion of this Note (without taking into account any limitations or restrictions on the convertibility of this Note) immediately before the date on which a record is taken for
the grant, issuance or sale of such Purchase Rights, or, if no such record is taken, the date as of which the record holders of shares of Common Stock are to be determined for the grant, issue or sale of such Purchase Rights.

 (d) Mechanics of Conversion. 

 

	 	(v)	Share Conversion Notice. To convert this Note into shares of Common Stock on any Conversion Date, the Holder shall (A) transmit by facsimile (or otherwise
deliver), for receipt on or prior to 11:59 p.m., New York City time, on the Conversion Date, a copy of an executed notice of conversion in the form attached hereto as Exhibit I (the “Conversion Notice”)

 to the Maker: 
 Regulus Therapeutics Inc. 
 3545 John Hopkins Court, Suite 210 

San Diego, CA 92121 
 Attn: President and CEO 
 Facsimile: (858) 202-6363 

With a copy to: 
 Cooley LLP 
 4401 Eastgate Mall 

San Diego, CA 92121 
 Attn: Thomas A. Coll, Esq. 
 Facsimile: (858) 550-6420 

  
 - 6 -

 and (B) physically surrender the Note to the Maker for cancellation in connection with
such conversion. 
  

	 	(vi)	Share Delivery. On or before the third Business Day following the date of receipt of a Conversion Notice and the Maker’s receipt of the Note from the
Holder, the Maker shall issue and deliver to such address of the Holder as is set forth in the Conversion Notice, a certificate, registered in the name of the Holder or its designee, for the number of shares of Common Stock to which the Holder shall
be entitled. The Person entitled to receive the shares of Common Stock issuable upon a conversion of this Note shall be treated for all purposes as the record holder or holders of such shares of Common Stock on the Conversion Date.

 (e) Availability of Authorized Shares. The Maker covenants and agrees that at all times from the Issuance
Date to the earlier of (i) a Conversion Date and (ii) the Maturity Date, the Maker shall reserve and keep available out of its authorized but unissued shares of capital stock such number of shares of Common Stock, as shall from time to
time be sufficient to effect the conversion of this Note. 
 3. Repayment and Setoff. 

(a) Subject to the provisions in Sections 2 and 4, the Outstanding Amount, if any, will be repaid in cash on the Maturity Date.

 (b) In the event the Holder terminates the Collaboration Agreement without cause or the Maker terminates the Collaboration
Agreement as a result of a material breach by the Holder, in each case, prior to the Maturity Date, this Note may be prepaid in cash, in whole but not in part and without any pre-payment penalty, prior to the Maturity Date at the election of the
Maker and without the prior written consent of the Holder. Except as provided in Section 2(a) and in this Section 3(b), the Maker shall not have the right to repay in cash, in whole or in part, any Outstanding Amount prior to the Maturity
Date. 
 (c) On or prior to the Maturity Date, the Holder, at its option, by delivery of written notice to the Maker, may setoff
any Outstanding Amount against any amount due and payable by the Holder or its Affiliates to the Maker under the Collaboration Agreement, including any milestone payment, and upon delivery of such written notice the Outstanding Amount shall be
reduced by the amount that is setoff, with such setoff first being applied to reduce any accrued and unpaid interest outstanding hereunder and then to reduce the principal amount of this Note. 

4. Fundamental Change. At least 20 days prior to the occurrence of any Fundamental Change (the effective date of the Fundamental Change, the
“Fundamental Change Date”), the Maker shall deliver written notice to the Holder describing in reasonable detail the terms of the 

  
 - 7 -

 
Fundamental Change. Upon receipt of such notice, the Holder may (but is not obligated to) by written notice to the Maker declare due and payable in cash on the Fundamental Change Date
(i) the Outstanding Amount under this Note as of the Fundamental Change Date and (ii) a fee (the “Make-Whole Premium”) in the amount equal to the projected interest that would have accrued pursuant to this Note from the
Fundamental Change Date to the Maturity Date assuming that no Outstanding Amount were prepaid, repaid, converted or offset pursuant to the terms hereof on or after the Fundamental Change Date. 

5. Events of Default. The Outstanding Amount under this Note shall become immediately due and payable without notice or demand upon the occurrence
at any time of any of the following events of default (individually, an “Event of Default” and collectively, “Events of Default”): 
 (a) the Maker fails to pay any of the principal or interest under this Note within 10 days of Maker’s receipt of written notice that such amount is due and payable; 

(b) the Maker or any of its Affiliates shall fail to make any payment due (whether by scheduled maturity, required prepayment,
acceleration, demand or otherwise) on any other Indebtedness in excess of $10,000,000 and such failure shall continue after the applicable grace period, if any, specified in the agreement or instrument relating to Indebtedness; 

(c) any material default by the Maker in the due performance or observance of any covenant or agreement contained in this Note that
remains uncured for 10 days after the date the Holder notifies the Maker of such default; 
 (d) any default by the Maker in due
performance or observance of the covenants and agreements set forth in Section 6 of this Note; 
 (e) the Maker files any
petition or action for relief under any bankruptcy, reorganization, insolvency or moratorium law or any other law for the relief of, or relating to, debtors, now or hereafter in effect, or seeks the appointment of a custodian, receiver, trustee (or
other similar official) of the Maker or all or any substantial portion of the Maker’s assets, or makes any assignment for the benefit of creditors or takes any action in furtherance of any of the foregoing, or fails to generally pay its debts
as they become due; 
 (f) an involuntary petition is filed, or any proceeding or case is commenced, against the Maker (unless
such proceeding or case is dismissed or discharged within 60 days of the filing or commencement thereof) under any bankruptcy, reorganization, arrangement, insolvency, adjustment of debt, liquidation or moratorium statute now or hereafter in effect,
or a custodian, receiver, trustee, assignee for the benefit of creditors (or other similar official) is applied or appointed for the Maker or to take possession, custody or control of any property of the Maker, or an order for relief is entered
against the Maker in any of the foregoing; 
 (g) with respect to any consolidated financial statements included in the
Maker’s annual report on Form 10-K filed pursuant to the Exchange Act, the failure of the Maker to obtain a report thereon that is unqualified as to going concern and scope of audit and issued by independent certified public accountants of
recognized national standing; or 

  
 - 8 -

 (h) termination of the Collaboration Agreement by the Holder (or its assignee or successor
under the Collaboration Agreement) in accordance with the terms thereof by reason of material breach of the Collaboration Agreement by the Maker. 
 Upon the occurrence of an Event of Default, the Holder shall have then, or at any time thereafter, all of the rights and remedies afforded creditors generally by the applicable federal laws or the laws of
the State of Delaware. 
 6. Subordination, Permitted Liens. This Note (including, but not limited to, the obligations with respect to
payment of the Outstanding Amount and the Make-Whole Premium) shall rank senior to all Indebtedness of the Maker and its subsidiaries, if any, whether issued, assumed or otherwise incurred prior to, on or after the Issuance Date, except for
Permitted Senior Indebtedness. So long as this Note is outstanding, without the prior written consent of the Holder, the Maker shall not and the Maker shall not permit any of its subsidiaries to, directly or indirectly, allow or suffer to exist any
mortgage, lien, pledge, charge, security interest or other encumbrance upon or in any property or assets (including accounts and contract rights) owned by the Maker or any of its subsidiaries (collectively, “Liens”) other than
Permitted Liens. 
 7. Miscellaneous. 
 (a) All payments by the Maker under this Note shall be made without set-off (except as provided in Section 3(c)) or counterclaim and be free and clear and without any deduction or withholding for any
taxes or fees of any nature whatever, unless the obligation to make such deduction or withholding is imposed by law. 
 (b) No
delay or omission on the part of the Holder in exercising any right under this Note shall operate as a waiver of such right or of any other right of the Holder, nor shall any delay, omission or waiver on any one occasion be deemed a bar to or waiver
of the same or any other right on any future occasion. 
 (c) The Maker hereby waives presentment, demand, protest and notices of
every kind and assents to any permitted extension of the time of payment and to the addition or release of any other party primarily or secondarily liable hereunder. 
 (d) Any notices, requests and other communications hereunder shall be in writing and shall be personally delivered or sent by express delivery service, registered or certified air mail, return receipt
requested, postage prepaid, or by facsimile (confirmed by prepaid registered or certified air mail letter or by international express delivery mail) (e.g., FedEx), and shall be deemed to have been properly served to the addressee upon receipt of
such written communication, to the following addresses of the parties, or such other address as may be specified in writing to the other parties hereto: 

  
 - 9 -

			
	if to Holder:	  	 Glaxo Group Limited
 980 Great
West Road
 Brentford, Middlesex TW8 9GS

United Kingdom
 Facsimile:
        44-20 8049 6904
 Attention:         Company
Secretary

		
	            with a copy to:	  	 GlaxoSmithKline
 200 N
16th Street

Mail Code FP2355
 Philadelphia, PA
19002
 Facsimile:         215-751-5349
 Attention:         Vice President Legal Operations
        Corporate Functions - US

		
	if to Maker:	  	 Regulus Therapeutics Inc.
 3545
John Hopkins Court, Suite 210
 Facsimile:
 Attention:         President and CEO

 (e) The Holder agrees that no director or officer of the Maker shall have any personal liability for the
repayment of this Note. 
 (f) This Note may not be amended or modified except by an instrument executed by the Maker and the
Holder. 
 (g) Until the conversion of this Note, the Holder shall not have or exercise any rights by virtue hereof as a member
or stockholder of the Maker. 
 (h) All rights and obligations hereunder shall be governed by the laws of the State of Delaware
(without giving effect to principles of conflicts or choices of law) and this Note is executed as an instrument under seal. 

(i) Upon receipt by the Maker of evidence reasonably satisfactory to the Maker of the loss, theft, destruction or mutilation of this Note,
and, in the case of loss, theft or destruction, of any indemnification undertaking by the Holder to the Maker in customary form and, in the case of mutilation, upon surrender and cancellation of this Note, the Maker shall execute and deliver to the
Holder a new Note (in accordance with Section 7(j)) representing the then outstanding principal amount hereof. 

  
 - 10 -

 (j) If the Maker is required to issue a new Note pursuant to the terms of this Note, such
new Note (i) shall be of like tenor with this Note, (ii) shall represent, as indicated on the face of such new Note, the principal remaining outstanding, (iii) shall have an issuance date, as indicated on the face of such new Note,
which is the same as the Issuance Date of this Note, (iv) shall have the same rights and conditions as this Note and (v) shall represent accrued Interest from the Issuance Date. 

(k) The remedies provided in this Note shall be cumulative and in addition to all other remedies available under this Note at law or in
equity (including a decree of specific performance and/or other injunctive relief), and nothing herein shall limit the Holder’s right to pursue actual and consequential damages for any failure by the Maker to comply with the terms of this Note.
Amounts set forth or provided for herein with respect to payments, conversion and the like (and the computation thereof) shall be the amounts to be received by the Holder and shall not, except as expressly provided herein, be subject to any other
obligation of the Maker (or the performance thereof). The Maker acknowledges that a breach by it of its obligations hereunder will cause irreparable harm to the Holder and that the remedy at law for any such breach may be inadequate. The Maker
therefore agrees that, in the event of any such breach or threatened breach, the Holder shall be entitled, in addition to all other available remedies, to seek an injunction restraining any breach, without any bond or other security being required.

 (l) If (i) this Note is placed in the hands of an attorney for collection or enforcement or is collected or enforced
through any legal proceeding or the Holder otherwise takes action to collect amounts due under this Note or to enforce the provisions of this Note or (ii) there occurs any bankruptcy, reorganization, receivership of the Maker or other
proceedings affecting the Maker’s creditors’ rights and involving a claim under this Note, then the Maker shall pay the documented costs incurred by the Holder for such collection, enforcement or action or in connection with such
bankruptcy, reorganization, receivership or other proceeding, including, but not limited to, attorneys’ fees and disbursements. 
 (m) The Holder shall be entitled to transfer or assign this Note to any of its Affiliates without the Maker’s consent. 

 

			
	 MAKER:
  

REGULUS THERAPEUTICS INC.

		
	By:	 	/s/ Kleanthis G. Xanthopoulos
	Title:	 	 President and CEO

 [Signature Page to Convertible Promissory Note] 

 
			
	 HOLDER:
  

GLAXO GROUP LIMITED

		
	By:	 	/s/ Catherine Springett
	Title:	 	 Authorized Signatory

 [Signature Page to Convertible Promissory Note]

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