RELEASE AND WAIVER OF CLAIMS

In connection with my resignation from Regulus Therapeutics Inc. (the “Company”) on May 4, 2017 (the “Resignation Date”), and in consideration of the payments and other benefits set forth herein, I, Paul C. Grint, M.D., hereby furnish the Company with the following release and waiver (“Release and Waiver”).

As used herein, “Severance Compensation” means (1) aggregate severance payments equal to 12 months of my base salary in effect on the Resignation Date, which will be paid in a lump sum payment within five business days of the Effective Date (as defined below), (2) a lump sum cash amount equal to 229.56% multiplied by the total cost of the projected premiums for group medical, dental and vision insurance for a period of 12 months (calculated in the manner provided in Section 5.3.2 of the Amended and Restated Employment Agreement between me and the Company, dated September 19, 2014), (3) vesting acceleration of all outstanding options or other equity incentive awards held by me that are subject to time-based vesting as of the Resignation Date, and (4) subject to my execution and delivery of a consent agreement in the form attached hereto as Exhibit A, the extension of the post-termination exercise period of the stock options held by me as of the Resignation Date from 90 calendar days to 365 calendar days following the Resignation Date.

In exchange for the Company’s agreement to provide the Severance Compensation described above, which I am not otherwise entitled to receive, I hereby generally and completely release the Company and its directors, officers, employees, stockholders, partners, agents, attorneys, predecessors, successors, parent and subsidiary entities, insurers, affiliates, and assigns (collectively, the “Released Parties”) from any and all claims, liabilities and obligations, both known and unknown, that arise out of or are in any way related to events, acts, conduct, or omissions occurring prior to my signing this Release and Waiver (collectively, the “Released Claims”). The Released Claims include, but are not limited to: (1) all claims arising out of or in any way related to my employment with the Company or the termination of that employment; (2) all claims related to my compensation or benefits from the Company, including, but not limited to, salary, bonuses, commissions, vacation pay, expense reimbursements, severance pay, fringe benefits, stock, stock options, or any other ownership interests in the Company; (3) all claims for breach of contract, wrongful termination, and breach of the implied covenant of good faith and fair dealing; (4) all tort claims, including, but not limited to, claims for fraud, defamation, emotional distress, and discharge in violation of public policy; and (5) all federal, state, and local statutory claims, including, but not limited to, claims for discrimination, harassment, retaliation, attorneys’ fees, or other claims arising under the federal Civil Rights Act of 1964 (as amended), the federal Americans with Disabilities Act of 1990 (as amended), the federal Age Discrimination in Employment Act of 1967, as amended (“ADEA”), the federal Family and Medical Leave Act (as amended), the California Labor Code, and the California Fair Employment and Housing Act (as amended). Notwithstanding the foregoing, the following are not included in the Released Claims (the “Excluded Claims”): (a) any rights or claims for indemnification I may have pursuant to any written indemnification agreement with the Company to which I am a party, the charter, bylaws, or operating agreements of the Company, or under applicable law; (b) any rights or claims to unemployment compensation, funds accrued in my 401K account, or any vested equity incentives; (c) any rights to receive the Severance Compensation subject to and in accordance with the terms of this Release and Waiver; (d) any rights that are not waivable as a matter of law; and (e) any claims arising from the breach of this Release and Waiver. In addition, nothing in this Release and Waiver prevents me from filing a charge or complaint with the Equal Employment Opportunity Commission, the California Department of Fair Employment and Housing, the National Labor Relations Board, the Occupational Safety and Health Administration, the Securities and Exchange Commission or any other federal, state or local governmental agency or commission (collectively, the “Government Agencies”). This Release and Waiver does not limit my ability to communicate with any Government Agencies or otherwise participate in any investigation or proceeding that may be conducted by any Government Agency, including providing documents or other information, without notice to the Company. While this Release and Waiver does not limit my right to receive an award for information provided to the Securities and Exchange Commission, I understand and agree that, to maximum extent permitted by law, I am otherwise waiving any and all rights I may have to individual relief based on the claims that I have released and the rights I have has

waived by signing this Release and Waiver. Furthermore, if there is a dispute over the amount of any portion of the Severance Compensation payable to me pursuant to this Release and Waiver, the Company will nevertheless pay to me all amounts that are not in dispute and my claim for such amounts that are in dispute shall also be deemed an Excluded Claim. I hereby represent and warrant that, other than the Excluded Claims, I am not aware of any claims I have or might have against any of the Released Parties that are not included in the Released Claims.

I also acknowledge that I have read and understand Section 1542 of the California Civil Code which reads as follows: “A general release does not extend to claims which the creditor does not know or suspect to exist in his or her favor at the time of executing the release, which if known by him or her must have materially affected his or her settlement with the debtor.” I hereby expressly waive and relinquish all rights and benefits under that section and any law of any jurisdiction of similar effect with respect to any claims I may have against the Company.

I acknowledge that, among other rights, I am waiving and releasing any rights I may have under ADEA, that this Release and Waiver is knowing and voluntary, and that the consideration given for this Release and Waiver is in addition to anything of value to which I was already entitled as an executive of the Company. I further acknowledge that I have been advised, as required by the Older Workers Benefit Protection Act, that: (a) the release and waiver granted herein does not relate to claims under the ADEA which may arise after this Release and Waiver is executed; (b) I should consult with an attorney prior to executing this Release and Waiver; (c) I have twenty-one (21) days in which to consider this Release and Waiver (although I may choose voluntarily to execute this Release and Waiver earlier); (d) I have seven (7) days following the execution of this Release and Waiver to revoke my consent to this Release and Waiver; and (e) this Release and Waiver shall not be effective until the eighth (8^th) day after I sign and deliver this Release and Waiver to the Company, provided I have not previously revoked this Release and Waiver (the date on which this Release and Waiver becomes effective, the “Effective Date”).

I acknowledge my continuing obligations under my Employee Confidentiality and Inventions Assignment Agreement, a copy of which is attached hereto as Exhibit B (the “CIAA”). Pursuant to the CIAA, I understand that among other things, I must not use or disclose any confidential or proprietary information of the Company and I must immediately return all Company property and all copies thereof in my possession or control. I understand and agree that my right to the Severance Compensation I am receiving is in exchange for my agreement to the terms of this Release and Waiver and is contingent upon my continued compliance with my CIAA.

This Release and Waiver and the exhibits hereto constitute the complete, final and exclusive embodiment of the entire agreement between the Company and me with regard to the subject matter hereof. I am not relying on any promise or representation by the Company that is not expressly stated herein. This Release and Waiver may only be modified by a writing signed by both me and a duly authorized officer of the Company.

Section 424(h) of the Code provides that if the terms of an ISO are modified, then such modification shall be considered as the granting of a new option. The Option Extension would be deemed a modification and, thus, the grant of new options. As a result, the Option Extension would require a new comparison of the option price and the current fair market value of the stock and would require employment status as of such date. Therefore, to the extent that any of my Options have an exercise price less than the fair market value of the Company’s common stock as of the date of the Option Amendment or to the extent that as of the date of the Option Amendment I am not an employee of the Company, then such Option would fail to be treated as an ISO. If any of my Options continue to be treated as ISOs because they meet all of the requirements under the Code to obtain ISO status as of the date of modification, the holding period with respect to the disposition of shares acquired pursuant to the Options necessary to obtain the favorable tax treatment of ISOs (i.e., 2 years from the date of grant) would restart as of the date of the modification.

Section 422(d) of the Code provides that to the extent that the aggregate fair market value of stock with respect to which ISOs are exercisable for the 1^st time by any individual during any calendar year exceeds $100,000, such options shall be treated as options which are not ISOs. The Option Extension would be treated as the grant of a new option (as described above) and, thus, would require a reapplication of the $100,000 exercisability limitation. As a result, a portion of my Options may fail to be treated as ISOs. In addition, the Option Acceleration may cause a portion of my Options to fail to be treated as ISOs due to exceeding the $100,000 exercisability limitation for 2017.

I understand that because I am not an employee of the Company as of the Option Amendment, any Options that are currently ISOs will immediately fail to be treated as ISOs. I understand that I am under no obligation to consent to the Option Amendment. I have read this consent and have had sufficient time to review and discuss this matter. I understand that in order for the Option Amendment to be effective, I must (1) properly execute and return my consent to the Option Amendment on or before June 2, 2017 in accordance with the “important instructions” below and (2) I must execute and allow the Release to become effective within the time period set forth therein.

I further understand that this consent is intended as a brief summary of the Option Amendment and, thus, if there is any inconsistency between the information included in this consent and the terms of the Options, the terms of the Options shall govern. I acknowledge that the Option Amendment shall not override any contrary provision in the equity incentive plan or award agreements under which the Options were granted that would provide for earlier termination of any unexercised Options in connection with a corporate transaction, change in control, or other similar transaction. I acknowledge that neither the Company nor its agents have recommended or influenced my decision to consent to the Option Amendment. I further acknowledge that I have had the opportunity to seek independent advice regarding this matter from my legal counsel and tax advisor and I waive any claims against the Company regarding the Option Amendment. Lastly, I acknowledge that the Options represent the entirety of the stock options and other stock awards covering shares of Company common stock that I hold which are outstanding as of my Resignation Date (other than any stock options that vest upon the achievement of specified performance related milestones).

After due consideration of the above, I hereby agree to the Option Amendment. I acknowledge that, for any portion of the Options that are ISOs the Option Amendment will cause a loss of ISO status.

                        

                        

Paul C. Grint, M.D.

                        

May 8, 2017