Stockholder Meeting Notice Regulus Therapeutics Inc.’s Annual Meeting of Stockholders will be held on June 9, 2022 at the company’s offices located at 4224 Campus Point Court, Suite 210, San Diego, CA 92121 at 9:00 a.m. Pacific Time. Proposals to be voted on at the meeting are listed below along with the Board of Directors’ recommendations. The Board of Directors recommend a vote FOR all the nominees listed and FOR Proposals 2, 3, 4, 5, 6 and 7: 1. To elect the ten nominees for director named in the proxy statement to serve until the next annual meeting of stockholders and their successors are duly elected and qualified; 2. To approve an amendment to our Amended and Restated Certificate of Incorporation to effect a reverse stock split of our common stock at a ratio in the range of 1- for-5 to 1-for-20, with such ratio to be determined in the discretion of our board of directors and with such reverse stock split to be effected at such time and date, if at all, as determined by our board of directors in its sole discretion; 3. To approve an amendment to our Amended and Restated Certificate of Incorporation to reduce, if and only if Proposal 2 is both approved and implemented, the number of authorized shares of our common stock to 300,000,000 shares; 4. To approve, on an advisory basis, the compensation of the Company’s named executive officers; 5. To ratify the selection by the Audit Committee of the Board of Directors of Ernst & Young LLP as the independent registered public accounting firm of the Company for its fiscal year ending December 31, 2022; 6. To approve the Regulus Therapeutics Inc. 2022 Employee Stock Purchase Plan, pursuant to which 1,291,072 shares of our common stock will be available for sale and issuance to our employees; and 7. To approve the authorization to adjournment of the Annual Meeting, if necessary, to solicit additional proxies if there are not sufficient votes in favor of Proposal 2 or Proposal 6. PLEASE NOTE – YOU CANNOT VOTE BY RETURNING THIS NOTICE. To vote your shares you must go online or request a paper copy of the proxy materials to receive a proxy card. If you wish to attend and vote at the meeting, please bring this notice with you. Here’s how to order a copy of the proxy materials and select delivery preferences: Current and future delivery requests can be submitted using the options below. If you request an email copy, you will receive an email with a link to the current meeting materials. PLEASE NOTE: You must use the number in the shaded bar on the reverse side when requesting a copy of the proxy materials. — Internet – Go to www.investorvote.com/RGLS. — Phone – Call us free of charge at 1-866-641-4276. — Email – Send an email to investorvote@computershare.com with “Proxy Materials Regulus Therapeutics Inc.” in the subject line. Include your full name and address, plus the number located in the shaded bar on the reverse side, and state that you want a paper copy of the meeting materials. To facilitate timely delivery, requests for a paper copy of proxy materials must be received by May 27, 2022.