UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d) of the

Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): October 10, 2012

Regulus Therapeutics Inc.

(Exact name of registrant as specified in its charter)

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

N/A

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

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

On October 10, 2012, Regulus Therapeutics Inc. (the “Company”) entered into an Investor Rights Agreement with AstraZeneca AB (“AstraZeneca”) in connection with the closing of a private placement in which the Company issued and sold 6,250,000 shares of its common stock (the “Shares”) to AstraZeneca on October 10, 2012, concurrently with the closing of the Company’s initial public offering of its common stock. The sale and issuance of the Shares was effected pursuant to the terms of that certain Common Stock Purchase Agreement between the Company and AstraZeneca dated August 14, 2012.

Pursuant to the Investor Rights Agreement, AstraZeneca will have the right to require the Company to register the Shares on a Form S-3 registration statement with the Securities and Exchange Commission or to include the Shares in a registration statement filed by the Company. AstraZeneca’s right to request a registration of the Shares will terminate upon the earlier of October 10, 2015 or at such time that all of the Shares may be sold by AstraZeneca pursuant to Rule 144 of the Securities Act of 1933, as amended (the “Securities Act”) during any 90-day period. A copy of the Investor Rights Agreement is attached as Exhibit 10.1 hereto and is incorporated herein by reference.

Pursuant to the terms of that certain Amended and Restated Convertible Promissory Note originally issued by the Company to Glaxo Group Limited (“Glaxo”) on February 24, 2010, as amended and restated on July 27, 2012, the Company agreed to issue Glaxo a Convertible Promissory Note upon the closing of a qualifying initial public offering of the Company’s common stock. Accordingly, on October 10, 2012, upon the closing of the Company’s initial public offering of shares of its common stock, the Company issued Glaxo a Convertible Promissory Note in the principal amount of $5,426,952.05 (the “New Glaxo Note”). The New Glaxo Note bears interest at a rate of 3.297% per annum on the basis of a 360 day year, compounded daily for the actual number of days elapsed. The maturity date of the New Glaxo Note is October 9, 2015, at which time all outstanding principal and accrued interest shall become due and payable by the Company. Glaxo may convert all or any portion of the outstanding principal and accrued and unpaid interest under the New Glaxo Note into shares of the Company’s common stock at any time on or prior to the maturity date at a conversion price of $4.00 per share, subject to complying with certain threshold ownership percentage limitations set forth in the New Glaxo Note. A copy of the New Glaxo Note is attached as Exhibit 10.2 hereto and is incorporated herein by reference.

The information relating to the issuance and sale of the Shares to AstraZeneca in Item 1.01 of this Current Report is incorporated herein by reference. The aggregate purchase price of the Shares was $25,000,000, representing a per Share price of $4.00, the price at which shares of the Company’s common stock were sold to the public in the Company’s initial public offering. The purchase price of the Shares was paid for by AstraZeenca in immediately available funds.

Pursuant to the terms of that certain Convertible Promissory Note issued by the Company to Biogen Idec MA Inc. (“Biogen Idec”) on August 15, 2012 in the principal amount of $5,000,000, the outstanding principal amount and accrued and unpaid interest under such Convertible Promissory Note automatically converted into 1,256,232 shares of the Company’s common stock concurrently with the closing of the Company’s initial public offering on October 10, 2012 at a conversion price of $4.00 per share.

Pursuant to the terms of that certain Amended and Restated Convertible Promissory Note originally issued by the Company to Glaxo on April 24, 2008 in the principal amount of $5,000,000, as amended and restated on July 27, 2012, the outstanding principal amount and accrued and unpaid interest under such Amended and Restated Convertible Promissory automatically converted into 1,447,037 shares of the Company’s common stock concurrently with the closing of the Company’s initial public offering on October 10, 2012 at a conversion price of $4.00 per share.

The sales and issuances by the Company of the shares of common stock described above under this Item 3.02 of this Current Report were not registered under the Securities Act or any state securities laws. The Company has relied on the exemption from the registration requirements of the Securities Act by virtue of Section 4(2) thereof and the rules and regulations promulgated thereunder.

Amendment and Restatement of Certificate of Incorporation

On October 10, 2012, the Company filed an amended and restated certificate of incorporation (the “Restated Certificate”) with the Secretary of State of the State of Delaware in connection with the closing of the Company’s initial public offering of shares of its common stock. The Company’s board of directors and stockholders previously approved the Restated Certificate to be filed in connection with, and to be effective upon, the closing of the Company’s initial public offering.

The Restated Certificate amends and restates in its entirety the Company’s amended and restated certificate of incorporation, as amended, to, among other things:

The foregoing description is qualified in its entirety by reference to the Restated Certificate, a copy of which is attached hereto as Exhibit 3.1 and is incorporated herein by reference.

Amendment and Restatement of Bylaws

On October 10, 2012, the Company adopted amended and restated bylaws in connection with the closing of the Company’s initial public offering of shares of its common stock. The Company’s board of directors and stockholders previously approved the amended and restated bylaws to be adopted in connection with, and to be effective upon, the closing of the Company’s initial public offering.

The amended and restated bylaws, among other things:

The foregoing description is qualified in its entirety by reference to the Company’s amended and restated bylaws, a copy of which is attached hereto as Exhibit 3.2 and is incorporated herein by reference.

(d) Exhibits.

SIGNATURES

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

EXHIBIT INDEX