As filed with the Securities and Exchange Commission on March 10, 2025

Registration No. 333-

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM S-8

REGISTRATION STATEMENT

UNDER

THE SECURITIES ACT OF 1933

ONKURE THERAPEUTICS, INC.

(Exact name of registrant as specified in its charter)

OnKure Therapeutics, Inc. 2024 Equity Incentive Plan
OnKure Therapeutics, Inc. 2024 Employee Stock Purchase Plan

(Full title of the plan)

Nicholas A. Saccomano
President and Chief Executive Officer
6707 Winchester Circle, Suite 400

Boulder, CO 80301

(720) 307-2892

(Name, address and telephone number, including area code, of agent for service)

Copies to:

Tony Jeffries

Jennifer Knapp

Phillip McGill

Wilson Sonsini Goodrich & Rosati, P.C.

1155 Canyon Blvd., Suite 400

Boulder, CO 80302

(303) 256-5900

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 7(a)(2)(B) of the Securities Act. ☐

EXPLANATORY NOTE

This Registration Statement on Form S-8 (the “Registration Statement”) is filed by OnKure Therapeutics, Inc. (the “Registrant”) for the purpose of registering (i) 667,355 additional shares of Class A common stock, par value $0.0001 per share (the “Class A Common Stock”) of the Registrant reserved for issuance under the 2024 Equity Incentive Plan (the “2024 Plan”), pursuant to the provision of the 2024 Plan providing for an automatic increase in the number of shares reserved for issuance under the 2024 Plan, and (ii) 133,471 additional shares of Class A Common Stock of the Registrant reserved for issuance under the 2024 Employee Stock Purchase Plan (the “2024 ESPP”), pursuant to the provision of the 2024 ESPP providing for an automatic increase in the number of shares reserved for issuance under the 2024 ESPP.

PART II

INFORMATION REQUIRED IN REGISTRATION STATEMENT

Item 3. Incorporation of Documents by Reference.

The Registrant previously registered shares of its Class A Common Stock for issuance under the 2024 Plan and the 2024 ESPP on a Registration Statement on Form S-8 filed by the Registrant with the Securities and Exchange Commission on December 9, 2024 (File No. 333-283693) (the “Previous Form S-8”). Accordingly, pursuant to General Instruction E of Form S-8, this Registration Statement hereby incorporates by reference the contents of the Previous Form S-8, including the information incorporated by reference therein and the periodic reports filed after the Previous Form S-8 to maintain current information about the Registrant, except as set forth below.

The following documents filed by the Registrant with the Securities and Exchange Commission (the “SEC”) are incorporated by reference into this Registration Statement:

All other reports or documents filed by the Registrant pursuant to Sections 13(a), 13(c), 14 and 15(d) of the Exchange Act on or after the date of this Registration Statement and prior to the filing of a post-effective amendment to this Registration Statement that indicates that all securities offered have been sold or that deregisters all securities then remaining unsold shall be deemed to be incorporated by reference in this Registration Statement and to be part hereof from the date of filing of such documents, shall be deemed to be incorporated by reference herein and to be a part of this registration statement from the date of filing such reports and documents; provided, however, that reports, documents and information, or portions thereof, deemed to have been furnished and not filed in accordance with the rules of the SEC shall not be deemed incorporated by reference into this Registration Statement. Any statement contained in a document incorporated or deemed to be incorporated by reference herein shall be deemed to be modified or superseded for purposes of this Registration Statement to the extent that a statement

contained herein or in any subsequently filed document which also is deemed to be incorporated by reference herein modifies or supersedes such statement. Any such statement so modified or superseded shall not be deemed, except as so modified or superseded, to constitute a part of this Registration Statement.

Item 8. Exhibits.

The Registrant has filed the exhibits listed on the accompanying Exhibit Index of this Registration Statement.

EXHIBIT INDEX

SIGNATURES

Pursuant to the requirements of the Securities Act of 1933, as amended, the Registrant certifies that it has reasonable grounds to believe that it meets all of the requirements for filing on Form S-8 and has duly caused this Registration Statement to be signed on its behalf by the undersigned, thereunto duly authorized, in the City of Boulder, State of Colorado, on March 10, 2025.

POWER OF ATTORNEY

KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below hereby constitutes and appoints Nicholas A. Saccomano and Jason Leverone, and each of them, as his or her true and lawful attorney-in-fact and agent with full power of substitution and resubstitution, for such person in any and all capacities, to sign any and all amendments to this Registration Statement (including post-effective amendments) on Form S-8, and to file the same, with all exhibits thereto and other documents in connection therewith, with the Securities and Exchange Commission, granting unto said attorney-in-fact, proxy, and agent full power and authority to do and perform each and every act and thing requisite and necessary to be done in connection therewith, as fully for all intents and purposes as such person might or could do in person, hereby ratifying and confirming all that any said attorney-in-fact, proxy and agent, or any substitute of any of them, may lawfully do or cause to be done by virtue hereof.

Pursuant to the requirements of the Securities Act of 1933, this Registration Statement has been signed by the following persons in the capacities and on the dates indicated: