March 10, 2025

OnKure Therapeutics, Inc.

6707 Winchester Circle, Suite 400

Boulder, CO 80301

Re: Registration Statement on Form S-8

Ladies and Gentlemen:

At your request, we have examined the Registration Statement on Form S-8 (the “Registration Statement”) to be filed by OnKure Therapeutics, Inc., a Delaware corporation (the “Company”), with the Securities and Exchange Commission (the “Commission”) on or about the date hereof, relating to the registration under the Securities Act of 1933, as amended (the “Act”), of shares of your Class A common stock, par value $0.0001 per share (the “Shares”), consisting of: (i) 667,355 shares of Class A common stock to be issued under the Company’s 2024 Equity Incentive Plan (the “2024 Plan”) and (ii) 133,471 shares of Class A common stock to be issued under the Company’s 2024 Employee Stock Purchase Plan (the “2024 ESPP” and, together with the 2024 Plan, the “Plans”). As your legal counsel, we have reviewed the actions proposed to be taken by you in connection with the issuance and sale of the Shares to be issued under the Plans.

On the basis of the foregoing, and in reliance thereon, we are of the opinion that the Shares, when issued and sold in the manner described in the Plans and pursuant to the agreements that accompany the Plans, will be legally and validly issued, fully paid and nonassessable.

We hereby consent to the filing of this opinion as an exhibit to the above-referenced Registration Statement and to the use of our name wherever it appears in the Registration Statement and in any amendments thereto. In giving such consent, we do not thereby admit that we are in the category of persons whose consent is required under Section 7 of the Act or the rules and regulations of the Commission thereunder.