Material Agreement, Private Placement, Management Change/Compensation (Form 8-K)

Item 1.01 Entry into a Material Definitive Agreement.

Securities Purchase Agreement

On March 27, 2026, OnKure Therapeutics, Inc. (the "Company") entered into a securities purchase agreement (the "Purchase Agreement") with certain institutional accredited investors (the "Investors"), pursuant to which the Company agreed to issue and sell to the Investors in a private placement (i) 26,713,636 shares (the "Shares") of the Company's Class A common stock, par value $0.0001 per share (the "Common Stock"), at a purchase price of $4.15 per Share, and (ii) pre-fundedwarrants (the "Pre-FundedWarrants" and together with the Shares, the "Securities") to purchase 9,430,959 shares of Common Stock (the "Warrant Shares"), at a purchase price of $4.1499 per underlying Warrant Share (the "Private Placement").

The Private Placement is expected to close on March 31, 2026 (the "Closing Date"), subject to the satisfaction of customary closing conditions. The aggregate gross proceeds from the Private Placement are expected to be approximately $150.0 million, before deducting placement agent fees and offering expenses. The Company intends to use the net proceeds from the Private Placement to fund the preclinical and clinical development of its next-generation PI3Kα pan-mutant-selectiveinhibitor candidates in breast cancer and vascular anomalies, as well as for working capital and general corporate purposes.

Leerink Partners LLC is acting as lead placement agent and Evercore Group L.L.C., LifeSci Capital LLC and Oppenheimer & Co. Inc. are serving as co-placementagents for the Private Placement.

The Purchase Agreement contains customary representations, warranties, covenants and agreements by the Company, indemnification obligations of the Company and the Investors, including for liabilities under the Securities Act of 1933, as amended (the "Securities Act"), and other obligations of the parties. The representations, warranties and covenants contained in the Purchase Agreement were made solely for the benefit of the parties to the Purchase Agreement and the placement agents expressly named as third-party beneficiaries therein, and may be subject to limitations agreed upon by the contracting parties.

Pursuant to the Purchase Agreement, the Company's executive officers and directors entered into letter agreements pursuant to which they agreed not to sell or transfer any Common Stock or any securities convertible into or exercisable or exchangeable for Common Stock, until the later of 180 days after the Closing Date and the effective date of the Registration Statement (as defined below), subject to certain customary exceptions. In addition, subject to certain customary exceptions, until the later of 180 days after the Closing Date and the effective date of the Registration Statement, the Company has agreed not to (without the prior written consent of AI Biotechnology LLC, the Lead Investor under the Purchase Agreement) issue any shares of Common Stock or Common Stock equivalents, effect a reverse stock split, recapitalization, share consolidation, reclassification or similar transaction affecting the outstanding Common Stock, or file with the Securities and Exchange Commission (the "SEC") a registration statement relating to any shares of Common Stock or Common Stock equivalents, except pursuant to the Registration Rights Agreement (as defined below).

The Purchase Agreement also provides AI Biotechnology LLC, the Lead Investor, with the right to designate a nominee to serve as a director on the Company's board of directors (the "Board"), subject to the Lead Investor continuing to own at least 50% of the Securities purchased by the Lead Investor at the closing of the Private Placement.

The Pre-FundedWarrants will be exercisable immediately at an exercise price of $0.0001 per Warrant Share and will not expire until exercised in full. The holders of Pre-FundedWarrants may not exercise a Pre-FundedWarrant if the holder, together with its attribution parties, would beneficially own more than a specified percentage of the number of shares of Common Stock outstanding immediately after giving effect to such exercise. The holders of Pre-FundedWarrants may increase or decrease such percentages not in excess of 19.99% by providing at least 61 days' prior notice to the Company.

The foregoing descriptions of the Purchase Agreement and the form of Pre-FundedWarrant do not purport to be complete and are qualified in their entirety by reference to the full text of the form of Purchase Agreement and the form of Pre-FundedWarrant filed as Exhibits 10.1 and 4.1, respectively, to this Current Report on Form 8-Kand are incorporated herein by reference.

Registration Rights Agreement

In connection with the Private Placement, the Company and the Investors also entered into a Registration Rights Agreement, dated March 27, 2026 (the "Registration Rights Agreement"), providing for the registration for resale of the Shares and the Warrant Shares, pursuant to a registration statement (the "Registration Statement") to be filed with the SEC within 30 days after the Closing Date. The Company has agreed to use reasonable best efforts to have the Registration Statement declared effective at the earliest possible date but no later than the earlier of (i) the 90^th calendar day after the date of the Registration Rights Agreement, (ii) the 120^th calendar day following the initial filing date of such Registration Statement if the SEC notifies the Company that it will "review" the Registration Statement and (iii) the 5^th business day after the date the Company is notified (orally or in writing, whichever is earlier) by the SEC

that such Registration Statement will not be "reviewed" or will not be subject to further review. The Company also agreed to keep the Registration Statement continuously effective until the earlier of such date (i) that all Shares and Warrant Shares covered by the Registration Statement have been sold or (ii) on which the Shares and Warrant Shares may be resold by the Investors without registration and without regard to any volume or manner-of-salelimitations by reason of Rule 144, without the requirement for the Company to be in compliance with the current public information requirement under Rule 144 under the Securities Act or any other rule of similar effect. The Registration Rights Agreement includes customary provisions regarding payment of fees and expenses, indemnification and payment of liquidated damages in certain circumstances if the Company fails to meet specified filing or effectiveness deadlines or if the Registration Statement is otherwise unavailable for resales.

The foregoing description of the Registration Rights Agreement does not purport to be complete and is qualified in its entirety by reference to the full text of the form of Registration Rights Agreement filed as Exhibit 10.2 to this Current Report on Form 8-Kand is incorporated herein by reference.

The disclosures set forth in Item 1.01 above regarding the Private Placement are incorporated in this Item 3.02.

The Securities described above have not been registered under the Securities Act in reliance on the exemption from registration afforded by Section 4(a)(2) of the Securities Act. Each of the Investors has provided representations appropriate for a private placement of securities. The sale of the Securities in the Private Placement did not involve a public offering and was made without general solicitation or general advertising.

Neither this Current Report on Form 8-Knor any exhibit attached hereto is an offer to sell or the solicitation of an offer to buy shares of Common Stock or other securities of the Company.

On March 27, 2026, in connection with the Private Placement, the Board elected Dr. Liam Ratcliffe as a Class I director of the Company, effective and contingent on the closing of the Private Placement. Dr. Ratcliffe was elected to the Board pursuant to the director designation right granted to the Lead Investor pursuant to the Purchase Agreement.

Dr. Ratcliffe has no familial relationships with any executive officer or director of the Company. Dr. Ratcliffe is affiliated with the Lead Investor.

The Company is not aware of any transaction involving Dr. Ratcliffe which would require disclosure under Item 404(a) of Regulation S-Kpromulgated under the Securities Act, other than as set forth in this Current Report on Form 8-K.

Dr. Ratcliffe will receive the standard compensation available to the Company's non-employeedirectors, as set forth in the Company's Outside Director Compensation Policy, which is attached as Exhibit 10.18 to the Company's Annual Report on Form 10-K,filed with the SEC on March 12, 2026. Dr. Ratcliffe will also enter into the Company's standard form of indemnification agreement in connection with his election to the Board, the form of which is attached as Exhibit 10.22 to the Company's Current Report on Form 8-K, originallyfiled with the SEC on October 8, 2024.