OnKure Therapeutics Inc-A美股招股说明书(2025-11-06版)

This prospectus supplement updates and amends the prospectus dated March 21, 2025 (as supplemented to date, the “Prospectus”), which forms a part of our RegistrationStatement on Form S-1 (Registration Statement No. 333-282792) for which Post-Effective Amendment No.1 was filed with the Securities and Exchange Commission (the “SEC”) onMarch 20, 2025 and declared effective by the SEC on March 21, 2025. The Prospectus and this prospectus supplement relate to the resale by certain of the selling securityholders named in the Prospectus (each a “selling securityholder” and,collectively, the “selling securityholders”) of 2,938,005 shares of Class A Common Stock, par value $0.0001 per share (the “Common Stock”) issued in the PIPE Financing (as defined inthe Prospectus). The Prospectus also covers any additional securities that may become issuable by reason of stock splits, stock dividends or other similar transactions. This prospectus supplement should be read in conjunction with the Prospectus, which is to be delivered with this prospectus supplement. This prospectus supplement updates,amends and supplements the information included or incorporated by reference in the Prospectus. If there is any inconsistency between the information in the Prospectus and thisprospectus supplement, you should rely on the information in this prospectus supplement. This prospectus supplement is not complete without, and may not be delivered or utilized except in connection with, the Prospectus, including any amendments or supplements toit. Quarterly Report on Form 10-Q and Current Report on Form 8-K We are an “emerging growth company,” as defined under the federal securities laws, and, as such, may elect to comply with certain reduced public company reportingrequirements for future filings. Investing in our securities involves a high degree of risk. Before buying any securities, you should carefully read the discussion of the risks of investing in our securities inthe section titled “Risk Factors” beginning on page9of the Prospectus. You should rely only on the information contained in the Prospectus, this prospectus supplement, or any further prospectus supplement or amendment hereto. We havenot authorized anyone to provide you with different information. Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securities or determined if this prospectus istruthful or complete. Any representation to the contrary is a criminal offense. The date of this prospectus supplement is November 6, 2025. Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrantwas required to file such reports), and (2) has been subject to such filing requirements for the past 90 days.Yes☒No☐ Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or forsuch shorter period that the registrant was required to submit such files).Yes☒No☐ 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 13(a) As of November 5, 2025, the registrant had 12,861,672 shares of Class A common stock, $0.0001 par value per share, and 686,527 shares of Class B common stock, $0.0001 par value per share, outstanding. Explanatory Note On October 4, 2024 (the “Closing Date”), the Delaware corporation formerly known as “Reneo Pharmaceuticals, Inc.” (“Reneo”) completed its previously announced mergertransaction pursuant to the terms of the Agreement and Plan of Merger, dated as of May 10, 2024 (the “Merger Agreement”), by and among Reneo, Radiate Merger Sub I, Inc., aDelaware corporation and a direct, wholly owned subsidiary of Reneo (“Merger Sub I”), Radiate Merger Sub II, LLC, a Delaware limited liability company and a direct, wholly ownedsubsidiary of Reneo (“Merger Sub II”), and OnKure, Inc., a Delaware corporation (“Legacy OnKure”). Pursuant to the Merger Agreement, on the Closing Date, (i) Reneo effected a reverse stock split of Reneo’s issued common stock at a ratio of 1:10 (the “Reverse StockSplit”), (ii) Reneo changed its name to “OnKure Therapeutics, Inc.”, (iii) Reneo reclassified all of its common stock as Class A Common Stock or Class B Common Stock, and