We are offering 18,625,000 shares of our common stock. Our common stock is traded on the Nasdaq Capital Market under the symbol “IMNM.” On December16, 2025, the last reported sale price of ourcommon stock on the Nasdaq Capital Market was $23.48 per share. We are an “emerging growth company” as that term is used in the Jumpstart Our Business Startups Act of 2012 and a “smaller reporting company” asdefined under the federal securities laws and, as such, have elected to comply with certain reduced public company disclosure and reportingrequirements. Clay Siegall, our Chief Executive Officer and Chairman of the Board, is purchasing 46,511 shares of our common stock offered by us in this offering atthe public offering price. The underwriters will receive the same underwriting discount and commissions with respect to shares of our common stock We have granted the underwriters an option to purchase up to an additional 2,793,750 shares of our common stock from us at the public offering price,less underwriting discounts and commissions, within 30 days from the date of this prospectus supplement. See “Underwriting” for more information. Investing in our common stock involves a high degree of risk. You should review carefully the risks and uncertainties describedunder the heading “Risk factors” of this prospectus supplement and in the documents incorporated by reference into thisprospectus supplement and the accompanying prospectus. Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securities ordetermined if this prospectus supplement or the accompanying prospectus is truthful or complete. Any representation to the contrary is acriminal offense. The underwriters expect to deliver the shares of our common stock to purchasers on or about December 18, 2025. LifeSciCapital Table of Contents TABLE OF CONTENTS Prospectus supplement PageS-iiS-1S-3S-5S-7S-9 About this prospectus supplementProspectus supplement summaryThe offeringRisk factors Prospectus ii16789 Table of Contents ABOUT THIS PROSPECTUS SUPPLEMENT This document is in two parts. The first part is this prospectus supplement, which describes the terms of this offering of common stock and also adds toand updates information contained in the accompanying prospectus and the documents incorporated by reference into this prospectus supplement andthe accompanying prospectus. The second part, the accompanying prospectus dated February13, 2024, including the documents incorporated byreference therein, provides more general information. Generally, when we refer to this prospectus, we are referring to both parts of this documentcombined. To the extent there is a conflict between the information contained in this prospectus supplement, on the one hand, and the informationcontained in the accompanying prospectus or in any document incorporated by reference that was filed with the Securities and Exchange Commission, We have not, and the underwriters have not, authorized anyone to provide any information other than that contained or incorporated by reference in thisprospectus supplement, the accompanying prospectus or in any free writing prospectus that we have authorized for use in connection with this offering.We and the underwriters take no responsibility for, and can provide no assurance as to the reliability of, any other information that others may give you.The information contained in this prospectus supplement, the accompanying prospectus, any free writing prospectus that we have authorized for use inconnection with this offering, including the documents incorporated by reference herein or therein, is accurate only as of the respective dates thereof,regardless of the time of delivery of this prospectus supplement and the accompanying prospectus or of any sale of our common stock. It is important for We and the underwriters are offering to sell, and seeking offers to buy, shares of our common stock only in jurisdictions in which offers and sales arepermitted. The distribution of this prospectus supplement and the accompanying prospectus and the offering of the common stock in certain jurisdictionsmay be restricted by law. Persons outside the United States who come into possession of this prospectus supplement and the accompanying prospectusmust inform themselves about, and observe any restrictions relating to, the offering of the common stock and the distribution of this prospectussupplement and the accompanying prospectus outside the United States. This prospectus supplement and the accompanying prospectus do not constitute, Except as otherwise indicated herein or as the context otherwise requires, references in this prospectus supplement, the accompanying prospectus andthe information incorporated by referenced herein or therein to “Immunome,” “the Company,” “we,” “us,” “our” and similar terms refer to Immunome, Table of Contents PROSPECTUS SUPPLEMENT SUMMARY Prospectus suppleme