Pre-Funded Warrants to Purchase 74,780,300 Shares of Common Stock We are offering pre-funded warrants to purchase up to 74,780,300 shares of our common stock pursuant to this prospectus supplement. Thepre-funded warrants have an exercise price of $0.0001 per share and will be immediately exercisable for one share of common stock, subject to thebeneficial ownership limitations described in the section “Description of Pre-Funded Warrants.” This prospectus supplement also relates to the offering Our common stock is listed on the Nasdaq Capital Market under the symbol “XLO.” On February11, 2026, the last reported sale price of ourcommon stock on the Nasdaq Capital Market was $0.535 per share. There is no established public trading market for the pre-funded warrants, and we donot expect a market to develop. We do not intend to list the pre-funded warrants on the Nasdaq Capital Market, any other national securities exchange or Offering price (1)See the section titled “Underwriting” beginning on page S-24 for a description of all compensation payable to the underwriter. Investing in our securities involves a high degree of risk. Before making an investment decision, please read theinformation under the heading “Risk Factors” beginning on pageS-11 of this prospectus supplement and in the Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securities orpassed upon the accuracy or adequacy of this prospectus supplement. Any representation to the contrary is a criminal offense. The underwriter expects to deliver the pre-funded warrants against payment on or about February13, 2026. See “Underwriting” for details. The pre-funded warrants will be delivered to purchasers in certificated form. Sole Bookrunner Leerink Partners The date of this prospectus supplement is February11, 2026. Table of Contents PROSPECTUS SUPPLEMENT S-2S-4S-5S-7S-9S-11S-14 PROSPECTUS ABOUT THIS PROSPECTUSWHERE YOU CAN FIND MORE INFORMATIONINCORPORATION BY REFERENCE Table of Contents ABOUT THIS PROSPECTUS SUPPLEMENT This document is in two parts. The first part is this prospectus supplement, which describes the specific terms of this offering and alsosupplements and updates information contained in the accompanying prospectus and the documents incorporated by reference herein. The second part,the accompanying prospectus, provides more general information. Generally, when we refer to this prospectus, we are referring to both parts of thisdocument combined. To the extent there is a conflict between the information contained in this prospectus supplement and the information contained inthe accompanying prospectus or any document incorporated by reference therein filed prior to the date of this prospectus supplement, you should rely on We further note that the representations, warranties and covenants made by us in any agreement that is filed as an exhibit to any document that isincorporated by reference herein were made solely for the benefit of the parties to such agreement, including, in some cases, for the purpose ofallocating risk among the parties to such agreements, and should not be deemed to be a representation, warranty or covenant to you. Moreover, such We have not, and Leerink Partners has not, authorized anyone to provide any information other than that contained or incorporated by reference inthis prospectus supplement, in the accompanying prospectus or in any free writing prospectus prepared by or on behalf of us or to which we have This prospectus supplement, the accompanying prospectus and any such free writing prospectus do not constitute an offer to sell, or a solicitationof an offer to purchase, the securities offered by this prospectus supplement, the accompanying prospectus and any such free writing prospectus in anyjurisdiction to or from any person to whom or from whom it is unlawful to make such offer or solicitation of an offer in such jurisdiction. You shouldassume that the information appearing in this prospectus supplement, the accompanying prospectus and the documents incorporated by reference hereinand in any free writing prospectus that we have authorized for use in connection with this offering is accurate only as of the date of those respective Other than in the United States, no action has been taken that would permit a public offering of the securities offered by this prospectussupplement in any jurisdiction where action for that purpose is required. The securities offered by this prospectus supplement may not be offered or sold,directly or indirectly, nor may this prospectus or any other offering material or advertisements in connection with the offer and sale of any suchsecurities be distributed or published in any jurisdiction, except under circumstances that will result in compliance with the applicable rules and Table of Contents When we refer to “Xilio Therapeutics,” “Xilio,” “we,” “our,” “us” and the “Company” in this p




