方舟生物医药美股招股说明书(2026-04-27版)

Filed Pursuant to Rule 424(b)(5)Registration No. 333-294852 The information in this preliminary prospectus supplement and the accompanying base prospectus is not complete and may bechanged. A registration statement relating to these securities has become effective under the Securities Act of 1933, asamended. This preliminary prospectus supplement and the accompanying base prospectus are not an offer to sell thesesecurities and are not soliciting an offer to buy these securities in any jurisdiction where the offer or sale is not permitted. SUBJECT TO COMPLETION, DATED APRIL 27, 2026 PRELIMINARY PROSPECTUS SUPPLEMENT(To Prospectus dated April 10, 2026) Common Stock We are offering $of shares of our common stock, par value $0.001 per share. Our common stock is listed on the Nasdaq Global Market under the symbol “ORKA.” On April 24, 2026, the last reported saleprice of our common stock was $69.03 per share. Investing in our securities involves a high degree of risk. See “Risk Factors” on page S-4 of this prospectus supplement andpage 2 of the accompanying prospectus and in the documents incorporated by reference. We are a “smaller reporting company” as defined by Rule 12b-2 of the Securities Exchange Act of 1934, as amended (the“Exchange Act”), and are subject to reduced public company reporting requirements. Public offering price Underwriting discounts and commissions(1)Proceeds, before expenses, to us (1)See “Underwriting” beginning on page S-12 of this prospectus supplement for a description of the compensation payable to theunderwriters. We intend to grant the underwriters an option for a period of 30 days to purchase up to an additional $[●] of shares of ourcommon stock, at the public offering price, less the underwriting discounts and commissions. Neither the Securities and Exchange Commission (the “SEC”) nor any state securities commission has approved ordisapproved of these securities or determined if this prospectus supplement is truthful or complete. Any representation to thecontrary is a criminal offense. The shares are expected to be delivered to purchasers on or about, 2026. Goldman Sachs & Co. LLC Leerink Partners Prospectus Supplement dated, 2026 TABLE OF CONTENTS PROSPECTUS SUPPLEMENT Page About This Prospectus SupplementS-iiSpecial Note Regarding Forward-Looking StatementsS-iiiProspectus Supplement SummaryS-1The OfferingS-3Risk FactorsS-4Use of ProceedsS-6DilutionS-7Dividend PolicyS-8Material U.S. Federal Income Tax Considerations to Non-U.S. HoldersS-9UnderwritingS-12Legal MattersS-18ExpertsS-18Where You Can Find More InformationS-18Incorporation of Certain Information by ReferenceS-19 PROSPECTUS Page About This ProspectusiiOruka Therapeutics, Inc.1Risk Factors2Use of Proceeds3Description of Capital Stock4Description of Depositary Shares8Description of Warrants9Plan of Distribution10Legal Matters12Experts12Where You Can Find More Information12Incorporation of Certain Information by Reference13Special Note Regarding Forward-Looking Statements14 ABOUT THIS PROSPECTUS SUPPLEMENT This document consists of two parts. The first part is this prospectus supplement, which describes the specific terms of thisoffering. The second part is the accompanying prospectus, dated April 10, 2026, and included as part of our registration statement onForm S-3 (File No. 333-294852) which is part of a registration statement that we filed with the SEC using a “shelf” registrationprocess. The accompanying prospectus provides you with a general description of the securities that may be offered by us, some ofwhich may not apply to this offering. This prospectus supplement and the information incorporated by reference in this prospectussupplement adds to, updates and, where applicable, modifies and supersedes information contained or incorporated by reference in theaccompanying prospectus. Before buying any of the securities that we are offering, you should carefully read both this prospectus supplement and theaccompanying prospectus with all of the information incorporated by reference in this prospectus supplement, as well as the additionalinformation described under the heading “Where You Can Find More Information” and “Incorporation of Certain Information byReference.” These documents contain important information that you should consider when making your investment decision. Wehave filed or incorporated by reference exhibits to the registration statement of which this prospectus supplement forms a part. Youshould read the exhibits carefully for provisions that may be important to you. To the extent there is a conflict between the information contained in this prospectus supplement, on the one hand, and theinformation contained in the accompanying prospectus or in any document incorporated by reference in this prospectus supplement, onthe other hand, you should rely on the information in this prospectus supplement, provided that if any statement in one of thesedocuments is inconsistent with