方舟生物医药美股招股说明书(2025-09-22版)

Prospectus Supplement No. 3(to prospectus dated March 11, 2025) Oruka Therapeutics, Inc. 8,719,000 Shares ofCommon StockOffered by the Selling Stockholders This prospectus supplement no. 3 is being filed to update and supplement information contained in the prospectus dated March 6, 2025(the “Prospectus”), which forms a part of our registration statement on Form S-1 (No. 333-283212), and was declared effective by theSecurities and Exchange Commission (the “SEC”) on March 11, 2025 related to the proposed resale or other disposition by the sellingstockholders identified herein (the “Selling Stockholders”) of up to (i) 5,600,000 shares of our common stock, par value $0.001 pershare (“Common Stock”), (ii) 2,439,000 shares of Common Stock issued upon the conversion of 2,439 shares of Series A preferredstock, par value $0.001 in November 2024 and (iii) 680,000 shares of Common Stock issuable upon the exercise of pre-fundedwarrants, with the information contained in our Current Report on Form 8-K, filed with the SEC on September 22, 2025. Accordingly,we have attached the Current Report to this prospectus supplement. Any document, exhibit or information contained in the CurrentReport that has been deemed furnished and not filed in accordance with SEC rules shall not be included in this prospectus supplement. This prospectus supplement updates and supplements the information in the Prospectus and is not complete without, and may not bedelivered or utilized except in combination with, the Prospectus, including any amendments or supplements thereto. This prospectussupplement should be read in conjunction with the Prospectus and if there is any inconsistency between the information therein andthis prospectus supplement, you should rely on the information in this prospectus supplement. Our Common Stock is traded on The Nasdaq Global Market under the symbol “ORKA.” On September 22, 2025, the last reported saleprice for our Common Stock was $17.09 per share. An investment in our securities involves a high degree of risk. You should carefully consider the information under the heading“Risk Factors” beginning on page 6 of the Prospectus and any applicable prospectus supplement. We are a “smaller reporting company” as defined by Rule 12b-2 of the Exchange Act and are subject to reduced publiccompany reporting requirements. Neither the SEC nor any state securities commission has approved or disapproved of these securities or determined if thisprospectus is truthful or complete. Any representation to the contrary is a criminal offense. The date of this prospectus supplement is September 22, 2025. UNITED STATESSECURITIES AND EXCHANGE COMMISSIONWASHINGTON, D.C. 20549 FORM8-K CURRENT REPORT Pursuant to Section 13 OR 15(d) of The Securities Exchange Act of 1934 Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrantunder any of the following provisions: Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) ☐ Securities registered pursuant to Section 12(b) of the Act: Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933(§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter). Emerging growth company☐ If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period forcomplying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.☐ Item 1.01 Entry into a Material Definitive Agreement. On September 17, 2025, Oruka Therapeutics, Inc., a Delaware corporation (the “Company”), entered into a Securities PurchaseAgreement (the “Purchase Agreement”) for a private placement (the “Private Placement”) with certain institutional and accreditedinvestors (each, a “Purchaser” and collectively, the “Purchasers”). The closing of the Private Placement occurred on September 19,2025. Pursuant to the Purchase Agreement, the Purchasers purchased (i) an aggregate of 10,933,405 shares (the “Common Shares”) of theCompany’s common stock, par value $0.001 per share (the “Common Stock”), at a price per share of $15.00, and (ii) pre-fundedwarrants (the “Pre-Funded Warrants”) to purchase an aggregate of 1,066,666 shares of Common Stock (the “Pre-Funded WarrantShares”) at a purchase price of $14.999 per Pre-Funded Warrant, which represents the per share purchase price of the Common Sharesless the $0.001 per share exercise price for each Pre-Funded Warrant, for an aggregate purchase price of approximately $18