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Oruka Therapeutics, Inc. 8,719,000 Shares ofCommon StockOffered by the Selling Stockholders This prospectus supplement no. 2 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 Quarterly Report on Form 10-Q for the quarter ended June 30, 2025 (the “QuarterlyReport”). Accordingly, we have attached the Quarterly Report to this prospectus supplement. Any document, exhibit or informationcontained in the Quarterly Report that has been deemed furnished and not filed in accordance with SEC rules shall not be included inthis 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 August 11, 2025, the last reported saleprice for our Common Stock was $13.05 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 August 11, 2025. UNITED STATESSECURITIES AND EXCHANGE COMMISSIONWashington, D.C. 20549 FORM 10-Q (Mark One)☒QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2025 OR ☐TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES ACT OF 1934 For the transition period from ________ to ________ Commission file number: 000-22873 Oruka Therapeutics, Inc.(Exact name of registrant as specified in its charter) Securities registered pursuant to Section 12(b) of the Act: Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the SecuritiesExchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was 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 submittedpursuant to Rule 405 of Regulation S-T during the preceding 12 months (or for such shorter period that the registrant was required tosubmit such files). Yes☒No☐ Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smallerreporting company or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smallerreporting 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 forcomplying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.☐ Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). Yes☐No☒ As of July 31, 2025, there were 37,450,745 shares of the registrant’s common stock outstanding. Table of Contents PagePART I. Financial InformationItem 1.Financial Statements (Unaudited)1Condensed Consolidated Balance Sheets1Condensed Consolidated Statements of Operations and Comprehensive Loss2Condensed Consolidated Statements of Convertible Preferred Stock and Stockholders’ Equity (Deficit)3Condensed Consolidated Statements of Cash Flows4Notes to Unaudited Condensed Consolidated Financial Statement