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Up to 250,000,000 Shares of Common Stock Offered by the Selling Stockholders This prospectus supplement supplements the prospectus dated September 30, 2025, relating to the offer and resale by theselling stockholders identified in this prospectus supplement of up to an aggregate of 250,000,000 shares of SAB Biotherapeutics,Inc. (the “Company”) common stock, par value $0.0001 per share (the “Common Stock”) which consists of (i) 100,000,000 shares ofCommon Stock issuable upon conversion of 1,000,000 shares (the “Shares”) of the Company’s Series B Convertible Preferred Stock,par value $0.0001 per share (the “Series B Preferred Stock”), (ii) 100,000,000 shares of Common Stock, issuable upon conversion of1,000,000 shares of Series B Preferred Stock (the “Enrollment Date Warrant Shares”) which are issuable upon exercise ofEnrollment Date Series B Preferred Stock Purchase Warrants (the “Enrollment Date Warrants”), and (iii) 50,000,000 shares ofCommon Stock issuable upon conversion of 500,000 shares of Series B Preferred Stock (the “Release Date Warrant Shares”, andtogether with the Enrollment Date Warrant Shares, the “Warrant Shares”) which are issuable upon exercise of Release Date Series BPreferred Stock Purchase Warrants (the “Release Date Warrants”, and together with the Enrollment Date Warrants, the “Warrants”).The Shares, Enrollment Date Warrant Shares, and Release Date Warrant Shares are collectively referred to herein as the “Series BShares.” The shares of Common Stock being registered under this prospectus, which consist of the shares of Common Stock issuableupon conversion of the Series B Shares, are collectively referred to as the “Resale Shares.”This prospectus supplement is solely being filed to update a footnote to the Selling Stockholders table. You should read this prospectus supplement, together with the related prospectus and the additional information describedunder the headings “Incorporation of Certain Information by Reference” and “Where You Can Find More Information” carefullybefore you invest in any of our securities. Our Common Stock is traded on The Nasdaq Capital Market under the symbol “SABS”. On November 5, 2025, the closingprice for our Common Stock, as reported on The Nasdaq Capital Market, was $3.18 per share. The Series B Preferred Stock is notlisted on a national securities and exchange and we do not intend to list the Series B Preferred Stock for trading on a nationalsecurities exchange. Investing in these securities involves certain risks. See “Risk Factors” on page 5 of the prospectus. See also “RiskFactors” in the documents incorporated by reference in the prospectus for a discussion of the factors you should carefullyconsider before deciding to purchase these securities. Neither the SEC nor any state securities commission has approved or disapproved of these securities or determined if thisprospectus supplement is truthful or complete. Any representation to the contrary is a criminal offense. The date of this prospectus supplement is November 12, 2025 SELLING STOCKHOLDERS The 250,000,000 Resale Shares being offered by the Selling Stockholders include (i) 100,000,000 shares of Common Stockissuable upon conversion of the Shares, (ii) up to 100,000,000 shares of Common Stock, issuable upon conversion of EnrollmentDate Warrant Shares, and (iii) up to 50,000,000 shares of Common Stock issuable upon conversion of Release Date Warrant Shares. We are registering the Resale Shares in order to permit the Selling Stockholders to offer the Resale Shares for resale from timeto time. For additional information regarding the Resale Shares being offered by the Selling Stockholders pursuant to this prospectussupplement and the prospectus, see “Recent Milestones–July 2025 Private Placement” in the prospectus. The following table setsforth, as of the date of this prospectus supplement, the names of the Selling Stockholders and the aggregate number of shares ofCommon Stock that the Selling Stockholders may offer pursuant to this prospectus supplement and the prospectus. In accordance with the terms of the Registration Rights Agreement, as applicable, this prospectus supplement and prospectuscover the resale of all Resale Shares. The fourth column of the table below assumes the sale of all of the Resale Shares offered by theSelling Stockholders pursuant to this prospectus supplement and prospectus. Pursuant to the Certificate of Designations, a Selling Stockholder shall not have the right to convert any portion of the Series BPreferred Stock, and such Series B Preferred Stock shall not be automatically converted, to the extent that after giving effect to suchconversion, such Selling Stockholder, together with its affiliates, any other persons acting as a group together, and any other personswhose beneficial ownership of Common Stock would be aggregated with the Selling Stockholder’s and the other attribution partiesfor purposes of Section 13(d) of the Exchange Act would beneficially ow