Orchestra BioMed Holdings Inc美股招股说明书(2025-11-21版)

Up to 8,027,890 Shares of Common Stock This prospectus relates to the offer and sale from time to time by the selling stockholders named in this prospectus (includingtheir permitted transferees, donees, pledgees and other successors-in-interest) (collectively, the “Selling Stockholders”) of up to anaggregate of 8,027,890 shares (the “Shares”) of common stock, $0.0001 par value per share (“Common Stock”), of Orchestra BioMedHoldings, Inc., a Delaware corporation (“Orchestra” or the “Company”), which consists of up to: ·4,209,709 Shares issued to Covidien Group S.à.r.l. (an affiliate of Medtronic plc) (“Covidien”) in private placements thatclosed on August 4, 2025 and August 28, 2025 (the “Medtronic Private Placements”);·1,818,181 Shares issued to Ligand Pharmaceuticals Incorporated (“Ligand”) in a private placement that closed on August 4,2025 (the “Ligand Private Placement” and, together with the Medtronic Private Placements, the “Private Placements”); and·2,000,000 Shares issuable upon the exercise of a Common Stock purchase warrant dated August 4, 2025, with an exerciseprice of $3.67 per share of Common Stock, issued to Ligand (the “Ligand Warrant”) pursuant to a Revenue ParticipationRight Purchase and Sale Agreement, dated as of July 31, 2025 (the “Revenue Purchase and Sale Agreement”). Investing in our Common Stock involves a high degree of risk. See “Risk Factors” beginning on page 4of thisprospectus. We are an “emerging growth company” under applicable federal securities laws and therefore subject to reducedpublic companyreporting requirements. Our Common Stock is listed on The Nasdaq Global Market under the symbol “OBIO.” On November 19, 2025, the lastreported saleprice of our Common Stock on The Nasdaq Global Market was $4.66 per share. Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved ofthese securities or passed upon the adequacy or accuracy of this prospectus. Any representation to the contrary is a criminaloffense. The date of this prospectus is November 20, 2025. TABLE OF CONTENTS ABOUT THIS PROSPECTUSiPROSPECTUS SUMMARY1THE OFFERING2RISK FACTORS4CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS5USE OF PROCEEDS7SELLING STOCKHOLDERS8PLAN OF DISTRIBUTION11WHERE YOU CAN FIND MORE INFORMATION13INCORPORATION OF CERTAIN INFORMATION BY REFERENCE14LEGAL MATTERS16EXPERTS17 ABOUT THIS PROSPECTUS On October 31, 2025, we filed with the U.S. Securities and Exchange Commission (the “SEC”) a registration statement onForm S-3 (the “Registration Statement”), of which this prospectus forms a part, using the “shelf” registration process. Under this shelfregistration process, the Selling Stockholders may, from time to time, sell the securities offered by them as described in thisprospectus. Neither we nor the Selling Stockholders have authorized any dealer, agent or other person to give any information or to makeany representation other than those contained or incorporated by reference in this prospectus and, if applicable, any accompanyingprospectus supplement or any free writing prospectus. Neither we nor the Selling Stockholders take any responsibility for, and provideno assurance as to the reliability of, any other information that others may give you. This prospectus and, if applicable, anyaccompanying prospectus supplement or any free writing prospectus, do not constitute an offer to sell or the solicitation of an offer tobuy any securities other than the Shares, nor do this prospectus and, if applicable, any accompanying prospectus supplement or anyfree writing prospectus constitute an offer to sell or the solicitation of an offer to buy the Shares in any jurisdiction to any person towhom it is unlawful to make such offer or solicitation in such jurisdiction. You should not assume that the information contained inthis prospectus and, if applicable, any accompanying prospectus supplement or any free writing prospectus, is accurate on any datesubsequent to the date set forth on the front of the document or that any information we have incorporated by reference is correct onany date subsequent to the date of the document incorporated by reference, even though this prospectus and, if applicable, anyaccompanying prospectus supplement or any free writing prospectus, is delivered or securities are sold on a later date. We further note that the representations, warranties and covenants made by us in any agreement that is filed as an exhibit toany document that is incorporated by reference herein were made solely for the benefit of the parties to such agreement, including, insome cases, for the purpose of allocating risk among the parties to such agreements, and should not be deemed to be a representation,warranty or covenant to you. Moreover, such representations, warranties or covenants were accurate only as of the date when made.Accordingly, such representations, warranties and covenants should not be relied on as accurately representing