SCHEDULE 13G/A 0001224962 XXXXXXXX LIVE 3 Common Stock, par value $0.0001 per share 09/30/2025 0001814114 Orchestra BioMed Holdings, Inc. 68572M106 150 Union Square Drive New Hope PA 18938 Rule 13d-1(c) Perceptive Advisors LLC b DE 0 5679480 0 5679480 5679480 N 9.99 IA Joseph Edelman b X1 0 5679480 0 5679480 5679480 N 9.99 IN Perceptive Life Sciences Master Fund, Ltd. b E9 0 5679480 0 5679480 5679480 N 9.99 CO Orchestra BioMed Holdings, Inc. 150 Union Square Drive New Hope, Pennsylvania 18938 The names of the persons filing this report (collectively, the "Reporting Persons") with respect to shares of Common Stock, par value $0.0001 per share (the "Common Stock") of Orchestra BioMed Holdings, Inc. (the "Issuer") are: (i) Perceptive Advisors LLC ("Perceptive Advisors") (ii) Joseph Edelman ("Mr. Edelman") (iii) Perceptive Life Sciences Master Fund, Ltd. (the "Master Fund") The address of the principal business office of each of the Reporting Persons is: 51 Astor Place, 10th Floor New York, NY 10003 Perceptive Advisors is a Delaware limited liability company Mr. Edelman is a United States citizen The Master Fund is a Cayman Islands corporation Y The information required by this item with respect to each Reporting Person is set forth in Rows 5 through 9 and 11 of the cover page to this Schedule 13G. The ownership percentages are based on 56,464,731 outstanding shares of Common Stock as of November 6, 2025, as reported in the Issuer's Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on November 10, 2025, and assume the exercise of Pre-Funded Warrants held by the Reporting Persons for 386,924 shares of Common Stock (the "Pre-Funded Warrants"). Neither Perceptive Advisors nor Mr. Edelman directly hold any shares of Common Stock or any Pre-Funded Warrants. The Master Fund directly holds 5,292,556 shares of Common Stock and 1,500,000 Pre-Funded Warrants immediately exercisable for shares of Common Stock at an exercise price of $0.0001 per share, subject to the Beneficial Ownership Limitation (as defined below). The terms of the Pre-Funded Warrants provide that the Pre-Funded Warrants may not be exercised if, after such exercise, the Reporting Persons would beneficially own, as determined in accordance with Section 13(d) if the Securities Exchange Act of 1934, as amended, more than 9.99% of the shares of Common Stock then issued and outstanding (the "Beneficial Ownership Limitation"). As of the date hereof, the Beneficial Ownership Limitation permits the Reporting Persons to exercise Pre-Funded Warrants for an aggregate of not more than 386,924 shares of Common Stock. In providing the beneficial ownership information set forth herein, the Reporting Persons have assumed that the aggregate remaining Pre-Funded Warrants held by the Reporting Persons are not exercisable due to the Beneficial Ownership Limitation. Perceptive Advisors serves as the investment manager to the Master Fund. Mr. Edelman is the managing member of Perceptive Advisors. Perceptive Advisors: 9.99% Mr. Edelman: 9.99% Master Fund: 9.99% Perceptive Advisors: 0 Mr. Edelman: 0 Master Fund: 0 Perceptive Advisors: 5,679,480 Mr. Edelman: 5,679,480 Master Fund: 5,679,480 Perceptive Advisors: 0 Mr. Edelman: 0 Master Fund: 0 Perceptive Advisors: 5,679,480 Mr. Edelman: 5,679,480 Master Fund: 5,679,480 Y Y Y Y Y N By signing below I certify that, to the best of my knowledge and belief, the securities referred to above were not acquired and are not held for the purpose of or with the effect of changing or influencing the control of the issuer of the securities and were not acquired and are not held in connection with or as a participant in any transaction having that purpose or effect, other than activities solely in connection with a nomination under ?? 240.14a-11. Perceptive Advisors LLC /s/ Joseph Edelman 11/14/2025 Joseph Edelman /s/ Joseph Edelman 11/14/2025 Perceptive Life Sciences Master Fund, Ltd. /s/ Joseph Edelman 11/14/2025