SCHEDULE 13D/A 0001493215 XXXXXXXX LIVE 4 Common Stock, par value $0.0001 per share 04/29/2025 false 0001814114 68572M106 Orchestra Biomed Holdings, Inc.

150 Union Square Drive New Hope PA 18938

Roderick Wong, M.D. (646) 597-6980 RTW Investments, LP, 40 10th Avenue Floor 7 New York NY 10014 Louis Rambo (212) 416-6800 Proskauer Rose, LLP, 1001 Pennsylvania N.W., Suite 600 Washington DC 20004-2533 0001493215 N RTW Investments, LP b AF Y DE 0 8306063 0 8306063 8306063 N 21.7 PN IA 0001493219 N RTW Master Fund, Ltd. b WC Y E9 0 4394985 0 4394985 4394985 N 11.5 CO 0001776733 N RTW Innovation Master Fund, Ltd. b WC Y E9 0 3053082 0 3053082 3053082 N 8.0 CO 0001493280 N Roderick Wong, M.D. b AF Y X1 0 8306063 0 8306063 8306063 N 21.7 IN HC Common Stock, par value $0.0001 per share Orchestra Biomed Holdings, Inc. 150 Union Square Drive New Hope PA 18938 Item 2(e) of the Schedule 13D is hereby amended and restated as follows: During the last five years, none of the Reporting Persons has been a party to a civil proceeding of a judicial or administrative body of competent jurisdiction and as a result of such proceeding was or is subject to a judgment, decree of final order enjoining future violations of, or prohibiting or mandating activities subject to, federal or state securities laws or finding any violation with respect to such laws, other than the previously announced settlement order entered into by RTW Investments, L.P. with the SEC dated May 30, 2023 (File No. 3-21473) (the "Settlement"). Pursuant to the Settlement, the SEC found violations of Sections 206(2) and 206(4) of the Investment Advisors Act of 1940 and Rule 206(4)-7 thereunder, and Section 13(d) of the Exchange Act and Rules 13d-1 and 13d-2 thereunder, relating to conflicts of interest disclosure and beneficial ownership reporting, respectively. Under the terms of the settlement, RTW Investments agreed to a cease-and-desist order, a censure, and a civil penalty of $1.4 million. Item 3 of the Schedule 13D is hereby amended and supplemented as follows: The source of funds used for the Common Stock reported herein was the working capital of the Funds. Items 5(a)-(c) of the Schedule 13D are hereby amended and supplemented as follows: RTW Master Fund is the record owner of 4,394,985 shares of Common Stock. RTW Innovation is the record owner of 3,053,082 shares of Common Stock. RTW Biotech Fund is the record owner of 857,996 shares of Common Stock. As the investment manager of the funds, RTW Investments may be deemed to own beneficially the shares of Common Stock held by the funds. As the Managing Partner of RTW Investments, Dr. Wong may be deemed to own beneficially the shares of Common Stock. The percentage of outstanding shares of Common Stock of the Issuer which may be deemed to be beneficially owned by each Reporting Person is set forth on Line 13 of such Reporting Person's cover sheet. Such percentage was calculated based on 38,312,512 outstanding shares of Common Stock as of April 28, 2025, as reported in the Issuer's Definitive Proxy Statement on Schedule 14A filed on April 30, 2025. See rows (7) through (10) of the cover pages to this Schedule 13D for the number of shares of Common Stock as to which each Reporting Person has the sole or shared power to vote or direct the vote and sole or shared power to dispose or to direct the disposition On April 29, 2025, the RTW Funds acquired an aggregate of 50,000 shares of Common Stock in the open market at a per-share purchase price of $2.53. On April 30, 2025, the RTW Funds acquired an aggregate of 49,900 shares of Common Stock in the open market at a per-share purchase price of $2.99. Other than as reported herein, the Reporting Persons did not effect any transactions with respect to the Shares during the past sixty (60) days. RTW Investments, LP /s/ Roderick Wong, M.D. 05/01/2025 RTW Master Fund, Ltd. /s/ Roderick Wong, M.D. 05/01/2025 RTW Innovation Master Fund, Ltd. /s/ Roderick Wong, M.D. 05/01/2025 Roderick Wong, M.D. /s/ Roderick Wong, M.D. 05/01/2025