Secured over $111 million in proceeds and committed capital following completion of strategic transactions and concurrent public and private equity offerings, led by over $71 million in committed capital from Medtronic and LigandAchieved multiple FDA regulatory milestones: Breakthrough Device Designation for AVIM therapy; approval for expanded BACKBEAT study enrollment criteria, and IDE approval for a U.S. pivotal Virtue SAB trial versus commercially available paclitaxel-coated balloon NEW HOPE, Pa., Aug. 12, 2025 (GLOBE NEWSWIRE) — Orchestra BioMed Holdings, Inc. (Nasdaq: OBIO, “Orchestra BioMed” or the “Company”), a biomedical company accelerating high-impact technologies to patients through risk-reward sharing partnerships, today announced financial results for the second quarter ended June 30, 2025, and provided a business update highlighting recent financial and regulatory milestones. Q2 2025 and Recent Business Highlights: Completed multiple strategic transactions and concurrent public and private equity offerings totaling an expected $111.2 million in gross proceeds to support continued advancement of the Company’s late-stage atrioventricular interval modulation (“AVIM”) therapy and Virtue Sirolimus AngioInfusion Balloon (“SAB”) clinical programs. Gross proceeds are comprised of: $55 million received or to be received by May 1, 2026, subject to certain conditions, from royalty-based, non-dilutive investments from Ligand Pharmaceuticals Incorporated (Nasdaq: LGND, “Ligand”) and Medtronic, plc (NYSE: MDT, “Medtronic”) Ligand committed $35 million in exchange for a tiered revenue interest in Orchestra BioMed’s future royalties from AVIM therapy and Virtue SABMedtronic committed $20 million in exchange for a secured subordinated promissory note convertible to capped prepaid revenue share $56.2 million received from a $40 million underwritten public offering of common stock and prefunded warrants and $11.2 million and $5 million received from private placements of common stock to Medtronic and Ligand, respectivelyProceeds expected to extend cash runway into the second half of 2027, supporting potentially significant value-creating catalysts, including: BACKBEAT study enrollment completion in mid-2026BACKBEAT study primary endpoint dataSubstantial enrollment of the Virtue Trial Medtronic and Orchestra BioMed expanded strategic collaboration to provide pathway for future development of AVIM therapy-enabled leadless pacemakers.U.S. Food and Drug Administration (“FDA”) Breakthrough Device Designation (“BDD”) granted for atrioventricular interval modulation (“AVIM”) therapy in patients with uncontrolled hypertension and increased cardiovascular risk, marking a major regulatory validation of the therapy’s potential to improve hypertensive heart disease outcomes.FDA-approved updated BACKBEAT study protocol now being implemented, broadening patient enrollment criteria for a more than 24-fold increase in the potentially eligible patient pool; full implementation to be completed in Q4 2025.FDA Investigational Device Exemption (“IDE”) Approval received for the Virtue SAB U.S. pivotal trial, a randomized head-to-head study comparing Virtue SAB with the commercially available AGENT™ DCB paclitaxel-coated balloon (the “Virtue Trial”). Trial initiation is currently targeted for the second half of 2025. Orchestra BioMed is sponsoring and in full operational control of the Virtue Trial; mediation with Terumo of certain other contractual terms is progressing, with conclusion of formal mediation process expected in Q3 2025. Intellectual Property Expansion continued with AVIM therapy patent estate reaching 137 issued patents worldwide, with recent additions bolstering coverage for both hypertension and heart failure indications. Chairman and Chief Executive Officer (“CEO”) Commentary from David Hochman: Mr. Hochman stated: “The successful completion of strategic financing transactions with Medtronic and Ligand, along with closing our first underwritten public offering are expected to give us up to $111 million in new capital to support execution of both AVIM therapy and Virtue SAB pivotal clinical studies. Our entire organization is focused on our mission to bring these high-impact, innovative, device-based therapies to market.” Mr. Hochman continued: “We were also proud to have achieved multiple key regulatory milestones for both AVIM therapy and Virtue SAB in the second quarter. The FDA Breakthrough Device Designation awarded to AVIM therapy for the treatment of uncontrolled hypertension in patients with increased cardiovascular risk has potentially significant implications to future regulatory submissions and opens up potential pathways for enhanced reimbursement for AVIM therapy-enabled devices. The FDA also approved an important update to the BACKBEAT study protocol that we are now rolling out to study centers that significantly expands eligibility criteria for enrollment and supports our enrollment completion objectives for next year. Finally, FDA approval of the updated IDE for our head-to-head pivotal trial comparing Virtue SAB to commercially available AGENT paclitaxel-coated balloon marks another significant regulatory milestone. These achievements will help us in our continued efforts to reshape clinical standards of care in both hypertensive heart disease and atherosclerotic artery disease.” Financial Results for the Second Quarter Ended June 30, 2025 Cash and cash equivalents and Marketable securities totaled $33.9 million as of June 30, 2025. Combined with net proceeds received from recent financing transactions, estimated Cash and cash equivalents and Marketable securities position was $101 million as of August 12, 2025. The Company has commitments from Ligand and Medtronic to receive a combined $35 million in additional proceeds on or before May 1, 2026, based on the terms of agreements with those parties.Net cash used in operating activities and for the purchase of fixed assets was $15.6 million during the second quarter of 2025, compared with $10.3 million for the second quarter in 2024, with the primary driver being increased research and development costs during the second quarter of 2025.Revenue for the second quarter of 2025 was $0.8 million, compared with $0.8 million for the second quarter in 2024.Research and development expenses for the second quarter of 2025 were $13.9 million, compared with $11.1 million for the second quarter in 2024. The increase was primarily due to additional costs associated with the ongoing BACKBEAT global pivotal study.Selling, general and administrative expenses for the second quarter of 2025 were $6.3 million, compared with $6.5 million for the second quarter of 2024. The decrease was primarily due to a decrease in professional fees.Net loss for the second quarter of 2025 was $19.4 million, or $0.50 per share, compared with a net loss of $16.0 million, or $0.45 per share, for the second quarter of 2024. Net loss for the second quarter of 2025 included $3.2 million in non-cash stock-based compensation expense as compared to $2.8 million for the same period in 2024. About Orchestra BioMed Orchestra BioMed (Nasdaq: OBIO) is a biomedical innovation company accelerating high-impact technologies to patients through risk-reward sharing partnerships with leading medical device companies. Orchestra BioMed’s partnership-enabled business model focuses on forging strategic collaborations with leading medical device companies to drive successful global commercialization of products it develops. Orchestra BioMed’s lead product candidate is AVIM therapy for the treatment of hypertension, the leading risk factor for death worldwide. Orchestra BioMed is also developing Virtue SAB for the treatment of atherosclerotic artery disease, the leading cause of mortality worldwide. Orchestra BioMed has a strategic collaboration with Medtronic, one of the largest medical device companies in the world, for development and commercialization of AVIM therapy for the treatment of hypertension in pacemaker-indicated patients, and a strategic partnership with Terumo, a global leader in medical technology, for development and commercialization of Virtue SAB for the treatment of artery disease. The Company has received four Breakthrough Device Designations from the U.S. FDA across these two core programs, reflecting the significant potential of its technologies to address high unmet needs in cardiovascular care. For further information about Orchestra BioMed, please visit www.orchestrabiomed.com, and follow us on LinkedIn. References to Websites and Social Media Platforms References to information included on, or accessible through, websites and social media platforms do not constitute incorporation by reference of the information contained at or available through such websites or social media platforms, and you should not consider such information to be part of this press release. About AVIM Therapy AVIM therapy is an investigational therapy compatible with standard dual-chamber pacemakers designed to substantially and persistently lower blood pressure. It has been evaluated in pilot studies in patients with hypertension who are also indicated for a pacemaker. MODERATO II, a double-blind, randomized pilot study, showed that patients treated with AVIM therapy experienced net reductions of 8.1 mmHg in 24-hour ambulatory systolic blood pressure (aSBP) and 12.3 mmHg in office systolic blood pressure (oSBP) at six months when compared to control patients. In addition to reducing blood pressure, clinical results using AVIM therapy demonstrate improvements in cardiac function and hemodynamics. The BACKBEAT (BradycArdia paCemaKer with atrioventricular interval modulation for Blood prEssure treAtmenT) global pivotal study will evaluate the safety and efficacy of AVIM therapy in lowering blood pressure in patients who have systolic blood pressure above target despite anti-hypertensive medication and who are indicated for or have recently received a dual-chamber cardiac pacemaker. AVIM therapy has been granted Breakthrough Device Designation by the FDA for the treatment of uncontrolled hypertension in patients who have increased cardiovascular risk. About Virtue SAB Virtue SAB is an investigational therapeutic combination drug-device designed to deliver a proprietary extended-release formulation of sirolimus, SirolimusEFR™ through a non-coated microporous AngioInfusion™ Balloon, protecting the drug in transit through the arteries and consistently delivering a large liquid dose, overcoming certain limitations of drug-coated balloons. SirolimusEFR delivered by Virtue SAB has been shown in published preclinical series involving hundreds of arterial deliveries to achieve sustained tissue levels well above the known required therapeutic tissue concentration for inhibiting restenosis (1 ng/mg tissue) for the entire critical healing period of approximately 30 days. Virtue SAB demonstrated positive three-year clinical data in coronary in-stent restenosis (“ISR”) in the SABRE study, a multi-center prospective, independent core lab-adjudicated clinical study conducted in Europe. Virtue SAB has been granted Breakthrough Device Designation by the FDA for specific indications relating to coronary ISR, coronary small vessel disease and peripheral artery disease below-the-knee. The FDA granted IDE approval for Orchestra BioMed to evaluate the efficacy and safety of Virtue SAB in the Virtue Trial, a pivotal trial that will randomize Virtue SAB against commercially available AGENT™ DCB, a paclitaxel-coated balloon. Forward-Looking Statements Certain statements included in this press release that are not historical facts are forward-looking statements for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements generally are accompanied by words such as “believe,” “may,” “will,” “estimate,” “continue,” “anticipate,” “intend,” “expect,” “should,” “would,” “plan,” “predict,” “potential,” “seem,” “seek,” “future,” “outlook” and similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These forward-looking statements include, but are not limited to, statements relating to the initiation, enrollment, timing, implementation and design of the Company’s planned and ongoing pivotal trials, including the timing of completion of enrollment in the BACKBEAT study and the timing of initiation of the Virtue Trial, the receipt of committed capital, the Company’s expected cash runway, the date of completion of the formal mediation with Terumo, the potential benefits of BDD, realizing the clinical and commercial value of AVIM therapy and Virtue SAB, the potential safety and efficacy of the Company’s product candidates, and the ability of the Company’s partnerships to accelerate clinical development. These statements are based on various assumptions, whether or not identified in this press release, and on the current expectations of the Company’s management and are not predictions of actual performance. These forward-looking statements are provided for illustrative purposes only and are not intended to serve as and must not be relied on as a guarantee, an assurance, a prediction, or a definitive statement of fact or probability. Actual events and circumstances are difficult or impossible to predict and may differ from assumptions. Many actual events and circumstances are beyond the control of the Company. These forward-looking statements are subject to a number of risks and uncertainties, including changes in domestic and foreign business, market, financial, political, and legal conditions; risks related to regulatory approval of the Company’s commercial product candidates and ongoing regulation of the Company’s product candidates, if approved; the timing of, and the Company’s ability to achieve expected regulatory and business milestones; the impact of competitive products and product candidates; and the risk factors discussed under the heading “Item 1A. Risk Factors” in the Company’s Annual Report on Form 10-K for the year ended December 31, 2024, which was filed with the SEC on March 31, 2025 and the risk factor discussed under the heading “Item 1A. Risk Factors” in the Company’s Quarterly Report on Form 10-Q for the quarterly period ended March 31, 2025, which was filed with the SEC on May 12, 2025. The Company operates in a very competitive and rapidly changing environment. New risks emerge from time to time. Given these risks and uncertainties, the Company cautions against placing undue reliance on these forward-looking statements, which only speak as of the date of this press release. The Company does not plan and undertakes no obligation to update any of the forward-looking statements made herein, except as required by law. Investor ContactSilas NewcombOrchestra BioMed Snewcomb@orchestrabiomed.com Media ContactKelsey Kirk-EllisOrchestra BioMedKkirkellis@orchestrabiomed.com ORCHESTRA BIOMED HOLDINGS, INC.Condensed Consolidated Balance Sheets(in thousands, except share and per share data)(Unaudited)   June 30, December 31,  2025 2024ASSETS      CURRENT ASSETS:      Cash and cash equivalents $18,749  $22,261 Marketable securities  15,175   44,551 Accounts receivable, net  83   92 Inventory  185   173 Prepaid expenses and other current assets  1,690   2,094 Total current assets  35,882   69,171 Property and equipment, net  1,366   1,384 Right-of-use assets  1,806   2,103 Strategic investments  2,495   2,495 Deposits and other assets  1,276   1,020 TOTAL ASSETS $42,825  $76,173        LIABILITIES AND STOCKHOLDERS’ EQUITY      CURRENT LIABILITIES:      Accounts payable $5,308  $5,134 Accrued expenses and other liabilities  6,650   6,084 Operating lease liability, current portion  642   550 Deferred revenue, current portion  4,461   4,439 Total current liabilities  17,061   16,207 Deferred revenue, less current portion  9,568   10,989 Loan payable  14,384   14,292 Operating lease liability, less current portion  1,328   1,687 Other long-term liabilities  189   40 TOTAL LIABILITIES  42,530   43,215        STOCKHOLDERS’ EQUITY      Preferred stock, $0.0001 par value per share; 10,000,000 shares authorized; noneissued or outstanding at June 30, 2025 and December 31, 2024.  —   — Common stock, $0.0001 par value per share; 340,000,000 shares authorized;38,643,553 and 38,194,442 shares issued and outstanding as of June 30, 2025 andDecember 31, 2024, respectively.  4   4 Additional paid-in capital  348,271   342,780 Accumulated other comprehensive income  16   52 Accumulated deficit  (347,996)  (309,878)TOTAL STOCKHOLDERS’ EQUITY  295   32,958 TOTAL LIABILITIES AND STOCKHOLDERS’ EQUITY $42,825  $76,173   ORCHESTRA BIOMED HOLDINGS, INC.Condensed Consolidated Statements of Operations and Comprehensive Loss(in thousands, except share and per share data)(Unaudited)   Three Months Ended June 30,  2025 2024Revenue:      Partnership revenue $667  $628 Product revenue  169   150 Total revenue  836   778 Expenses:      Cost of product revenues  46   44 Research and development  13,853   11,126 Selling, general and administrative  6,264   6,467 Total expenses  20,163   17,637 Loss from operations  (19,327)  (16,859)Other (expense) income:      Interest (expense) income, net  (36)  902 Loss on fair value of strategic investments  –   (23)Total other (expense) income  (36)  879 Net loss $(19,363) $(15,980)Net loss per share      Basic and diluted $(0.50) $(0.45)Weighted-average shares used in computing net loss per share, basicand diluted  38,392,716   35,800,273 Comprehensive loss      Net loss $(19,363) $(15,980)Unrealized loss on marketable securities  (21)  (15)Comprehensive loss $(19,384) $(15,995)

$56.2 million in proceeds from completed public offering and concurrent private equity purchase by Medtronic and Ligand$55 million in proceeds and funding commitments from royalty-based, non-dilutive investments from Medtronic and LigandProceeds extend expected cash runway into the second half of 2027 and expected to fund completion of enrollment and follow up for the primary endpoint of the BACKBEAT study, as well as substantial enrollment of the Virtue Trial NEW HOPE, Pa., Aug. 05, 2025 (GLOBE NEWSWIRE) — Orchestra BioMed Holdings, Inc. (Nasdaq: OBIO, “Orchestra BioMed” or the “Company”), a biomedical company accelerating high-impact technologies to patients through risk-reward sharing partnerships, today announced the successful completion of strategic transactions and concurrent public and private equity offerings totaling an expected $111.2 million in gross proceeds to support continued advancement of the Company’s late-stage atrioventricular interval modulation (“AVIM”) therapy and Virtue Sirolimus AngioInfusion Balloon (“SAB”) clinical programs. The aggregate $111.2 million in expected gross proceeds from transactions that formally closed or were committed to on August 4, 2025, is comprised of: $55 million received or to be received by May 1, 2026, subject to certain conditions, from royalty-based, non-dilutive investments from Ligand Pharmaceuticals Incorporated (Nasdaq: LGND, “Ligand”) and Medtronic, plc. (NYSE: MDT, “Medtronic”) Ligand committed $35 million in exchange for a tiered revenue interest in Orchestra BioMed’s future royalties from AVIM therapy and Virtue SABMedtronic committed $20 million in exchange for a secured subordinated promissory note convertible to capped prepaid revenue share $56.2 million received from a $40 million underwritten public offering of common stock and prefunded warrants (the “Public Offering”) and $11.2 million and $5 million received from private placements of common stock to Medtronic and Ligand, respectively (collectively, the “Private Placement”)   “We are very proud to have secured significant long-term capital from strategic transactions with Medtronic and Ligand and the completion of our first underwritten public equity offering. We believe the success of these financing transactions reflects confidence from strategic partners and shareholders in the transformative potential of our two high impact, late-stage therapeutic programs,” said David Hochman, Chairman and Chief Executive Officer of Orchestra BioMed. “With Ligand, an established royalty investor, joining us as a strategic capital partner and Medtronic, the global market leader in cardiac rhythm management, expanding their commitment to our existing collaboration, this new capital strongly positions us to advance our core technologies, AVIM therapy and Virtue SAB, toward fundamental clinical and regulatory milestones that have the potential to create significant value for all stakeholders.” Orchestra BioMed currently intends to use the net proceeds from these transactions to fund potential significant value-creating catalysts, including: Full enrollment of the BACKBEAT global pivotal study (“BACKBEAT study”) evaluating AVIM therapy for the treatment of uncontrolled hypertension in patients indicated for a pacemakerCompletion of follow-up for the BACKBEAT study primary endpointsCompletion or near-completion of enrollment of the Virtue Trial evaluating Virtue SAB in the treatment of Coronary in-stent restenosis (ISR) In the Public Offering, which closed on August 4, 2025, Orchestra BioMed sold 9,413,637 shares of its common stock at a price of $2.75 per share, and, in lieu of shares of common stock to certain investors, pre-funded warrants to purchase up to an aggregate of 5,136,363 shares of common stock at a price of $2.7499 per pre-funded warrant. Medtronic purchased 4,077,427 shares, and Ligand purchased 1,818,181 shares also at $2.75 per share in the Private Placement. The gross proceeds from the Public Offering and Private Placement combined were approximately $56.2 million, with net proceeds of approximately $51.8 million after deducting underwriting discounts, commissions, placement fees and offering expenses. This press release shall not constitute an offer to sell or a solicitation of an offer to buy any of these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the applicable securities laws of such state or jurisdiction. About Orchestra BioMed Orchestra BioMed (Nasdaq: OBIO) is a biomedical innovation company accelerating high-impact technologies to patients through risk-reward sharing partnerships with leading medical device companies. Orchestra BioMed’s partnership-enabled business model focuses on forging strategic collaborations with leading medical device companies to drive successful global commercialization of products it develops. Orchestra BioMed’s lead product candidate is AVIM therapy for the treatment of uncontrolled hypertension, the leading risk factor for death worldwide. Orchestra BioMed is also developing Virtue SAB for the treatment of atherosclerotic artery disease, the leading cause of mortality worldwide. Orchestra BioMed has a strategic collaboration with Medtronic, one of the largest medical device companies in the world, for development and commercialization of AVIM therapy for the treatment of uncontrolled hypertension in pacemaker-indicated patients, and a strategic partnership with Terumo, a global leader in medical technology, for development and commercialization of Virtue SAB for the treatment of artery disease. The Company has received four Breakthrough Device Designations from the FDA across these two core programs, reflecting the significant potential of its technologies to address high unmet needs in cardiovascular care. For further information about Orchestra BioMed, please visit www.orchestrabiomed.com, and follow us on LinkedIn. References to Websites and Social Media Platforms References to information included on, or accessible through, websites and social media platforms do not constitute incorporation by reference of the information contained at or available through such websites or social media platforms, and you should not consider such information to be part of this press release. About AVIM Therapy AVIM therapy is an investigational therapy compatible with standard dual-chamber pacemakers designed to substantially and persistently lower blood pressure. It has been evaluated in pilot studies in patients with hypertension who are also indicated for a pacemaker. MODERATO II, a double-blind, randomized pilot study, showed that patients treated with AVIM therapy experienced net reductions of 8.1 mmHg in 24-hour ambulatory systolic blood pressure (aSBP) and 12.3 mmHg in office systolic blood pressure (oSBP) at six months when compared to control patients. In addition to reducing blood pressure, clinical results using AVIM therapy demonstrate improvements in cardiac function and hemodynamics. The BACKBEAT (BradycArdia paCemaKer with atrioventricular interval modulation for Blood prEssure treAtmenT) global pivotal study will further evaluate the safety and efficacy of AVIM therapy in lowering blood pressure in patients who have systolic blood pressure above target despite anti-hypertensive medication and who are indicated for or have recently received a dual-chamber cardiac pacemaker. AVIM therapy has been granted Breakthrough Device Designation by the FDA for the treatment of uncontrolled hypertension in patients who have increased cardiovascular risk. About Virtue SABVirtue SAB is designed to deliver a proprietary extended-release formulation of sirolimus, SirolimusEFR™ through a non-coated microporous AngioInfusion™ Balloon that protects the drug in transit to consistently deliver a large liquid dose overcoming certain limitations of drug-coated balloons. SirolimusEFR delivered by Virtue SAB has been shown in published preclinical series involving hundreds of arterial deliveries to achieve sustained tissue levels well above the known required therapeutic tissue concentration for inhibiting restenosis (1 ng/mg tissue) for the entire critical healing period of approximately 30 days. Virtue SAB demonstrated positive three-year clinical data in coronary ISR in the SABRE study, a multi-center prospective, independent core lab-adjudicated clinical study of 50 patients conducted in Europe. Virtue SAB has been granted Breakthrough Device Designation by the FDA for specific indications relating to coronary ISR, coronary small vessel disease and peripheral artery disease below-the-knee. Forward-Looking Statements Certain statements included in this press release that are not historical facts are forward-looking statements for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements generally are accompanied by words such as “believe,” “may,” “will,” “estimate,” “continue,” “anticipate,” “intend,” “expect,” “should,” “would,” “plan,” “predict,” “potential,” “seem,” “seek,” “future,” “outlook” and similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These forward-looking statements include, but are not limited to, statements relating to receipt of committed capital , the use of proceeds from the transactions, the Company’s expected cash runway, the enrollment, implementation and design of the Company’s planned and ongoing pivotal trials, realizing the clinical and commercial value of the Company’s product candidates, the potential safety and efficacy of the Company’s product candidates, and the ability of the Company’s partnerships to accelerate clinical development. These statements are based on various assumptions, whether or not identified in this press release, and on the current expectations of the Company’s management and are not predictions of actual performance. These forward-looking statements are provided for illustrative purposes only and are not intended to serve as and must not be relied on as a guarantee, an assurance, a prediction, or a definitive statement of fact or probability. Actual events and circumstances are difficult or impossible to predict and may differ from assumptions. Many actual events and circumstances are beyond the control of the Company. These forward-looking statements are subject to a number of risks and uncertainties, including changes in domestic and foreign business, market, financial, political, and legal conditions; risks related to regulatory approval of the Company’s commercial product candidates and ongoing regulation of the Company’s product candidates, if approved; the timing of, and the Company’s ability to achieve expected regulatory and business milestones; the impact of competitive products and product candidates; and the risk factors discussed under the heading “Item 1A. Risk Factors” in the Company’s Annual Report on Form 10-K for the year ended December 31, 2024, which was filed with the SEC on March 31, 2025 and the risk factor discussed under the heading “Item 1A. Risk Factors” in the Company’s Quarterly Report on Form 10-Q for the quarterly period ended March 31, 2025, which was filed with the SEC on May 12, 2025. The Company operates in a very competitive and rapidly changing environment. New risks emerge from time to time. Given these risks and uncertainties, the Company cautions against placing undue reliance on these forward-looking statements, which only speak as of the date of this press release. The Company does not plan and undertakes no obligation to update any of the forward-looking statements made herein, except as required by law. Contacts For Orchestra BioMed:Investors:Silas NewcombSnewcomb@orchestrabiomed.com Media: Kelsey Kirk-EllisKkirkellis@orchestrabiomed.com

NEW HOPE, Pa., Aug. 01, 2025 (GLOBE NEWSWIRE) — Orchestra BioMed Holdings, Inc. (Nasdaq: OBIO, “Orchestra BioMed” or the “Company”), a biomedical company accelerating high-impact technologies to patients through risk-reward sharing partnerships, announced today the pricing of an underwritten public offering of 9,413,637 shares of its common stock at a price to the public of $2.75 per share and, in lieu of common stock to certain investors, pre-funded warrants to purchase 5,136,363 shares of its common stock at a price to the public of $2.7499 per pre-funded warrant, which represents the per share public offering price for the shares of common stock less the $0.0001 per share exercise price for each pre-funded warrant (the “Offering”). In addition, the Company granted the underwriters a 30-day option to purchase up to an additional 2,182,500 shares of its common stock at the public offering price per share, less underwriting discounts and commissions. All of the securities are being offered by the Company. The Offering is expected to close on August 4, 2025, subject to customary closing conditions. The gross proceeds from the Offering, before deducting underwriting discounts and commissions and estimated offering expenses, are expected to be approximately $40.0 million, assuming no exercise of the underwriters’ option. The Company intends to use the net proceeds from the Offering, together with its existing cash and cash equivalents, to fund the Company’s atrioventricular interval modulation (“AVIM”) therapy program and the execution of the BACKBEAT study and to fund its Virtue Sirolimus AngioInfusion Balloon (“SAB”) program and the planned Virtue SAB trial, as well as research and clinical development of other current or additional product candidates, and the remainder for working capital and other general corporate purposes. Piper Sandler and TD Cowen are acting as joint book-running managers for the Offering. The securities described above are being offered pursuant to a shelf registration statement on Form S-3 (File No. 333-279430) that was filed with the Securities and Exchange Commission (the “SEC”) on May 15, 2024 and declared effective on May 24, 2024. A preliminary prospectus supplement relating to the Offering has been, and a prospectus supplement relating to the Offering will be, filed with the SEC. The Offering is being made only by means of a prospectus supplement and an accompanying prospectus that form a part of the registration statement. Copies of the prospectus supplement and accompanying prospectus relating to the Offering may be obtained free of charge on the SEC’s website located at www.sec.gov. Copies of the prospectus supplement and accompanying prospectus relating to the Offering may also be obtained, when available, from: Piper Sandler & Co., Attention: Prospectus Department, 350 North 5th Street, Suite 1000, Minneapolis, MN 55401, or by telephone at (800) 747-3924, or by email at prospectus@psc.com; or TD Securities (USA) LLC, 1 Vanderbilt Avenue, New York, New York 10017, by telephone at (833) 297-2926, or by email at TD.ECM_Prospectus@tdsecurities.com. This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation, or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. About Orchestra BioMed Orchestra BioMed (Nasdaq: OBIO) is a biomedical innovation company accelerating high-impact technologies to patients through risk-reward sharing partnerships with leading medical device companies. Orchestra BioMed’s partnership-enabled business model focuses on forging strategic collaborations with leading medical device companies to drive successful global commercialization of products it develops. Orchestra BioMed’s lead product candidate is AVIM therapy for the treatment of hypertension, the leading risk factor for death worldwide. Orchestra BioMed is also developing Virtue SAB for the treatment of atherosclerotic artery disease, the leading cause of mortality worldwide. Orchestra BioMed has a strategic collaboration with Medtronic, one of the largest medical device companies in the world, for development and commercialization of AVIM therapy for the treatment of hypertension in pacemaker-indicated patients, and a strategic partnership with Terumo, a global leader in medical technology, for development and commercialization of Virtue SAB for the treatment of artery disease. The Company has received four Breakthrough Device Designations from the U.S. Food and Drug Administration across these two core programs, reflecting the significant potential of its technologies to address high unmet needs in cardiovascular care. Forward-Looking Statements Certain statements included in this press release that are not historical facts are forward-looking statements for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements generally are accompanied by words such as “believe,” “may,” “will,” “estimate,” “continue,” “anticipate,” “intend,” “expect,” “should,” “would,” “plan,” “predict,” “potential,” “seem,” “seek,” “future,” “outlook” and similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These forward-looking statements include, but are not limited to, statements regarding the proposed Offering, including the completion and timing of the Offering and the anticipated use of proceeds from the Offering. These statements are based on various assumptions, whether or not identified in this press release, and on the current expectations of the Company’s management and are not predictions of actual performance. These forward-looking statements are provided for illustrative purposes only and are not intended to serve as and must not be relied on as a guarantee, an assurance, a prediction, or a definitive statement of fact or probability. Actual events and circumstances are difficult or impossible to predict and may differ from assumptions. Many actual events and circumstances are beyond the control of the Company. These forward-looking statements are subject to a number of risks and uncertainties, including changes in domestic and foreign business, market, financial, political, and legal conditions; risks related to regulatory approval of the Company’s commercial product candidates and ongoing regulation of the Company’s product candidates, if approved; the timing of, and the Company’s ability to achieve expected regulatory and business milestones; the impact of competitive products and product candidates; and the risk factors discussed under the heading “Item 1A. Risk Factors” in the Company’s Annual Report on Form 10-K for the year ended December 31, 2024, which was filed with the SEC on March 31, 2025, and the risk factor discussed under the heading “Item 1A. Risk Factors” in the Company’s Quarterly Report on Form 10-Q for the quarterly period ended March 31, 2025, which was filed with the SEC on May 12, 2025, as such discussion may be updated from time to time by subsequent filings the Company may make with the SEC, as well as the risks identified in the registration statement and the preliminary prospectus supplement relating to the Offering. The Company operates in a very competitive and rapidly changing environment. New risks emerge from time to time. Given these risks and uncertainties, the Company cautions against placing undue reliance on these forward-looking statements, which only speak as of the date of this press release. The Company does not plan and undertakes no obligation to update any of the forward-looking statements made herein, except as required by law. Investor ContactSilas NewcombOrchestra BioMedSnewcomb@orchestrabiomed.com Media ContactKelsey Kirk-EllisOrchestra BioMedKkirkellis@orchestrabiomed.com

• Ligand to invest $35 million in exchange for a tiered royalty on future sales of Orchestra’s AVIM therapy and Virtue SAB and an additional $5 million in an equity private placement • Medtronic to invest $10 million in an equity private placement and an additional $20 million in a secured subordinated promissory note convertible to prepaid revenue share • Medtronic and Orchestra BioMed expand strategic collaboration to provide pathway for development of AVIM therapy-enabled leadless pacemakers NEW HOPE, Pa., July 31, 2025 (GLOBE NEWSWIRE) — Orchestra BioMed Holdings, Inc. (Nasdaq: OBIO, “Orchestra BioMed” or the “Company”), a biomedical company accelerating high-impact technologies to patients through risk-reward sharing partnerships, today announced that the Company has secured $70 million in new capital from Ligand Pharmaceuticals Incorporated (Nasdaq: LGND, “Ligand”) and Medtronic, plc. (NYSE: MDT, “Medtronic”) to advance its late-stage partnered cardiology programs.   Simultaneously, Orchestra BioMed and Medtronic, which have an existing strategic collaboration for atrioventricular interval modulation (“AVIM”) therapy for the treatment of uncontrolled hypertension in pacemaker-indicated patients, have amended their agreement to include the potential future development of AVIM therapy-enabled leadless pacemakers. Unlike traditional pacemakers that are placed in a patient’s chest with leads (or wires) running to the heart, minimally-invasive Medtronic Micra™ leadless pacemakers are implanted directly into the heart, reducing potential sources of complications. Ligand $40 million Investment Todd Davis, Chief Executive Officer of Ligand commented: “We are pleased to partner with Medtronic and Orchestra BioMed in this important endeavor. This investment expands our pipeline of development-stage products and demonstrates our confidence in Orchestra BioMed’s scientific advancements, as well as the strong capabilities of its partner, Medtronic. We are proud to support Orchestra BioMed as they develop novel high-impact, device-based therapies such as AVIM therapy and Virtue SAB targeting high-risk patient populations with hypertension and arterial disease, two of the most significant global health challenges.” David Hochman, Chairman and Chief Executive Officer of Orchestra BioMed stated, “Ligand has been one of the inspirations for our partnership-driven approach to creating long-term, capital-efficient value through royalty-based collaborations. We are thrilled to welcome them as a strategic capital partner. Ligand’s decision to invest in our partnered programs and our team reflects our shared conviction in the transformative potential of both AVIM therapy and Virtue SAB – our late-stage flagship technologies aimed to address important unmet medical needs in large, established global markets. This transaction provides foundational financial support to enable our potential achievement of key value creating milestones for both of our high-impact clinical programs.” Under the terms of the agreement, Ligand will pay $20 million to Orchestra BioMed at closing with an additional $15 million to be funded, subject to certain conditions precedent, at the nine-month anniversary of the transaction closing date. Ligand has also agreed to invest an additional $5 million to purchase shares of the Company’s common stock in an equity private placement at the public offering price per share in Orchestra BioMed’s next public offering of its equity securities. In exchange, Ligand will receive a low double-digit royalty on the first $100 million in commercial revenues from Orchestra’s AVIM therapy and Virtue SAB programs in all indications. Ligand will also earn a mid-single-digit royalty on annual revenues exceeding $100 million in commercial revenues from AVIM therapy in the uncontrolled hypertension and increased cardiovascular risk indication and Virtue SAB in coronary artery disease indications. Medtronic $30 million Additional Investment & Future Leadless AVIM Therapy Device Development Robert C. Kowal, M.D., Ph.D., Vice President and General Manager of Cardiac Pacing Therapies within the Medtronic Cardiac Rhythm Management operating unit, commented: “Our expanded investment in Orchestra BioMed reflects confidence in their clinical progress. Broadening our collaboration to include integrating AVIM therapy into future leadless pacing technology reaffirms our commitment to transform care for patients who need pacing therapy and have uncontrolled hypertension.” Mr. Hochman added, “Medtronic continues to be an outstanding partner for the AVIM therapy program. We believe their $30 million additional commitment to Orchestra BioMed reflects their belief in the clinical and commercial potential for this therapy to benefit patients with uncontrolled hypertension and increased cardiovascular risk in the pacemaker population. Expanding our existing collaboration to provide for potential future integration of AVIM therapy into a leadless pacemaker system deepens our strategic alignment and creates a potential pathway for patients to benefit from both AVIM therapy and cutting-edge leadless pacing technology, simultaneously.” Subject to the terms of the agreement, Medtronic’s $30 million additional investment commitment to Orchestra BioMed includes a $10 million agreement to purchase shares of the Company’s common stock in a private placement at the public offering price in the Company’s next public offering of its equity securities. Medtronic also made a $20 million commitment to purchase a five-year term secured subordinated promissory note, to be funded in nine months which automatically converts to a prepaid revenue share upon U.S. Food and Drug Administration (“FDA”) approval of AVIM therapy. The prepaid revenue share will be credited back to Medtronic at a low double-digit percentage of actual AVIM therapy revenue share paid to Orchestra BioMed, up to $40 million in cumulative revenue share. About Ligand PharmaceuticalsLigand is a biopharmaceutical company enabling scientific advancement through supporting the clinical development of high-value medicines. Ligand does this by providing financing, licensing our technologies or both. Ligand’s business model seeks to generate value for stockholders by creating a diversified portfolio of biotech and pharmaceutical product revenue streams that are supported by an efficient and low corporate cost structure. Ligand’s goal is to offer investors an opportunity to participate in the promise of the biotech industry in a profitable and diversified manner. Ligand’s business model is based on funding programs in mid- to late-stage drug development in return for economic rights, purchasing royalty rights in development stage or commercial biopharmaceutical products and licensing its technology to help partners discover and develop medicines. Ligand partners with other pharmaceutical companies to attempt to leverage what they do best (late-stage development, regulatory management and commercialization) in order to generate revenue. Ligand operates two infrastructure-light royalty generating technology IP platform technologies. Ligand’s Captisol® platform technology is a chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs. Ligand’s NITRICIL™ platform technology facilitates tunable dosing, permitting an adjustable drug release profile to allow proprietary formulations that target a broad range of indications. Ligand has established multiple alliances, licenses and other business relationships with the world’s leading pharmaceutical companies including Amgen, Merck, Pfizer, Jazz, Gilead Sciences and Baxter International. For more information, please visit www.ligand.com. Follow Ligand on X and LinkedIn. Ligand uses its investor relations website and X as a means of disclosing material non-public information and for complying with our disclosure obligations under Regulation FD. Investors should monitor our website and our X account, in addition to following our press releases, SEC filings, public conference calls and webcasts. About Orchestra BioMed Orchestra BioMed (Nasdaq: OBIO) is a biomedical innovation company accelerating high-impact technologies to patients through risk-reward sharing partnerships with leading medical device companies. Orchestra BioMed’s partnership-enabled business model focuses on forging strategic collaborations with leading medical device companies to drive successful global commercialization of products it develops. Orchestra BioMed’s lead product candidate is AVIM therapy for the treatment of hypertension, the leading risk factor for death worldwide. Orchestra BioMed is also developing Virtue SAB for the treatment of atherosclerotic artery disease, the leading cause of mortality worldwide. Orchestra BioMed has a strategic collaboration with Medtronic, one of the largest medical device companies in the world, for development and commercialization of AVIM therapy for the treatment of hypertension in pacemaker-indicated patients, and a strategic partnership with Terumo, a global leader in medical technology, for development and commercialization of Virtue SAB for the treatment of artery disease. The Company has received four Breakthrough Device Designations from the FDA across these two core programs, reflecting the significant potential of its technologies to address high unmet needs in cardiovascular care. For further information about Orchestra BioMed, please visit www.orchestrabiomed.com, and follow us on LinkedIn. References to Websites and Social Media Platforms References to information included on, or accessible through, websites and social media platforms do not constitute incorporation by reference of the information contained at or available through such websites or social media platforms, and you should not consider such information to be part of this press release. About AVIM Therapy AVIM therapy is an investigational therapy compatible with standard dual-chamber pacemakers designed to substantially and persistently lower blood pressure. It has been evaluated in pilot studies in patients with hypertension who are also indicated for a pacemaker. MODERATO II, a double-blind, randomized pilot study, showed that patients treated with AVIM therapy experienced net reductions of 8.1 mmHg in 24-hour ambulatory systolic blood pressure (aSBP) and 12.3 mmHg in office systolic blood pressure (oSBP) at six months when compared to control patients. In addition to reducing blood pressure, clinical results using AVIM therapy demonstrate improvements in cardiac function and hemodynamics. The BACKBEAT (BradycArdia paCemaKer with atrioventricular interval modulation for Blood prEssure treAtmenT) global pivotal study will further evaluate the safety and efficacy of AVIM therapy in lowering blood pressure in patients who have systolic blood pressure above target despite anti-hypertensive medication and who are indicated for or have recently received a dual-chamber cardiac pacemaker. AVIM therapy has been granted Breakthrough Device Designation by the FDA for the treatment of uncontrolled hypertension in patients who have increased cardiovascular risk. About Virtue SABVirtue SAB is designed to deliver a proprietary extended-release formulation of sirolimus, SirolimusEFR™ through a non-coated microporous AngioInfusion™ Balloon that protects the drug in transit to consistently deliver a large liquid dose overcoming certain limitations of drug-coated balloons. SirolimusEFR delivered by Virtue SAB has been shown in published preclinical series involving hundreds of arterial deliveries to achieve sustained tissue levels well above the known required therapeutic tissue concentration for inhibiting restenosis (1 ng/mg tissue) for the entire critical healing period of approximately 30 days. Virtue SAB demonstrated positive three-year clinical data in coronary ISR in the SABRE study, a multi-center prospective, independent core lab-adjudicated clinical study of 50 patients conducted in Europe. Virtue SAB has been granted Breakthrough Device Designation by the FDA for specific indications relating to coronary ISR, coronary small vessel disease and peripheral artery disease below-the-knee. Forward-Looking Statements Certain statements included in this press release that are not historical facts are forward-looking statements for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements generally are accompanied by words such as “believe,” “may,” “will,” “estimate,” “continue,” “anticipate,” “intend,” “expect,” “should,” “would,” “plan,” “predict,” “potential,” “seem,” “seek,” “future,” “outlook” and similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These forward-looking statements include, but are not limited to, statements relating to the enrollment, implementation and design of the Company’s planned and ongoing pivotal trials, realizing the clinical and commercial value of the Company’s product candidates, the potential safety and efficacy of the Company’s product candidates, the ability of the Company’s partnerships to accelerate clinical development, and the Company’s ability to satisfy funding and closing conditions of the transactions described in this press release. These statements are based on various assumptions, whether or not identified in this press release, and on the current expectations of the Company’s management and are not predictions of actual performance. These forward-looking statements are provided for illustrative purposes only and are not intended to serve as and must not be relied on as a guarantee, an assurance, a prediction, or a definitive statement of fact or probability. Actual events and circumstances are difficult or impossible to predict and may differ from assumptions. Many actual events and circumstances are beyond the control of the Company. These forward-looking statements are subject to a number of risks and uncertainties, including changes in domestic and foreign business, market, financial, political, and legal conditions; risks related to regulatory approval of the Company’s commercial product candidates and ongoing regulation of the Company’s product candidates, if approved; the timing of, and the Company’s ability to achieve expected regulatory and business milestones; the impact of competitive products and product candidates; and the risk factors discussed under the heading “Item 1A. Risk Factors” in the Company’s Annual Report on Form 10-K for the year ended December 31, 2024, which was filed with the SEC on March 31, 2025 and the risk factor discussed under the heading “Item 1A. Risk Factors” in the Company’s Quarterly Report on Form 10-Q for the quarterly period ended March 31, 2025, which was filed with the SEC on May 12, 2025. The Company operates in a very competitive and rapidly changing environment. New risks emerge from time to time. Given these risks and uncertainties, the Company cautions against placing undue reliance on these forward-looking statements, which only speak as of the date of this press release. The Company does not plan and undertakes no obligation to update any of the forward-looking statements made herein, except as required by law. Contacts For Orchestra BioMed:Investors:Silas NewcombSnewcomb@orchestrabiomed.com Media: Kelsey Kirk-EllisKkirkellis@orchestrabiomed.com For Ligand:Investors:Melanie Hermaninvestors@ligand.com(858) 550-7761 Media:Kellie Walshmedia@ligand.com(914) 315-6072

FDA Breakthrough Device Designation Awarded to AVIM Therapy FDA IDE Approved for Virtue SAB U.S. Pivotal Trial for Launch NEW HOPE, Pa., May 12, 2025 (GLOBE NEWSWIRE) — Orchestra BioMed Holdings, Inc. (Nasdaq: OBIO, “Orchestra BioMed” or the “Company”), a biomedical company accelerating high-impact technologies to patients through risk-reward sharing partnerships, today announced financial results for the first quarter ended March 31, 2025, and provided a business update highlighting continued regulatory momentum, disciplined operational execution, and a strengthening clinical development pipeline. Q1 2025 Highlights: U.S. Food and Drug Administration (“FDA”) Breakthrough Device Designation (“BDD”) granted for atrioventricular interval modulation (“AVIM”) therapy in patients with uncontrolled hypertension and increased cardiovascular risk, with or without an indication for a pacemaker, marking a major regulatory validation of the therapy’s potential to improve hypertensive heart disease outcomes. FDA BDD enables prioritized regulatory interactions and strengthens potential access to add-on reimbursement.BACKBEAT Global Pivotal Study execution continuing to progress in strategic collaboration with Medtronic (NYSE: MDT).New Clinical Data presented demonstrating the favorable impact of AVIM therapy on cardiac function in patients with diastolic dysfunction, a key contributor to the development of heart failure, as late breaker at THT 2025.Intellectual Property Expansion continues with AVIM therapy patent estate reaching 137 issued patents worldwide, with recent additions bolstering coverage for both hypertension and heart failure indications.FDA Investigational Device Exemption (“IDE”) Approval received for the Virtue® Sirolimus AngioInfusion Balloon (“SAB”) U.S. pivotal trial, a randomized head-to-head study comparing Virtue SAB with the commercially available AGENTTM DCB paclitaxel-coated balloon (the “Virtue Trial”). Trial initiation is currently targeted for the second half of 2025. Orchestra BioMed is sponsoring and in full operational control of the Virtue Trial; mediation with Terumo of certain other contractual terms is progressing. Key Chief Executive Officer (“CEO”) Commentary: David Hochman, Chairman and CEO of Orchestra BioMed, stated: “We continued to make meaningful progress during the first quarter with significant inflection points for both our AVIM therapy and Virtue SAB programs. We believe the FDA’s Breakthrough Device Designation for AVIM therapy signals meaningful recognition of its potential to meet the clinical needs of millions living with hypertensive heart disease, a population in which chronic high blood pressure can lead to various heart problems like left ventricular hypertrophy, diastolic dysfunction, heart failure, and coronary artery disease. We believe that AVIM therapy has the potential to provide a potent additional therapeutic option for these patients. We are focused on execution of the BACKBEAT global pivotal study alongside our strategic partner Medtronic as the critical pathway toward making AVIM therapy available to patients globally.” Mr. Hochman continued, “In parallel, we secured full IDE approval to conduct the Virtue Trial, a U.S. pivotal coronary study that will evaluate Virtue SAB, our investigational, non-coated drug-eluting balloon designed to deliver a large liquid dose of proprietary extended-release sirolimus, head-to-head against the commercially available AGENT paclitaxel-coated balloon. We believe the updated design of the trial, which we currently plan to initiate in the second half of the year, offers the most direct path to regulatory approval while showcasing the distinctive pharmacokinetic and therapeutic advantages of our proprietary technology. Taken together, these milestones mark tangible progress on multiple fronts. We continue to execute methodically and remain focused on advancing our pivotal trials, generating clinical evidence, and building long-term value for patients, physicians, shareholders and strategic partners alike.” Financial Results for the First Quarter Ended March 31, 2025 Cash and cash equivalents and Marketable securities totaled $49.9 million as of March 31, 2025.Net cash used in operating activities and for the purchase of fixed assets was $16.7 million during the first quarter of 2025, compared with $13.1 million for the first quarter in 2024, with the primary driver being increased research and development costs during the first quarter of 2025.Revenue for the first quarter of 2025 was $0.9 million, compared with $0.6 million for the first quarter in 2024. The increase was primarily due to recognition of partnership revenues earned under the agreement with Terumo.Research and development expenses for the first quarter of 2025 were $13.5 million, compared with $9.1 million for the first quarter in 2024. The increase was primarily due to additional costs associated with the ongoing BACKBEAT global pivotal study.Selling, general and administrative expenses for the first quarter of 2025 were $6.3 million, compared with $5.9 million for the first quarter of 2024. The increase was primarily due to an increase in stock-based compensation and increased professional fees associated with the overall growth of the business.Net loss for the first quarter of 2025 was $18.8 million, or $0.49 per share, compared with a net loss of $13.5 million, or $0.38 per share, for the first quarter of 2024. Net loss for the first quarter of 2025 included $3.0 million in non-cash stock-based compensation expense as compared to $2.6 million for the same period in 2024. About Orchestra BioMed Orchestra BioMed (Nasdaq: OBIO) is a biomedical innovation company accelerating high-impact technologies to patients through risk-reward sharing partnerships with leading medical device companies. Orchestra BioMed’s partnership-enabled business model focuses on forging strategic collaborations with leading medical device companies to drive successful global commercialization of products it develops. Orchestra BioMed’s lead product candidate is AVIM therapy for the treatment of hypertension, the leading risk factor for death worldwide. Orchestra BioMed is also developing Virtue SAB for the treatment of atherosclerotic artery disease, the leading cause of mortality worldwide. Orchestra BioMed has a strategic collaboration with Medtronic, one of the largest medical device companies in the world, for development and commercialization of AVIM therapy for the treatment of hypertension in pacemaker-indicated patients, and a strategic partnership with Terumo, a global leader in medical technology, for development and commercialization of Virtue SAB for the treatment of artery disease. The Company has received four Breakthrough Device Designations from the U.S. FDA across these two core programs, reflecting the significant potential of its technologies to address high unmet needs in cardiovascular care. For further information about Orchestra BioMed, please visit www.orchestrabiomed.com, and follow us on LinkedIn. References to Websites and Social Media Platforms References to information included on, or accessible through, websites and social media platforms do not constitute incorporation by reference of the information contained at or available through such websites or social media platforms, and you should not consider such information to be part of this press release. About AVIM Therapy AVIM therapy is an investigational therapy compatible with standard dual-chamber pacemakers designed to substantially and persistently lower blood pressure. It has been evaluated in pilot studies in patients with hypertension who are also indicated for a pacemaker. MODERATO II, a double-blind, randomized pilot study, showed that patients treated with AVIM therapy experienced net reductions of 8.1 mmHg in 24-hour ambulatory systolic blood pressure (aSBP) and 12.3 mmHg in office systolic blood pressure (oSBP) at six months when compared to control patients. In addition to reducing blood pressure, clinical results using AVIM therapy demonstrate improvements in cardiac function and hemodynamics. The BACKBEAT (BradycArdia paCemaKer with atrioventricular interval modulation for Blood prEssure treAtmenT) global pivotal study will further evaluate the safety and efficacy of AVIM therapy in lowering blood pressure in patients who have systolic blood pressure above target despite anti-hypertensive medication and who are indicated for or have recently received a dual-chamber cardiac pacemaker. AVIM therapy has been granted Breakthrough Device Designation by the FDA for the treatment of uncontrolled hypertension in patients who have increased cardiovascular risk. About Virtue SAB Virtue SAB is an investigational therapeutic combination drug-device designed to deliver a proprietary extended-release formulation of sirolimus, SirolimusEFR™ through a non-coated microporous AngioInfusion™ Balloon, protecting the drug in transit through the arteries and consistently delivering a large liquid dose, overcoming certain limitations of drug-coated balloons. SirolimusEFR delivered by Virtue SAB has been shown in published preclinical series involving hundreds of arterial deliveries to achieve sustained tissue levels well above the known required therapeutic tissue concentration for inhibiting restenosis (1 ng/mg tissue) for the entire critical healing period of approximately 30 days. Virtue SAB demonstrated positive three-year clinical data in coronary in-stent restenosis (“ISR”) in the SABRE study, a multi-center prospective, independent core lab-adjudicated clinical study conducted in Europe. Virtue SAB has been granted Breakthrough Device Designation by the FDA for specific indications relating to coronary ISR, coronary small vessel disease and peripheral artery disease below-the-knee. The FDA granted IDE approval for Orchestra BioMed to evaluate the efficacy and safety of Virtue SAB in the Virtue Trial, a pivotal trial that will randomize Virtue SAB against commercially available AGENTTM DCB, a paclitaxel-coated balloon. Forward-Looking Statements Certain statements included in this press release that are not historical facts are forward-looking statements for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements generally are accompanied by words such as “believe,” “may,” “will,” “estimate,” “continue,” “anticipate,” “intend,” “expect,” “should,” “would,” “plan,” “predict,” “potential,” “seem,” “seek,” “future,” “outlook” and similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These forward-looking statements include, but are not limited to, statements relating to the initiation, enrollment, timing, implementation and design of the Company’s planned and ongoing pivotal trials and reporting of top-line results, including the timing of initiation of the Virtue Trial, the potential benefits of BDD, including its ability to expedite FDA reviews and allow access to add-on reimbursement, realizing the clinical and commercial value of AVIM therapy and Virtue SAB, the potential safety and efficacy of the Company’s product candidates, and the ability of the Company’s partnerships to accelerate clinical development. These statements are based on various assumptions, whether or not identified in this press release, and on the current expectations of the Company’s management and are not predictions of actual performance. These forward-looking statements are provided for illustrative purposes only and are not intended to serve as and must not be relied on as a guarantee, an assurance, a prediction, or a definitive statement of fact or probability. Actual events and circumstances are difficult or impossible to predict and may differ from assumptions. Many actual events and circumstances are beyond the control of the Company. These forward-looking statements are subject to a number of risks and uncertainties, including changes in domestic and foreign business, market, financial, political, and legal conditions; risks related to regulatory approval of the Company’s commercial product candidates and ongoing regulation of the Company’s product candidates, if approved; the timing of, and the Company’s ability to achieve expected regulatory and business milestones; the impact of competitive products and product candidates; and the risk factors discussed under the heading “Item 1A. Risk Factors” in the Company’s Annual Report on Form 10-K for the year ended December 31, 2024, which was filed with the SEC on March 31, 2025 and the risk factor discussed under the heading “Item 1A. Risk Factors” in the Company’s Quarterly Report on Form 10-Q for the quarterly period ended March 31, 2025, which was filed with the SEC on May 12, 2025. The Company operates in a very competitive and rapidly changing environment. New risks emerge from time to time. Given these risks and uncertainties, the Company cautions against placing undue reliance on these forward-looking statements, which only speak as of the date of this press release. The Company does not plan and undertakes no obligation to update any of the forward-looking statements made herein, except as required by law. Investor ContactSilas NewcombOrchestra BioMed Snewcomb@orchestrabiomed.com Media ContactKelsey Kirk-EllisOrchestra BioMedKkirkellis@orchestrabiomed.com ORCHESTRA BIOMED HOLDINGS, INC.Condensed Consolidated Balance Sheets(in thousands, except share and per share data)(Unaudited)            March 31,     December 31,   2025 2024ASSETS      CURRENT ASSETS:      Cash and cash equivalents $18,348  $22,261 Marketable securities  31,536   44,551 Accounts receivable, net  89   92 Inventory  135   173 Prepaid expenses and other current assets  1,795   2,094 Total current assets  51,903   69,171 Property and equipment, net  1,413   1,384 Right-of-use assets  1,956   2,103 Strategic investments, less current portion  2,495   2,495 Deposits and other assets  1,284   1,020 TOTAL ASSETS $59,051  $76,173        LIABILITIES AND STOCKHOLDERS’ EQUITY      CURRENT LIABILITIES:      Accounts payable $5,563  $5,134 Accrued expenses and other liabilities  5,392   6,084 Operating lease liability, current portion  590   550 Deferred revenue, current portion  3,944   4,439 Total current liabilities  15,489   16,207 Deferred revenue, less current portion  10,752   10,989 Loan payable  14,338   14,292 Operating lease liability, less current portion  1,516   1,687 Other long-term liabilities  99   40 TOTAL LIABILITIES  42,194   43,215        STOCKHOLDERS’ EQUITY      Preferred stock, $0.0001 par value per share; 10,000,000 shares authorized; none issued or outstanding at March 31, 2025 and December 31, 2024.  —   — Common stock, $0.0001 par value per share; 340,000,000 shares authorized; 38,312,512 and 38,194,442 shares issued and outstanding as of March 31, 2025 and December 31, 2024, respectively.  4   4 Additional paid-in capital  345,449   342,780 Accumulated other comprehensive income  37   52 Accumulated deficit  (328,633)  (309,878)TOTAL STOCKHOLDERS’ EQUITY  16,857   32,958 TOTAL LIABILITIES AND STOCKHOLDERS’ EQUITY $59,051  $76,173  ORCHESTRA BIOMED HOLDINGS, INC.Condensed Consolidated Statements of Operations and Comprehensive Loss(in thousands, except share and per share data)(Unaudited)     Three Months Ended March 31,   2025  2024 Revenue:      Partnership revenue $732  $497 Product revenue  136   123 Total revenue  868   620 Expenses:      Cost of product revenues  44   34 Research and development  13,482   9,112 Selling, general and administrative  6,263   5,897 Total expenses  19,789   15,043 Loss from operations  (18,921)  (14,423)Other income (expense):      Interest income, net  166   1,016 Loss on fair value of strategic investments  —   (45)Other expense  —   (11)Total other income  166   960 Net loss $(18,755) $(13,463)Net loss per share      Basic and diluted $(0.49) $(0.38)Weighted-average shares used in computing net loss per share, basic and diluted  38,235,409   35,777,877 Comprehensive loss      Net loss $(18,755) $(13,463)Unrealized (loss) gain on marketable securities  (15)  2 Comprehensive loss $(18,770) $(13,461)