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)

NEW HOPE, Pa., March 31, 2025 (GLOBE NEWSWIRE) — Orchestra BioMed Holdings, Inc. (Nasdaq: OBIO, “Orchestra BioMed” or the “Company”), a biomedical innovation company accelerating high-impact technologies to patients through risk-reward sharing partnerships, today reported its full year 2024 financial results and provided a fourth quarter business update. “We remain highly focused on execution of the BACKBEAT global pivotal study, which we believe has the potential to deliver landmark results that can establish AVIM therapy as a new standard of care for the treatment of uncontrolled hypertension in patients already indicated for a pacemaker. We also believe it can lay the foundation for expanding use of AVIM-enabled devices to manage blood pressure and improve cardiovascular function for hypertensive patients with high cardiovascular risk,” commented David Hochman, Chairman, Chief Executive Officer and Founder of Orchestra BioMed. “As we age, our arteries naturally lose elasticity and become stiffer, a process that increases the risk of cardiovascular problems and is linked to changes in blood pressure and heart function. One of the characteristics of this process is the development of diastolic dysfunction, a condition where the heart’s ventricles cannot relax and fill with blood properly during the diastolic phase of the cardiac cycle. Our late-breaking data in patients with diastolic dysfunction recently presented at THT showed AVIM therapy’s ability to significantly improve ventricular relaxation and passive filling, highlighting its potential to drive better clinical outcomes through blood pressure reduction, as well as improvement of cardiac function.” “In parallel, we are encouraged by the progress of our Virtue SAB program as we actively prepare to initiate a U.S. coronary pivotal study with an updated trial design, currently under FDA review. The study is expected to randomize patients with coronary in-stent restenosis to treatment with Virtue SAB or Boston Scientific’s AGENT drug-coated balloon. We believe this design will optimally highlight the potential advantages of Virtue SAB’s proprietary design advantages which enables protected delivery of extended focal-release sirolimus without the need for a balloon coating,” continued Mr. Hochman. “With regard to our strategic partnership, we and Terumo are moving our negotiations into a formal mediation process. We believe this is the most efficient way to drive our relationship to a resolution, ideally during the second quarter of this year, ahead of potential initiation of the updated Virtue ISR-US pivotal study in the second half of the year.” Fourth Quarter 2024 and Recent Highlights Continued site activation and patient enrollment of the BACKBEAT global pivotal study, in collaboration with Medtronic (NYSE: MDT), evaluating the efficacy and safety of atrioventricular interval modulation (“AVIM”) therapy in hypertensive pacemaker patients.Submitted a revised design to the U.S. Food and Drug Administration (“FDA”) for the Virtue ISR-US pivotal study in coronary in-stent restenosis (“ISR”), which will randomize Virtue® Sirolimus AngioInfusion™ Balloon (“SAB”) against Boston Scientific’s AGENT drug-coated balloon; initiation is targeted for the second half of 2025, pending FDA approval of an amended investigational device exemption (“IDE”) which is expected to be secured in the second quarter of 2025.To accelerate potential completion of ongoing partnership restructuring negotiations, Orchestra BioMed and Terumo have elected to enter a mediation process and are currently working on a procedural plan that would aim to conclude the mediation process in the second quarter of 2025.Enhanced board of directors with the appointment of three highly experienced independent directors: Christopher Cleary, former Senior Vice President of Corporate Development at Medtronic, where he played a key role in establishing the strategic collaboration between Orchestra BioMed and Medtronic for AVIM therapyJohn Mack, former President of Cardiac Surgery at Medtronic with extensive operational and strategic experience in the medical device industryDavid Pacitti, Chief Executive Officer of Avanos Medical, former President of Siemens Medical Solutions USA, Inc. and Head of the Americas, Siemens Healthineers, with nearly 30 years of experience in cardiovascular device and procedural imaging Strengthened senior leadership team with the appointment of Mark Pomeranz as Executive Vice President & General Manager, Interventional Therapies. Mr. Pomeranz has over two decades of experience in medical devices, with particular emphasis on cardiology and gastrointestinal verticals. He most recently served as Chief Executive Officer of Motus GI Holdings. Financial Results for the Year Ended December 31, 2024 Cash and cash equivalents and Marketable securities totaled $66.8 million as of December 31, 2024. During the year, our cash inflows included approximately $15.0 million in net cash proceeds from the sale of our Common Stock under a market sales agreement and approximately $15.0 million from the initial draw on our credit facility.Net cash used in operating activities and for the purchase of fixed assets was $50.8 million during 2024, compared with $46.2 million for 2023, with the primary driver of this increase being increased cash outflows for research and development during 2024.Revenue for 2024 was $2.6 million, compared with $2.8 million for 2023. The decrease was primarily due to decreased recognition of partnership revenues earned under the agreement with Terumo.Research and development expenses for 2024 were $42.8 million, compared with $33.8 million for 2023. The increase was primarily due to additional costs associated with the ongoing BACKBEAT global pivotal study.Selling, general and administrative expenses for 2024 were $23.9 million, compared with $20.3 million for 2023. The increase was primarily due to increased expenses related to stock-based stock compensation.Net loss for 2024 was $61.0 million, or ($1.66) per share, compared with a net loss of $49.1 million, or ($1.48) per share, for 2023. Net loss for the year-ended 2024 included non-cash stock-based compensation expense of $10.6 million, compared with $7.6 million for the same period in 2023. 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 atrioventricular interval modulation (AVIM) therapy (also known as BackBeat Cardiac Neuromodulation Therapy (CNT™)) for the treatment of hypertension, the leading risk factor for death worldwide. Orchestra BioMed is also developing the Virtue® Sirolimus AngioInfusion™ Balloon (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. 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, also known as BackBeat CNT™, 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. 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 a similar target population of patients who have been indicated for, and recently implanted with, a dual-chamber cardiac pacemaker. About Virtue SAB Virtue SAB is a patented drug/device combination product candidate in development for the treatment of certain forms of artery disease that is designed to deliver a proprietary, investigational, extended-release formulation of sirolimus, SirolimusEFR™, to the vessel wall during balloon angioplasty without any coating on the balloon surface or the need to leave a stent or other permanent implant in the artery. 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 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. Orchestra BioMed has a strategic partnership with Terumo (Terumo, TSE: 4543), a global leader in medical technology headquartered in Tokyo, Japan, as well as Terumo Medical Corporation, its U.S. subsidiary, to collaborate on the global development and commercialization of Virtue SAB in coronary and peripheral vascular indications. 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, realizing the clinical and commercial value of BackBeat CNT and Virtue SAB, the Company’s ability to conclude the mediation process with Terumo in the second quarter of 2025, and the potential safety and efficacy of the Company’s product candidates. 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 Securities and Exchange Commission (“SEC”) on March 31, 2025, and under the heading “Item1A. Risk Factors” in Part II of the Company’s subsequently filed quarterly reports on Form 10-Q. 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 Contact:Jeremy FefferLifeSci AdvisorsJfeffer@lifesciadvisors.com Media Contact:Kelsey Kirk-EllisOrchestra BioMed(484) 682-4892kkirkellis@orchestrabiomed.com ORCHESTRA BIOMED HOLDINGS, INC.Consolidated Balance Sheets(in thousands, except share and per share data)     December 31,     December 31,   2024 2023ASSETS        CURRENT ASSETS:        Cash and cash equivalents $22,261  $30,559 Marketable securities  44,551   56,968 Strategic investments, current portion  —   68 Accounts receivable, net  92   99 Inventory  173   146 Prepaid expenses and other current assets  2,094   1,274 Total current assets  69,171   89,114 Property and equipment, net  1,384   1,279 Right-of-use assets  2,103   1,555 Strategic investments, less current portion  2,495   2,495 Deposits and other assets  1,020   769 TOTAL ASSETS $76,173  $95,212        LIABILITIES AND STOCKHOLDERS’ EQUITY        CURRENT LIABILITIES:        Accounts payable $5,134  $2,900 Accrued expenses and other liabilities  6,084   5,149 Operating lease liability, current portion  550   649 Deferred revenue, current portion  4,439   2,510 Total current liabilities  16,207   11,208 Deferred revenue, less current portion  10,989   14,923 Loan payable  14,292   — Operating lease liability, less current portion  1,687   1,038 Other long-term liabilities  40   — TOTAL LIABILITIES  43,215   27,169        STOCKHOLDERS’ EQUITY        Preferred stock, $0.0001 par value per share; 10,000,000 shares authorized; none issued or outstanding at December 31, 2024 and December 31, 2023.  —   — Common stock, $0.0001 par value per share; 340,000,000 shares authorized; 38,194,442 and 35,777,412 shares issued and outstanding as of December 31, 2024 and December 31, 2023, respectively.  4   4 Additional paid-in capital  342,780   316,903 Accumulated other comprehensive income (loss)  52   (10)Accumulated deficit  (309,878)  (248,854)TOTAL STOCKHOLDERS’ EQUITY  32,958   68,043 TOTAL LIABILITIES AND STOCKHOLDERS’ EQUITY $76,173  $95,212  ORCHESTRA BIOMED HOLDINGS, INC.Consolidated Statements of Operations and Comprehensive Loss(in thousands, except share and per share data)     Year Ended December 31,   2024 2023Revenue:        Partnership revenue $2,005  $2,106 Product revenue  633   654 Total revenue  2,638   2,760 Expenses:        Cost of product revenues  204   186 Research and development  42,804   33,822 Selling, general and administrative  23,931   20,258 Total expenses  66,939   54,266 Loss from operations  (64,301)  (51,506)Other income (expense):        Interest income, net  3,356   3,849 Loss on fair value adjustment of warrant liability  —   (294)Loss on debt extinguishment  —   (1,151)Loss on fair value of strategic investments  (68)  (18)Other expense  (11)  — Total other income  3,277   2,386 Net loss $(61,024) $(49,120)Net loss per share        Basic and diluted $(1.66) $(1.48)Weighted-average shares used in computing net loss per share, basic and diluted  36,821,042   33,225,227 Comprehensive loss       Net loss $(61,024) $(49,120)Unrealized gain (loss) on marketable securities  62   (2)Comprehensive loss $(60,962) $(49,122)

The BACKBEAT global pivotal study is currently enrolling patients to evaluate the efficacy and safety of atrioventricular interval modulation (“AVIM”) therapy for patients who have uncontrolled hypertension and a pacemaker indicationA globally recognized thought leader and innovator in cardiovascular technologies, including electrophysiology and cardiac rhythm management, Dr. Reddy currently serves as the Director of Cardiac Arrhythmia Services at The Mount Sinai Fuster Heart Hospital, the Director of Electrophysiology for the Mount Sinai Health System, and the Leona M. and Harry B. Helmsley Charitable Trust Professor of Medicine in Cardiac Electrophysiology at the Icahn School of Medicine at Mount Sinai NEW HOPE, Pa., Feb. 18, 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 appointment of Vivek Reddy, M.D., as Executive Chairman of the Company’s BACKBEAT Study Steering Committee and Chairman of its Bioelectronic Therapies Scientific Advisory Board. In these roles, Dr. Reddy will provide critical leadership in continuing to execute the BACKBEAT global pivotal study and further develop scientific evidence and clinical value for the Company’s bioelectronic therapies portfolio. Dr. Reddy commented, “I believe strongly in the transformative potential of AVIM therapy to help address uncontrolled hypertension in populations with increased cardiovascular risk such as the pacemaker-indicated patients we are focusing on in the BACKBEAT study. Hypertension is a critical global health challenge affecting hundreds of millions of patients worldwide. For patients with increased cardiovascular risk, the prospect of integrating an always-on, adjustable hypertension treatment that doesn’t rely on patient adherence is truly exciting. I am dedicated to driving the successful completion of the BACKBEAT study and synchronizing efforts among Orchestra BioMed’s clinical advisors to fully realize the potential of AVIM therapy for hypertension populations with increased cardiovascular risk. I’m also excited about exploring other therapeutic applications for which we believe there is potential utility for this novel technology.” “We are thrilled to have Dr. Vivek Reddy assume these key leadership roles to help drive successful completion of the BACKBEAT global pivotal study and maximize the clinical value AVIM therapy can potentially offer to patients with uncontrolled hypertension worldwide,” said David Hochman, Chairman, Chief Executive Officer, and Founder of Orchestra BioMed. “While Dr. Reddy has been a long-standing advisor to this exciting program, his expanded role will allow him to further engage in establishing awareness of AVIM therapy in the clinical community and drive effective communication across our distinguished team of clinical advisors. We believe his leadership will be instrumental in educating the clinical community about the BACKBEAT study and AVIM therapy, ultimately helping us and our colleagues at Medtronic deliver this exciting device-based treatment option to patients worldwide. We also look forward to collaborating closely with Dr. Reddy as we continue research and development of our proprietary bioelectronic therapies for additional indications such as heart failure.” Dr. Reddy currently serves as the Director of Cardiac Arrhythmia Services at The Mount Sinai Fuster Heart Hospital, the Director of Electrophysiology for the Mount Sinai Health System, and the Leona M. and Harry B. Helmsley Charitable Trust Professor of Medicine in Cardiac Electrophysiology at the Icahn School of Medicine at Mount Sinai. Dr. Reddy has led groundbreaking work in catheter ablation for atrial fibrillation and ventricular tachycardia, as well as leadless pacing and has been at the forefront of device therapies for stroke prevention, positioning him as one of the most respected experts in electrophysiology. Under his leadership, Mount Sinai has served as the lead investigational site for many pioneering clinical trials, and in 2014 implanted the world’s first leadless pacemaker. Dr. Reddy’s commitment to advancing medical innovation and his track record in clinical study leadership will play a pivotal role in the continued success of Orchestra BioMed’s efforts to revolutionize device-based cardiovascular solutions. About Orchestra BioMedOrchestra 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 atrioventricular interval modulation (“AVIM”) therapy for the treatment of hypertension, a significant risk factor for death worldwide. Orchestra BioMed is also developing Virtue® Sirolimus AngioInfusion™ Balloon (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. 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. 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 potential efficacy and safety of the Company’s commercial product candidates, additional indications of the Company’s proprietary bioelectronic therapies, implementation of the Company’s ongoing BACKBEAT global pivotal study, the ability of the Company’s partnerships to accelerate clinical development, and the Company’s late-stage development programs, strategic partnerships and plans to expand its product pipeline. 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 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, 2023, which was filed with the U.S. Securities and Exchange Commission on March 27, 2024, as updated by any risk factors disclosed under the heading “Item 1A. Risk Factors” in the Company’s subsequently filed quarterly reports on Form 10-Q. 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 (908) 723-4489 Snewcomb@orchestrabiomed.com Media ContactKelsey Kirk-EllisOrchestra BioMed(484) 682-4892Kkirkellis@orchestrabiomed.com

Medical device industry veteran brings over three decades of expertise in M&A, as well as structured research and development (“R&D”) collaborations aligned with Orchestra BioMed’s partnership-enabled business model Mr. Cleary previously served as Senior Vice President (“SVP”) of Corporate Development at Medtronic plc (NYSE: MDT) (“Medtronic”), where he played a key role in establishing the strategic collaboration between Orchestra BioMed and Medtronic for atrioventricular interval modulation (“AVIM”) therapy in hypertension with increased cardiovascular riskEric A. Rose, M.D. to transition from Board Member to Board Member Emeritus and Strategic Advisor, continuing to provide invaluable expertise and guidance to Orchestra BioMed NEW HOPE, Pa., Feb. 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 appointment of Christopher Cleary to its Board of Directors as an independent member, effective as of January 30, 2025. Mr. Cleary brings over three decades of experience in corporate development, mergers, acquisitions, strategic investments and structured R&D collaborations, having significantly impacted the medical technology industry through his strategic leadership and visionary approach. “We’re thrilled to welcome Chris as an independent member of the Orchestra BioMed Board of Directors, a role in which we expect he will provide invaluable guidance to help us more effectively execute our novel, partnership-enabled business model,” said David Hochman, Chairman, Chief Executive Officer and Founder of Orchestra BioMed. “We got to know Chris well over the last several years as he played a key role in shaping our strategic collaboration with Medtronic. With his extensive experience in global strategy, dealmaking, investing, and partnering, Chris brings knowledge and experience that is directly relevant to our strategy, technologies, and pathways to success. He shares our vision that risk-reward sharing partnerships can be a powerful tool for advancing high-impact medical device innovations like AVIM therapy and Virtue SAB and we are excited to work closely with him on our Board.” Mr. Cleary commented, “I am excited to join the Orchestra BioMed Board of Directors and contribute to the Company’s bold mission of accelerating medical device innovation in cardiovascular disease through strategic partnerships. I believe their pioneering approach addresses key challenges limiting leading corporations’ abilities to deploy financial and operational resources to directly drive the development of promising high-impact device-based therapies. Orchestra BioMed’s collaboration with Medtronic for AVIM therapy, which I had the opportunity to help shape, is a great example of this business at work. I look forward to working with the experienced Board of Directors and entire Orchestra BioMed team to continue driving groundbreaking advancements in cardiovascular medicine like AVIM therapy, Virtue SAB and beyond.” During his time as SVP of Corporate Development at Medtronic, Mr. Cleary facilitated over 35 acquisitions and multiple structured and venture investments and orchestrated the $6 billion sale of Covidien Group S.à.r.l ‘s medical supply assets to Cardinal Health Inc. His strategic acumen and negotiation skills helped drive Medtronic’s growth and market expansion. Before joining Medtronic, Chris was the CEO of Alesia Capital Services, a management consulting firm for Fortune 500 companies, including Medtronic, Goldman Sachs, Ally, Macquarie Capital and Terex. He also led M&A teams within several businesses at GE Capital, closing acquisitions totaling more than $60 billion across 200+ transactions in the US, Canada, Europe, Asia and Latin America. Mr. Cleary also currently serves on the Board of Enterra Medical, Inc., and Pristine Surgical LLC. Mr. Cleary earned his B.A. in Biology from Colorado College. After seven years of dedicated service on Orchestra BioMed’s Board of Directors, Eric A. Rose, M.D. will transition to Board Member Emeritus and Strategic Advisor to Orchestra BioMed. This new role will allow Dr. Rose to continue contributing his wealth of industry expertise, supporting key initiatives and long-term objectives. His leadership has been instrumental in helping shape the Company’s growth and will remain a valuable asset in this advisory capacity. 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 atrioventricular interval modulation (AVIM) therapy for the treatment of hypertension, a significant risk factor for death worldwide. Orchestra BioMed is also developing the Virtue® Sirolimus AngioInfusion™ Balloon (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. 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. 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 a similar target population of patients who have been indicated for, and recently implanted with, a dual-chamber cardiac pacemaker. 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 potential efficacy, safety and commercial value of the Company’s commercial product candidates, the ability of the Company’s partnerships to accelerate clinical development, and the Company’s late-stage development programs and strategic partnerships. 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 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, 2023, which was filed with the U.S. Securities and Exchange Commission on March 27, 2024, as updated by any risk factors disclosed under the heading “Item 1A. Risk Factors” in the Company’s subsequently filed quarterly reports on Form 10-Q. 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 (908) 723-4489 Snewcomb@orchestrabiomed.com Media ContactKelsey Kirk-EllisOrchestra BioMed(484) 682-4892Kkirkellis@orchestrabiomed.com

NEW HOPE, Pa., July 30, 2024 (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 appointment of John Mack to its Board of Directors, effective as of July 29, 2024. Mr. Mack brings over 30 years of medical device, healthcare technology, and finance experience to the Company. Mr. Mack most recently served as President of Cardiac Surgery at Medtronic plc., where he successfully led the division to market leadership. During his tenure at Medtronic, he also served as Vice President & General Manager, Extracorporeal Therapies and Vice President, Business Development, Strategy & Portfolio Management where he led the business development operations for the coronary and structural heart business, a $3.2B global enterprise with over 12,000 employees.