Atherosclerotic occlusive disease

Novel bioresorbable scaffold system being developed for expanded indications LOS ALTOS, Calif., Feb. 14, 2024 /PRNewswire/ -- Efemoral Medical, developer of advanced interventional bioresorbable therapies, today announced that the United States Food & Drug Administration (FDA) has granted its novel Efemoral Vascular Scaffold System (EVSS) Breakthrough Device status for the treatment of de novo or restenotic lesions of the infrapopliteal arteries in patients with Chronic Limb Threatening Ischemia (CLTI). Continue Reading The Efemoral Vascular Scaffold System (EVSS) offers a new approach to treating peripheral arterial occlusive disease (PAOD) by addressing the specific anatomic challenges and complex biomechanics of patients with athero-occlusive disease in the leg. Using multiple, serial, intravascular scaffolds, the patented FlexStep Technology combines flexibility with support to open clogged vessels and sustain healthy blood flow while accommodating tortuosity and skeletal movement. Formulated with sirolimus antiproliferative drug elution, the bioresorbable scaffolds restore normal vessel diameter at the time of the procedure, deliver therapeutic benefits across all lesion lengths and morphologies, and maintain durable patency while leaving no permanent implant behind. The device designed for above-the-knee (femoropopliteal) intervention is currently being tested in a first-in-human trial, EFEMORAL I, in investigative sites in New Zealand and Australia. Encouraged by the early clinical results, Efemoral Medical is now developing an additional device for treating below-the-knee (infrapopliteal) arteries in patients with CLTI. "FDA has recognized the potential of the EVSS to benefit these patients by granting Breakthrough Device status" Post this "Diseased human arteries are most simply, reliably, and successfully treated with drug-eluting, balloon-expandable stents," said Lewis B. Schwartz, MD, Co-Founder and CMO of Efemoral Medical, "however, it is extremely challenging to implant these permanent devices in the long and twisting arteries of the lower extremities. The EVSS uses a unique design of alternating, dissolvable, drug-eluting scaffolds that, for the first time, allows the long arteries of the legs to be treated with the same, effective, drug-eluting technology proven to be successful in multiple other vascular beds." The Breakthrough Devices Program is reserved for novel medical technologies that potentially provide for more effective diagnosis and/or treatment of life-threatening or irreversibly debilitating diseases. It is intended for patients to enjoy more timely access to novel devices by expediting their development, assessment, and review. Vascular disease of the lower extremities, known as "peripheral arterial occlusive disease" (PAOD), is a virtual epidemic, afflicting approximately 10% of the global population over the age of 50 and 20% of the population over the age of 70.1 Symptomatic PAOD causes poor physical health, loss of mobility and independence, decreased quality of life, premature functional decline and early mortality.2 An estimated 10% of patients with PAOD have its most severe form: chronic limb-threatening ischemia (CLTI). CLTI arises when the lesions of PAOD have become so numerous and severe that the blood flow to the foot is inadequate to sustain its viability. Only about half of all diagnosed patients will be alive after six months, and only about half of the survivors will have intact limbs. Given this dismal outcome, the prognosis of CLTI is worse than most cancers.3,4 "PAOD has a significant negative impact on the health of as many as 20 million Americans," said Christopher Haig, Co-Founder and CEO of Efemoral Medical.5 "It is especially devastating for those 10% of patients suffering from its most severe form, CLTI. We are extremely gratified that the FDA has recognized the potential of the EVSS to benefit these patients by granting Breakthrough Device status to our device." About Efemoral Medical, Inc. Efemoral Medical, Inc. is developing next-generation bioresorbable solutions to treat patients with vascular disease. The company's initial product, the Efemoral Vascular Scaffold System (EVSS) with FlexStep Technology, is designed to offer a dedicated strategy for PAOD interventions. The Efemoral Vascular Scaffold System (EVSS) is an OUS Investigational Device only. To learn more, please visit efemoralmedical.com. 1 Eid MA, Mehta K, Barnes JA, Wanken Z, Columbo JA, Stone DH, et al. The global burden of peripheral artery disease. J Vasc Surg. 2023;77:1119-26. 2 McDermott MM, Liu K, Ferrucci L, Tian L, Guralnik JM, Liao Y, et al. Decline in functional performance predicts later increased mobility loss and mortality in peripheral arterial disease. J Am Coll Card. 2011;57:962-70. 3 Engelhardt M, Boos J, Bruijnen H, Wohlgemuth W, Willy C, Tannheimer M, et al. Critical limb ischaemia: Initial treatment and predictors of amputation-free survival. Eur J Vasc Endovasc Surg. 2012;43:55-61. 4 Mustapha JA, Katzen BT, Neville RF, Lookstein RA, Zeller T, Miller LE, et al. Determinants of long-term outcomes and costs in the management of critical limb ischemia: A population-based cohort study. J Am Heart Assoc. 2018. DOI: 10.1161/JAHA.118.009724. 5 Eid MA, Mehta K, Barnes JA, Wanken Z, Columbo JA, Stone DH, et al. The global burden of peripheral artery disease. J Vasc Surg. 2023;77:1119-26. SOURCE Efemoral Medical

Orchestra BioMed and Medtronic, Inc., have an exclusive strategic collaboration for development and commercialization of AVIM therapy for hypertensive pacemaker population, which is estimated to be more than 750,000 patients annually worldwide NEW HOPE, Pa., Jan. 08, 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 first patient was randomized in the BACKBEAT pivotal study in late December 2023. The BACKBEAT pivotal study will evaluate the efficacy and safety of atrioventricular interval modulation (“AVIM”) therapy (also known as BackBeat CNT™), for the treatment of pacemaker-indicated patients with uncontrolled hypertension despite the use of antihypertensive medications. AVIM therapy is an investigational patented bioelectronic therapy, administered using a standard dual-chamber pacemaker, designed to immediately, substantially and persistently reduce blood pressure. Orchestra BioMed and Medtronic, Inc. (NYSE: MDT) (“Medtronic”) formed a strategic collaboration for the development and commercialization of AVIM therapy for hypertensive pacemaker patients in July 2022. If approved, Medtronic will have exclusive global rights to commercialize AVIM-enabled pacing systems for this target population, and Orchestra BioMed will share in the revenues generated from Medtronic sales of the AVIM-enabled pacing systems. “Our collaboration with Orchestra BioMed will explore how cardiac pacing can go beyond management of bradycardia and conduction disease to treat hypertension as well,” said Robert C. Kowal, M.D., Ph.D., vice president and general manager of Cardiac Pacing Therapies within the Medtronic Cardiac Rhythm Management operating unit. “Our goal is to deliver the best possible outcomes for patients; this study will help us understand the potential role of AVIM therapy in treating hypertension, a major source of cardiovascular illness and a comorbidity in more than 70% of patients receiving pacing therapy.” Suman Pasupuleti, M.D., from Citrus Cardiology Consultants, the first site to randomize a patient in the BACKBEAT pivotal study, commented: “Blood pressure management with currently available treatments is especially challenging in many elderly patients who also are prone to side effects from medications. This leaves a gap in the care of these patients and increases their risk for heart attack, stroke and heart failure progression. We are excited to be among the first to enroll patients in the BACKBEAT study, which will evaluate the efficacy and safety of this therapy in patients with high blood pressure who also need pacemakers.” “We are thrilled to announce the initiation of the BACKBEAT pivotal study. This is an essential milestone as we evaluate how this therapy may benefit pacemaker patients who confront the mortality and morbidity risks of elevated blood pressure,” commented David Hochman, chairman, chief executive officer and founder of Orchestra BioMed. “We have activated multiple clinical sites and are screening patients in the U.S. and Europe. We are grateful to the clinical sites, our team and Medtronic for their dedication to finalizing all the study initiation deliverables. Most importantly, we are thankful to the patients who will participate in this landmark study.” The BACKBEAT pivotal study is a global, multi-center, prospective, randomized, double-blind study investigating the efficacy and safety of AVIM therapy in patients who have recently undergone implantation of a Medtronic dual-chamber cardiac pacemaker and have uncontrolled hypertension despite the use of antihypertensive medications. Orchestra BioMed is actively screening patients for enrollment in the BACKBEAT pivotal study. Site activations are expected to continue throughout 2024 with a target of activating approximately 80 centers in the U.S. and Europe. The study will randomize approximately 500 patients 1:1 to AVIM therapy combined with continued medical therapy (treatment) or continued medical therapy and standard pacing alone (control). The study’s primary efficacy endpoint will determine at three months post-randomization whether AVIM-treated patients experience a statistically significant reduction in daily average blood pressure (mean 24-hour ambulatory systolic blood pressure or “aSBP”) as compared to control patients. The primary safety endpoint will determine at three months post-randomization whether AVIM-treated patients experience serious adverse device effects that are not anticipated with cardiac pacing. Double-blind follow up will continue through 12 months to enable the collection of additional clinical endpoints. All patients will be eligible to cross over upon completion of the 12-month blinded follow-up phase. The BACKBEAT pivotal study investigational device exemption (“IDE”) was supported by encouraging results from MODERATO II, a prospective, multi-center, randomized, double-blind, pilot study of pacemaker patients with persistent hypertension conducted in Europe. MODERATO II showed that patients treated with AVIM therapy experienced net reductions of 8.1 mmHg in 24-hour aSBP and 12.3 mmHg in office systolic blood pressure (oSBP) at six months when compared to control patients. There were no major adverse cardiac events in the treatment group, compared to three events in three patients in the control group (0.0% vs. 14.3%).1 More information on the BACKBEAT pivotal study can be found at: https://clinicaltrials.gov/study/NCT06059638. About Hypertension and the Risk of High Blood Pressure in the Pacemaker Population Hypertension (“HTN”) is characterized by elevated blood pressure which increases the force of blood pushing against blood vessels, requiring the heart to work harder and consume more oxygen. HTN accelerates the progression of atherosclerosis and leads to increased risk of major cardiac events like heart attack, heart failure, kidney disease and other end organ damage. HTN is the leading global risk factor for death, affecting an estimated 1.28 billion adults worldwide. In the United States, 122 million adults, or approximately 47% of all adults, are estimated to have HTN. While many patients do not notice high blood pressure, cardiovascular risk doubles for every 10 mmHg increase in systolic blood pressure and the mortality rate doubles with an increase of 20 mmHg in systolic blood pressure.2 It is estimated that more than 70% of the approximately 1.1 million people globally who are implanted with cardiac pacemakers each year are also diagnosed with HTN. Based on updated American College of Cardiology/American Heart Association guidelines, an even higher percentage (approximately 80%) of U.S. patients that are indicated for the implant of a pacemaker have HTN. Pacemaker patients tend to be elderly and are more likely to suffer from co-morbidities such as atherosclerosis, hyperlipidemia, diabetes mellitus and chronic kidney disease, and harder to treat effectively with medical therapy for many reasons including co-morbidities and a high prevalence of isolated systolic HTN. About AVIM Therapy (BackBeat CNT™) 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 global IDE pivotal BACKBEAT (BradycArdia paCemaKer with atrioventricular interval modulation for Blood prEssure treAtmenT) 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 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, 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. Orchestra BioMed has additional product candidates and plans to potentially expand its product pipeline through acquisitions, strategic collaborations, licensing and organic development. For further information about Orchestra BioMed, please visit www.orchestrabiomed.com, and follow us on LinkedIn and X (formerly Twitter). 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 enrollment, timing, implementation and design of the BACKBEAT pivotal study, the potential efficacy and safety 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, 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; failure to realize the anticipated benefits of the business combination; risks related to regulatory approval of the Company’s product candidates; 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 quarterly report on Form 10-Q filed with the U.S. Securities and Exchange Commission on May 12, 2023, 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. References: The formal final Data Safety Monitoring Board report for MODERATO II included a revised major adverse cardiac event rate in the control group from 9.5% to 14.3% to reflect another event of heart failure in a third control patient after publication of the study results. This report was provided to the FDA.Benjamin EJ, Blaha MJ, Chiuve SE, et al., Heart Disease and Stroke Statistics – 2017 Update: A Report from the American Heart Association. Circulation. 2017; 135: e146. Investor Contact:Bob YedidLifeSci Advisors(516) 428-8577Bob@lifesciadvisors.com Media Contact:Kelsey Kirk-EllisOrchestra BioMed(484) 682-4892Kkirkellis@orchestrabiomed.com

U.S. FDA granted Investigational Device Exemption (“IDE”) approval to initiate the BACKBEAT pivotal study evaluating AVIM therapy (BackBeat CNT) in hypertensive pacemaker patientsBACKBEAT pivotal study on track to start enrollment before the end of 2023, with a mid-2025 target for completion of enrollment Expected operating cash runway sufficient into 2H 2026, beyond anticipated BACKBEAT top-line results readout, based on internal forecastFDA also granted conditional IDE approval for pivotal study of Virtue® SAB in coronary in-stent restenosis (“ISR”) patients; Virtue ISR-US study initiation targeted for 2024, pending Terumo partnership restructuring NEW HOPE, Pa., Nov. 13, 2023 (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 reported its third quarter 2023 financial results and provided a business update. “This past quarter marked two major regulatory milestones for Orchestra BioMed, with the FDA granting IDE approval for pivotal studies for both BackBeat CNT (AVIM therapy) and Virtue SAB. We are excited to initiate enrollment of the BACKBEAT pivotal study imminently, taking a critical step closer to enabling Medtronic, our strategic partner, to deliver this highly innovative blood pressure treatment to patients,” stated David Hochman, Chairman, Chief Executive Officer and Founder of Orchestra BioMed. “We believe the design of the BACKBEAT pivotal study positions us to report topline data from this landmark study within the timeframe of our anticipated operating cash runway.” “We are actively engaged with our colleagues at Terumo with the goal of updating our Virtue SAB strategic agreement and aligning our plans to advance this differentiated technology through pivotal studies and to the market,” Mr. Hochman continued. “As the only non-coated balloon angioplasty system that enables protected delivery of extended release sirolimus directly to target arterial lesions, Virtue SAB has the potential to redefine the class of drug-eluting balloons, which are emerging as a preferred solution for the treatment of coronary artery disease.” Lead Program BackBeat CNTTM (atrioventricular interval modulation (AVIM) therapy): large global opportunity for treating hypertension in targeted populations Dual-chamber pacemaker-indicated patients with uncontrolled hypertension despite the use of antihypertensive medications BACKBEAT pivotal study evaluating the efficacy and safety of AVIM therapy in hypertensive pacemaker patients on track to start by the end of 2023.Study to enroll up to 500 patients across approximately 80 sites globally, with a target for completion of enrollment in mid-2025. High-risk hypertension (non-pacing) and heart failure patients Orchestra BioMed continues to explore future opportunities to utilize AVIM therapy for high-risk, older patients with hypertension and co-morbidities that are not already indicated for a pacemaker, as well as to develop cardiac neuromodulation therapy specifically for the treatment of heart failure (CNT-HF). Pipeline Program Virtue® Sirolimus AngioInfusionTM Balloon (SAB): large global opportunity for treatment of coronary and peripheral artery disease with differentiated “leave nothing behind” solution Virtue SAB – Coronary Indications U.S. Food and Drug Administration (“FDA”) granted IDE approval with conditions to initiate Virtue ISR-US pivotal study evaluating Virtue SAB in adult patients with coronary ISR.Initiation of Virtue ISR-US study targeted for 2024 pending ongoing negotiations with Terumo to restructure existing strategic partnership agreement.Planned Japanese Pharmaceutical and Medical Devices Agency submissions are on track to support Japanese registrational studies of Virtue SAB in coronary ISR and coronary small vessel disease. Financial Results for the Third Quarter Ended September 30, 2023 Cash and cash equivalents and Marketable securities totaled $108.5 million as of September 30, 2023.Operating cash runway extended into the second half of 2026 based on internally prepared forecast reflecting updated operating priorities.Net cash used in operating activities and for the purchase of fixed assets was $10.3 million during the third quarter of 2023, compared with $7.5 million for the same period in 2022, with the primary drivers of increased spending being costs associated with preparation for the initiation of the BACKBEAT pivotal study as well as expenses associated with being a public company.Revenue for the third quarter of 2023 was $0.4 million, compared with $1.2 million for the same period in 2022. The decrease was primarily due to decreased recognition of partnership revenues earned under the agreement with Terumo.Research and development expenses for the third quarter of 2023 were $8.6 million, compared with $5.9 million for the same period in 2022. The increase was primarily due to additional costs associated with preparation for the initiation of the BACKBEAT pivotal study.Selling, general and administrative expenses for the third quarter of 2023 were $6.3 million, compared with $5.3 million for the same period in 2022. The increase was primarily due to additional personnel costs, legal, insurance and finance costs, and additional costs related to being a public company.Net loss for the third quarter of 2023 was $13.3 million, or $0.38 per share, compared with a net loss of $10.3 million, or $0.51 per share, for the same period in 2022. Net loss for the third quarter of 2023 included non-cash stock-based compensation expense of $3.5 million, compared with $2.2 million for the same period in 2022. 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 flagship product candidate is atrioventricular interval modulation (AVIM) therapy (also known as BackBeat Cardiac Neuromodulation Therapy CNT™) 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. Orchestra BioMed has additional product candidates and plans to potentially expand its product pipeline through acquisitions, strategic collaborations, licensing, and organic development. For further information about Orchestra BioMed, please visit www.orchestrabiomed.com, and follow us on LinkedIn and X (formerly Twitter). 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 (BackBeat CNT™) 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 IDE-approved global pivotal BACKBEAT (BradycArdia paCemaKer with atrioventricular interval modulation for Blood prEssure treAtmenT) 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 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. The FDA granted IDE approval to initiate the Virtue ISR-US study to evaluate this novel treatment in coronary ISR patients. 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 and timing of the Company’s planned pivotal trials and reporting of top-line results, realizing the clinical and commercial value of BackBeat CNT and Virtue SAB, the expected runway of the Company’s current cash and cash equivalents, the potential efficacy of the Company’s product candidates, the ability of the Company’s partnerships to accelerate clinical development, the Company’s late-stage development programs, strategic partnerships and plans to expand its product pipeline, and the Company’s ability to negotiate mutually agreeable adjustments to its current agreements with Terumo. 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; failure to realize the anticipated benefits of the business combination; risks related to regulatory approval of the Company’s product candidates; 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 quarterly report on Form 10-Q filed with the U.S. Securities and Exchange Commission on November 13, 2023 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. ORCHESTRA BIOMED HOLDINGS, INC.Condensed Consolidated Balance Sheets(in thousands, except share and per share data)(Unaudited) September 30, December 31, 2023 2022ASSETS CURRENT ASSETS: Cash and cash equivalents $19,078 $19,784 Marketable securities 89,410 63,915 Strategic investments, current portion 362 86 Accounts receivable, net 86 96 Inventory 137 276 Prepaid expenses and other current assets 1,116 533 Total current assets 110,189 84,690 Property and equipment, net 1,355 1,489 Right-of-use assets 1,714 2,187 Strategic investments, less current portion 2,495 2,495 Deposits and other assets 604 4,711 TOTAL ASSETS $116,357 $95,572 LIABILITIES AND STOCKHOLDERS’ EQUITY CURRENT LIABILITIES: Accounts payable $3,150 $3,968 Accrued expenses and other liabilities 4,301 5,376 Operating lease liability, current portion 747 697 Warrant liability — 2,089 Deferred revenue, current portion 3,676 6,436 Loan payable, current portion 9,599 — Total current liabilities 21,473 18,566 Deferred revenue, less current portion 13,845 13,103 Loan payable, less current portion — 9,490 Operating lease liability, less current portion 1,117 1,683 Other long-term liabilities 266 196 TOTAL LIABILITIES 36,701 43,038 STOCKHOLDERS’ EQUITY Preferred stock, $0.0001 par value per share; 10,000,000 shares authorized; none issued or outstanding at September 30, 2023 and December 31, 2022. — — Common stock, $0.0001 par value per share; 340,000,000 shares authorized; 35,743,972 and 20,187,850 shares issued and outstanding as of September 30, 2023 and December 31, 2022, respectively. 4 2 Additional paid-in capital 315,765 252,274 Accumulated other comprehensive loss (77) (8)Accumulated deficit (236,036) (199,734)TOTAL STOCKHOLDERS’ EQUITY 79,656 52,534 TOTAL LIABILITIES AND STOCKHOLDERS’ EQUITY $116,357 $95,572 ORCHESTRA BIOMED HOLDINGS, INC.Condensed Consolidated Statements of Operations and Comprehensive Loss(in thousands, except share and per share data)(Unaudited) Three Months Ended September 30, 2023 2022 Revenue: Partnership revenue $271 $986 Product revenue 148 177 Total revenue 419 1,163 Expenses: Cost of product revenues 41 56 Research and development 8,558 5,899 Selling, general and administrative 6,344 5,275 Total expenses 14,943 11,230 Loss from operations (14,524) (10,067)Other income (expense): Interest income, net 915 63 Gain on fair value adjustment of warrant liability — 36 Loss on debt extinguishment — — Gain (loss) on fair value of strategic investments 293 (314)Total other income (expense) 1,208 (215)Net loss $(13,316) $(10,282)Net loss per share Basic and diluted $(0.38) $(0.51)Weighted-average shares used in computing net loss per share, basic and diluted 35,243,598 20,187,773 Comprehensive loss Net loss $(13,316) $(10,282)Unrealized loss on marketable securities 19 — Comprehensive loss $(13,297) $(10,282) Investor Contact:Bob YedidLifeSci Advisors(516) 428-8577Bob@lifesciadvisors.com Media Contact:Kelsey Kirk-EllisOrchestra BioMed(484) 682-4892Kkirkellis@orchestrabiomed.com