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Orchestra BioMed Corporate Overview February 2026 Nasdaq: OBIO
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Forward-Looking Statements This presentation has been prepared for informational purposes only from information supplied by Orchestra BioMed Holdings, Inc., referred to herein as “we,” “our,” “Orchestra BioMed,” and “the Company,” and from third-party sources indicated herein. Such third-party information has not been independently verified. Orchestra BioMed makes no representation or warranty, expressed or implied, as to the accuracy or completeness of such information. Certain statements included in this document 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 safety and efficacy of our product candidates, the initiation, enrollment and timing of our planned pivotal trials and reporting of top-line results, expected market sizes for our product candidates, the ability of our partnerships to accelerate clinical development and the benefits of Breakthrough Device Designation. These statements are based on various assumptions, whether or not identified in this document, 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; 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 filed with the U.S. Securities and Exchange Commission on March 31, 2025 as updated by any risk factors disclosed under the heading “Item 1A. 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 presentation. The Company does not plan and undertakes no obligation to update any of the forward-looking statements made herein, except as required by law. 2 | Corporate Overview February 2026
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Orchestra BioMed 2026 Vision Leveraging Partnerships to Bring Innovation to Patients & Yield Exceptional Future Profitability Actively Enrolling Pivotal Trials for Two High - Impact Proprietary Programs: AVIM Therapy and Virtue SAB Targeting Major Cardiovascular Indications in Large, Established Global Markets with Unmet Clinical Need Partnership - Driven Commercialization with Substantial Royalty - Based Revenue Model Funded Through Completion of Enrollment in Both Pivotal Trials and AVIM Therapy Primary Endpoint Data Readout 3 | Corporate Overview February 2026
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Two Pivotal Trial-Stage Flagship Technologies Targeting Major Global Unmet Needs in Cardiovascular Disease 4 | Corporate Overview February 2026 >$17 billion Annual global hypertensive heart disease market opportunity • Patented therapy delivered as pacemaker firmware enhancement, designed to drive immediate, substantial and sustained blood pressure reduction • Actively enrolling BACKBEAT Global Pivotal Trial for uncontrolled hypertension in pacemaker-indicated patients • Granted FDA Breakthrough Device Designation for uncontrolled hypertension in patients with increased cardiovascular risk* >$10 billion Annual global atherosclerotic artery disease Market opportunity • First-of-its-kind non-coated drug delivery system designed to deliver large liquid dose of proprietary extended-release SirolimusEFR during angioplasty • Actively enrolling the US pivotal Virtue Trial randomizing vs. Boston Scientific's AGENT paclitaxel-coated balloon • Granted FDA Breakthrough Device Designation for the treatment of coronary ISR, coronary small vessel disease and below-the-knee peripheral artery disease Strategic Collaboration Strategic Rights Agreement AVIM Therapy Cardiac pacing-based hypertensiontreatment Virtue SAB Extended-release sirolimus treatment for artery disease *Th e U.S. FDA granted Breakthrough Device Designation fo r an imp lan tab le system (i.e., a p acemaker) to d eliver AVIM Therapy using cond uction system p acing to redu ce blo od p ressure in p atients with increased ten-year athero sclero tic cardio vascu lar disease risk, preserv ed left ventricular systo lic function, and un co ntrolled hy perten sion, despite the use of an ti-hyp erten siv e medicatio ns or in patien ts w ho may h ave in to lerance to an ti-hypertensive med ications.
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Recent Accomplishments and Expected 2026-2027 Major Catalysts 5 AVIM Therapy ✓ Received broad FDA Breakthrough Device Designation for uncontrolled hypertension in patients with increased CV risk ✓ Updated BACKBEAT global pivotal studyprotocol to significantly expand eligibility o Complete BACKBEA T study enrollment o BACKBEAT study primary efficacy & safety data readout Virtue SAB ✓ Secured FDA IDE clearance and launched the Virtue Trial in coronary ISR ✓ Entered into newstrategic rights (ROFR) agreement with Terumo o Complete Virtue Trial study enrollment Corporate ✓ Secured cash runway into Q4 2027 primarily through strategic transactions with Medtronic, Ligand, and T erumo ✓ Received initial tranche of cash proceeds (up to $21M expected) from Haemonetics’ acquisition of Vivasure Medical o Receive $35 million in committed tranche payments from Medtronic and Ligand | Corporate Overview February 2026
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Expert Leadership, Proven Impact 300+ Combined years in the industry experience 25+ Average years of experience, bringing deep expertise to every challenge 100+ Successful product approvals, delivering innovation globally 600+ Authored patents shaping the future of healthcare Our leadership team is highly experienced, has a successful track record of bringing high-impact medical technologies to market, and includes individuals who have worked together for years Independent Board Members Jason Aryeh Pamela Connealy Chris Cleary Eric S. Fain, M.D. David Pacitti John Mack 4 | Corporate Overview February 2026
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AVIM Therapy 7 | Corporate Overview February 2026 A purpose-built solution for uncontrolled hypertension with increased cardiovascular risk Designed to drive immediate, substantial, and sustained blood pressure reduction Supported by robust clinical and mechanistic data
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>$17 Billion Annual Global Opportunity AVIM Therapy Addresses a Large & Clearly Targeted Global Opportunity HTN & Pacemaker ~70% of pacemaker patients 1 750,000 highly addressable patients >$2 Billion HTN with Increased CV Risk / HFpEF ~0.3% of HTN patients 3,700,000 highly addressable patients >$15 Billion FDA Breakthrough Designation for beachhead market and beyond Same patients, device implant, and treating physicians Existing reimbursement structure Uncontrolled HTN in older, higher-risk patients drives MI, stroke and heart failure Similar treatment challenges as pacemaker patients with increased cardiovascular risk Potential benefit in HFpEF *Total addressable market in 2025 based on company estimates 1Company estimates based on published sources, including National Inpatient Survey (NIS) and National Health and Nutrition Examination Survey (NHANES); Definition: Hypertension (HTN) 8 | Corporate Overview February 2026 While hypertension is the leading global risk factor for death, affecting 1.2B patients worldwide, older, higher-risk patients face hypertensive heart disease, which directly drives increased risk of MI, stroke and heart failure.
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Developed AVIM Therapy fromconcept stage Owns all related intellectual property: 120 issued global patents related to hypertension Conducted all prior development and theMODERATO I & II clinical studies Sponsor for the BACKBEAT Global Pivotal Study Global market leader in cardiac pacing therapy: >$2B in annual revenues Integrated AVIM Therapy for download into premium commercial pacemakers for the BACKBEAT study Exclusive global commercial rights for pacemaker-indicated HTN patients; recent expansion for future leadless pacemakers Right of first negotiationto expand global rights for the treatment of non-pacemaker patients with HTN 1 Amount is based on higher of (1) a fixed dollar amount per device (amount varies materially on a country -by-county basis) or (2) a percentage of sales AVIM Therapy Strategic Collaboration with Medtronic $61.6M equity investment plus $20 million strategic capital commitment $500 - $1,600 revenue share per AVIM-enabled device assuming existing reimbursement structures1 9 | Corporate Overview February 2026
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AVIM Therapy is a Novel Investigational Treatment for Uncontrolled Hypertension AVIM On Systolic BP (mmHg) Short AV intervals: Reduce cardiac preload, immediately lowering blood pressure Intermittent longer AV intervals: modulate autonomic nervous system response (baroceptor reflex) and reduce afterload (total peripheral resistance), sustaining blood pressure reduction AVIM Off 1Kalarus et al. Journal of the American Heart Association. 2021;10:e020492ahajournals.org/doi/10.1161/JAHA.120.020492. 2Kuck, Hemodynamics Effects of AVIM Therapy, Technology and Heart Failure Therapeutics Meeting 2024 Definitions: AV (Atrioventricular), RV (Right Ventricular) Novel & Potent Mechanism Independent of lead position : compatible with traditional RV pacing or conduction system pacing 30 Sec Utilizes well-characterized physiologic mechanisms (Frank -Starling) to favorably impact circulatory hemodynamics 2: • Reduces intra-cardiac volumes and pressures • Improves cardiovascular efficiency • No adverse impact on contractility Designed to Have an Immediate, Substantial, and Sustained Effect1 10 | Corporate Overview February 2026
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Substantial -11.1 mmHg Reduction in 24-Hour aSBP at 6 months Sustained -17.5 mmHg Reduction in oSBP at 2 years 0% Major Adverse Cardiac Events vs. 14.3% in control group at 6 months5 AVIM Therapy showed encouraging results in MODERA TO II, a prospective, multi-center, randomized, controlled, double-blind, pilot study of pacemaker patients with uncontrolled hypertension despite medical therapy2,3 MODERATO II Randomized, Double-Blind Results Significant Reduction in Systolic Blood Pressure (SBP) Control (n=20)4 AVIM Therapy (n=26) 6 Months 24 Months 24-Hour Ambulatory SBP (aSBP) Office SBP (oSBP) 6 Months 0 -5 -10 -15 -20 -11.1 P < 0.001 -12.4 P < 0.001 -0.1 P = 0.94 -17.5 P < 0.01 Δ in BP (mmHg) -3.1 P =0.17 -15.6 P < 0.001 -1.5 P = 0.5 1 day Δ -14.1 p = 0.001 Δ -8.1 p = 0.01 Δ -12.3 p = 0.02 1Ettehad et al. Lancet . 2016;387(10022):957 –967. doi:10.1016/S0140 -6736(15)01225 -8. 2Kalaras et al. Journal of the American Heart Associat ion. 2021;10:e020492 ahajournals.org/ doi/10.1161/JAHA.120.020492; 3Burkhoff MODERATO II Study 2 -Year Results TCT 2021; 424-Hr aSBP Control (n=19), 1 control patient could not be measured despite repeat measurement (patient had extremely high blood pressure); 5A blinded evaluation Dat a Safety Monitoring Board report for MODERATO II included a revised MACE rate, from 9.5% t o 14.3%, in the control group to reflect a heart failure after publication of the study results. Definitions : Major Adverse Cardiac Event s (MACE) included death, heart failure, clinically significant arrhythmias (i.e., persist ent or increased atrial fibrillation, serious ventricular arrhythmias), myocardial infarction, stroke and renal failur e in treatment group calculated per patient. 11 | Corporate Overview February 2026 Reductions of 10 mmHg in oSBP decrease the relative risk of major cardiovascular events and conditions by over 20%1
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Favorable Impact on Hypertensive Heart Disease Clinical data demonstrate AVIM Therapy can reduce pulse pressure, improve diastolic dysfunction and induce reverse remodeling in older, higher-risk patients 1Burkhoff MODERATO II Study 2-Year Results TCT 2021. 2Vaccarino V, et al. Am J Cardiol. 2001 3N=14 AVIM therapy and n=11 control group. 4Fudim M, THT’25. Definitions: aSBP (ambulatory Systolic Blood Pressure), oSBP (Office Systolic Blood Pressure), LV (Left Ventricular), PV (Pressure Volume), M (Months). LVEF (Left Ventricular Ejection Fraction), NYHA (New York Heart Association), SBP (Systolic Blood Pressure). AVIM Therapy Induced Reverse Remodeling in Noninvasive PV Loop Study 1,3 AVIM Therapy Induced Reverse Remodeling Control Group Developed Ventricular Remodeling Significant Reduction in Challenging -To-Treat Isolated Systolic Hypertension (ISH) 1 − 9.5 mmHg in 24-Hour aSBP at 6 months − 15.8 mmHg in oSBP at 2 years − 9.6 mmHg ∆ in Ambulatory PP at 6 months − 13.9 mmHg ∆ in Office PP at 2 years >88% of AVIM Therapy patients in MODERATO II had ISH Improved Diastolic Dysfunction (DD) In Echocardiographic Analysis 4 AVIM therapy significantly reduced SBP in patients with and without DD AVIM therapyimproved myocardial relaxation and improved diastolic compliance (significantly increased e’ and E/A) Retrospective, treatment -blinded analysis of core lab echocardiograms from MODERATO II, hypertensive pacemaker patients with LVEF ≥ 50% and NYHA class < II, with independent blinded adjudication >61% of AVIM Therapy patients in MODERATO II had DD Increased PulsePressure (PP) an independent risk factor for heart failure & stroke2 12 | Corporate Overview February 2026
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The BACKBEAT Study – Global Pivotal Hypertension Trial Designed to Secure Regulatory Approval & Showcase Novel Approach to Blood Pressure Management Primary Efficacy Endpoint Mean change in 24-hour aSBP at 3-months Randomized, prospective, multi- center, double-blind, controlled trial Up to 500 patients across 130 sites in U.S., EU & APAC countries Actively enrolling trial participants Patients previously implanted with or indicated for a Medtronic Astra or Azure dual- chamber pacemaker who have uncontrolled hypertension despite 1 -3 anti-HTN medications AVIM Therapy download & setup R AVIM Therapy + Medical Therapy Medical Therapy 13 | Corporate Overview February 2026 Primary Safety Endpoint Freedom from unanticipated serious adverse device events at 3 months Secondary Endpoints Efficacy and safety endpoints after 12-month follow-up
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Virtue SAB 14 | Corporate Overview February 2026 First-of-its-kind drug delivery system featuring proprietary extended-release SirolimusEFR and non- coated, microporous balloon Designed to provide protected delivery of gold standard drug to the artery during angioplasty and maintain required drug levels through critical healing period Supported by best-in-class pilot clinical data and robust preclinical pharmacokinetic data
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Virtue SAB Offers Key Potential Advantages In Large, Established Global Market Opportunity Coronary ~3,700,000 patients >$7.5 Billion Peripheral ~1,250,000 patients >$2.5 Billion >$10 Billion Annual Global Opportunity 1Total addressable market in 2025 based on company estimates; Definitions: Coronary Artery Disease (CAD), Peripheral Artery Disease (PAD); Drug -eluting balloon (DEB), Drug -coated balloon (DCB), Paclitaxel -coated balloon (PCB) 15 | Corporate Overview February 2026 New significant clinical evidence supports DEBs as non-inferior to drug-eluting stents for de novo coronary disease , reinforcing potential advantages of “leave-nothing- behind” treatment strategies All current DEBs are drug coated balloons (DCB) predominantly using paclitaxel Multibillion dollar market for additional potential vascular indications AGENT PCB U.S. commercialization indicating positive sales growth Enhanced reimbursement supports highly attractive U.S. commercial opportunity Rapidly unfolding paradigm shift to “leave-nothing-behind” treatment with drug-eluting balloons (DEB) creates high-growth opportunity in large $10B established market1
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Compelling Opportunity For Virtue SAB Coatings have challenges, such as limited dosing, risk of emboli from large particulates, and drug loss in transit A Novel Solution is Required to Realize Advantages of Sirolimus 1Xinlin Zhang, et. al. PLOS ONE 2014 May 20;9(5):e97934 Superiority of sirolimus safety and efficacy over paclitaxeldemonstrated in large meta-analysis of 76 drug-eluting stent studies including 26 RCTs1 Sirolimus requires extended release through the critical healing period to achieve full benefits (~30 days of >1ng/mg tissue concentration) Paclitaxel became “drug of choice” for coated balloons because it is easier, not better(fast tissue absorption and long tissue retention) + Protected Delivery of Extended Release Sirolimus SirolimusEFR Microporous AngioInfusion Balloon 16 | Corporate Overview February 2026
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Protected Delivery of Extended Release Sirolimus Virtue® SAB – Optimal Drug, Dose and Delivery 1Granada et al. EuroIntervention 2016;12:740 -747. 2 Animals included in the analysis of distant organs received average dose of 20.4 mg ≈10X the largest clinical dose SirolimusEFR Microporous AngioInfusion Balloon Large Liquid Dose Loaded and Protected in Dose Unit Delivered Through the Micropores During Inflation NO coating = NO drug loss in transit, NO rush and NO large particulate 1000 100 10 1 0.1 0.01 0.001 0.0001 2Lung, liver & kidney below level of assay quantification (0.1 ng/mg) in <1 week 0 5 10 15 20 25 30 Target Lesion Distal Myocardium Kidney Liver Lung Time (Days) N = 753 porcine coronary artery segments Sirolimus Tissue Concentration (ng/mg) Published Data Demonstrates Therapeutic Tissue Concentrations Through Critical Healing Period (~30 Days) 1 Required Therapeutic Concentration > 1ng/mg 17 | Corporate Overview February 2026
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Low 2.8% Target Lesion Failure (TLF) at 1 year Low 0.12mm Late Lumen Loss (LLL) at 6-months 0% Target Lesion Revascularization (TLR) between 1-3 years Virtue® SAB demonstrated encouraging safety and efficacy results in patients with coronary in-stent restenosis (ISR) in prospective, multi- center SABRE Trial1,2,3 Compelling SABRE Trial Results in Coronary ISR Patients Virtue SAB Low Event Rates Out to 3 Years Single-Layer Restenosis 0% 5% 10% 15% 20% 25% 5.6% 2.8%2.8%2.8% 0%0%0%0%0%0%0% 2.8% Cardiac Death TV-MI TLR TLF Event Rates (%) 30 days 1-year 3-years 1Verheye et al. JACC Cardiovasc Interv 2017 Oct 23;10(20):2029-2037. DOI: 10.1016/j.jcin.2017.06.021.2 Revised per protocol analysis set meets the criteria of the proposed In-Stent Restenosis IDE study population. 3Granada 3-Year Clinical Results TCT 2018. Definitions: Target lesion failure (TLF), late lumen loss (LLL), target lesion revascularization (TLR) and Myocardial Infarction (MI). 18 | Corporate Overview February 2026
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AGENT 13.5% T arget Lesion Failure (TLF) at 1 year No angiographic follow-up in IDE AGENT LLL = 0.397mm at 6 months 3 Boston Scientific ’s Agent DCB demonstrated a reduction in TLF versus POBA in patients with single-layer restenosis in randomized IDE Trial1,2 AGENT IDE Trial Results Show Clear Opportunity for Virtue SAB 0% 5% 10% 15% 20% 25% 20.2% 13.5% 1 Year 2 Year Event Rates (%) AGENT POBA (n=341) AGENT TLF Out to 2 years Single-Layer Restenosis 1Yeh RW, Shlofmitz R, Moses J, et al. JAMA. 2024;331(12):1015 –1024. doi:10.1001/jama.2024.136. 2Moses, J Two -Year Outcomes from the AGENT IDE Trial CRT 2025. 3Boston Scientific AGENT DCB Brochure 2017. Definitions: Drug-Coated Balloon (DCB), Plain old balloon angioplasty (POBA), late lumen loss (LLL) 26.6% 20.7% AGENT 53% relative increase in TLF from 1 to 2 years 19 | Corporate Overview February 2026
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The Virtue Trial – U.S. Pivotal Coronary ISR Trial Randomizing Virtue SAB to Commercially Available AGENT Paclitaxel-Coated Balloon Designed to Secure Regulatory Approval & Showcase Differentiation of Virtue SAB R 740 Pts with ISR Lesions in Arteries 2.00 – 4.00mm Virtue Sirolimus AngioInfusion Balloon 1:1 370 Pts. 370 Pts. 12 M 12 M Clinical Follow-Up out to 5 Years Primary Endpoint: Target Lesion Failure (TLF) at 12 months Primary analysis non-inferiority comparison Additional superiority test performed upon confirming non -inferiority AGENT Paclitaxel Coated Balloon FDA IDE approved 1:1 RCT vs AGENT N=740 Up to 75 US Sites Primary endpoint 12-Month TLF Actively enrolling trial participants 20 | Corporate Overview February 2026
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Developed Virtue SAB (SirolimusEFR, AngioInfusionballoon) from concept stage; owns all related IP Conducted all prior development work including SABRE study in coronary ISR Sponsoring the Virtue Trial, US pivotal coronary ISR study Retains all development and distribution rights in all indications Free to engage actively with all strategic parties and solicit proposals Global leader in interventional cardiology accessory devices: >$2.4B in annual revenues1 Purchased ROFR for Virtue SAB with respect to the global coronary market o Has 30 days to exercise ROFRfollowing notice of a third-party proposal acceptable to Orchestra o Expires 90 days after disclosure of Virtue Trial primary endpoint data $65M in total payments to and investments in Orchestra o $10M in consideration of ROFR, plus $20M purchase of non-voting preferred with minimum $12/share conversion after Virtue Trial results announced o Initially paid $30M for prior Virtue SAB rights agreement plus $5M equity investment Terumo ROFR Agreement Highlights Strategic Interest & Optionality ROFR = Right of First Refusal; 1Based on Terumo’s consolidated financial results for the fiscal year ended March 31, 2025.21 | Corporate Presentation February 2026
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Target Disease Program Target Population Preclinical Clinical Feasibility Clinical Pivotal Hypertensive Heart Disease Atrioventricular Interval Modulation (AVIM) Therapy Hypertension (HTN) & Pacemaker HTN with Increased CV Risk (Non-pacemaker indicated) HTN & Heart Failure AVIM/Cardiac Neuromodulation Therapy may have additional clinical application in advanced heart failure. Atherosclerotic Artery Disease Virtue® Sirolimus AngioInfusion Balloon (SAB) Coronary In-Stent Restenosis (ISR) Coronary Small Vessel (SV) Below-the-Knee (BTK) Other Coronary & Peripheral Indications SirolimusEFR may have potential clinical application in a variety of non-vascular indications. IDE Approved & FDA Breakthrough FDA Breakthrough BACKBEAT Global Pivotal Study Enrolling & FDA Breakthrough FDA Breakthrough Orchestra BioMed’s High-Impact Pipeline * Two Pivotal Trial Stage Programs with Significant Future Expansion Opportunities FDA Breakthrough *For more detailed information relating to our pipeline, please see the disclosure under “Item 1. Business” in our Form 10-K for the year ended December 31, 2024 filed with the SEC on March 31, 2025.22 FDA Breakthrough$17 Billion Annual Global Opportunity $10 Billion Annual Global Opportunity | Corporate Overview February 2026
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Orchestra BioMed 2026 Vision Leveraging Partnerships to Bring Innovation to Patients & Yield Exceptional Future Profitability Actively Enrolling Pivotal Trials for Two High - Impact Proprietary Programs: AVIM Therapy and Virtue SAB Targeting Major Cardiovascular Indications in Large, Established Global Markets with Unmet Clinical Need Partnership - Driven Commercialization with Substantial Royalty - Based Revenue Model Funded Through Completion of Enrollment in Both Pivotal Trials and AVIM Therapy Primary Endpoint Data Readout 23 | Corporate Overview February 2026
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Bringing Medical Innovations to Life Through Partnerships