Bringing medical inn vation to life Orchestra BioMed Corporate Presentation Q1 2023 Forward - Looking Statements 2 This presentation has been prepared for informational purposes only from information supplied by Orchestr

Bringing medical inn vation to life Orchestra BioMed Corporate Presentation Q1 2023

Forward - Looking Statements 2 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. This presentation contains forward - looking statements within the meaning of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995 and other federal securities laws, including, without limitation, statements relating to our expected financial runway, the potential safety and efficacy of our product candidates, the timing of our planned pivotal trials, expected market sizes for our product candidates, the ability of our partnerships to accelerate clinical development, and our estimated future financial performance and financial position. These statements are often identified by the use of words such as "anticipate," "believe," "can," "continue," "could," "estimate," "expect," "intend," "likely," "may," "might," "objective," "ongoing," "plan," "potential," "predict," "project," "should," "to be," "will," "would," or the negative or plural of these words, or similar expressions or variations, although not all forward - looking statements contain these words. We cannot assure you that the events and circumstances reflected in the forward - looking statements will be achieved or occur and actual results could differ materially from those expressed or implied by these forward - looking statements. Factors that could cause or contribute to such differences include, but are not limited to, those identified herein, and those identified under the heading "Risk Factors - Risks Related to Orchestra's Business and New Orchestra Following the Business Combination" in the definitive proxy statement/prospectus of Health Sciences Acquisitions Corporation 2 (Orchestra BioMed's predecessor) filed with the U.S. Securities and Exchange Commission pursuant to Rule 424(b)(3) on December 16, 2022 and in our other filings with the SEC. These risks are not exhaustive. New risk factors emerge from time to time, and it is not possible for our management to predict all risk factors, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward - looking statements. In addition, statements that "we believe" and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date hereof and while we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted an exhaustive inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain, and investors are cautioned not to unduly rely upon these statements. Except as required by law, we undertake no obligation to update any forward - looking statements to reflect events or circumstances after the date of such statements.

Orchestra BioMed Executive Summary Strategic collaboration Double - digit revenue share Strong balance sheet and outstanding investors Partnership - enabled business model designed to accelerate innovation to patients, drive strong partner and shareholder value and yield exceptional future profitability Statistically significant double - blind, randomized preliminary trial efficacy data Plan to initiate pivotal trial H2 2023 Strategic collaboration Double - digit revenue share Strong 3 - year multi - center preliminary trial safety and efficacy data Plan to initiate pivotal trial H1 2023 3 Ed & Virtue SAB targets >$3B annual artery disease markets Protected sirolimus delivery, non - coated balloon

Enable new growth opportunities Outsource development Minimize P&L dilution 4 Orchestra BioMed's Partnership - enabled Model Benefits All Development Strategic Partners Commercialization Improve patient lives Accelerate development Leverage expertise & resources ^ K D Shared Benefits

Avi Fischer, M.D. SVP, Medical Affairs & Innovation J.C. Simeon SVP, Quality Inessa R. Wheeler VP, Marketing Bob Laughner VP, Regulatory Affairs Stephen A. Zielinski VP, Product Dev., Bioelectronic Therapies Ziv Belsky VP, Research, Bioelectronic Therapies Juan Lorenzo VP, Product Dev., Focal Therapies Highly Accomplished Executive Team & Board Executive Team: >250 Years of Experience, ~25 Avg Industry Years, >100 Product Approvals & >600 Authored Patents David Hochman Chairman, CEO, Co - Founder Darren R. Sherman President, COO, Director, Co - Founder Michael Kaswan Chief Financial Officer George Papandreou, Ph.D. GM & SVP, Focal Therapies , W ^ D W K 5 Eric S. Fain, M.D. Board Member Eric A. Rose, M.D. Board Member Pamela Connealy Board Member Geoffrey W. Smith Board Member Jason Aryeh Board Member Yuval Mika, Ph.D. GM & CTO, Bioelectronic Therapies

Product Platforms Target Indications Preclinical Clinical Feasibility Clinical Pivotal Partner Study Sponsor Next Milestones & Expected Timing 6 BackBeat Cardiac Neuromodulation Therapy (CNT ) Hypertension (HTN) (pacing patients; HTN+P) Global Pivotal Study Start H2 2023 High - Risk HTN (non - pacing patients) ROFN Will Seek to Leverage Data from HTN+P 2 CNT - HF Heart Failure Acute Clinical Data 2023 Potential Chronic Study Start 2024 Virtue Sirolimus AngioInfusion Balloon (SAB) Coronary In - Stent Restenosis (ISR) FDA Breakthrough 3 US Pivotal Study Start H1 2023 Japan Pivotal Study Start H1 2024 Coronary Small Vessel (SV) 1 FDA Breakthrough 4 Japan Pivotal Study Start H1 2024 US Pivotal Study Start 2024 Below - the - Knee (BTK) 1 FDA Breakthrough 5 Global BTK Study Start 2024/2025 SirolimusEFR / Urethral Strictures & BPH Preclinical Development Milestones Microporous Balloon Osteoarthritis 2023/2024 Advancing a High - Impact Pipeline 6 1 Plan to leverage existing coronary ISR data to support potential Pivotal Study, although there have only been limited discussions with the FDA or a comparable foreign regulator in this regard. 2 Will seek to leverage data from HTN+P pilot and pivotal trials to support clinical and regulatory development for High - Risk HTN indication given that age and other demographic factors of the target population are expected to be similar, the type of hypertension treated will likely be isolated systolic hypertension which is predominant in the HTN+P population, and other co - morbidities are also expected to be common to both target populations. However, there have been no discussions with the FDA or a comparable foreign regulator in this regard. 3 Virtue SAB has received Breakthrough Device Designation for the balloon dilatation of the stenotic portion (up to 26 mm length) of a stented coronary artery (in - stent restenosis (ISR)) that is 2.25 to 4.0 mm in diameter, for the purpose of improving lumen diameter; 4 Virtue SAB has received Breakthrough Device Designation for the balloon dilatation of the de novo stenotic portion (up to 26mm in lesion length) of a native coronary artery of 2.0 mm to 2.5 mm in diameter (small coronary arteries), for the purpose of improving lumen diameter; 5 Virtue SAB has received Breakthrough Device Designation for the balloon dilatation of the stenotic portion (up to 18 mm length) of an infrapopliteal artery (P - 3 segment or distal, below the knee, with reference vessel diameter (RVD) 2.25 - 4.0 mm), for the purpose of improving lumen diameter. All references to clinical study initiations for HTN+P, Coronary ISR and Coronary SV indications are based on ongoing interactions with US FDA regarding IDE approvals or Japan PMDA regarding CTN approvals, which are required to start clinical studies. With respect to BackBeat CNT for HTN, Orchestra and Medtronic have had initial interactions with the FDA regarding IDE approval and expect to continue interactions regarding clinical trial design and submission requirements ahead of submitting documentation for approval in the second half of 2023. A pre - CTN discussion with the PMDA is planned for December 2022 with submission for CTN approval anticipated in the second half of 2023. With respect to Virtue SAB for Coronary ISR, Orchestra has been working on IDE approval with the FDA under the breakthrough designation program to define all of the elements necessary for IDE approval and Orchestra expects to complete the agreed upon work and submit documentation for approval in Q1 of 2023. Orchestra and Terumo have had initial interactions with the PMDA and expect to submit for CTN approval for Coronary ISR and SV studies in the second half of 2023. FDA and PMDA responses are expected approximately 30 days following formal submissions; clinical study enrollment is expected to begin approximately 6 - 8 weeks after regulatory approvals; study enrollment timelines are currently estimated to be 12 - 18 months for all referenced studies although actual study enrollment timeframes may be longer; final primary endpoint results for all studies are at 12 months from enrollment with the exception of Japan Coronary ISR & SV studies, which are expected to be at 6 months from enrollment.

7 BackBeat Cardiac Neuromodulation Therapy (CNT )

BackBeat CNT Overview 1 Company estimates based on published sources, including National Inpatient Survey (NIS) and National Health and Nutrition Examination Survey 8 (NHANES); 2 Kalaras et al. Journal of the American Heart Association. ahajournals.org/doi/10.1161/JAHA.120.020492; 3 Burkhoff. MODERATO II Study 2 - Year Results TCT 2021;. Definitions: Ambulatory Systolic Blood Pressure (aSBP) and Office Systolic Blood Pressure (oSBP) Opportunity Hypertension is #1 comorbidity in pacemaker population affecting over 70% of patients 1 Older population at increased risk for major events & challenges with drug compliance Innovation Bioelectronic therapy designed to substantially & persistently lower blood pressure Compatible with standard pacemaker device & leverages existing treatment paradigm Compelling clinical data from double - blind randomized study : significant 8.1 mmHg net reduction in 24 - Hr aSBP at 6 months & 17.5 mmHg reduction in oSBP at 2 years 2,3 Collaboration with Global pacemaker leader providing technology and development/clinical/regulatory support for Orchestra BioMed - sponsored global pivotal trial Following regulatory approval, Medtronic has exclusive global rights to commercialization in the pacemaker - indicated patient population with double - digit revenue sharing for Orchestra BioMed of BackBeat CNT - enabled pacemaker sales

Large Global Opportunity for Treating Hypertension in Target Populations Total addressable market in 2025 based on company estimates; 1 Company estimates based on published sources, including National Inpatient Survey (NIS) and National Health and Nutrition Examination Survey (NHANES); 2 Known and well - characterized population, multiple references available; Definition: Hypertension (HTN) 9 >$10 Billion Potential Annual Global Market Opportunity >3.1 M Addressable HTN Patients HTN + Pacemaker Over 70% of pacemaker patients have HTN 1 Older, co - morbid population at increased risk of major events 2 High Risk HTN (Non - pacemaker) Older patients with isolated systolic hypertension (ISH) and comorbidities 750,000 patients >$2 Billion Annual Global Opportunity 2,400,000 patients >$8 Billion HTN + Pacemaker High Risk HTN

Bioelectronic therapy designed to leverage standard rhythm management device procedures (dual - chamber pacemaker) - Same implant procedure and lead positions - Large trained physician pool - Same target patient population - Leverageable existing reimbursement Mechanism of action - Designed to substantially reduce blood pressure by reducing preload through programmed pacing with short AV delays - Designed to maintain reduction by modulating sympathetic tone and reducing afterload through programmed variable pressure patterns Designed to Substantially Lower BP & Maintain Reduction BackBeat CNT 10 Designed to Substantially and Persistently Lower Blood Pressure 1. Reducing Preload Lowers BP 2 . Modulating Sympathetic Tone & Reducing Afterload Maintains Reduction in BP SBP (mmHg) Time (s) 155 150 145 140 135 130 0 50 100. 150 200 250 300

MODERATO II Double - Blind, Randomized Results Ed DKZdK // Ed D d D d 1 Kalaras et al. Journal of the American Heart Association. 2021;10:e020492 ahajournals.org/doi/10.1161/JAHA.120.020492 ; 2 Burkhoff MODERATO II Study 2 - Year Results TCT 2021; 3 24 - Hr aSBP Control (n=19),1 control patient could not be measured despite repeat measurement (patient had extremely high blood pressure); Definitions: Major Adverse Cardiac Events (MACE) included death, heart failure, clinically significant arrhythmias (i.e., persistent or increased atrial fibrillation, serious ventricular arrhythmias), myocardial infarction, stroke and renal failure in treatment group calculated per patient, Office Systolic Blood Pressure (oSBP), Ambulatory Systolic Blood Pressure (aSBP) 11 Significant Reduction in aSBP 24 Hours a Day - 11.1 mmHg in 24 - Hour aSBP at 6 months - 17.5 mmHg in oSBP at 2 years 0% MACE vs. 9.5% in control group at 6 months 85% of patients with reduction in aSBP oSBP 6 Months 24 Months ^ Z , ^W ^W aSBP 6 Months 0 - 5 - 10 - 15 - 20 - 3.1 P = 0.17 W - 12.4 P < 0.001 - 0.1 P = 0.94 - 17.5 P < 0.01 - 12.3 p = 0.02 - 8.1 p = 0.01 in BP (mmHg) 150 145 140 135 130 125 120 115 110 24 - Hr aSBP (mmHg) P < 0.01 for all times of day Control (n=20) 3 BackBeat CNT (n=26) Pre - activation (n=26) 6 months (n=26) 6 Month Mean Pre - activation Mean

Ed D Medtronic is the global leader in pacemakers - >$1.5 billion annual pacemaker revenues 1 Key Terms: (Hypertension + Pacemaker population) - Orchestra BioMed drives and finances development as sponsor of global pivotal trial - Medtronic provides certain development/clinical/regulatory resources funded by Orchestra to support integration into a Medtronic pacemaker and execution of the pivotal trial - Medtronic has exclusive global rights for commercialization upon regulatory approval - Orchestra is expected to receive between $500 and $1,600 per BackBeat CNT enabled device sold based on a formula of the higher of (1) a fixed dollar amount per device (amount varies materially on a country - by - country basis) or (2) a percentage of sales. - BackBeat CNT enabled devices expected to be sold under existing reimbursement codes . - Medtronic has a right of first negotiation to expand its global rights to BackBeat CNT for the treatment of HTN patients not indicated for a pacemaker $50 million equity investment in Orchestra BioMed 12 Aligned with Global Market Leader in Pacemakers and Device - based Hypertension Treatment 1 Based on MDTs consolidated financial results for the fiscal year ended April 29, 2022

BackBeat CNT Pivotal Trial Design 13 Current anticipated trial design: Randomization of ~650 - 750 patients with uncontrolled HTN despite medical therapy who are indicated for a dual - chamber pacemaker Inclusion and exclusion criteria for enrollment in the BackBeat CNT Pivotal Study will be similar to the criteria used in the MODERATO II study Patients will be randomized 1:1 in a double - blinded manner to either active treatment with the BackBeat CNT - with continued antihypertensive drug treatment or to standard pacing - only with continued antihypertensive drug therapies Anticipated primary efficacy and safety endpoints: - Efficacy endpoint: Superiority of treatment as compared to control based on mean change in 24 - hour aSBP at 3 months post randomization - Safety endpoint: Non - inferiority between the treatment and control groups comparing Major Adverse Cardiovascular Events (MACE) at 12 months post randomization Enroll patients across ~80 study sites planned for United States, Europe and, potentially, Japan

Virtue Sirolimus AngioInfusion Balloon (SAB)

Virtue SAB Overview 1 Total addressable market is 2025 market data based on company estimates; ; 2 von Birgelen et al. JACC Vol. 59, No. 15, 2012 April 10, 2012:1350 - 61; Virtue SAB has received Breakthrough Device Designation for: 3 The balloon dilatation of the stenotic portion (up to 26 mm length) of a stented coronary artery (in - stent restenosis (ISR)) that is 2.25 to 4.0 mm in diameter, for the purpose of improving lumen diameter; 4 The balloon dilation of the de novo stenotic portion (up to 26mm in lesion length) of a native coronary artery 15 of 2.0 mm to 2.5 mm in diameter (small coronary arteries), for the purpose of improving lumen diameter; 5 The balloon dilatation of the stenotic portion (up to 18 mm length) of an infrapopliteal artery (P - 3 segment or distal, below the knee, with reference vessel diameter (RVD) 2.25 - 4.0 mm), for the purpose of improving lumen diameter. Opportunity Significant need for "leave nothing behind" treatment for coronary and peripheral indications representing an > $3B global market opportunity 1 Drug - eluting stents (DES) carry risks of long - term restenosis and late thrombosis; require extended dual antiplatelet therapy; not effective/approved for select patients/lesions Innovation Highly - differentiated, non - coated drug/device combination product candidate designed to enable angioplasty with protected delivery of extended release sirolimus Compelling clinical results in multi - center coronary ISR clinical trial with 3 - year follow - up 2 FDA Breakthrough Device Designation received for indications in coronary ISR 3 , coronary SV 4 and BTK 5 Partnership with Global commercial leader with >$2.5B annual interventional cardiology revenue responsible for commercializing Virtue SAB as flagship therapeutic offering Collaboration driving multi - indication pivotal trial program starting with coronary ISR Orchestra BioMed to receive double - digit royalties and per unit drug payments

Large Opportunity for Leave Nothing Behind Solution 16 >$3 Billion Annual Global CAD & PAD Market Opportunity * > ^ /^Z ^s d< >3.2M Addressable CAD & PAD Patients (2025 Estimate) ~2,000,000 patients >$1.8 Billion Annual Global Opportunity ~1,250,000 patients >$1.2 Billion Peripheral *Total addressable market in 2025 based on company estimates; Definitions: Coronary Artery Disease (CAD), Peripheral Artery Disease (PAD), In - stent Restenosis (ISR), Small Vessel (SV, 2.5mm), High bleeding Risk De Novo (>2.5mm), Below - the - Knee (BTK, Rutherford 3 - 6, w/out severe comorbidities).

Virtue SAB / Designed to Enable Angioplasty with Protected Sirolimus Delivery while Leaving No Metal Behind 17 1 Granada et al. EuroIntervention 2016;12:740 - 747 W Inflated to deliver dose through micropores ^ &Z & 1000 1 0.1 0.01 0.0001 ^ d Required Therapeutic Concentration > 1ng/mg > 0 5 10 25 Coronary Distal Kidney Liver Lun g d N = 753 porcine coronary artery segments Protected Delivery/No Drug Coating No drug loss in transit No time limits on delivery No drug coating particulates

^Z d Z /^Z W 1 Verheye et al. JACC Cardiovasc Interv 2017 Oct 23;10(20):2029 - 2037. DOI: 10.1016/j.jcin.2017.06.021. 2 Granada 3 - Year Clinical Results TCT 2018. 3 - Year SABRE Trial Clinical Report on file. Definitions: Target lesion failure (TLF), late lumen loss (LLL), target lesion revascularization (TLR) and Myocardial Infarction (MI). Virtue SAB preliminarily demonstrated encouraging safety and efficacy results in patients with coronary in - stent restenosis (ISR) in prospective, multi - center SABRE Trial 1 >>> 2.8% Target Lesion Failure at 1 year 0% New TLR between 1 to 3 years Preliminarily Demonstrated Safety with Low Event Rates Out to 3 Years 2 W Z ^ > > > 1 RVD reported using Internormal values; 2 Trial primary performance endpoint; 3 Trial secondary performance endpoint (binary restenosis = >50% lumen diameter stenosis). 4 Data is based on per protocol population criteria revised to be consistent with proposed Virtue ISR - US pivotal study population. Z TLR d>& 10% 9% 8% 7% 6% 5% 4% 3% 2% 1% 0% 30 days 1 - year 3 - years 0% 0% 0% 0% 0% Cardiac Death TV - MI 0% 2.8% 2.8% 5.6% 4

Virtue SAB Terumo Partnership d s ^ d < d K D d s /^Z h^ K D d K D W>h^ ^ &Z K D s ^ 19 D D > W ' Z > d 1 Based on Terumo's consolidated financial results for the fiscal year ended March 31, 2022

s ^ /^Z h^ W d 20 Double - blind, multi - center, prospective, randomized controlled study in patients with single - layer coronary ISR Virtue SAB N=200 Z Primary Endpoint Target Lesion Failure (CD, TV - MI and TLR) at 12 months ^ s ^ d>& W d>& Success Considerations Virtue SAB: 2.8% TLF at 12 months in SABRE trial per protocol population PBA: 33 - 46% TLF at 12 months in coronary ISR published studies D W 12 - 18 Months Enrollment Key Inclusion RVD 2.5 to 4.0 mm, <30% DS (vs. RVD 2.5 to 3.5, <40% DS SABRE 1 Trial) PBA N=100 W /^Z Virtue SAB N=100 < / Zs ^ Zs ^ ^Z d Primary Endpoint Target Lesion Failure (CD, TV - MI and TLR) at 12 months s ^ : / / Z /^Z ^ ^ W W Z / ^ Z / Randomized Study Arm to Support Regulatory Approval: Single - Layer Coronary ISR Non - Randomized Study Arm: Double - Layer Coronary ISR Study Objective Provide additional clinical data in support of use in double - layer Coronary ISR without confounding TLF performance results in single - layer Coronary ISR

D Virtue SAB - Coronary ISR s /^Z h^ & / W H1 2023 , 21 BackBeat CNT - HTN + Pacemaker FDA IDE Approval 1 st Pt. Enrollment Ed ,& Z s ^ /^Z : WD dE s ^ ^s : WD dE ^ &Z W & Z 1 Timing estimated and subject to Terumo execution since Terumo controls development of Virtue SAB for SV indication and for ISR in Japan 2 Assumes focus on a device/drug combination balloon - based solution targeting indication such as urethral strictures or BPH Ed Ed ,& s ^ ^ &Z

22 d W d > D ^ W d W d - BackBeat CNT >$10 billion annual market Randomized, controlled study shows efficacy potential Collaboration with - Virtue SAB $3 billion annual market 3 - year pilot study results show potential safety & efficacy Partnered with Strong Balance Sheet and Committed Strategic and Financial Investors Bringing Medical Inn vations to Life Through Partnerships W D > d - Designed to accelerate innovation to patients, enable pipeline expansion and drive strong partner and shareholder value ,

Partnership - Enabled Business Model

Significant Barriers Prevent Innovation From Reaching Patients 24 Startups often struggle for resources to reach commercial value inflection > Z Increasing burden of cost, time, and work to bring medical innovation to patients Product Development 1 Pitchbook - Analysis of 430 companies since 2015 that completed at least Series B financing 2 SVB Healthcare Report 2019 3 Capital IQ D Avg 7% of revenue spent on R&D by top 20 med device vs. 20% in pharma 2,3

Orchestra BioMed Can Accelerate Innovation to Patients 25 Z Z ^ W K /

26 ^ K K Develop for Partnership W Key Pipeline Criteria Large Market with Unmet Needs Large market, significant unmet needs, established distribution channels Potential for High Impact Designed to improve standard of care, fit existing treatment paradigm, disrupt market dynamics Favorable for Partnering Significant differentiation, attractive economics for partnership, durable IP protection Innovation Royalty - based R&D Programs

Orchestrating Inn 27 W W D W Combined, our leadership team has z Average years of experience each New product approvals/clearances Authored patents 25 600+ > d