Secured over $111 million in proceeds and committed capital following completion of strategic transactions and concurrent public and private equity offerings, led by over $71 million in committed capital from Medtronic and LigandAchieved multiple FDA regulatory milestones: Breakthrough Device Designation for AVIM therapy; approval for expanded BACKBEAT study enrollment criteria, and IDE approval for a U.S. pivotal Virtue SAB trial versus commercially available paclitaxel-coated balloon NEW HOPE, Pa., Aug. 1 ...

Table of Contents ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from __________________ to __________________ Commission file number: 001-39421 ORCHESTRA BIOMED HOLDINGS, INC. (Exact name of registrant as specified in its charter) Delaware 92-2038755 (State or other jurisdiction of incorporation or organization) (IRS Employer Identification No.) UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ ...

Core Viewpoint - Orchestra BioMed Holdings, Inc. announced a significant update to the BACKBEAT study protocol, approved by the FDA, which expands patient eligibility criteria for evaluating AVIM therapy in patients with uncontrolled hypertension who require pacemakers [1][5]. Summary by Relevant Sections Patient Eligibility Expansion - The updated protocol increases the eligible patient pool by more than 24-fold compared to the original protocol, supporting the company's target for mid-2026 completion of enrollment [2][5]. - New eligibility criteria include hypertensive patients who have received or are scheduled to receive a Medtronic Azure™ or Astra™ pacemaker, including device replacements [5][6]. Clinical Implications - The expanded criteria align the study population with the characteristics of the FDA Breakthrough Device Designation for AVIM therapy, potentially representing millions of U.S. patients needing better options for managing elevated systolic blood pressure [3][4]. - AVIM therapy is designed specifically for older, higher-risk hypertensive patients who may also require a pacemaker, reflecting its transformative potential [3][8]. Company Overview - Orchestra BioMed focuses on accelerating high-impact biomedical technologies through partnerships with leading medical device companies, with AVIM therapy as its lead product candidate for uncontrolled hypertension [4]. - The company has received four Breakthrough Device Designations from the FDA for its core programs, indicating significant potential to address unmet needs in cardiovascular care [4].

Core Viewpoint - Orchestra BioMed Holdings, Inc. announced a public offering of 9,413,637 shares at $2.75 per share, along with pre-funded warrants for 5,136,363 shares at $2.7499 each, aiming to raise approximately $40 million before expenses [1][2]. Group 1: Offering Details - The offering includes a 30-day option for underwriters to purchase an additional 2,182,500 shares at the public offering price [1]. - The expected closing date for the offering is August 4, 2025, subject to customary conditions [1]. Group 2: Use of Proceeds - The net proceeds will fund the atrioventricular interval modulation (AVIM) therapy program, the BACKBEAT study, and the Virtue Sirolimus AngioInfusion Balloon (SAB) program, along with general corporate purposes [2]. Group 3: Company Overview - Orchestra BioMed focuses on high-impact biomedical technologies through partnerships with leading medical device companies [6]. - The company’s lead product candidate, AVIM therapy, targets hypertension, while Virtue SAB addresses atherosclerotic artery disease [6]. - The company has strategic collaborations with Medtronic and Terumo for the development and commercialization of its key therapies [6].

Core Insights - Orchestra BioMed Holdings, Inc. presented key clinical insights on AVIM therapy for high-risk hypertension at the CSI 2025 Meeting, emphasizing its potential to address hypertensive heart disease, a significant cardiovascular syndrome affecting an aging population [1][6] Company Overview - Orchestra BioMed is a biomedical innovation company focused on accelerating high-impact technologies through risk-reward sharing partnerships with leading medical device companies [5] - The company’s lead product candidate is AVIM therapy, designed for hypertension, which is a leading risk factor for mortality worldwide [5][8] AVIM Therapy Insights - AVIM therapy is a novel, device-based approach specifically targeting patients with hypertensive heart disease, who are at increased risk for major adverse cardiac events and currently lack sufficient therapeutic options [2][3] - The therapy aims to reduce cardiac preload and modulate autonomic nervous system responses to lower blood pressure and improve cardiovascular function, representing a potential paradigm shift in blood pressure management [3][4] Clinical Data and Studies - Pilot studies have shown that AVIM therapy resulted in net reductions of 8.1 mmHg in 24-hour ambulatory systolic blood pressure and 12.3 mmHg in office systolic blood pressure at six months compared to control patients [10] - The BACKBEAT global pivotal study is currently enrolling patients with uncontrolled hypertension who are indicated for a dual-chamber pacemaker, in collaboration with Medtronic [7][10] Market Opportunity - Hypertensive heart disease affects over 7.7 million patients in the U.S., highlighting a significant market opportunity for AVIM therapy, especially given its recent FDA Breakthrough Device Designation [6][10]

Summary of the Conference Call Company Overview - **Company**: Orchestra Lab - **Industry**: Medical Devices Key Points and Arguments Business Model - Orchestra Lab operates a partnership-driven business model aimed at advancing and commercializing high-impact medical device therapies, inspired by successful biotech partnerships [3][4] - The company aims to address the lack of partnership activity in the medical device sector, which contrasts with the pharmaceutical industry where partnerships are common for drug development [4] - The average R&D spending for the medical technology industry is around 7% of revenue, compared to 20% for pharmaceuticals, indicating a significant R&D constraint for med tech companies [5] Revenue Generation - Orchestra Lab plans to generate revenue through significant long-term royalty interests, which can yield high gross margins [6] - The company is focused on driving top-line growth without compromising EBITDA and EPS through collaborations with larger companies like Medtronic and Terumo [5][6] Core Capabilities - The founding team has extensive experience in innovation, clinical execution, regulatory expertise, and financial management [9] - Orchestra's lead program, ABIM therapy, aims to enhance existing pacemaker technology to reduce blood pressure in high-risk patients [12][13] Clinical Programs - **BackBeat Program**: Focuses on a therapy that upgrades existing pacemakers to reduce blood pressure, targeting older patients with hypertension [12][13] - The pivotal study is expected to provide data that could establish this therapy as a standard of care for managing hypertension in pacemaker patients [15] - Previous studies showed significant reductions in systolic blood pressure, with an 11 mmHg reduction in the treatment group [16][17] - The study has been adjusted to widen eligibility criteria, with completion expected in 2026 [24] - **Virtue Program**: A novel sirolimus drug-eluting balloon aimed at treating coronary artery disease [39][42] - Terumo is the strategic partner responsible for regulatory and commercial operations, with Orchestra receiving royalties and payments for the drug [42] - The program has faced delays due to changes in Terumo's management but remains a priority for both companies [43][45] Market Potential - The partnership with Medtronic allows Orchestra to tap into a significant market, with a potential revenue share of $500 to $1,600 per device sold, targeting approximately 750,000 patients annually who have hypertension and require pacemakers [32][33] - The Virtue program is positioned to address unmet needs in both coronary and peripheral artery disease, with breakthrough designations in various indications [63][64] Future Opportunities - There is potential for expanding the partnership with Medtronic to include broader patient populations beyond those needing pacemakers [35][36] - The Virtue program is exploring applications in below-the-knee treatments and other areas where inflammation and post-procedural healing are critical [64][65] Additional Important Content - The company ended the last quarter with over $50 million in cash, sufficient to fund operations for nearly a year, with options for equity financing if needed [25][26] - The business model is designed to minimize capital needs while maximizing growth potential through strategic partnerships [27] This summary encapsulates the key insights from the conference call, highlighting Orchestra Lab's innovative approach to the medical device industry, its strategic partnerships, and the promising clinical programs underway.

Core Insights - Orchestra BioMed Holdings (NASDAQ: OBIO) is experiencing significant momentum that is not yet reflected in its stock price [1] - The company possesses two proprietary medical device therapies that target large, established markets [1] Company Overview - Orchestra BioMed Holdings focuses on innovative medical device therapies [1] - The company is positioned in the biotech and pharmaceutical sectors, which are known for their growth potential [1] Market Potential - The medical device therapies owned by the company are considered best-in-class, indicating a strong competitive advantage [1] - The target markets for these therapies are large and well-established, suggesting substantial revenue opportunities [1]

Summary of Orchestra BioMed Holdings (OBIO) Conference Call Company Overview - **Company Name**: Orchestra BioMed Holdings (OBIO) - **Ticker Symbol**: OBIO - **Founded**: 2018 - **Business Model**: Leveraging partnerships with established market leaders in the medical device space to drive commercialization of products, focusing on generating revenue through long-term revenue shares with partners [3][5][41] Key Programs 1. Atrioventricular Interval Modulation (AVIM) Therapy - **Target Condition**: High blood pressure (hypertension) in older, high-risk patients - **Addressable Market**: Estimated at $17 billion worldwide [4] - **Efficacy Data**: Strong statistically significant results from phase two double-blind studies; currently enrolling patients in the BackBeat global pivotal study [4][28] - **FDA Designation**: Recently awarded breakthrough device designation [5][22] - **Partnership**: Collaborating with Medtronic, a leader in pacemaker technology, with a double-digit revenue share [5][15] - **Market Opportunity**: - Immediate market opportunity for AVIM therapy is approximately $2 billion, targeting 750,000 patients who receive pacemakers annually [13] - Broader market potential includes over 3.7 million patients globally with hypertension and increased cardiovascular risk, representing a potential market of over $15 billion [15] - **Revenue Potential**: Projected royalty stream of up to $750 million annually based on a $1,000 average royalty per device sold [19] 2. Virtu Sirolimus Angio Infusion Balloon (SAB) - **Target Condition**: Treatment of coronary and peripheral artery disease - **Initial Market Size**: Estimated at $4 billion annually [6] - **Efficacy Data**: Strong safety and efficacy data from multicenter pilot studies; recently received FDA approval to run the Virtu trial against Boston Scientific's paclitaxel-coated balloon [6][32] - **Partnership**: Collaborating with Terumo, with a high revenue share [40] - **Market Shift**: Transitioning from drug-eluting stents to drug-coated balloons, with Virtu positioned as a best-in-class product [31][33] Industry Context - **Market Dynamics**: Medtech companies spend significantly less on R&D compared to biopharma, with averages of 7% versus 20% of revenue [7] - **Competitive Landscape**: Medtronic faces competition from companies like Abbott and Boston Scientific, which often engage in discounting strategies to secure market share [46] Additional Insights - **Clinical Impact**: AVIM therapy aims to provide significant clinical benefits without the side effects associated with traditional drug therapies [44] - **Regulatory Pathway**: The BackBeat study is expected to establish a new standard of care for blood pressure management in the pacemaker population [29] - **Future Opportunities**: Potential applications for Virtu in treating below-the-knee artery disease, addressing a high unmet medical need [48] Conclusion - Orchestra BioMed is positioned for significant growth through its innovative therapies and strategic partnerships, particularly with Medtronic and Terumo, while addressing critical healthcare needs in hypertension and coronary artery disease [41][42]

Company Performance - Orchestra BioMed Holdings, Inc. reported a quarterly loss of $0.49 per share, which was worse than the Zacks Consensus Estimate of a loss of $0.46, and compared to a loss of $0.38 per share a year ago, indicating a decline in performance [1] - The company posted revenues of $0.87 million for the quarter ended March 2025, exceeding the Zacks Consensus Estimate by 122.56%, and up from $0.62 million in the same quarter last year [2] - Over the last four quarters, the company has surpassed consensus EPS estimates only once, and has topped consensus revenue estimates two times [2] Stock Performance - Shares of Orchestra BioMed Holdings, Inc. have declined approximately 33.8% since the beginning of the year, while the S&P 500 has only declined by 3.8% [3] - The current consensus EPS estimate for the upcoming quarter is -$0.49 on revenues of $0.61 million, and for the current fiscal year, it is -$1.99 on revenues of $2.5 million [7] Industry Outlook - The Medical - Biomedical and Genetics industry, to which Orchestra BioMed belongs, is currently ranked in the top 34% of over 250 Zacks industries, suggesting a favorable outlook compared to lower-ranked industries [8] - Empirical research indicates a strong correlation between near-term stock movements and trends in earnings estimate revisions, which can impact investor sentiment and stock performance [5]

Core Insights - Orchestra BioMed Holdings, Inc. reported financial results for Q1 2025, highlighting regulatory progress and a strengthening clinical pipeline [1][4] - The company received FDA Breakthrough Device Designation for its AVIM therapy, indicating significant recognition of its potential in treating hypertensive heart disease [3][6] - The company is advancing its clinical trials, including the BACKBEAT global pivotal study in collaboration with Medtronic and the initiation of the Virtue Trial for its Virtue SAB product [3][6] Financial Performance - Revenue for Q1 2025 was $0.9 million, an increase from $0.6 million in Q1 2024, primarily due to partnership revenues from Terumo [12] - Research and development expenses rose to $13.5 million in Q1 2025 from $9.1 million in Q1 2024, driven by costs associated with the BACKBEAT study [12] - The net loss for Q1 2025 was $18.8 million, or $0.49 per share, compared to a net loss of $13.5 million, or $0.38 per share, in Q1 2024 [12][19] Regulatory Developments - The FDA granted Breakthrough Device Designation for AVIM therapy, which aims to improve outcomes for patients with uncontrolled hypertension [6][10] - The company received FDA IDE approval for the Virtue SAB U.S. pivotal trial, which will compare its investigational product against a commercially available drug-coated balloon [6][13] Clinical Advancements - AVIM therapy has shown promising results in pilot studies, with reductions of 8.1 mmHg in 24-hour ambulatory systolic blood pressure and 12.3 mmHg in office systolic blood pressure [10] - The Virtue SAB is designed to deliver a proprietary extended-release formulation of sirolimus, demonstrating positive clinical data in coronary in-stent restenosis [11][13] Strategic Partnerships - Orchestra BioMed has strategic collaborations with Medtronic for AVIM therapy and Terumo for Virtue SAB, enhancing its commercialization efforts [8][10] - The company continues to expand its intellectual property portfolio, with 137 issued patents worldwide related to AVIM therapy [6]