Summary of Orchestra BioMed FY Conference Call Company Overview - **Company**: Orchestra BioMed (NasdaqGM:OBIO) - **Focus**: Biomedical innovation with two pivotal stage cardiovascular programs: - **Virtue Sirolimus AngioInfusion Balloon** for coronary artery disease - **Atrioventricular Interval Modulation (AVIM) therapy** for hypertensive heart disease in high-risk patients, partnered with Medtronic [7][36] Key Programs and Developments Virtue Sirolimus AngioInfusion Balloon - **Current Status**: Enrolling pivotal trials, with expectations to finish the BACKBEAT trial this year and data anticipated shortly thereafter [8] - **Market Potential**: Positioned in an almost $8 billion market, with a paradigm shift from drug-eluting stents to drug-eluting balloons [18][19] - **Competitive Landscape**: Currently, only Boston Scientific has a commercial coronary drug-coated balloon in the U.S. [18] - **Clinical Advantage**: Virtue aims to deliver better clinical results with a proprietary drug delivery method that encapsulates sirolimus, leading to significantly higher drug levels compared to existing products [25][26] Atrioventricular Interval Modulation (AVIM) Therapy - **Trial Progress**: Enrollment is accelerating with over 100 sites engaged, and protocol changes have improved participation [38] - **Therapeutic Impact**: AVIM therapy shows immediate blood pressure reduction in patients, with significant double-digit drops observed [40][41] - **Market Opportunity**: Estimated 1 million patients worldwide receiving pacemakers annually could benefit from AVIM therapy [42] - **Regulatory Path**: Medtronic is responsible for regulatory and manufacturing aspects, with a focus on U.S. market approval expected around 2028 [51][54] Financial and Strategic Partnerships - **Recent Financing**: Secured over $60 million from partners including Medtronic and Terumo, minimizing equity dilution and providing a strong balance sheet [14][15] - **Business Model**: Focused on leveraging strategic partnerships for commercialization, with significant royalty interests from products [7] Market Dynamics and Clinical Insights - **Physician Engagement**: High enthusiasm from physicians regarding the unique delivery method of Virtue and the potential clinical advantages [34] - **Clinical Data**: Ongoing education for physicians about the differences between sirolimus and paclitaxel, emphasizing the benefits of sirolimus in healing vessels [33] - **Hypertension and Heart Failure**: AVIM therapy targets a unique patient population with uncontrolled systolic hypertension, potentially impacting quality of life and cardiac function [60][63] Conclusion - **Outlook**: Orchestra BioMed is well-positioned for future growth with innovative products addressing significant market needs, strong partnerships, and a clear path towards commercialization [36][64]

Summary of Orchestra BioMed FY Conference Call (March 03, 2026) Company Overview - **Company**: Orchestra BioMed (NasdaqGM:OBIO) - **Focus**: Development of innovative medical technologies, particularly in the fields of hypertension and coronary artery disease through partnerships with established companies like Medtronic and Terumo [1][2] Key Programs and Developments AVIM Therapy - **Indications**: Targets hypertensive heart disease and coronary artery disease, utilizing a pacemaker for delivery [3][4] - **Market Opportunity**: Estimated over $17 billion annual global opportunity in treating hypertension within the pacemaker population [5] - **Clinical Trials**: Actively enrolling in the BACKBEAT pivotal trial for AVIM therapy, with a goal to complete enrollment in 2026 and data readout expected in 2028 [4][24] - **Mechanism**: AVIM therapy modulates blood pressure by shortening the timing of atrial and ventricular contractions, leading to immediate and sustained blood pressure reduction [16][17] - **Clinical Data**: Demonstrated significant reductions in systolic blood pressure (average drop of 15.5 mmHg) and improvements in diastolic function in patients with isolated systolic hypertension [20][22] VIRTUE Sirolimus AngioInfusion Balloon - **Product Description**: A first-of-its-kind non-coated drug-eluting balloon designed for coronary artery disease treatment, leveraging a proprietary sirolimus formulation [25][26] - **Market Shift**: The market is transitioning from permanent implants like stents to drug-coated balloons, with a significant opportunity in both coronary and peripheral artery disease [25][26] - **Clinical Trials**: Enrolling patients in a pivotal trial against Boston Scientific's AGENT balloon, aiming for non-inferiority and potential superiority [30][44] - **Performance Metrics**: Achieved a low target lesion failure rate of 2.8% at one year, indicating strong clinical outcomes [29] Financial Position - **Funding**: Well-capitalized through late 2027, with recent transactions bringing in additional capital, including $21 million from the sale of Vivasure and $35 million in tranche payments from partnerships [7][8] - **Royalty Structure**: Potential royalties of $500 to $1,600 per device sold by Medtronic, with significant revenue opportunities anticipated from AVIM therapy [14][15] Strategic Partnerships - **Medtronic**: A key partner, holding over 50% of the global pacing market, with exclusive rights to commercialize devices incorporating AVIM therapy [15][16] - **Terumo**: Holds a right of first refusal for the VIRTUE product, with a recent investment of $65 million [30][31] Market Trends and Insights - **Hypertension and Heart Failure**: Elevated systolic blood pressure is a major driver of heart failure progression, with AVIM therapy positioned as a preventive treatment for patients at risk [34][35] - **Drug-Eluting Balloon Market**: Increasing adoption of drug-coated balloons in coronary procedures, particularly in Europe and Asia, with a growing recognition of the need for differentiated products [41][42] Conclusion - **Outlook**: 2026 is positioned as a pivotal year for Orchestra BioMed, with significant clinical trials underway and a strong financial foundation to support growth and innovation in the medical device sector [31][32]

Group 1 - Orchestra BioMed Holdings Inc. is recognized as a promising biotech penny stock, with TD Cowen initiating coverage with a Buy rating and a $15 price target, highlighting its leadership in cardiovascular device innovation [1] - The company's royalty-based model is supported by two significant programs: AVIM for hypertension and Virtue SAB for atherosclerotic disease, addressing substantial market gaps [1] - Orchestra BioMed is approaching critical data and commercialization milestones that could be transformative, aided by partnerships with blue-chip companies and high-margin potential [1] Group 2 - The company is advancing two pivotal programs, with the Virtue Trial enrollment starting in Q3 2025, comparing Virtue SAB against AGENT paclitaxel-coated balloon for treating coronary in-stent restenosis, targeting enrollment completion by mid-2027 [2] - The BACKBEAT global pivotal study for AVIM Therapy has seen recent FDA-approved protocol enhancements, expanding the eligible patient pool over 24-fold, with enrollment expected to complete by mid-2026 [2] Group 3 - Orchestra BioMed has expanded its partnership with Medtronic to develop AVIM Therapy-enabled leadless pacemakers, while retaining all development and distribution rights for Virtue SAB across all indications despite Terumo holding a right of first refusal for certain transactions [3][4]

Core Insights - Orchestra BioMed announced new data from its AVIM therapy program, indicating sustained blood pressure-lowering effects for years after activation, with reversibility and no rebound hypertension observed [1][4][5] - The AVIM therapy has been presented at the HRX Live 2025 Meeting and published in a peer-reviewed journal, highlighting its potential as a novel treatment for uncontrolled hypertension [2][4] - The company has a strategic collaboration with Medtronic to develop and commercialize AVIM therapy, targeting an estimated global population of over 750,000 patients annually [4][6] Summary by Sections AVIM Therapy Findings - Long-term follow-up of patients treated with AVIM therapy showed sustained reductions in 24-hour ambulatory systolic blood pressure (aSBP) of 8.9 mmHg after an average of 3.6 years [5] - Upon deactivation of AVIM therapy, blood pressure returned to baseline levels without rebound hypertension, demonstrating the treatment's reversibility [5] - Reactivation of AVIM therapy resulted in a significant reduction in aSBP to 124.4 mmHg, indicating reproducibility of the treatment effect [5] Clinical and Mechanistic Data - Dr. Avi Fischer presented data supporting AVIM therapy's role in managing uncontrolled hypertension, emphasizing its sustainability and safety profile [2][4] - The BACKBEAT global pivotal study is currently investigating the efficacy and safety of AVIM therapy in patients with uncontrolled hypertension [2][8] Strategic Collaborations and Market Potential - Orchestra BioMed's partnership with Medtronic aims to commercialize AVIM therapy for patients indicated for a pacemaker, addressing a significant market need [4][6] - AVIM therapy has received FDA Breakthrough Device Designation for treating uncontrolled hypertension in patients with increased cardiovascular risk, representing a potential market of over 7.7 million patients in the U.S. [4][8]

Core Viewpoint - Orchestra BioMed Holdings, Inc. announced favorable hemodynamic effects of AVIM therapy for patients with uncontrolled hypertension, as published in the Journal of the American College of Cardiology: Clinical Electrophysiology [1][2][3] Group 1: AVIM Therapy Findings - AVIM therapy demonstrated statistically significant reductions in systolic blood pressure (SBP) by an average of 17.1 mmHg (RV pacing) and 19.2 mmHg (CSP), compared to 1.7 mmHg with standard pacing [6] - The therapy improved left ventricular hemodynamics, with end-diastolic volume decreasing by 12.6 mL (RV) and 18.6 mL (CSP), and end-systolic volume decreasing by 11.0 mL (RV) and 14.1 mL (CSP) [6] - AVIM therapy also significantly reduced cardiac workload, with stroke work decreasing by 1,596 mL (RV) and 1,870 mL (CSP), compared to 42 mL with standard pacing [6] Group 2: Clinical Implications - The publication of the data in a peer-reviewed journal reinforces the therapeutic rationale behind AVIM therapy, highlighting its potential to deliver differentiated clinical benefits for patients with uncontrolled hypertension [3][7] - AVIM therapy has received FDA Breakthrough Device Designation for treating uncontrolled hypertension in patients with increased cardiovascular risk, estimated to be over 7.7 million patients in the U.S. [5][10] - The strategic collaboration between Orchestra BioMed and Medtronic aims to develop AVIM therapy for the treatment of uncontrolled hypertension in pacemaker-indicated patients, a population of over 750,000 patients annually [5][10] Group 3: Research and Development - The BACKBEAT global pivotal study is currently evaluating the safety and efficacy of AVIM therapy in patients with systolic blood pressure above target despite anti-hypertensive medication [10] - The MODERATO II study showed that patients treated with AVIM therapy experienced 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] - AVIM therapy is compatible with standard dual-chamber pacemakers and aims to substantially and persistently lower blood pressure [10]

Core Viewpoint - Orchestra BioMed announced the publication of clinical data demonstrating that AVIM therapy significantly improves cardiac function in patients with hypertension and diastolic dysfunction, which are key contributors to heart failure with preserved ejection fraction (HFpEF) [1][2]. Group 1: Clinical Data and Findings - The publication titled "Effects of AtrioVentricular Interval Modulation (AVIM) Therapy in Subjects with Hypertension and Diastolic Dysfunction" reports a retrospective treatment-blinded analysis of MODERATO II patients [2]. - AVIM therapy significantly reduced systolic blood pressure (SBP) and improved echocardiographic markers of diastolic dysfunction, which is a common comorbidity in patients with isolated systolic hypertension [2][7]. - Key findings include a reduction in office SBP by 12.1±12.8 mmHg and ambulatory SBP by 8.3±9.7 mmHg over six months, both statistically significant (p<0.01 vs baseline) [8]. Group 2: Expert Commentary - Dr. Marat Fudim emphasized the clinical link between long-standing hypertension, diastolic dysfunction, and the development of HFpEF, noting that AVIM therapy may address this unmet medical need by providing sustained blood pressure reductions and improving ventricular compliance [4]. - Dr. Avi Fischer highlighted the potential of AVIM therapy to offer a differentiated, device-based approach for earlier intervention in disease progression, targeting both elevated systolic blood pressure and impaired diastolic function [4]. Group 3: Ongoing Studies and Future Directions - AVIM therapy is currently being evaluated in the BACKBEAT global pivotal study, which aims to support potential U.S. regulatory approval for use in pacemaker-indicated patients with uncontrolled hypertension [4][11]. - The BACKBEAT study will assess the safety and efficacy of AVIM therapy in patients with systolic blood pressure above target despite anti-hypertensive medication [11].

Core Insights - Orchestra BioMed Holdings, Inc. announced financial results for Q2 2025, highlighting significant capital raised and regulatory achievements [1][2][3] Financial Highlights - The company secured over $111 million in proceeds from strategic transactions and equity offerings, including $71 million from Medtronic and Ligand [4][5] - Cash and cash equivalents totaled $33.9 million as of June 30, 2025, with an estimated position of $101 million as of August 12, 2025, after recent financing [11] - Revenue for Q2 2025 was $0.8 million, unchanged from Q2 2024, while net loss increased to $19.4 million, or $0.50 per share, compared to a net loss of $16.0 million, or $0.45 per share, in the prior year [11][20] Regulatory Milestones - The FDA granted Breakthrough Device Designation for AVIM therapy aimed at treating uncontrolled hypertension, which may enhance future regulatory submissions and reimbursement pathways [4][6] - The BACKBEAT study protocol was updated and approved by the FDA, significantly expanding patient enrollment criteria [4][6] - IDE approval was received for the Virtue SAB U.S. pivotal trial, which will compare Virtue SAB with commercially available paclitaxel-coated balloons [4][6] Strategic Collaborations - The company has expanded its collaboration with Medtronic to develop AVIM therapy-enabled leadless pacemakers [5] - Ligand Pharmaceuticals committed $35 million for a tiered revenue interest in future royalties from AVIM therapy and Virtue SAB [5] Product Development - AVIM therapy has shown promising results in pilot studies, demonstrating significant reductions in blood pressure [12] - Virtue SAB is designed to deliver sirolimus effectively, with positive clinical data supporting its use in treating coronary in-stent restenosis [13]

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].

Financial Data and Key Metrics Changes - Total revenue for Q2 2025 grew 15% year over year to $47.6 million, with adjusted EPS rising 14% to $1.6 per share, reflecting solid execution and continued operating leverage [32] - Royalty revenue increased 57% from the prior year to $36.4 million, underscoring the strength and momentum of partnered programs [32] - GAAP net income for the quarter was $4.8 million or $0.24 per diluted share, compared to a GAAP net loss of $51.9 million or $2.88 per share in the prior year period [38] Business Line Data and Key Metrics Changes - Key drivers of royalty revenue growth included strong performance from Varonis O2VARE, Trevyr's FILSPARI, Recordati's Carziva, and Merck's CapXiv and Vaxnuvanse [33] - Varonis reported a 45% sequential increase in Q2 2025 sales to $103 million, with expectations for continued strong launch trajectory [34] - FILSPARI showed strong commercial momentum, with Trevyr reporting Q2 sales in line with internal estimates, indicating robust year-over-year growth [34] Market Data and Key Metrics Changes - Merck's CapXiv generated $129 million in sales, a 21% sequential increase, while Vaxnuvanse generated $229 million in net sales, representing a 20% year-over-year increase [35] - Record ID reported sales of Carziva grew 12% in 2025, reaching €78.5 million, with Ligand earning a high teens royalty on Carziva sales [12] Company Strategy and Development Direction - The company aims to deliver profitable compounding growth by remaining disciplined in its investment approach and identifying high-quality assets that address significant unmet needs [21] - The strategic merger of Pylthos with Channel Therapeutics and a $40 million investment in Orchestra Biomed reflect the company's commitment to innovative therapies and expanding its portfolio [8][26] - The company is optimistic about the potential of its royalty assets, particularly with the expected blockbuster status of O2VARE by 2027 [20] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism regarding the strong launch trajectories of therapies and the potential for significant revenue growth from O2VARE and FILSPARI [44] - The company anticipates that Merck's acquisition of Verona will accelerate the launch of O2VARE, enhancing its market potential [76] - Management acknowledged the ongoing pricing pressure in the pharmaceutical industry but emphasized the importance of investing in high clinical value drugs to navigate this environment [63] Other Important Information - The company ended the quarter with $245 million in cash and investments, with approximately $450 million in deployable capital factoring in its undrawn credit facility [32] - The deconsolidation of Peltos effective July 1 will impact future financial reporting, with the estimated fair value of Ligand's stake in Peltos at approximately $100 million [41] Q&A Session Summary Question: Expectations for the Peltos launch - Management is optimistic about the launch of ZELSUMI, citing strong demand and a capable commercial team [47][48] Question: Impact of Vilsparri REMS removal on uptake - The removal of REMS restrictions is expected to enhance uptake, particularly among earlier stage patients [50][51] Question: Guidance on revenue and EPS growth - Management explained that operating expenses are being cautiously managed, and tax rates are impacting net income due to increased foreign revenue [56][57] Question: Merck's ownership of Verona and its impact on O2VARE - Management believes Merck's global capabilities will accelerate O2VARE's rollout compared to its previous management by Verona [76] Question: Orchestra Biomed's commercialization pathway - Medtronic and Tarumo are the commercial partners for Orchestra Biomed's AVIM technology and Virtu SAB balloon, respectively [77]

Financial Performance & Guidance - Q2 2025 royalty revenue increased by 57% compared to Q2 2024, driven by Ohtuvayre, Filspari, Qarziba, Capvaxive and Vaxneuvance[3, 26] - Q2 2025 adjusted EPS grew 14% to $1.60[3, 24, 25] - The company increased revenue guidance for 2025 from $180 million-$200 million to $200 million-$225 million, a 13% increase[3, 24, 33] - Adjusted EPS guidance for 2025 was raised from $6.00-$6.25 to $6.70-$7.00 per diluted share, a 12% increase[3, 24, 33] Portfolio & Investments - Ligand has approximately 50% equity interest in Pelthos and is entitled to a 13% royalty on Zelsuvmi sales[3, 6] - The company committed $35 million in long-term capital for royalty interest in Orchestra BioMed's AVIM therapy and Virtue SAB and invested $5 million in equity private placement[3, 20, 21] - Merck is set to acquire Verona for $10 billion, which will impact Ligand's 3% royalty on Ohtuvayre[3, 4, 8] Strategic Outlook - The company anticipates a long-term royalty revenue CAGR of greater than 22%[3, 27] - Ohtuvayre peak-sales consensus updated from $1.2 billion in December 2024 to $3.4 billion in August 2025[30] - Ligand has ~$450 million in deployable capital as of June 30, 2025[3, 24]