Summary of Orchestra BioMed Holdings Q3 2025 Corporate Update Call Company Overview - **Company**: Orchestra BioMed Holdings (NasdaqGM:OBIO) - **Industry**: Medical Devices, specifically focusing on interventional cardiology and cardiac rhythm management Key Points and Arguments 1. **Business Model**: Orchestra BioMed aims to accelerate medical device innovations through strategic partnerships with global market leaders, focusing on high-impact therapies for unmet medical needs in hypertensive heart disease and artery disease [3][4] 2. **Flagship Programs**: The company has two main programs: AVIM Therapy for hypertension and Virtue SAB for coronary artery disease, both targeting multi-billion dollar markets [4][30] 3. **Pivotal Trials**: The company is currently enrolling patients in pivotal IDE trials for both therapies, designed to generate clinical data for regulatory approvals and commercial adoption [4][5] 4. **Funding Achievements**: Orchestra BioMed raised nearly $150 million in capital, including a $117.6 million strategic financing led by Medtronic and Ligand, and an additional $30 million from Terumo [5][14] 5. **Strategic Collaborations**: The company strengthened its collaboration with Medtronic and entered a new agreement with Terumo, enhancing its financial position and strategic options [5][15] 6. **Regulatory Designation**: AVIM Therapy received FDA breakthrough device designation, highlighting its potential to address significant unmet needs in hypertension management [30][31] 7. **Market Potential**: The global market opportunity for AVIM Therapy is estimated to exceed $17 billion, targeting high-risk hypertensive patients [31] 8. **Clinical Data**: Initial results from the SABER pilot study of Virtue SAB showed a target lesion failure rate of 2.8%, indicating strong clinical outcomes compared to existing treatments [25][26] 9. **Innovative Technology**: Virtue SAB utilizes a proprietary Sirolimus EFR formulation and a novel delivery system designed to optimize drug delivery without the need for permanent stents [22][23] 10. **Competitive Landscape**: The Virtue trial is positioned against Boston Scientific's Agent Paclitaxel-Coated Balloon, with the aim to demonstrate superior clinical outcomes [18][19] Additional Important Content 1. **Financial Health**: The company reported a cash balance of $96 million at the end of the quarter, with additional capital expected from strategic partners [36] 2. **Enrollment Expectations**: The company anticipates completing enrollment for the AVIM trial by mid-next year and is actively working on site activations for the Virtue trial [38][40] 3. **Long-term Strategy**: Orchestra BioMed is focused on maintaining operational control and exploring various strategic partnership structures to maximize the potential of its therapies [16][48] 4. **Market Dynamics**: The shift towards leave-nothing-behind treatment strategies in coronary artery disease is gaining momentum, with a market valued at approximately $7.5 billion annually [18][19] 5. **Physician Engagement**: There is growing excitement among physicians regarding the innovative technologies being developed, which is expected to facilitate enrollment in clinical trials [52][54] This summary encapsulates the critical insights from the call, highlighting the strategic direction, financial health, and clinical advancements of Orchestra BioMed in the medical device industry.

Core Insights - Orchestra BioMed Holdings, Inc. reported a quarterly loss of $0.4 per share, which was worse than the Zacks Consensus Estimate of a loss of $0.38, representing an earnings surprise of -5.26% [1] - The company generated revenues of $0.86 million for the quarter ended September 2025, exceeding the Zacks Consensus Estimate by 15.42%, although this was a decline from $0.99 million in the same quarter last year [2] - The stock has underperformed the market, losing approximately 4.8% year-to-date compared to the S&P 500's gain of 14.4% [3] Earnings Outlook - The current consensus EPS estimate for the upcoming quarter is -$0.36 on revenues of $0.75 million, and for the current fiscal year, it is -$1.71 on revenues of $3.15 million [7] - The estimate revisions trend for Orchestra BioMed Holdings, Inc. was favorable prior to the earnings release, resulting in a Zacks Rank 2 (Buy) for the stock, indicating expected outperformance in the near future [6] Industry Context - The Medical - Biomedical and Genetics industry, to which Orchestra BioMed belongs, is currently ranked in the top 36% 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 be tracked by investors [5]

Core Insights - Orchestra BioMed Holdings, Inc. reported strong financial results for Q3 2025, securing nearly $150 million in capital to advance its pivotal-stage programs [3][4][5] - The company is actively enrolling patients in the Virtue Trial, which compares its Virtue® Sirolimus AngioInfusion™ Balloon to commercially available options [3][4] - The company has expanded its strategic collaborations with Medtronic and Terumo, enhancing its business model and financial position [3][4][5] Financial Highlights - Cash and cash equivalents and marketable securities totaled $95.8 million as of September 30, 2025, with a cash runway extended into Q4 2027 [10] - Revenue for Q3 2025 was $0.9 million, a slight decrease from $1.0 million in Q3 2024 [10] - The net loss for Q3 2025 was $20.8 million, or $0.40 per share, compared to a net loss of $15.4 million, or $0.41 per share, in Q3 2024 [10][19] Strategic Partnerships - The company secured $71.6 million in committed capital from Medtronic and Ligand, along with $30 million from Terumo, which includes a right of first refusal agreement [3][4] - The collaboration with Medtronic aims to develop AVIM Therapy-enabled leadless pacemakers, while the agreement with Terumo provides strategic options for the Virtue SAB [4][5] Clinical Development - The BACKBEAT study is expected to complete enrollment by mid-2026, while the Virtue Trial aims for completion by mid-2027 [4][5] - AVIM Therapy has received FDA Breakthrough Device Designation for treating uncontrolled hypertension, targeting a significant patient population in the U.S. [7][11] - Virtue SAB is designed to deliver a proprietary sirolimus formulation and has also received FDA Breakthrough Device Designation for multiple indications [12]

Financial Performance - As of September 30, 2025, Orchestra BioMed has raised a cumulative $334.9 million in gross proceeds, with net losses of $58.9 million and $44.9 million for the nine months ended September 30, 2025 and 2024, respectively[202]. - The accumulated deficit of Orchestra BioMed as of September 30, 2025, stands at $368.8 million[202]. - Net loss for the nine months ended September 30, 2025, was $58.946 million, a decrease of $14.077 million or 31% from a net loss of $44.869 million in 2024[244]. - Net losses for the nine months ended September 30, 2025, were $58.9 million, compared to $44.9 million for the same period in 2024, reflecting an increase of approximately 31%[266]. - Cash and cash equivalents totaled $95.8 million, consisting of $42.0 million in cash and cash equivalents and $53.8 million in marketable securities[266]. - Net cash used in operating activities for the nine months ended September 30, 2025, was $46.7 million, compared to $37.0 million for the same period in 2024, indicating a 26% increase in cash outflow[274][276]. - Net cash provided by financing activities for the nine months ended September 30, 2025, was $75.7 million, significantly higher than $15.2 million for the same period in 2024[279][280]. Research and Development - The company has focused on research and development, primarily funding operations through stock issuances and proceeds from the Business Combination[202]. - The company expects research and development expenses to increase in absolute dollars as it continues to develop new products and enhance existing technologies[236]. - Research and development expenses rose by $9.5 million, or approximately 30%, to $41.4 million for the nine months ended September 30, 2025, from $31.8 million in 2024[251]. - Research and development expenses increased by $2.4 million, or approximately 21%, to $14.0 million for the three months ended September 30, 2025[262]. - Research and development costs are estimated at each reporting date based on discussions with internal personnel and service providers regarding the progress of trials[302]. - Nonrefundable advance payments for research and development activities are deferred and capitalized until the related goods or services are accepted or performed[302]. Clinical Trials and Studies - The company is conducting the BACKBEAT study, enrolling up to 500 patients with uncontrolled hypertension, expected to complete enrollment by mid-2026[199]. - The Virtue Trial, comparing Virtue SAB to Boston Scientific's AGENT drug-coated balloon, is expected to enroll 740 patients in the U.S., with completion planned for mid-2027[204]. - An exclusive license and collaboration agreement with Medtronic for AVIM Therapy is in place, targeting uncontrolled hypertension patients indicated for a cardiac pacemaker[199]. Revenue and Partnership Agreements - The company has recognized product revenues from FreeHold's intracorporeal organ retractors, with revenues recognized upon shipment to customers[232]. - Partnership revenue increased by $192,000, or approximately 10%, to $2.1 million for the nine months ended September 30, 2025, compared to $1.9 million for the same period in 2024[245]. - Total revenue for the nine months ended September 30, 2025, was $2.565 million, an increase of $180,000 or 8% from $2.385 million in 2024[244]. - The company may sell up to $100.0 million of shares of common stock under a sales agreement to meet liquidity needs[270]. - The Terumo Agreement was terminated on October 24, 2025, which may impact future partnership revenues[288]. - The company has not recognized any revenue under the Medtronic Agreement through September 30, 2025, indicating ongoing development efforts[299]. Expenses and Financial Obligations - Selling, general and administrative expenses increased by $1.6 million, or approximately 9%, to $19.6 million for the nine months ended September 30, 2025[253]. - Selling, general and administrative expenses increased by $1.4 million, or approximately 25%, to $7.1 million for the three months ended September 30, 2025[264]. - The company anticipates an increase in selling, general, and administrative expenses as it expands operations as a public company[237]. - The company has a secured term loan facility of up to $50.0 million, with the first tranche of $15.0 million drawn on November 6, 2024[240]. - The company entered into a Royalty Purchase Agreement with Ligand Pharmaceuticals for $35.0 million, granting Ligand tiered royalty payments based on worldwide net product sales[239]. Stock and Compensation - Stock-based compensation for the three months ended September 30, 2025, was $3.0 million, compared to $2.4 million for the same period in 2024, reflecting a 25% increase[308]. - For the nine months ended September 30, 2025, stock-based compensation totaled $9.2 million, up from $7.7 million in 2024, indicating an increase of approximately 19.5%[308]. - As of September 30, 2025, the company had approximately $16.2 million of total unrecognized stock-based compensation, expected to be recognized over a weighted-average period of 2.3 years[308]. Company Status and Compliance - The company expects to lose its emerging growth company status on December 31, 2025, but will continue as a smaller reporting company[315]. - The company is not required to comply with auditor attestation requirements of Section 404 of the Sarbanes-Oxley Act as long as annual revenue is less than $100 million and market value of common stock held by non-affiliates is below $700 million[315]. - The fair value of stock options is estimated using the Black-Scholes option-pricing model, with subjective inputs requiring significant management judgment[307].

Core Insights - Orchestra BioMed Holdings, Inc. is set to host a business update call on November 12, 2025, focusing on significant clinical, strategic, and financing developments [1][2] Company Developments - The update will cover a strategic investment and collaboration expansion with Medtronic, a new capital relationship with Ligand, and a right of first refusal agreement with Terumo [2] - Enrollment in the BACKBEAT pivotal study of AVIM Therapy is accelerating, and patient enrollment has begun in the Virtue SAB US pivotal IDE coronary trial [2] Product Information - Orchestra BioMed's flagship products include Atrioventricular Interval Modulation (AVIM) Therapy and Virtue® Sirolimus AngioInfusion™ Balloon (Virtue SAB), both undergoing pivotal clinical trials [3] - AVIM Therapy targets uncontrolled hypertension and has FDA Breakthrough Device Designation, with an estimated 7.7 million patients in the U.S. affected [3] - Virtue SAB is a drug delivery angioplasty balloon system designed for treating atherosclerotic artery disease and has also received FDA Breakthrough Device Designation [3]

Core Insights - Orchestra BioMed has entered into a termination and right of first refusal agreement with Terumo Corporation regarding the Virtue® Sirolimus AngioInfusion™ Balloon for coronary artery disease treatment, with Terumo making an upfront payment of $10 million [1] - Terumo will invest an additional $20 million in Orchestra BioMed through a new series of non-voting preferred stock, convertible into common stock at a minimum of $12 per share [1] - The new agreements highlight the clinical and commercial potential of Virtue SAB, which is positioned to become a leading therapy in the global coronary market [2] Agreement Details - The ROFR Agreement allows Orchestra BioMed to seek development and commercialization partnerships for Virtue SAB in any therapeutic indication, while Terumo has the first right to respond to third-party offers related to the global coronary market [3] - The ROFR period lasts for 90 days after the disclosure of primary endpoint data from the Virtue Trial [3] - The transactions are expected to close by November 7, 2025, subject to customary closing conditions [4] Company Overview - Orchestra BioMed focuses on accelerating high-impact biomedical technologies through strategic collaborations, with flagship products including AVIM Therapy and Virtue SAB, both targeting multi-billion-dollar global market opportunities [5] - Virtue SAB is a first-of-its-kind drug delivery angioplasty balloon system designed to deliver an extended-release formulation of sirolimus, showing positive clinical data in treating coronary in-stent restenosis [8] - The company has received FDA Breakthrough Device Designation for Virtue SAB for multiple indications, including coronary ISR and small vessel disease [7][8] Market Context - Coronary in-stent restenosis (ISR) is a significant complication affecting up to 10% of stented patients in the first year, leading to over 325,000 lesions annually that may require treatment [9] - Current FDA-approved treatments for coronary ISR are limited, with traditional balloon angioplasty having high retreatment rates, indicating a need for innovative solutions like Virtue SAB [9]

Core Insights - Orchestra BioMed has initiated the first patient enrollments in the Virtue Trial, a pivotal U.S. IDE trial comparing its Virtue® Sirolimus AngioInfusion Balloon (Virtue SAB) to the AGENT paclitaxel-coated balloon, the only FDA-approved drug-coated balloon for coronary indications [1][5] - The Virtue Trial aims to enroll 740 patients across up to 75 centers in the U.S., with completion expected by mid-2027 [1][5] - Virtue SAB is designed to optimize the delivery and extended release of sirolimus, addressing limitations of traditional drug-coated balloons [2][8] Company Overview - Orchestra BioMed is focused on accelerating high-impact biomedical technologies through strategic partnerships with leading global medical device companies [9] - The company’s flagship products include the Virtue SAB and Atrioventricular Interval Modulation (AVIM) Therapy, both of which are undergoing pivotal clinical trials and represent significant market opportunities [9] - Virtue SAB has received FDA Breakthrough Device Designation for treating coronary in-stent restenosis (ISR), coronary small vessel disease, and below-the-knee peripheral artery disease [3][9] Product Details - Virtue SAB is the first non-coated drug-eluting balloon system designed to deliver a large liquid dose of proprietary extended-release sirolimus (SirolimusEFR) [3][8] - The device aims to enhance tissue uptake and drug bioavailability, surpassing previously published target tissue concentrations of drug-eluting stents [2][8] - Clinical data from the SABRE pilot study indicated promising results for Virtue SAB in treating single-layer coronary ISR [8] Market Context - The global market opportunity for drug-eluting balloons is estimated to exceed $10 billion annually [5] - Coronary ISR affects approximately 100,000 patients in the U.S. each year, representing a significant clinical challenge [3][7] - The Virtue Trial's primary endpoint is a non-inferiority comparison of Target Lesion Failure (TLF) at 12 months, which includes cardiac death, nonfatal myocardial infarction, and ischemia-driven target lesion revascularization [5]

Core Insights - Orchestra BioMed is presenting data on Atrioventricular Interval Modulation (AVIM) Therapy, highlighting its potential to transform the management of hypertensive heart disease at the Georgia Innovation Summit on October 10, 2025 [1][2] - AVIM Therapy is recognized as a novel, device-based approach that could redefine standards of care for hypertension, which is a major contributor to heart failure [2][4] Company Overview - Orchestra BioMed is a biomedical innovation company focused on accelerating high-impact technologies through strategic partnerships with leading medical device companies [3] - The company's primary product candidate is AVIM Therapy, aimed at treating hypertension, the leading risk factor for mortality globally [3][6] AVIM Therapy Details - AVIM Therapy is designed to work with standard dual-chamber pacemakers to significantly lower blood pressure and has shown promising results in pilot studies [8] - The MODERATO I and II pilot studies demonstrated substantial reductions in 24-hour ambulatory systolic blood pressure, with reductions of 11.6 mmHg and 15.6 mmHg at one day, respectively [5] - Long-term follow-up indicates sustained blood pressure reduction and improvements in cardiac function, with no significant adverse effects on heart metrics [5][8] Strategic Collaborations - Orchestra BioMed has a strategic partnership with Medtronic to develop and commercialize AVIM Therapy for patients with uncontrolled hypertension who are indicated for a pacemaker, targeting an estimated global population of over 750,000 patients annually [4][6] - The therapy has received FDA Breakthrough Device Designation for treating uncontrolled hypertension in patients at increased cardiovascular risk, representing a U.S. population of over 7.7 million patients [4][8]

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]