Presentation to provide comprehensive overview of AVIM Therapy clinical evidence demonstrating the potential to halt the progression of hypertensive heart diseaseOrchestra BioMed and Medtronic (NYSE: MDT) have a strategic collaboration to develop and commercialize AVIM Therapy for the treatment of uncontrolled hypertension in patients indicated for a pacemaker, an estimated global population of over 750,000 patients annuallyAVIM Therapy has received FDA Breakthrough Device Designation for the treatment of u ...

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 is expanding its intellectual property portfolio, securing 10 new patents related to hypertension treatment, bringing the total to 120 patents in this area [2][6] - The company has also increased its patent estate for heart failure treatment to 17 issued patents, enhancing its overall IP platform [2][6] - AVIM therapy is currently being evaluated in the BACKBEAT global pivotal study for treating uncontrolled hypertension in patients indicated for pacemakers, highlighting its potential impact on broader cardiovascular health [2][8] Intellectual Property Expansion - The global intellectual property portfolio for AVIM therapy includes patent protection in key markets such as the United States, Europe, Japan, and China [3] - The hypertension-specific patent estate now consists of 46 issued U.S. patents and 91 patents outside the U.S., collectively comprising over 2100 claims related to hypertension and heart failure [6] Strategic Collaborations - Orchestra BioMed has a strategic collaboration with Medtronic for the development and commercialization of AVIM therapy, focusing on hypertension treatment in pacemaker-indicated patients [4] - The company is also partnered with Terumo for the development of the Virtue Sirolimus AngioInfusion™ Balloon for treating atherosclerotic artery disease [4] Regulatory Designations - AVIM therapy has received Breakthrough Device Designation from the U.S. FDA for treating uncontrolled hypertension with increased cardiovascular risk, which may expedite its development and market access [2][6][9]

Core Insights - Orchestra BioMed Holdings, Inc. is actively participating in multiple institutional investor conferences to discuss its innovative biomedical technologies and partnerships [1][2][3] Group 1: Upcoming Conferences - The company will participate in Chardan Capital's Trending Issues in Drug Development Conference on April 29, 2025, featuring a fireside chat with CEO David Hochman [1] - Management will also engage in a live fireside chat at the Jefferies Global Healthcare Conference on June 5, 2025, along with one-on-one meetings with investors [2] - Additionally, a live presentation is scheduled for the H.C. Wainwright 3rd Annual BioConnect Investor Conference on May 20, 2025, where management will host one-on-one meetings [3] Group 2: Company Overview - Orchestra BioMed focuses on accelerating high-impact biomedical technologies through risk-reward sharing partnerships with leading medical device companies [4] - The company's lead product candidate is atrioventricular interval modulation (AVIM) therapy for hypertension, a major global health risk [4] - Orchestra BioMed is also developing the Virtue Sirolimus AngioInfusion™ Balloon for atherosclerotic artery disease, which is a leading cause of mortality worldwide [4] - The company has strategic collaborations with Medtronic for AVIM therapy and with Terumo for the Virtue SAB [4]