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 Viewpoint - Orchestra BioMed Holdings, Inc. has successfully completed strategic transactions and equity offerings totaling an expected $111.2 million to advance its late-stage AVIM therapy and Virtue SAB clinical programs [1][2]. Financial Summary - The $111.2 million in expected gross proceeds includes $56.2 million from a public offering and private placements, with net proceeds of approximately $51.8 million after expenses [2][4]. - Medtronic and Ligand have committed a total of $55 million in royalty-based, non-dilutive investments, with Ligand contributing $35 million and Medtronic $20 million [3][4]. Use of Proceeds - The net proceeds will fund significant value-creating catalysts, including the completion of enrollment and follow-up for the BACKBEAT study and substantial enrollment of the Virtue Trial [3][5]. Clinical Programs - AVIM therapy aims to treat uncontrolled hypertension and has shown promising results in pilot studies, with reductions of 8.1 mmHg in 24-hour ambulatory systolic blood pressure [9]. - Virtue SAB is designed to deliver sirolimus for treating coronary in-stent restenosis and has demonstrated positive three-year clinical data in prior studies [10]. Strategic Partnerships - The company has established collaborations with Medtronic for AVIM therapy and Terumo for Virtue SAB, enhancing its potential for successful commercialization [7]. - The partnerships reflect confidence in the transformative potential of the company's therapeutic programs [2]. Market Position - Orchestra BioMed focuses on high-impact technologies in the biomedical sector, addressing significant unmet needs in cardiovascular care [7]. - The company has received four Breakthrough Device Designations from the FDA for its core programs, indicating the high potential of its technologies [7].

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 has secured $70 million in new capital from Ligand Pharmaceuticals and Medtronic to advance its late-stage cardiology programs [1][3][4] Investment Details - Ligand Pharmaceuticals will invest a total of $35 million, which includes $20 million at closing, $15 million subject to conditions, and an additional $5 million in an equity private placement [3][5] - Medtronic will invest $30 million, comprising $10 million in an equity private placement and $20 million in a secured subordinated promissory note convertible to prepaid revenue share [4][5][6] Strategic Collaboration - The agreement between Orchestra BioMed and Medtronic has been amended to include the development of AVIM therapy-enabled leadless pacemakers, enhancing their existing collaboration [2][5][6] - The partnership aims to address significant health challenges such as uncontrolled hypertension and arterial disease, targeting high-risk patient populations [3][9] Product Development - AVIM therapy is designed to lower blood pressure in patients with hypertension who are indicated for a pacemaker, showing promising results in pilot studies [12] - Virtue SAB is being developed for the treatment of atherosclerotic artery disease, with positive clinical data supporting its efficacy [13] Market Potential - Both AVIM therapy and Virtue SAB have received Breakthrough Device Designation from the FDA, indicating their potential to meet high unmet medical needs in cardiovascular care [9][12][13]

Core Insights - Orchestra BioMed is focused on executing the BACKBEAT global pivotal study, which aims to establish AVIM therapy as a new standard of care for uncontrolled hypertension in pacemaker patients [2][5] - The company is also preparing to initiate a U.S. coronary pivotal study for the Virtue SAB program, with an updated trial design currently under FDA review [2][5] - The company is entering a formal mediation process with Terumo to resolve partnership negotiations, aiming for a resolution in the second quarter of 2025 [2][5] Financial Results for 2024 - Cash and cash equivalents and marketable securities totaled $66.8 million as of December 31, 2024 [10] - Revenue for 2024 was $2.6 million, a decrease from $2.8 million in 2023, primarily due to reduced partnership revenues from Terumo [10] - Research and development expenses increased to $42.8 million in 2024 from $33.8 million in 2023, driven by costs associated with the BACKBEAT study [10] - The net loss for 2024 was $61.0 million, or ($1.66) per share, compared to a net loss of $49.1 million, or ($1.48) per share, in 2023 [10][17] Product Development and Partnerships - AVIM therapy has shown promising results in pilot studies, with 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 [8] - Virtue SAB is designed to deliver an extended-release formulation of sirolimus during balloon angioplasty without the need for a coating on the balloon surface [9] - The FDA has granted Breakthrough Device designation to Virtue SAB for specific indications, enhancing its development prospects [11] Leadership and Governance - The board of directors has been enhanced with the appointment of three experienced independent directors, including former executives from Medtronic and Siemens [5] - Mark Pomeranz has been appointed as Executive Vice President & General Manager, bringing over two decades of experience in medical devices [5]