Investor Blog: OBIO at ICI 2025 - The Triangle of Innovation in Action

This week, at the Innovation in Cardiovascular Intervention (“ICI”) meeting in Israel, Orchestra BioMed highlighted the strategic and clinical progress behind its two pivotal programs - Atrioventricular Interval Modulation Therapy (“AVIM Therapy”)and Virtue® Sirolimus AngioInfusion™ Balloon (“Virtue SAB”).

OBIO CEO David Hochman’s joint presentation with Robert Kowal, M.D., Ph.D., Medtronic’s Vice President and General Manager of Cardiac Pacing Therapies, alongside updates from OBIO innovation and corporate strategy leaders, provided clear insight into how the Company’s partnership-enabled business model is driving disciplined execution across both flagship programs.

The Triangle of Innovation: OBIO & Medtronic’s AVIM Therapy Strategic Collaboration Case Study

In a session called the Triangle of Innovation, Mr. Hochman and Dr. Kowal provided context and perspective on how the AVIM Therapy partnership between Orchestra BioMed and Medtronic was established and explained the critical role clinical researchers are playing in helping the two companies achieve their shared innovation objectives. The joint presentation emphasized the interdependent and collaborative efforts required to advance complex cardiovascular therapies.

• Orchestra BioMed provides entrepreneurial innovation, originating AVIM Therapy, owning 120 issued global hypertension-related patents, and sponsoring pilot clinical and mechanistic studies as well as the currently ongoing global pivotal study execution.
• Medtronic brings established, market-leading technology and device platforms along with global clinical and commercial infrastructure, including the integration of AVIM into its Astra™ and Azure™ pacemaker systems for the BACKBEAT pivotal trial.
• Clinicians serve as essential partners, providing clinical understanding and driving patient engagement and care underpinning effective clinical study day-to-day workflow across the more than 100 BACKBEAT clinical site global network.

The joint presentation further detailed the multi-year path that enabled AVIM Therapy to advance into global pivotal evaluation, spanning technical diligence, integration of AVIM into Medtronic pacemakers, steering committee-driven trial design, and coordinated clinical site engagement and activation. The AVIM Therapy case study of this powerful “Triangle of

Innovation” showcases a practical framework for how this long-term partnership has produced meaningful operational leverage, from product integration to the ongoing global pivotal trial execution.

Dr. Avi Fischer, SVP of Medical Affairs and Innovation, gave an additional talk during a device-based hypertension therapy session in which he focused on the potential clinical impact and utility of AVIM Therapy within the broader context of hypertensive heart disease.

Virtue SAB: Growing Momentum for OBIO’s Pivotal-Stage Breakthrough Device for Coronary Artery Disease

Bill Little, EVP of Corporate Development and Strategy at OBIO also presented an update on the Virtue SAB program, reviewing the design and strategic rationale behind the Virtue Trial, OBIO’s U.S. pivotal IDE study comparing Virtue SAB to the AGENT™ paclitaxel-coated balloon for the treatment of coronary in-stent restenosis (ISR).

Key points reinforced at ICI included:

• The significant differentiation and potential advantages of Virtue SAB’s extended-release SirolimusEFR™ formulation and non-coated, liquid drug-delivery approach
• Prior positive data from the SABRE study, demonstrating low 2.8% target lesion failure (measures major adverse cardiac events and need for re-treatment) at 12 months and 0% target lesion revascularization (need for re-treatment) from 12 months through 36 months
• The significance of a first-ever pivotal, head-to-head comparison of a sirolimus-eluting balloon versus an FDA-approved paclitaxel-coated balloon

Virtue SAB’s progress underscores OBIO’s ability to execute multiple pivotal-scale programs in parallel.

Why ICI Matters for Investors

Three investor-relevant themes emerged from last week’s presentations:

1. OBIO’s partnership model is delivering measurable operational leverage.

The multi-year collaboration with Medtronic reflects impactful and active collaboration across technical, clinical, and strategic business functions.

2. Both flagship programs now have clear, active pivotal studies underway.

AVIM Therapy and Virtue SAB - each FDA Breakthrough Device–designated - are progressing in pivotal clinical studies in parallel, reinforcing OBIO’s successful operational execution in 2025.

3. The “Triangle of Innovation” case study articulates OBIO’s long-term competitive advantage.

The AVIM Therapy strategic collaboration with Medtronic showcases how OBIO’s business model unlocks value across clinical, regulatory, and ultimately commercial milestones.

Looking Ahead

With BACKBEAT enrollment ongoing, Virtue Trial sites activated, and strong global partners supporting execution, OBIO continues to advance high-impact cardiovascular therapies through a disciplined, partnership-driven model.

Investors should expect additional clinical and operational updates as both programs progress toward major milestones in 2026 and beyond.

- Team OBIO
Published December 2025

Forward-Looking Statements

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