First Quarter 2025 Business Highlights

Fellow Shareholders:

Orchestra BioMed has demonstrated good momentum so far in 2025 as we continue to execute on our mission of advancing high-impact cardiovascular innovations through strategic, capital-efficient partnerships.

Our two flagship programs – atrioventricular interval modulation (“AVIM”) therapy for hypertension and Virtue® Sirolimus AngioInfusion Balloon (“SAB”) for coronary artery disease - each achieved key U.S. Food and Drug Administration (“FDA”) and clinical milestones that deepen our conviction in their long-term potential.

Here are several highlights from our Q1 earnings announcement and business update that underscore our steady, value-focused approach:

Regulatory Progress Highlights AVIM’s Growing Clinical Relevance

• In March, AVIM therapy received Breakthrough Device Designation from the FDA for the treatment of uncontrolled hypertension in patients at increased cardiovascular risk, with or without pacemaker indication. This milestone builds on the growing body of clinical evidence related to AVIM therapy and could offer significant benefits in terms of regulatory efficiency and reimbursement upside. 
• Meanwhile, our U.S. Virtue SAB program cleared an important milestone with full FDA approval of an IDE to initiate a head-to-head pivotal trial against a commercially available paclitaxel-coated balloon. We currently plan to begin this study in the second half of 2025.

Key CEO Callouts

David Hochman, OBIO’s Chairman and CEO, offered the following insights in this quarter’s update:

• “The FDA granting Breakthrough Device Designation to AVIM therapy... reflects growing recognition of our novel, proprietary therapy’s strong clinical foundation and potential to address critical unmet needs for millions of patients.”
   
• “Managing hypertension is crucial to prevent or slow the progression of hypertensive heart disease... We believe that AVIM therapy has the potential to provide a potent additional therapeutic option.” 
   
• “We are focused on execution of the BACKBEAT global pivotal trial alongside our strategic partner Medtronic as the critical pathway toward making AVIM Therapy available to patients globally.”

As we move deeper into 2025, OBIO remains focused on disciplined execution, strategic clinical advancement, and building durable shareholder value through a methodical, partnership-driven approach.

With multiple FDA milestones achieved, ongoing enrollment in a global pivotal study, and a growing body of supportive clinical data, we believe OBIO is well-positioned for long-term impact.

We appreciate your continued support and look forward to updating you on our progress.

— Team OBIO