Strengthening AVIM Therapy’s Regulatory Pathway: A Second FDA Breakthrough Device Designation

Orchestra BioMed Investor Relations Blog | April 2026

The second Breakthrough Device Designation awarded to AVIM Therapy underscores its potential in a defined high-risk population and supports an accelerated development pathway.

Our POV

Atrioventricular Interval Modulation Therapy (“AVIM Therapy”) has received a second Breakthrough Device Designation (“BDD”) from the U.S. Food and Drug Administration (“FDA”) specific to patients who have uncontrolled hypertension despite the use of anti-hypertensive medications and who are also indicated for a pacemaker. This is the same patient population being evaluated in the BACKBEAT Global Pivotal Trial (“BACKBEAT Trial”), which Orchestra is conducting in collaboration with Medtronic, the global market leader in cardiac pacing therapy.

BDD is granted to investigational therapies that the FDA deems to be potentially more effective than currently available treatments for serious or life-threatening conditions, reflecting the agency’s recognition of both the unmet need in this population and the potential of AVIM Therapy to address it.

This is a meaningful advancement for the AVIM Therapy program that helps to clarify our regulatory strategy and may provide strategic optionality on future reimbursement pathways.

Attributes of Breakthrough Device Designation

• Designed to accelerate development and review for technologies addressing serious condition
• Requires potential for meaningful improvement over existing treatment or diagnostic options
• Enables more frequent, interactive engagement with the FDA throughout development
• Supports alignment with the FDA on trial design and evidence expectations
• Provides a prioritized pathway toward potential marketing authorization

Why it Matters: Two BDDs Across the Full AVIM Therapy Opportunity

With this latest designation, the FDA has now granted two BDDs for AVIM Therapy that both apply to strategically and commercially relevant indications:

• The first granted BDD applies to a larger downstream opportunity to address patients with uncontrolled hypertension despite the use of anti-hypertensive medications who have increased cardiovascular risk, representing an estimated 7.7M+ U.S. adults.
• The second granted BDD applies more specifically to patients who have uncontrolled hypertension despite the use of anti-hypertensive medications and an indication for a pacemaker, representing over 320,000 adults in the U.S. annually.

The two designations together reflect the way Orchestra has always envisioned AVIM Therapy reaching patients. Our team and Medtronic are highly focused on completing the BACKBEAT Trial, which is intended to generate data that could support regulatory approval for the treatment of uncontrolled hypertension in pacemaker-indicated patients. With the right clinical evidence, we expect to work toward expanded use in the broader population of patients with uncontrolled hypertension and elevated cardiovascular risk who could benefit from a device-based, adherence-independent therapy.

Commenting on the news, David Hochman, Chairman and Chief Executive Officer of Orchestra BioMed, said, “We are pleased to receive this additional Breakthrough Device Designation from the FDA. We believe it is directly aligned with the patient population being studied in our ongoing BACKBEAT Trial, which we are executing in collaboration with Medtronic. Continued alignment from the FDA, alongside our strategic relationship with Medtronic and accelerated enrollment in the BACKBEAT Trial, puts us in a strong position to advance AVIM Therapy to pivotal trial results.”

A Differentiated Reimbursement Pathway

Having a BDD positions AVIM Therapy to potentially benefit from streamlined FDA reviews, as well as favorable reimbursement pathways under the Centers for Medicare & Medicaid Services. Specifically, BDD supports potential eligibility for incremental inpatient reimbursement through the New Technology Add-on Payment program and outpatient Transitional Pass-Through payments. These mechanisms are designed to bridge the gap between innovation and reimbursement for breakthrough technologies, helping support more timely access for patients and earlier adoption by providers once a device reaches the market.

Strategic Alignment with Medtronic

We and Medtronic are jointly focused on the development and commercialization of AVIM Therapy for the treatment of uncontrolled hypertension in pacemaker-indicated patients. Under our existing collaboration agreement, Medtronic holds a right of first negotiation to obtain global commercialization rights to AVIM Therapy in patients who do not have an indication for a pacemaker, the broader population for which FDA has granted BDD.

Looking Ahead: Focused on Execution

AVIM Therapy is currently being evaluated in the BACKBEAT Trial, a randomized, prospective, multi-center, double-blind, controlled IDE study (NCT06059638) sponsored by Orchestra BioMed and conducted in partnership with Medtronic. The trial is enrolling patients across the United States, Europe, and Asia-Pacific who have or are scheduled to receive a Medtronic Astra™ or Azure™ dual-chamber pacemaker and who remain hypertensive despite 1 to 3 classes of medication.

With this additional BDD, an actively enrolling pivotal program, and a strategic partner with global commercial reach in cardiac pacing, our priorities remain the same as those we have consistently communicated. We are focused on advancing the BACKBEAT Trial to pivotal trial results, deepening the body of clinical evidence supporting AVIM Therapy, and continuing to build the regulatory and commercial foundation AVIM Therapy needs to reach the patients who could benefit most.

- Team OBIO

Published April 2026

Forward-Looking Statements

Certain statements included in the content contained in or accessible through this blog post (the “Content”) that are not historical facts are forward-looking statements for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements generally are accompanied by words such as “believe,” “may,” “will,” “estimate,” “continue,” “anticipate,” “intend,” “expect,” “should,” “would,” “plan,” “predict,” “potential,” “seem,” “seek,” “future,” “outlook” and similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These forward-looking statements include, but are not limited to, statements relating to the potential clinical benefits, mechanism of action, development pathway, and commercial opportunity for AVIM Therapy; the potential benefits of Breakthrough Device Designation, including its ability to expedite FDA reviews and support favorable reimbursement pathways; the design, enrollment progress, timing, and anticipated results of the BACKBEAT Trial; and the benefits of the strategic partnership between Orchestra BioMed Holdings, Inc. (the “Company”) and Medtronic. These statements are based on various assumptions, whether or not identified in the Content, and on the current expectations of the Company’s management and are not predictions of actual performance. These forward-looking statements are provided for illustrative purposes only and are not intended to serve as and must not be relied on as a guarantee, an assurance, a prediction, or a definitive statement of fact or probability. Actual events and circumstances are difficult or impossible to predict and may differ from assumptions. Many actual events and circumstances are beyond the control of the Company. These forward-looking statements are subject to a number of risks and uncertainties, including changes in domestic and foreign business, market, financial, political, and legal conditions; risks related to regulatory approval of the Company’s commercial product candidates and ongoing regulation of the Company’s product candidates, if approved; the timing of, and the Company’s ability to achieve expected regulatory and business milestones; the impact of competitive products and product candidates; and the risk factors discussed under the heading “Item 1A. Risk Factors” in the Company’s Annual Report on Form 10-K for the year ended December 31, 2025, which was filed with the SEC on March 12, 2026. The Company operates in a very competitive and rapidly changing environment. New risks emerge from time to time. Given these risks and uncertainties, the Company cautions against placing undue reliance on these forward-looking statements, which only speak as of the date of the Content. The Company does not plan and undertakes no obligation to update any of the forward-looking statements made in the Content, except as required by law.