Virtue SAB: Redefining Arterial Drug-Delivery — and Why It Matters for Shareholders

Dear Shareholders,

During our recent public business update call, Chairman & CEO David Hochman discussed a number of key developments achieved over the last several months, including why Orchestra BioMed believes Virtue SAB represents a fundamentally different approach to the treatment of coronary artery disease and a major long-term value driver for our Company and shareholders.

This post summarizes that part of the discussion and explains what differentiates Virtue SAB — and why it matters for investors, especially in connection with the recent strengthening of the Company’s balance sheet and strategic partnership positioning.

A New Category Within an Established Market

Drug delivery balloons are rapidly becoming an accepted “leave-nothing-behind” treatment option for coronary artery disease, an annual global market estimated at approximately $7.5 billion. Yet, every such balloon device is a drug-coated balloon or “DCB” with the exception of Orchestra’s Virtue SAB.

All DCB — whether paclitaxel- or sirolimus-based — faces the same inherent limitations: restricted drug-loading capacity, a thin and fragile surface coating that sheds during navigation to the target lesion, and large particulate release that has the potential to cause downstream micro-embolization. These constraints seem to cap efficacy and create procedural challenges for physicians.

Virtue SAB is different by design. The Virtue® Sirolimus AngioInfusion™ Balloon (SAB) is the only non-coated balloon-based drug-delivery system in development for coronary indications.

Engineered specifically to deliver Orchestra BioMed’s proprietary SirolimusEFR™ (Extended Focal Release) formulation, Virtue SAB enables optimized uptake and extended release of sirolimus, the proven “gold standard” drug class used on all currently available drug-eluting stents, with targeted vessel delivery through our patented microporous balloon delivery system.

How Virtue SAB Works:

• Large, Liquid-Dose Delivery, NO surface Coating: 
  The SirolimusEFR formulation is prepared separately, a specific dose is loaded at the back of the balloon catheter system, and then drug is delivered as a measured, large liquid dose only upon inflation. No drug is lost in transit, so the therapeutic payload reaches the target lesion.
• Sustained, Optimized Therapeutic Drug Levels in Target Tissue: 
  Published preclinical data show that Virtue SAB achieves tissue drug levels that are 10-fold higher than those achieved by leading drug-eluting stents as shown in published studies using similar methods. Therapeutic drug levels remain above the known therapeutic threshold for the entire critical healing period after angioplasty.
• No Large Particulate, No Permanent Metal Stent: 
  Virtue SAB has passed all FDA particulate tests and leaves no permanent implant, aligning with the global shift toward safer, “leave nothing behind” drug-delivery interventions.
• Promising Clinical Signal: 
  In the SABRE pilot study, Virtue SAB achieved a 12-month target-lesion failure rate of 2.8% in single-layer restenosis — among the lowest reported for coronary ISR — with no repeat interventions from 12 through 36 months.

These data underpin the recently launched Virtue Trial, the first U.S. pivotal IDE study to compare a sirolimus-eluting balloon head-to-head with an approved paclitaxel-coated balloon for coronary ISR.

Why Virtue’s Differentiation Matters to Our Investors:

1. Pivotal-Stage Asset in a Proven Market
   Virtue SAB targets a large, established interventional cardiology category already supported by enhanced reimbursement for emerging drug-delivery balloon and robust adoption trends. Positive pivotal data could position Virtue SAB as a unique and stand-out treatment option within an important and growing market opportunity.
2. Technology Moat
   The combination of the SirolimusEFR formulation and microporous AngioInfusion™ delivery system creates meaningful IP protection and performance differentiation versus conventional coated balloons.
3. Strategic Validation and Optionality
   Terumo Corporation’s new right-of-first-refusal agreement with OBIO, for which it paid the Company $10 million and its $20 million convertible preferred stock investment - on top of the $35 million of investment previously made - reflect continued industry interest in the Virtue SAB platform’s potential, while Orchestra maintains strategic optionality as it advances the program.
4. Clinical Momentum Yields Additional Future Optionality
   Successful execution of the Virtue Trial could unlock regulatory and partnership pathways across our expanded target indications in coronary and peripheral artery disease as well as other therapeutic areas.
5. Platform Synergy
   Virtue SAB joins AVIM Therapy as a Breakthrough Device-Designated, pivotal-stage program, reinforcing Orchestra BioMed’s profile as a late-stage, platform-driven medtech innovator.

Key Final Takeaways:

Virtue SAB embodies the kind of disruptive, de-risked innovation that can redefine an established medical market. It addresses the key limitations of coated balloons while preserving the procedural simplicity physicians want — and it does so within a strong reimbursement and adoption framework that already supports premium pricing.

For shareholders, this means exposure to a large, visible market and a clear, data-driven pathway toward potential U.S. approval that could materially expand Orchestra BioMed’s long-term value creation potential.

— Team OBIO Published November 2025

Forward-Looking Statements

Certain statements included in the content distributed by Orchestra BioMed Holdings, Inc. (the “Company”) to which this disclaimer relates (including, but not limited to, visual, auditory, or written statements accessible through the link included in the Company’s digital communication) (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 initiation, enrollment, timing, implementation and design of the Company’s ongoing pivotal trials and reporting of top-line results, the potential benefits of regulatory approvals or designations received from domestic and foreign regulatory bodies with respect to the Company’s product candidates and/or ongoing trials, the potential safety and efficacy of the Company’s product candidates, the ability of the Company’s partnerships to accelerate clinical development, the realization of the clinical and commercial value of the Company’s product candidates, the Company’s ability to achieve expected regulatory and business milestones and the Company’s ability to maintain strategic optionality in light of the Terumo right of first refusal it has granted Terumo with respect to certain Virtue SAB transactions in the coronary market. 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 Form 10-K for the year ended December 31, 2024, and under the heading “Item 1A. Risk Factors” in the Company’s quarterly report on Form 10-Q for the quarter ended March 31, 2025. 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.