Unlocking the Value of Virtue SAB with the Achievement of Two Major Milestones - Why Investors Should Take Notice

Dear Shareholders,

In recent days, Orchestra BioMed announced two complementary milestones that together reflect the Company’s continued progress in executing its strategy to accelerate high-impact cardiovascular innovations through strategic partnerships and disciplined clinical advancement.

First, Orchestra BioMed announced first patient enrollments in the Virtue Trial, the U.S. pivotal IDE study designed to support regulatory approval of Virtue SAB for the treatment of coronary in-stent restenosis (ISR).

Orchestra BioMed and Terumo Corporation also entered into a new strategic rights agreement and a stock purchase agreement providing $30 million in cash to OBIO as well as strategic optionality for the Company’s Virtue® Sirolimus AngioInfusion™ Balloon (“Virtue SAB”) platform, while illustrating Terumo’s continued interest in the Virtue SAB program.

These developments represent a significant shift for OBIO’s Virtue SAB program to active pivotal trial execution and significant future value creation opportunities.

New ROFR Agreement Highlights Strategic Interest & Optionality 

We believe the new Right of First Refusal (ROFR) agreement, which 1) terminates and replaces the previous agreement between the companies and 2) will remain in effect until 90 days after Orchestra BioMed discloses the primary endpoint data of the Virtue Trial to Terumo, provides strategic optionality to both companies. Orchestra BioMed can now seek development and commercialization partnerships or other strategic transactions for Virtue SAB in any therapeutic indication, including coronary artery disease treatment. If Orchestra BioMed receives an attractive proposal related to the global coronary market rights for Virtue SAB that it wants to accept, it will notify Terumo, which will have 30 days to provide notice to us of its election to exercise its right of first refusal and 90 days after providing such notice to negotiate and enter into a transaction with us with respect to Virtue SAB. Importantly, Orchestra BioMed retains full global development and distribution rights to Virtue SAB across all markets and indications.

In connection with the new agreement, Orchestra BioMed receives $30 million, comprised of a $10 million payment for the ROFR agreement and a $20 million non-voting preferred equity investment, convertible at a minimum of $12 per share only on or after the earlier of (i) the date that (a) the data from the Virtue Trial is disclosed publicly and (b) OBIO’s common stock is trading above $15 per share and (ii) a change of control of Orchestra BioMed

The $30 million in proceeds, in addition to the $117.6 million in gross proceeds from multiple strategic financial transactions since August, provide an expected financial runway into late 2027 to advance both pivotal-stage programs—Virtue SAB and AVIM Therapy—toward key regulatory milestones, including completion of enrollment for the BACKBEAT global pivotal study and primary results readout, as well as completion of enrollment for the Virtue Trial.

David Hochman, OBIO’s Chairman & CEO commented: “The $30 million in proceeds from Terumo provides meaningful additional capital resources to advance both of our pivotal stage programs to key clinical and regulatory milestones. We are glad to be aligned with our colleagues at Terumo and are thrilled to have initiated the Virtue Trial evaluating our fundamentally different approach to treating coronary in-stent restenosis.”

Advancing Virtue SAB into U.S. Pivotal Phase

The Virtue Trial is a 740-patient, up to 75-site U.S. pivotal IDE study comparing Virtue SAB - OBIO’s non-coated, extended-release sirolimus delivery balloon to Boston Scientific’s AGENT™, currently the only FDA-approved paclitaxel-coated coronary balloon. The trial represents the first head-to-head evaluation of a sirolimus-eluting balloon to a paclitaxel-coated balloon in a pivotal trial setting and is designed to support U.S. regulatory approval for Virtue SAB in the treatment of coronary ISR.

Virtue SAB and its proprietary SirolimusEFR™ formulation are designed to achieve sustained therapeutic tissue levels during the critical healing period without the particulate embolization and dosing limitations associated with coated balloons. Prior data from the SABRE study demonstrated 12-month target lesion failure of just 2.8% and no reinterventions through 36 months, supporting the rationale for the U.S. pivotal program.

Jarrod Frizzell, MD, MS, FACC, FSCAI, Director of Complex Coronary Therapeutics, Interventional Cardiology, The Christ Hospital Health Network, commented: “The Virtue Trial will allow us to evaluate the performance of this fundamentally different approach to delivering sirolimus, which has shown promising results in a prior pilot clinical study in coronary ISR treatment, in direct comparison to the AGENT paclitaxel-coated balloon.”

OBIO COO, Darren R. Sherman added: “We designed Virtue SAB and its key enabling technology, our proprietary SirolimusEFR, to overcome these limitations and realize the full potential of arterial drug delivery during angioplasty. With the launch of the Virtue Trial, we’re taking a major step toward realizing our vision of improving patient outcomes.”

Strategic and Clinical Significance

These announcements are linked by a common theme: momentum with control. Both reinforce Orchestra BioMed’s position as a late-stage, platform-driven medtech innovator with two Breakthrough Device-designated programs in pivotal development—Virtue SAB and AVIM Therapy.

Investor Summary Table

Key Takeaways for Shareholders

For shareholders, the combined impact of these announcements is clear:

• Financially, Orchestra BioMed is better capitalized to advance its pivotal programs to key inflection points;
• Strategically, the Company has strategic optionality with regard to maximizing Virtue SAB’s global opportunity while Terumo remains a strong potential commercial partner; and
• Clinically, the Virtue Trial marks a pivotal advancement toward FDA approval in a major coronary indication.

These developments together demonstrate the Company’s disciplined execution and reinforce confidence in its long-term strategy to deliver high-impact therapies through selective global partnerships and rigorous clinical validation.

For more detailed information, see the Form 8-K filed by Orchestra BioMed with the SEC on October 28, 2025.

- Team OBIO

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 planned and 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 expected benefits of the new Terumo agreement. 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 most recent annual report on Form 10-K filed with the SEC , and under the heading “Item 1A. Risk Factors” in the Company’s subsequently filed quarterly reports on Form 10-Q.  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.