OBIO Orchestra BioMed Holdings Inc

Orchestra BioMed Holdings, Inc. (Nasdaq: OBIO) (“Orchestra BioMed” or the “Company”), a biomedical company accelerating high-impact technologies to patients through risk-reward sharing partnerships, today announced a late-breaking oral presentation of data on the benefits of atrioventricular interval modulation (“AVIM”) therapy on patients with diastolic dysfunction at the Technology and Heart Failure Therapeutics (“THT”) 2025 Conference in Boston, Massachusetts. The retrospective analysis of data from the MODERATO II study demonstrated that AVIM therapy significantly improved echocardiographic (“Echo”) markers of diastolic dysfunction, an important component in the development of heart failure, in hypertensive patients.

The presentation titled "Effects of Atrioventricular Interval Modulation (AVIM) Therapy in Subjects with Hypertension and Diastolic Dysfunction" is being delivered in a late-breaking clinical science session at THT by Marat Fudim, M.D., M.H.S.​ Advanced Heart Failure Cardiologist, Duke Health on Wednesday, February 12, 2025, at 10:43am ET.

Dr. Fudim commented, “For many patients with long-standing hypertension, the heart can undergo structural and functional changes that result in diastolic dysfunction, the progression of which is directly linked to the development of heart failure. By reducing systolic blood pressure and favorably impacting intra-cardiac pressures and volumes, AVIM therapy directly affects diastolic filling and myocardial relaxation. This analysis of MODERATO II data provides exciting insights that suggest that, beyond lowering systolic blood pressure, AVIM therapy improves diastolic function and leads to favorable ventricular remodeling. Given the strong link between uncontrolled hypertension, diastolic dysfunction, and heart failure, these findings highlight the opportunity to intervene earlier and leverage AVIM therapy for the prevention of heart failure.”

Key Findings:

A retrospective, treatment-blinded analysis of MODERATO II assessed the impact of 6 months of AVIM therapy on systolic blood pressure (“SBP”) and Echo markers of diastolic dysfunction (“DD”) using core lab Echos with independent blinded adjudication. Patients were classified as with DD (“DD+”) or without DD (“DD-”) using ​the American Society of Echocardiography Guidelines. From the MODERATO II study cohort (n=47), 36 patients had technically sufficient Echo data, and 61% of this group (22/36) had Echo evidence of DD.

Using key measures of diastolic function, AVIM therapy:

• Significantly reduced office and ambulatory SBP in patients ​with DD through 6 months
  • Ambulatory SBP (“aSBP”) was reduced in AVIM-treated DD+ patients (N=12) by 8.3±9.7 mmHg (p<0.01 vs baseline) compared to 2.2±9.8 mmHg in the control DD+ group (N=10)
  • Office SBP (“oSBP”) was reduced in AVIM-treated DD+ patients by 12.1±12.8 mmHg (p<0.01 vs baseline) compared to an increase of 2.9±26.4 mmHg in the control DD+ group (N=10)
  • SBP reduction was similar in patients with and without DD
• Significantly improved key measures of diastolic dysfunction​
  • In patients with DD, AVIM therapy demonstrated favorable Echo changes consistent with improved myocardial relaxation and diastolic compliance. Specifically, in comparison to DD+ control patients, AVIM-treated DD+ patients experienced a significant increase in e’ (from 5.9±2.0 to 8.8±3.4cm/sec; P<0.01) consistent with an improvement in left ventricular relaxation and a significant increase in E/A (from 0.86±0.39 to 1.60±0.84; P<0.01) consistent with improved passive filling of the left ventricle despite reduced filling time (the designed effect of AVIM therapy) with no significant changes in left atrial size.

“The late-breaking data shared at THT present a broader view of the potential benefits of AVIM therapy for patients with uncontrolled hypertension and increased cardiovascular risk. These findings provide further evidence that AVIM therapy, in addition to significantly reducing systolic blood pressure, may also favorably influence ventricular function in important ways for patients with diastolic dysfunction and at risk for heart failure,” said Avi Fischer, M.D., Senior Vice President of Medical Affairs and Innovation at Orchestra BioMed. “This could provide a new paradigm for the treatment of hypertension and its many associated risks in pacemaker-indicated patients and other higher risk populations, offering the opportunity to potentially intervene earlier in disease progression. We are eager to continue exploring the clinical effects of AVIM therapy through the ongoing BACKBEAT global pivotal study in which we fully expect to see many hypertensive patients like these that are not adequately controlled with antihypertensive medication and also have diastolic dysfunction and increased risk for heart failure. We believe this robust, double-blind, randomized study will define AVIM therapy’s potential role in the management of uncontrolled high blood pressure and its broader cardiovascular effects.”

About Orchestra BioMed

Orchestra BioMed (Nasdaq: OBIO) is a biomedical innovation company accelerating high-impact technologies to patients through risk-reward sharing partnerships with leading medical device companies. Orchestra BioMed’s partnership-enabled business model focuses on forging strategic collaborations with leading medical device companies to drive successful global commercialization of products it develops. Orchestra BioMed’s lead product candidate is atrioventricular interval modulation (AVIM) therapy for the treatment of hypertension, a significant risk factor for death worldwide. Orchestra BioMed is also developing the Virtue® Sirolimus AngioInfusion™ Balloon (SAB) for the treatment of atherosclerotic artery disease, the leading cause of mortality worldwide. Orchestra BioMed has a strategic collaboration with Medtronic, one of the largest medical device companies in the world, for development and commercialization of AVIM therapy for the treatment of hypertension in pacemaker-indicated patients, and a strategic partnership with Terumo, a global leader in medical technology, for development and commercialization of Virtue SAB for the treatment of artery disease. For further information about Orchestra BioMed, please visit www.orchestrabiomed.com, and follow us on LinkedIn.

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About AVIM Therapy

AVIM therapy is an investigational therapy compatible with standard dual-chamber pacemakers designed to substantially and persistently lower blood pressure. It has been evaluated in pilot studies in patients with hypertension who are also indicated for a pacemaker. MODERATO II, a double-blind, randomized pilot study, showed that patients treated with AVIM therapy experienced net reductions of 8.1 mmHg in 24-hour ambulatory systolic blood pressure (aSBP) and 12.3 mmHg in office systolic blood pressure (oSBP) at six months when compared to control patients. The BACKBEAT (BradycArdia paCemaKer with atrioventricular interval modulation for Blood prEssure treAtmenT) global pivotal study will further evaluate the safety and efficacy of AVIM therapy in lowering blood pressure in a similar target population of patients who have been indicated for, and recently implanted with, a dual-chamber cardiac pacemaker.

Forward-Looking Statements

Certain statements included in this press release 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 efficacy, safety and commercial value of the Company’s commercial product candidates, including the ability of AVIM therapy to favorably influence ventricular function, implementation of the Company’s ongoing BACKBEAT global pivotal study, the ability of the Company’s partnerships to accelerate clinical development, and the Company’s late-stage development programs and strategic partnerships. These statements are based on various assumptions, whether or not identified in this press release, 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 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, 2023, which was filed with the U.S. Securities and Exchange Commission on March 27, 2024, as updated by any risk factors disclosed 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 this press release. The Company does not plan and undertakes no obligation to update any of the forward-looking statements made herein, except as required by law.

Investor ContactSilas NewcombOrchestra BioMed (908) 723-4489 Snewcomb@orchestrabiomed.com

Media ContactKelsey Kirk-EllisOrchestra BioMed(484) 682-4892Kkirkellis@orchestrabiomed.com