Orchestra BioMed Investor Relations Blog | April 2026
Recently presented clinical and mechanistic findings reinforce the potential of Atrioventricular Interval Modulation Therapy (“AVIM Therapy”) to immediately reduce blood pressure and have a favorable cardiac hemodynamic impact, expanding its potential therapeutic relevance beyond hypertension into hypertensive heart disease.
AVIM Therapy is an investigational, device-based treatment for uncontrolled hypertension, initially aimed at treating patients indicated for a dual-chamber pacemaker. Delivered through programmable pacing, it is designed to acutely modulate cardiac function and reduce blood pressure independent of patient adherence.
New data presented at the 2026 Heart Rhythm Society Annual Meeting (“HRS 2026”) add to the growing body of evidence of AVIM Therapy’s potential to produce an immediate and sustained reduction in systolic blood pressure, while also driving measurable improvements in cardiac function.
Importantly, these findings extend beyond blood pressure control alone, supporting the therapy’s potential role in addressing the broader progression of hypertensive heart disease. In the context of the ongoing BACKBEAT Global Pivotal Trial (“BACKBEAT Trial”), this reinforces both the mechanistic rationale and the clinical relevance of AVIM Therapy in high-risk hypertension populations.
Hypertension, or high blood pressure, is a progressive cardiovascular condition that drives structural and functional changes in the heart over time. Despite the availability of numerous anti-hypertensive medications, roughly seven in ten older adults on anti-hypertensive medications remain inadequately controlled.
Prof. Karl-Heinz Kuck, M.D., Medical Director of LANS Cardio Hamburg, presented pre-randomization setup data from MODERATO II -- the randomized, prospective, multi-center, double-blind, pilot study that helped establish the clinical foundation for the BACKBEAT Trial. Complementing the clinical results, Prof. Milan Chovanec, M.D., of Na Homolce Hospital, presented a poster summarizing favorable mechanistic findings from a pressure-volume loop study of AVIM Therapy. Taken together, the HRS 2026 presentations help frame the potential role of AVIM Therapy in addressing the persistent unmet global need in hypertension management.
1. Immediate, Near-Universal Blood Pressure Response at AVIM Set Up
As part of enrollment in MODERATO II, AVIM Therapy was set up in a patient’s pacemaker and briefly turned on to measure an acute therapy response. Across enrolled patients, AVIM Therapy drove a mean immediate reduction of 13.2 mmHg in office systolic blood pressure (“oSBP”) at set up, and 97% of patients experienced an immediate reduction of greater than 5 mmHg in oSBP prior to randomization.
The pre-randomization setup data tie the chronic blood pressure benefits previously reported from MODERATO II -- net reductions of 8.1 mmHg in 24-hour ambulatory systolic blood pressure (“aSBP”) and 12.3 mmHg in oSBP at six months versus control -- to an immediate, consistent response observable in the majority of evaluated patients at the time of therapy activation. This acute responder rate offers the clearest view yet of the immediacy, magnitude, and reproducibility of the AVIM Therapy effect, and provides important context as the BACKBEAT Trial, which is actively enrolling using the same setup methodology, moves toward completion of patient enrollment.
2. Sustained Blood Pressure Control with Long-Term Durability
AVIM Therapy also demonstrated consistent, durable blood pressure control in MODERATO II. At six months, mean 24-hour aSBP in treated patients was 125.2 mmHg, with 89% of patients achieving aSBP below 140 mmHg, the threshold defined by current European Society of Cardiology guidelines for optimal blood pressure control. Further, 58% of patients achieved aSBP below 130 mmHg, the more stringent target recommended by the American Heart Association and American College of Cardiology. A long-term sub-cohort showed sustained reductions in aSBP through approximately 3.6 years of follow-up, with no evidence of rebound hypertension following deactivation and reactivation of therapy.
Slide reproduced from Prof. Kuck’s HRS 2026 presentation. Six-month aSBP control rates and durability of effect through approximately 3.6 years of follow-up in a long-term sub-cohort.
The observed control rates exceeded those typically reported with additional pharmacologic therapy in similar older, comorbid hypertensive populations, in which fewer than half of treated patients achieve guideline-recommended targets despite multi-drug regimens. Additionally, the durability of effect through several years of follow-up, together with previously reported sub-analyses showing reduced pulse pressure, improved diastolic function, and reverse cardiac remodeling, points to the potential of AVIM Therapy to influence the underlying progression of hypertensive heart disease rather than simply manage a number on a cuff.
Commenting on the totality of the dataset, Prof. Kuck stated, “The observed response rate and mean blood pressure reduction in the MODERATO II study provide a clear and consistent baseline signal of AVIM Therapy’s potential effect. The magnitude of ambulatory blood pressure reduction brought the majority of patients well within contemporary guideline-recommended targets for optimal blood pressure control. We look forward to further results from the BACKBEAT Trial as AVIM Therapy, in combination with a modest medical regimen, may offer a differentiated path to sustained blood pressure control in this older, higher-risk patient population.”
3. Mechanistic Insights from Pressure-Volume Loop Analysis
The pressure-volume analysis showed that AVIM Therapy acutely reduced systolic blood pressure by decreasing cardiac preload and effective arterial elastance (afterload), independent of ventricular lead location, without affecting left ventricular contractility. Compared with standard AV pacing, AVIM Therapy drove statistically significant (p<0.05) reductions in systolic blood pressure, end-diastolic volume, end-diastolic pressure, and end-systolic volume using both CSP and RV configurations, as well as reductions in stroke work without significantly reducing stroke volume, and a reduction in total peripheral resistance with no change in contractility. These findings support a favorable cardiovascular safety profile in hypertensive heart disease and demonstrate consistent hemodynamic effects across pacing strategies commonly used in clinical practice.
Looking Ahead: Focused on Clinical 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 BACKBEAT Trial is intended to generate the clinical evidence required to support potential regulatory approval and adoption of AVIM Therapy in patients with uncontrolled hypertension despite medical therapy who also have an indication for a pacemaker, an estimated annual global target population of 1 million patients. Orchestra BioMed also remains focused on continuing to build the scientific foundation supporting AVIM Therapy’s potential use in broader patient populations beyond those indicated for a pacemaker.
- Team OBIO
Published April 2026
Forward-Looking Statements
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