Orchestra BioMed Holdings, Inc. announced the first patient was randomized in the BACKBEAT pivotal study in late December 2023. The BACKBEAT pivotal study will evaluate the efficacy and safety of atrioventricular interval modulation (?AVIM?) therapy (also known as BackBeat CNT?), for the treatment of pacemaker-indicated patients with uncontrolled hypertension despite the use of antihypertensive medications. AVIM therapy is an investigational patented bioelectronic therapy, administered using a standard dual-chamber pacemaker, designed to immediately, substantially and persistently reduce blood pressure.

Orchestra BioMed and Medtronic, Inc. (?Medtronic?) formed a strategic collaboration for the development and commercialization of AVIM therapy for hypertensive pacemaker patients in July 2022. If approved, Medtronic will have exclusive global rights to commercialize AVIM-enabled pacing systems for this target population, and Orchestra BioMed will share in the revenues generated from Medtronic sales of the AVIM-enabled pacing systems. The BACKBEAT pivotal study is a global, multi-center, prospective, randomized, double-blind study investigating the efficacy and safety of AVIM therapy in patients who have recently undergone implantation of a Medtronic dual-chamber cardiac pacemaker and have uncontrolled hypertension despite the use of antihypertensive medications. Orchestra BioMed is actively screening patients for enrollment in the BACKBEAT pivotal study.

Site activations are expected to continue throughout 2024 with a target of activating approximately 80 centers in the U.S. and Europe. The study will randomize approximately 500 patients 1:1 to AVIM therapy combined with continued medical therapy (treatment) or continued medical therapy and standard pacing alone (control). The study?s primary efficacy endpoint will determine at three months post-randomization whether AVIM-treated patients experience a statistically significant reduction in daily average blood pressure (mean 24-hour ambulatory systolic blood pressure or ?aSBP?) as compared to control patients.

The primary safety endpoint will determine at three months post-randomization whether AVIM-treated patients experience serious adverse device effects that are not anticipated with cardiac pacing. Double-blind follow up will continue through 12 months to enable the collection of additional clinical endpoints. All patients will be eligible to cross over upon completion of the 12-month blinded follow-up phase.

The BACKBEAT pivotal study investigational device exemption (?IDE?) was supported by encouraging results from MODERATO II, a prospective, multi-center, randomized, double-blind, pilot study of pacemaker patients with persistent hypertension conducted in Europe. MODERATO II showed that patients treated with AVIM therapy experienced net reductions of 8.1 mmHg in 24-hour aSBP and 12.3 mmHg in office systolic blood pressure (oSBP) at six months when compared to control patients. There were no major adverse cardiac events in the treatment group, compared to three events in three patients in the control group (0.0% vs.

14.3%). Hypertension (?HTN?) is characterized by elevated blood pressure which increases the force of blood pushing against blood vessels, requiring the heart to work harder and consume more oxygen. HTN accelerates the progression of atherosclerosis and leads to increased risk of major cardiac events like heart attack, heart failure, kidney disease and other end organ damage.

HTN is the leading global risk factor for death, affecting an estimated 1.28 billion adults worldwide. In the United States, 122 million adults, or approximately 47% of all adults, are estimated to have HTN. While many patients do not notice high blood pressure, cardiovascular risk doubles for every 10 mmHg increase in systolic blood pressure and the mortality rate doubles with an increase of 20 mmHg in systolic blood pressure.

It is estimated that more than 70% of the approximately 1.1 million people globally who are implanted with cardiac pacemakers each year are also diagnosed with HTN. Based on updated American College of Cardiology/American Heart Association guidelines, an even higher percentage (approximately 80%) of U.S. patients that are indicated for the implant of a pacemaker have HTN. Pacemaker patients tend to be elderly and are more likely to suffer from co-morbidities such as atherosclerosis, hyperlipidemia, diabetes mellitus and chronic kidney disease, and harder to treat effectively with medical therapy for many reasons including co-morbidities and a high prevalence of isolated systolic HTN.

AVIM therapy, also known as BackBeat CNT?, 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 global IDE pivotal BACKBEAT (BradycArdia paCemaKer with atrioventricular interval modulation for Blood prEssure treAtmenT) 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.