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First Clinical Investigation of a Gene Therapy (YAP101) to Induce Cardiac Regeneration to Treat Heart Failure Passes Initial Safety Hurdle

via Business Wire
  • Medley Therapeutics (formerly YAP Therapeutics) has dosed the first cohort (n=3) with YAP101 in the Phase 1 SALVADOR-HF trial at The Texas Heart Institute at Baylor College of Medicine in the Baylor St. Luke’s Medical Center (Houston).
  • This is the first clinical investigation of a genetic medicine to induce endogenous regeneration.
  • YAP101 is an investigational, first‑in‑class AAV genetic medicine that uses a cardiomyocyte‑specific promoter to express shRNA, transiently suppressing Hippo signaling and activating YAP to enable self‑limiting myocardial regeneration.
  • Following favorable safety findings, the independent Safety Review Team recommended escalation to the next protocol-defined dose level.

Medley Therapeutics, Inc. (formerly YAP Therapeutics), a company developing regenerative genetic medicines and advanced biologics, today announced completion of dosing in the first cohort (n=3) of the Phase 1 SALVADOR-HF clinical trial evaluating YAP101 in patients with advanced ischemic heart failure with reduced ejection fraction (HFrEF) at The Texas Heart Institute at Baylor College of Medicine and at the St. Luke’s Medical Center (Houston). Following favorable safety findings, the study’s independent Safety Review Team recommended escalation to the next protocol-defined dose level.

YAP101 is an investigational, first-in-class adeno-associated virus (AAV) genetic medicine designed to stimulate endogenous myocardial regeneration. Using a cardiomyocyte-specific promoter to express short hairpin RNAs (shRNAs), YAP101 transiently suppresses Hippo signaling and activates YAP, with the goal of enabling self-limiting regeneration of heart muscle. The core technology for YAP101 was developed in the Martin Laboratories at The Texas Heart Institute (THI) at Baylor College of Medicine (BCM).

The SALVADOR-HF trial includes three planned dose levels in a dose-escalation phase (target enrollment 9-18 subjects), followed by a dose-level expansion of up to six additional subjects.

“Induction of endogenous regeneration of human heart muscle is the holy grail of modern medicine,” said James F. Martin, MD, PhD, Founder of Medley Therapeutics; Director, Cardiomyocyte Renewal Laboratory and the Vivian L. Smith Chair in Regenerative Medicine, BCM. “YAP101 is designed to unlock the heart’s own repair mechanism by transiently lifting the Hippo pathway ‘brake’ and activating YAP via shRNAs delivered directly to cardiomyocytes. We successfully regenerated cardiomyocytes in preclinical studies, and we are excited about the next step—healing the hearts of patients with limited treatment options.”

“Until now, there has not been a way to regenerate human heart tissue,” said Emerson Perin, MD, PhD, Medical Director, Medley Therapeutics; and Director, Center for Clinical Research, THI. “YAP101 offers new hope for patients with heart failure. Our aim is to enable the heart to repair itself and reverse heart failure through a brief cardiac catheterization procedure.”

“For the tens of millions of people living with heart failure, progress can’t come soon enough,” said Olav Bergheim, Founder, Chairman and Chief Executive Officer of Medley Therapeutics. “Completing the first cohort and advancing to the next dose level is a decisive milestone for SALVADOR-HF—and an important step toward a potentially transformative treatment option. We are grateful to our partners at The Texas Heart Institute at Baylor College of Medicine, and to our Medley team, for bringing this vision closer to reality.”

About SALVADOR-HF (Phase 1)

SALVADOR-HF is a first-in-human, dose-escalation and dose-expansion study evaluating the safety, feasibility, and exploratory biologic activity of YAP101 in adults with HFrEF. The trial is being conducted at the Texas Heart Institute at Baylor College of Medicine St. Luke’s Medical Center in Houston (NCT06831825).

About Medley Therapeutics, Inc.

Medley Therapeutics pioneers the development of advanced biologics and genetic medicines to treat chronic and life-threatening diseases. Founded by Dr. James F. Martin, Olav Bergheim, and the late Dr. James Willerson with a vision to regenerate heart tissue, the company’s portfolio includes genetic medicines to endogenously regenerate organs and treat cardiac arrhythmias, as well as advanced biologics targeting oncology and fibrotic diseases. Medley’s lead gene therapy candidate, YAP101, is designed to drive cardiac regeneration through modulation of the Hippo/YAP signaling pathway and related mechanisms.

For further information, visit www.medleytx.com.

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