HAYA Therapeutics Doses First Patients in Phase 1 Trial of HTX-001 for Cardiac Fibrosis
Key Insights
HAYA Therapeutics (search) has dosed the first cohort in its Phase 1 clinical trial of HTX-001, a first-in-class antisense oligonucleotide targeting cardiac fibrosis (search) in nonobstructive hypertrophic cardiomyopathy (search) patients.
HTX-001 works by downregulating WISPER (search), a long non-coding RNA that drives fibrosis in the heart, aiming to reprogram cardiac myofibroblasts from a disease-driving state to a healthier profile.
The Phase 1a/b study will evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy volunteers and nHCM patients across multiple ascending-dose cohorts.
Swiss biotech company HAYA Therapeutics (search) has achieved a significant milestone by dosing the first cohort in its Phase 1 clinical trial of HTX-001, an investigational RNA-based therapy targeting cardiac fibrosis (search) in patients with nonobstructive hypertrophic cardiomyopathy (search) (nHCM). This advancement marks the company's entry into the clinical stage with a potentially disease-modifying approach for a condition with significant unmet medical needs.
Novel Mechanism Targets Cardiac Fibrosis
HTX-001 represents a first-in-class antisense oligonucleotide designed to downregulate WISPER (search), a long non-coding RNA (lncRNA) that is overexpressed in patients with hypertrophic cardiomyopathy (search) and serves as a driver of fibrosis in the heart. The therapy aims to address fibrosis, or scarring, in the heart—a process linked to reduced heart function and disease progression that current treatments do not directly target.
"By decreasing WISPER (search) expression in cardiac myofibroblast cells, HTX-001 is intended to promote cell-state reprogramming of this fibrotic and pathological cell population back toward a healthy state," according to the company. Preclinical studies demonstrated that HTX-001 reduces pathological cardiac fibrosis (search) and improves heart function.
Addressing Unmet Medical Need
Nonobstructive hypertrophic cardiomyopathy (search) accounts for an estimated 30-60% of all hypertrophic cardiomyopathy (search) cases. The condition is characterized by increased wall thickness in the heart, hypertrophy in the left ventricular cavity, impaired diastolic function, and marked fibrosis. Current treatments for nHCM mainly focus on managing symptoms and improving blood flow but do not directly target the fibrotic changes driving the condition.
"A targeted anti-fibrotic therapy for nHCM offers the potential to address an important unmet medical need as currently available treatments fail to address the underlying fibrotic process that drives disease," said Jordan Shin, M.D., Ph.D., CMO of HAYA Therapeutics (search).
Clinical Trial Design and Scientific Foundation
The Phase 1a/b study will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of HTX-001 in healthy volunteers and nHCM patients through multiple ascending-dose cohorts. This represents the translation of foundational regulatory genome science into a potentially new therapeutic approach.
WISPER (search) was first discovered in 2017 by Samir Ounzain, Ph.D., co-founder and CEO of HAYA Therapeutics (search), who identified its role in cardiac fibrosis (search) and remodeling. Building on this discovery, Dr. Ounzain co-founded HAYA with Daniel Blessing, Ph.D., co-founder and CSO, who has led the research and development team responsible for advancing HTX-001 from scientific concept into clinical development.
"Our approach is built on our belief that the regulatory genome holds the instructions that drive diseased cell states," said Dr. Ounzain. "With HTX-001, we are translating that biology into an investigational precision RNA-guided therapy that is designed to enable the reprogramming of cardiac fibroblasts, the sentinel effector cells of cardiac fibrosis (search) and pathological remodeling of the myocardium."
Regulatory Status and Company Background
HTX-001 remains an investigational therapy and has not yet been approved by regulatory authorities, including the U.S. Food and Drug Administration or the European Medicines Agency. Its safety and ability to translate into clinical benefit remain to be established.
HAYA Therapeutics (search), winner of the Top100 Swiss Startup Award 2023 and recipient of Venture Kick funding, is headquartered at the life sciences park Biopôle in Lausanne, Switzerland, with laboratory facilities at Lilly Gateway Labs in San Diego, California. The company is developing a broad pipeline of RNA-guided medicines for fibrosis-driven and chronic, age-related diseases using its innovative platform that decodes the causal biology of pathological cell states and the long non-coding RNAs that regulate them.