Atrium Therapeutics Secures FDA Clearance of IND for ATR-1072, First Disease-Modifying Therapy for PRKAG2 Syndrome
核心洞察
Atrium Therapeutics (搜索) received FDA clearance for its IND application for ATR-1072 (搜索), an siRNA-based therapy targeting the genetic cause of PRKAG2 syndrome (搜索).
The Corventis™ Phase 1/2 open-label, multicenter trial will enroll approximately 37 participants and evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy.
First participant enrollment is expected by the end of 2026, with initial proof-of-concept data anticipated in the second half of 2027.
Atrium Therapeutics (搜索), Inc. (Nasdaq: RNA) announced that the U.S. Food and Drug Administration has cleared its Investigational New Drug application for ATR-1072 (搜索), the company's lead precision cardiology candidate, clearing the path for the first clinical trial evaluating a treatment targeting the underlying genetic driver of PRKAG2 syndrome (搜索).
"PRKAG2 syndrome (搜索) and other rare genetic cardiomyopathies represent a profound unmet need — these are progressive, life-altering and life-threatening diseases that often strike early, affect multiple members of the same family, and have no approved therapy to address their root cause," said Kathleen Gallagher, President and Chief Executive Officer, Atrium Therapeutics (搜索). "FDA clearance of our IND and the launch of the Corventis™ Phase 1/2 trial reinforce our team's ability to move with speed on behalf of patients with the goal of delivering potential disease-modifying treatments."
Mechanism of Action and Therapeutic Rationale
ATR-1072 (搜索) employs Atrium's precision RNA delivery technology, utilizing small interfering RNA (siRNA) to silence mutant PRKAG2 (搜索) messenger RNA (mRNA). By reducing expression of the mutated gene product, the therapy aims to normalize AMP-activated protein kinase (AMPK (搜索)) activity and reduce pathogenic glycogen accumulation in cardiac tissue, potentially leading to improved heart function. The company's proprietary platform — originally designed at Avidity Biosciences, Inc. — combines the tissue selectivity of monoclonal antibodies and other targeted delivery ligands with the precision of oligonucleotides, enabling non-viral, targeted delivery of siRNA to the heart.
Corventis™ Trial Design
The Corventis™ Phase 1/2 clinical trial is an open-label, multicenter study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of ATR-1072 (搜索). The study will enroll approximately 37 participants across two parts. Part A consists of multiple ascending dose cohorts to characterize safety and support dose selection. Part B is a single-arm expansion cohort at the recommended Phase 2 dose to further evaluate safety and efficacy trends in cardiac structure and function.
Clinical site initiation activities are currently underway, and Atrium expects the first participant to be enrolled by the end of 2026. Initial trial data demonstrating proof of concept is anticipated in the second half of 2027.
Disease Background and Unmet Need
PRKAG2 syndrome (搜索) is a rare, autosomal dominant, early-onset cardiomyopathy caused by mutations in the PRKAG2 (搜索) gene, which encodes the Gamma 2 regulatory subunit of AMPK (搜索). These gain-of-function mutations enhance AMPK activity, leading to abnormal glycogen accumulation in the heart, thickened heart muscles, electrical conduction problems, and arrhythmias. Based on current scientific literature estimates, there are at least 1,000 to 2,000 people with PRKAG2 syndrome in the United States. Current management is limited to symptomatic treatment, and no approved therapies exist to address the underlying genetic driver of the disease.
Pipeline and Platform
ATR-1072 (搜索) represents Atrium's first precision cardiology program to enter the clinic. The company's pipeline also includes ATR-1086 (搜索) for phospholamban (PLN) cardiomyopathy and two undisclosed research targets in rare cardiomyopathies. Atrium's RNA delivery platform builds upon learnings from demonstrated delivery to skeletal muscle and applies them for efficient delivery to the heart, with the potential to overcome challenges associated with non-specific tissue delivery.