Fractyl Health Submits First CTA Module in Europe for AAV Gene Therapy RJVA-001 in Type 2 Diabetes

BURLINGTON, Mass. – May 19, 2025 – Fractyl Health, Inc. (Nasdaq: GUTS) announced it has submitted the first module of its Clinical Trial Application (CTA) in Europe for RJVA-001, an adeno-associated virus (AAV) gene therapy candidate from its Rejuva platform. RJVA-001 is designed to use an AAV vector to express GLP-1 locally in pancreatic beta cells under nutrient control, aiming for physiologic hormone secretion without the systemic side effects of GLP-1 drugs. First-in-human dosing is anticipated in 2026, pending regulatory clearance.

This one-time AAV gene therapy is delivered directly to the pancreas via endoscopic ultrasound. The construct uses a proprietary insulin promoter to trigger GLP-1 secretion from transduced beta cells in response to nutrients. Fractyl Health believes this local AAV-mediated GLP-1 signaling could offer comparable or better efficacy than current drugs with improved tolerability. Preclinical data presented at ASGCT 2025 showed safety, dose-dependent potency, and nutrient-responsive secretion of RJVA-001 with low systemic GLP-1 levels in animals.

CEO Dr. Harith Rajagopalan stated that this CTA submission is a major step in their mission to develop best-in-class incretin therapies, aiming for a one-time, durable AAV gene therapy to normalize blood glucose and body weight with better tolerability and convenience than injectable drugs.

The upcoming Phase 1/2 study will evaluate the safety, tolerability, and preliminary efficacy of this AAV gene therapy in adults with inadequately controlled T2D. Participants will receive RJVA-001 via intrapancreatic injection and be monitored for 12 months.

Professor Jacques Bergman highlighted the potential of this AAV-based approach to reverse T2D at its source by directly targeting beta cells, potentially transforming diabetes treatment from daily management to a single intervention.

The Rejuva platform focuses on developing next-generation AAV-based, locally delivered gene therapies for obesity and T2D, targeting the pancreas to address the root causes of metabolic diseases.