Key inclusion criteria for participants in the study include adults aged 35 to 70, with HbA1c levels between 7.0 and 10.0%, and a BMI of 30 to 40 kg/m², who have previously tolerated GLP-1 receptor agonists.

Pending regulatory authorization, Fractyl expects to begin dosing patients in the first-in-human study and report preliminary data in 2026.

The gene therapy will be administered through a minimally invasive endoscopic ultrasound-guided infusion directly into the pancreas, enabling nutrient-triggered GLP-1 secretion.

Fractyl Health, Inc. has submitted the first module of its Clinical Trial Application (CTA) in Europe for RJVA-001, a gene therapy designed to target type 2 diabetes (T2D) and obesity.

The Rejuva platform from Fractyl Health focuses on developing local gene therapies that aim to transform the treatment of metabolic diseases from chronic management to durable, disease-modifying therapies.

This innovative platform seeks to provide a one-time, durable gene therapy solution that normalizes blood glucose and body weight, potentially reducing the reliance on lifelong injectable treatments.

RJVA-001 is designed to express glucagon-like peptide-1 (GLP-1) locally in pancreatic beta cells, offering a physiologic alternative to systemic GLP-1 therapies that often cause side effects due to high circulating levels.

An upcoming Phase 1/2 study will be an open-label, multicenter trial evaluating the safety, tolerability, and early efficacy of RJVA-001 in adults with inadequately controlled T2D.

The study will monitor participants for 12 months, with a long-term follow-up extending up to 5 years, assessing safety, glucose control, immune response, and GLP-1 expression.

Data presented at the American Society of Cell and Gene Therapy (ASGCT) 2025 meeting demonstrated the safety, potency, and nutrient-responsive secretion of RJVA-001 with low circulating GLP-1 levels in preclinical models.

Harith Rajagopalan, Co-Founder and CEO of Fractyl Health, emphasized the company's goal to develop best-in-class incretin therapies that offer enhanced durability, potency, and tolerability compared to conventional GLP-1 drugs.

Professor Jacques J.G.H.M. Bergman highlighted the study as a potential shift from managing T2D as a chronic disease to treating it at its source by directly targeting beta cells.