Fractyl Health, Inc. showcased promising preclinical data for its RJVA-001 pancreatic gene therapy at the ASGCT 2025 Annual Meeting, indicating potential for durable metabolic improvements in type 2 diabetes (T2D) with minimal systemic GLP-1 exposure.

Biodistribution studies revealed that RJVA-001 significantly localizes to the pancreas while minimizing systemic distribution, which suggests effective delivery and a reduced risk of systemic side effects.

CEO Dr. Harith Rajagopalan highlighted RJVA-001's transformative potential for metabolic medicine, emphasizing its ability to modify disease without the adverse effects commonly associated with current therapies.

The therapy facilitates glucose-dependent GLP-1 secretion in human beta cells, mimicking natural hormone regulation rather than relying on continuous drug stimulation.

In preclinical models, a single dose of RJVA-001 led to significant metabolic enhancements, including over 200 mg/dL reductions in fasting blood sugar and improved insulin levels in db/db mice over a six-week period.

RJVA-001 demonstrated more than five-fold lower systemic GLP-1 exposure compared to traditional GLP-1 drugs, suggesting a reduced risk of side effects such as nausea and vomiting while achieving similar metabolic control.

The therapy exhibited adaptive expression based on metabolic state, showing higher GLP-1 secretion in diabetic models compared to healthy controls, which underscores its selective action.

Fractyl's Rejuva platform aims to shift the treatment of metabolic diseases from chronic management to durable, disease-modifying therapies that target the root causes of obesity and T2D.

In large animal studies, RJVA-001 was delivered via endoscopic ultrasound, achieving targeted pancreatic expression without observed toxicity, indicating a favorable safety profile for future clinical applications.

Fractyl Health plans to submit its first Clinical Trial Application (CTA) for RJVA-001 by June 2025, with the goal of initiating first-in-human studies by 2026.