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Fractyl Health has unveiled promising new preclinical results for RJVA-001, a novel gene therapy from its Rejuva® Smart GLP-1™ platform, at the ASGCT 2025 Annual Meeting. Unlike traditional GLP-1 drugs that deliver high, constant levels of hormone throughout the body, RJVA-001 uses a one-time gene therapy to enable the pancreas to secrete GLP-1 in a natural, nutrient-responsive way. This approach could avoid many of the side effects seen with current drugs, such as nausea, while still delivering long-lasting improvements in blood sugar control and weight management.
In a gold-standard diabetic mouse model, RJVA-001 led to significant reductions in blood sugar and weight gain, with over a 200 mg/dL drop in fasting glucose and more than a twofold rise in insulin levels. Crucially, it achieved these effects with GLP-1 levels 5 times lower than typical drug therapies, mimicking the levels seen after gastric bypass surgery. These lower hormone levels may reduce the risk of side effects while still offering strong metabolic benefits.
The therapy also demonstrated precise control of hormone release. In both lab-grown and ex vivo human pancreatic cells, GLP-1 secretion more than doubled in response to high glucose levels, suggesting RJVA-001 can mimic the body’s natural hormone rhythms. Furthermore, diabetic mice showed more pronounced GLP-1 expression than healthy controls at the same dose, indicating the therapy can adapt to the body's metabolic needs.
Safety and feasibility were confirmed in a large animal model, where an endoscopic ultrasound technique successfully delivered RJVA-001 directly to the pancreas with minimal spread to other organs and no signs of toxicity. Based on these findings, Fractyl Health plans to submit a clinical trial application and aims to begin human testing in 2026. If successful, this approach could represent a new era in treating type 2 diabetes and obesity through targeted, durable, and safer gene therapies.
