Fractyl Health presents preclinical data on Rejuva Smart GLP-1 platform

Fractyl Health (GUTS) announced new preclinical data from its Rejuva Smart GLP-1 pancreatic gene therapy platform at the American Diabetes Association’s 85th Scientific Sessions. The abstract, titled “Single-Dose GLP-1-Based Pancreatic Gene Therapy Prevents Obesity and Diabetes in High-Fat Fed Mice,” demonstrated that a single dose of Rejuva was well-tolerated in healthy mice, and prevented weight gain and hyperglycemia following a switch to a high-fat diet. These findings further validate Rejuva’s potential as a one-time, durable therapy with strong activity in obesity and diabetes and a favorable toxicity profile across multiple preclinical models. Importantly, these data highlight Rejuva’s distinct mechanism of action, setting it apart from systemic GLP-1 receptor agonists. The Smart GLP-1 design of Rejuva enables nutrient-responsive secretion, exerting no physiologic effect under healthy metabolic conditions and only activating in the presence of metabolic stress. This targeted activity, which mimics the body’s endogenous GLP-1 physiology, highlights the potential for Rejuva to offer superior potency and tolerability. The study evaluated Rejuva treatment using an AAV vector designed for beta-cell-specific expression of a GLP-1 analog in four groups of mice. Key results include: In a diet-induced obesity model, Rejuva treatment resulted in a 20% reduction in body weight and a 38% decrease in blood glucose by day 21. These effects were maintained through the end of the study on day 37 despite continued exposure to a high-fat diet. In lean animals treated with Rejuva and then exposed to a high-fat diet, weight gain and hyperglycemia were fully prevented. By the end of the study, Rejuva treated animals maintained baseline body weight and showed an 8% reduction of blood glucose relative to baseline. Rejuva was well-tolerated across all treatment groups, with no signs of toxicity, excessive weight loss, or hypoglycemia in healthy animals. These findings reinforce the nutrient-responsive, self-limiting nature of Rejuva’s mechanism of action, which activates only under metabolic stress and remains inactive under healthy conditions. These new preclinical results complement previously reported data showing the durable impact of Rejuva in diabetes and obesity models and further establish the platform’s potential as both a therapeutic and preventative approach to metabolic disease. Fractyl has completed key in vivo studies for RJVA-001, its first clinical candidate from the Rejuva platform targeting T2D. Pending regulatory authorization, Fractyl expects to dose the first patients with RJVA-001 and report preliminary data in 2026, which the Company believes could lead to a potentially first-in-class, smart, durable gene therapy designed to reprogram the pancreas to deliver natural metabolic control.