Fractyl Health announces preclinical results from RJVA-002

Fractyl Health (GUTS) announced new preclinical data from RJVA-002, the second candidate from the Company’s Rejuva Smart GLP-1 platform, at the 2025 Cell & Gene Meeting on the Mesa. The new data expand the potential of the Rejuva platform from the durable treatment of T2D to obesity. RJVA-002 encodes both GIP and GLP-1 hormones, driven by an engineered human insulin promoter to enable beta cell-specific, nutrient-responsive expression. In a diet-induced obesity mouse model with a humanized GIP receptor, a single administration of RJVA-002 led to ~30% weight loss over 5 weeks, with the weight loss trajectory not yet plateaued. No adverse effects were observed in treated animals. These results suggest potent and durable activity in the translationally relevant diet-induced model of obesity, supporting the platform’s potential as a next-generation alternative to chronic drug therapy in obesity. In this ongoing preclinical study, male mice engineered to express a humanized GIP receptor were fed a 60% high-fat diet to induce obesity and were then randomized into one of four treatment cohorts: vehicle control, RJVA-001 mid-dose, RJVA-002 mid-dose, and RJVA-002 high-dose. All mice were continued on HFD for the duration of the study. Treatment with RJVA-002 resulted in a robust, dose-dependent reduction in body weight compared to vehicle control. By day 35, mice in mid- and high-dose cohorts had lost a mean of 18% and 29% of their body weight after a single dose of RJVA-002, respectively. Rejuva is Fractyl’s gene therapy platform designed to enable long-term remission of T2D and obesity by durably reprogramming pancreatic islet cells to endogenously produce metabolic hormones. RJVA-001, the first Rejuva candidate, is expected to enter first-in-human clinical trials in 2026 for patients with inadequately controlled T2D. RJVA-002 expands the platform into obesity, targeting dual incretin biology with the goal of achieving durable, well-tolerated, weight loss from a single intervention.