Fractyl Health
Fractyl Health Announces Potent Preclinical Results from RJVA-002, a Dual GIP/GLP-1 Gene Therapy
BURLINGTON, Mass., -- Fractyl Health, Inc., a metabolic therapeutics company focused on pattern-breaking approaches to treat the root causes of obesity and type 2 diabetes (T2D), today announced potent 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 (DIO) 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 (Biocytogen) were fed a 60% high-fat diet (HFD) 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 (n=7 per group). 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% (p<0.01) and 29% (p<0.0001) 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.
About Fractyl Health
Fractyl Health is a metabolic therapeutics company focused on pioneering new approaches to the treatment of metabolic diseases, including obesity and T2D. Despite advances in treatment over the last 50 years, obesity and T2D continue to be rapidly growing drivers of morbidity and mortality in the 21st century. Fractyl’s goal is to transform metabolic disease treatment from chronic symptomatic management to durable disease-modifying therapies that target the organ-level root causes of disease. The Company has a robust and growing IP portfolio, with 33 granted U.S. patents and approximately 40 pending U.S. applications, along with numerous foreign issued patents and pending applications. Fractyl is based in Burlington, MA.
