RJVA-001 / Fractyl Health - LARVOL DELTA

Fractyl Health Announces Potent Preclinical Results from RJVA-002, a Dual GIP/GLP-1 Gene Therapy Candidate for Obesity (GlobeNewswire) - "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....RJVA-001, the first Rejuva candidate, is expected to enter first-in-human clinical trials in 2026 for patients with inadequately controlled T2D."

New trial • Preclinical • Type 2 Diabetes Mellitus

Fractyl Health Presents New Data at the American Diabetes Association’s 85th Scientific Sessions Demonstrating its Rejuva Smart GLP-1 Pancreatic Gene Therapy Platform Prevents Obesity and Type 2 Diabetes in Preclinical Models (GlobeNewswire) - "Key results include: In a diet-induced obesity (DIO) 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....Fractyl expects to dose the first patients with RJVA-001 and report preliminary data in 2026..."

New trial • Preclinical • Obesity • Type 2 Diabetes Mellitus

Endoscopic Ultrasound-Guided Delivery of Human Glucagon-like Peptide-1 Pancreatic Gene Therapy: Safety and Feasibility in a Porcine Model (ASGCT 2025) - "Taken together, these data suggest that RJVA-001 can be safely and reproducibly delivered transgastrically to the pancreas leading to local, beta-cell specific production of GLP-1. These findings represent a major stride forward toward advancing this PGTx delivery procedure and candidate toward T2D first-in-human studies. Disease Focus of Abstract:Diabetes"

Gene therapy • Preclinical • Diabetes • Gene Therapies • Inflammation • Metabolic Disorders • Obesity • Pancreatitis • Type 2 Diabetes Mellitus • NEFL

FEASIBILITY AND SAFETY OF ENDOSCOPIC ULTRASOUND-GUIDED DELIVERY OF HUMAN GLP-1 PANCREATIC GENE THERAPY IN A PORCINE MODEL (DDW 2025) - "These data suggest that RJVA-001 can be safely delivered by endoscopic ultrasound-guided intra-pancreatic infusion, resulting in high levels of active GLP-1 expression, in a clinically relevant large-animal model. RJVA-001-driven human pancreatic GLP-1 production demonstrates the feasibility of one-time local gene therapy as a durable strategy for the treatment of metabolic diseases."

Gene therapy • Preclinical • Gene Therapies • Metabolic Disorders • Pancreatitis

Fractyl Health to Present Compelling Preclinical Data from its Rejuva Single-Administration Smart GLP-1 Pancreatic Gene Therapy Platform at the American Society of Gene and Cell Therapy (ASGCT) 2025 Annual Meeting (GlobeNewswire) - "Fractyl Health...today announced that it will deliver an oral presentation of compelling preclinical data from its Rejuva single-administration Smart GLP-1 pancreatic gene therapy platform at the American Society of Gene and Cell Therapy (ASGCT) 2025 Annual Meeting, taking place May 13-17, 2025, in New Orleans, Louisiana....The Company plans to submit the first Clinical Trial Application (CTA) module for RJVA-001 in type 2 diabetes to regulators in H1 2025, and if the CTA is authorized, expects to report preliminary data in 2026."

Clinical data • New trial • Preclinical • Obesity • Type 2 Diabetes Mellitus

Fractyl Health Unveils Promising Preclinical Data Demonstrating Safety and Feasibility of Local Delivery of RJVA-001 Rejuva Smart GLP-1 Pancreatic Gene Therapy at the World Congress Insulin Resistance, Diabetes and Cardiovascular Disease (WCIRDC) (GlobeNewswire) - "Fractyl Health, Inc...will present new data from its preclinical Rejuva Smart GLP-1 pancreatic gene therapy program in a poster...at the 22nd World Congress Insulin Resistance, Diabetes & Cardiovascular Disease (WCIRDC)....At Day 34 post-procedure pancreatic biopsies showed that active GLP-1 protein expression capacity within pancreatic islets was greatly enhanced. RJVA-001 achieved therapeutically relevant GLP-1 expression levels based on observations in disease models and were five times higher in treated than untreated animals (p< 0.02). Pancreatic lipase, a marker of pancreatitis, remained in the normal range in all animals. These results demonstrate the potential of RJVA-001 to dramatically enhance GLP-1 production capacity to therapeutically relevant levels without any observed adverse safety signals."

Preclinical • Metabolic Disorders • Obesity

Fractyl Health Announces Nomination of RJVA-001 as First Clinical Candidate in Its Rejuva GLP-1 Gene Therapy Platform (GlobeNewswire) - "RJVA-001 is the first GLP-1 pancreatic gene therapy (GLP1 PGTx) candidate to be nominated by the Company and is designed to improve upon known issues of treatment discontinuation and metabolic rebound typically seen with existing GLP-1 based therapies...Fractyl Health has engaged with European regulators to align on an IND-enabling path for RJVA-001 for the treatment of T2D. The Company anticipates completing IND-enabling studies, or its equivalent, for RJVA-001 in the second half of 2024."

Preclinical • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus