Fractyl Health, Inc. presented new data from its preclinical Rejuva pancreatic gene therapy program in an oral presentation at the American Diabetes Association (ADA)?s 84th Scientific Sessions in Orlando, FL. The presentation titled ?Single-Dose GLP-1-Based Pancreatic Gene Therapy Durably Maintains Body Composition and Glycemia After Semaglutide Withdrawal in a Murine Model of Obesity. Rejuva is the Company?s adeno-associated virus (AAV)-based GLP-1 pancreatic gene therapy program (PGTx), designed to enable durable production of GLP-1 in the pancreas for the treatment of obesity and T2D.

The study presented at ADA compared the effects of a single dose of Rejuva and daily semaglutide treatment on body composition and glycemic parameters in the well-validated mouse model of diet-induced obesity (DIO). It also examined the effects of single-dose Rejuva in the DIO mice after semaglutide was discontinued. In the study presented at ADA, obese (DIO) mice were randomized 1:1:1 to one of the following and followed for 4 weeks: Arm 1: single administration of a Rejuva GLP-1-based gene therapy candidate, Arm 2: daily semaglutide injections, or Arm 3: placebo.

At the end of 4 weeks, semaglutide was discontinued for mice in Arm 2 and those animals were further randomized 1:1 to receive either a single administration of the Rejuva gene therapy candidate or placebo, and all animals were followed for an additional 4 weeks, leading to the following assessment arms at 8 weeks: Arm 1: continued follow-up of a single administration of a Rejuva GLP-1-based gene therapy candidate. Arm 2a: semaglutide withdrawal at week 4. Arm 2b: semaglutide withdrawal with crossover to single administration Rejuva at week 4. Arm 3: continued follow up of placebo. At the end of 8 weeks, the pancreatic islets were then isolated to study the effect of glucose exposure on GLP-1-based transgene release from genetically modified islets.

At week 4, the Rejuva arm experienced reduced fat mass of 21% versus 16% of body weight with semaglutide (both p<0.0001 versus placebo, p<0.05 Rejuva versus semaglutide) while both Rejuva and semaglutide preserved lean mass with a loss of only 5% of body weight (both, p<0.0001 versus placebo). At week 8, fat mass rebounded to 1% below baseline (n.s.) in the semaglutide withdrawal group (Arm 2a), whereas semaglutide-withdrawn mice treated with Rejuva (Arm 2b) maintained fat reduction of 17% (p<0.01) and weight loss of 22% (p<0.0001) at week 8. Glucose and insulin levels in all intervention groups corresponded to changes observed in fat mass, with statistically significant improvements in fasting glucose and fasting insulin in semaglutide-treated and Rejuva treated mice at 4 and 8 weeks, but no improvement in glucose or insulin in semaglutide-withdrawn mice that did not crossover to Rejuva at week 8.