Fractyl raises $110m IPO, nominates GLP-1 gene therapy candidate

Obesity drug developer plots path to human trials following NASDAQ debut in challenging IPO market.

Metabolic therapeutics company Fractyl Health raised $110 million in its initial public offering last week. The company, which floated on the NASDAQ under the symbol GUTS, has since seen its stock fall by around 13%, showing the IPO market still has some way to go following two years of uncertainty.

Fractyl announced today that it has nominated the first clinical candidate from its Rejuva gene therapy platform. RJVA-001, a GLP-1 pancreatic gene therapy, is designed to address known issues associated with treatment discontinuation and metabolic rebound commonly observed with existing GLP-1 based therapies.

Based in Lexington, MA, Fractyl is developing disease-modifying therapies for metabolic diseases, including obesity and Type 2 Diabetes, that target the root causes of these conditions. The company’s Rejuva platform aims to achieve durable remission of obesity and T2D by delivering locally administered genetic medicines to the pancreas. The platform is designed to enable the sustained production of nutrient-responsive hormones, representing a potential advancement in GLP-1 therapy. Fractyl believes that the Rejuva platform could offer advantages such as high local concentration of GLP-1 in the pancreas without high circulating levels and durable efficacy from sustained transgene expression within islets.

Claiming “encouraging” head-to-head proof-of-concept studies of RJVA-001 against semaglutide in validated disease models, Fractyl says its therapy demonstrated superior glucose-lowering potency in a rodent model of T2D and durable weight loss in the diet-induced obesity rodent model with a single administration of the therapy.

Revealing it has engaged with European regulators to align on a clinical trial-enabling path for RJVA-001, Fractyl says it anticipates completing IND-enabling studies, or their equivalent, in the second half of 2024, paving the way for a first-in-human study in T2D.

“Successful demonstration of safety, feasibility, and activity of RJVA-001 in humans may open the door to a suite of genetic medicines targeting the pancreas that aim to durably remit metabolic diseases altogether,” said Dr Harith Rajagopalan, CEO of Fractyl.

Fractyl also continues to advance its lead “Revita” program, which is designed to remodel the duodenal lining to address abnormal intestinal nutrient sensing and signaling mechanisms associated with metabolic diseases. Revita has already received CE mark approval in Europe and reimbursement authorization in Germany. In the United States, Revita is in a clinical trial for patients with inadequately controlled T2D, which is currently enrolling participants.

Rajagopalan added that the Fractyl also plans to test Revita “for maintenance of weight loss after GLP-1 drug discontinuation for patients who cannot remain on GLP-1 therapies.”

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