Sagimet Biosciences Inc. (Nasdaq: SGMT) is set to advance its lead drug candidate, denifanstat, into Phase 3 development for metabolic-dysfunction associated steatohepatitis (MASH) following successful end-of-Phase 2 interactions with the FDA. The FDA has granted Breakthrough Therapy designation to denifanstat for the treatment of non-cirrhotic MASH with moderate to advanced liver fibrosis (F2-F3). This designation underscores the potential of denifanstat to address the unmet need for new therapies for this serious liver disease.
The planned Phase 3 program will consist of two double-blind, placebo-controlled, multicenter registrational trials: FASCINATE-3, focusing on patients with F2/F3 (non-cirrhotic) MASH, and FASCINIT, evaluating patients with suspected or confirmed metabolic dysfunction-associated steatotic liver disease (MASLD)/MASH. The program is designed to include a minimum of 1,800 patients exposed to denifanstat.
FASCINATE-2 Trial Results
Results from the Phase 2b FASCINATE-2 clinical trial of denifanstat were recently published in The Lancet Gastroenterology & Hepatology. The study, titled "Denifanstat for the treatment of Metabolic-dysfunction Associated Steatohepatitis: a multicentre, double-blind, randomised, placebo-controlled, ph2b trial," highlighted that denifanstat treatment achieved statistically significant and clinically meaningful improvements in disease activity, MASH resolution, and fibrosis.
Upcoming Phase 3 Trials
The FASCINATE-3 trial is expected to evaluate the efficacy and safety of denifanstat in patients with F2/F3 MASH, with primary endpoints being liver biopsy assessments at 52 weeks. Sagimet plans to seek accelerated approval in the US and Europe based on these results. The trial will continue until the required number of clinical outcomes is reached, estimated at 3.5 years.
The FASCINIT trial will evaluate the efficacy and safety of denifanstat in patients with suspected or confirmed MASLD/MASH, with primary endpoints being safety and tolerability at 52 weeks. Non-invasive biomarkers will be assessed as part of the secondary endpoints, with no liver biopsy endpoint.
Financial Position
As of September 30, 2024, Sagimet reported cash, cash equivalents, and marketable securities totaling $170.0 million, which are expected to fund operations through 2025. Research and development expenses for the three and nine months ended September 30, 2024, were $12.7 million and $24.2 million, respectively.
About Denifanstat
Denifanstat is an oral, once-daily, selective fatty acid synthase (FASN) inhibitor designed to target dysfunctional metabolic and fibrotic pathways in diseases resulting from the overproduction of the fatty acid, palmitate. Sagimet believes its differentiated mechanism of action enables denifanstat to improve the key drivers of MASH: fat accumulation, inflammation, and fibrosis.
About MASH
Metabolic-dysfunction associated steatohepatitis (MASH) is a progressive and severe liver disease estimated to impact more than 115 million people worldwide. The recent renaming of non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated steatotic liver disease (MASLD) and nonalcoholic steatohepatitis (NASH) to MASH aims to establish an affirmative, non-stigmatizing name and diagnosis.
