Sagimet Biosciences Announces Successful Completion of End-of-Phase 2 Interactions With FDA on the Development of Denifanstat for MASH; Phase 3 Program Initiation Expected by End of 2024

Sagimet Biosciences Inc. recently announced the successful completion of end-of-Phase 2 interactions with the US FDA, supporting the advancement of denifanstat into Phase 3 in metabolic-dysfunction associated steatohepatitis (MASH). The planned program will include two Phase 3 trials: FASCINATE-3, evaluating patients with F2/F3 (non-cirrhotic) MASH, and FASCINIT, evaluating patients with suspected or confirmed diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD)/MASH. The Phase 3 program is expected to initiate by the end of 2024.

“Following the recent Breakthrough Therapy designation for denifanstat for treatment of non-cirrhotic MASH, we are pleased with the outcome of our end-of-Phase 2 interactions with the FDA and are appreciative of the agency’s support and guidance on our Phase 3 program for denifanstat in MASH,” said Dave Happel, Chief Executive Officer of Sagimet. “The agency supports our strategy to conduct two Phase 3 trials to assess the safety and efficacy of denifanstat in F2/F3 MASH, a complex disease where treatments with novel/differentiated mechanisms of action that directly target the three main drivers of liver injury: fat accumulation, inflammation, and fibrosis are urgently needed.”

Based on ongoing discussions with the FDA, the planned Phase 3 program will consist of two double-blind, placebo-controlled multicenter registrational trials:

• FASCINATE-3 in patients with F2/F3 (non-cirrhotic) MASH: The trial will evaluate the efficacy and safety of denifanstat in this population, with primary endpoints being liver biopsy and 4.5-year clinical outcomes.
• FASCINIT in patients with suspected or confirmed diagnosis of MASLD/MASH: The trial will evaluate the efficacy and safety of denifanstat in this population, with primary endpoints being safety and tolerability. Non-invasive biomarkers will be assessed as part of the secondary endpoints, and there will be no end-of-treatment liver biopsy.

The Phase 3 program is designed to comprise a minimum of 1,800 patients exposed to denifanstat.

Metabolic-dysfunction associated steatohepatitis (MASH) is a progressive and severe liver disease which is estimated to impact more than 115 million people worldwide, for which there is only one recently approved treatment in the United States and no currently approved treatments in Europe. In 2023, global liver disease medical societies and patient groups formalized the decision to rename non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated steatotic liver disease (MASLD) and nonalcoholic steatohepatitis (NASH) to MASH. Additionally, an overarching term, steatotic liver disease (SLD), was established to capture multiple types of liver diseases associated with fat buildup in the liver. The goal of the name change was to establish an affirmative, non-stigmatizing name and diagnosis.

Sagimet is a clinical-stage biopharmaceutical company developing novel fatty acid synthase (FASN) inhibitors that are designed to target dysfunctional metabolic and fibrotic pathways in diseases resulting from the overproduction of the fatty acid, palmitate. Sagimet’s lead drug candidate, denifanstat, is an oral, once-daily pill and selective FASN inhibitor in development for the treatment of MASH. FASCINATE-2, a Phase 2b clinical trial of denifanstat in MASH with liver biopsy-based primary endpoints, was successfully completed with positive results. For additional information, visit www.sagimet.com.