Sagimet Biosciences Inc. presented positive data from its FASCINATE-2 Phase 2b clinical trial of denifanstat versus placebo in biopsy-confirmed metabolic dysfunction-associated steatohepatitis (MASH) patients at the European Association for the Study of the Liver (EASL) Congress being held in Milan, Italy. Sagimet?s lead drug candidate, denifanstat, is an oral, once-daily pill and selective FASN inhibitor in development for the treatment of MASH. In the EASL presentation, additional 52-week ITT and F3 subgroup efficacy data included: The primary endpoint of =2-point reduction in NAS (NAFLD Activity Score) without worsening of fibrosis (16% placebo vs 38% with denifanstat, p=0.0035) or MASH resolution with =2-point reduction in NAS resolution without worsening of fibrosis (11% placebo vs 26% with denifanstat, p=0.0173) in the intention to treat (ITT) population.

Secondary endpoints of fibrosis improvement by = 1 stage with no worsening of MASH in the ITT (14% placebo vs 30% with denifanstat, p=0.0199) and F3 (13% placebo vs 49% with denifanstat, p=0.0032) populations, and fibrosis improvement by = 2 stages with no worsening of MASH in the mITT (2% placebo vs 20% with denifanstat, p=0.0065) and F3 (4% placebo vs 34% with denifanstat, p=0.0050) populations. Data on significant increase in beneficial polyunsaturated triglycerides at the end of 52 week of treatment (-4% placebo vs +42% denifanstat, p<0.001) in the mITT population. A biomarker of denifanstat activity (tripalmitin) showed an early and sustained reduction in de novo lipogenesis at 4-weeks (-0.4ug/mL placebo vs -2.4ug/ml with denifanstat, p=0.001) and 13-weeks (-0.1ug/mL placebo vs -2.1ug/mL with denifanstat, p=0.005) in the mITT population.

Safety and Tolerability: As in prior studies, no treatment-related serious adverse events (SAEs) were observed, and the majority of adverse events (AEs) were mild to moderate in nature (Grades 1 and 2). There were no Grade =3 treatment-related AEs, and no drug-induced liver injury (DILI) signal in the study. The most common treatment-related AEs by system organ class (observed in =5% of patients in the study) were eye disorders (denifanstat 15.2%, placebo 16.1%), gastrointestinal disorders (denifanstat 11.6%, placebo 8.9%), and skin and subcutaneous tissue disorders (denifanstat 22.3%, placebo 7.1%).

The incidence of treatment emergent adverse events (TEAEs) leading to treatment discontinuation was 19.6% in the denifanstat group compared to 5.4% in placebo.