Sagimet Biosciences announced positive results from FASCINATE-1, the Phase 2 clinical trial of its oral, once-daily FASN inhibitor TVB-2640, the company's lead product candidate that is currently being evaluated as a potential treatment for nonalcoholic steatohepatitis (NASH). The preliminary data showed that TVB-2640 significantly reduced liver fat, the primary efficacy endpoint of this trial, with a 61% responder rate in the 50 mg group. Participants also showed improvement in markers of liver function and fibrosis.

"These results are extremely encouraging in light of the increasing global prevalence of NASH and a significant unmet medical need for safe and effective treatment options," said Sagimet Chief Medical Officer Bill McCulloch. "We show that well-tolerated, oral TVB-2640 reduces liver fat, a major driver of NASH, and has the potential to be a foundational therapy for this disease either alone or in combination."

In the Phase 2 randomized, placebo-controlled trial of 99 NASH patients in the United States, clinicians evaluated the safety and efficacy of oral, once-daily dosing of TVB-2640 for 12 weeks. Study participants were required to have at least 8% liver fat at baseline, as measured by magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF), and evidence of stage F1 to F3 liver fibrosis. The study demonstrated a statistically significant, dose-dependent relative reduction in liver fat of 28.2% in the 50 mg group versus an increase of 4.5% in the placebo group. TVB-2640 also significantly decreased ALT by up to 20.4% and LDL-cholesterol by up to 7.6% at week 12. These decreases indicate improved liver function and metabolic health.

TVB-2640 was well-tolerated with a benign adverse event profile, predominantly grade 1 events and no on-treatment serious adverse events.

"These promising clinical results are the first of their kind for a FASN inhibitor, showing a high response rate in liver fat reduction, which correlate with histological improvement as demonstrated in multiple other clinical trials," said Rohit Loomba, M.D., director, NAFLD Research Center, University of California San Diego, and coordinating investigator of the study. "The strong effect and benign safety profile observed to date also indicate a solid foundation for advancing TVB-2640 into later stages of clinical development."

TVB-2640 is an orally bioavailable, first-in-class fatty acid synthase (FASN) inhibitor. FASN is a key enzyme in the de novo lipogenesis (DNL) pathway that is responsible for the synthesis of excess fat in the liver of patients with NASH. Sagimet's approach targets this key driver of NASH. The company announced the initiation of dosing in April 2019 in a randomized, placebo-controlled Phase 2 trial (FASCINATE-1), which evaluated the impact of TVB-2640 in 99 NASH patients in the United States. The primary efficacy endpoint was the impact of TVB-2640 on liver fat reduction by MRI-PDFF following 12 weeks of once-daily, continuous dosing. The trial also evaluated TVB-2640's impact on levels of plasma lipids, liver enzymes, inflammatory and fibrotic biomarkers.