Sagimet presents preclinical results on FASN inhibitor, FASCINATE-2 data

Sagimet Biosciences announced the presentation of preclinical results detailing artificial intelligence based digital pathology of Sagimet’s FASN inhibitor alone or in combination with semaglutide in a preclinical mouse model of nonalcoholic steatohepatitis. A comprehensive lipidomic analysis from the interim analysis of the FASCINATE-2 Phase 2b clinical trial will also be presented in a late-breaking poster session at the American Association for the Study of Liver Diseases – The Liver Meeting 2023 held November 10-14, 2023 in Boston. Highlights from the posters include: Poster (2400-C): Artificial Intelligence Based Digital Pathology Reveals Fatty Acid Synthase Inhibitor Alone or in Combination with Semaglutide Improves Fibrosis in Diet-Induced Obese Mice with Biopsy-Confirmed NASH and Fibrosis In diet-induced obese mice with biopsy confirmed NASH and fibrosis, a combination treatment of Sagimet’s FASN inhibitor with semaglutide, a GLP-1 analogue, significantly decreased ALT, liver triglycerides and cholesterols. A single treatment of a FASN inhibitor or semaglutide – improved the NAFLD activity score, or NAS. The combination of a FASN inhibitor and semaglutide showed further improvement of NAS. Semaglutide reduced body weight by greater than20% in NASH mice, alone, or in combination with a FASN inhibitor. The digital AI pathology assessment showed that treatment with a FASN inhibitor alone, or in combination with semaglutide significantly reduced liver fibrosis. Treatment with semaglutide alone did not show significant reduction of liver fibrosis. These results support the further clinical evaluation of denifanstat in combination with GLP-1 receptor agonists. Late-Breaking Poster (5051-C): Interim Analysis of FASCINATE-2 A Phase 2b Randomized, Placebo Controlled Trial Demonstrated Denifanstat Reduces Circulating Saturated Diacylglycerols and Triacylglycerols, Markers of Lipotoxicity Lipidomic results demonstrated a beneficial shift in lipid profile for the 52 denifanstat-treated patients assessed in the interim analysis of the FASCINATE-2 Phase 2b clinical trial. Treatment with denifanstat was associated with reduced circulating saturated lipids and ceramides associated with cardiovascular risk such as LDL, tripalmitin and C16-ceramide, with numerical separation from placebo at week 4 and statistically significant responses at week 13. There was also an increase in beneficial unsaturated lipids and polyunsaturated fatty acid content at week 13. These improvements are consistent with the results previously presented at the European Association for the Study of the Liver Congress in June 2023 and the FASCINATE-1 Phase 2a clinical trial findings.