Sagimet Biosciences (SGMT) Earnings Call Presentation

Denifanstat in MASH Treatment - Denifanstat, a FASN inhibitor, addresses three independent mechanisms of MASH development and progression: blocking steatosis, reducing inflammation, and blunting fibrosis[20, 21, 22] - In the FASCINATE-2 Phase 2b trial, denifanstat achieved statistical significance in NAS ≥ 2 points improvement without worsening of fibrosis, with 52% in the denifanstat group compared to 20% in the placebo group (mITT population)[35] - Denifanstat achieved statistically significant improvement in liver fibrosis ≥ 1 stage without worsening of MASH, with 41% in the denifanstat group compared to 18% in the placebo group (mITT population)[38] - AI-based digital pathology showed that denifanstat significantly reduced fibrosis in advanced patients, with a p-value of 0.0023 for the change from baseline in qFibrosis continuous value[41, 43, 44, 46] Combination Therapy Rationale - Preclinical studies in mouse models showed beneficial impact of FASN inhibitor + resmetirom combination on histology and MASH biomarkers[70] - In a patient subset on stable GLP1-RA at baseline in Phase 2b, 42% of patients receiving denifanstat + GLP1 achieved resolution of MASH without worsening of fibrosis, compared to 0% in the placebo + GLP1 group[66, 67] - The combination of denifanstat and resmetirom has potential synergies in the MOA, with denifanstat decreasing de novo lipogenesis and resmetirom increasing fatty acid oxidation[71, 73] FDC Clinical Development Program - A Phase 1 clinical trial to evaluate the pharmacokinetics (PK) and tolerability of a combination of denifanstat and resmetirom is planned to initiate in 2H 2025, with data readout expected in 1H 2026[75, 78] - A Phase 2 clinical combination study with denifanstat and resmetirom in F4 MASH patients is being considered[76] - The combination of denifanstat and resmetirom has filed an IP application in 2024, and if granted, the patent would last until 2044, with potential PTE to 2048[78] MASH Market and Disease Burden - In the United States, the estimated number of MASH patients in 2030 is 27 million, with 35 million having cirrhosis F4[13]