Sagimet Biosciences Inc. - Series A · NASDAQ:SGMT
Sagimet Biosciences Inc. - Series A — Sagimet Biosciences — 2025 Keystone MASH symposium
18 slides from Sagimet Biosciences Inc. - Series A's conference presentation, March 2025
Slide 1: Denifanstat Increased Circulating Polyunsaturated Triglycerides and Decreased LDL-Cholesterol in MASH
Denifanstat, a Fatty Acid Synthase Inhibitor, Increased Circulating Polyunsaturated Triglycerides and Decreased LDL-Cholesterol in MASH Patients with Advanced Fibrosis - a Post-Hoc Analysis of FASCINATE-2 Study Wen-Wei Tsai, Ph.D. 1
Slide 2: Outline
Outline • Introduction of fatty acid synthase (FASN) and denifanstat MOAs • Denifanstat phase 2b FASCINATE-2 study results in F2/F3 MASH • Histological endpoints • Lipidomic analysis of circulating lipids 2
Slide 3: FASN Plays a Key Role in Three Major Cell Types in MASH
FASN Plays a Key Role in Three Major Cell Types in MASH Denifanstat Increases Increases Increases Fatty acids Cytokines Fibrogenesis Triglycerides Chemokines Cell activation Lipotoxins Cell activation DNL: de novo lipogenesis 3
Slide 4: FASN Inhibition Directly Blocks Human Liver Stellate Cell Function
FASN Inhibition Directly Blocks Human Liver Stellate Cell Function Stellate cells require DNL for fibrogenesis Primary human stellate cell assay Denifanstat blocks stellate cell activation Denifanstat directly inhibits fibrogenic activity Denifanstat Collagen / total protein (μg/mg) 60 40 * * 20 * *
Slide 5: FASCINATE-2: Biopsy Trial Design Focused on Histological Endpoints
FASCINATE-2: Biopsy Trial Design Focused on Histological Endpoints Denifanstat (50 mg) Primary endpoints Screening Placebo • NAS ≥2 points improvement w/o worsening of fibrosis Study Weeks • MASH resolution + NAS ≥2 improvement w/o 0 52 worsening of fibrosis Baseline Final Selected secondary endpoin
Slide 6: Histology Endpoints of MASH Resolution and Liver Fibrosis at Week 52
Histology Endpoints of MASH Resolution and Liver Fibrosis at Week 52 Denifanstat Achieved Statistical Significance (Endpoints per FDA Draft Guidance 2020) Improvement in liver fibrosis ≥ 1 stage Resolution of MASH & No Worsening of MASH w/o worsening of fibrosis 41% 38% p=0.0051 p=0.0043 p=0.0102 %
Slide 7: Additional Fibrosis Endpoint Analysis at Week 52
Additional Fibrosis Endpoint Analysis at Week 52 Denifanstat Achieved Strong Improvement in F3 Population Fibrosis Endpoints Subgroup Placebo Denifanstat p-value All pts 18% 41% 0.0102** >1 stage improvement in fibrosis w/o worsening of MASH F3 only 13% 49% 0.0032** All pts 2% 20% 0.0065** >2 stage
Slide 8: Rapidly Reduced De Novo Lipogenesis and Decreased Liver Fat
Denifanstat Rapidly Reduced De Novo Lipogenesis and Decreased Liver Fat Denifanstat Tripalmitin Liver Fat Change from Baseline Change from Baseline Placebo Denifanstat n=52 n=111 Liver fat by MRI- Placebo Denifanstat LS mean change (ug/mL) PDFF n=38 n=69 -0.4 Relative decrease +5% -23% p=0.0036 Week
Slide 9: Decreased LDL-Cholesterol in MASH Patients
Denifanstat Decreased LDL-Cholesterol in MASH Patients LDL-C (baseline > 100 mg/dL) Change from Baseline Week 26 Week 52 -1.80 -1.80 Mean change, mg/dL p>0.05 p>0.05 -9.10 -12.60 p>0.05 Placebo Denifanstat -23.10 n=27 n=27 n=32 n=32 9
Slide 10: Significantly Decreased LDL-Cholesterol and LDL Particle Number
Denifanstat Significantly Decreased LDL-Cholesterol and LDL Particle Number Lipoprotein fractionation by NMR spectroscopy Baseline Week 26 Week 52 Size Placebo Denifanstat Placebo % Denifanstat Placebo % Denifanstat Lipoprotein Variable (nm) (n=44) (n=73) change % change change % change IDL-C 25-35
Slide 11: FASN Inhibition Reduced LDL-Cholesterol in Ldlr-/- MASH Mice
FASN Inhibition Reduced LDL-Cholesterol in Ldlr-/- MASH Mice Ldlr-/- mice fed with fast food diet (FFD) for 18 weeks, then treated with FASN inhibitor (TVB-3664) for 10 weeks Cholesterol Cholesterol Data mean ± SD, * p<0.05; Ldlr-/-.Leiden mice fed with high fat (41%), high fructose (44%) diet (FFD)
Slide 12: FASN Inhibition Reduced Total Atherosclerotic Lesion Area of Aortic Root
FASN Inhibition Reduced Total Atherosclerotic Lesion Area of Aortic Root in Ldlr-/- MASH Mice FASN inhibitor (TVB-3664) inhibited inflammation by reducing chemokines Graphs represent data mean + SD, ** p<0.01, *** p<0.001 12
Slide 13: Changed Circulating Lipidomic Profiles Over Time in MASH Patients
Denifanstat Changed Circulating Lipidomic Profiles Over Time in MASH Patients Week 4 Week 13 Week 26 Week 52. vs. baseline 476 analytes Placebo Denifanstat Placebo Denifanstat Placebo Denifanstat Placebo Denifanstat Plasma lipidomics Mass Spectrometry analytic platform Triglycerides 13 13
Slide 14: Rapidly Increased Polyunsaturated TG and Decreased Saturated TG
Denifanstat Rapidly Increased Polyunsaturated TG and Decreased Saturated TG Triglycerides composition Triglycerides composition Week 4 vs. baseline Week 52 vs. baseline Placebo Denifanstat Placebo Denifanstat *p<0.05, **p<0.01, ***p<0.001 14
Slide 15: Increased Circulating Polyunsaturated Triglycerides Over Time
Denifanstat Increased Circulating Polyunsaturated Triglycerides Over Time Polyunsaturated triglycerides Saturated triglycerides (% change; > 3 double bonds) (% change) 150 400 300 % (mean, SD) % (mean, SD) 100 200 *** *** ** +36% +42% 50 +30% 100 NS * Deni Placebo +13% 0 Deni 0 +6% +4% Placebo -100
Slide 16: Provides a Differentiated Mechanism of Action in MASH
Denifanstat Provides a Differentiated Mechanism of Action in MASH • Denifanstat is not only a liver fat blocker, but acts directly on stellate cells -> tackles both “initiating” (liver fat synthesis) and “progressing” (fibrosis) events • Denifanstat showed significant improvement in MASH resolution
Slide 17: Acknowledgements
Acknowledgements • Investigators, sites and patients involved in FASCINATE-2 studies • Sagimet Team • Sagimet Advisors • OWL Metabolomics Team • TNO Metabolic Health Research Team 17
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