Sagimet Biosciences Inc. - Series A · NASDAQ:SGMT
Sagimet Biosciences Inc. - Series A — Sagimet Biosciences — Corporate Update (March 2025)
36 slides from Sagimet Biosciences Inc. - Series A's corporate update, Mar 12, 2025
Slide 1: Targeting Metabolic Dysfunction with Novel Therapies to Treat MASH, Acne & Cancer
Targeting Metabolic Dysfunction with Novel Therapies to Treat M ASH, Acne & Cancer March 2025
Slide 2: Forward-Looking Statements and Disclaimer
2 March 2025 Forward - Looking Statements and Disclaimer This presentation contains forward - looking statements within the meaning of, and made pursuant to the safe harbor provisions of, The Private Securities Litigation Reform Act of 1995 . All statements contained in this document, other than sta
Slide 3: Leadership Team with Proven Development and Commercialization Experience
3 March 2025 Leadership Team with Proven Development and Commercialization Experience Dave Happel President & CEO >20 years of experience in executive leadership in biotech and pharma Brought multiple innovative healthcare products to the market George Kemble Executive Chairman >20 years of experien
Slide 4: Sagimet at a Glance
4 March 2025 Sagimet at a Glance • Our lead molecule, denifanstat, is a novel fatty acid synthase (FASN) inhibitor with a differentiated MOA with the potential to target multiple underserved disease states • Clinical data demonstrates denifanstat’s proof of concept across multiple disease states • W
Slide 5: Development Pipeline: Indications and Clinical Milestones
5 March 2025 Expected Milestone / Status Stage of Development Indication Therapeutic Area Phase 3 Phase 2 Phase 1 Preclinical Phase 2b positive topline data announced 1Q2024 ; Pivotal Phase 3 program initiated 4Q2024, FPI anticipated 1H2025; FDA Breakthrough Therapy designation MASH F2/F3 population
Slide 6: MASH: A Burgeoning Epidemic
6 March 2025 MASH: A Burgeoning Epidemic 1 Estes, et al. 2018; http://dx.doi.org/10.1016/j.jhep.2018.05.036 . Note: MASH, or metabolic dysfunction - associated steatohepatitis, was formerly known as NASH, or nonalcoholic steatohepatitis Disease challenges Estimated Patients in 20 30 1 United States
Slide 7: FASN Inhibition Addresses Three Independent Mechanisms of MASH Development and Progression
7 March 2025 Sagimet’s lead drug candidate, denifanstat, is a specific and potent inhibitor of FASN that functions through three independent mechanisms in MASH : FASN Inhibition Addresses Three Independent Mechanisms of MASH Development and Progression Blocking steatosis via inhibiting de novo lipog
Slide 8: FASN Inhibition Directly Blocks Human Liver Stellate Cell Function
8 March 2025 FASN Inhibition Directly Blocks Human Liver Stellate Cell Function Stellate cells require DNL for fibrogenesis Denifanstat blocks stellate cell activation Primary human stellate cell assay Denifanstat directly inhibits fibrogenic activity Denifanstat • Stimulated by TGF - beta to activa
Slide 9: Treatment Goals for MASH Across Fibrosis Staging
9 March 2025 Treatment Goals for MASH Across Fibrosis Staging F4 (Compensated) F3 F2 F1 MASH STAGING Risk Staging based on: • Fat • Inflammation • Fibrosis • Liver & CV Events Primary Treatment Objectives Primary Therapeutic Interventions (based on Primary Objectives) Improve Glycemic Control / Impr
Slide 10: MASH Clinical Development Program
MASH Clinical Development Program
Slide 11: FASCINATE-2: Biopsy Trial Design Focused on Histological Endpoints
11 March 2025 FASCINATE - 2: Biopsy Trial Design Focused on Histological Endpoints AI: Artificial Intelligence, MRI - PDFF; magnetic resonance imaging derived proton density fat fraction, NAS; NAFLD Activity Score . • Biopsy confirmed F2 - F3 MASH patients • 52 weeks, 2:1 randomization to 50mg or pl
Slide 12: FASCINATE-2: Baseline Characteristics Were Typical of the F2/F3 MASH Population
12 March 2025 FASCINATE - 2: Baseline Characteristics Were Typical of the F2/F3 MASH Population Denifanstat , n=81 Placebo, n=45 Parameter 56.1 (+/ - 10.8) 59.6 (+/ - 10.9) Age , years 48 (59%) 27 (60%) Sex , female 73 (90%) 41 (91%) Race , White 27 (33%) 15 (33%) Ethnicity , Hispanic or Latino 34.6
Slide 13: Primary Endpoints: Liver Biopsy
13 March 2025 Primary Endpoints: Liver Biopsy Cochran - Mantel - Haenszel Test – two sided at the 0.05 significance level. * ≥1 - point improvement in ballooning or inflammation. Denifanstat Achieved Statistical Significance at Week 52 NAS ≥ 2 points improvement* w/o worsening of fibrosis p=0.0001 M
Slide 14: Secondary Endpoints: Liver Fibrosis and MASH Resolution
14 March 2025 Secondary Endpoints: Liver Fibrosis and MASH Resolution Cochran - Mantel - Haenszel Test – Two sided at the 0.05 significance level Denifanstat Achieved Statistical Significance at Week 52 18% 41% Placebo n=45 Denifanstat n=81 % response Improvement in liver fibrosis ≥ 1 stage & no wor
Slide 15: Secondary Endpoints: Liver Fibrosis
15 March 2025 Secondary Endpoints: Liver Fibrosis *One sided at the 0.05 significance level, **Two sided at the 0.05 significance level Denifanstat Achieved Statistically Significant Improvement of Fibrosis p - value Denifanstat Placebo Subgroup Fibrosis Endpoints 0.040** 30% 14% ITT > 1 stage impro
Slide 16: Additional Fibrosis Analysis Using AI-based Digital Pathology
16 March 2025 Additional Fibrosis Analysis Using AI - based Digital Pathology Supporting Evidence that Denifanstat Significantly Reduced Fibrosis Pre - Treatment Pt A NASH - CRN Fibrosis stage F3 Post - Treatment Pt A NASH - CRN Fibrosis stage F1 Denifanstat 0.10 - 0.30 Placebo n=45 Denifanstat n=81
Slide 17: Patient Subset on Stable GLP1-RA at Baseline: Liver Biopsy
17 March 2025 Patient Subset on Stable GLP1 - RA at Baseline: Liver Biopsy Cochran - Mantel - Haenszel Test – One sided at the 0.05 significance level. mITT population GLP patients were on stable dose for 6 months prior to first biopsy Denifanstat Improved MASH Resolution and Fibrosis Resolution of
Slide 18: FASCINATE-2: Safety
18 March 2025 FASCINATE - 2: Safety Denifanstat Was Generally Well - Tolerated • No DILI (drug - induced liver injury) signal and no muscle wasting were detected, and GI (gastrointestinal) effects were comparabl e to placebo • AE of hair thinning stabilized with a 2 - to - 4 week dose pause and then
Slide 19: Denifanstat Decreased Liver Fat by MRI-PDFF and Reduced FAST Score
19 March 2025 Denifanstat Decreased Liver Fat by MRI - PDFF and Reduced FAST Score > 30% reduction: Cochran - Mantel - Haenszel Test. Relative reduction: Mixed - effects Model for Repeated Measures. mITT population. Two sided at the 0.05 significance level. Denifanstat Achieved Statistical Significa
Slide 20: Secondary Endpoints: Liver Enzymes
20 March 2025 Secondary Endpoints: Liver Enzymes Mixed - effects Model for Repeated Measures – Two sided at the 0.05 significance level. mITT population Denifanstat Decreased ALT and AST Levels ALT Percent Change from Baseline AST Percent Change from Baseline - 2.70 - 16.20 - 23.10 - 30.60 LS mean c
Slide 21: Cardiometabolic Health
21 March 2025 Cardiometabolic Health mITT population. Mixed - effects Model for Repeated Measures – Two sided at the 0.05 significance level. *p<0.05, **p<0.01, ***p<0.001 1 For LDL - c, baseline > 100 mg/dL. Denifanstat Decreased LDL - c Levels and Increased Polyunsaturated Triglycerides LDL - c 1
Slide 22: Denifanstat Reduced De Novo Lipogenesis
22 March 2025 Denifanstat Reduced De Novo Lipogenesis Two sided at the 0.05 significance level , ITT population Tripalmitin • A saturated triglyceride which is a biomarker of DNL inhibition • Reduced by denifanstat as early as week 4 of treatment Next steps • Continue the development of tripalmitin
Slide 23: Mechanism of Action Supports Combination Therapy Opportunity
23 March 2025 Mechanism of Action Supports Combination Therapy Opportunity MOA - Mechanism of Action Combination therapy offers: • Denifanstat MOA that is complementary to other MOAs – resmetirom , GLPs • Opportunity for fixed dose combinations with other oral medications Preclinical combination stu
Slide 24: Phase 3 Program for Denifanstat in MASH
24 March 2025 Phase 3 Program for Denifanstat in MASH Screening Placebo Denifanstat (50 mg) 1 0 52 Study Weeks Baseline Final Biopsy Biopsy Placebo Denifanstat (50 mg) 1 Registration portion Clinical outcome portion ~3.5 years Screening Placebo Denifanstat (50 mg) 0 52 Study Weeks FASCINATE - 3 • 1,
Slide 25: Denifanstat Potential in Cirrhotic (F4) Patients
25 March 2025 1 Kamm DR and McCommis KS. doi : 10.1113/JP281061. 2 Sheka AC, et al. doi:10.1001/jama.2020.2298. 3. CLIN - 009 data on file. 4. Loomba, et al. doi : 10.1016/S2468 - 1253(24)00246 - 2 Differentiated Mechanism of Action • In vitro data demonstrates that denifanstat reduces pro - fibroti
Slide 26: Pediatric MASH Continues to be an Area of Significant Unmet Need
26 March 2025 1Yu EL and Schwimmer JB. doi : 10.1002/cld.1027. 2 Softic S and Rohit K. doi : 10.1002/hep.32322. 3 Kleiner DE and Makhlouf HR. doi : 10.1016/j.cld.2015.10.011. Pediatric MASH • T he prevalence rate of childhood MASLD is estimated at 5 - 10% in the general population and 10 - 20% of ch
Slide 27: Precision Medicine: Blood Tests May Lead to Improved Patient Outcomes
27 March 2025 Precision Medicine: Blood Tests May Lead to Improved Patient Outcomes 1Signature has 6 metabolites: ursodeoxycholic acid, DL - 2 - aminocaprylic acid, sarcosine, glycoursodeoxycholic acid, D( - ) - 2 - aminobutyric acid, PC(0 - 18:0/22:4). Accuracy 79%, PPV 88%, NPV 63%. • MASH is a mu
Slide 28: Additional Denifanstat Indications
Additional Denifanstat Indications
Slide 29: FASN Also Plays a Key Role in Other Diseases With Significant Unmet Need
29 March 2025 FASN Also Plays a Key Role in Other Diseases With Significant Unmet Need FASN in cancer Supports t umor survival Enables t umor proliferation Establishes r esistance to drugs FASN in acne Increases sebum production Exacerbates sebum composition Cancer cell Membrane synthesis, intracell
Slide 30: DNL Pathway Plays a Critical Role in the Pathogenesis of Acne
30 March 2025 DNL Pathway Plays a Critical Role in the Pathogenesis of Acne Sebum is a significant part of acne pathogenesis • Acne is associated with sebum over production by sebocytes in the skin • Sebocytes rely on DNL/FASN to produce >80% of key sebum lipids such as palmitate and sapienic acid F
Slide 31: Acne US Market Overview
31 March 2025 Blackheads Whiteheads Papules & Pustules Cysts & Nodules Acne US Market Overview Acne market in dermatology is large and highly aligned to a FASN inhibitor TPP value proposition 5.1 million US acne patients are treated by dermatologists annually (total US acne market is 50 million peop
Slide 32: Data Support Mechanism of Action of a FASN Inhibitor in Acne
32 March 2025 Data Support Mechanism of Action of a FASN Inhibitor in Acne • FASN inhibitor demonstrated a >90% reduction in sebum lipids by day 15 1 • FASN inhibitor maintained the reduced level of sebum lipids through the entire study 1 • FASN inhibitor demonstrated a dose responsive impact on seb
Slide 33: Ascletis Announced Positive Phase 2 Clinical Data in Acne
33 March 2025 EFFICACY RESULTS – 12 WEEKS 75 mg n=45 50 mg n=44 25 mg n=45 Placebo n=45 - 48.4% ** - 51.5% ** - 49.5% ** - 34.9% Total lesions^ - 49.4% * - 56.7% ** - 54.7% ** - 36.5% Inflammatory lesions^ - 46.5 - 46.6% - 44.4% - 35.0% Non - inflammatory lesions^ 22.2% 31.8% 31.1% 15.6% IGA (2 - gr
Slide 34: FASN Is Integral to Tumor Cell Proliferation and Survival
34 March 2025 FASN Is Integral to Tumor Cell Proliferation and Surviv al KRASM – KRAS mutant. KRASWT - KRAS wild type FASN dependence • Certain cancers are dependent on DNL/FASN for proliferation especially downstream of driver oncogenes • Strategy kill tumor cells and/or avoid drug resistance by co
Slide 35: Cancer Program Focuses on 4 FASN-Dependent Tumor Types
35 March 2025 GBM Prostate HCC NSCLC KRASM Cancer Program Focuses on 4 FASN - Dependent Tumor Types *Brenner et al., 2023; **Wang at al., 2022; ***GBM (glioblastoma), HCC (hepatocellular carcinoma), KRASM (mutant KRAS), NSCLC ( non small cell lung cancer) Phase 3 ongoing In China by Ascletis , denif
Slide 36: Denifanstat: Differentiated MOA with Potential to Treat Multiple Disease States
36 March 2025 Denifanstat: Differentiated MOA with Potential to Treat Multiple Disease States • Our lead molecule, denifanstat, is a novel fatty acid synthase (FASN) inhibitor with a differentiated MOA with the potential to target multiple underserved disease states • Clinical data demonstrates deni