Sagimet Biosciences Inc. - Series A · NASDAQ:SGMT
Sagimet Biosciences Inc. - Series A — Sagimet Biosciences — Investor Presentation (May 2025)
39 slides from Sagimet Biosciences Inc. - Series A's investor presentation, May 8, 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 May 2025
Slide 2: Forward-Looking Statements and Disclaimer
2 May 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 state
Slide 3: Leadership Team with Proven Development and Commercialization Experience
3 May 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 Eduardo Martins CMO >20 years of leadership of large - s
Slide 4: Sagimet at a Glance
4 May 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 diseases • Strong clinical data demonstrates denifanstat’s proof of concept across multiple disease states Uniq
Slide 5: Strong IP, Cash Position, and Collaboration Potential
5 May 2025 Strong IP, Cash Position, and Collaboration Potential • Phase 3 clinical trial in patients with moderate to severe acne vulgaris in progress in China • Topline results expected in 2Q2025 • Phase 3 clinical trial in recurrent glioblastoma multiforme (GBM) in combination with bevacizumab in
Slide 6: Development Pipeline: Multiple Indications and Clinical Milestones
6 May 2025 Expected Milestone / Status Stage of Development Indication Therapeutic Area Phase 3 Phase 2 Phase 1 Preclinical Phase 2b positive topline data announced 1Q2024 ; FDA Breakthrough Therapy designation; Phase 3 F2/F3 ready MASH Metabolic Disease Phase 1 hepatic impairment results reported 1
Slide 7: MASH: A Burgeoning Epidemic
7 May 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 10
Slide 8: FASN Inhibition Addresses Three Independent Mechanisms of MASH Development and Progression
8 May 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 lipogen
Slide 9: FASN Inhibition Directly Blocks Human Liver Stellate Cell Function
9 May 2025 FASN Inhibition Directly Blocks Human Liver Stellate Cell Function Stellate cells require DNL for fibrogenesis Denifanstat blocks stellate cell activation Denifanstat directly inhibits fibrogenic activity Primary human stellate cell assay Denifanstat • Stimulated by TGF - beta to activate
Slide 10: Treatment Goals for MASH Across Fibrosis Staging
10 May 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 / Impro
Slide 11: Strong MASH Data Creates Opportunities to Reach Advanced Patient Populations
Strong MASH Data Creates Opportunities to Reach Advanced Patient Populations
Slide 12: FASCINATE-2: Biopsy Trial Design Focused on Histological Endpoints
12 May 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 (n=168) • 52 weeks, 2:1 randomization to 50mg
Slide 13: FASCINATE-2: Baseline Characteristics Were Typical of the F2/F3 MASH Population
13 May 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 14: Primary Endpoints: Liver Biopsy
14 May 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 MAS
Slide 15: Secondary Endpoints: Liver Fibrosis and MASH Resolution
15 May 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 worse
Slide 16: Secondary Endpoints: Liver Fibrosis
16 May 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 improve
Slide 17: Additional Fibrosis Analysis Using AI-based Digital Pathology
17 May 2025 Additional Fibrosis Analysis Using AI - based Digital Pathology Digital Imaging Showed that Denifanstat Significantly Reduced Fibrosis in Advanced Patients Pre - Treatment Pt A NASH - CRN Fibrosis stage F3 Post - Treatment Pt A NASH - CRN Fibrosis stage F1 Denifanstat 0.10 - 0.30 Placebo
Slide 18: qFibrosis Zonal Analysis Demonstrated Improvement in Parameters Linked to Liver Outcomes
18 qFibrosis Zonal Analysis Demonstrated that Denifanstat Improves Parameters Linked to Liver Outcomes Zone 1 Zone 2 Zone 3 Central Vein Portal Vein HA BD Response at the individual zonal parameter level was defined as ”at least” 30% relative decrease from baseline. FASCINATE - 2, AASLD 2024 Fibrosi
Slide 19: Differentiated Mechanism of Action
19 May 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 5.HistoIndex FASCINATE - 2 data on file Differentiated Mechanism of Action • In vitro data demonstrates
Slide 20: qF4 Patients on Denifanstat Showed 1 to 2-Stage Reductions in Fibrosis
20 May 2025 Source: FASCINATE - 2 HistoIndex data on file 85% of qF4 Patients on Denifanstat Showed 1 to 2 - Stage Reductions in Fibrosis • AI may detect fibrosis regression at an earlier point in time, compared to conventional pathology • qF4 population (defined on AI platform by HistoIndex ) are l
Slide 21: Patient Subset on Stable GLP1-RA at Baseline: Liver Biopsy
21 May 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 MA
Slide 22: FASCINATE-2: Safety
22 May 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 r
Slide 23: Denifanstat Decreased Liver Fat by MRI-PDFF and Reduced FAST Score
23 May 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 Significanc
Slide 24: Secondary Endpoints: Liver Enzymes
24 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 25: Cardiometabolic Health
25 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 26: Denifanstat Reduced De Novo Lipogenesis
26 May 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 27: Precision Medicine: Blood Tests May Lead to Improved Patient Outcomes
27 May 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 mult
Slide 28: Mechanism of Action Supports Combination Therapy Opportunity
28 May 2025 Mechanism of Action Supports Combination Therapy Opportunity MOA - Mechanism of Action Combination therapy potential: • Denifanstat MOA that is complementary to other MOAs – THR - beta, GLPs • Opportunity for fixed dose combinations with other oral medications Potential improved clinical
Slide 29: Phase 1 Clinical PK Drug Interaction Trial Planned with Denifanstat and Resmetirom
29 May 2025 Phase 1 Clinical Pharmacokinetic (PK) Drug Interaction Trial Planned with Denifanstat and Resmetirom Objectives • Phase 1 clinical trial to measure pharmacokinetics of denifanstat and of resmetirom when co - administered, compared to monotherapy of each drug • Once daily oral administrat
Slide 30: FASN Inhibition Offers Potential Benefit in Multiple Indications
FASN Inhibition Offers Potential Benefit in Multiple Indications
Slide 31: FASN Also Plays a Key Role in Other Diseases With Significant Unmet Need
31 May 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, intracellul
Slide 32: DNL Pathway Plays a Critical Role in the Pathogenesis of Acne
32 May 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 FAS
Slide 33: Acne US Market Overview
33 May 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 people
Slide 34: Clinical Data Support Mechanism of Action of a FASN Inhibitor in Acne
34 May 2025 Clinical 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
Slide 35: Ascletis Announced Positive Phase 2 Clinical Data in Acne
35 May 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 - grad
Slide 36: TVB-3567 FIH Phase 1 Study Design
36 May 2025 A double - blind, randomized, placebo - controlled trial to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple ascending doses of TVB - 3567 in healthy and acne participants • Includes sebum analysis as pharmacodynamic readout SAD = Single ascen
Slide 37: FASN Is Integral to Tumor Cell Proliferation and Survival
37 May 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 comb
Slide 38: Cancer Program Focuses on 4 FASN-Dependent Tumor Types
38 May 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 , denifan
Slide 39: Sagimet at a Glance
39 May 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 diseases • Strong clinical data demonstrates denifanstat’s proof of concept across multiple disease states Uni
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