Sagimet Biosciences Inc. - Series A · NASDAQ:SGMT
Sagimet Biosciences Inc. - Series A — Sagimet Biosciences — Investor Presentation (August 2025)
50 slides from Sagimet Biosciences Inc. - Series A's investor presentation, Aug 13, 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 August 2025
Slide 2: Forward-Looking Statements and Disclaimer
2 August 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 st
Slide 3: Leadership Team with Proven Development and Commercialization Experience
3 August 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
Slide 4: Sagimet at a Glance
4 August 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 U
Slide 5: Strong IP, Cash Position, and Collaboration Potential
5 August 2025 Strong IP, Cash Position, and Collaboration Potential • Denifanstat met all primary and secondary endpoints in Phase 3 clinical trial in patients with moderate to severe acne vulgaris in China • Phase 3 clinical trial of denifanstat in recurrent glioblastoma multiforme (GBM) in combina
Slide 6: Development Pipeline: Multiple Indications and Clinical Milestones
6 August 2025 Expected Milestone / Status Stage of Development Indication Therapeutic Area Phase 3 Phase 2 Phase 1 Preclinical Phase 2b met histology primary and multiple secondary endp oints , data announced 1Q2024 ; FDA Breakthrough Therapy designation; Phase 3 F2/F3 ready MASH Metabolic Disease P
Slide 7: MASH: A Burgeoning Epidemic
7 August 2025 MASH • Complex disease with h eterogeneous patient population • Significant opportunity for differentiated MOA MASH: A Burgeoning Epidemic Note: MASH, or metabolic dysfunction - associated steatohepatitis, was formerly known as NASH, or nonalcoholic steatohepatitis. 1. Estes C, et al.
Slide 8: FASN Inhibition Addresses Three Independent Mechanisms of MASH Development and Progression
8 August 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 lipo
Slide 9: FASN Inhibition Directly Blocks Human Liver Stellate Cell Function
9 August 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 1 Primary human stellate cell assay Denifanstat • Stimulated by TGF - beta to act
Slide 10: Treatment Goals for MASH Across Fibrosis Staging
10 August 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 / Im
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 August 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 5
Slide 13: FASCINATE-2: Baseline Characteristics Were Typical of the F2/F3 MASH Population
13 August 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.
Slide 14: Primary Endpoints: Liver Biopsy
14 August 2025 Loomba R, et al. Lancet Gastroenterol Hepatol. 2024;9(12):1090 - 1100 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 W
Slide 15: Secondary Endpoints: Liver Fibrosis and MASH Resolution
15 August 2025 Loomba R, et al. Lancet Gastroenterol Hepatol. 2024;9(12):1090 - 1100 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 Denif
Slide 16: Secondary Endpoints: Liver Fibrosis
16 August 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 impr
Slide 17: Additional Fibrosis Analysis Using AI-based Digital Pathology
17 August 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 Plac
Slide 18: qFibrosis Zonal Analysis Improves Parameters Linked to Liver Outcomes
18 August 2025 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. 2. Rinella M, et al.
Slide 19: Denifanstat Potential in Cirrhotic (F4) Patients
19 August 2025 Differentiated Mechanism of Action • In vitro data demonstrates that denifanstat reduces pro - fibrotic signaling in stellate cells , suggesting that denifanstat has the potential to remove fibrotic scar tissue and reestablish the basal extracellular matrix ( ECM ) scaffold even in ci
Slide 20: 85% of qF4 Patients on Denifanstat Showed 1 to 2-Stage Reductions in Fibrosis
20 August 2025 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 likely the most advanced subgroup of F3 pati
Slide 21: FASCINATE-2: Safety
21 August 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 the
Slide 22: Denifanstat Decreased Liver Fat by MRI-PDFF and Reduced FAST Score
22 August 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 Signific
Slide 23: Secondary Endpoints: Liver Enzymes
23 August 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
Slide 24: Cardiometabolic Health
24 August 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
Slide 25: Denifanstat Reduced De Novo Lipogenesis
25 August 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 tripalmit
Slide 26: Precision Medicine: Blood Tests May Lead to Improved Patient Outcomes
26 August 2025 Precision Medicine: Blood Tests May Lead to Improved Patient Outcomes 1. Signature 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
Slide 27: Combination Therapy Development Program for MASH
Combination Therapy Development Program for MASH
Slide 28: Combination of FASN Inhibitor and Semaglutide Improved Histological Features in MASH Mouse Model
28 August 2025 Combination of FASN Inhibitor and Semaglutide Improved Histological Features in MASH Mouse Model - SMA: a marker of activated hepatic stellate cells NC VEH FASN SEMA COMBO 0 5 10 s c o r e Phenotypic Fibrosis Composite Score * ** NS Fibrosis NC VEH FASN SEMA COMBO In a mouse model, co
Slide 29: Patient Subset on Stable GLP1-RA at Baseline: Liver Biopsy
29 August 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 30: Mechanism of Action Supports Combination Therapy Opportunity
30 August 2025 Mechanism of Action Supports Combination Therapy Opportunity MOA - Mechanism of Action 1. Tsai WW, et al. Presented at: EASL 2024; June 5 - 8, 2024; Milan, Italy. https://sagimet.com/wp - content/uploads/2024/06/2024 - EASL - poster - GAN - model - final.pdf Tsai WW, et al. Presented
Slide 31: Potential Benefits of Combination Therapy in Advanced MASH Patients
31 August 2025 Potential Benefits of Combination Therapy in Advanced MASH Patients Note: These data are placebo - adjusted, derived from different clinical trials at different points in time, with differences in t rial design and patient populations. As a result, cross - trial comparisons cannot be
Slide 32: Potential Clinical Development Program for Denifanstat and Resmetirom Combination
32 August 2025 Step 1 - Phase 1 PK study for denifanstat and resmetirom • PK to evaluate any drug/drug interaction • Assess safety/tolerability • Confirm optimal combination dose levels for later clinical efficacy study in MASH Step 2 - Phase 2 clinical combination study with denifanstat and resmeti
Slide 33: Attractiveness of a Potential Denifanstat / Resmetirom Combination
33 August 2025 Attractiveness of a Potential Denifanstat / Resmetirom Combination • Phase 1 clinical trial to evaluate the pharmacokinetics ථ (PK) and tolerability of a combination of denifanstat and resmetirom planned to initiate in 2H 2025; data readout expected 1H 2026 • If the outcome of this Ph
Slide 34: FASN Inhibition Offers Potential Benefit in Multiple Indications: Acne
FASN Inhibition Offers Potential Benefit in Multiple Indications: Acne
Slide 35: FASN Also Plays a Key Role in Other Diseases With Significant Unmet Need
35 August 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, intracel
Slide 36: Acne Pathogenesis and Potential Role of FASN Inhibitors
36 August 2025 Multifactorial pathogenesis of acne involves 4 key aspects: • Increased sebum in sebaceous glands (80% of lipids produced through DNL) • Abnormal or excessive follicular hyper - keratinization • Accelerated bacterial growth (C. acnes) • Localized inflammatory response Acne Pathogenesi
Slide 37: Acne Market Overview
37 August 2025 Blackheads Whiteheads Papules & Pustules Cysts & Nodules Acne Market Overview Global acne market is expected to reach $17B in next decade 1 5.1 million US acne patients are treated by dermatologists annually (total US acne market is 50 million people ) 2,3 • Acne is the #1 or #2 patie
Slide 38: Acne Treatment Algorithm
38 August 2025 Moderate to Severe Disease Mild Disease Acne Treatment Algorithm • Most acne patients receive skin care routines that include OTC cleansers and moisturizers to address AEs associated with their treatment Disease management involves flare and prevention intervention Treatment includes
Slide 39: Clinical Data Support Mechanism of Action of a FASN Inhibitor in Acne
39 August 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 1,2 • FASN inhibitor maintained the reduced level of sebum lipids through the entire study 1,2 • FASN inhibitor demonstrated a dose responsive
Slide 40: Ascletis Acne Phase 3 Clinical Trial Design
40 August 2025 Ascletis Acne Phase 3 Clinical Trial Design • Moderate to severe acne • Multi - center placebo controlled • 1 :1 randomization • D ouble - blind • Once daily oral dosing • 480 patients in China Primary endpoints at week 12 • % patients who receive IGA success (defined as at least a 2
Slide 41: Ascletis Acne Phase 3 Clinical Trial: All Primary and Secondary Endpoints Met
41 August 2025 Ascletis Acne Phase 3 Clinical Trial: All Primary and Secondary Endpoints Met Placebo (n=240) 50mg denifanstat (n=240) Baseline Characteristics 102.1 102.2 Total lesion count 43.1 42.1 Inflammatory lesion count 85.8 85.8 IGA=3 (moderate), % 14.2 14.2 IGA=4 (severe), % p value 50mg den
Slide 42: Ascletis Acne Phase 3 Clinical Trial Safety Data
42 August 2025 Ascletis Acne Phase 3 Clinical Trial Safety Data Denifanstat 50mg was generally well tolerated during the 12 - week study Treatment - emergent adverse events (TEAEs) : • TEAE incidence rates were comparable between denifanstat and placebo • No incidence rate of TEAE in any category ex
Slide 43: Second FASN Inhibitor TVB-3567 Entered FIH Phase 1
43 August 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 Note: SAD = Sin
Slide 44: Potential Clinical Development Program for TVB-3567 in Acne
44 August 2025 Potential Clinical Development Program for TVB - 3567 in Acne Step 1 - Phase 1 first - in - human pharmacokinetic (PK) clinical trial of TVB - 3567 in healthy volunteers • PK and pharmacodynamics (PD) evaluation to confirm profile • Assess safety/tolerability • Confirm potential doses
Slide 45: Attractiveness of TVB-3567 in Acne
45 August 2025 Attractiveness of TVB - 3567 in Acne • Our second FASN inhibitor, TVB 3567, received Investigational New Drug (IND) clearance in March 2025 • First - in - human Phase 1 clinical trial of TVB 3567 initiated in June 2025 for development in acne • Upon completion of Phase 1, will consult
Slide 46: FASN Inhibition Offers Potential Benefit in Multiple Indications: Oncology
FASN Inhibition Offers Potential Benefit in Multiple Indications: Oncology
Slide 47: FASN Also Plays a Key Role in Other Diseases With Significant Unmet Need
47 August 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, intracel
Slide 48: FASN Is Integral to Tumor Cell Proliferation and Survival
48 August 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 c
Slide 49: Cancer Program Focuses on 4 FASN-Dependent Tumor Types
49 August 2025 GBM Prostate HCC NSCLC KRASM Cancer Program Focuses on 4 FASN - Dependent Tumor Types GBM (glioblastoma), HCC (hepatocellular carcinoma), KRASM (mutant KRAS), NSCLC (non small cell lung cancer) 1. Kelly W, et al. Clin Cancer Res. 2023;29(13):2419 - 2425. 2. ClinicalTrials.gov. NCT0511
Slide 50: Sagimet at a Glance
50 August 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
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