Sagimet Biosciences Inc. - Series A · NASDAQ:SGMT
Sagimet Biosciences Inc. - Series A — Sagimet Biosciences — Investor Presentation (October 2025)
51 slides from Sagimet Biosciences Inc. - Series A's investor presentation, Oct 23, 2025
Slide 1: Targeting Metabolic Dysfunction with Novel Therapies to Treat MASH, Acne & Cancer
Targeting MetabolicDysfunction with Novel Therapies to Treat MASH, Acne&Cancer October 2025
Slide 2: Forward-Looking Statements and Disclaimer
October 2025 2 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 statem
Slide 3: Leadership Team with Proven Development and Commercialization Experience
October 2025 3 Leadership Team with Proven Development and Commercialization Experience DaveHappel 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-sc
Slide 4: Sagimet at a Glance
October 2025 4 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
Slide 5: Strong IP, Cash Position, and Collaboration Potential
October 2025 5 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 conducted by license partner for China, Ascletis • Ascletis announced that it completed its
Slide 6: Development Pipeline: Multiple Indications and Clinical Milestones
October 2025 6 Therapeutic Area Indication Stage of Development Expected Milestone / Status Preclinical Phase 1 Phase 2 Phase 3 Metabolic Disease MASH Phase 2b met histology primary and multiple secondary endpoints, data announced 1Q2024; FDA Breakthrough Therapy designation; Phase 3 F2/F3 ready Pha
Slide 7: MASH: A Burgeoning Epidemic
October 2025 7 MASH • Complex disease with heterogeneous 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. J
Slide 8: FASN Inhibition Addresses Three Independent Mechanisms of MASH Development and Progression
October 2025 8 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
October 2025 9 FASN Inhibition Directly Blocks Human Liver Stellate Cell Function Stellate cells require DNL for fibrogenesis Denifanstat blocks stellate cell activation Denifanstat directly inhibits fibrogenic activity1 Primary human stellate cell assay Denifanstat • Stimulated by TGF-beta to activ
Slide 10: Treatment Goals for MASH Across Fibrosis Staging
October 2025 10 Treatment Goals for MASH Across Fibrosis Staging MASH STAGING F1 F2 F3 F4 (Compensated) Risk Staging based on: • Fat • Inflammation • Fibrosis • Liver & CV Events Primary Treatment Objectives Primary Therapeutic Interventions (based on Primary Objectives) Improve Glycemic Control / I
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
October 2025 12 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 or
Slide 13: FASCINATE-2: Baseline Characteristics Were Typical of the F2/F3 MASH Population
October 2025 13 FASCINATE-2: Baseline Characteristics Were Typical of the F2/F3 MASH Population Parameter Placebo, n=45 Denifanstat, n=81 Age, years 59.6 (+/- 10.9) 56.1 (+/- 10.8) Sex, female 27 (60%) 48 (59%) Race, White 41 (91%) 73 (90%) Ethnicity, Hispanic or Latino 15 (33%) 27 (33%) BMI, kg/m2
Slide 14: Denifanstat Achieved Statistical Significance at Week 52
October 2025 14 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 Week 52
Slide 15: Secondary Endpoints: Liver Fibrosis and MASH Resolution
October 2025 15 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 Denifansta
Slide 16: Denifanstat Achieved Statistically Significant Improvement of Fibrosis
October 2025 16 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 Fibrosis Endpoints Subgroup Placebo Denifanstat p-value >1 stage improvement in fibrosis w/
Slide 17: Denifanstat Achieved Statistically Significant VCTE Improvement at Weeks 26 and 52
October 2025 17 Denifanstat Achieved Statistically Significant VCTE Improvement at Weeks 26 and 52 FASCINATE-2 Phase 2b Sagimet Biosciences data on file. FASCINATE-2 posthoc analysis. mITT population. Chi-square test. VCTE: Vibration-controlled transient elastography. VCTE <=30% means magnitude of d
Slide 18: Additional Fibrosis Analysis Using AI-based Digital Pathology
October 2025 18 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 n=45 D
Slide 19: qFibrosis Zonal Analysis Improves Parameters Linked to Liver Outcomes
October 2025 19 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 20: Denifanstat Potential in Cirrhotic (F4) Patients
October 2025 20 Differentiated Mechanism of Action • In vitro data demonstrates that denifanstatreduces pro-fibrotic signaling in stellatecells, suggesting that denifanstat has the potential to remove fibrotic scar tissue and reestablish the basal extracellular matrix (ECM) scaffold even in cirrhoti
Slide 21: 85% of qF4 Patients on Denifanstat Showed 1 to 2-Stage Reductions in Fibrosis
October 2025 21 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 patien
Slide 22: FASCINATE-2: Safety — Denifanstat Was Generally Well-Tolerated
October 2025 22 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 comparable to placebo • AE of hair thinning stabilized with a 2-to-4 week dose pause and then reversed
Slide 23: Denifanstat Decreased Liver Fat by MRI-PDFF and Reduced FAST Score
October 2025 23 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 Significance 21%
Slide 24: Secondary Endpoints: Liver Enzymes
October 2025 24 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 chang
Slide 25: Cardiometabolic Health
October 2025 25 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. 1For LDL-c, baseline > 100 mg/dL. Denifanstat Decreased LDL-c Levels and Increased Polyunsaturated Triglycerides LDL-c1 Change
Slide 26: Denifanstat Reduced De Novo Lipogenesis
October 2025 26 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 tripalmiti
Slide 27: Precision Medicine: Blood Tests May Lead to Improved Patient Outcomes
October 2025 27 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 multi-face
Slide 28: Combination Therapy Development Program for MASH
Combination Therapy Development Program for MASH
Slide 29: Combination of FASN Inhibitor and Semaglutide Improved Histological Features in MASH Mouse Model
October 2025 29 Combination of FASN Inhibitor and Semaglutide Improved Histological Features in MASH Mouse Model α-SMA: a marker of activated hepatic stellate cells Fibrosis NC VEH FASN SEMA COMBO In a mouse model, combination treatment showed: 1) an additive effect on fibrosis reduction, 2) a direc
Slide 30: Patient Subset on Stable GLP1-RA at Baseline
October 2025 30 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 FASCINATE-2 Phase 2b - Denifanstat Improved MASH Resolution and Fibr
Slide 31: Mechanism of Action Supports Combination Therapy Opportunity
October 2025 31 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 at: EASL 2024;
Slide 32: Potential Benefits of Combination Therapy in Advanced MASH Patients
October 2025 32 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 trial design and patient populations. As a result, cross-trial comparisons cannot be made
Slide 33: Potential Clinical Development Program for Denifanstat and Resmetirom Combination
October 2025 33 Step 1 - Phase 1 PK trial for combination of 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, subject to consultation with regulatory authorit
Slide 34: Attractiveness of a Potential Denifanstat/Resmetirom Combination
October 2025 34 Attractiveness of a Potential Denifanstat/Resmetirom Combination • Phase 1 clinical trial to evaluate the pharmacokinetics (PK) and tolerability of a combination of denifanstat and resmetirom initiated in September 2025; data readout expected 1H 2026 • If the outcome of this Phase 1
Slide 35: FASN Inhibition Offers Potential Benefit in Multiple Indications: Acne
FASN Inhibition Offers Potential Benefit in Multiple Indications: Acne
Slide 36: FASN Also Plays a Key Role in Other Diseases With Significant Unmet Need
October 2025 36 FASN Also Plays a Key Role in Other Diseases With Significant Unmet Need FASN in cancer Supports tumor survival Enables tumor proliferation Establishes resistance to drugs FASN in acne Increases sebum production Exacerbates sebum composition Cancer cell Membrane synthesis, intracellu
Slide 37: Acne Pathogenesis and Potential Role of FASN Inhibitors
October 2025 37 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 Pathogenesis
Slide 38: Acne Market Overview
October 2025 38 Blackheads Whiteheads Papules & Pustules Cysts & Nodules Acne Market Overview Global acne market is expected to reach $17B in next decade1 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 patien
Slide 39: Acne Treatment Algorithm
October 2025 39 Mild Disease Moderate to Severe 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 40: Clinical Data Support Mechanism of Action of a FASN Inhibitor in Acne
October 2025 40 Clinical Data Support Mechanism of Action of a FASN Inhibitor in Acne • FASN inhibitor demonstrated a >90% reduction in sebum lipids by day 151,2 • FASN inhibitor maintained the reduced level of sebum lipids through the entire study1,2 • FASN inhibitor demonstrated a dose responsive
Slide 41: Ascletis Acne Phase 3 Clinical Trial Design
October 2025 41 Ascletis Acne Phase 3 Clinical Trial Design • Moderate to severe acne • Multi-center placebo controlled • 1:1 randomization • Double-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-point
Slide 42: Ascletis Acne Phase 3 Clinical Trial: All Primary and Secondary Endpoints Met
October 2025 42 Ascletis Acne Phase 3 Clinical Trial: All Primary and Secondary Endpoints Met Baseline Characteristics 50mg denifanstat (n=240) Placebo (n=240) Total lesion count 102.2 102.1 Inflammatory lesion count 42.1 43.1 IGA=3 (moderate), % 85.8 85.8 IGA=4 (severe), % 14.2 14.2 Efficacy endpoi
Slide 43: Ascletis Acne Phase 3 Clinical Trial Safety Data
October 2025 43 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 • Only two categories of TEAEs had an incidence ra
Slide 44: Second FASN Inhibitor TVB-3567 Entered FIH Phase 1
October 2025 44 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 = Single a
Slide 45: Potential Clinical Development Program for TVB-3567 in Acne
October 2025 45 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 for an
Slide 46: Attractiveness of FASN Inhibition in Acne
October 2025 46 Attractiveness of FASN Inhibition in Acne • First-in-human Phase 1 clinical trial of TVB-3567 initiated in June 2025 for development in acne • Upon completion of TVB-3567 Phase 1, will consult with regulatory authorities regarding Phase 2 trial design, with goal of initiating TVB-356
Slide 47: FASN Inhibition Offers Potential Benefit in Multiple Indications: Oncology
FASN Inhibition Offers Potential Benefit in Multiple Indications: Oncology
Slide 48: FASN Also Plays a Key Role in Other Diseases With Significant Unmet Need
October 2025 48 FASN Also Plays a Key Role in Other Diseases With Significant Unmet Need FASN in cancer Supports tumor survival Enables tumor proliferation Establishes resistance to drugs FASN in acne Increases sebum production Exacerbates sebum composition Cancer cell Membrane synthesis, intracellu
Slide 49: FASN Is Integral to Tumor Cell Proliferation and Survival
October 2025 49 FASN Is Integral to Tumor Cell Proliferation and Survival KRASM – KRAS mutant. KRASWT- KRAS wild type FASN dependence • Certain cancers are dependent onDNL/FASN for proliferation especiallydownstream of driver oncogenes • Strategy kill tumor cells and/or avoid drug resistance by comb
Slide 50: Cancer Program Focuses on 4 FASN-Dependent Tumor Types
October 2025 50 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. ClinicalTrials.gov. NCT05743621. https://clinicaltrials.gov/study/NCT05743621. 2. Wang H,
Slide 51: Sagimet at a Glance
October 2025 51 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
Sagimet Biosciences — Investor Presentation (October 2025) on 6ix