Sagimet Biosciences Inc. - Series A · NASDAQ:SGMT
Sagimet Biosciences Inc. - Series A — Sagimet Biosciences — Corporate Update (August 2024)
34 slides from Sagimet Biosciences Inc. - Series A's corporate update, Aug 14, 2024
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 2024
Slide 2: Forward Looking Statements
2 August 2024 Forward Looking Statements 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 statements of histo
Slide 3: Leadership Team with Proven Development and Commercialization Experience
3 August 2024 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 experie
Slide 4: FASN Inhibitor Denifanstat Offers a Unique and Validated Approach to MASH
4 August 2024 FASN Inhibitor Denifanstat Offers a Unique and Validated Approach to MASH • As the only fat synthesis inhibitor, denifanstat directly targets the 3 key drivers of MASH – liver fat, inflammation, and fibrosis • FASN is a key enzyme in de novo lipogenesis responsible for excess liver fat
Slide 5: Denifanstat: A Novel Small Molecule FASN Inhibitor Protected By Strong IP
5 August 2024 Designed for once - daily, oral dosing Rigorous and de - risked development strategy Direct DNL inhibition demonstrated in Phase 1b Improvements in liver fat and other non - invasive biomarkers in Phase 2a Topline data of successfully completed 52 - week Phase 2b biopsy study announced
Slide 6: Development Pipeline: Indications and Clinical Milestones
6 August 2024 Therapeutic Area Indication Stage of Development Expected Milestone / Status Preclinical Phase 1 Phase 2 Phase 3 Metabolic Disease MASH F2/F3 population Phase 2b positive topline data announced 1Q2024 ; MASH Phase 3 estimated start 2H 2024 Phase 1 hepatic impairment results reported 1Q
Slide 7: MASH: A Burgeoning Epidemic
7 August 2024 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 2 Yonoussi et al. 2023; The Growing Economic and Clinical Burd
Slide 8: FASN Inhibition Addresses Three Independent Mechanisms of MASH Development and Progression
8 August 2024 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 2024 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 activ
Slide 10: Treatment Goals for MASH Across Fibrosis Staging
10 August 2024 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 / Im
Slide 11: MASH Clinical Development Program
MASH Clinical Development Program
Slide 12: FASCINATE-2: Biopsy Trial Design Focused on Histological Endpoints
12 August 2024 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 p
Slide 13: FASCINATE-2: Baseline Characteristics Were Typical of the F2/F3 MASH Population
13 August 2024 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
Slide 14: Primary Endpoints: Liver Biopsy
14 August 2024 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 52 Weeks NAS ≥ 2 points improvement* w/o worsening of fibrosis p=0.0001
Slide 15: Secondary Endpoints: Liver Fibrosis and MASH Resolution
15 August 2024 Secondary Endpoints: Liver Fibrosis and MASH Resolution Cochran - Mantel - Haenszel Test – One sided at the 0.05 significance level Denifanstat Achieved Statistical Significance 18% 41% Placebo n=45 Denifanstat n=81 % response Improvement in liver fibrosis ≥ 1 stage & No Worsening of
Slide 16: Secondary Endpoints: Liver Fibrosis
16 August 2024 Secondary Endpoints: Liver Fibrosis *One sided at the 0.05 significance level, **Two sided at the 0.05 significance level Denifanstat Achieved Profound Improvement of Fibrosis Fibrosis Endpoints Subgroup Placebo Denifanstat p - value > 1 stage improvement in fibrosis w/o worsening of
Slide 17: Additional Fibrosis Analysis Using AI-based Digital Pathology
17 August 2024 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=8
Slide 18: Patient Subset on Stable GLP1-RA at Baseline: Liver Biopsy
18 August 2024 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 19: FASCINATE-2: Safety
19 August 2024 FASCINATE - 2: Safety Denifanstat Was Generally Well Tolerated • No DILI signal and no muscle wasting were detected, and GI were comparable to placebo • AE of hair thinning stabilized with a 2 to 4 week dose pause and then reversed with down titration or study completion • Consistent
Slide 20: Denifanstat Decreased Liver Fat by MRI-PDFF and Reduced FAST Score
20 August 2024 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 21: Secondary Endpoints: Liver Enzymes
21 August 2024 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 22: Cardiometabolic Health
22 August 2024 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 23: Denifanstat Rapidly and Robustly Reduced De Novo Lipogenesis
23 August 2024 Denifanstat Rapidly and Robustly 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 • Rapidly reduced by denifanstat as early as 4 weeks of treatment Next steps • Continue
Slide 24: Mechanism of Action Supports Combination Therapy Opportunity
24 August 2024 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 st
Slide 25: Denifanstat Potential in Cirrhosis
25 August 2024 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. EASL 2024 Compensated Cirrhotic Patients (MASH F4) • Denifanstat reduces pro - fibrotic signaling stellate cells which retain the ability to
Slide 26: Pediatric MASH Continues to be an Area of Significant Unmet Need
26 August 2024 1Yu EL and Schwimmer JB. doi : 10.1002/cld.1027. 2Softic S and Rohit K. doi : 10.1002/hep.32322. 3Kleiner 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 chi
Slide 27: Precision Medicine: Blood Tests May Lead to Improved Patient Outcomes
27 August 2024 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 m
Slide 28: Additional Denifanstat Indications
Additional Denifanstat Indications
Slide 29: FASN Also Plays a Key Role in Other Diseases With Significant Unmet Need
29 August 2024 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 30: DNL Pathway Plays a Role in the Pathogenesis of Acne
30 August 2024 DNL Pathway Plays a Role in the Pathogenesis of Acne FASN is an attractive therapeutic target for acne • Acne is associated with sebum over production by sebocytes in the skin • Acne resolution is associated with reduced sebum production • Sebocytes rely on DNL/FASN to make sebum • >8
Slide 31: Ascletis Announced Positive Early Clinical Data in Acne; Phase 3 Study Ongoing
31 August 2024 Ascletis Announced Positive Early Clinical Data in Acne; Phase 3 Study Ongoing * p<0.05. ** p<0.01. ^Lesion data are mean relative reduction from baseline to 12w, n= number in cohort. Ascletis has exclusive rights to denifanstat in Greater China 2 9 EFFICACY RESULTS – 12 WEEKS Placebo
Slide 32: FASN Is Integral to Tumor Cell Proliferation and Survival
32 August 2024 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 33: Cancer Program Focuses on 4 FASN-Dependent Tumor Types
33 August 2024 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 , deni
Slide 34: FASN Inhibitor Denifanstat Offers a Unique and Validated Approach to MASH
34 August 2024 FASN Inhibitor Denifanstat Offers a Unique and Validated Approach to MASH • As the only fat synthesis inhibitor, denifanstat directly targets the 3 key drivers of MASH – liver fat, inflammation, and fibrosis • FASN is a key enzyme in de novo lipogenesis responsible for excess liver fa