Sagimet Biosciences Inc. - Series A · NASDAQ:SGMT
Sagimet Biosciences Inc. - Series A — Sagimet Biosciences — Investor Presentation (January 2024)
32 slides from Sagimet Biosciences Inc. - Series A's investor presentation, Jan 22, 2024
Slide 1: Targeting Metabolic Dysfunction with Novel Therapies to Treat NASH, Acne and Cancer
Targeting Metabolic Dysfunction with Novel Therapies to Treat NASH, Acne and Cancer January 202 4
Slide 2: Forward Looking Statements
Forward Looking Statements 2 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 historical facts o
Slide 3: Proven Team with Development and Commercialization Experience
Dave Happel President & CEO • Cognoa: President & CEO Chrono Therapeutics: President & CEO Senior E xecutive and C ommercial roles at Horizon, Raptor, Dynavax, Chiron • M.B.A. – Indiana State University; B.A. C hemistry – Indiana University George Kemble Executive Chairman • AstraZeneca (formerly Me
Slide 4: Sagimet Investment Highlights
Sagimet Investment Highlights Critical role of FASN enzyme in NASH x Key enzyme in de novo lipogenesis – responsible for excess liver fat in NASH x FASN inhibition directly improves the 3 key drivers of NASH – liver fat, inflammation, fibrosis x Differentiated MOA to treat growing underserved patien
Slide 5: Development Pipeline: Indications and Clinical Milestones
Therapeutic Area Stage of Development Indication Expected Milestone / Status Preclinical Phase 1 Phase 2 Phase 3 Metabolic disease • Phase 2b successfully completed NASH - F2/F3 • Phase 1 hepatic impairment results 1Q 2024 Dermatology Acne • IND 1H 2024 filing planned • Phase 3 clinical study initia
Slide 6: NASH: A Burgeoning Epidemic
NASH: A Burgeoning Epidemic • No approved drugs in U.S. or Europe • Complex disease, heterogeneous patient population • Improving regulatory clarity, but liver biopsy still required • Many molecules moved forward on weak mechanism and data • Inappropriate biomarkers for mechanism that did not transl
Slide 7: Denifanstat in NASH
Denifanstat in NASH 7
Slide 8: Denifanstat: Differentiated Mechanism Believed to Target Key Drivers of NASH
Denifanstat: Differentiated Mechanism Believed to Target Key Drivers of NASH Adapted from Wegermann et al, Clinical Liver Disease, Vol 11, No 4, April 2018, DOI: 10.1002/cld.709 Denifanstat has independent mechanisms designed to: ඹ Block steatosis via inhibiting de novo lipogenesis in hepatocytes ය
Slide 9: Denifanstat: Well Tolerated at 25/50mg Doses in FASCINATE-1
Denifanstat: Well Tolerated at 25/50mg Doses in FASCINATE - 1 • No dose - related significant adverse events relative to placebo • No serious AEs • Majority of AEs were Grade 1; no Grade ≥3 drug - related AEs 9
Slide 10: FASCINATE-2 Phase 2b Biopsy Trial Design
FASCINATE - 2 Phase 2b Biopsy Trial Design Measuring Histological Improvement 10 FASCINATE - 2 Phase 2b trial design • Biopsy confirmed F2 - F3 NASH patients • 52 weeks, 2:1 50mg or placebo, double - blind Primary endpoints Other selected endpoints • NAS ≥2 points improvement w/o worsening of fibros
Slide 11: Primary Endpoints: Liver Biopsy
Primary Endpoints: Liver Biopsy Denifanstat Achieved Statistical Significance Cochran - Mantel - Haenszel Test – One sided at the 0.05 significance level. mITT population. * ≥1 - point improvement in ballooning or inflammation. 11 20% 52% Placebo n=45 Denifanstat n=81 % response NAS ≥ 2 points impro
Slide 12: Secondary Endpoints: Liver Biopsy
Secondary Endpoints: Liver Biopsy Denifanstat Achieved Statistical Significance 12 Resolution of NASH w/o worsening of fibrosis p= 16% 38% Placebo n=45 Denifanstat n=81 % response p=0.0021 Cochran - Mantel - Haenszel Test – One sided at the 0.05 significance level. mITT population 18% 41% Placebo n=
Slide 13: Independent Fibrosis Analysis by AI-based Digital Pathology
Independent Fibrosis Analysis by AI - based Digital Pathology Supporting Evidence that Denifanstat Significantly Reduced Fibrosis 13 0.10 - 0.30 Placebo n=45 Denifanstat n=81 LS mean change qFibrosis Continuous Value Change from Baseline p=0.0023 Cochran - Mantel - Haenszel Test – One sided at the 0
Slide 14: Patient Subset on Stable GLP1-RA at Baseline: Liver Biopsy
Patient Subset on Stable GLP1 - RA at Baseline: Liver Biopsy Denifanstat Improves NASH Resolution and Fibrosis 14 Resolution of NASH w/o worsening of fibrosis Improvement in liver fibrosis ≥ 1 stage w/o worsening of NASH 0% 42% Placebo n=4 Denifanstat n=12 % response 0% 42% Placebo n=4 Denifanstat n
Slide 15: Biomarkers of Fibrosis: FAST Score and ELF
Biomarkers of Fibrosis Denifanstat Decreased FAST Score and ELF Mixed - effects Model for Repeated Measures – Two sided at the 0.05 significance level. mITT population. *Baseline ELF > 9.8 (mean). 15 p= p= - 0.11 - 0.12 - 0.40 - 0.41 Week 26 Week 52 LS mean change Placebo n=22/23 Denifanstat n=32/30
Slide 16: Secondary Endpoint: Liver Fat by MRI-PDFF
Secondary Endpoint: Liver Fat by MRI - PDFF Denifanstat Achieved Statistical Significance 16 21% 65% Placebo n=38 Denifanstat n=69 % response MRI - PDFF ≥ 30% Relative Reduction, Week 52 p<0.0001 MRI - PDFF Relative Change from Baseline 5% - 8% - 25% - 31% Week 26 Week 52 LS mean change Placebo n=37
Slide 17: Secondary Endpoints: Liver Enzymes
Secondary Endpoints: Liver Enzymes Denifanstat Decreased ALT and AST Levels 17 ALT Percent Change from Baseline AST Percent Change from Baseline Mixed - effects Model for Repeated Measures – Two sided at the 0.05 significance level. mITT population - 2.80 - 16.30 - 23.10 - 30.60 Week 26 Week 52 LS m
Slide 18: Cardiometabolic Health: Denifanstat Decreased LDL-c Levels
Cardiometabolic health Denifanstat Decreased LDL - c Levels 18 LDL - c* Change from Baseline p>0.05 p>0.05 Triglycerides Median values 70 90 110 130 150 170 190 210 230 250 0 4 8 13 26 39 52 TG, mg/dL Weeks Placebo Denifanstat - 1.60 - 9.10 - 12.60 - 19.10 Week 26 Week 52 Mean change, mg/dL Placebo
Slide 19: FASCINATE-2: Safety
FASCINATE - 2: Safety Denifanstat was Generally Well Tolerated 19 Parameter Placebo n=56 Denifanstat N=112 Any TEAE (treatment emergent adverse event) 45 (80.4%) 96 (85.7%) TEAE related to study drug 20 (35.7%) 51 (45.5%) Most common TEAE related to study drug in ≥ 5% of patients by system organ cla
Slide 20: NASH Development Program
NASH Development Program 18
Slide 21: Progression from Phase 2b to Phase 3
Progression from Phase 2b to Phase 3 Phase 2b – baseline Fibrosis stage Phase 2b – 26 weeks Non - invasive interim Phase 2b – 52 weeks Histology Will use Phase 2b results including AI pathology scores to design and power Phase 3 Primary endpoint s • NAS ≥2 improvement w/o worsening of fibrosis; or N
Slide 22: Denifanstat is Differentiated in the Evolving NASH Landscape
We Believe Denifanstat is Differentiated in the Evolving NASH Landscape Mechanism FASN inhibitors THRß A gonists FGF - 21 GLP - 1 agonists PPAR agonists ACC inhibitors FXR agonists Category DNL pathway Nuclear receptor Growth factor GLP - 1 Nuclear receptor DNL pathway Nuclear receptor Route Oral Or
Slide 23: Precision Medicine: Blood Tests May Lead to Improved Patient Outcomes
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%. Blood test for predictive m
Slide 24: Strong Monotherapy Opportunity for Denifanstat in NASH
Strong Monotherapy Opportunity for Denifanstat in NASH Expansion as backbone of combinations Illustrative potential combo mechanisms FXR GLP - 1, PPAR, FGF21 DGAT2 →→ThR HSP47, integrins NLRP3 Chemokines, ARO - HSD x Oral, once - daily tablet ideal for chronic administration • Tablets generally more
Slide 25: Additional Expansion Opportunities in NASH
Additional Expansion Opportunities in NASH • Compensated cirrhotic patients (NASH F4) • Denifanstat directly targets stellate cells • Hepatocytes continue to be functional, and patients frequently have increased liver fat • Next steps • Characterize PK profile in patients with impaired hepatic funct
Slide 26: Other Indications
Other Indications 24
Slide 27: FASN Hyper-Activity Plays a Key Role in Multiple Diseases Beyond NASH
FASN Hyper - Activity Plays a Key Role in Multiple Diseases Beyond NASH Cancer cell Membrane synthesis, intracellular signaling, protein modification FASN in cancer 1. Supports tumor survival 2. Enables tumor proliferation 3. Establishes resistance to drugs FASN in NASH 1. Drives steatosis 2. Activa
Slide 28: DNL Pathway Plays a Role in the Pathogenesis of Acne
DNL Pathway Plays a Role in the Pathogenesis of Acne • Acne is associated with excess sebum production by sebocyte cells in the skin • Acne resolution is associated with reduced sebum production • Sebocytes upregulate and rely on DNL/FASN to make sebum • >80% of key sebum lipids such as palmitate an
Slide 29: FASN is Integral to Tumor Cell Proliferation and Survival
FASN is Integral to Tumor Cell Proliferation and Survival Reprogramed metabolism is one of the hallmarks of cancer • Certain cancers are dependent on DNL/FASN for proliferation especially downstream of driver oncogenes • eg. KRASM in non - small cell lung cancer (NSCLC) • Strategy – > exploit this v
Slide 30: FASN-Dependent Tumor Types Identified that Meet Core Criteria
FASN - Dependent Tumor Types Identified that Meet Core Criteria Program focused on 4 selected tumor types Preclinical ongoing • Combination with KRAS inhibitor in mouse models x Encouraging Phase 1 results with denifanstat Translational ongoing • Patient selection bioinformatics x Positive preclinic
Slide 31: Strong Financial Position and Intellectual Property Portfolio
Strong Financial Position and Intellectual Property Portfolio Financial highlights Nasdaq: SGMT x Upsized IPO completed in July 2023 raised $96.4 million of gross proceeds x Cash and equivalents expected to fund current operations into the first quarter of 2025 Strong patent estate x Composition of
Slide 32: Development Pipeline: Indications and Clinical Milestones
Therapeutic Area Stage of Development Indication Expected Milestone / Status Preclinical Phase 1 Phase 2 Phase 3 Metabolic disease • Phase 2b successfully completed NASH - F2/F3 • Phase 1 hepatic impairment results 1Q 2024 Dermatology Acne • IND 1H 2024 filing planned • Phase 3 clinical study initia
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