Sagimet Biosciences Inc. - Series A · NASDAQ:SGMT
Sagimet Biosciences Inc. - Series A — Sagimet Biosciences — Investor Presentation (December 2023)
30 slides from Sagimet Biosciences Inc. - Series A's investor presentation, Dec 29, 2023
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 December 2023
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
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 biopsy results 1Q 2024 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 Showed Dose-Dependent Reduction of Liver Fat in FASCINATE-1
Denifanstat Showed Dose - Dependent Reduction of Liver Fat in FASCINATE - 1 Improved Key Drivers of NASH and Metabolic Health FASCINATE - 1 Liver Fat Change - 50 - 40 - 30 10 0 - 10 - 20 20 + 4.5% - 9.6% - 28.1%** Placebo n=27 25 mg n=30 50 mg n=28 Mean relative MRI - PDFF at wk12 vs baseline 1 Loom
Slide 10: 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 10
Slide 11: Phase 2b Biopsy Trial: Measuring Histological Improvement
Phase 2b Biopsy Trial: Measuring Histological Improvement FASCINATE - 2 Phase 2b trial design • Biopsy confirmed F2 - F3 NASH patients • 52 weeks, 2:1 50mg or placebo, double - blind • Fully enrolled: 168 patients in U.S., Canada, and Europe • Prespecified interim analysis of the first 52 patients w
Slide 12: FASCINATE-2 Phase 2b Interim Analysis Demographics
FASCINATE - 2 Phase 2b Interim Analysis Demographics Mean (SD) Placebo (22) Denifanstat (30) Combined Age (years) 56.8 ( 9.4) 56.1 (12.4) 56.4 (11.1) Female/Male (%) 14 (63.6%) / 8 (36.4%) 17 (56.7%) / 13 (43.3%) 31 (59.6%) / 21 (40.4%) Not Hispanic or Latino 16 (72.7%) 24 (80.0%) 40 (76.9%) Weight
Slide 13: FASCINATE-2 Interim Results Consistent with FASCINATE-1
FASCINATE - 2 Interim Results Consistent with Comprehensive Positive Readouts from FASCINATE - 1 • FASCINATE - 2 interim analysis showed consistent improvements in key drivers of NASH as observed in FASCINATE - 1 • Improvements observed in multiple biomarkers of metabolic health • LDL - cholestero
Slide 14: Denifanstat Decreased Liver Fat; Responders Correlate with Biopsy Improvement
Denifanstat Decreased Liver Fat Responders Correlate with Liver Biopsy Improvement ** p < 0.01,*** p < 0.001. • Denifanstat induced statistically significant reduction of liver fat • 67% (p<0.001) MRI - PDFF response rate • About half of responders decreased liver fat by ≥50% • A relative reduction
Slide 15: Denifanstat Decreased PRO-C3 and ELF – Suggests Fibrosis Reduction
Denifastat Decreased PRO - C3 and ELF – Suggests Fibrosis Reduction • ALT decrease suggested a decrease in inflammation with denifanstat • PRO - C 3 decrease suggested a decrease of liver fibrosis with denifanstat • ELF score decrease suggested decrease of liver fibrosis with denifanstat. ELF score
Slide 16: Denifanstat Improved Markers of Cardiometabolic Health
Denifanstat Improved Markers of Cardiometabolic Health • LDL - cholesterol decrease: denifanstat may have cardiovascular benefit • FGF 21 increase : denifanstat may induce improvement in insulin sensitivity • Tripalmitin decrease: reflects denifanstat inhibited FASN and reduced palmitate synthesis F
Slide 17: Denifanstat Passed Planned IDMC Safety Review in FASCINATE-2
Denifanstat Passed Planned IDMC Safety Review in FASCINATE - 2 Treatment Emergent Adverse Event (TEAE) Classification N=168 Number of Patients with Event at Stated Grade Any TEAE Gr 1: 115 (68.5%) Gr 2: 69 (41.1%) Gr 3: 10 (6.0%) Gr 4: 1 (0.6%) TEAE leading to drug/placebo discontinuation 21 Treatme
Slide 18: NASH Development Program
NASH Development Program 18
Slide 19: 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 Expect to use Phase 2b results including AI pathology scores to design and power Phase 3 Primary endpoints • NAS ≥2 improvement w/o worsening of fibrosis;
Slide 20: 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 21: 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 22: 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 23: 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 24: Other Indications
Other Indications 24
Slide 25: 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 26: 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 27: 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 28: 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 29: 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 30: 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 biopsy results 1Q 2024 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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