Sagimet Biosciences Inc. - Series A · NASDAQ:SGMT
Sagimet Biosciences Inc. - Series A — Sagimet Biosciences — Investor Presentation (March 2024)
33 slides from Sagimet Biosciences Inc. - Series A's investor presentation, Mar 25, 2024
Slide 1: Targeting Metabolic Dysfunction with Novel Therapies to Treat MASH, Acne and Cancer
Targeting Metabolic Dysfunction with Novel Therapies to Treat M ASH, Acne and Cancer March 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 M ASH x Key enzyme in de novo lipogenesis – responsible for excess liver fat in MASH x FASN inhibition directly improves the 3 key drivers of M ASH – liver fat, inflammation, fibrosis x Differentiated MOA to treat growing underserved pati
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; MASH Phase 3 study planned to start 2H 2024 MASH - F2/F3 • Phase 1 hepatic impairment results 1Q 2024 Dermatology Acne • IND - enablin
Slide 6: MASH: A Burgeoning Epidemic
M ASH: A Burgeoning Epidemic x Designed for once - daily, oral dosing x Rigorous and de - risked development strategy x Direct DNL inhibition demonstrated in Phase 1b x Improvements observed across biomarkers in Phase 2a x Topline data of successfully completed Phase 2b announced in 1Q 20 24 x Preci
Slide 7: Denifanstat in MASH
Denifanstat in M ASH 7
Slide 8: Denifanstat: Differentiated Mechanism Believed to Target Key Drivers of MASH
Denifanstat : Differentiated Mechanism Believed to Target Key Drivers of M ASH 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
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 MASH 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: FASCINATE-2 Baseline Characteristics
FASCINATE - 2 Baseline Characteristics Typical F2/F3 MASH Population Modified intent - to - treat population ( mITT ) includes all patients with paired biopsies. Data are mean (SD) or n (%) 11 Parameter Placebo, n=45 Denifanstat , n=81 Age , years 59.6 (+/ - 10.9) 56.1 (+/ - 10.8) Sex , female 27 (6
Slide 12: 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. 12 20% 52% Placebo n=45 Denifanstat n=81 % response NAS ≥ 2 points impro
Slide 13: Secondary Endpoints: Liver Biopsy
Secondary Endpoints: Liver Biopsy Denifanstat Achieved Statistical Significance 13 Resolution of MASH 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 14: Independent Fibrosis Analysis by AI-based Digital Pathology
Independent Fibrosis Analysis by AI - based Digital Pathology Supporting Evidence that Denifanstat Significantly Reduced Fibrosis 14 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 15: Patient Subset on Stable GLP1-RA at Baseline
Patient Subset on Stable GLP1 - RA at Baseline: Liver Biopsy Denifanstat Improves MASH Resolution and Fibrosis 15 Resolution of MASH w/o worsening of fibrosis Improvement in liver fibrosis ≥ 1 stage w/o worsening of MASH 0% 42% Placebo n=4 Denifanstat n=12 % response 0% 42% Placebo n=4 Denifanstat n
Slide 16: Biomarkers of Fibrosis
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). 16 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 17: Secondary Endpoint: Liver Fat by MRI-PDFF
Secondary Endpoint: Liver Fat by MRI - PDFF Denifanstat Achieved Statistical Significance 17 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 18: Secondary Endpoints: Liver Enzymes
Secondary Endpoints: Liver Enzymes Denifanstat Decreased ALT and AST Levels 18 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 19: Cardiometabolic Health: LDL-c Levels
Cardiometabolic health Denifanstat Decreased LDL - c Levels 19 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 20: FASCINATE-2: Safety
FASCINATE - 2: Safety Denifanstat was Generally Well Tolerated 20 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 21: MASH Development Program
MASH Development Program 18
Slide 22: 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 Using 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 MASH
Slide 23: Denifanstat is Differentiated in the Evolving MASH Landscape
We Believe Denifanstat is Differentiated in the Evolving M ASH 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 O
Slide 24: 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 25: Strong Monotherapy Opportunity for Denifanstat in MASH
Strong Monotherapy Opportunity for Denifanstat in M ASH 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 mor
Slide 26: Additional Expansion Opportunities in MASH
Additional Expansion Opportunities in M ASH • Compensated cirrhotic patients ( MASH 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 fun
Slide 27: Other Indications
Other Indications 24
Slide 28: FASN Hyper-Activity Plays a Key Role in Multiple Diseases Beyond MASH
FASN Hyper - Activity Plays a Key Role in Multiple Diseases Beyond M ASH 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 M ASH 1. Drives steatosis 2. Acti
Slide 29: DNL Pathway Plays a Role in the Pathogenesis of Acne
DNL Pathway Plays a Role in the Pathogenesis of Acne FASN is an attractive therapeutic target for 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 seb
Slide 30: 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 31: 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 32: 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 $86.2 million of net proceeds x Follow - on financing completed in January 2024 raised net proceeds of $105.8 million. x Cash and equivalents expected to fund c
Slide 33: 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; MASH Phase 3 study planned to start 2H 2024 MASH - F2/F3 • Phase 1 hepatic impairment results 1Q 2024 Dermatology Acne • IND - enablin
Sagimet Biosciences — Investor Presentation (March 2024) on 6ix