Gain Therapeutics, Inc. · NASDAQ:GANX
Gain Therapeutics — Investor Presentation (May 2021)
40 slides from Gain Therapeutics's investor presentation, May 4, 2021
Slide 1: Leading the Discovery of Allosteric Binding Sites to Create New Medicines
© 2021 - GAIN THERAPEUTICS Corporate Presentation Leading the Discovery of Allosteric Binding Sites to Create New Medicines
Slide 2: Forward-Looking Statements
Page 2 © 2021 - GAIN THERAPEUTICS Corporate Presentation Forward-Looking Statements Certain statements set forth in this presentation contain forward-looking statements that reflect the Company’s plans, beliefs, expectations and current views with respect to, among other things, future events and fi
Slide 3: Executive Summary
Page 3 © 2021 - GAIN THERAPEUTICS Corporate Presentation Platform Technology Robust Pipeline Upcoming Milestones • Proprietary and patented SEE-Tx platform identifies allosteric (non-catalytic) binding sites in proteins and enzymes that can regulate proper protein folding to restore functional activ
Slide 4: Gain leverages its proprietary platform technology to engineer novel therapeutics
Page 4 © 2021 - GAIN THERAPEUTICS Corporate Presentation Gain leverages its proprietary platform technology to engineer novel therapeutics targeting conditions with significant unmet needs SEE-Tx Discovery Platform • Proprietary supercomputer-driven drug discovery platform • Identifies novel alloste
Slide 5: Lysosomal Storage Disorders
Page 5 © 2021 - GAIN THERAPEUTICS Corporate Presentation Lysosomal Storage Disorders LSDs represent significant markets with high unmet needs, especially in neurological conditions Neurodegeneration A multi billion-dollar market with high unmet needs in a growing patient population SOC Challenges: I
Slide 6: Binding allosteric sites to regulate misfolded enzymes
Page 6 © 2021 - GAIN THERAPEUTICS Corporate Presentation Binding allosteric sites has the potential to provide superior regulation of misfolded enzymes implicated in diseases. Misfolded enzymes cannot properly catalyze their intended substrates, leading to toxic substrate accumulation. Structurally
Slide 7: SEE-Tx platform: identify, screen and select, optimize
Page 7 © 2021 - GAIN THERAPEUTICS Corporate Presentation IDENTIFY Using the 3D structure of proteins and supercomputing technology, SEE-Tx identifies novel druggable binding hotspots SCREEN & SELECT Utilizing proprietary supercomputer driven screening methodology, SEE-Tx filters up to 10 million com
Slide 8: Advantages of Drugging Allosteric Binding Sites
Page 8 © 2021 - GAIN THERAPEUTICS Corporate Presentation Allosteric Binding Site • Non-competitive with the natural substrate • High specificity for the targeted enzyme • Superior drug-like properties • Offer a broader therapeutic window Active Binding Site • Site where enzyme binds substrate to cat
Slide 9: SEE-Tx Platform Produces Novel STARs
Page 9 © 2021 - GAIN THERAPEUTICS Corporate Presentation Criteria for Selection of STARs 1 2 5 3 • STARs: Novel small molecule compounds selected to bind to allosteric sites and restore protein function, cross blood-brain barrier and access bone, cartilage and other hard to reach tissues • Easily sc
Slide 10: Diversified Pipeline Targeting Multi-Billion Dollar Markets
Page 10 © 2021 - GAIN THERAPEUTICS Corporate Presentation Discovery Pre-Clinical Clinical Gene Disease in vitro in vivo Lead OP IND- Enabling Phase 1 Phase 2 Phase 3 GLB1 gene Morquio B / GM1 Gangliosidosis GBA1 gene Gaucher Disease GBA1 gene Parkinson’s Disease IDUA gene Mucopolysaccharidosis type
Slide 11: GM1 Gangliosidosis/Morquio B Programs
© 2021 - GAIN THERAPEUTICS Non-Confidential Presentation GM1 Gangliosidosis/Morquio B Beta-galactosidase (GLB1) The Programs
Slide 12: GLB1-related Disorders: GM1 and Morquio B
Page 12 © 2021 - GAIN THERAPEUTICS Corporate Presentation Deficiency of acid β -galactosidase causes GM1 gangliosidosis and Morquio disease type B (MPS IVB) Currently, no effective medical treatment for GLB1-related disorders. Symptomatic treatment for some neurologic sequelae but does not alter the
Slide 13: GM1/Morquio B Program Summary: Lead Candidate GT-00513
Page 13 © 2021 - GAIN THERAPEUTICS Corporate Presentation GM1/Morquio B Program Summary: Lead Candidate GT-00513 Mechanism of Action • Dose-dependent binding of β-gal • Non-competitive activity • Support proper folding and protein maturation Drug Properties • High oral bioavailability • Penetrates w
Slide 14: GT-00513 Increases Delivery of β-Gal to the Lysosome
Page 14 © 2021 - GAIN THERAPEUTICS Corporate Presentation HEK293 were transfected with either GLB1 WT, GLB1 I51T, GLB1 R201C and GLB1 W273L with HaloTag. 30 hours later, compounds (25 µM) and a fluorescent Halo ligand that covalently binds to a pocket in the tag were added for 17 hours. Once the pro
Slide 15: GT-00513 Reduces GM1 Ganglioside Accumulation
Page 15 © 2021 - GAIN THERAPEUTICS Corporate Presentation GT-00513: Reduces GM1 Ganglioside Accumulation GM1 gangliosidosis canine fibroblasts (p.R60H/p.R60H; equivalent to R59H mutation in humans) were loaded with GM1 ganglioside for 2 days followed by culture in the presence of GT-00413 at 25 µM f
Slide 16: GT-00513 Demonstrates High Oral Bioavailability
Page 16 © 2021 - GAIN THERAPEUTICS Corporate Presentation GT-00513: Demonstrates High Oral Bioavailability Plasma pharmacokinetics of GT-00513.HCl following a single intravenous and oral administration to male C57BL/6 mice. n=3 and data are expressed as mean ± SD. GT-00513.HCl salt oral bioavailabil
Slide 17: GT-00513 Penetrates Well into Brain and Bone
Page 17 © 2021 - GAIN THERAPEUTICS Corporate Presentation GT-00513: Penetrates well into both Brain and Bone 0 2000 4000 6000 8000 Time (h) C o n c .. ( n g / m L o r n g / g ) Plasma (90 mg/kg,po) Brain (90 mg/kg,po) Left femur (90 mg/kg,po) Plasma (180 mg/kg,po) Brain (180 mg/kg,po) Left femur (18
Slide 18: GM1/Morquio B Program Status and Next Steps
Page 18 © 2021 - GAIN THERAPEUTICS Corporate Presentation GM1/Morquio B Program Status and Next Steps Lead Candidate GT-0513 • Demonstration of mechanism of action indicative of specific binding and bypassing protein quality control of protein misfolding • Demonstration of in vitro of target engagem
Slide 19: Gaucher/Parkinson's Disease Programs
© 2021 - GAIN THERAPEUTICS Non-Confidential Presentation Gaucher/Parkinson’s Disease Beta-glucosidase (GBA) The Programs
Slide 20: GBA1 Related Disease: Gaucher and Parkinson's Disease
Page 20 © 2021 - GAIN THERAPEUTICS Corporate Presentation GBA1 Related Disease: Gaucher and Parkinson’s Disease Mutations in the GBA1 gene are responsible for build-up of glucosylceramide in Gaucher disease and is associated with α- synuclein accumulation in Parkinson’s. Gaucher Disease • There are
Slide 21: GBA Program: Lead Candidates GT-02287 and GT-02329
Page 21 © 2021 - GAIN THERAPEUTICS Corporate Presentation GBA Program: Lead Candidates GT-02287 and GT-02329 Mechanism of Action • Dose-dependent and non-competitive binding to GCase • Stabilization of target enzyme, support proper folding and protein maturation in vivo Target Engagement • In vivo G
Slide 22: GT compounds enhance GCase activity in a dose-dependent manner
Page 22 © 2021 - GAIN THERAPEUTICS Corporate Presentation GT compounds enhance GCase activity in a dose-dependent manner WT fibroblasts STARs Enhance GCase at Sub-Micromolar Concentrations Gaucher-patient fibroblasts were treated with compounds at different concentrations (0.2 – 25 µM) in sextuplica
Slide 23: STARs Enhance Enzyme Activity in Patient Fibroblasts
Page 23 © 2021 - GAIN THERAPEUTICS Corporate Presentation GT compounds enhance GCase activity in wild-type and patient-derived Gaucher fibroblasts Gaucher patient-fibroblasts, WT fibroblasts were treated with GT compounds, isofagomine at 12.5 µM. After 4-day treatment, GCase activity was assessed us
Slide 24: STARs increase GCase activity in neuronal cellular model
Page 24 © 2021 - GAIN THERAPEUTICS Corporate Presentation Dopaminergic neurons BE(2)-M17 carrying either wild-type or mutant N370S, L444P or D409V GBA1 mutations were treated for 4 days with 25 µM of GT-compounds. GCase activity was measured with 4-methylumbelliferyl-β-D-glucopyranoside. For the 10
Slide 25: STARs Decrease α-Synuclein Levels in a Neuronal Cell Model
Page 25 © 2021 - GAIN THERAPEUTICS Corporate Presentation STARs Decrease α-Synuclein Levels in a Neuronal Cell Model Decrease in syn levels. Phosphorylated–synuclein (S129) detected by immunofluorescence in 3 differentiated neuronal cell lines (WT, N370S and L444P) treated for 15 days with 25 µM of
Slide 26: STARs Enhance WT GCase Activity in Plasma and Striatum
Page 26 © 2021 - GAIN THERAPEUTICS Corporate Presentation Statistical analysis was performed using GraphPad Prism software version 5.0. and used One way ANOVA followed by Dunnett’s post-hoc test; All the values are expressed as Mean ± SEM. *P<0.05 Vs Vehicle control GT-02329 was administered orally,
Slide 27: STARs Show Alpha-Synuclein Depletion and Locomotor Improvement in Rotenone Rat Model
Page 27 © 2021 - GAIN THERAPEUTICS Corporate Presentation STARs Show Depletion of alpha-Synuclein, Increase in Tyrosine Hydroxylase and Improvement in Locomotor Activity and Markers in a Rotenone Rat Model Data is shown as Mean ± S.E.M.(n=10). Unpaired T test. Significant difference as compared to R
Slide 28: Gaucher and Parkinson's Disease Program Summary
Page 28 © 2021 - GAIN THERAPEUTICS Corporate Presentation Gaucher and Parkinson’s Disease Program Summary Lead Candidates • Demonstration of mechanism of action indicative of specific binding and bypassing protein quality control of protein misfolding • Demonstration of in vitro of target engagement
Slide 29: Mucopolysaccharidosis Type I (MPS I) Program
© 2021 - GAIN THERAPEUTICS Non-Confidential Presentation Mucopolysaccharidosis Type I (MPS I) alpha-L-iduronidase (IDUA) Program to bring forward
Slide 30: IDUA Related Disorders: Mucopolysaccharidosis Type I
Page 30 © 2021 - GAIN THERAPEUTICS Corporate Presentation Current treatments are enzyme replacement therapy and stem cell transplant. Significant unmet medical are related to hard-to-treat tissues such bone and cartilage Mucopolysaccharidosis type I (MPS I) is an autosomal recessive inherited disord
Slide 31: MPS-I Program Summary
Page 31 © 2021 - GAIN THERAPEUTICS Corporate Presentation Status Animal PoC Druggable allosteric site identified T est compound displays: - Stabilization and prevention of enzyme denaturation in physiological conditions - Enzymatic enhancement of ERT - In vivo stabilization of recombinant IDUA (laro
Slide 32: Academic and Development Partners
Page 32 © 2021 - GAIN THERAPEUTICS Corporate Presentation Academic Partnerships with Centers of Research, Translational Science & Clinical Excellence Patient Associations and Advocacy Groups Academic and Development Partners
Slide 33: Patent Estate
Page 33 © 2021 - GAIN THERAPEUTICS Corporate Presentation Patent Estate Patent Status Technology Platform Patent: • WO2013092922 (Published June 2013) • National Phases granted GLB1 Program: • WO2018122746A1 (Published July 2018) • National Phases filed GBA1 Program: • WO2018122775 (Published July 2
Slide 34: Upcoming Milestones
Page 34 © 2021 - GAIN THERAPEUTICS Corporate Presentation 2021 2022 Morquio B / GM1 Gangliosidosis: IND filing Gaucher / Parkinson’s Disease: IND filing Krabbe: Animal Proof of Concept MorquioB / GM1 Gangliosidosis: Animal POCs – completion (Q3), IND-enabling studies – initiation (Q4) Gaucher / Park
Slide 35: Diversified Pipeline Targeting Multi-Billion Dollar Markets
Page 35 © 2021 - GAIN THERAPEUTICS Corporate Presentation * Data provided by S&P CapIQ and Company Websites as of October 22, 2020 ** Grandview Market Research Report, Published Oct, 2019. “Enzyme Replacement Therapy Market Size, Share & Trends Analysis By Enzyme (Pancreatic Enzymes, Agalsidase Beta
Slide 36: Financing History and Stakeholders
Page 36 © 2021 - GAIN THERAPEUTICS Corporate Presentation Research Funding & Grants: Originally established in Switzerland in 2017 as Gain Therapeutics, SA with 16 employees in Lugano, Switzerland, Barcelona, Spain – HQ in Bethesda, Maryland Completed $10m Series B Financing in July 2020 Completed $
Slide 37: Strong Board of Directors
Page 37 © 2021 - GAIN THERAPEUTICS Corporate Presentation Eric I. Richman CEO and Member Khalid Islam, PhD Founder and Chairman Dov Goldstein, MD Independent Member Gwen Melincoff Independent Member Claude Nicaise, MD Independent Member Hans Peter Hassler Independent Member Jeffrey Riley Independent
Slide 38: Experienced Management Team
Page 38 © 2021 - GAIN THERAPEUTICS Corporate Presentation Ana Maria Garcia Collazo, PhD Head of Research Roberto Maj, PharmD Head of Development Xavier Barril, PhD CSO Manolo Bellotto, PhD President & General Manager Eric I. Richman CEO Salvatore Calabrese CFO Experienced Management Team - Extensive
Slide 39: Diverse Group of Scientific Advisors
Page 39 © 2021 - GAIN THERAPEUTICS Corporate Presentation Joanne Taylor, PhD Advisor Michel Vellard, PhD Advisor Lorenzo Leoni, PhD Advisor Samuel Broder, MD Advisor Diverse Group of Scientific Advisors
Slide 40: Executive Summary
Page 40 © 2021 - GAIN THERAPEUTICS Corporate Presentation Platform Technology Robust Pipeline Upcoming Milestones • Proprietary and patented SEE-Tx platform identifies allosteric (non-catalytic) binding sites in proteins and enzymes that can regulate proper protein folding to restore functional acti