Gain Therapeutics, Inc. · NASDAQ:GANX
Gain Therapeutics — Investor Presentation (August 2021)
40 slides from Gain Therapeutics's investor presentation, August 2021
Slide 1: Leading the Discovery of Allosteric Binding Sites to Create New Medicines
Leading the Discovery of Allosteric Binding Sites to Create New Medicines © 2021 - GAIN THERAPEUTICS Corporate Presentation
Slide 2: Forward-Looking Statement
Forward-Looking Statement 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 financial performance (collective
Slide 3: Executive Summary
Executive Summary • Addressing Protein Misfolding by identifying and targeting novel previously undruggable allosteric binding sites Therapeutic Focus • Initial focus on lysosomal storage and CNS diseases -- large & growing markets with unmet medical need • Proprietary and patented SEE-Tx platform i
Slide 4: Gain Therapeutics' Dual-pronged Approach to Value Generation
Gain Therapeutics’ Dual-pronged Approach to Value Generation 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 all
Slide 5: Key Markets: Broad Platform Applicability
Key Markets: Broad Platform Applicability SOC Challenges: Inability to access hard to reach tissues Lysosomal Storage Disorders Neurodegeneration Future Applications LSDs represent significant A multi billion-dollar market Oncology, Mitochondrial markets with high unmet with high unmet needs in a Di
Slide 6: Corrected Folding of Enzymes to Restore Functional Activity
Corrected Folding of Enzymes to Restore Functional Activity Misfolded enzymes cannot properly catalyze their intended substrates, leading to toxic substrate accumulation. Structurally Targeted Allosteric Regulators (STARs) Binding allosteric sites has the potential to provide superior regulation of
Slide 7: SEE-Tx Discovery Platform
SEE-Tx™ Discovery Platform DIFFERENTIATED and PATENTED highly-specific, efficient and cost-effective drug discovery approach DEFECTIVE PROTEIN Caused by genetic mutation, ageing, and disease. Results in loss of protein function and toxic substrate buildup. IDENTIFY SCREEN & SELECT OPTIMIZE Using the
Slide 8: SEE-Tx is different from other drug discovery platforms
SEE-Tx™ is different from other drug discovery platforms DIFFERENTIATED and PATENTED highly-specific, efficient and cost-effective drug discovery approach Without SEE-Tx With GAIN’s SEE-Tx SEE-Tx only requires the 3D structure of the protein implicated in AI approaches only work when there is a larg
Slide 9: Advantages of Drugging Allosteric Binding Sites
Advantages of Drugging Allosteric Binding Sites Active Binding Site Allosteric Binding Site • Site where enzyme binds • Non-competitive with the natural substrate to catalyze reaction substrate • Traditional drugs bind to active • High specificity for the targeted sites enzyme • Competes with active
Slide 10: SEE-Tx Platform Produces Novel STARs
SEE-Tx™ Platform Produces Novel STARs STARs: Robust Small Molecules 1 2 3 4 5 Early-stage Targets multiple different Crosses BBB and Orally Stabilizes misfolded disease disease mutations accesses hard to bioavailable and proteins and reduces intervention (65-70% of known mutations) reach tissues hig
Slide 11: Diversified Pipeline Targeting Multi-Billion Dollar Markets
Diversified Pipeline Targeting Multi-Billion Dollar Markets Discovery Pre-Clinical Clinical IND- Gene Disease in vitro in vivo Lead OP Phase 1 Phase 2 Phase 3 Enabling Morquio B / GLB1 gene GM1 Gangliosidosis GBA1 gene Gaucher Disease GBA1 gene Parkinson’s Disease Mucopolysaccharidosis IDUA gene typ
Slide 12: Gaucher/Parkinson's Disease
The Programs Gaucher/Parkinson’s Disease Beta-glucosidase (GBA) © 2021 - GAIN THERAPEUTICS Non-Confidential Presentation
Slide 13: GBA1 Related Disease: Gaucher and Parkinson's Disease
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 approximately 1,000-2,000 patients with Neuronopathic (Typ
Slide 14: GBA Program: Lead Candidates GT-02287 and GT-02329
GBA Program: Lead Candidates GT-02287 and GT-02329 GT02287 and GT02329 are small molecules of 350-450 Da with good drug-like properties Mechanism of Action in vivo Target Engagement • Dose-dependent and non-competitive binding to • In vivo GCase enzyme and protein GCase enhancement • Stabilization o
Slide 15: STARs Decrease α-Synuclein Levels in a Neuronal Cell Model
STARs Decrease α-Synuclein Levels in a Neuronal Cell Model N370S L444P Vehicle STARs Hoechst Phosphorylated-α-synuclein (S129) 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
Slide 16: STARs Enhance WT GCase Activity and Protein in Plasma & Striatum
STARs Enhance WT GCase Activity and Protein in Plasma & Striatum Oral administration of GT-02329 significantly enhances WT GCase activity and protein levels Plasma Striatum 400 400 25.86% 34.80% GCase level (ng/mg of protein) * GCase level (ng/mg of protein) ** 300 300 200 200 100 100 0 0 Vehicle Co
Slide 17: STARs Show Depletion of alpha-Synuclein and Improvement in Locomotor Activity
STARs Show Depletion of alpha-Synuclein, Increase in Tyrosine Hydroxylase and Improvement in Locomotor Activity and Markers in a Rotenone Rat Model alpha-Synuclein Depletion Dopaminergic Neurons Activity Improvement Improvement in Locomotor Activity Data is shown as Mean ± S.E.M.(n=10), Ove-way ANOV
Slide 18: Gaucher and Parkinson's Disease Program Summary
Gaucher and Parkinson’s Disease Program Summary Lead Candidates Upcoming milestones • Demonstration of mechanism of action indicative • Gaucher and Parkinson animal models POC of specific binding and bypassing protein quality (2021) control of protein misfolding • CD Characterization/Synthesis scale
Slide 19: GM1 Gangliosidosis/Morquio B
The Programs GM1 Gangliosidosis/Morquio B Beta-galactosidase (GLB1) © 2021 - GAIN THERAPEUTICS Non-Confidential Presentation
Slide 20: GLB1-related Disorders: GM1 and Morquio B
GLB1-related Disorders: GM1 and Morquio B Deficiency of acid β -galactosidase causes GM1 gangliosidosis and Morquio disease type B (MPS IVB) GM1 Gangliosidosis • Indidence worldwide (1:100,000-200,000 newborns).1 • β-galactosidase is responsible for breaking down GM1-ganglioside, abundance of gangli
Slide 21: GM1/Morquio B Program Summary: Lead Candidate GT-00513
GM1/Morquio B Program Summary: Lead Candidate GT-00513 Small (400 Da) molecule with good drug-like properties Mechanism of Action Drug Properties • Dose-dependent binding of β-gal • High oral bioavailability • Non-competitive activity • Penetrates well into Brain (CNS) and • Support proper folding a
Slide 22: GT-00513: Increases the Delivery of β-Gal to the Lysosome
GT-00513: Increases the Delivery of β-Gal to the Lysosome GLB1 WT GLB1 W273L GLB1 I51T 300 1000 300 HT fragment (% to DMSO) HT fragment (% to DMSO) HT fragment (% to DMSO) 800 200 200 600 400 100 100 200 0 0 0 ol 3 1 ol ol 3 3 1 1 51 A 51 51 A A tr tr tr in on 00 in in on on 00 00 yc yc yc T- C T- T
Slide 23: GT-00513: Reduces GM1 Ganglioside Accumulation
GT-00513: Reduces GM1 Ganglioside Accumulation GM1 ganglioside GM1 ganglioside GLB1 fibroblasts 0.04 GM1 ganglioside (ng/µg ) accumulate GM1 Untreated ganglioside GT-00413 (25 µM) 0.03 GT-00513 (25 µM) 0.02 STARS are effective in reducing substrate accumulation 0.01 0.00 GM1 gangliosidosis canine fi
Slide 24: GT-00513: Demonstrates High Oral Bioavailability
GT-00513: Demonstrates High Oral Bioavailability Dose Tmax aCo/Cmax AUClast AUCinf T1/2 CL Vss % Route (mg/ Test System (hr) (ng/mL) (hr*ng/mL) (hr*ng/mL) (hr) (mL/min/kg) (L/kg) Fb kg) GT-00513 IV 2 male C57BL/6 mice - 1181.29 1195.16 1314.68 4.39 25.35 6.12 - GT-00513 PO 10 male C57BL/6 mice 0.5 1
Slide 25: GT-00513: Penetrates well into both Brain and Bone
GT-00513: Penetrates well into both Brain and Bone 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) ng/mL or ng/g) 8000 Left femur (180 mg/kg,po) 6000 Plasma, brain and left femur concentration-time data of GT-0513 in male C57BL/6 mice on d
Slide 26: GM1/Morquio B Program Status and Next Steps
GM1/Morquio B Program Status and Next Steps Lead Candidate GT-0513 Upcoming milestones • Demonstration of mechanism of action • In vivo POCs (Morquio B + GM1) (2021) indicative of specific binding and bypassing protein quality control of • CD Characterization/Synthesis scale-up protein misfolding (2
Slide 27: Mucopolysaccharidosis Type I (MPS I)
Program to bring forward Mucopolysaccharidosis Type I (MPS I) alpha-L-iduronidase (IDUA) © 2021 - GAIN THERAPEUTICS Non-Confidential Presentation
Slide 28: IDUA Related Disorders: Mucopolysaccharidosis Type I (MPS I)
IDUA Related Disorders: Mucopolysaccharidosis Type I (MPS I) Mucopolysaccharidosis type I (MPS I) is an autosomal recessive inherited disorder of metabolism where large sugar molecules glycosaminoglycans (GAGs) cannot be adequately degraded Mucopolysaccharidosis Type I • Annually, there are approxim
Slide 29: MPS-I Program Summary
MPS-I Program Summary Status Next Steps Animal PoC Industry Collaboration Druggable allosteric site identified - in vitro efficacy study (2021) Test compound displays: 3 Bone Joint Cartilage - Stabilization and prevention of enzyme denaturation in physiological conditions Tissue IDUA activity (nmol/
Slide 30: Academic and Development Partners
Academic and Development Partners Patient Associations and Advocacy Groups Academic Partnerships with Centers of Research, Translational Science & Clinical Excellence © 2021 - GAIN THERAPEUTICS Corporate Presentation Page 30
Slide 31: Patent Estate
Patent Estate Patent Status • WO2013092922 (Published June 2013) Technology Platform Patent: • National Phases granted • WO2018122746A1 (Published July 2018) GLB1 Program: • National Phases filed • WO2018122775 (Published July 2018) GBA1 Program: • National Phases filed • WO2021105908 (Published Jun
Slide 32: Upcoming Milestones
Upcoming Milestones MorquioB / GM1 Gangliosidosis: Animal POCs – completion (Q3), IND-enabling studies – initiation (Q4) 2021 Gaucher / Parkinson’s Disease: Animal POC – completion (Q3), IND-enabling studies – initiation (Q4) Krabbe: Lead Optimization & Characterization Morquio B / GM1 Gangliosidosi
Slide 33: Revolutionizing Drug Discovery with Unprecedented Computational Power
Revolutionizing Drug Discovery with Unprecedented Computational Power SEE-Tx™ uses big data and supercomputing to discover novel allosteric sites • Increased target hit rate from 0.1% to 10% (100X) • Unprecedented operational speed and scale • Reduced failure rates and lower drug development costs •
Slide 34: Large Market Opportunity
Large Market Opportunity © 2021 - GAIN THERAPEUTICS Corporate Presentation Page 34
Slide 35: Diversified Pipeline Targeting Multi-Billion Dollar Markets
Diversified Pipeline Targeting Multi-Billion Dollar Markets Global ERT Sales** Global Neurodegenerative Enzyme Replacement Therapy (ERT)* Diseases Drug Market† GR GR 7. 7% CA C A $62.8B % 7.4 Gene Therapy, Chaperones, & Others* $12.1B $35.5B $6.7B 2018 2026 2018 2026 * Data provided by S&P CapIQ and
Slide 36: Financing History and Stakeholders
Financing History and Stakeholders 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 $46m IPO in March 2021,
Slide 37: Strong Board of Directors
Strong Board of Directors - (>$30B in transactions) Khalid Islam, PhD Eric I. Richman Gwen Melincoff Hans Peter Hassler Dov Goldstein, MD Jeffrey Riley Claude Nicaise, MD Founder and Chairman CEO and Member Independent Member Independent Member Independent Member Independent Member Independent Membe
Slide 38: Experienced Management Team
Experienced Management Team - Extensive biotech and pharma experience (>$3B transactions) Eric I. Richman Manolo Bellotto, PhD Salvatore Calabrese Xavier Barril, PhD Terenzio Ignoni, Roberto Maj, PharmD Ana Maria Garcia CEO President & General CFO CSO PharmD VP of Development Collazo, PhD Manager SV
Slide 39: Diverse Group of Scientific Advisors
Diverse Group of Scientific Advisors Joanne Taylor, PhD Samuel Broder, MD Michel Vellard, PhD Lorenzo Leoni, PhD Advisor Advisor Advisor Advisor © 2021 - GAIN THERAPEUTICS Corporate Presentation Page 39
Slide 40: Executive Summary
Executive Summary • Addressing Protein Misfolding by identifying and targeting novel previously undruggable allosteric binding sites Therapeutic Focus • Initial focus on lysosomal storage and CNS diseases -- large & growing markets with unmet medical need • Proprietary and patented SEE-Tx platform i
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