Gain Therapeutics, Inc. · NASDAQ:GANX
Gain Therapeutics — Investor Presentation (May 2022)
44 slides from Gain Therapeutics's investor presentation, May 2022
Slide 1: Novel Allosteric Modulators: A Solution To Undruggable Targets
Novel Allosteric Modulators: A Solution To Undruggable Targets Corporate Presentation May 2022 © 2022 - 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: Investment Highlights
Investment Highlights ▪ Small molecule discovery platform and therapeutics company Therapeutic Focus ▪ Developing small molecule treatments for patients with high unmet medical needs that stabilize defective enzymes, treating protein misfolding disorders at their source – in CNS and Oncology ▪ Propr
Slide 4: Novel Allosteric Modulators: A Solution To Undruggable Targets
Novel Allosteric Modulators: A Solution To Undruggable Targets THE PROBLEM Majority of disease-causing proteins cannot be targeted by current therapies due to the lack of a known addressable binding site THE SOLUTION Gain’s physics-based platform provides quantitative predictions of druggable bindin
Slide 5: Advantages of Drugging Allosteric Binding Sites
Advantages of Drugging Allosteric Binding Sites Active Binding Site Allosteric Binding Site • Site where natural ligand • Any site that is not the active binding site binds to the protein • Emerging targeting approach unlocked • Traditional drugs bind to by computational target discovery active site
Slide 6: Allosteric Modulators Cover All Mechanisms for Protein Target Engagement
Allosteric Modulators Cover All Mechanisms for Protein Target Engagement Stabilization Destabilization Degradation Allosteric Inhibition Allosteric Activation ▪ Gain of function ▪ Loss of function approach ▪ Loss of function approach ▪ Loss of function approach ▪ Gain of function approach ▪ Stabiliz
Slide 7: 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 8: SEE-Tx Discovery Platform
SEE-Tx® Discovery Platform Target Protein 1 SEE-Tx® 2 SEE-Tx® 3 SEE-Tx® Development Disease related proteins Allosteric site Hotspot guided Experimental Candidate (experimental or predicted discovery with mixed virtual screening Validation and structure) solvent simulations optimization Candidates a
Slide 9: SEE-Tx By the Numbers
SEE-Tx® By the Numbers STEP 1 Identify Allosteric Sites 1-2 weeks on Target Proteins STEP 2 Virtual Screening 3-4 weeks STEP 3 Experimental 2-3 weeks Compound Validation REPRESENTS 1000-FOLD Average Hit Rate 14% ENRICHMENT COMPARED TO HTS © 2022 - GAIN THERAPEUTICS Corporate Presentation Page 9
Slide 10: SEE-Tx: A Highly Differentiated Approach
SEE-Tx: A Highly Differentiated Approach Proprietary algorithms and know-how enable the discovery of novel allosteric sites and small molecules MD-Mix Simulations Quantitative Predictions Dynamic Undocking Simulations with organic Quantifies “druggability” of hotspots Uses intramolecular forces for
Slide 11: Platform with Broad Applicability
Platform with Broad 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 Diseases,
Slide 12: Diversified Pipeline in High Unmet Need Disorders across Four Therapeutic Areas
Diversified Pipeline in High Unmet Need Disorders across Four Therapeutic Areas © 2022 - GAIN THERAPEUTICS Corporate Presentation Page 12
Slide 13: The Programs: Parkinson's / Gaucher Disease
The Programs Parkinson’s / Gaucher Disease Beta-glucosidase (GBA) © 2022 - GAIN THERAPEUTICS Corporate Presentation
Slide 14: GBA1-related Disease: Parkinson's Disease & Gaucher Disease
GBA1-related Disease: Parkinson’s Disease & Gaucher Disease Mutations in the GBA1 gene are associated with α-synuclein accumulation in Parkinson’s and build-up of glucosylceramide in Gaucher disease. Parkinson’s Disease HETEROZYGOUS GBA MUTATION Gaucher Disease HOMOZYGOUS GBA MUTATION ▪ Parkinson’s
Slide 15: 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 (STARs) Allosteric Regulators Binding allosteric sites has the potential to provide superior regulation of
Slide 16: GT-02287 Improves Locomotion in a Rotenone-induced Rat PD Model
GT-02287 Improves Locomotion in a Rotenone-induced Rat PD Model Differences in locomotion (Open field test) obtained by video-tracking software system, of a representative rotenone-treated rat versus a rotenone-treated rat with oral admin of GT-02287 (60 mg/kg) for 7 days A. Representative videos of
Slide 17: Key Findings GBA-associated Parkinson's Disease in Rotenone Rat Model
Key Findings GBA-associated Parkinson’s Disease in Rotenone Rat Model Depleted Improved Improved Toxic Substrate Neuronal Activity Locomotion GT-02287 Reduces Toxic GT-02287 Improves GT-02287 Improves Substrate, α-synuclein in Dopaminergic Neuronal Locomotion Deficit the Substania Nigra Activity in
Slide 18: KOL: Dr. Ricardo Feldman, University of Maryland
KOL: Dr. Ricardo Feldman, University of Maryland • Prof. Feldman is using patient-derived induced pluripotent stem cells (iPSC) to study the molecular mechanisms by which mutations in lysosomal glucocerebrosidase cause GBA-associated neurodegeneration in Gaucher and Parkinson’s diseases • As such, t
Slide 19: Key Findings GBA-associated Parkinson's Disease in iPSC model
Key Findings GBA-associated Parkinson’s Disease in iPSC model Increased Depleted Improved Lysosomal GCase Enzyme Levels Toxic Substrate Function Increased GCase enzyme levels in Reduced GlcCer toxic substrate in Increased autophagic flux in Dopaminergic Neurons Cortical Neurons Dopaminergic Neurons
Slide 20: GT-02287 increases GCase levels and transport to the lysosome
GT-02287 increases GCase levels and transport to the lysosome in dopaminergic neurons WT DA Neurons GD2 (L444P/RecNciI) DA Neurons GD3 (L444P/L444P) DA Neurons GT-02287 Intensity GT-02287 GT-02287 Intensity Intensity 2.0 GCase Levels Mean Fluorescence Intensity 2.0 Mean Fluorescence Intensity 2.0 Fl
Slide 21: α-synuclein-p129 reduction in dopaminergic neurons
α-synuclein-p129 α-synuclein-p129 α-synuclein-p129 (Western Blot) aggregates Normalized to α-SYN-p129 % of α-SYN-p129 Relative Fluorescence Intensity -SYN-p129 levels Normalized toLevels aggregates Neurons in THaggregates % of a-SYN-p129 Relative fluorescence of α-ASYN-p129 Neurons in THIntensity o
Slide 22: GT-02287 effectively reduces the production of inflammatory cytokines
GT-02287 effectively reduces the production of inflammatory cytokines GCase IL-6 TNF GCase levels (Fold change) (N370S/N370S) Gaucher type I 4000 500 macrophages 2.0 TNF pgmL IL-6 (pg/mL) 400 3000 1.5 300 1.0 2000 200 ** 0.5 1000 ** * 100 * 0.0 0 0 NT 12.5 μM 25 μM NT 12.5 μM 25 μM NT 12.5 μM 25
Slide 23: Key Findings in an In Vitro Neuronal Alzheimer's Disease Model
Key Findings in an In Vitro Neuronal Alzheimer's Disease Model GT-STAR compound protects against Amyloid Beta 1-42-induced neurotoxicity Decreased Improved Neuronal Improved Hyperphosphorylated Survival Neurite Network Tau GT-STAR compound improved GT-STAR compound improved GT-STAR compound decrease
Slide 24: GT STAR Compound is Neuroprotective against Amyloid Beta 1-42 Oligomers
GT STAR Compound is Neuroprotective against Amyloid Beta 1-42 Oligomers Neuronal Survival Neurite Network Hyperphosphorylation of Tau Neuronal survival Neurite network Hyperphosphorylation of Tau 150 150 250 Control ****24h) Aβ (15 µM, **** Neuronal survival Neurite network **** 200 ** * *** (% of c
Slide 25: GBA1 Program Summary - Parkinson's Disease and Gaucher Disease
GBA1 Program Summary - Parkinson’s Disease and Gaucher Disease BOTH INDICATIONS ▪ Mechanism of action established in in vitro assays ▪ Target engagement shown in in vitro assays, including increase in GCase enzyme activity and synuclein and glucosylceramide clearance ▪ Drug properties suitable for t
Slide 26: Company Background
Company Background THE TECHNOLOGY THE PIPELINE INTELLECTUAL PROPERTY ▪Established in 2017 Supercomputer-powered SEE-Tx® Program pipeline with Strong intellectual target and drug discovery platform demonstrated targeted property estate – patent ▪Approx. 30 employees in three combines physics-based mo
Slide 27: Experienced Management Team
Experienced Management Team EXTENSIVE BIOTECH AND PHARMA EXPERIENCE (>$13B TRANSACTIONS) Manolo Bellotto, Terenzio Ignoni, Roberto Maj, Ana Maria Garcia Eric I. Richman Matthias Alder Salvatore Calabrese Xavier Barril, PhD PhD PharmD PharmD Collazo, PhD CEO COO CFO CTO President & GM SVP of Quality/
Slide 28: 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 Member
Slide 29: Upcoming Milestones
Upcoming Milestones THERAPEUTIC AREA INDICATION GENE DISCOVERY RESEARCH PRECLINICAL PHASE 1 UPCOMING MILESTONES IND-enabling toxicology study – Q3 2022 Neurodegenerative Parkinson’s Disease GBA1 HREC submission and first in human study – Q4 2022/Q1 Diseases 2023 IND-enabling toxicology study – Q4 20
Slide 30: Investment Highlights
Investment Highlights ▪ Small molecule discovery platform and therapeutics company Therapeutic Focus ▪ Developing small molecule treatments for patients with high unmet medical needs that stabilize defective enzymes, treating protein misfolding disorders at their source – in CNS and Oncology ▪ Propr
Slide 31: Appendix
APPENDIX © 2022 - GAIN THERAPEUTICS Non-Confidential Presentation
Slide 32: STAR Compound GT-02287 Decreases Total and Phosphorylated α-synuclein
STAR Compound GT-02287 Decreases Total and Phosphorylated α-synuclein in the Substania Nigra in a Roteneone Rat Model Total α-synuclein Phosphorylated α-synuclein vehicle controls rotenone rotenone + GT-02287 (60 mg/kg) rotenone + GT-02287 (90 mg/kg) Data is shown as Mean ± S.E.M. (n=9-10), Two-way
Slide 33: STAR Compound GT-02287 Increases Dopaminergic Neuron Activity TH in the Striatum
STAR Compound GT-02287 Increases Dopaminergic Neuron Activity TH1 in the Striatum and Decreases Neuroinflammatory marker (Iba-1)2 in Substantia Nigra Tyrosine Hydroxylase Iba-1 vehicle controls rotenone rotenone + GT-02287 (60 mg/kg) rotenone + GT-02287 (90 mg/kg) 1Tyrosine hydroxylase is the enzyme
Slide 34: Scientific Advisory Board
Scientific Advisory Board Luca Benatti, PhD Joanne Taylor, PhD Samuel Broder, MD Lorenzo Leoni, PhD Michel Vellard, PhD Chairman © 2022 - GAIN THERAPEUTICS Corporate Presentation Page 34
Slide 35: SEE-Tx Target Discovery
STEP 1 SEE-Tx® Target Discovery Molecular Dynamics Quantitative Binding Site Protein Structure Simulation & DGbind Identification Density Analysis ■ Protein is immersed in virtual • Cluster of hot spots are water and organic solvents automatically identified as ■ Entire universe of protein that comp
Slide 36: SEE-Tx Virtual Screening
STEP 2 SEE-Tx® Virtual Screening Hit Selection for Multiple–probe Docking/HT-Virtual Dynamic Experimental MD Simulations Screening Undocking Validation Docking protocol ■ Computational and medicinal chemistry ■ Docking protocol provides ■ Compounds are parameters are applied to rough evaluation of c
Slide 37: SEE-Tx Experimental Validation
STEP 3 SEE-Tx® Experimental Validation MoA Structure-based Biophysical Cell-based Assays Confirmation Optimization Characterization ▪ Protein stability (DSF) ▪ Structure-Activity ▪ Structural elucidation ▪ Functional assays ▪ Binding Relationships (SAR) by crystallography or ▪ Patient fibroblasts ▪
Slide 38: 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 June 2021) G
Slide 39: GBA1 Program: STAR Lead Candidates GT-02287 and GT-02329
GBA1 Program: STAR Lead Candidates GT-02287 and GT-02329 GT-02287 and GT-02329 are small molecules of 350-450 Da with good drug-like properties Mechanism in vivo Target in vitro Target Drug of Action Engagement Engagement Properties • Dose-dependent and • Enhancement of brain • Enhancement of GCase
Slide 40: Allostery Focused Companies: Gain is Significantly Undervalued Compared to Peers
Allostery Focused Companies Gain is Significantly PHASE 1 Undervalued Compared to Peers $3.1B NASDAQ: RLAY IND-ENABLING Development Stage > $71M $225M DISCOVERY $210M Private (Series B) Private (Series C) $270M $2B Private (Series B) Bayer Acquisition $156M $225M Private (Series B) Private (Series B
Slide 41: Computational Drug Discovery: Gain is Significantly Undervalued Compared to Peers
Computational Drug Discovery Gain is Significantly PHASE 1 Undervalued Compared to Peers $2.5B $3.1B $3.2B NASDAQ: EXAI NASDAQ: RLAY $2.8B NASDAQ: RXRX Private (Series B) IND-ENABLING Development Stage > $2.6B NASDAQ: SDGR $71M DISCOVERY $2B Bayer Acquisition < $100 M $2B > $3B > Estimated Valuation
Slide 42: Comparative Focus
Comparative Focus Allostery Focused Approaches AI/ML Knowledge- Based Methods Structure- Based Methods © 2022 - GAIN THERAPEUTICS Corporate Presentation Page 42
Slide 43: Pharmacological Chaperones Target the Start of the Disease Cascade
Pharmacological Chaperones Target the Start of the Disease Cascade Gene Therapy Replace mutant DNA with correct DNA Key issues with safety, not applicable to all patients Gain's Solution Pharmacological chaperones to Enzyme Replacement (ERT)/ stabilize misfolded proteins Substrate Reduction (SRT) Re
Slide 44: Parkinson's Disease Treatment Aimed at Disease Modification and Early Intervention
Parkinson’s Disease Treatment Aimed at Disease Modification and Early Intervention Gain’s approach focused on neuroprotection to delay neurodegeneration and disease development © 2022 - GAIN THERAPEUTICS Corporate Presentation Page 44