Gain Therapeutics, Inc. · NASDAQ:GANX
Gain Therapeutics — Investor Presentation (May 2025)
33 slides from Gain Therapeutics's investor presentation, May 2025
Slide 1: Gain Therapeutics Corporate Presentation
Corporate Presentation September 2024 GAIN THERAPEUTICS Corporate Presentation May 2025 NASDAQ: GANX
Slide 2: Forward-Looking Statements
Forward-Looking Statements Certain statements set forth in this presentation are forward-looking andreflect the Company’s plans, beliefs, expectations and current views with respect to, among other things, future events and financial performance (collectively referred to herein as “forward-looking s
Slide 3: GANX Corporate Highlights
GANX Corporate Highlights • Allosteric modulator of glucocerebrosidase enzyme (GCase) Lead Product GT-02287 • Disease modifying potential: slowing/stopping progression of motor and cognitive decline in GBA1 and Advancing into Parkinson’s idiopathic PD Disease Patients • Safe and well tolerated in Ph
Slide 4: Experienced Leadership: Extensive Biotech And Pharma Experience
Experienced Leadership: Extensive Biotech And Pharma Experience Gene Mack, MBA Jonas Hannestad, Gianluca Fuggetta MD, PhD Senior Vice President, Chief Executive Officer Chief Medical Officer Finance Terenzio Ignoni, Joanne Taylor, PharmD PhD SVP Technical SVP Research Operations © 2025 - GA I N T HE
Slide 5: Experienced Board of Directors: Extensive Biotech And Pharma Experience
Experienced Board of Directors: Extensive Biotech And Pharma Experience (>$30b Transactions) Khalid Islam, PhD Claude Nicaise, MD Eric I. Richman Gwen Melincoff Founder and Independent Member Member Independent Member Chairman Hans Peter Dov Goldstein, Jeffrey Riley Hasler MD Independent Member Inde
Slide 6: Gain Therapeutics Pipeline
Gain Therapeutics Pipeline ASSET INDICATION TARGET DISCOVERY RESEARCH PRECLINICAL PHASE 1 Parkinson’s Disease GCase Gaucher’s Disease GCase GT-02287 Dementia with Lewy Bodies GCase Alzheimer’s Disease GCase Multiple GALC Lysosomal Storage Disorders Undisclosed GLB1 Undisclosed Metabolic Diseases AAT
Slide 7: Lead Clinical Program
Lead Clinical Program GT-02287 GBA1 Parkinson’s Disease 7
Slide 8: Parkinson's Disease – Market Opportunity
Parkinson’s Disease – Market Opportunity Parkinson’s Disease US Market Potential: $4B Parkinson’s disease is the second most common neurodegenerative disease1 Current therapies only treat symptoms and do not prevent disease progression Parkinson’s Disease Up to15% US Market Potential: $3B (PD) 1M+ o
Slide 9: Dysfunctional GCase triggers disease cascade leading to neurodegeneration
Dysfunctional GCase triggers disease cascade affecting multiple organelle functions and leads to neurodegeneration Healthy Dopaminergic Neuron Diseased Dopaminergic Neuron Mutated Nucleus GBA1 Gene GBA1 Gene GCase protein misfolding Defective GCase Normal GCase • Increased ER stress and ER -associat
Slide 10: GT-02287 restores GCase function, improving disease cascade and neuronal survival
Allosteric modulator GT-02287 restores GCase function, which improves disease cascade and neuronal survival Dopaminergic Neuron with Reduced ER Stress GCase Activity Toxic Substrate Restoration Depletion Restored GCase Function 1.0 8 (relative to untreated) 100 BiP protein level fibroblasts (ng/mg %
Slide 11: Single- and Multiple-ascending Dose First-in-human Phase 1 Study
Single- and Multiple-ascending Dose First-in-human Phase 1 Study Participants: SAD/MAD endpoints: MAD Cohort 4: • Healthy men and women ages 18-65 • Treatment-emergent adverse events • CSF drug levels • 8 subjects per cohort • Clinical labs, vital signs, ECGs, C-SSRS • GCase activity in dry • 2 plac
Slide 12: GT-02287 was Generally Well-Tolerated, No Serious Adverse Events Observed
GT-02287 was Generally Well-Tolerated, No Serious Adverse Events Observed TEAE SAD GT-02287 SAD Placebo MAD GT-02287 MAD Placebo All GT-02287 All Placebo N=30 N=10 N=25 N=8 N=55 N=18 Any 17 (56.7%) 4 (40.0%) 16 (64.0%) 4 (50.0%) 33 (60%) 8 (44%) Related to study drug 10 (33.3%) 1 (10%) 11 (44.0%) 0
Slide 13: Adverse Event Profile
Adverse Event Profile Most common TEAEs in MAD: • Nausea 32% • Abdominal pain 8% • Diarrhea 8% • Headache 8% Nausea: • >90% of events were mild • >90% of events were <3h in duration • Incidence increased with dose level • Incidence decreased with continued dosing © 2025 - GA I N T HE RAP EUT I C S 1
Slide 14: Phase 1 PK Data in Healthy Volunteers
Therapeutic Range: Phase 1 PK Data in Healthy Volunteers Human AUC from MAD Study : Day 1 and Day 14 12000 10000 R² = 0.9663 8000 R² = 0.9975 AUC: ng.h/mL 6000 4000 Onset of Therapeutic Effect 2000 (Animal Models) Linear Regression Day 14 0 Linear Regression Day 1 4 5.5 7 8.5 10 11.5 13 14.5 16 Dose
Slide 15: GT-02287 Demonstrates CNS Exposure Comparable to that Observed in Rodents
GT-02287 Demonstrates CNS Exposure Comparable to that Observed in Rodents • CSF levels in Humans comparable to those observed at efficacious dose levels in rodents • CSF levels are low in all species due to low aqueous solubility and high protein binding • Observed total brain levels in rodents are
Slide 16: GT-02287 Demonstrates GCase Target Engagement In Healthy Volunteers
GT-02287 Demonstrates Gcase Target Engagement In Healthy Volunteers • GCase activity in dry blood spots was GCase Activity (DBS) measured in MAD Cohort 4 ✱✱✱ ✱✱ • In GT-02287 subjects, 5 out of 6 had ✱ increased GCase activity 12 GCase activity (μmol/l/h) ns • In placebo subjects, no increase was 10
Slide 17: Phase 1 Blinded, Placebo Controlled SAD/MAD Trial
Phase 1 Blinded, Placebo Controlled SAD/MAD Trial Safety GT-02287 is safe and generally well tolerated in SAD (40 HV) and MAD (32 HV, daily dosing 14 days) No SAEs, Grade 3 AEs, or clinically-significant changes in ECGs, BP/HR Plasma Exposure Plasma exposures in the projected therapeutic range Adequ
Slide 18: Upcoming Anticipated Milestones and Potential Value Inflection Points
Upcoming Anticipated Milestones and Potential Value Inflection Points 1H 2025 2H 2025 Potential clinical POC based on Start of Phase 2 planning biomarkers of GBA1-Parkinson’s disease IND submission (first analysis from Phase 1b clinical trial) © 2025 - GA I N T HE RAP EUT I C S 18
Slide 19: Design of Phase 1b Trial in Parkinson's Disease Patients
Design of Phase 1b Trial in Parkinson’s Disease Patients An Open-label Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GT-02287 in Participants with Parkinson’s Disease With or Without a Pathogenic GBA1 Mutation • Open-Label, single-arm, multicenter study • Approx
Slide 20: Phase 1b Study Objectives
Phase 1b Study Objectives Study Objectives Endpoints Primary • To evaluate the safety and tolerability of GT-02287 • To characterize the single-dose and steady state plasma PK Secondary profile of GT-02287 • To assess levels of GT-02287 in CSF after at least 12 weeks of Concentration of GT-02287 in
Slide 21: GT-02287 Prevents GBA1 Disease Cascade and Improves Motor Function in Mouse Model
GT-02287 Prevents GBA1 Disease Cascade in Mouse CBE Model of GBA1-PD GBA1-PD Model: CBE causes partial knockdown and Improves of GCase Motor Function activity in the GBA1-PDMouse Model • CBE is an irreversible GCase inhibitor • Administration of CBE models the effects of dysfunctional GCase seen in
Slide 22: GT-02287 displays a rescue and disease-modifying effect in animal models
GT-02287 displays a rescue and disease-modifying effect in animal models of GBA1 and iPD GBA1- PD Model (CBE+PFFs) Idiopathic PD Model (PFFs only) α-Syn PFFs α-Syn PFFs Low Level CBE No drug GT-02287 Washout No drug GT-02287 Washout Mouse Wire Hang Rescue & Washout Data is shown as Mean ± S.E.M.(n=1
Slide 23: Fast-onset rescue effect of GT-02287 driven by enhanced GCase activity
Fast-onset rescue effect of GT-02287 driven by enhanced GCase activity, reduced ER stress and increased lysosomal and mitochondrial integrity 2h post-treatment GCase Activity IRE-1 LAMP-1 Miro1 ER stress Lysosomal Integrity Lamp-1 Mitochondrial Integrity GCase activity Miro-1 ✱✱✱ ✱ ns ✱✱✱✱ ✱✱✱✱ Fluo
Slide 24: Brain biomarker changes maintained following GT-02287 washout
Brain biomarker changes maintained following GT-02287 washout ➢ Taken together, data support GT-02287’s disease modifying effect d29 GCase activity IRE-1 LAMP-1 MIRO-1 Aggregated α-syn (ER stress) (lysosomal integrity) (mitochondrial health) $$$$ LAMP-1 (fluorescence intensity) IRE-1 (fluorescence i
Slide 25: Translational plasma-based biomarkers of GT-02287 rescue effect
Translational plasma-based biomarkers of GT-02287 rescue effect Plasma GlcCer Plasma GlcSph Plasma NfL Control plasma NFL CBE/PFFs ✱✱ + GT-02287 30mg/kg ✱ + GT-02287 60mg/kg p=0.09 + GT-02287 90mg/kg ns ✱✱ 1000 Vehicle Controls 800 CBE + PFF CBE+PFF+GT-02287 600 pg/ml post-8days 400 CBE+PFF+GT-02287
Slide 26: GT-02287 Improves Nest Building Performance in Therapeutic Model of GBA1-PD
GT-02287 Improves Nest Building Performance in Therapeutic Model of GBA1-PD Improvements in Nest-building Performance Improvements in Relevant Biomarkers Nest building is a non- invasive test to study activities of daily living Plasma NfL Aggregated α-syn (SN) and cognitive performance in rodent mod
Slide 27: Nesting score unaffected by drug washout
Nesting score unaffected by drug washout: evidence of disease modifying effect on complex behaviors CBE+PFFs (GBA1-PD) Mouse Nesting Building PFFs only (iPD) WASHOUT WASHOUT Washout 5 Control 5 Control CBE+PFFs PFFs Nesting Score Nesting Score GT-02287 90mg/Kg GT-02287 90mg/Kg 4 4 GT-02287 90mg/Kg +
Slide 28: Brain biomarker changes maintained following GT-02287 washout
Brain biomarker changes maintained following GT-02287 washout ➢ Data support GT-02287’s disease modifying effect d29 Tyrosine Hydroxylase (SN) Striatal dopamine Phospho Tau (SN) Iba-1 (SN) CBE+PFFS PFFS CBE+PFFS PFFS CBE+PFFS PFFS CBE+PFFS PFFS $$$$ $$$$ **** 100 Striatal Dopamine (pg/mg) $$$$ Iba-1
Slide 29: GT-02287 has Best-in-Class Profile for GBA1-Parkinson's Disease
GT-02287 has Best-in-Class Profile for GBA1-Parkinson's Disease Effect on DiseaseCascade GT-02287 BIA 28-6156 VQ-101 Increases LysosomalGCase Activity ? Reduces ERStress ? ? Reduces ToxicLipid Substrates GCase Mechanism Reduces Aggregated α-Synuclein ? of Action Improves LysosomalFunction Improves M
Slide 30: Large Market Potential for GT-02287 for Various Neurodegenerative Diseases
Large Market Potential for GT-02287 for Various Neurodegenerative Diseases Number of Indication Rationale Patients (US) Patients have dysfunctional GCase due to GBA1-Parkinson’s Disease 150,000 heterozygous GBA1 mutation Idiopathic Parkinson’s Disease Increase in GCase activity and target activation
Slide 31: Company Background
Company Background COR POR ATE BACKGR OU ND FINANCIAL AND STOCK DATA Established in 2017 IPO (NASDAQ: GANX) 27 employees in three locations: HQ in Bethesda, − March 2021 − Led by BTIG and Oppenheimer & Co. Maryland, Lugano, Switzerland, Barcelona, Spain CAPITAL STRUCTURE Founder and Executive Chairm
Slide 32: Company Contacts
Company Contacts Gene Mack President & CEO gmack@gaintherapeutics.com Apaar Jammu Manager, Investor Relations and Public Relations ajammu@gaintherapeutics.com
Slide 33: Appendix
Appendix