Gain Therapeutics, Inc. · NASDAQ:GANX
Gain Therapeutics — Investor Presentation (June 2025)
31 slides from Gain Therapeutics's investor presentation, June 2025
Slide 1: Gain Therapeutics Corporate Presentation
Corporate Presentation September 2024 GAIN THERAPEUTICS Corporate Presentation June 2025 NASDAQ: GANX
Slide 2: Forward-Looking Statements
Forward-Looking Statements Certain statements set forth in this presentation are forward-looking and reflect 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
Slide 3: GANX Corporate Highlights
GANX Corporate Highlights • Allosteric modulator of glucocerebrosidase enzyme (GCase) Lead Product GT-02287 • Disease modifying potential: altering progression of motor/cognitive decline in GBA1 and iPD Being Evaluated in • Safe and well tolerated in Phase 1 SAD/MAD study and demonstrated target eng
Slide 4: Leadership: Extensive Biotech And Pharma Experience
Leadership: Extensive Biotech And Pharma Experience Gene Mack, MBA Jonas Hannestad, Gianluca Fuggetta MD, PhD Chief Executive Officer Senior Vice President, Chief Medical Officer Finance Terenzio Ignoni, Joanne Taylor, PhD PharmD SVP Research SVP Technical Operations © 2025 - GA I N T HE RAP EUT I C
Slide 5: Board of Directors: Extensive Biotech And Pharma Experience
Board of Directors: Extensive Biotech And Pharma Experience (>$30b Transactions) Khalid Islam, PhD Claude Nicaise, MD Gwen Melincoff Hans Peter Hasler Founder and Chairman Independent Member Independent Member Independent Member Jeffrey Riley Dov Goldstein, MD Eric I. Richman Gene Mack, MBA Independ
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 GT-02287
Lead Clinical Program GT-02287 GBA1 Parkinson’sDisease
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 symptomsand do not prevent disease progression Parkinson’s GBA-PD Disease (PD) 10-15% of PD GBA1-Parkinson
Slide 9: GCase Plays Integral Role in Organelle and Cellular Health
GCase Plays Integral Role in Organelle and Cellular Health Healthy Dopaminergic Neuron Diseased Dopaminergic Neuron 1 GBA1 Gene Mutated Nucleus GCase protein misfolding GBA1 Gene 2 Increased ER stress and ER- Normal GCase Defective associated protein degradation GCase Endoplasmic 3 Reticulum Lysosom
Slide 10: Allosteric modulator GT-02287 restores GCase function
Allosteric modulator GT-02287 restores GCase function, which improves disease cascade and neuronal survival DopaminergicNeuron with GCase Activity Restored Lysosomal Toxic Substrate RestoredGCase Function Restoration Function Depletion Mutated GBA1 Gene Neuronal Survival GT- 02287 Defective GCase No
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 blood spots
Slide 12: GT-02287 was Generally Well-Tolerated, No Serious Adverse Events Observed
GT-02287 was Generally Well-Tolerated, No Serious Adverse Events Observed SAD GT-02287 SAD Placebo MAD GT-02287 MAD Placebo All GT-02287 All Placebo TEAE 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 TEAEsin 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 13
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 Rodents
GT-02287 Demonstrates CNS Exposure Comparable to that Observed in Rodents Mean CSF level Total brain level Mean plasma Cmax Species Timepoint Dose (mg/kg) (ng/mL) (ng/mL) (ng/mL) mean Day 14 Human (MAD4) 3.1 (1.7-4.9) Nd 850 Day 13 13.5 PO Mouse 4 6592 2414 15 min 10 IV Rat 3 2441 680 1 hour 30 PO •
Slide 16: GT-02287 Demonstrates GCase Target Engagement In Healthy Volunteers
GT-02287 Demonstrates GCase Target Engagement In Healthy Volunteers Healthy Volunteer Results GCase Activity in Dried Blood Spots (DBS) • GCase activity in dry blood spots was measured in MAD Cohort 4 • In GT-02287 subjects, 5 out of 6 had increased GCase activity • In placebo subjects, no increase
Slide 17: Phase 1 Blinded, Placebo Controlled SAD/MAD Trial
Phase 1 Blinded, Placebo Controlled SAD/MAD Trial • GT-02287 is safe and generally well tolerated in SAD (40 HV) and MAD (32 HV, daily dosing 14 days) Safety • No SAEs, Grade 3 AEs, or clinically-significant changes in ECGs, BP/HR Plasma • Plasma exposures in the projected therapeutic range Exposure
Slide 18: 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 19: Phase 1b Study Objectives
Phase 1b Study Objectives Objectives Endpoints Primary • To evaluate the safety and tolerability of GT-02287 • To characterize the single-dose and steady state plasma Secondary PK profile of GT-02287 • To assess levels of GT-02287 in CSF after at least 12 Concentration of GT-02287 in CSF at 4 hours
Slide 20: GT-02287 Prevents GBA1 Disease Cascade in Mouse CBE Model
GT-02287 Prevents GBA1 Disease Cascade in Mouse CBE Model of GBA1-PD CBE-Model Aggregated a-syn (SN) Tyrosine Hydroxylase (SN) Striatal Dopamine Iba-1 (SN) • CBE is an irreversible GCase inhibitor • CBE models the effects of dysfunctional GCase seen in GBA1-PD GluCer (Cortex) NeuN (Cortex) NfL Wire
Slide 21: Rescue and Disease-Modifying Effect in Animal Models of GBA1 and iPD
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 Day Day Data is shown as Mean ± S.
Slide 22: Fast-onset rescue effect of GT-02287
Fast-onset rescue effect of GT-02287 driven by enhanced GCase activity, reduced ER stress and increased lysosomal and mitochondrial integrity 2 Hours Post-Treatment IRE-1 LAMP-1 Miro1 GCase Activity GCase activity ER Stress LysosomalLamp-1 Integrity Mitochondrial Integrity Miro-1 ✱ ✱✱✱ ns ns Fluores
Slide 23: Brain biomarker changes maintained following GT-02287 washout
Brain biomarker changes maintained following GT-02287 washout Data from CBE+PFF Model support GT-02287’s disease modifying effect No Washout Washout Day 20 – Day 29 IRE-1 LAMP1 MIRO-1 Aggregated GCase Activity GCase Activity ER Stress Lysosomal Integrity Mitochondrial Health a-Syn $$$$ $$$$ **** ***
Slide 24: Translational plasma-based biomarkers of GT-02287 rescue effect
Translational plasma-based biomarkers of GT-02287 rescue effect Plasma GlcCer Plasma GlcSph Plasma NfL Control CBE + PFFs +GT-02287 (30mg/kg) +GT-02287 (60mg/kg) +GT-02287 (90mg/kg) Data shown as Mean ± S.E.M. (n=10). Significant difference as compared to PFFs or PFFs + CBE. © 2025 - GA I N T HE RAP
Slide 25: GT-02287 Improves Nest Building Performance in GBA1-PD Model
GT-02287 Improves Nest Building Performance in Therapeutic Model of GBA1-PD Improvements in Nest-building Performance Improvements in Relevant Biomarkers Nest building is a non- invasive test to study activities of daily Aggregated α-syn (SN) Plasma NfL living and cognitive performance in rodent mod
Slide 26: Nesting Score Unaffected by Drug Washout
Nesting Score Unaffected by Drug Washout Evidence of disease modifying effect on complex behaviors CBE+PFFs (GBA1-PD) PFFs only (iPD) WASHOUT WASHOUT Mouse Nesting Building Washout $ $$ $$$ $$$ $$$ $$$$ $$$$ $$$$ $$$$ Data is shown as Mean ± S.E.M.(n= 7). $Significant difference as compared to sham
Slide 27: Brain biomarker changes maintained following GT-02287 washout
Brain biomarker changes maintained following GT-02287 washout GT-02287 Washout Day 20 - Day 29 Tyrosine Hydroxylase (SN) Striatal Dopamine Phospho Tau (SN) Iba-1 (SN) CBE+PFFS PFFS CBE+PFFS PFFS CBE+PFFS PFFS CBE+PFFS PFFS Control CBE + PFFs +GT-02287 (60mg/kg) +GT-02287 (90mg/kg) PFFs +GT-02287 (60
Slide 28: 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 29: Large Market Potential for GT-02287 for Various Neurodegenerative Diseases
Large Market Potential for GT-02287 for Various Neurodegenerative Diseases Indication Rationale Number of Patients Patients have dysfunctional GCase due to heterozygous GBA1-Parkinson’s Disease 150,000 GBA1 Mutation Increase in GCase activity and target activation in Idiopathic Parkinson’s Disease (
Slide 30: Company Background
Company Background Corporate Background Financial and Stock Data • Established in 2017 IPO (NASDAQ: GANX) − March 2021 • 27 employees in three locations: HQ in Bethesda, − Led by BTIG and Oppenheimer & Co. Maryland, Lugano, Switzerland, Barcelona, Spain • Founder and Executive Chairman: Dr. Khalid I
Slide 31: Appendix
Appendix © 2025 - GA I N T HE RAP EUT I C S 31 31
Gain Therapeutics — Investor Presentation (June 2025) on 6ix