Slide 1: Parkinson's Disease KOL Event
Corporate Presentation September 2024 GAIN THERAPEUTICS Parkinson’s Disease KOL Event Biomarkers, Clinical Endpoints, and the Path to Disease Modification Contextualizing the emerging data from GT - 02287 October 14, 2025 NASDAQ: GANX
Slide 2: Forward-looking statements
© 2 0 2 5 - G A I N T H E R A P E U T I C S 2 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
Slide 3: Gene Mack, President & CEO
© 2 0 2 5 - G A I N T H E R A P E U T I C S 3 Gene Mack, President & CEO, Gain Therapeutics
Slide 4: Today's Agenda
© 2 0 2 5 - G A I N T H E R A P E U T I C S 4 Opening comments, Overview of Parkinson’s Disease and Phase 1b study of GT - 2207 Gene Mack President & Chief Executive Officer GT - 02287 Phase 1b recent data overview Jonas Hannestad . M.D. , Chief Medical Officer All 01 Today’s Agenda Q&A session 02 K
Slide 5: About Kenneth Marek, M.D.
© 2 0 2 5 - G A I N T H E R A P E U T I C S 5 About Kenneth Marek, M.D. Kenneth Marek, M.D. is President and senior scientist at the Institute for Neurodegenerative Disorders. Dr. Marek's major research interests include identification of biomarkers for early detection, assessment of disease progres
Slide 6: About Karl Kieburtz, M.D., M.P.H.
© 2 0 2 5 - G A I N T H E R A P E U T I C S 6 About Karl Kieburtz , M.D., M.P.H. Karl Kieburtz M.D., M.P.H. is a Co - Founder of Clintrex Research LLC, a Board member of BlueRidge Life Sciences, and a Professor (part time) of Neurology at the University of Rochester. In his academic career, he was t
Slide 7: Parkinson's Disease
© 2 0 2 5 - G A I N T H E R A P E U T I C S 7 Parkinson’s Disease 7 1.“Parkinson’s Disease: Challenges, Progress, and Promise.” National Institute of Neurolog i cal Disorders and Stroke, U.S. Department of Health and Human Services 2. Smith L and Schapir a AHV. G BA Variants and Parkinson Disease: M
Slide 8: GT-02287 and Glucocerebrosidase: A Differentiated Mechanism of Action
© 2 0 2 5 - G A I N T H E R A P E U T I C S 8 GT - 02287 and Glucocerebrosidase: A Differentiated Mechanism of Action Nucleus Endoplasmic Reticulum Lysosome and Mitochondria GBA1 Gene Normal GCase GCase M aintains C ell H ealth Depletes toxic lysosomal substrates Stabilizes mitochondrial respiratory
Slide 9: GT-02287 demonstrates a broad neuroprotective effect in preclinical models
© 2 0 2 5 - G A I N T H E R A P E U T I C S 9 GT - 02287 demonstrates a broad neuroprotective effect in preclinical models Reduced ER Stress Restored Lysosomal Function Restored Mitochondrial Function Toxic Substrate Depletion Alpha - Synuclein Depletion Neuronal Survival GCase Activity Restoration
Slide 10: Design of Phase 1b Trial in Parkinson's Disease Patients
© 2 0 2 5 - G A I N T H E R A P E U T I C S 10 Design of Phase 1b Trial in Parkinson’s Disease Patients Site Visit 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
Slide 11: Phase 1b Study Objectives and Endpoints
© 2 0 2 5 - G A I N T H E R A P E U T I C S 11 Phase 1b Study Objectives and Endpoints Endpoints Study Objectives To evaluate the safety and tolerability of GT - 02287 Primary To characterize the single - dose and steady state plasma PK profile of GT - 02287 Secondary Concentration of GT - 02287 in
Slide 12: Ken Marek, M.D.
© 2 0 2 5 - G A I N T H E R A P E U T I C S 12 Ken Marek., M.D.
Slide 13: What is a biomarker?
A biological marker or biomarker is a characteristic that is objectively measured and evaluated as an indicator of a normal biological processes, pathogenic processes, or pharmacologic response to a therapeutic intervention. Surrogate endpoints (SE) are a subset of biomarkers intended to substitute
Slide 14: Why do we need biomarkers?
Why do we need biomarkers? ● Objective measure of disease biology ● May be present earlier then clinical symptoms or at specific stages of disease ● May identify biologically defined disease subsets ● May allow for targeted treatment ● For clinical trials - reduce the sample size required and/or sho
Slide 15: Biomarkers have a context of use
Biomarkers have a context of use Drug development - Target engagement, Pharmacokinetics,Pharma codynamics 15 Disease onset – start of neurodegeneration Disease progression Biologic subtypes disease subtypes Clinical Subtypes - Non dopamine responsive markers - speech, cognition, balance, psychosis S
Slide 16: Paradigm shift: Biologic Definition of Neuronal Synuclein Disease
Paradigm shift: Biologic Definition of Neuronal Synuclein Disease (NSD) 16 Neuronal Synuclein disease (NSD) is defined by presence of disease - specific neuronal alpha - synuclein (a - syn) pathology (or fully penetrant pathogenic variants in SNCA gene) Two anchors : a - syn pathology (S) As measure
Slide 17: Investigating the start of neurodegeneration: a paradigm shift to NSD
Investigating the start of neurodegeneration: a paradigm shift to NSD (Parkinson, Dementia with LEWY Bodies) 17 Source: Kalia, LV, Lang AE et al, Lancet 2015 RBD: REM - sleep Behavior Disorder; EDS: Excessive Daytime Sleepiness; MCI: Mild Cognitive Impairment 3 - 5yr Immune Mitochondrial Lysosomal S
Slide 18: PPMI Clinic Study Population
PPMI 18 CLINIC STUDY POPULATION N=5500 ASSESSMENTS/ CLINICAL DATA COLLECTION BIOLOGIC COLLECTION SHARED DATA & BIOSAMPLES » 1100 PPMI current participants » 700 PD » 100 HC » 300 Prodromal » 1000 newly enrolled at clinical site » 900 PD » 100 HC » 2000 Prodromal PD – Enrolled through staged risk (DA
Slide 19: PPMI Core Biomarkers
Ongoing evaluation of new platforms as available PPMI Core Biomarkers N>3000 participants aSyn SAA (CSF).DAT imaging WGS Targeted Neurodegeneration Analytes N>1000 BL and longitudinal NFL & GFAP (plasma) p - tau 217 (plasma) AB40/42, p - tau 181(CSF) MTBR CSF NULISA N> 1000 BL and longitudinal CNS &
Slide 20: PPMI Imaging
20 Molecular Imaging • DAT imaging • VMAT2 • Substudies – • Tau • Inflammatory • SV2a • Synuclein MR battery: • 3D T1 MRI (MP - RAGE) • 3D FLAIR • Neuromelanin • Diffusion: Multi shell DTI • EPI - BOLD for rs - fMRI DAT Methods Neuromelanin Resting State fMRI PPMI - Imaging
Slide 21: Alpha Synuclein Imaging Landscape 2025
Alpha Synuclein Imaging Landscape 2025 [ 18 F] ACI - 12589, from AC Immune, demonstrated uptake in Multiple System Atrophy (MSA) consistent with the asyn deposition in this disease ( Smith R, Capotosti F, Schain M, et al, Nature Comm 2023); follow - up tracer in development [ 11 C]MK - 7337, Merck,
Slide 22: Defining clinical and biological disease characteristics to enable targeted trials
Defining clinical and biological disease characteristics to enable targeted precision therapeutic trials to accelerate drug development 22 Defining a population Genetics Understanding the biologic of the disease Establishing the key determinant and modifiers of neurodegeneration Tracking the the tem
Slide 23: Karl Kieburtz, M.D., M.P.H.
© 2 0 2 5 - G A I N T H E R A P E U T I C S 23 Karl Kieburtz , M.D., M.P.H.
Slide 24: MDS-UPDRS: Overview and Regulatory Relevance
Part IV Part III Part II Part I Part Motor Complications Motor Examination Motor Aspects of Experiences of Daily Livings Non - motor Aspects of Experiences of Daily Livings Domain Investigator/Clinician Investigator/Clinician Patient and/or Caregiver Patient and/or Caregiver Rater Dyskinesia and mot
Slide 25: MDS-UPDRS: Overview and Regulatory Relevance
Such designs may have sample size savings over trial powered on mean score changes. MDS - UPDRS: Overview and Regulatory Relevance MDS UPDRS scores can be used to calculate mean changes or used in a ‘time to event’ analysis, using a pre - set level of worsening to define the ‘event’ Ongoing trials (
Slide 26: Jonas Hannestad, M.D., Chief Medical Officer
© 2 0 2 5 - G A I N T H E R A P E U T I C S 26 Jonas Hannestad, M.D. Chief Medical Officer, Gain Therapeutics
Slide 27: Phase 1b Initial Data: Demographics and Baseline Characteristics
© 2 0 2 5 - G A I N T H E R A P E U T I C S 27 Phase 1b Initial Data: Demographics and Baseline Characteristics 27 individuals were screened and 21 enrolled from March through September 2025; e nrollment in Part 1 i s now complete The 21 participants include 3 women and 18 men , 2 treatment - naïve,
Slide 28: Phase 1b Initial Data: Safety and Tolerability
© 2 0 2 5 - G A I N T H E R A P E U T I C S 28 Phase 1b Initial Data: Safety and Tolerability One participant interrupted dosing for 7 days due to constipation One participant had dosing withheld for 30 days due to transient increases in ALT, ALP, and GGT; upon reinitiation of dosing at a lower dose
Slide 29: Phase 1b Initial Data: Plasma PK
© 2 0 2 5 - G A I N T H E R A P E U T I C S 29 Phase 1b Initial Data: Plasma PK Plasma concentration versus time on Day 1, n=14 Plasma exposures were within the projected therapeutic range and comparable to exposures observed in healthy volunteers in Phase 1
Slide 30: Phase 1b Initial Data: MDS-UPDRS Changes
© 2 0 2 5 - G A I N T H E R A P E U T I C S 30 Phase 1b Initial Data: MDS - UPDRS Changes • No mean imp rovement by Day 30, but mean improvement by Day 90 • This indicates that there is no acute, dopaminergic, symptomatic effect, but that a slower effect may occur • Reduction of 1 - 2 points on UPDR
Slide 31: What's Next?
© 2 0 2 5 - G A I N T H E R A P E U T I C S 31 What’s Next? 02 Results 03 IND Filing 04 Insights Final results from Phase 1b study extension expected 2H26 • Updates will be available throughout 1H26 Further insights into mechanism of action and continued clinical development, increase conviction IND
Slide 32: Q&A
© 2 0 2 5 - G A I N T H E R A P E U T I C S 32 Q&A
Slide 33: Thank you
Corporate Presentation September 2024 Thank you