Slide 1: Fabry Disease: AMT-191 investigational gene therapy preliminary safety and biomarker data
FABRY DISEASE AMT-191 investigational gene therapy in adult males with classic Fabry disease; preliminary safety and biomarker data of Phase I/IIa study Maryam Banikazemi1, Ozlem Goker-Alpan2, William Wilcox3, Christy Quintana4,Arian Pano4 1 NYC Health + Hospitals, NYC, US; 2LDRTC, Fairfax, VA, US;
Slide 2: Fabry Disease (FD) Pathophysiology
Fabry Disease (FD) Pathophysiology Enzyme Deficiency Cellular and Tissue Impact Mutation in Reduced Globotriaosyl- Accumulations Blood vessel wall GLA gene enzyme ceramide Premature death Glomerular Hypertrophic Neuropathic Angiokeratomas sclerosis, Stroke, Abdominal pain, cardiomyopathy pain Nephro
Slide 3: Systemic Administration of AAV Therapy
Systemic Administration of AAV Therapy Transduction of liver cells with IV Delivery AAV5 vector @ Liver specific production Cross correction via circulation to key organs such as Vector decapsulation heart and kidney AAV, adeno-associated virus; GLA, alpha-galactosidase A. 3
Slide 4: AMT-191: Development Program
AMT-191: Development Program AMT-191 is an investigational AAV5 gene therapy being developed by uniQure biopharma B.V. uniQure initiated this Phase I/IIa first-in-human clinical study to evaluate the safety, PK/PD, and exploratory efficacy of AMT-191 in classical Fabry disease males currently treate
Slide 5: Phase I/IIa Clinical Trial Design
AMT-191: Phase I/IIa Clinical Trial Design First-in-Human Dose Ranging Study Key Eligibility Criteriaa Cohort # 1b (6.0x1013 gc/kg) N=3 or more • Males 18-50 years old with genetically confirmed FD (pathogenic/likely pathogenic) Cohort 2 (2.0x1013 gc/kg) and suboptimal response to ERT N=3 or more •
Slide 6: Clinical Trial Enrollment Progress
AMT-191: Clinical Trial Enrollment Progress EXPOSURE (in weeks)a Total of 11 patients were dosed across three cohorts: • Cohort 1 (n=4, 6.0x10¹³ gc/kg) 20 • Cohort 2 (n=3, 2.0x10¹³ gc/kg) • Cohort 3 (n=4, 4.0x10¹³ gc/kg) 10 Six of 11 patients have withdrawn from ERT and remained stable on their own
Slide 7: Demographics and Baseline Disease Characteristics
Demographics and Baseline Disease Characteristics Dose Ranging (ongoing) Age (median range) 35 (20-50 years old) Sex Male 11 Female 00 ERT status On ERT 11 Naïve/Pseudo naive 00 eGFR 90-120 10 60-90 01 40-60 00 ERT, enzyme replacement therapy. 7
Slide 8: Exploratory Efficacy Biomarkers: Sustained α-GAL activity
AMT-191: Exploratory Efficacy Biomarkers Sustained α-GAL activity as of cutoff date post dosinga,b (regardless of ERT status) GGC plasma: α-GAL 2x1013 gc/kg GGC plasma: α-GAL 6x1013gc/kg GGC plasma: α-GAL 4x1013gc/kg 10000 10000 10000 1000 1000 1000 nmol/hr/mL nmol/hr/mL nmol/hr/mL 100 100 100 ULN 8
Slide 9: Exploratory Efficacy Biomarkers: Stable Lyso-GB3
AMT-191: Exploratory Efficacy Biomarkers Stable Lyso-GB3 as of cutoff datea,b post dosing (regardless of ERT status) Lyso-GB3 plasma 6x1013 gc/kg Lyso-GB3 plasma 4x1013 gc/kg Lyso-GB3 plasma 2x1013 gc/kg 80 80 80 70 70 70 60 60 60 50 50 50 ng/mL 40 40 40 30 30 30 20 20 20 10 10 10 ULN 2.7 ULN 2.7 UL
Slide 10: Dose ranging of plasma α-GAL in study cohorts
AMT-191: Dose ranging of plasma α-GAL in study cohorts Observed enzymatic production supports further developmenta,b ALL cohorts α-GAL plasma (- median, all data) - log axis 10000 1000 6x1013 gc/kg nmol/hr/mL 4x1013 gc/kg Therapeutic Goal 100 2x1013 gc/kg ULN 8.66 10 Mean Normal 3.57 LLN 1.38 1 ti 1
Slide 11: Safety Data To Cutoff Date
AMT-191: Safety Data To Cutoff Datea Manageable Safety Profile • No Infusion-Related Reactions Reported • Treatment-Emergent Adverse Events: • Majority Grade 1-2 laboratory values • One Grade 3 laboratory values (LFT elevations) - resolved with brief corticosteroid treatments • SAEs: • Two SAEs cons
Slide 12: Summary of Data
AMT-191: Summary of Data Preliminary results support further development Overall Safety Profile • Manageable safety profile across cohorts • No infusion reactions observed across all participants • Transient LFT elevations manageable with corticosteroids as needed All Cohort Exploratory Efficacy • S
Slide 13: Acknowledgements
Acknowledgements AMT-191 Clinical Trial uniQure Clinical Trial Team Fabry Community Centers Active in Cohorts 1- • Arian Pano, MD, MPH, • National Fabry Disease 3 Consultant, Program Lead and Foundation, Fabry Support • Maryam Banikazemi MD, NYC Clinical Lead and Information Group, Fabry Health + Ho