Sio Gene Therapies — Technical Presentation (February 2022)
15 slides from Sio Gene Therapies's technical presentation, Feb 9, 2022
Slide 1: Phase 1/2 Trial of AXO-AAV-GM1 Gene Therapy for GM1 Gangliosidosis
Phase 1/2 Trial of AXO-AAV-GM1 (AAV9-GLB1) Gene Therapy for Infantile- and Juvenile-Onset GM1 Gangliosidosis Cynthia Tifft, MD, PhD National Human Genome Research Institute National Institutes of Health (NIH) Exhibit 99.1 1
Slide 2: Disclosure Information: Cynthia Tifft, MD, PhD
2 Disclosure Information: Cynthia Tifft, MD, PhD 2 • I have nothing to disclose • I will discuss the following investigational use in my presentation: AXO-AAV-GM1 (AAV9-GLB1), an investigational gene therapy for infantile- and juvenile-onset GM1 gangliosidosis AXO-AAV-GM1 is an investigational thera
Slide 3: GM1 Gangliosidosis: A Devastating Pediatric Disease
3 GM1 Gangliosidosis: A Devastating Pediatric Disease Rare, autosomal recessive lysosomal storage disorder that is uniformly fatal Leads to rapid neurodegeneration and multisystem disease manifestations No disease modifying treatments are currently available Most patients are compound hetero
Slide 4: AXO-AAV-GM1 Study Design: First-in-human, Open-label Phase 1/2 Study
Registrational Study using Optimal Dose from Stage 1 STAGE 1: Dose Ranging STAGE 2: Efficacy & Safety Study Open-label, single-arm trial (NCT03952637, IND 18831) Low-Dose 1.5 x 1013 vg/kg (n=5) High-Dose 4.5 x 1013 vg/kg (n=3) Type II: Late-infantile/Juvenile: •3-year assessment •2-year long term fo
Slide 5: Key Eligibility Criteria and Study Endpoints
AXO-AAV-GM1 Study: Key Eligibility Criteria and Study Endpoints 5 6-12 MONTHS 1-12 YEARS • Genetic/biochemical diagnosis of GM1 • AAV antibody status • Disease severity • Vineland-3 ≥ 40 (Type II) Type I: Infantile-onset Type II: Late infantile & Juvenile-onset Key Patient Eligibility Criteria Key S
Slide 6: Subject Demographics
6 Subject Demographics *Diagnosed based on sibling diagnosis ꝉOnly safety data and CGI are included for Pt8, Pt9, and Pt10 AXO-AAV-GM1 is an investigational therapy. Safety and efficacy have not been established by any health authority. Participants (N = 10) Dose Gene Transfer Demographics Disease O
Slide 7: Overview of Adverse Events
7 Overview of Adverse Events Adverse Events (number of events) Low Dose (n = 7 subjects) High Dose (n = 3 subjects) Any treatment-emergent adverse events 47 25 Serious adverse events (all unrelated to AXO-AAV-GM1) 3 - AXO-AAV-GM1 is an investigational therapy. Safety and efficacy have not been estab
Slide 8: Dose-Related Increases in Serum β-galactosidase Activity
Dose-Related Increases in Serum β-galactosidase Activity 0 2 4 6 8 10 12 14 16 18 -30 0 2 4 6 8 10 12 14 16 18 -30 0 30 60 90 120 150 180 210 240 270 300 330 360 Days after gene therapy administration High Dose at 6M: β-gal Increases to Normal Range ß- ga la ct os id as e en zy m e ac tiv ity in se
Slide 9: Dose-Related Decreases in GM1 Ganglioside Levels in CSF
Mean level in healthy pediatric population1-3 Gene transfer 0 50 100 150 200 250 -30 0 50 100 150 200 250 -30 G M 1 G an gl io si de in CS F (n g/ m L) 30 60 90 120 150 180 210 240 270 300 330 360 Days after gene therapy administration Pt1 (LD, Juv) Pt2 (LD, Li) Pt3 (LD, Li) Pt4 (LD, Li) Pt5 (LD, Li
Slide 10: Consistent Declines in Major Oligosaccharides in Urine
0 0.1 0.2 0.3 0.4 0.5 -30 30 Hex4HexNAc3Hex5HexNAc3 0 0.5 1 1.5 2 2.5 -30 30 LD = Low dose, HD = High dose Juv = Juvenile, Li = Late infantile 1. Lawrence R. et al. Mol Genet Metab Rep. 2019; 21; Bruggink C. et al. Anal Bioanal Chem. 2012;403:1671–1683. 0 0.005 0.01 0.015 0.02 90 150 210 270 330 Day
Slide 11: Change in Total Brain Volume
AXO-AAV-GM1 Gene Therapy Study Change in Total Brain Volume Volumetric MRI Data: Change in Total Brain Volume GM1 Natural History Study1 Change in Total Brain Volume 1. Nestrasil I. et al. Mol Genet Metab. 2018; 123(2):97–104. To ta l B ra in V ol um e (m L) Age (months) 500 1000 1500 12 24 36 48 60
Slide 12: Vineland-3 Adaptive Behavior Scale
Vineland-3 Adaptive Behavior Scale Gross Motor Skills G ro w th Sc al e Va lu e Sc or e Fine Motor Skills Pt1 (LD, Juv) Pt2 (LD, Li) Pt3 (LD, Li) Pt4 (LD, Li) Pt5 (LD, Li) Pt6 (HD, Juv) Pt7 (HD, Juv) LD = Low dose, HD = High dose, Juv = Juvenile, Li = Late infantile Vineland-3 Evaluation points: Bas
Slide 13: Floor and Upright Mobility Assessments
13 Floor and Upright Mobility Assessments AXO-AAV-GM1 is an investigational therapy. Safety and efficacy have not been established by any health authority. Ambulates independently with mobility aid due to unsteady gait Non-ambulatory, dependent for wheeled mobility Able to pull to stand, unable to a
Slide 14: Disease Severity: Clinical Global Impression (CGI) Scale
14 Disease Severity: Clinical Global Impression (CGI) Scale Subject CGI-Severity Baseline CGI-Improvement from Baseline 1 Month 3 Months 6 Months 12 Months Pt1: LD, Juv Borderline ill No change No change No change Minimally improved Pt2: LD, Li Markedly ill No change Minimally improved Minimally imp
Slide 15: Summary and Acknowledgments
15 Summary and Acknowledgments AXO-AAV-GM1 was generally well-tolerated with no drug-related serious adverse events Biomarker results to-date demonstrate a dose-related increase in β-gal enzyme activity in serum, a dose-related decrease in GM1 ganglioside in CSF (indicating signs of CNS penetrat
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