Abeona Therapeutics Inc. · NASDAQ:ABEO
Abeona Therapeutics — Technical Presentation (February 2018)
22 slides from Abeona Therapeutics's technical presentation, Feb 9, 2018
Slide 1: A Global Phase 1/2 Clinical Trial of Systemic Gene Transfer of scAAV9.U1a.hSGSH for MPS IIIA
A Global Phase 1/2 Clinical Trial of Systemic Gene Transfer of scAAV9.U1a.hSGSH for MPS IIIA: Safety, Tolerability, and Efficacy Kevin M. Flanigan, MD Center for Gene Therapy Nationwide Children’s Hospital Columbus, OH 1
Slide 2: Disclosure Information
Disclosure Information ASGCT 2017 Kevin Flanigan, MD I have the following financial relationships to disclose: Consultant for Sarepta Therapeutics; PTC Therapeutics; Audentes ; Tivorsan ; Marathon; Italafarmico . Grant/Research support from CureDuchenne ; Ben’s Dream/The Sanfilippo Research Foundati
Slide 3: Sanfilippo Syndrome (MPSIII)
Sanfilippo Syndrome (MPSIII) Sanfilippo syndromes (MPS IIIA & IIIB) are inherited monogenic disorders that cause lysosomal enzyme deficiency • Two most common forms, each categorized by a deficient enzyme: - MPS IIIA ( SGSH ) - MPS IIIB ( NAGLU ) • Results in abnormal accumulation of glycosaminoglyc
Slide 4: Intravenous Administration of AAV9 as route and vector of choice for MPS gene therapy
Intravenous Administration of AAV9 as route and vector of choice for MPS gene therapy • Systemic delivery of AAV9 demonstrated safety in Non - Human - Primates (n=8) for MPS IIIB up to 6 months • AAV9 efficiently crosses the blood - brain - barrier • Expressed in multiple CNS cell types • Demonstrat
Slide 5: Clinical Trial Readiness: The NCH MPSIII Natural History Study
Clinical Trial Readiness: The NCH MPSIII Natural History Study • 25 subjects: 15 MPS IIIA and 10 MPS IIIB • Assessments at 0, 6, and 12 months • Established standards for biochemical (serum and CSF) studies and volumetric (MRI) relevant to the clinical trial • Validated neurocognitive and behavior o
Slide 6: Phase I/II gene transfer clinical trial of scAAV9.U1a.hSGSH for MPS IIIA
Phase I/II gene transfer clinical trial of scAAV9.U1a.hSGSH for Mucopolysaccharidosis (MPS) IIIA ClinicalTrials.gov : NCT02716246 • Phase 1/2 open - label, dose - escalation clinical trial - Cohort 1 : 5 X 10 12 vg/kg (n=3 subjects): ages 6.5, 7.0 and 5.4 - Cohort 2 : 1 X 10 13 vg/kg (n=3 subjects):
Slide 7: Dosing and short-term monitoring
Dosing and short - term monitoring • Day - 1: subjects receive first dose of oral prednisolone elixir at 1 mg/kg/day. • Day 0: subjects receive gene transfer delivered under sedation within the Procedure Center over 15 minutes. • First 48 hours: Subjects are monitored in the Pediatric Intensive Care
Slide 8: No drug-related serious adverse events through >3,100 days cumulative post-injection
No drug - related serious adverse events (SAE) through >3,100 days cumulative post - injection Most common non - serious adverse events (AE): • Irritability (n=6), attributed to prednisolone therapy • Vomiting (n=5), judged unrelated/unlikely related • Upper respiratory infection (n=5), judged unrel
Slide 9: AAV9 Capsid Peptide Pool immune response and ALT levels
AAV9 Capsid Peptide Pool 1 AAV9 Capsid Peptide Pool 2 AAV9 Capsid Peptide Pool 3 hSGSHPeptide Pool 1 hSGSHPeptide Pool 2 Subject C Subject A Subject B S c r e e n i n g D a y - 1 D a y 1 D a y 7 D a y 1 4 D a y 3 0 D a y 4 5 D a y 6 0 D a y 7 5 D a y 9 0 O f f s t e r o i d M o n t h 6 M o n t h 1 2
Slide 10: Immune response and ALT levels by subject
S c r e e n i n g D a y - 1 D a y 1 D a y 7 D a y 1 4 D a y 3 0 D a y 4 5 D a y 6 0 D a y 7 5 D a y 9 0 M o n t h 6 M o n t h 1 2 0 25 50 75 100 125 150 0 25 50 75 100 125 150 MPS-IIIA-07 Day U / L Last steroid dose Begin taper S c r e e n i n g D a y - 1 D a y 1 D a y 7 D a y 1 4 D a y 3 0 D a y 4
Slide 11: Immune response and ALT levels by subject (continued)
Begin taper Begin taper S c r e e n i n g D a y - 1 D a y 1 D a y 7 D a y 1 4 D a y 3 0 D a y 4 5 D a y 6 0 D a y 7 5 D a y 9 0 0 25 50 75 100 125 150 175 200 0 25 50 75 100 125 150 175 200 MPS - IIIA - 09 Day U / L M o n t h 6 M o n t h 1 2 Begin taper S c r e e n i n g D a y - 1 D a y 1 D a y 7 D
Slide 12: Durable, Time and Dose-dependent Reduction in CSF Heparan Sulfate
Durable, Time and Dose - dependent Reduction in CSF Heparan Sulfate 12 - 25.8% - 58.7% - 69.3% - 48.8% - 57.1% - 64.4% -80% -70% -60% -50% -40% -30% -20% -10% 0% Day 30 Day 180 Day 360 % Reduction in CSF Heparan sulfate (HS) Cohort 1 Cohort 2 Cohort 3 All Cohorts/ timepoints are n=3 except Cohort 1
Slide 13: Durable, Time and Dose-dependent Reduction in Urine Heparan Sulfate
13 Durable, Time and Dose - dependent Reduction in Urine Heparan Sulfate - 64.2% - 64.2% - 54.2% - 29.2% - 29.2% - 54.0% - 65.2% - 63.1% - 55.0% - 91.9% - 73.4% - 94.9% -110% -100% -90% -80% -70% -60% -50% -40% -30% -20% -10% 0% Day 30 Day 60 Day 90 Day 180 Day 360 % Reduction in Urine Heparan sulfa
Slide 14: Durable, Time and Dose-dependent Reduction in Urine Total GAG
14 Durable, Time and Dose - dependent Reduction in Urine Total GAG - 60.4% - 51.5% - 30.7% - 30.6% - 18.3% - 37.4% - 55.9% - 45.4% - 39.9% - 61.5% - 58.3% - 68.2% -100% -90% -80% -70% -60% -50% -40% -30% -20% -10% 0% Day 30 Day 60 Day 90 Day 180 Day 360 % Reduction in Urine Total GAG Cohort 1 Cohort
Slide 15: Durable, Time and Dose-dependent Reduction in Liver Volume by MRI
Cohort 1 % Normal Liver Volume Subject A Subject B Subject C Screening ϮϮϱй 202% ϮϮϱй Day 30 ϭϴϯй ϭϳϰй ϭϱϳй Day 180 ϭϰϳй ϭϱϬй ϭϭϵй Day 360 ϭϰϳй 149% ϭϭϲй Cohort 2 % Normal Liver Volume Subject D Subject E Subject F Screening 211% 194% 183% Day 30 171% 157% 168% Day 180 151% 140% 138% Durable, Time a
Slide 16: Cohort 1: Evidence for Neurocognitive Stabilization (Leiter) Compared to Natural History Study
16 Cohort 1: Evidence for Neurocognitive Stabilization ( Leiter ) Compared to Natural History Study at 1 Year Follow - Up NHS C1 age equivalent group (n=8): • age 4.2 - 6.4 years • Mean decline for 12 observations over six month periods *Cohort 1 (n=2): • 1 subject was unable to be assigned a valid
Slide 17: Cohort 2: Neurocognitive Stabilization (Leiter) Compared to Natural History Study
17 Cohort 2: Neurocognitive Stabilization ( Leiter ) in 2 of 3 Subjects Compared to Natural History Study at 6 - months Follow - Up NHS C2 age equivalent group (n=3): • age 2.1 - 2.8 years • Mean decline for 3 observations over six month periods
Slide 18: Cohort 1: Stabilization (Vineland) of Adaptive Behavior Compared to Natural History Study
18 Cohort 1: Stabilization (Vineland) of Adaptive Behavior Compared to Natural History Study at 1 Year Follow - Up NHS C1 age equivalent group (n=9): • age 4.2 - 6.4 years • Mean decline for 12 observations over six month periods
Slide 19: Cohort 2: Adaptive Behavior (Vineland) Compared to Natural History Study
19 Cohort 2: Adaptive Behavior (Vineland) Compared to Natural History Study at 6 - months Follow - Up NHS C2 age equivalent group (n=3): • age 2.1 - 2.8 years • Mean decline for 3 observations over six month periods
Slide 20: Systemic delivery of scAAV9.U1a.hSGSH for MPSIIIA is well tolerated and demonstrates a biological effect
Systemic delivery of scAAV9.U1a.hSGSH for MPSIIIA is well tolerated and demonstrates a biological effect • Well - tolerated following systemic delivery in 10 subjects through > 3,100 follow - up days • Evidence of efficacy , including: – Decreased CSF GAGs (HS fragments) at 30, 180 and 360 days – Di
Slide 21: Further demonstration of Systemic AAV9 Safety and Efficacy in Phase 1/2 Clinical Trial for MPS IIIB
Further demonstration of Systemic AAV9 Safety and Efficacy in Phase 1/2 Clinical Trial for MPS IIIB ~300 fold increased enzyme activity In plasma post gene transfer 0% - 60% -70% -60% -50% -40% -30% -20% -10% 0% Screening Day 30 % Decrease in Plasma Heparan sulfate from baseline (pmol/mL) Cohort 1 (
Slide 22: Acknowledgments
Acknowledgments • Nick Smith, MD, Ph.D – PI – Adelaide • Maria Couce , MD – PI – Santiago de Compostella • Maria Castro , MD – Sub - Investigator, Santiago de Compostella • Kristen Truxal, MD – Co - Investigator, NCH • Kim McBride, MD – Co - Investigator, NCH • Maria Fuller, Ph.D – Director, SA Path
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