Abstract Details

Title Safety, Tolerability, and Preliminary Evidence of Biopotency in Transpher B, a Multicenter, Single-dose, Phase 1/2 Clinical Trial of ABO-101 Gene Therapy for Sanfilippo Syndrome Type B (Mucopolysaccharidosis IIIB)

Topic Child Neurology and Developmental Neurology

Presentation(s) S27 - Child Neurology and Developmental Neurology: Neurogenetics: Translating Knowledge to Therapy (2:00 PM-2:12 PM)

Poster/Presentation
Number 006

Objective

To develop a gene therapy treatment for Mucopolysaccharidosis IIIB (MPS-IIIB) based on intravenous administration of ABO-101.

Background

MPS-IIIB is a lysosomal storage disorder manifesting early in childhood with severe neurodegeneration.

Design/Methods

Transpher B is Phase 1/2 clinical trial assessing the safety and efficacy of a single intravenous administration of ABO-101, a single-stranded AAV9-based vector expressing the human NAGLU gene for the treatment of MPS-IIIB. Primary endpoints are safety and neurocognitive development and secondary endpoints include, among others, evaluation of biomarkers and liver volume.

Results Six patients have been enrolled across two dose cohorts (Cohort 1, 2x10¹³ vg/kg, n=2; Cohort 2, 5x10¹³ vg/kg, n=4) with a mean follow-up of 15 months in Cohort 1 (range 9-22 months) and 3 months in Cohort 2 (range 0.5-5 months). Intravenous administration of ABO-101 was well tolerated with no serious drug-related adverse events. Cohort 1 subjects showed a rapid decrease in CSF heparan sulfate fragments at Day30 (n=2, 53%), which decreased further at Months 6 and 12 (n=1, 60% and 70% respectively), as well as significant reductions in urine HS and glycosaminoglycans by Day 90 (Cohort 1: 33.3% and 56.8% respectively n=2, Cohort 2: 64.3% and.83.3% respectively n=1). These reductions were sustained to Month 18 in the patient followed longer (63.3% and 53.9% respectively, n=1). Liver volume excess decreased 33% by Day 30 (Cohort 1, n=2) and 73.6% and 69.8% by Months 6 and 12, respectively (Cohort 1, n=1). Plasma enzyme activity was normalized in patients from Cohort 1 to Day 60-90 and returned to baseline levels by Month 6 (n=2) while remaining normal in Cohort 2 patients by Day 60-90 (n=2).

Conclusions

Overall, these data show a good safety and tolerability profile of ABO-101 administered intravenously to children with MPS-IIIB and provide proof of biological activity in several tissues including liver and CNS.

Authors/Disclosures
PRESENTER	No disclosure on file
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	No disclosure on file
Kevin M. Flanigan, MD, FAAN (Nationwide CHildrens Hospital)	Dr. Flanigan has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sarepta. Dr. Flanigan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Apic Bio. Dr. Flanigan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AavantiBio. Dr. Flanigan has stock in 4D Molecular Therapeutics. The institution of Dr. Flanigan has received research support from Abeona Therapeutics. The institution of Dr. Flanigan has received research support from Sarepta Therapeutics. The institution of Dr. Flanigan has received research support from Astellas Therapeutics. Dr. Flanigan has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
J Ruiz	J Ruiz has received personal compensation for serving as an employee of Abeona Therapeutics. J Ruiz has received stock or an ownership interest from Abeona Therapeutics.

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