Abstract Details

Title Preclinical Pharmacology and Toxicology of intrathecally infused AAV9-hABCD1, a gene therapy candidate for AMN, in Non-Human Primates

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S29 - Preclinical and Observational Studies of Neuromuscular Diseases (1:12 PM-1:24 PM)

Poster/Presentation
Number 002

Background Adrenomyeloneuropathy (AMN) is a form of X-linked Adrenoleukodystrophy (ALD) caused by mutations in the gene encoding the ATP Binding Cassette subfamily D member-1 (ABCD1). AMN is characterized by a dying-back axonopathy affecting spinal cord tracts leading to loss of mobility. We are developing SBT101, an AAV9-based gene therapy encoding a functional hABCD1, for use as a treatment for AMN.

Objective To evaluate the safety and biodistribution of SBT101, an AAV9 based gene therapy vector capable of delivering functional copy of the human ABCD1 (hABCD1) gene into intrathecal space in Non-Human Primates (NHP).

Design/Methods Preclinical studies to assess the clinical chemistry, neurological function, biodistribution, safety, immune responses of ST101 were performed in naïve cynomolgus monkeys with low pre-existing neutralizing antibodies (NAb) to AAV9. Animals were injected with a single intrathecal dose of SBT101 at doses of 1.5E13, 3.5E13 and 7.5E13 vector genomes (VG)/animal and observed for 6 months.

Results

SBT101 was well tolerated and no adverse events were noted. Biodistribution studies indicated a dose dependent presence of AAV9 VG and hABCD1 transcript in Central Nervous System (CNS) tissues. Histopathological evaluations showed a slight to moderate increase in the incidence of axonal degeneration and presence of mononuclear infiltrates in CNS and peripheral tissue at 3 months, which were found to be reduced or unremarkable by 6 months. High titers of NAb and antibodies against AAV9 were observed at the end of the study and are dose dependent.

Conclusions These results provide evidence that delivery of SBT101 at doses predicted to be clinically relevant in AMN patients has a promising and relatively unremarkable safety profile in non-human primates, and further enables our path to the clinic for the potential treatment of AMN.

Authors/Disclosures
Vidyullatha Vasireddy, PhD (SwanBio Therapeutics Inc.) PRESENTER	Dr. Vasireddy has stock in SwanBio Therapeutics.
	No disclosure on file
	No disclosure on file
Karen Kozarsky, PhD (SwanBio Therapeutics)	Dr. Kozarsky has received personal compensation for serving as an employee of SwanBio Therapeutics. Dr. Kozarsky has received stock or an ownership interest from SwanBio Therapeutics.
David W. Anderson, PhD (SwanBio Therapeutics Inc.)	Dr. Anderson has received personal compensation for serving as an employee of SwanBio Therapeutics Inc. Dr. Anderson has received personal compensation for serving as an employee of Spark Therapeutics Inc. An immediate family member of Dr. Anderson has received personal compensation for serving as an employee of GSK. An immediate family member of Dr. Anderson has received personal compensation for serving as an employee of Novartis. Dr. Anderson has stock in SwanBio Therapeutics Inc. An immediate family member of Dr. Anderson has stock in GSK. Dr. Anderson has stock in Roche . An immediate family member of Dr. Anderson has stock in Novartis.