- Data to be presented at the 24th Annual Meeting of the American Society of Gene and Cell Therapy show up to 1000-fold higher transgene expression in the brain compared with conventional AAV gene therapy following IV administration
CAMBRIDGE, Mass., May 11, 2021 (GLOBE NEWSWIRE) -- Voyager Therapeutics, Inc. (NASDAQ:VYGR), a clinical-stage gene therapy company focused on developing life-changing treatments for serious neurological diseases, today will present new preclinical data demonstrating high transduction efficiency of the company's novel adeno-associated virus (AAV) capsids in the central nervous system (CNS) after intravenous dosing in non-human primates. Data will be presented at the 24th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) taking place virtually May 11-14, 2021.
"Efficient targeting of the CNS, including the ability to penetrate the blood brain barrier and transduce target cells, have represented a significant challenge in gene therapy hindering the field's ability to effectively address many serious neurological diseases," Omar Khwaja, M.D., Ph.D., Chief Medical Officer and Head of Research & Development at Voyager. "We've now been able to show that our novel capsid variants not only cross the blood brain barrier but achieve widespread transduction of multiple brain regions including the cortex, thalamus, striatum, cerebellum, brainstem and spinal cord. We believe these capsids can provide a new way forward to treat a broad range of CNS indications, potentially at significantly lower doses than currently available AAV serotypes."
Data will be shared in an oral presentation titled, "RNA-driven Evolution of AAV Capsid Libraries Identifies Variants with High Transduction Efficiency in Non-Human Primate Central Nervous System," (Abstract #51) by Mathieu Nonnenmacher, Ph.D., Director and Head of Capsid Discovery, showing that several capsid variants derived from the company's directed evolution RNA-based screening platform, TRACERTM (Tropism Redirection of AAV by Cell-type-specific Expression of RNA), demonstrated significantly enhanced activity relative to AAV9, the most commonly used vector for CNS gene therapy.
- A subset of capsids showed a 10-fold or higher improvement in transduction of the brain and spinal cord, compared to AAV9.
- The most efficient capsid identified in the work to be presented, TRACER 9P801, displayed more than 1,000-fold higher transgene expression in the brain and 100-fold higher transgene expression in the spinal cord.
- The overall tolerability of 9P801 was favorable and no toxicity was observed in the liver, spinal cord or dorsal root ganglia (DRG).
- Immunohistochemical analysis indicated that 9P801 displayed predominant neuronal tropism and achieved widespread transduction of multiple brain regions including the cortex, thalamus, putamen and brainstem.
- The TRACER platform generates large data sets on engineered capsid performance in a relevant primate species suitable for in silico approaches to optimizing capsid selection for specific cellular targeting and tropism.
Voyager's TRACER system is a broadly-applicable, RNA-based functional screening platform that allows for rapid in vivo evolution of AAV capsids with cell-specific transduction properties in wild-type animals. TRACER candidates were tested individually by low dose intravenous injection and their tropism for the CNS analyzed by measuring transgene RNA expression, viral DNA biodistribution and immunohistochemistry.
Further information about the Company's TRACER platform and pipeline, including novel capsid-enabled new programs, will be shared at an upcoming investor and analyst event in July 2021.