Apertura Gene Therapy has announced multiple licensing agreements for its blood-brain barrier-penetrant AAV capsid technology, marking a significant advancement in central nervous system gene therapy delivery. The biotechnology company has licensed its human transferrin receptor 1 capsid (TfR1 CapX) to Galibra Neuroscience and Emugen Therapeutics, with a third undisclosed venture-backed company entering an option agreement for multiple CNS indications.
Revolutionary Capsid Technology Addresses Critical Delivery Challenge
The TfR1 CapX capsid represents a breakthrough in gene therapy delivery, building on foundational work from Ben Deverman, Senior Director of Vector Engineering at The Broad Institute of Harvard and MIT. The intravenously dosed AAV capsid binds to the human transferrin receptor, TfR1, enabling it to cross the blood-brain barrier and broadly transduce brain tissues.
"Genetic therapy medicines are often limited by delivery challenges, particularly to crucial areas like the CNS, creating an urgent need for advanced capsids that can effectively access these tissues," said Dr. Diego Garzón, Apertura's Vice President of Corporate Development. "Not only is it important to target the CNS but equally important to avoid other tissues to avoid triggering adverse events."
In extensive preclinical testing conducted independently by several groups, TfR1 CapX has demonstrated remarkable selectivity to the CNS compared to other tissues, achieving more than 50% neuron transduction and 90% astrocyte transduction across different brain regions.
Targeting GABA-Related Disorders
Galibra Neuroscience will utilize TfR1 CapX for GABA-related disorders, focusing on the major brain inhibitory neurotransmitter that maintains neural communication balance and prevents over-excitation. GABA levels in healthy individuals are highly regulated by over 20 genes responsible for GABA signaling, with genetic variants leading to GABA imbalance and several rare pediatric disorders.
"Our work at Boston Children's Hospital demonstrated that the symptoms of a rare GABA disorder, succinic semialdehyde dehydrogenase deficiency (SSADHD) are reversible by gene replacement therapy," said Dr. Henry Lee, Co-Founder of Galibra Neuroscience. The company plans to combine Apertura's TfR1 CapX with proprietary payloads for a brain-wide and systemic gene replacement approach.
Alexander Rotenberg, Professor of Neurology at Boston Children's Hospital and Harvard Medical School and Co-Founder of Galibra Neuroscience, emphasized the technology's potential: "We are excited to use the Apertura technology to safely deliver critical genetic materials to desired cellular targets, resulting in highly effective and safe therapeutic options for patients in need."
Addressing Neurodevelopmental and Neurodegenerative Diseases
Emugen Therapeutics is developing novel gene therapy solutions targeting neurodevelopmental and neurodegenerative diseases. "We are advancing therapeutic strategies that target the root causes of complex neurological disorders," said Dr. Tyler Brown, Emugen's Chief Operating Officer. "TfR1 CapX enables us to overcome one of gene therapy's key challenges—delivering payloads across the blood-brain barrier—by providing a non-invasive capsid platform."
The company aims to leverage this technology alongside transformative gene therapy payloads designed to restore neural function and improve outcomes for patients with high unmet medical need.
Industry-Wide Impact and Future Prospects
The licensing agreements reflect broader industry recognition of the critical need for effective CNS delivery systems. "Across the industry, partners are looking for capsids that not only reach the CNS effectively but also support safe, systemic delivery—without triggering adverse immune responses," said Andrew Steinsapir, Director and Gene Therapy Program Lead at Deerfield Management and Acting CTO of Apertura.
Apertura, founded in 2021 on technology from the Broad Institute with support from Deerfield Management Company, has positioned itself at the forefront of addressing severe unmet medical needs through advanced gene therapy solutions. The company's TfR1 CapX technology addresses fundamental challenges in gene therapy delivery, potentially accelerating the development of treatments for various CNS disorders.
These collaborations represent a significant step forward in overcoming delivery challenges that have historically limited the effectiveness of gene therapies for neurological conditions, offering new hope for patients with rare genetic disorders and complex neurological diseases.
