Capsida Biotherapeutics Announces Publication in Caltech’s Nature Neuroscience Demonstrating Robust, Noninvasive IV Gene Delivery Targeted to the Brain While Avoiding the Liver

THOUSAND OAKS, Calif., December 9, 2021 /PRNewswire/ — Capsida Biotherapeutics, Inc., an industry-leading gene therapy platform company creating a new class of targeted, non-invasive gene therapies for patients with debilitating and life-threatening genetic disorders , announced today a research published in Natural neuroscience which demonstrated the ability to design and select novel capsid variants, with enhanced enrichment in the brain and decreased hepatic targeting after intravenous (IV) administration in rodents and non-human primates. The research was carried out by the laboratory of Viviana Gradinaru, Ph.D., Professor of Neuroscience and Biological Engineering and Director of the Center for Molecular and Cellular Neuroscience at the Chen Institute of Neuroscience in California Institute of Technology (Caltech). The publication, titled “AAV capsid variants with brain-wide transgene expression and decreased hepatic targeting after intravenous administration in mice and marmosets”, was published online today and can be accessed at https://go.nature.com/31I3osS.

Gene therapy is accelerating as a life-saving and life-enhancing treatment option for disorders affecting the brain. For a genetic intervention to be safe and effective, a gene therapy must express a transgene in affected brain cells while minimizing off-target expression. Adeno-associated viral (AAV) vectors are powerful options for delivering genetic payloads, but naturally occurring AAV serotypes have limited and overlapping tropisms, representing a significant barrier to therapeutic development. Research published in Natural neuroscience describes how multi-loop AAV combinatorial engineering was used to select capsids with brain-scale gene expression and liver scaling after IV administration in mouse and marmoset models. To achieve organ-specific targeting after intravenous administration, sequential engineering of multiple surface-exposed loops was performed. The work identifies capsid variants that were enriched in the brain by positive selective pressure and targeted away from the liver by negative selective pressure in Cre transgenic mice. These findings have extended to non-human primates after IV administration, enabling robust and non-invasive gene delivery to the central nervous system (CNS). Importantly, the identified capsids resulted in distinct transgene expression patterns in the brain, one of which showed high specificity for neurons.

“The work described in the Natural neuroscience highlights Caltech’s groundbreaking research that has provided a roadmap for Capsida’s noninvasive, proprietary, targeted gene therapy platform,” said Nick Goeden, Ph.D., Chief Technology Officer at Capsida, the first co-author of the study due to his previous research as a Caltech postdoctoral researcher. “We are pursuing several in-house programs using intravenous administration in humans and expect to file an IND in the second half of 2022.”

“The power of this engineering approach demonstrates the ability to create capsids that can target anatomical regions and cell types, while avoiding off-target involvement. The technology opens up the potential for safer and more effective therapeutic possibilities not achievable with traditional AAV gene therapy,” added Nicholas Flytzanis, Ph.D., Chief Scientific Officer at Capsida, and first co-author of the study. of research done while he was Chief Scientific Officer at Caltech.”Many gene therapy companies use surgical approaches to deliver drugs to the CNS, but our non-invasive technical approach offers the possibility of a broader option and more convenient to treat genetic diseases.

Capsida, co-founded by Flytzanis, Goeden and Gradinaru, holds an exclusive license to this technology, which has been developed in-house into a robust platform by which diverse, large-scale libraries with over 60 billion capsid sequences each are designed and screened in primates and disease-relevant human cell lines. Sequence and structure-based analyzes are combined with a fully automated engineering platform to quickly prioritize capsids with the most promising characteristics. Importantly, the AAV constructs of Capsida have been studied in hundreds of non-human primates to improve the predictability of these constructs in human clinical trials. Capsida has established collaborations with industry leaders AbbVie and CRISPR Therapeutics to develop next-generation gene therapies for CNS diseases.

About Capsida Biotherapeutics

Capsida Biotherapeutics Inc. is an industry-leading gene therapy platform company creating a new class of targeted, non-invasive gene therapies for patients with debilitating and life-threatening genetic disorders. Capsida’s technology allows targeted penetration of cells and organs, while limiting the collateral impact on non-target cells and organs, in particular the liver. This technology allows gene therapy to be administered non-invasively intravenously. Capsida’s technology is protected by a growing intellectual property portfolio that includes more than 30 patent applications and issued US patent 11,149,256. The company is exploring the use of the technology in a wide range of life-threatening genetic disorders. Its initial pipeline consists of several neurological disease programs. The company has strategic collaborations with AbbVie and CRISPR, which provide independent validation of Capsida’s technology and capabilities. Capsida is a multifunctional, fully integrated biotechnology company with proprietary adeno-associated virus (AAV) engineering, multimodal cargo development and optimization, translational biology, process development and advanced manufacturing, and extensive clinical development experience. Capsida’s high-throughput and biological AAV cargo engineering and optimization platform is the result of groundbreaking research in the laboratory of Viviana Gradinaru, Ph.D., Professor of Neuroscience at California Institute of Technology. Visit us at www.capsida.com to learn more.

SOURCECapsida Biotherapeutics