Gene therapy developers rely on engineered viruses to carry genetic cargo to cells. Adeno-associated virus, the viral vector that has been the backbone of this burgeoning field, shows a particular preference for targeting liver cells. That’s great for liver disorders or diseases associated with proteins produced by the liver, but the inability to target other cells limits gene therapy’s reach.
Capsida Biotherapeutics aims to overcome those limitations with technology that takes AAV beyond the liver. The Thousand Oaks, California-based company can now ramp up its research, supported by a recently announced $50 million Series A round of financing from Versant Ventures and Westlake Village BioPartners. In addition to that funding, the startup also announced a multi-drug research alliance with pharmaceutical giant AbbVie. That partnership brings Capsida an additional $80 million up front plus a $10 million equity investment.
There two FDA-approved gene therapies, Luxturna, from Roche subsidiary Spark Therapeutics, and Zolgensma from Novartis, both use AAV, as do many gene therapies in development. Capsida says the problem with using naturally occurring variations of AAV is that these viruses have limited ability to deliver their genetic cargoes to certain cell types in the body. That means these therapies may require higher doses, which increases the risk of an immune response or other complications associated with the viral vector. That dosing limitation leaves many diseases unaddressed, including neurodegenerative disorders.
Capsida’s approach is conveyed by its name. The startup engineers capsids, the protein shells that envelop a gene therapy and deliver it to the target cell. The company says its AAV engineering platform generates capsids that are optimized to target specific types of tissue and limits their ability to introduce genetic material into tissues and cells that aren’t the targets of the treatment.
The Capsida technology comes from the laboratory of Viviana Gradinaru, professor of neuroscience and biological engineering at Caltech. Using machine learning, the platform screen billions of engineered capsids to identify the ones with the ability to precisely target the desired tissue types, including those of the central nervous system (CNS).
“Our high-throughput AAV engineering platform is designed to identify differentiated capsids and cargos that will successfully deliver gene therapies with superior cell and tissue targeting and safety profiles than current-generation products in both CNS and non-CNS diseases,” Capsida CEO Robert Cuddihy said in a prepared statement.
According to Capsida, the company’s engineered capsids have demonstrated an enhanced ability to bring their genetic cargo into neurons versus other types of CNS cells, demonstrating potential for treating disorders that require targeted delivery to these cells.
The ability of Capsida to bring AAV to the brain caught the attention of AbbVie. The North Chicago, Illinois, company’s alliance with the startup covers three undisclosed CNS targets. For all three programs, Capsida will take the lead on capsid discovery efforts. If AbbVie exercises its option for the first two programs, Capsida could earn $530 million in option and development milestone payments. Upon exercising its options, AbbVie will be responsible for further development, and if approved, commercialization of the therapies. Capsida would receive royalties from sales if these treatments reach the market.
If AbbVie exercises its option for the third disease target, the deal gives Capsida the right to develop that program through human-proof-of-concept studies. After that, the partners would split further research costs, and if approved, the profits from sales of the therapy. AbbVie would lead late-stage development and commercialization, while Capsida would have the option to co-promote the therapy, if approved, in the U.S.
Capsida isn’t the only company working to take gene therapy into CNS disorders. Dallas-based Taysha Gene Therapies launched about a year ago with a pipeline of gene therapy candidates for CNS disorders and research that included the engineering of new capsids. Others developing AAV-based gene therapies for CNS disorders include Philadelphia-based Passage Bio and Neurogene of New York.
Capsida also isn’t the only company applying trying to find better capsids. Harvard University spinout Dyno Therapeutics is using artificial intelligence and machine-learning techniques to screen for AAV capsids that can target particular tissues or cells, have a greater payload capacity, and are less likely to prompt an immune response. So far, the Cambridge, Massachusetts-based startup isn’t developing its own drugs and is instead using its technology to help other companies advance their gene therapy pipelines. Last fall, Dyno unveiled a research alliance with Roche that aims to develop new gene therapies for liver and CNS disorders. That deal followed similar partnerships that Dyno struck last year. The alliance with Sarepta Therapeutics is focused on muscular disorders, while the one with Novartis aims to develop gene therapies for eye diseases.
Capsida’s internal research will focus on neurodevelopmental and neurodegenerative disorders. Those diseases were not disclosed but the company said that they will address areas in which gene therapies haven’t gained traction because of the difficulties of getting gene therapy to target the brain. Capsida expects to start this year the preclinical work that would support an investigational new drug application for its first gene therapy candidates. If those plans stay on track, the company could enter the clinic next year.
In addition to supporting the ongoing preclinical research of its lead gene therapy candidates, the Series A cash will also go toward a manufacturing facility slated to open later this year. Capsida will also use its technology to develop gene therapies for diseases other than CNS disorders.
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