Gene remedy builders depend on engineered viruses to hold genetic cargo to cells. Adeno-associated virus, the viral vector that has been the spine of this burgeoning subject, exhibits a specific choice for concentrating on liver cells. That’s nice for liver problems or illnesses related to proteins produced by the liver, however the incapability to focus on different cells limits gene remedy’s attain.
Capsida Biotherapeutics goals to beat these limitations with expertise that takes AAV past the liver. The Thousand Oaks, California-based firm can now ramp up its analysis, supported by a just lately introduced $50 million Sequence A spherical of financing from Versant Ventures and Westlake Village BioPartners. Along with that funding, the startup additionally introduced a multi-drug analysis alliance with pharmaceutical large AbbVie. That partnership brings Capsida a further $80 million up entrance plus a $10 million fairness funding.
There two FDA-approved gene therapies, Luxturna, from Roche subsidiary Spark Therapeutics, and Zolgensma from Novartis, each use AAV, as do many gene therapies in growth. Capsida says the issue with utilizing naturally occurring variations of AAV is that these viruses have restricted potential to ship their genetic cargoes to sure cell varieties within the physique. Which means these therapies might require greater doses, which will increase the danger of an immune response or different issues related to the viral vector. That dosing limitation leaves many illnesses unaddressed, together with neurodegenerative problems.
Capsida’s strategy is conveyed by its title. The startup engineers capsids, the protein shells that envelop a gene remedy and ship it to the goal cell. The corporate says its AAV engineering platform generates capsids which can be optimized to focus on particular varieties of tissue and limits their potential to introduce genetic materials into tissues and cells that aren’t the targets of the remedy.
The Capsida expertise comes from the laboratory of Viviana Gradinaru, professor of neuroscience and organic engineering at Caltech. Utilizing machine studying, the platform display screen billions of engineered capsids to establish those with the power to exactly goal the specified tissue varieties, together with these of the central nervous system (CNS).
“Our high-throughput AAV engineering platform is designed to establish differentiated capsids and cargos that may efficiently ship gene therapies with superior cell and tissue concentrating on and security profiles than current-generation merchandise in each CNS and non-CNS illnesses,” Capsida CEO Robert Cuddihy stated in a ready assertion.
Based on Capsida, the corporate’s engineered capsids have demonstrated an enhanced potential to convey their genetic cargo into neurons versus different varieties of CNS cells, demonstrating potential for treating problems that require focused supply to those cells.
The flexibility of Capsida to convey AAV to the mind caught the eye of AbbVie. The North Chicago, Illinois, firm’s alliance with the startup covers three undisclosed CNS targets. For all three applications, Capsida will take the lead on capsid discovery efforts. If AbbVie workouts its choice for the primary two applications, Capsida might earn $530 million in choice and growth milestone funds. Upon exercising its choices, AbbVie will probably be liable for additional growth, and if accepted, commercialization of the therapies. Capsida would obtain royalties from gross sales if these therapies attain the market.
If AbbVie workouts its choice for the third illness goal, the deal provides Capsida the fitting to develop that program by human-proof-of-concept research. After that, the companions would break up additional analysis prices, and if accepted, the earnings from gross sales of the remedy. AbbVie would lead late-stage growth and commercialization, whereas Capsida would have the choice to co-promote the remedy, if accepted, within the U.S.
Capsida isn’t the one firm working to take gene remedy into CNS problems. Dallas-based Taysha Gene Therapies launched a couple of yr in the past with a pipeline of gene remedy candidates for CNS problems and analysis that included the engineering of recent capsids. Others growing AAV-based gene therapies for CNS problems embrace Philadelphia-based Passage Bio and Neurogene of New York.
Capsida additionally isn’t the one firm making use of looking for higher capsids. Harvard College spinout Dyno Therapeutics is utilizing synthetic intelligence and machine-learning strategies to display screen for AAV capsids that may goal specific tissues or cells, have a larger payload capability, and are much less more likely to immediate an immune response. Up to now, the Cambridge, Massachusetts-based startup isn’t growing its personal medicine and is as an alternative utilizing its expertise to assist different firms advance their gene remedy pipelines. Final fall, Dyno unveiled a analysis alliance with Roche that goals to develop new gene therapies for liver and CNS problems. That deal adopted comparable partnerships that Dyno struck final yr. The alliance with Sarepta Therapeutics is concentrated on muscular problems, whereas the one with Novartis goals to develop gene therapies for eye illnesses.
Capsida’s inner analysis will concentrate on neurodevelopmental and neurodegenerative problems. These illnesses weren’t disclosed however the firm stated that they may tackle areas during which gene therapies haven’t gained traction due to the difficulties of getting gene remedy to focus on the mind. Capsida expects to start out this yr the preclinical work that will help an investigational new drug software for its first gene remedy candidates. If these plans keep on observe, the corporate might enter the clinic subsequent yr.
Along with supporting the continued preclinical analysis of its lead gene remedy candidates, the Sequence A money may even go towards a producing facility slated to open later this yr. Capsida may even use its expertise to develop gene therapies for illnesses aside from CNS problems.
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