- Gene editing company CRISPR Therapeutics is expanding its research manipulating genetic code to treat disease, entering into an agreement with private company Capsida Biotherapeutics to collaborate on therapies for two neurodegenerative disorders. The partners plan to rely on Capsida's technology to better target tissues in the central nervous system.
- Under the collaboration, CRISPR will develop the gene editing tools for both programs, while Capsida will engineer the viral protein shells that will deliver the treatments. Each company will lead research and development of a single program, however.
- After attracting billions of dollars of investment following two Food and Drug Administration gene therapy approvals in 2017 and 2019, the field has recently hit setbacks on safety, manufacturing and more modest-than-expected efficacy. More and more, companies are focusing on developing better delivery technologies, which promise to expand treatment "payload" and target cells more precisely to improve safety and effectiveness.
Capsida emerged publicly in April with a funding round that included $50 million from two venture capital firms and $90 million from AbbVie for the development of three experimental programs. The startup's technology comes from the California Institute of Technology's neuroscience institute, and can screen billions of potential protein shells called capsids to choose ones that target human tissues precisely.
Improving delivery is particularly important in neuroscience. Neurological disorders are challenging to treat with gene-based treatments because of the biological barrier between blood and the central nervous system, which is designed to prevent pathogens from passing through.
One harmless virus, an adeno-associated virus 9 or AAV9, can cross, and is the delivery tool used by Novartis' gene therapy Zolgensma, which is infused systemically in patients younger than 2. For older patients, however, the Swiss pharma has experimented with infusing the treatment directly into the spinal cord fluid to bypass the blood-brain barrier.
Capsida's technology is also based around AAV strains. But the company says it has been able to optimize them for the cells in the nervous system that are most affected by degenerative disorders.
AAV is a tool used most frequently by companies that aim to replace broken genes with functional copies, rather than edit them. But more companies are exploring repurposing the viral vectors to shuttle gene editing systems like CRISPR-cas9 into the body's cells, as CRISPR hopes to with Capsida.
Under the collaboration, the two companies will develop gene editing therapies for Friedreich's ataxia, on which CRISPR will lead, and familial amytrophic lateral sclerosis, on which Capsida will lead. The companies didn't disclose the financial terms of the deal.
The two projects will add to four other experimental gene therapies in CRISPR's pipeline that aim to treat rare diseases by manipulating genetic expression through editing inside the body. None have been tested in humans yet, however.
Those four in vivo products emerged from a collaboration with StrideBio, and are aimed at rare diseases of muscles, lungs and metabolism. But the company had also developed some approaches to editing genes associated with central nervous system disorders, and needed to find a delivery technology, Lawrence Klein, CRISPR's chief operating officer, said in an interview.
"We've done the gene editing work. What we were sort of missing was the best-in-class, nervous system-directed AAV, and that's where we landed with Capsida," he said.
CRISPR's most-advanced experimental drugs, which have been tested in patients, use gene editing to alter human cells outside the body. The lead project is CTX001, which treats the blood conditions beta thalassemia and sickle cell disease and is partnered with Vertex Pharmaceuticals.
Recently reported results from 22 patients across two trials of CTX001 were promising, suggesting the treatment could dramatically change the course of both diseases and, potentially, offer a functional cure.