Last week, the California Institute for Regenerative Medicine (CIRM) approved a new funding program aimed at accelerating gene therapies for rare diseases by moving away from traditional approaches that develop a single therapy at a time. The initiative sets aside $100 million over two years to create a scalable model for delivering platform-based genetic therapies for rare diseases.
The so-called Rare Disease Acceleration Platform and Innovation and Delivery (RAPID) program aims to build on the recent success story of baby KJ Muldoon. Scientists first shared KJ’s story last year at the annual meeting of the American Society for Gene and Cell Therapy. They reported successfully developing a personalized CRISPR therapy for a child born with a rare genetic metabolic disorder known as severe carbamoyl phosphate synthetase 1 deficiency.
CIRM, a state agency that has funded cell and gene therapy development for more than a decade, has funded a large portfolio of programs spanning both rare and prevalent diseases. The RAPID initiative marks a shift from that approach, said Shyam Patel, PhD, CIRM associate vice president of preclinical development, in an interview. At least 10,000 unique rare diseases cumulatively affect over 30 million people in the United States. About half of all CIRM awards support clinical trials for several of these diseases, including LAD-1, forms of muscular dystrophy, Danon syndrome, Machado-Joseph disease, Pitt Hopkins syndrome, and others.
“This is an attempt to fund a different way of funding those projects as well as to create a different model for development” that works “across different types of diseases and therapeutic technologies,” Patel told GEN. It is especially timely given the growing regulatory and technical momentum behind platform strategies, including new guidance from the U.S. Food and Drug Administration.
CIRM’s RAPID program will fund two types of proposals aimed at advancing in vivo genetic therapies for rare diseases. One set of awards will support projects that have already engaged with the FDA and received pre-IND feedback on their platform approach. CIRM awards will fund activities from IND-enabling studies through completion of first-in-human clinical trials across multiple indications. Patel expects these awards will focus on disease areas where platform approaches have gained traction, such as metabolic, immune, retinal, and hearing disorders.
The second track will support emerging platforms that are still optimizing candidates and at the early stages of regulatory discussions. By supporting early-stage projects, Patel said, the agency hopes to bring new technologies into the pipeline and expand the range of diseases addressed.
Funding will be allocated in two $50 million cycles—one in each fiscal year for the next two years—with no specific cap per project. So, for example, “we could have something where one project is proposing maybe three candidates and another one proposing 10 candidates [so] the dollars should scale accordingly,” he explained. Projects will be reviewed and scored by a panel of experts made up of scientists, clinicians, product developers, and others, before being submitted to the CIRM board for approval.
Lead applicants for projects must be California-based, and they could be companies, academic institutions, or independent nonprofit organizations. Though the lead organizations have to be local, projects could include collaborations with investigators, suppliers, vendors, and service producers outside of California. Additionally, applicants will have to justify their proposed budgets based on the scope of their work. Applications will likely be due early to late summer of this year. Funded projects that support IND-enabling work through early clinical trials can receive funding for up to six years, while the earlier-stage ones are capped at 3.5 years to encourage faster progress.
RAPID projects will also be expected to participate in near real-time knowledge sharing within the CIRM awardee network, as well as in sharing data and knowledge with the public more broadly. To that end, CIRM is putting in place a structured knowledge-sharing approach that includes clear requirements and timelines.
Data sharing is critical because, as awardees “execute on their milestones, we want them to be able to leverage the other RAPID projects as well as [the] massive portfolio of awards that we are funding,” Patel said. “We expect them to share their study designs, their emerging data, and their regulatory strategy and interactions within the CIRM network to help inform their strategy and execution.” Awardees are also expected “to share the regulatory correspondences as well as appropriate study designs and emerging data with the public, and we’re going to set specific timelines for that sharing,” he added.
Additionally, Patel said that CIRM hopes to coordinate data sharing efforts with those of agencies like the National Institutes of Health and the Advanced Research Projects Agency for Health. “Instead of trying to build our own data system, we are reaching out to federal agencies with similar programs to see if we can coordinate and have it all in a centralized repository instead of each one having their own.”
The official program announcement will be released in the next few months, which will provide additional details about requirements. In the meantime, CIRM plans to have more outreach sessions, including a workshop that will bring relevant stakeholders together, including patient advocacy organizations, scientists, and others. These meetings will provide a platform for the community to “talk about and socialize approaches for platform-based therapy development,” Patel said. He expects that those conversations will “inform the RAPID proposals that eventually come in” and “raise awareness of what’s actually been tried and been successful in the field so far.”
