ALL STEM CELLS

Born out of discontent with the federal restrictions on research with cells from human embryos, California’s stem cell agency is at a key juncture.
Over the past decade, it’s spent a large portion of its $3 billion budget nurturing fledgling disease therapies, but that state money may run out before most of the treatments are ready for the clinic.
The California Institute for Regenerative Medicine (CIRM), created in 2004 through a state ballot initiative, is down to its last $759 million in grant funding. CIRM has so far propelled 23 stem cell projects into clinical trials, and made California a magnet for research in regenerative medicine. But none of its efforts have yet produced an approved treatment, and only 8% of the academic projects it funds have found industry partners to help commercialize discoveries. “CIRM has built an infrastructure,” says Rocky Tuan, a stem cell biologist at the University of Pittsburgh School of Medicine in Pennsylvania, “but substantive delivery still is to come.”
Although CIRM’s leadership is already pursuing new sources of cash to keep the agency alive after 2020, for now the agency intends to spend its remaining dollars as though they’ll be the last. Last month, its independent governing board signed off on an ambitious 5-year plan to award its final funds by 2020 and to push more potential treatments toward the clinic.
The new plan focuses on making CIRM funded projects attractive to pharmaceutical companies and investors who could bankroll large clinical trials. These players have historically become interested in a stem cell treatment only after it has demonstrated proof of concept, typically at the end of a phase II trial, says CIRM’s board chairman, investment banker Jonathan Thomas in Oakland, California. So the agency hopes to create two new resources for its grantees: a “translating center” that would develop manufacturing processes and run basic safety studies to prepare for a clinical trial; and an “accelerating center,” which would manage clinical trials and coordinate filings with the Food and Drug Administration.
The two centers would be selected from existing organizations that submit applications to CIRM.
Each would receive $12 million to $15 million over the next 5 years to provide their services to CIRM-funded investigators.
The plan also creates a program, called Accelerating Therapies through Public-Private Partnership (ATP), which allows industry applicants - pharma companies, venture capital firms, or individual investors, for example - to compete for a licensing agreement that bundles multiple CIRM projects of their choosing. The winner would commit up to $75 million in upfront capital, which CIRM would match, likely in the form of a loan, to further develop the therapies.
And the license winner would continue to benefit from CIRM funding flowing into the projects. Both the new centers and the partnership are unusual models for a state agency, said Stephen Juelsgaard, a former Genentech executive and CIRM board member, at a 17 December board meeting in Los Angeles, California. “This plan is full of experiments - things that I’ve never seen done before.
We’ll have to see how they play out.” The board unanimously approved the proposal, with other members describing it in terms such as “inspiring” and “seismic.”
Even if all goes according to plan, however, most CIRM-funded projects will not finish phase II trials in the next 5 years, and may not be ready for an industry partner, Thomas told the board. “If [CIRM doesn’t] have additional funding at that point, we will have only partially met our obligation to develop therapies and cures.”
The agency has a number of options to survive past 2020. Partnerships catalyzed by ATP3 and other CIRM programs could, if they pan out, generate large royalty payments.
CIRM can also seek private gifts—a strategy Thomas says he has begun to discuss with potential donors. Finally, it could ask California voters to approve more funding.
Real estate developer Robert Klein in Palo Alto, California, who led the campaign to create CIRM in 2004 and served as the first chair of the governing board, hopes to spearhead a new ballot effort. The medical research advocacy group Klein founded and directs, Americans for Cures, intends to use polling in 2017 to gauge voter interest. If the polling finds support, Klein says his “goal would be in 2018 to have a major new initiative.” CIRM, as a public agency, couldn’t help gather signatures to place the measure on the ballot. Its leaders could directly ask state lawmakers to sponsor the measure. But one member of the CIRM board, vice chair and former state senator Art Torres in San Francisco, California, is uneasy about that idea.
At the December meeting, he noted that this past summer some members of the California legislature proposed an audit of Planned Parenthood to investigate its distribution of tissue from aborted fetuses - a source of stem cells for various disease research, including some funded by CIRM. There are people that don’t believe in what we do, who are members of the legislature,” Torres warned, and they “could invariably impact any [CIRM funding] proposal.” Democratic lawmakers ultimately blocked the tissue investigation. And whether there will be enough believers in CIRM to keep the agency afloat may depend on how well it can build - and publicize - a track record for moving stem cell discoveries to the clinic.