CIRM considers hold on grants amid deluge of applications

California’s $12 billion stem cell agency is under “’unprecedented strain” and is ready to impose a five-month hold on applications for the key, $15 million research awards that support the final steps in bringing revolutionary treatments to patients.

A “very large and unprecedented number” of applications for clinical trial awards has swamped the agency. The $4 million to $15 million grants finance clinical-stage work on stem cell and gene therapies, clearing the way for their use in patients.

The unusual suspension has come under fire from a number of scientists.  “It would be a shame to see a further delay in the translation of regenerative medicine therapies to patients…,” said Karen L. Christman, a professor of bioengineering at UC San Diego, in a letter to the 35-member CIRM board. “Devastating” was another comment from Leslie Thompson at UC Irvine.

“Worse, it will bring a negative cast to efforts by UCI and other academic institutions to educate the California public about the potential of cell and gene therapies to improve their lives,” said Aileen J. Anderson, also of UC Irvine.

Delays in funding research were once anathema to CIRM. One former president, Randy Mills, dramatically accelerated the award process in 2014, declaring that delays in searching for cures mean “more dead kids.”

The agency’s directors are scheduled to meet publicly on Thursday and are likely to approve the five-month hold recommended by its staff. The suspension would begin this month and leave Christman’s application and others hanging.

The application deluge is not the only major issue currently facing the stem cell agency, officially known as the California Institute for Regenerative Medicine (CIRM). Other matters include:

• The search for a new president: CIRM is still in a relatively early stage of finding a new leader. The last one resigned abruptly last November. CIRM has published a timetable that calls for a decision by the end of May. Past searches have taken 10 months.
• A performance audit recently cited 13 areas where improvements are needed at the agency. The issues range from employee morale problems and an excessively large governing board to pay inequity and royalty income issues.
• A 2020 voter mandate requires CIRM to devise ways to make multimillion-dollar treatments affordable and accessible. The effort remains in an embryonic state.
• Plus the board has a new salaried chair, Vito Imbasciani, who is just completing his first year on the job. Many members of the board are also relatively new to the agency and the byzantine, 17,000-word law that governs CIRM.

The application hold comes three years after California voters narrowly approved $5.5 billion in state borrowing (bonds) to refinance the agency, which was about to go broke. CIRM was created with $3 billion in 2004, also through a ballot initiative. Interest on the borrowed money brings the estimated cost to taxpayers to $12 billion.

The 2004 ballot campaign raised voter expectations that miraculous cures were right around the corner. However, CIRM has yet to finance research that has led to a stem cell therapy that is available to the general public.

Two-edged sword for stem cell agency
In the last three months, CIRM has received an average of 12 clinical applications a month, compared to about four a month since 2020. Seven applications are scheduled to be acted on Thursday. Seventeen additional applications are scheduled for closed-door reviews this month and next by out-of-state reviewers plus final ratification by the board. Nine additional applications are awaiting resubmission.

CIRM has never faced this sort of two-edged problem with its clinical awards. While the flood of complex applications has strained the limited staff, the influx brings multiple, new opportunities to produce a gene or stem cell therapy, the goal of the 2004 campaign that created CIRM.

Delays in funding research were once an anathema to CIRM. One former president, Randy Mills, dramatically accelerated the award process in 2014, declaring that delays in searching for cures mean “more dead kids.”

Nonetheless, reviewing and processing the applications is by nature slow. Among other things, it requires bringing together CIRM staff, a handful of board members and 15 out-of-state scientists and often additional specialist researchers to review the applications each month during online deliberations.

Then the applications must go to the directors for further examination and final ratification. Negotiating the final details in the award contracts can take many weeks. The hold would apply only to clinical stage applications, but their consideration involves many members of the small, 65-person staff ranging from legal to scientific.

CIRM budget under pressure
The amount of money being requested also could be a budget buster for CIRM, at least for the current fiscal year.

In response to questions from Capitol Weekly, CIRM said the total requested in clinical applications already awaiting review, including resubmissions, stands at $167 million without the hold.  (About 50 to 60 percent of applications win approval.)  The $167 million figure far exceeds the budgeted $90 million that would remain Thursday, assuming board approval of recommended awards on its agenda.

CIRM currently has $177 million on hand and expects $208 million more from the state bond sale this spring, CIRM says. It could use those funds to make additional clinical awards. However, it has other programs, including basic research, that require many millions of dollars.

Another financial complexity involves restrictions on CIRM’s access to the $4 billion that remains for research from the $5.5 billion, 2020 ballot measure. It limits CIRM to $540 million a year.

“We are being fiscally responsible by adhering to our budget and the operational constraints,”  CIRM told Capitol Weekly in a statement.

Other limits are also imposed by the ballot measure, which caps the number of CIRM employees at 70, with some exceptions. It could attempt to raise that limit to deal with the increased interest in CIRM awards.

But, in response to a question, CIRM said it does not expect to ask the legislature to raise the cap, which would take a super, super majority of both houses of the legislature and the governor’s signature, a requirement imposed by the ballot initiative. The ballot measure also restricts the size of CIRM’s administrative budget, whose largest component is employee compensation.

Concern about “wasted” work
The hold would begin this month and extend through June for what CIRM calls its CLIN1 and CLIN2 programs. The suspension could hamper the research efforts of small stem cell and gene therapy companies, which are often strapped for cash and may not have good alternative financial sources. However, the hold does not affect CIRM’s other awards programs, including basic research.

UC San Diego’s Christman is not likely to be alone in worrying about the situation. She has retooled a once-rejected application in consultation with CIRM staff for resubmission. She says it is ready to be approved. In her letter to the CIRM board, Christman asked that any hold not begin until after the next scheduled application deadline of Feb. 29.

“I am sure many groups in addition to ours spent significant time and effort on proposals over the past month, which would be wasted if their applications are not allowed to be reviewed as planned,” she wrote.

For more details from CIRM regarding its finances and the hold see the California Stem Cell Report for a Q&A.

Jensen is a retired newsman and has covered CIRM for 18 years on his newsletter, the California Stem Cell Report. He authored the book, “California’s Great Stem Cell Experiment,” in 2020.