California Stem Cell Agency Backs Away from Covid Vaccine Plan; Concerns Raised About Mission Creep

Directors of the $3 billion California stem cell agency have rejected a Covid-19 proposal to extend the agency's reach beyond stem cells, expressing concerns about mission creep, public relations and dilution of cash for other important research.

The case in point last Friday was "emergency" consideration of a plan to fund Covid-19 vaccine development as part of a $5 million special round of funding. The federal government has already allocated nearly $1 billion for vaccine development. More than 100 vaccine projects are underway globally.

Shlomo Melmed of Cedars-Sinai in Los Angeles was one of the directors of the California Institute for Regenerative Medicine (CIRM) who opposed the proposal. He described the likelihood of CIRM being successful in helping to develop a vaccine was "pie in the sky."  He said, 

"We should be realistic about how that may look good on our website...but the reality is that this whole project (is) not going to have major, short-term impact barring some wonderful serendipity.

"And, and to come back to the original trust of the voters of California in CIRM, I really do think that we are deviating from our mission and ought not dilute our impact, which is so necessary and so vital."

Friday's discussion was triggered by a proposal to declare vaccine development a "vital research opportunity(VRO)" and make it eligible for state funding.

CIRM directors have approved a VRO only twice in the 15 years that the agency has existed. One was for gene therapy research. Another involved blood plasma, a possible Covid-19 treatment.

The VRO loophole is contained in the ballot initiative that created the agency in 2004, but was little noticed at the time. The same provision exists in the proposed initiative to refinance the financially strapped agency with $5.5 billion more. The initiative also contains language that would expand the scope of CIRM and, in some cases, require it to delve into major new areas. The initiative has not yet qualified for the November ballot.

Director Jeff Sheehy, an HIV/AIDs patient advocate member of the board, said,

"As an agency we're taking a much broader and much more sophisticated view of what our mission is. It's morphed. If we were being true to our original mission, we would only be doing embryonic stem cell research....(T)hat's what we the voters asked us to do in 2004."

Director Steve Juelsgaard, a former top executive at Genentech, said that the amount of funding that CIRM could provide was only "a drop in the bucket," given its financial condition. He added, "I think we're just getting way off course here."

Director Keith Yamamoto, vice chancellor of science policy at UC San Francisco, said the search for Covid treatments is "urgent and important." But he added that the agency would be "well advised to kind of stay in our lane" because of the important work that it was intended to do. He reminded directors of the hundreds of millions of dollars already allocated by other entities for vaccine work.

During an earlier part of the discussion, Jonathan Thomas, chairman of the CIRM board, said that the vaccine proposal had been the subject of robust internal discussion at the agency. He said that the idea behind it was to assist in the Covid crisis: "going a little bit above and beyond to try to help."

Thomas gave Sheehy, chairman of the board's science committee, a "shout-out" for suggesting the idea of discussing the concept of a VRO in connection with a vaccine. During his comments, Sheehy suggested that if the agency wanted to make an impact on vaccine development it would need to remove "the stem cell handcuffs." But he added he was "agnostic" on the matter.

Over the weekend, Sheehy, who has raised questions about the $5.5 billion initiative, responded at length to a follow-up inquiry by the California Stem Cell Report. He said:

"To sum up, I'm not really sure what the board is trying to accomplish with its Covid program.  I'm not sure that the board has a clear, coherent view of the scope of CIRM's research.  And I am not sure the board has a clear idea of what the scientific mission of CIRM should be in the event that new funding comes from the voters."

The full text of his remarks can be found here.

Ultimately, the CIRM board said it would vigorously support research platforms that have stem cell elements that could help in vaccine development. That position, however, was not as expansive as originally proposed. It does not require a VRO and falls within the agency's normal scope.

Directors also approved raising the funding cap on some elements within the current $5 million Covid-19 round. They are scheduled to meet again this Friday at 1 p.m. to consider more Covid applications. The online sessions are open to the public, members of which can comment on all matters. Directions are on the agenda.

Here is a link to CIRM's news release on the Friday meeting.

California's Big Research Tent: Beyond Stem Cells and Into VROs

California's $3 billion stem cell research program is unprecedented in state history, and it is now ready to mark another first: Backing a couple of clinical "VROs"  with $13.5 million.

VRO is a term that only a policy wonk could love or perhaps a researcher seeking funding under the rubric. It is not exactly posted on the home page of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known. It is nestled comfortably among the 10,000 words of the 2004 ballot initiative that created CIRM.

VRO stands for vital research opportunity. It is fair to say that few persons are aware of the language or know that CIRM's funding authority is something of a big tent that can go well beyond stem cells. Or that CIRM's program could be more expansive under a new, proposed $5.5 billion ballot initiative.

CIRM's governing board set the stage for the awards last November when it approved a VRO process for gene therapy research that did not involve stem cells but involved an aspect of regenerative medicine.

According to the meeting transcript, an application for an award would be considered a VRO if, among other things, "the approach is intended to replace, regenerate, or repair the function of aged, diseased, damaged, or defective cells, tissues, and/or organ. This basically constitutes the definition of regenerative medicine and brings that as a requirement."
 
A VRO designation also requires a two-thirds vote of the grant reviewers, who conduct their meetings behind closed doors.

On Thursday, the board is expected to approve its first two VRO proposals. One for $8 million targets Parkinson's disease. The summary of the review said the research has "the potential to slow disease progression and provide amelioration of motor symptoms."

The other is a $5.5 million award for treatment of a rare autoimmune disease called IPEX. The summary of the review said the research offered "a valuable alternative to the current standard of care options, which have significant toxic side effects."

VRO awards are permitted under the 2004 ballot measure, which says:

"The institute shall have the following purposes: (a) To make grants and loans for stem cell research, for research facilities, and for other vital research opportunities to realize therapies, protocols, and/or medical procedures that will result in, as speedily as possible, the cure for, and/or substantial mitigation of, major diseases, injuries, and orphan diseases."

Currently on file with state election officials is a proposed ballot initiative that would provide an additional $5.5 billion for the agency, which is soon expected to run out of cash for new awards.

The measure would make a number of changes in CIRM, including permitting the agency to venture even farther afield than permitted under the 2004 language.

The measure would impose a new requirement that the agency support training programs for "careers in stem cell research and other vital research opportunities." It would establish experience in "other vital research opportunities" as acceptable criteria for the selection of governing board members and the chair of CIRM. The criteria would apply also to the grant review group and appointments to a new scientific advisory board.

The proposed ballot measure also defines a VRO as including personalized medicine, genetics and aging. Here is the proposed, new language:

"Vital research opportunity means scientific and medical research and technologies, includinq but not limited to qenetics, personalized medicine, and aqinq as a patholoqy, and/or any stem cell research not actually funded by the institute under paragraph (3) of subdivision (c) of Section 125290.60 which provides a substantially superior research opportunity, vital to advance medical science as determined by at least a two-thirds vote of a quorum of the members of the Scientific and Medical Research Funding Working Group (reviewers) and recommended as such by that working group to the ICOC (the governing board),or as determined by the vote of a majority of a quorum of members of the ICOC. Human reproductive cloning shall not be a vital research opportunity."

The language still can be modified by the initiative backers prior to being certified for the November 2020 ballot. Here is how that mechanism works.