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. 

The 'Permissible' and 'Impermissible:' Admonitions Involving the California Stem Cell Agency and a $5.5 Billion Proposal

The 29 directors of the California stem cell agency are hearing a warning this week that certain types of their possible activities on behalf of a proposed $5.5 billion ballot initiative could lead to a criminal investigation by state or local law enforcement agencies. 

While that would seem to be an unlikely event, it has caught up another California public enterprise (the Bay Area Rapid Transit District). That's because state law restricts the use of public funds in connection with ballot campaigns. It is a complex subject, however, and laden with lots of gray areas. 

James Harrison
Remcho Johansen & Purcell photo

James Harrison, the former and longtime general counsel for the state stem cell agency, is scheduled to brief the board Thursday on the subject of "the permissible" and "the impermissible." Harrison is  well-known and respected for his work on election law and initiatives. 

He was deeply involved in drafting the $3 billion, 2004 ballot initiative that created the agency, known formally as the California Institute for Regenerative Medicine (CIRM). Harrison is also immersed in the proposed $5.5 billion measure for the 2020 ballot. It is designed to re-fund the agency, which expects to run out of cash this year for new awards. 

Harrison's memo to the CIRM board and his slide presentation on the use of public funds have been posted by the agency on its web site. In short, he says the key principles are:

"Communications about a ballot measure should be delivered through CIRM’s ordinary communication methods, like its website, blog, newsletter, emails to interested persons, and public meetings, in the style CIRM normally uses to communicate other information. CIRM should avoid passionate or inflammatory language and modes of communication that it does not regularly employ, and should not encourage voters to vote in a particular manner. For example, CIRM should not 'borrow the voices and the sympathy' of individuals who could benefit from the passage of the stem cell funding measure when discussing the measure, as BART did for Measure RR. CIRM should also take care to state past or present facts in a fair and dispassionate manner, and avoid using graphics, text, or video aesthetics that are similar to campaign advocacy (and different from CIRM’s normal practices). Taking steps like these will help ensure that the FPPC (Fair Political Practices Commission) or a court will conclude that CIRM is engaging in information sharing, rather than overt campaigning."

Harrison's presentation specifically discusses the BART case and others. The memo contains a list of specific permissibles and impermissibles. One permissible allows the board to vote on whether it supports the initiative. Another allows the agency to "prepare staff reports and other analyses to assist decision-makers in determining the impact of the measure and what position to take." 

Impermissibles include gathering signatures on the initiative and preparing materials for the public to use in support of the agency's position on the initiative. Working for an initiative on state time is barred, but CIRM employees can work for the campaign on their own time. 

Given the history and nature of California ballot campaigns, the state stem cell agency is certain to see public complaints that it is using public resources to support the initiative. The key, Harrison is telling CIRM directors, is to think about the context and content of proposed activities. 

His admonitions also include:

• "Ask legal counsel when you are not sure about a proposed activity.

• "Remember that even minimal use of public funds related to a measure can lead to investigation and litigation."

California Stem Cell Agency Posts $54 Million in Good News for Eight Researchers

Eight California researchers may be able to breathe a sigh of relief this morning with the news that the California stem cell agency has enough cash on hand to fund their applications to develop therapies for afflictions ranging from Parkinson's to eye diseases.

All eight of the applications have been approved already by the agency's reviewers. The agency's  governing board very rarely reverses the reviewers' actions. 

Until a day ago, it was uncertain whether the agency had the money to fund all the proposals. The good news for the scientists came in the form of a posting late yesterday on the web site of the agency, formally known as the California Institute for Regenerative Medicine (CIRM). The posting said that the agency has $54.2 million available for new awards as of Wednesday of this week (Oct. 23). The total for the eight application is about $52 million. 

Of course, it is possible that the board could move in a different direction based on considerations not readily apparent from the agenda for its meeting next Thursday. 

If the agency has $2 million or so left after next week's meeting, it is also unclear what it will do with the cash. One possibility is that it could retain the cash for awhile and combine it with funds that might be recovered from awards that have not met milestones.  So far this year, the agency has recovered $30.3 million.

CIRM has expected to run out of cash this year for new awards after dispensing $2.7 billion over the last 15 years to 1,017 recipients. It is hoping voters will approve $5.5 billion more via a ballot initiative in November 2020. 

Thursday's meeting does have another financial fillip. Listed on the agenda is a line that says a report will be made on private donations. That could be good news or not-so-good news depending on how successful its private funding efforts have been over the last couple of years. Results of that drive are yet to be publicly announced. 

(Editor's note for careful readers: The CIRM document that contains the $54.2 million figure also lists $57.2 million in applications. One of those applications, a $5 million proposal, was not approved by reviewers, however.) 

Want to Speak to the Directors of the California Stem Agency? Here is Your Chance.

The $3 billion California stem cell agency meets Oct. 31 to consider applications for $52 million in research funding. Also on the table are issues ranging from its finances to an initiative that would re-fund it with $5.5 billion. The agency expects to run out cash for new awards by the end of the month.

The meeting is open to the public with its main location at its headquarters in Oakland. Here is the current list of locations, which may change. The public can also participate via the Internet as the meeting is streamed live. See the agenda for instructions. 

Here are links to items dealing with issues before the board. "Last Research Awards...." "Competition for $52 Million..."

CIRM HQ: 1999 Harrison Street Suite 1650, Oakland, CA 94612

Other locations, which are usually hosted by a member of the agency's governing board: 

10901 N. Torrey Pines Road, La Jolla, CA 92037
4005 N Fresno St., Fresno, CA 93726
765 Market Street, #31D, San Francisco, CA 94103
9500 Gilman Drive #0602, La Jolla, CA 92093-0602
291 Campus Drive, Stanford, CA 94305
Medical Sciences 1C, Room 110, Davis, CA 95616

California Stem Cell Researchers Compete Next Week for $52 Million in Awards

Directors of the California stem cell agency will make yes-or-no decisions next week  on eight applications for $52 million to seek cures for afflictions ranging from Parkinson's to an incurable eye disease called retinitis pigmentosa.

All eight have been approved behind closed doors by the agency's grant reviewers, but it is yet to be determined whether the agency has enough cash to ratify that action.

Prior to voting on the applications, the 29-member board is scheduled to discuss how the agency's final funding will be parceled out. The agency expects to run out of cash for new awards at the end of the Oct. 31 meeting. However, also on its agenda are a few words promising a report on the status of its search for private donations. 

Below is a table on the applications. It includes links to the review summaries prepared by the agency, which is formally known as the California Institute for Regenerative Medicine. Links to the review summary can be found on the application numbers.

Some of the applicants have filed additional letters with the board seeking to bolster their pitches. The letters can be found by clicking on the researcher's name. Some of the applicants are expected to address the board personally Oct. 31 in Oakland.

The agency has a non-embarrassment policy of not disclosing the names of applicants and their institutions until a vote by its board.  However, when they write the board, their names become a public record. The names of applicants who fail to win approval are never disclosed by the agency.

Look for more stories in the upcoming days from the California Stem Cell Report on the agency's Halloween meeting.

Application Number	Amount In millions	Institution	Principal  Investigator	Target
CLIN1-11591	$5.5	Stanford	Rosa Bacchetta	IPEX
CLIN1-11472	$6.6	Not disclosed	Not disclosed	Retinitis pigmentosa
CLIN2-11620	$10.5	Not disclosed	Not disclosed	Retinitis pigmentosa
CLIN2-11661	$8.0	Brain Neurotherapy Bio	Krystof S. Bankiewicz	Parkinson’s Disease
CLIN2-11650	$10.3	UCLA	Sophia Deng	Limbal stem cell deficiency
TRAN1-11536	$4.9	UCLA	Caroline Y. Kuo	Immune deficiency
TRAN1-11555	$3.2	UCLA	Yvonne Y. Chen	Myeloma
TRAN1-11544	$2.9	Not disclosed	Not disclosed	Ovarian cancer