California Stem Cell Agency's 'Holiday' Awards: $25 Million for Research Ranging from Liver Failure to Dementia

OAKLAND, Ca. -- Directors of the California stem cell agency last week approved nearly $25 million for research but dashed the hopes of two scientists who were pushing extra hard for funding from the 13-year-old state enterprise.

Thirteen researchers ultimately received awards for tackling such afflictions as diabetes, dementia and liver failure. Thirty-two scientists who applied in the round were originally rejected by reviewers for the California Insitute for Regenerative Medicine, (CIRM), as the agency is formally known.

Reviewers make the de facto decisions on awards by the agency, although its governing board can override their actions. Four researchers whose proposals were nixed during an earlier, closed-door reviewer session sought to reverse those decisions.

Only two out of the four won over the board. One was Mark Tuszynski, director of the Translational Neuroscience Institute at UC San Diego, who sought $2.1 million to support his research to use neural stem cells to grow new connections through injured spinal cord. In a letter to the board prior to the meeting, he said ,

"As the present round of...funding winds down, this may be our last opportunity to develop this work to benefit the citizens of the state of California."

Tuszynski's application received a score of 80 out of 100, five points below the cutoff line of 85.

CIRM directors discussed the application briefly during which San Diego researcher addressed the board.

In addition to Tuszynski's application, the board reversed reviewers on an application for a cellular treatment for epilepsy. The $1.6 million proposal by Neurona Therapeutics of South San Francisco scored 80. Arnold Kriegstein, co-founder of the firm and head of the UC San Francisco stem cell program, spoke on behalf of the Neurona. 

The other appellants were Alice Tarantal of  UC Davis and Gregorio Chazenbalk of UCLA.

Tarantal filed a $1.1 million application (DISC2-10599) that she said involved "total-body positron emission tomography (PET) imaging technology, which currently is only available in California."

Her application was scored at 84 by reviewers, just one point below the cutoff line. Board members in the past have noted that such narrow differences are statistically meaningless.

Chazenbalk's $2.2 million application (DISC2-10473) involved a "new population of pluripotent stem cells" known as Muse cells, which he said can be used to treat acute myocardial infarction with a "high potential rate of success." His score was not disclosed but appears to be below 65.

Both Tarantal and Chazenbalk addressed the board but none of the directors discussed their applications. 

No discussion of the winning applications was conducted by the board members. A list of their names, institutions and projects is below.  

Here is the CIRM press release on the awards. It includes the application numbers for all proposals, which can be used to find the summaries of reviewer comments and scores. The specific review summaries can be found by scrolling more deeply into that document.

APPLICATION	TITLE	INSTITUTION	CIRM COMMITTED FUNDING
DISC2-10591	Preclinical development of an immune evasive islet cell replacement therapy for type 1 diabetes	ViaCyte	$1,470,987
DISC2-10524	Genome Editing of Sinusoidal Endothelial Stem Cells for Permanent Correction of Hemophilia A	Saswati Chatterjee City of Hope	$2,182,193
DISC2-10679	Towards hepatocyte cell replacement therapy: developing a renewable source of human hepatocytes from pluripotent stem cells	Irv Weismann Stanford	$2,201,136
DISC2-10748	Engineering Lifelong Cellular Immunity to HIV	Scott Kitchen U.C. Los Angeles	$1,701,178
DISC2-10714	iPS Glial Therapy for White Matter Stroke and Vascular Dementia	Stanley Thomas Carmichael U.C. Los Angeles	$2,096,095
DISC2-10604	Stimulating endogenous muscle stem cells to counter muscle atrophy	Helen Blau Stanford	$2,198,687
DISC2-10753	Generation and in vitro profiling of neural stem cell lines to predict in vivo efficacy for chronic cervical spinal cord injury.	Aileen Anderson U.C. Irvine	$1,575,613
DISC2-10751	Silicon Nanopore Membrane encapsulated enriched-Beta Clusters for Type 1 Diabetes treatment	Shuvo Roy U.C. San Francisco	$1,113,000
DISC2-10695	Identification and Generation of Long Term Repopulating Human Muscle Stem Cells from Human Pluripotent Stem Cells	April Pyle U.C. Los Angeles	$2,184,000
DISC2-10747	Targeting Cancer Stem Cells in Hematologic Malignancies	Tannishtha Reya U.C. San Diego	$2,167,200
DISC2-10559	Development of immune invisible beta cells as a cell therapy for type 1 diabetes through genetic modification of hESCs	Yang Xu U.C. San Diego	$2,167,200
DISC2-10525	Development of a cellular therapeutic for treatment of epilepsy	Neurona Therapeutics	$1,616,536
DISC2-10665	Neural Stem Cell Relays for Severe Spinal Cord Injury	Mark Tuszynski U.C. San Diego	$2,100,581

Chart by CIRM

A Rare, Written Self-Exploration: California's Stem Cell Agency Slices and Dices its Own Spending

It is a rare day that the $3 billion California stem cell agency actually explains in writing its budget and finance choices. Today it did.

Usually the agency relies on Power Point slide presentations at its public meetings that amount to little more than an outline. Today, the California Institute for Regenerative Medicine (CIRM), as the agency is formally known, filed a 652-word item on its blog discussing its spending plans.

Written by Kevin McCormack, the agency's senior director of communications, said the CIRM team had examined CIRM's financial picture during the last few months. He wrote,

"It boiled down to a few options.

• "Keep funding at the current rate and run out of money by 2019

• "Limit funding just to clinical trials, which would mean we could hit our 50 clinical trial goal by 2020 but would not have enough to fund Discovery and Translational level research

• "Place caps on how much we fund each clinical trial, enabling us to fund more clinical trials while having enough left over for Discovery and Translational awards"

McCormack continued,

"The board went for the third option for some good reasons. The plan is consistent with the goals laid out in our strategic plan and it supports Discovery and Translational research, which are important elements in our drive to develop new therapies for patients."

Nearly all of what McCormack wrote is familiar to readers of this web site. But it may be new to many of other followers of the agency.

McCormack noted that budgets are "rarely exciting things." Some might argue that precisely how the agency is spending $6 billion (including interest) of public money is at least as exciting as the arcane world of, let's say,  generating a "mesenchymal stromal cell-seeded small intestinal submucosa  decellularized extracellular matrix,"

CIRM's spending is directly important to hundreds of California scientists and the institutions that benefit financially from CIRM awards. The stem field in general has already benefited from the loads of CIRM research that is laying the groundwork for greater developments -- not only in California but globally.

It can arguably said that CIRM is the largest single source of stem cell research funding in the world. And one of its greatest products is hope -- hope by hundreds of thousands of persons, perhaps millions, that CIRM's research will speed development of therapies that will ease their suffering or the suffering of those who come after them.

Nothing boring about that. And kudos to CIRM for taking a longer look at the nickels and dimes that make it happen.

$5 Billion Bond Measure: California Stem Cell Agency Sets a Course to Secure Its Financial Future

CIRM spending plan for next year and beyond. 
Educ refers to educational  grants. Discovery 
refers to basic research. Tran refers to translational, 
and Clin refers to clinical trial related awards. 
CIRM spent $213 million this year on Clin awards. 

OAKLAND, Ca. -- Directors of the California stem cell agency today virtually endorsed a plan to stave off its financial death, pinning their hopes on a possible $5 billion bond measure and a private fundraising effort to bring in an additional $222 million.

The California Institute for Regenerative Medicine (CIRM), as the agency is formally known, expects to run out of cash for new awards in late 2019 because of limits in the ballot measure that created it in 2004.

Robert Klein, who led the 2004 initiative campaign, appeared before the governing board meeting and touted the new bond proposal. The Palo Alto real estate investment banker told directors that California had a "moral imperative" to continue its stem cell work. He said,

"This is California’s contribution to the future of medicine....This is the bridge to the future of health care."

No vote was taken on endorsement of a ballot measure that has yet to be written or qualified for the ballot. But no objection was raised by board members to moving forward on what Thomas called the best option.

Under that scenario, Klein would lead a new, $5 billion initiative that would require hundreds of thousands of voter signature to qualify for the November 2020 ballot. Then it would require raising roughly $50 million to run a successful campaign, Klein told the California Stem Cell Report last month.

The $222 million fundraising effort is already underway and would continue until the end of 2019, with the expectation that it would provide bridge funding until voter approval of the new, multibillion dollar bond measure.

Klein told directors that 70 percent of California voters favor continuing funding of the agency. However, last month he declined a request by the California Stem Cell Report for a copy of the poll or the name of the firm that conducted it.

The 2004 campaign led voters to believe that miraculous stem cell cures were right around the corner. The agency has yet to help finance a treatment that is in widespread use. But it has currently invested $300 million in 26 clinical trials, the last stage before a proposed therapy can be certified for general use. Trials, however, can take years.

The agency is funded by money that the state borrows -- bonds. The authority to issue those bonds is expiring, and the agency is down to its last $269 million.

A fallback funding scenario would involve asking the legislature to place a bond measure on the ballot. There was no discussion of that today but it would involve negotiating with lawmakers and possibly making major changes in the way CIRM operates.

Prior to discussion of the bond measure, directors approved $68 million in cuts to the size of awards so that more awards could be made over the next two years. They also approved spending $270 million on awards next year, including $130 million on awards related to clinical trials, $30 million for research bridging the gap between the clinic and basic research and $10 million for basic research.

$68 Million Saving: California Stem Cell Agency Cuts Size of Clinical Trial Awards

CIRM's new caps on its clinical trial programs

OAKLAND, Ca. -- Directors of the California stem cell agency this morning cut the size of its key awards, saving $68 million that will allow it to support more "shots on goal" as it pursues development of a stem cell therapy available for widespread use. 

The move was made in the clinical trials program of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known. Clinical trials are the last stage of research prior to federal approval of a therapy for general use. 

The unanimous action will allow the agency to continue backing its non-clinical programs as well as generating support for 50 trials by the end of 2019. 

The agency is running out of cash for new awards because of limits in the ballot initiative that created it in 2004. The board will discuss funding for the more distant future at today's meeting. 

The California Stem Cell Agency, 'Lost' Opportunities and its Financial Lifeblood

A UC San Diego scientist has zeroed in on the declining finances of the $3 billion California stem cell agency, stressing that tomorrow may be the "last opportunity" for the agency to back a new approach to severe spinal injuries.

Mark Tuszynski, UCSD photo

Mark Tuszynski, director of the Translational Neuroscience Institute at UC San Diego, is
seeking $2.1 million to support his research to use neural stem cells to grow new connections through injured spinal cord. In a letter to the board, he said,

"As the present round of...funding winds down, this may be our last opportunity to develop this work to benefit the citizens of the state of California."

Tuszynski's comment could apply to almost any of the grant applications that will be submitted to the agency between now and late 2019. The California Institute for Regenerative Medicine (CIRM), as the agency is formally known, expects to run out of cash for new awards in 2019.

Tuszynski's comment was also unusual. The public silence from the California scientific stem cell community has been, as they say, "deafening" concerning the looming demise of CIRM. Researchers have not been heard from in any real way at the four public CIRM meetings in 2017 that have dealt with the issue.

The San Diego scientist's letter is part of the agenda at tomorrow's meeting of the CIRM governing board. At the forefront of the session is once again the question of whether the agency can find a way to continue its existence at the level at which it has operated since 2004.

CIRM's financial lifeblood is money that the state borrows -- state bonds. That source was provided by voters when they created the agency with a ballot initiative 13 years ago. However, the authority to issue those bonds is expiring, and the agency needs a major infusion.

Enter Bob Klein, a Palo Alto real estate investment banker and who headed the 2004 ballot campaign. He appeared before the board last month and talked about a $5 billion bond measure on the November 2020 ballot. He is expected to appear again tomorrow. 

Also on the table will be a strategy unveiled last month by CIRM Chairman Jonathan Thomas to raise privately $222 million between now and the beginning of 2020 to keep the agency sufficiently funded prior to a bond election. The board is also scheduled to act on a proposal to cut the size of awards so that more overall can be financed.

Then there are $21 million in applications for research into matters ranging from diabetes to dementia. That is were Tuszynski comes in. CIRM's all-important grant reviewers nixed his application (DISC2-10665), giving it a score of 80. The cutoff line for funding was 85.

He is asking the CIRM board to overturn the reviewers' decision, which would be a rare event. Another two researchers are also appealing negative decisions by reviewers, who meet behind closed doors and do not have to publicly disclose their professional or financial conflicts of interest.

The other scientists are Alice Tarantal of UC Davis and Gregorio Chazenbalk of UCLA.

Tarantal's $1.1 million application (DISC2-10599) involves, she said, "total-body positron emission tomography (PET) imaging technology, which currently is only available in California."

 Her application received a score of 84. In a letter to the board, she said her research, which also involves Simon Cherry of UC Davis, would "set the stage for stem cell applications and the transformative (imaging) tools developed, tested, and successfully applied in California."

In 2018, Tarantal said Cherry will place in operation "the world's first total-body PET scanner for humans that allows all tissues and organs to be imaged simultaneously."

Chazenbalk's $2.2 million application (DISC2-10473) involves a "new population of pluripotent stem cells" known as Muse cells, which he said can be used to treat acute myocardial infarction with a "high potential rate of success."  His score was not disclosed but appears to be below 65.

Scores on the applications can be found here. Summaries of reviewers' remarks on applications can be found  by scrolling more deeply into that document. CIRM withholds the names of applicants until after its board meeting. The three "appealing" scientists' names became public record when their letters were received by CIRM.

Eleven applications were approved by reviewers and 32 rejected.

The full agenda of the meeting with additional information can be found here. The meeting is based at the Oakland CIRM headquarters with teleconference locations where the public can participate in New York City, Sacramento, Santa Cruz, San Diego, Stanford and two in La Jolla.

The meeting is being audiocast as well. Full details on all locations and the audiocast can be found on the agenda. 

The California Stem Cell Report will be covering the meeting live from Oakland and filing stories as warranted.

California Stem Cell Board to Hash Over Cuts, Future Financing Plans Next Week

Directors of the $3 billion California stem cell agency, which is facing the loss of its funding, are scheduled for one of their more consequential meetings late next week -- a session that will deal with cutting the size of awards and planning for life after 2019.

The meeting Dec. 14 will continue a discussion that began last September and that now involves a possible $5 billion bond ballot measure, a private, $222 million fundraising campaign and major  reductions in the size of awards over the next two years.

The agency projects it will run out of cash for new awards in 2019. It is financed by California state bonds but that source is drying up under the terms of the ballot measure that created the effort in 2004.

Details of what exactly will be presented next week to the 29-member governing board were not available -- as of this writing -- on the web site of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known. More information is expected to be posted in the next few days, but it is likely to resemble closely the matters discussed in late November by the directors. 

Also on tap are changes in the basic research and translational award programs and ratification of reviewer decisions on grant applications in the "Quest" program, which is aimed at development of technology that is uniquely enabled by stem cells. 

The meeting will be based in Oakland with teleconference locations where the public can participate in New York City, Stanford, Santa Cruz and San Diego. The meeting will be audiocast on a listen- only basis. More details can be found on the agenda.  Regarding the New York City site, from time to time teleconference sites have been set up out-of-state when a director is traveling.

The California Stem Cell Report will be covering the meeting live from CIRM's Oakland headquarters.

California Stem Cell Research and a 'Heart-Tugging Media Blitz'

The critical, financial circumstances of the $3 billion California stem cell agency have drawn the attention of the San Francisco Business Times. 

The newspaper, which covers the biotech industry in the Bay Area, carried a piece last week that discussed the likelihood of a $5 billion stem cell bond measure on the November 2020 ballot supported by a powerful, emotional campaign. Also covered by the Times were plans to reduce the size of the awards next year along with a brief overview of the agency's progress.

The agency is on track to run out of money for new awards in 2019 and is down to its last $269 million. But it has made a big push into clinical trials and  anticipates many more in the next couple of years.

Reporter Ron Leuty wrote,

"The potential success of clinical trials would allow backers of a new bond measure to show real-world examples of how the 2004 measure (that created the agency) paid off in an intense, heart-tugging media blitz."

Leuty keyed off  Robert Klein's appearance before the agency's directors last month. Klein, sometimes known as the father of the stem cell agency, is touting the bond measure as a longer term financing solution, but did not respond to requests from the Business Times for additional comment.

Leuty continued with quotes from Maria Millan, CEO of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known:

"Because we're running so well and have so many potential projects — and we know there are more than what we can fund — the challenge is balancing the funding to as many as possible while making sure that resources are programmed well...We'd like to continue to deliver what we are currently delivering." 

"The next couple of years what we're doing is driving that mission because we're starting to take off. In the past, it was mainly hope; now that hope is based on something tangible."

Hope and the 'Helping Patients Part': The Uncertain Future of California's Stem Cell Program

One of the big selling points of the $3 billion California stem cell agency has always been hope. And it still is. 

It is a difficult matter to argue with. Hope underpins all our lives. But no more so than with persons suffering from terrible and incurable diseases. And those are precisely the targets of the 13-year-old stem cell research effort financed by the people of California. 

Currently the agency is on a course to run out of cash for new awards in 2019, ironically a fate dictated by Proposition 71, the ballot initiative that also created the agency in 2004. The measure provided $3 billion but no further stream of income. The agency is now wrestling with a variety of possibilities to extend its life for another decade or so, including mounting a $5 billion bond measure on the November 2020 ballot. 

A stem cell researcher at UC Davis, Paul Knoepfler, today addressed those critical matters -- and hope -- in a post on his blog, The Niche. He wrote, 

"The California Institute for Regenerative Medicine, more widely known as CIRM, has accomplished big things over the course of its history of about a decade and sparked a great deal of innovation, but what does the future hold for our stem cell agency?"

Knoepfler mentioned coverage of CIRM meeting last week by the California Stem Cell Report, noting that last week's item included the phrase "withering death." Knoepfler wrote,

"I don’t see things as so bleak and remain hopeful on the agency’s future. It’s unclear how California voters will be feeling about all this in 2020, but with our stem cell agency we are just now getting to the exciting part. The helping patients part. As a past grantee myself, I know how much the funding can make impact to advance science, whether basic, clinical, or somewhere in between. 

"At the recent brainstorming meeting on the agency’s future, there were apparently some upbeat reports of voter sentiment as described by (David) Jensen (producer of the California Stem Cell Report):

"'Robert Klein, a Palo Alto real estate investment banker who ran the 2004 campaign that created the agency, told the CIRM directors of a private poll that he said showed 70 percent of Californians supported stem cell research and continued funds for the stem cell agency.'

"What do you think about our stem cell agency’s future? 

"In terms of clinically relevant science, it is at the most promising point in its history with support for loads of clinical trials. Not all of them will work out, but I’m convinced that some will and other fresh trials that could be initiated with CIRM’s new funding in the future beyond 2020 would bring more hope."

The  California Stem Cell Report welcomes your thoughts on the agency's future and its strategy for getting there. You can submit them either by clicking on the word "comments" at the end of the item or by emailing them to djensen@californiastemcellreport.com.