A Man Named Lucas and the Future of the California Stem Cell Agency

Lucas Lindner, photo by Cait Covers the Bases

The news last fall from a California stem cell firm was leaden and dense. Terms such as "Phase 1/2a SCiStar study" and "Full enrollment of Cohort 3 (AIS-A; 20 million AST-OPC1 cells)" littered the company's statement. 

Today the state's $3 billion stem cell agency turned the jargon into a heart-warming, human story -- the type that is critical to sustaining the life of the 13-year-old research effort, which is running out of cash.

The story involves Asteria Biotherapeutics, Inc., of Fremont, the California Institute of Regenerative Medicine(CIRM), as the stem cell agency is formally known, a clinical trial for a treatment for spinal injury and a young man named Lucas Lindner.

He is one of the patients in Asterias' clinical trial for a human embryonic stem cell therapy for spinal cord injury.  CIRM has funneled $21 million into the research. 

Writing on the agency's blog, Kevin McCormack, senior director for CIRM communications, said,

"On a Sunday morning in early 2016, Lucas Lindner was driving to get some donuts for his grandmother. A deer jumped in front of his truck. Lucas swerved to avoid it and crashed, suffering a severe spinal cord injury that left him paralyzed from the neck down."

But after the treatment, McCormack wrote,

"Lucas can now type 40 words a minute, use a soldering iron and touch his pinkie to his thumb, something he couldn’t do after the accident.

"In August of last year Lucas did something else he never imagined he would be able to do, he threw out the first pitch at a Milwaukee Brewers baseball game. At the time, he said 'I’m blown away by the fact that I can pitch a ball again.'"

Of course, there are scientific caveats and qualifications in the story. But what the tale really can do is resonate with nearly all California voters if the story ever reaches them.

Those voters are key to continuing the work of the agency, which expects to run out of state funds in 2019 and is hoping that voters will pump an additional $5 billion into the agency through a bond measure on the November 2020 ballot. (A private fund-raising effort is underway to bridge the cash gap.)

The agency has largely functioned in obscurity during the last 10 years or so. Its story is not well known by the public. And it has yet to help finance a therapy that is available to the general public. But CIRM's 44 clinical trials, including the one by Asterias, provide hope for patients and the agency.

The key lies, however, in how the story is told and how well CIRM supporters can turn mind-numbing scientific jargon and public policy issues into compelling yarns that will open both the hearts and purses of California voters.

California Makes a $25 Million Kidney Transplant Wager: Its 44th Stem Cell Clinical Trial

The California stem cell agency this week more than doubled down on its bet on a potentially breakthrough treatment for kidney transplants, raising to $25.4 million its support for a project that is entering its final stages.

The hope is that the treatment will not only improve the success rate of kidney transplants but also lead to use in liver, heart and other solid organ transplants. If successful, the therapy would eliminate the need for immunosuppressive drugs in genetically matched kidney transplant patients.

Maria Millan, CIRM photo 

Maria Millan, president of the agency, said in a news release:

“These immunosuppressive drugs not only can cause harmful side effects, but they are also expensive and some patients lose their transplant either because they can’t afford to pay for the drugs, or because their effectiveness is not adequate."

The award also could help save the life of the stem cell agency, which is facing its financial demise as its funding runs out.

The award brings to 44 the number of clinical trials being assisted by the $3 billion agency, formally known as the  California Institute for Regenerative Medicine(CIRM). Clinical trials are the last stages of research prior to certification by the federal government of a treatment for widespread use.

The stem cell agency is hoping that one of its trials will soon produce a therapy that will resonate with California voters who may be asked in 2020 to provide $5 billion more. The agency expects to run out of state funding next year and is attempting to raise more than $200 million privately to tide it over until a bond election in  November 2020.

Action on the award was swift on Thursday. It took less than eight minutes for the agency governing board to unanimously approve an $18.8 million award to Medeor Therapeutics, Inc., of San Mateo, Ca. The award comes on top of a $6.7 million investment in the firm's research in 2016.

Steven Deitcher, Medeor photo

The vote simply ratified a decision on the Phase 3 trial that was already made by the agency's reviewers, who gave the research strong support during a meeting behind closed doors weeks earlier.

Steven Deitcher, co-founder and president of Medeor, said in the agency's news release,

"CIRM funding accelerates our timelines, and these timelines are what stand between needy patients and potential transformative therapies. This CIRM award combined with investor support represent a public-private collaboration that we hope will make a difference in the lives of organ transplant recipients in California, the entire U.S., and beyond."

A Look at Whether California's Stem Cell Agency Can Carry the Day Two Years From Now

One of California's more respected news operations today posted an overview of the state's $3 billion stem cell research agency, asking the question:

"Should California Voters OK $5 Billion More for Stem Cell Research?"

The piece by David Gorn on KQED's web site recapped the history of the program, its current condition and included comments from Robert Klein, the man behind the $5 billion proposal and who is often regarded as the father of the agency.

Barbara Koenig
 UCSF photo

Also included were comments from folks not always heard from publicly in the discussions about the agency. Quoted was Barbara Koenig, head of the bioethics program at UC San Francisco, who said she supports stem cell research but voted against the ballot measure that created the agency in 2004. She said,

“I didn’t like the overhyping of the immediate idea that there were cures around the corner.  I think we need to be honest about how we’re investing in research.”

Gorn continued,

"Ask Koenig how she might use that proposed $5 billion differently, and she responds with a moment of stunned silence.

"'Oh my, so many things,' she said. 'I would try to figure out how to make sure every child in California has access to basic health services, nutrition, clean water . . . not just make high-priced products, but to improve public health.'

"She said stem cell research privileges these quick-fix biotech approaches, which may make a lot of money but may not benefit the general public.'". 

Gorn's piece had some reach into the general public in the Golden State. In addition to its online news site, the San Francisco-based KQED operates a public TV station including news and  a public radio station with syndicated programming throughout the state. A version of today's story is expected to run next week on KQED's California Report, which the station says reaches 775,500 persons each week.

Gorn's report was pretty much down the middle, exploring the expectations for cures that emerged from the 2004 campaign directed by Klein, who also oversaw the writing of the initiative. His view is that that agency has "out-achieved" the promises of the campaign. Gorn wrote that Klein said that the campaign "never promised cures during the lifetime of the stem cell agency, only progress toward attaining them."

The governing board of the California Institute for Regenerative Medicine, as the agency is formally known, has all but endorsed Klein's current plan to place another initiative on the 2020 ballot, a presidential election year that will generate the large turnout that tends to favor bond measures.

Bonds -- money that the state borrows -- are the only significant source of cash for the agency. Ironically, the measure that created the agency -- also provided the seeds of its death by terminating its bonding authority after a specified period. Today the agency is down to its last few hundred million.

Zev Yaroslavsky, UCLA photo

Bonds additionally are usually used for long-lived assets such as roads and buildings and roughly double the cost of the research to taxpayers because of the interest expense. 

Gorn concluded with a comment from Zev Yaroslavsky, an authority on state politics and government at UCLA, as saying  that even if voter attitudes are highly favorable toward stem cell research that may not be enough to carry the day.

Yaroslavsky said,

"People do see stem cell research as something they have a stake in, but you’re going to have to explain what we got with the first $3 billion. I suspect their case with the voters will be that we need to keep momentum going. But the question is, ‘Will they buy it?’"

California Stem Cell Spending: Priming a $1.5 Billion Research Influx

California's $3 billion stem cell agency this week reported on "what you may not know" about the unusual, 13-year-old research organization. 

Its "disclosure" did not deal with such matters as the fact that it is the first such enterprise in state history or that it operates outside of the purview of the governor and the legislature. Rather it dealt with, among other things, leverage -- a term used often in the real estate business to describe, for example, using  $10 to create $1,000.

In the case of the California Institute for Regenerative Medicine (CIRM), as the Oakland-based agency is formally known, it said it has created $1.5 billion in leveraged funds. It also noted that it has served as a "validator" for a significant amount of research, meaning that its awards re-assure the nervous nellies of finance about making an investment in a particular project. 

CIRM's seal of approval has led to $528 million in additional "partnership" funding for specific research, the agency said, along with more than $395 million in awards from other agencies that were built on CIRM-backed research. . 

News about the agency often focuses on stories about people and their afflictions. Those emotional tales are powerful ways to tell the CIRM story, but its less well known ventures into leverage and validation also speak to its impact, both short term and long term. 

Kevin McCormack, CIRM's senior director of communications, wrote about all this earlier this week with specific numbers and details in the agency's blog, The Stem Cellar, in a preview of the agency's annual report.

"Our goal is to do all we can to support the best science and move it out of the lab and into clinical trials in people. Obviously, providing funding is a key step, but it’s far from the only step. For us, it’s really just the first step."

CIRM does report its impact in the best possible light. However, there is little doubt that it has played an important role in "de-risking" much stem cell research and creating a friendly environment that is more likely to attract additional financing for a still young field. 

California Pumping $19 Million More into Stem Cell Effort to Improve Kidney Transplant Success

The California stem cell agency is set to make a nearly $19 million bet next week on a treatment that is aimed at significantly improving the success of  kidney transplants and helping to reduce healthcare costs.

The agency's board is expected to ratify a decision to award $18.8 million to Medeor Therapeutics, Inc.,  of San Mateo, Ca., for a phase 3 clinical trial, the last stage before its proposed product can be widely used.

Next week's award will bring to $25.4 million that the state has invested in the work. The agency awarded $6.7 million for the research in 2016.

The company's chief medical officer, D. Scott Batty, Jr.,  said last spring that its product, dubbed MDR-101, "has the potential to address the two most critical transplant patient needs: preventing organ rejection and mitigating anti-rejection treatment-associated toxicities. " He added that the technology could potentially be used in all solid organ transplant patients.

Fierce Biotech reporter Phil Taylor wrote last April,

"Patients who undergo organ transplants may no longer have to rely on lifelong immune-suppressing drugs, if Medeor Therapeutics has its way."

Taylor continued,

"More than 30,000 Americans get an organ transplant every year, and while success rates for these procedures are improving, it is estimated that up to a third of the most common transplants—such as heart, kidney, and liver—fail within 5 years."

The Medeor treatment uses adult stem cells to create a condition in which the transplanted kidney "is no longer viewed as foreign by the recipient," according a summary of the closed-door review of the company's application (CLIN2-10411). 

The agency's reviewers, who do not have to publicly disclose if they have  potential conflicts of interest, voted 11-1 to fund the research. The agency's board almost never overturns the decisions of its reviewers, who come from out-of-state. The names of persons reviewing specific applications are not disclosed by the agency, which also does not disclose the name of applicants until after board action. The California Stem Cell Report identified the firm from public records.

Samuel Strober, Stanford photo

Last November, Medeor announced it had raised $57 million in Series B financing, "led by RA Capital Management. Additional new investors included Sofinnova Ventures and 6 Dimensions Capital, who were joined by existing investors Vivo Capital and WuXi Healthcare Ventures."

The scientific founder of the firm is Samuel Strober, a professor of medicine at Stanford and who is a member of its scientific advisory board. 

The estimated date of completion of the trial is January 2022, according to clinicaltrials.gov. The governing board of the $3 billion stem cell agency is scheduled to meet Jan. 18 to approve the award. No other action is scheduled.

California Stem Cells, 'Rapture' and a $5 Billion Bond Measure

This past weekend brought news about a "rapturous agreement among Republicans and Democrats" to support development of new therapies by financing biomedical research with billions of dollars.

The New York Times article indicated that the rapture could have something to do with the fact that many key political leaders on Capitol Hill are "aging in place."

The piece by Robert Pear also carried implications for the $3 billion California stem cell agency, which has virtually endorsed a yet-to-be-written, $5 billion bond measure to stave off its own death.

Pear wrote on Sunday:

"For the third straight year, lawmakers (in Congress) are planning to increase the budget of the National Institutes of Health by $2 billion. In the process, they have summarily rejected cuts proposed by President Trump.

"The push for additional funding reflects a fascination among legislators with advances in fields like molecular biology, genetics and regenerative medicine, even as they wage bitter battles over just how large a role the government should play in financing health care and providing coverage."

Pear continued, 

"Why is medical research so much less contentious than fundamental issues like health insurance coverage?

"Anthony J. Mazzaschi, a lobbyist at the national organization representing schools of public health, said that 'the charisma of the cure, the hope and promise of curing disease, seems to excite members of Congress,' including some in their 70s and 80s who are 'facing the prospect of disease and disability head-on.'"

The Times piece said, 

"The challenges facing patients and policymakers were illustrated this past week when a Philadelphia company said it would charge $850,000 for a new gene therapy to treat a rare inherited form of blindness. (The company, Spark Therapeutics, said it would pay rebates to certain insurers if the medicine, given in a one-time injection, did not work as promised.)"

California's stem cell agency is running out of money. It is looking at a November 2020 ballot measure to fill its shrinking coffers with $5 billion more. But such public policy decisions involve trade-offs concerning the health of Californians.

Several questions (among others) arise theoretically and otherwise:

• Would it be better to spend $5 billion to provide much needed, immediate health care to poor Californians, including mothers and children, which could provide a quicker payoff in improved health. 
• Is it better for the state to spend $20 million to help reduce infant mortality rates in Fresno and Mendocino that are nearly twice the statewide average or give the cash instead to a stem cell researcher (and his employing institution) who can also win the cash from the NIH. 
• The impetus for creation of the California stem cell agency was based on a restriction in federal funding for human embryonic stem cell research. That restriction no longer exists, but could be restored by the Trump administration. But should California spend its billions when researchers can seek funding at the federal level? 

These are sort of bottom-line policy questions that ignore the fact that bond issues generally are used for long-lived assets, such as prisons, educational buildings, highways, etc., -- not services such as health care. The bond measure that provided the stem cell agency with its only significant cash was an historic exception.

Nonetheless, in the public's eyes the stem cell agency is all about health. As the campaign that created the agency in 2004 noted, medical problems that affect nearly half of California families "could benefit from stem cell research."

The likely cost of the therapies that are being developed in the agency's clinical trials are almost never discussed in public. Yet many are likely to be as expensive as the Spark Therapeutics blindness treatment. One can only imagine the kind of opposition advertising that is likely to surface in a campaign for a $5 billion bond measure: "Vote No on Million Dollar Cures for Billionaires!" On the other hand, that pitch might seem too harsh and blow back on agency opponents.

Nonetheless, Americans believe drug costs are too high, something that will come into play during a 2020 campaign. According a recent Gallup poll, 78 percent of the people also say total health care costs are too expensive. Drug costs have become an easy litmus test for the expense of staying healthy.

The New York Times story noted the importance of age as helping to create support for spending on medical research. California is headed for a sharp increase in the numbers of seniors in the next decade. One study is even projecting a "silver tsunami" of cancer in older patients nationally. Generally, however, older voters are considered more likely to be conservative. and may not buy into more government spending. How that plays out in California is not clear when it comes to stem cell research or the hope for stem cell cures.

Hope is one of the more powerful products of the California stem agency. Ultimately that could be the deciding selling point. But the November 2020 election is 34 months away, and much is likely to change.

Tracking the $3 Billion California Stem Cell Agency Month by Month

Directors of the California stem cell agency plan to meet 12 times during the coming year, including four valuable face-to-face sessions that are likely to be based at its Oakland headquarters.

Valuable because those sessions offer an opportunity to chat directly with directors and the agency's staff. The face-to-face sessions are scheduled for March 13, June 28, Sept. 20 and Dec. 13. Topics for the meetings will come later when agendas are posted 10 days before the sessions. But the June and December meetings have often dealt with important financial and strategic issues.

Researchers who have attended the board sessions in the past have benefited from gaining a greater understanding of the application review process and procedures of the board as it ratifies reviewer decisions and hears appeals.

The other eight meetings are telephonic and are scheduled to occur on Jan. 18, Feb. 22, April 26, May 24, July 26, Aug. 23, Oct. 18 and Nov. 29.

To be announced during the year on an ad hoc basis are meetings of the committees of the governing board, which regularly consider important issues and approve policies and actions that are often summarily ratified by the board.

All of the meetings can be tracked by subscribing to notifications from the agency and by reading the California Stem Cell Report, which tries to provide a deeper look at some of the matters facing the stem cell agency.

The public can attend all the meetings at either remote locations and the CIRM headquarters and can address the board directly. If you just want to listen, an audiocast is available. After the meetings, which are also accessible as a recording, transcripts become available a couple of weeks later. 

Places to Go, Stem Cell Science to See in 2018

The $3 billion California stem cell agency did all you stem "cellists" out there a big favor this week with a rundown of the hottest and most interesting conferences coming up in 2018. A UC Davis researcher also has put his own list on his own blog.

First, the agency's list of what it describes as "awesome" conferences. They range from industry-oriented events to ones devoted to science. Coming up next week is a "state of the industry" briefing by the Alliance for Regenerative Medicine in San Francisco. The World Stem Cell Summit runs at the end of this month in Miami.

A discussion of the agency's Alpha Clinics program is scheduled for April 19 at UCLA. Last year's Alpha program at the City of Hope was excellent. December will bring a Cedars-Sinai conference on Translation of Stem Cells to the Clinic, Challenges and Opportunities, which could be illuminating as the stem cell agency pushes to fulfill the promises of the ballot initiative campaign that created the research effort.

Of course, there are many more -- much too many to list here.The Oakland-based agency has also provided links to the conferences it highlights

Over at UC Davis, scientist Paul Knoepfler's list included some of the same sessions. He also is soliciting information on conferences that he has not listed. You can send him your information by clicking here. 

Stem Cell Person of the Year: Michele DeLuca of Italy

An Italian scientist has been named Stem Cell Person of the Year for 2017 by The Niche, a stem cell blog produced by a California researcher.

Michele DeLuca, CMR photo

Paul Knoepfler of UC Davis announced the selection of Michele DeLuca on his blog last week.
Knoepfler wrote,

"I chose him because of his exceptional track record in stem cell and regenerative medicine science combined with a long record of advocating for responsible translational science."

The award carries of a cash prize of $2,000, which Knoepfler funds himself. The California stem cell scientist commented,

"Dr. De Luca also led an international team that recently published a groundbreaking paper on epidermal regeneration in a pediatric patient with epidermolysis bullosa. The new paper reported an innovative combination stem cell-gene therapy approach to this terrible disease. I reviewed the paper here in journal club style. The manuscript is an important starting point in new therapy development. It’s the kind of work that is very risky and needs to be done in a meticulous way. Dr. De Luca is one of the few people in the world who could have led this work."

Knoepfler is the sole arbiter on the award but does ask his readers to indicate their preference. In the case of DeLuca, he received 2.98 percent of votes cast. 

Knoepfler started the awards in 2012 with an initial prize of $1,000.

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.

California Researchers Score $16 Million Plus in State Stem Cell Awards

The California stem cell agency today handed out $16.4 million in research grants seeking therapies for afflictions ranging from gum disease and cancer to vision loss and Parkinson's Disease.

The award for Parkinson's was relatively tiny -- only $150,000 -- but represented a rare case in which the agency's governing board overturned its reviewers, who make the de facto decisions on awards.

The reversal came after one board member, David Higgins, of San Diego, who has Parkinson's, noted that the most common drug that Parkinson's patients take is 70 years old. He told the board.

David Higgins, CIRM photo

“I’m a fourth generation Parkinson’s patient and I’m taking the same medicine that my grandmother took. They work but not for everyone and not for long. People with Parkinson’s need new treatment options and we need them now. That’s why this project is worth supporting. It has the potential to identify some promising candidates that might one day lead to new treatments.”

The award went to Zenobia Therapeutics, Inc., of San Diego, whose president and co-founder, Vicki Nienaber, had filed an appeal on the reviewers' decision.  Another applicant rejected by reviewers, Toshio Miki of USC, also filed an appeal with the board. His appeal was not discussed. Miki's application sought $5.9 million for research involving metabolic disorders.

The largest award today, $5.6 million, went to Anthony Oro of Stanford, who will be testing a therapy to treat an affliction that creates wounds that will not heal. Dan Kaufman of UC San Diego received $5.5 million to produce "killer cells" to help people with a form of leukemia. Catriona Jamieson, also of UC San Diego, received $2.7 million for leukemia research.

Here is a link to summaries of reviewer remarks, including scores, on the three winners and the 11 other applications that were rejected in the translational awards category. (Scroll down on the page to see the reviews.)

In addition to the "discovery" award for Parkinson's, here are the names of the other winners in that category:

•  DISC1-10603, Ngan F Huang, iPSC-Derived Smooth Muscle Progenitors for Treatment of Abdominal Aortic Aneurysm, Palo Alto Veterans Institute for Research, $172,621
• DISC1-10475, Semil P Choksi, Generation of human airway stem cells by direct transcriptional reprogramming for disease modeling and regeneration, U.C. San Francisco, $238,408
• DISC1-10643, Dmitriy Sheyn, IVD rejuvenation using iPSC-derived notochordal cells, Cedars-Sinai, $241,992 
• DISC1-10598, Alice F. Tarantal, Enhanced Branching Morphogenesis and Pluripotent Cell Lineage Differentiation for Pediatric Regenerative Therapies, U.C. Davis, $235,80
• DISC1-10583, John R Cashman, Human Pancreatic Cancer Stem Cells: Developing a Novel Drug for Cancer Eradication, Human BioMolecular Research Institute, $303,894 
• DISC1-10555, Hiromitsu Nakauchi, Optimizing self-renewal signaling kinetics to stabilize ex vivo hematopoietic stem cell expansion, Stanford, $235,836 
• DISC1-10620, David J. Baylink, Bone Marrow Targeting of Hematopoietic Stem Cells Engineered to Overexpress 25-OH-VD3 1-α- hydroxylase for Acute Myeloid Leukemia Therapy, Loma Linda University, $178,967 
• DISC1-10513, Guillem Pratx, Novel metabolic labeling method for tracking stem cells to irradiated salivary glands using PET, Stanford, $235,613 
• DISC1-10522, Gerald P Morris, Identification of antigenic neo-epitopes from in vitro reprogrammed human tissue precursors for regenerative therapy, U.C. San Diego, $193,500
• DISC1-10588, Julia J. Unternaehrer-Hamm, Targeting cancer stem cells with nanoparticle RNAi delivery to prevent recurrence and metastasis of ovarian cancer, Loma Linda University, $172,870 
• DISC1-10721, Karl J. Wahlin, An IPSC cell based model of macular degeneration for drug discovery, U.C. San Diego, $232,200 
• DISC1-10516, Alyssa Panitch, Development of treatments to improve healing of ischemic wounds, U.C. Davis, $235,800 
• DISC1-10718, Alireza Moshaverinia, Gingival mesenchymal stem cells as a novel treatment modality for periodontal tissue regeneration, U.C. Los Angeles, $194,483

Here is a link to all the review summaries and scores in the round, including the 28 rejected applications.  Here is a link to the CIRM press release.