The Quest for Stem Cell 'Franchise Players:' California's $47 Million Recruitment Program

 Robert Weschler-Reya briefly discusses some of the implications of his research.

Nine years ago this month, the California stem cell agency kicked off a $47 million recruiting effort to lure star stem cell scientists to the Golden State in what was then an even more fledgling field than it is today.

The first recipient was Robert Weschler-Reya, who left Duke University to join the Sanford Burnham Prebys Medical Discovery Institute in La Jolla, Ca. Weschler-Reya surfaced again last week in an item on the stem cell agency's blog, The Stem Cellar, which discussed the research that he hopes will help children with a deadly brain cancer.

Back in April 2010, directors of the state's $3 billion stem cell agency awarded nearly $6 million to Weschler-Reya. But it took him months to make the decision to come to California. (For more on the process see here and here.)

Ultimately, the agency helped to bring eight other scientists to California through the recruitment effort. All of the awards in the program benefited institutions with past or present representation on the agency's governing board. Those directors could not vote on specific grants to their institutions, but they all voted in favor of creating the recruitment effort.

The overall approach was approved in 2009 by directors of the agency, known formally as the California Institute for Regenerative Medicine (CIRM). Backers said it would lure "paradigm-shifting," "franchise players" to the state.

CIRM Director William Brody, then head of the Salk Institute in La Jolla but also a former president of John Hopkins University in Maryland, said that when California voters created the stem cell agency in 2004,

"I was sitting in Baltimore (and) the big concern was that there would be this big sucking sound for the senior people. And that, by and large, I don't think has happened because there's not been an appropriate mechanism to bring them, and I think this would do that."

As for Weschler-Reya, CIRM quoted him on its blog last week as saying that his research has developed "a valuable tool that will increase our understanding of the biology of the cancer and allow us to identify and test novel approaches to therapy. This advance brings us one step closer to a future where every child survives—and thrives—after diagnosis with CPC (choroid plexus carcinoma).

In his year-seven report on his CIRM research, Weschler-Reya said,

"The goal of our studies has been to elucidate the role of stem cells in development, regeneration and tumorigenesis in the cerebellum. We have made significant progress towards this goal during the course of our work.

"Our studies have provided insight into the types of cells derived from cerebellar stem cells during development, and shown that cerebellar stem cells can serve as cells of origin for pediatric brain tumors. Moreover, we developed several new stem cell-based animal models of pediatric brain tumors, and used them to study mechanisms driving tumorigenesis and metastasis. Importantly, we also used these models to screen for compounds that might be effective inhibitors of tumor growth, and identified a number of promising candidates. 

"Our long-term goal is to move these agents toward clinical trials, to improve outcomes for pediatric brain tumor patients."

Here is a list of all the recipients in CIRM's recruitment program. 

Institution	Researcher name	Grant Title	Award Value
University of California, Berkeley	Xavier Darzacq	Single Molecule Biophysics and Biology of Cellular Identity	$4,247,155
Gladstone Institutes, J. David	Todd McDevitt	Engineering microscale tissue constructs from human pluripotent stem cells	$5,884,058
University of California, Los Angeles	John Chute	Niche-Focused Research: Discovery & Development of Hematopoietic Regenerative Factors	$5,174,715
Cedars-Sinai Medical Center	Barry Stripp	Epithelial progenitors and the stromal niche as therapeutic targets in lung disease	$4,841,830
Stanford University	Hiromitsu Nakauchi	Generation of functional cells and organs from iPSCs	$5,427,512
University of California, San Diego	Eric Ahrens	Molecular Imaging for Stem Cell Science and Clinical Application	$5,920,899
University of Southern California	Andrew McMahon	Repair and regeneration of the nephron	$5,672,206
University of California, Santa Barbara	Peter Coffey	Development of Cellular Therapies for Retinal Disease	$4,690,963
Sanford-Burnham Medical Research Institute	Robert Wechsler-Reya	The role of neural stem cells in cerebellar development, regeneration and tumorigenesis	$5,226,049
			47085387

Backed by California Stem Cell Agency: $5 Million Measure for Spinal Cord Research Advances in Sacramento

Legislation supported by stem cell research advocates to provide $5 million for work on spinal cord injuries easily cleared its first hurdle this week in Sacramento.

On a 15-0 vote, the proposal, AB 214, was approved Tuesday by the Assembly Health Committee and sent to the Appropriations Committee for placement on the "consent calendar."  Such a move could speed action on the bill.

Assemblyman Kevin Mullin, D-San Mateo, authored the bill, which is backed by Americans for Cures, the Palo Alto stem cell advocacy group created by Bob Klein, the first chairman of the $3 billion California stem cell agency.

The agency, known formally as the California Institute for Regenerative Medicine (CIRM), is also listed as a supporter of the legislation. Other supporters included Aivita Biomedical of Irvine, Ca, the California Life Sciences Association and the Miami Project to Cure Paralysis.

The CEO of Aivita is Hans Keirstead, a stem cell researcher formerly with UC Irvine.

No opposition was listed in the legislative staff analysis of the bill.

The measure provides $5 million to support the Roman Reed Act of 1999, named after a man who was paralyzed as the result of a spinal cord injury. Roman and his father, Don Reed, are long-time backers of the stem cell agency's work.  The elder Reed is a vice president of Americans for Cures.

The legislative analysis carried this comment sourced to the bill's author:

"The previous allocations of approximately $15 million in state funding to the Roman Reed program was leveraged over five times that amount in new grants benefiting spinal cord research all across the state. It’s time to reinstate a modest amount of state funding so these efforts can continue."

California Legislation Targets Unregulated "Stem Cell" Clinics but Not Until Next Year

Legislation that may lead to regulation of dubious stem cell clinics is now before California lawmakers, but it is not likely to result in action until sometime next year at the earliest. 

Assemblyman Kevin Mullin, D-San Mateo, announced the measure (AB617) last week. He said in a news release, 

Kevin Mullin, LA Times photo

“It is clear that more must be done to ensure the proper regulation of for-profit stem cell clinics."

More than 100 unregulated "stem cell" clinics exist in California and hundreds more throughout the nation. They use what they describe as stem cells in untested treatments that cost thousands of dollars. A number of injuries, including blindness, have been reported. (See here, here, here and here.)

Jonathan Thomas, chairman of the $3 billion California stem cell agency, told its governing board last week that the clinics were peddling "snake oil."

Mullin's bill would create an advisory board within the state Department of Public Health to study the problems involving unregulated stem cell clinics and make recommendations to the legislature. 

The panel would also have the power to enact emergency regulations. If passed by the legislature this year, it would not take effect until next January. In addition to requiring hearings, the board could not implement emergency regulations without at least a 90-day waiting period.

Art Torres

Asked for comment on the legislation, Art Torres, vice chairman of the state stem cell agency and a former state lawmaker, told the California Stem Cell Report that he would withhold remarks on the bill until  "we work out final language/amendments before its first hearing in April."

Generally, proposed laws, including Mullin's measure, do not take effect until January of the following year after they are approved by both houses of the legislature and signed by the governor. 

Legislation that has "urgency" status can go into effect immediately, but such measures require a two-thirds vote of both houses instead of a simple majority. Securing a two-thirds vote can sometimes be difficult. 

The problems surrounding unregulated clinics have existed for years, but received little attention at the state or federal level until UC Davis researcher Paul Knoepfler and Leigh Turner of the University of Minnesota documented the scope of the business in 2016.

California's state medical board, which regulates physicians, is also looking into the unregulated clinics.

Down to its Last $67 Million: California Stem Cell Agency Awards $4 Million to Improve Bone Healing

A look at the the spinal affliction targeted by CIRM-backed research. Video by NuVasiveInc

OAKLAND, Ca. -- California's state stem cell agency is down to its last $67.3 million following a decision today to back research to enhance bone healing in elderly patients who undergo spinal surgery.

The $4 million award went to Ankasa Regenerative  Therapeutics following little discussion among members of the governing board of the $3 billion California Institute for Regenerative Medicine or CIRM, as the stem cell agency is known. 

Ankasa, which has locations in La Jolla and South San Francisco, is supporting the award with a matching amount of $1 million. Sandy Madigan, CEO of Ankasa, told the California Stem Cell Report that his firm has raised $19 million in venture capital. Its only current potential product, he said, is tied to the CIRM-backed research, which the agency has previously funded with $8.6 million. 

(See here and here for more on the Ankasa work.)

CIRM said at today's meeting that the award leaves the agency with $67.3 million for research for the remainder of the year. It has budgeted a total of $93 million for clinical stage awards this year.

The stem cell agency was created in 2004 with $3 billion in funding. It expects to run out of cash for new awards later this year. CIRM is seeking to raise $220 million privately to tide it over until November 2020, when it hopes voters will approve another $5 billion in funding through the use of state bonds. 

CIRM board Chairman Jonathan Thomas did not report at the meeting today on the status of the private fundraising effort. 

The only significant source of cash for the agency is the $3 billion in bonds approved by voters in 2004 via the ballot initiative process. The 2020 effort would also involve a ballot initiative. 

The deadline for filing such a measure is Aug. 19. That would set the stage for actually gathering the 585,407 valid  signatures needed to qualify for placement on the ballot. 

Today's award was approved Feb. 28 behind closed doors by the agency's out-of-state reviewers, who sent it to the CIRM board for routine ratification. 

The six-page, CIRM summary of the review said the proposal (CLIN1-11256) addresses "the need for a spinal fusion material that can increase the chance for a solid bony union in the lumbar spine." The review said, "There are other products on the market that fulfill this need but have safety concerns that have been raised in the past."

Jill Helms, chief scientific officer of Ankasa and a professor at Stanford University, led the research backed by CIRM. 

The review summary said the proposed treatment could have application in other areas as well. It is likely to be some years before the procedure would be widely available. Today's award supports efforts by Ankasa to gain federal approval to begin clinical trials.

See here for the CIRM press release on the award. 

Making 'Stem Cell Lemonade' in California

Trump visiting lab in China in 2017, whose research output is
surpassing the U.S. Photo: Andy Wong/AFP/Getty Images

California's $3 billion stem cell agency has what some might call an "unconscious" ally in its search for more billions to fuel its drive to create stem cell therapies and cures.

It is no small matter. The agency expects to run out of cash for new awards by the end of this year. It is hoping that voters will approve, in November of 2020, another $5 billion to carry on with its 14-year-old program, which is a pretty big ask.

Now comes President Trump with his latest proposed budget, which whacks away at scientific research. He is seeking to slash as much as $6 billion from the National Institutes of Health, the chief source of research funding in the country.

The American Association of Immunologists said this week that Trump's cuts “would devastate important research intended to prevent, treat, and cure innumerable diseases."

Trump's cuts play into a narrative that worked successfully in 2004 when California voters created the stem cell agency with 59 percent of them voting for Proposition 71. The campaign pushed the ballot initiative with the argument that then President Bush was crippling stem cell research and thus preventing development of new, nearly miraculous therapies.

Like Bush, Trump is something of a scientific villain, so to speak, one that can be used as a foil to convince the people of California to provide more money for stem cell research. Never let good villain go to waste might be the marching orders for the 2020 ballot campaign.

If not for California and its stem cell agency, voters would be told, children would have died (see here and here) and more than 50 clinical trials for stem cell treatments would have not existed.

It is no matter that Congress may not go along with Trump's reductions. The threat, which is likely to continue as long as Trump is president, is sufficient to fuel a ballot campaign.

Obviously, cuts in federal research funding are not something the scientific and biotech community applauds. Nonetheless, they could be picked apart to find morsels to feed a ballot campaign. The agency's backers might even say, "When the president gives you stem cell lemons, make stem cell lemonade."

Cash and the California Stem Cell Agency: A Critique Notes August Deadline for New Funding Initiative

California's $3 billion stem cell program is facing a cash crunch this year, and the latest commentary on its financial fate raises a host of questions. 

The critique comes from the Center for Genetics and Society, a Berkeley group that has long been critical of the California Institute for Regenerative Medicine (CIRM), as the state stem cell agency is known. 

Writing on the center's blog, Pete Shanks briefly recapped the history of CIRM and its current financial situation. The agency expects to run out of funds for new awards this year and is  trying to raise privately more than $200 million. The cash is intended to bridge the gap between now and presumed voter approval of an additional $5 billion in November 2020. 

Quoting CIRM board transcripts, Shanks wrote: 

"They are still looking for an 'anchor investor,' who might encourage others (as an anchor store draws people to a shopping mall). Which makes CIRM board member Jeff Sheehy (long-term AIDS activist and former San Francisco Supervisor) sound prescient, since in September 2017 he had suggested that savvy voters might say (pp. 78–9 ): 

'So you went to fund-raise. You didn’t get enough to keep you going, so you’re coming back to me with your hand out. So why didn’t you get enough? Why did the people who you’ve been asking for money not think you were a good investment? Why should I?' 

"Good point. Indeed, some of the board members were over-optimistic in that 2017 assessment."

Shanks also raised other questions about the nature of CIRM's private fund raising effort and looming deadlines for qualifying a bond measure, along with a ballot initiative that will likely retool the existing law that created the agency in 2004. 

Shanks concluded,

"Propositions take considerable time to be approved. The deadline for submitting a proposed measure to the attorney general that’s intended for the November 2020 election is August 20, 2019 . In practice, that means that the proposition is probably being written now, or will be completed very soon, and preliminary backers have likely been identified and contacted already. Unless, of course, such funders cannot be found. 

"Will CIRM’s problems be solved? We’ll soon know."

Stem Cell Hype: The Latest Warning from Researchers

The Scientist journal last week carried a cautionary note concerning iPS cell therapies, particularly a recent, "exciting" announcement concerning their use for treatment of spinal paralysis.

"Ethical Challenges in Using iPS Cells to Treat Paralysis," was the headline on the opinion piece. It carried a subheading that said,

"Uncertainties about the cells’ risk profiles and the potential for hyping unproven therapies mean scientists and the media must tread carefully."

The article dealt primarily with what it termed "exciting" news about an experiment in Japan. But the article has broader implications for the entire field including in California, where the state stem cell agency is currently helping to fund 46 research projects involving iPS, induced pluripotent stem cells. 

The piece was written by John D. Loike, a professor of biology at Touro College and University Systems in Brooklyn and who has a regular column on bioethics in The Scientist, and Martin Grumet, a professor of cell biology and neuroscience at Rutgers.

Writing about the Japanese research, they said, 

"Caution is warranted here, for at least three reasons: the uncertainty of the stem cell type to be used in their clinical trial, the safety of transplanting stem cells into humans, and the responsibility of scientists and the press to communicate clearly the benefits and risks of the stem cell treatments, especially to desperate patients who would seek such unproven treatments."

They continued.

"The excitement of the press release may be misinterpreted by patients, who may think that now is the time to treat human spinal cord injury with stem cell transplants. With difficulties getting admitted to legitimate sub-clinical trials, could this hype for hope lead poorly informed patients to seek out other “stem cells” to treat their spinal cord injuries or other conditions? We must avoid anything that may promote “medical tourism” to unapproved interventions.

"The fact that there are more than 700 'stem cell clinics' advertised in the United States alone highlights the desperation of so many patients with terminal illnesses seeking unapproved or unproven therapies. There are no studies documenting the therapeutic successes of these clinics and some of their patients have developed serious side effects. Scientists and the press must ensure an ethical and realistic presentation and communication of new and potentially exciting discoveries and caution readers about the realities of initial clinical trials.

The FDA and the Loss of Gottlieb: What Does it Mean for Stem Cell Research?

Scott Gottlieb at his earlier Senate confirmation hearing

"Panic Attack" --That's what the headline this morning said about the resignation of Scott Gottlieb as head of the Food and Drug Administration(FDA). 

The STAT article addressed the general biotech field and its worries. Gottlieb's departure, however, also creates some uncertainty involving California's $3 billion stem cell agency. Known as the California Institute for Regenerative Medicince (CIRM), the agency is backing 51 clinical trials, all of which are regulated by the FDA.

STAT is one of the more authoritative outlets dealing with medical research news. Its Gottlieb piece reviewed his impact on stem cell and regenerative medicine and what his loss might mean. The full headline said, 

"Scott Gottlieb's Sudden Resignation Will Give Biotech a Panic Attack"

The article by Matthew Herper and Adam Feuerstein said,

"Without Gottlieb at the helm, there is uncertainty. And there is nothing that scares investors and biopharma more."

Most of the news coverage of Gottlieb's surprise resignation focused on his efforts regarding vaping and opiods.  But STAT was not alone on discussing the stem cell/regenerative medicine issues. A piece on Politico said, 

"Gottlieb worked to advance cell and gene therapies, a promising new area of medicine. Under his leadership, the FDA put out a framework for regenerative medicines, designed to accelerate the approval of the most promising gene therapies. At the same time, Gottlieb balanced promoting legitimate new treatments with crackdowns on bad actors who were taking advantage of patients by marketing unapproved, unproven and potentially dangerous treatments."

In California, the state has invested roughly $2.5 billion so far in stem cell research with goal of bringing products to market. That is a process that heavily involves the FDA.

Indeed, a top official of the FDA will be speaking next month at a San Francisco conference sponsored by the agency and UC San Francisco. The topic? "Regulation and the Office of Cell Therapy and Gene Therapies Expedited Reviews"

It is far from clear what will emerge at the FDA concerning regenerative medicine or whether Gottlieb's approach will continue.  President Trump may leave the post vacant for some time. He will be heavily lobbied by interests that have opposed Gottlieb's more visible efforts concerning vaping and opiods. 

Trump also will feel pressure from the regenerative medicine industry. But given the multiplicity of issues facing the president, the FDA is not likely to be high on Trump's priority list. And then there are Senate confirmation hearings on any appointment.

Meanwhile we can expect to see more analysis in the coming weeks of what it all means for stem cells and regenerative medicine. 

A Chance to Peek Inside a $50 Million California Stem Cell Program

Video from 2017 Alpha Clinic symposium

One of the better stem cell, show-and-tell conferences is coming up this spring in San Francisco, plus it is free and open to the public.

The day-long session will provide a peek inside one of the signature efforts of California's 14-year-old, $3 billion stem cell research program, which is edging closer to ever more critical financial times. 

The meeting April 18 is the fourth annual Alpha Clinic symposium. The Alpha Clinic Network was created in 2015 by the California Institute for Regenerative Medicine(CIRM), as the stem cell agency is formally known. 

CIRM has pumped $50 million into the network, which is aimed at delivering clinical trials to patients, creating strategic relationships between science and industry and leveraging statewide resources. Sites for the network are located at the City of Hope and at UC campuses in San Francisco, Davis/Sacramento, San Diego, UCLA and UC Irvine.

For those interested in California public policy issues dealing with health, medical mattters and research, the symposium will offer an up-close opportunity to check out the impact of the state stem cell agency. 

The session promises updates on stem cell research and clinical trials on afflictions ranging from sickle cell disease to cancer along with a look at gene editing. Scientists and patient advocates will be telling their stories and detailing the research.

CIRM is scheduled to run out of cash for new awards this year. It is attempting to raise privately $220 million to bridge a financial gap before hoped-for voter approval of $5 billion more in funding in November 2020.

Geoff Lomax, CIRM's senior officer for strategic infrastructure, told the California Stem Cell Report via email last week:

"It’s an exciting time in medicine as we have the tools to literally mend cells at the DNA level. The annual symposium is an opportunity to hear from the pioneers who developed these tool, the Alpha Clinic doctors and nurses that use them and the patients that have benefited from them."

Here are links to more information about the Alpha Clinic Network: Agenda for the symposium. CIRM's Alpha Clinic page, a CIRM blog item on the April meeting. 

The session this spring is financed with $60,000 from the stem cell agency.

California Stem Cell Program Trying to Build $220 Million Financial Bridge: An Update

For many months now, California's stem cell research program, which expects to run out of cash by the end of this year, has been seeking to raise privately $220 million. But it has yet to report that it has snagged a significant chunk of that amount.

The most recent overview of the current fundraising effort came last December at a meeting of the governing board of the California Institute for Regenerative Medicine (CIRM), as the state stem cell agency is formally known. 

Jonathan Thomas
CIRM photo

Jonathan Thomas, chairman of the CIRM board, briefed the panel on the progress of the effort to create a financial bridge to the hoped-for passage of a possible $5 billion ballot measure in November 2020. 

The fund-raising effort is targeting high net-worth, potential donors and medically oriented foundations with a smorgasbord of philanthropic options. The choices can be tailored to a potential donor's appetite, including supporting specific types of research, Thomas said. 

Thomas is expected to update the board on the fundraising effort at its next meeting March 21, which will be based at its Oakland headquarters. The session will also be available on the Internet with remote hook-ups that will allow members of the public to comment and ask questions.

CIRM was created by voters in 2004 who also provided it with $3 billion in state bond funding. No additional source of cash was established.  At the beginning of this year, the agency was down to its last $144 million for new awards. It has set aside cash for administering its final awards should a new bond measure fail to pass. 

Here is the text of what Thomas told the 29-member board in December about the fund-raising drive. The text comes from the transcript of the meeting.

“So I'm going to move next to a report on the bridge fundraising, sort of a year-in-review summary. As you recall, through the end of last year (2017), we had secured 7 million from Bill Bowes and Pitch Johnson. We talked about that earlier (2015). (The funds are allocated for a "wind-down.")

“At our December board meeting last year, when we reported on the fact we were aware we're going to be out of funds potentially by the end of 2019, we talked about a couple things. One, Bob Klein (former chairman of the agency’s governing board) was here and talked about his potential intent to run a new bond measure in the november 2020 general election for $5 billion. 

We, also at that meeting, discussed the fact that we would like to be able to keep things going at a normal pace between the time we had run out of money, which we anticipated to be late 2019, and the election. And so we decided at that point that we would look to pursue bridge funding to fill that gap ideally in an amount equal to roughly the average of what we put out over the last few years.

“So the vision at that time was to raise bridge funds to not only go through 2020, but, if successful in 2020, the next actual realization of bond proceeds would be in the spring issuance by the state treasurer of bonds on behalf of all state agencies funded out of the state treasurer's office. So it would really be getting from late 2019 to spring of 2021.

“The idea was all of that money had to be raised in a staggered way through the last installment in the middle of 2020. A note that this is just referring to research funds. We have admin funds earmarked currently all the way through 2023.

“The strategy at that point to pursue the vision was to identify the most likely parties interested in medical research both in California and in the rest of the country. We spent a great deal of time doing that.
“Secondly, to tailor the asks to specific candidates that we felt would be the most successful in terms of what we were pitching. Thirdly, to approach those candidates either directly or through third-party intermediaries well known to the candidates. And the theory there is not only is how you ask is important, but who gets you in the door to ask is vital.

“So we've spent a lot of time analyzing who the correct third-party intermediary would be who would have individual and direct contact with the candidates in question. We've had weekly meetings of our fund-raising team, consisting of myself, Maria Millan (CIRM president and CEO), Maria Bonneville (vice president of administration for CIRM), Scott Tocher (CIRM general counsel), and Eliana Barnett (senior executive assistant in CIRM's office of president), to discuss strategy as we continue to update. And we have coordinated with Bob Klein's office and with Melissa King (executive director of Americans for Cures) of Bob Klein's office on these discussions. (Klein founded Americans for Cures.)

“The plan to implement the strategy is to offer a menu of fund-raising options including charitable gifts, the loan product that we discussed that tied to the election, program-related investments, and other derivatives of those ideas. We developed that menu of options in consultation with legal counsel, bond counsel for the state, the state treasurer's office, the state controller's office, and other outside parties with relevant input, such as those that have had programs that we might wish to emulate. Note that we're asking for a variety of things, including unrestricted gifts or loans or gifts or loans to specific projects or conditions or whatever.

“The idea with the gift would be, or loan, if you put money in, not only would it enable the bridge period, but it would allow for giving us the most credible shot of getting an election passed in 2020, at which time, whatever your particular interest would be, if the measure passed, you would have a tremendous leveraging effect. 

“So if you were to put in, for example, 50 million and the measure passed, you've have a hundred-to-one leverage that would result from that, a good chunk of which could go towards whatever your specific interest was.

“So as we've been developing those ideas, we've been refining the asks as we've gone along in terms of what feedback we get as to what sounds more appealing or less appealing.

“To date, implementing that plan, which is connected to the strategy, we've met or had confidential calls with dozens of stakeholders, including ultra high net worth individuals whether individually or in groups.

“I referenced an event that Bob and I did in the summer in the Palo Alto area for a number of family offices. We've also talked, met with major foundations, with corporations who have an interest in the medical research space, and with numerous third-party intermediaries of the kind I described earlier. The way it sort of is broken down, been looking at funding either CIRM generally or with respect to specific projects, which I've sort of taken the lead on. Maria Millan has done a lot of great work in developing project-specific related asks for different initiatives that CIRM either has or would consider having that would get the fundraisers in the game.

“To date, as you might expect, a number of the meetings that we've had, the people we have talked to have, as far as the pitches go, either declined respectfully, others are ongoing as we speak. Since the last board meeting, we've continued our strategy discussions of third-party intermediaries. We've had several approaches to specific ultra high net worth individuals either in person or through these intermediaries. As before, a number of those have declined. However, there are a number of those discussions which are ongoing.

“We've calendared a number of meetings with potential stakeholders between now and the next board meeting, including meetings with major foundations, ultra high net worth, again, either in person or through third-party intermediaries. In addition, we have two group meetings similar to the one we had in the summer with family offices scheduled for the first quarter, which are one in San Diego and one in Los Angeles.

“So that is sort of where we are at this point. We continue to look for our anchor investor. And if we can do that, the strategy is when you get the anchor investor on board, that anchor investor typically has a number of friends that he or she can then rope into the fold. We're also going to focus more beyond the anchor investment to the smaller potential gifts. We've spent a great deal of our time on the anchor effort. And we will be, as we have successes, reporting in real time back to the board and in the next in-person meeting in March.

“So that's a review of the year. Are there questions? Thank you. That is most definitely a subject to be continued and continued and continued.”

Shilling for Stem Cell Treatments? A Look at the Journal Nature and an Advertising Matter

For UC Davis scientist, Paul Knoepfler it was something "very strange." For Pulitzer Prize-winning Los Angeles Times columnist Michael Hiltzik, it had the earmarks of a "race to the bottom."

And it all involved a stem cell matter published by the prestigious journal Nature.

The headline on Hiltzik's column yesterday summarized the case like this. 

"Did a world-famous science journal become a shill for a questionable stem cell claim?"

Hiltzik wrote,

"Readers of Nature, one of the world’s most important scientific journals, might have been struck recently by an audacious claim appearing on its website about a possible stem cell treatment for heart attacks.

"The published item asserted that MUSE cells, a subset of stem cells, could regenerate heart tissue after acute myocardial infarctions, which are deadly sudden heart attacks. This could be a significant advance in both cardiac treatment and the use of stem cells.

"Here’s the problem. The published item wasn’t a peer-reviewed article subject to Nature’s rigorous professional vetting procedure. It was an advertisement placed by the Translational Research Center for Medical Innovation, the Japanese research lab that says it performed the reported study on MUSE cells using white rabbits.

"It looked like a Nature article, however, at least to Paul Knoepfler, a stem cell expert at UC Davis who has become one of our most assiduous debunkers of stem-cell quackery. Knoepfler thought the layout of the item might cause some readers to mistake it for a peer-reviewed paper, and promptly queried Nature. The journal responded by taking the advertisement offline Feb. 22. Knoepfler’s brief chronicle of the affair can be found on his website here."

Hiltzik concluded:

"The Food and Drug Administration has its hands full monitoring these claims and treatments. The agency has issued multiple warnings to steer the public away from such clinics and has taken administrative and legal action against some of them. The signs point to more exploitation and more danger to the public health. Important journals such as Nature shouldn’t be participating in a race to the bottom."

For the record, Knoepfler has been critical in the past about some of Hiltzik's commentary, including the columnist's views about the state stem cell agency.  

'Getting Stanford's Attention:' The Transcript of a $1.7 Million Matter

The California stem cell agency has posted online the 24-page transcript from last week's meeting during which the agency's governing board raised sharp questions about Stanford University and its obligation to provide co-funding on a $19 million award to one of its scientists.

The board voted unanimously last Thursday to condition additional millions for the research on receiving by May 1 the co-funding, which totals $1.7 million.

Just before casting his vote, Art Torres, vice chairman of the board and a former longtime state lawmaker, said, 

"I do think that we have put forward this motion in order to get Stanford's attention as to what their commitment has been in the past, and what it will continue to be given the nature of the arrangement that we made with them."

Stanford researcher Judith Shizuru sought $6 million for continuation of a phase one clinical trial to develop a potentially "transformative" product that would eliminate the toxic impact of chemotherapy for a number of diseases. 

The $3 billion agency reduced the amount that would be given to Shizuru to $3.75 million along with imposing the deadline for co-funding. 

The agency expects to run out of money for new awards by the end of this year. 

Correction

An early version of the Stanford item today incorrectly reported the deadline for co-funding of the award in question. The correct date is May 1 -- not April 1. Judith Shizuru's last name was also incorrectly spelled. 

California's Stem Cell Agency Smacks Stanford for Failing to Deliver on Financial Promises

The California stem cell agency today delivered an unusual and sharp rebuke to Stanford University, declaring that it needs to stand by its financial commitments to help back state-funded research. 

The message came during consideration of a request for more research cash from a Stanford researcher, Judith Shizuru. She sought $6 million for continuation of a clinical trial to develop a potentially "transformative" product that would eliminate the toxic impact of chemotherapy for a number of diseases. 

"It boggles my mind," said Jeff Sheehy, a member of the agency's governing board and chairman of its Science Committee, that Stanford, which has an endowment of $27 billion, has not stepped forward to provide the co-funding. 

The amount involved is $1.7 million and is due May 1. It is connected to an earlier $19 million award to Shizuru that kicked off her clinical trial. 

Sheehy noted that Stanford and its researchers have received $379 million from the agency since 2005. It is the top recipient of funds from the California Institute for Regenerative Medicine (CIRM), as the agency is formally known. Stanford also has a member on CIRM's board. 

Steve Juelsgaard, chairman of the board's Finance Committee and a former top executive at Genentech, said that Stanford is "very well taken care of in terms of its economics." 

He said that the agency requires all institutions and businesses to sign agreements to deliver on promises of co-funding. CIRM cannot have two standards for its grantees, Juelsgaard said. 

Today was the first time that the $3 billion research agency has publicly rebuked a grantee on co-funding. Recipients of awards, be they institutions or individual researchers, are generally  treated tenderly in public.  (The full transcript of the meeting is available here.)

CIRM directors did not take issue with the quality of the research, which they described as good. Specifically, today's application sought to advance Shizuru's phase one clinical trial to develop a way to avoid the necessity of chemotherapy in a genetic affliction, popularly known as the bubble baby syndrome.

Nine researchers in the field sent letters to the CIRM board praising the work. Several called it "transformative" and said it could have use in afflictions ranging from blood cancer to diabetes. 

Shizuru applied for $6 million. However, the CIRM board reduced the award to $3.7 million and only on the condition that the previous co-funding be delivered.  

Shizuru told the CIRM board she accepted responsibility for raising the co-funding, which she said has been difficult. Board members noted that agreements on awards are signed by both the recipient researcher and his/her insitution. She said she would discuss today's action with Stanford officials.

Her application came before directors in January with a seal of approval from the agency's reviewers, who make their decisions behind closed doors. Normally, approval by reviewers means a rubber stamp by directors.

Action in January, however, was deferred until this month after directors raised questions about research delays and financial matters. The agency also publicly released a slough of information concerning Shizuru's work, most of which she provided to them.  

Here are links to key documents involving Shizuru application. 

• CIRM's news release on today's action
• CIRM's summary of reviewer comments on Shizuru's application, CLIN2-11431. The agency does not disclose the full application.
• CIRM staff's presentation today concerning the application
• Transcript of the January directors' meeting, including a relatively lengthy discussion and comments by Shizuru
• Today's meeting agenda, which includes links to the letters of support, most of them from prominent researchers in the field
• CIRM award details on the $19 million award, including three progress reports 
• Shizuru successful appeal letter on her 2012 application, which had a median score of 50 and was rejected by reviewers. 
• Clinicaltrials.gov information on Shizuru's clinical trial (start date and last update, both Nov. 15, 2016

(An early version of this item misspelled Shizuru's last name.)

A Peek Inside the California Stem Cell Research Machine: $25 Million, Babies, Bonds and Dwindling Cash

California's stem cell agency this week dished up rare public details of an advanced effort to create "transformative" therapies that would help cure afflictions ranging from diabetes to always fatal immune disorders.

The disclosure involves Stanford University researcher Judith Shizuru, severely ill babies, toxic chemical treatments, delays in clinical trials and stem cell agency board members who are acutely aware of the $3 billion agency's rapidly dwindling resources.

Judith Shizuru
Photo by Flynn Larsen, Ludwig Institute

All this plus more is on the table Thursday at a meeting of the directors of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known. 

The agenda nominally contains one item, an application by Shizuru for $6 million from CIRM. But the issues reach back to 2013 and provide insight into difficult research pathways and how the agency manages its programs. 

At the top of the matter is the fact that the state agency expects to run out of cash for new awards by the end of this year. It is pinning its hopes on a proposed $5 billion bond measure on the November 2020 ballot.  Meanwhile, directors are trying to raise privately $200 million to tide it over until then. 

Avoiding Toxic Chemotherapy

That was the backdrop Wednesday Jan. 30 when directors convened to consider application number CLIN2-11431 by Shizuru for $6 million. She is seeking a way to avoid chemotherapy treatments and their toxic side effects in the case of a rare genetic affliction often referred to as the bubble baby syndrome. 

In December, CIRM's grant reviewers, meeting behind closed doors, approved Shizuru's application, an action that nearly invariably is rubber-stamped by directors. But last month was different, and a bit of CIRM history was brought up.

Shizuru received  a $19 million CIRM award in 2012 which has led to a phase one clinical trial with positive results for her therapy. Cost per each of the six patients so far averages $917,000, according to a CIRM document. 

However, additional patients are needed, along with more funding, before the potential product can reach the marketplace. The average cost of per patient will run about $333,333 during the final portion of the phase one trial.  Her latest application is aimed providing assistance with those costs. 

Questions about Delays and Co-Funding

Last month, questions arose among directors about months of delays in the clinical trial and a current shortfall in co-funding, among other things.

Steve Juelsgaard

Steve Juelsgaard, a former Genentech executive and chair of the directors' Finance Committee, said, 

"It's not clear to me that they're being frugal with the money that they have been given."

Juelsgaard also said,

"Delay doesn't necessarily add up to more money. They obviously spent the money on something that they didn't anticipate or under-budgeted or something. There's something more to it."

Another director, Jeff Sheehy, chair of the board's Science Committee, said,

"Financially, it seems very muddy to me."

Other directors weighed in as well, ultimately leading to a motion to delay action on the application to provide more time to find answers to questions.

At that point, Shizuru, who was in the audience, rose to respond.

"I understand CIRM's concerns, and I can see you're very thoughtful about how this money is being spent," she said, according to the transcript.

 The Sheehy-Shizuru Exchange

The Stanford researcher said that without additional funding the trial would have to suspend enrollment of additional patients, prompting this exchange between her and Sheehy.

"Shiruzu: Budgetarily we're better off using it (the remaining funding) to continue to follow the patients that we've already transplanted. From that budgetary standpoint, we should delay the trial. We should delay treating any more patients on the trial.

"Sheehy: So Stanford won't front you 1.6 million to (treat) patients if we don't give you the money today?

"Shiziru: I hesitate to say what they would do.

"Sheehy: To Stanford...they would actually put patients at risk?

"Shiziru: I'm not at liberty to say what Stanford would do."

Stanford is the No. 1 recipient of CIRM awards, chalking up $379 million over the past 14 years. It also has always had a member on the CIRM board of directors, who is not allowed to speak or vote on awards to Stanford.

Following Shizuru's comments, CIRM directors approved the motion to delay action until this week's meeting. Since the January session, Shizuru has provided the agency with more than five, single-spaced pages of explanation about her research, plus other material that has been kept under wraps for what CIRM has indicated are proprietary and legal reasons.

The information from Shizuru, as well as additional documents from CIRM, provided an unusual, public look into the agency's grant-making process as well as the hurdles encountered in advanced clinical research. In the past, reviews of applications approved by reviewers have received little or no discussion.

Shizuru's Perspective

In her material, which is available on the agenda for this week's meeting, Shiruzu said one, eight-month delay was caused by CIRM itself because of internal concerns. Another nine-month delay was caused by age-restrictions on patients.

"Significant delay" was also caused because of what might be called a supply and demand issue. The bubble baby syndrome is rare. Only one in out of 50,000 to 100,000 births results in a baby with the affliction: severe combined immunodeficiency.

Three other clinical trials are also competing for those rare patients. 

Nine letters of support were received by CIRM supporting the research, with some describing the potential result as "transformative." The letters also said Shizuru's approach could find use in a wide range of other afflictions, an expectation also agreed upon by CIRM. 

Shizuru said she is working on securing the needed co-funding for her first award, which is not yet concluded. As for commercialization, she said she and her colleagues have formed a company, whose name was not disclosed. She said she has a letter of support from one investor regarding "an intention to co-fund pending completion of due diligence."

In a final comment during the vote last month to delay consideration, one CIRM board member, a San Diego patient advocate for Parkinson's disease, praised the board's close examination of the application. David Higgins said, 

"I want to acknowledge fellow board members (for) their continued concern about spending taxpayer's money wisely because I think this is a great example of that."

(The public can listen to and participate in the Thursday meeting via the Internet. Instructions are on the meeting agenda.) 

California Stem Cell Opposition: Conservative Writer Declares Golden State Efforts a 'Bust'

In a preview of what is likely to be a heated ballot campaign next year,  a conservative writer declared this week that California's efforts to develop stem cell therapies are "a scientific and financial bust." 

"Back in 2004, the $3 billion California Stem Cell Research and Cures Initiative, Proposition 71, promised life-saving cures and therapies for Alzheimer’s, Parkinson’s and other diseases. The cures and therapies, in turn, would send money flowing into state coffers, so the project, in effect, would pay for itself. It didn’t exactly work out that way," said Lloyd Billingsley on two different web sites.  

"CIRM proved itself a scientific and financial bust, and almost completely off limits to state oversight."

Billingsley has written in the past about the agency, known as CIRM and formally as the California Institute for Regenerative Medicine. His latest columns appeared on the California Globe, which was founded by Ken Kurson, who has ties to the Trump family and Rudy Guiliani, and The Beacon.  

Billingsley likened the agency to the troubled bullet train project in California and efforts to solve some of California's water problems by building a tunnel under the California delta east of San Francisco. 

CIRM expects to run out of cash this year for new awards and hopes to survive with voter approval of a proposed, $5 billion bond measure on the November 2020 ballot.

It could be a hard-fought campaign, but conservatives and other likely opponents could well be diverted if President Trump is on the ballot. 

See here and here for more on Kurson, founder of the  California Globe, and here for the advisors to the Beacon web site and its parent organization.

Position of the California Stem Cell Agency on Gene-Edited Babies? No Go.

California's $3 billion stem cell agency may be on the leading edge of regenerative medical research, but it is clearly opposed to the type of work that has led to the international flap over the gene-edited babies in China. 

Its regulations have long barred that sort of experimentation. In 2016, the agency, known formally as the California Institute for Regenerative Medicine (CIRM), convened an international conference to discuss the issues involved.

The session in Los Angeles went on for hours, generating a 223-page transcript touching on the difficulty of regulating gene editing, among a host of other difficult issues. 

One patient advocate in the audience, Adrienne Bell Cors Shapiro, noted that it is nearly impossible to control all that might happen. She said,  

"People are messy. And if you develop this technology, somebody is going to find a way to use it."

Last week the MIT Technology Review published an article about a Stanford University investigation into what two of its researchers knew about the Chinese research. The scientists also have received CIRM funds for research unrelated to the Chinese work. 

Asked for a comment, a spokeswoman for the state stem cell agency said in an email:

"CIRM’s regulations prohibit nuclear genome editing for reproductive purposes. In February 2016, CIRM convened the Scientific and Medical Accountability Standards Working Group (SWG) for a workshop on Human Gene Editing. The SWG subsequently recommended that no changes be made to CIRM’s existing prohibition on nuclear genome editing for reproductive purposes."

In 2016, Hank Greely, a law professor at Stanford who deals with bioethical issues, told the gene editing conference:

"CIRM is in the human embryo experimentation world. It funds research as long as the embryos are not implanted. It funds it with special protections and special review considerations and special informed consent considerations. I don't think CRISPR-cas9 changes that."

The controversial research in China triggered a global uproar in the scientific community. The leading stem cell research organization, the International Society for Stem Cell Research, issued a statement opposing such experimentation. 

He Jiankui, the Chinese scientist who performed the experiment, has lost his job in that country, according to news reports, and may be facing criminal charges. His work has not been confirmed by an independent review.