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."

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.”

'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. 

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 Agency Approves Assault on "Terrorizing" Affliction: Huntington's Disease

Frances Saldana, at a stem cell agency meeting last year, spoke emotionally about the loss of her three children to Huntington's disease. 

Directors of the California stem cell agency this morning approved $18 million in clinical stage research awards, including a "high risk" plan to tackle a degenerative brain disease for which there is no treatment.

Action on the proposal to create a therapy for the genetic disorder, Huntington's disease, came after a woman who lost all of her three children to the affliction said it has "terrorized my family for generations."

Frances Saldana of Fountain Valley, Ca., wept as she pleaded for approval of the $6 million effort to treat the disease that  lingers in her family. 

Another patient advocate, Bill Waddington, whose mother died from the affliction, told the agency in a letter, 

"Huntington’s disease isn’t just death.  It’s complete and utter devastation to families."

Maria Millan, president of the stem cell agency, said later in a news release that children born to parents with Huntington's have a 50/50 chance of getting the disease.

Huntington's affects 30,000 persons with another 200,000 at risk. It  progresses slowly. Symptoms are unrelenting and include inability to control movement and declining cognition leading to dementia, according to experts. Affected persons usually die within 15 to 20 years after diagnosis,. 

The applicant for state stem cell funding, Leslie Thompson of UC Irvine, told the board in a letter,

Leslie Thompson
UC Irvine photo

"Given the relatively slow progression of HD, care-giving stretches over 10 years or more after the patient loses independence. Patients become completely dependent on family and caregivers, who in turn have an emotional and debilitating economic burden managing the physical, cognitive and psychiatric manifestations of the disease.  

"HD can lead to catastrophic events such as homelessness, prolonged hospitalization awaiting placement, or long-term psychiatric placement. The length and severity of the disease has a profound financial and emotional impact on families and health systems. The direct medical costs and costs of disability and care giving for each patient are substantial and pass from one generation to the next."

Members of the governing board of the agency, formally known as the California Institute for Regenerative Medicine (CIRM), discussed the application at some length because of a split involving the application reviewers. The summary of comments by reviewers said,

"Reviewers disagreed on whether the treatment offers a significant value to the patients and caregivers. Some reviewers thought the immunosuppression and surgical risk that is required for this cell therapy may outweigh any potential therapeutic benefits given that there are other less invasive treatment options being tested. Others thought that despite the stated risks, any potential treatment for slowing down disease progression is worth pursuing as current alternative therapeutic approaches are still many years away from commercial use."

Last month, the agency's reviewers, meeting behind closed doors, approved the award on an 8-1-5 vote with five against funding, eight for funding and one saying the application needs improvement and could be resubmitted. The latest application was, in fact, a resubmission after changes were made to deal with reviewers' concerns.  The summary of the latest version described the effort as "high risk."

In one of the six letters of support for Thompson's research, Michael West, CEO of AgeX Therapeutics, Inc., of Alameda, Ca., said the work could have application in treatment of other neurodegenerative diseases such as Alzheimers and Parkinson's.

Six is a relatively high number of letters for the board to receive on an application.  Advocates dealing with Huntington's have been active in the past, appearing before the CIRM board on a number of occasions.

The second award today went to Everett Meyer of Stanford and totalled $12 million. It involves a clinical trial for renal failure. 

Here are links to review summaries for each application considered today, the principal investigator, institution and other information. 

Application number, CLIN1-10953; amount, $6.0 million; title, "An hESC-derived hNSC Therapeutic for Huntington’s Disease;" principal investigator, Leslie Thompson; institution, UC Irvine; review summary; letters of support, letter to the board CLIN1-10953, letter to the board #2 CLIN1-10953,​ letter to the board #3 CLIN1-10953, letter to the board #4 CLIN1-10953, letter to the board #5 CLIN1-10953, letter to the board #6 CLIN1-10953, letter to the board CLIN2-11431, other CIRM funding for the PI, $12 million.

Application number, CLIN2-11400; amount, $12.0 million; title, "Induction of Tolerance by Combinatorial Therapy w/ Donor Stem Cells and Expanded Recipient Treg cells in HLA-mismatched Kidney Transplant Recipients;" principal investigator, Everett Meyer; institution, Stanford; review summary; letters of support, none; other CIRM funding for the PI, none.

Action on the following application was put off until Feb. 21 to provide time to answer financial questions raised by board members today: 
Application number, CLIN2-11431; amount, $6.0 million; title, "A monoclonal antibody that depletes blood stem cells and enables chemotherapy free transplants;" principal investigator, Judith Shizuru; institution, Stanford; review summary; one letter of support; other CIRM funding for the PI, $20.4 million.

Tax Breaks and $220 Million for California Stem Cell Agency

The California stem cell agency, which is facing its financial demise, is seeking assurances of "continued tax breaks" for private donors who are being courted for $220 million to support the enterprise, Bloomberg Law reported this week. 

The article by Joyce Cutler referred to the effort to bridge a looming and major stem cell funding gap. The agency says it will run out of cash for new awards at the end of next year. But it does not see additional public funding until November 2020, when the agency hopes that California voters will refinance it with $5 billion from a yet-to-be written ballot initiative. 

Cutler wrote,

"Closing the deal, however, involves getting assurances from elected officials of continued tax breaks to get donors to open their checkbooks and keep CIRM operating until another bond measure can be passed." 

CIRM is the abbreviation for the California Institute for Regenerative Medicine, the formal name of the stem cell agency. It was created in 2004 by voters who provided it with $3 billion in state bonds, but no more. 

Asked for comment by the California Stem Cell Report, Kevin McCormack, senior director for communications at CIRM, said,

"With regard to the tax deductibility issue, that’s really out of our hands but, of course, we’re hopeful that all incentives to potential donors are preserved going forward."

Cutler wrote, 

"Contributions to state agencies currently are deductible from income under state and federal law, H.D. Palmer, state Department of Finance spokesman, told Bloomberg Law in an email.

"'Going forward, that’s going to fall to the next folks who get the keys to the car' in the governor’s office and Legislature, who will decide whether the California deductions remain.

"But the federal Internal Revenue Service is considering regulations to disallow deductibility if the tax credit is for more than 15 percent of the contribution. The Tax Cuts and Jobs Act of 2017 limits the amount of state and local taxes (SALT) an individual can deduct on taxes to $10,000 a year. The proposed regulations crack down on state workarounds to the SALT deduction cap."

Jonathan Thomas, chairman of the CIRM board, is leading the effort to raise funds privately. Bob Klein, who preceded Thomas as chairman, has a role but the agency has declined to go into details. Klein is a real estate investment banker and founder and chairman of Americans for Cures, a nonprofit organization supporting stem cell research. 

Klein has said he has a poll that shows that more than 70 percent of Californians support refinancing the agency. But he has declined to release the poll or identify the firm that provided it when asked by the California Stem Cell Report.  

Klein oversaw the writing of the ballot initiative that created the stem cell agency in 2004 and led the electoral campaign on its behalf. He has said he will try again in 2020 if polls show sufficient support. 

At last week's CIRM board meeting, Thomas gave a short report on the private fundraising effort, which has been underway for many months. He did not announce any contributions or discuss the tax break issue. 

At the meeting, board member Jeff Sheehy expressed concern about progress on a possible 2020 bond measure, noting that there is a relatively short amount of time to mount a major political effort.

Art Torres, vice chairman of the board and a former state legislator, said no real effort can be mounted until after the elections next month. Torres and CIRM general counsel Scott Tocher also noted there are legal limits on what the agency can do in terms of a ballot campaign. 

$144 Million California Stem Cell Research Program Set for 2019

Directors of the California stem cell agency this morning approved a $144 million research budget for next year, which could well be its last for dispensing any major cash in its search for stem cell therapies.

The amount compares to $148 million expected to be awarded this year.  At its peak, the agency was handing out close to $300 million a year in research awards, but the amount varied from year to year.

Most of the funds for the next year will be devoted to clinical stage work. The agency, formally known as the California Institute for Regenerative Medicine (CIRM), is already backing 49 clinical trials, the last stage before a therapy is approved for widespread use. But it has yet to help finance a therapy that can be used by the population at large, despite expectations of voters who approved creation of the $3 billion agency in 2004.

CIRM expects to run out of cash for new awards next year. Possibilities exist for continued funding of research in 2020, but the agency is budgeting conservatively. CIRM Chairman Jonathan Thomas is attempting to raise privately $220 million to maintain the agency's funding. Thomas briefed directors today on that effort but notably did not report that specific additional funding had been secured.

CIRM also expects to recover possibly as much as $30 million in 2019 from projects that do not meet their milestones and possibly use the funds for awards next year or in 2020.

The agency is pinning its hopes for ultimate survival on a yet-to-be-written $5 billion bond measure on the November 2020 ballot.

Where Has The Money Gone? A 10-cent Look at $3 Billion in California Stem Cell Spending

CIRM graphic

California has spent about $2.6 billion on stem cell research over the last 14 years. It has roughly $144 million left for new awards. Here is a quick overview of where cash has gone, based on the agency's records.

Keep in mind that an examination of the state stem cell agency's spending can be like the blind men and the elephant. A lot depends on what you grab.

And tomorrow directors of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known, will  be grabbing a piece of the program to determine what is going to be handed out in 2019.

Since 2004 when the agency was created with $3 billion in funding, CIRM reports that it has spent $898 million on various stages of basic research, which it generally calls "discovery," the largest single category.

It has plowed $632 million into clinically connected research dealing with afflictions ranging from cancer to blindness. The amount involves both more recent clinical research and CIRM's earlier disease team programs. Kevin McCormack, senior director for communications, said the money went for late stage research leading to a clinical trial as well as the trials themselves.

The agency's clinical trial dashboard shows that it has supported 49 clinical trials. The dashboard provides more detail on the status of each trial. (Here is a link to a June CIRM spreadsheet on the trials. Here is a link to a table on the trials released in connection with this week's directors' meeting.) 

CIRM has sunk $482 million into "infrastructure," a term that includes a $271 million building program for new facilities at institutions ranging from Stanford to UC Davis.  (See here and here for more on the infrastructure program.

The agency spent $219 million on education, which probably does not include a more than $40 million program to lure star scientists to the Golden State academic institutions. Those awards were specifically for research projects.

In terms of diseases, CIRM research covers 24 disease areas, ranging from Alzheimer's to strokes. A third of the clinical trial money has gone for cancer. Nineteen percent has targeted blood diseases and 12 percent neuro afflictions.

For a full list of institutions, see here.

Stanford, an already well-endowed institution in 2004, was the top institutional recipient with $360
million. UC Davis was the over-achiever in the top 10 recipient list with $138 million. In 2004, it had what could only be described as a tiny stem cell program.

ViaCyte, Inc., of San Diego, is the only business to make the top ten list, snagging $72 million. With the exception of ViaCyte, all of the institutions in the top ten had or have representatives on the CIRM governing board who are not permitted to vote on awards to their institutions.

As mentioned at the beginning of this item, this was the 10-cent tour of CIRM spending, which may tweak your interest. The high-priced excursion will come another day.

Stalled California Stem Cell Projects Now Set for Financing: Bladder Cancer, Autism, Deafness, Blindess Among the Targets

Key directors of the California stem cell agency this afternoon moved to juggle some cash and fund six research proposals ranging from bladder cancer to autism, which had been stalled since July.

The action by the directors' Science Subcommittee came only hours after the affected researchers and patients appealed to another board group to approve the funding. It was stalled because of budgetary issues.

Those financial issues came up again before the Science Committee which approved a workaround on the $7.9 million needed to approve the research. The action may receive final approval by the full board next Thursday.

You can read more here about the session earlier in the day.  

Stem Cell Scientists' Hopes for Research Cash Survive Another Round in California

(Late News Break: It looks like the six applications in the story below are now headed for approval, perhaps as early as next Thursday. See this story.)

Six stem cell research proposals targeting bladder cancer, autism, liver failure and more escaped rejection today as the $3 billion California stem cell agency struggles with its finances.

The agency expects to run out of cash for new awards by the end of next year. In 2019, it is considering awarding only $144 million compared to $300 million in some years. "We are coming to the end," said CIRM board member Oswald Steward, director of the Reeve, Irvine Research Center at UC Irvine, in July.

The applications had already been held over from July when the agency's directors were presented with a $19 million list of applications approved by its out-of-state reviewers in an earlier closed-door session.

However, the round was budgeted for only $10 million by the governing board of the agency, known formally as the California Institute for Regenerative Medicine (CIRM).

Ten letters of support were filed on behalf of five rejected awards, whose scores ranged from 90 to 87. The agency in July approved three awards with scores of 85.

Some of the researchers and supporters appeared before the board today. Philip Beachy of Stanford, who is seeking $1.4 million for bladder cancer research, said his team was seeking a long term cure for bladder, which has a tendency to recur and is the most expensive cancer to treat per patient.

Other researchers and patients also made a direct appeal to CIRM directors, and on an 11-0 vote, the board kept the applications alive during a telephonic meeting.

Here is a link to the scores and review summaries in this round. Here is the presentation by staff on its recommendations.

Here is a list of letters supporting applications in this round and their authors:

• Daniel Geschwind, director of UCLA Center for Autism Research and Treatment, on behalf of application DISC2-11070, treatment for autism, PI Stuart Lipton of Scripps Research of La Jolla (score 87 out of 100)
• Bridget Vissari, president, Achroma Corp., Butler, Pa., in support of DISC2-10973, PI Jonathan Lin of UC San Diego, dealing with photoreceptor diseases (score 88 out of 100)
• Laura Brady, research manager, Fighting Blindness of Dublin, Ireland, also in support of DISC2-10973
• Avril Daly, CEO, Retina International, also in support of DISC2-10973.
• Philip Beachy, Ernest and Amelia Gallo professor, Stanford, in support of his application, DISC2-11105, dealing with bladder cancer (score 90 out of 100)
• Don Reed, vice president of public policy, Americans for Cures, also in support of DISC2-11105
• David Russell, chief scientific officer, Universal Cells, Inc., of Seattle, a subsidiary of Astellas Pharma, in support of DISC2-10979 PI Tracy Grikscheit of USC, dealing with liver failure therapy (score 90 out of 100)
• Paul Viviano, CEO Childrens Hospital Los Angeles, and two others, also in support of DISC2-10979
• Neil Seigel, co-director USC Hearing and Communication Neuroscience Training Program, in support of his application DISC2-11183, dealing with hearing loss (score 87 out of 100)
• Robert Rainey, research associate of Neil Segil Lab, USC, also in support of application DISC2-11183 (Rainey's letter is in the same file as Segil's)

The Final $144 Million and the California Stem Cell Agency's Future

The Golden State's stem cell research program is down to its last $144 million after nearly 14 years of financing searches for therapies for everything ranging from diabetes to bubble baby syndrome. 

Funded with $3 billion in November 2004, California's stem cell agency has yet to back a therapy that is widely available to the public. Its directors are scheduled to meet on Wednesday to approve plans for what could be the last year for new awards. 

Known formally as the California Institute for Regenerative Medicine (CIRM), the agency was created by voters through a ballot initiative. The measure provided $3 billion in bond support but no additional cash beyond that. 

The agency is pinning its hopes for survival on a yet-to-be-written $5 billion bond measure for the November 2020. It is attempting privately to raise $200 million to bridge the gap between the end of 2019 and the election. 

On Thursday, CIRM's 2019 research award budget is slated to come before the Science Committee of its board of directors. The public can participate in the meeting via the Internet and at a number of locations throughout the state. More information about access can be found on the agenda. 

The agency's staff has proposed $123 million in awards for clinical trials during 2019 with another $20 million going for translational research, which is an effort to take basic research and translate it into a clinical application. An additional $600,000 is slated for "educational" awards. 

CIRM documents said there were "insufficient" funds to finance additional basic research. The agency also aims to limit its clinical/translational awards to research that has been previously backed by the agency.

By the end of this year, CIRM expects to have made $2.6 billion in awards. The remainder of the $3 billion has gone or will have gone for administrative expenses, which will continue for a few years as multi-year awards wind down. 

The agency may recover an estimated $30 million in 2019 from research that does not pan out, making those possible funds available for awards in 2020. 

Currently, CIRM is backing 49 clinical trials, the last stage before a therapy is certified for widespread use. But there is no guarantee that any of those trials will generate a treatment prior to the November 2020 election.