Stem Cell Perseverance in California: CIRM Tells Its Jam-Packed Story

A page from CIRM's annual report, which says that the girl is alive today
as a result of a clinical trial at UCLA that CIRM helped to finance.

The California stem cell agency, which is facing financial extinction, this week unveiled its latest annual report, which is a paean to its work and indirectly a pitch to California voters to refinance it with $5.5 billion. 

In an item yesterday on the agency's blog, The Stem Cellar, Kevin McCormack, wrote, 

"This latest CIRM Annual Report covers 2019 through June 30, 2020. Why? Well, as you probably know we are running out of money and could be funding our last new awards by the end of this year. So, we wanted to produce as complete a picture of our achievements as we could – keeping in mind that we might not be around to produce a report next year."

State law requires the California Institute for Regenerative Medicine (CIRM), as the agency is formally known, to produce an annual report, much as publicly traded companies do. State law also forbids the use of taxpayer funds in ballot campaigns. But it does not forbid state agencies from engaging in their normal public information work. 

Dubbed "Perseverance: From Theory to Therapy," the annual report cost $34,000, according to the agency. The document makes a compelling case for adding $5.5 billion to the $3 billion voters provided in 2004 when they created CIRM. 

The multibillion dollar figures, however, do not include the projected interest costs to taxpayers, which bring the total estimated expense to something in the neighborhood of $13 billion. 

The $13 billion is also not mentioned in the annual report from CIRM, which is in keeping with the usual annual report traditions involving both public and private enterprises. They generally do not dwell on information that could be construed as less than upbeat, if at all possible. 

As expected, the report speaks highly of the agency's work, citing the 64 clinical trials in which it is involved. At the same time, a casual reader is likely left with the impression that CIRM financed the total cost of all of those trials, which is not the case. 

In another example of pushing the envelope, the document celebrates a study last fall that said that CIRM had an economic impact of more than $12 billion. CIRM characterized the report as "independent." CIRM actually paid USC, which has received $114 million from CIRM for stem cell research, another $206,000 to prepare the economic report. 

The annual report stated that the agency's efforts had a "significant impact" on the state's economy, which was estimated at $3.2 trillion annually in 2019. Twelve billion is 0.4 percent of that overall figure, something less than significant.  

CIRM's $5 million Covid-19 round is mentioned prominently at the front of the annual report in a move that CIRM hopes will resonate with voters when they are marking their ballots for or against Proposition 14, the stem cell measure. The $5 million is, again, a tiny amount when compared to the billions being spent nationally for Covid research. 

All that is not to say that CIRM has not performed significant work. It definitely has left a major mark on the stem cell field nationally and even globally. Some of the 2,000 people participating in the clinical trials have benefited. The agency has fostered collaboration on stem cell research between institutions that probably would not have occurred without a financial stimulus from CIRM. And it has created a new, speedy, grant-review model that puts research money in the hands of researchers more quickly.  

More can be said, but you can find it all in what perhaps will be the last annual report from an enterprise that is unique in California history and unique in size and scope among all the 50 states.

Read the California Stem Cell Report regularly for the latest and most in-depth coverage of the effort to save the California stem cell agency from financial extinction. 

Bakersfield Californian Says No to Proposition 14, the Multibillion-Dollar Stem Cell Measure

The Bakersfield Californian is likely the first paper in the state to take a stand on the $5.5 billion California stem cell measure, advising its readers to reject the "mega-bond" as financially unwise. 

In an editorial published online yesterday, the newspaper said, 

"As California continues to struggle under the catastrophic burden of the coronavirus pandemic, increasing state budget deficits loom, public service cuts are likely and economic recovery is likely to take more than a decade.

"In 2009, President Barack Obama lifted most of the restrictions on federal funding for embryonic stem cell research and demand for the cells has been greatly reduced as other research and technologies have advanced.

"Adding $5.5 billion to the state debt for just stem cell research would be unwise in these economically dire times. Vote NO on Proposition 14."

The newspaper also said that the agency, officially known as the California Institute for Regenerative Medicine (CIRM),  "created an impressive infrastructure of research institutes." The Californian continued,

"Stem cell research greatly advanced in California, but the promised spectacular breakthroughs have lagged – a result of the tedious and time-consuming nature of research.... 

"Voters and earlier proposition advocates should be proud of the progress the initial $3 billion stem cell investment has accomplished. But times have changed and passage of another mega-bond now would be unwise."

How important are newspaper endorsements nowadays? They are one concrete standard that campaign managers can be measured against, so they may take on outsized importance. But newspapers are a dying breed, reaching fewer and fewer readers. Even in their heyday, decades ago, only about 25 percent or so of readers turned to the editorial pages on a regular basis. 

However, a wave of negative editorials could take on a life of its own, leading to mentions in the coverage of Proposition 14 as an indicator that the measure is in trouble.  That said, don't expect heavy coverage of the proposal. 

Both print and online news media are short-staffed. Most of their efforts will focus on higher-profile issues, including presidential matters, local ballot races and other propositions, such as rent control and property taxes involving the state's sacrosanct Proposition 13. 

And for the record, Proposition 14 will cost taxpayers an estimated $7.8 billion because of the interest on the $5.5 billion that the state will have to borrow.

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Read the California Stem Cell Report regularly for the latest and most in-depth coverage of the effort to save the stem cell agency from financial extinction. 

UC Irvine Named for Covid-19 Trial Backed by California Stem Cell Agency and Giuliani

A New Jersey firm backed by $750,000 from the California stem cell agency today announced that the California location of its Covid-19 trial will be at UC Irvine.

The firm is Celularity, Inc., and its proposed therapy is supported by Rudi Giuliani, President Trump's personal lawyer.  Celularity expects to complete its work by Nov. 30.

CIRM said the research involves "a phase I/II study of human placental hematopoietic stem cell derived natural killer cells for the treatment of adults with COVID-19."

The award was made June 26 by the agency's governing board, which expected its Covid grantees to be ready to start work within 30 days under its fast-track Covid round. Celularity had not responded to questions about the trial location prior to its news release today. The stem cell agency cannot fund research outside of California. 

The company's news release indicated there would be more locations in California, but did not disclose any. 

The UC Irvine work will be overseen by Leonid Groysman, a neurologist. Here is a link to a summary of the review of Celularity's application (CLIN2COVID19-11857 #2). 

California's $5.5 Billion Stem Cell Campaign and Covid-19: How Science and Politics Marry

Editor's note: The following item written by the producer of the California Stem Cell Report appeared yesterday on the Capitol Weekly online news service. 

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The California stem cell agency has just finished pumping $5.3 million into the fight to save the lives of COVID-19 victims. And — in a ballot-box bonus — its efforts are already surfacing in the ballot campaign to rescue the agency from its own demise.

The agency is running out of money. It will begin closing its doors this fall without major financial support that it hopes will come from Proposition 14, a $5.5 billion bond measure on the November ballot.

The $5.3 million in the fast-track, Covid program is tiny by comparison. But the awards are likely to play a heftier role than might be anticipated based on their size. Stories about the Covid awards have appeared on the campaign website in a move to tap into the deep public concern about the coronavirus.

The Covid research piggybacks on the federal “warp speed” drive to develop Covid treatments and is aimed at demonstrating that the agency is part of what CIRM officials describe as a worldwide, “all-hands-on-deck” effort.

Three clinical trials have been funded, which involve actual patients as opposed to laboratory research. If the trials are successful, patients who have benefited are likely to surface in campaign video advertising aimed at refinancing the agency, formally known as the California Institute for Regenerative Medicine (CIRM).

CIRM sorely needs research results that will resonate with voters. The 2004 ballot campaign that created the $3 billion program raised expectations that stem cell therapies were right around the corner. But the agency has yet to produce a stem cell treatment that is widely available to the public.

The agency launched its Covid round on March 27 when CIRM board chairman Jonathan Thomas declared, “The coronavirus is creating an unprecedented threat to all of us, and, as one of the leading players in regenerative medicine, we are committed to doing all we can to develop the tools and promote the research that will help us respond to that threat.”

Indeed, failure by CIRM to respond to the COVID-19 threat — it could be argued — would be a breach of CIRM’s public responsibilities.CIRM’s Covid research financing is a case where an urgent medical need marries nicely with ballot-box politics. The agency is forbidden by law to campaign for the ballot measure. But its charter also allows it to pursue a wide range of research possibilities.

Late last month, CIRM directors capped off the round by approving two awards and adding nearly $300,000 to the original authorization of $5 million. All of the awards have been made under an emergency process that requires awardees to be ready to begin research within 30 days and achieve “a clear deliverable within six months.”

The final awards went for basic level research. Earlier, CIRM approved funds to assist in the three clinical trials, which are the final stage before a treatment can be approved for widespread public use. The trial awards range from $1 million to $701,000 each, a bargain price for joining a trial. Most of CIRM’s previous clinical trial awards run into many millions.

CIRM now counts a total of 64 clinical trials that it is helping to finance. Two of the Covid trials are taking place at the University of California, San Francisco-UC Davis and the City of Hope in the Los Angeles area. The third involves a New Jersey firm called Celularity, Inc., which has failed to respond to multiple questions about the California location of its trial. The agency is limited to funding activities within the state. CIRM directors approved the Celularity award on June 26, more than 30 days ago.

The Celularity award has another interesting angle. It involves a treatment supported by President Trump’s personal attorney, Rudi Giuliani. 

You can find more information about all the awards in a series of items on CIRM’s blog, The Stem Cellar, using the search term “covid.”   Five CIRM/Covid stories, including CIRM blog items about the Covid round, have been placed on the campaign website by the campaign staff. 

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​Read all about California's stem cell agency, including Proposition 14,  in David Jensen's new book. Buy it on Amazon:  California's Great Stem Cell Experiment: Inside a $3 Billion Search for Stem Cell Cures. Click here for more information on the author.

Quote of the Day

Jonathan Shestack, in 2013 and then a patient advocate member of the governing board of the California stem cell agency, speaking about patient advocates appearing before the board:

"We have a responsibility to look those people in the face.... So I would like to be very careful as we retool that process to make it neater and less chaotic and not upsetting to the press or to people in Sacramento, but to understand that is part of our responsibility, to look at those people and listen to them and take some of what they have to say into consideration."

From a meeting of the CIRM board Jan. 23, 2013

California's Stem Cell Covid Round Ends: Three Clinical Trials, 17 Awards

The California stem cell agency has finished its special round of Covid-19 awards, adding three clinical trials to bring its total to 64 plus 14 other awards totaling in all $5.3 million. 

The final awards were made on Friday in the emergency, fast-track round. However, the agency noted that additional Covid awards are possible through its existing awards process and today issued a "special call" for applications in its Quest awards program.  The deadline is Aug. 31.

The agency said in an email, 

"For this special edition of DISC2, the overall timeline and award amount have been capped at 12 months and $250,000, respectively. The expected outcome, at the end of the award, is a candidate therapeutic, diagnostic, medical device, or tool that can immediately progress to translational stage activities."

Last week's awards of $250,000 each went to Karen Christman at UC San Diego and Lili Yang at UCLA.

Christman hopes to develop a treatment for acute respiratory distress syndrome, the agency said, a life-threatening lung injury that occurs when fluid leaks into the lungs and is prevalent in COVID-19 patients.  Her research involves extracellular matrix hydrogels, a structure that provides support to surrounding cells.

Yang is seeking to use blood stem cells to create invariant natural killer T (iNKT) cells, a powerful type of immune cell with the potential to clear virus infection and mitigate harmful inflammation.

For more details, the agency's review summary for Christman's application (DISC2COVID19-12007 #2 ) can be found here. The summary of Yang's review (DISC2COVID19-12020) can be found here. Yang also sent a letter to the agency board as did Christman.

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​Read all about California's stem cell agency, including Proposition 14,  in David Jensen's new book. Buy it on Amazon:  California's Great Stem Cell Experiment: Inside a $3 Billion Search for Stem Cell Cures. Click here for more information on the author.

Quote of the Day

"In science, true hope is clear-eyed and brings a tight focus on the barriers and potential setbacks that exist along the path to desired results." 

-- Jerome Groopman, in his New Yorker article titled "The Long Game of Coronavirus Research."

Covid Clinical Trial Location Still Missing on $750,000 California Stem Cell Grant

The California stem cell agency stipulates that winners of research awards in its fast-track, Covid-19 round must be ready to start work within a month of approval, but a New Jersey firm that snagged $750,000 three weeks ago has yet to report the location of its California work.

The  firm is Celularity, Inc. Its proposed therapy is backed by Rudi Giuliani, the president's personal lawyer, who has also touted other possible Covid therapies, including one that has been rejected by the Food and Drug Administration.

The $750,000 is intended to finance a clinical trial someplace in California. The stem cell agency funds only California work.

In creating the Covid round, CIRM said award winners must be "ready to start work within 30 days of approval and propose achieving a clear deliverable within six months." It has been 21 days since the Celularity award was approved. 

The California Stem Cell Report has asked the firm repeatedly for the location of the California site but it has not responded with this routine information. The agency itself also has not disclosed the location and defers to the company.  

Celularity updated the information today that it files with the National Institutes of Health on the trial. However, the locations of the trial still did not show any in California. 

California's $40 Million Stem Cell Genomics Center: Its Fate and Outcomes

California's stem cell agency hit something of a milestone six years ago when it approved $40 million to create a genomics center that was aimed at positioning the state as a global leader in stem cell genomics. 

The round triggered complaints about irregularities, unfairness, score manipulation and the role of its then president, Alan Trounson. The $40 million, at the time the largest single research award by the agency, was ultimately divided three ways and now has been spent. 

The California Stem Cell Report queried the agency this week about the award, its status and results. Here is the response in Q&A format.

Q: How was the $40 million shared and with which institutions?
A: The genomics grant was split into three awards: $22.7M to Stanford (GC1R-06673-A), $13.2M to the Salk Institute (GC1R-06673-B), $4M to UC Santa Cruz (GC1R-06673-C). (The application numbers carry links to the progress reports on the CIRM website.) 

Q: Is there any requirement for the grantees to come up with a plan for continued funding? 

A: There was no requirement for the grantees to come up with a plan for continual funding in the concept RFA.  Stanford and Salk provided co-funding to support the centers during the award period.

Q: If not, what prevents the doors from closing at the genomics center(s) in the next couple of years?

A: The Stanford sequencing center established by the genomics awards continues to operate with other sources of funding.  The Stem Cell Data Hub established by UCSC continues to be supported.  UCSC has no plans to shut down the site even though its CIRM award has ended. 

Q: How much time remains on the grant(s)? I See there was at least one extension given, but it is unclear why there was delay.

A: All three genomics grants have ended as of May 31^st.  The sequencing centers at Stanford and the Salk were given six month award extensions to continue supporting projects with technical delays in sequencing activities.  The data hub at UCSC was given a 12 month extension to process data generated by the sequencing centers.

Q: What else do readers need to know about this award? 

A: A number of outputs were generated from genomic center projects, including:

• 60 publications connected to CESCG funding
• 10 data analysis/visualization tools created
• 1 new sequencing technique developed
• 300 new iPSC lines created
• Central online data hub created with standard metadata, analysis pipelines, restricted access
• Data repository of human single cell global transcription in heart, pancreas, blood, brain, brain
• 84TB data generated from sequencing activities across projects

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​Read all about California's stem cell agency, including Proposition 14,  in David Jensen's new book. Buy it on Amazon:  California's Great Stem Cell Experiment: Inside a $3 Billion Search for Stem Cell Cures. Click here for more information on the author.

Former Chief of California Stem Cell Agency Returns to California as Head of Sanford Burnham

C. Randal Mills, who led California's $3 billion stem cell agency for three years, this afternoon was named as chief executive officer of the Sanford Burnham Prebys Medical Discovery Institute in La Jolla, Ca.

Randy Mills
Sanford Burnham photo

The institute said in a news release that Mills brought to Sanford "decades of experience as an entrepreneur and transformational leader in the biomedical industry."

Most recently, Mills was president of the National Marrow Donor Program/Be The Match nonprofit, an international leader in facilitating and supporting bone marrow transplantation.

Mills left Be The Match in February of this year, citing personal reasons.
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Mills, who goes by Randy, was  president and CEO of the California stem cell agency from May 2014 until July 2017. 

During his time at the agency, which is formally known as the California Institute for Regenerative Medicine (CIRM), Mills instituted something he called CIRM 2.0. It streamlined and sped up the work of the agency, sharpening its focus with an emphasis on performance metrics. The structure of the effort remains in place today. 

When Mills left the agency, CIRM Chair Jonathan Thomas, who recruited Mills, said his efforts had created a "bold strategic plan, the results of which include an 82 percent reduction in approval time, a 3-fold increase in the number of clinical trials, and a 65 percent reduction in the time it takes to enroll those trials."

Sanford Burnham has received $39.4 million from CIRM over the years. Its president, Kristiina Vouri, sits on the governing board of the stem cell agency, which has included a Sanford representative since 2004. 

Vouris said in the news release that Mills "comes to us with extensive organizational and executive leadership experience. His diverse background and knowledge of translational research and drug discovery will help us propel the Institute into a bright and successful future.”

Mills will begin his work immediately at Sanford Burnham, which has 700 employees in the San Diego area.  

Covid Research Backed by California's Stem Cell Agency: 15 Awards, Including Help with Three Clinical Trials

The California stem cell agency is down to its last $272,357 in its special, $5 million effort to help finance research involving Covid-19.

The research round began in May and has approved 15, fast-track research projects, including participation in three clinical trials. The latest awards were approved last Friday by agency directors. 

• Evan Snyder of Sanford Burnham Prebys Medical Discovery Institute received $250,000  to create lung organoids to test two drug candidates for treatment of the virus.
• John Zaia of the City of Hope received an additional $250,000 for his previously approved study dealing the use of convalescent plasma treatments. 
• Steven Dowdy at UC San Diego was awarded $150,000 to study a more effective way of delivering a genetic medicine, called siRNA, into the lungs of infected patients.

Summaries of the CIRM application review on the grants can be found here, including the six rejected.  

Approval of the latest awards came as a New Jersey firm that two weeks ago received a $750,000 award still has not disclosed the location of its clinical trial site in California. By law, the stem cell agency can only finance work within California.

The awardee is Celularity, Inc., a business whose proposed therapy is backed by Rudi Giuliani, the president's personal lawyer, who has also touted other possible Covid therapies, including one that has been rejected by the Food and Drug Administration.

In creating the Covid round, CIRM said award winners must be "ready to start work within 30 days of approval and propose achieving a clear deliverable within six months." It has been 16 days since the Celularity award was approved. 

The California Stem Cell Report has asked the firm repeatedly for the location of the California site but it has not responded. The agency itself also has not disclosed the location and defers to the company.

Sheehy Steps Back from Stem Cell Agency Positions; Cites His Opposition to Prop. 14

A longtime member of the governing board of the $3 billion California stem cell agency has stepped away from two leadership roles in the wake of his vote against the ballot measure that would refinance the research enterprise, which is running out of money. 

Jeff Sheehy, an HIV/AIDs patient advocate on the board since 2004, made the moves after becoming the only member of the 29-member board to vote against endorsing Proposition 14, which would provide $5.5 billion for the California Institute of Regenerative Medicine (CIRM), as the agency is formally known. 

The proposal would also make significant changes in the operations of the agency, enlarge its scope, lock up money for certain purposes and expand the size of its board from 29 to 35.

Sheehy voted against the endorsement on June 26 and released a statement to the California Stem Cell Report which cited a wide range of reasons for his negative vote. 

The actual vote on Proposition 14 was 21-1. Some members of the board were not present. Two vacancies also exist on the board. 

Sheehy was chairman of the board's science subcommittee. He was also a member of CIRM's grant working group and for years directed the evaluation by the full board of the billions of dollars in grant applications. 

Responding to a question last week, Sheehy said,

 "I instigated the change. I believe that it doesn't make sense for me to have any leadership roles given that I do not support Proposition 14.  I can imagine a scenario where the reality of my opposition becomes stark, and I don't want to drag the functionality of the board or the agency into any potential, campaign back-and-forth."

The changes in Sheehy's role became apparent last Friday when another board member led the evaluation of the Covid-19 applications. It came as a surprise to at least one board member, Vice Chairman Art Torres, who inquired at the beginning of the Friday meeting about the change. 

"What happened to Mr. Sheehy? He's not running these things anymore?" Torres asked.

Chairman Jonathan Thomas replied briefly, "Mr. Sheehy is is not going to be running the application review."

Torres replied, "Sorry to hear that."

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​Read all about California's stem cell agency, including Proposition 14,  in David Jensen's new book. Buy it on Amazon:  California's Great Stem Cell Experiment: Inside a $3 Billion Search for Stem Cell Cures. Click here for more information on the author.