"California's Great Stem Cell Experiment: Inside a $3 Billion Search for Cures:" A New Book on the State's Stem Cell Agency

David Jensen

A new book devoted to the life and times of California's nearly 16-year-old stem cell research program is now available on Amazon. The book chronicles the stem cell agency's story from its early days to its current imperiled existence. 

The book is called "California's Great Stem Cell Experiment: Inside a $3 Billion Search for Cures." It was written by yours truly, David Jensen, who has covered the agency since January 2005 and who has published some 5,000 items about the program on this blog, the California Stem Cell Report.

The book explores the agency's performance as 20 million Californians vote this month and next to decide whether to provide $5.5 billion more for the California Institute for Regenerative Medicine (CIRM), as the agency is officially known. Questions addressed include: 

• Has CIRM fulfilled the expectations raised by the 2004 campaign?
• Has its work since then been worth $4 billion (CIRM's cost including interest on the state bonds that finance its work)?
• What are the important elements and new directions created by Proposition 14 in addition to the $5.5 billion ($7.8 billion with interest), and does the measure fit with the state's current priorities? 

CIRM is unique in California's history, which has never seen an enterprise like this. It is also unique nationally. No other state has launched a scientific stem cell program of this magnitude.  And it is an agency that operates outside of the bounds of what many consider normal state government controls and finance. 

At the same time, even its opponent will acknowledge the significance of CIRM's work, which includes helping to finance 64 clinical trials and the creation of what it calls an Alpha Clinic Network throughout the state. 

In 2012, CIRM heard from the Institute of Medicine, which CIRM hired to conduct a $700,000 examination of the agency's work. The book re-examines the IOM findings, which were both laudatory and critical, and reviews CIRM's response.  

Along with critics, the book brings to readers the voices of CIRM supporters, its executives and former officials, including the first president of the agency, Zach Hall; its first chairman and leader of the 2020 campaign, Robert Klein; its current president, Maria Millan; its current chairman, Jonathan Thomas, and former president, Randy Mills, who introduced CIRM 2.0 and who is now president of the Sanford Burnham Prebys Medical Discovery Institute in La Jolla, Ca.

One also cannot forget the CIRM governing board director who early on who looked at the 2004 Proposition 71 governance structure for the agency and called it a "dog's breakfast." 

You can purchase "California's Great Stem Cell Experiment" by clicking on this sentence, which will take you to Amazon.  

Death of Patient Halts Clinical Trial That Involved California Stem Cell Agency

A clinical trial based on a $4 million award from the California stem cell agency has been suspended after one of the patients died.

The phase one safety trial was being conducted by Poseida Therapuetics, Inc., of San Diego.  In 2018, Poseida received $4 million for the proposed therapy from the California Institute for Regenerative Medicine (CIRM), as the stem cell agency is officially known. 

Clinical trials are the last stage before a treatment is approved by the federal government for widespread use. 

The death of the patient comes as CIRM supporters are backing a measure, Proposition 14, on the November ballot that would provide $5.5 billion more for the agency. 

CIRM is running out of the $3 billion provided in 2004, when it was created via a ballot initiative. It will begin closing its doors this fall without additional funding.

In response to a request for comment, the agency released the following statement:

"Our sympathy goes out to the family of the individual who died and to the team at Poseida. We know how deeply committed they are to the work they are doing and how big an impact moments like this have on researchers.

"We did fund the late stage pre-clinical research, but as we are not involved in this clinical trial itself we have no additional information. The (Food and Drug Administration) has put a hold on the trial to determine what happened and we will continue to follow the results of this matter very closely."

CIRM said in a 2018 news release that the proposed treatment was an effort to "supercharge a patient’s own immune system cells to attack and kill a treatment-resistant form of prostate cancer."

Maria Millan, CEO and president of CIRM, said in the news release:

“This is a promising approach to an incurable disease where patients have few options.

"The use of chimeric antigen receptor engineered T cells has led to impressive results in blood malignancies and a natural extension of this promising approach is to tackle currently untreatable solid malignancies, such as castrate resistant metastatic prostate cancer.

The $4 million was for work that immediately preceded the trial -- not the trial itself -- and led to the preparation of an Investigation New Drug (IND) program.  

On Feb. 28 of this year, Poseida initiated the phase one trial, which is aimed at determining the safety of the proposed treatment, according to documents filed with the federal government. The company hoped to enroll 40 patients. 

In a filing yesterday with the Security and Exchange Commission, Poseida said that the Food and Drug Administration had placed the trial on "clinical hold."

The company said, 

"Although the direct cause of the hepatic failure has not yet been confirmed, the patient developed symptoms consistent with macrophage activation syndrome (MAS). MAS is a serious and potentially fatal overactivation of the immune system which has been associated with CAR-T therapies, but can have other causes such as infection and autoimmune disease. 

"The patient also developed blurred vision which was diagnosed as uveitis. The clinical investigator has assessed the SAE (serious adverse event) as possibly related to P-PSMA-101 pending further investigation."

P-PSMA-101 is the name of the therapy involved. 

CIRM's summary of the review of Poseida's application (CLIN1-10999) in 2018 said the proposed therapy "had the potential to improve survival in this patient group, which faces a poor and fatal prognosis." 

It also said, 

"Some reviewers noted the potential for off-target toxicity with a PSMA CAR-T product, which should be carefully assessed in the clinical studies."

Here is the text of the discussion at the CIRM meeting at which the grant was approved. 

Poseida's stock price plummeted on the news. It closed yesterday $13.00 a share. As of this writing, it was trading at $9.01. 

Just this July, Poseida went public and has traded as high as $17.62. Prior to the stock offering, Novartis invested $142 million in the firm. The public offering valued the company at $1 billion.

CIRM has also backed Poseida with $20 million for a clinical trial involving a different approach for a disease called multiple myeloma. 

(Editor's note: An earlier version of this item did not carry the comment from CIRM, which came after the item was posted. Also added was the link to the CIRM discussion of the award in 2018.)

Tough Editorial Calls for Rejection of $5.5 Billion Stem Cell Measure; Therapies Have not Materialized

 A hard-hitting editorial this morning ripped this fall's $5.5 billion ballot measure to refinance the California stem cell agency, declaring that the proposal was unnecessary and "out of the question."

The article appeared online in the the San Jose Mercury News and the East Bay Times in the San Francisco Bay Area. It declared: 

"Long-term, sustained funding was never the intent when California voters passed Proposition 71 in 2004, authorizing the state issuance of $3 billion of bonds for stem-cell research....

"It’s time for California’s stem-cell agency to continue its work as a self-sustaining non-profit or close down and allow federal grants and private business to push the industry forward."

The editorial on Proposition 14 was the toughest of the four that have surfaced so far, going point by point through expectations aroused by the campaign of 2004 and CIRM's performance since then. 

On the state vs. federal research, the editorial said,

"Finding therapies for devastating diseases such as Alzheimer’s, Parkinson’s and diabetes should be primarily the federal government’s responsibility."

On theoretical cost savings running as high as $1.1 trillion, it said,

"If those eye-popping, speculative estimates sound familiar, they should. Prop. 14 supporters made similar suggestions in 2004. But 16 years later the savings and life-saving therapies have not materialized."

On financial returns to the state, the editorial said, 

"In 2004, overzealous promoters of Prop. 71 said the state could expect as much as $1.1 billion in royalties from stem-cell research within 35 years. But, so far, the independent Legislative Analyst Office’s reports the state’s stem-cell efforts have provided just $350,000 in royalties."

On conflicts of interest, it said, 

"Prop. 14 does little to eliminate that ethical issue. If anything, it makes it worse by adding an additional six members to its board without substantially altering the selection criteria. Don’t look for elected state officials to provide the needed oversight. Prop. 14 prevents the Legislature from making any amendments to the law without a 70% vote of approval from both the state Senate and Assembly."

The editorial concluded, 

"California’s stem-cell research effort does not merit another $5.5 billion investment of state taxpayer funds. Vote no on Prop. 14."

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. 

 

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.