Editor's note: The following item was written by the producer of the California Stem Cell Report and appeared last week on the Capitol Weekly online news service.
Monday, August 31, 2020
Friday, August 28, 2020
Tuesday, August 25, 2020
An article in the Los Angeles Times today took on scientific research and "grand goals and grander ambitions, all to be achieved with record speed."
The piece was written by Pulitzer Prize-winning Times columnist and author Michael Hiltzik. He was not writing about the California stem cell program.
But, as readers know, the stem cell agency hopes voters will approve a $5.5 billion bond measure this fall to allow it to continue its own ambitious pursuit of stem cell cures.
Hiltzik, author of "Big Science" and the just-published "Iron Empires," wrote about the Trump Administration and its "warp speed" therapies for Covid-19. But he also mentioned the Golden State's stem cell effort. Here is the text of what Hiltzik had to say:
"Hype has become an inextricable part of science because it can generate millions of dollars of support. Consider the 2004 campaign to pass Proposition 71, which created the $3-billion California stem cell program (known formally as the California Institute for Regenerative Medicine, or CIRM).
"As I’ve reported before, the measure 'was sold to a gullible public via candy-coated images of Christopher Reeve walking again and Michael J. Fox cured of Parkinson’s.'
"The hype got the proposition passed, but CIRM has struggled ever since to live up to promises that it has been unable to deliver. That could be a burden this election season, when CIRM is seeking an additional $5.5 billion from voters and will have to explain why all the cures it predicted haven’t materialized.
"'That still might be a worthwhile public investment,' (Leigh) Turner (of the University of Minnesota) observes, adding that the research actually funded by CIRM has been conducted along responsible scientific lines. 'But you have this disconnect between what’s used to float the entire enterprise, and what the actual results are.'"
Turner, who is a bioethicist, was also quoted as saying,
“In human biology often as you proceed with your research, as you think you’re getting closer and closer to the finish line, you begin to discover it’s more and more distant. You become increasingly aware of the complexity you’re dealing with.”
California Gov. Gavin Newsom today endorsed three of the measures on the fall ballot but skipped over Proposition 14, the $5.5 billion stem cell bond measure. The move does not necessarily mean he will not take a position, however.
Newsom was a big supporter of the stem cell agency in 2004 and 2005. When he was mayor of San Francisco, he helped to put together a $17 million package that lured the agency, formally known as the California Institute for Regenerative Medicine (CIRM), to San Francisco.
When the free rent deal expired, CIRM switched its headquarters to Oakland because of the costs of renting office space in San Francisco.
It is a good political move to delay an endorsement until next month when the news is less likely to be filled with stories about fire, presidential conventions and Covid 19. But the endorsement -- if there is one -- should come at least a couple of weeks before voting begins in early October.
Of course, if Newsom is seriously out of public favor by that time, an endorsement may not help Proposition 14.
Monday, August 24, 2020
Four significant events are coming up this fall that offer golden opportunities to draw attention to the $5.5 billion ballot measure that would financially revive the California stem cell agency and send it along a new and more expansive road.
The measure is Proposition 14, sponsored by Robert Klein, the Palo Alto, Ca., real estate developer and attorney who was the first chairman of the California Institute for Regenerative Medicine(CIRM). He crafted the proposal and is leading the campaign.
The measure would provide $5.5 billion more for CIRM at a total estimated cost of $7.8 billion, which includes the interest on the state bonds. The agency was funded with $3 billion in 2004, which will run out this year. In addition to providing more cash, Proposition 14 would make major changes in CIRM itself. (See here for full text.)
August is a bit of a sleepy month for public attention to state ballot initiatives, although much campaign work has long been underway behind the scenes. After Labor Day, activities will step up, especially this year. All of California's 20 million voters will be getting ballots in the mail and can begin voting in early October. There will be no waiting until Nov. 3.
The Democratic presidential campaign is also urging early voting, which is likely to trigger higher than normal ballot returns in October. So voters need to be persuaded early.
The online events coming up create an opportunity for voters to learn more about the stem cell agency and its accomplishments. They also create a first-class springboard for generating coverage in the media about the agency. Opponents, as well, could use them to mount their own stories.
Here are the events that are known so far. More may be coming. If you know of others, please send an email to email@example.com
CIRM's grantee meeting, Sept. 14-15 -- Sponsored by CIRM and which will bring together grantees for an exploration of the work financed by the agency. Speakers include Maria Millan, CEO of CIRM, researcher Irv Weissman of Stanford and Larry Goldstein of UC San Diego.
CIRM's Alpha Clinic Symposium, Oct. 8 -- Sponsored by UC Davis, site of one of the clinics, which specialize in delivering stem cell therapies. CIRM kicked off the Alpha network with $50 million. Topics will include a look at CIRM's $5 million Covid effort, which includes involvement in two clinical trials. Register here.
UC Irvine panel, Oct. 6, sponsored by UC Irvine. This event is focused sharply on Proposition 14. It is still being organized but expects to feature researchers, opponents and media. We will post more details as they become available.
Cell and Gene Meeting on the Mesa, Oct. 12-16 -- Organized by the Alliance for Regenerative Medicine, this is an industry event that requires fees. It has attracted as many 1,200 persons in the past and has a robust preliminary agenda that digs into the future of cell therapies. The event was previously staged in La Jolla, Ca., but is now online.
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.
(Editor's note: An earlier version of this item incorrectly said that the Irvine panel was Oct. 5.)
Tuesday, August 18, 2020
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."
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.)
Here is the text of the presentation of the application (CLIN1-10999) from Poseida Therapeutics, Inc., to directors of the California stem cell agency.
The presentation was made by Shyam Patel, associate director for portfolio development and review at the stem cell agency. The directors did not discuss the application and gave it the go-ahead July 19, 2018,on a 14-0 vote.
The application was approved sometime prior to that date by the agency’s grant reviewers in a closed-door session, as is the practice for handling all applications. The agency’s governing board routinely rubber stamps the decisions of reviewers in virtually all cases.
The grant was designed to fund work leading up to the trial in question. The award was closed before the trial began.
Here is what Patel had to say, based on the CIRM transcript of the meeting.
“This is a late stage preclinical therapy study for a therapy for prostate cancer. The therapy itself is CAR-T cells, and these are stem memory T cells that compose this particular product.
"The indication is for patients with metastatic castrate resistant prostate cancer. This is the most advanced form of this particular disease. The goal for this particular project is to conduct product manufacturing, conduct the preclinical safety and efficacy studies, as well as prepare and submit the IND. And they're requesting roughly $4 million for CIRM funding, and they're going to be co-funding $1 million.
"To give you an idea about this particular project, we've prepared a few items. First of all, the potential impact for this therapy. There are 165,000 new cases of prostate cancer submitted for this particular year, and roughly 30,000 prostate cancer deaths for 2018 as estimated by the NIH.
"Now, the particular disease indication that this product is going for, which is the metastatic castrate resistant prostate cancer population, that represents a very small percentage of the overall prostate cancer population, but an overwhelming majority of the deaths for this particular disease. If successful, this particular therapy would target that most needy, highest risk patient population.
"In terms of the value proposition, over the last decade or so, there has been a steady improvement in the standard of care for prostate cancer. Currently available therapies for prostate cancer for metastatic castrate resistant prostate cancer includes hormone therapy, chemotherapy, as well as an autologous T-cell product, which is an activated T-cell product, all of which have shown modest survival benefit in clinical trials.
"The proposed therapy has a potential to induce long-term remission with possibly a single treatment. In terms of why this is a stem cell project, as I mentioned earlier, this particular product is composed of memory stem T-cells.
"To give you a brief overview of the current portfolio for CIRM with respect to related projects, we are not currently funding any prostate cancer-directed projects, but we do have some solid tumor projects, including therapies including therapies of cell-derived therapies as well as small molecule antibody-based therapies, all in early phase or IND-enabling studies. This particular applicant has received CIRM funding before.
"They are currently conducting a phase 1 trial for a CAR-T based therapy for multiple myeloma, which is funded by CIRM. Lastly, the GWG (grant review group) reviewed this application and unanimously gave it a tier one recommendation. There were 12 scores for tier one, zero scores for tier two, and zero scores for tier three. The CIRM team recommendation follows the GWG recommendation for the award amount of $3,992,090."
Friday, August 14, 2020
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.
Two more media outlets this week took positions on Proposition 14, the $5.5 billion ballot initiative that would save the California stem cell agency from financial extinction.
One outlet recommended approval. The other did not.
"For one thing, times have changed and the original rationale — California doing what the feds wouldn’t — is no longer applicable. For another, private enterprise has taken a bigger interest and stepped up research in this field.
For another, Prop. 14 doesn’t resolve a longstanding lack of oversight and accountability. And finally, imposing new costs on residents is hardly merited when most are struggling....Stem cell research will go on, CIRM or no CIRM. No on Prop. 14."
The editorial did not mention that UC Irvine, which is in its circulation area, has received $125 million from the agency.
"Continuing medical research is vital. While CIRM board member Jeff Sheehy, a gay man who's a former San Francisco supervisor, has been quoted as saying he is 'troubled' by the proposal because he thinks it might oversell potential benefits of stem cell research, Robert Klein, the real estate investment banker who spearheaded the 2004 initiative, has created an accessibility and affordability working group. The state needs to continue this research."
News media positions on the measure now total three. The Bakersfield Californian is the third. It is recommending a no vote.
(CIRM, of course, is the anacronym for the official name of the stem cell agency.)
Thursday, August 13, 2020
Want to be one of the last researchers in the Golden State to get cash from the $3 billion California stem cell agency?
That's a possibility if you act before Aug. 31. The agency has reopened its clinical trial stage round and has issued a special call for proposals. The agency is running out of money and is hoping that voters will provide $5.5 billion more by approving Proposition 14 on the fall ballot.
But it has enough left that to be able to finance two proposals in this area. The agency said in an announcement,
"The objective of this program announcement is to create a highly competitive partnering opportunity to accelerate the completion of a clinical trial for a promising stem or progenitor cell-based treatment that addresses an unmet medical need.
"Under this program, CIRM will act not only as a funding agency, but will also devote significant internal resources and leverage its external team of world-class subject matter experts to actively advance the project. The result of a successful application will be the formation of a true partnership that both accelerates the program and gives it the greatest opportunity for success."
Don't be fooled by the talk about an election in November. Voting on the $5.5 billion stem cell bond measure, Proposition 14, actually begins early in October -- not Nov. 3.
That is a critical fact of life for the campaign on behalf of the measure. With voting starting in October, backers and opponents will have to persuade voters early. Late October or Nov. 3 will be too late to capture the votes of millions.
It is not as if the folks in the mainstream media are trying to deceive when they refer to the November date. The first Tuesday in November has long been a traditional election day in presidential races. But it is the final day for voting -- not the only one -- something that is well known to political professionals.
It is especially important this year because all 20 million or so registered voters in California are scheduled to receive their ballots by mail -- not just those who have previously signed up for absentee ballots.
That means that many voters will be casting their ballots in less than two short months -- not three -- and making their decisions on whether the California stem cell agency should live or die. The agency is running out of its original $3 billion and will begin closing its doors this fall if Proposition 14 fails.
Tuesday, August 11, 2020
“I realized early on that when you deal in the heady company of presidents, cabinet secretaries and members of Congress and are asked for advice, you must be prepared to disappoint people with the truth and risk never getting asked back into the inner circle. I accepted that concept. Science is truth, and as a scientist I told the truth.” -- Anthony Fauci, in a speech accepting 2007 Lasker Award, as quoted by UC Davis medical student Samantha Wong in her prize-winning essay, "Science as a Voice of Reason."