Stem Cell Treatment for Covid-19: 'Probably Not Going to Happen'

A stem cell researcher at UC Davis is taking a dim view of the likelihood of development of a stem cell therapy for Covid-19, declaring that efforts in the area amount to little more than throwing spaghetti against a wall. 

The bottom line in the article by Paul Knoepfler is:

"There is buzz out there that some kind of stem cells or other cells will help with COVID-19. The reality is that that’s probably not going to happen....A whole range of people and firms are somewhat exaggerating and, in a few cases, outright hyping the odds of success. That is harming patients and the cell medicine field."

Knoepler's somewhat lengthy remarks appeared on his blog, The Niche, two days ago.

They drew a comment on the blog from a member of governing of the state stem cell agency, which has allocated $5 million to help in the fight against the virus. Francisco Prieto, a Sacramento physician, said, 

"Thanks for, as usual, injecting a little thoughtful perspective. There has been a great deal of breathless hype and general agita around everything having to do with COVID-19. Count me as one of those hopeful that something will 'stick to the wall,', but I won’t hold my breath. I would love sometime to sit down and talk about science (and tomatoes!) although I suppose that may have to wait until this pandemic and my time on the board have ended."

Knoepfler's comments come as the stem cell agency, known officially as the California Institute for Regenerative Medicine(CIRM), is scheduled to meet this morning to consider 12 applications for Covid-19 funding. Only two out of 12 were approved earlier by the agency's anonymous reviewers, who meet behind closed doors. The approved applications total $300,000. The agency has previously awarded $1 million in its Covid-19 round. 

Asked yesterday whether his remarks applied to the two approved applications, Knoepfler said, 

"No, but it does apply to a number of the not-recommended-for-funding ones."

The two applications involve small molecule drugs. The agency is permitted to finance research other than stem cells if it is a vital research opportunity. That provision -- some might call it a loophole -- also persists in the proposed ballot initiative that would provide CIRM with an additional $5.5 billion. 

Knoepfler is not alone in his skepticism about stem cell possibilities related to Covid-19. Another California stem cell researcher privately told this writer recently that the CIRM Covid-19 round was "ridiculous." And early in April a Texas researcher also expressed skepticism in an account on Knoepfler's blog. On the other hand, a couple of comments on Knoepfler's piece this week took issue with his position. 

The California researcher covered a lot of ground, ranging from the science to the PR. Here are some excerpts.

 "Part of the problem here at least in the US and probably in many other countries is that regulatory bodies like the FDA have dropped the bar so low for IND clearance (or equivalent abroad) for COVID-19 INDs that it incentivizes various teams to try just about anything for the novel coronavirus. Of course, the stem cell and cellular medicine field isn’t the only one having such a low bar from the FDA for COVID-19, but it’s problematic all around.

"The FDA is likely under enormous political pressure to quickly clear INDs for COVID-19 trials, but it should do its best to only clear things that actually have a logical premise and a foundation of solid, even if early data. Note that Celularity was able to get Rudy Giuliani to plug what it was doing and shortly thereafter the FDA cleared their IND."

"The news media also sometimes don’t quite know how to handle the cellular medicine approach to COVID-19. I’ve seen many good stories but then some others just take interviewees’ statements at face value or even hype things further."

Knoepler asked rhetorically: 

"What’s wrong with throwing a whole bunch of stem cell therapies at COVID-19 and just hoping something sticks?

"If the logic just isn’t there to start with then you are giving people false hope. You’re also setting yourself up to try to squeeze something hopeful out of the data once you get it, which is a road to potential big trouble. Your firm may also find itself hyping things. In addition, you’re wasting resources that could go somewhere else like to another clinical trial that makes more sense. For some other things like grant writing, the throw-the-spaghetti-on-the-wall approach can be effective."

The $5.5 Billion Stem Cell Count: No New Figures Today

California elections officials late this afternoon reported no new totals for the number of signatures gathered to place a $5.5 billion stem initiative on the November ballot. Backers of the ballot measure also have not responded to a query earlier today concerning their take on the signature verification. 

Counting Stem Cell Signatures in California: $5.5 Billion Initiative Edges Closer to Ballot

Backers of a $5.5 billion stem cell ballot initiative have turned in more than 760,000 signatures, edging closer to success in their efforts to qualify the measure for the November ballot.

At stake is the survival of California's stem cell agency, which is running  out of money and will begin shutting down this year unless more cash is forthcoming.  Known formally as the California Institute for Regenerative Medicine (CIRM), the agency was provided with $3 billion when voters created it in 2004.

Whether the initiative will be presented to voters is still in question. The proposal requires only 623,212 valid signatures to make the ballot, but many may be disqualified. Indeed, the very early disqualification rate is running at nearly 18 percent. The total number of signatures in the state's raw count is 760,601.

The disqualification rate is based on results from only four small counties out of 58 in California.   

Election officials have not finished their preliminary look at big counties such as Los Angeles which has reported 298,147 unverified signatures and San Diego with 99,899 unverified signatures. Orange County has not even filed its raw count.

The lowest number of valid signatures were reported in the remote counties of Alpine (five verified signatures) and Modoc(six). 

Today's signature figures are the first independent look at how well the initiative's backers have done with their petition drive. They have said they have turned in 925,000, but that was not yet substantiated by the state figures which are still missing reports from several large counties. 

The door has closed for submission of any further signatures, according to the California Secretary of State's office. The deadline for county officials to finish their verification process is June 24. 

Here is how the state election officials explain how the count proceeds:

"If the raw count of signatures equals 100% or more of the total number of signatures needed to qualify the initiative or referendum measure, the Secretary of State notifies the county elections officials that they will have to randomly sample signatures for validation, to ensure petitions were signed by registered voters.

"If the result of the random sample indicates that the number of valid signatures represents between 95% and 110% of the required number of signatures to qualify the initiative or referendum measure for the ballot, the Secretary of State directs the county elections officials to verify every signature on the petition. This process is referred to as a full check of signatures. 

"If the total number of valid signatures is less than 95% of the number of signatures required to qualify the initiative or referendum measure, the proposed measure will fail to qualify for the ballot. 

"For an initiative measure, if the number of valid signatures is greater than 110% of the required number of signatures, the initiative measure will be eligible for the ballot. Eligible initiative measures will become qualified for the ballot on the 131st day prior to the next statewide general election unless withdrawn by the proponent(s) prior to its qualification by the Secretary of State."

Look for a fresh report and update on the latest figures early this evening right here on the California Stem Cell Report. 

A Call for $5.5 Billion More and 'Silence' from Scientists

The story of jCyte, Inc., the California stem cell firm that notched a $252 million deal last week, contains a chapter that might be titled  "Golden Eggs and Buttering Your Bread."

What makes that chapter significant is that it involves steps taken by jCyte to give some credit to California's stem cell 'goose,' so to speak: The creature that has laid $2.7 billion in the laps of hundreds of scientists and institutions over the last 14 years. JCyte readily acknowledges and publicizes the importance of the $34 million that the California stem cell agency has provided directly and indirectly to the firm and its founders. 

"What?" you might ask incredulously. "Isn't that to be expected?" 

Well, no actually, based on the performance of institutions and researchers over the past few years. When they issue news releases about major developments in research funded by the agency, most often the state's beneficence is omitted or buried.  And that means that the state stem cell agency's financing is also not mentioned in the subsequent news stories about the research.  (See here and here also.)

The California Stem Cell Report holds no brief for or against the agency and its quest for $5.5 billion more to save it from financial extinction. But should the multibillion-dollar initiative reach the ballot in November, California voters deserve a full and robust exploration of the pluses and minuses of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known. 

If the seemingly tongued-tied institutions and researchers do not speak up about whether they think CIRM is worthy, they do not serve the public well or their own self-interest. The same applies to CIRM's opponents, who owe it to themselves and to voters to make a well-reasoned, fact-based case for letting the agency slowly expire. 

The stem cell agency is all but invisible to the voters of the Golden State. The media rarely write or broadcast stories about it nowadays, which has been the practice for the past decade or more. And CIRM is certainly a much different creature than it was 10 or so years ago.

JCyte deals with rare eye diseases. It is also rare among CIRM recipients in that it clearly recognizes the critical role that the agency has played in its short life. The firm's web site attests to that impact on its "missions" page.  Its news release on the $252 million deal demonstrates that as well. And it was demonstrated again yesterday morning when its president, Paul Bresge, was quoted on the CIRM blog as saying, 

“jCyte is extremely grateful to CIRM, which was established to support innovative regenerative medicine programs and research such as ours.  CIRM supported our early preclinical data all the way through our late stage clinical trials.  This critical funding gave us the unique ability and flexibility to put patients first in each and every decision that we made along the way. In addition to the funding, the guidance that we have received from the CIRM team has been invaluable. jCell would not be possible without the early support from CIRM, our team at jCyte, and patients with degenerative retinal diseases are extremely appreciative for your support.”

Bresge clearly understands where his bread is buttered, so to speak, and what produces the golden eggs. We do not intend to say that in any kind of demeaning way. The financial component of scientific research is far below the radar of the overwhelming majority of voters. It is up to those who have something at stake to strive diligently to explain how the money works and sustains science. No cash. No research. 

The deal with jCyte has big numbers attached. Not all research results can say that. Most are considerably less dramatic as far as the public is concerned. But researchers -- if they are to well serve themselves and their institutions -- should be clear with the public that they would not be doing much research in any area if state and federal funding did not exist. Informing voters is an incremental task and slow. One bit of information on top of another.  It requires perseverance and patience. Just like culturing something in a petri dish. Not just ballot campaigns every 15 years.

Quarter-of a-Billion Dollar 'Salute' to California Stem Cell Agency; Japanese Firm and jCyte Sign Big Licensing Deal

A California stem cell company with major backing from the state's stem cell agency received a $252 million boost today when a Japanese firm cut a deal to develop the firm's therapy for an eye disorder that affects nearly 1.9 million people globally. 

The California company is jCyte, Inc., of Newport Beach. It has received $15 million from the California stem cell agency over the last few years to develop a treatment for retinitis pigmentosa. Its co-founder, Henry Klassen of UC Irvine, has received an additional $19 million from the agency for his work that led to creation of jCyte. The Japanese firm is Santen Pharmaceutical Co. Ltd., a publicly traded firm. 

In a comment for the California Stem Cell Report, Maria Millan, CEO of the agency, formally known as the the California Institute for Regenerative Medicine (CIRM), said, 

"This is exciting news for everyone at jCyte. They have worked so hard over many years to develop their therapy and this partnership is a reflection of just how much they have achieved.

"For us at CIRM it’s particularly encouraging. We have supported this work from its early stages through clinical trials. The people who have benefitted from the therapy, people like Rosie Barrero (see video above), are not just patients to us, they have become friends. The people who run the company, Dr. Henry Klassen, Dr. Jing Yang and Paul Bresge, are so committed and so passionate about their work that they have overcome many obstacles to bring them here, an RMAT designation from the Food and Drug Administration, and a deal that will help them advance their work even further and faster. That is what CIRM is about, following the science and the mission."

In its news release, jCyte said, 

"The treatment is a minimally-invasive intravitreal injection, which can be performed in an ophthalmologist’s office with topical anesthetic. The entire procedure takes less than 30 minutes. The principal mechanism of action is the release of neurotrophic factors that may rescue diseased retinal cells. jCell therapy aims to preserve vision by intervening in the disease at a time when host photoreceptors can be protected and potentially reactivated."

The company's statement continued, 

"Under the terms of the licensing agreement, jCyte will receive $50 million in upfront cash, $12 million in a convertible note offering, and $190 million in clinical and sales milestones based on regulatory approval and initial sales in Europe, Asia and Japan. The total deal is valued at up to $252 million. jCyte is also entitled to receive tiered, double-digit royalty payments on net sales of jCell therapy once commercialized outside the U.S."

Currently there no federally approved treatments for the rare, genetic affliction. In its clinical trials, jCyte has treated more than 100 patients,, and the federal government has given it a regenerative medicine advanced therapy designation based on the early results. That designation is aimed at speeding further federal review.  The company says the treatment could have application in other degenerative retinal diseases, including age-related macular degeneration and diabetic retinopathy.

In another rare instance, jCyte featured CIRM's role in funding the work. The agency was cited in the fifth paragraph of the company news release. The firm's web site also contains a glowing acknowledgement of the importance of CIRM support. In virtually all news releases from businesses or academic institutions, the role of CIRM's funding, which totals $2.75 billion over the last 14 years, is omitted. 

The deal with jCyte undoubtedly will be cited during possible efforts this fall to keep CIRM operating. It is running out of cash and is hoping a proposed $5.5 billion ballot initiative will be approved by voters to keep the agency operating.

Klassen co-funded the company along with Yang, also of UC Irvine. The cells used in the treatment are manufactured at a facility at UC Davis that was financed with funds from the stem cell agency. 

Signature Drive Ends for $5.5 Billion California Stem Cell Initiative; Will it Qualify for the Ballot?

Backers of a $5.5 billion ballot initiative to save the California stem cell research program from financial extinction said today that they had finished their petition drive to qualify the measure for the November ballot and expressed confidence that they had the more than 600,000 signatures needed. 

The announcement came after the campaign had missed three of its self-imposed deadlines for collecting 950,000 signatures as well as the state-recommended deadline of April 21.  The campaign said that the petitions have been delivered to county election officials around the state for verification of the signatures, a lengthy process that must be completed by June 15. If the work is not finished by then, the measure will not appear on the ballot. 

The initiative needs 623,212 valid signatures to qualify. The campaign's news release today said it had 925,000, down from its goal of 950,000. However, disqualification rates can run as high as 50 percent. Early last month after its public signature-gathering was halted because of coronavirus restrictions, it said had only 915,000. The campaign then kicked off what it called an "unprecedented," Internet, mail-in campaign to solicit signatures.  Later it began a direct mail effort, also unusual for an initiative qualification drive. 

The stem cell agency was created in 2004 by another ballot initiative and financed with $3 billion in state borrowing. It is now running out of money and will begin closing down in the fall if substantial funding is not received. 

Robert Klein, chairman of the campaign, said he was "confident" that the campaign had enough valid signatures to qualify for the ballot. He said, 

“Submitting signatures in time to qualify for the general election would not have been possible without our coalition of patient advocates, who banded together to help us
overcome the unprecedented challenge of signature gathering during a global pandemic – the effort is emblematic of our movement that has been widely supported and driven by patients and their families from the beginning”

Klein, who led the 2004 ballot campaign that created the agency, also cited the $5 million special, Covid-19, grant round now being conducted by the stem cell agency as example of the valuable work performed by the agency, officially known as the California Institute for Regenerative Medicine (CIRM).

One of the recipients of  a $750,000 award in the covid round, John Zaia of the City of Hope, was quoted in the campaign news release as saying,  

“We could be on the brink of medical discoveries that could save the lives of patients impacted by Covid-19 and other diseases, and this research simply would not be possible without the initial investment Californians made in the state’s stem cell program in 2004.

“Now, it is absolutely critical that this investment is renewed, allowing researchers like myself to continue to discover treatments and cures that can improve or save the lives of patients today and for generations to come.”

The City of Hope and many other recipient institutions have had a seat on the CIRM governing board since its inception.  According to CIRM figures, the City of Hope has received $117 million in grants since 2005. Zaia has received $33 million. 

The process of verifying and counting signatures is tedious under normal circumstances. County officials are now further hampered by work-related restrictions created by the coronavirus crisis. 

It is not clear whether enough signatures can be verified by June 25. That's the state deadline for qualifying for the November ballot. Two other unrelated initiatives failed or were withdrawn yesterday, state election officials said. Ironically one of the proposals would have allowed for the gathering of signatures online as a way to speed the task. 

The campaign has removed from its web site the outdated information concerning its petition solicitation effort, including the phrase "time is running out," which ran on its home page. But here is a link to the petition page from April 22 as archived by the California Stem Cell Report:  

A Stem Cell Ballot Initiative in Your Mailbox: Thank you Montgomery Ward

The campaign to refinance California's stem cell agency took a tool from Montgomery Ward in its effort to qualify a $5.5 billion measure for the ballot this fall. The unusual -- for a ballot initiative -- tactic was part of a last gasp push to secure 950,000 signatures. Whether it was successful will be determined in the upcoming weeks. Here is a piece from Capitol Weekly, where it was initially posted, that examined how the direct mail effort worked. The article was written by yours truly.

For survival, stem cell agency hunts for ‘wet signatures’

BY DAVID JENSEN POSTED 05.05.2020

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The folks who are trying to save the $3 billion California stem cell agency from financial extinction are using a well-worn technique that goes back to ancient Egypt, at least by some accounts.

It is expensive, depending on what you are peddling, and generates a return as low as 1 percent. It is direct mail, but with a significant twist. It involves the collection of “wet signatures” and the signing of documents that must be produced in a fussy, legal fashion.

The process requires a bit more commitment from voters than, say, returning a pitch from the Readers Digest Sweepstakes. And it is likely that the effort is the first time that anyone has made a major push — both by direct mail and online — to collect tens of thousands of voters’ signatures to qualify an initiative for the ballot in California.

It is a life or death matter for the California Institute for Regenerative Medicine (CIRM), otherwise known as the state stem cell agency. CIRM is running out of money and will begin to close its doors next fall unless it receives a life-preserving jolt of cash. The proposed ballot initiative would do that nicely with an injection of $5.5 billion.

Ordinarily, qualifying a measure for the ballot in the Golden State is simple. All you need is money. The cash goes to firms that hire hundreds of people to solicit hundreds of thousands of signatures in public places. The coronavirus put a stop to that sort of public behavior back in March.

The result was a big crimp in the plans of the “Californians for Stem Cell Research, Treatment and Cures,” as the campaign has dubbed itself.

It announced that 35,000 more signatures were needed. “Time is running out,” the campaign warned on its web site.

On hand were 915,000 signatures. Qualifying the measure for the ballot requires only 623,212 signatures of registered voters. But disqualification rates for ballot initiative signatures can run as high as 50 percent, and the campaign wanted a bigger cushion.

It fired up what it described as an “unprecedented,” effort online, but one that is a tad complicated.

First, someone interested in finding a stem cell petition to sign must know that they can find one on the Internet, which is a big ask. Then, if their search leads them to the proper web site, they will encounter lengthy instructions.

The process is not simple. The campaign’s web site mentions “wet signatures,” ones that are signed in ink. Then there is the need to print out the 16 pages of the petition from the web site and the need to complete the “circulator declaration.” A seven-minute, “sign-at-home training”  video was posted by the campaign to guide wandering supporters along the signature trail. 

About April 13, the campaign quietly boosted its cyberspace pitch with direct mail, presumably targeting households likely to be sympathetic to spending $5.5 billion for stem cell research via the ballot initiative.

A packet of the direct mail material surfaced recently in Santa Barbara.  The California Stem Cell Report subsequently asked the campaign about the direct mail effort, but it has remained all but mum, with the exception of providing a rough start date for direct mail effort. Unanswered are such questions as how many packets were mailed, their return rate and cost and whether there is a precedent for mailing out petitions in this fashion?

The campaign’s direct mail effort is significant and holds some promise. But the  tasks for recipients take time and pose some barriers that can lower a response rate.

The question is whether the unusual effort will pay off?  To answer that, let’s assume that the direct mail pitch generates a 2% return with an average of one signature per household, which may be generous based on what is known about direct mail efforts. Let’s assume that the campaign would like to gather by direct mail only a portion of the 35,000 signature shortfall, for example, about 15,000. That would mean producing and mailing 750,000 packets to collect 15,000 signatures, which, of course, also need to come from verified registered voters.

Costs are not insignificant. Aside from postage, one web site estimates that production costs for business direct mail range from 30 cents to $10 each, depending on size and complexity.

Direct mail does work. That’s why it has been around in a significant way for many decades and fills your mailbox every day. It is not clear who in the campaign came up with its direct mail plan. But the campaign is very much the creature of Robert Klein, a Palo Alto real estate developer who also directed the 2004 campaign that led to the creation of the stem cell agency. He spent more than six years as its first chairman and is the chairman of his own stem cell advocacy group, Americans for Cures, which has offices in Klein’s Palo Alto building.

Klein is acutely aware that next November could mean the extinction of an enterprise he has devoted years to. Few good alternatives exist beyond passage of this year’s initiative. It’s this year or never, he basically told CIRM directors in 2017.  No one, however, could have predicted the coronavirus crisis that halted normal signature gathering. So today Klein is emulating the direct marketing examples of a landowner in ancient Egypt and of a man named Aaron Montgomery Ward who launched his first one-page catalog in 1872 and who can be considered the father of modern direct mail.

California will soon know whether Klein has been as successful as Mr. Ward, whose catalog became imbued in American culture as the nation’s “Wish Book.”

The Covid-19 Fight: More Applications for Cash Coming into California's Stem Cell Agency

California's $3 billion stem cell agency has now collected 12 fresh applications from researchers hoping to tap into it for millions to fight the coronavirus and Covid-19. Today is the deadline for more. Another deadline for applications comes up in two weeks.

The agency reported that the 12 include three from biotech firms. The other nine are from nonprofits.  The agency's application reviewers will meet online May 12 and in private make the de facto decisions on which to fund.

The agency's directors are expected to meet a few days after the application review session and ratify the decisions.

Last month the directors approved a total of $1 million for three applications. The funds went to the City of Hope and two to researchers at UCLA.  The agency has allotted $5 million for the covid effort.

The total number of applications to come before researchers now stands at 24, including new 12.

News Coverage of Capricor and California Stem Cell Agency Less Than Abundant

Capricor Therapeutics' stock price retreated today after soaring 253 percent yesterday on the news that one of its products had successfully treated a small group of critically ill, Covid-19  patients.

The price closed today at 7.00, down from yesterday's close of $8.50. That was the highest price for the Beverly Hills firm since 2018.

While the news about its CAP-1002 treatment excited investors, it did not stir the news media. In the glut of hundreds of stories about the coronavirus, the mainstream media did not even mention Capricor. Nor did the Los Angeles Times, virtually the home town paper for the firm. As for the California stem cell agency, which has pumped nearly $25 million into Capricor-related research, the role of the agency was also among the missing.

The Los Angeles Business Journal did carry a tidy and straight forward story, again one that did not mention the stem cell agency, which is hoping that California voters will save its financial life next fall. That is, if they approve a proposed, $5.5 billion, ballot measure that has already missed one state-recommended deadline (April 21) for qualifying for the ballot. BioWorld also had a story that did not mention the California agency's role. 

The agency is running out of the $3 billion that voters provided for it in 2004 when they created the unprecedented state research program. It will begin closing its door in six months unless major funding is found.

The sparse news coverage of the agency will be a challenge for the agency's backers as they seek voter approval of the ballot measure, assuming it qualifies.

A Covid-19 Success, 300 Percent Stock Price Increase and the California Stem Cell Agency

A company that the California stem cell agency has backed with nearly $18 million scored big this morning on news that one of its products had generated a 100 percent survival rate with a small group of critically ill Covid-19 patients.

The company is Capricor, Inc., a publicly traded company based in Beverly Hills, Ca. Its stock soared more than 320 percent at one point this morning from its previous close of $2.41 based on the news about its CAP-1002 therapy. Shares stood at $9.09 at the time of this writing.  

The company said in a news release that it had generated "100 percent survival in critical Covid-19 patients who were treated with Capricor’s lead asset, off-the-shelf ('allogeneic') cardiac cell therapy CAP-1002, at Cedars-Sinai Medical Center as part of six compassionate care cases." 

The company said the federal government has approved 20 additional patients for treatment. Capricor also said it is developing "a randomized, placebo-controlled trial planned to treat patients with moderate and severe disease which is intended to be funded by non-equity capital."

Capricor and its underlying research have long been embedded with the state stem cell agency, which is formally known as the California Institute for Regenerative Medicine (CIRM). In addition to $17.8 million given directly to the company, another $7 million went to Cedars-Sinai for much of the early development work that led to the creation of Capricor. 

Speaking to the agency's governing board in 2016 concerning CAP-1002, CIRM director Jeff Sheehy, chair of its Science Committee, said, 

"This is pretty much a pure CIRM product. They came into our first disease team to develop the product. We've supported two of the three clinical trials. So if this turns out to be a major success, this will be a real feather for CIRM. We've been with them all the way. So I'm optimistic." 

In 2018, a clinical trial involving CAP-1002 was begun at UC Davis as part of CIRM's separate Alpha Clinics program, an ambitious statewide effort to lead the way nationally on stem cell research.

In a news release this morning, Linda Marban, CEO of Capricor, said, 

"As the global medical community continues to come together in its battle against COVID-19, the results of our initial compassionate care cases are extremely promising and what we had anticipated. We look forward to continuing to treat additional patients under our recently approved expanded access program Investigational New Drug application.

“CAP-1002 is an easy-to-deliver intravenous therapy that has been administered successfully to over 150 patients to date. Given its novel mechanism of action, it could be a potential game-changer in helping countless Covid-19 patients.”

The Capricor product initially targeted Duchenne muscular dystrophy (DMD), "a muscle wasting condition that steadily destroys the muscles in the arms and legs, heart and respiratory system" of boys and "never lets up," CIRM says.

The CAP-1002 treatment has demonstrated immunomodulatory properties that come into play with Covid-19. Capricor said, 

"Multiple published peer-reviewed studies of CDCs have demonstrated favorable modulation of various inflammatory cytokines and regulation of the immune response. The current understanding of Covid-19’s later stages are thought to be due to overstimulation of the immune system, which triggers a cytokine storm in which the body is overwhelmed with pro-inflammatory molecules. This immune response may become excessive and pathologic, inducing pneumonia, organ failure and death. Therefore, it can be the body's overreaction to Covid-19, rather than the virus itself, that delivers the fatal blow."

Capricor is also working on a Covid-19 vaccine involving a different technology.

The Covid-19 Fight: $1 Million Awarded by California Stem Cell Agency for Research

The California stem cell agency this morning awarded $1 million to three researchers for work aimed at battling the coronavirus, which has taken more than 1,500 lives in California and nearly 45,000 nationally.

The grants are the first coronavirus research to be funded by the agency, formally known as the California Institute for Regenerative Medicine (CIRM). Maria Millan, CEO and president of CIRM, said in a news release,

“We are in the midst of very challenging times where there is not yet an approved treatment for COVID-19. In response to this, CIRM launched and executed an emergency COVID-19 funding program, which was made possible by our board, patient advocates, California scientists, external scientific expert reviewers and our dedicated team."

Millan cited one application in particular.  She said,

“With CIRM funding, the City of Hope COVID-19 Coordination program will tap into CIRM’s network of researchers, physicians, and our Alpha Clinics to deliver this treatment to patients in need.  It will also serve the critical role of gathering important scientific data about the plasma, safety, and clinical data from treated patients.”

The City of Hope application received the most funding in today's round, $749,999. It went to a team led by John Zaia.

The proposed research would involve development of a program in California to identify potential blood plasma donors who could take part in a Covid-19 treatment program. A summary of the reviewers' comments on the Zaia application (Clin2dovid19-117) said,

“This will help develop a new screening tool for the California public health arsenal by identifying what patient and (plasma) donor factors predict clinical benefit.”

The other two awards went to Gay Crooks of UCLA, $150,000, (Disc2covid19-11817) and Brigitte Gomperts, also of UCLA, $149,998 (Disc2covid19-11764).

Crooks is seeking to enhance the ability to generate specialized immune cells in the lab and use them to discover viral antigens that have the highest potentcy for vaccines.

Gomperts is aiming identifying a federally approved lead compound that could be repurposed for Covid-19 infection.

CIRM's out-of-state reviewers had questions or concerns about each proposal, which can be found in the summaries of reviewer comments. Zaia wrote a letter dealing with some of the reviewer comments, noting that the application was prepared on a short timeline and more work had answered some of the key questions.

CIRM directors gave higher prior to plasma applications that had strong plans for "outreach and study participation by under-served and disproportionately affected populations." Zaia's three-page letter devoted full page to an outline of that effort. Other applicants did not submit a letter to the CIRM board.

Nine applications were rejected by reviewers, whose decisions are nearly invariably rubber-stamped by the board. The board continued that longstanding tradition today. 

CIRM has speeded up its normal processes to gather applications and act on them. Winners are expected to begin work 30 days from today. "Deliverables" are expected in six months. 

The applications considered today were among 19 submitted April 7, the first deadline for the $5 million round. The seven not reviewed did not meet the eligibility criteria.  Sixteen more applications were received last Tuesday. The next deadline for applications is May 5.

Directors expect to act in the middle of next month on more applications. 

Skating Past Deadlines: $5.5 Billion Stem Cell Campaign Silent on Critically Needed Signatures

Backers of a $5.5 billion stem cell research proposal this week dodged past another critical, but self-imposed deadline for placing the measure before California voters. They eliminated it. 

It was the fourth deadline that the campaign has either missed or eliminated. The move came as the campaign itself has noted.

"Time is running out."

The ballot initiative -- if it makes the fall ballot and is approved by voters -- would save the state stem cell agency from financial extinction. Originally funded in 2004 with $3 billion in borrowed state money, the agency is expected to be down to its last $26 million by the end of the day today. Formally known as the California Institute for Regenerative Medicine (CIRM), the agency is expected to award $1.0 million this morning for Covid-19 research. 

The campaign is seeking 950,000 signatures of registered voters to qualify its initiative for the ballot. As of early this month, it said it had 915,000 but has remained mum since then on the number of signatures it has gathered. 

Legally, the measure needs 623,212 signatures of registered voters. Typically, however, a high percentage of signatures collected for initiatives are disqualified, sometimes as high as 50 percent. 

State election officials recommend that the signature petitions be submitted to election officials in 58 counties by April 21 to allow officials to perform the time-consuming work of verifying hundreds of thousands of signature. County election offices, however, are hard hit by stay-at-home, Covid-19 restrictions affecting their operations. If the verification work is not completed by June 15, the initiative will not be placed on the ballot. 

The campaign has laid out its changing deadlines on a web page exhorting supporters to engage in an unusual Internet and mail-in petition effort. Earlier this week, after the campaign missed its third deadline, wording on the page was changed to remove a specific date. As of this writing, the latest "deadline"  exhortation said, 

"The campaign must gather the last 35,000 signatures through mail-in submissions ASAP."

On Wednesday, the campaign told the California Stem Cell Report it would be submitting petitions to county officials "in the next two weeks." The campaign did not respond this morning by the time of this writing to questions about the signature-gathering effort. However, one Santa Barbara resident told us that he received a petition packet this morning in standard postal mail from the campaign asking him to sign the petition and return it to the campaign. 

(As this item was being posted, the campaign emailed a response concerning the status of its signature-gathering. However, the statement only repeated what the campaign said days earlier and did not contain any new information.)

California Stem Cell Agency Set to Award Millions on Friday for Coronavirus Research

The California stem cell agency is moving with dispatch to approve millions of dollars for stem-cell related research that would assist in the battle to fend off Covid-19 and ease the coronavirus crisis.

Meeting behind closed doors yesterday, the agency's reviewers  evaluated 12 applications seeking $2.7 million in total funding, including one proposal at a clinical stage. The proposals were received about two weeks ago and were the first in the agency's special Covid-19s round. 

It is standard practice for the reviewers to meet privately when considering applications. 

The reviewers' decisions, still undisclosed, are expected to be ratified by the agency's governing board on Friday. The researchers are expected to be ready to begin work 30 days later. 

Also yesterday, the agency received 16 more applications in the $5 million, rolling, coronavirus round. Four involved clinical applications. Three came from businesses and the rest from non-profits, including academic institutions. 

The board's meeting is open to the public via the Internet. Instructions are available on the agenda of the meeting, which begins at 11 a.m. PDT. 

Supporters of $5.5 Billion California Stem Cell Measure Miss Third Deadline, Including One Recommended by the State

Backers of a $5.5 billion, California stem cell research proposal this morning once again missed their self-imposed, but important deadline for qualifying the measure for the ballot this fall in hopes of saving the financial life of the state stem cell agency. 

It was the third time that the ballot initiative campaign has missed its own deadlines for gathering signatures as time is running out. The first deadline was April 11. The second deadline was April 18. The third deadline was April 21 (yesterday). The next deadline is April 23 (tomorrow).

Yesterday was also the deadline recommended by state election officials for submitting the signatures to all of California's 58 counties.  The state's recommendation is not a legal cutoff, but appears aimed at ensuring enough time exists to complete the lengthy certification process for the November ballot.

The proposed ballot initiative would refinance the state stem cell agency, known formally as the California Institute for Regenerative Medicine (CIRM). It is running out of its original $3 billion and is expected to begin closing its doors next fall. 

The campaign, which is independent of the agency, had little to say about its signature-gathering problems. The California Stem Cell Report this morning asked the campaign how many signatures it has on hand.  Sarah Melbostad, a spokeswoman for the campaign, replied:

"They are still in the process of counting them but we will let you know as soon as we have an updated number to share."

It was not clear whether the campaign actually knows how many signatures it currently has or whether, on the other hand, it has an actual number but is simply not releasing it publicly. The campaign did not respond to a question this morning on that matter. 

Several weeks ago, the campaign said it had 915,000 signatures. That was when it set its April 11 deadline to secure 35,000 more. It needs only 623,212 to qualify for the ballot, but many signatures are disqualified as elections official in each county checks to see whether the signatures represent actual registered voters. 

Melbostad said, 

"We’re continuing to get petitions in the mail every day from our patient advocacy-driven and direct-mail signature gathering efforts. The campaign is planning to submit signatures to the counties in the next two weeks to ensure that the counties and the state have sufficient time to count and verify signatures for the November ballot."

If election officials have not certified the necessary signatures by June 15, the stem cell measure will not appear on the ballot. The certification process can be prolonged and likely more so under the difficult conditions imposed by the coronavirus crisis. 

State election officials provide recommended deadlines under normal conditions for submitting petitions to qualify ballot measures. They depend on the method used for qualification: random sampling or "full check." Under the random sample method, the recommendation is to submit petitions to county election officials by yesterday (April 21). Under the full check method, March 3 was the recommended deadline. 

Two Deadlines Missed by Supporters of $5.5 Billion, California Stem Cell Measure

Backers of a $5.5 billion stem cell research proposal in California today have once again missed a self-imposed, but critical deadline as they continue to struggle with securing enough signatures to place the measure on the November ballot.

The campaign's website this morning listed what is now its third deadline for gathering the signatures of 950,000 voters. Previously, the campaign had set an April 11 deadline and then an April 18 deadline. The latest deadline is tomorrow (April 21). The rolling extensions do not augur well for its "unprecedented" attempt to collect signatures via a combined online and mail-in effort. 

In response to questions from the California Stem Cell Report, Sarah Melbostad, a spokeswoman for the campaign, declined to elaborate on the campaign's progress or lack of it beyond a statement she released on Friday.

The questions ranged from just how many signatures the campaign currently has in hand to when they might be presented to election officials. (Here is a link to the text of all the questions.)

The campaign's ballot initiative is aimed at staving off the financial demise of California's stem cell agency, which has all but run out of the $3 billion that it was provided by voters in 2004, also through a ballot initiative.  Known formally as the California Institute for Regenerative Medicine (CIRM), the agency has no other significant funding source than state-issued bonds.

The coronavirus crisis has blocked the usual method of gathering of ballot initiative signatures at shopping malls and other public locations. The campaign said earlier it needed another 35,000 signatures to hit its goal of 950,000. The legal requirement is only 623,212 but many signatures are disqualified as invalid, sometimes as high as 50 percent.

Another obstacle involves officials in the state's 58 counties, who must certify the signatures. Most, if not all, are short-staffed because of the coronavirus and/or must provide a working environment that is likely to slow the signature count. If the count is not completed by June 15, the stem cell measure will not be on the November ballot and the agency will begin closing its doors.

Text of Questions to Campaign for $5.5 Billion Stem Cell Intiative

Here are the questions that the campaign for a $5.5 billion California stem cell research measure declined to address this morning. The questions were directed to the campaign by the California Stem Cell Report last Friday in connection with the campaign's then April 18 deadline for collecting signatures to qualify the measure for the fall ballot. 

• How many signatures have been gathered for presentation to election officials? Is that number based on an estimate or actual count?
• The campaign has said it has "no estimates to share." Does that mean that, in fact, it has estimates that it does not want to share? Is the campaign keeping a rolling total of signatures each day since it began its new mail-in effort?
• When will the petitions be presented to election officials?
• How long does the campaign think the count will take?
• Does the campaign plan to try to gather more signatures either beginning this week or after it receives information about the disqualification rate?
• Is there anything else I need to know?

Correction

A item earlier today dealing with the signature-gathering campaign for a $5.5 billion ballot measure incorrectly said that the campaign had said it had gathered 935,000 signatures. The correct figure is 915,000.

$5.5 Billion California Stem Cell Proposal: Campaign Mum on Its Ballot Qualification Numbers

Backers of a $5.5 billion, proposed ballot measure said this morning that they still cannot provide a fresh estimate of the number of voter signatures they have in their effort to save the California stem cell research program from financial extinction.

The campaign faces a self-imposed deadline of Saturday to gather the needed signatures in its initiative petition drive, which was stymied when the coronavirus crisis hit the Golden State.  While the deadline is self-imposed, it reflects the upcoming, tedious and time-consuming pace of signature verification by county election officials, who are additionally hampered by workplace restrictions currently in place.

If county officials have not verified 623,212 signatures of registered voters by June 15, the stem cell initiative will not be placed on the ballot. The campaign has said early this month that it has 915,000 signatures and needs to collect a total of 950,000 by tomorrow. That reflected a slippage from last Saturday on an earlier deadline. 

The excess beyond 623,212 is needed because high percentages of signatures are determined to be invalid in normal petition circulation efforts, sometimes as high as 50 percent.

Responding to questions from the California Stem Cell Report, the campaign released a statement this morning that said, 

"The campaign is receiving petitions in the mail every day, however it takes time to count and verify incoming petitions. 

"While we don’t have an estimate to share, we do know that over the last week website traffic has increased, with more than 10,000 people visiting our signature gathering page....

"The campaign is aiming to give the counties as much time as possible to verify signatures. However, the landscape is changing on a daily basis, and adapting to new challenges during these uncertain times requires nimble decision-making and flexibility."

The state stem cell agency, formally known as the California Institute for Regenerative Medicine (CIRM), is running out of the $3 billion it was originally provided in 2004. That was when another ballot initiative created the agency, supporting it with state bond funding. The agency has no other significant source of cash. CIRM could have asked the legislature and the governor for more financial support earlier, but such an effort would have faced a difficult political road. 

Without additional funding, the agency will begin to close its doors next fall. 

Other ballot initiatives are facing the same signature-gathering pressures in California and elsewhere in the country. The Guardian newspaper in the United Kingdom carried a piece yesterday looking at the issues throughout the United States. It quoted a backer of one initiative effort in California to permit collection of signatures for future initiatives electronically as saying, "It's a killer. We're done."

See here for the exact process of verifying signatures and certifying a measure for the ballot.

Correction: An earlier version of this item incorrectly said that the campaign had said that it had gathered 935,000 signatures. The correct figure is 915,000.

Info Sources on Stem Cells and Covid-19

A California stem cell blog is digging into research involving cell therapies aimed at the coronavirus, and this week it posted a summary of the work that is underway from Texas to Israel.

The blog is called The Niche and is produced by UC Davis stem cell researcher Paul Knoepfler. On Monday, he posted a quick look at six efforts. He also has probed claims involving Rudy Giuliani. On Tuesday, Knoepfler recommended a comprehensive view of of Covid-19 efforts published by the Alliance for Regenerative Medicine, an industry group.

From the East Coast, STAT news has made its impressive coronavirus coverage available free online. STAT's stories are generally several cuts above, in terms of quality, most of the mainstream media. The STAT coverage explores more deeply many of the scientific issues along with how the work is financed and carried out by biomedical companies, including stem cell approaches. Here is a link to the STAT coronavirus lineup. 

Time Running Out for $5.5 Billion California Stem Cell Ballot Initiative

Backers of a proposed $5.5 billion, stem cell ballot initiative are pressing on with their cyberspace campaign to assure that the measure will qualify for the November ballot despite "a landscape (that) is changing on a daily basis."

But as the campaign's website notes, "Time is running out."

No fresh figures for the number of signatures have been released since early this month. The campaign has also extended to this Thursday its self-imposed deadline for collecting 950,000 signatures. The campaign originally hoped to have the signatures in hand last Saturday.  

At stake is the financial life of the California stem cell agency, which is running out of money and is expected to begin the process of closing its doors next fall unless it receives an infusion of cash. The ballot initiative needs 623,212 signatures of registered voters to make the November ballot.  At last report, it had 935,000. However, the disqualification rate of signatures on petitions can run as high as 50 percent. 

County election officials are also working under Covid-19 conditions, which can mean a reduced work force and limited hours for verifying signatures. At some point, moreover, the mechanics of printing and delivering the ballot information that must go to nearly 20 million voters come into play for state election officials. 

Responding to a query from the California Stem Cell Report, campaign spokeswoman Sarah Melbostad released a statement yesterday that said:

"This new virtual signature gathering effort was launched just last week, and as it takes time to count the incoming signatures by mail, we do not have an updated number to share. 

"The campaign is aiming to give the counties as much time as possible to verify signatures, however the landscape is changing on a daily basis, and adapting to new challenges during these uncertain times requires nimble decision-making and flexibility. 

"Voters can continue to visit our website https://caforcures.com/help-us-qualify/ to sign the petition and learn how they can help ensure the continuation of treatments and cures that could save or improve the lives of millions."

The stem cell measure is not the only initiative that is facing problems. It could well be that the governor may take some sort of emergency action to extend deadlines for all of them. 

Earlier this month, the stem cell campaign launched an "unprecedented" electronic, mail-in effort to gather the final number of signatures that were judged to be needed. It is a daunting process to conduct online and then have the petitions returned in the mail. 

The campaign web site stresses the urgency and pressing need for more signatures. "The campaign must gather the last 35,000 signatures through mail-in submissions by April 16th," the web site says.