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.