Text of Sheehy's comments re Covid-19, CIRM, Its Mission and Other Matters

The discussion at the May 23, 2020, meeting of the governing board of the California stem cell agency ranged from Covid-19 and the agency's strapped financial condition to its mission and priorities. One of the directors, Jeff Sheehy, elaborated on the matters and more when he responded to an inquiry following the meeting from the California Stem Cell Report. 

The California Stem Cell Report has a policy of running verbatim comments from stem cell agency board members and other interested parties.  If other readers would like to submit their comments on this subject or other stem cell matters, please direct them to djensen@californiastemcellreport.com.

Below is the verbatim text of Sheehy's comments.  
"First, I felt a great deal of uncertainty around CIRM proposing a COVID program.  Having worked towards stem cell therapies for HIV since I came onto the board in 2004, I felt some skepticism around stem cell approaches targeting infectious diseases (ID).  Infectious disease has not been a particularly major focus of regenerative medicine efforts and many of the approaches we have tried have struggled.  I think there could be a role, but we have a long way to go.  

"I thought, in general, a focus on ID is a bit overdue, but I was very concerned about taking funds from sickle cell, where I think there is a strong case for believing we are on track for a cure using stem cell technology, and there are well constructed clinical trials such as the one we just funded.  

"Given that CIRM is using its last of its funding, I was also concerned about the funding needed.  One of the most telling moments in Friday's meeting was the descriptions by (CIRM Director) Dr. (Keith) Yamamoto (vice chancellor for science policy at UCSF)  of the ready and ample availability of Covid funding from the NIH and other federal sources, not just in new funds but also the ability to repurpose existing grants towards Covid.

"Btw, I am not alone in my skepticism around stem cells for Covid-19.  I offer first the tweet from Dr. Sean Morrison, former head of ISSCR on March 29:

"'There is no stem cell therapy for Covid19. We would not expect stem cells to have any therapeutic value for people with Covid19.
@ISSCR'"

"Then a couple of weeks ago, Dr. Paul Knoepfler on his blog, the NICHE, offered this:
"'The idea of testing stem cells for Covid-19 may be music to the ears of some folks as an opportunity, but to me from the beginning it sounded mostly like a spaghetti on the wall road to trouble.
"'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.
"'Even so, 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.'"

"I offer these two comments in support of my doubts.  But, I also feel the urgency surrounding Covid.  This is my second pandemic, having lived through HIV/AIDS and lost and continue to lose countless people that I care deeply about and living with the disease myself, having endured enormous stigma and outright hatred along with indifference from a president, seeing marginalized communities suffering death and disease disproportionately and indifference because people don't recognize the humanity of the populations most impacted, feeling triggered and re-traumatized by this second pandemic and the enormous stupidity from all points in trying to make a disease fit their self described perceptions of reality in the face of what is real and undeniable.

"I voted to support the COVID program despite my doubts due to urgency, but we know what tools work against infectious diseases -- antivirals and vaccines, and I became an enthusiastic and vocal supporter of the vital research opportunity for convalescent plasma.  Convalescent plasma is about as far removed from CIRM as a project could be--a technology at least 100 years old with zero barriers to receiving funding from any source.  But, in the absence of a vaccine or antivirals, it represented to me the best and most rational chance to make a difference in patients now. Plus, Zaia et al at City of Hope have the cell handling and manufacturing ability to address some of the factors limiting use and evaluation of convalescent plasma, e.g. potency and consistency of product to name a couple.

"After having participated in reviews, our two clinical projects are the convalescent plasma one and an ongoing $14 million trial for mesenchymal stem cells for ARDS, the lung complication suffered by critical COVID patients necessitating ventilator support.  That UCSF/UC Davis trial is already treating COVID patients at SF General and in Houston to name a couple of sites, and it was supportable because we were availing more patients of access to that therapy like we are doing with convalescent plasma. But both approaches are well supported outside of CIRM and the $750K we gave each project.  

"The $150K Discovery projects we funded are interesting, but they are very early in development and given the time and money it takes to move from discovery into translation into clinical trials, these antiviral products could likely be superseded by the host of antiviral products in trials around the world.
In that context, we did see a couple of interesting vaccine proposals that were very far afield and did not score in the fundable range.  I had a feeling -- having looked at the vaccine trials underway (and I'm not an expert btw)  -- that they seemed very much based in the most part on proven tech that a far-out, left field approach might be useful to explore.  HIV has been stubbornly resistant to vaccine development, so I'm very cautious about that field.  I was heartened to hear (CIRM Director) Dr. (Kristiina) Vuori from Sanford Burnham opine that she thought that current vaccine approaches were, to paraphrase, following usual pathways, and I thought I heard a suggestion that opening up CIRM to vaccine work might elicit something novel.

"However, the board thought otherwise and I defer to their wisdom.

"I would note that I was intrigued by the discussion around CIRM's mission.  As Dr. (Gil) Sambrano (CIRM vice president for portfolio development)  noted, stem cells are ubiquitous in the body, and I took that to mean that one could either be elastic or inelastic in accepting products.  A vaccine, for instance, would almost necessarily  impact T memory stem cells, which are a crucial part of the adaptive immune response to disease (and a vaccine).  We have begun to recognize the limits of stem cell centric therapies through our VRO for gene therapy.

"I then asked myself, does CIRM hews to its original mission per Prop. 71?  I looked up the original funding mission for the Grants Working Group :

"'(C) In order to ensure that institute funding does not duplicate or supplant existing funding, a high priority shall be placed on funding pluripotent stem cell and progenitor cell research that cannot, or is unlikely to, receive timely or sufficient federal funding, unencumbered by limitations that would impede the research. In this regard, other research categories funded by the National Institutes of Health shall not be funded by the institute....Notwithstanding subparagraph (C), other scientific and medical research and technologies may be funded by the institute if at least two-thirds of a quorum of the members of the Scientific and Medical Research Funding Working Group recommend to the ICOC that such a research proposal is a vital research opportunity.'

"With the federal ban ended, all of CIRM's research is really a vital research opportunity by default at this point.  Per COVID and ample federal funding, any funding in that arena is about as far afield as one could get.

"Even with fetal tissue research, which, btw, has fallen off the radar in the media and with some in Congress and the Administration, I can guarantee no one is talking about banning that.  You simple cannot develop vaccines or antivirals without mice with humanized immune systems created by using fetal tissue.

"To sum up, I'm not really sure what the board is trying to accomplish with its COVID program.  I'm not sure that the board has a clear, coherent view of the scope of CIRM's research.  And I am not sure the board has a clear idea of what the scientific mission of CIRM should be in the event that new funding comes from the voters.

"I would note as an aside that CIRM has never submitted its scientific program, including all grants made and their impact, to a rigorous, independent scientific review.  

"In short, I don't think we really know at CIRM where we've been and where we want to go.  We have anecdotes...."

(Sheehy’s own ellipses in the last paragraph)

The $5.5 Billion California Stem Cell Countdown: One-Thirteenth Along the Way

Supporters of a $5.5 billion, proposed ballot initiative this morning are 13.3 percent along the way to qualifying the measure for the November ballot and possibly saving the California stem cell agency from financial extinction. 

The proposal now has 82,723 valid or projected valid signatures of registered voters, which state election officials say is the key category. The measure needs 623,212 in signatures in that category to qualify.

The total of "raw," unverified signatures statewide is 924,183.  At this point, only 77.57 percent of the signatures are valid. But major counties such Los Angeles and San Diego have not yet completed their validation process. 

Twenty-two of the state's 58 counties have reported their counts. The  highest number of valid signatures has come from Sacramento with 26,761. The lowest number is from Modoc with four. 

The stem cell agency was created by California voters in 2004 when they approved a ballot initiative that also provided it with $3 billion of borrowed money but no other funding. The agency is running out of cash and will begin closing its doors next fall unless more substantial funding is forthcoming. 

Look for an update on the count Tuesday evening or early Wednesday right here on the California Stem Cell Report. 

Editor's note: An earlier version of this item incorrectly stated that Mono County had the lowest number of valid signatures. It was actually Modoc.

$5.5 Billion California Stem Cell Countdown: Total Raw Signatures Now in With 924,213

One key step is now complete in the effort to qualify a $5.5 billion stem cell initiative for the November ballot in California and save its stem cell research program from running out of money.

The "raw" count of signature is finished with a total of 924,213, according to state election officials. That is almost exactly the same as the 925,000 figure that  campaign backers said they had submitted weeks ago.

The proposed ballot measure needs 623,212 valid signatures of registered voters to qualify. The count of valid or projected valid signatures stands at 75,484 as of late yesterday afternoon. The rate of rejected signatures is running at 22 percent. 

A number of populous counties have yet to report on their validation figures including Los Angeles, with 298,147 raw signatures, and San Diego, with 99,899. 

Counties have until June 24 to complete their count.

Look for an update later today or early tomorrow on the count right here on the California Stem Cell Report. 

Parkinson's and the Unseen Offspring of California's Stem Cell Agency

On the surface, Aspen Neurosciences, Inc., a tiny firm in La Jolla, Ca., does not seem to have much of a connection to California's $3 billion stem cell agency.

It is not alone. A good chunk of the collateral benefits of agency is all but invisible. While the agency's web site is chock-a-block with videos, statistics, testimonials and pie charts, not everything significant rises to the top. Most of the information can be classified as high profile. Aspen, however, is barely a footnote for the agency. 

 

Yet the firm, over the last six months, has received a $76 million validation from the private sector, more than any business has received from the California Institute for Regenerative Medicine (CIRM), as the stem cell agency is formally known. Viacyte, Inc., of San Diego, is No. 1 among the business beneficiaries of CIRM, collecting $72.3 million.  

The lack of visibility of some benefits from CIRM may not seem all that important to some. But when plans are afoot to ask California voters for $5.5 billion to forestall the financial demise of the stem cell agency, voter perceptions of the agency become paramount. 

Aspen's story has elements that could resonate with many voters. It involves a well-regarded woman scientist, pursuit of millions of dollars, failures and success and patients with stories of their terrible times with a dreadful affliction.  

The tale begins within walking distance of what is now Aspen's headquarters in La Jolla. Aspen is located just down the street from the Scripps Research Institute, where Jeanne Loring was director of the Center for Regenerative Medicine and who also earlier co-founded a firm that morphed into Viacyte. 

While she was at Scripps, she embarked on research aimed at Parkinson's Disease, stimulated and aided by a patient advocacy group called Summit for Stem Cell. It is an energetic group and once collected $120,000 in a fundraising effort that took nine Parkinson's patients on a hike at Machu Pichu in Peru. 

Summit members also trekked to meetings of the governing board of the stem cell agency to build a case -- sometimes with tears and trembling voices -- for more money and more speed on Parkinson's research. (See here also.)

Loring filed for grants for her research as well. She ultimately collected nearly $22 million from CIRM, but the agency did not follow through on additional applications. Loring cast about for other possibilities, and she and Andres Bratt-Leal, also of Scripps and Summit for Stem Cell, co-founded Aspen Neurosciences. 

Loring strongly supports renewing the financially endangered stem cell agency with $5.5 billion. She has told the California Stem Cell Report, 

"All of my CIRM awards contributed to (Aspen). We used those funds to develop our genomics tools and databases and to develop improved methods for handling the cells." 

Loring is now Aspen's chief scientific officer. Bratt-LealHer is vice president of research and development. Their ongoing work now at Aspen is aimed at creating the "first autologous neuron replacement therapy to treat Parkinson's disease," Aspen said in a news release. 

Aspen expects to use its private financing to launch a phase one trial for the therapy, which begins with a patient's own skin cells. They are reprogrammed to become pluripotent and converted into neurons. The neurons are transplanted into a patient to replace the ones that Parkinson's has destroyed. 

Whether Aspen can produce a commercial treatment that is widely available remains to be seen. Whether CIRM's supporters can produce a $5.5 billion victory in November remains to be seen as well. It is likely to depend entirely on how voters see the benefits of CIRM's work over the last 15 years -- invisible and otherwise. 

(Note to readers: If you know of other unseen offspring of the stem cell agency -- good or bad -- please send a note to djensen@californiastemcellreport.com. Your emails will be held in confidence. Thank you.)

(After this item was posted, the agency posted a blog item dealing with Parkinson's. In addition to information on the search for a cure or treatment, the item carried the following advice for persons seeking some sort of unregulated treatment. Here is what the agency had to say in a Q&A format,

"If you go online you can find lots of stem cells clinics, all over the US, that claim they can use stem cells to help people with Parkinson’s. Should I go to them?

("In a word, no! These clinics offer a wide variety of therapies using different kinds of cells or tissues (including the patient’s own blood or fat cells) but they have one thing in common; none of these therapies have been tested in a clinical trial to show they are even safe, let alone effective. These clinics also charge thousands, sometimes tens of thousands of dollars these therapies, and because it’s not covered by insurance this all comes out of the patient’s pocket.

("These predatory clinics are peddling hope, but are unable to back it up with any proof it will work. They frequently have slick, well-designed websites, and  'testimonials' from satisfied customers. But if they really had a treatment for Parkinson’s they wouldn’t be running clinics out of shopping malls, they’d be operating huge medical centers because the worldwide need for an effective therapy is so great.

("Here’s a link to the page on our website that can help you decide if a clinical trial or “therapy” is right for you.")

"Emergency" Meeting Tomorrow Morning; California Stem Cell Agency Wants to Expand Scope of its Covid Awards

With only 24 hours notice, California's $3 billion stem cell agency today called a meeting for tomorrow to significantly expand the scope of its Covid-19 round to include vaccine development and to permit "supplemental funding."

If the changes are approved tomorrow, scientists could file their applications up until next Tuesday to be considered in the next application review session, probably within 10 days to two weeks.  They would have an opportunity to submit another application about two weeks later if all the Covid funds have not been awarded.

Agency directors allotted $5 million for the Covid round. They have awarded about $2 million.

Here is what the agency listed this afternoon to describe the proposed changes:

• "Increase scope of early stage opportunities (DISC and TRAN) to include vaccine development studies as a potential vital research opportunity.

 • "Include opportunity for studies on novel ideas and biological mechanisms by opening the DISC1 program announcement.

 • "Allow supplemental funding for active COVID-19 clinical trial awards to expand their efforts.

 • "Include requirement for outreach to underserved populations in all clinical trial proposals 

• "Increase award limit on DISC2 projects and adjust language on 6-month deliverables."

The DISC term generally refers to basic research. The TRAN term refers to translational research.

The full concept plan can be found here.

Normally the agency would not fund vaccine research because it does not involve stem cells. Under the proposal for tomorrow, it would be officially deemed a "vital research opportunity," a loophole in state stem research cell law that allows such funding.  The agency has already invoked the provision in a handful of other instances. 

The supplemental funding change would permit researchers who have already received funding under the Covid-19 round to ask the agency for more cash for their applications. The change would allocate up to $1 million for such awards. 

Under normal conditions the agency's governing board could not meet legally with only 24 hours public notice. The normal legal requirement is 10 days. However, the board is invoking emergency provisions to lift the 10-day notice. 

The 11 a.m. meeting will be available for public participation by the public via phone connections and the Internet. Details are on the agenda.

$5.5 Billion California Stem Cell Countdown: No Significant Changes Today

California election officials this afternoon reported no significant changes to the count to determine whether a $5.5 billion stem cell ballot initiative will qualify for the November ballot. 

Here are the results as of 4:55 p.m. PDT today:

Raw signature count -- Unchanged at 917,722, San Mateo County still not reporting

Valid signatures -- 5,202, up from 3,803 yesterday

Disqualification rate of signatures -- Nearly 23 percent, down from 24 percent yesterday

The proposal needs 623,212 valid signatures of registered voters to qualify for the ballot. The proposal is aimed at refinancing the California stem cell agency, which is running out of money. 

Sickle Cell Trial, Backed by $2 Million from State of California, Will be Based in Los Gatos

More details emerged today about a $2 million sickle cell award and clinical trial involving the California stem cell agency, including the location of the trial in Los Gatos and the involvement of a Stanford University researcher. 

The award was approved last Friday by the agency. It went to a Canadian firm, ExCellThera, Inc.,  which is partially matching the state award with $857,143. With the addition of ExCell, the stem agency is now involved in 63 clinical trials. 

                                                                                                                  

The company said yesterday that the Phase 1 trial, which involves safety, will use its ECT-001 product, and will be conducted at the Lucile Packard Children's Hospital. It will be led by Sandeep Soni of Stanford University. The safety phase trial is aimed at children and young adults.

Guy Sauvageau, CEO and founder of ExCellThera, said in a news release.

"The current standard of care for severe sickle cell disease is a blood stem cell transplant, which is only available to patients who have a matched donor. 

“However, the unique properties of ECT-001 cell therapy enable patients without a matched donor to receive treatment, with a greatly reduced risk of post-transplant complications. This study introduces a new indication into the ongoing evaluation of our ECT-001 technology, which we hope will make this life-saving therapy available to a far greater number of  severely ill patients."

The trial has not yet been posted on clinicaltrials.gov. It is not clear whether recruitment of patients is  underway.  Here is a link to a summary of  the stem cell agency's review of ExcellThera's application (CLIN2SCD-11674).

$5.5 Billion California Stem Cell Countdown: Proposal Inches Towards Ballot

Efforts to place a $5.5 billion stem cell measure on California's November ballot edged slowly ahead yesterday with a slight increase in the number of valid voter signatures, which are critical to qualifying the proposal for presentation to voters. 

The proposal, which is aimed at saving the financial life of the state stem cell agency, needs 623,212 valid signatures of registered voters to make the ballot. Tuesday's total was 71,873, up from 45,407 the previous day. 

The total of unverified, raw signatures was unchanged at 917,722. Only one county, San Mateo, has not reported its raw totals.

The overall rejection rate for signatures stood at 23 percent, also nearly unchanged. Disqualification rates are higher in the more populous counties so far. If campaign has actually submitted 925,000 signatures, as it has claimed, it will need a disqualification rate statewide of no more than 32.6 percent to reach the required number. 

Without an infusion of substantial cash, the stem cell agency, which is running out of money, will begin closing its doors next fall.

County officials have until June 24 to complete their validation of signatures and submit the figures to the state. 

Look for an update on the signature count this evening or early tomorrow right here on the California Stem Cell Report. 

The $5.5 Billion Stem Cell Count: A Bright Spot and a Not-So-Bright Spot

The effort to save the $3 billion California stem cell agency from financial extinction received some bad news and some good news late today, both of which could be expected. 

At stake is whether a $5.5 billion bond measure will be placed on the November ballot. The funds would be used to refinance the agency, which is running out of money and will begin closing its doors beginning next fall without an infusion of cash.

Qualifying the measure for the ballot requires 623,212 valid signatures of registered voters.  

Late today, the updated count of "raw," unvalidated signatures rose to 917,222 from 824,777 last Friday. The campaign for the ballot initiative has said it submitted 925,000 signatures to county election officials. Only one county, San Mateo, has not yet completed its raw count. 

The bad news is that the interim percentage of invalid signatures now stands at 24 percent, up from 18 percent. It is common to see large percentages of signatures disqualified during the verification process, sometimes as high as 50 percent. 

Today's rate rose because Sacramento reported that it disqualified 25.2 percent of the 35,792 raw signatures turned in by the campaign, The statewide rate will change as more counties report their validation numbers.

If campaign has actually submitted 925,000 signatures, it will need a disqualification rate statewide of no more than 32.6 percent to reach the required number. 

County officials have until June 24 to complete their validation of signatures and submit the figures to the state. 

Look for an update on the signature count Tuesday evening or early Wednesday right here on the California Stem Cell Report. 

The $5.5 Billion Stem Cell Count: Stagnant at 824,777 'Raw' Signatures

The signature count to determine whether a $5.5 billion stem cell research initiative will come before California voters next fall remains unchanged this morning at 824,777 "raw" signatures. 

Also stagnant is the number of valid signatures -- 12,440. 

The proposal needs 623,212 valid signatures to qualify, but many of the "raw" signatures are likely to be disqualified. Only those from registered voters are accepted. The current disqualification rate is running at 18 percent, according to state election officials.  That rate involves smaller counties and could change. Also changing will be the number of valid signatures as county officials wade through the petitions. 

The raw total this morning is up from 760,601 earlier in the week. The campaign says it has submitted 925,000 "raw" signatures to county election officials. 

Known officially as the California Institute for Regenerative Medicine (CIRM), the state agency is running out of the $3 billion provided by voters in 2004. It will begin shuttering its doors late this year without a financial infusion. 

Look for an update on the signature count Monday evening right here on the California Stem Cell Report. 

Today's California Stem Cell Research Awards: $2 Million for Sickle Cell, $1 Million for Covid-19

Guy Sauvageau, founder and CEO, of ExcellThera. 

The firm was awarded $2 million today for a 

clinical trial for sickle cell disease. Video from 

Meeting on the Mesa, October 2019

The California stem cell agency this morning awarded $2 million for research to treat sickle cell disease plus another $1 million to  assist in the battle against Covid-19, which has killed 304,000 persons worldwide and 2,934 in California. 

The sickle cell award went to a Canadian firm, ExcellThera, Inc., that is conducting a clinical trial involving the disease, which afflicts as many as 100,000 Americans, principally African-Americans. The firm is providing $857,143 in matching funds. 

Pierre Caudrelier, chief medical officer at the Montreal firm, is using umbilical cord stem cells from healthy donors, which could help solve the issue of matching and availability of sickle cell treatments. The location of the California work is not yet known. 

Winners in today's Covid round are:

Michael Matthay at UC San Francisco, $750,000, to assist in a clinical trial to develop an injectable biomaterial platform that can induce T memory stem cells and boost immunoactivation to vaccines against SARS-CoV-2, which will help protect elderly people. The trial also involves UC Davis. (application number CLIN2COVID19-11823)

Stuart Lipton at Scripps Research Institute, $150,000, to develop a drug that is both anti-viral and protects the brain against coronavirus-related damage. (application number DISC2COVID19-11811)

 

Justin Ichida at the USC, $150,000, to determine if a drug called a kinase inhibitor can protect stem cells in the lungs, which are selectively infected and killed by the novel coronavirus. (application number DISC2COVID19-11901)

The three Covid-19 awards today leave about $2.9 million in the Covid-19 round. It has rolling application deadlines that surface every two weeks with next coming next Tuesday.

In addition to Matthay, two of the 12 Covid-19 applicants filed appeal letters with the CIRM governing board. They are Song Li of UCLA, appeal letter, and Celularity Inc., of New Jersey, appeal letter. 

The CIRM governing board rejected Li's and Celularity's applications, but they may resubmit them next Tuesday with modifications. Their scores and rankings can be found here along with the summary of their reviews, as well as summaries of all reviews. 

The stem cell agency, officially known as the California Institute for Regenerative Medicine(CIRM), is expected to run out of cash this year. It is hoping that a $5.5 billion, refinancing proposal will qualify for the ballot this fall and be approved by voters. Currently, election officials are trying to determine whether the measure as the necessary number of signatures of registered voters to qualify. 

Here is a link to CIRM's news release on today's meeting.

The $5.5 Billion Stem Cell Count: Latest Report Climbs to 824,777 'Raw' Signatures

The latest count in the race to save California's stem cell research program from financial extinction shows that its backers have chalked up 824,777 "raw" signatures in their effort to place a $5.5 billion proposal on the November ballot. 

The number this morning is up from 760,601 yesterday. The proposal needs only 623,212 valid signatures to qualify, but many of the "raw" signatures are likely to be disqualified. Only those from registered voters are accepted. The current disqualification rate is running at 18 percent, according to state election officials.  That rate involves smaller counties and could change. 

The campaign says it has submitted 925,000 signatures to county election officials. 

This morning's increase in signatures reflects the addition of signatures from Orange County and less populous areas. Still to be heard from are San Bernardino and San Mateo. Officials in California's 58 counties have until June 24 to complete verification of signatures. 

Known officially as the California Institute for Regenerative Medicine (CIRM), the state agency is running out the $3 billion provided by voters in 2004. It will begin shuttering its doors late this year without a financial infusion. 

Look for an update on the signature count this evening or early tomorrow right here on the California Stem Cell Report. 

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.