"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 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.
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."
"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."
"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."
“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.”
"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."
"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."
"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."
“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”
“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 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.
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.”
"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.
"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.
"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."
