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.

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. 

Covid-19 and California Stem Cell Agency: Plasma Research to be Funded in $5 Million Round

California's stem cell research agency, in an "emergency" move this morning, joined the search for a plasma treatment for Covid-19, stressing the importance of extending access to minority communities. 

It was only the second time in the 15-year history of the agency that its governing board invoked its "vital research opportunity" clause, which gives it authority to divert funding from stem cell research to other purposes.

Maria Millan, CEO and president of the agency, said in a statement,

“The intent behind this amendment is to be responsive to this COVID-19 crisis by leveraging CIRM’s funding programs, processes and infrastructure within the scientific ecosystem that it has supported to date.

"By providing an opportunity for the medical and scientific community to gather important data while using convalescent plasma treatment protocols on an emergency basis, CIRM is joining the global effort to  expedite treatments to patients in need in the midst of this global pandemic."

This morning's action, approved unanimously, adds plasma research to a $5 million grant round aimed at the coronavirus.  The round has rolling application deadlines. The first was last Tuesday and drew 19 applications. The next deadline is expected in about two weeks.

The board unanimously added a provision to the plasma proposal aimed at ensuring that it would reach into minority and medically under served areas of the state. 

The agency, formally known as the California Institute for Regenerative Medicine (CIRM), is speeding its award process and expects winning applicants to be ready to begin their work within 30 days of approval of an award.

The use of plasma in treating Covid-19 has attracted international attention as well as here in California.   

CIRM directors also approved additional members to its panel of grant reviewers, all of whom come from out-of-state. The agency selects reviewers from the panel depending on the nature of their expertise. 

Here is a link to the CIRM news release on the action today.

California Stem Cell Agency Set to Finance Anti-Covid-19 Plasma Research

In a rare move, California's stem cell agency is set to expand beyond its traditional scope and finance research involving the use of blood plasma for treatment of Covid-19 patients. 

It would be only the second time that the agency, known formally as the California Institute for Regenerative Medicine (CIRM), has invoked the "vital research opportunity" clause in the 10,000-word ballot initiative that created the agency in 2004. 

Under the initiative, CIRM is restricted to using its $3 billion for stem cell research -- not the vast array of possibilities for the entire field of biomedical research. But a little-noticed provision also allowed for exceptions in the case of "vital research opportunities."  

The proposed action tomorrow would include plasma research in a new, $5 million effort approved two weeks ago to support stem cell research involving Covid-19. On Tuesday, the agency received 19 applications for funding under that fresh, ongoing effort. Another deadline for applications is expected in about two weeks. 

The expansion to include plasma will be presented to the CIRM governing board tomorrow at 11 a.m. PDT during a public, online meeting. It includes funding "proposals to study convalescent plasma or its derivatives (e.g., immunoglobulin) for the treatment of patients with COVID-19."

The plan also said,

"Clinical studies of convalescent plasma may propose use of the FDA’s single-patient emergency IND (eIND investigational new drug) pathway to satisfy the (agency's) CLIN2 eligibility requirements for a traditional IND."

CIRM's $5 million coronavirus effort might seem skimpy to those used to thinking of the agency as a $3 billion program. It was a $3 billion effort 15 years ago. Today the agency is running out of cash and is down to its last $27 million, which is largely committed to a sickle cell round. 

CIRM is hoping that a proposed, $5.5 billion ballot initiative will qualify for the November ballot, be approved by voters and give it at least another 10 years of life.  

The first occasion for invoking the "vital research" clause involved gene therapies. 

The public can listen in on tomorrow's meeting and make comments. Instructions for online access can be found on the meeting agenda. 

Here is a look at a national plasma effort already underway. Here are federal recommendations concerning such research. 

$5 Million Allotted: California Stem Cell Agency Receives 19 Applications for Research Targeting Covid-19

Nineteen scientists seeking to crush the coronavirus submitted applications this week for research grants from the California stem cell agency, which has set aside $5 million for the job. 

Details on the nature of the proposed work were not disclosed by the agency, known formally as the California Institute for Regenerative Medicine (CIRM). That's in keeping with its usual practice concerning applications that are yet to be reviewed or approved. 

The research must involve a stem cell or a drug or antibody targeting stem cells. The agency said that only research involving "development or testing of a treatment for Covid-19 (is) eligible."

The "emergency" coronavirus round was established by the agency just two weeks ago. CIRM plans to deliver funds quickly to the winning applicants. The researchers are expected to be ready to begin work within 30 days of approval of the awards. 

The agency allocated the $5 million on March 27. Yesterday was the first deadline for applications. The next is expected in about two weeks.  The agency has said it would fund all stages of research from basic to clinical. Maria Millan, president and CEO of the agency, said earlier in a statement, 

“These are clearly extraordinary times and they require an extraordinary response from all of us.... California researchers have made us aware that they are pursuing potential stem cell based approaches to the COVID-19 crisis, and we felt it was our responsibility to respond by doing all we can to support this research and doing so as quickly as we possibly can."

Some scientists have expressed doubt that a stem cell approach can generate the results needed. In posting Sunday on The Niche stem cell blog, Sean Morrison, chairman of the Public Policy Committee at the International Society for Stem Cell Research and director of Children’s Research Institute at University of Texas Southwestern, responded to a question that asked about "potential roles for cellular therapies for COVID-19? Is there something unique they might be able to achieve that other approaches like anti-viral drugs could not?"

Morrison replied,  

"I’m afraid I’m skeptical about cellular therapies for Covid-19. Some have suggested that transplantation of immune effector cells, such as NK cells, into patients might promote a more effective immune response. I worry it will take too long for the transplanted cells to engraft and mount an effective immune response against a virus that often kills patients within days of hospitalization. 

"Others have suggested that mesenchymal stem cell (MSC) transplants might provide a benefit by attenuating the hyper-inflammation that occurs in late stage patients. While there has been some evidence that MSCs can attenuate pathological immune responses in some contexts, most clinical trials that tested this strategy failed. The other red flag is that all of the cell therapies I have seen proposed for Covid-19 have been repurposed from very different indications.

"To some extent that’s to be expected when dealing with a novel pathogen. However, it gives one pause when a cell therapy under development for cancer is suddenly touted as also having anti-viral activity. Immunologically, these are two very different problems that require very different kinds of pre-clinical testing."

The next step in CIRM's Covid-19 round is for the agency to convene a panel of scientists from out-of-state to review the applications behind closed doors and make the de facto decisions on whether to fund them. Their decisions then go to the CIRM governing board for ratification. 

At that point, summaries of the anonymous reviewers' comments on the applications become public. 

Five of the applications were from private companies and the rest from nonprofits. 

The reviewers do not publicly disclose their financial or professional conflicts of interest. Members of the governing board are barred from voting on applications involving their institutions. The research is required to be performed in California. 

California Pumps $5 Million into Search for Stem Cell Treatment for Covid-19

Coronavirus

California's stem cell agency, in an emergency action, has allocated $5 million for research into treatments for Covid-19 and set the deadline for the first applications for one week from today. 

The agency, formally known as the California Institute for Regenerative Medicine (CIRM), approved the funding last Friday during an emergency meeting of its governing board. 

In an item yesterday on the CIRM blog, Maria Millan, CEO and president, said,

"California researchers have made us aware that they are pursuing potential stem cell based approaches to the Covid-19 crisis, and we felt it was our responsibility to respond by doing all we can to support this research and doing so as quickly as we possibly can."

The agency set accelerated timetables for action, both by the agency and applicants. It said it would expect winning applicants to begin work within 30 days of being approved. 

CIRM's move comes as itself is facing a mortal financial threat. It was created by voters CIRM in 2004 with $3 billion. It is now down to its last $27 million and is hoping voters will approve $5.5 billion more via a proposal that is yet to qualify for the November ballot. Otherwise CIRM's doors will begin to close in the fall. 

Presumably, billions of private and public dollars are already pouring globally into the search for various aspects of Covid-19, so the $5 million is a relatively tiny amount. CIRM has developed a speedy process, however, for bringing funds to bear on research and is acting to accelerate that even further. 

Jonathan Thomas, chairman of the CIRM board, said, 

"The coronavirus is creating an unprecedented threat to all of us and, as one of the leading players in regenerative medicine, we are committed to doing all we can to develop the tools and promote the research that will help us respond to that threat." 

The campaign to qualify the $5.5 billion initiative for the ballot released a statement heralding the action by CIRM. Robert Klein, the Palo Alto real estate developer behind both the original ballot measure and this year's funding initiative for CIRM, said, 

"The investment by California’s stem cell institute to combat Covid-19 highlights the remarkable potential of this research and therapy development to impact the lives of every Californian. ...We urge Californians to think back on this moment, when they decide the fate of future life-saving stem cell discoveries and treatments come November."

The campaign said 10 days ago that it has suspended the gathering of signatures. It is not clear whether it has enough to qualify for the fall ballot. More than 600,000 valid signatures are required. 

Here are links to additional CIRM information on its Covid-19 program:

• Concept statement
• Application information and timetables
• Presentation slides from last week's meeting
• CIRM's news release