Text of CIRM Consideration of $4 Million Award to Poseida Therapeutics

Here is the text of the presentation of the application (CLIN1-10999) from Poseida Therapeutics, Inc., to directors of the California stem cell agency.

The presentation was made by Shyam Patel, associate director for portfolio development and review at the stem cell agency. The directors did not discuss the application and gave it the go-ahead July 19, 2018,on a 14-0 vote. 

The application was approved sometime prior to that date by the agency’s grant reviewers in a closed-door session, as is the practice for handling all applications. The agency’s governing board routinely rubber stamps the decisions of reviewers in virtually all cases.

The grant was designed to fund work leading up to the trial in question. The award was closed before the trial began.  

Here is what Patel had to say, based on the CIRM transcript of the meeting.

“This is a late stage preclinical therapy study for a therapy for prostate cancer. The therapy itself is CAR-T cells, and these are stem memory T cells that compose this particular product. 

"The indication is for patients with metastatic castrate resistant prostate cancer. This is the most advanced form of this particular disease. The goal for this particular project is to conduct product manufacturing, conduct the preclinical safety and efficacy studies, as well as prepare and submit the IND. And they're requesting roughly $4 million for CIRM funding, and they're going to be co-funding $1 million.

"To give you an idea about this particular project, we've prepared a few items. First of all, the potential impact for this therapy. There are 165,000 new cases of prostate cancer submitted for this particular year, and roughly 30,000 prostate cancer deaths for 2018 as estimated by the NIH. 

"Now, the particular disease indication that this product is going for, which is the metastatic castrate resistant prostate cancer population, that represents a very small percentage of the overall prostate cancer population, but an overwhelming majority of the deaths for this particular disease. If successful, this particular therapy would target that most needy, highest risk patient population. 

"In terms of the value proposition, over the last decade or so, there has been a steady improvement in the standard of care for prostate cancer. Currently available therapies for prostate cancer for metastatic castrate resistant prostate cancer includes hormone therapy, chemotherapy, as well as an autologous T-cell product, which is an activated T-cell product, all of which have shown modest survival benefit in clinical trials. 

"The proposed therapy has a potential to induce long-term remission with possibly a single treatment. In terms of why this is a stem cell project, as I mentioned earlier, this particular product is composed of memory stem T-cells. 

"To give you a brief overview of the current portfolio for CIRM with respect to related projects, we are not currently funding any prostate cancer-directed projects, but we do have some solid tumor projects, including therapies including therapies of cell-derived therapies as well as small molecule antibody-based therapies, all in early phase or IND-enabling studies. This particular applicant has received CIRM funding before.

"They are currently conducting a phase 1 trial for a CAR-T based therapy for multiple myeloma, which is funded by CIRM. Lastly, the GWG (grant review group)  reviewed this application and unanimously gave it a tier one recommendation. There were 12 scores for tier one, zero scores for tier two, and zero scores for tier three. The CIRM team recommendation follows the GWG recommendation for the award amount of $3,992,090."

Need Money? California Stem Cell Agency Offering Cash for Clinical Stage Proposals

 Want to be one of the last researchers in the Golden State to get cash from the $3 billion California stem cell agency?

That's a possibility if you act before Aug. 31. The agency has reopened its clinical trial stage round and has issued a special call for proposals.  The agency is running out of money and is hoping that voters will provide $5.5 billion more by approving Proposition 14 on the fall ballot. 

But it has enough left that to be able to finance two proposals in this area. The agency said in an announcement, 

"The objective of this program announcement is to create a highly competitive partnering opportunity to accelerate the completion of a clinical trial for a promising stem or progenitor cell-based treatment that addresses an unmet medical need. 

"Under this program, CIRM will act not only as a funding agency, but will also devote significant internal resources and leverage its external team of world-class subject matter experts to actively advance the project. The result of a successful application will be the formation of a true partnership that both accelerates the program and gives it the greatest opportunity for success."

For more information see here. 

UC Irvine Named for Covid-19 Trial Backed by California Stem Cell Agency and Giuliani

A New Jersey firm backed by $750,000 from the California stem cell agency today announced that the California location of its Covid-19 trial will be at UC Irvine.

The firm is Celularity, Inc., and its proposed therapy is supported by Rudi Giuliani, President Trump's personal lawyer.  Celularity expects to complete its work by Nov. 30.

CIRM said the research involves "a phase I/II study of human placental hematopoietic stem cell derived natural killer cells for the treatment of adults with COVID-19."

The award was made June 26 by the agency's governing board, which expected its Covid grantees to be ready to start work within 30 days under its fast-track Covid round. Celularity had not responded to questions about the trial location prior to its news release today. The stem cell agency cannot fund research outside of California. 

The company's news release indicated there would be more locations in California, but did not disclose any. 

The UC Irvine work will be overseen by Leonid Groysman, a neurologist. Here is a link to a summary of the review of Celularity's application (CLIN2COVID19-11857 #2). 

Covid Clinical Trial Location Still Missing on $750,000 California Stem Cell Grant

The California stem cell agency stipulates that winners of research awards in its fast-track, Covid-19 round must be ready to start work within a month of approval, but a New Jersey firm that snagged $750,000 three weeks ago has yet to report the location of its California work.

The  firm is Celularity, Inc. Its proposed therapy is backed by Rudi Giuliani, the president's personal lawyer, who has also touted other possible Covid therapies, including one that has been rejected by the Food and Drug Administration.

The $750,000 is intended to finance a clinical trial someplace in California. The stem cell agency funds only California work.

In creating the Covid round, CIRM said award winners must be "ready to start work within 30 days of approval and propose achieving a clear deliverable within six months." It has been 21 days since the Celularity award was approved. 

The California Stem Cell Report has asked the firm repeatedly for the location of the California site but it has not responded with this routine information. The agency itself also has not disclosed the location and defers to the company.  

Celularity updated the information today that it files with the National Institutes of Health on the trial. However, the locations of the trial still did not show any in California. 

An American Vaccine Disaster 65 Years Ago: Lessons for Today

"Remember the Cutter Incident!" The phrase is not exactly the same sort of watch word as "Remember the Alamo." 

But it does have fresh resonance today. The Cutter Incident was a vaccine disaster in America 65 years ago. The case is the keystone of a column yesterday in the Los Angeles Times that said, "History tells us that speed kills."

The comment came from Arthur Caplan, a bioethicist at NYU Langone Medical Center and a co-author of an article this week in the Journal of the American Medical Association (JAMA) that sounded a warning in the rush for a Covid-19 vaccine. 

Caplan spoke about the matter with Michael Hiltzik, a business columnist at the Times and author of "Big Science." Hiltzik's column appeared one day before the California stem cell agency is set this afternoon to consider more applications in its $5 million Covid-19 funding round. (Vaccines also came up at last Friday's meeting of the agency's governing board.)

Hiltzik wrote, 

"If anything is known for sure about the scientific battle against the novel coronavirus, it’s that the quest for a vaccine has been unprecedentedly intense, with rapid development and speedy production the paramount goals."

The Cutter Incident, Hiltzik said, is example of the perils of speed. It involved errors in a polio vaccine produced in 1955 by Cutter Laboratories. An estimated 40,000 children contracted polio from the vaccine. About 200 were permanently paralyzed. Ten died. 

Hiltzik wrote, 

"The so-called Cutter incident was 'one of the worst biological disasters in American history, exploded the myth of the invulnerability of science and destroyed faith in the vaccine enterprise,' observed Paul Offit, a vaccine expert at the University of Pennsylvania whose 2005 book is the definitive account of the episode."

The polio vaccine was halted in its tracks during the summer of 1955. Hiltzik wrote, 

"Public confidence in the vaccine was shattered. 'The summer of 1955 came and went with few children getting their shots,' historian David Oshinsky, a co-author of the JAMA article, recounted in his 2005 history of the epidemic. Major outbreaks occurred in Boston and Chicago. 'It seemed like old times, with beaches and movie theaters once again deserted and people fleeing the cities to escape the evil germs.'"

Hiltzik concluded, 

"Clinical trials won’t be the final hurdle in bringing vaccines to the world. Managing the public’s expectations will be crucial, since no vaccine for anything is 100% effective. So will ensuring that the manufacturing process is airtight.

"With anti-vaxxers and conspiracy theorists already spreading wild stories about the coronavirus, it would be a shame to give them more ammunition.

"'In this world, where there’s so much vaccine hesitancy and doubt,' Caplan said, 'you better get it right, out of the box. You can’t afford a failure. Even knowing that we’re in desperate need of a vaccine and the deaths are happening, I worry that if we don’t do it right, it’s going to be worse.'"

California Stem Cell Funding Flap: Stanford Ponies Up $1.8 Million

Stanford University has come through on matching funds for state-financed stem cell research, coughing up $1.8 million after California's stem cell agency applied a little financial pressure.

The matter involves Stanford  researcher Judith Shizuru, who is conducting a clinical trial that is aimed at treating the "bubble boy" genetic affliction without requiring high-risk chemotherapy or radiation. Her work has implications for reducing the need for the dangerous treatments in other diseases. 

In 2012, Shizuru was awarded $19 million by the stem cell agency for her trial. Late last year, she applied for $6 million more. 

Sharp questions arose, however, from the governing board of the $3 billion California Institute for Regenerative Medicine (CIRM), as the stem cell agency is formally known. It was the first time that the CIRM board had publicly rebuked a grantee and an institution on co-funding.

The board noted that the $19 million grant required $1.8 million in matching funds that had not been forthcoming.  

Directors pointed out that Stanford was well-endowed and should not be hard-pressed to provide cash to help develop a potentially "transformative" product that would eliminate the toxic impact of chemotherapy for a number of diseases. 

That was back in January. The CIRM directors set a May 1 deadline for seeing the cash. 

Last month the agency, which expects to run out of funds for new awards later this year, received a letter from Robert Harrington, the chairman of the Department of Medicine at Stanford. 

The letter said, 

"This letter is to confirm that the Department of Medicine will provide funding in the amount of $1,784,953 to meet the required co-funding for Operational Milestones #3 and #4 disbursements as referenced in your email dated 3/14/19 for the above referenced grant. These funds are available immediately to Dr. Shizuru for the study."

The flap also led to an inside look at how research funding works at the stem cell agency in a case involving a rare affliction, delays in clinical trials and the financial pressures now facing CIRM. 

Over its 14-year life, the agency has awarded $2.6 billion. Stanford is the No. 1 recipient with $383 million. Its total far exceeds the No. 2 recipient, UCLA, which has chalked up $284 million. 

Nine out of the top 10 recipient institutions, including Stanford and UCLA, have members on the CIRM governing board. They are not allowed to vote on awards to their institutions, but they establish the research award programs and their rules. 

From Cystic Fibrosis to Zika: California Awards $21 Million for Stem Cell Research

The California stem cell agency last week approved nearly $21 million for research to tackle afflictions ranging from cystic fibrosis to Zika.

Awards were made to only 11 researchers although the agency's reviewers had earlier approved 14 awards totaling $25.5 million. The governing board, however, had allotted only $21 million for the awards, and it decided to stick to its budget.

The awards are part of an effort by the agency to finance projects that can move forward rapidly within the next two years.

Six scientists sent letters to the board prior to the meeting discussing details of their research and dealing with concerns of the agency's reviewers, who approved awards earlier in a closed-door session, prior to ratification by the board.

Here are links to letters of each researcher: Rosa Bacchetta, Stanford, application number DISC2-
09526; Tejal A. Desai, UC San Francisco, DISC2-09559; Mark Mercola, Stanford, DISC2-09542 (rejected); Julie Sneddon, UC San Francisco, DISC2-09635; Jin Nam, UC Riverside, DISC2-09645 (rejected), and Matthew Porteus, Stanford, DISC2-09637.

Reviewers rejected any application that scored below 85. All of the three applications denied by the board stood right at the cutoff line with scores of 85. Mercola was the only one of the three to write a letter to the board. The agency did not disclose the names of the other two on its web site since they had not written a letter, which is a public record. The Nam application scored 84 and was not recommended for funding by reviewers.

Here is a link to a document that contains summaries of the reviews of all applications scored at 65 or above.

Here is a link to the agency's press release that contains the names of all the winners and a one line summary of their research. More details can be found in the summaries of the reviews.

Latest Targets of the California Stem Cell Agency: $26 Million for Zika, Heart Disease and Much More

The California stem cell agency next Thursday expects to award nearly $26 million to 14 scientists to seek therapies for afflictions ranging from cystic fibrosis to Zika.

The awards have all been approved by the agency's out-of-state reviewers in a round called "Quest." The $3 billion agency's board is scheduled to ratify reviewers' decisions at a telephonic meeting next week. The board almost never overturns its reviewers' decisions.

The expected outcome of a Quest award is "a candidate therapeutic, medical device, diagnostic or tool that is ready for translational stage activities."

The application receiving the highest score, 95, is seeking to develop "CRISPR/Cas9 mediated FOXP3 gene editing in patient-derived hematopoietic stem cells as a cure for IPEX syndrome."

The review summary on the $1.1 million proposal said,

"Using CRISPR/Cas9 gene editing, we will insert a wild type copy of the FOXP3 gene into patient derived HSCs, enabling pre-clinical proof of concept data for clinical trials that could reduce IPEX patient pathologies. This work will the first-in-man demonstration of the curative potential of edited HSCs and will help maintain California’s lead position in stem cell research and cure."

IPEX syndrome is a rare disease that can lead to diabetes and severe enlargement of secondary lymphoid organs.

The Zika award received the second highest score, 93. It is aimed at determining the "the impact of the Zika virus during human neurodevelopment and to test a FDA-approved therapeutic candidate to treat Zika infection." The research is budgeted for $2.1 million. 

The largest award, $2.4 million, is aimed at a gene therapy to "regenerate heart muscle for the 23 million adult and pediatric patients with heart failure, for whom there are currently no disease-modifying therapeutic approaches."  It received a score of 88.

The cystic fibrosis application was scored at 85, which was right at the cutoff line for funding. The proposal is aimed at "genome editing to correct cystic fibrosis mutations in airway  stem cells."  The application sought $2.2 million.

The reviews of 14 applications can be found here along with the reviews of unsuccessful applicants who scored from 84 to 65. None of the names of the applicants have been released yet by the agency, which withholds the information until after the board ratifies the reviewer decisions. 

Here is a link to the agenda for the meeting, which includes remote locations throughout the state at which the public can participate in the meeting and speak to the board. The meeting is also expected to be available through an audiocast. 

Remote locations include Oakland, San Diego, Napa, Irvine, Los Gatos, Elk Grove and San Francisco. Specific addresses can be found on the agenda.  

California Approves $15 Million for Stem Cell Research Ranging from Arthritis to Alzheimer's, But Not Without a "Hair-Cut"

Highlights
Snafu in November
Ankasa whacked
Across-the-board cuts rejected

After a hiccup last month, the California stem cell agency today coughed up $15 million for a quartet of researchers looking into Alzheimer's disease, cartilage repair, arthritis and sickle cell disease, but not before lopping off a big chunk of one proposal.

Action by the governing board of the $3 billion agency came after a snafu at its Nov. 17 meeting. The proposals, all previously approved by the agency's reviewers, hit a roadblock when the budgeted cash was not enough to fund all four. The session last month also stalled as a result of quorum problems and research priorities.

Normally applications approved by reviewers during their closed-door sessions slip through the later public meetings of the agency board with no discussion. But this time around, reviewers approved the four applications, but gave one of the researchers a sizable, financial "hair cut."

Despite concerns about fairness and imposing new conditions on applicants, the board stripped $1.6 million from a $3.7 million application to develop a stem cell therapy for osteoarthritis by Ankasa Regenerative Therapeutics of La Jolla.

The action came after the lead researcher, Jill Helms of Stanford, said her company would make up the shortfall.  She made the comment after being told she could re-submit the application, which was the last to come up for a vote. She indicated that she would prefer to pursue that route rather attempting a problematic and "onerous" re-application with a new set of reviewers early next year.

The other three applications were approved with full funding after a motion to cut all four by about 10 percent failed on a 1-9 vote with one board member abstaining. Board members used the term "hair cut" to describe the reductions, which the applicants would have to make up.

Helms' application was the only one in this round from a business. The others came from non-profit institutions.

Randy Mills, president of the California Institute of Regenerative Medicine or CIRM as the stem cell agency is formally known, opposed the 10 percent cuts on all four awards. He said he and his staff did not want to see programs cut "on the fly." He said applicants were not told that they would have to come up with matching funds when they originally applied.

The other three researchers winning awards are Yadong Huang of the Gladstone Institutes, $6 million for Alzheimer's;  Mark Walters of Children's Hospital, Oakland, $4.5 million for sickle cell, and Denis Evseenko of USC, $2.5 million for cartilage repair.

All the awards went to researchers or institutions that have links to persons who sit on the 29-member board. Overall, about 90 percent of the money awarded by CIRM since 2004 has gone to institutions with ties to past or present board members. While board members set rules for funding and the scope of awards, they are not allowed, however, to vote on specific applications from institutions with which they are connected.  

Summaries of reviewers comments, scores and more can be found on this document from CIRM, which is based in Oakland.  Here is a link to the CIRM press release.

California's $150 Million Public/Private Plan to Commercialize Stem Cell Therapies: An Update

California's plan to create an ambitious, $150 million public/private partnership to commercialize state-funded stem cell research edged forward this week as the deadline for applications closed on Monday afternoon.

Little is known about the nature of the applications -- not even the number received. The state's stem cell agency yesterday declined to reveal the figure, declaring that the proposals needed to be examined to determine eligibility.

Traditionally the $3 billion agency does not disclose the names of applicants for its funding or details of their applications, although there have been exceptions. Their proposals are reviewed behind closed doors by scientific grant reviewers whose names are not disclosed. Nor are the reviewers' statements of economic interest publicly revealed.

A CIRM document calls for the proposal to be evaluated by reviewers during the first quarter of next year with final board action also coming during that period. The recommendations of reviewers are almost never overturned by the board.

The public/private partnership could well be one of the landmark legacies of the stem cell agency, formally known as the California Institute for Regenerative Medicine(CIRM). The project would be unique in California history and nationally.

The eligibility requirements include the following:

• A California location for the work
• Documentation of an "upfront financial commitment" of $75 million(no in-kind services)
• Readiness to begin work as required by CIRM
• Incorporation by the date of the application

The recipient must begin work on the project within 45 days of the award, which translates to before the middle of next year.

$4 Million in Big Ideas Approved by California Stem Cell Agency

The $3 billion California stem cell agency this week welcomed the first members of its "Great Ideas" club and gave them a total of  nearly $4 million to pursue the scientific gleams in their eyes.

Nineteen researchers received awards at a meeting yesterday of the governing board of the agency. They were the first such grants approved by the nearly 12-year-old enterprise.

Writing on the agency's Stem Cellar blog, Kevin McCormack, senior director of communications, said,

"The goal...is to provide seed funding for great, early-stage ideas that may impact the field of human stem cell research but need a little support to test if they work. If they do work out, the money will also enable the researchers to gather the data they’ll need to apply for larger funding opportunities, from CIRM and other institutions, in the future."

Basically, all the applicants had to do was demonstrate was a "strong scientific rationale." The awards were small, only a maximum of $150,000 each, with overhead costs at recipients' institutions adding as much as $87,000 more, depending on the institution. Agency employees have used terms like "big ideas" and "great ideas" to describe the grant round.

All but one of the recipients came from institutions with ties to members of the agency's governing board. About 90 percent of the $1.9 billion the agency has awarded has gone to institutions with links to board members, who, however, are not permitted to vote on grants to their institutions.

Randy Mills, president of the California Institute for Regenerative Medicine (CIRM), as the Oakland-based agency is formally known, said in a news release,

“This is a program supporting early stage ideas that have the potential to be ground breaking. We asked scientists to pitch us their best new ideas, things they want to test but that are hard to get funding for. We know not all of these will pan out, but those that do succeed have the potential to advance our understanding of stem cells and hopefully lead to treatments in the future.”

Here are three examples of the type of work involved. Alysson Muotri at UC San Diego plans to examine treatments for inflammation of the brain, which is an important component of such afflictions as Alzheimer’s, autism, Parkinson’s, lupus and multiple sclerosis. Stanley Carmichael at UCLA wants to see if reprogrammed adult stem cells can help repair damage caused by strokes. Holger Willenbring at UC San Francisco is looking at creation of mini livers with stem cells to help patients waiting for liver transplants.

California's Latest, $4 Million Effort to Transform Human Stem Cell Research

The California stem cell agency's "great ideas" program is set to give away $4 million next week to 18 researchers to help them pursue fledgling pathways to a new therapy or cures for stroke, bladder injury, eye problems, Parkinson's disease and more.

In its solicitation for applications, the agency said the seed funding was aimed at supporting "exploration of transformational ideas that hold the potential to greatly impact the field of human
stem cell research." The expectation is that these awards will provide more information that will help generate more funding to carry the efforts forward.

"Great ideas" is how Gil Sambrano, the agency's director of portfolio and review, described the round in a slide prepared for the meeting of the governing board of the agency next Thursday. Board approval of the positive recommendations by the reviewers is routine. At that point, the agency will identify the winners but not the unsuccessful applicants.

The field of applicants began at 101 earlier this year and was winnowed down to 60 before the final 18 were selected.

Approval of the applications was performed behind closed doors by the agency's blue-ribbon, out-of-state reviewers. The identities of reviewers in a specific round are not disclosed nor are their professional and economic interests.

None of the awards exceeds $238,000. Researchers will receive only a maximum of $150,000 for "direct costs." The excess goes to the institution or business involved for a variety of overhead costs. Duration of the awards varies.

Here is a link to summaries of the scientific reviews of the applications, including comments scores on both winning and losing applicants.

Going for the Gold: Pitches for $12.5 Million in Rejected Stem Cell Research Applications

Highlights

New scoring system

IOM team member appeal

New information on application

Olympic gold medalist, one of “America’s Top Doctors” and the head of the Scripps Institute’s stem cell program are lobbying the California stem cell agency this week to fund requests for $12.5 million in research grants. 

The two different grants have been rejected by the agency’s blue-ribbon reviewers, who meet behind closed doors and and make decisions without disclosing publicly their financial and professional interests. However, the proposals will come before a public meeting tomorrow of the governing board of the $3 billion agency for official ratification of reviewer actions.

Directors of the agency, officially known as the California Institute for Regenerative Medicine(CIRM), have been loath to override reviewers’ decisions, especially in the past couple of years. Plus this week's applications were considered under a new scoring system, which cuts off funding at a scientific score of 85. In the past, the agency has approved awards that were scored as low as 61.

Jeanne Loring, director of the Center for Regenerative Medicine at Scripps, wrote the board to seek funding for her $8 million application (TRAN1-08468) for a treatment involving Parkinson's disease. The proposal was scored at 70.

But first, here are details on the other application (TRAN1-08527). It seeks $4.5 million for research on a treatment for tendon and ligament injuries, something that the agency has not yet funded, according to the three letters supporting the application. The proposal was scored at 83, two points below the cut off. In the past, board members have noted that such small scoring definitions are statistically insignificant.

The identity of the applicant has not been released by the agency. Its practice is to withhold that information until the board acts, although there are notable exceptions to that policy.

Cato Laurencin, UConn photo

One of the letters of support came from Cato Laurencin, an eminent orthopedic surgeon at the University of Connecticut and who is listed as one of “America’s Top Doctors.” Laurencin also served on the Institute of Medicine’s team that conducted a $700,000 study of the California stem cell agency. 

In the letter dated yesterday, he said hundreds of thousands of persons suffer from tendon and ligament injuries. (All letters are clumped under the same URL.)  Laurencin wrote, 

"This seems to me like a marvelous opportunity to support an excellent study with tremendous potential clinical impact on patients in California and throughout the United States."

Jason Lezak, an Olympic swimmer with four gold medals, said in his letter that there is a "clear need" for legitimate research and treatment for such injuries, given the appeal of untested stem cell treatments attracting patients here and abroad.

 

A CIRM document shows that while the application had an overall score of 83, its median score was 85 with scoring ranging from 75 to 92. 

In her March 11 letter, Loring focused on "signicant new information" concerning her application that

Jeanne Loring, Scripps photo

was submitted Nov. 20 of last year. The proposal was not reviewed until Feb. 11.

Loring said, 

"Between November and February, we generated new information that was not available to the GWG(grant review group). Importantly, we also received guidance from the FDA that alleviates the major concerns of the reviewers."

Her nine-page letter itemized reviewer concerns and provided her responses. She wrote, 

"In summary, based on our new data, our DNA sequencing publication, the recent approvals of two of our quality control-focused CIRM grants, and feedback from our meeting with the FDA, we believe that we are ready to proceed on our pilot studies to inform our IND-enabling studies. Some of the GWG concerns conflict with the guidance given by the FDA, and had the GWG been aware of the feedback we had received from the FDA, many of their concerns would have been addressed."

Loring's scientific and median scores were identical: 70. Scoring ranged from 60 to 80. 

David Higgins
 Parkinson's Association photo

The San Diego-based Summit4StemCell group has strongly supported Loring's research and raised funds for it. Representatives from the group have attended a number of CIRM board meetings, laying out the urgency of their needs. One meeting last year became emotional and left some CIRM representatives uneasy and irritated. (See here and here.)

The 29-member CIRM board includes one patient advocate from the Parkinson's community, David Higgins of San Diego. 

Of the $1.9 billion that the agency has handed out, $44 million has gone for Parkinson's. The relatively meager rate of funding was a long a sore point for the first Parkinson's patient advocate on the CIRM board, Joan Samuelson, who has since left the board as her affliction advanced. 

Aussie Clinical Trial for California Firm's Stem Cell Therapy for Parkinson's Disease

A Southern California firm that repeatedly and unsuccessfully sought funding from the $3 billion California stem cell has received the go-ahead in Australia for human testing of a treatment for Parkinson’s Disease, it was reported today. 

In an article today in the San Diego Union-Tribune, reporter Bradley Fikes described the move involving International Stem Cell Corp. (ISCO) of Carlsbad as appearing to be a “medical first.” The company's stock price jumped nearly 16 percent today on the news.

Fikes wrote,

“If all goes according to plan, doctors will implant replacement brain cells into 12 Parkinson’s patients, probably in the first quarter of 2016, said Russell Kern, the company’s chief scientific officer. These are called neural precursor cells, a slightly immature kind of neuron. The cells will finish maturing in the brain into the kind of neurons destroyed by the movement disorder.

“The neural precursor cells are derived from the company’s parthenogenetic stem cells, which are produced from unfertilized human egg cells.”

International Stem Cell is a publicly traded firm whose researchers pitched proposals with some regularity to the stem cell agency a few years back. It was not known whether any of the applications involved the Parkinson's therapy. The firm’s personnel also attended CIRM board meetings with some frequency. (For earlier items on the company, see here, here, here, here and here.)

The day after Fikes' story appeared, the stem cell posted an item on its Stem Cellar blog about the effort.

Fikes wrote that the firm’s trial will be the first Parkinson’s trial  using replacement brain cells grown from stem cells, according to clinicaltrials.gov. The trial will be conducted by the firm’s Australian subsidiary, Cyto Therapeutics. 

Fikes reported that company’s effort is similar to other research in the San Diego area.

“That’s also the approach Summit for Stem Cell will take, said stem cell scientist Jeanne Loring, a leader of the Summit for Stem Cell project. The cells make proper connections with the brain better when they are still maturing, said Loring, who’s also head of the regenerative medicine program at The Scripps Research Institute in La Jolla.”

Loring is applying for an award from the stem cell agency but her research is at an earlier stage than that of the Carlsbad firm. Fikes wrote,

“Loring said she views ISCO as a partner in fighting Parkinson’s. One of her former students is working for the company, she said….

“ISCO’s choice of Australia for its streamlined regulatory process makes sense, Loring said. Her team, with U.S.-based academics and medical professionals, doesn’t have the same flexibility as ISCO in looking for clinical trial locations, she said.”

The firm’s stock closed at $5.00 today, up nearly 16 percent. Its 52-week high was $12.30 and low was $1.25. Here is a link to the company’s press release on the news today.

(The information concerning the agency posting an item on the San Diego news was added to this item 24 hours after it was first published.)

California's New $105 Million Stem Cell Surge: The Creation of an Industrial Powerhouse

Highlights

National biotech interest likely

$75 million alone for public-private effort

High risk, high reward

More support for Alpha clinics

California is hoping to fire up the state’s stem cell industry this month with $105 million aimed at creation of an unprecedented, “industrial stem cell therapeutic powerhouse” on the nation’s West Coast. 

The money is coming from the state’s stem cell agency, which has already spent $2 billion on stem cell research in the last decade. The agency is now on its last $900 million and pushing hard to translate stem cells into therapies and cures. It is expected to run out of money for new awards in 2020.

Earlier this week, a key panel of the agency’s governing board approved the $105 million surge, a decision that is certain to be ratified by the full board at a meeting Dec. 17 in Los Angeles. The action will initiate a 2016 competition for the cash, which is likely to draw national interest, although the money can be spent only within the state.

The largest component of the $105 million is $75 million for a program that the agency has dubbed the “Accelerating Therapies through Public-Private Partnership” or ATP3. The award would be one of the largest ever made by the agency, which is formally known as the California Institute for Regenerative Medicine (CIRM).

Also approved was a $15 million round for an "accelerating center" and another $15 million round for a "translating center." All of the awards are scheduled to be made by late 2016. 

Under the ATP3 public-private round, the recipient would be required to match the $75 million from California taxpayers. The program would bundle together for continued CIRM funding the most promising current CIRM projects. Those projects -- a “portfolio of  ‘high risk’ but high reward projects” -- would be selected by the recipient for development for commercialization, the agency said in a memo.

CIRM’s plan for the project said,

“The aggregation of a basket of otherwise unpartnered CIRM projects offers the successful applicant ‘multiple shots on goal.’ This increases the probability of successfully developing and commercializing a stem cell treatment and makes significant industry investment in stem cell technology more attractive.”

The agency said in a presentation that industry is “beginning to show interest” in stem cell therapies but only 8 percent of CIRM’s 71 active therapeutic programs have industry partners.

CIRM’s presentation said the awardee must have a “top-tier” track record and “could be an established company, a spin-off or a new company with a team formed by Pharma, biotechnology or by an investor.”

CIRM said Californians would benefit from "creation of an industrial stem cell therapeutic powerhouse that increases the likelihood of the commercialization of stem cell treatments for patients with unmet medical needs."

The other CIRM award rounds that are up for ratification later this month aim also at bringing stem cell therapies into widespread use.

The $15 million accelerating center round, which is open to non-California-based organizations, would fund the following activities:

• “Regulatory management services (including IND preparation and submission)
• “Clinical trial planning and management, including site selection, contracting, and clinical site management (e.g., patient recruitment and operational and logistical support)
• “ Data management, biostatical and analytical services
• “Provision of services to (CIRM’s) Alpha Clinics Network, CIRM-funded investigators and sponsors with translational and clinical stage projects, and clinical sites seeking to join the Alpha Clinics Network”

The translating center would fund the following activities:

• “Project planning in coordination with CIRM and the Accelerating Center.
• “Project management for pre-clinical IND-enabling development programs, including pivotal pharmacology and toxicology studies.
• “Process development and product manufacturing activities suitable for production of cell products under good manufacturing practices (GMP).
• “Assembly and authorship of documents to support IND submissions and FDA interactions.
• “Development and execution of a business plan to sustain operations beyond CIRM funding.”

Faster Action Approved in California on Stem Cell Therapy for Parkinson's

To cheers and applause, directors of the $3 billion California stem cell agency this morning moved to speed action on a much-lobbied effort to fund research on a therapy for Parkinson's disease.

Randy Mills, president of the agency, said the action would mean that a request for applications would be posted within the next seven days instead of sometime next spring.

He spoke from the Sanford Consortium in La Jolla during a teleconference meeting with 18 locations. Parkinson's advocates at his site cheered and applauded the news.

A giddy Jenifer Raub, one of the leaders of the Summit4StemCells group, told agency directors,

"I feel like a kid at Christmas."

It was a feeling echoed by other members of the group, which had protested the delay at a CIRM board meeting in July and also earlier this month. About 17 were in attendance at Mills' location this morning.

The San Diego Parkinson's group is backing research by Jeanne Loring, head of stem cell research at the Scripps Institute in La Jolla. (See here and here.)

The unanimous vote by the board gave Mills more flexibility in scheduling upcoming rounds of awards involving basic and translational research. Loring's research fits in the translational area. The basic research round will now apparently be put off until next spring.

Parkinson's and the California Stem Cell Agency: Advocates Cite 'Overwhelming' Need to Air Unhappiness

The California stem cell agency has posted a letter online from Parkinson’s patient advocates that says that an emotional outpouring at a July stem cell meeting grew out of an “overwhelming” need to protest agency delays in funding research.

The letter was signed by Sherrie Gould and Jenifer Raub, leaders of Summit4StemCell, a San Diego group, and was sent to the agency's board. Gould and Raub wrote about the July 23 meeting of the board during which the patients protested after they learned that no funding for the research they were backing would be available until about 2017. (See here for full text of the protest.)

The link to the Aug. 2 letter is part of the agenda for this Thursday’s teleconference meeting of the directors of the $3 billion research effort. It said, 

“Our group at Summit4StemCell (has) been regularly attending the CIRM meetings for the past 18 months. Out of respect for Jeanne Loring PhD, we have typically shown up in ‘silent solidarity’ but this meeting was different and many of us had an opportunity to speak publicly about our project, our progress and our desperate need for funding.

“The outpouring on Thursday (July 23) was spontaneous and unexpected. We at Summit feel strongly that we communicate with all board members that our presence at any of the CIRM board meeting is not orchestrated by Jeanne Loring, Dr. Melissa Houser (of the Scripps Clinic) or anyone from the Loring lab.

“We are a passionate group of dedicated Californians that believe strongly in the probability of success of this research using pluripotent stem cell technology. Dr. Loring has always counseled respect and brevity. We believe she would prefer that we be the face of the issue and not the strident voice.

“When confronted with the possibility that there could be no help (or hope) for over a year, the need to speak and be heard was overwhelming. We sincerely believe that you and the board heard us and will do all you can to find an exception or some way to help.” 

The reference to Loring, who is head of the stem cell program at the Scripps Research Institute in La Jolla, has to do with the Summit group’s support of her research. It also seems to be linked to an anonymous comment filed on the California Stem Cell Report’s account of the July protest.

The writer indicated that Loring had submitted an application earlier that was scored unfavorably by the agency, based on a conversation that the writer had overheard at the Oakland meeting. In response, Loring said no such conversation took place. She said an earlier application in another round did not meet CIRM criteria and was withdrawn. The agency does not publicly comment on such grant review processes, which are conducted in secret. It also does not release the names of unsuccessful applicants. (See Loring's and the writer's complete comments at the end of this item.)

Summit4StemCell is also not happy with teleconference nature of this week’s meeting. Earlier this month, they said their voice was “diminished” because of the inability to speak to the governing board face-to-face.

The California Stem Cell Report item on the teleconference/Parkinson’s flap is the most widely read post this month, exceeding the readership of the item dealing with the agency’s announcement concerning its $32 million stem cell bank. 

Openness and Transparency: Backsliding at California Stem Cell Agency

Highlights
$34 million Alpha Clinics involved
Information failure on proposal
Discourages public/researcher participation
California’s stem cell agency this past couple of weeks skidded significantly backwards in its efforts to improve clarity and transparency in its $3 billion operation.

The latest example came this week and involved its ambitious, $34 million Alpha stem cell clinic program at four major California institutions: the City of Hope, UCLA and UC Irvine and UC San Diego. 

A proposed, multimillion dollar project involving the effort was scheduled for action next Tuesday by the Science Subcommittee of the agency’s governing board.  As of early this morning -- only one full business day from the meeting -- the agency had released only nine words about it to the public. Here is the full text:

“Consideration of concept plan for Alpha Clinics Accelerating Center.” 

Opaque is the only way to describe the process. And it was bound to create issues with affected parties, which it has in this case.

Such cryptic notices make it impossible for the public to comment intelligently or otherwise, given the lack of information. The failure to provide the information in a timely fashion also feeds suspicion and distrust.

Clarity is one of the watch words that Randy Mills has invoked in his 15-month tenure at the California Institute for Regenerative Medicine(CIRM), as the agency is formally known. He has done much to sharpen CIRM’s focus and provide additional clarity through his analysis of the agency’s work.  

But failing to provide material in a timely fashion removes more than the shine on his efforts. The meetings of the agency’s directors are CIRM’s most important public events.  They are where patients, advocates, researchers, biotech executives and even the unwashed public can come together to hear and see the board in action and discuss issues informally with directors and the CIRM staff. Attendance should be encouraged – not discouraged. Which is what happens when important information is withheld from the public.

Last Friday the California Stem Cell Report carried an item on another mysterious agenda item, one that involved forgiveness of agency loans and potential royalty revenue, something that was promised in the election campaign that created the agency in 2004. 

That too was a case of missing information until it was much too late for the public or affected parties to make thoughtful comments. (See here and here.)

CIRM can and should do better than this. 

(The California Stem Cell Report this morning asked CIRM for comment on the failure to provide information on the Alpha proposal scheduled for Tuesday.  About ninety minutes later, CIRM spokesman Don Gibbons responded, saying that the item was now being postponed "to allow more time for refinement and consideration.")

(By this afternoon, the agency had also posted the first explanation of another cryptic item on the Tuesday agenda for the Science Subcommittee. This one would eliminate the specific schedule for RFAs in the upcoming basic research (discovery) and translational RFAs. The reason for the change is to provide more flexibility.)

(Editor's note: The last paragraph of this item was added several hours after the original posting.)

The California Stem Cell Agency and its Mysteries of Fiscal Alchemy

In just four business days, the $3 billion California stem cell agency is going to perform a bit of financial alchemy. But like most alchemists, its methods are less than transparent.

The case in point involves a session of the intellectual property subcommittee of the agency’s board of directors. The committee is scheduled to meet next Thursday to deal with an unknown amount of cash that the agency has given to an unidentified recipient.

According to the very limited information on the meeting agenda, the cash was once a loan. But that loan has been forgiven by the agency. Now the plan is to turn that forgiven loan into a grant.

Why? How much money is involved? What is the rationale? What is the benefit to the people of California, if any? It is all something of a mystery.

Also on the agenda are unspecified changes in the “loan election policy” for clinical awards, a program that is budgeted for $100 million this year. Again, no rationale or explanation is publicly available as of this morning.

One of the favorite words of agency’s president, Randy Mills, is clarity. He reminds folks regularly that the agency should have clarity in what it does.

Mills has indeed improved the clarity of the organization in his one-year tenure at the California Institute for Regenerative Medicine, as the agency is formally known. He has brought analytic and presentation skills that have opened new insights into how the organization spends the taxpayers’ billions.  The result has been an improvement in the way the agency operates.

But in this case, the agency is falling short. Its rules call for notifying the public about meetings 10 calendar days in advance of the sessions. However, cryptic agendas that raise more questions than answers do not add up to clarity. Instead, they are opaque and can generate suspicions about the conduct of the agency on the part of the public and interested parties.

Trust in government – and the stem cell agency is part of our government – is at all-time lows. It behooves the California stem cell agency to do what it can avoid feeding that distrust and to make its operations as transparent and open as possible.

From Fraud Checks to Unspent Funds: California's Proposed Rules for Stem Cell Researchers

The California stem cell agency today put off adoption of  new rules for the way it will hand out its last $1 billion, speeding the money to researchers and attempting to improve the quality of research proposals.

The agency's staff deferred action on the proposal in order to spend more time refining it prior to action in March. The interim grant administration rules are designed to implement the CIRM 2.0 plan laid out by agency president Randy Mills, who has been on the job since last May. 

The rules will apply to the initial phase of CIRM 2.0, which closes the first of its new, rolling application rounds tomorrow, and is subject to adjustment. CIRM (the California Institute for Regenerative Medicine) expects to extend the new rules in one form or another to all upcoming award rounds.

The agency calls the fast-track effort a radical change from previous years. It is certain to have a major impact on many scientists.

The agency is funded by money that the state borrows (bonds). It has handed out roughly $2 billion and figures its remaining $1 billion will last until about 2020 when it will need additional financing.

The new regulations talk about such things as “real-time course corrections,” background fraud checks, early and stringent budget review, restrictions on appeals by rejected applicants and elimination of paper work.

Here are some excerpts from an agency memo identified as coming from the “legal team.”  It unfortunately does not contain a marked-up version showing language that has been deleted from the previous grant administration policy along with the new language.

Money

“Prior to CIRM 2.0, payments to grantees were made primarily based on the calendar – disbursements keyed off the start date of the project and were periodically made based on some given period of time following that date. Under the proposed GAP(grant administration policy), however, for clinical stage projects, CIRM will shift to a milestone-based payment schedule. Thus, this section of the GAP describes the importance of the milestones and how payments on the grant will only be made upon successful completion of the milestones.

“Additionally, in many circumstances the grantee will be allowed to keep unspent CIRM funds upon successful completion of the project, to be spent on any other project of the grantee’s that is consistent with advancing CIRM’s mission. This new process will incentivize grantees to advance the project in the most efficient and shortest time possible, fulfilling CIRM’s goal to accelerate such projects.”

Background checks

“The eligibility section has been drafted to reflect that applicants will undergo a background check to ensure no prior or pending records of fraud or misuse of funds.” 

Budgets

“This new review will examine the proposed budget to identify where proposed costs diverge from established market rates and where opportunities for budget tightening may be found. To incentivize efficient budgeting, where CIRM determines that a budget differs significantly from market rates, conforming adjustments will have to be made before the application will be brought forward for review by the GWG (the grant review group).” 

Fast-track

“Rather than require submission of extensive documentation regarding compliance with myriad protocols and processes – some CIRM-imposed and others external – the proposed process will rely on certification of compliance by the applicant, with the ability for CIRM to request supporting documentation if cause to do so arises.” 

Elimination of paper work

“Because most prior approval requests were routinely granted, and therefore added little value to the process, prior approval requests for rebudgeting and carryforward have been eliminated. We have also eliminated prior approval requests for no-cost extensions because our new CIRM awards will have project end dates that will be extended automatically as needed to complete the final Operational Milestone. CIRM intends to increase the latitude for grantees to pursue their research, while maintaining visibility into and approval of any changes to key components of clinical trials, manufacturing processes, or any other activities that meaningfully impact milestones or suspension events.” 

Clinical advisory panels (CAP)  for each award

“CAPs will provide real-time course correction and will focus more on acceleration opportunities than pure evaluation. CAPs will be tailored for the needs of each project and will consist of CIRM and external members, more nimbly sized than prior CDAP panels. CAPs will meet on a quarterly basis (instead of annually with CDAP) and examine all relevant information regarding project progression, possible roadblocks, and avenues for progression.” 

Appeals from rejected applicants

“Finally, in light of the rolling nature of the programs which will allow unsuccessful applicants in many instances to reapply with improvements to their applications, CIRM will limit the grounds for appeal of Scientific Review to those based on demonstrable conflicts of interest (as defined in the conflict of interest policy applicable to GWG members).”