Stem Cell Scientists' Hopes for Research Cash Survive Another Round in California

(Late News Break: It looks like the six applications in the story below are now headed for approval, perhaps as early as next Thursday. See this story.)

Six stem cell research proposals targeting bladder cancer, autism, liver failure and more escaped rejection today as the $3 billion California stem cell agency struggles with its finances.

The agency expects to run out of cash for new awards by the end of next year. In 2019, it is considering awarding only $144 million compared to $300 million in some years. "We are coming to the end," said CIRM board member Oswald Steward, director of the Reeve, Irvine Research Center at UC Irvine, in July.

The applications had already been held over from July when the agency's directors were presented with a $19 million list of applications approved by its out-of-state reviewers in an earlier closed-door session.

However, the round was budgeted for only $10 million by the governing board of the agency, known formally as the California Institute for Regenerative Medicine (CIRM).

Ten letters of support were filed on behalf of five rejected awards, whose scores ranged from 90 to 87. The agency in July approved three awards with scores of 85.

Some of the researchers and supporters appeared before the board today. Philip Beachy of Stanford, who is seeking $1.4 million for bladder cancer research, said his team was seeking a long term cure for bladder, which has a tendency to recur and is the most expensive cancer to treat per patient.

Other researchers and patients also made a direct appeal to CIRM directors, and on an 11-0 vote, the board kept the applications alive during a telephonic meeting.

Here is a link to the scores and review summaries in this round. Here is the presentation by staff on its recommendations.

Here is a list of letters supporting applications in this round and their authors:

• Daniel Geschwind, director of UCLA Center for Autism Research and Treatment, on behalf of application DISC2-11070, treatment for autism, PI Stuart Lipton of Scripps Research of La Jolla (score 87 out of 100)
• Bridget Vissari, president, Achroma Corp., Butler, Pa., in support of DISC2-10973, PI Jonathan Lin of UC San Diego, dealing with photoreceptor diseases (score 88 out of 100)
• Laura Brady, research manager, Fighting Blindness of Dublin, Ireland, also in support of DISC2-10973
• Avril Daly, CEO, Retina International, also in support of DISC2-10973.
• Philip Beachy, Ernest and Amelia Gallo professor, Stanford, in support of his application, DISC2-11105, dealing with bladder cancer (score 90 out of 100)
• Don Reed, vice president of public policy, Americans for Cures, also in support of DISC2-11105
• David Russell, chief scientific officer, Universal Cells, Inc., of Seattle, a subsidiary of Astellas Pharma, in support of DISC2-10979 PI Tracy Grikscheit of USC, dealing with liver failure therapy (score 90 out of 100)
• Paul Viviano, CEO Childrens Hospital Los Angeles, and two others, also in support of DISC2-10979
• Neil Seigel, co-director USC Hearing and Communication Neuroscience Training Program, in support of his application DISC2-11183, dealing with hearing loss (score 87 out of 100)
• Robert Rainey, research associate of Neil Segil Lab, USC, also in support of application DISC2-11183 (Rainey's letter is in the same file as Segil's)

Dollars Dribbling Away: California Stem Cell Scientists Appeal for More Research Cash

When the cash spigot starts to dry up, the appeals stack up.

Such is the case this week at the now $144 million California stem cell agency, which has been mostly referred to as a $3 billion enterprise. But the cash is dribbling away quickly. And the agency is sticking to its budget in a way that did not happen eight years ago.

The latest evidence comes on the agenda for Thursday's meeting of directors of the agency, known formally as the California Institute for Regenerative Medicine or CIRM. The agenda contains 10 letters appealing to the directors to approve awards for various research projects.

These are projects that have been recommended for funding by the agency's scientific reviewers. However, the reviewers did not have the constraints of meeting the agency's budget for this round of awards.

Only $865,282 is available under the agency's budget. The five applications in question total close to $7 million.

So letters appealing for the cash have been directed to the agency's board.
Here are a couple of samples from the letters.

Phil Beachy, Stanford photo

This one is from Philip Beachy of Stanford University, whose application (DISC2-11105), Beachy wrote, was scored at 90 out of 100 by reviewers. He is seeking $1.4 million for work related to bladder cancer.

"In July we were surprised to learn that our application was not selected for funding, whereas four proposals ranked below ours were funded. We have subsequently learned that an important component of the funding decision made by the ICOC (the CIRM board) is comments from scientists and patient advocates. We wish to have the opportunity to present our comments at the October 11 ICOC meeting, at which our proposal will be considered. Four scientists involved in this proposal will be attending the meeting, including myself (Philip Beachy, Ph.D.), Kyle Loh, Ph.D., Lay Teng Ang, Ph.D., and Joe Liao M.D., Ph.D.)." 

They also enlisted assistance from a patient advocate, Don Reed of Fremont, who is a regular at CIRM board meetings. He wrote,

"Is there a path to defeating the cancer and restoring the bladder’s natural function? Today I had lunch with two people, Drs. Lay Teng Ang and Kyle Loh, who (along with Drs. Philip Beachy and Joe Liao) may have the answer to this particular cancer. Their goal is to use embryonic stem cells to grow a healthy new lining of the bladder....But they need a grant from the California stem cell agency to do it."

Robert Rainey, USC photo

Here is an excerpt from another letter. This one was written by Robert Rainey, the primary research associate involved in an application (DISC2-11183) that seeks $833,282 to create a screen to protect against hearing loss caused by chemotherapy.  The proposal by Neil Segil, co-director of the USC Hearing and Communications Neuroscience Training Program, received a score of 87 from reviewers.

Rainey, who is profoundly deaf, wrote,

"In the entire history of CIRM, only three hearing loss-related grants have been awarded. This is not an oversight of CIRM, but rather a reflection of the paucity of experimental approaches for studying problems related to hearing loss in humans. Our approach can now overcome these problems, and the work described in this proposal will allow us to simultaneously improve the efficiency of our direct-reprogramming technique from human iPSCs, while allowing us to immediately begin pilot testing small libraries of FDA-approved drugs for hair cell-protective qualities during cancer treatment."
(Rainey's letter is in the same file as Segil's.)

Segil wrote,

"Talk about adding insult to injury! Imagine that you are the parent of a 4 year old child who has just been diagnosed with a deadly pediatric cancer. You are told that, in spite of this horrible diagnosis, a cure is possible, with a good chance of success. However, the cure has an extremely common side-effect, namely that your child will likely go deaf as a result of the chemotherapy. In fact, more than 60% of kids treated for pediatric cancer end up profoundly deaf."

Neither Segil's or Beachy's applications will be funded if the board sticks with its budget and abides by staff recommendations, which it has usually done in recent years.

You can find on the meeting agenda all the appeal letters, summaries of the application reviews and CIRM's rationale for the last award in this round. The transcript from the July board meeting also carries considerable discussion related to the financial pressures generated in this round along with how the initial decisions were made.

California Stem Cell Agency's 'Holiday' Awards: $25 Million for Research Ranging from Liver Failure to Dementia

OAKLAND, Ca. -- Directors of the California stem cell agency last week approved nearly $25 million for research but dashed the hopes of two scientists who were pushing extra hard for funding from the 13-year-old state enterprise.

Thirteen researchers ultimately received awards for tackling such afflictions as diabetes, dementia and liver failure. Thirty-two scientists who applied in the round were originally rejected by reviewers for the California Insitute for Regenerative Medicine, (CIRM), as the agency is formally known.

Reviewers make the de facto decisions on awards by the agency, although its governing board can override their actions. Four researchers whose proposals were nixed during an earlier, closed-door reviewer session sought to reverse those decisions.

Only two out of the four won over the board. One was Mark Tuszynski, director of the Translational Neuroscience Institute at UC San Diego, who sought $2.1 million to support his research to use neural stem cells to grow new connections through injured spinal cord. In a letter to the board prior to the meeting, he said ,

"As the present round of...funding winds down, this may be our last opportunity to develop this work to benefit the citizens of the state of California."

Tuszynski's application received a score of 80 out of 100, five points below the cutoff line of 85.

CIRM directors discussed the application briefly during which San Diego researcher addressed the board.

In addition to Tuszynski's application, the board reversed reviewers on an application for a cellular treatment for epilepsy. The $1.6 million proposal by Neurona Therapeutics of South San Francisco scored 80. Arnold Kriegstein, co-founder of the firm and head of the UC San Francisco stem cell program, spoke on behalf of the Neurona. 

The other appellants were Alice Tarantal of  UC Davis and Gregorio Chazenbalk of UCLA.

Tarantal filed a $1.1 million application (DISC2-10599) that she said involved "total-body positron emission tomography (PET) imaging technology, which currently is only available in California."

Her application was scored at 84 by reviewers, just one point below the cutoff line. Board members in the past have noted that such narrow differences are statistically meaningless.

Chazenbalk's $2.2 million application (DISC2-10473) involved a "new population of pluripotent stem cells" known as Muse cells, which he said can be used to treat acute myocardial infarction with a "high potential rate of success." His score was not disclosed but appears to be below 65.

Both Tarantal and Chazenbalk addressed the board but none of the directors discussed their applications. 

No discussion of the winning applications was conducted by the board members. A list of their names, institutions and projects is below.  

Here is the CIRM press release on the awards. It includes the application numbers for all proposals, which can be used to find the summaries of reviewer comments and scores. The specific review summaries can be found by scrolling more deeply into that document.

APPLICATION	TITLE	INSTITUTION	CIRM COMMITTED FUNDING
DISC2-10591	Preclinical development of an immune evasive islet cell replacement therapy for type 1 diabetes	ViaCyte	$1,470,987
DISC2-10524	Genome Editing of Sinusoidal Endothelial Stem Cells for Permanent Correction of Hemophilia A	Saswati Chatterjee City of Hope	$2,182,193
DISC2-10679	Towards hepatocyte cell replacement therapy: developing a renewable source of human hepatocytes from pluripotent stem cells	Irv Weismann Stanford	$2,201,136
DISC2-10748	Engineering Lifelong Cellular Immunity to HIV	Scott Kitchen U.C. Los Angeles	$1,701,178
DISC2-10714	iPS Glial Therapy for White Matter Stroke and Vascular Dementia	Stanley Thomas Carmichael U.C. Los Angeles	$2,096,095
DISC2-10604	Stimulating endogenous muscle stem cells to counter muscle atrophy	Helen Blau Stanford	$2,198,687
DISC2-10753	Generation and in vitro profiling of neural stem cell lines to predict in vivo efficacy for chronic cervical spinal cord injury.	Aileen Anderson U.C. Irvine	$1,575,613
DISC2-10751	Silicon Nanopore Membrane encapsulated enriched-Beta Clusters for Type 1 Diabetes treatment	Shuvo Roy U.C. San Francisco	$1,113,000
DISC2-10695	Identification and Generation of Long Term Repopulating Human Muscle Stem Cells from Human Pluripotent Stem Cells	April Pyle U.C. Los Angeles	$2,184,000
DISC2-10747	Targeting Cancer Stem Cells in Hematologic Malignancies	Tannishtha Reya U.C. San Diego	$2,167,200
DISC2-10559	Development of immune invisible beta cells as a cell therapy for type 1 diabetes through genetic modification of hESCs	Yang Xu U.C. San Diego	$2,167,200
DISC2-10525	Development of a cellular therapeutic for treatment of epilepsy	Neurona Therapeutics	$1,616,536
DISC2-10665	Neural Stem Cell Relays for Severe Spinal Cord Injury	Mark Tuszynski U.C. San Diego	$2,100,581

Chart by CIRM

The California Stem Cell Agency, 'Lost' Opportunities and its Financial Lifeblood

A UC San Diego scientist has zeroed in on the declining finances of the $3 billion California stem cell agency, stressing that tomorrow may be the "last opportunity" for the agency to back a new approach to severe spinal injuries.

Mark Tuszynski, UCSD photo

Mark Tuszynski, director of the Translational Neuroscience Institute at UC San Diego, is
seeking $2.1 million to support his research to use neural stem cells to grow new connections through injured spinal cord. In a letter to the board, he said,

"As the present round of...funding winds down, this may be our last opportunity to develop this work to benefit the citizens of the state of California."

Tuszynski's comment could apply to almost any of the grant applications that will be submitted to the agency between now and late 2019. The California Institute for Regenerative Medicine (CIRM), as the agency is formally known, expects to run out of cash for new awards in 2019.

Tuszynski's comment was also unusual. The public silence from the California scientific stem cell community has been, as they say, "deafening" concerning the looming demise of CIRM. Researchers have not been heard from in any real way at the four public CIRM meetings in 2017 that have dealt with the issue.

The San Diego scientist's letter is part of the agenda at tomorrow's meeting of the CIRM governing board. At the forefront of the session is once again the question of whether the agency can find a way to continue its existence at the level at which it has operated since 2004.

CIRM's financial lifeblood is money that the state borrows -- state bonds. That source was provided by voters when they created the agency with a ballot initiative 13 years ago. However, the authority to issue those bonds is expiring, and the agency needs a major infusion.

Enter Bob Klein, a Palo Alto real estate investment banker and who headed the 2004 ballot campaign. He appeared before the board last month and talked about a $5 billion bond measure on the November 2020 ballot. He is expected to appear again tomorrow. 

Also on the table will be a strategy unveiled last month by CIRM Chairman Jonathan Thomas to raise privately $222 million between now and the beginning of 2020 to keep the agency sufficiently funded prior to a bond election. The board is also scheduled to act on a proposal to cut the size of awards so that more overall can be financed.

Then there are $21 million in applications for research into matters ranging from diabetes to dementia. That is were Tuszynski comes in. CIRM's all-important grant reviewers nixed his application (DISC2-10665), giving it a score of 80. The cutoff line for funding was 85.

He is asking the CIRM board to overturn the reviewers' decision, which would be a rare event. Another two researchers are also appealing negative decisions by reviewers, who meet behind closed doors and do not have to publicly disclose their professional or financial conflicts of interest.

The other scientists are Alice Tarantal of UC Davis and Gregorio Chazenbalk of UCLA.

Tarantal's $1.1 million application (DISC2-10599) involves, she said, "total-body positron emission tomography (PET) imaging technology, which currently is only available in California."

 Her application received a score of 84. In a letter to the board, she said her research, which also involves Simon Cherry of UC Davis, would "set the stage for stem cell applications and the transformative (imaging) tools developed, tested, and successfully applied in California."

In 2018, Tarantal said Cherry will place in operation "the world's first total-body PET scanner for humans that allows all tissues and organs to be imaged simultaneously."

Chazenbalk's $2.2 million application (DISC2-10473) involves a "new population of pluripotent stem cells" known as Muse cells, which he said can be used to treat acute myocardial infarction with a "high potential rate of success."  His score was not disclosed but appears to be below 65.

Scores on the applications can be found here. Summaries of reviewers' remarks on applications can be found  by scrolling more deeply into that document. CIRM withholds the names of applicants until after its board meeting. The three "appealing" scientists' names became public record when their letters were received by CIRM.

Eleven applications were approved by reviewers and 32 rejected.

The full agenda of the meeting with additional information can be found here. The meeting is based at the Oakland CIRM headquarters with teleconference locations where the public can participate in New York City, Sacramento, Santa Cruz, San Diego, Stanford and two in La Jolla.

The meeting is being audiocast as well. Full details on all locations and the audiocast can be found on the agenda. 

The California Stem Cell Report will be covering the meeting live from Oakland and filing stories as warranted.

State Lawmaker Aims to End California Stem Cell Program, Calls It a 'Boondoggle'

State Sen. John Moorlach in video from his office

A California legislator has launched an effort to terminate the $3 billion California stem cell agency, which is already set to go out of business in about three years.

Republican state Sen. John Moorlach of Costa Mesa said in a video,

"It's time to shut this down....We as taxpayers need some protection. We need to stop the boondoggle."

Moorlach has authored a proposed constitutional amendment that has been referred to the Senate Health Committee. No hearing date has been set. The measure would strip from the state constitution the language that created the agency in 2004.

The proposal, SCA7, requires a two-thirds vote of both houses of the legislature and approval by a vote of the people. Given the Democratic dominance of the legislature, that makes the chances of enactment of SCA7 unlikely.

Nonetheless, Moorlach's effort reflects the sentiments of a certain segment of the public. It also provides ammunition for those seeking to fund the agency with another $5 billion, which would additionally be placed before voters, probably in November 2018.  It is useful for campaigns for such measures to be able to point to what they consider threats to science and medical progress.

Backers of a $5 billion bond measure are proposing it because the agency is slated to run out of cash for new research awards by June 2020.

Moorlach's office produced a short statement in support of elimination of the California Institute for Regenerative Medicine or CIRM as the agency is formally known. It said,

"California voters approved a ten year stem cell program that they thought would produce widespread cures and save thousands of lives. They were also promised revenue-producing intellectual property that would help the state financially. These remain empty promises.

"More than thirteen years after its passage, around $2 billion in funds have been dispersed and $1.2 billion has been spent on servicing the principal and interest of the debt . With a $1.6 billion dollar budget deficit and crumbling infrastructure, we need to stop the issuance of bonds on an ineffective and unaccountable agency. Scarce taxpayer funds could be of better use elsewhere."

Asked for a comment on the legislation, an agency spokesman, Kevin McCormack, said,

"We are aware of the bill and are monitoring it." 

California Stem Cell Appeals: Zika, Parkinson's and 'Heart-on-a-Chip'

Three California researchers are asking the directors of the state's stem cell agency today to reject the decisions of its blue-ribbon scientific reviewers and grant them awards ranging up to $2 million.

The scientists are Alysson Muotri, director of the UC San Diego stem cell program; Birgitt Schuele, director of gene discovery and stem cell modeling at the Parkinson's Institute in Sunnyvale, and Kevin Healy, professor in the department of bioengineering at UC Berkeley.

Muotri is seeking $1 million from the California Institute for Regenerative Medicine (CIRM), as the stem cell agency is known. Schuele has applied for $2 million and Healy $1 million.

Alysson Muotri, UCSD photo

In a letter to CIRM's board, Muotri said he is attempting to "set up a human stem cell platform to measure the impact of the Zika virus in the nervous system and to screen potential drugs to alleviate the neurological problems associated with the infection." His application (DISC2-09095) is aimed at filling "fundamental gaps" in Zika knowledge. Muotri, who is from Brazil, wrote,

"I never debated over a grant fund decision before . However, in this case I feel I have the responsibility to alert the ICOC (the CIRM board) about neglecting studies on what we call now the ' Zika virus syndrome.' I can tell by personal experience dealing with this virus in my own lab that this is one of the most dangerous infectious agent I (have) ever seen – one can witness the virus killing brain cells in less than a day."

Birgitt Schuele, TSN photo

Schuele's letter pointed out a new study that she said demonstrated the feasibility of her research (DISC2-08953) involving a therapy for Parkinson's disease. She also included additional information that she hoped would be persuasive to the CIRM board.

Kevin Healy
photo by Laura Peterson, AAAS

In his letter, Healy said his research is aimed at developing "patient specific ‘heart-on-a-chip’ diagnostics that will have a significant impact on the early screening of drugs used to manage hypertrophic cardiomyopathy . Currently, there are no drugs that target specific disease alleles of hypertrophic cardiomyopathy."

He said the main criticism of CIRM reviewers involved the "level of maturity of cardiomyocytes" in his proposed study (DISC2-08990). But he said he proposed using the same protocol as already used by a number of currently funded CIRM researchers.

All three applications were ranked below the cutoff line for funding, which was 85. The score for Healy was 83, Muotri 77 and Schuele 72.

CIRM has funded some applications in the past with lower scores than 85. But in the last two years, it has revised its review and scoring protocols. Since then it has not overridden reviewers' negative recommendations.

The board is scheduled to act on about $30 million in awards today in a telephonic meeting with public locations throughout the state. (See here and here. ) The public can participate in the meeting at those locations, whose addresses can be found on the meeting agenda. The session will be audiocast on the Internet and through an 800-number. Complete information about the Internet access and phone number can be found on the agenda.

California Awards $37 Million for Stem Cell Research; Parkinson's Grant Deferred After Emotional Session

Directors of the California stem cell agency today approved nearly $37 million for translational stem cell research into possible therapies for afflictions ranging from cancer to Canavan disease.

The vote came routinely after a lengthy and sometimes emotional discussion involving an $8 proposal for Parkinson's disease from Scripps Institute in La Jolla that was rejected by the agency's grant review group.

Their voices cracking and tears welling up, persons with the disease appealed to the agency's directors to provide "a future without fear, a future with hope."

Cassandra Peters, who was diagnosed with Parkinson's 15 years ago, told stem cell agency president, Randy Mills, via a phone link to San Diego,

"I hope that I have the opportunity to kneel in front of you and say thank you."

On an 8-4-2 vote, the board ultimately sent the application from Jeanne Loring, head of the stem cell program at the Scripps Institute, back to reviewers for an accelerated re-examination of her proposal, which was submitted last Nov. 20. It was reviewed on Feb. 11 behind closed doors and given a score of 70, well below the cutoff of 85.

This week, Loring said in a letter to the board that new information, including comments from the FDA, has emerged since November that will satisfy the concerns of reviewers. CIRM officials estimated it would take about two months to have the proposal re-examined. Then it would have to come back to the board for final action.

Loring's proposal and the others were reviewed under new procedures that are aimed at providing more, regular opportunities for researchers to apply for funding. Old procedures for appeals have been scrapped after failing to deal with the emotional appeals that have been generated for awards over the last decade.

Some board members were concerned that the exception granted for Loring today would stimulate a fresh wave of public pitches by scientists and patients whose proposals have not fared well with reviewers. The board is reluctant to second-guess its reviewers. Agency directors do not see the full applications for cash, just the same review summaries seen by the public, with the exception of proprietary information, which the board can see during executive sessions.

While seven other translational awards were approved, the board rejected another effort to fund research that was rejected by reviewers. In this case, the application scored only two points below the cutoff.

Speaking after the long debate on Loring's proposal, Thomas Kremen of Cedars-Sinai and Olympic gold medalist Jason Lezak appeared to appeal to the board to overturn the rejection. The board, however, did not discuss the application or respond to their comments.

All seven winning institutions in this round all had ties to members of the governing board of the agency, formally known as the California Institute for Regenerative Medicine (CIRM). However, those board members are not allowed to vote on such applications. About 90 percent of the $1.98 billion in CIRM awards has gone to institutions with links to past or present CIRM board members.

Randy Mills, president of the agency, said in a press release,

“Many of the programs we are funding today are focused on helping find treatments for diseases that affect children, often in infancy. Because many of these diseases are rare there are limited treatment options for them, which makes it all the more important for CIRM to focus on targeting these unmet medical needs.”

Here is a link to the agency's press release on today's meeting, which includes the names of the recipients.

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. 

$25 Million for Stem Cell Research Plus Sharp Criticism of California Stem Cell Board

The California stem cell agency today approved $25.2 million for preclinical research aimed at speeding development of therapies for afflictions that include arthritis, Alzheimer's and “bubble boy” syndrome.

The action came during an agency governing board session that was marked by sharp criticism from an executive with a La Jolla firm associated with one of the rejected grant applicants, Jill Helms of Stanford. The executive, Sanford Madigan of Ankasa Regenerative Therapeutics, told the board he was "disturbed by board members not willing to do their jobs."

Sanford Madigan, LinkedIn photo

Several board members said they were offended by Madigan's remarks, although he later apologized. He appeared to be irritated by the reluctance of the board to override its reviewers. Five board members subsequently abstained from voting to overturn staff and reviewer rejection of Helms' application. The motion that would have funded her proposal failed on a vote of 5-1-5.

The public flare-up involving the board and a member of the public was unusual, although comments such as Madigan's are sometimes heard in private.

His remarks came at the end of a discussion about the weaknesses of the agency's closed-door review process. The discussion involved other applications in addition to Helms' proposal. Randy Mills, president of the agency, acknowledged the review process was "sub-optimal" and was being replaced by new procedures he has dubbed CIRM 2.0.

Ankasa was created by Avalon Ventures, which is raising $16 million to help commercialize Helm's work to develop a stem cell therapy to improve skeletal healing of elderly people.

The governing board of the agency handed out awards to seven scientists with the goal of moving their research closer to federal approval for a start of a clinical trial. The board approved applications from two researchers who made special appeals to the board after reviewers and staff nixed their proposals.

Prior to the vote on her application, Helms was told that she could revise her $7 million application and submit it for later consideration. She said the soonest that would occur would be in about 10 months, given the agency's timetable. By that time, she said the research team would be disbanded through lack of funding and the effort would "disintegrate." 

CIRM has already put $7 million into Helms' research. She has been something of a bright star for the agency, which has featured her on its Web site and asked her to appear on its panels.

The rejection of the Helms proposal highlighted some of the vagaries of the agency's longstanding review process.  She received an average scientific score  of 72 which knocked her out of the funding category(tier one). However, her median score was 75, a figure that two reviewer-approved grants received. What skewed the average figure was a low score of 45. No other grant in the top 10 received that a ranking that low. Eight reviewers recommended funding the proposal, Four did not with three recommending it be placed in "tier two," a grey area for applications.

No reviewers were listed as having conflicts of interest on the Helms proposal. However, their finanicial and professional interests are not disclosed to the public. Nor are they identified to the public.

On another proposal, John Cashman, CEO of Human BioMolecular Research Institute of San Diego, asked for a re-review of his firm's application for a treatment involving spinal fusion. He said that his firm has worked with CIRM for several years to make changes that the agency had requested. Nonetheless, he said reviewers do not seem to agree.  Cashman said,

"Certainly the system is broken."

The board did not act on Cashman's request for a re-review.

Here is the roll call vote on the Helms' application: Yes -- David Higgins, Steve Juelsgaard, Kathy LaPorte, Lauren Miller, Art Torres. No -- Jonathan Thomas. Abstain -- Francisco Prieto, Robert Quint, Al Rowlett, Jeff Sheehy, Diane Winokur.

Summaries of the reviews of the winning applications can be found on this 90-page document.

(Editor's note: An earlier version of this item did not contain the two paragraphs that deal with the vagaries of the grant review process and conflicts of interest.) 

California Stem Cell Awards $7.7 Million for Therapy to Alter Arthritis Progress

The governing board of the California stem cell agency today approved $7.7 million to develop the first therapy that would alter the progression of osteoarthritis.

The action came on a proposal by Daryll D’Lima of Scripps Health, whose application was rejected earlier by reviewers of the agency and its staff. 

D’Lima told the board that arthritis is the No. 1 cause of disability in the nation. Annually, arthritis has a more than $120 billion economic impact, which exceeds 2 percent of the gross domestic product.  D’Lima’s research has already received $3.1 million from CIRM.

$32 Million or $16 Million for California Preclinical Stem Cell Research?

The California stem cell agency board has begun discussion of the preclinical awards to be approved today. Reviewers approved five grants totaling $15.8 million. Three rejected researchers are asking the board to approve another $16 million. The board budgeted $40 million for the effort. At least one rejected researcher, Jill Helms of Stanford, is expected to address the full board.

Arthritis, Alzheimer's, Healing: California Stem Cell Agency Urged to Help Elderly

Three California scientists are asking the state’s stem cell agency to come to the aid of tens of millions of elderly persons and provide $16 million to develop therapies to treat Alzheimer’s and arthritis and to speed skeletal healing in the elderly.

The researchers have asked the governing board of the $3 billion agency to overturn at its meeting tomorrow the rejection of the proposals by both scientific reviewers and the agency staff.  All of the potential therapies are close to moving into clinical trials.

Jill Helms, Stanford photo

One of the scientists, Jill Helms of Stanford, said in a letter to the board that her team is addressing healing issues -- “an unmet medical need in an under-served and often overlooked patient population, namely, the aged….Elderly patients are entitled to the same level of healthcare afforded to younger patients.”

The California Institute for Regenerative Medicine (CIRM), as the agency is formally known, has already pumped $7 million into Helms’ research. She is seeking another $7 million to advance the potential therapy closer to clinical trials.

The two other researchers are Daryll D’Lima of Scripps Health and David Schubert of Salk.

D’Lima is seeking $7.7 million to develop the first therapy that would alter the progression of osteoarthritis, which is the No. 1 cause of disability in the nation. Annually, arthritis has a more than $120 billion economic impact, which exceeds 2 percent of the gross domestic product.  D’Lima’s research has already received $3.1 million from CIRM.

Schubert has applied for $1.7 million for work on an Alzheimer’s therapy that he said was “highly effective at reversing the memory deficits” in mice. His proposal, he said, could move very quickly into clinical trials under new federal regulations.

The researchers’ rejected applications were scored at either at an average of 71 or 72 by the agency’s blue-ribbon scientific grant reviewers, who do their work behind closed doors. The reviewers approved five grants with scores ranging from 89 to 76. Two of the approved grants had the same median score of 75 as the three rejected grants.

During public sessions in the past, a number of board members have said that a few points difference on scores is not statistically significant.

In a memo to the board, Randy Mills, president of the agency, recommended rejection of the applications. He said the applicants could re-apply next summer under the agency’s new CIRM 2.0 program or possibly under the preclinical round that is now open.

Mills’ memo also includes the range of scores and summaries of reviewers' comments. The agency does not identify applicants by name until after the board acts and then only the winners. However, Helms' application is 08105; D’Lima’s is 08128, and Schubert’s is 08086. 

The CIRM board originally budgeted $40 million for the research to be approved tomorrow. Only five applications were okayed by reviewers for a total of $15.8 million.

Helms noted in her March 20 letter to the board that CIRM has been a big supporter of her research since 2009.  The agency has also considered her something of a bright light, using her on panels and presentations.

About the review of her application, she wrote,

“Reviewers had nothing negative to say about the proposed product, the preclinical data, the approach, the veracity of the indications, the MOA, the proposed plan of action, or the milestones.”

Helms said that Avalon Ventures is backing her research to the tune of $16 million, including creation of a new firm, Ankasa Regenerative Therapeutics of La Jolla, to push it forward.

Daryll D'Lima, Scripps photo

In his March 19 letter, D’Lima said his research has demonstrated “very convincing proof" that his possible therapy was “very successful in repairing osteochondral defects (a major factor leading to osteoarthritis)." 

Schubert said in his letter that “there are currently no drugs that halt (Alzheimer’s) progression so the potential benefits of moving CAD- 

031(the name of the treatment) into human trials are enormous."

David Schubert, Salk photo

Schubert’s letter was dated March 16 but was only posted on CIRM Web site within the last two days as were the other letters(dated March 19 and

March 20). The delay in posting makes it difficult for patient advocates to attend the board meeting tomorrow to express directly to the board their opinions about the proposals.

The D’Lima and Schubert applications also involve organizations that do not have seats on the agency’s governing board. D’Lima’s is the only award to Scripps Health. Schubert works at Salk which has not had a representative on the CIRM board since 2011. Salk has received $50 million from the agency.

About 88 percent of the funds that the CIRM board has awarded have gone to institutions with ties to persons who have been members of the board.

(Editor's note: An earlier version of this item said that Helms had received $11 million from the agency, based on information on the CIRM Web site. She said, however, the correct figure is $7 million.)

Budget Scrutiny and Background Checks: Big Changes for California Stem Cell Researchers

From cash payments to conflicts of interest, the $3 billion California stem cell agency this week is set to ratify a radical change in how it awards its largess and oversees the research it funds.

Coming up for approval today by a key panel of the agency’s directors are new rules governing how scientists apply for millions of dollars and how they will receive payments.

Instead of checks rolling in primarily on a calendar basis, for example, they will reach researchers only if they meet milestones approved by the agency, formally known as the California Institute for Regenerative Medicine (CIRM).

The proposals are part of CIRM 2.0, a label coined by UC Davis researcher Paul Knoepfler and adopted by Randy Mills, who has been president of the agency since last May.

With CIRM 2.0, Mills hopes to generate faster and better results than in the past. The main, direct impact will fall on the hundreds of California researchers who will have future agency funding. But if Mills is successful, it will also pay off for California citizens who are financing the agency with borrowed money at a total cost of $6 billion including interest.

The rules will apply immediately only to three clinical stage rounds, but Mills expects to extend them to all future rounds. Officially they are called interim and are subject to additional vetting through the state’s official rule-making process.

Here is a brief look at some of the key features of the new rules, based on a memo prepared by Mills and his team. The rules were first considered in January but final approval was put off until this month.

Payments: Made only on completion of successful milestones. A CIRM memo said, “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 check: Applicants will “undergo a background check to ensure no prior or pending records of fraud or misuse of funds”

External budget review: As soon as an application is received, it will scrutinized by an external contractor “to identify where proposed costs diverge from established market rates and where opportunities for budget tightening may be found.” This is in addition to budget reviews by staff, the grant review group and the board.

Severe appeal restrictions:  Appeals by applicants will be restricted to “a demonstrable financial, professional, or personal conflict of interest, as defined in the (agency’s) conflict of interest policy, (that) had a negative impact on the review process and resulted in a flawed review. Differences of scientific opinion between or among PIs (principal investigators) and reviewers are not grounds for appeal.” State law, however, permits researchers to communicate directly with the CIRM board on any matter. It is almost impossible for applicants to identify conflicts of interests because the names of persons who review their applications are withheld by the agency. Plus reviewers’ professional and financial interests are withheld by the agency.

Clinical advisory panels (CAPs): These new panels “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 (advisory) panels. CAPs will meet on a quarterly basis (instead of annually…) and examine all relevant information regarding project progression, possible roadblocks and avenues for progression.”

Elimination of documentation: Instead of requiring awardees to produce many documents, the agency “will rely on certification of compliance by the applicant, with the ability for CIRM to request supporting documentation if cause to do so arises”

The proposed rules are expected to be approved today at the 2:30 p.m. PDT meeting of the Science Subcommittee of the CIRM board and ratified on Thursday by the full board at its meeting in Berkeley. The public can address the subcommittee at meeting locations in Washington, D.C., two in the Los Angeles area and one each in San Francisco, San Jose, Irvine, Oakland and La Jolla.  Specific addresses can be found on the agenda.