California's 'Incredible' Stem Cell Invention

C. Randal Mills - CIRM 2.0. Building a better stem cell agency (Part 2) from MCC Industry Relations on Vimeo.

Randy Mills, the president of the $3 billion California stem cell agency, was selling hard a couple of months ago in San Diego.

Animated and gesticulating, Mills said,

"There's nothing like CIRM.  It's an incredible invention that probably only could have taken place in California."

But he said the agency was on its way to being better and faster, delivering cash to researchers in 120 days instead of the previous average of 22 months.

"We are an accelerating agency. We are in the time business. So we can't be slow...Urgency matters."

Mills' comments were made to a symposium at the Moores Cancer Center in San Diego Feb. 19. But his full remarks surfaced recently in a video posted on Vimeo(see above).

Mills took only a little more five minutes in his presentation about CIRM 2.0, his radical overhaul of the agency's grant-making process. He is seeking higher quality applications, higher success ratios and stronger partnerships with researchers and patient advocates.

CIRM  2.0 is still in the process of being fully implemented in all of the agency's award efforts. Mills said there will be bumps.
"Buckle up. It's going to be a wild ride."

'Born in Hype:' The California Experiment and Stem Cell Research

A California newspaper with a daily readership of 1.5 million this week thrashed the field of stem cell science, declaring that it “is slathered with so much money that immoderate predictions of success are common.”

“Infected with hype” is the way the headline put it on the March 31 piece in the Los Angeles Times. The paper has the largest circulation in the state and is an agenda-setter for much of the state’s mainstream media.

The comments came in an article by Pulitzer Prize-winning columnist and author Michael Hiltzik, who holds the California stem cell agency in low regard.

Kalina Kamenova
 U. of Alberta photo

Timothy Caulfield
U. of Alberta photo

His starting point was a study in Science Translational Medicine by Timothy Caulfield and Kalina Kamenova of the University of Alberta law school.  Their content analysis research focused primarily on newspaper coverage of timelines for stem cell therapies before and after Geron bailed out of the first clinical trial for a human embryonic therapy in the United States. They did not have warm words for scientists as public communicators.

Neither did Hiltzik, but he also faulted the media. He wrote, 

“The authors mostly blame the scientists, who need to be more aware of ‘the importance of conveying realistic ... timelines to the popular press.’ We wouldn't give journalists this much of a pass; writers on scientific topics should understand that the development of drugs and therapies can take years and involve myriad dry holes and dead ends. They should be vigilant against gaudy promises.”

Hiltzik then took on the California Institute for Regenerative Medicine (CIRM), as the stem cell agency is known.  He wrote about the cash that was "slathered" about. He said,

“The best illustration of that comes from California's stem cell program -- CIRM, or the California Institute for Regenerative Medicine -- a $6-billion public investment (including interest) that was born in hype. 

“The promoters of Proposition 71, the 2004 ballot initiative that created CIRM, filled the airwaves with ads implying that the only thing standing between Michael J. Fox being cured of Parkinson's or Christopher Reeve walking again was Prop. 71's money. They commissioned a study asserting that California might reap a windfall in taxes, royalties and healthcare savings up to seven times the size of its $6-billion investment. One wouldn't build a storage shed on foundations this soft, much less a $6-billion mansion.”

 He wrote about how CIRM played a dubious role in funding the Geron clinical trial only a couple of months before the company pulled the plug for financial reasons, something that the California Stem Cell Report has dealt with as well.  The $26 million loan to Geron involved a major departure from the agency’s normal procedures.  Abandonment of the trial also raised ethical questions that should be of continuing concern to the agency and its ethical advisors who are meeting today and tomorrow in Los Angeles.  

Caulfield’s views on stem cell hype are well-known in the small stem cell research community. But rarely does his sort of perspective, which is shared by others in the field, reach a mass audience such as the 1.5 million readers of the Los Angeles Times.

All of which poses a challenge for the California stem cell agency whose finite amount of cash is now expected to run out in 2020. As Hiltzik noted, the overblown expectations led voters to believe that miraculous cures were just around the corner.

Today, more than a decade after creation of the agency, the promised cures have not materialized and none are likely for some years. The agency has undoubtedly made a major contribution to stem cell science. But the unfulfilled promises of the campaign hype gave its foes the kind of tools they need to battle any efforts to provide more state funding for the agency.  How CIRM deals with that scientific and PR challenge will be one of the major tests for it over the next several years.

Moratorium on Possible Genetic Alteration of Human Race on Agenda Tomorrow at California Stem Cell Agency

The select panel that helps the $3 billion California stem cell agency set  research standards meets tomorrow and Friday in Los Angeles, its first session since 2013.

The agenda appears modest but it does include a discussion involving possible genetic modifications to the human race and the germ line letter signed by Nobel prize winner David Baltimore, among many others.

The starting point for the discussion is a statement by the International Society for Stem Cell Research that said,

“The International Society for Stem Cell Research calls for a moratorium on attempts at clinical application of nuclear genome editing of the human germ line to enable more extensive scientific analysis of the potential risks of genome editing and broader public discussion of the societal and ethical implications.” 

Scientist Paul Knoepfer of UC Davis has an ongoing look at the issues on his blog, ipscell.com. The latest is a March 29 piece headlined “Genetically Modified Humans Now Inevitable?” Knoepfler wrote, 

“Rumors are swirling that upwards of four papers reporting production of GM(genetically modified) human embryos are in various stages of review at high-profile journals, sparking a sense of urgency for some kind of steps to deal with this new reality. Could these papers report germ line correction of the CTFR mutation in cystic fibrosis or of a BRCA1 mutation? Were these GM human embryos used to make embryonic stem cell lines or are they cryopreserved?

“The prime concern now is that GM human embryos could in principle be rather simply turned into GM humans at any one of thousands of IVF clinics around the world with a surrogate mother. That simple technological step of going from GM human embryo to GM human being of course invokes incredibly complicated, thorny legal, bioethical and societal issues.”

Although Baltimore once served on the stem cell agency’s governing board and the agency has been active with the international stem cell research group, it is not clear that it will do anything in regard to a moratorium.

The agency board has shied away from such matters since 2011, when Robert Klein left as its chairman. He often pressed for the agency to take on legislative and other policy matters during his tenure.

The moratorium is not scheduled to be officially voted on so legally it would difficult for the standards panel to do anything significant. But the group could make an expression of sentiment and ask that the full board consider the matter.

The standards group’s last meeting was Oct. 1, 2013, according to the CIRM Web site. However, it was quite active in the early days of the agency when it was formulating the first comprehensive stem cell research regulations in the country. 

The public can attend tomorrow’s session, which beings at noon PDT in Century City in Los Angeles, and speak to the committee on any matter. 

Here is a link to a list of its members. Its chairman is Bernie Lo of UC San Francisco. 

California's Stem Cell Bank and Its Fujifilm Moment

A CIRM slide from last week on the Cellular Dynamic stem cell bank project.

Remember the “Kodak Moment?” California’s $3 billion stem cell agency yesterday experienced a “Fujifilm Moment.”

It came when the Japanese firm announced it was buying Cellular Dynamics International (CDI) for $307 million. That doubled the price of the company stock overnight, probably leading to moments of ecstatic celebration in some circles. The stock closed at $16.43 today, well above its 52-week low of $4.72.

The purchase was part of what FierceBiotech today called a “fresh frenzy of biotech-related buyouts.”

Cellular Dynamics is a Wisconsin firm that has a $16 million grant from CIRM, as the stem cell agency is known, to create what could be the world’s largest bank of induced pluripotent stem cells (iPSCs). The firm was founded by noted University of Wisconsin researcher Jamie Thomson. The bank is located at the Buck Institute in Novato, north of San Francisco. The 155-employee CDI is also the prime subcontractor on a related $10 million award to the Coriell Institute.

At the CIRM board meeting last week, Uta Grieshammer, a science officer at the agency, gave an update on the $32 million project that directors approved in March 2013. From the tenor of her briefing, the effort seems to be on track. (Here is the CIRM-CDI contract dated Oct. 25, 2013.)

It is not entirely clear what, if anything, the Fujifilm purchase means for the CIRM contract with CDI.  Sometimes new owners have different views of previous business arrangements and seek modifications. The Fujifilm press release said CDI work will continue in California and Wisconsin. But the release also said Fujifilm will “seek synergies and efficiencies,” which can be industry-speak for cutbacks and layoffs.

The California Stem Cell Report yesterday queried the agency about its thoughts but no response has been forthcoming.

In June 2014, Kerry Grens of The Scientist magazine wrote about the stem cell banking business. The article said,

“The California Institute for Regenerative Medicine (CIRM) has the ambitious goal of creating the world’s largest iPSC bank. This will include cell lines from people with cardiomyopathy, blinding eye diseases, and Alzheimer’s, among other things. Michael Yaffe, the associate director for research activities at CIRM, said it was important not to duplicate the efforts of other iPSC banking initiatives. In planning the program, Yaffe explained, 'We wanted to make as many [cell lines] as possible. Then it became an economic argument: How many could we afford and how much could we push a deriver to handle?' 

“CIRM settled on a goal of 9,000 lines derived from 3,000 individuals. Yaffe said he anticipates that the first of these will be available for distribution by the end of the year or early 2015. What’s still unsettled, however, is the cost. It’s a tricky calculation, given that the utilization of the lines is unknown. 

“'If a few large pharmaceutical companies buy a complete set of all the lines, that would keep the bank established and running for many years,’ Yaffe said. ‘If academic researchers are going to buy a few lines at a time or a few lines each, it will create some challenges for the sustainability of the bank.’”

In December 2013, CIRM’s staff recommended a $2 million addition to the stem cell banking program. The CIRM governing board rejected the proposal after one board member called the plan dodgy. Jeff Sheehy, who serves on the grant review committee, said it needed to be peer reviewed and competitive.

The Fujifilm purchase attracted considerable news coverage but little mention of the CIRM connection. Here are links to some samples: Madison.com, ipscell.com, xconomy. Here is a link to CDI’s one-year progress report with CIRM.

Three-Month Birthday: California Dances Forward With its Fast Track Stem Cell Plan

Randy Mills' chart last week on changes coming as a result of CIRM 2.0

On New Year’s Eve, the California stem cell agency and its relatively new president, Randy Mills, kicked off a radical and fresh way to hand out money to researchers and speed development of therapies.

Today, nearly three months later, the agency is still wrestling with some key issues, including virtual termination of its old, $500 million loan program.

Nonetheless, at a meeting last week in Berkeley, the governing board of the agency did put behind it many aspects of implementation of what it calls CIRM 2.0, a term drawn from its official name, the California Institute for Regenerative Medicine(CIRM).

Approved were new rules involving administration of grants and beefed up oversight of the research -- with the agency as an ever more engaged partner with researchers, some of whom may not care for more suggestions from the back seat.

Background checks will be required on recipients. Budgets that are out of whack will not even be submitted to agency’s application reviewers. Much paperwork will be eliminated. The out-of-state researchers who approve the grants will now also scrutinize progress and make recommendations. That’s on top of clinical advisory panels that will be created to monitor research progress on a quarterly basis.  Researchers will be encouraged to save money and will have more freedom to spend surplus cash. (For more details, see here and here.)

The goal says Mills, who has been in place only since last May, is to send checks to researcher 120 days after they submit an application instead of the previous average of 22 months. New clinical stage projects are now being accepted every month instead of only once or twice a year.

Most of the CIRM 2.0 matters are much too granular to impress the public, which really only cares about production of useful therapies. But if Mills is successful, it will likely mean speedier development of the treatments that were promised 10 years ago ago when voters created the stem cell agency. Researchers and stem cell firms, as opposed to the general public, need to pay close attention, however, to the details, which can mean millions of dollars for them.

Another stem cell filip is coming up this spring: the agency's strategic plan, which appears ready to be revised as a CIRM 2.0 document. Mills avows his continued support for basic research, strongly favored by board members from academia and research institutions. But heavy pressure exists to bring a product to market quickly or much closer to market. Without such a demonstration, the agency will find it tough to secure additional funding after 2020, the latest estimate when its cash will run out. 

Still hanging out there are the details of what will be left of the agency’s once ambitious, seven-year-old loan program, which was a favorite of the agency’s first chairman, Robert Klein.

Only five loans were made. Only two are still active. In a memo to the board, Mills said the program was “overly complex, administratively burdensome, and, as reflected in the number of loans issued, it does not appear to be attractive to industry.”  He told the board last week that small companies balk at the loans because they do not want the debt on their balance sheets. Grants, however, carry royalty requirements that companies also dislike.

Mills said,

"If we can't make it better, maybe it shouldn't exist."

The board’s intellectual property committee was scheduled to act on a new loan policy in January but that meeting was cancelled with no public explanation. Again this month, a meeting was scheduled but postponed with no immediate explanation. The link to the proposed policy was removed from the CIRM Web site, although the document can be found here. 

 CIRM spokesman Kevin McCormack, in response to a question from the California Stem Cell Report, said,

“The meeting was postponed so we could work on the proposal some more before bringing it to the subcommittee. The document was removed from the Web site because it was actually the wrong document. It was an earlier, outdated version of the proposal and didn't reflect many of the changes that were made.”  

Last week's action directly involved only the first stage of CIRM 2.0, but Mills plans to extend the process to the entire portfolio, making adjustments as necessary. The rules are officially interim. The state’s official regulation adoption process is much lengthier and will provide more opportunity for the public to comment.

Mills has told the board that implementation of his changes will not necessarily be smooth. He also said the effort is likely to be modified as CIRM 2.0 progresses.

CIRM chart on status of CIRM 2.0 applications

Mills has now scheduled the first, closed-door review session for a CIRM 2.0 application, one of two received in January. The 90-minute telephonic meeting is set for tomorrow. The second application from January was sent back to the applicant for re-working. The agency received two CIRM 2.0 applications in February. One was sent back to the applicant. The other is expected to be reviewed and scored April 27.

More CIRM 2.0 applications are expected at the end of this month, next Tuesday.

The public can address tomorrow's meeting from CIRM's headquarters in San Francisco during the public portion of the session.  As usual, however, the name of the researcher and the target of the research are being withheld from the public.

See here, here and here for the text of key documents on CIRM 2.0 approved at last week's meeting.

California's Stem Cell Directors Adjourn, More News Coming up Tomorrow

The directors of the California stem cell agency have adjourned their meeting in Berkeley. We do not expect additional stories today but will have more tomorrow including an update on the agency's search for a new home and an overview of the progress on CIRM 2.0. We call your attention to the item below that involves a flap over the agency's grant review process, which its president calls "sub-optimal."

(The progress report on CIRM 2.0 can be found here. The update on the search for a new CIRM home has been delayed.)

$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.

California Okays $1.7 Million for Alzheimer's Treatment

Directors of the California stem cell agency today all but approved a $1.7 million award to a Salk researcher to develop a therapy that would alter the progression of Alzheimer's Disease.

The action came on a 11-1-1 vote.

Researcher David Schubert of the Salk Institute appealed to the board to overturn rejection of the proposal by reviewers and CIRM staff.  Schubert was told that the application needed to be improved.

Schubert appeared before the board today and sent a letter to the board earlier this month. He said the proposed treatment 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 vote came on a motion to move the application into a category that will be approved by the full board later today. 

Voting Conflict List on California Stem Cell Preclinical Awards

Here is the list of California stem cell agency directors with conflicts of interest on today's preclinical research awards. The list comes from the stem cell agency. The directors on the list are not allowed to vote on the applications in question.

  Voting Conflict List Preclinical CIRM Awards

$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.

Four Applications Submitted Under CIRM 2.0 Fast-track Plan

CIRM President Randy Mills has begun his update on the status of CIRM 2.0 and has even mentioned the possibility of CIRM 2.1 in the not too distant future. His slides can be found here.

He said the first application under CIRM 2.0 will be sent to the full board on April 23. The second application that came in during January has been sent back to the reviewer for revision.

Of the two applications that came in during February, one is going to application reviewers. The other has been sent back to the researcher.

California Stem Cell Board Begins Meeting

The governing board of the California stem cell agency opened its meeting at 9:07 PDT this morning with its usual pledge of allegiance and roll call. The meeting in Berkeley was scheduled to start at 9 a.m

An Update on California's New Fast-Track Stem Cell Research Plan

This morning's session of the governing board of the $3 billion California stem cell agency has not yet begun but the agency has just posted the presentation slides to be used by its president, Randy Mills. 

Most of Mills's presentation deals with the progress of CIRM 2.0, his plan to speed cash to researchers and improve the quality of the applications. He also offered up the above slide concerning the end of the existing, $500 million loan program.

Coming Up This Morning: Gavel to Gavel Coverage of California Stem Cell Meeting

The 29-member governing board of California's $3 billion stem cell research effort, the only such organization of its size in the nation, meets at 9 a.m. PDT in Berkeley to award millions of dollars and to ratify radical changes in the way it operates.

The California Stem Cell Report will provide live, day-long coverage and stories as warranted from its perch in Mazatlan, Mexico, based on the Internet audiocast of the session.

For those would like to follow directly all of the meeting, the agenda contains instructions for dialing in. For those who have not used the process, it is helpful to begin setting it up about 15 minutes before the meeting.  To view the presentations as they are being made, log into the WebEx url.

Correction

The "arthritis, alzheimer's" item earlier today incorrectly said that researcher Jill Helms had already received $11 million from the agency, based on figures on the CIRM Web site. However, Helms said the correct figure is $7 million.

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.)

California's Stem Cell Grant Reviewers Set for More Oversight on Research Awards

The California stem cell agency today moved forward on creation of new rules for its research awards, ranging from more fiscal scrutiny to elimination of paperwork.

The aim of the move is to improve the quality of the research and speed development of stem cell therapies by the $3 billion agency.

The Science Subcommittee of the agency’s governing board, as expected, unanimously approved the rules, which are nearly certain to be ratified Thursday by the full board at its meeting in Berkeley.

The proposals are part of CIRM 2.0, a major change at the agency initiated by Randy Mills, who became president of the agency last May. 

In addition to the grant regulations, the subcommittee unanimously approved changes in procedures involving the conduct of the closed-door grant review meetings. 

The grant reviewers, formally known as the Grants Working Group, make the de facto decisions on all applications. The agency’s board has legal authority to accept or reject applications, but has almost never rejected a positive recommendation from its blue-ribbon scientific reviewers.

One change involving the scientific reviewers, all of whom come from out-of-state, calls for them to exercise oversight on the progress of the research and on “continued funding.” The reviewers would report their findings to the full CIRM board or the agency’s president. That would be in addition to CIRM staff monitoring and quarterly reviews by new panels of advisors.

Another change in the review process calls for a patient advocate member of the review group to be more actively involved in the review of applications. One advocate would be asked for his or her views on an application but would not score the application. All of the patient advocate members of the review panel are also members of the agency board.

In addition to the seven members from the agency board, including its chairman, each group of reviewers for a particular award round includes 15 scientists from outside California. They are drawn from a list of more than 100.  Their financial and professional interests are not disclosed to the public. Applicants are not notified which researchers review their applications.

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.

Effort to End $500 Million California Stem Cell Research Loan Program Stalls Again

The California stem cell agency has postponed action on a proposal that would have all but eliminated its $500 million loan program, which has been deemed less than worthy.

A subcommittee of the agency’s board had been scheduled to act on the new plan last Thursday. However, the meeting was postponed at the last minute with no public explanation.

In response to a question, Kevin McCormack, senior director for communications, said last week,

“The meeting was postponed so we could work on the proposal some more before bringing it to the subcommittee. The document was removed from the website because it was actually the wrong document. It was an earlier, outdated version of the proposal and didn't reflect many of the changes that were made.” 

However, the plan (dated March 13) remains on the agenda for the full board meeting on this Thursday. Presumably, failure to remove it as well was an oversight. 

(On Monday March 23, the loan item was re-labelled as postponed on the full board meeting agenda. The plan was still available online via the link above as of this writing.)

This is the second postponement on the loan overhaul. The first came in January and also was cancelled late with no public explanation.

Randy Mills, who was named president of the agency about 11 months ago, said in the March 13 memo to the board that the existing loan effort was “overly complex, administratively burdensome, and, as reflected in the number of loans issued, it does not appear to be attractive to industry.”

Only five loans have been made since the program was begun in 2008.  Only two loans are currently active.

The agency has not responded to a March 18 query concerning whether any businesses provided direct input into the loan changes proposed by Mills. 

The existing loan program was the brainchild of Robert Klein, a real estate investment banker who was the agency’s first chairman.

Mills plans to replace the loan program as part of his efforts to speed development of stem cell therapies. No awards have yet been approved under that effort, which began only on Jan. 1.