California's $40 Million Stem Cell Genomics Award Still Hanging Fire

The California stem cell agency's $40 million award to a Stanford-Salk group for stem cell genomics research is not yet a done deal.

The award was approved more than two months ago by the agency's board. However, the proposal is now caught up in a staff review of the nitty-gritty of its details.

 Agency employees, as a routine matter, go through all board-approved applications to be sure all matters are in order, ranging from commitments on matching funds to overall considerations concerning the recipient's research budget.

Sometimes changes are made as the result of the staff review. In rare cases, the recipient declines the award. (See here and here for two stories about recipient rejection of the California agency's cash.)

The California Stem Cell Report earlier today inquired about the status of the stem cell genomics award.

Kevin McCormack, senior director of public communications for the agency, said it had not cleared the staff review. Asked whether there were particular issues, McCormack replied,

“No. Some things just take time.”

The stem cell genomics round was marked by complaints about irregularities, unfairness, score manipulation and the role of its president, Alan Trounson.

In the wake of the award, which was approved on a 6-1 vote by the 29-member board, the agency initiated an examination of the grant review process in the genomics round.

Board member voting on the award was limited because of widespread conflicts of interest among the agency's governing board.

The Long Odds Story of Stem Cell Research

It was the sort of story that Californians did not see during the ballot campaign 10 years ago that created the state's $3 billion stem cell agency.

The story line then was of hope and the imminent prospect of cures for a host of diseases that afflicted half of California's population.

Today in the San Francisco Chronicle, Stephanie Lee wrote of biotech companies that go for more than two decades without ever developing a commercial product. Lee's poster child was Geron Corp., which abandoned stem cell research in 2011 along with a $25 million loan from the stem cell agency.

Lee wrote,

“A company that goes 24 years without ever selling a product may sound unusual. But in biotechnology, it's not that uncommon. 

“Take Geron Corp. in Menlo Park, which has struggled to develop a therapy - any therapy - since its founding in 1990.”

Lee noted that Geron has an accumulated deficit of $893 million in debt since its founding and is now facing a number of lawsuits from unhappy investors.

“Faced with 10- to 15-year timelines and uncertain regulatory outcomes, companies and investors might plow hundreds of millions of dollars into therapies that will never see the light of day.”

Besides Geron, Lee also mentioned Isis Pharmaceuticals and Dendreon Corp. as examples of biotech firms with a lengthy development history.

She wrote,

“Overall, the odds of getting a drug to market aren't much better than gambling in Las Vegas. Only 1 in 5,000 to 10,000 compounds discovered in the lab gains FDA approval.”

Those odds, we should note, do not reflect development of stem cell therapies, but rather simpler substances. The expectation is that odds will go higher for stem cell therapies.

All of which is not the best news for the stem cell agency, although the information is not all that new. It was out there during the 2004 stem cell campaign, but the stem cell community did not want to talk about it, and the mainstream media largely did not report it.

The figures remained unchanged today, although a more positive aura surrounds biotech than has existed for several years. Nonetheless, the story of long odds and fruitless research is one that bedevils the stem cell agency. It will run out of funds for new awards in 2017 and is looking for ways to avoid its financial demise. Creating a new narrative, one with a brighter future, is the agency's task as it tries to develop new funding.

Blog on Break

The California Stem Cell Report will go dark for about a week or so while its producer makes an ocean passage from Zihuatanejo to Puerto Vallarta. Prepare for more stem cell excitement later this month.

Sunlight, Stem Cells and Feathers

California stem cell researcher​/blogger Paul Knoepfler is reporting that he has ruffled some elite feathers in the stem cell community.

In a post last week, the UC Davis scientist said that his heavy coverage of the STAP stem cell flap appears to have offended some. He wrote,

“It seems (the) concept of not talking about bad news is well-entrenched in the stem cell field.... I’ve been informed that I’ve ruffled the feathers of a couple elite VIPs of the stem cell world by covering the STAP stem cell story on my blog and doing the stem cell crowdsourcing experiment. 

“Would they really prefer that we all just skip along merrily singing kumbaya? 

“The reality is that the STAP stem cell situation is a serious threat to the stem cell field. As someone who is a big fan of stem cells and advocates actively for stem cell research, I wasn’t going to turn a blind eye.”

Earlier, Knoepfler also defended his blogging on the subject after stem cell scientist George Daley of Harvard expressed “concern” about the use of social media to discuss the subject. I wrote about that situation on March 7, noting the value of social media as a communications tool.

To get another perspective on the subject, I asked Deborah Blum, the Helen Firstbrook Franklin Professor in the School of Journalism and Mass Communication at the University of Wisconsin, Pulitzer Prize winner and author of five books, for her thoughts. She replied,

“I like social media as a tool for transparency, Dave. It gets criticized for being overwrought, or witch-hunting in nature. But I didn't see that in Paul's post. This may explain, though, why he contacted me on Twitter about a post I wrote a while back called "The Trouble With Scientists" that is a defense of bloggers and smart scientist bloggers. Think of Rosie Redfield's blog post on the so-called arsenic-based life report that helped show the flaws. Or the blog Retraction Watch, by Ivan Oransky, who's both an MD and a journalist. The kind of thoughtful online discussion that I think you saw in Paul's piece adds to efforts to make research more open and more accessible. And acknowledging its flaws is just as important in the process as praising its successes. 

“And I do NOT believe a scientist should be punished for writing responsibly about issues in research. I think it's praiseworthy.”

Knoepfler has added this note to his ruffled feathers item,

“It’s important to point out here that I don’t think this STAP situation, even if it gets even worse, can derail the positive momentum of our field overall, but it can slow things down. Also, the stem cell field needs public trust. When I am out there communicating with the public about stem cells and answering their questions, sadly they often spontaneously mention 'scandals' and 'controversy.' Many folks seem to associate these with the stem cell field already.”

Our take: Trying to bury dubious matters and hide questionable activities has led to the downfall of many organizations and individuals. If the stem cell field is to prosper, especially in age of lightning communications, its leaders should be forthright, open and transparent, whether the matter involves replication of research or conflicts of interest. As the late U.S. Supreme Court Justice Louis Brandeis has been famously quoted, 

“Sunlight is said to be the best of disinfectants."

The Boom in Privatized Science and the California Stem Cell Agency

Billionaire science is booming, the New York Times said today, and it is raising serious concerns along with a hearty huzzah for the infusion of increasingly scarce cash for research.

The lengthy piece by William Broad was headlined, 

“Billionaires with big ideas are privatizing American science."

 Broad wrote,

“American science, long a source of national power and pride, is increasingly becoming a private enterprise. 

“In Washington, budget cuts have left the nation’s research complex reeling. Labs are closing. Scientists are being laid off. Projects are being put on the shelf, especially in the risky, freewheeling realm of basic research. Yet from Silicon Valley to Wall Street, science philanthropy is hot, as many of the richest Americans seek to reinvent themselves as patrons of social progress through science research. 

“The result is a new calculus of influence and priorities that the scientific community views with a mix of gratitude and trepidation.”

The trend has implications for California's $3 billion stem cell agency, which will run out of cash for new awards in 2017. It is currently engaged in what it calls a “sustainability” effort, which simply means it is searching for ways to raise more money. One possibility is another state bond measure, which would require voter approval and an expensive ballot campaign. Another more likely prospect is some sort of private funding arrangement, including creation of a nonprofit organization to accept donations from the very sort of billionaires, plus businesses, that the Times discussed.

In 2008, Eli and Edythe Broad gave $25 million
to UC San Francisco to help build a stem cell
research center funded by the California stem
cell agency. Then Gov. Schwarzenegger (at left)
attended the groundbreaking. Broad stands with
 his wife. Former CIRM Chairman Robert Klein
is in the background with a gray tie.
UCSF photo

The list in the Times is relatively long and includes Bill Gates of Microsoft, Eric Schmidt of Google and Larry Ellison of Oracle. Also mentioned was Eli Broad, who has made large contributions to stem cell efforts in California. Not mentioned, oddly enough, was Denny Sanford, who last fall donated $100 million for stem cell research at UC San Diego.

The Times article said the “personal setting of priorities is precisely what troubles some in the science establishment.” Also raising concerns is the enrichment of elite universities at the expense of poorer ones.

Nonetheless, reporter Broad wrote that the influence of billionaire donors is likely to grow given their wealth and the national budget wars. One study cited in his piece shows that at the 50 leading science research universities, private donors already account for roughly 30 percent of the schools' research money.

One of the priorities of the private donors is translational research, the type currently being emphasized by California's stem cell agency, which some fear could lead to the neglect of basic research. The Times cited an effort begun in 2000 by the Cystic Fibrosis Foundation. The Broad story said,

“With great skill, it used the money to establish partnerships across industry and academia, smashing through the walls that typically form around research teams. By early 2012, the financial surge produced the first treatment for an underlying cause of cystic fibrosis.”

The timeline on that treatment is not too different than what might be considered the timeline set in Prop. 71, which created the California stem cell agency. The ballot measure provided for 10 years of funding via money borrowed by the state. Although the measure was passed in 2004, legal battles delayed issuance of the bonds, meaning that the agency's financial clock has not yet completely run out. As for commercial cures built on agency research, no one at the agency is publicly predicting their entry into the market place within the next three years.

Stem Cell Agency Directors Adjourn Until the End of May

The governing board of the California stem cell agency has concluded its meeting. Here is a link to the agency's press release on the events of the day. The board's next meeting is at the end of May. According to board Chairman Jonathan Thomas, the $3 billion program should have a new president by then.

California Stem Cell Directors Reject Conflict Charge on $13 Million Heart Research Proposal

Directors of the California stem cell agency today rejected a $13 million application for heart research despite allegations that the agency's review involved a conflict of interest.

The vote was 3-8 on the proposal by Eduardo Marban, director of the Cedars-Sinai Heart Institute, who complained that a conflict existed during the review of the application.

The agency said it conducted an "extensive" examination of Marban's charges and determined that no legal violation of the agency's conflict of interest rules had taken place.

Appearing before the board, Marban said that the review was a "white-wash." He also said the CIRM staff's re-examination of the scientific issues was inadequate.

Marban did not disclose specifics of his complaints about the nature of the conflict. Nor did the agency. But he referred to unspecified actions by a "venture capitalist." CIRM said no venture capitalists were involved in the review.

CIRM Director Jeff Sheehy asked CIRM staff whether any California residents were among the reviewers during the grant round involving Marban. Gil Sambrano, CIRM's associate director, review, said there were and indicated they served as "specialists." Sambrano also said one of  the reviewers in the round had a conflict because he was involved in one of the grant applications being reviewed.

CIRM has long contended that to avoid conflicts of interest no persons from California served as grant reviewers. However, Sambrano said that provision applied legally only to members of the grant review group, formally known as the Grant Working Group, and did not apply to the use of specialists. Sambrano said the specialists do not participate in the actual act of scoring during the closed-door reviews of grant applications.

Marban's application received a score of 48 out of 100 with a range of  20 to 74, CIRM disclosed today.

Several members of the board, including Chairman Jonathan Thomas, said it was necessary for the board to respect the opinions of grant reviewers and the conclusions of its staff.

Marban has been highly regarded by the agency, which cited his research during a review earlier today of CIRM's accomplishment. He has received $7 million in grants and a company he founded, Capricor, has received $20 million.

CIRM has long cloaked its grant review process in secrecy, in keeping with the traditions of scientific peer review, even though the awards involve public money. The reviews are conducted in private. The names of the applicants are not disclosed. The names of reviewers are not disclosed. The reviewers' economic, personal and professional interests are not disclosed. Scores on rejected grants are not disclosed, unless the applicant appears publicly before the board. Names of applicants appealing reviewer decisions are not disclosed unless they also communicate publicly with the board. That provision was put in place last year by the board.

The total number of directors voting on the application was only 11 compared to 29 on the board. The number is small because of conflict of interest rules at the agency.

For more on the Marban story, see here and here.

$13 Million Heart Disease Application Up

Directors of the California stem cell agency are taking up the appeal on a $13 million application involving a conflict of interest. 

Link to Approval of $72 Million for Commercialization of Stem Cell Research

The California stem cell agency today approved $72 million for spending in new awards rounds aimed at commercialization of research. Here is a link to the full story, which also involves issues dealing with recruitment of a new president.

Only $402 Million Left for California's Stem Cell Agency

Here is the CIRM chart from today's board meeting

The $3 billion California stem cell agency is down to its last $402 million, according to figures released today.

The nearly 10-year-old research effort is scheduled to run out of cash in 2017 and is looking for ways to continue funding, including possibly asking California voters to authorize more borrowing for stem cell research. The agency operates on funds borrowed by the state (bonds). The borrowing roughly doubles the cost of the program to $6 billion because of the interest on the bonds.

The agency has handed out $1.8 billion so far. About $512.5 million more has been approved in concept. That figure is subject to change until the award rounds officially start with the release of an RFA. The remaining amount is for administration of the CIRM program, which is capped by law at 6 percent of spending.

The figures assumed approval of $72 million in new concept proposals today.

Lunch Break for CIRM Board

Directors of the California stem cell agency are taking a break for lunch. They should resume their formal meeting in about an hour. During lunch, they are hearing a presentation about autism research.

California Approves $72 Million for Stem Cell Commercialization

Directors of the California stem cell agency today approved $72 million to help drive stem cell research into the clinic and commercialization, despite concerns that it would damage the agency's ability to hire a new president.

The total for two concept proposals will consume roughly 14 percent of the agency's remaining cash, leaving only $402 million for future awards.

Director Jeff Sheehy said that the agency is going through money at an "alarming pace" and that approval of the plans would limit the agency's future ability to take advantage of research opportunities. He said the board was basically telling presidential candidates that we want "to hire you to manage the last embers of a dying fire."

The agency is scheduled to run out of cash in 2017.

Other directors were concerned about losing the agency's research momentum. Some said businesses could not wait many months or a year to gain funding.

A motion to delay a decision was rejected on a 7-12 vote. Directors then approved one of the two concept proposals, a $32 million program, on a 14-3 vote with two abstentions.

The proposal will provide up to $32 million for possibly three awards in the agency's business-friendly strategic partnership program ranging from $10 million to $12 million. The objective would be completion of a phase one or phase two clinical trial within three years. Matching funding would be required. Both businesses and non-profits would be eligible with forgivable loans a possibility for businesses.

The largest new proposal will provide up to $40 million for four or five preclinical development awards and was approved on a 19-0 vote. It is aimed both at development activities prior to a phase one clinical trial and at helping to attract future funding. Businesses and non-profits would eligible with businesses possibly taking a forgivable loan.

The posting of a request for applications is scheduled for April and May. Board action on applications would come early next year.

(Editor's note: This item has been revised from an earlier version to reflect action on both proposals and to add new figures on the amount of cash remaining for CIRM.)

Monitoring CIRM at 1 a.m.,

CIRM Director Ken Burtis of UC Davis is participating in today's meeting of the governing board of the California stem cell agency from a teleconference location in Japan. He said that his current time at his location is a little after 1 o'clock in the morning.

Briefing on Stem Cell Portfolio

The first order of business at today's meeting of the governing board of the California stem cell agency is a briefing on the agency's development portfolio. Ellen Feigal, senior vice president for research and development, is speaking.

California Stem Cell Directors Open Meeting

Directors of the $3 billion California stem cell this morning began their meeting in Burlingame, Ca., at 9:05 a.m. PDT. On the agenda is a $13 million grant application that has been rejected by agency reviewers and staff. The applicant, Eduardo Marban, director of the Heart Institute at Cedars-Sinai, has filed an appeal, contending that the review involved an unspecified conflict of interest. Also to be considered are proposals for $72 million for new grant rounds to advance research into the clinic.

Conflict of Interest Charge On California Stem Cell Agenda Today

The California Stem Cell Report will provide live coverage of today's daylong meeting in Burlingame, Ca., of the governing board of the $3 billion California stem cell agency.

On the agenda are $72 million worth of concept proposals aimed at speeding stem cell therapies into the clinic, along with an allegation that a conflict of interest was involved in a $13 million grant application.

The meeting begins at 9 a.m. PDT. For those who would like to listen in live via the Internet, the agenda contains instructions and information about how to see the Power Point presentations being used.

The public can also participate in the meeting, make statements and ask questions at teleconference locations in Japan, Los Angeles(2) and La Jolla. Specific locations are on the agenda.

Conflict of Interest Alleged: Cedars-Sinai Scientist Appeals Rejection of $13 Million for Heart Research

The director of the Cedars-Sinai Heart Institute today asked the governing board of the California stem cell agency to approve his application for $13 million for heart research, declaring that the agency's review of the proposal was tainted by a conflict of interest.

Eduardo Marban
Cedars-Sinai photo

In a letter, Eduardo Marban contested the findings of a CIRM staff review of the conflict allegations. He said,

“The initial review was tainted by conflict of interest concerns. The re-review was conducted by staff in a peremptory manner without the usual CIRM due process: no patient advocates were involved, no comparator grants were evaluated, and no formal review reports have been provided. Only a pithy, dismissive summary by CIRM staff has appeared, and that only yesterday.”

Marban's application was the subject of an article on the California Stem Cell Report yesterday, which discussed the lack of transparency in the agency's grant review process, particularly in relationship to conflicts of interest. The application was quietly removed from CIRM board consideration in December and has been placed on the board's agenda for action tomorrow in Burlingame, Ca.

The agency withheld Marban's name, the names of reviewers and the nature of the conflict charges. Marban did not go into specifics concerning the conflict in his letter today. We have emailed him, seeking details.

Marban has previously received $7 million for research from the agency. Capricor, a company he founded, has received $20 million. The company is scheduled to be highlighted in tomorrow's CIRM governing board meeting as one of its success stories.

In his letter, Marban noted his previous research along with the latest proposal and its clinical potential, an increasingly important consideration for the CIRM board. Marban wrote,

“The commercial potential of (the earlier funded product) has been validated by a collaborative/option agreement between Capricor (the company I founded to develop regenerative therapeutics) and Janssen, an arm of the pharmaceutical giant Johnson and Johnson. This represents the first time that 'big pharma' has partnered with a regenerative medicine biotech to develop a product.”

Marban also said,

“The present proposal (DYNAMIC) is ready to go into patients immediately; it is FDA and IRB approved. In fact, we have a list of 30+ patients who are waiting to be screened for enrollment, as soon as funds are available. These patients are ill, with a mortality exceeding that of many cancers. Indeed, several eligible patients have died in the interlude between the last ICOC meeting, when this proposal might have been funded, and the present.

“DYNAMIC would be the first study in the CIRM portfolio to target hard clinical endpoints (mortality and re-hospitalization) in a very high-risk population (that of advanced heart failure). The population to be studied is very different, and much sicker, than in the ALLSTAR trial.”

Cedar-Sinai's Marban Files Appeal on $13 Million Heart Research Application

Eduardo Marban of Cedars-Sinai today filed a public appeal on his application for $13 million for heart research from the California stem cell agency. The application is the subject of an investigation by the agency into allegations by Marban of a conflict of interest involving the grant review. We will have more details shortly.

California Stem Cell Agency Reviews Its Response to Blue Ribbon Recommendations for Major Changes

The outside counsel for the $3 billion California stem cell agency has revisited actions taken by the agency in the wake of the Institute of Medicine report that recommended sweeping changes to deal with conflicts of interest at the agency, its controversial dual executive arrangement and the fundamental nature of its governing board.

James Harrison of Remcho Johansen and Purcell of San Leandro, Ca., prepared a 21-page report, including attachments, as part of an earlier plan to examine actions by the board in response to the blue ribbon report by the IOM, which cost CIRM $700,000.

The CIRM board greeted the IOM study in 2012 with something less than enthusiasm(see here and here), but has taken some steps to deal at least partially with issues raised by the IOM. Last week the California Stem Cell Report asked the chairman of the study, Harold Shapiro, former president of Princeton University, for his take on Harrison's recap. Shapiro has not responded.

Harrison repeated the agency's contention that only perceived conflicts of interest exist at the agency. And he said the board's alteration of voting procedures appear “to have largely addressed the perception of conflict of interest.” However, most of the document was merely descriptive as opposed to an evaluation of the pros and cons of each agency response. Nor did he compare the CIRM's responses to each of the recommendations of the IOM.

 

Live Coverage of Tomorrow's California Stem Cell Board Meeting

The California Stem Cell Report will provide live coverage of tomorrow's daylong meeting in Burlingame, Ca., of the governing board of the $3 billion California stem cell agency.

On the agenda are $72 million worth of concept proposals aimed at speeding stem cell therapies into the clinic, along with proposed changes in the administration of grants involving hundreds of researchers.

The meeting begins at 9 a.m. PDT. For those who would like to listen in live via the Internet, the agenda contains instructions and information about how to see the Power Point presentations being used.

The public can also participate in the meeting, make statements and ask questions at teleconference locations in Japan, Los Angeles(2) and La Jolla. Specific locations are on the agenda.