USC Loses Appeal on $20 Million Proposal

Directors of the California stem cell agency this evening rejected an application for a $20 million research grant to a team at the University of the Southern California. 

The team, led by Roberta Diaz Brinton, filed an appeal last month in the $200 million disease team round, which first came up for consideration in July. CIRM staff pointed out that normally such appeals are considered at the time the round is first considered by the board.

The vote was split on the application, but actual tally was not announced by the agency following the vote. (Later, at the request of the California Stem Cell Report, a board spokesman said the vote was 4-10 on the 29-member board.)

Brinton and other investigators spoke to the board along with several patient advocates.

(An earlier version of this item did not contain the 4-10 vote.)

UCLA's Nelson and Miceli Win $6 Million from California Stem Cell Agency

Directors of the California stem cell agency today approved a $6 million research grant for Stanley F. Nelson and M. Carrie Miceli  of UCLA, who appealed a negative decision  by grant reviewers on its earlier $20 million request.

Following a re-review of the proposal, a special CIRM panel recommended the lower amount and conversion of the proposal to an early translational grant instead of a disease team. The UCLA team will be asked to send a revised proposal to CIRM prior to funding.

Nelson told the board that he was "okay" with the revision and said his team would be back later for more funding for a larger project.

UC Irvine's Klassen Wins $17.3 Million from California Stem Cell Agency

Directors of the California stem cell agency this evening approved a $17.3 million grant to Henry Klassen of UC Irvine following a re-review of the application in the agency's disease team round. The action came with no debate.

Capricor Wins $20 Million from California Stem Cell Agency

Directors of the California stem cell agency this evening approved an award of up to $20 million to Capricor, Inc., of Los Angeles, rejecting a negative decision on the application by agency reviewers.

Approval of the application came after a re-review triggered by Capricor's appeal in July. The governing board also declined to impose a staff-recommended condition dealing with the patient cohort.

Discussion of Disease Team Appeals Begins

The CIRM board is beginning the discussion of the appeals on disease team appeals. Thomas is reviewing the procedure for re-reviews of the applications.

Busy Agenda Tonight for CIRM Directors

CIRM Chairman J.T. Thomas just announced that he is going to try act tonight on most of the items on the agenda. Exceptions will be the basic biology grant, recruitment grant and resolutions, which will be taken up tomorrow. Discussion is now underway on the grants administration policy changes.

Routine Reports Being Heard at CIRM Directors Meeting

CIRM directors are now hearing routine financial and other reports from CIRM staff, including President Alan Trounson. The grant appeals have not yet been taken up.

CIRM Directors Meeting Begins

Directors of the $3 billion California stem cell agency have begun their meeting. However, the audiocast was down until just 20 minutes after the hour.

Upcoming Coverage of Action on $243 Million Disease Grants

The California Stem Cell Report will bring you gavel-to-gavel coverage this afternoon and evening of the meeting of the governing board of the $3 billion California stem cell agency. A spokesman says the primary order of business tonight will be finishing action on appeals in the $243 million disease team round and approval of changes in the grants administration policy. The meeting begins at 4 p.m. PDT. It resumes tomorrow at 9 a.m. PDT and is scheduled to go all day.

The session is being audiocast on the Internet. It is also accessible via an 800 number. Interested parties can participate from teleconference locations in La Jolla, Los Angeles and Pleasanton. Details are on the agenda.

Appeals in $243 Million Stem Cell Round Climb to a Record 11

A Stanford researcher is seeking to overturn reviewer rejection of his application for $20 million in the California stem cell agency's largest ever research round and bringing to a record 11 the number of appeals in the round.

The previous record number of appeals in a round was nine in 2010. In the current $243 million disease team round, 11 of 15 applicants rejected by reviewers filed appeals, nine in July and two since then, including the Stanford researcher. Two of the appeals were successful in July. And it appears that three more appeals will be approved, albeit with conditions, later today. 

In his petition to the agency's governing board, Albert Wong of Stanford said,

“This science has been favorably reviewed by CIRM in the past and was on the cusp of funding. Moreover, three recent publications support our approach.”

He said that his team can “refute nearly every negative comment made either through referencing available scientific information or our application.”  Additionally he indicated that his team did not fully understand the opportunities for appeals during the application review process.

Wong and CIRM did not disclose the score on the application (5373), but it was listed next to last on the CIRM list of reviewer summaries.  Generally, those summaries are listed in order of their scientific score ranking.

Wong's appeal is on the agenda for today's meeting of the CIRM governing board, which is expected to act tonight on all the appeals filed in the $243 million disease team round. The $35 million basic biology round is expected to be acted on tomorrow.

Good News on Three Appeals; Not-so-Good News for StemCells Inc. and Klein

A Los Angeles biotech firm, Capricor, Inc., and a UC Irvine researcher, Henry Klassen, appear to be assured tonight of winning their appeals for nearly $20 million each from the California stem cell agency.

A research team at UCLA – Stanley F. Nelson and M. Carrie Miceli – also apparently won its appeal on its application but only on a substantially revised basis, according to a CIRM document. The agency indicated it would fund the grant but at reduced scope and cost – $6 million instead of $20 million.

However, StemCells, Inc., which was publicly supported by the former chairman of the stem cell agency, Robert Klein, lost its appeal for $20 million. The CIRM document said research cited by Klein as contradicting what reviewers identified as a key weakness did not contain “compelling data.”

A fifth applicant who appealed, Tim Hoey of OncoMed Pharmaceutical of Redwod City, Ca., was also rejected during the re-review process on a $20 million application.

The CIRM governing board, in July, sent all five applications back for reconsideration as a result of appeals of negative decisions by reviewers. The move followed a record-breaking level of appeals by researchers during an emotional meeting filled with testimony from patient advocates. The appeals came in a round that was budgeted originally for $243 million and that represents one of the agency's key efforts to commercialize stem cell research.

It was also the first time the agency's governing board has engaged in such an extensive re-review process on applications.

The revised recommendations for funding are scheduled to be acted on tonight at a meeting of the CIRM board in Burlingame, Ca. The panel has almost never rejected positive decisions by its review group and is likely to accept the latest recommendations. The board is deeply concerned about maintaining the integrity of the review process and not rejecting reviewer decisions without ample consideration.

The recommendations for funding on Capricor's application by Linda Marban, CEO of the firm, and the one from UC Irvine by Henry Klassen both contain conditions, but those probably will not stand in the way of acceptance by the applicants. (The executive chairman of Capricor is Frank Litvack, who last year was a candidate for chairman of the California stem cell agency.)

StemCells, Inc., of Newark, Ca., which is a publicly traded firm, had two applications in the disease team round. One dealing with spinal injuries was approved. However, the agency in its re-review of the second, dealing with Alzheimer's, said,

“The reviewers did not feel there was compelling data for neuron migration in the submitted manuscript. This is the manuscript specifically referenced at the ICOC (CIRM governing board) meeting (in July) that prompted the call for additional analysis. The manuscript is not yet accepted, it is 'potentially acceptable' but requires 'major revisions' according to the journal editor note. In addition, however, the studies in this manuscript used mouse NSCs, not the human NSCs proposed for the disease team award....”

In his pitch to the CIRM board, Klein said, “....(W)e have brand-new data that demonstrates and totally contradicts the key weakness on which it was downgraded.”

In the document prepared for the CIRM board, Ellen Feigal, senior vice president for research and development, discussed the re-review process and gave more details on the decisions. She said,

“In consultation with the Chair of the ICOC and CIRM scientific staff, the President and the Co-Vice Chair determined that the additional analysis should be conducted by the Review Chair of the GWG(grant review group), another scientific member of the review panel, and a patient advocate member of the GWG. The additional scientist reviewer was selected based on the expertise necessary to assess the new information. Each of the 3 individuals (chair, scientist, and patient advocate) voted on whether the information changed the funding recommendation by the GWG. A new score was not assigned."

Feigal continued,

“For each application, the information provided or referenced at the board meeting, and associated specific additional material were requested from the applicant. The new information was evaluated in all cases by the GWG Review Chair as well as one of the originally assigned reviewers and a patient advocate.”

Feigal's report does not identify the applicants by name – only by application number. Here is the number and name for those who do not want to wade through the CIRM web site to determine who is who: 5735 Capricor, 5739 Klassen, 5426 UCLA, 5352 Oncomed, 5416 StemCells, Inc.

The California Stem Cell Report will provide gavel-to-gavel coverage of tonight's and tomorrow's meeting of the CIRM board. The session will be audiocast live on the Internet. Interested parties can participate in the meeting at teleconference locations in Pleasanton, Los Angeles and La Jolla. The agency has added another way of listening to the proceedings -- a dial-in method using an 800 number. Details are on the agenda. 

Seven Researchers Appeal in $35 Million California Stem Cell Round

Three more researchers are attempting to overturn rejection of their applications for millions from the $3 billion California stem cell agency, including one who reported detecting an "evil" stem cell earlier this year.

They are competing in the $35 million basic biology grant round to be acted on tomorrow and Thursday by the governing board of the agency. They join four other scientists who are also asking the board to overturn reviewer rejection of their applications.

The latest three appellants are Song Li of UC Berkeley, who is seeking $1.3 million: Yanhong Shi of the City of Hope, who is asking for $1.4 million, and Wange Lu of USC, who is seeking $1.3 million..

Of the total of seven researchers appealing decisions, five received higher scientific scores on their applications than the lowest approved by reviewers.

Of the latest three appellants, Shi received a scientific score of 70, ranking above three grants approved by reviewers. Li's application received a scientific score of 67, ranking above two grants approved by reviewers. Li received international attention last June with published research that identified an “evil” stem cell involving heart disease. CIRM did not release a score for Lu's application but its review summary was listed below that of the lowest scoring application that was approved.

The lower scoring but successful applications were all given the go-ahead on the basis of “programmatic” reasons, which one CIRM document says is designed to allow “consideration of issues beyond scientific merit, such as disease representation and societal impact.” 

Shi defended her application on what CIRM might call programmatic grounds. She also pointed to new developments in her research. Li pointed to his “ground-breaking” findings in June to support his application, research, in this case, that was published. (Li's research on "evil" stem cells was reported early in June, more than two weeks prior to the review of his application. It is unclear whether the research was part of the discussion about his application.)  Lu said that reviewer comments on her application were “biased away from the current state of the art.”

The seven appeals follow a record outpouring in July. During this week's week meeting, the CIRM governing board is expected to move to curb researcher appeals. More are likely be heard in the future as the reviewers diverge from scientific scores as they make their decisions.

(Editor's note: The information on the timing of Li's research on "evil" stem cells and review of his application was not included last night in the original version of this item.)

Serrano Sewell Confirms Departure from Stem Cell Agency

David Serrano Sewell has confirmed that he has resigned as a director of the $3 billion California stem cell agency.

In an email to the California Stem Cell Report, he said he is “excited and honored about the new assignment” on the California state board that regulates physicians. Gov. Jerry Brown appointed Sewell, who is a deputy city attorney for the city of San Francisco, to the board last week.

We reported Sewell's departure from the stem cell agency on Saturday. In his Aug. 30 letter of resignation, he said:

“As a founding ICOC (CIRM governing board) member, it was a privilege to work with Robert Klein, his drive to fulfill our mission – fudning the best science to discover cures – is inspiring. Collectively, our innovative approach has made California the world leader in stem cell research.”

A Business Perspective on Stem Cell Grant Appeals

A stem cell company business executive sent the following comment via email concerning the item on the four appeals that have been filed on grant applications to be considered by the board of the California stem cell agency Wednesday and Thursday:

“I find it very interesting that the academics have found a way to appeal decisions that they do not agree with.  Outstanding for-profit company grant applications have been denied any right of appeal for years. In my discussions with some of the school who are appealing, their common complaint is that the reviewers did not read their applications, must have been someone else’s!  WOW!  Ninety-seven percent of funds to date have gone to the academics. Of the 3 percent, most of it went to three handpicked companies.  Looks like the status quo is not changing.  I predict that a year from now the percentages will be about the same.”

California Stem Cell Agency: A New Board Member and a New Vacancy

The chairs are shifting a tad on the governing board of the $3 billion California stem cell agency as a French immigrant is added, a Latino leaves and a veteran patient advocate is reappointed.

Coming on board for next week's meeting is Anne-Marie Duliege, chief medical officer of Affymax Inc., of Palo Alto, a publicly traded biopharmaceutical company that deals with kidney disease. Leaving is David Serrano Sewell, who has been named to the state Medical Board by Gov. Jerry Brown. Reappointed is Jeff Sheehy, an HIV/AIDs patient advocate who may be the most public face of patient advocates on the stem cell agency.

Anne-Marie Duliege
Affymax Photo

State Controller John Chiang appointed Duliege to the CIRM post, saying, 

“Dr. Duliege brings first-hand knowledge of what is required to take a drug from research phase through FDA approval.”

In May, Duliege made a presentation to the Bioscience Forum in South San Francisco called “Beating the Odds,” a discussion of Affymax's first commercial product. According to information posted by the group, Duliege led the way by shepherding it through a 10-month gauntlet at the FDA.

Duliege has been with Affymax since 2007. Her prior positions included time at Chiron and Genentech. She is a practicing physician, working part-time, and received her medical degree from Paris Medical School.

Affymax has had a previous tie to the stem cell agency. Ted Love, one of the initial members of the CIRM board, also sits on the Affymax board of directors. Indeed, Duliege fills the seat vacated by Love when he resigned from the CIRM board. The position must be filled by an officer of a California life science company.  

David Serrano Sewell
CIRM Photo

Serrano Sewell, who has also served on the CIRM board since its inception, is apparently resigning to accept an appointment to the board that regulates California physicians. Apparently – because the stem cell agency has not confirmed that he is leaving, although this morning it placed a resolution honoring him on the agenda for next week's meeting.  That almost invariably means a board member is departing.

Serrano Sewell, an attorney for the city of San Francisco, was one of 10 patient advocate members on the 29-member board. Sewell was apppointed by the California lieutenant governor. His seat will remain vacant until the current lieutenant governor, Gavin Newsom, makes an appointment, who must also be a patient advocate.

Jeff Sheehy
CIRM Photo

Sheehy was reappointed recently by state Senate President Pro Tem Darrell Steinberg. Sheehy is a communications manager at UC San Francisco and a nationally known HIV/AIDS advocate. He is co-chairman of CIRM's Science Subcommittee and vice chairman of the grants review group. Sheehy leads the discussion of grant applications when they come before the full board in public session.

With the latest shuffling, the board has essentially lost its only African-American member – Ted Love. Eugene Washington, dean of the UCLA medical school, is a member of the board but never attends the meetings. Instead he sends a surrogate. Serrano Sewell's departure brings the number of Hispanics to three, co-vice chairman Art Torres, Francisco Prieto and Marcy Feit. No Asians sit on the board.

Bob Klein, "Lobbying" and Reader Reaction

A robust discussion has arisen concerning Bob Klein and his appearance last month before the governing board of the $3 billion California stem cell agency, a body that he once chaired and an enterprise that he once oversaw.

The comments were triggered by the original "unseemly performance" item on the California Stem Cell Report and a subsequent comment by Francisco Prieto, a longtime member of the board.

The comments discussed whether Klein was manipulated and whether he was engaged in so-called “revolving door” activity – the practice of former government officials, such as Klein, becoming paid representatives of enterprises that were involved with their former agency.

The comments raise a number of interesting questions that we will discuss on the California Stem Cell Report during the next few days.

You can read the remarks by going to this item and scrolling down to the end of the piece.

(Editor's note: Our apologies to some of those who commented for the delay in posting their remarks.)

Nearly $6 Million Sought: Four Scientists Seek to Overturn Rejection by CIRM Reviewers

Four researchers are appealing rejection of their proposals to win millions of dollars from the California stem cell agency just as the agency is moving to curb such reconsideration efforts by scientists.

The latest appeals come in what the agency calls its basic biology round. The agency's governing board meets next Wednesday and Thursday to hand out as much as $35 million to as many as 25 scientists competing for the research dollars.

The four appeals follow a record outpouring last month of attempts at reconsideration in another round. One upshot has been a proposal that would tighten the review process. That plan also comes before directors next week.

In three of the latest appeals, the applications were given scientific scores that exceeded those of some proposals that were approved by reviewers. The lower scoring proposals were given the go-ahead on the basis of “programmatic review,” which one CIRM document says is designed to allow “consideration of issues beyond scientific merit, such as disease representation and societal impact.” 

The latest appeals – formally known as extraordinary petitions – were filed by Michael Teitell of UCLA, Deborah Lieu of UC Davis, Tony Hunter of Salk and Hanna Mikkola, also of UCLA. In all, their applications seek nearly $6 million from CIRM.

Hunter's $1.8 million application had the highest scientific score, 70,  of the four appeals. It ranked above three grants approved by reviewers. 

In his appeal, Hunter said “no major scientific issues were found” by reviewers concerning his application. He also reported new data involving a “major concern” of reviewers. Hunter said the information was developed after the application was submitted April 25.

In the case of Lieu, reviewers said she was “relatively inexperienced.” Lieu's appeal said she has “24 publications with over 6 years of experience in the differentiation of cardiac muscle cells from human pluripotent stem cells, 12 publications (3 co-corresponding author) on human pluripotent stem cells and their cardiac derivatives, and 3 publications on the engineering of pacemaker cells” in addition to other related professional experience.

She is seeking $1.3 million. Her application received a score of 68, ranking it above two other grants approved by reviewers and equal to a third also approved by reviewers.

Mikkola said her application built on work previously funded by CIRM. She also cited new data that the reviewers did not have access to. Mikkola's application for $1.4 million received a score of 65, which ranks it above one grant approved by reviewers.

Teitell's letter to the board also cited new data that is scheduled to published in November that deals with one of the concerns of reviewers. Teitell additionally disputed some of the critical information in the summary of reviewer comments.

He is seeking $1.4 million. CIRM did not release a score on his application, although it appears to be below 63, the lowest score disclosed publicly by the agency.

Stem Cell Agency Moving to Curb Free-Wheeling Appeals by Researchers

The $3 billion California stem cell agency on Tuesday released details of proposed, major changes in how scientists are allowed to appeal decisions when their applications for millions of dollars are rejected by grant reviewers.

The agency posted on its web site a 4 ½ page plan to curb the free-wheeling pitches that reached a record level at last month's governing board meeting. Some of the changes would formalize ad hoc procedures that have emerged over the last several years. The plan would also make it clearer exactly what can and cannot be done or expected under the agency's appeal process, which is poorly understood by at least some researchers.

The agency's proposal, due to be acted on at the CIRM board meeting next Wednesday and Tuesday, is heavily nuanced, dealing with such matters as “supplemental information,” an “additional analysis option,” “criteria for material dispute of fact,” “criteria for material new information” – not to mention the old standby – “extraordinary petition.”

CIRM also reiterates in a footnote its distinction between an “appeal” and an “extraordinary petition.” However, it is a distinction without a difference except to those in thrall of bureaucratic jargon. Both are appeals. Their purpose is to provide a method for overturning reviewers' decision under certain conditions.

Details on CIRM's proposed changes came only four business days prior to next week's governing board meeting – a little late to generate thoughtful comment and constructive suggestions from those most likely to be affected by the changes – the 500 or so recipients of $1.6 billion in CIRM funding. Before final action on the changes, the board may well want to send out the proposal to all of its grant recipients and ask them for written comment that could then be considered at a public meeting of its Science Subcommittee.

The CIRM board has been bedeviled by the appeal process for more than four years, including the presentations at its public meetings by scientists. Ironically, the first such public appearance was made by Bert Lubin, who is now a member of the CIRM board  and CEO of Childrens Hospital in Oakland, Ca..

As the California Stem Cell Report wrote at the time, the pitch by Lubin, who was unsuccessful, disturbed some board members. Gerald Levey, then dean of the UCLA medical school and a member of the board, said,

"I don't think we can run a board this way. If we do, it would be chaos." 

Lubin was later quoted in the journal Nature as saying that his rejected application did not come from “the in crowd” of stem cell researchers or organization.

“So a project that was really going to go into patients was essentially triaged.”

A final note: CIRM's proposal for changes in the appeal process also uses language that obfuscates exactly what researchers can do under state law. The document says that scientists “may” make oral and written comments to the board, which is a state government entity. In fact, state law makes it clear that researchers as well as any member of the public have the “right” to comment. The board legally cannot prevent them from speaking or making comments. And the board, to its credit, has always allowed ample public comment even when it slows the board's work.  

USC Researchers Appeal Rejection of $20 Million Proposal

Researchers from the University of Southern California are making a pitch to overturn rejection of their $20 million grant application by reviewers in one of the signature commercialization rounds of the California stem cell agency.

The appeal by Roberta Diaz Brinton and Lon Schneider will be taken up one week from tomorrow by the governing board of the $3 billion state enterprise.

The USC application deals with Alzheimer's. It came in the $243 million disease team round that was considered last month during a record-breaking outpouring of appeals and a day of emotion-filled appearances by patients. CIRM directors adjourned their meeting without completing action on a number of items, leaving open the possibility of additional appeals such as the one from USC.

The Brinton-Schneider application received a score of 63 from reviewers. They said in a letter to the board,

“We are submitting the petition at this time as we are new to the CIRM ICOC(governing board) process and after listening to the July 26 ICOC meeting deliberations now understand that the petition process allows the ICOC to further consider our proposal. We noted that the proposal scored one point above ours and another two points below ours, each utilized the extraordinary petition strategy to gain ICOC review which resulted in funding approval in the former, and reconsideration in the latter instance.”

Their statement reinforced a concern expressed by CIRM Director Oswald Steward, director of the Reeve Center at UC Irvine,  at last month's board meeting about fairness in the grant process. He said,

“I'm not really quire sure that all of the applicants clearly understood that they could come back to us to address the criticisms(of reviewers).”

Concerns about whether all applicants fully understand the appeal process have surfaced on a number of occasions over the last several years. The CIRM board, however, is generally reluctant to overturn negative recommendations by reviewers. It also almost never reverses positive recommendations.

Next week the board is scheduled to make unspecified changes in the appeal process. No further details on those changes have yet been released by the agency although the meeting is just four business days away.

In the Brinton-Schneider letter to the CIRM board, the scientists defended their scientific approach and responded to criticism by reviewers, especially those related to sedation. Reviewers expressed reservations about over-sedation, which the researchers said were erroneous.

It is not clear whether other scientists will be making appeals during next week's board meeting.

Researcher Alert: Troubling CIRM Grant Appeal Process Up for Revision

Directors of the California stem cell agency next week are expected to make unspecified changes in how scientists can appeal denials of their applications for millions of dollars in research grants.

The move follows a jam-packed and emotional meeting last month in which the CIRM governing board faced a record outpouring of appeals of negative decisions by grant reviewers. The board is the ultimate arbiter on applications. While it almost never overturns positive decisions by reviewers, it sometimes approves applications that they have rejected. 

No details of the proposed changes in the appeal process are yet available for the meeting Sept. 5-6 in Burlingame, Ca. All that is known at this point is the following item from the board agenda: “consideration of modifications to the extraordinary petition policy and adoption of additional information policy.” Extraordinary petitions are the key vehicle for appeals.

The appeals process has long troubled the CIRM board. It has made changes in the procedures, but last month's high stakes, $243 million round posed new challenges and consumed so much time that the board was unable to complete action on several items.

As a result of the July appeals, the board sent five applications back for re-review. (See here, here and here.) Some of those are expected to come up next week and others at the end of October. The board agenda, however, did not specify which applications would be considered next week. Nor did it specify how many additional appeals have been filed in the round that was up for approval in July.