Thursday, August 02, 2012

Stem Cell Blowback from Proposition 71

Proposition 71 last week once again stood in the way of action by the $3 billion California stem cell agency.

This time it was a bit of minutia embedded in state law that prevented the agency's governing board from going forward. The result is that the board will have to hold another meeting in August to approve matters that need to be acted on in a timely fashion.

The minutia involves the supermajority quorum requirement for the board, the percentage of board members needed to conduct business legally. Proposition 71, the 10,000-word ballot initiative that created the agency in 2004, stipulates that 65 percent of the 29 members of the board be present for action.

Here is what happened: Late last Thursday afternoon, CIRM directors were moving fast after a long day of dealing with $151 million in research awards. But as they attempted to act on proposed changes in the agency's important intellectual property rules, one of the board members left the meeting, presumably to catch a flight. The result was that the meeting quickly ended after it was decided to deal with the IP proposal and another matter during a telephonic meeting this month.

The quorum problem has plagued the CIRM board since its inception, although the situation has eased since J.T. Thomas, a Los Angeles bond financier, was elected chairman in 2011. A few years back, the board also changed its rules to allow a limited number of board members to participate in meetings by telephone, reducing the pressure on board members to physically attend meetings.

The obvious solution would be to change the quorum to 50 percent, a reasonable standard. However, the board is legally barred from doing that. To make the change would require a super, supermajority vote, 70 percent of each house of the state legislature and the signature of the governor. That is another bit that is embedded in state law, courtesy of Proposition 71. To attempt to win a  70 percent legislative vote would involve a political process that could be contentious and also involve some horse-trading that the stem cell agency would not like to see.

Why does the 65-percent quorum requirement exist? Normally, one would think such internal matters are best left to the governing board itself. It is difficult to know why former CIRM Chairman Bob Klein and his associates wrote that requirement into law. But it does allow a minority to have effective veto power over many actions by the governing board.

Of course, there is another way to look at the problem: CIRM board members could change their flights and stick around until all the business is done. But that would ignore the reality that all of them are extremely busy people and have schedules that are more than full.

All of this goes to one of the major policy issues in California -- ballot box budgeting and the use of initiatives that are inflexible and all but impossible to change, even when the state is in the midst of a financial crisis in which the poor, the elderly and school children are the victims. One California economist has called the situation "our special hell."

Tuesday, July 31, 2012

$20 Million in Stem Cell Irony

A bit of irony popped up this week in the wake of approval of $151 million in awards by the California stem cell agency.

One of the awards was $20 million to StemCells, Inc., of Newark, Ca., which is also fighting hard for another $20 million from the state research enterprise.

However, back in 2008, Kenneth Stratton, general counsel for the firm, put some distance between his company and the agency, which is handing out $3 billion in toto.

Stratton said,
"We will take CIRM money last. We don't want to be in a position where, years from now, we are actually forced to sell [our products] in California at a loss."
But last week, Martin McGlynn, CEO of StemCells, said in a press release,
“We are extremely grateful to CIRM for its support.”
Times have changed for both the company and CIRM, which is in the process of altering the intellectual property rules that offended Stratton in 2008. The changes were due to be approved last Thursday, but action was put off by the CIRM board. It was overwhelmed as it dealt with the record pace of appeals by researchers who were scrambling to overturn negative decisions by grant reviewers.

StemCells' application for another $20 million is one of those being appealed. The board will take it up again in either September or late October, after it undergoes additional scrutiny by the agency.

CIRM is touting its IP changes as being more friendly to business. They also can be made retroactive to cover awards to business made in the past. CIRM directors expect to meet by telephone, probably in August, to approve the new IP rules.

Friday, July 27, 2012

News Coverage of CIRM Awards: Substantial but Not Extensive

The California stem cell agency today enjoyed substantial, if sparse, news coverage of the
$151 million in research funding approved by its board yesterday.

Both the San Francisco Chronicle and The Sacramento Bee carried solid stories on the grant awards. In the case of the Chronicle, the story included compelling photos of patients who spoke during emotional, tear-filled presentations.

The stories represent a modest change from the past, when media outlets all but ignored the agency's awards.

The Bee's Richard Chang wrote,
“For Melissa Biliardi of Santa Maria, the (CIRM board) vote symbolizes hope. Her son, James Birdsall, 32, was diagnosed four years ago with Huntington's disease. The degenerative brain disorder could prove fatal over the next 10 to 15 years. There is currently no cure or treatment, but with the grant, UC Davis researchers hope to deliver an effective therapy in four years.
"'This is the most hope we've ever had for a cure or treatment,' Biliardi said.”
The Chronicle's Erin Allday wrote,
“California's stem cell funding agency on Thursday approved nearly $100 million in grants for research into heart disease, cancer and spinal cord injuries, and to the cheers of dozens of patients and their supporters, it also awarded money to rare but devastating diseases with no cure.”
The articles demonstrated the effectiveness of patients and patient advocates in telling the CIRM story. Reporters are always looking for a warm human dimension – especially to enhance a dry, bare-bones science and government story.

Responding to a question from the California Stem Cell Report, Kevin McCormack, spokesman for CIRM, also mentioned radio news coverage in the San Francisco Bay Area. He said the awards were covered in “two different stories on KCBS-AM radio, one that ran several times yesterday and another that ran several times today. KGO-AM radio also ran a story several tim, and, of course, the best of all, today's KQED-FM Forum.”

The KQED show, which was also carried nationally on Sirius radio, consisted of an hour-long look at CIRM, with some calls from listeners. Guests on the show were CIRM President, Alan Trounson, UC Davis stem cell researcher Jan Nolta and yours truly, David Jensen.

Other stories appeared in the SanFrancisco Business Times and Genetic Engineering News. The Bee's story appeared in the Modesto Bee as well.

Thursday, July 26, 2012

Coverage of Directors Meeting Concludes

Coverage of today's meeting of the governing board of the California stem cell agency is now concluded. Late in the afternoon, the board lost its quorum, a supermajority dictated by Prop. 71, and adjourned, leaving a number of items to be dealt with either by a telephonic meeting or the regular session scheduled for early September.

Two More Disease Team Applications Sent Back for More Review

Directors of the California stem cell agency today referred two additional research applications for $37 million in disease team funding back to reviewers for further consideration.

Both were the subjects of appeals by researchers whose proposals were rejected by grant reviewers.

One was from Timothy Hoey of OncoMed Pharmaceuticals in Redwood City, who sought $20 million.  The other was from Henry Klassen of UC Irvine, who sought $17 million. (See here and here for their appeals.)

The  board began the day by directing staff to come back to the board in early September. But with the large number of grants to be reassessed, it was acknowledged some might not be acted on until the board's meeting in late October.

Disease Team Round Hits $151 Million with Final Action

Directors of the California stem cell agency approved an additional $20 million disease team grant today before adjourning their meeting. The grant brought the disease team round to a total of $151 million.

The award went to Judith  Shizuru  of Stanford. Scientist Irv Weissman and Robert Klein, former chairman of the stem cell agency, both spoke on behalf of her appeal of a negative decision by grant reviewers. 

At the suggestion of the current board chairman, J.T. Thomas, the board placed conditions on the grant would stipulate Stanford pick up certain unknown, additional costs if necessary. 

Here is a link to the CIRM press release on today's action.

CIRM Directors Continue Discussion on Disease Team Grants

The CIRM directors are continuing to purse action on the remaining disease team applications. Two more have been sent back for more review. Another is up for approval.

Stem Cell Directors Approve $151 Million to Commercialize Stem Cell Research

Directors of the California stem cell agency today approved $151 million in research awards aimed at commercializing stem cell research and pushing therapies into clinical treatment.


Patients and researchers cheered when the action was announced. 


The awards of up to $20 million each were ratified by CIRM's governing board, which added two to the six applications approved by reviewers. The original six totalled $113 million. Directors budgeted $243 million for today's round.


Five of the applications involving appeals were sent back by the board for more review. (See here, here and here.) They will be considered again in early September or October.

The awards are the second largest research round in CIRM's history, surpassed only by an another, earlier $211 million “disease team” round. The latest effort is aimed at bringing proposed clinical trials to the FDA for approval or possibly starting trials within four years. That deadline coincides roughly with the date when CIRM is scheduled to run out of cash unless new funding sources are developed.

CIRM is currently exploring seeking private financing. It could also ask voters to approve another state bond issue. (Bonds currently provide the only real source of cash for CIRM.)  In either case, the agency needs strong, positive results from its grantees to support a bid for continued funding.

Today's action came after nine out of the 15  applicants who were rejected by reviewers appealed the  negative decisions. Two of the appeals were successful at today's meeting. It is a good bet that at least some of those referred for more review will be ratified by the board in September. 

The appeals were based on a variety of issues, ranging from technical science questions to inconsistencies in CIRM's research approaches and mistakes by reviewers. The outpouring of appeals was the largest in CIRM history in terms of the percentage of applicants seeking to overturn reviewer decisions.

The round also marked another first in terms of the total initially approved by reviewers. On occasion in the past, reviewers have not approved enough awards to consume all the funds budgeted by the CIRM board. But never before has the amount fallen so far short.

Most of the awards went to enterprises connected to persons on 29-member CIRM governing board, continuing a trend that has existed throughout CIRM's history. Board members with conflicts, however, are not allowed to vote or participate in the

The full list of the winners and the CIRM press release can be found here.

(Editor's note: This item was updated from an earlier version and the figures increased as the CIRM board added another grant and took additional action.)

CIRM Board in Executive Session

The governing board of the $3 billion California stem cell agency has gone into executive session to consider confidential information on applications for $20 million disease team awards.

Harvard's McMahon on His Way to USC

Andy McMahon
Harvard photo
The governing board of the California stem cell agency this afternoon approved a $5.7 million grant to lure a Harvard researcher to the University of Southern California in Los Angeles.

The scientist is Andrew McMahon, who serves on the executive committee of the Harvard Stem Cell Institute. CIRM officials said McMahon is ready to begin his work immediately at USC.

McMahon won stellar reviews from CIRM's grant reviewers who said he was an “exceptional scientist and one of the leading young developmental biologists.” Reviewers gave his proposal a score of 90 and, in summary, said,
“Major strengths include the candidate's exceptional productivity and contributions to the fields of mammalian embryology and kidney development, the significance and potential of the research program, the PI's proven leadership capabilities, and the outstanding institutional commitment.”

$18 Million Cedars Sinai ALS Proposal Headed for Approval

The California stem cell agency today cleared the way for approval of an $18 million grant to develop a new cell-based therapy for treatment of ALS.

The agency's governing board moved the application into a category that is expected to approved later today.

The action came on an appeal by researcher Clive Svendsen of Cedars Sinai. Also supporting the application were a number of persons with ALS.

StemCells, Inc., and Capricor Stave Off Rejection from Stem Cell Agency

Two California stem cell firms today won a reprieve from rejection in their bids for $40 million in funding from the California stem cell agency.

They are StemCells, Inc., of Newark and Capricor, Inc. of Beverly Hills. StemCells was founded by Stanford researcher Irv Weissman. Capricor was formed to commercialize research at Cedars of Sinai that had been previously financed in part by the state's $3 billion enterprise. Frank Litvack, who unsuccessfully vied for the chairmanship of the stem cell agency in June 2011, is the recently appointed executive chairman of Capricor.

The CIRM board sent the firms' bids back for more scientific review based on their appeals of reviewers' negative decisions as well as testimony at the board meeting today. The board will take up the applications, which seek $20 million each, again in early September.

Robert Klein, who was the first chairman of the stem cell agency, appeared before his old board as a member of the public on behalf of the StemCells appeal. He said new evidence will be published soon in a scientific journal that supports the StemCells approach. Klein also said that he was personally involved in three CIRM grant reviews in which scientists affirmed the company's approach. (Here are links to the appeal and to grant reviewer comments.)

The other application also involved new information. Litvack, former CEO of Conor Medsystem, told the board the firm has made considerable progress since CIRM's closed-door review of applications last April, both in terms of management and science. The firm's appeal said Litvack's appointment is part of the management improvements at the firm.

Sherry Lansing, a member of the CIRM board and former CEO of a Hollywood film studio, enthusiastically recalled a presentation last year before the board about the results of the initial research. She the firm has solved the problems cited by reviewers. She said,
“We have a fiduciary responsibility to select the best science.”

Stem Cell Directors Order More Consideration on $20 Million UCLA Research Application

Directors of the California stem cell agency today deferred action on a $20 million proposal that was rejected by its grant reviewers and sent it back for more consideration. 

The move involved an application by Stanley Nelson and M. Carrie Miceli of UCLA dealing with Duchenne muscular dystrophy. They are parents of a child with the affliction, which is usually fatal by age 25. The CIRM review summary said it is “a devastating and incurable muscle-wasting disease caused by genetic mutations in the gene that codes for dystrophin, a protein that plays a key role in muscle cell health.”

Nelson had filed an appeal seeking to overturn reviewers' action. Five  mothers and two fathers with children suffering from the disease made emotional appeals to CIRM directors on behalf of the application. Following their presentation, Art Torres, co vice chairman of the CIRM board, responded equally emotionally that the board is dedicated to finding therapies for such afflictions as Duchenne muscular dystrophy

The board approved more review for the application after it was disclosed that a company issued a press release two days ago that showed that  a drug involved in the proposal was more effective than reviewers believed. Philip Pizzo, a member of the board and dean of the Stanford medical school, expressed caution about the press release, given its timing and source. His comments came prior to the appearance of the parents.

The application is scheduled to be brought back to the full board in September for further action.

Rejected Grants May Be Sent Back for More Review

California stem cell agency chairman J.T. Thomas has raised the possibility of sending some of the disease team applications back for additional review if the board feels that is necessary to consider new information and resolve scientific disputes. 

Thomas discussed such a move at the beginning of the discussion of the $243 million disease team round. Nine out of 15 rejected applicants have appealed to the full board.  Some have presented new information. Others have disputed the scientific work of reviewers. 

The board used such a referral process for one application in the past. That grant was ultimately approved.

Discussion Beginning on Disease Team Grants

The governing board of the $3 billion California stem cell agency has begun discussion of applications in the $243 million disease team round. A large number of speakers are in the audience and will be limited to three minutes each.

Short-term Borrowing to Continue to Provide California Stem Cell Cash

The California stem cell agency will continue to be funded with short-term borrowing -- commercial paper -- provided through the state treasurer's office, J.T. Thomas, chairman of the agency's governing board, said today. 

Until late last year, the $3 billion agency was funded through state bond funds, but California Gov. Jerry Brown is trying to reduce the state's long-term debt load, which has skyrocketed in the last decade. 

Thomas told directors this morning that short-term funding comes at "the lowest possible interest rate." He said the arrangement leaves the agency in "very good shape."

The state will provide the funding to CIRM on a month-to-month basis in addition to providing a two month cushion, Thomas said. 

At some point, the short-term debt is likely to covered by state bonds.  As of June 30, CIRM
had $50.9 million on hand, down $42 million from April 30. During the fiscal year ending June 30, the agency paid out $232.7 million compared to $201.4 million in the previous fiscal year. 

California Stem Cell Directors Open Meeting

Today's session of the governing board of the $3 billion California stem cell agency has begun. The major item on the agenda is a $243 million grant round that has triggered a record pace for appeals by rejected applicants. At the request of the California Stem Cell Report, the agency has provided the conflict of interest list used by the agency to determine which directors will not be allowed today to vote or participate in the discussion of specific applications.  The list can be found below. Conflict of Interest List  -- CIRM Directors Meeting 7-26-12ound below.  

Live Coverage of Today's CIRM Board Meeting

The California Stem Cell Report will provide gavel-to-gavel coverage of today's meeting of the governing board of the $3 billion California stem cell agency. Among other things, the board is scheduled to give away anywhere from $113 million to $243 million to help push research into the clinic. Stories will be filed as warranted, based on the Internet audiocast.  Instructions for listening directly to the audiocast can be found on the agenda. The meeting is scheduled to begin at 9 a.m. PDT in Burlingame, Ca., with remote teleconference locations in Los Angeles, La Jolla and Pleasanton. The public can participate and comment from those locations. Addresses can be found on the agenda.

Wednesday, July 25, 2012

The Harsh Message at the California Stem Cell Agency

Grant reviewers have delivered a harsh message in the latest $243 million research round at the California stem cell agency – at least that is one way to look at it.

In effect, they told the governing board of the $3 billion enterprise that the overwhelming majority of applicants in its signature disease team round do not measure up, despite the fact that CIRM had early on partially vetted their efforts. Indeed, the reviewers said that the researchers deserve only $113 million instead of the full $243 million that was budgeted.

Obviously the results of the review can be interpreted in other ways as well. But the review outcome should raise some flags within the stem cell agency and its 29-member board, which meets tomorrow in Burlingame. It may not auger well for future rounds that also involve CIRM's newly energized drive to push research into the clinic.   

One interpretation of the review results could well be that CIRM's goals are unrealistic, that the agency is trying to move too fast for the normally glacial pace of research and development. Another interpretation is that the science is not good enough in California to accomplish what the agency is seeking to do, a view expressed by some in the early days of the nearly 9-year-old program. Another is that the reviewers themselves don't know enough or have failed to do their homework, which some of the rejected applicants have argued in their appeals. Yet another is that the CIRM review process is inadequate to the task of meeting CIRM's goals. And still another interpretation is that the normal peer review process on which CIRM's procedures are based is mightily flawed, a general contention argued by some(See here, here and here.)

Or quite possibly the result of the disease team reviews could reflect a combination of all of the above, to one degree or another.

Little is known about the substance of what goes on during the grant review process, aside from the staff-written review summaries. Even CIRM board members, who see only the summaries, have complained from time to time about not having enough information to make a good judgment on an application. Reviews are conducted behind closed doors. Information about the economic and professional interests of reviewers is withheld from the public by the stem cell agency.  

Here is a look, however, at what we do know. Initially the universe of applicants in this round totalled 36. That was the number that applied for planning grants for this round. Without a planning grant, they could not apply for a full $20 million award, with some exceptions. The exception process was controlled by CIRM President Alan Trounson, not reviewers. CIRM used the planning grants and the exception process not only to assist applicants but to winnow out weak applications.

Nineteen researchers won planning awards. With exceptions included and minus dropouts, 22 applied later for the big money. Out of the 22, only six were recommended for funding by reviewers, who are known more or less formally as the Grants Working Group. (See the four items at the end of this piece for a list of reviewers involved.)

In the past, reviewers have sometimes not approved sufficient applications to consume the entire amount budgeted for a round. But they have never produced a shortfall as great as in this case. It is all the more dramatic since this round carries a lot of weight for CIRM, which is pushing hard to commercialize research and fulfill at least part of the promises that were made to California voters in 2004 to win approval of creation of the stem cell agency.

One reflection of the unusual nature of the round is the record pace of researchers' appeals of negative decisions by reviewers. At least nine of the 15 rejected scientists are willing to say publicly that something is is not quite right in the review process, ranging from missing facts to inconsistencies in CIRM's endorsement of particular paths of research.

It is safe to say that CIRM directors tomorrow will pluck some applications out of the reject bin and increase the total awarded. But they should also examine the process to determine what generated this particular outcome. The Institute of Medicine, which is currently engaged in a $700,000 examination of CIRM, also might scrutinize this round with some care, given its size and importance to the California stem cell research effort.

Riding the Stem Cell Financial Wave in Newark

The stock price of StemCells, Inc., of Newark, Ca., has more than doubled this month following the publication of several “good news” stories about the company, including the virtual certainty that it will receive a $20 million loan tomorrow from the state of California.

The company also could well receive $20 million more if its appeal on another award from the California stem cell agency is successful.

StemCells, Inc., founded by Stanford researcher Irv Weissman, has seen its stock plummet as low as 59 cents during the last 12 months. On July 16, its price stood at 88 cents. On July 17, it jumped to $1.80. Today it is running about $2.28 at the time of this writing. (The latest stock price can be found here.)

All of which is to the benefit of Weissman, who acquired 15,433 shares of StemCells, Inc., on July 2 at no cost. According to SEC filings, the stock was given by the company to Weissman as a quarterly retainer for his services on the firm's scientific advisory board. Weissman also serves on the board of directors and currently holds 88,612 shares of the company.

Most of the good news about the company focused on its research into an Alzheimer's therapy. The California Stem Cell Report also reported on July 18 that the company was in line for a $20 million award from CIRM for its spinal cord injury therapy. CIRM's grant reviewers rejected the company's bid for $20 million for an Alzheimer's treatment but the firm is appealing that decision to the full board. (See here and here.)

Here are links to recent stories on StemCells, Inc.

Seeking Alpha by Chris Katje – July 17

California Stem Cell Report by David Jensen – July 18
First public report that StemCells, Inc. was in line for a $20 million loan from CIRM development of human neural stem cells to treat chronic cervical spinal cord injury

Technology Review by Susan Young – July 24

Tech24 – July 24

StreetInsider.com -- July 24

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