Tuesday, November 30, 2010

Nature Reports on CIRM External Review and Industry Reaction

“Positive review for California stem cell agency” – that's the headline on the Nature magazine's Web site concerning the assessment of CIRM by a blue-ribbon panel.

The piece by Alla Katsnelson began:
"The first comprehensive external review of the California Institute for Regenerative Medicine (CIRM) has come to overwhelmingly positive conclusions about the state stem cell agency’s progress. But some in the biotech community continue to grumble that the agency, which began operations in 2006(sic), is focusing too much on basic research rather than fulfilling its mandate of taking stem cell therapies from bench to bedside."
The Nature article noted that the report recommended more engagement with industry. Katsnelson then wrote,
"But some say that many of these things should already have been done. 'You’ve got to remember, their whole mandate is commercialization,' says Bill Caldwell, CEO of Massachusetts-based(sic) stem cell company Advanced Cell Technology (ACT). What the agency should have done, he says, is identified 3-5 potential therapies that were “low-hanging fruit' in terms of clinical development. 'Let’s get those through and into the clinic so that we can demonstrate to the world that the [human embryonic stem cell] platform has value,' he says.
"Also, Caldwell notes, the agency should already have called for project proposals that tackle some technical areas that need work, such as techniques for the cryoprotection of cells, as well as methods to coax cells into dividing more rapidly. 'These are commercial issues that can help these products move into the market,' he says."
Nature also quoted an item from this Web site.
"A commenter to the California Stem Cell Report blog, identified as 'an executive/scientist from a California biotech firm who must remain anonymous,' echoed Caldwell’s sentiments. 'If CIRM was to hold true to its promise to deliver products in 10 years, then it needed to start translational activities immediately and not building infrastructure for already rich universities like Stanford, who enjoy $10B plus endowments,' the commenter wrote."

(Editor's note: An earlier version of this item incorrectly carried Caldwell's first name as Bob not Bill.)

Monday, November 29, 2010

Torres and Bernstein Mentioned as Potential Candidates for CIRM Chair

The mystery of who will be nominated to chair the $3 billion California stem cell agency for the next six years could be answered this week if four of the state's top elected officials respond in a timely fashion.

It is up to those officials to make the nominations, but already at least two names are floating about – Art Torres, co-vice chair of the agency, and, surprisingly, Alan Bernstein, head of the external review panel that just filed its report on CIRM's programs. Duane Roth, the other co-vice chair of CIRM, is possibly in the mix as well. There could be more.

Bernstein's name has been mentioned by several sources and is reportedly being pushed by outgoing Chairman Robert Klein. Bernstein, executive director of the New York-based Global HIV Vaccine Enterprise, was not involved with CIRM until he led the external review. He has held his current position since 2007. A Canadian, he also was the founding president of the Canadian Institutes of Health Research, which had a budget of $1 billion.

We queried Bernstein about whether he was seeking the post. He replied,
“As to your second question, under Proposition 71, the constitutional officers are the individuals empowered to nominate candidates. To my knowledge, they have not yet sent their nominations to CIRM. If I were nominated, I would make a comment at that time.”
Some of the CIRM board members were skeptical of Torres when he came aboard as vice chairman in 2009, but he seems to have acquired a following. A former state legislator, he brought much-needed Capitol savy to the agency, which was plagued by serious legislative missteps early on, largely the result of actions by Klein. It is clear that Torres is seriously thinking about the post.

Roth comes out of the San Diego business community and has worked on legislative issues as well, particularly in Washington. He has been a strong advocate of bringing CIRM closer to the biotech industry, a position he shares with others on the board.

Also on the table is the question of a salary for the chairman, which he is entitled to under law. No one is publicly discussing numbers. But in 2008, the latest available figure, Bernstein was paid $593,133, including $60,836 in other compensation, at Global Vaccine. Torres currently receives $225,000 on an 80 percent basis. Roth does not receive a salary.

Klein, a real estate investment banker, initially declined a salary in 2004. But he sought one in 2008. The board decided to pay him $150,000 annually for what it considered a half-time position. The current salary range for chairman tops out at $529,000, which is also the maximum for the president and the yet-to-be-filled position of vice president of research and development. Should the new chairman receive a salary anywhere close to the maximum, it is bound to trigger cries of outrage from certain segments of the public. Such a move also would not help CIRM in its dealings in Sacramento, where lawmakers are mired in a financial swamp.

The four constitutional officers who are required by Prop. 71 to make nominations are the governor, lieutenant governor, the treasurer and the controller. The treasurer is a longtime colleague of Torres and is expected to nominate him. The controller has been critical of the agency in his role as chair of the Citizens Financial Accountability Oversight Committee, a panel created by Prop. 71 as a watchdog over CIRM's financial affairs. But he has given no sign of his preferences.

CIRM is hoping to see nominations this week. However, nothing compels the four officeholders to make them. No penalty exists for failure to do so. In cases of other state agencies, top spots are sometimes left open for months, if not longer. Nonetheless, the governor and lieutenant governor may want to make nominations before they leave office. CIRM directors also do not have to actually elect a chairman. If they fail to do so, Klein could continue as chair. Or he could leave the position, and the board could choose another person as acting chair. The board could then ask the politicians for different nominations. If the governor and lieutenant governor do not make nominations by early January, the task would fall to Jerry Brown and Gavin Newsom, who will assume office then as governor and lieutenant governor respectively.

The process for nominating persons for chair, essentially freezing the board out of an important role, was written into Prop. 71 by Klein and his co-authors of the measure. It is another case of inartful language that has made it difficult for the board to do its work.

The state's Little Hoover Commission, California's good government agency, last year recommended changes in the procedure to give directors more authority but those proposals have gone nowhere.

The board is not expected to take up the chairmanship at its Dec. 8 meeting, much of which will be devoted to a discussion and perhaps decisions on recommendations of the external review panel. The board's actions on the proposals could influence a later decision on chairmanship, which could come at a meeting in mid-December.

Bernstein, although chairman of the external panel, told the California Stem Cell Report that he will not be making the group's presentation to the board on Dec. 8. He said that task will be carried out by another member of the panel, Richard Klausner, managing director of The Column Group, venture capital fund.

Bernstein said,
“As you may know, the External Advisory Panel (EAP) has not yet presented its report to CIRM's governing board. EAP's Reporting Chair, Dr. Rick Klausner, will present the report and lead the discussion at the Board's December 8 meeting. In light of this, it would be inappropriate for me to make any comment about the report at this time, let alone respond to an anonymous blogger before CIRM's board has had an opportunity to review and discuss the report.”
In a follow-up email, Bernstein said he was not referring to the California Stem Report in his reference to an anonymous blogger.

BioTime and CIRM Join in hESC Deal

The California stem cell agency has reached an agreement with BioTime of Alameda, Ca., to make five clinical grade hESC cell lines available to California-based researchers, it was announced this morning.

In a news release, Michael West, president of the publicly traded BioTime, said,
“We believe this agreement is in the best interests of both the people of California and BioTime. There are at least three potential benefits to the parties: First, access to cGMP-manufactured cell lines may help CIRM-funded researchers accelerate their work in a wide array of new cell-based therapies and drugs, and more quickly translate the research into improved medical outcomes for people with difficult to treat diseases. Second, the publication of the research results using these cell lines may benefit BioTime's own work to better understand the characteristics of the lines when used to manufacture human therapeutics. Lastly, BioTime may benefit from future commercial revenues from products developed as a result of this collaboration through a royalty-bearing license. The development of standards and open platforms often allows new fields of science and technology to move forward more quickly.”
The BioTime news release continued,
“Research grade versions of the cell lines will be provided to CIRM grantees and California-based institutions free of charge until April 30, 2011 for research use only.

“The GMP grade versions of these cell lines along with a letter of cross-reference to a biologics master file containing manufacturing and controls information and additional documentation needed to establish GMP compliance, and the complete genomic DNA sequence information on the cell lines, will be available to California-based researchers at a price approximating BioTime’s cost of materials by November 22, 2011. Although no royalties will be payable to BioTime by researchers who acquire the cell lines for research use, entities that desire to use the GMP-compliant cell lines for therapeutic or other commercial purposes, may do so only after signing commercialization agreements acceptable to BioTime and entitling BioTime to receive royalties on net sales not to exceed 2.0% of net sales, reducible to 1.5% if the researcher must pay any other royalties in connection with the resulting product commercialization. The researchers will be responsible for obtaining any licenses that may be needed from third parties to use the GMP cell lines in their products. Lastly, the form of a material transfer agreement has been agreed to by CIRM and BioTime for research use. The pre-negotiation of terms will serve to help accelerate research by eliminating protracted negotiations.”

CIRM had not made an announcement of the deal at the time of this writing.

Sunday, November 28, 2010

Biotech Exec Says CIRM Review Misguided, Biased and Disservice to Public

Last week the blue-ribbon panel reviewing the programs at the $3 billion California stem cell agency released its report. We carried an item on the group's recommendations and asked for comment from our readers, promising to carry them verbatim. The following was submitted by an exective/scientist from a California biotech firm who must remain anonymous.
“The review by the external panel is nothing short of froth and it is disingenuous in its honesty towards Californian citizens, who are funding CIRM. The review board was composed of academics and lacked industry experts. The review board continued to suggest focusing on basic research, which is what led to CIRM's current disastrous state in the first place. If the architects of CIRM initially sold the public on the idea that stem cells will deliver products that reduce the healthcare burden within 10 years, and the average drug development process from entry into IND-enabling phase to completion of phase III takes 10 years, then the focus on CIRM from the start should have been on funding game changing translational projects as well as programs that are entering the IND phase. The board is completely misguided in its recommendations and this is not at all a surprise considering its bias. Moreover the board is asking CIRM to fund outside of California research, and this is ridiculous. CIRM is not NIH, and even NIH is perceived to mismanage public dollars and has been scrutinized for its extremely poor translational output to date. Why would we the public of California wish to adopt a broken model and subsidize non-California research with California dollars?

“The external review board should be filled with industry leaders, all of which should come from within the state. California is the birthplace of the greatest biotechs in the world (Amgen, Genentech, Gilead, amongst many others), and yet CIRM refuses to leverage this asset and instead recruits unqualified (in the business realm) academics who have generated very few if any commercial products in their lifetime of work. This is disgraceful and has been a complete waste of $3B of taxpayer dollars. If CIRM was to hold true to its promise to deliver products in 10 years, then it needed to start translational activities immediately and not building infrastructure for already rich universities like Stanford, who enjoy $10B plus endowments. Let Stanford spend from their endowment to build its infrastructure goals, not California's public dollars. This is a complete fraud architected by CIRM insiders, and it will all implode under this failed strategy of making CIRM serve as a funding buffer for drying NIH dollars.

“CIRM’s job is not become a global stem cell leader. Its job is to fund commercialization of stem cell-based technologies that can reduce suffering of Californians. Its job is not to fund basic science. Its job is to focus on translation. Its job is not look to fund research outside of California, as this is 100% California dollars.

“Moreover, the board told an executive attending the meeting during an exchange, that CIRM will not be able to deliver on its promises and it is in trouble. The board shared that it should forget about ever reaching that goal, as there will not be any products coming in 5 years as originally promised to California citizens. Yet, this alarming reality is not reflected in the comments, showing how dishonest and filtered this review report truly is. It is a disservice to the public to lie to them. I am appalled and disgusted by the whole thing to be quite frank, and feel the entire CIRM body needs to be completely overhauled.

“The public would better be served if we treated CIRM as an early stage regenerative medicine focused venture capital firm, since the limited partners (LPs) are the public citizens, and they expect the same return on investment in the same horizon (10 yrs) as what is expected by LPs that invest in venture capital, and have to endure the same risks. Life science VCs do not invest in infrastructure, they do not invest in university programs at the clip of 97%, if at all. They invest in people within corporate structures that have the intellect and talent and experience to bring products to market that solve unmet medical needs, and deliver value over current products. This is not rocket science.”

Bee Readers' Commentary on CIRM Not Warm and Fuzzy

As of late Sunday afternoon, 25 readers of The Sacramento Bee had filed comments on the newspaper's Web site dealing with the California stem cell agency, ranging from violent opposition to mild disgust with the research effort.

The readers were reacting to two pieces on the front page of the Bee's Sunday Forum section dealing with the agency – one by yours truly and one by Larry Goldstein of UC San Diego. The number of comments was quite modest but provides some inkling of the public perception problem facing CIRM. One good sign for CIRM is that the number of comments was small. That can be interpreted to mean that the public doesn't know much about the agency or simply doesn't care, which is better than vehement opposition if CIRM is successful in placing another multibillion dollar bond measure on the ballot. Keep in mind when reading the comments below that those who hold the strongest opinions are the most likely to make public comments. Those in mild support of CIRM are not likely to make the effort.

Here is a sample of the comments:

From "John_Toradze:"
“I am a scientist, one of those rare ones who is also an entrepreneur. And, I'm sorry, but Dr Goldstein is simply not competent to discuss whether California is going to profit by its stem cell investments. Professors learn to spend money in a system that is disconnected from applications. They never learn how money is made in that system. In the grants world, money grows on trees, and it falls into the laps of people who "write good" and have buddies who like them. Peer review committees are notoriously incestuous (at best). Further, science is (and should be) disconnected from profit. Science is about finding out how things work.

“Here's the cold water reality. Currently, there are two clinical trials for stem cells. Neither one came out of the California bond issue. And both of these are simply safety tests. It will be years more before efficacy tests happen. Even if things go extremely well, medicine moves at a snail's pace. So even if both these trials were ours, California won't see money back for a decade.

“But the real kicker is that the California money is a tiny pittance compared to what NIH hands out each year. Simply put, in a Bayh-Dole environment, the relative size of investment makes California's investment into a play against the house at a casino. Science is about being smart, but more than that, it is about being lucky and stumbling across something. Odds are stacked against us.

“Last, as others have pointed out already, embryonic stem cells have problems.”
From “donghofamily:”
“Do we really have $300 million a year to divert from education and basic services of the state? While this is a noble effort, we as California taxpayers cannot afford to fund stem cell research for the world when we can't even meet the basic education and health care needs of our state's citizens. The idea that we would go further into the hole on this is laughable.”
From “Speede:”
“CIRM is one of the greatest scams ever foisted on the people of California.....Now, CIRM, with $2 billion in its coffers, is asking for more taxpayer dollars. It is time to end CIRM and its unquenchable thirst for taxpayer dollars. A history of 10 years with not one therapy to show for $1 billion in expenditures is enough. California taxpayers can't afford another con job designed to enrich a small coterie of insiders.”
From “pressto:”
“Proposition 71 has been a complete waste of $6 billion in taxpayer dollars. What we need is reform on ballot measures so that any spending measure that would be funding out of the general fund requires a 2/3 vote to pass because it has been ridiculous bond measures like Prop 71 that has been the real cause of driving up our deficit.”

The California Stem Cell Agency and the Promises of its Creators

The California stem cell agency drew attention this morning on the front page of The Sacramento Bee's Sunday opinion section in two articles – one by yours truly and one by a San Diego stem cell researcher.

The scientist is Larry Goldstein of UC San Diego, who has received more than $14 million in grants from CIRM. Goldstein wrote that that “viewed against scientific principles, medical need, history and logic – the state's stem cell agency is a calculated but not reckless risk, and it is not merely a bet on a narrow research avenue.” In many ways, Goldstein's article seems to have been written in response to a piece in the New York Times this month that said that CIRM is a risky research endeavor, compared to the NIH, because it is narrowly focused on stem cells instead of a broader range of possible therapies.

Our piece was an overview of CIRM in connection with the promises of the election campaign of 2004 that created the program.

The article noted that the agency this month is facing the results of an external review and the departure of its chairman, Robert Klein. The article said,
"This confluence of self-examination and changing of the guard comes amid criticism over the agency's promise of transparency and openness as it operates independently from oversight of the governor and Legislature; conflicts of interest by a board of directors who have directed $1 billion in grants to universities and research enterprises to which they have links; and the fact that no embryonic stem cell therapy is ready for patients, although the 2004 campaign for Proposition 71 seemed to offer hope for speedy development of cures."
The article concluded,
"Regardless of the outcome of a future bond measure, CIRM is likely to be in business for another decade. It still has about $2 billion to hand out. And despite the 10-year time frame bandied about in the 2004 campaign, no sunset date exists for the stem cell agency. Whether the historic $6 billion investment, which includes $3 billion in interest, ultimately pays off for California – with therapies – is still very much an open question."
You can read the full piece here in The Bee and here.

Text of Bee Article on the State of Affairs at CIRM

Here is the overview piece on the California stem cell agency that appeared Nov. 28, 2010, on the front page of The Sacramento Bee's Sunday's opinion section. The version in The Bee can be found here.  The author is also the publisher/editor of the California Stem Cell Report.

With a review pending, the state's stem cell agency looks for new leadership, new therapies and more money

By David Jensen
Special to The Bee

Lured by visions of nearly magical medical solutions for everything from cancer to Alzheimer's, California voters six years ago approved a plan to borrow billions of dollars to pay scientists to look into human embryonic stem cell research.

Today the unprecedented $3 billion research effort by the California Institute for Regenerative Medicine faces a watershed moment, including the most sweeping review yet of its progress along with the departure of the man whose name has become synonymous with California stem cell research. Additionally, leaders of the program are pressing hard for concrete results that will persuade voters to cough up billions more to continue the effort.

This confluence of self-examination and changing of the guard comes amid criticism over the agency's promise of transparency and openness as it operates independently from oversight of the governor and Legislature; conflicts of interest by a board of directors who have directed $1 billion in grants to universities and research enterprises to which they have links; and the fact that no embryonic stem cell therapy is ready for patients, although the 2004 campaign for Proposition 71 seemed to offer hope for speedy development of cures.

Proposition 71 was described as a 10-year effort that would sidestep the Bush administration's ban on funding of human embryonic stem cell research. Actors Michael J. Fox, who has Parkinson's disease, and the late Christopher Reeve, who played Superman, were featured in ads promising cures in the campaign.

The ballot initiative gave the new state agency $3 billion in state bond financing and has fueled a lab building spree at California research organizations and universities, fed by $271 million in seed money from the California Institute for Regenerative Medicine, known as CIRM. As of this month, CIRM has handed out $1.1 billion to about 400 California scientists and research institutions. That is a pace that runs close to $56,000 an hour since the state treasurer first sold California stem cell bonds on Oct. 4, 2007.

The campaign was headed by Robert Klein, a Palo Alto real estate investment banker who was subsequently chosen chairman of CIRM. Klein says he is stepping down in December at the end of his six-year term. The agency's 29 directors are expected to meet next month to pick a new leader.

Longtime CIRM observer John M. Simpson, stem cell project director for Consumer Watchdog of Santa Monica, said Klein's influence has been so pervasive that it is hard to predict what his departure will mean. "Perhaps, now the agency will move out of its ongoing startup mode and finally develop more routine procedures," Simpson said.

Also next month, the agency's directors will deal with a key, strategic report from a blue-ribbon panel that recently conducted the most sweeping review ever of CIRM's programs. CIRM barred the public from nearly all of the review sessions that were orchestrated over a three-day period at its headquarters in San Francisco.

The report, released Wednesday, had high praise for the agency's work, but it made no attempt to measure CIRM against the campaign promises of 2004. The panel recommended closer ties with the biotech industry, some segments of which have been unhappy with CIRM. It also recommended performing a triage on existing research to weed out nonproductive efforts, a process it warned will irk some patient advocate groups that supported Proposition 71. Also recommended was an improved public relations and public education effort, which will be necessary if voters are to approve more funding. It said the board should consider some management and structural changes in a suggestion that echoed some proposals last year from the state's Little Hoover Commission, the state's good government agency.

In an 88-page report, the Hoover commission proposed a wide range of changes at CIRM. It suggested reducing the size of the unwieldy, 29-member board and the elimination of conflicts in the roles of the chairman and president of CIRM. It also called for more oversight, disclosure of the votes of individual board members on grants and more openness and transparency.

Noting that most of CIRM's grants have gone to institutions connected to its directors, the Hoover commission said that suspicions that CIRM is an "insiders' club" undermine the legitimacy of the agency. Even the prestigious British scientific journal Nature warned in 2008 of "cronyism" at the stem cell agency.

In January, a sister panel to the CIRM board of directors unanimously called for more openness at the agency and endorsed the findings of the Hoover commission. The panel, the Citizens Financial Accountability Oversight Committee, was created by Proposition 71 to provide financial oversight of CIRM. State Controller John Chiang, the state's top fiscal officer and chairman of the committee, said, "To ensure that taxpayer dollars are spent lawfully, wisely and successfully, the stem cell program must pursue the highest standards of transparency to be fully accountable to the public."

In February, state Sen. Elaine Kontominas Alquist, D-San Jose, chair of the Senate Health Committee, introduced something of a reform bill for CIRM. She said in a news release that the agency is "essentially accountable to no one."

But a CIRM lobbying effort, led by former state Sen. Art Torres, now co-vice chair of CIRM, was successful in watering down much of Alquist's proposal, which was ultimately signed into law and will eliminate a 50-person cap on CIRM staff when the legislation goes into effect Jan. 1. Removed from the bill was a provision that would have directed Chiang's committee to conduct a performance audit, the first ever, of the agency. Instead, CIRM itself will commission the performance audit and control its terms.

CIRM laid out its own assessment of its performance last month in a document prepared for the three-day review. The stem cell agency said its spending "contributed" to research published in nearly 600 articles in scientific journals. It said that its awards played a partial role in research that has led to the initial stages of two clinical trials. It cited the funding of labs at institutions throughout the state and points to the spending as a benefit to the California economy. CIRM as well has had a significant impact on the embryonic stem cell scene nationally, keeping it alive and talked about despite the Bush ban.

However, CIRM has not delivered on the overheated campaign rhetoric of 2004. A TV ad featured twin brothers, one with cerebral palsy. The healthy brother said, "His life is different. With stem cells it doesn't have to be that way." In the ballot pamphlet sent to every voter in California, supporters said, "Vote yes on Prop. 71. It could save the life of someone you love."

Consumer Watchdog's Simpson said the "unrealistic expectations created in most voters' minds will continue to haunt the agency."

The campaign rhetoric ignored the slow and tedious nature of scientific inquiry, not to mention the required approval of therapies by federal authorities. Only one clinical trial using human embryonic stem cells is currently under way in the nation. A second was given the go-ahead by the federal government last week. Both are privately funded and do not involve California's stem cell agency. CIRM's strategic plan in 2006 acknowledged that use of the actual therapies will come only years from now.

As Klein gets ready to step down, he is publicly touting another huge bond measure for the ballot – up to $5 billion – that could come as early as 2012. He has pushed for tangible research results that can be used to sell the bond measure to voters, who don't seem to be in a mood for additional government spending.

Regardless of the outcome of a future bond measure, CIRM is likely to be in business for another decade. It still has about $2 billion to hand out. And despite the 10-year time frame bandied about in the 2004 campaign, no sunset date exists for the stem cell agency. Whether the historic $6 billion investment, which includes $3 billion in interest, ultimately pays off for California – with therapies – is still very much an open question.

(David Jensen has been writing about the California stem cell agency since 2005 on his website, the California Stem Cell Report, californiastemcellreport.blogspot.com.)

Wednesday, November 24, 2010

New Directions for CIRM? Closer Links with Industry, Aggressive Search for Innovation, Better Communication

The $3 billion California stem cell agency has done an “extraordinary” job so far, a blue-ribbon review panel said today, and should expand its efforts internationally, create closer ties with the biotech industry and perform triage on its existing portfolio of research grants.

The panel's 19-page report said that the agency now stands at a critical point as its first and only chairman, Robert Klein, is departing, and as it moves more aggressively into development of clinical applications.

The panel encouraged CIRM to seek out innovative projects, even from out-of-state and bring them to California, instead of merely posting requests for grant applications. Industry needs to play a much larger role in funding, the panel said, and it urged changing grant review processes to meet industry needs. “Considerable obstacles to industry engagement remain,” echoing a view stated by biotech firms for past several years. (See here and here.)

The eight-member panel was recruited by CIRM and conducted three days of mostly closed door hearings orchestrated by the agency in San Francisco in October. It was convened as part of the agency's strategic planning process. The panel was not asked to measure CIRM's current results against the campaign promises made in 2004 when voters created the program.

The 29-member CIRM board will discuss the report at its meeting Dec. 8 in Irvine. The subject could come up as early as next Wednesday at a meeting of the directors' Governance Committee.

One recommendation dealt directly with the board itself and the overlapping responsibilities of the chairman and president of the agency, which have been troublesome in the past. Noting that the board has had a “very hands-on approach” during the past six years, the panel's report said.
“We believe this is an appropriate time for the Governing Board to examine its role and composition, mindful of the legal reporting, fiduciary and accountability requirements of the state of California. With the imminent stepping down of the founding Governing Board Chair and CIRM visionary Mr. Robert Klein, it is imperative that the roles and responsibilities of the Governing Board Chair and CEO positions remain distinct but complementary to ensure the continued positive, collaborative partnership between these two key individuals. There should be clarity of the roles and responsibilities of the Governing Board Chair and CEO as it pertains to CIRM’s strategic directions, its policies, international partnerships, funding decisions, public communications and oversight.”
The panel also recommended improvements in CIRM's public relations and education efforts. The panel said,
"(It) strongly encourages CIRM to significantly increase both the quality and breadth of its community outreach and education programs. The objective should be to ensure state-wide visibility and awareness of the contributions that California is making to the global research effort and to create opportunities for Californians to be informed about advances in the research, and to engage in dialogue with the scientific and clinical community about the benefits, limits and resulting guidelines for this exciting area of biomedicine."
Such an effort is all the more important if CIRM is to win approval of the  new, multibillion dollar bond measure that Klein is touting.

The panel had strong praise for CIRM's program so far, particularly since the agency was operating with a staff of less than 50. “Remarkable” and “extraordinary” were a couple of the adjectives. The report said,
“CIRM has built significant additional research capacity in the state, has attracted scores of talented young people to stem cell research, and has catalyzed large and important stem cell projects across the state. The (panel) was most impressed with this rapid start up, the overall quality of the scientists and projects that have been funded, the development of major buildings and other facilities for stem cell research, the forging of several important international partnerships and the innovative training programs that are in place.”
The panel warned that some patient advocate groups might have to lower their expectations as the result of the grant triage, which it called “portfolio prioritization.” The report said,
“While the (the panel) appreciates the natural wishes of disease groups to move forward on particular diseases or conditions, CIRM’s Governing Board, guided by management and external advisors, must begin the difficult process of focusing the number of disease areas to those that it believes have the greatest chance of development progress and clinical success, given reasonable timelines and budget. Attempting to move forward across too broad a front might compromise moving forward on any disease. Undoubtedly, these will be difficult decisions....”
Backers of basic science might also find some reason to be concerned about the emphasis on funding development of clinical applications. However, the report said,
"We strongly encourage CIRM to continue to invest in the research programs, intellectual infrastructure, training and development necessary to advance the understanding of stem cells."
On the international front, the panel said CIRM's efforts should be expanded into non-stem cell areas that could support CIRM's mandate. The agency should "sharpen the focus on meaningful, targeted excellence required for global leadership in the development of innovative treatments based on regenerative medicine."

You can find a list of all the reports recommendations here.

The California Stem Cell Report is interested in hearing from readers about their views on the panel's recommendations and conclusions. You can post them directly by clicking on the word “comments” or you can email them to djensen@californiastemcellreport.com. We will post them verbatim. We encourage writers to identify themselves but anonymous comments are permitted.

Recommendations for CIRM from Blue-ribbon Panel

Here is a list of the recommendations of the blue-ribbon panel concerning the California stem cell agency.
• Build on CIRM’s previous and ongoing investments
• Sharpen the focus on meaningful, targeted excellence required for global leadership in
the development of innovative treatments based on regenerative medicine
• Sustain a vigorous program of fundamental discovery while, at the same time, make
critical choices in translating results from the laboratory to the clinic
• Transition to a much more proactive strategy of funding that aligns CIRM’s peer review
and other processes with its mandate of delivering new treatments to the clinic
• Adopt a porous approach to strategic opportunities, scanning the global environment for
scientific advances that have the potential to enrich CIRM’s portfolio
• Prioritize the investment portfolio, with input from CIRM’s diverse stakeholders
• Build on and expand CIRM’s current international strategy, continuing to develop strategic
international partnerships that will create both scientific and financial synergies
• Assume a global leadership role in addressing not just the scientific, but also the
economic, regulatory, ethical and health delivery issues associated with stem cell
research and regenerative medicine
• Expand engagement with the healthcare industry and explore innovative partnerships that
will catalyze the movement of research from the laboratory to the clinic
• Increase greatly public awareness within the state and internationally of CIRM’s progress
on all fronts of regenerative medicine and the potential and realized health and economic
benefits , through outreach via patient advocacy groups, grantees and their host
institutions, conferences and the internet
• Clarify the roles and responsibilities of the Governing Board and senior management and
specifically between the Governing Board Chair and President in order to maximize the
likelihood of success of CIRM’s mission


The 19-page report from the blue-ribbon panel that reviewed the operations of the California stem cell agency is now available. We will have an item on the report, plus excerpts, a little later this afternoon.

CIRM Management Stumbling at Routine Tasks

Only four business days remain before a key California stem cell agency meeting that will deal with its financial future and the future of its departing chairman, Robert Klein, but the $3 billion state enterprise still is not providing any information to the public on those matters beyond cryptic hints.

The failure to provide the information represents a continuing and inexplicable problem with CIRM, which operates outside the normal oversight for nearly all state agencies. Its standard practice for a year and more has been to delay posting for the public background material on issues to be considered by directors, effectively denying interested parties and the public the ability to comment intelligently on major matters.

The issues coming before the Governance Subcommittee of the CIRM board of directors next Wednesday are not trivial. They could well deal with spending priorities for the next $2 billion that CIRM will hand out and whether it will be able to fulfill the promises of the campaign that created it six years ago. However, the only information that CIRM deigns to give the public describes the matters only as “budget allocations and structural priorities.”

Also up for consideration is the future role for Klein, who has said he will leave as chairman next month at the end of his term. The subcommittee agenda only mentions  “future assignments to and volunteer support by Chair Emeritus.” One likely role for Klein is work on the beginning stages of a campaign for a multibillion dollar bond measure to continue funding CIRM's effort. Unclear is whether CIRM directors intend to pay Klein for work after he leaves the board. Klein has considerable expertise and knowledge that should not be lost to the agency. However, building support for a bond election campaign should not be financed with CIRM's public funds.

The Governance group might also consider his role in the context of the other departing members of its board. They too have history and knowledge that should not be lost. Again, the question of compensation does arise.

Just why the agency does not provide timely information to the public on its meeting agendas is unclear. But at least two possible reasons exist. The agency may not be capable producing of the documents in a timely fashion for a variety of reasons. One likely possibility is that they are stalled on the desk of one of CIRM's top officials, but there are obviously more possibilities. Given that the failure to provide the public with important information is CIRM's standard mode of operation, it could reflect a management breakdown. The inability of an enterprise to perform routine tasks in a routine fashion is also one sign of serious, embedded management problems that are likely to extend well beyond the routine matters.

Another reason for not providing the information to the public is an overt decision by the agency itself to withhold the material, which is a matter of public record by law. Government agencies, both federal and state, sometimes stall in the release of documents for a variety of reasons, which can include a desire to restrict public input in the decision-making process. Another reason could involve an unwillingness to release to the public information that could be embarrassing or involve sensitive – but legally public – information having to do with salaries or compensation.

We cannot say exactly why CIRM does not make the information available in a timely fashion, but for whatever reasons it reflects poorly on the enterprise. The track record the agency is compiling on its lack of transparency will certainly come back to haunt CIRM come bond election time. It would be relatively easy to solve the situation, but CIRM does not seem to have the will to do so.

As for the specific issues coming up next week, the agency just posted a notice that another important meeting will occur one week from Friday that involves the future of the agency. The meeting of the directors' Finance Subcommittee will consider significant changes in its fledgling biotech loan program, once billed as a $500 million effort. Also on the table is an examination of the current, rocky state of the government bond market and the implications for CIRM, which has no other source of funds than state bonds.

All the information that CIRM has provided to the public, which includes the many biotech firms throughout California and hundreds of scientists, is the following:

“Consideration of risk premium options for loan programs, including amendments to warrant coverage requirements in Loan Administration Policy and adoption of interim regulations to offer payback of multiple of loan amount as alternative to warrant coverage. “

“Discussion regarding bond market and future implications for CIRM.”

Tuesday, November 23, 2010

California Stem Cell News: A Not-So-Good Story Line

If one is to believe Google, the top of the news today about the California stem cell agency is a story that relates how its $3 billion effort has failed to deliver on the emotion-ladened campaign promises of 2004.

The piece in the Los Angeles Times, the state's largest circulation newspaper, was ranked No. 2 in a Google news search this morning on the term “California Institute for Regenerative Medicine.” Ranked at No. 1 was a summary of the article. Yahoo news placed the Times article a tad higher than Google, declaring it was No. 1.

The story yesterday by Jack Dolan of the Times' Capitol bureau follows one earlier this month in the New York Times that warned that California voters are not likely to see a good return on their unprecedented investment in stem cell research.

Both stories highlight one of the major challenges facing the state stem cell agency, especially if CIRM seeks another $3 billion to $5 billion from voters in a couple of years.

To win approval of such a bond measure in a statewide election, it will take more than a few hundred research papers, one of the measures of success that CIRM uses. The papers may contribute to the development of the science, but voters expect more tangible results. They want to see paralyzed people walk, blindness cured and memories recovered – all of which are not likely between now and time for an election for more funding for CIRM.,

That is not to say that another bond measure is doomed, but it will take some great science and top-notch marketing – not to mention luck – to win approval of more cash for research.

The story that CIRM wants to see should be much different than Dolan's piece, which does not give the agency much to celebrate, at least in terms of PR.

Dolan wrote,
"Under (CIRM Chairman Robert Klein's) stewardship, the agency has funded research leading to hundreds of scientific papers, but scientists say marketable therapies for maladies such as cancer, Alzheimer's and spinal cord damage promised during the campaign remain years, if not decades, away."
Dolan cited the built-in conflicts of interest at CIRM. He wrote,
"'When you're talking about spending $1.1 billion dollars, there's absolutely no excuse for people making the decision to give themselves the money,' said Robert Fellmeth, executive director of the Center for Public Interest Law at the University of San Diego.

"While board members recuse themselves from voting on grants where they have a direct conflict, the mere presence of so many conflicted members is a concern, Fellmeth said. 'There is a quid pro quo atmosphere that develops, because you defer to each other.'"
Dolan additionally hammered at the high salaries at the upper levels of CIRM, a matter that resonates roundly and negatively with voters.

Little of what he wrote is new to the readers of this blog, but a piece in the Los Angeles Times reaches a new and far wider audience than that of the California Stem Cell Report. A story in the Times also stimulates additional links to the article, sometimes in a manner that does not cast CIRM in the best light.

The Scientist magazine linked to the story in a three-paragraph item that began like this:
“The California Institute for Regenerative Medicine has been plagued with criticisms and doubts during its first six years in operation, yet the chairman of the institute plans to ask state voters for another $3 billion in bonds in 2014 to keep the institute up and running.”

Then there was this headline from blogger Wesley Smith: “CIRM to Try and Sucker Californians Into Letting It Borrow Even More Money." Smith wrote,
"Who cares that California is falling into the ocean fiscally?  Who cares that our taxpayers are groaning under high taxes and an astonishing level of bond debt?  Not the California Institute of Regenerative Medicine.  Like the man-eating plant in (the play) 'Little Shop of Horrors,' its appetite is insatiable.  It wants more!"
Rankings of news stories on Internet search engines, of course, change over time, sometimes in a matter of hours. But pieces such as those in the New York and Los Angeles Times will still be part of the news background for CIRM come election time. Reporters from around the state and nation will find them as part of their coverage of the bond measure. More questions will be asked. And CIRM will need to find some good answers.

Second hESC Trial Scores Significant Media Coverage

FDA's approval of a second clinical trial involving a human embryonic stem cell therapy developed by Advanced Cell Technology attracted wide spread media coverage yesterday and today, but missing were some interesting sidelights.

Stories appeared from Boston to Los Angeles about the effort by the firm, which is headquartered in Santa Monica, Ca.

Alla Katsnelson of Nature magazine wrote,
"The trial will examine the safety of a therapy for Stargardt’s Macular Degeneration, an inherited juvenile eye disease affecting an estimated 1 in 10,000 young people in the US. As the disease progresses, a layer of the retina called the retinal pigment epithelium (RPE) degenerates, causing vision loss. It's hoped the new therapy would also work for other types of macular degeneration, a widespread cause of blindness, particularly in the elderly....

“Macular degeneration has been seen as stem cell therapy’s low-hanging fruit because the cells that need replacing are so accessible, both for delivering the treatment and for monitoring its effects. The eye is also an immune-privileged site – meaning that injections won’t elicit an immune response. Last year, the pharmaceutical giant Pfizer agreed to back the work of researchers at University College, London, who are developing a similar therapy."
Carolyn Johnson of the Boston Globe was one of the few mainstream media writers to note the company's stock price. She said,
"ACT has withstood financial struggles over the past few years, and its stock price closed on Friday at under 5 cents a share. But the small clinical trial that it has gained approval for — to treat 12 patients with Stargardt’s macular dystrophy — will make it the second company in the United States to test a human embryonic stem cell treatment.

"'It’s been a long road. . . . We’ve had our telephones turned off a few times,'’ said Dr. Robert Lanza, chief scientific officer for ACT. 'We’ve hung in there.'"
Unmentioned in the stories was the fact that ACT, lured by the passage of the measure that created the $3 billion California stem cell agency, moved its headquarters from Massachusetts to California in 2005. While ACT has never received a grant from the stem cell agency, it is one of the few companies that has complained publicly at a meeting of CIRM directors about a conflict of interest on the part of a grant reviewer.

The comments by Stephen Kessler in August 2008 were cut off by CIRM Chairman Robert Klein, who said directors needed to discuss the names for CIRM-funded labs before going to lunch.

Also not mentioned were reports that ACT is one of the few companies likely to have applied in CIRM's $50 million clinical trial round.

CIRM carried a straight-forward item about the trial on its research blog.

Writing on his blog, researcher Paul Knoepfler of UC Davis called it “a great day.” He said,
“I think there is reason for cautious optimism. Cell therapy-based approaches to treating blindness together represent a fundamentally new, exciting area.”
Here are links to other stories: New York Times, USA Today, Xinhau, AFP, Science, Los Angeles Times, ACT news release.

Sunday, November 21, 2010

California Stem Cell Directors Take Up Klein's New Role, Future Priorities

An old saying in the world of governance and politics goes like this: “The king is dead. Long live the king.”

It all has to do with transition, power and, in the case of the California stem cell agency, possibly new initiatives.

On Dec. 1, those issues and more will be on the table publicly at the agency. The CIRM directors' Governance Subcommittee is scheduled to deal with at least one aspect of the looming departure of Robert Klein, who has been the majordomo of the Golden State's stem cell experiment since its inception six years ago.

Klein has said he will leave in December at the expiration of his six-year term as chairman. However, should a successor not be chosen, it is conceivable that he would stay on.

The Governance Subcommittee, headed by former Hollywood film studio chief Sherry Lansing, is making plans, however, for the “chair emeritus” after he vacates the post. The agenda for the Dec. 1 meeting has this tidbit: “Consideration of future assignments to and volunteer support by Chair Emeritus.” The agency, however, provided no further information for the public, as is its wont.

One likely possibility is that Klein will continue to work on the multibillion dollar bond measure that he has been talking up for CIRM during the last several months. The proposal could range as high as $5 billion and be on the ballot in less than two years. It is not too early to begin lining up that effort, given magnitude of the challenge. California is mired in a $25 billion financial mess that makes approval of another bond measure problematic, unless something changes. And over the weekend The Sacramento Bee published a piece by Kevin Yamamura that said that state is most likely to be “swimming in red ink” for the next four years.

Also on tap at the Governance meeting is a related and equally cryptic proposal: “Consideration of budget allocations and structural priorities.” Again, the public was not given access to any additional information about this $2 billion matter. That is the amount that the agency has left to spend out of its original $3 billion.

However, the topic of the future spending was explored behind closed doors for three days in October by a blue-ribbon, external panel selected by CIRM, which orchestrated the proceedings. Nonetheless, it was – or should have been --- the most sweeping review ever of CIRM's program. The panel's report is scheduled to be released about the time of the Dec. 1 Governance session.

The panel is expected to make recommendations about future initiatives, possibly identifying some ripe targets that past funding did not hit. CIRM is already sharply focused on funding activities that are likely to generate results that will find favor with voters when a new bond measure is presented.

The Governance meeting is a prelude to the Dec. 8-9 meeting of the full board of directors in Irvine. Last month Klein said he was hoping to bring the entire review panel, including Nobel Laureate Sir Martin Evans from Great Britain, to that meeting for a discussion of the panel report.

Klein also said last month that he wanted to have another full board meeting around Dec. 15 to deal with selection of a new chairman and vice chairman or chairmen. The board cannot pick any individual they want. Instead it must choose from candidates nominated individually by the governor, treasurer, controller and lieutenant governor. Of course, CIRM directors do not have to vote for any of the candidates if they are not to the directors' liking. The board could instead ask for new candidates to be submitted by the politicos. Also, if the current holders of those statewide offices do not make a nomination, the responsibility would fall to those elected earlier this month to replace them.

The public can participate in the Governance meeting at site in San Francisco(2), Los Angeles(2), Palo Alto, Sacramento, Emeryville and Irvine. Specific addresses can be found on the agenda.

Wednesday, November 17, 2010

Knoepfler: NY Times Piece on Stem Cells Not Up to Snuff

We asked Paul Knoepfler, a UC Davis stem cell scientist, if he would care to comment additionally on our item Monday concerning the critical remarks about stem cell research, particularly in California, by Nicholas Wade of the New York Times.

Knoepfler had sharply criticized the article in a piece on his blog, which we differed with on Monday.

Here is what Knoepfler sent along to the California Stem Cell Report.
“David, I disagree with your take on Wade's article. In my opinion the bottom line of what Wade is arguing in his NYT article can be summed up as follows:

“'Scientists, funding agencies, and research rarely succeed. When they do succeed, it is a result of luck. Most often scientists fail spectacularly, in which case they create an illusion that their work is actually making progress when it isn't, or they commit fraud. NIH, NSF, and CIRM have different approaches to funding research, but none are or will be successful overall.'

“To support these arguments, Wade presents no data and no quotes. Apparently readers are supposed to simply rely upon his wisdom.

“The 'icing on the cake' for me is that Wade, despite serving up a veritable Las Vegas buffet of negativity, provides absolutely no proposed solutions to the problems he perceives. He also shares no keen insight into what the future holds, except presumably research, in his opinion, continuing to waste massive amounts of taxpayer money. Where are his prognostications for 2011?

“Contrast Wade's article with the piece by Gina Kolata in the same special section of the NYT. Ms. Kolata's piece is clear, well written, balanced, includes quotes from scientific leaders, and makes predictions. My opinion is that Wade's piece was thrown together at the last minute without editing as a counterpiece to Ms. Kolata's.

“The end result is a confusing article that disparages science and misinforms readers. As someone who has read loads of Wade's previous articles and enjoyed them, I found this one disappointing and disturbing.”

Monday, November 15, 2010

Kerfuffle over NY Times Take on California's Stem Cell Program

Last week, the New York Times published an article that was critical of California's approach to funding scientific research, quickly prompting denunciations that called it a “hit piece” and an “unbelievable attack.”

We differ with those characterizations, some of which seem to stem from a misunderstanding of a comment in the Times about how the NIH is like a manager of a stock index fund, as opposed to California's narrower focus.

The Nov. 8 piece was written by Nicholas Wade, who has had a long and respectable career in science reporting. The article was carried in a special section on “prognostications” about what could be coming up in 2011 in science. The article was not intended as a “balanced” news story. Rather it was an analysis based on Wade's years of covering science. That distinction might have been clear in the print version of the section, but it was easily overlooked on the Web version of the Times. That led to some misunderstandings by readers based on comments that we have read.

Basically Wade said that California – as opposed to the NIH – has made a $6 billion bet (including interest) on a narrow field of science. He wrote,
“By allocating so much money to a single field, California is placing an enormous bet on a single horse, and the chances are substantial that its taxpayers will lose their collective shirt.”
Wade contrasted that approach to the NIH, which funds all sorts of scientific research, instead of just stem cells. He wrote,
“...(T)he National Institutes of Health and the National Science Foundation are like the managers of a stock index fund: they buy everything in the market, and the few spectacular winners make up for all the disasters.

“But just as index fund managers often go astray when they try to improve on the index’s performance by overweighting the stocks they favor, the government can go wrong when it tries to pick winners.”
Writing on his blog Nov. 9, UC Davis stem cell researcher Paul Knoepfler described Wade's article as a “hit piece.” Knoepfler said,
“The NY Times has allowed Mr. Wade to publish in essence an opinion piece smearing stem cell researchers in their Science section.

“NIH is incredibly strict and deliberate in what it funds. NIH funds approximately only the top 10-15% of all grant applications after thorough peer review, which is an extremely low percentage. This hardly reflects 'buying everything', but rather is just the opposite.”
It is clear that Wade's piece reflects his opinion and would not be carried on the front page of the NY Times as a news article. However, his broad-brush analogy about the NIH being akin to a manager of a stock index fund is on the mark. The NIH does not limit its funding to only one brand of research. It is certainly deliberate and approves a small fraction of applications, but those represent a broad range of approaches, just as an index fund for the entire stock market has oil, auto, tech, health, insurance, soap and other companies represented in its portfolio. If Wade were to carry his comments further, he might say that California has only bet on or invested in the biotech sector. That creates an investment risk, looking at it from a financial viewpoint.

Knoepfler also differs with Wade's assertion related to dubious claims involving stem cell research. Wade wrote,
“Stem cell researchers have created an illusion of progress by claiming regular advances in the 12 years since human embryonic stem cells were first developed. But a notable fraction of these claims have turned out to be wrong or fraudulent, and many others have amounted to yet another new way of getting to square one by finding better methods of deriving human embryonic stem cells.”
Knoepfler described that as an attack on embryonic stem cell research and researchers.
“He(Wade) says that us scientists have 'created an illusion of progress' with our claims and that a 'notable fraction of these claims have turned out to be wrong or fraudulent'. Wow. Can you please give me some facts to support such aggressive claims?”
Wade did not carry any evidence supporting his assertion but also carried this sentence,
“Stem cell scientists, while generally avoiding rash promises themselves, have allowed politicians to portray stem cells as a likely cure for all the major diseases.”
Stem cell research has indeed been susceptible to considerable hyperbole, much of it coming during the 2004 election campaign that created the California stem cell program. We are likely to see more as the stem cell agency becomes increasingly serious about asking voters for another $5 billion(actually perhaps $10 billion including interest), as early as 2012.

California patient advocate Don Reed weighed in with a comment on Knoepfler's blog. Reed described the Times article as an “unbelievable attack.” He said that the California stem cell agency has awarded $1 billion and “received” $1 billion in matching funds. In fact, the agency has not received anything remotely like that sum. It has required matching funds on some grants, notably lab construction projects, but that cash is ginned up by applicants. It is reasonable to assume that a goodly portion of those funds would have found their way to the respective institutions even without CIRM's matching requirements.

Wade also had this to say,
“Strangely, for a project that is aimed at regenerative medicine, the arbiters of stem cell research have largely neglected the free lesson that nature is offering as to how regenerative medicine could actually work. Many little animals, like newts and zebra fish, do regenerate parts of their bodies. But their recipe is the reverse of that presented by the advocates of stem cell therapy. Instead of taking a stem cell and trying to convert it into a well-behaved adult tissue, animals like the zebra fish start with the adult cell at the wound site, and walk it backward into a stemlike state from which a new limb grows.

“For the California Institute for Regenerative Medicine to invest its $3 billion in studying newts, rather than building new science buildings on every state campus, might seem the best way of understanding regeneration, but that would be hard to explain to California’s voters, who have been assured stem cell cures are just around the corner. Even if governments do better to avoid picking winners among basic research fields, they can play a necessary role in supporting specific scientific infrastructure that lies beyond the means of individual researchers or universities, like atom-smashers or the human genome project. But even these projects are not guaranteed success.”
Wade's bottom line?
“Basic research, the attempt to understand the fundamental principles of science, is so risky, in fact, that only the federal government is willing to keep pouring money into it. It is a venture that produces far fewer hits than misses.”

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