$40 Million Genomic Research Effort Planned by California Stem Cell Agency

The California stem cell agency is proposing a $40 million program to set up two stem cell genomic research centers, including possibly one at a for-profit research enterprise.

The plan would augment an existing program in genomics or bioinformatics, according to a CIRM document. The goal is to rapidly build "an effective stem cell genomics infrastructure that will provide a new platform for the application of genomics tools to stem cell biology and regenerative medicine."

The proposal is scheduled to be considered at a meeting of the CIRM directors Science Subcommittee next Wednesday. It will then go to the full CIRM board at its Jan. 17 meeting.

The stem cell agency's proposal said,

"Genomics technologies and the data sets they yield are fast becoming the currency of biology and medicine. The cost of genome sequencing is dropping exponentially, a trend that will soon make genome-scale characterization a practical tool for fundamental studies of stem cell biology and for advancing therapeutic applications. Meanwhile, cell therapeutics are advancing toward clinical trials, and hES and hiPS cells have become the gold standard for studying human cell biology, tissue and organ development and repair, and disease. Combining genomic technologies with stem cell research will accelerate fundamental understanding of human biology, disease mechanisms, tissue engineering and cell therapies...."

The RFA for the proposal would be released in May with board approval of applications in the winter of 2013.

Interested parties can participate in the meeting at locations in San Francisco, Irvine, Oakland, Pleasanton, Duarte, Los Angeles (2), Stanford, Healdsburg and Irvine. Addresses can be found on the agenda for the meeting.

Golden State Stem Cell Agency to Give Away $42,237 an Hour This Year

The California stem cell agency plans to hand out $370 million this year, including a whopping $240 million in what it calls its disease team round.

That amounts to $42,237 every hour of every day of 2012.

Amy Adams, CIRM's communications manager, reported the $370 million figure in the CIRM research blog, which she edits. The other rounds of funding for 2012, Adams wrote, include $95 million for early translational research, $35 million for basic biology and $2.2 million for stem cell research by high school students. Those funds would be routed through universities.

So far CIRM has handed out $1.2 billion to 454 recipients in the seven years it has been in business. It is expected to run out of its $3 billion in about 2017 unless it secures voter approval of more bond funding or some other source of revenue.

Adams' item on the funding expected to be approved this year is part of CIRM's efforts to make its research blog more lively and newsy. Indeed, unless we are mistaken, it is the first time in the history of the agency that it has laid out its funding plans for a forthcoming year in a single public document.

In her item, Adams also pointed to various locations on the CIRM web site where interested parties can track the agency's affairs.

The changes in the blog are a step in the right direction, laying out not only more information but also racheting up the interest level.

A Stem Cell Word Cloud: Slicing and Dicing CIRM Grants

The $3 billion California stem cell agency has handed out 454 grants since its inception in 2004 but what does it all mean?

Stem cell researcher Paul Knoepfler took a crack at an unusual analysis a couple of days ago, generating a word cloud from the titles of all the CIRM grants.

Writing on his blog, the UC Davis scientist and CIRM grant recipient said he was surprised by some of the results, including how small the word "induced" was in the cloud considering the hooha over induced pluripotent cells. Knoepfler also wrote,

"I found it fascinating that the next top word was 'differentiation.' As much as we all focus on stem cells in their native state, clearly the differentiation of stem cells is critically important."

Knoepfler used a free, word-cloud forming utility(Wordle) to generate the results, which Amy Adams, CIRM's communications manager, called "cool."

San Jose Merc to California Stem Cell Agency: Time to Bow Out

The $3 billion California stem cell agency should shut its doors when its cash runs out in about six years and turn over development of stem cell therapies to industry and academe, the San Jose Mercury News said in an editorial on Saturday.

The piece in the leading newspaper in California's Silicon Valley was headlined, "Stem Cell Institute Should Take a Bow (Out)."

The newspaper wrote,

"This state is in financial crisis with no full recovery in sight. Bankrolling the next phase of research would come at the expense of other critical state services, including public education, that are state government's core mission and already are starved by budget cuts. It would be a mistake to pile more debt onto the state's already heavy bond obligations, which are paid off from the same general fund that pays for schools and other services. Medical research is important, but it is not at the heart of state government's mission. Bond measures now need to deal with water supplies and other looming crises."

The editorial said CIRM has provided a "strong foundation from which universities and companies can move toward cures."

But the newspaper concluded,

"Cures remain elusive -- there is never a guarantee with scientific research -- but the 10-year start voters approved was meant to be just that. The promise of stem cell treatments now must be kept alive with funding from industry, academic institutions and private foundations and philanthropists."

The editorial comes as the seven-year-old agency is driving to turn research into therapies that can actually be used in treatments. At the same time, CIRM is considering asking California voters to approve another multibillion bond measure in the next few years, a proposal that seems to be fresh news to many in the media.

The San Jose newspaper covered the stem cell agency with some detail in its first year of operation. In the last few years, however, the paper's coverage has been all but non-existent, like most of the news media in California.

Earlier this month, the paper published an overview of the agency, which highlighted the discussions by former CIRM Chairman Bob Klein about another bond issue, along with the fact that the cures promised by the campaign of 2004 have not materialized. The proposed bond issue is old news for most persons who have followed CIRM; the plan has been around publicly for more than a year. But the call for more cash comes a surprise to many of in the media. And to the public. So it is likely to pop up again as other news outlets re-visit the agency from time to time.

The presence of another electoral campaign also imposes a different sort of burden on CIRM – something quite removed from such matters as the basic biology of stem cells. It means that the stem cell agency's endeavors are being evaluated in a political context, which involves such questions as whether its actions are designed to generate the millions in campaign contributions necessary to win a statewide election or whether it is neglecting valuable research for something that will instead generate a high profile result for the benefit of the campaign but not add much to the science.

It is all part of tactics and strategy involved in the "communications war" that CIRM Chairman Jonathan Thomas discussed with CIRM board members last June in his bid to win election to his post.

ACT and CIRM: Fresh Life in a Troubled California Stem Cell Courtship?

Advanced Cell Technology, which has unsuccessfully sought funding several times from the $3 billion California stem cell agency, drew some attention today in a piece in a Massachusetts newspaper.

The Worcester Telegram took a look at the firm, headquartered in Santa Monica, Ca., with labs in Marlboro, Mass., in the wake of Geron's departure from hESC research. The move left ACT as the only firm in the country with an hESC trial and perhaps with a better shot at CIRM funding.

Reporter Lisa Eckelbecker wrote,

"Advanced Cell, publicly traded since 2005, has spent years developing its technologies. The company brings in little revenue and has an accumulated deficit of $180.9 million. About 1.6 billion shares of Advanced Cell common stock is outstanding, a result of numerous financings over the years. It trades for about 10 cents a share on the Over-the-Counter Bulletin Board, an electronic exchange for small companies. No analysts from major Wall Street banks report on the company.

"The company's treatment for Stargardt's macular dystrophy and dry age-related macular degeneration — the treatment that required (a) mountain of paperwork before the FDA — first went into the eyes of patients in July in Los Angeles. The retinal pigment epithelial cells, generated from embryonic stem cells, were developed to slow the progression of the eye disorders, which can lead to blindness."

ACT moved its headquarters to California following the passage of Prop. 71 in 2004, the ballot initiative that created the California stem cell agency. The company said at the time it expected to "gain significant momentum by being able to take advantage of a favorable environment for funding."

ACT initially landed in Alameda, Ca., but has since moved to Southern California. Its official opening in 2006 in Alameda was attended by the state treasurer and at least one CIRM official, according to the company. The firm has never secured funding from the stem cell agency, which does not release the names of rejected applicants. However, the California Stem Cell Report carried an item in 2008 that pointed out that a researcher for ACT complained publicly about a reviewer's conflict of interest in connection with an ACT application(see here and here). At the time, Robert Klein, then CIRM chairman, brushed off the complaint. The journal Nature has also reported that ACT has applied unsuccessfully several times for CIRM awards.

It is a fair bet that ACT was an initial applicant in the round that provided funding to Geron last spring. However, by the time Geron's application went to the full CIRM board, the other applicants had withdrawn – the first time such an event had occurred at CIRM.

Since Geron pulled out of the hESC business last month, it is likely that ACT and CIRM have opened fresh discussions, given their mutual interest in producing a stem cell therapy. CIRM also has a new chairman who is familiar with ACT. After Geron was awarded its $25 million loan from CIRM last May, the agency's board elected as chairman a Los Angeles bond financier, Jonathan Thomas, who led an early round of financing for ACT in 2000. Thomas last summer sold his remaining 17,046 shares in ACT for $3,239. Thomas said he had a "significant loss" on the sale but did not disclose the amount.

Geron's flight from hESC and ACT's perserverance come as the stem cell agency is pushing aggressively to drive research into the clinic. Plus CIRM needs tangible results that voters can understand if CIRM is win ballot-box approval for continued funding in the next few years. The agency will run out of cash in about 2017 and is considering mounting a campaign for another multibillion bond issue.

IOM Looking for New Member for Its CIRM Performance Panel

If you want to serve on the Institute of Medicine panel examining the $3 billion California stem cell agency, you have a chance during the next few weeks.

The panel has lost a member because of a conflict of interest and is now engaged in the process of replacing him. The IOM will consider both expressions of interest and suggestions for candidates. Currently, the panel has no member from California, which leaves it minus an important perspective.

Christine Stencel, senior media relations officer for the IOM, told the California Stem Cell Report that the IOM expects to fill vacancy by its meeting Jan. 24 in California.

David Scadden of Harvard resigned from the IOM/CIRM panel earlier this month because of his ties to Fate Therapeutics of San Diego, which lists him as a scientific founder.

Persons interested in serving or nominating candidates can email Adrienne Stith at Astith@nas.edu.

Stem Cell Awards of the Year: From Geron to iPS 'Warts'

The end of the year is a traditional time for the media to come up with lists of both the dubious and meritorious events and personages of the year. This year's nominations from a California stem cell researcher include Geron, Roman Reed and the new chairman of the California stem cell agency.

Paul Knoepfler, a stem cell scientist at UC Davis and one of the few stem cell scientists who blogs regularly, today revealed his awards for 2011. They ranged from the political cartoon of the year to the stem cell scientific issue of the year.

Geron was named in the "misstep of the year." Knoepfler wrote,

"You guys really screwed up by dropping your stem cell program in this manner. I believe this bordered on the unethical. I commend the actual stem cell scientists at Geron, but the person(s) who as leaders pulled the trigger on killing the stem cell program did wrong."

Roman Reed was named "stem cell activist of the year." Reed is the man who came up with the CIRM motto several years ago, "Turning stem cells into cures." He has long been active on stem cell issues, along with his equally hard-working father, Don Reed.

Jonathan Thomas, the relatively new chairman of the stem cell agency, was named "stem cell leader of the year." Thomas was elected chairman of the agency in June, replacing Bob Klein, who stepped down. Knoepfler wrote that Thomas "has impressed the stem cell community and made some very positive changes at CIRM to make an awesome organization even better."

Knoepfler has much more,  including the stem cell biotech of the year –
Advanced Cell Technology of Santa Monica, Ca. – which Knoepfler said has two hESC trials on track and an "impressive scientific leadership." Not to be overlooked is the stem cell scientific issue of the year – "warts" or genetic changes -- at least possible ones involving iPS cells. Knoepfler points out that the subject has drawn a vast number of citations in journal articles.

We should not forget the stem cell blog of the year, which came in as a tie between Stem Cell Network of Canada and Stem Cell Assays by William Gunn of San Diego and Alexey Berseney of Philadelphia. Knoepfler also mentioned the CIRM Research Blog, overseen by Amy Adams, and the California Stem Cell Report. Knoepfler said the California Stem Cell Report "is read by a who’s who of the stem cell world, and is a source of important information about CIRM," although Knoepfler said he wished the blog was more balanced "in terms of positive and critical stories." However, Knoepfler did note that several more positive items have appeared recently, but this analyst warns of the perils of excessive exuberance.

New Multibillion Dollar Stem Cell Bond Measure Wins Endorsement with a Caveat

A blogger on the web site of Los Angeles television station KNBC today supported a new multibillion bond measure for the California stem cell agency but with an interesting qualification.

Joe Mathews, author and a senior fellow at the New America Foundation, said the new bonds should be backed by a tax on the people and companies involved in the business of health care. He wrote,

"New stem cell moneys can't come out of funds that would otherwise go to other programs."

Mathews said voters "probably" shouldn't approve another multibillion dollar bond measure for CIRM that is paid back through the state's general fund. He wrote, however,

"(T)hat doesn't necessarily mean there shouldn't be another stem cell bond. California's major universities have invested in stem cell research, with help from the agency.

"Major researchers have relocated to the state. And the unknown nature of stem cell research's promise, while frustrating efforts to justify the research dollar for dollar, argues for doing more to learn more.

"What the state budget picture does require is that any stem cell bond should have a clear funding mechanism -- a specific tax or new revenue source (some sort of levy on companies and people involved in the business of health care) -- that would be more than enough to pay back any bond."

Mathews is co-author of "California Crackup: How Reform Broke the Golden State and How We Can Fix It," which declares that the initiative process is one of major fault points in California government. The initiative was used to create the $3 billion stem cell agency in 2004, making it immune from normal state government accountability and locking in funding that cannot be touched by the legislature or government despite any other financial needs of the state.

CIRM's Thomas Blogs on Geron and the Stem Cell Business

The chairman of the $3 billion California stem cell agency has made his second entry into the blogosphere, this time adding a bit more on Geron's abandonment of what would have been its historic hESC clinical trial.

Jonathan Thomas, a Los Angeles bond financier, wrote yesterday on the CIRM research blog, which has recently been the site of more spritely and relevant items.

Geron's action has particular relevance for CIRM, which awarded the company a $25 million loan last May to help with the clinical trial.

Thomas said CIRM's "immediate concern" when officials heard the surprise news was for the patients and the families involved in the trials. Thomas continued,

"However, Geron is a business. The company decided that their cancer therapies were farther along than the stem cell trial and when they held the stem cell program against the prism of economic reality they made a business decision to end the trial."

Thomas also minimized the importance of Geron to CIRM. He said,

"CIRM’s award to Geron was just one of the 44 projects in 26 disease areas that are in various stages of working toward clinical trials."

It was a somewhat different story last May when former stem cell agency chairman Robert Klein said in a widely distributed CIRM news release,

"Supporting the Geron trial is a landmark step for CIRM."

Regardless of the spin on Geron from either CIRM or others who are more skeptical, Thomas' entry into the world of electronic media is to be applauded as is what appears to be a new direction in the research blog.

The CIRM blog is now newsier, more lively with more variety and more voices. All of which should redound, albeit modestly, to CIRM efforts to improve its communications with the public and opinion makers. The difficult thing about blogs, however, is the time and effort required to sustain them, and the task could be something of a communications test for CIRM. Blogs constantly need to be fed. Indeed, blogs are voracious, sort of like the carnivorous plant called Seymour in "The Little Shop of Horrors." As many of you may recall, Seymour had a simple but insistent refrain, "Feed me, feed me, feed me."

Klein, Moral Mandates and Stem Cells

Just a few days ago, the California Stem Cell Report carried an item about the state's stem cell agency and its supporters' mantra that the agency has a mandate from voters albeit one that is seven years old.

We mentioned that Robert Klein, the former chairman of the agency and head of the 2004 ballot campaign that launched CIRM, is one of those fond of citing voter mandates with great regularity.

Indeed, Klein found shelter again this week under a voter mandate, but this time it was a moral one.

Klein popped up in a San Jose Mercury story about the status of the stem cell agency. Writer Steve Johnson said that Klein declared that he quit as chairman last June in part because he wants to raise money for a campaign for another multibillion bond measure for CIRM. Johnson quoted Klein as saying,

"It would be a huge failing in meeting our moral mandate" to let CIRM die. "We can't afford to break the momentum."

As we noted on Dec. 6, mandates come and go, as another multibillion California bond program, high speed rail, has discovered.

San Jose Mercury News: California Stem Cell Agency Eyeing More Bonds but Has No Treatments

In an overview of the $3 billion California stem cell agency, the San Jose Mercury News says that CIRM "still has no treatments on the market and is at a critical juncture that could determine how much longer it stays in operation. "

The story is the second significant piece about CIRM this week in a major California newspaper, which has not received much coverage in the mainstream media in the state in the last year or so. The Los Angeles Times earlier this week carried a column that raised questions about the "Geron fiasco" involving CIRM and the conduct of the agency's business.

The San Jose article yesterday by Steve Johnson said that voters "may not be as enthusiastic" about providing several billion dollars more to finance the agency as they were when they created it seven years ago.

The newspaper, located in the heart of California's Silicon Valley, quoted John Simpson, stem cell project director of Consumer Watchdog of Santa Monica, Ca., as saying,

"I think it's crazy. The state's economy is in a far different position now. We're not even able to provide adequate funding for education."

Johnson also reported that former CIRM Chairman Robert Klein, who led the 2004 Prop. 71 campaign, is raising or intends to raise funds for another bond issue, perhaps in 2014. The agency will run out of cash in about 2017, according to its projections.

The article noted that CIRM has awarded only $83.4 million to 15 businesses, which are the key to pushing research into the clinic,  out of the $1.3 billion it has handed out. Johnson wrote,

"Many businesses have been deterred from even trying to make stem-cell treatments because of how long it might take.

"'It's a challenge,' said Rodney Young, chief financial officer at Newark-based StemCells, which hopes early next year to obtain a $20 million institute grant to determine if a type of adult stem cell can slow the loss of cognitive function in Alzheimer's patients. 'It's an expensive, uncertain and long process.'"

Johnson additionally noted that CIRM has received criticism for the high salaries it pays its top executives and for conflicts of interests.

Directors of the California Stem Cell Conclude Meeting

Directors of the California stem cell agency have just ended their meeting in Los Angeles. Our coverage of the session today is now concluded. Here is a link to the CIRM news release on the meeting.

$30 Million 'Disease-in-Dish" Plan Wins Go-ahead from California Stem Cell Agency

Directors of the California stem cell agency today approved a $30 million program that could generate "disease-in-a-dish models" that "have the potential to make drug discovery faster, more efficient and more personalized to individual patients."

The "human pluripotent stem cell (hPSC) initiative" is aimed at generating high quality stem cell-based tools for use by the researchers and drug developers.

The proposal includes four elements, one of which is a $300,000 collaboration with the NIH to develop cell lines from patients with Huntington’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis. The plan includes a $4 million disease line award round, a $16 million core hiPSC derivation round and a $10 million stem cell bank round. The RFAs would go out in May of next year with funding expected early in 2013.

The initial staff memo on the initiative did not mention human embryonic stem cells, but a spokeswoman for the agency said they were not excluded from the effort.

California Stem Cell Agency Approves $27 Million To Hasten Stem Cell Therapies

Efforts to speed development of stem cell therapies received a $27 million boost today from directors of the $3 billion California stem cell agency.

They approved two initiatives that grew out of recommendations from a blue-ribbon panel that CIRM organized last year to review its operations.

One element in the plan is a $12 million "bridging fund" that would apply only to current CIRM-funded projects in three areas: disease team grants, some early translational projects and clinical development projects. The bridging fund would provide up to $3 million for up to one year for each recipient.

As originally proposed by CIRM staff, CIRM President Alan Trounson would have been authorized to approve each project. However, the board altered that process to require board approval with "peer review input."

Director Shlomo Melmed, a senior vice president at Cedars-Sinai in Los Angeles, argued that leaving the decision to Trounson and staff could place Trounson in an "untenable" position and lead to second-guessing. Melmed and others also said that process could open the agency to public criticism.

Trounson and other staff members said that biotech firms often need speedier action than can be provided by a more extended process. Director Jonathan Shestack, a Hollywood producer, agreed, but he was the lone vote to oppose removing the authority from Trounson.

No biotech companies spoke out at the meeting concerning the proposal (see here for an earlier version of the plan).

The second part of the response to the review panel's finding is a $15 million "external innovation initiative" to support collaborative efforts of CIRM grantees to work with teams that CIRM said are "making extraordinary progress outside California."

The $15 million program would provide awards as often as two times a year. The maximum amount on each award was not specified. The program was approved on a unanimous voice vote.

Ellen Feigal, CIRM's vice president of research and development, said in a memo to directors that examples of potential projects included collaborative efforts with the NIH and work with the Harvard Stem Cell Institute and its disease-focused programs. CIRM is planning to spend $300,000 over two years in work with the NIH.

Some of the latest CIRM initiatives are open to biotech businesses. Others are open only to non-profit or academic researchers.

Internet Audiocast of CIRM Directors Meeting Resumes

The Internet audiocast of today's meeting of directors of the $3 billion California stem cell agency in Los Angeles is once again available. Currently, the board is engaged in a disease spotlight involving heart failure. The business meeting is scheduled to resume in about 30 minutes.

CIRM Board Audiocast Down

The California stem cell agency said the audiocast today of its directors meeting in Los Angeles is down but that the service provider is working to restore service.

As of this writing, the broadcast has been interrupted for nearly one hour. We will resume coverage if the audiocast is restored.

A footnote on the vagaries of the Internet: Here in Panama the government provides free WiFi to many areas. However, it also limits what can be seen or read. For example, YouTube is banned, also Internet broadcasts of college football games by CBS. If you look up odds on football games, those sites are barred as well. Certain information from cellular phone companies that compete with the firm that is financially backed by the government also cannot be accessed. And this morning, the government's WiFi network blocked the audiocast of the CIRM board meeting.  We picked it up after we found a private WiFi network about an hour after the meeting started.

California Stem Cell Agency Approves $5.6 Million to Lure Harvard Researcher to Golden State

Directors of the California stem cell agency today approved a $5.6 million grant to bring a star researcher to California -- a Harvard scientist currently collaborating with a director of the stem cell agency.

The recipient is Zhigang He, who is negotiating with UC Berkeley, which also has a representative on the CIRM board, one who did not vote on the grant or speak during the discussion.

Responding to a query from the California Stem Cell Report, the researcher later said, "I am still talking to Berkeley about the details of my move."

Zhigang He
Harvard Photo

CIRM governing board Oswald Steward, director of the Reeve-Irvine Research Center, Anatomy & Neurobiology at the UC Irvine School of Medicine , was also disqualified from voting or participating in the discussion. He left the room, saying that he has been "directly collaborating with this person."

The name of the Harvard researcher was not mentioned prior to the vote on the grant, although a member of the public, patient advocate Don Reed, told directors he knew the applicant and recommended him highly.

The grant is part of a $44 million recruitment effort by CIRM. It has awarded about $11 million to bring two researchers to California institutions, both of which have representatives on the CIRM board.

(An earlier version of this item said Zhigang He "is slated to go to work" at UC Berkeley, based on comments at the CIRM board meeting.)

CIRM Directors Meeting Underway

Directors of the California stem cell agency have begun their meeting in Los Angeles and are now discussing a $5.6 million recruitment grant to a researcher who is connected to CIRM Director Oswald Steward of UC Irvine. Steward is not eligible to vote and has left the room, according to the Internet audiocast.

Los Angeles Times: 'Geron Fiasco' Poses Questions About California Stem Cell Agency

The Los Angeles Times, California's largest circulation newspaper with more than 900,000 subscribers, today said the "Geron fiasco" raises questions about the conduct of business at the California stem cell agency and whether it "does a disservice to patients and taxpayers."

The comments came in a column by Pulitzer Prize-winning journalist and author Michael Hiltzik, who wrote about Geron's abandonment of its hESC trial only five months after the firm was awarded a $25 million loan by the stem cell agency. Hiltzik said,

"So we're talking at least about months of wasted effort by CIRM and Geron's researchers, crushing disappointment for those patients and conceivably a major setback for stem cell science generally. (CIRM Chairman Jonathan) Thomas observes that Geron said it made its decision strictly on financial grounds, not because of scientific reversals. But for an R&D company financial considerations always encompass scientific judgments, and Geron plainly concluded that the prospect for profits from stem cell therapies was receding.

"The Geron fiasco underscores the old questions, and raises new ones, about what CIRM is supposed to accomplish, how it does business and whether its addiction to hype does a disservice to patients and taxpayers."

Hiltzik's column contained brief remarks from Thomas. The columnist wrote,

"'There are going to be fits and starts,' its chairman, Jonathan Thomas, told me last week. Even so, he maintained, 'we remain unwavering in our commitment to pursuing the science.'"

Hiltzik has followed CIRM since the 2004 ballot initiative campaign that created the $3 billion enterprise. The effort was headed by real estate investment banker Robert Klein, who later served as CIRM's chairman for seven years. Hiltzik wrote,

"CIRM loves to compare itself to the federal government's biomedical research agency, the National Institutes of Health, but the two bodies are very different. The responsibilities of NIH are broad enough for it to make disinterested judgments about programs and scientific approaches. CIRM, however, was designed from the start (by Klein, who oversaw the drafting of Proposition 71) to focus on a very narrow field of biomedical science — embryonic stem cell research — and to promote that research in California as a sort of economic development tool.

"These two goals have always been ethically and scientifically incompatible, and the Geron case points to why."

Hiltzik said evidence exists to show that CIRM "downplayed legitimate questions about the state of Geron's science and the design of the clinical trial" in its efforts to fulfill the excessive promises of the electoral campaign. The issues, he said, included over-promising results, questions by other researchers about the trial and whether a spinal cord injury was the best subject for the first tests of stem cell therapies on humans.

Hiltzik continued,

"None of these issues were aired publicly in the run-up to the vote, because CIRM didn't disclose in advance that Geron was the loan applicant. Nor did it disclose that its own scientific review panel had awarded the Geron trial a scientific score of only 66 out of 100; that fact, along with other details of the board's consideration of the Geron loan, was pried out of CIRM later by David Jensen, the tireless proprietor of the indispensable California Stem Cell Report.

"CIRM told Jensen that although it customarily discloses its reviewers' scientific scoring of funding proposals, it didn't in this case because it was using 'new criteria' and thus the public might not find the result 'meaningful.' Call me a cynic, but I'd bet that if the score were, say, 90 out of 100, CIRM would have shouted it from the rooftops, rather than pleading that Californians were too dumb to understand what the number meant."

Hiltzik concluded,

"Another problem illuminated by the Geron case is that CIRM remains infected by the hype virus. Only a week after Geron parachuted out of the stem cell business, Thomas issued a statement bemoaning the public impression that CIRM isn't making any progress toward therapies. He declared: 'CIRM is turning stem cells into cures.'

"Well, no it isn't, not yet. Geron's now-halted project was the most advanced human clinical trial in CIRM's portfolio; yet it was at an extremely early stage, involved all of five human subjects and might still have been years away from showing that a cure was even possible. CIRM needs to take a good look at whether it pushed too hard for the Geron loan and overplayed the significance of the trial; otherwise its path toward building credibility with the public will only get longer."

The California Stem Cell Report has asked CIRM Chairman Thomas if he would like to respond in more detail to the Los Angeles Times column, with a commitment to carry his remarks verbatim.

Correction

The CIRM CFO item on Dec. 6, 2011, incorrectly stated that he began work on Nov. 11. The correct date is Nov. 28.

Live Coverage and Public Participation Locations for CIRM Board Meeting Tomorrow

A second teleconference location has been added to where the public can participate in tomorrow's meeting of the directors of the California stem cell agency, which will be covered live via the Internet by the California Stem Cell Report.

The actual meeting will be in Los Angeles at Cedars-Sinai, but interested parties can weigh in from sites at Stanford and UC San Francisco. The meeting will also be audiocast on the Internet.

Here are specific addresses from the agenda for the teleconference locations.
Stanford School of Medicine
Li Ka Shing Center for Learning and Knowledge/291
Campus DriveLK3CO2 3rd Floor/MC5216/
Stanford CA 94305-5101

UCSF School of Medicine
513 Parnassus Avenue, Room S224
San Francisco, CA 94143

Here are instructions for the audiocast:
To access the live event or archive, use this URL:
https://im.csgsystems.com/cgi-bin/confCast
Enter Conference ID# 224434 then click Go.

California Stem Cell PR and Spongy Voter Mandates

Some connected to the California stem cell agency, notably its founding father Robert Klein, are fond of declaring that the $3 billion enterprise has an immutable mandate from voters to pursue its endeavors.

Well, mandates come and go.

That lesson was learned once again this morning with the results of a Field Poll that showed that another big ticket effort, the California high speed rail project which was approved by 53 percent of voters, has lost not only its luster but its support. According to the poll, 64 percent of voters would now like another chance to vote on it. And 59 percent would reject it.

The reasons for the change of heart? Severe economic conditions in California, increased mainstream media coverage of high speed rail's deficiencies and bungling by its management.

While a San Francisco Chronicle columnist last summer called CIRM "the high speed rail of medicine," the stem cell agency has not suffered from the same sort of heavy and critical media attention. CIRM is all but invisible to the public. But agency is now is embarking on an ambitious PR effort to raise its profile and to move forward to win voter approval of another multibillion bond measure. Otherwise it will run out of funds in 2017.

CIRM must tread carefully with its new communications campaign. It has a legitimate responsibility to better inform Californians, and its PR could be more robust(which is a sort of the word of the day at CIRM).

But downsides do exist. With a possible ballot measure coming up, some ungenerous folks might construe aggressive CIRM PR as electioneering at taxpayer expense, including its subsidies of patient advocate activities, such as attendance at conventions. Even without a looming election campaign, the high speed rail project's $12.5 million PR effort attracted negative attention in at least two major newspapers just this week(see here and here).

Klein, who led the campaign that created CIRM and served as its chairman for seven years, is now gone, but his footprints remain. The agency, however, cannot assume that voter support seven years ago, in a much, much different world, translates to support today.

Researcher Alert: CIRM Making Changes in Grant Administration

The California stem cell agency is readying a long list of changes that will affect all of its 453 grant recipients and all future awards.

Many of the changes are minor. Some have been requested by grantees. Others are aimed at dealing with issues posed by larger grants. Some reflect the agency's move to more streamlined reporting.

Amy Lewis, CIRM's grant management officer, has prepared an introductory memo along with the proposed changes for discussion at Thursday's board meeting in Los Angeles. She said the proposal is in its early stages and will not require a vote this week.But it would behoove those affected to carefully check the grant administration policy to see how it might alter their lives.

Former iPierian Exec Joins California Stem Cell Agency as CFO

A former executive at a California stem cell firm has been named as the first chief financial officer of the seven-year-old, $3 billion California stem cell agency, it was announced today.

Matthew Plunkett, CIRM CFO
CIRM Photo

Matthew Plunkett, former vice president and chief financial officer of iPierian Inc., has been at work at CIRM since late last month. The agency said in a news release today that Plunkett is overseeing "budgeting, forecasting, financial compliance and reporting, and implementation of the industry loan award program."

Plunkett will also "play a key role in securing opportunities to leverage CIRM funds with additional outside capital," said CIRM Chairman Jonathan Thomas.

Plunkett worked for iPierian from 2009 until last April. While he was at the firm, it received $7 million in grants from CIRM. The South San Francisco business has a unique connection to CIRM. Major investors in iPierian, including John Doerr of Kleiner Perkins Caulfield Byers of Menlo Park, pumped nearly $6 million into the 2004 ballot campaign that created CIRM. That amounted to 25 percent of the total contributed to the campaign, which was headed by Robert Klein, who later became the first chairman of the stem cell agency.

CIRM has said no connection exists between the contributions and subsequent awards to iPierian.

The agency has needed a chief financial officer for some time. It has sometimes struggled with routine budget matters, although that problem seems to have been largely solved even before Plunkett was hired. Plunkett will report to both the agency's chairman, Jonathan Thomas, and CIRM President Alan Trounson, in a continuation of the troublesome dual executive arrangement at the stem cell agency.

Prior to joining iPierian, Plunkett worked for Oppenheimer/CIBC World Markets from 2000 to 2009. In his last position there, he was managing director/head of West Coast biotechnology. He holds Ph.D. in organic chemistry from UC Berkeley.

Plunkett, who is earning $260,004 annually, began work on Nov. 28. Today's press release on his hiring came after the California Stem Cell Report inquired on Saturday about progress in filling the position.

Here is a link to a brief article in the San Francisco Business Times about the Plunkett announcement.
(An earlier version of this item incorrectly said Plunkett started work on Nov. 11 based on his resume which said "11/11.")

The Back Story on Baylis and the Ethics of Geron's hESC Trial

Last week Canadian bioethicist Francoise Baylis raised ethical questions about Geron's abandonment of its hESC clinical trial in an article that, it turned out, has a bit of a history.

When we notified her that we had written about her piece and its implications for the California stem cell agency, Baylis replied with a thank you and said,

"As an aside, you might be interested to know that I sought to publish a version of this commentary as a letter to the editor in a peer reviewed stem cell science journal and received the following response: I and two experts 'found the overall tone and presentation of the letter inappropriately strong and confrontational. As a result, it does not seem appropriate for us to offer to consider it further.'

"In my view, this was an unfortunate editorial decision as I believe the stem cell science community needs to engage with this issue. Moreover, I know of responsible stem cell researchers who share my point of view. Beside which, I disagree with the characterization of the piece as confrontational ...

"Another posting of mine on The Mark News makes the same point, but in a more journalistic style."

In that piece, Baylis also wrote about Geron's position that the results with four clinical trial participants would "be a fair reflection of what would have happened if we had completed the study(with 10).” She said,

"I want to suggest, however, that this is an ethically problematic response to a situation that could have been anticipated, and thus avoided. Failure to name the problem in this way leaves future participants in safety studies of novel hESC interventions at risk of abandonment whenever a private biotech company decides to end a trial mid-stream for business reasons."

Our take? The California Stem Cell Report agrees that the decision by the unnamed journal was unfortunate, to put it mildly. Baylis' comments were neither inappropriate nor confrontational, but they did raise questions that could well make some persons uncomfortable. Nonetheless, the questions were the sort that the general public and patient advocates raise in one form or another in their dealings with the enterprises that develop therapies and drugs. Either the questions are addressed now or later -- when they may well have to be dealt with under much more difficult circumstances when things go awry.

Conflict of Interest: Harvard Researcher Resigns from IOM Inquiry into California Stem Cell Agency

One of the members of the Institute of Medicine panel conducting a 17-month investigation into the $3 billion California stem cell agency has resigned because of a conflict of interest involving a San Diego stem cell firm.

David Scadden, co-director of the Harvard Stem Cell Institute, withdrew last week after conferring with IOM officials concerning his connection to Fate Therapeutics, which lists him as a scientific founder.

In an email to the California Stem Cell Report, Scadden said,

"I have a relationship with a start-up company in CA and, after discussion, with the IOM, we concluded that it would constitute a conflict of interest. I would have enjoyed helping out, but didn't want to compromise the perception of objectivity of the report."

Fate Therapeutics does not hold an award from the California stem cell agency. It is not known whether the company has applied for CIRM funding. The agency does not release the names of applicants that are not approved.

We have queried the IOM about whether Scadden will be replaced on the now 13-member panel.

Strategy at CIRM: New Sources of Cash, More Funding Transparency, Better PR?

The California stem cell agency is huddling with industry, scientists and public as it wades through a revision of its strategic plan to determine how to spend its remaining $1.4 billion before the cash runs out.

CIRM officials have held at least 10 meetings with a variety of groups, including three public sessions. The next public hearing is Thursday in Los Angeles at the CIRM board meeting.

The revision comes as the agency wrestles with the increasing need to generate results that will resonate with California voters. CIRM's original $3 billion, which consists of cash borrowed by the state, will run out in roughly 2017. The agency is considering mounting a ballot campaign for another multibillion dollar bond measure. The agency is also under examination by the prestiguous Institute of Medicine and is likely to hear recommendations for changes from that report next fall.

Ellen Feigal, senior vice president for research and development, summarized stakeholder comments so far on CIRM's plans in a 13-page documment prepared for the meeting at Cedars-Sinai. She identified several key themes from stakeholders, including the need to find "alternate funding resources," presumably non-public financing. Feigal also cited a need to make the grant funding process more transparent, apparently reflecting complaints from industry. But she noted that stakeholders have said the agency has made "great initial progress" in its first seven years.

Here are four of the five themes Feigal identified. The fifth dealt mentioned CIRM's progress.

• "CIRM needs to become more aggressive in finding alternate funding resources and to implement greater creativity in identifying the types of organizations that may be able to contribute to the sustainability of CIRM's work"
• "Robust public affairs tactics are necessary, and CIRM needs to better communicate the organizational initiatives, as well as educate the public more broadly."
• "Greater transparency in the funding process is needed, and there is a great need for the process to be less bureaucratic and easier to navigate."
• "CIRM needs to provide greater opportunities for networking and breed collaborative projects that unite academic and industry as well as researchers across geographic reasons."

Feigal also mentioned a number of recommendations from industry, which has been less than happy with its meager share of CIRM funding. The suggestions included creation of "communications bridges" and better communication of the funding process. Also recommended was a "split review process – (academic vs. industry)" and a faster approval process that takes into account the high "burn rate" of cash at biotech companies. Another industry suggestion was creation of an "in-house champion" to help businesses navigate the CIRM funding process.

Feigal will come back to the board in January with a draft revision. It is scheduled to be approved March 21. The final plan will be shipped off to the IOM panel studying CIRM. It is scheduled to conclude its work next fall.

Interested parties can email their comments on the plan to CIRM (info@cirm.ca.gov) or speak at CIRM board meetings. The specific address for Thursday's meeting can be found on the agenda. A teleconference location is also available at UC San Francisco, where members of public can take part.

Luring Stem Cell Researchers to California: A $5.6 Million Bid

The $3 billion California stem cell agency has played a role in bringing two star researchers to the Golden State through its $44 million recruitment program and is about ready to bring in a third.

Next Thursday in Los Angeles, CIRM's governing board is expected to approve a $5.6 million grant to an unidentified scientist to lure him or her to an unidentified California institution.

The funds will go for the researcher's efforts to develop "a regeneration-based functional restoration treatment for spinal cord injury," according to a summary of reviewer comments on the CIRM web site. The grant was scored at 86 by scientific reviewers.

The summary quoted the researcher as saying,

"We recently made breakthrough discoveries in identifying key biological mechanisms stimulating the re-growth of injured axons in the adult nervous system, which led to unprecedented extents of axon regeneration in various CNS injury models. While our success was compelling, we found that many regenerated axons were stalled at the lesion sites by the injury-induced glial scars. Furthermore, it is unclear whether the regenerated axons can form functional synaptic connections when they grow into the denervated spinal cord. This proposed research program is aimed at solving these obstacles by using human stem cell technologies."

The summary said,

"The PI was described by reviewers as a superb scientist and emerging leader with outstanding accomplishments and exceptional promise. The candidate has already made key contributions to the understanding of mechanism underlying axonal regeneration that have significantly advanced the field of neuroregeneration. He/she has been extremely productive, publishing a number of seminal papers in the highest profile journals including Science, Nature, Neuron and Nature Neuroscience."

The stem cell agency's recruitment efforts have helped to bring Peter Coffey ($4.9 million from CIRM)from the UK to UC Santa Barbara and Robert Wechsler-Reya ($6 million)- to Sanford Burnham in La Jolla from Duke University.

California Stem Cell Agency and Geron: Ethical Issues with Sale of hESC Trial

A Canadian bioethicist is raising ethical questions about Geron's hESC trial that have implications for the attempt by the California stem cell agency to salvage the once-vaunted effort.

Writing yesterday on the Hastings Center Bioethics Forum, Francoise Baylis of Dalhousie University said,

"It is one thing to close a trial to further enrollment for scientific reasons, such as a problem with trial design, or for ethical reasons, such as an unanticipated serious risk of harm to participants. It is quite another matter to close a trial for business reasons, such as to improve profit margins."

Geron last month said it was ending the trial because of financial reasons and to pursue development of its cancer treatments. CIRM awarded Geron a $25 million loan just last May and was surprised by the Geron move. The $3 billion state research program is now attempting to find a buyer/partner for Geron's hESC business.

Baylis noted that Stephen Kelsey, chief medical officer of the Menlo Park, Ca., firm, has been quoted as saying that the results of Geron trial – now with five patients instead of the projected 10 – "will be a fair reflection of what would have happened if we had completed the study."

Baylis wrote,

"This statement is deeply problematic, however."

Baylis, a professor and the Canada Research Chair in the departments of philosophy and of obstetrics and gynecology at Dalhousie, continued,

"No clinical trial should involve too few or too many participants. It is important that the trial not be underpowered and thus unable to generate scientific knowledge. It is equally important than no more research participants than necessary be exposed to potential research risks. If only five participants were needed to generate the scientific knowledge, then why would Geron and the F.D.A. have agreed to expose additional persons to the potential harms of trial participation?

"On the other hand, if Kelsey’s statement is false, and the findings from five research participants will be underpowered, then they may have been exposed to the potential harms of trial participation without the potential for benefit in the form of scientific knowledge."

She concluded,

"In either case, the scenario forces us to consider what measures should be taken with respect to future trials funded in the private sector so that participants are not left stranded. Perhaps regulators and institutional review boards should critically examine whether a company has both the financial (and other) resources and the will to complete a trial under review before granting regulatory or ethics approval.  If there are doubts about this, then either the trial should not be approved, or there should be stringent disclosure requirements so that prospective research participants are aware of the possibility that research may stop mid-trial for financial reasons."

Researcher Alert: CIRM Readying $57 Million in New Opportunities

The California stem cell agency is proposing to pump $30 million into new research involving reprogrammed adult stem cells and another $27 million into fresh efforts to speed development of clinical therapies.

In a memo prepared for the CIRM directors meeting next week in Los Angeles, the agency's staff said the $30 million effort could generate "disease-in-a-dish models" that "have the potential to make drug discovery faster, more efficient and more personalized to individual patients."

The "disease-in-a-dish" plan was dubbed a "human pluripotent stem cell (hPSC) initiative" by the staff. The goal is to generate high quality stem cell-based tools for use by the researchers and drug developers.

The proposal includes four elements, one of which is collaboration with the NIH to develop cell lines from patients with Huntington’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis. No cost was specified on that effort. Also recommended to directors was a $4 million disease line award round, a $16 million core hiPSC derivation round and a $10 million stem cell bank round. The RFAs would go out in May of next year with funding expected early in 2013.

The staff memo on the initiative did not mention human embryonic stem cells, but a spokeswoman for the agency said they were not excluded from the effort.

The other new grant proposals up next week grew out of a recommendations from a blue-ribbon panel that CIRM organized last year to examine its operations. One element in the plan is a $12 million "bridging fund" that would apply only to current CIRM-funded projects in three areas: disease team grants, some early translational projects and clinical development projects. The bridging fund would provide up to $3 million for up to one year for each recipient, if CIRM President Alan Trounson approves the project. Trounson would be assisted in his evaluation by staff and external consultants, if necessary.

The second part of the response to the review panel's finding is an "external innovation initiative" to support collaborative efforts of CIRM grantees to work with teams that CIRM said are "making extraordinary progress outside California."

The $15 million program would provide awards as often as two times a year. The maximum amount on each award was not specified.

Ellen Feigal, CIRM's vice president of research and development, said in a memo to directors that examples of potential projects included collaborative efforts with the NIH and work with the Harvard Stem Cell Institute and its disease-focused programs.

Some of the latest CIRM initiatives are open to biotech businesses. Others are open only to non-profit or academic researchers.

(Editor's note: An earlier version of this item did not include the sentence dealing with human embryonic stem cells.)

Stem Cell Agency Provides Early Access to Multimillion Dollar Proposals Coming Before its Directors

Could this be a trend?

The California stem cell agency, working under the direction of a new chairman, has once again posted a handsome amount of background material well in advance of its regular board meeting – in this case the Dec. 8 session at Cedars-Sinai in Los Angeles.

For the past several years, the agency has failed to post in a timely fashion important information on many decisions to be made by agency directors, making it virtually impossible for interested parties to plan to attend meetings or prepare thoughtful suggestions or recommend possible changes.

That situation has begun to change under Chairman Jonathan Thomas, a Los Angeles bond financier, who controls the board agenda and who was elected to his post at the end of June. In August, the agency also posted in a timely fashion a healthy dollop of information on matters to come before the board.

For December's meeting, the agenda contains links to information on a proposed $5.6 million recruitment award to lure a star researcher to the Golden State, an update on CIRM's proposed changes in its strategic plan, two new initiatives totalling $27 million that would accelerate progress to the clinic, grant administration changes that could affect the hundreds of CIRM grant recipients and proposed new scientific members for the group that makes the de facto decisions on which scientists receive CIRM cash.

We will have more on the details of all this later, but readers who have a special interest might want to dip in early. All the background information can be found via the agenda, which also says a remote site in San Francisco will be available for participation of those who cannot make it to Los Angeles.

Hype, Geron and Stem Cell Research: A Hard-eyed View from the North

From Canada last week came a stem cell "reality check" that pulled together a professional football quarterback, a Yankee baseball pitcher, a Republican presidential hopeful and Geron.

Timothy Caulfield,
U. of Alberta Photo

What do they all have in common? Stem cell therapy, answered Timothy Caulfield, a Canadian academic, writing on the Canadian version of the Huffington Post. Declaring that stem cell treatments are being ballyhooed as a "miracle cure" and "elixir of life," Caulfield wrote,

"But does it actually work? I think not -- at least not yet."

Caulfield is not one of your stereotypical opponents of stem cell research. In fact, he describes himself as a "believer" in the likelihood of development of effective stem cell therapies. Caulfield also springs from a deep academic background. He is research director of the Health Law Institute at the University of Alberta and has published a plethora of scholarly articles related to stem cell research.

Caulfield wrote that Geron's abandonment of hESC research "underscores the cavernous gap between the well-publicized (and completely legitimate) promise of stem cell research and actual, efficacious, therapies."

He said the California company's decision "generated both shock and anger. And for the patients hoping for a near-future cure, it was nothing less than heartbreaking."

Caulfield continued,

"Not only did the company decide to stop this particular trial, it decided to get out of the field of stem cell therapies altogether. So definitive was the decision that Geron gave back millions of public research dollars(to the California stem cell agency)."

Caulfield warned, however,

"We need to be careful not to over-interpret the Geron pull out. This is one company and one trial. There are now a few other clinical experiments in the pipeline (emphasis on a few), such as one to treat a form of blindness. And we must remember that not all things that are called 'stem cell therapies' are the same. "

Caulfield continued with his "reality check,"

"First, ignore the hype. I believe there is little evidence that any of the often advertised stem cell therapies, embryonic or otherwise, work. Yes, there are a handful of decades-old treatments ….

"(Peyton) Manning, (Bartolo) Colon and (Rick)Perry may have had a positive experience (the placebo effect is a powerful thing, after all), but, to date, I believe good clinical evidence simply does not exist.

"Second, despite the hope of many, it isn't going to be easy to make money off stem cell research -- at least with a treatment that is scientifically legitimate, appropriately tested and approved by the relevant regulatory agencies (three characteristics missing from most of the stem cell therapies currently offered in clinics around the world). "Economic growth has often been one of the ways that the huge public investment in stem cell research has been justified. Just a few weeks ago, for example, the UK government announced that it was committing millions in a stem cell research centre with the hope that it will help drive the UK economic recovery.

"But the ability of emerging stem cell technologies to stimulate the economy and create jobs is far from certain. Indeed, economics is the explicit reason for the Geron pull out. The company press release stated that the decision was made after a strategic review of the costs, timelines and 'clinical, manufacturing and regulatory complexities associated' with this kind of research. In other words, stem cell research is not, from the perspective of this company, worth it."

Caulfield concluded,

"I don't mean to be a downer. In fact, I believe that stem cell research holds tremendous potential. I remain fully confident that, one day, therapies will emerge. But the inappropriate hype associated with this area hurts policy debates, leads to unmet expectations, and has the potential to mislead the public about the actual state of the science. The Geron story is a sober reminder that promise is not reality, even in a field as exciting as stem cell research."

The CIRM 'Debt' to George Bush and Disgraced Korean Researcher

It was brief but pointed comment on the differences in the stem cell world of 2004 compared to the stem cell world of 2011.

Larry Ebert, a patent attorney, made the remark on his blog, IPBiz. He was writing about an observation on this website that without George Bush and his restrictions on federal hESC research, there would have been no California stem cell agency.

Ebert said,

"IPBiz notes that when the California voters voted Prop. 71 in, scientists thought Huang Woo Suk's work on hESC was real. In 2011, the current state of the art is still not up to what Huang Woo Suk falsely reported in the journal Science. Californiastemcellreport should give Huang Woo Suk some credit for the passage of Prop. 71."

Consider Woo Suk duly credited.

California Stem Cell Agency Takes Initiative in PR 'War'

Jonathan Thomas, chairman of the $3 billion California stem cell agency, took to the blogosphere today with an item promoting CIRM's progress, declaring that it is a record of which Californians can be proud.

In his debut performance as a blogger, Thomas declared that the agency has 43 research projects that are in various stages of moving towards clinical trials. He wrote on CIRM's research blog,

"Given that it normally takes a decade or longer for a basic science discovery to reach clinical trials, 43 projects seemed to me like quite an achievement – an achievement that the people of California should take pride in supporting. Not only is CIRM driving stem cell science in our state, but through our national and international collaborations California has become a stem cell hub that accelerates stem cell progress worldwide."

Thomas, a Los Angeles bond financier, pointed to a new document from CIRM, titled "Funding therapies: Fueling Hope." It summarizes some of the agency's work and touts the "incredible potential" of stem cells.

The document also explains the laborious process for creating a therapy before it can be brought to market and actually used to treat patients. The document said,

"Altogether, carrying out the basic research, translational work and preclinical data leading up to a clinical trial can take a decade or longer, and that's just to start the clinical trial. CIRM’s funding approach speeds that timeline by providing stable funding that eliminates pauses in the research to raise new funds, by strategically funding areas thought to be barriers to the clinic and by forming teams of researchers who work in parallel rather than sequentially to reach clinical trials faster."

When Thomas was elected chairman of the agency last June, he told directors that the agency was in a "communications war" in which its record was not fully appreciated by the public. He made telling the CIRM story one of his top priorities.

Today's blog posting by Thomas and, more particularly the "Fueling Hope" document, will be useful to CIRM in dealing with the overblown expectations of rapid cures that were generated by the hype of the 2004 ballot initiative campaign that created the stem cell research program.

The campaign generated impressions among voters that cures – specifically human embryonic stem cell cures – were just around the corner and that the Bush Administration, with its restrictions on hESC research, was the only thing standing in the way. Indeed, without George Bush, there would be no state stem cell agency  since his stand against hESC created an apparent need for alternative funding. For voters who expected instant cures, however, CIRM must be a sad disappointment since it has developed no therapy that is being used to treat people.

Managing expectations is a critical task for CIRM, which will run out of funds in 2017 and which is expected to be asking voters for another multibillion dollar bond measure sometime in the next few years.

A Look Inside the CIRM-Geron Loan Documents

The $25 million loan that the California stem cell agency awarded to Geron was the largest ever made by the research enterprise.

Directors approved the loan last May during a hearing that was a major departure from its usual procedures. The loan agreement was signed Aug. 1., about three months before Geron announced that it was abandoning the hESC business.

Geron last week repaid the $6.42 million that it had received from CIRM up to that point. Geron also paid the agency $36,732.33 in interest. CIRM additionally received 537,893 warrants to buy Geron stock at $3.98, CIRM told the California Stem Cell Report. Geron closed at $1.50 yesterday. The warrants expire in 10 years.

Last summer the California Stem Cell Report requested copies of the loan documents, which can be found at the end of this item, although the agency blacked out much of the information.

In a note accompanying the documents, Ian Sweedler, deputy legal counsel to CIRM, said,

"Geron requested and justified redactions to the milestone document, to those parts that describe specific activities, plans and data within the overall project.  Geron asserted and justified a claim that these details meet the legal standard for trade secrets that are exempt from production.  For the milestones, Geron agreed to leave enough unredacted to give a sense of the intent, at a level of detail that is not confidential.  For example, it will be possible to see that a milestone refers to enrolling a certain number of patients, but not what that number is, or other specifics about that stage of the project.  There are also accompanying comments with technical details and alternative approaches considered.  For these comments, we were unable to find a way to leave any meaningful text that would not disclose trade secret information.  The comments have therefore been completely redacted.

"Geron similarly justified redaction of information about how it will divide funds among different aspects of the project.  They explained that their internal costs, processes, and sequences are confidential, competitive trade secret information.  The redacted versions therefore show the amount of funding CIRM will provide, but not when and how Geron will allocate that to different activities."

Here are the loan documents.
CIRM-Geron 8-1-11 Loan Agreement

CIRM 7-28-11 Geron Loan Term Letter

Geron-CIRM Loan Agreement Appendix B

Geron-CIRM Loan Timetable Appendix C

The Ins and Outs of CIRM's Push to Keep the Geron hESC Effort Alive

The $3 billion California stem cell agency has confirmed that it is looking for companies to take over Geron's hESC business, but remained vague on the details of just what it is proposing as well as any financial incentives.

A certain ambiguity may appropriate because Prop. 71, the ballot initiative that created CIRM seven years ago, constrains the state research effort, which is engaged in an aggressive push to bring stem cell therapies into the marketplace.

After last week's New Scientist article in which CIRM President Alan Trounson said he was talking to at least three companies, the California Stem Cell Report emailed this inquiry to the agency:

"Re Trounson's comments about CIRM trying to find an enterprise to pick up the Geron hESC business, what form is that taking? Are CIRM officials contacting companies, asking them to consider the Geron business? Are promises being made that Geron's loan would be passed along to a new company? Are CIRM officials giving any sort of assurance that the new enterprise would be looked on favorably in terms of possible CIRM financing help, even a wink or some such thing?"

In response, Maria Bonneville, executive director to the CIRM board, said yesterday,

"Dr. Trounson is encouraging companies to take a hard look at the potential of this project. If any companies express a solid desire to continue the project, they would be thoroughly vetted through CIRM's existing procedures."

The stem cell agency is limited by law in what it can do encourage a deal for Geron's orphan business. Nonetheless it will have to move quickly if it wants to keep Geron's hESC team intact. Otherwise, those folks will be heading for more secure employment.

With some crafty lawyering, however, CIRM might be able to move its $25 million Geron loan over to a some sort of new entity if the clinical trial remains virtually identical.

The agency might also find a way to use a newly created $30 million "strategic partnership" program to support a deal involving Geron's stem cell program. CIRM's new program is industry friendly and aimed at early stages of clinical development.

However, by law, only a public vote of the 29-member board of directors can approve a loan or grant. That vote is taken in what is supposed to be a blind process in which the names of the applicants are not known. However, it is clear from last May's approval of the Geron loan that the directors knew the identity of the applicant although it was not announced publicly until after the formal 16-1 vote. The agency's procedures also call for action prior to the board vote by its grant review group, which makes the de facto decisions on grants.

The timeline on normal award rounds is lengthy – more than a year from concept to finish – and may not be appropriate in this case. Plus the rounds are open to more than one applicant.

CIRM's current award rounds for business involve loans not grants. The loan policy was developed, in part, because businesses objected to the financial hooks in grants. Originally, the loan program was created to fund business projects that otherwise could not find funding. The program was originally slated to run as high as $500 million. The interest was expected to finance additional research.

The agency also has geographic constraints. It cannot pay for work outside of California. So that would mean that a potential buyer probably would need a substantial presence in California unless the agency could put together a deal in which Geron is still in the game and doing some of the work.

The agency can receive warrants in loan deals but does not make stock investments. It probably cannot legally directly buy a stake in a company and thus provide a cash infusion.

A new arrangement for Geron's hESC business would need some likelihood of a substantial stream of cash over the next several years, based on what Geron said last week. But the current environment for early stage biotech investment is quite difficult. And then there is the FDA, which authorized the clinical trial and is likely to have something to say about who operates it.

Whether CIRM can overcome all these obstacles would seem to be problematic. But, of course, Geron is also shopping its business around. And some buyers might be attracted by a bargain basement price enhanced by the expectation of continued cash from the California stem cell agency.

California Stem Cell Agency Trying to Line Up Buyers for Geron hESC Business

The president of the $3 billion California stem cell agency, Alan Trounson, says it is in talks with at least three firms in an effort to salvage Geron's orphan stem cell business.

Andy Coghlan of New Scientist magazine reported Trounson's remarks in an article on Friday headlined, "Is there life for stem cells after Geron."

The Menlo Park, Ca., firm last Monday abandoned its stem cell therapy development program and terminated a much-heralded clinical trial that was the first-ever in the nation for an hESC therapy. The California stem cell agency loaned the firm $25 million just last May as part of its push towards bringing therapies to market. Geron last week paid back the $6 million of the loan that it had received up to that date.

Details were sketchy in New Scientist about CIRM's attempt to serve as a stem cell matchmaker. Coghlan had only this to say,

"Alan Trounson, the institute's president, told New Scientist that CIRM is now talking to at least three other possible backers to take over the spinal trial. 'We'll have to wait and see, but it's important that it happens in a short time [because] once it gets beyond a couple of months, it gets very difficult to hold people together,' he said."

Coghlan noted that Geron, in addition to the spinal therapy clinical trial, had three other hESC possible trials lined up for diabetes, heart disease and arthritis.

Last week, several names surfaced in the media of a number of possible buyer/partners/backers for Geron's stem cell business. They included Pfizer, which is involved with Peter Coffey of UC Santa Barbara in another possible hESC trial; BioTime of Alameda, Ca., which has a number of Geron alums, and Teva Pharamaceutical of Israel. UC Irvine researcher Hans Kierstead, whose work led to the Geron spinal trial, was also in the mix, according to a report in the Orange County Register. Pat Brennan, who interviewed Kierstead, wrote that the researcher said "he is exploring alternative funding to continue the trials." Keirstead, who is on the scientific advisory board of California Stem Cell of Irvine, Ca., also said the trial may well go overseas.

The California Stem Cell Report queried the firms identified last week concerning their intentions towards Geron. All declined to comment specifically. Michael West, CEO of BioTime, also said,

"I think the commentary you heard was a deduction based on my prior role at Geron, our being so geographically close to Geron, and, of course, our entire focus on hES cells and reprogramming. I will only add that I continue to believe passionately in the cause. More than ever, we have an historic opportunity to impact the practice of medicine. That is about as far as I can go."

West founded Geron and has served as president of Advanced Cell Technology of Santa Monica, Ca., which is conducting an hESC trial at UCLA involving eye disease.

Brokering a deal for Geron's stem cell business places the California stem cell agency in a novel position and will test its business skills. CIRM's activities have been largely devoted to awarding grants and loans. Its loan to Geron was only approved by directors just six months ago. The loan agreement was not actually signed until August.

Under CIRM's procedures, companies receiving loans are supposed to be vetted during a private due diligence process. However, one might question the quality of that due diligence given Geron's withdrawal from the business only three months after the loan was finalized.

The key question, in trying to attract buyers for Geron's orphan stem cell project, will be not so much about whether it is good science but whether it is a good business.

Geron hESC Withdrawal 'Real Blow' to California Stem Cell Agency, Says CGS

In a sharp-edged analysis of Geron's abandonment of stem cell research, the Center for Genetics and Society yesterday described the action as a "real blow" to the California stem cell agency.

Written by Pete Shanks, a regular contributor to the Berkeley center's Biopolitical Times, the piece chronicled some of the history and hype involving Geron and hESC research. The center has long taken a skeptical view of the California stem cell agency and Geron. Shanks wrote,

"Geron has been in trouble for a while. Former CEO Thomas Okarma, who left abruptly in February, was the subject of ridicule for his repeated announcements that ESC-based clinical trials would begin "next year" — that is, 2005, 2006, 2007, 2008 — and the trial they eventually came up with was so dubious that Arthur Caplan called it "nuts and hugely risky." Even experts in the field thought that targeting spinal cord injury in the first ESC trial was dubious, though some seem to be more willing to be critical now it has ended.

"And that was on the scientific and perhaps commercial merits. The ethical problems were much worse, since the trial was intended for people who had recently suffered damage to their spinal cords. Bioethicist Laurie Zoloth (who was once on Geron's ethics advisory board, and basically approved of the study), noted at the time of its announcement that:

"'True informed consent in this very vulnerable population, people who have suffered a devastating and life-changing injury a week prior to being asked to enter the first clinical trial for such long-awaited, highly publicized and desperately needed treatment, is hard to obtain and will need to be carefully thought through.'"

Shanks also wrote,

"What of CIRM's role? After Geron's announcement, they issued a remarkably bland press statement, followed by an internal memo that expressed deep disappointment (the California Stem Cell Report has the text). It's a real blow to them: Geron was the first private company to receive funds from CIRM to run a clinical trial using ESCs.

"This was a loan, not a grant, and was only made, as the indefatigable David Jensen (publisher of the California Stem Cell Report) discovered, after a 'major departure from longstanding procedures.' The proposal received a low score (66/100) that was not publicly revealed until Jensen specifically asked for it. And the other applicants who might have competed for those funds rather surprisingly all withdrew.

"The suspicion arises that CIRM, or some people within it, badly wanted the trial to proceed in the hope that it would give them a therapeutic success to boast about. If so, the decision just backfired."

CIRM Chairman on Geron: Agency in for the Long Haul

Commenting on Geron's decision to abandon hESC research, the chairman of the California stem cell agency, Jonathan Thomas, says the agency knew "the road to new therapies would be arduous, and that for each success, there would be setbacks as well."

In a memo Monday to the agency's 29 board members, Thomas reiterated that Geron maintains the decision had nothing to do with safety concerns. He said the company's action underscores the agency's commitment to long-term development of stem cell therapies.

Thomas also said the $3 billion agency will retain the stock warrants it received from Geron, but did not disclose their numbers. We have queried CIRM for more details. CIRM loaned Geron $25 million, which was paid back by Geron on Monday.

A copy of the Thomas memo was provided to the California Stem Cell Report. Here is the full text.

"Dear Board Members:

"Earlier this afternoon, we learned that Geron made a decision to discontinue its stem cell research program, including the CIRM-funded clinical trial involving spinal cord injury. Geron made this decision in order to shift its focus to its oncology program. Geron has assured us that its decision to discontinue the trial had nothing to do with safety concerns; the cells have been well-tolerated and the patients have experienced no adverse effects. Geron will continue to follow all enrolled patients and has committed to accrue data and update the FDA and the medical community regarding the patients’ progress.

"In addition, Geron has returned CIRM’s funds, with accrued interest. CIRM will maintain the warrants it received.

"Of course, we remain committed to funding clinical development of stem cell therapies. We have always recognized that the road to new therapies would be arduous, and that for each success, there would be setbacks as well. We also know that companies make decisions for business reasons, and that it is not unusual for a company to pursue a new strategy, as Geron has done. CIRM, by contrast, is focused on its long-term goal of delivering therapies and cure to patients, and today’s events underscore the importance of CIRM’s long-term commitment to funding therapy development.

"This trial represented the first-ever clinical trial of human embryonic stem cells and we expected that it would be challenging. We share the frustration of all the patients for whom this trial offered great hope. I spoke personally with both Don and Roman Reed to express my commitment to the on-going search for therapies.

"Although we are deeply disappointed by Geron’s decision, we are grateful that Geron has established a regulatory pathway for human embryonic stem cell therapies and we are confident in the potential of stem cells to treat patients suffering from chronic disease and injury.

"Here is a link to CIRM’s press release: http://www.cirm.ca.gov/PressRelease_2011-11-14"