Tuesday, November 29, 2011

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.

Sunday, November 27, 2011

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.

Wednesday, November 23, 2011

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

Tuesday, November 22, 2011

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.

Sunday, November 20, 2011

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.

Thursday, November 17, 2011

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."

Wednesday, November 16, 2011

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"

Tuesday, November 15, 2011

Possible Buyers for Geron's Stem Cell Business: BioTime, Pfizer, Celgene

The mainstream media is climbing all over the Geron story today with more analysis and a  discussion of firms that might snag the San Francisco area firm's orphan stem cell business.

Reporter Peter Loftus of the Wall Street Journal mentioned Pfizer, which is involved an hESC project with researcher Peter Coffey, who was lured from the UK this fall to UC Santa Barbara. Among the incentives was a $4.9 million grant from the California stem cell agency, which also financed Geron to the tune of $25 million.

Matthew Perrone of The Associated Press had this to say about buyers:
"Analysts say Geron's stem cell business could be acquired by Alameda, Calif.-based BioTime, a company founded by former Geron scientists. Other potential acquirers could include larger pharmaceutical companies like Celgene Corp., Pfizer Inc. and Teva Pharmaceuticals, which have dabbled in stem cells without making major investments."
BioTime's shares were up 7 percent today, closing at $4.52. Geron's shares were down as much as 28 percent and hit a five-year low. It closed at $1.71, down 22 percent.

The AP also wrote,
"Joseph Pantginis, an analyst with Roth Capital Partners, said it would have taken five to ten years before Geron's lead stem cell product reached the market.

"'This is still very much a fledgling space and some people would even consider stem cells to be a science experiment, so there's still a long way to go,' said Pantginis.

"University of Wisconsin professor Alta Charo said Geron's move 'may suggest that a different business model is needed, one with a longer timeline for return on investment.'"
Charo had close ties early on with the $3 billion California stem cell agency, which loaned $25 million to Geron just six months ago. The loan was part of an aggressive effort to produce clinical results that will help extend the agency's life beyond 2017, when funds are expected to run out. Currently CIRM is financed through California state bonds, which will need to be approved by voters again if CIRM is to continue.

Here are more excerpts from today's coverage.

Gretchen Vogel of Science magazine wrote,
"Some observers had reservations about the trial from the start, worrying that the animal results were not strong enough to justify a human trial. But many had been pulling for the company nonetheless. 'It's with a sense of loss that I see this news,' says Roger Pedersen of the University of Cambridge in the United Kingdom, who was one of the researchers to receive funding from Geron in the mid-1990s to attempt to derive hES cells. He says the company may be reacting not only to the long timeline to bring cell therapies to the clinic, but also to a possible weakening of its intellectual property portfolio. The development of induced pluripotent stem (iPS) cells, which are adult cells genetically reprogrammed to resemble embryonic ones, means that Geron's exclusive licenses may be worth less. 'Advances in the stem cell field are disruptive innovations that have the potential to supercede earlier innovations, hES cells being one of those. I don't know if Geron looks at it that way, but I do,' Pedersen says."
Ben Hirschler and Kate Kelland of Reuters reported:
"A decision by one of the biggest names in stem cell research to throw in the towel will not stop other pioneering work that could yet produce cures for blindness and help mend broken hearts.

Scientists were shocked by U.S. biotech company Geron Corp's decision on Monday to quit embryonic stem cell research -- a move it blamed on a lack of money and the complexities of getting regulatory approval....

"Robert Lanza, chief scientific officer of ACT, is not giving up hope on the embryonic front but said Geron's exit put more pressure on his firm to succeed.

"'Of course, it's the second mouse that often gets the cheese,' he said."
Sarah Boseley of The Guardian in the UK wrote:
"The dream of Superman actor Christopher Reeve and others of paralysed people being able to walk again after injections of stem cells has receded, following the announcement by biotech company Geron in the US that it is to abandon the first-ever human trial of its kind."
Jef Akst of The Scientist magazine wrote:
"'It’s certainly going to have a very chilling effect,' said Robert Lanza, chief scientific officer at Advanced Cell Technology, the only other company currently engaged in clinical trials involving hESCs. 'There’s a lot of exciting potential here in this field, and it would just be a real shame for this not to move ahead full steam.'...

"One thing working in the field’s favor is the fact that Geron helped pave the regulatory way for other stem cell therapies, said Sheng Ding, a stem cell biologist at the Gladstone Institutes and the University of California, San Francisco. 'Geron’s past efforts had cleared out a FDA path for pluripotent stem cells,” he wrote in an email to The Scientist."
The Financial Times of London altered its original story by Andrew Jack without notifying its readers that the story was changed or why. The old version began.
"Geron, the pioneering stem cell therapy company, has dealt a powerful blow to one of the most hyped areas of medicinal research by withdrawing entirely from the field."
The new version, posted at least 12 hours later, begins:
"Geron, the Californian biotech company, is abandoning its pioneering embryonic stem cell work, after concluding that the costs and length of further development were too great."
Matthew Herper of Forbes published a comment from Jamie Thomson of the University of Wisconsin, whose hESC discoveries were financed in part by Geron. Thomson wrote,
"Geron’s decision to discontinue their stem cell work reflects how genuinely difficult it is to build a business around embryonic stem cell-based transplantation therapies. They also chose a particularly challenging target for the first therapeutic application. They are to be commended, however, for blazing a trail that others can follow in getting the first clinical trial approved by the FDA, as such approvals should be easier in the future."
Herper continued,
"Thomson initially shied away from the idea of building businesses around embryonic stem cells or their successors, induced pluripotent stem cells, which don’t involve destroying embryos. (He told me three years ago, 'I really believe personally that the value of these cells is not in transplantation,' and that '90% of the value of these cells will be in things that don’t make the front pages.') When Thomson did decide to become an entrepreneur, it was through a Madison, Wisconsin-based startup called Cellular Dynamics International, which uses the cells to create better ways of testing the safety and effectiveness of experimental drugs. Drug giants including Roche, Pfizer, and AstraZeneca have taken their own steps toward embracing stem-cell-based research. This field is slowly gaining steam just as the one Geron is abandoning its own attempts to heal the lame."
Brian Orelli on the MotleyFool investment web site wrote,
"Geron is giving up on stem cells. That's like Krispy Kreme Doughnuts without glazed treats, or Apple without Macintosh."
Adam Feuerstein on thestreet.com wrote:
"Geron's  decision to shut down its embryonic stem cell research programs is a blow to the controversial research field and a painful reminder that only dreamers and fools invest in embryonic stem cell stocks....But does anyone believe that Geron would jettison stem-cell research if the ongoing clinical trial in spinal cord injury were helping patient recover neurological or motor function?"

Geron Flight from hESC Research is 'Powerful Blow'

The news about Geron's abrupt departure from hESC research is rippling around the world this morning, casting a pall over the entire field.

The Financial Times of London, in a story by Andrew Jacksaid,
"Geron, the pioneering stem cell therapy company, has dealt a powerful blow to one of the most hyped areas of medicinal research by withdrawing entirely from the field."
Ron Leuty at the San Francisco Business Times said in an analysis,
"Just why would I want to invest in a space where one of the most promising companies just called it quits."
In a Washington Post article by Rob Stein, a patient advocate expressed bitterness.
"'I’m disgusted. It makes me sick,' said Daniel Heumann, who is on the board of the Christopher and Dana Reeve Foundation. 'To get people’s hopes up and then do this for financial reasons is despicable. They’re treating us like lab rats.'"
Geron, based in the San Francisco peninsula city of Menlo Park, cited financial problems when it announced yesterday that it was giving up on its stem cell efforts in favor of its cancer drug program. Geron is laying off 38 percent of its staff and says it will try to find a buyer for the stem cell program. Geron also settled its accounts with the California stem cell agency, which loaned it $25 million last May amidst considerable publicity.

The stem cell agency and other advocates expressed optimism about the long term potential of the field and noted the difficulties of bringing any therapy to production. Geron produced 21,000 pages of material over a years-long period to get FDA permission to begin only the first step in the long clinical trial process.

But the dominant tone of the news stories was negative. Heidi Ledford of Nature said Geron is "walking out on the field." Steve Johnson of the San Jose Mercury News said the decision casts "a cloud over the commercial viability of stem cell treatments."

Here are other excerpts:

San Francisco Business Times:
"What does this mean for companies that the California Institute for Regenerative Medicine, the state’s stem cell research funding agency, is pushing toward clinical trials? Will they only get so far before they, too, exit the business?" 
Fergus Walsh, medical correspondent for the BBC(see here), wrote:
"The decision does seem to be extraordinary given the huge investment of time and resources. When I visited Geron nearly three years ago, the then chief executive claimed the technology had an incredible future. 
"John Martin, professor of cardiovascular medicine at University College London said: 'The Geron trial had no real chance of success because of the design and the disease targeted. It was an intrinsically flawed study. And for that reasons we should not be describing this as a set back. 
"The first trials of stem cell that will give an answer are our own in the heart. The heart is an organ that can give quantitative data of quality.'"
Ryan Flinn of Business Week wrote,
"Geron fell 16 percent to $1.86 in extended trading. The shares have declined 58 percent this year.  
Robert Lanza, chief scientific officer of Advanced Cell Technology Inc.(of Santa Monica, Ca.), the second company to win permission from the U.S. Food and Drug Administration to test human embryonic stem cells in people, said the news wasn’t surprising, given the small patient population affected with spinal cord injuries. 
"'It was a very difficult choice to go in and treat spinal cord injury,' Lanza said in an interview. 'There was considerable concern in the scientific community that that might not have been the ideal first indication."
As first reported by the California Stem Cell Report, Geron's loan application was scored as a 66 on a scale 100 last May by scientific reviewers for the California stem cell agency. The score was not disclosed publicly at the time CIRM directors approved the award as has been the practice for all the other 400-plus awards that the agency has granted. The Geron approval process departed radically from the agency's regular procedures.

The news coverage in California of the Geron decision was marked by the absence of a story in the Los Angeles Times, the state's largest circulation newspaper. The San Francisco Chronicle carried only a brief story buried on page 6 of its business section. The California stem cell agency is based in San Francisco and the Bay Area contains one of the larger and more important biotech business and academic research communities in the world.

Monday, November 14, 2011

Geron Quits Stem Cell Research; Move Deemed Setback to the Field

In a surprise move, Geron today said it was terminating its stem cell business and what was the first-ever clinical trial of an hESC therapy, a potential product backed by a $25 million loan made by the California stem cell agency only six months ago.

Geron's move has "stark implications" for development of stem cell therapies in the United States, The Associated Press said. Andrew Pollack of the New York Times reported,
"The move is expected to be widely seen as a setback for the field, because of Geron’s central role."
The Menlo Park, Ca., company said it will fire 66 employees, 38 percent of its workforce, and will try to find buyers for its stem cell business.

The company's CEO, John Scarlett, cited the need to "focus our resources" given the "current environment of capital scarcity and uncertain economic conditions." The clinical trial of its spinal cord treatment will be closed to further enrollment, although it will continue to follow all four enrolled patients. The company said it now plans to focus on cancer drugs.

The company did not mention CIRM or the $25 million loan in its statement. The stem cell agency issued a press release that said,
"Geron had received $6.42 million of their loan, which the company today repaid in full with accrued interest."
In the news release, CIRM's Ellen Feigal, senior vice president for research and development, did not comment directly on Geron's move. She said CIRM remained optimistic about "many exciting stem cell programs in California." She said moving a therapy into the clinic is a "highly complicated process."

Absent from CIRM's press release were any comments from its new chairman, Jonathan Thomas, and CIRM President Alan Trounson.

Dropping stem cell research will improve Geron's cash situation. The New York Times' Pollack said,
"Geron will be able to last without needing to raise new money until it receives results of clinical trials of its cancer drugs over the next 18 months. By contrast, Dr. Scarlett said, given all the precautions in the stem cell field, he did not think there would be results from the stem cell trial until 2014."
The AP quoted stock analyst Steve Brozak of WBB Securities as saying Geron had encountered difficulty in finding partners for its stem cell program. He said potential partners wanted to see "later stage results." Of the clinical trial, Brozak said,
"It could be outsourced to a place like China very easily. In that case, this would be the de facto abdication of U.S. leadership in biotechnology."
With Geron's departure, Advanced Cell Technology of Santa Monica, Ca., is the only company with a clinical trial involving hESC, one targeting macular degeneration. ACT has never received an award from the California stem cell agency although it relocated its headquarters to California in the wake of the passage of Prop. 71, which created the state's $3 billion research program.

ACT was widely believed to have applied in CIRM's financing round last spring involving Geron.

CIRM directors approved the loan to Geron last May in a meeting that departed radically from its normal awards process.

As reported by the California Stem Cell Report in August,
"The Geron application was not given a public scientific score, standard practice for all the other 433 applications that the agency has approved over the last six years. The usual summary of grant reviewer comments was not provided to the public or the board. The three other applicants in the $50 million round all withdrew prior to presentation to the CIRM board – another first in CIRM's grant program. And no public explanation was provided at the time for the departures from long-established procedures." 

Sunday, November 13, 2011

$127 Million in 'Good News' for San Diego Stem Cell Researchers

Earlier today, an anonymous reader posted a comment on the California Stem Cell Report wondering where the "good news" was about the stem cell agency. We are not sure whether the reader was wondering about the content of this site or the mainstream media or both.

Sanford Consortium lab from live Webcam shot this weekend
on the Sanford web site. 
But the comment came less than 24 hours after a San Diego area newspaper published a glowing piece about the opening of a new stem cell research building under the auspices of five powerful research organizations – Salk, Scripps, Sanford Burnham, UC San Diego and the La Jolla Institute for Allergy and Immunology, a recent addition to the consortium.

Bradley Fikes of the North County Times wrote the story. He may be the last reporter in California to regularly, albeit infrequently, cover California stem cell issues for a mainstream newspaper.

Fikes' story heralded the $127 million structure. (The cost includes equipment.) He wrote,
"San Diego County's bid for supremacy in the fast-growing field of stem cell research will gain an iconic new image Nov. 29, when a gleaming headquarters for some of San Diego County's top stem cell researchers officially opens.

"The 132,000 square-foot building off in La Jolla will become the headquarters of the Sanford Consortium for Regenerative Medicine...."
The consortium was formed in the wake of voter approval of Prop. 71, which created California's $3 billion stem cell program and provided hundreds of millions of dollars for new labs. Edward Holmes, formerly vice chancellor at UC San Diego, is president and CEO of the consortium. Holmes is also chairman of the National Medical Research Council in Singapore. (For Holmes perspective on the consortium, see this 2010 interview.)

The building was financed with $43 million from the California stem cell agency, $65 million in bonds guaranteed by the University of California and $19 million from T. Denny Sanford, a South Dakota billionaire banker.

After CIRM approved funding for the building in May 2008, the consortium struggled with finding cash beyond what CIRM provided. The roadblocks delayed work on the facility, which was supposed to be completed by May 2010 at a cost of $155 million, according to the stem cell agency.

Like the other new labs assisted by $271 million in stem cell agency construction funds, the San Diego building is touted as conducive to bringing scientists together. Indeed, it has been dubbed a "collaboratory."

Fikes wrote,
"Even the staircases have been designed in keeping with the goal of making as much space as possible serve collaboration. The Sanford Consortium's staircases are wide, open and airy. They connect multiple 'laboratory neighborhoods' on different levels, so that scientists from different labs and floors will inevitably pass each other on their way to work."
Fikes said that at each level the staircases include areas with tables and chairs for quick chats. He quoted Louis Coffman, chief operating officer of the consortium, as saying,
"It's a lively interlude between floors. It creates an interesting space. More than that, it connects the physical locations of two different floors. So whereas people on different floors, who would otherwise be as disconnected as they would be in different buildings, hopefully they're going to make connections."

Monday, November 07, 2011

Searching for Facts About Cash: CIRM to Treasurer to Finance

"Even if your mother says it is true, check it out," an old saying goes. So we did.

The case in point was the new financial arrangement for the $3 billion California stem cell agency.

CIRM Chairman Jonathan Thomas laid out the plan last month for the California Stem Cell Report in the wake of a state bond issue that provided only $51 million for the agency, which fell far short of its needs over the next year or so. He said, however, a new arrangement was in place that amounted to a win-win for the state and the stem cell agency. The plan minimizes the amount of state bond borrowing immediately needed and instead provides, if necessary, short-term commercial paper, also backed by the state, but at less interest cost.

Thomas said both the state treasurer and the Brown Administration, through its state Department of Finance, were on board.

But -- keeping the admonition about mothers in mind -- we routinely asked the Finance Department and the state treasurer's office about the arrangement. What happened then provides some insight into how difficult it is sometimes to verify even what appear to be simple facts. It also tells a story about the responsiveness of state agencies and their dedication to openness and transparency.

Let's start with CIRM and Thomas. After we raised questions by email following the state bond sale Oct. 19, he offered a telephone interview about the situation and persisted despite dropped cellular signals and several callbacks from our post here in the bay off Panama City.

After we filed our item on the interview, we queried on Oct. 24 the other two agencies involved. The state treasurer's office responded quickly. The state Department of Finance, on the other hand, has remained silent on the subject to this day, despite three emailed queries.

Unfortunately, the state treasurer office's initial response was off the mark. "We haven’t seen any agreement.  We were not aware of the reported agreement until we read about it in your blog.  So, we have no comment about the reported agreement," the treasurer's office said initially.

That raised eyebrows a bit. So we renewed our queries to the Finance Department, even suggesting that a failure to respond could be construed as an indication that the Brown Administration is not fully behind CIRM.

Ten days after our initial query to the two agencies, we sent an email to Thomas briefly describing what we had planned to write and asking him if he would like to comment. He did not respond. But the next day, Steve Cooney, chief deputy state treasurer, said in an email that the earlier comment from the treasurer's office was incorrect. Cooney said,
"Our office DOES (Cooney's capitalization) and DID know that CIRM and the Department of Finance reached an understanding about future funding.

"The Treasurer’s Office has been aware since before last month’s sale of GO (general obligation) bonds that the Department of Finance and CIRM are in general agreement that the state will take necessary action to ensure that CIRM has adequate funds to meet its operational, grant funding and reserve needs, including the use of the state’s commercial paper line in the event the state cannot timely access the bond market.  It is neither necessary nor usual for our office to be informed of the specifics, if any, of any future commitment made by the Administration to any other state agency, including CIRM, and this case is no exception."
Cooney additionally re-affirmed the commercial paper arrangements for CIRM as laid out in the initial response from the treasurer's office.

The response said,
"The issuance of commercial paper has always been a part of our bond financing program.  The size of the CP line is about $1.5 billion, and it is available for use by all infrastructure programs, including stem cell research.  When we issue commercial paper to finance infrastructure projects, including CIRM, the paper is repaid with bond-sale proceeds.  So, if CIRM received funds from the issuance of commercial paper, the 'loan' would be retired not by CIRM, but by the proceeds of a subsequent bond sale."
Cooney also said,
"If you still need further clarification on the issue of future CIRM funding beyond the proceeds of the recent bond sale, the best place to get that information continues to be the Department of Finance."
Silence, however, has only been heard from the state Department of Finance.

Trounson, Parthenotes and International Stem Cell

The president of the California stem cell agency, Alan Trounson, popped up in a recent article in Scientific American dealing with a method for creating pluripotent stem cells from unfertilized human eggs.

The piece by Julia Galef said that "many investigators remain frustrated" that the method "remains offlimits" for federal funding, a barrier that does not apply to financing from the $3 billion California stem cell agency.

Galef wrote that one California firm, International Stem Cell Corp., of Carlsbad, is using the method to develop products. She said the firm's work involves "a process called parthenogenesis, in which researchers use chemicals to induce the egg to begin developing as if it had been fertilized. The egg—called a parthenote—behaves just like an embryo in the early stages of division. Because it contains no genetic material from a father, however, it cannot develop into a viable fetus."

Trounson was quoted as saying, nonetheless, that "proving that unfertilized eggs will produce stable tissues in humans remains an obstacle." He said other labs need to replicate the work.

International Stem Cell has applied unsuccessfully several times for research funding from the California stem cell agency.

The Scientific American article said,
"International Stem Cell scientists have converted them into liver cells and plan to convert them into neurons for treating Parkinson’s disease, pancreatic cells for diabetes, and other tissues. Meanwhile teams at the Massachusetts-based Bedford Stem Cell Research Foundation are working to improve the efficiency of methods of deriving stem cells from parthenotes."
As researcher interest in parthenotes gains attention, the NIH is being urged to change its negative position. Late last year, Teresa Woodruff, founder and director of the Institute for Women's Health Research at Northwestern University Feinberg School of Medicine, and others called for a lifting of the NIH ban on funding for parthenotes.

California is not constrained by NIH limitations. One of the key reasons, if not the only reason, that voters approved in 2004 the ballot initiative that created the $3 billion stem cell agency was to fund research that the federal government did not. At the time, the focus was on the Bush ban on financing hESC research.

Ken Aldrich, co-chairman of International Stem Cell, circulated the Scientific American article, touting its significance.

We found this posting on the Stem Cell Pioneers web site in which Aldrich said,
“We at International Stem Cell Corporation (ISCO.OB) are finding it increasingly gratifying that mainstream and highly respected publications like Scientific American are now beginning to take notice of the fact that our parthenogenetic stem cells may well turn out to be a viable alternative to the embryonic stem cells that have dominated research and headlines for the last 10 years.

"Like embryonic stem cells, our parthenogenetic stem cells can be converted into almost any kind of cell that might ever be needed for therapy, but can also provide a solution to the two biggest issues that have surrounded embryonic stem cell research: 1) the ethics of destroying a fertilized embryo, which our process never does, and 2) the problem of immune rejection by the patient. We hope you enjoy the attached article." 

Wednesday, November 02, 2011

Stem Cell Agency's Lobbyist Now Ranked No. 1 in California

The $3 billion California stem cell agency likes to align itself with the very best science. And as of today it is also hooked up with the best lobbyist in California – at least based on earnings.

CIRM hires many firms to perform work, given its unusual needs, rather than building a large and relatively permanent staff. The tasks of the outside contractors range from publishing the annual report to grant review matters. Today Laurel Rosenhall of The Sacramento Bee reported that one of the firms that CIRM has hired now ranks as the No. 1 lobbyist in California, based on its earnings.

The firm of Nielsen, Merksamer, Parrinello, Gross & Leoni pulled down nearly $5 million during the first three quarters of this year. The firm knocked KP Public Affairs out of the top spot, which it had held for at least the last 10 years.

Nielsen has had a contract with CIRM since its earliest days in 2005, but it doesn't amount to much in the scope of Nielsen's business. According to the latest CIRM report on outside contracting, Nielsen was paid $79,984 during the fiscal year 2010-2011 for services that also extended into the current fiscal year. The report did not list payments for earlier years, but it is our recollection that Nielsen was paid about $50,000 every year since 2005. It is not known whether the firm continues to hold a contract for the current fiscal year.

One of Nielsen's partners, Gene Erbin, was one of the drafters of Prop. 71, the ballot initiative that created the California stem cell agency in 2004. Merck and Pfizer, in addition to CIRM, are among the firm's clients.

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