ACT Seeks hESC Clinical Trial

Advanced Cell Technology has become the second U.S. company to seek permission to begin clinical trials for a therapy based on human embryonic stem cells.

The Santa Monica, Ca., firm said yesterday that it has applied to the FDA to start trials aimed at reversing vision loss with retinal cells created from the stem cells.

The firm, which has labs in Massachusetts, is only the second business to seek to perform clinical trials involving hESC. Geron, another California company, was the first, but its efforts are now on hold until late next year because of FDA safety concerns.

Neither of the firms has received funding from the California stem cell agency. ACT, however, moved its headquarters to California, partly to seek funding from CIRM.

The firm's announcement received modest news coverage. Steve Connor of the Independent in Great Britain quoted Robert Lanza, ACT's chief scientific officer as saying,

"'We've seen absolutely no adverse effects whatsoever in any of the preclinical experiments and our cells are more than 99.9 per cent pure. We certainly expect them [the FDA] to come back with comments and questions but our hope is that we will start sometime early next year. We're optimistic and certainly confident in our own data. We've been in dialogue [with the FDA] and we know what was on their mind and what they wanted us to do. We're hoping, assuming no hitches, to begin early next year, perhaps March."

Here are links to additional coverage: Los Angeles Times, Science, Nature, MassHighTech. Sphere: Related Content

Scripps' Loring Teams with International Stem Cell Corp.

The Scripps Research Institute and scientist Jeanne Loring are collaborating with International Stem Cell Corp. of Oceanside, Ca., to study parthenogenic stem cells and their potential therapeutic use, it was announced today.

In a news release from the company, Loring, director of the Center for Regenerative Medicine at Scripps, said,

“"Parthenogenetic cell lines are uniquely valuable for our quest to understand the genetic and epigenetic processes that control stem cells. We are excited about the opportunity to collaborate with scientists at ISCO."

International Stem Cell said its scientists have derived a type of cell found in the human eye from parthenogenetic stem cells that may have application in treatment of macular degeneration. The company said it and Loring and will study these cells as part of the collaboration.

Kenneth Aldrich, chairman of International Stem Cell said,

“Our intent is to begin to provide these parthenogenetic stem cell lines to advance the field of regenerative medicine, as well as to commercialize our cells for cell transplant therapies.”

The firm has applied for grants from the California stem cell agency, but so far has not been successful. CIRM, however, is currently trying to link more closely with industry. Sphere: Related Content

Biotech Firms: The Undead of Capitalism?

The Wall Street Journal today did not describe biotech companies as zombies but it might as well have.

That, despite an increasingly brighter financial picture for the biotech business.

All this was contained in a piece by Brett Arends. He said the good news – the brighter picture – is the bad news. He wrote that the biotech industry, which includes stem cells, is “incredibly popular with many private investors,” but is a “risky area with very mixed results.”

Arends said,

“It's hard enough to value a profitable company that makes widgets or coffee. How do you value a speculative science project that may not come to fruition for years, if ever? ...(A)nalysts in the sector sometimes talk about 'the probability-adjusted net present value of peak sales,' essentially guessing how much a company might make off a drug at peak sales, lowering that value to reflect how long it will take to get there, and then calculating the probability that a drug will make it through clinical trials and win approval.”

He continued,

“And then there's the dormancy risk—few biotech companies go bankrupt....Many of them just go nowhere.”

Sort of like zombie enterprises, the undead of capitalism.

Arends quoted Don Collins of Ironwood Capital Management as saying,

"They don't have any debt, so there is no one to force them out of business. So as the cash dwindles, the companies just shrink and shrink and shrink, until they have three guys working there and a business development manager going out looking for money.. They can stay like that for a long time.'

“Old biotechs, in other words, never die.”

The WSJ article pointed out that the average retiurn on a biotech IPO since 2001 has been minus 18 percent. Between 1995 and 2000, it was a meager 8.44 percent. You could have earned more investing in plain old bonds or cash.

Arends concluded,

“Capitalism famously depends on 'creative destruction,' in which bad or weak companies get weeded out. The strong survive. The best industries in which to invest are often those which have been starved of capital for a generation—think gold and oil. The worst, in turn, are often those like biotech, where it's all too easy to get capital without showing results.”

Something for the California stem cell agency to think about as it kicks off its unprecedented, $500 million biotech loan program, which optimistically projects “profits” of $100 million despite default rates of up 50 percent.

(The WSJ may have restricted the Arends article to subscribers. If you cannot access it, send an email to djensen@californiastemcellreport.com, and we will send the article to you.) Sphere: Related Content

CIRM Releases Bank Info That It Once Withheld

The California stem cell agency late today released information on a $250,000 contract with Square 1 bank that the agency previously had refused to disclose at the request of Square 1.

The move was prompted by inquiries from the California Stem Cell Report about the withholding of the information, which is public record and should have been released earlier.

Don Gibbons, chief communications officer for CIRM, said in an email,

“After your inquiry, we contacted Square 1 to see if they would reconsider their request to treat the pricing information as confidential, in the interest of public disclosure. Square 1 has agreed that we should produce an unredacted copy of attachment B to the contract, but they would like to note that they sought to protect the pricing information because they do regard it as proprietary (i.e., it is not known to their competitors and could give them a competitive advantage), but that they will waive their objection to producing the information in the interests of transparency. The unredacted document is attached.

“CIRM staff initially redacted the pricing information at Square 1’s request, but we remain responsible for deciding whether to honor such requests. We could have asked Square 1 to waive its request before we produced the document. In retrospect, we should have slowed down and taken the time to do that.”

CIRM is to be commended for pushing forward with its effort to release the information. Square 1 did the right thing as well, even though it contends the information should be proprietary. We wrote earlier about the implications for CIRM in connection with failing to comply with state public record law.

John M. Simpson, stem cell project director for Consumer Watchdog of Santa Monica, Ca., was harshly criticial of the earlier censorship of the Square 1 contract. Following the release of the information, he said,

“I'm glad CIRM is doing the right thing. I hope the staff learns something from this experience.”

One of the downsides for many businesses in dealing with the state is that it does require disclosure of information that many business would like to keep out of the public gaze. But there can be great benefits as well. In the case of Square 1, this initial contract gives it a leg up on competitors in terms of securing much a more lucrative, long-term contract with CIRM for its fledgling, $500 million biotech loan program.

The current contract will serve as a baseline for future arrangements. Square 1 and CIRM staff will be working together to smooth out the process and build relationships that will be valuable in the future. The linkage between Square 1 and the $3 billion stem cell agency, the world's largest source of funding for human embryonic stem cell research, will also enhance the bank's prestige and ability to secure additional profitable business.

It is also likely that the fee structure, as now disclosed by CIRM, will be modified in future arrangements, which will require a new, public bidding process.

The redacted contract can be found here. The newly released information can be found here. Sphere: Related Content

CIRM's Openness Failures Raise Broader Questions

The chairman of the California stem cell agency, Robert Klein, frequently is given to declaring that the $3 billion research effort adheres to the highest standards of openness and transparency.

Recently, however, the agency has had difficulty even complying with the basic state public records law and the state Constitution's public access guarantees, much less achieving a higher level of performance.

The specific instances are relatively minor, but they raise important questions concerning the conduct of the public's business. How is CIRM, which cannot operate without outside contractors, overseeing their efforts? Is CIRM becoming too cozy with industry? And how can CIRM maintain its credibility unless it is forthright about its affairs?

One longtime CIRM observer, John M. Simpson, stem cell project director of Consumer Watchdog of Santa Monica, Ca., described as “outrageous” CIRM's most recent failure to comply with the open records law.

In response to a query, he said,

"CIRM's lawyers need to learn who their client is when they are employed at a public agency. It's the citizens of California, not vested special interests."

The two most recent cases involving CIRM's failure to comply with state public records law both concern contracts with private firms. The first is a $100,000 contract with Levin & Co., of Boston, Mass., to help search for candidates for the position of vice president for research and development. The second involves a $250,000 contract with Square One Bank to conduct a financial review of Novocell, which was approved for a $20 million loan by CIRM directors last month.

In the case of Levin, the censored material involved 16 pieces of information including its legal business name, address, whether it is a partnership or corporation, name of the person signing the document and his or her title along with his signature and date of the signing. Even the names of those categories were blacked out.

(See page 14 of the contract for a look at the redaction. A blank copy of the state form involved can be found here.

Previously CIRM had posted such information for other companies voluntarily on its Web site, so we had assumed that the redactions were a mistake and consequently did not write about the matter. (After we questioned the redaction, CIRM ultimately provided the material it had chosen to withhold.)

Then came the response to our Oct. 16 request for a copy of the contract with Square One bank. It was another relatively routine matter, although it involves the start-up stages of a $500 million biotech loan program that is expected to have default rates up to 50 percent.

The copy of the contract showed that it was capped at $250,000, but that information had been reported earlier. Censored was the following information: underwriting fee to be paid per loan, annual service fee, warrant administration fee and the legal fee to be paid by CIRM to Square One

Such information is public record and commonly disclosed by state agencies. Otherwise, invoices to CIRM and payments by the agency containing that information would be cloaked in secrecy.

On Nov. 8, we asked CIRM for the legal justification for not providing the Square One fee information. Yesterday (Nov. 16), Don Gibbons, chief communications officer for CIRM, replied with one sentence,

“From our legal team: The redactions were made at the request of Square 1 Bank, based on its determination that the fee structure is confidential and proprietary.“

In response, we emailed Gibbons,

“I assume that your response ...means that the lawyers agree that the material is confidential under state law. It does not directly say that, however. Please let me know if CIRM lawyers think otherwise.”

Gibbons' complete reply:

“We let all contractors make initial decisions on what is proprietary. Square One made the decision that the structure of their fees, not the ultimate amount paid, was proprietary. In the interest of transparency, we have asked them to reconsider that decision.”

As of this writing, we have received no further response from Gibbons. Also yesterday, we asked Square One about its justification for censoring the information, but have received no response. (We will carry its response verbatim if we receive one.)

As Consumer Watchdog's Simpson indicated earlier, CIRM's actions raise questions about the management of its outside contractors, which are essential to the agency's operations. CIRM would cease to function without its outside help. It is restricted by an ill-considered provision in Prop. 71 to only 50 employees. Currently the cost of contracting is the second largest item ($3.1 million) in its operational budget, just behind salaries and benefits.

In the case of Square One, CIRM's attorneys should have told the firm that its request did not comply with state law. CIRM should have then released the entire document. In our case, we have had decades of experience with public record law and can generally tell when there is a flagrant violation. But other members of the public are likely to accept whatever CIRM, driven by desires of its suppliers, deigns to pass along.

The contracts signed by Levin and Square One are state documents. CIRM is required by law to determine what is public or confidential, not the outside contractors. Certainly they can and should be consulted, but their wishes must not be blindly followed. To do so is to open CIRM to unnecessary legal challenges by foes of stem cell research.

Failure to be forthright also raises questions about other areas of CIRM that bear attention, such as the problems with the software that is critical to the oversight of what is now a $1 billion grant portfolio along with the $250,000 federal lobbying contract with Tony Podesta, also heavily censored and we suspect unnecessarily so.

Managing outside contractors has always been difficult for government, both at the state and national levels. The stories of abuses are legion, whether it is a Defense Department boondoggle or fouled up databases at the state Department of Motor Vehicles. CIRM must make it clear to its contractors that the agency's needs must be met and that the interests of the taxpayers do not necessarily coincide with those of the contractors. Sphere: Related Content

Some Question CIRM Grant Oversight as Excessive

The California stem cell agency is receiving “mixed reviews” for its oversight of its research grants, which now total $1 billion, according to an article today in The Scientist magazine.

Commonly governmental agencies are chastised for failing to ensure that taxpayer funds are spent effectively. In this case, the stem cell agency is being faulted -- by some -- for being too tough.

The case in point is the termination -- first reported by the California Stem Cell Report -- of three out of more than 300 grants. The amounts are tiny compared to the $3 billion that CIRM expects to give away, accounting for only $1.8 million in a $46 million round approved in 2007.

The Scientist article by Jef Akst said,

“Clearly, funding agencies need to offer some oversight of grants to avoid misuse of funds. But can there be too much of a good thing? “

She continued,

“There are mixed reviews among the scientific community about whether CIRM's close watch of their grantees is a good thing. To some, it is an important practice for public funding agencies such as CIRM to show the taxpayers that their money is going towards productive and fruitful research. 'I think the oversight is outstanding,' said John Simpson, the stem cell project director at the advocacy group Consumer Watchdog in California. 'It shows that they're not asleep at the switch. CIRM is functioning as both a grant making agency [and] also something of a steward of the funds it hands out.'

“But others say this kind of intense supervision can burden investigators -- and the science itself. 'In theory, it's a terrific thing,' agreed David Kaplan of Case Western Reserve University in Ohio, who has written about the peer review system at NIH. "To have the granting agency being involved enough to be helpful to their grantees, I think that is a terrific idea. The problem with that kind of a system is that you can be too intrusive. That eliminates that kind of serendipity [in scientific discovery].'“

Akst wrote that CIRM's “short timeline” may lie behind its grant monitoring, which is more rigorous than performed by the NIH.

She said,

“While the NIH will exist for many years to come, CIRM has a 10-year lifespan, as approved by California voters in 2004. 'CIRM has very defined goals,' said the Burnham Institute for Medical Research's Huei-Sheng Vincent Chen, another SEED grant recipient. '[They] wanted something within 10 years so they have to be more aggressive.'"

The Scientist magazine also chose to publish the names of the scientists whose grants were terminated. Their names are by law public record. Only one of the three scientists spoke with Akst, John Cooke of Stanford.

Akst's story said,

"'I anticipated that they would be happy with that [new] proposal,' Cooke recalled. 'But] they weren't happy.' In January 2009, after a second, more detailed progress report, follow up phone discussions, and a petition for reconsideration from Cooke, CIRM revoked his second year of funding -- nearly half of what he had originally been awarded -- citing the new directions his research had taken.

'I can understand their reasoning,' Cooke said. 'I just wish I had understood that that applied to the SEED grants.'"

Last month, CIRM approved $230 million for 14 grants up to $20 million each that appear to require even more rigorous oversight than earlier rounds. Some CIRM directors said publicly that they expect to see some of the latest grants terminated early because they will fail to meet the required benchmarks.

You can find a list here of all the items published on the California Stem Cell Report concerning the terminated grants. They include comments from the other two scientists, who we have chosen not to identify for previously discussed reasons. Sphere: Related Content

$30 Million Available for Immunology Research

The California stem cell sweepstakes began another round this week with a $30 million jackpot for about 20 researchers.

CIRM is looking for applications from both research institutions and businesses as well as proposals for scientific collaboration with researchers from Germany and Australia.

This round will finance “transformative” research into cell transplantation immunology. The hope is that it will lead to development of immune tolerance of pluripotent stem cell derivatives and potential correction of autoimmunity.

Mandatory letters of intent are due Dec. 15. Winners should expect checks in the mail next summer.

Applications and details can be found here.
Sphere: Related Content

A Look at Tucson's Calimmune and $20 Milllion

The global headquarters of Calimmune, Inc., which shares in a $20 million grant from the California stem cell agency, stands on one of the more unlovely thoroughfares in Arizona.

The three-year-old firm is only a short walk on East Broadway in Tucson from O'Reilly Chevrolet and a Burger King. While Calimmune's address may not electrify folks on Wall Street, it has a pedigree that it is hard to quibble with.

By one account, Calimmune was founded by David Baltimore (see photo), a former member of the board of directors of the $3 billion California stem cell agency. Baltimore also is a Nobel Prize winner and former president of Caltech. Other accounts state that Irvin Chen, director of the UCLA AIDS Institute, was a co-founder.

Late last month, California's stem cell agency approved a $20 million grant to Chen and Geoff Symonds, chief scientific officer of Calimmune, a little-known company with no Web site but a laboratory in Australia, lab space in Pasadena, Ca., and more facilities soon to come at UCLA.

CIRM said the grant was aimed at generating an FDA application in four years for a clinical trial “to treat HIV/AIDS using an RNA interference approach to modify the patient’s blood-forming stem cells. When transplanted back, those cells will produce T cells that are resistant to HIV infection.”

The proposal echoes Calimmune goals articulated earlier on the Web site of Grayhawk Capital, a private equity investment company in Phoenix, Az., that has cash in Calimunne. Some initial research involving Symonds and UCLA was published last February with partial funding from Johnson & Johnson in Australia.

In response to email queries, Calimmune's CEO, Louis Breton, told the California Stem Cell Report that Symonds will perform his CIRM-funded work in California. He said the closely held firm is aware that CIRM is barred from funding out-of-state grants. Breton did not respond to questions about the number of Calimmune employees and their locations, although he said he anticipated more hiring for the CIRM grant. He said the Tucson location houses a small administrative staff. The company is incorporated in Delaware.

As for Calimmune's funding, we asked Breton whether any originated with Johnson & Johnson. Until the last year or so, Symonds was senior research director at Johnson & Johnson Research Pty Ltd. in Sydney, Australia, where the Calimmune lab is located. According to one report earlier this year, he holds more than $10,000 in Johnson & Johnson stock. At least one of the other Calimmune scientists in Australia worked as well for Johnson & Johnson until February. Breton, however, said none of the company's funding originated with Johnson & Johnson. Grayhawk did not respond our email query.

A Johnson & Johnson company document said in 2008 that the purpose of the Johnson & Johnson research operation involving Symonds was “to identify new medical discoveries in Australia and facilitate their commercial development into new products for Johnson & Johnson.”

CIRM reviewers were enthusiastic about Chen and Symonds disease team project. A CIRM summary of the application said,

“Reviewers stated that the resources and investigators are outstanding and the team is superb, both scientifically and in therapy development. The Disease Team comprises a collaboration between two complementary groups, one academic and one corporate. Each brings unique expertise to the project, with the academic group providing scientific know-how and proof of concept and the corporate group providing expertise in biologics development and commercialization. The team leaders are accomplished, highly productive investigators with a demonstrated track record in the field of HIV research, gene therapy, and/or clinical drug development. Key members of this team made the initial scientific observations leading to their hypothesis and demonstrated proof of concept in tissue culture and relevant models. A subset of the team has direct experience with a gene therapy trial in humans.”

Sphere: Related Content