CIRM 2.0 -- California's New Urgency for Stem Cell Therapies

This is a big week for Randy Mills, the man who took control of the $3 billion California stem cell agency just seven months ago.

His proposals for radical changes at the agency are expected to be approved by its governing board on Thursday along with a restructuring aimed at improving speed, efficiency and innovation.

It all comes under the rubric of “CIRM 2.0,” a phrase coined by UC Davis stem cell researcher Paul Knoepfler and adopted by Mills after he became president of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known.  

 How important are the changes? Important enough for the agency to tout their mere outline in a press release out of last October’s board meeting instead of focusing on the hard news of the approval of its much-ballyhooed Alpha stem cell clinic program.

Randy Mills
CIRM photo -- Todd Dubnicoff

Mills has made his career in business, serving as 10 years as the CEO of Osiris Therapeutics of Maryland. He managed to make Prochymal the world's first government-approved stem cell drug approved for use on an off-the-shelf basis. Mills likes to move fast, which is largely the point of CIRM 2.0, and says that he wants to make the agency “radically more effective and efficient.”

The agency’s news release in October quoted Mills as saying,

“Right now it can take almost two years for a promising idea to go from the application to the final funding stage. That’s just unacceptable. We are going to shorten that to just 120 days.”

He also told directors at their October meeting,

 “We are in the business of trying to save people’s lives….We have to behave with the appropriate sense of urgency.” 

Mills knows that stem cell companies can’t sit around waiting two years for cash. Most operate on a short financial leash and are perpetually having to raise money. Mills also knows that researchers with non-profit institutions cannot wait for whenever it is convenient for the agency to bless them with greenbacks. Those researchers want to be first with their findings. And they need cash to meet payrolls and to satisfy their sponsoring institutions.

So Mills says,

“We’re not just making it faster, we’re also making it easier for companies or institutions with a therapy that is ready to go into clinical trials to be able to get funding for their project when they need it. Under this new system they will be able to apply anytime, and not have to try and shoehorn their needs into our application process.” 

At the end of January, the agency will begin accepting grant applications related to clinical trials on a monthly basis. The promise is for quick decisions and quick cash. Rejected researchers will – if their thinking has CIRM potential – be coached and guided into preparing a fundable project. Accepted researchers will find themselves working more closely than ever with CIRM staffers to develop something that will emerge as a marketable product. 

Mills is convinced that CIRM 2.0 will also improve applications, generating more proposals that will be scored at 95 out of 100 by scientific reviewers instead of the many applications scored at 75 that have been regularly approved.  

All of the details of the plan are still not clear. But $50 million will be set aside for the first six months of next year. Applicants can ask for whatever amount they want, but budgets will be scrutinized before they even get to the scientific reviewers. Appeals will not be allowed.  Milestones must be met or the cash dries up.  

The whole process sounds a bit like a venture capital operation minus face-to-face pitch meetings.

 

New rules dealing with conflicts-of-interest on the part of reviewers will be in place. They will allow applicants to seek to disqualify up to three reviewers for almost any reason. However, applicants will not be told who is reviewing their applications behind closed doors. They will have to guess by ferreting out reviewer names from CIRM’s list of more than 100.

Little public criticism of the plan has been heard at the two initial briefings that Mills has given board members. It is clear that there will be hiccups or worse, like any new process. One question involves transparency. Will the public or other scientists know which applications have been rejected along with the subject of their research, as they do currently. Another question involves board involvement. Currently seven members of governing board sit on the review committee. How will they participate on a monthly basis?

Coaching rejected applicants can lead to better or more targeted proposals. But is that something that researchers will readily accept? Does the whole process move the board farther away from the grant-making process. Already the directors have turned over what once were public appeals by rejected applicants to agency staff to be handled behind closed doors. However, applicants can still speak directly to the board on their own on any subject under a state law that CIRM cannot change.  But none has been successful recently in winning grant approval through that route.

Mills says his reorganization plan for CIRM staff – he prefers the word “team” – will create “organizational clarity and operational efficiency.”  It will certainly help to break up ossified structures that may have grown up during the tenure of former President Alan Trounson, who was not known for his managerial or organizational skills.

The plan also would seem to have some impact on the controversial dual executive arrangement involving the president and the chairman of the agency, Jonathan Thomas, who is also salaried. On the surface, the reorganization would seem to remove some responsibilities from the chairman and cost him some of his staff. However, the agency has not responded to questions concerning that area.

Kevin McCormack, senior director of communications for CIRM and who is also one of the top executives at the agency, will no longer be reporting, for example, to both the chairman and the president. That shared reporting was insisted on by former Chairman Robert Klein when the position that McCormack came to occupy was created. 

The dual executive arrangement, which is enshrined in state law, has been criticized for minimizing accountability at the agency. It has also led to tussles between Klein and other executives, although no serious disputes have surfaced in public for several years.

CIRM 2.0 holds great promise. It also depends mightily on Mills' leadership and managerial skills in a considerably different environment than he has previously experienced. Will CIRM 2.0 make a favorable impression in the scientific community and with the public? That depends, of course, on the outcome of the research it generates. So far, CIRM 2.0 is barely visible in the stem cell community -- at least according to an item on the blog of UC Davis researcher Knoepfler. His readers were recently asked to vote on the top stem cell story of 2014. CIRM 2.0 came in last with 0.44 percent of the vote.

That sort of response does not discourage Mills.  He said, in an item on Knoepfer’s blog prior to the 0.44 percent showing:

 “We think the more the word gets out about this and all of the other great features of CIRM 2.0, the more high quality interest we will see from industry and academia alike.”

The details of the plan were approved yesterday by the Governance Subcommittee of the CIRM governing board. The plan will come before the full board at its meeting Thursday in Berkeley, with teleconference locations in Los Angeles, San Francisco and Sacramento and is virtually certain to be approved.

 (Here are links to the CIRM blog item on the 2.0 plan and to Mills’ slides that he presented to CIRM directors nearly two months ago. The transcript of that meeting has not yet been posted by the agency. Perhaps Mills can add posting of transcripts to his fast-track efforts.)

California Stem Cell Agency Overhauls Grant Review Conflict Rules; Secrecy Remains

The California stem cell agency this week is expected to begin sweeping out its current conflict-of-interest rules for multi-million dollar research applications and giving applicants wider range to disqualify some grant reviewers in advance.

Little about the operation of the rules, however, will be disclosed to the public or applicants, although the regulations are critical to the integrity of the $3 billion operation.

The new grant review procedures received a preliminary go-ahead Nov. 24 from the Governance Subcommittee of the governing board of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known. The proposals will come before the full board this Thursday at a meeting in Berkeley.

James Harrison, the outside counsel to the CIRM board, described the changes concerning scientific grant reviewers as “substantial” in a memo to the board. One key provision would involve “a screening mechanism that would permit applicants to identify up to a total of three individuals (including labs and companies) whom the applicants believe could be biased (whether for personal, professional, competitive, or any other reasons).”

The exact mechanism was not otherwise described in Harrison’s memo. 

CIRM’s grant review process is currently shrouded in secrecy in keeping with tradition in the scientific research community and will remain that way under the new rules. Virtually all of the grant review is performed behind closed doors. Identities of specific reviewers on an application are withheld. Names of applicants are withheld. Financial and professional interests of the reviewers are withheld, revealed only to some CIRM staffers.

When an applicant files a complaint about a financial conflict of interest on the part of reviewers, all of the information is withheld.

That is the environment in which the agency’s scientific reviewers operate while they make the de facto decisions on virtually all of the $1.8 billion that has been handed out over the last 10 years. The governing board rarely overturns a positive decision by its reviewers, all of whom come from out of state.  

In response to a question today, Kevin McCormack, a spokesman for the agency, said that the secrecy would continue under the new rules. He said applicants could examine the list of more than 100 potential reviewers if they had concerns about conflicts. A much, much smaller number is actually involved in a specific application review. Those names are withheld. 

No restrictions exist, however, on applicants publicly disclosing their conflict-of-interest concerns either directly to the board or to any other private or public entity.

The proposed conflict changes would also disqualify reviewers from evaluating an application from a person who has “been on opposing sides of a formal legal dispute.”  A reviewer would be required “to recuse himself or herself if the member believes his or her objectivity could be compromised for any reason.”

Other changes would expand the scope of financial conflicts by including relationships with partnering organizations and subcontractors.

The Harrison memo said,

“The intent of this change is to capture other financial interests that could create a conflict of interest with respect to a particular application because they are significant participants in the proposed project or stand to benefit financially if the project is successful.”

The proposed rules originated more than a year ago as an outgrowth of a discussion at a stem cell agency board meeting involving earlier possible changes. The board was told that only two cases have surfaced involving violations by reviewers. No names were mentioned during the board meeting.

One case involved reviewer Lee Hood, a renown scientist from Washington state, in a conflict connected to another internationally known scientist, Stanford researcher Irv Weissman, in a $40 million round. The other involved John Sladek of the University of Colorado, who was head of the grant review group, in a $45 million round.  The violations were first disclosed publicly by the California Stem Cell Report. The agency did not post the violations on its Web site, reporting them only to the California legislative leadership as required by law.

At the October 2013 agency meeting of the agency governing board meeting, Jeff Sheehy, a board member and communications manager at UC San Francisco, asked if the Hood and Sladek violations would also be considered violations under the rules being proposed at that 2013 meeting.  Sheehy was told that they would not, according to the transcript of the meeting. Sheehy replied,

“Well then, I think it's not possible for me to even support the initiation of this process because in the last case(Hood-Weissman), at least what I've been told, the identification of the conflict, which was the reviewer and the grantee held property together, and the identification of that conflict was made by a fellow reviewer. So if we have a conflict that is deemed material by members of the scientific community, it's hard for me to understand why the net that we're casting should make the holes bigger in order to let the fish out.”

After some discussion of Sheehy’s remarks and other concerns voiced by board member Stephen Juelsgaard, former executive vice president of Genentech, the proposed changes were sent to the Governance Subcommittee for revision.  

Harrison’s memo for this week’s meeting did not specify whether the two past violations would now also be considered violations under the latest rules.

The new rules would apply initially to the agency’s new, $50 million fast-track clinical program and then be extended to all applications.  The action this week will impose the regulations on an interim basis while they work their way through the state’s official rule-making process during which the public may comment.

In addition to the Berkeley meeting location, interested parties can participate at a teleconference location in Sacramento and two in Los Angeles.  Specific addresses can be found on the agenda. Room numbers can be learned by emailing mbonneville@cirm.ca.gov.  Comments or suggestions can be sent to that email address as well.

'Radical' Improvements Coming at California Stem Cell Agency

The new president of the $3 billion California stem cell agency is not interested in “staying the course” on development of stem cell therapies in the Golden State.

Randy Mills has bigger goals in mind. He told ipscell.com that the opportunities in California go well beyond what has already been done at California Institute for Regenerative Medicine (CIRM), as the agency is formally known.  Mills said,

“If you believe in the potential of regenerative medicine and cell therapy as I do, there is no place in the world you could go to have a bigger impact. No company, no other state, not even a country can have the impact California can have in bringing these treatments to patients.

“My interest at CIRM isn’t to ‘stay the course’ – it is to be as innovative as possible to make the agency radically more effective and efficient.”

For a look at some of what's coming, see the $50 million, California stem cell speed-up item here.

Mills’ remarks were reported last Friday in an email interview on the blog produced by Paul Knoepfler, a stem cell scientist at UC Davis.

Mills had high praise for the CIRM staff, discussed CIRM’s financial position, identified his top priority for stem cell therapy treatments and named his favorite stem cells.

Mills, who made his career in business prior to joining CIRM last May, described the CIRM team as “remarkable.” He said,

“It is such a gift for a new leader to be able to come into an organization and have such talent to work with.”

Mills also discussed his revision of previous CIRM predictions that its funding for new grants would run out in 2017. He said,

“It’s funny, I was able to extend the funding life of CIRM until at least 2020 by using a little trick I once learned called “math.” Not to put to fine of a point on it, but I basically looked at how much money we actually had left to spend (approximately $1 billion) and divided it by how much money we actually awarded each year – about $190 million. And there you have it, 2020.”

Mills also questioned assumptions that all concepts approved by the board would be funded at the amount initially proposed.

Knoepfler asked about the challenges facing the regenerative medicine field. Mills replied,

“The single most important thing for us to do in cell therapy is to generate clear and convincing evidence of efficacy in humans. All of the other major issues surrounding regenerative medicine, such as high product cost and scalability can and will be solved once there is obvious and compelling proof of concept data for a product. Looking ahead, I am really excited about some of the things coming down the CIRM pipeline that have the potential to reach this high standard.”

Knoepfler also asked,

“Do you have a favorite kind of stem cell and why?”

Mills replied,

“It’s a toss up between mesenchymal mint chip and pluripotent pasticcio – they are both delicious! 

“In reality, no. I am agnostic as to stem cell type. My favorites are the ones that help patients.”

California Stem Cell Speed-Up: $50 Million for New, Rapid-Action Program

The mystery at the $3 billion California stem cell agency has cleared up.

The agency yesterday posted a document that provided some details on just what is to be considered next week by the agency’s board of directors, and it is very big stuff -- $50 million worth.

It involves what the agency’s new president, Randy Mills, calls CIRM 2.0 and is intended to speed considerably the agency’s work on research that is closer to reaching the public. (The agency is commonly referred to as CIRM after its official name. the California Institute for Regenerative Medicine.)

The information on the new effort came only one business day prior to scheduled action on the plan by the directors’ Scientific Subcommittee, which meets Monday. The proposal is expected to win approval at the board’s full meeting next Thursday in Berkeley.

Mills’ plan calls for spending $50 million between now and next July on grant applications that will be received every month, instead of sporadically as in the past.  The objective of the program is to create "a more streamlined process for awarding and administering grants that will include frequent and predictable submission opportunities followed by rapid review, quick funding decisions, streamlined contracting and the prompt initiation of research."

Applicants can ask for as much money as they want. No caps are being set in advance, but the research budgets will be thoroughly analyzed prior to review. Indirect costs will be limited, however, to only 10 percent of the award. That is a major reduction.  Kevin McCormack, a spokesman for CIRM, said last year that a 20 percent cap exists on indirect costs on awards. Grants also provide for “facilities” costs at an additional percentage that can be much higher than the 20 percent.  The rate varies from institution to institution.  

Matching funds will be required by both business and nonprofit applicants in some cases in the three-stage program. Business applicants will have to show that they have six months of “cash on hand” from the date of the application submission. 

Applications will be due on the last business day of each month, presumably beginning Wednesday Dec. 31. The CIRM board would act on the award about 90 days following submission. Work must begin within 45 days of approval of awards by the full board, about 130 days after submission of the application, according to Mills' memo to the CIRM board. 

Mills’ plan also calls for a major change in appeals of negative reviews, saying they would be limited to “demonstrable conflicts of interest” as defined by CIRM’s existing policies. Mills’ memo said the change was being made because of “the open opportunity to apply and amend  rejected applications.”

Mills has said successful applicants will be strongly guided by CIRM. Unsuccessful applicants will be coached by CIRM on how to alter their proposals if the agency feels their plans have strong potential.

Parties interested in commenting on the plan or suggesting changes can send their remarks to the directors by emailing them to mbonneville@cirm.ca.gov. They can also participate in Monday’s 90-minute meeting at teleconference locations in San Francisco, Duarte, Los Angeles, Irvine, La Jolla and Oakland. Addresses can be found on the meeting agenda, but specific room numbers are not given. Those can be obtained by calling CIRM at 415-396-9100 or email to mbonneville@cirm.ca.gov.

The California Stem Cell Report will have more on this and other CIRM 2.0 changes prior to next Thursday’s meeting.

A Public Mystery at the $3 Billion California Stem Cell Agency

The latest proposal by the California stem cell agency for apparent clinical testing of stem cell therapies could be a $2 million effort or $20 million effort. It could be designed to tackle Alzheimer’s or cancer. It could involve commercial firms or just research institutions.

But no one – outside of the agency – really knows. With only two business days before the proposal is scheduled to be considered by the agency’s directors, it remains under wraps as far as the public is concerned. It is a public mystery.

All that the public is allowed to see as of noon today is a cryptic, eight-word description – “concept plan for new clinical phase development program.”  Indeed, it might not even be a clinical testing program. The language is so vague it could be some other sort of clinically related effort.

The agency’s transparency rules require that agendas for meetings be posted 10 days in advance. However, they do not require that anything truly meaningful be supplied on the agenda. Back in the not-so-good, old days at the agency, important material explaining what was to be considered sometimes was not even available until the day of a meeting. Sometimes board members complained about delays in seeing material for meetings. Sometimes meetings were cancelled as a result.

In many ways, CIRM, as is the agency is known, is now exceedingly open and transparent. In other ways much less so. The problem with the clinical item to be considered Monday by the CIRM directors’ Scientific Subcommittee is an example of the latter.

The agency makes much of its attempts to engage and inform the public – not to mention researchers and the stem cell community.  CIRM says it wants input from all the stakeholders. But no comment – good, bad or indifferent – can be made when the only information available is so limited that it is meaningless.

Researchers particularly have something at stake. Poorly conceived concepts result in poor requests for applications which then result in poor proposals from scientists. Without spelling out just what is being considered well in advance, it is impossible for researchers to comment constructively or otherwise in a timely fashion.

CIRM can and should do better. 

California Stem Cell Research: Juggling Safety and Speed

Robert Klein, the first chairman of the California stem cell agency, is a relentless salesman for the potential of stem cell research.

Certainly such was the case on Nov. 20 when he and a host of others celebrated the 10th anniversary of the Golden State’s $3 billion research effort. Klein said the dream of patients has already become a reality.  But Klein, as he has done in the past, also warned that there would be setbacks.

He might be called prescient. One day later, news emerged from Great Britain about the deaths of four children involved in a stem cell transplant.

It was a reminder that there are considerable risks involved in the field, which is often viewed uncritically by patients and the public. In the case of the British children, Owen Bowcott of The Guardian reported on Nov.25 that the exact cause of the problem with the treatment is still not known.  The cells involved passed all the normal protocols, however.

The California stem cell agency is now involved in 10 clinical trials of stem cell treatments. These are very early stage trials primarily involving safety. The agency will be pushing aggressively and rapidly in the next few years for more trials. “We need a home run,” said Sherry Lansing, a member of the board of directors of the agency, late last year.

The agency is expected to run out of money for new grants in 2020, a date that has been revised from 2017.  Future funding will depend in large part on marketable successes that resonate with future potential sources of funding, be they private or the general public via another bond issue.

Balancing speed with care and safety can be a difficult task. But a catastrophic event can squash the agency’s efforts just as thoroughly as the lack of home runs.

Bubble Babies, Cures and California's Stem Cell Agency

Alysia Padilla-Vacarro and daughter, Evangelina, on the day
 of the baby's life-saving gene therapy treatment at UCLA.
UCLA photo

Numbers speak loudly in America. We focus intently – sometimes obsessively -- on everything from baseball statistics to the latest count of illegal immigrants. Numbers appear to create certainty and tend to drive discussion of public issues.

Which is where the California stem cell agency comes in.  Executives at the agency point with pride to the 10 clinical trials that it has helped to fund. They do not point to the zero number of therapies that the agency has placed in the public marketplace despite the apparent promises of the ballot campaign that created the research effort 10 years ago this month.

Nonetheless, agency has chalked up some indirect scores that are difficult to quantify but deserve ample consideration when evaluating the California Institute for Regenerative Medicine(CIRM), as the agency is formally known.

One dramatic example gained national media attention last week. The case involves work at UCLA for what appears to be a cure for the fatal “bubble boy” syndrome. The term was coined back in the 1970s when stories involving a youngster in Texas made headlines across the country.  The child had to live inside a plastic bubble because his immune system was compromised. The case even inspired a 1976 movie called “The Boy in the Plastic Bubble” starring John Travolta. (See here, here and here.)

Enter Donald Kohn, many years later.  Kohn is director of the Human Gene Medicine program at UCLA. And last week, the Los Angeles university announced that Kohn and his team have developed a treatment that cures the “bubble boy” syndrome by altering the genes of the afflicted children.  In clinical trials, the UCLA announcement said, the lives of 18 children were saved.

Kohn used a virus delivery system that he first developed in his lab in the 1990s. But the work on the gene treatment began in earnest in 2009 and involved two, multi-year clinical trials.

UCLA's Nov. 18 news release described the treatment simply like this:

“During the trials, the patient's blood stem cells were removed from their bone marrow and genetically modified to correct the defect.”

The stem cell agency did not directly fund Kohn’s “bubble” research, but some of its other funding at UCLA contributed to the effort. Specifically, the work was performed in the stem cell research facility that CIRM helped to finance. Kohn’s lab is in the “shared research lab” space funded by CIRM in still another program. The research was also aided by persons working in two other separate CIRM training programs.

The next step for Kohn will be to use the research in proposed clinical trials involving sickle cell anemia, which are being financed by CIRM to the tune of $13.1 million. They will also be part of the agency’s Alpha clinic program.

Steve Peckman, associate director of the UCLA stem cell center, said the Kohn research “is a perfect example of how CIRM support at all levels is critical to achieve the goal of driving scientific discoveries to the clinic.”

Kohn’s work was cited last week at a Los Angeles media event celebrating CIRM’s 10th birthday. Maria Shriver, the former first lady of California and whose father died of Alzheimer’s Disease, wrote about the research and linked it glowingly to the stem cell agency in an item on the Huffington Post on Nov. 20.  She said,

“The news about 'bubble baby' disease is just the start. I am convinced that stem cell research means we Baby Boomers will be the last generation to have to watch our parents die of Alzheimer's or watch our children die prematurely of sickle cell disease. Proposition 71 (which created the stem cell agency) set this research in motion. Now we have to make sure this research keeps moving forward.” 

While CIRM deserves credit for its role in Kohn’s work, it is only one of 10 entities cited by UCLA as contributing but without providing figures.  Accurately quantifying CIRM’s contribution is difficult if not impossible. That said, it was significant. The agency’s programs do ripple out – not only at UCLA but globally.  They add to the bank of knowledge about stem cells, all of which creates an easier path to the ultimate development of new therapies.

 

Ironically, one of the CIRM programs -- the "shared labs" -- that helped Kohn has expired despite pleas by some of the state’s top stem cell scientists. News about that program surfaced again a few days after the Kohn announcement. Without mentioning Kohn, Jeanne Loring, head of the stem cell program at Scripps, discussed the importance of the "shared labs" in a piece on the blog of UC Davis stem cell researcher Paul Knoepfler.

Loring said the program has had “an enormous impact beyond (its) original intention.” 

In her “open letter to CIRM,” she said,

“Unwittingly, CIRM’s shared lab program jump-started human stem cell research in California, sending it on a trajectory that has led to stem cell clinical trials in just 6 years….CIRM did not expect that there would be interaction among the labs that would make the whole greater than the sum of the parts. The network of shared labs became our means to communicate and share ideas. It sparked new partnerships between institutions throughout the state, and became a conduit for trainees to move from CIRM’s Bridges internships to graduate school. One scientist described the shared labs as ‘the beating heart of California’s stem cell program.’”

She noted that the program was discussed by the CIRM governing board in December 2013 at a time when the directors were being told that the money for new grants would run out in 2017. Today, however, Randy Mills, the new CIRM president, has reexamined the financial assumptions and says the money will be around until 2020.

Loring and 11 other researchers are asking the CIRM governing board at its December board meeting to provide the go-ahead for applications for another round of funding for what they say is the key maintaining the rapid pace of stem cell research in California.

Anything less, they say, would impede the development of stem cell treatments and waste a good portion of the $20 million already spent on the “shared labs” effort.

Perhaps Donald Kohn would agree as well. 

Here is a two-minute CIRM video of Kohn explaining his work.

Correction

The "birthday party" item Nov. 20, 2014, incorrectly stated that Anne Holden wrote CIRM blog piece on the "bubble boy" researchat UCLA. It was actually Todd Dubnicoff who wrote the article on the agency's blog, The Stem Cellar.

Birthday Party for California's 10-year-old Stem Cell Research Program

Fred Lesikar, a heart attack victim aided by
a CIRM-backed cell treatment
CIRM photo

The California stem cell agency today celebrated its 10^th birthday with a media event in Los Angeles where its supporters declared that the effort marked “one of the seminal events in the history of medical research.”

Attending the party in Los Angeles were a number of scientists and university officials whose institutions and research have received hundreds of millions of dollars from the program, which is funded by money that the state borrows(bonds).

California voters created the program in 2004 when they approved a ballot initiative that established the California Institute for Regenerative Medicine(CIRM), as the San Francisco-based agency is formally known.

CIRM has awarded $1.8 billion so far out of its $3 billion allotment. Because the money is borrowed, the effort will cost taxpayers about $6 billion, including interest. The agency is controlled by a 29-member board of directors. Eighty-eight percent of the $1.8 billion in awards has gone to institutions linked to current or past directors, according to calculations by the California Stem Cell Report. (For a recent assessment of the agency, see here.)

CIRM Chairman Jonathan Thomas told the gathering at USC, which has received $88.5 million in funding, that the state research effort amounted to a “seminal event.” California began its program when stem cell research was at a low ebb, Thomas said. He said it helped to keep stem cell research alive and  “galvanized” efforts globally.

He and others celebrated the 10 early stage clinical trials that CIRM now expects to be part of this year. None of the speakers mentioned studies that show that only one out 10 potential conventional treatments that enter clinical trials emerges as a therapy that is widely available to the public. The odds for stem cell therapies are unknown because they are so new.

Thomas and others pointed to news this week from UCLA about a genetic treatment that they said saved the lives of 18 children who had an immune deficiency affliction called the “bubble boy syndrome.” The cure involved insertion of a missing gene into the child’s blood stem cells. The work by researcher Donald Kohn received national attention. Oddly, however, the Los Angeles Times has not written about the research, according to a Google search this afternoon. CIRM's Todd Dubnicoff wrote a very nice piece about the research earlier this week.

The stem cell agency did not directly fund the “bubble boy” experiment, although CIRM awards, ranging from training programs to lab construction, did help to make the effort a reality.  The research is expected to be used in devising a sickle cell treatment in a $13 million CIRM program involving Kohn. 

The man sometimes referred to as the father of the California stem cell effort, Robert Klein, was also on hand today.  Klein led the $35 million ballot campaign in 2004 to win approval for creation of CIRM, which functions outside of the normal controls on nearly all state departments. Klein, a Palo Alto real estate investment banker, was also the first chairman of the agency. 

Klein said that a “revolution is underway” in medicine and that CIRM is leading the way. The dream of patients has become a reality, Klein said.

Only one patient appeared along with researchers, Fred Lesikar, a heart attack patient who was treated with his own heart cells at Cedars-Sinai in Los Angeles a few years ago.

Lesikar told the audience that “little by little over the next six months to a year, they (the cells) went in and started replacing the dead tissue.” He said he is now feeling great.

The researcher involved in that treatment, Eduardo Marban, has moved forward with a trial that CIRM is helping to fund through Capricor, Inc., a publicly traded  Beverly Hills firm.

On the podium today were researchers or officials from USC, UCLA, Cedars-Sinai and the City of Hope. All have representatives on the agency’s board. A researcher from ViaCyte, Inc., of San Diego, another CIRM award recipient, also spoke.

Today’s media event, which was available by a telephonic link, represents a major push to generate favorable coverage of the California stem cell program. It was held early enough in the day to meet deadlines for the early TV news shows along with allowing enough time for preparation of fulsome stories. However, Los Angeles is a tough news market. We will be watching later today and tomorrow for coverage of the event and bring you additional information as warranted.

(An earlier version of this item incorrectly said that Anne Holden wrote the CIRM blog item on Kohn's work.)

Correction

The 10th anniversary media event item today incorrectly said that the news conference will be at UCLA. It will be at USC.

10th Anniversary Media Event Tomorrow in Los Angeles for California Stem Cell Agency

The $3 billion California stem cell agency will celebrate its 10^th anniversary with a media event tomorrow in Los Angeles aimed at demonstrating the impact of the Golden State’s research program.

The news conference is scheduled for 11 a.m. PST, and members of the public can listen in by dialing 866-528-2256 with a participant code of 1594399. The event will be at the Broad stem cell center at USC.

A note on the agency’s blog, The Stem Cellar, said,

“(The) money has helped make California a global leader in stem cell research and led to ten clinical trials that the stem cell agency is funding this year alone. Those include trials in heart disease, cancer, leukemia, diabetes, blindness, HIV/AIDS and sickle cell disease.”

The item continued,

“To hear how that work has had an impact on the lives of patients we are holding a media briefing to look at the tremendous progress that has been made, and to hear what the future holds.”

The Los Angeles media market is a tough one. It is also the state's largest. Great competition exists for coverage of events.  Kevin McCormack, the agency’s communications director, is promising to have patients on hand who have benefited from stem cell therapies along with researchers and key figures in the state stem cell effort.

The California Stem Cell Report last Sunday carried a 10th anniversary rundown on the agency.

(An earlier version of this item incorrectly said that the event will be at UCLA. The news conference will be at USC.)

A Look at Spinal Cord Injury Treatments from California's Stem Cell Agency

The California stem cell agency today took to the Internet to conduct a nearly hour-long video briefing concerning the state of stem cell treatments for spinal cord injury.

The Google Hangout event featured Jane Lebkowski, president of research and development for Asterias Biotherapeutics of Menlo Park, Ca., which is involved in an early stage clinical trial for a human embryonic stem cell therapy.

The firm is backed by $14.3 million from the stem cell agency. Asterias is carrying forward the Geron spinal cord trial, which that company abandoned for financial reasons. Asterias expects to enroll more patients next year.

She and Kevin Whittlesey, a science officer with the state agency, discussed the multiple stem cell approaches involving spinal injuries that have surfaced since Geron began the first trial with human embryonic stem cells in 2010.

Lebkowski said that first stage of her firm’s trials demonstrated the initial safety of the treatment. She also said it showed some evidence of “preferential restoration” and “prevention of further deterioration.” The patients involved were treated less than a month after their injuries.

Whittlesey gave an overview of other research around the country. He commented on a case in Poland in which one paralyzed man is reportedly now walking with the help of a walker following treatment with cells from his nasal cavity. The cells were extracted by going in through his skull.

Whittlesey said that it is “hard to draw any conclusions from this one patient.” He said the man “enjoyed significant benefit.” However, he said that it is not possible to attribute the benefits entirely to the cell treatment because the experiment was not scientifically controlled.

California’s stem cell agency has put together a healthy portfolio of Webinars, You Tube videos and Google Hangouts involving a wide range of issues. It is all part of its effort to inform the public and spread good news about its $3 billion program.

However, today’s effort demonstrated the difficulty in drawing an audience. Spinal cord injuries affect as many as an estimated 332,000 persons in this country.  Despite promotion online, in the social media and notices in some publications, only 39 persons checked in for today’s Hang Out.

Kevin McCormack, who hosted the event and who is the director of communications for the agency, said that it is pretty much the pattern for these sort of events. The payoff, he said, is the 1,000 or more viewers that are picked up as people go to You Tube to view the video event.   We might add that the information is current, authoritative and useful, although at times a tad technical for non-scientists.

California's Grand, $3 Billion Stem Cell Experiment: An Evaluation at Age 10

The $3 billion California stem cell agency turns 10 this month, an anniversary that naturally raises the question of what has it done for the first decade of its life.

Today The Sacramento Bee published an anniversary overview of the agency written by the publisher of this blog, David Jensen.  However, as is the nature of the print media, space was at a premium. So the article was limited in what it could cover. Newsprint costs money. Many stories and many topics are competing for space – not unlike the battle for state budget dollars or research funding.

In preparing the article, I asked for comments by email from a number of persons, including some directors of the agency and its executives, and its first president, Zach Hall, and promised to carry the full text of their comments on this Web site. I knew that most of what they had to say would wind up on the cutting room floor and not in the printed piece.  

But for those who follow the agency and its fortunes, what they have to say is important. It is also important for those who may want to tell the tale of California’s Great Stem Cell Experiment some 10, 20 or more years down the road. 

All those who responded to my inquiries were told that the article for The Bee was expected to address generally the questions of whether the agency’s efforts would be worth the $6 billion total cost, including interest, and whether it has fulfilled voter expectations from 2004, when the agency was created. They were also asked about their views on the agency’s achievements and shortcomings and advised to speak freely about any other issues as well.  I would like to thank them all for responding. Their comments contribute significantly to current and future evaluations of this important enterprise.

The agency responded to my request for fresh, pithy quotes from Chairman Jonathan Thomas and President Randy Mills, along with statistics many of which were submitted to The Bee for possible use in an infographic.  

With that said, separate items follow with their statements and more on the topic of the standing of the California Institute for Regenerative Medicine at age 10.  (By the way, the traditional gift for a 10th anniversary is something tin. A romance novel writer working for Hallmark, Stacey Donovan, suggests as a gift “an old-fashioned metal lunch box to take to work.”)

Comments from readers on all this are welcome. They can be filed by using the "post a comment" function at the end of this item or by sending an email to me at djensen@californiastemcellreport.com.

Here are links to the text of comments.

Ten Year Performance of Stem Cell Agency: Top Execs' Comments

The California Stem Cell Agency Numbers

Comments From the First President of the California Stem Cell Agency

CIRM Board Member Sheehy on Stem Cell Agency Performance

Former California Stem Cell Board Member Shestack Comments on the Agency's Record

CIRM Board Member Prieto on 10-year Performance of Stem Cell Agency

Comments From a Former Communications Director at CIRM

A CIRM Performance Perspective from Chief Staff Person on Oversight Panel

Ben Kaplan of Prop. 71 Campaign on Performance of Stem Cell Agency

Patient Advocate Roman Reed on Stem Cell Agency Record

Here is The Bee piece

   Evaluating California’s Stem Cell Experiment _ the Sacramento Bee

Ten Year Performance of Stem Cell Agency: Top Execs' Comments

Here is the text of what Jonathan Thomas, chairman of the California stem cell agency, and Randy Mills, president of the agency, had to say about its performance over the last 10 years.

Their remarks came after the agency was asked for comments from them for an article that appeared in The Sacramento Bee Nov. 16, 2014. The piece was written by David Jensen, publisher of this blog.   

The agency was told that it was likely that their comments would be severely limited in the piece in The Bee because of the space limitations of the print media. They and others queried were also told that the full text of their comments would be carried on this Web site.

Here are the comments from Jonathan Thomas: 

"In just a few short years we have helped accelerate the pace of research in California so that we are now funding ten projects that have moved out of the lab and into clinical trials in patients. These include trials in heart disease and diabetes, cancer and blindness, HIV/AIDS and sickle cell disease. By any standards this is a remarkable achievement. But this is really only the start. We have a pipeline of other truly promising therapies that we hope to  move into clinical trials in people in the next few years." 

 "We are a long way from running out of money. We have almost one billion dollars left to award to researchers. At our current rate of spending we'll be able to continue funding new projects until 2020, and we are already working on developing new sources of income to help us keep funding the most promising projects long after that. Without us, without our support, many of the most promising stem cell research projects in California could come to a stop. Those projects are far too important to the millions of people suffering from a wide range of deadly diseases and disorders. We don't intend to let that happen.”

"In ten years and more than 660 grants there have only been a handful of cases where there have been concerns about a conflict of interest and those were all acted upon quickly to remove even the perception of any conflict. The changes we made in response to the IOM report further strengthened the integrity of our process and demonstrated just how seriously we take these matters."  

Here is the comment from Randy Mills: 

"Everything we do centers around the patients, about developing successful therapies for people in need. Our first ten years laid the groundwork and now we are making changes to speed up the way we work, to make it easier for the most promising projects to get the funds they need when they need them, to accelerate the development of effective therapies and to do everything possible to ensure that we live up to the faith the people of California showed in us when they created the stem cell agency.”

The California Stem Cell Agency Numbers

​For today’s 10-year anniversary piece in The Sacramento Bee on the California stem cell agency, the agency was asked for statistics and numbers that would be useful in illustrating what it believes is the progress of the program.

The freelance article was written by David Jensen, publisher of this blog. Given the space limitations of the print media, the California Stem Cell Report is carrying all of the information provided by the agency.

Kevin McCormack, senior director for communications, supplied the following, which has been edited slightly for clarity.  

“One (graphic) is a pie chart that breaks down all the different disease areas where we are funding research at the most advanced levels, the pre-clinical (or translational as the graphic calls it) and the

clinical trial level (shown at right).  As you can see this covers 80 different programs and involves $627 million in funding. Obviously a lot of other money goes to fund other projects such as basic research, developing tools and technologies, etc., but I think this is a graphic that people will be interested in because it highlights the areas where we are closest to developing treatments for patients.

“For other numbers here are some that might be useful: 

“More than 1,750 published discoveries

“Trained more than 1,500 students for future careers in stem cell research

“Lured more than 130 senior scientists, and their teams, to California

“Research facilities helped leverage $543 million for the state 

“Generated more than $280 million in new tax revenues by the end of this year

“Generated more than 38,000 job years by end of 2014

“The second item is our Ten @ Ten list (10 clinical trial investments after 10 years) which shows the ten clinical trials we're funding right now. It's actually a little (off) because we have only been funding research for seven years – it took a couple of years after Prop. 71 was passed for us to get through the legal challenges and set up the infrastructure for the agency, etc., before we began funding – but Ten @ Ten has a much nicer ring to it. 

“HIV, Calimmune 

“Heart disease, Capricor 

“Solid Tumors, UCLA 

“Leukemia, UCSD 

“Sickle Cell Anemia, UCLA

“Solid Tumors, Stanford

“Diabetes, Viacyte

“Spinal Cord Injury, Asterias

“HIV, City of Hope

“Blindness AMD, USC

“We also funded research that led to six other clinical trials and you can find out information about them here: 

http://www.cirm.ca.gov/our-progress/cirm-funded-clinical-trials

“In terms of money there are probably a few things to mention, and as always it gets a little complicated. So far the Board has awarded $1.9 billion in funding but only $1.4 billion has actually been spent. When you talk about our accomplishments to date, as I am sure you will, the $1.4B is the most accurate number to use because it reflects what has gone out the door and been used for research. 

“We also estimate that we'll be able to recover around $100 million of the money that has been awarded through cost savings on projects and on projects that have been cancelled because they failed to meet their milestones. So, if you add that to the $843 million that we still have left to award that means the Board has close to $1 billion left on hand for funding. And that means that, at our current rate of spending, we'll be able to continue funding new projects until 2020, and because those are multi-year awards we'll be continuing to supervise that funding for several more years after that date.”

Comments From the First President of the California Stem Cell Agency

The following is the text of what Zach Hall, the first president of the California stem cell agency and who served from 2005 to 2007, had to say about its performance over the last decade.

Hall, who is retired and currently on the board of the New York Stem Cell Foundation, developed the California agency’s strategic plan that largely remained in place until the last couple of years. He commented for a freelance piece written by David Jensen, the publisher of this blog. The article appeared in the Nov. 16, 2014, edition of The Sacramento Bee.

Hall and others queried were told that it was likely that their comments would be limited in the piece in The Bee because of the space limitations of the print media. They were also told that the full text of their comments would be carried on this Web site.

Zach Hall
NY Stem Cell photo

They were told that the print article would address such questions as whether the work of the agency would be worth its $6 billion cost(including interest), whether it had fulfilled the expectations of voters in 2004 along with discussing the achievements and shortcomings of the agency.

Here is what Hall, former director of the National Institute of Neurological Disorders and Stroke, said via email. 

“CIRM: 10 years after
 “From a scientific standpoint, there is no doubt that CIRM has been an unqualified success. The passage of Proposition 71 in California not only provided much-needed funds for research and training, but gave stem cell scientists around the world a huge psychological boost in a dark time when NIH funds for stem cell research were severely restricted. The funds in California attracted new scientists to the field and supported the training of a new generation of stem cell scientists.  The result has been the establishment of a number of major centers of stem cell research in California and a steady stream of significant results in basic and applied research, some of which now underlie current efforts to develop therapies.  In contrast to some state efforts, CIRM can be proud that it has spent public money in this area wisely and with integrity.  

“CIRM has also clearly played an important role in promoting and encouraging pre-clinical and clinical therapeutic development, breaking new ground in developing ways for government and the private sector to work together. Because this road has been less-travelled, these efforts have been more difficult and CIRM’s ultimate success in promoting therapeutic development remains to be determined.  Nevertheless, CIRM’s attention to this difficult problem is of major significance, since CIRM has been one of the few government entities to try to address the problem in new and creative ways. 

“Are new stem cell therapies available?  The thought that therapies might be developed over the 10 year life-span of CIRM was always more a hope than a realistic outcome, but there is now reasonable expectation, partly because of CIRM, that cell-replacement therapy may be effective for a number of major diseases.  Will the investment of $6 B pay off in terms of economic development?  This question probably will not be answered for another ten years.  Could things have been done differently or better? Undoubtedly.  With such a huge (some would say excessive) budget, not all the money was spent wisely. In addition, the agency was burdened with a cumbersome and conflicted governance structure whose difficulties consumed far too much of the agency’s time and energy.   

“In sum, CIRM is a bold, new initiative that has given new life in California to a field of biomedical research that looks ever more promising for curing disease and saving lives. The visionary investment by California in this burgeoning field will likely pay dividends for decades to come.”    

CIRM Board Member Sheehy on Stem Cell Agency Performance

The following is the text of what Jeff Sheehy, a 10-year veteran of the governing board of the California stem cell agency, had to say about its performance over the last decade.

He commented for a piece written by David Jensen, the publisher of this blog, that appeared in today's edition of The Sacramento Bee. Sheehy and other board members queried were told that it was likely that their comments would be severely limited in the article in The Bee because of the space limitations of the print media. They were also told that the full text of their comments would be carried on this Web site.

Those queried were given generally free rein but were told that the print article would address such questions as the achievements and shortcomings of the agency along with whether its work would be worth its $6 billion cost(including interest) and whether it had fulfilled the expectations of voters in 2004.

Jeff Sheehy
CIRM photo

Here is what Sheehy, a UC San Francisco communications manager and patient advocate member of

the board, said via email.

“It’s really too early to assess your first question, I believe.  It is ten years since Proposition 71 was passed, but it’s just over seven years since the litigation that blocked access to the bond funding was decided (May 2007).  We did start issuing grants in 2006 with some funds via bond anticipation notes and the Governor did provide $100 million. (I am extremely grateful to those who purchased the BANS and to Governor Schwarzenegger). But, we were obviously slowed down in the beginning by the lawsuit and we could not implement the full program envisioned in our initial strategic plan until we had access to the bond funding.  If one wants to look at our progress at a ten-year mark, I think 2017 or 2018 is a fairer date. And I would note that CIRM funded projects are being approved for clinical trials at an accelerating pace and we should have at least some initial results by then.

“As for your second question, I am certain that the investment in the California Institute of Regenerative Medicine is a wise one that has benefitted and will continue to benefit the state significantly.  CIRM has led the way in creating in California an impressive research infrastructure in regenerative medicine, a critical, cutting edge biomedical research approach that will lead to cures in several diseases and conditions.   In a period that included the Great Recession, facilities construction funded by CIRM alleviated some of its impact.  In addition, with NIH funding flat, CIRM keeps California researchers working and has brought numerous top and emerging researchers to California.  CIRM funding has helped the San Francisco Bay Area and San Diego sustain their rating as two of the three top biotech clusters in the country.

“And the importance of biotech and healthcare to California should not be underestimated.  In San Francisco, one in four jobs are healthcare related.  The emergence of biotechnology as a driver of the California economy will offer Californians early access to the latest therapies along with the wealth created from developing these therapies. Plus, biotech development and clinical delivery in the regenerative medicine space will be relatively labor intensive and will provide numerous well paying, highly skilled jobs.  These are jobs that will be resistant to outsourcing.

“Ultimately the core value of the investment will be the CIRM funded cures and therapies that improve the health and lives of Californians.”
 After sending the above, Sheehy added the following later:   “I had one other thought, and couldn't figure out how to blend it in.  I wonder if those working on legalizing marijuana would consider deriving revenue (i.e. taxes) and dedicating enough of that revenue to keep CIRM funded.
 “I think that legalizing marijuana has been advanced by the success of Prop. 216 and the medical marijuana movement.  I know Dennis Peron, campaigned with him in 1996, protested with him when (then state Attorney General Dan) Lundgren shut down his dispensary, and observed the benefits of marijuana for people with HIV/AIDS.  The Harvey Milk LGBT Democratic Club held its meetings at the dispensary when it re-opened (I was the club's president then).
 “So from my standpoint, marijuana is now associated with relieving human suffering due to disease and other health conditions.  And, funding research towards cures out of revenue derived from legalization seems sensible.”

Former California Stem Cell Board Member Shestack Comments on the Agency's Record

Jonathan Shestack, a former member of the board of the California stem cell agency, was interviewed by telephone during the reporting for the 10th anniversary article today on the California stem cell agency.

Jonathan Shestack (left) and CIRM Chairman J.T. Thomas
at 2012 board meeting. CSCR photo

Shestack served on the board from 2004 until 2013. A Hollywood producer, he has been a longtime patient advocate for autism. He and his wife co-founded Cure Autism Now in 1995. Here is a link to Shestack's resignation letter from the board.

The 10th anniversary article was written by David Jensen, the publisher of this blog, and appeared in The Sacramento Bee.

Here is a summary of Shestack’s comments, which were trimmed from print article for space reasons.

He said, “CIRM has funded an amazing amount of great projects. It does an amazing amount of good.” He said, however, it should be “more bold going forward.”

Shestack was critical of the senior staff at the agency. He said they did “not like to do what the board wants.” He said, “The staff made a monkey out of the (10) patient advocates (on the board) for eight years.” There was no mechanism by which the board could pressure the staff on “programmatic” issues, he said.

Shestack said he was disappointed in the funding for research funding for autism. He said the agency wants to take credit for more funding on autism than is justified. He suggested that alternative grant-making proposals would been useful, such as creating a round for research on specific diseases.

Shestack was critical of the way in which grant rounds were handled. He said it led to “bloated proposals that people felt they had to approve.” He said the agency could have “more ruthless” on the “big disease” rounds and more willing to spend on basic research. “Ossified” is the way he described the grant-making process. During the review of grant applications, he said the staff “exerted a lot of pressure but in a passive-aggressive way.”

On conflict of interest issues, he said, “Trying to legislate away all conflict is a way to install permanent idiocy.”  Knowledgeable people in a small field such as stem cell research are nearly always going to have conflicts. He said the key is to manage them properly.

Shestack remarked on the impact of the state laws concerning open meetings. Compared to the private sector, they were “incredibly onerous” and made it difficult to do things, although he recognized they were necessary.

Shestack said the board is one of the best he has ever served on.  He said all the members were “pulling incredibly hard for the success of the agency. None of them had a hidden agenda.”

CIRM Board Member Prieto on 10-year Performance of Stem Cell Agency

The following is the text of what Francisco Prieto, a 10-year veteran of the governing board of the California stem cell agency, had to say about its performance over the last decade.

He commented for a freelance article written by David Jensen, the publisher of this blog, that appeared in today's edition of The Sacramento Bee. Prieto and other board members queried were told that it was likely that their comments would be severely limited in the article in The Bee because of the space limitations of the print media. They were also told that the full text of their comments would be carried on this Web site.

Francisco Prieto
CIRM photo

They were additionally informed that the print article would address such questions as whether the work of the agency would be worth its $6 billion cost(including interest), whether it had fulfilled the expectations of voters in 2004 along with discussing the achievements and shortcomings of the agency.

Here is what Prieto, a Sacramento physician and patient advocate member of the board, said via email.

“Has the agency fulfilled the promises of the 2004 campaign? 

“I think that largely, yes, it has. The principal promise of the prop 71 campaign was that here in California, we would not abandon or throttle this incredibly promising avenue of research, as the Federal administration was threatening to do at that time, and instead would try to push it forward. The promise was that we would aggressively push towards finding cures for the debilitating chronic diseases that are responsible for most of our chronic illnesses, premature death and healthcare expenses. CIRM has made that push, and has made California probably the preeminent site for stem cell research in the world. 

“Will its efforts be worth the $6-$7 billion that will have been spent, including interest? 

“This will be hard to judge until we see what the results are of some of the stem cell related treatments that are just now entering or about to enter clinical trials. If even 1 or 2 of the major ones result in a cure for something like diabetes or one of the major cancers that some of our CIRM funded researchers are working on, I think we will have to consider that it was a bargain. 

“What are its current achievements and shortcomings? 

This one could go on much longer and I'm afraid I don't really have the time right now. I think to some extent I answered this above.  California has become one of if not the Center for stem cell research in the world. We could have done better, especially early in the history of the agency in terms of transparency, and could have perhaps involved the public more in the discussions of our priorities. Some of the conflict of interest issues and events that came up particularly in the recent past caught us by surprise, and I wish we could have foreseen them, but I'm glad once they happened that CIRM and our new Pres. responded appropriately. 

“I think our understanding of this field is going to some day (soon, I hope) transform medicine and make the things I do every day look as primitive as leeches and blood letting.  Speaking of which, I have patients waiting so I’m afraid I need to go find those leeches.”