Diabetes to Arthritis: California Awards $33 Million for Clinical Stage Stem Cell Work

The California stem cell agency today approved nearly $33 million for clinical stage research projects testing treatments for type 1 diabetes, arthritis of the knee, ALS and an immunodeficiency affliction.

The awards were quickly approved with little discussion during a meeting at the Oakland headquarters of the California Institute for Regenerative Medicine or CIRM, as the agency is formally known.

The award likely to have an impact on the most people -- if it is successful -- is a relatively small, $2.3 million award to the Cellular Biomedicine Group,  a Chinese firm with operations in Cupertino, Calif. The stem cell agency by law only finances work in California. The research would also be supported by $572,993 in co-funding.

The project is aimed at treating osteoarthritis of the knee. More than 51 million people in the United States suffer from arthritis, which is particularly common in the knee.

The goal of the research is to regenerate knee cartilage through the use of a mesenchymal progenitor cell treatment, according to the agency's application review summary. The funding would go to manufacture the product and complete work to secure Food and Drug Administration approval for a phase one safety trial. A treatment for the public would likely be years in the future.

Here are the other winners today of California stem cell cash with links to the summaries of the reviews.

Caladrius Biosciences of New Jersey won $12.2 million for a clinical trial for young people ages 12-17 for newly diagnosed type 1 diabetes. The firm plans to use regulatory T cells from the patients themselves to treat the disease. Caladrius has a California location in Mountain View. (Caladrius' press release can be found here.)

St. Jude's Research Hospital in Memphis, Tenn., was awarded $11.9 million for a phase one/two trial to treat infants with X-linked severe combined immunodeficiency. The trial would aim at enrolling at least six patients suffering from the catastrophic affliction. The treatment would use the patients own bone marrow stem cells after the cells were specially handled. The agency said in a press release that St. Jude's is working with UC San Francisco. (St. Jude's press release can be found here.)

Cedars-Sinai Medical Center in Los Angeles was awarded $6.2 million for a phase 1/2A trial to test a treatment for ALS, which has no treatment or cure. The CIRM review summary said a "huge unmet need" existed. About 20,000 persons in the United States suffer from the affliction.

CIRM's press release did not identify the researchers involved in any of the awards.

The agency is on a push to support more clinical trials, which are the last and most expensive research prior to the possibility of winning federal approval for widespread use of a therapy.

Currently the agency is participating in 27 trials and is planning on adding 37 more in the next 40 months. The agency is expected to run out of funds for new awards in June 2020 and has no source of future financing.

The awards were previously approved behind closed doors by the agency's out-of-state reviewers, who do not disclose publicly their economic or professional interests. The agency's directors rarely overturn a positive decision by the reviewers.

All of the winners have links to two or more members of the 29-member CIRM governing board. Those members are not allowed to vote on applications where they have conflicts of interest.
About 90 percent of the funds awarded by the board since 2005 have gone to institutions that have ties to members of the board, past or present, according to calculations by the California Stem Cell Report.

(Editor's note: An earlier version of this item incorrectly said the total amount of awards was $37 million.)

California Stem Cell Agency Ends Today's Session

Directors of the California stem cell agency concluded their meeting at about 3:10 p.m. PST today. The California Stem Cell Report will carry an item a little later today on the awards made at the session.

First Time: California Stem Cell Directors Open Session in CIRM HQ in Oakland

CIRM graphic showing state of its administrative budget as of today 

The governing board of the $3 billion California stem cell agency this morning opened its meeting at 9:10 a.m. PST at its Oakland headquarters, the first time such a meeting has been held at the physical offices of the 12-year-old enterprise.

In the past, the 29-member board has held meetings at hotels and university campuses. Those sessions cost thousands of dollars for room rental, audio services and more. Today's meeting is a face-to-face session of the board. About half of the directors' meetings are currently conducted via telephone and are much less expensive than the face-to-face sessions, which were standard earlier.  About 12 meetings are scheduled each year. 

Reducing administrative costs is critical for the agency, which has a lifetime, operational budget that is capped by law at $180 million, 6 percent of the $3 billion in bond funding that voters allotted when they created the California Institute for Regenerative Medicine (CIRM) in 2004. 

Its staff numbers slightly more than 50 persons and was in the 20s during its early days, not much more than it takes to staff a 24-hour Burger King, if that. 

The agency projects it will run out of cash for grants sometime in 2020 but will need to fund operational expenses beyond then as multi-year awards wind down.

(The CIRM graphic was not included in an early version of this item.)

Looking at CIRM's Clinical Trials: Focus on Opthalmology

Directors of California's $3 billion research program will receive a briefing later today on the agency's investment in clinical trials, but here is a brief look at what they are going to hear about some of the 27 trials.

Maria Millan, vice president of therapeutics, will make the presentation on the existing trials and has posted 17 slides for her presentation, which focuses on opthalmology. 

Among other things, the slides show that 22 percent of the clinical trial funding involves oncology. Next comes hematology with 14 percent and opthalmology with 13 percent. 

Three awards have been made for phase three trials, four for phase two and 19 for phase one. The agency plans to participate in another 40 clinical trials between now and the end of 2020.

The California Stem Cell Report will carry more on Millan's presentation after it is concluded. 

Today's meeting begins at 9 a.m. PST and can be heard via an audiocast. See the agenda for details. 

Defying Basic Medical Know-how, Stem Cell Treatments and Fake News

A racing car driver, a celebrity TV surgeon and allegations of stem cell "fake news" surfaced this week on California stem cell blogs.

It was a matter of Dr. Oz, A.J. Foyt and a company called Cell Surgical Network Corp. of Rancho Mirage, Ca., which UC Davis stem cell scientist Paul Knoepfler says is the largest affiliated group of stem cell clinics in the United States.

But first Oz and Foyt. They were the subject of an item on the The Stem Cellar, the blog of California's $3 billion stem cell agency,

Kevin McCormack, communications director for the Oakland-based agency, wrote the piece, which was headlined "TV's Dr. Oz takes on clinics offering dubious stem cell treatments."

Foyt has said he has signed up for stem cell treatment in Mexico for issues stemming from his many injuries sustained in his very successful career in auto racing. Oz this week ran an investigative piece dealing with some of the 570 clinics in this country that offer unproven treatments.

The Oz show said that complications and death have resulted in some cases from treatments at these clinics here and abroad.

McCormack's concluding sentence:

 "Perhaps someone should tell A.J. Foyt."

Michael Hiltzik, a Pulitzer Prize winning columnist with the Los Angeles Times, also had an article concerning the Oz show, which reported that the treatments being offered at many of the 570 medical clinics defy "basic medical know-how."

Hiltzik also wrote that the Oz provided a "a withering assessment of doctors who claim to be engaged in clinical trials of stem cell treatments but 'ask you to give money upfront and mortgage your house and borrow from your friends’ credit cards — that’s not how medicine should be practiced.'"

Davis' Knoepfler dealt with the Cell Surgical Network and discussed its possible use of "laboratory-proliferated stem cells" in patients, which Knoepfler indicated would require federal approval.

The matter was addressed in an email Q-and-A with the leaders of the corporation, Mark Berman and Elliott Lander.

Berman and Landers' final point:

"All we care about is our patients. Providing them with the best and safest regenerative medical care in the world is what Americans deserve. We are not interested in anyone who desires to slow or obstruct this patient care by manipulating regulators into criminalizing certain medical practices. Therefore, we continue on our mission and ignore the fake news and rumors that generate blog ratings and spread fear and mistrust."

California to Hand Out $32 Million for Stem Cell Research Next Week

The California stem cell agency next week is expected to award as much as $32 million for late stage research and clinical trials involving therapies for arthritis of the knee, type 1 diabetes, an immunodeficiency affliction and ALS. 

Also on tap for the Feb. 23 governing board meeting are concept proposals for expansion of the Alpha Clinic program along with unspecified changes in the $3 billion agency's discovery, translation and clinical plans. 

Four awards are already approved by the agency's reviewers and are scheduled for routine ratification by the board. Their review summaries can be found on the agenda. The reviewers also rejected one proposal for research involving Parkinson's disease. That summary can also be found on the agenda.

More details on the concept plans are expected to be posted soon. The meeting will take place in Oakland with public teleconference locations in in San Diego, Los Angeles and two in La Jolla. Addresses can be found on the agenda. 

Cost of a Stem Cell Therapy? An Estimated $900,000

What is the likely cost of a freshly minted stem cell therapy? Close to $900,000. That's at least by one current estimate.

In the United States, such calculations are rare. Researchers and biotech executives shy away from discussing in public such daunting figures.

The figure emerged last week, however, in news from Japan about groundbreaking research to treat macular degeneration with reprogrammed adult stem cells.

While stem cell insiders are not keen on discussing $900,000 therapies -- at least their cost -- the public, however, is deeply interested. Development of expensive therapies is also likely to play a role in the future of California's $3 billion stem cell agency, which expects to run out of cash in 2020. Voters may look askance at publicly financed therapies that appear to be out of reach.

Exorbitant health care costs are on the minds of many. Forty-seven percent of the public said in 2016 that cost and access are the nation's most urgent health care problems, according to a Gallup Poll. Of all the nearly 4,300 items published on the California Stem Cell Report over the last 12 years, the most widely read article deals with the cost of stem cell treatments.

As of this morning, the 2013 article had recorded 21,963 page views, a standard way of measuring readership on web sites. Another related document chalked up 27,699 views on Scribd, where it was also published by the California Stem Cell Report. The figures are roughly four and five times higher than other relatively well-read pieces.

Readers do not give reasons for choosing the articles. But it is likely that their pocketbooks and hopes of affordable therapies are driving their interest.

Affordability was a big issue in the creation of the stem cell agency via a ballot initiative in 2004, Proposition 71. The agency, formally known as the California Institute for Regenerative Medicine (CIRM), has not devoted any significant attention to the matter in the last few years.

But if the agency wants to secure additional public or even private funding, it will need to make the case that its work is more than just another entry in the medical arms race.

Just yesterday, OncLive,  an oncology news site, carried a report on the skyrocketing expense of cancer drugs alone, which cost the nation $16 billion annually in 2010 and jumped to $38 billion in 2015. As for individual cancer patients, they are looking at costs of more than $150,000 a year for drugs, figures that have generated a ruckus in the cancer treatment community.

Drug costs are a small part of the total health care bill for country. But they are a litmus test for policy makers and the public. The costs are relatively straight forward compared to some other health care measures. But they are readily understandable by most families, who usually have one member or more involved in prescription purchases.

 As efforts to repeal-and-replace the Affordable Care Act gain increasing attention over the next year, the public is likely to focus even more on the costs of treatments and drugs, whether it is a $19 aspirin or a $900,000 stem cell therapy.

The "good" news, however, last week out of Japan was that the $900,000 cost of the stem cell macular degeneration treatment could be reduced to below $200,000 as the kinks are worked out and the treatment becomes more common -- if it clears its clinical trials.

As for California, CIRM  has pumped $125 million into research dealing with blindness, including macular degeneration which afflicts 1.7 million Americans. Nearly one million Americans are blind from all causes and another 2.4 million suffer significant visual impairment. More information on the state research can be found here. A CIRM video on vision issues is below.

Sampling Stem Cell News: $1 Million Gift, Unsettling Thoughts and Paolo Macchiarini

New-fangled pigs, $1 million donations and a recommendation to wind down the stem cell agency, it was all part of the stew of stem cell news recently.

Here is the first bite from recent bits and pieces from the media:

Eli and Edythe Broad added another $1 million to the many millions they have already contributed to stem cell research, much of it in California. The latest cash went to USC, UCLA and UC San Francisco, which have already received many millions more from the Broads. Charlie Rose also interviewed Eli in a six-minute segment that can be found here. Broad told Rose that he does not think the government is doing enough for science.

The Sacramento Bee carried an opinion piece headlined "To fulfill stem cell agency’s promise, consider winding it down." Joe Radato, who was an aide to former California Gov. Pete Wilson, and Bernard Munos of FasterCures were the authors. Instead of providing more funding for the California stem agency, they said a better approach would be to "provide funds directly to California-based companies developing new drugs to cure diseases and prolong healthy lives."

Paul Knoepfler, a UC Davis stem cell researcher and blogger, authored a piece in the Washington Post dealing with the "unsettling thought" of human-pig hybrids. He wrote that more than 100,000 people in the United States are waiting for organ transplants and that these new-fangled pigs could be a source, down the road. Knoepler said the ethical and other obstacles are like to be overcome.

The latest on former super surgeon Paolo Macchiarini was reported by Radio Free Europe Radio Liberty. He is in Russia after being fired by the Karolinska Institute in Sweden after some of his patients died following surgery involving stem cells. The story reported that his activities have been newly restricted in Russia. Macchiarini's operations, which included a 2010 procedure at UC Davis, drew wide-ranging, favorable international attention for a number of years.

Politics Could Be Key to Future of California's $3 Billion Stem Cell Program

The Los Angeles Times, California's largest circulation newspaper, is carrying an article this weekend that says the future of the state's $3 billion stem cell agency could "depend more on politics than science."

The assertion was carried in a column by Michael Hiltzik, a Pulitzer Prize winner and author, that popped up on the Internet last night. He provided a broad overview of the agency that was less harsh than some of his previous pieces dealing with the California Institute for Regenerative Medicine or CIRM, as the agency is formally known.

Hiltzik wrote,

"CIRM’s leadership knows that the public’s inflated expectations threaten to obscure the program’s real accomplishments. With multiple clinical trials of CIRM-funded research underway, the first government approval of treatments is expected 'in the not-too-distant future,' C. Randal Mills, the program’s president, said in an interview.

"But he acknowledged that expectations 'need to be tempered with humility at the enormity of the task before us. We don’t want to overpromise or overhype. CIRM is doing what it was set up to do, but it might be taking longer than people thought or hoped.' "

Hiltzik continued,

"Still, the program’s future may depend more on politics than science. 'If it looks like Washington is flipping off California, that could have political ramifications' at the ballot box, (Hank) Greely (director of the Center for Law and the Biosciences at Stanford)  says. Some researchers aren’t optimistic about the prospects for independent, federally funded science under the Trump administration."

The reference to the Washington involves the likelihood that the Trump Administration would impose restrictions on federal funding of human embryonic stem cell research. The administration is populated by appointees who hold anti-abortion views that are generally coupled with opposition to embryonic stem cell research on the grounds that it is tantamount to murder. 

Hiltzik's column noted changes at the agency that make it significantly different than its earlier days, including a step-up in funding of clinical trials, the success of which could pay an important role in the success of a new funding measure. 

He wrote, 

"A new funding campaign could give the program a much-needed reboot. The ballot measure could restructure CIRM as an 'ordinary agency of the state' subject to legislative oversight, open meetings laws and other good-government statutes, says Marcy Darnovsky, executive director of the Berkeley-based Center for Genetics and Society."

"If it returns to the ballot, CIRM would have a chance to reconsider its administrative structure, the inflated expectations it gave voters in 2004, its embedded conflicts of interest and even whether it should be limited to funding research into stem cells. All these features of Proposition 71 (which authorized the agency) have created complications during the program’s first decade."

Hiltzik's column is scheduled to appear in print on Sunday, a day on which the Times says it has 2.4 million readers.

Here are links to two other recent overviews of the agency, including one last month on the California Stem Cell Report and Stat News.

Clarifying the Path to Cash: California Looking for Money from Its Stem Cell Investments

CIRM chart

The $3 billion California stem cell agency is moving to revise its rules for royalties and revenues that may be derived from its research, simplifying them while focusing more sharply on likely cash-generating products.

The proposal comes before the agency's Intellectual Property  (IP) Subcommittee Thursday at a 10 a.m. meeting that has a number of locations throughout California where the public can participate.

A document prepared for the meeting said the complexity of the existing IP regulations has led to disagreements, created an excessive administrative burden and treated for-profit and non-profit enterprises differently.

John M. Simpson of Consumer Watchdog in Santa Monica, Ca., who participated extensively in the early development of the IP rules, praised the proposed changes.

Responding to an inquiry from the California Stem Cell Report, he said:

"The proposed changes in the IP regulations should simplify oversight for CIRM and make expectations for all awardees clearer.  It puts nonprofit and commercial entities on the same footing with regard to their revenue sharing responsibilities. Most importantly the new rules will emphasize getting revenue for the state  from  companies who actually commercialize the results of CIRM-funded research.  That’s exactly as it should be. 

“Nonetheless, despite the overblown promises of Prop. 71 campaigners, the state as yet to realize any revenue from research CIRM has funded.  There could be a little money this year."

"This change in the IP rules makes sense and is the best way forward,  but realistically I doubt the state will ever see significant revenue from the research it has funded."

Proposition 71 created the California stem cell effort, known officially as the California Institute for Regenerative Medicine or CIRM. One of the promises of the 2004 campaign was that it would lead to as much as $1.1 billion in revenues to the state. No royalties have yet been announced. 

Telephonic locations for the public exist in Irvine, Napa, South San Francisco, San Diego and San Francisco in addition to the agency's headquarters in Oakland. Specific addresses can be found on the agenda, which also includes directions for a listen-only audiocast.
 

From Cystic Fibrosis to Zika: California Awards $21 Million for Stem Cell Research

The California stem cell agency last week approved nearly $21 million for research to tackle afflictions ranging from cystic fibrosis to Zika.

Awards were made to only 11 researchers although the agency's reviewers had earlier approved 14 awards totaling $25.5 million. The governing board, however, had allotted only $21 million for the awards, and it decided to stick to its budget.

The awards are part of an effort by the agency to finance projects that can move forward rapidly within the next two years.

Six scientists sent letters to the board prior to the meeting discussing details of their research and dealing with concerns of the agency's reviewers, who approved awards earlier in a closed-door session, prior to ratification by the board.

Here are links to letters of each researcher: Rosa Bacchetta, Stanford, application number DISC2-
09526; Tejal A. Desai, UC San Francisco, DISC2-09559; Mark Mercola, Stanford, DISC2-09542 (rejected); Julie Sneddon, UC San Francisco, DISC2-09635; Jin Nam, UC Riverside, DISC2-09645 (rejected), and Matthew Porteus, Stanford, DISC2-09637.

Reviewers rejected any application that scored below 85. All of the three applications denied by the board stood right at the cutoff line with scores of 85. Mercola was the only one of the three to write a letter to the board. The agency did not disclose the names of the other two on its web site since they had not written a letter, which is a public record. The Nam application scored 84 and was not recommended for funding by reviewers.

Here is a link to a document that contains summaries of the reviews of all applications scored at 65 or above.

Here is a link to the agency's press release that contains the names of all the winners and a one line summary of their research. More details can be found in the summaries of the reviews.

STAT News: California Slow on its Stem Cell Clinical Trials Over Last 10 Years

The $3 billion California stem cell agency has been "slow to move" into clinical trials, a major reason it has not yet produced a therapy that is widely available to the public, STAT reported today.

In a lengthy piece on the 12-year-old agency, West Coast editor Charles Piller wrote,

"The National Institutes of Health has supported three and a half times as many human trials of stem cell therapies, dollar for dollar, as the California agency has funded since it started making grants in 2006. Just two of its clinical trials have been completed."

Piller continued,

"'I am floored by the disparity,' said Jim Lott, a health care consultant and member of the state board that monitors the agency, known as CIRM. If the numbers are correct, he told STAT, 'that doesn’t settle well with me as a voter. That doesn’t settle well with me as a taxpayer. That doesn’t settle well with me as a member of the oversight committee.'"

The committee that Lott referred to is the Citizens Financial Accountability and Oversight Committee, which is the only the state body specifically charged with overseeing the stem cell agency, known formally as the California Institute for Regenerative Medicine or CIRM.

Under the ballot initiative that created CIRM in 2004, it operates outside of the control of the governor or the legislature. Its funding also bypasses both the governor and legislature.

Piller said that the agency has provided more than $300 million for work that supports preclinical and clinical trials compared to $540 million for new labs and buildings. He wrote,

"In part, that’s because its directors chose to focus on infrastructure early on, as well as bench experiments and animal studies given that the biology of embryonic stem cells was not well-understood and there are formidable roadblocks to moving into human studies. Much more is known about the bone marrow stem cells that are the focus of many NIH-funded clinical trials."

Randy Mills, president of the agency since 2014, "declined to comment on STAT’s specific findings, but defended the initial emphasis on labs and basic science as underpinning future clinical work," Piller wrote.

Mills said,

“If we’re behind [NIH], we’re going to get better.”

Mills has refocused the agency since coming aboard, pushing hard to fund clinical work, including 10 clinical trials in 2016 and projecting 40 new trials before the agency's money runs out in three years.

The possibility of another multi-billion dollar bond measure exists in 2018. However, Lott said he would not support such a measure again. He told Piller,

“We were all caught up in the time, and the events were different when we first looked at this. But not today. Not at all.”

The STAT piece covered some familiar ground for readers of the California Stem Cell Report. But it also had fresh comments from the Center for Genetics and Society, Paul Knoepfler, the blogging stem cell scientist at UC Davis, and George Daley, dean of the Harvard Medical School.

STAT is a relatively new national, online news effort dealing with health, medicine and scientific discovery.  It was started in November 2015 by John Henry, owner of Boston Globe Media and the Boston Red Sox. The well-regarded news operation is independent of the Globe but shares content.

The 'Overstated' Stem Cell Debate: A Perspective from the California Stem Cell Agency

The statement came like an unpleasant dose of plain-speaking about stem cell therapies, which sometimes seem to have been hailed as a panacea for all that ails the human race.

Not only that, the statment came from a Nobel Prize-winning stem cell scientist, Shinya Yamanaka of Japan who was quoted in the New York Times on Monday as saying,

"We can help just a small portion of patients by stem cell therapy."

Yamanaka said that only about 10 diseases would benefit directly from stem cell therapies: Parkinson's, retinal and corneal diseases, heart and liver failure, diabetes, spinal cord injuries, joint and some blood disorders. 

"But maybe that's all," he said, "The number of human diseases is enormous."

California's $3 billion stem cell agency took a crack yesterday at putting the statement in perspective on its fine blog, The Stem Cellar where Karen Ring wrote about the Times piece. She is the social media guru for the agency and has been a regenerative medicine researcher herself with a Ph.D. in biomedical science from UC San Francisco.

Karen Ring, Linked In photo

She had the advantage of hearing Yamanaka, who also has a lab at the Gladstone Institute in San Francisco, speak last fall. Ring wrote,

"At the World Alliance Forum in November, Yamanaka revealed that generating a single patient iPS cell line can cost up to one million dollars which isn’t feasible for the 1000’s of patients who need them. He admitted that the fate of personalized stem cell medicine, which once seemed so promising, now seems unrealistic because it’s time consuming and costly."

Ring predicted that a "larger conversation" will emerge from Yamanaka's comments. But Ring said, that she has heard Yamanaka speak many times and that the Times' edited interview failed to capture his optimism that current obstacles can be overcome with sufficient time and money. She wrote,

"Which brings me to my point, I don’t believe the promise of stem cells has been overstated. I think that it has yet to be realized, and it will take more research and more time to get there. As a community, we need to be understanding, patient, and supportive....
"What I took from Yamanaka’s comments is that stem cell treatments can help a small number of patients with specific diseases right now. That’s not to say that stem cell research won’t produce promising treatments for other diseases in the future."

Ring cited the emotional success stories related last month at the agency's board meeting and predicted more of those in the next decade. She concluded with a quote from Hank Greely, director Law and the Biosciences at Stanford, one that he recently made to the California Stem Cell Report.

“The next few years should determine just how good California’s investment has been. It is encouraging to see CIRM supporting so many clinical trials; it will be much more exciting when – and I do expect ‘when’ and not ‘if’ – one of those trials leads to an approved treatment.”

We recommend Ring's perspective and the Yamanaka piece. 

$16 Million Expansion of Alpha Stem Cell Clinics Planned for California

California's stem cell agency plans to expand its Alpha Clinic network this year with two more locations, including probably the first in Northern California, and financing the effort with $16 million. 

The proposal comes before the agency's Science Subcommittee one week from today (Jan. 25) and could be of considerable interest to enterprises, both public and private, that are ready to move quickly. The $3 billion agency has set a deadline of May 15 for applications. 

The Alpha Clinic program is aimed at being sort of a one-stop center for clinical trials and stem cell research. Currently sites are all located in Southern California at UC San Diego, the City of Hope in the Los Angeles area, UCLA and UC Irvine. 

The agency, known formally as the California Institute for Regenerative Medicine (CIRM), said in its proposal, 

"Twenty-nine clinical trials are being conducted at these sites and hundreds of patients have been enrolled. These trials emanate from CIRM’s funding pipeline as well as non-CIRM funded investigator and industry-sponsored projects."

One of the goals of the expansion is to enhance the value of the network. The agency said, 

“Proposed sites could enhance the value by, for example, broadening the network’s geographic reach, providing expertise in new disease areas, providing new/unique technical capability, or other elements that accelerate/support stem cell clinical trials.”

The session next week will provide an opportunity for potential applicants to ask questions and make suggestions. The proposal will also go to the governing board of the agency, but most of the work by board members goes on at the committee level.

Applicants may also be interested in a CIRM symposium on Alpha Clinics scheduled for March 23 at the City of Hope.

Next week's committee meeting will be based at the agency's Oakland headquarters with five telephonic locations, all public, two in Los Angeles, and one each in San Diego, Irvine and La Jolla, where the public can participate. The meeting will also be audiocast with listen-only capabilities. Details are on the agenda.

Also on the agenda are unspecified changes in three other types of CIRM award rounds: Discovery, Translation and Clinical. The agency has not yet posted material spelling out what is to be considered.

The $22,000-an-Hour California Stem Cell Story: Rosy Expectations, Fuzzy Future

Evangelina Padilla Vaccaro
CIRM photo

Highlights
Trump and state bond issue?
More than 60 clinical trials projected

No therapies yet for general public
Siren appeal for reseachers
$2.2 billion out the door

Evangelina Padilla Vaccaro – a pink bow in her hair – was likely the first four-year-old ever to address the leaders of California’s $3 billion stem cell research program.

“Thank you,” she whispered. Her mother said more: "Thank you for keeping my family complete." 

Alysia PadillaVaccaro’s voice cracked, and tears flowed on that cool December morning at the meeting at an Oakland hotel.

Evangelina had much to be thankful for. She was born with “bubble baby” syndrome, which meant that she had no functioning immune system. Scientist Donald Kohn of UCLA cured her of the rare affliction by using her own blood stem cells to alter a troublesome gene. It was an experimental treatment not readily available to the public at large. Kohn’s research has been heavily supported with nearly $52 million by the state stem cell agency, known formally as the California Institute for Regenerative Medicine (CIRM) .

Evangelina’s story is just what Californians hoped for when they created the Oakland-based agency in 2004 via Proposition 71. Voters were told that stem cell therapies would ease afflictions found in nearly 50 percent of California families. The agency would create the “cures for tomorrow,” said then Gov. Arnold Schwarzenegger.

Since its first awards in 2005, the agency has given away money at a rate of $22,000 an hour, seven days a week, 24 hours a day. But it has yet to come up with a therapy that reaches the general public despite rosy expectations raised by the ballot campaign.

Today, the future of the program is unclear. The agency calculates that it will run out of cash in just three years. Whether it lives on could depend on the likelihood of another multibillion-dollar bond issue, not to mention the success – or the lack of success – of as many as 60 or more clinical trials and even the policies of the newly elected president of the United States, Donald Trump.

Stem cell therapies, it turns out, are expensive and difficult to bring to market, and their use may be

Shinya Yamanaka, UCSF photo

limited to a handful of diseases. On Monday, Nobel Prize winning stem cell scientist Shinya

Yamanaka said as much in an interview with Wallace Ravven of The New York Times. Because of a wide variety of constraints, he said, 

“We can help just a small portion of patients with stem cell therapy.”

In this context, heartwarming stories of patients such as Evangelina could be some of the strongest selling points for CIRM’s continued existence. They could fire the enthusiasm of voters and embolden businesses to partner with CIRM to bring therapies into the marketplace. The number of these emotional stories is increasing.

Evangelina was not alone at the CIRM meeting last month. Three more patients stepped up during a look at the agency’s performance. They included a 22-year-old man, also with a rare, immune-deficiency disease, a paralyzed 19-year-old man and a 70-year-old cancer patient -- all of whom had experienced major improvements during clinical trials. All told, the agency has pumped $113 million into the research that has benefited the four patients.

Evangelina’s story had special significance for Jan Nolta, head of the UC Davis stem cell program.

Jan Nolta, UCD photo

Nolta began her career working with Donald Kohn at Childrens Hospital in Los Angeles in early research involving the “bubble baby” affliction.

“CIRM has funded Don’s continued work in this area, and he has now functionally cured over 20 children with this disease,” she said in an email. “These kids now need no expensive medicine and treatments to keep them alive. They are functionally cured.” 

In Evangelina’s case, she was able to join her fraternal twin sister, Annabella, in living a normal childhood.

CIRM funding has also fueled the growth of the UC Davis stem cell program, which barely existed prior to creation of the stem cell agency. Today Davis has chalked up $129 million from the agency. “We have 16 stem cell or regenerative medicine clinical trials ongoing or recently completed, with more than 20 in the pipeline,” Nolta said.

Davis ranks as the No. 5 recipient of funds from the agency, trailing only such institutions as Stanford, $314 million; UCLA, $269 million; UC San Diego, $170 million, and UC San Francisco, $139 million.

Nolta is one of a number of researchers attracted by CIRM, lured by the cash and research environment created by the stem cell agency. program. She returned to California from Washington University in St. Louis. (See the full text of Nolta's remarks here.)

The appeal of the California largess was highlighted last week by George Daley, dean of the Harvard Medical School.  He was quoted in a lengthy piece about San Francisco Bay Area biotech written by STAT news service editor Charles Piller.

"'I’ve been looking at this from the outside, and franly have been very envious as a scientist based in Massachusetts,' Daley said. CIRM funds have turned many research centers in California, including UCSF, into world leaders in stem cell science, he said, adding: 'I heard the siren song of CIRM early. I considered making a move,' as did more than two dozen of his Harvard stem cell colleagues."

Since CIRM’s inception, it has awarded $2.2 billion to 853 California researchers and institutions. It estimates that it will award another $692 million before money runs out. This year it plans to give away $328 million.  (The awards are separate from the agency’s operational budget, which is capped by the ballot initiative and is about $19 million for the current fiscal year.)

Like most other recipient institutions, UC Davis has representation on the CIRM governing board. The California Stem Cell Report, which has monitored the agency since 2005, has calculated that about 90 percent of the agency’s cash has gone to institutions with links to past or present board members. Those members are barred from voting on awards to their institutions, but they do vote on the nature of the award rounds and approve the rules.

Concerns about conflicts of interest have long been a bugaboo for the agency. Last September,The Sacramento Bee reported that its former president, Alan Trounson, received $443,500 in total compensation after being named in 2014 to the board of directors of StemCells, Inc., of Newark, Ca. Trounson’s appointment to the company’s board came only seven days after he left the agency at the end of June 2014.

Randy Mills, FDA photo

Trounson was replaced by C. Randal Mills, who had been president of Osiris Therapeutics, Inc., of Maryland. Under Mills’ leadership, Osiris was the first company in the world to commercialize a stem cell drug, qualifying it for use in Canada.

Mills and the CIRM team – currently comprised of 48 people – re-crafted the agency’s objectives and established measurable benchmarks for success, winning board approval for what Mills called radical change. The results were summarized at last month’s board meeting and in the 2016 annual report. They included:

• Over the last two years, the agency has helped to finance 27 clinical trials and is looking for another 40 by 2020. (Clinical trials are the last stage before a therapy is approved by the Food and Drug Administration (FDA) for widespread use. Only one out of 10 conventional drug products emerge successfully from the trials.)

• More than 250 projects are currently being managed by the CIRM team.

• Twelve "world-class" research facilities have been created over the last 12 years.

• Three Alpha Clinics, intended to be one-stop stem cell centers, are in operation. A fourth is scheduled for this year.

• A $30 million stem cell "pitching machine" to speed clinical trials and help guide development through federal regulations began operations in 2016.

Nonetheless, development of stem cell therapies -- much less cures -- is a risky business and could be stymied by a number of issues. The agency itself acknowledges risk factors that include reluctance by businesses to invest in stem cell therapies and safety concerns, including the possible death of a patient in a clinical trial.

Mills makes a practice of presenting risk, an innovation at the agency, as he offers up new programs to its governing board. In the annual report, he quoted the poet T.S. Eliot as saying,

“Only those who will risk going too far can possibly find out how far one can go.”

The agency has experienced a few hiccups since Mills arrived. He acknowledges he is still working hard on attracting businesses to partner with scientists to turn their research into cures. 

An ambitious effort to create a unique, public-private, $150 million enterprise to develop stem cell therapies and cures stumbled late last year when no qualified applicants surfaced from the private sector. The agency hopes to recast the proposal in such a manner that it will find a partner.

One of those watching the agency since its beginning is Hank Greely, director of the Center for Law

Hank Greely, Stanford Law photo

and the Biosciences at Stanford.

He said in an email,

“CIRM has been spending money from Proposition. 71 for about 10 years. Once initial hopes of finding low-hanging fruit disappeared, this kind of slog toward treatments became inevitable.  (Although, in biomedicine, 10 years is not (Greely's boldface) a long time - see the 35 plus years it has taken gene therapy to get to the edge of an FDA-approved product.)

“The next few years should determine just how good California's investment has been. It is encouraging to see CIRM supporting so many clinical trials; it will be much more exciting when – and I do expect ‘when’ and not ‘if’ – one of those trials leads to an approved treatment.” 

John M. Simpson of Consumer Watchdog of Santa Monica, Ca., has also observed the agency for years. He said in an email,

“CIRM’s fundamental problem is that supporters of Proposition 71 wildly oversold what passage of the measure would deliver. Voters were led to believe that miraculous cures were just around the corner if only the proposition passed.

“CIRM-funded research has made important contributions to science, but has yet to deliver what voters were promised,” Simpson said. He added that agency management has improved under the regime of CIRM Chairman Jonathan Thomas and Mills “and the most blatant conflicts of interest were mitigated after the scathing Institute of Medicine report.”

In 2012, the highly respected Institute of Medicine, in a $700,000 report commissioned by the agency, recommended sweeping changes at CIRM to deal with conflicts of interest, its dual executive arrangement and the composition of its governing board. The CIRM board initially greeted the report coldly but made some changes to deal with the critical findings.

California patient advocate Don C. Reed, who campaigned for stem cell research long before CIRM surfaced, however, hailed the agency's work as already saving lives and creating hope for millions. He said in an email it was a "quiet triumph" that can be built on. (See here for full text.)

Simpson, who was heavily involved in development of the agency’s intellectual property policy,

John M. Simpson
 Consumer Watchdog photo

raised questions about the failure of the agency to generate the $1.1 billion in royalties for the state promised by its backers. Simpson said,

“The CIRM annual report cites the number of ‘inventions’ CIRM has funded — more than 180.  What share of royalties have taxpayers received as a result? Anticipated revenue from CIRM-funded inventions was a big selling point for Proposition 71.”

(See here for the full text of Simpson's comments.)

 Ironically, another selling point for the ballot measure came inadvertently from former President George Bush, who had restricted federal funding for human embryonic stem cell research. Backers of the ballot measure said it was needed to compensate for Bush’s action. His restrictions were lifted by President Obama. But many researchers are worried that the Trump administration will once again limit federal support for stem cell research.

Stanford’s Greely said,

“The election of Donald Trump and the continuation of a Republican-controlled Congress could create an increased need for extending CIRM.  If the federal government pulls out of some research on basically religious grounds, California may want to step in again.  It depends both on exactly how restrictive the federal government becomes and, more subtly, on how promising the stem cell trials appear.

“I suspect some federal funding restrictions are inevitable but their scope is unpredictable. As to the trials, if they are tremendously exciting, private funds might take over; if they flop, state funds may not be appropriate.  But if the results are very promising but not spectacular, more state funding might be invaluable.” 

(For more on a possible bond election and Trump's position, see here, here, here and here.)

Simpson has another view. He said,

“No doubt CIRM-funded research has made some important contributions to scientific knowledge. The results, however, in no way justify another bond issue to fund the agency.  If CIRM continues after the current funds run out, it should be financed like any other state agency— out of the state’s operating budget approved by the Legislature on annual basis. CIRM’s operating budget could also be augmented by private contributions.”

Mills avoids public discussion of such things as bond measures. But at a meeting last fall, he likened the research program to a “giant flywheel.”

“It takes a long time to get started, and you move it imperceptibly. Once that thing gets turning, it's almost impossible to stop.”

(Editor's note: A shorter version of this story can be found in the print edition of The Sacramento Bee for Jan. 17, 2017, and also on The Bee's website. The full text of various comments follows this story, which also has links to them. Greely's complete comments were included in the article above.)

(On Jan. 19, STAT news carried a lengthy piece on the agency that said it was slow in financing clinical trials, a major factor that has hampered development of a therapy.)

(An earlier version of this item also incorrectly stated Evangelina's age.)

Text of Nolta's Comments

Here is the full text of the remarks made by Jan Nolta, head of the stem cell program at UC Davis, for the overview piece today on California's stem cell agency.

"CIRM is making fantastic progress, with numerous stem cell therapies in clinical trials throughout California. The Major Facility Institutes that CIRM built in its earlier years are now thriving centers, each is a hub for stem cell and regenerative medicine therapies in its own region of the state. Currently at UC Davis we have 16 stem cell or regenerative medicine clinical trials ongoing or recently completed, with more than 20 in the pipeline.

"As one dramatic example of cures funded by CIRM:

"As you may know, I started my career as the first technician and graduate student for Donald Kohn, MD, at Children’s Hospital Los Angeles. Together our team did the initial hematopoietic stem cell gene therapy clinical trials for “bubble babies”- children with ADA deficient severe combined immune deficiency (SCID), back in the early 90’s. (refs = pubmed PMID:7489356, and PMID:9662367). We collected the baby’s umbilical cord blood right after it was born, added a good copy of the faulty gene in our clean room area in the laboratory, and Don transplanted the babies at day 3 after birth.

"CIRM has funded Don’s continued work in this area, and he has now functionally cured over 20 children with this disease. One of them, with her family, is featured in the recent “cures” video and in their annual report.

These kids now need no expensive medicine and treatments to keep them alive, they are functionally cured. 

"That is just one example of the power of stem cell therapy. There are many examples now of CIRM-funded clinical trials that are successful, and the numbers of people who are cured grow each day.

"There is so much potential for making a difference for patients who do not have other options through conventional medicine. It is a truly exciting time to be in California!"

Text of Don Reed's Comments

Here is the full text of comments from patient advocate Don Reed on the current state of the California stem cell agency. He offered them as part of the reporting process for the overview of the agency which can be found here.

THE CALIFORNIA STEM CELL PROGRAM: A Patient Advocate’s Viewpoint

By Don C. Reed

In its ten years of active existence (lawsuits blocked its funding for the first two and a half years) the California Institute for Regenerative Medicine (CIRM) has saved lives, eased suffering and brought the realistic hope of cure to millions.

Children with the “Bubble Baby” disease have had death sentences commuted and are now living healthy lives. Paralyzed young men have recovered hand and arm function. Blind people have begun to see outlines and colors, where there was only darkness before.

 It is a quiet triumph: not flashy or fancy: but every step is carefully documented, reliable, repeatable, so it can be built upon.

When CIRM began, the obstacles against us were so tremendous one scientist predicted we would be lucky to bring even one stem cell therapy to FDA-approved clinical trials. Instead, more than two dozen conditions have either begun human trials, have completed them or are expected to begin within six months.

I remember twenty-two years ago, when my son Roman was first paralyzed. The doctors gave us no hope, saying there was nothing that could be done. Today, there is plenty we can do, and California is doing it.

Thanks to the wisdom of the voters who said yes to Proposition 71, the citizens’ initiative which became our state stem cell program, CIRM has challenged many chronic diseases and disabilities--and is making steady progress.

As a patient advocate, I am eager for cure. But I know every step of the way will be difficult, as we systematically attack “incurable” disease. We need the faith of the farmer, who plows and plants his field, knowing it will take time for the seeds to open underground, and fight their way upward through the soil, to the sun.

Already, we are seeing the first fruits of cure: like the stem cell device to be implanted under a diabetic’s skin, after which it will distribute the insulin required.But I believe the best is yet to come. 

As legendary entertainer Al Jolson once said, “Hang onto your hats, folks—you ain’t seen nothin’ yet!”

Text of Comments from John M. Simpson of Consumer Watchdog

Here is the full text of the remarks from John M. Simpson made by email for the overview piece today on the California stem cell agency.

"It’s a slick (annual) report that allows CIRM to put its best forward as it its leadership tries to make a case for future funding, quite possibly another bond issue.  I’d be interested in knowing how much the annual report cost to produce and how many copies have been printed.

"CIRM’s fundamental problem is that supporters of Prop. 71 wildly oversold what passage of the measure would deliver.  Voters were led to believe that miraculous cures were just around the corner if only the proposition passed.

"CIRM-funded research has made important contributions to science, but has yet to deliver what voters were promised.

"Agency management has improved under the Thomas-Mills regime and the most blatant conflicts of interest were mitigated after the scathing Institute of Medicine report.

"The CIRM annual report cites the number of  'inventions' CIRM has funded — more than 180.  What share of royalties have taxpayers received as a result? Anticipated revenue from CIRM-funded inventions was a big selling point for Prop. 71.

"No doubt CIRM-funded research has made some important contributions to scientific knowledge. The results, however, in no way justify another bond issue to fund the agency.

"If CIRM continues after the current funds run out, it should be financed like any other state agency— out of the states’s operating budget approved by the Legislature on annual basis. CIRM’s operating budget could also be augmented by private contributions."

Latest Targets of the California Stem Cell Agency: $26 Million for Zika, Heart Disease and Much More

The California stem cell agency next Thursday expects to award nearly $26 million to 14 scientists to seek therapies for afflictions ranging from cystic fibrosis to Zika.

The awards have all been approved by the agency's out-of-state reviewers in a round called "Quest." The $3 billion agency's board is scheduled to ratify reviewers' decisions at a telephonic meeting next week. The board almost never overturns its reviewers' decisions.

The expected outcome of a Quest award is "a candidate therapeutic, medical device, diagnostic or tool that is ready for translational stage activities."

The application receiving the highest score, 95, is seeking to develop "CRISPR/Cas9 mediated FOXP3 gene editing in patient-derived hematopoietic stem cells as a cure for IPEX syndrome."

The review summary on the $1.1 million proposal said,

"Using CRISPR/Cas9 gene editing, we will insert a wild type copy of the FOXP3 gene into patient derived HSCs, enabling pre-clinical proof of concept data for clinical trials that could reduce IPEX patient pathologies. This work will the first-in-man demonstration of the curative potential of edited HSCs and will help maintain California’s lead position in stem cell research and cure."

IPEX syndrome is a rare disease that can lead to diabetes and severe enlargement of secondary lymphoid organs.

The Zika award received the second highest score, 93. It is aimed at determining the "the impact of the Zika virus during human neurodevelopment and to test a FDA-approved therapeutic candidate to treat Zika infection." The research is budgeted for $2.1 million. 

The largest award, $2.4 million, is aimed at a gene therapy to "regenerate heart muscle for the 23 million adult and pediatric patients with heart failure, for whom there are currently no disease-modifying therapeutic approaches."  It received a score of 88.

The cystic fibrosis application was scored at 85, which was right at the cutoff line for funding. The proposal is aimed at "genome editing to correct cystic fibrosis mutations in airway  stem cells."  The application sought $2.2 million.

The reviews of 14 applications can be found here along with the reviews of unsuccessful applicants who scored from 84 to 65. None of the names of the applicants have been released yet by the agency, which withholds the information until after the board ratifies the reviewer decisions. 

Here is a link to the agenda for the meeting, which includes remote locations throughout the state at which the public can participate in the meeting and speak to the board. The meeting is also expected to be available through an audiocast. 

Remote locations include Oakland, San Diego, Napa, Irvine, Los Gatos, Elk Grove and San Francisco. Specific addresses can be found on the agenda.  

More Than $300 Million to be Awarded: California Schedules 12 Stem Cell Agency Board Meetings This Year

California's $3 billion stem cell agency has scheduled governing board meetings every month this year as it plans to give away more than $300 million.

The board has two types of meetings: telephonic, which are usually routine, ratifying earlier decisions on individual grant applications, and face-to-face meetings, of which there are only four. The face-to-face meetings often involve approval of concepts for new award rounds or significant changes in rules or policies.

Readers interested in the agency should think about taking in one of the four face-to-face sessions. They provide an opportunity to chat informally with board members along with the top staff of the agency.

The telephonic sessions are run out of the agency's Oakland headquarters, another opportunity for face-to-face encounters with some CIRM board members and staff. 

In addition to board meetings, subcommittees meet off and on during the year, sometimes by telephone and face-to-face. But there is no set schedule.

In both types of meetings, they can be listened to via the Internet and also participated in via remote locations at board member sites. All the meetings can be found at this Web site, which provides transcripts of the sessions. Readers can sign up for automatic notifications at that site. 

Here is the rundown.

January 19th, 2017, Telephonic
February 23rd, 2017 Bay Area, face to face
March 23rd, 2017, Telephonic
April 27th, 2017, Telephonic
May 25th, 2017, Telephonic
June 29th, 2017, Bay Area, face to face
July 20, 2017, Telephonic
August, 24th, 2017, Telephonic
September 21st, 2017, Bay Area, face to face
October 26th, 2017, Telephonic
November 30, 2017, Telephonic
December 14th, 2017, Bay Area, face to face

Meeting dates and locations are subject to change

Update: Lengthier Look at CIRM Delayed

The lengthier look at the performance of the California stem cell agency that was promised earlier this week has been delayed for reasons beyond our control.

But it will be forthcoming, nonetheless. If you would like to add your thoughts to the piece, please direct them to djensen@californiastemcellreport.com.

California Stem Cell Agency Director Sheehy Named to SF Board of Supervisors

Jeff Sheehy at podium today at San Francisco announcement

A long time member of the governing board of the $3 billion California stem cell agency, Jeff Sheehy, today was appointed to the San Francisco board of supervisors.

Sheehy is the first HIV-positive person to serve on the powerful, five-member board, which directs the $9 billion budget of the City of San Francisco. Sheehy's appointment means that he will be on the San Francisco board until 2018 when he must stand for election.  He fills a vacancy created when a former supervisor, Scott Wiener, was elected to the state Senate last year. 

It is not uncommon for San Francisco supervisors to be elected to higher office, including U.S. Senator Dianne Feinstein. 

Sheehy will continue to be an AIDS patient advocate member of  the board of the stem cell agency, which he has served on since its inception. He is vice chairman of the grants review group, which makes the de facto decisions on the research awards handed out by the California Institute for Regenerative Medicine (CIRM), as the Oakland-based agency is formally known.  Sheehy is also chairman of the Science Subcommittee of the agency's board and is director of communications for the UC San Francisco Aids Research Institute.

Jonathan Thomas, chairman of CIRM, and vice chairman Art Torres, former head of the state Democratic Party, issued a statement saying they were "delighted" by the appointment. They said Sheehy has brought "intelligence, dedication and compassion to everything he does."

Sheehy was appointed to the supervisorial board by San Francisco Mayor Ed Lee. 

The 2016 Report From the California Stem Cell Agency: Challenges and Accomplishments

Stem cell agency's annual report cover

California's $3 billion stem cell agency has filed its 2016 annual report, which is chockablock with stories about people aided by stem cell research plus discussions of speed, clarity and clinical trials. 

The posting of the 20-page report on the agency's web site came 12 hours before the end of year on Friday.

"Challenges remain but new cures are emerging" was the headline on the document. "All in. All out" was how the agency's work was characterized.

Much of what was contained in the report has been written about previously on the California Stem Cell Report. But the annual report provides a useful and valuable summary of the agency's work for those interested in whether it is fulfilling the promises of the 2004 ballot initiative that created the agency, which is unprecedented in state history. 

Some of the notable numbers for the Oakland-based, 48-person agency, which is known formally as the California Institute for Regenerative Medicine(CIRM):

Over the last two years, the agency has helped to finance 27 clinical trials and is looking for another 40 by 2020.

More than 180 "inventions" have been chalked up.

More than 250 projects are currently being managed by the CIRM team.

Twelve "world-class" research facilities have been created over the last 12 years.

Three Alpha Clinics, intended to be one-stop stem cell centers, are in operation. A fourth is scheduled for this year.

A $30 million stem cell "pitching machine" to speed clinical trials and help guide development through federal regulations began operations in 2016.

Jonathan Thomas, chairman of the agency, said in the report, 

"However, there can be no greater return on our investment than the restoration of health. That is now occurring because of CIRM. Evangelina (featured on the cover), stricken with a previously incurable immune system disorder, is now cured. That’s right, cured. And we are working to quicken the pace at which this treatment is available to others. This is the promise of stem cell therapy."

The California Stem Cell Report will have a lengthier look at the agency later this week.

Holiday Break for California Stem Cell Report

This web site will go dark for the holidays. If we are lucky, it will resume on Jan. 3. Best wishes to all and Happy New Year.