Research for Arthritic Knee Treatment Survives Challenge at California Stem Cell Agency

The California stem cell agency today awarded $33 million for clinical trial research, but not before some governing board members questioned the appropriateness of backing an effort to treat osteoarthritis of the knee.

The awards today bring to 43 the number of clinical trials funded by the stem cell agency, formally known as the California Institute for Regenerative Medicine (CIRM). The agency is pushing hard to fulfill the promise of the 2004 ballot campaign that created the $3 billion effort. Clinical trials are the last stage before a treatment can win federal approval.

The agency expects to run out of money in mid 2020, but so far has failed to back research that has resulted in a therapy that is available for widespread use. 

At today's telephonic CIRM board meeting, the arthritis research by La Jolla's California Institute for Biomedical Research encountered opposition from some members of the board who expressed concern that it did not square with the mission of the agency. 

At issue was the use of a small molecule drug, KA34, to stimulate stem cells to create new cartilage in knees. Jeff Sheehy, a board member and San Francisco county supervisor, said small molecule development is widely done already by the pharmaceutical industry. Noting that the research is a treatment and not a cure, he said funding the arthritis award would mean not funding other research that would be more focused on direct stem cell cures.

Art Torres, vice chairman of the board and a former state senator, supported the application, declaring that "if we can show we are finding some treatment we may be moving forward to getting support in other ways."

Both men have suffered from severe knee problems.  About one in five persons over 45 are afflicted with arthritis of the knee.

The vote by the board on the application, which involves a phase one safety trial, was 9-5. Last month, the agency's grant reviewers, meeting behind closed doors last month, approved the award following a more detailed examination of the proposal.

It was the third CIRM award for the San Diego not-for-profit firm, which has already received $4 million for work on arthritis. 

The largest award, $19.8 million, went to another San Diego area firm, Poseida Therapeutics.  A CIRM news release on today's action said the research will test "the safety of a gene modified cell therapy to treat multiple myeloma, the abnormal growth of malignant plasma cells of the immune system."

Maria Millan, president of the stem cell agency, said, 

“Multiple myeloma disproportionately affects people over the age of 65 and African Americans, and it leads to progressive bone destruction, severe anemia, infectious complications and kidney and heart damage from abnormal proteins produced by the malignant plasma cells. Less than half of patients with multiple myeloma live beyond 5 years.”

About 12,590 deaths are expected from multiple myeloma this year in the United States, according to the American Cancer Society. The award was the first for Poseida from CIRM. The company is providing $8.6 million in co-funding.

Like all the awards today, the Poseida award was approved earlier in a closed door meeting by reviewers who do not have to publicly disclose their economic or professional conflicts of interest.

There was no board discussion today of the Poseida award nor of the third award, $4.8 million to Childrens' Hospital of Los Angeles. Its phase one trial involves testing the feasibility of using engineered T-cells to fight viruses that can kill patients with weakened immune systems. Those patients include persons undergoing chemotherapy, bone marrow or cord blood transplants.

Childrens' Hospital Los Angeles earlier had received $26.3 million from the agency.

The agency has helped to finance 16 clinical trials in 2017 alone. Whether it will continue at this pace in 2018 is expected to be discussed at its December board meeting.  Some board members have indicated it would be of some benefit to slow the pace of funding to extend the life of the agency.

Here is a link to the overall staff presentation on the applications. Here are links to the summaries of the grant reviewers comments:  California Institute for Biomedical Research application CLIN2
-10388, Poseida application CLIN2-10392, and Childrens' Hospital application CLIN2-10392.

More information on the Poseida clinical trial, which is now recruiting, can be found here.

More information on all the agency's clinical trials can be found on CIRM’s Clinical Dashboard.

Preview of Bond Campaign: California Stem Cell Agency Described as 'Dismal,' 'Disappointing' and a 'Waste'

A couple of die-hard opponents of the $3 billion California stem cell agency minced no words this weekend. In an op-ed piece in the Orange County Register, they described the agency as nothing more than an "advanced high school science project."

The article was written by Jon Coupal, president of the Howard Jarvis Taxpayers Association in Sacramento, and state Sen. John Moorlach, R-Costa Mesa. 

They described the agency's efforts as "dismal" and declared that "this disappointing abuse of taxpayer dollars" should be terminated.

The print version of the article appeared in Sunday's paper, which has a circulation of about 312,000. Both the print and online version carried photographs involving stem cell research. But neither was from UC Irvine, which has received $108 million from the agency and has a member on the board of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known.  UC Irvine is located only 17 minutes away from the offices of the newspaper. 

The piece is a relatively tame preview of the rhetoric that will confront CIRM if it goes to the ballot in 2020 for more billions from California taxpayers. The article cited arguments from the 2004 Prop. 71 ballot measure campaign that created the agency. 

Coupal and Moorlach said, 

"According to the ballot pamphlet mailed to voters, proponents promised the bond proceeds would advance the 'cure and treatment' of  'cancer, diabetes, heart disease, Alzheimer’s, Parkinson’s, spinal cord injuries, blindness, Lou Gehrig’s disease, HIV/AIDS, mental health disorders, multiple sclerosis, Huntington’s disease, and more than 70 other diseases and injuries.' 

"But actual outcomes for these promised advances are speculative at best and nonexistent at worst. Similar benefits were promised to the California economy to 'generate millions of new tax dollars.' 

"With such a dismal record, this would be a good time to shut the spigot on issuing the remaining $345 million — meaning some $690 million would be saved by state taxpayers. That money could be better spent on pensions, schools, roads, housing or better basic medical care for our residents."

As for the high school project business, the article said CIRM "continues to operate as a kind of advanced high-school science project, instead of moving toward the cures promised to voters in Prop. 71."

Thinking About Its Demise: California Stem Cell Agency Launches Examination of Alternatives

California's $3 billion stem cell research agency, which is facing its financial demise in a few short years, has formed a team of its directors to tackle transition planning and examine possible alternatives, including ones that would extend its life.

The first meeting of the group of directors is tentatively scheduled for Sept. 18. Jonathan Thomas, chairman of the governing board of the California Institute for Regenerative Medicine(CIRM), as the agency is formally known, said earlier this summer:

"The legislature has asked that we put together and start thinking about a transition plan, which can contemplate a variety of factors."

In response to a question last week, a spokesman for the agency, Kevin McCormack, said that a notice with more details would be posted 10 days prior to the meeting.

At a meeting in June, Thomas laid out the need for the transition team. He said all options are on the table including asking the legislature for cash or to place a measure on the ballot for more bond funding.

The agency's only real source of money is state bonds, authorized by voters in 2004. It has roughly $600 million left. The agency has projected it will run out of cash for new awards in mid 2020, although that could vary, depending on whether it slows down the pace of awards.

Several directors at the board meeting in June expressed a "sense of urgency" about dealing with the fate of the agency. CIRM Director Jeff Sheehy, a member of the San Francisco board of supervisors and an HIV/AIDS patient advocate, voiced concern about the uncertain nature of the agency's future.

Sheehy said,

"It seems to me that we will be talking about a substantial scaling back of the organization in 2020....We've kind of created this expectation that we were going to go to 2018 and come back with new money."

Sheehy referred to talk that a new bond initiative might be launched in 2018, a move that the board's former chairman, Robert Klein, has publicly advanced. Sheehy said, however, that he spoke with Klein, who told him that he was now considering 2020 instead.  Klein's method would require the gathering of hundreds of thousands of valid voter signatures to place the proposal on the ballot and would bypass the legislature. 

The year 2020 includes a presidential election, which has higher voter turnout and generally is considered a better time to win approval of bond measures. Presumably, the agency might be able to secure extra funding to span any financial gap or, alternatively, lower the frequency of awards to stretch out the cash. 

The members of the transition group are Thomas, Sheehy, Art Torres, Steve Juelsgaard, Joe Panetta, Kristiina Vuori, Linda Malkas, Diane Winokur, Shlomo Melmed, Al Rowlett and Judy Gasson. Short bios on each of them can be found via this page. 

The California Stem Cell Report will carry an item with the date and location of the September meeting when it becomes available. 

California's $3 Billion Stem Cell Agency Loses CEO Randy Mills

C. Randal Mills
CIRM photo

In a surprise move, the president of California's $3 billion stem cell research effort this morning announced his resignation as the program enters what some are calling its "final test."

C. Randal Mills said that he has taken a position as president of the National Marrow Donor Program in Minneapolis, Minn. He said he will leave the California Institute for Regenerative Medicine (CIRM), as the stem cell agency is formally known, at the end of June.

Maria Millan, CIRM photo

Maria Millan, vice president of therapeutics, will become interim president of the 12-year-old agency in July. The governing board of the agency plans a meeting of its search committee in July to consider its options regarding the appointment of a permanent president for CIRM, which expects to run out of cash for new awards in three years.

Just last week, the prestigious journal Nature described the Oakland-based agency as entering its "final test" and "last stage."

Mills, 45, joined the agency almost exactly three years ago and promptly launched a more focused effort than previously existed to fulfill the promises and expectations created by the 2004 ballot initiative campaign that created the agency.

Jonathan Thomas, CIRM chairman and who recruited Mills, said in a press release,

“CIRM has experienced a remarkable transformation since Randy’s arrival. He has taken the agency to a new level by developing and implementing a bold strategic plan, the results of which include an 82 percent reduction in approval time, a 3-fold increase in the number of clinical trials, and a 65 percent reduction in the time it takes to enroll those trials.

"CIRM’s mission is to accelerate stem cell treatments to patients with unmet medical needs, and under Randy’s leadership, CIRM has done just that. The opportunity for Randy to lead a tremendously important organization such as NMDP is consistent with the values he demonstrated at CIRM, which put the well-being of patients above all else."

In an interview with the California Stem Cell Report, Mills said the offer to lead the donoro program "came out of the blue." He said the opportunity to join the world's largest bone marrow effort was unique. The organization, he said "does not do anything that doesn't save lives."

Mills said in the interview that Millan was an obvious choice to succeed him on a permanent basis. In the agency's press release, Mills said,

"What this team has been able to accomplish in that time is remarkable by any objective measure and I thank them for their 'All In' attitude and effort. As a trailblazing institute, CIRM is setting new highs in productivity and efficiency and will continue to deliver on its mission under the leadership of Dr. Millan."

Millan, a physician, has been with the agency since 2012, joining it from StemCells, Inc., where she was acting medical officer and vice president. Prior to that, she was an associate professor of transplant surgery for eight years at Stanford University.

Thomas said,

“One of the most valuable contributions Randy has made at CIRM is the strength of the team he has assembled. Maria is exceptionally well qualified and completely engaged in the operations of CIRM, having worked with Randy as member of the leadership team that created and is executing the strategic plan. With her leadership, we are well positioned for continued success,

Millan was paid $281,000 last year, according to The Sacramento Bee's state worker database. Mills was paid $573,000.

Mills' departure comes as supporters of the agency are concerned about whether its work will effectively end in 2020. However, its first chairman, Bob Klein, is talking about asking California voters for another $5 billion. Klein also led the $34 million ballot campaign.

Klein's organization, Americans for Cures, is planning to conduct a poll this fall to determine the level of public support for CIRM. He has said that if support is in the 70 percent range he would mount a bond issue in 2018. Otherwise, he might try in 2020, a presidential election year, with a larger voter turnout.

The organization that Mills is joining is "the world's largest the world's largest registry of unrelated adult donors and umbilical cord blood (UCB) units," according to Nature. It has been heavily funded by the federal government with an annual budget of $383 million, according to 2014 figures, and has about 1,000 employees. CIRM currently has 46 employees and has ranged up into the middle 50s.

Accompanying Mills in the move to Minneapolis will be his wife, Anna, and two children, Elise, 13, and Chase, 10.

(The agency posted an item on its blog, The Stem Cellar, dealing with Mills' resignation shortly after this item was posted.)

The Journal Nature Says: 'Last Stage' for California's Stem Cell Research Program

The prestigious journal Nature this week is calling it the "final test" for California's $3 billion plunge into development of stem cell therapies for afflictions ranging from cancer to arthritis.

The California Institute for Regenerative Medicine (CIRM), as the stem cell agency is formally known, expects to run out of cash for new awards in June 2020. The 12-year-old agency was created by a ballot initiative campaign that led voters to believe that nearly miraculous stem cell treatments were just around the corner. So far the agency has not backed a stem cell therapy that is widely available.

For Nature, the situation merited this headline yesterday on its web site,

"California’s $3-billion bet on stem cells faces final test
"Major investment in regenerative medicine enters its last stage — and the money might run out before treatments are ready."

Amy Maxmen wrote the article. She said,

"Now, the pot of money — one of the biggest state investments in science — is running dry before treatments have emerged, raising questions about whether Californians will pour billions more into stem-cell research."

Maxmen continued,

"If they don’t, that could leave hundreds of scientists without support, and strand potentially promising therapies before they reach the market. 'It’s an issue of great concern,' says Jonathan Thomas, chair of the board for the California Institute for Regenerative Medicine (CIRM) in Oakland." 

Maxmen also noted the critical assessment of CIRM in 2012 by the Institute of Medicine and some subsequent changes made by the agency's board. She said,

"Jim Lott, a member of the state board that oversees CIRM’s finances, says that he is not satisfied with the changes. He also argues that CIRM may not have been strategic enough in directing research. 'Some people say if they had a better focus, they might have achieved cures.'"

The Nature piece covered familiar ground for readers of the California Stem Cell Report. But she had further news from Bob Klein, a Palo Alto, Ca., real estate investment banker. Maxmen wrote,

"Bob Klein, the property developer who put Proposition 71 on the ballot and established CIRM, isn’t waiting for the money to run out. He leads an advocacy group, Americans for Cures, which will soon poll voters  to see whether they would approve another $5 billion in funding. If it looks like at least 70 percent of Californians support that plan, he’ll start a campaign to put another initiative on the ballot in 2018.

"Klein hopes that Californians will rise in support of science at a time when the Trump administration has proposed drastic cuts to the NIH budget. If public enthusiasm is not so strong, Klein says, he’ll aim for the 2020 elections, when voter turnout should be higher because it will coincide with the next presidential race."

Maxmen concluded with this comment from Eric Verdin, president of the Buck Institute on Aging in Novato, Ca., which has received nearly $35 million from CIRM.

“It would be a catastrophe for California if people say CIRM did not do what it was expected to do. They’ve built the foundation for the field and attracted people from around the world — you can’t just now pull the plug.”

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.

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.)

Multi-Billion Dollar Ballot Measure for California Stem Cell Agency in 2018?

California's $3 billion stem cell research effort is scheduled to run out of cash in three short years, but the likelihood seems to be increasing that voters will be asked again to come up with additional billions for the state's stem cell agency.

In fact, the chairman of the stem cell agency, Jonathan Thomas, is saying flatly this week that his predecessor, real investment investment banker Bob Klein, intends to place a funding measure on the November 2018 ballot.

Klein led the ballot initiative campaign in 2004 that created the unusual -- for a state -- stem cell research program, officially called the California Institute for Regenerative Medicine (CIRM). The agency is financed with cash that the state is borrowing. increasing total costs to roughly $6 billion because of the interest expense.

Jonathan Thomas, left, with Don Reed,
vice president of public policy, Americans
for Cures, Klein's advocacy group --
CIRM photo

Thomas' statement was contained in a letter to the governing board that recapped his work since he was elected by the board in 2011 to replace Klein. One section of the letter dealt with funding of the agency.

Thomas wrote,

"Bob has already announced that he intends to put a measure on the November 2018 ballot. We keep him updated on CIRM's progress so that he is fully informed."

Thomas added that he and two key CIRM staffers have "initiated discussions with a number of philanthropists and foundations interested in medical research who could be potential sources of funds to keep CIRM going in the event Bob's measure is not successful."

The California Stem Cell Report has queried Klein about his plans. The full text of his response will be carried when it is received.

Robert Klein, Americans for Cures
photo

Klein has publicly mentioned a possible bond measure in the past, most recently in 2014, including a figure as high as $5 billion. It is unclear whether he has spoken more specifically on the matter since then.

Klein maintains a stem cell advocacy group, Americans for Cures, which has an active web site and an impressive list of scientific advisors, including Irv Weissman of Stanford, Rusty Gage of the Salk Institute and Owen Witte of UCLA.

Klein's 2004 stem cell campaign cost $34 million to convince California voters that the state needed to begin its own human embryonic stem cell (hESC) research effort in the wake of then President Bush's restrictions on federal funding in that area. The campaign created the impression that cures were close at hand, according to opponents and media observers. The agency is yet to back a therapy that is available for widespread use.

The election of Donald Trump as president is widely expected to trigger new, Bush-like restrictions on human embryonic stem cell research that could create the same sort of climate that helped lead to the success of the 2004 ballot initiative in California. 

From Royalties to Real Products: The Journal Science Looks at the Prospects for the California Stem Cell Agency

The headlines last week in the journal Science spoke of California’s stem cell “end game,” its “a race to the clinic” and its “prospects for new money.”

The article by Kelly Servick provided a quick status report on the Golden State’s $3 billion stem cell agency. The research effort last month approved a plan for spending its last $800 million in an attempt to fulfill the promises of the 2004 ballot campaign that created the research effort.

Servick wrote that the new plan could be critical to survival of the agency. She said,

“(W)hether there will be enough believers in CIRM to keep the agency afloat may depend on how well it can build—and publicize—a track record for moving stem cell discoveries to the clinic.”

The agency has been largely ignored for the last several years by the mainstream media, but its fresh, five-year plan has attracted some modest attention, including  Servick’s piece in Science Jan. 1.

The article largely sprang out of the December meeting at which the board of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known, approved its strategy for the next five years.

Servick also quoted Robert Klein, the former chairman of the agency, as saying he hopes to spearhead a new ballot initiative in 2018 to fund the agency beyond 2020, when its cash is expected to run out. At the December meeting, the board specifically avoided approval of a ballot effort and referred the question of future funding to a board subcommittee. No public meetings of that panel have been announced.

Servick began her story like this:

“Born out of discontent with the federal restrictions on research with cells from human embryos, California’s stem cell agency is at a key juncture: Over the past decade, it’s spent a large portion of its $3 billion budget nurturing fledgling disease therapies, but that state money may run out before most ments are ready for the clinic.”

She continued,

“Even if all goes according to plan, however, most CIRM-funded projects will not finish phase II trials in the next 5 years, and may not be ready for an industry partner, (Chairman Jonathan) Thomas told the board. ‘If [CIRM doesn’t] have additional funding at that point, we will have only partially met our obligation to develop therapies and cures.’”

She noted that one funding possibility is “large royalty payments” from CIRM-related research, something that was promised by backers of the stem cell ballot initiative in 2004. However, if any royalties do surface, they will go to the state general fund -- not to the stem cell agency. Lawmakers would have to approve an appropriation for the agency -- one that would also have to be approved by the governor. Currently, the agency is financed by money that the state borrows and which flows directly to the agency without the need for legislative or gubernatorial approval.

At the December meeting, Art Torres, vice chairman of the board and a former, longtime state lawmaker, expressed reservations about dealing with the Legislature.

Servick wrote,

“There are ‘people that don’t believe in what we do, who are members of the legislature,’ Torres warned, and they ‘could invariably impact any [CIRM funding] proposal.’”

The Science article is behind a paywall. If you would like a copy, please email me at djensen@californiastemcellreport.com.

Fallout From the Trounson Affair: A Taint on the California Stem Cell Agency

Directors of the $3 billion California stem cell agency meet tomorrow in the San Francisco Bay Area, but the hottest topic is not on the agenda, and that is the Trounson Affair.

Alan Trounson
SF Business Times photo

The term is shorthand for the host of questions raised by the appointment July 7 of Alan Trounson, former president of the agency, to the board of StemCells, Inc. The company is the recipient of $19.4 million from the agency, cash that was awarded under unusual circumstances on a narrow 7-5 vote.(See here and here.)

Two days after Trounson’s appointment, the agency’s new president, Randy Mills, announced a “full review” of the activities involving StemCells, Inc., a publicly traded firm based in Newark, Ca.

News and commentary about the matter has slowly emerged since the appointment. None of it reflects well on the agency, which is trying to devise some way to secure public or private funding beyond 2017 when the cash for new awards runs out.

The most visible article appeared in the Sunday Los Angeles Times, which has a readership of 4 million in print and online. Michael Hiltzik wrote that cronyism is rife at the California Institute for Regenerative Medicine(CIRM), as the agency is formally known.  He said,

“How bad are the conflicts? When the (29-member) board considered a proposal earlier this year to spend $16 million to attract three star scientists to California, so many members had to recuse themselves that only nine were left to vote. (Six ended up voting in favor.)

“When conflicts of interest are so rife that only one-third of your board can weigh in on a major policy issue, that's tantamount to not having any board at all.”

The tone was echoed in other pieces, including one in the San Francisco Business Times, where the headline said,

 “'Trounson affair' another strike against California stem cell agency.”

Other articles appeared in the San Diego U-T and the San Francisco Chronicle. The Orange County Register published an editorial that said the agency has “operated as a cash cow for a tiny circle of well-connected individuals and institutions.”

The Trounson appointment “reignites charges of cronyism,” said a headline on allgov.com. Pete Shanks of the Biopolitical Times wrote, 

"Let's be blunt: This looks like a pay-off. Technically, what Trounson and (Irv) Weissman (of Stanford) and StemCells, Inc., just did may not be illegal. But it's shameless.”

The Scientist magazine wrapped the Trounson appointment into a piece that included news about a lawsuit against StemCells, Inc., that charged the company was endangering patients in clinical trials. 

The talk ricocheted around California’s stem cell community. One longtime reader of the California Stem Cell Report, who is a patient advocate, said in an email that Trounson’s conflicts of interest are “now even more transparent and make the previous grant decisions even more suspect.” “Self-dealing” is how this supporter of stem cell research described the situation.

Another reader and knowledgeable observer, who also must remain anonymous, described the Trounson appointment as “brazen.” And yet another who is quite familiar with the agency said,

“No one seems to understand what conflict of interest means.  I don't understand how they can even think that it is OK to do this.”

We should note that these remarks come from persons who back stem cell research and the agency.

In some ways, however, public attention to the matter could be described as minimal. The stem cell agency is little known to most people, and the Trounson Affair did not garner front page headlines. But like some sort of immortal cell, the stories will live on. Twenty years ago, the individual stories would have faded, buried in the morgues of the mainstream media. However, today, given Google searches, they will become embedded in all future reporting about the agency – not to mention knife-edged opposition research should another bond measure be placed before voters to fund the agency.

The Trounson Affair also highlights the need for the agency to stiffen its revolving door restrictions – the regulations that would have prevented his immediate appointment to a post at an enterprise that has benefited from the agency’s largess. It is a problem that will grow as the agency nears its financial demise. CIRM staffers will naturally be looking for places where they can find future employment.

The state has some minimal laws restricting future employment by agency personnel. But the agency needs to do more, a difficult task given that such action basically will change the terms of employment for staffers. But failure to confront the issue will only lead to more debacles.

CIRM’s “full review” of the situation is well-taken. However, the agency has not publicly defined even generally what a full review entails nor has it responded to questions from the California Stem Cell Report about the nature of the inquiry. The agency also has not indicated whether it is seeking an outside, independent entity to conduct the review. One possibility would be State Controller John Chiang, who is the chairman of the only state body (the Citizens Finanancial Accountability and Oversight Committee) charged with oversight of the agency. Another would be the state’s Fair Political Practices Commission, the state department charged with enforcing conflict of interest laws.

One California researcher and CIRM grant recipient has noted that the flap obscures the work that the stem cell agency has done. In a comment filed on an item on the California Stem Cell Report, Jeanne Loring, director of the Center for Regenerative Medicine at The Scripps Research Institute, said that despite “the errors in judgment” at the agency, 

“CIRM is at the heart a remarkably effective driver of cutting edge research. By focusing on a narrow area of research and encouraging international collaboration, CIRM has singlehandedly pushed the whole world's stem cell research forward. If CIRM were a drug company, it would be considered miraculous that so many promising treatments are in the pipeline just eight years after it started."

Loring makes a good point. And it would be a shame if the good work of CIRM is discredited because of a failure to deal forthrightly, quickly and publicly with conflict of interest issues at the agency. 

Los Angeles Times: California Stem Cell Agency Rife with Conflicts and Unrealistic Expectations

The Los Angeles Times, California’s largest circulation newspaper, is carrying a piece this weekend about “cronyism,” conflicts of interest and “inflated expectations” at the state’s $3 billion stem cell agency.

The column by Pulitzer Prize-winning writer and author Michael Hiltzik used this month’s Trounson Affair as a starting point to dissect the situation at the California Institute for Regenerative Medicine (CIRM), as the agency is formally known.

Trounson was appointed to the board of StemCells, Inc., of Newark, Ca., on July 7, just seven days after leaving the agency. StemCells, Inc., holds a $19.4 million award from the agency.  CIRM has ordered a full review of the situation and barred its staff from communicating about StemCells, Inc., matters with Trounson. 

But even before Trounson’s appointment, there were issues involving StemCells, Inc.(See here and here.)  Hiltzik said,

 “The relationship already reeked of cronyism.”

Hiltzik wrote,

“Trounson's move comes as CIRM must begin looking to the future, but any discussions about extending the agency's life span will have to address the flaws created by Proposition 71 (the ballot initiative that created the agency in 2004). Among them is the program's very structure, and even its scientific goals.”

Hiltzik continued,

“How bad are the conflicts? When the board considered a proposal earlier this year to spend $16 million to attract three star scientists to California, so many members had to recuse themselves that only nine were left to vote. (Six ended up voting in favor.)

“When conflicts of interest are so rife that only one-third of your board can weigh in on a major policy issue, that's tantamount to not having any board at all.”

Some of the issues at the agency have to do with the ballot campaign that created it in 2004, an election in which California voters were led to believe that miraculous stem cell therapies were imminent.

Hiltzik wrote,

“Programs like CIRM are always susceptible to inflated expectations.

"”Since Big Science needs great public support it thrives on publicity,’ the physicist Alvin Weinberg, a veteran of the Manhattan Project, wrote in a famous 1961 article in "Science" about the drawbacks of big-money scientific research. He added: ‘The inevitable result is the injection of a journalistic flavor into Big Science which is fundamentally in conflict with the scientific method.... The spectacular rather than the perceptive becomes the scientific standard.’"

Hiltzik acknowledged the contributions that CIRM has made to stem cell science.

“CIRM-funded labs have produced genuine achievements. But the agency tends to delineate its progress in buildings built, papers published, and big-name scientists lured to California. But the specific cures promised by the Proposition 71 campaign haven't materialized, which doesn't surprise anyone steeped in the realities of the scientific method.”

Hiltzik concluded,

“Even if one believes the need for California to devote $3 billion to a narrow, extremely speculative field of science, the Trounson case and other CIRM administrative missteps have made clear that Proposition 71 created the wrong framework to manage a complex research effort. The initiative left the public with no way to tell if its money has been well spent, and no accountability if it hasn't.

“Moreover, the program deprived potentially more promising research efforts of resources and contributed to the general impoverishment of California's entire higher-education system. If its sponsors have the audacity to ask taxpayers for even more money under the same terms as Proposition 71, the reply should be a resounding ‘no.’ If the voters are gullible enough to repeat the same mistake they made in 2004, there's no cure for them.”

The Hiltzik column appeared online last night. It is scheduled to appear in the Sunday print edition of the Times, which says it has a combined print and online reach of 4 million readers.