$20 Million, California-backed Stem Cell Trial Discloses Disappointing News

Capricor Therapeutics, Inc., today announced some bad news about its state-of-California financed clinical trial for a cardiac, stem cell therapy and said that it planned to lay off an unspecified number of employees.

Capricor's stock price plummeted 62 percent following what the company called the "unexpected" news, dropping from $1.89 to $1.16. California's stem cell agency has backed the trial with $20 million, plus an additional $7 million for earlier, related research.

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

"Obviously this is disappointing news for everyone involved, but we know that not all clinical trials are going to be successful. CIRM supported this research because it clearly addressed an unmet medical need and because an earlier Phase 1 study had showed promise in helping prevent decline in heart function after a heart attack."

In response to a question, Kevin McCormack, senior director of communications, said the agency is talking to Capricor about the next steps. The agency regularly halts funding of awards when recipients do not meet milestones. McCormack did not respond to a question about how much money the firm had already received from CIRM.

Capricor, which is headquartered in Beverly Hills, said in a press release that an interim analysis on the phase two trial has "has demonstrated a low probability (futility) of achieving a statistically-significant difference in the 12-month primary efficacy endpoint." The company said there was "no notable difference" between treatment groups.

The company said it would cut its workforce to focus more sharply on its treatment of Duchenne muscular dystrophy, which the stem cell agency is also backing with $3.4 million. The Duchenne treatment had better news the last month, clearing its phase one trial with no adverse effects.

Timothy Henry and Rajenda Makkar of the Cedars-Sinai Heart Institute in Los Angeles are the principal investigators for the clinical trial.

The highest price for Capricor stock over the last 12 months was $5.40 and the lowest was $1.13.

Here are links to additional news stories today on Capricor: BiopharmaDive, MarketWatch, Genetic Engineering News, 

The "Other" and Stem Cell Blogs

Ever wonder who reads stem cell blogs? The "other" are the predominant readers of the one produced by a UC Davis stem cell researcher. At least that is the latest result from a survey that Paul Knoepfler is conducting about his cyberspace effort.

Knoepfler posted the survey request today. The results are still coming as you read this item. The initial tally this afternoon showed that 21 percent of respondents placed themselves in the "other" category when asked about their background. Next were academic and industry scientists, both with 18 percent, and physicians, 15 percent.

Most liked posts? Investigations, 33 percent; opinion pieces, 21 percent; newsy items, 17 percent.

The results are ever-changing as more readers respond. You can express your own preferences by going to this item. Respondents will be entered in a drawing for a stem cell T-shirt and signed copies of Knoepfler's two books.

Embedded in a Stem Cell Lab: Melton, Diabetes and Keeping Cells Happy

Yi Yu, a research assistant at the Melton lab at Harvard with flasks containing
human embryonic stem cells -- Photo Chloé Hecketsweiler/Undark

From a "mouse house" to growth cocktails, a web site called Undark has it all in a piece headlined "A Month in the Life of a Stem Cell Lab."

The photo essay was prepared by Chloé Hecketsweiler, a Paris-based journalist with Le Monde. She recorded events and people during six weeks this year in the laboratory of Douglas Melton at the Harvard Stem cell Institute.

Melton is digging into diabetes. A firm he co-founded, Semma Therapeutics, is the recipient of a $5 million award from the California stem cell agency, formally known as the California Institute for Regenerative Medicine.

About Melton's lab, Hecketsweiler wrote,

"I watched their experiments, learned about the complex science of stem cells, and talked with the researchers about their work and hopes. I was allowed to take pictures, and for this photo essay I tried to pick out moments and details that I found revealing, although scientists may see them as business as usual."

Her photos are first-rate, her reporting personal and the presentation strong. One member of Melton's team, Maria Keramari, told her,

"You have to keep the cells happy before you keep yourself happy."

It echoed an axiom from America's old family farming days when livestock was fed and cared for as the sun rose, long before before the family sat down for breakfast.

Another Melton researcher, Ornella Barrandon, said,

"We spend so much time on our projects, they are like our babies."

Hecketsweiler's work tells a science story in a way not regularly seen. It is a good example of making stem cell research accessible to a wide audience and leaving them wanting more.

A Scripps Scientist Deflates Cancer-Stem Cell Nexus

The sky is not falling, says a Scripps Research Institute scientist, despite headlines that seem to link "mutation" and "cancer" and "stem cells."

That comes from Jeanne Loring, head of the stem cell program at Scripps, who was writing on the blog of UC Davis stem cell researcher Paul Knoepfler. Loring said,

"'Mutation' and 'cancer' are eye-catching words for a headline; add 'stem cells' and there is a good chance that a lot of people will hear about it. These words have been liberally used in the press to describe the results of a recent publication: 'Human pluripotent stem cells recurrently acquire and expand dominant negative P53 mutations.'"

Loring said she has been on a soapbox on this issue since 2000.  She said, 

"Every time a scientific report suggests that human stem cells are dangerous, I feel the need to reassure both scientists and non-scientists that we should not panic.  The sky is NOT falling (contrary to Henny Penny), and pluripotent stem cells remain valuable for cell replacement therapies."

Loring went into the rather technical reasons for her position as well as identifying issues having to do with not knowing enough about the cells used in research. She also provided some tools for researchers to use to identify cells with "functionally important mutations."

Loring's bottom line to researchers:

"Don't panic! Check your cells instead."

NY Times Offers Overview of $3 Billion California Stem Program

The New York Times took a look yesterday at California's $3 billion search for a stem cell therapy in a piece that almost incidentally reported the departure of its president, Randy Mills.

The article was more of a  blog item than the heavily and independently reported news story that is often characteristic of the Times. However, it marked one of the few occasions that the newspaper has attempted an overview of the California Institute for Regenerative Medicine (CIRM), as the stem cell agency is formally known.

Mike McPhate did the online article as part of his California Today column, which is provided online subscribers. The article began:

"More than a decade ago, Californians made a $3 billion wager on the healing potential of stem cell research.
"Today, with that money projected to start running out in the next few years, what does the state have to show for it?"

After recounting a bit of CIRM history, McPhate answered, 

• "More than 750 grants distributed
• "A dozen research facilities constructed
• "Roughly 2,000 scholarly papers published
• "More than 2,400 students and young scientists trained
• "About 30 projects that include clinical trials funded
"Still, the agency has yet to finance a therapy approved for commercial use."

McPhate concluded by saying that Robert Klein is eyeing another bond measure to continue the work at CIRM, which says it will run out of cash for new awards in about three years.

McPhate wrote,

"It would appear on the 2018 ballot. The ask this time? $5 billion."

More Media: San Diego Weighs in With Story on Randy Mills' Departure from Stem Cell Agency

The San Diego Union-Tribune, which covers the large biotech community in its area, today carried a hefty piece on the departure of Randy Mills as CEO of the $3 billion California stem cell agency.

Bradley Fikes wrote the story, which was headlined,

"Amid uncertain future, state's stem cell agency loses transformational leader "

Fikes, the only reporter on a major daily, California newspaper to regularly cover stem cell matters, reported that Mills said the agency will do fine without him. Fikes wrote, 

"'If me leaving CIRM is a problem, then I didn’t do a good job at CIRM,' Mills said. 'Whether it’s because I’m going to be the head of the National Marrow Donor Program or I get hit by a car, the success of this organization, or any organization that’s healthy and functional, should never pivot on one person,'  Mills said. 'I’ve assembled a team at CIRM that I have absolute, absolute confidence in.'"

The article also said,

"Jeanne Loring, a CIRM-funded stem cell scientist at The Scripps Research Institute, said Mills made the agency friendlier and more predictable for the scientists it funds.

"'The first and most dramatic thing he did was to end the process of independent grants,' Loring said. Under that process, each grant proposal was considered on its own, with no consideration for success under a previous grant for an earlier stage of the research.

"'It was always very troubling to people, I think, that they could do very well with CIRM money on an early-stage grant, and that would earn them nothing in a further application to continue the work,' Loring said."

Mills' Departure: Surprise and Concern About California Stem Cell Agency

Disappointment, shock and surprise are surfacing in the wake of the news that Randy Mills is leaving his post as CEO of the California stem cell agency. However, the news drew little attention in the media.

Mills, 45, yesterday announced that he will depart at the end of June to become head of the National Bone Marrow Donor Program in Minneapolis. Maria Millan, vice president for therapeutics, will take over on an interim basis while the agency's  board decides on a permanent successor.

The agency is entering what will be the last three years of its life unless it can round up additional funding. It has relied almost entirely on money borrowed by the state (bonds) which is expected to run out by June 2020.

Mills' unexpected move triggered expressions of dismay and amazement. "Wow!" was the one-word, email remark from a Southern California scientist, who declined to be identified.

Jeanne Loring, head of the stem cell program at the Scripps Research Institute in La Jolla, said in an email,

"I don’t understand why Randy Mills would leave CIRM now, when the rebirth of CIRM that he initiated is beginning to succeed.  I would have expected him to follow through on his vision.  I’m disappointed."

Paul Knoepfler, a UC Davis stem cell researcher, said in an email,

"Overall CIRM has prospered under Mills’ leadership with important, concrete accomplishments during his tenure. The agency's current trajectory is also very positive. He deserves a lot of credit for the positive impact he has brought to CIRM in just three years. The timing of his departure probably isn’t ideal as CIRM looks to the future with some challenges such as the nature of future funding for the agency and three years is a short tenure, but just as Mills brought in a new, helpful vision, the next leader may likewise provide new ideas and energy to successfully tackle the next phase for CIRM. Who that new leader ends up being could make all the difference for CIRM’s future so it’s a crucial decision. I’ll be curious how the Board approaches this challenge, and I’m excited to see what develops."

Knoepfler also posted more of his thoughts in an item on his blog.

John M. Simpson, stem cell maven for Consumer Watchdog of Santa Monica, Ca., said,

"Dr. Mills made substantial contributions to the agency during his tenure, improving both efficiency of the grant making process and transparency of CIRM's operations. Given the uncertain future as CIRM's current funding winds down, it is not at all surprising that he has opted to move onto another opportunity.

"Significantly, unlike the departure of his predecessor Dr. Alan Trounson, this move does not appear to raise any  conflicts of interest."

Another scientist who could not be identified said Mills' departure could lead to the loss of others of the 46 agency employees.

On the media side, Ron Leuty of the San Francisco Business Times wrote a straightforward piece on Mills' departure. Alex Lash of Xconomy offered a lengthier take. He covered some of the history of the agency along with the status of some its current projects. The Sacramento Bee carried a freelance piece by yours truly as well.

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.)

Asterias and Capricor: Good News for California's Stem Cell Research Effort

Pat Furlong, CEO of Parent Project Muscular Dystrophy, spoke earlier 

this year about losing her two sons to Duchenne muscular dystrophy

California's $3 billion stem cell agency last week reported encouraging results from two of its clinical trials, news that came as the prestigious journal Nature was declaring that the state effort was in its "last stage."

The trials are being conducted by Capricor Therapeutics, Inc., of Beverly Hills, Ca., and Asterias Biotherapeutics, Inc., of Fremont, Ca. Both are publicly traded firms.

The news was reported by The Stem Cellar, the blog of the California Institute for Regenerative Medicine (CIRM), as the Oakland-based agency is formally known.

CIRM declared,

"Asterias Biotherapeutics continues to keep a steady pace and to hit the proper milestones in its race to develop a stem cell-based treatment for acute spinal cord injury."

The agency has pumped $20.7 million into the company's program, including $6.4 million when the research was being performed by Geron Corp. CIRM said that the latest data show that the treatment is safe and should continue with 10 million and 20 million cell doses with new trial participants. CIRM  blog author Todd Dubnicoff said,

"About a month ago, Asterias reported that six of the six participants who had received a 10 million cell dose – which is transplanted directly into the spinal cord at the site of injury – have shown improvement in arm, hand and finger function nine months after the treatment. These outcomes are better than what would be expected by spontaneous recovery often observed in patients without stem cell treatment. So, we’re hopeful for further good news later this year when Asterias expects to provide more safety and efficacy data on participants given the 10 million cell dose as well as the 20 million cell dose."

CIRM's Karen Ring reported on the good news from Capricor, which has received $23.2 million from CIRM, not all of it for Duchenne muscular dystrophy, however. The disease follows a devastating course and significantly reduces life expectancy. Ring wrote,

"The company reported positive results from their Phase I/II HOPE trial that’s testing the safety of their cardiosphere stem cell-based therapy called CAP-1002. The trial had 25 patients, 13 of which received the cells and 12 who received normal treatment. No serious adverse effects were observed suggesting that the treatment is 'generally safe' thus far."

Linda Marban, president of the company said that it plans to seek permission from the FDA to move into one of the agency's programs to expedite making the treatment available.

The announcements on the trial results came during a week when Nature, which reports only intermittently on CIRM, did something of an overview of the California research program. The Nature headlines said,

"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."

Capricor's stock closed at $3.12 Friday with a 52-week price range of $2.12 to $5.40. Asterias closed at $3.70 with a 52-week range of $2.30 to $5.80.

Below is an Asterias video on its research.

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.”

California Stem Cell Agency Plumps Its Program as It Eyes Need for More Funding

California's 12-year-old stem cell agency today launched a "statewide outreach tour" that is aimed "partly" at building support for pumping $5 billion more into the program which is nearing the end of its financial life.

The agency has billed the one-hour, public program in San Diego as a "patient advocate event." Reporter Bradley Fikes of the San Diego Union-Tribune discussed the event in an article this morning that was headlined:

"Should Californians give more money for stem cell research?"

In addition to being sponsored by the California Institute for Regenerative Medicine (CIRM),  as the agency is formally known, the event is backed by UC San Diego, which has received $177 million from the agency.

Fikes said the event is the first in a series that is "is partly meant as a way to persuade voters to further support the institute with more funding."

He continued,

"Jonathan Thomas, CIRM’s chairman, said the San Diego event and others like it in other parts of the state are meant to update patients and all Californians about how their money has been spent, and to hear from the public."

Robert Klein, the multimillionaire real estate investment banker who led the 2004 ballot campaign that created the $3 billion agency, said last month that he expects that a public opinion poll this fall will show strong support for adding $5 billion to the effort. It is scheduled to run out of cash for new awards in June 2020 and perhaps sooner.

The 2004 campaign cost $34 million. Klein has not publicly discussed his plans to raise money for the ballot effort.

The agency has yet to finance a commercially available stem cell therapy.

UC Irvine Stem Cell Blog: Troubling New Federal Law on Stem Cell Research

The stem cell blog at UC Irvine this week published a piece that warned that a new federal law aimed at speeding commercialization of stem cell therapies is worrisome and could lead to harm to patients and damage the entire field of research.

The April 10 article was written by Navied Akhtar, a Ph.D. candidate in the biomedical engineering department.

Akhtar's topic was the 21st Century Cures Act. He wrote that the law, signed by President Obama and which had a broad range of supporters,

"...utilitizes evidence from clinical experience to 'help to support the approval of a new indication for a drug approved under [accelerated approval]' and 'to help to support or satisfy post approval study requirements.' The only requirements written in for accelerated approval past a 'reasonable likelihood' that there will be clinical benefit, is that one or both of two requirements are met: (1) That the manufacturer conducts studies after accelerated approval to verify the predicted effect on mortality or other clinical benefit and (2) That the manufacturer submits copies of marketing materials for the drug during the preapproval period." 

Akhtar said that the law 

"will allow for what is effectively anecdotal evidence to be used as actual evidence to support the requirement for accelerated approval. Furthermore, the verbiage surrounding the term 'surrogate endpoint' is loose at best. The idea of a surrogate endpoint is to produce a clinically relevant point in which to be able to measure the efficacy and safety of a drug. In the Cures Act, the definition of what constitutes a surrogate endpoint is left rather open-ended. It reads as such: "The term ‘surrogate endpoint’ means a marker, such as a laboratory measurement, radiographic image, physical sign, or other measure, that is not itself a direct measurement of clinical benefit, and is known to predict clinical benefit and could be used to support traditional approval of a drug or biological product; or is reasonably likely to predict clinical benefit and could be used to support the accelerated approval of a drug or biological product.' It is worrisome to write that this endpoint can be a marker that is not a direct measurement of clinical benefit, but is known to predict clinical benefit. This leaves open a large workaround for accelerated approval of drugs that may have no business being approved."

Akhtar goes on to cite cases of drugs that ultimately proved harmful even after clearing the usual approval process. 

In the case of novel stem cell therapies, he argued, serious mishaps or death because of loose federal standards could endanger progress in the entire field. 

New Top Lawyer Likely Coming Soon to California's $3 Billion Stem Cell Agency

California's $3 billion stem cell agency appears set to announce a new general counsel, a key position that pays nearly $400,000 a year.

The agency has closed applications and has only one candidate to replace James Harrison, who has announced he will be leaving the agency's service at the end of June.

A job opening notice was posted last month seeking applicants for the position, which has an annual salary range of $208,483 to $384,537.

Harrison worked as outside contractor with the Oakland-based agency in an agreement that totalled $575,000 this fiscal year. The agency is expected to run out of funds for new awards in June 2020.

Harrison has been the top lawyer for the agency since its inception in 2004.

California's Unregulated Stem Cell Clinics: Will State Regulators Step In to Cure Abuses?

The state of California has laws regarding substandard and questionable medical care, and now questions are being raised about whether it should step in to deal with the unregulated stem cell clinics that appear to flourishing in the Golden State.

The concerns come as the Los Angeles Times reported during the weekend about an enterprise in La Jolla, StemGenex Medical Group, which describes itself as "the premiere leader in the United States for regenerative medicine." 

The Times' Pulitzer Prize-winning columnist Michael Hiltzik wrote about the case of Jim Durgeloh, 59, a construction contractor from Washington state, who was looking for a solution to his hip problems, as well as other cases. Durgeloh paid StemGenex $15,000 for a treatment.

Hiltzik interviewed Durgelogh who was in Southern California with his wife following treatment. Hiltzik wrote,

"They were preparing to fly home, infused with the hope communicated by the clinic staff, who 'seemed very optimistic,' Durgeloh told me.

"A lawsuit in San Diego federal court suggests that StemGenex may have given the Durgelohs nothing but hope. Three StemGenex patients — two with diabetes and one with lupus — say they were misled by the medical group’s marketing pitch to pay $14,900 each in 2015 and 2016 for therapies that have had no effect.

"The lawsuit, which seeks class-action status, claims that StemGenex has made its money by 'targeting the ill and the elderly' with 'false, fabricated and purposefully misleading' claims about patient satisfaction."

Hiltzik continued,

"StemGenex, in its reply to the ... lawsuit, asserts that the plaintiffs 'cannot prove' that its 'representations regarding the efficacy of its stem cell treatments are actually false.' The plaintiffs, it continues, 'do not cite to a single scientific study that disproves [StemGenex’s] advertised claims.'"

UC Davis stem cell scientist Paul Knoepfler wrote yesterday on his blog about Hiltzik's article. Knoepfler was the co-author of a 2016 study that attracted nationwide attention with the disclosure that 570 unregulated stem cell clinics exist in the United States. California leads the way with 113.

Knoepfler focused on Hiltzik's disclosure that one of the StemGenex physicians, Scott Sessions, was placed on three years probation last February involving treatments not related to StemGenex. Sessions was accused of negligence "related to cosmetic surgery and other procedures he performed on two patients at an unrelated facility in 2011 and 2013."

Knoepfler continued,

"Sessions photo was up on the Stemgenex website...and then suddenly it wasn’t. Hiltzik also mentions that Stemgenex has had other questionable information on its web site in the past.

"With California having the most stem cell clinics selling non-FDA approved interventions of any state I hope the state medical board here will wake up to the fact that it needs to give this arena more attention."

The state has wide-ranging authority to regulate physicians. A document on the state Department of Consumer Affairs web site says that physicians can be disciplined for such things as  "not using accepted, effective treatments or diagnostic procedures," "not referring a patient to a specialist when
appropriate" and "continuing to use a procedure that is unnecessary."

California's Alpha Stem Cell Clinics: A 21-Video Overview of the $40 Million Effort

The great mysteries and not-so-great mysteries of the stem cells and their likely applications are the subject of a host of videos drawn from a day-long meeting this month at the City of Hope in California.

The occasion for presentation of the clips on You Tube was a symposium on California's Alpha Clinic network, which is scheduled to expand from three to five sites this year. That will boost the state investment in the network to $40 million.

The March 23 session included discussion of the results of some of the research at the sites -- City of Hope, UC San Diego and UCLA/UC Irvine. Patients spoke as well, and there were discussions of the economic barriers involving commercialization of stem cell therapies.

Of particular interest was a nine-minute look at "stem cell therapy value and reimbursement considerations" by Jennifer Malin of United Healthcare.  That video is at the top of this item.

The Alpha network was initiated by California's $3 billion stem cell agency. Geoff Lomax, the agency's senior officer for strategic initiatives, presented an overview of the program. Below is a video of Bob Klein, the agency's former chairman, in which he indicates he will be backing a $5 billion bond measure to keep the agency going beyond 2020, when its funds run out.

Twenty-one videos are available. Here is a link to the agenda, which is useful as a guide to pick videos that are more likely to be relevant to a viewer's particular interests.

State Lawmaker Aims to End California Stem Cell Program, Calls It a 'Boondoggle'

State Sen. John Moorlach in video from his office

A California legislator has launched an effort to terminate the $3 billion California stem cell agency, which is already set to go out of business in about three years.

Republican state Sen. John Moorlach of Costa Mesa said in a video,

"It's time to shut this down....We as taxpayers need some protection. We need to stop the boondoggle."

Moorlach has authored a proposed constitutional amendment that has been referred to the Senate Health Committee. No hearing date has been set. The measure would strip from the state constitution the language that created the agency in 2004.

The proposal, SCA7, requires a two-thirds vote of both houses of the legislature and approval by a vote of the people. Given the Democratic dominance of the legislature, that makes the chances of enactment of SCA7 unlikely.

Nonetheless, Moorlach's effort reflects the sentiments of a certain segment of the public. It also provides ammunition for those seeking to fund the agency with another $5 billion, which would additionally be placed before voters, probably in November 2018.  It is useful for campaigns for such measures to be able to point to what they consider threats to science and medical progress.

Backers of a $5 billion bond measure are proposing it because the agency is slated to run out of cash for new research awards by June 2020.

Moorlach's office produced a short statement in support of elimination of the California Institute for Regenerative Medicine or CIRM as the agency is formally known. It said,

"California voters approved a ten year stem cell program that they thought would produce widespread cures and save thousands of lives. They were also promised revenue-producing intellectual property that would help the state financially. These remain empty promises.

"More than thirteen years after its passage, around $2 billion in funds have been dispersed and $1.2 billion has been spent on servicing the principal and interest of the debt . With a $1.6 billion dollar budget deficit and crumbling infrastructure, we need to stop the issuance of bonds on an ineffective and unaccountable agency. Scarce taxpayer funds could be of better use elsewhere."

Asked for a comment on the legislation, an agency spokesman, Kevin McCormack, said,

"We are aware of the bill and are monitoring it." 

Slim Coverage of California's Ambitious Alpha Stem Cell Clinic Network

CIRM chart showing jump in clinical trials at institutions
 currently in the Alpha Clinic Network

Last week California's soon-to-be $40 million Alpha stem cell clinic network drew attention from within the stem cell community but little notice in the media.

A symposium last Thursday at the City of Hope on the effort covered aspects of the effort ranging from its results to what patients had to say. As of this morning, only one story had surfaced.

Claudia Palma of the Pasadena Star-News wrote a piece that sketched out something of an overview, including quotes from John Zaia, the principal investigator for the Alpha clinic at the City of Hope. Other clinics are in place at UC San Diego and UCLA/UC Irvine.

The $3 billion, California stem cell agency initiated the program in 2014 and plans to add two more sites this year.

Capitol Weekly, an online news service focusing on state government, picked up the article from the symposium by the California Stem Cell Report on an effort to keep the agency going after it runs out of money in 2020.

Stem cell agency officials also appeared at the conference, including Geoff Lomax, senior officer for strategic initiatives, who laid out the Alpha Clinic program. His presentation highlighted the boost in number of stem cell trials at the three institutions plus

CIRM graphic on Alpha trials and range of afflictions

Fresh $5 Billion for California Stem Cell Research? Voter Poll Scheduled for This Fall

The man often called the father of the California stem cell agency today all but said he is set to launch an effort to pump an additional $5 billion in state funding into the research effort, which is scheduled to run out of cash in about three years. 

Robert Klein, a wealthy real estate investment banker, told a packed audience at the City of Hope in

Robert Klein at City of Hope today

the Los Angeles area that a public opinion poll would be taken next fall in California to gauge support for a new bond measure to support the agency. 

He said that California has the "opportunity and privilege" to "lift the human condition." Klein said,

 "A revolution is underway."

Klein managed the 2004 campaign that created the stem cell agency, and he oversaw the writing of the 10,000-word initiative that placed the agency's spending outside of the control of the legislature and governor. Klein spoke at a daylong symposium involving the state's soon-to-be $40 million, Alpha stem cell clinic network, which is scheduled to grow from three to five sites later this year. 

Researchers, business executives and patients praised the performance of the clinics which were initiated with support from the California Institute for Regenerative Medicine, as the Oakland-based agency is formally known.

Klein, who served as the agency's first chairman until 2011, praised its work. He also noted that California has 50 percent of the nation's biotech infrastructure. He said the state has an historic opportunity to carry the current stem cell research forward.

Klein did not say specifically he would organize a new campaign for a bond measure for the agency. But he was more specific about the voter poll this fall and was optimistic about the future of the research in California. He said,:

"This fall when the citizens of California are polled, I believe they will say (the agency's) results are encouraging."

The agency has yet to produce a stem cell therapy for widespread public use despite the expectations raised by Klein's campaign 12 years ago.

Klein did not say who would fund the poll or how campaign funds would be raised. However, he has an organization called Americans for Cures, which had its origins in the campaign of 2004. That ballot measure effort cost $34 million.

A new bond measure would likely be mounted in the 2018 November general election, which would improve the likelihood of approval plus help to provide timely financial continuity for the agency.

Alpha Clinic Session Streaming Live Today

The symposium on Thursday dealing with California's Alpha stem cell clinics will be available online or via a phone connection that day and also later on YouTube later.

Here is the information provided by the City of Hope, which is hosting the one-day event, on accessing the proceedings, which involves a $40 million effort by the California stem cell agency. You can find the agenda here for some idea on the timing of each segment and speakers.

Click the link below Thursday to join the webinar:

https://cityofhope.zoom.us/j/193680670

Or iPhone one-tap (US Toll): +14086380968,193680670# or +16465588656,193680670#

Or Telephone:

Dial: +1 408 638 0968 (US Toll) or +1 646 558 8656 (US Toll)

Webinar ID: 193 680 670

International numbers available: https://cityofhope.zoom.us/zoomconference?m=rHRfXr-NQJ9VHlWI_6V4iao8Z4JbxpqJ

The Gottlieb Effect: Dismantling of FDA Silos, Less Regulation of Stem Cells?

A California stem cell researcher is predicting a possible "roller-coaster ride" in the wake of the appointment of Scott Gottlieb as the new head of Food and Drug Administration(FDA). 

President Trump named Gottlieb to the post earlier this month. Gottlieb has said in the past that "less is more" in terms of regulation of stem cell research, according to UC Davis research Paul Knoepfler.

He wrote on his blog last week about the Gottlieb's views and what they could mean for stem cell research. Knoepfler reviewed some of Gottlieb's publications and speeches for the analysis, including a 2016 speech in Berkeley which contained "some pretty radical language."  Mentioned was dismantling silos within the FDA.

The California scientist said,

"The use of powerful words like 'dismantled' by Gottlieb last year, now bode for potentially highly disruptive changes at the FDA in the Trump administration under his leadership. Since he stated that regenerative medicine products 'don’t easily fall into FDA’s current buckets,' I wonder what the could mean for CBER (a branch of the FDA).

"I’m hoping that Gottlieb will rightly see the central distinction between empowering more efficient stem cell and regenerative medicine product development by good actors in the field (he could do this, for example, by shaping how the 21st Century Cures Act regenerative medicine-related directives are implemented) versus enabling many dubious actors at a host of for-profit businesses. These companies don’t do preclinical studies, don’t respect the FDA, and put patients at risk."

Knoepfler covered additional ground in his March 14 piece, which may be the only serious, current analysis of Gottlieb and stem cells. Knoepfler concluded:

"Change at the FDA overall or on stem cells isn’t necessarily a bad thing, but in this case it could be a roller-coaster ride."

California Stem Cell Agency Says Its Top Lawyer Is Departing After More Than 12 years

James Harrison, Remcho photo

The $3 billion California stem cell agency today said it is losing one of its top leaders, James Harrison, one of the authors of the measure that created the agency and who most recently is serving as its “unflappable” general counsel.

The agency announced this afternoon that Harrison would be departing at end of June “to focus full-time on his legal practice.”

Harrison has worked with the agency under contract since its inception in 2004. He was known for his exceptional legal skills and aplomb when matters became muddled or worse at meetings of the agency’s 29-member board.

Randy Mills, president of the agency, said in a press release,

“James is more than wise counsel at CIRM, he has also been a highly effective leader, responsible for designing and implementing many of CIRM 2.0’s more innovative features.

“He is unflappable and maintains a sense of humor and perspective, even in the most challenging of situations. We thank him for his many years of service and wish him the very best.”

Harrison was one of five persons who drafted Proposition 71, the ballot initiative that created the California Institute for Regenerative Medicine or CIRM as the agency is formally known. He is a partner in the Oakland law firm of Remcho, Johansen and Purcell, which also has an office in Sacramento. The firm specializes in political, election, ethics, constitutional and public policy law.

Harrison was known for his work on ballot measures well before he became involved in the Proposition 71 campaign, He also has worked in election law and campaign finance.

Harrison never was formally classified as an employee of the stem cell agency. His services came under a contract with his law firm. For the current fiscal year, that contract amounts to $575,000.

A 2009 memo to the stem cell agency board recounted Harrison’s value to CIRM, ranging from defending its constitutionality to its public records policy. The memo, prepared at the behest of Bob Klein, the agency’s first chairman, said that Harrison had been “has been involved in virtually every aspect of the agency’s operations, including defending the agency in litigation, drafting and reviewing agency policies, advising the agency on conflict of interest issues, and interfacing with constitutional officers and legislators on matters ranging from financing to proposed legislation.”

Mills said that Scott Tocher, deputy general counsel for the agency, will work closely with Harrison to ensure continuity during a transition period. Tocher is also a longtime veteran of CIRM affairs, joining the agency in 2005.

A "Blind" Warning to Patients: Beware Unproven, Unregulated Stem Cell Treatments

“Disastrous” is how the New York Times this week described an ostensible stem cell treatment in Florida that left three older women blind or nearly blind. "Chilling reading" said the $3 billion California stem cell agency.

If you haven’t read about the matter yet, it is worth some attention. Denise Grady of the New York Times wrote,

“The cases expose gaps in the ability of government health agencies to protect consumers from unproven treatments offered by entrepreneurs who promote the supposed healing power of stem cells.”

Her article was based on a report in the New England Journal of Medicine that dug into the medicial and scientific details.

The matter involves loosely or non-regulated stem cell treatments in clinics that have shot up around the country, Paul Knoepfler, a stem cell research at UC Davis, and Leigh Turner, a bioethicist at the University of Minnesota, reported last year that at least 570 exist around in the country, with the most in California.

Kevin McCormack, director of communications at California's stem cell agency, wrote about the Florida matter on the agency's blog, He said,

"The report makes for chilling reading."

McCormack said it is a "warning to all patients about the dangers of getting unproven, unapproved stem cell therapies."

Knoepfler wrote on his blog,

“Is this just the tip of the iceberg for negative stem cell clinic outcomes given that there are around 600 such clinics in the US today largely operating generally without FDA approvals, lacking preclinical data to support what they are doing, and experimenting on thousands of patients for profit? 

“Where was the FDA in all of this and are they doing anything about it now?”

Knoepfler continued,

“The clinicaltrials.gov website remains a great, but also very problematic resource. Many patients seem to view anything listed on there as a legitimate, NIH-approved full-blown clinical trial and some clinics encourage that view, but that’s clearly not the case. I interviewed the leader of clinicaltrials.gov in 2014 and problems were already apparent to me back then from that discussion. Clinicaltrials.gov needs to provide patients with much more information (e.g. IND status, fee as inclusion criteria, etc.) and consider excluding certain listings.”While it is quite possible that it lacks the budget, the flexibility, and/or the authority to make such changes quickly, a lot is at stake. They need to make changes ASAP.”

California's Alpha Clinics: A Unique, Stem Cell 'Clincher' for Patients, Doctors and Researchers

California's $3 billion stem cell agency this week explored the status of its ambitious Alpha Clinic network, touting its impact and progress over the last two years involving hundreds of patients.

The network, which now has bases only in Southern California, is slated to add two more this year in what will be a $40 million investment by the state of California. It is likely to be a major part of the legacy of the California Institute of Regenerative Medicine or CIRM, as the Oakland-based stem cell agency is formally known. The agency runs out of cash for new awards in 2020.

Geoff Lomax, senior officer for CIRM's strategic initiatives, yesterday wrote about the Alpha network in an item on the agency's blog, The Stem Cellar.

He noted the state’s position as a world leader in stem cell research, helped mightily by the efforts of the 12-year-old agency. He wrote,

“But the real clincher is that California has something that no one else has: a network of medical centers dedicated to stem cell-based clinical trials for patients.”

Lomax, who was one of the first employees at the agency in 2005, said,

“So far, hundreds of patients have been treated at our Alpha Clinics. These top-notch medical centers use CIRM-funding to build teams specialized in overseeing stem cell trials. These teams include patient navigators who provided in-depth information about clinical trials to prospective patients and support them during their treatment. They also include pharmacists who work with patients’ cells or manufactured stem cell-products before the therapies are given to patients. And lastly, let’s not forget the doctors and nurses that are specially trained in the delivery of stem cell therapies to patients.

“The Alpha Clinics Network also offers resources and tools for clinical trial sponsors, the people responsible for conducting the trials. These include patient education and recruitment tools and access to over 20 million patients in California to support successful recruitment. And because the different clinical trial sites are in the same network, sponsors can benefit from sharing the same approval measures for a single trial at multiple sites….

“This collective expertise has resulted in a 3-fold (from 12 to 36 – two trials are being conducted at two sites) increase in the number of stem cell clinical trials at the Alpha Clinic sites since the Network’s inception.”

The agency is seeking applications to open two more Alpha Clinics this year, funding them with $8 million each. One of the criteria is geographic diversity. The application deadline is May 15.

In just 13 days, folks interested in Alpha Clinics can take part in a one-day symposium at the City of Hope in the Los Angeles area, which is one of the current Alpha sites. Advance registration is requested for the free event.

The other Alpha sites are at UC San Diego and UCLA/UC Irvine.

California Award Recipient: 'Promising' Results from Chinese Stem Cell Trial for Knee Arthritis

Cellular Biomed has a four-year U.S. history

A Chinese biomedical firm that popped up last month with an award from the $3 billion California stem cell agency is working with the University of Southern California and Children's Hospital in Los Angeles to ready an arthritis therapy for a clinical trial in the United States.

The publicly traded enterprise is Cellular Biomedicine Group, Inc., which has an office in Cupertino, Ca., as well as China. It was awarded $2.3 million from the California Institute for Regenerative Medicine or CIRM, as the state stem cell agency is formally known.

The company said in a press release that the therapy, known as AlloJoin, is already in a phase one clinical trial in China where it is showing "promising interim 3-month safety data." The company described the therapy as an “off-the-shelf, allogeneic, human adipose-derived, mesenchymal stem cell" treatment.

Qing Liu-Michael, USC photo

Thomas Vangsness, USC photo

The company said it is working with C. Thomas Vangsness, Jr., at the Keck School of Medicine at USC, and Qing Liu-Michael of the Broad Center for Regenerative Medicine, also at USC. Vangsness will be principal investigator on the company's phase one U.S. trial.


The company said the CIRM grant is the first step in bringing its arthritis treatment to the United States. It is also contributing $572,993 to the work  being funded by the state agency.

In an interview last week with Javier Hasse of Benzinga, an online financial information site, Tony Liu, chief executive officer of Cellular, said his company is also working on  immune cell therapies involving cancer. He said his company's focus is on China because of the size of the market.

Liu said,

"In China, 57 million people have a knee issue; in the U.S., 27 million [people] have a knee issue. Stem cells can help knees regenerate by doing two things. First, by helping with the pain, providing symptom relief and functional improvements. Secondly, they regenerate the cartilage, which originally caused the knee problem. Nowadays, patients can only opt between pain pills or a knee replacement.

Today, if you do a knee replacement, you are looking at tens of thousands [of dollars]. So, any way you look at it, [it’s a] multi-billion [market] for knee treatments."

Liu continued,

“Our management team was educated in the U.S., and has experience managing large businesses.... “Our chief scientific officer is a former MedImmune/AstraZeneca plc (ADR) (NYSE: AZN) director. Some of our oncology scientists are from there as well. We also have scientists from the National Cancer Institute. We also have a person who is leading our manufacturing capabilities who worked for Harvard for 30 years and a top German company, leading research for seven years total.”

“So, we have this kind of people with skills come to China. Our company has 130 people with PhDs, and more than 30 with post-doctorate studies, so there is a lot of brain power, I believe, and we have a  common vision that is to create the best, first in class, biotech business in China.”

As for the company's finances, Liu said,

"CBMG’s stock is really thinly traded. Much of the stock is owned by those who have been with the company for a long time; so, they don’t sell. Having said this, there are many reasons that drive stocks: the U.S. election, the pricing discussion… Many investors don’t discriminate, and just punish biotech as a whole. However, CBMG is not really subject to most of these pricing pressures. In fact, because we have a different cost structure, I expect CBMG to do extremely well." 

'Pressure testing' a $150 Million California Plan to Lure Business into Development of Stem Cell Therapies

The California stem cell agency's far-reaching plan to crate a $150 million, public-private partnership to speed development of stem cell therapies remains on hold as the agency looks for ways to lure in private enterprises.

In an interview last week with the California Stem Cell Report, Randy Mills, president of the $3 billion agency, said he had nothing fresh to report on the project, which did not draw any eligible applicants last fall.

Mills said his team is "pressure testing (the project) to make sure people really understand the terms."

In December, Mills said that the firms that responded to the request for applications in October were seeking to make a "better deal" than the agency had offered. Under the proposal, a new company would be created to develop therapies. It would be backed by a $75 million state loan (discounted to 50 percent payback)  with a matching $75 million coming from a successful applicant. The company would have the pick of agency research that did not already have a commercial partner.

Mills said that the unusual nature of the proposal posed challenges for the company and the agency.

In the interview last week, Mills said the agency is seeking to determine if having more time to prepare proposals will trigger more applications. Another factor is whether the terms do not meet the needs of potential applicants.

California Popping for $40 Million for its Alpha Clinic Stem Cell Centers

CIRM video

California this year expects to add two new Alpha stem cell clinics to the three already in Southern California, boosting its investment in the effort to as much as $40 million.

The move came last Thursday when directors of the state's $3 billion stem cell agency approved seeking additional Alpha Clinic applications this spring. The purpose of the clinics is to accelerate development of stem cell therapies, a key goal of Proposition 71, the ballot measure that created the California Institute for Regenerative Medicine or CIRM as the Oakland-based program is known.

Expansion of the program could also mean that an Alpha site may be located somewhere in Northern California by the end of this year. One of the objectives of the latest proposal is to broaden the "geographic reach" of the Alpha network.

According to CIRM, the existing Alpha clinics already have 33 clinical trials underway for 12 different afflictions. Randy Mills, president of the agency, said in an interview Friday with the California Stem Cell Report that the clinics doubled the number of stem cell trials that they had prior to launching their CIRM Alpha programs. Many of those trials do not require agency funding, which allows the cash to be used elsewhere.

Maria Millan, CIRM's vice president for therapeutics, told CIRM directors last week,

"Once we built it, they did come."

The latest expansion is aimed at increasing capacity and access to stem cell trials, training physician/scientists in clinical trials and bringing additional assets to California's Alpha clinic network, which is also positioned to help establish the state as the global leader in stem cell treatment.

The request for applications, with a deadline of May 15, will also require that the clinics -- whether non-profit or for-profit -- create a "sustainability plan," which will keep them operating after the CIRM funding terminates in four years. The agency itself expects to run out of cash for any new awards even sooner -- June 2020.

CIRM is offering to provide two winners in the Alpha round $8 million each over a four-year period with milestones required to keep the cash flowing.

During Friday's interview, Mills said that applicants from Northern California will need to make a case for the "added value" that they will bring to their proposals and demonstrate that their populations are underserved. Additional applications are likely to come in from Southern California, which has the bulk of the state's population and patients.

The current Alpha Clinics are located at the City of Hope in Duarte, which is in the Los Angeles area, UC San Diego and UCLA/UC Irvine.

A symposium on Alpha Clinics is scheduled for March 23 at the City of Hope. Advance registration is requested.  

City of Hope video

Correction

An item yesterday on the meeting of the governing board of the stem cell agency incorrectly stated that the board approved $37 million in awards. The correct figure is about $33 million.