California Stem Cell Agency: $20 Million Cancer Award from 2012 Bears Clinical Trial Fruit

California's stem cell agency this week took the relatively unusual step of a firing off a double-barreled salute to the beginning of one of its clinical trials -- a $20 million effort based out of UCLA.

Antoni Ribas, UCLA photo

The press release and blog item heralded research by Antoni Ribas, who received the award in 2012 from the California Institute for Regenerative Medicine (CIRM), as the agency is formally known.

The potential treatment deals with the spread of cancer to other
parts of the body, which the agency said is responsible for 90 percent of cancer deaths. Ribas' trial will test a stem cell-based treatment that is better at tracking down and destroying hard-to-treat cancer stem cells. In a news release from UCLA, which is also funding the research, Ribas said,

"(F)ew options exist for the treatment of patients whose cancers have metastasized due to resistance to current therapies. This clinical trial will allow us to try a new approach that engineers the body’s immune system to fight metastasized tumors similar to how it fights germs and viruses.”

Siwen Hu-Lieskovan,
co-investigator, UCLA photo

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

“Backed by rigorous science, the stem cell derived T cell immunotherapy being developed by Dr. Ribas and his team has the potential to address advanced cancers that have spread beyond the primary tumor and which are associated with very low survival.

"This trial is the first step in developing a therapy that could alleviate the complications resulting from cancer metastases as well as potentially improving outcomes in cancer patients where there are currently no effective treatment options. We are confident that CIRM’s funding and partnership, in combination with the expertise provided by our Alpha Stem Cell Clinic network, will give provide critical support for the successful conduct of this important clinical trial.”

The $3 billion stem cell agency is actively supporting 33 clinical trials (five involving cancer), which are the last stage prior to approval of a therapy for widespread use. Why the CIRM salute in this case?  The blog item by Todd Dubnicoff said,

"The reality is this: the launch of a clinical trial isn’t a beginning. It represents many years of effort by many researchers and a lot of funding to take an idea and develop it into a tangible product that has been given clearance to be tested in people to potentially save their lives. That’s why this important milestone deserves to be recognized.

More information on the award (DR2A-05309) can be found here. Persons interested in participating in the trial can contact Clinical Research Coordinator Justin Tran by email at justintran@mednet.ucla.edu or by phone at 310-206-2090.

Curtailing Research Awards and Other End-of-Life Matters at California Stem Cell Agency

If you are interested in whether the $3 billion California stem cell agency is going to live or die, you may want to check in on a meeting one week from today.

A new committee of the agency's directors that was formed to deal with transition issues is scheduled to meet for three hours next Monday to consider various scenarios and how the agency might deal with them.

The impetus for the meeting is a projection that it will run out of cash for new awards in mid 2020 with no funding  in realistic sight.

One of the possibilities for extending the life of the agency is to curtail its award programs, which could possibly give the agency another one or two years of existence. The California Institute for Regenerative Medicine, as the agency is formally known, has roughly $650 million left but has been taking on clinical trials, some of which have been running $20 million a pop.

The session will be based out of the agency's headquarters, but teleconference locations are listed in Los Angeles, Duarte and La Jolla. The public can ask questions or make statements from those locations in addition to the main site in Oakland. Listen-only access is also available on the Internet. Full instructions and addresses can be found on the meeting agenda.

San Francisco Business Times: Can Clinical Trials Save California's Stem Cell Agency?

Tippi McKenzie on front page of San Francisco Business Times

Long, difficult and expensive -- that's how the San Francisco Business Times describes stem cell therapy development in an article about the 33 clinical trials currently backed by the $3 billion California stem cell agency.

Will it all prove to be worthwhile? Reporter Ron Leuty addressed the matter in an Aug. 25, front-page piece that featured Tippi McKenzie of UC San Francisco. She recently received a $10.9 million award from the California Institute of Regenerative Medicine (CIRM), as the agency is formally known, to test her possible therapy on 10 pregnant women.

In what will be the first clinical trial of an in-utero blood stem cell transplant, McKenzie will transplant a mother's own stem cells into her fetus. Leuty wrote that it could be a precursor to pre-birth cures for other blood diseases, such as sickle cell disease.  He continued,

"It’s also the sort of high-profile medical breakthrough that could give the state stem cell funding research agency momentum as it prepares to (possibly) seek billions in fresh money to extend its life beyond 2020."

Leuty wrote,

"Still, any potential treatments are years into the future. Are trials such as MacKenzie’s too little, too late to help CIRM? "  

"It’s all an illustration of the long, difficult and expensive path for bringing any drug to market. Only four of every 10 late-stage trials succeed, according to a 2016 Biotechnology Innovation Organization study of clinical trials from 2006 to 2015. As a relatively new field, in which regulators and companies are seeking a new pathway to Food and Drug Administration approval, stem cell therapies take eight years to translate into clinical trials; non-stem cell therapies take 3.2 years, according to CIRM Chairman Jonathan Thomas. That’s a potentially awkward narrative as efforts ramp up to keep CIRM alive longer. "

Leuty said,

"CIRM can point to 33 projects that have reached clinical trials. For example, an $11.9 million grant to UCSF and St. Jude Children’s Research Hospital is paying for a mid-stage study in 'bubble boy disease.' The agency wants to fund another 40 clinical trials over the next four years, and it is pitching that scale and scope as a reason to keep CIRM going."

The article continued,

 "If anyone has a chance of showing CIRM’s value, it may be MacKenzie, an associate professor of surgery at UCSF’s pediatric surgery unit and head of its Fetal Treatment Center. Her lab since 2010 has been awarded $14.9 million in grants, including cash for basic research, translational research and now in the clinic. 

"CIRM is about more than funding for studies, MacKenzie said. Agency staff has provided advice about how to translate animal studies into work in humans, she said, as well as hiring an FDA consultant, writing an investigational new drug application and setting up a clinical protocol. 'I’m a clinician, but running a clinical trial is different,' MacKenzie said. 'CIRM’s been incredibly helpful in helping me navigate that.'"

The Dual Images of Stem Cell Medicine Highlighted in the Headlines

Google news stem cell headlines this week

A couple of notable headlines surfaced this week dealing with stem cell matters, capturing something of the dichotomy in a field that has been heralded for its possible production of miracle cures. 

One story told of a person who plays football for a living, Doug Baldwin, who is known as the $46 million man.  He decided to spend some time in England this summer receiving what he believes was a stem cell treatment to prevent his knees from deteriorating. It was the type of story that gives many others hope that some sort of stem cell therapy could cure a serious or fatal condition despite the fact that no such cure has been approved for widespread use in this country. 

The other story told of a modest crackdown by the Food and Drug Administration (FDA) on a couple of unregulated stem cell clinics in this country, a move that many believe was long overdue. More than 500 such clinics exist in the United States.  One of the California clinics identified by the FDA was using a restricted small pox vaccine as part of its treatment. 

Your average health care consumer could justifiably wonder, "What in the world is going on? Is this stuff safe or what?" Some scientists have been long frustrated by the dueling public faces of stem cell medicine. On one hand, stories of miracle cures involving professional athletes generate great attention and tend to create faith in the efficacy of stem cell treatments, although the therapies involved do not measure up to scientific standards. On the other hand, the FDA is now taking a more active role in policing dubious actors in this business.

Our average medical consumer might believe that the FDA action signals a new assurance of stem cell safety or is it the other way around? Is the stem cell glass half full or half empty?

Paul Knoepfler, a stem cell researcher at UC Davis, has been the bellwether for seven years regarding news about unregulated and dubious stem cell clinics. He once even went sort of undercover to attend a public marketing session produced by one clinic in the Sacramento area. 

Knoepfler wrote this week on his blog about the FDA action, its implications and the questions that remain. He said the FDA action was a "very big deal." 

But Knoepfler said six important questions remain:

• "How much further will the FDA go with actual enforcement actions?
• "Will the FDA define fat stem cells as a drug (or not) in upcoming guidances?
• "How will the FDA handle non-homologous use of bone marrow cells in the commercial sector?
• "Will the FDA work to deal with the growing problem of unapproved, amniotic stem cell offerings? 
• "What about networks of stem cell businesses?
• "Will other entities like state medical boards use this FDA action as a spring-board to get off the sidelines and take positive action too?"

Meantime, patients will continue to have to wade through conflicting claims, hype and the possibility of serious medical harm or death as they ponder whether they should undergo a stem cell treatment. 

Calimmune's HIV Clinical Trial and the California Stem Cell Agency: Decisions Looming on the State-backed Research

The HIV clinical trial involving Calimmune and the California stem cell agency appears to be headed today for several major decision points following the purchase of the company in a deal that could total more than $400 million. 

CSL Behring announced yesterday that it was acquiring the company. One published report said that CSL was not interested in the Calimmune HIV research, which has been funded with $8.3 million by the California Institute for Regenerative Medicine (CIRM), as the agency is formally known. 

Responding to a query from the California Stem Cell Report, Natalie deVane, a spokeswoman for CSL, said today, 

"Our only comment regarding (the trial) was the following – 'We are currently evaluating our options for developing this pipeline candidate, which could include licensing or partnering. Given our areas of focus, it is unlikely that we will develop this candidate on our own.'

"We made no comments regarding timing, and at this point is would be premature to comment further."

Asked for a comment, Kevin McCormack, a CIRM spokesman said yesterday,

"Calimmune plans to complete the clinical trial that CIRM is funding, and CIRM has every intention of continuing the partnership with Calimmune in funding this essential research. Based on the findings of the trial, Calimmune hopes to make a decision as to whether or not it is feasible to move ahead with the next phase of this work."

The trial is scheduled to be completed in October.

$400 Million Deal Leaves California-backed HIV Trial Hanging

A California-financed clinical trial testing a promising stem cell therapy for HIV is up in the air this morning following the purchase of its California backer by an Australian corporation in what could be a more than $400 million deal.

The firm being acquired is Calimmune, which has an $8.3 million award from the California Institute of Regenerative Medicine (CIRM), as the state stem cell agency is formally known. 

CSL Behring announced this morning that it is buying Calimmune for $91 million and as much as $325 million more depending on whether its research meets success milestones. 

However, CSL is not interested in the early phase Calimmune trial, which began in 2013 and was scheduled to be completed by this October. John Carroll, writing on the Endpoint News web site, reported this morning, 

"CSL, though, plans to let go of control of Calimmune’s lead, clinical program on HIV as soon as possible. In a follow-up to a query, a company spokesperson replied:
'We are currently evaluating our options for developing this pipeline candidate, which could include licensing or partnering. Given our areas of focus, it is unlikely that we will develop this candidate on our own.'"

The California stem cell agency had no immediate comment on the potential impact of the deal. In response to a query this morning, Ronald Mitsuyasyu of UCLA, listed by the NIH as the principal investigator, said he had no comment.

The latest CIRM progress report on the research indicated that the trial had been advancing. A notice on the NIH clinical trials web site said, however, that it is no longer recruiting patients. The CIRM progress report said,

"The objective of the Cal-1 therapy is to increase the number of protected cells in the body of an individual infected with HIV to the point where the virus is incapable of causing harm. This would potentially reduce or eliminate the need for a lifetime of antiretroviral therapy."

Calimmune was co-founded by David Baltimore, a Nobel Prize winner and former member of the governing board of the state stem cell agency.

California Stem Cell Agency's First Royalty Payment: Beginning of a $1 Billion Flood? No One is Saying

The check is in the mail for California's $3 billion stem cell research effort. But it is something of a secret.

So reports Ron Leuty of the San Francisco Business Times concerning the expectation that the agency, formally known as the California Institute for Regenerative Medicine (CIRM), would generate $1 billion in royalties. In an article online yesterday afternoon, Leuty said,

"We are expecting the first check to be delivered to the state very soon," CIRM spokesman Kevin McCormack said in an email.

"Yet even as a public state agency, CIRM officials are holding tight to key information about the first royalty check: How large (or small) is the check? When will the check actually be forwarded to the general fund? And from which CIRM-funded project did it spring?

"'The royalty check is something that is still being worked out so it’s premature to say anything at the moment,' McCormack said in a followup email. 'Sorry to sound so secretive but it is a big deal, the first of what we hope will be many such repayments for the state’s investment.'"

During the ballot initiative campaign that led voters in 2004 to create the stem cell agency, supporters said that the agency's research could generate up to $1.1 billion in royalties. None have yet surfaced. And at least one description of the royalty promise has called it a "cynical ruse."

California Stem Cell Agency Pushes $23 Million into Clinical Trials for Leukemia, Bone Marrow Transplants

California's 12-year-old stem cell research program this morning popped for $23 million to help finance clinical trials to "confuse and kill" leukemia cells and to develop a better alternative to bone marrow transplants.

The two awards are part of the stem cell agency's effort to produce a widely available stem cell therapy before its money for new awards runs out in less than three years. So far, the agency, known formally as the California Institute for Regenerative Medicine (CIRM), has not been successful in producing such a therapy.

CIRM has now funded 35 clinical trials, which are the final stage of testing before a therapy is approved by the federal government for widespread use.  Thirty-one of the trials are still active.

Today's largest award, $18.3 million, will go to Thomas Kipps of UC San Diego. An additional Oncternal Therapeutics, also of San Diego.  Kipps is a scientific advisor to the firm. The other award, $5 million,  goes to Angiocrine Bioscience, Inc., of San Diego. The company will add $2.7 million to the effort.

Thomas Kipps, Oncternal photo

$13.3 million will be provided by

The Kipps project targets the most common form of lymphoma, chronic lymphocytic leukemia (CLL) the agency said in a news release. The agency said Kipps is "using a combination strategy to kill the cancer stem cells that help CLL – and other cancers – survive traditional therapies, such as chemotherapy, and cause a relapse."

Every year, about 20,000 people nationwide are diagnosed with CLL.

The Angiocrine research is aimed at increasing the supply of cord blood for bone marrow transplants, when no matched donor is available.  Its product is called AB-110.

Maria Millan, interim CEO of the stem cell agency, said,

 "This (Phase 1) clinical trial will be the first step in determining if AB-110 is able to provide a way to improve the results of cord blood transplants."

Today's award appears to advance work previously funded by CIRM at a cost of $4 million.  Paul Finnegan was listed as the principal investigator on that work.

Angiocrine's key technology  is licensed from Weill Cornell Medical College and was invented and developed by Shahin Rafii.

The awards were approved in less than 10 minutes this morning with no discussion by the CIRM governing board, which simply ratifies the decisions of its out-of-state, grant reviewers, who considered the applications in July behind closed doors.

A summary of the reviewers' comments can be found here for Kipps' application, CLIN2 -101, and here for Angiocrine's, CLIN2-10386. Information on the Kipps trial can be found here on clinicaltrials.gov. Catriona Jamieson of UC San Diego is listed as the principal investigator on the Kipps' award.

The Angiocrine trial was not yet listed on clinicaltrials.gov at the time of this writing.

$185 Million California Rumpus over Researcher Raiding

To some outside the California scientific and academic community, it might seem like a cat fight replete with allegations of  a "law-of-the-jungle mindset," loyalty oaths, "petty academic politics" and -- literally -- paper clip theft.

All of which is mentioned in court filings in the squabble, if you want to call it that. But this is not minor stuff. It involves a $185 million, 2015 lawsuit by the University of California (UC) against the University of Southern California (USC), a private school in Los Angeles. Basically, UC wants the money from USC because UC thinks one of its high-powered scientists was hijacked by USC.

Some of the details emerged today in the Los Angeles Times, which wrote about the case in connection with the Carmen Puliafito affair. He is the former dean of the USC school of medicine as well as being a member of the governing board of the $3 billion California stem cell agency, a position he no longer holds.

The headline on the story said,

"USC dean drug scandal could take costly toll on school's legal battle with UC system"

Puliafito was dean of the medical school when it hired away from UC San Diego a star Alzheimer's disease researcher, Paul Aisen, who had the potential of bringing $340 million in research grants to USC. In addition to the prestige of having Aisen on campus, the school would receive a significant percentage of the grants as part of overhead costs.

The Times reported that during Puliafito's eight years at USC, he spearheaded an effort that lured more than 70 "transformative faculty" from UC schools, Stanford, Harvard and other prestigious rivals.

One was USC's longtime athletic rival, UCLA. According to the Times, the successful wooing of Arthur Toga and Paul Thompson, two well-funded neurology researchers, in 2013 "outraged" UCLA, which complained to federal regulators.

The Times wrote,

"It was not unusual for professors to move to other institutions, often with the first university cooperating in the transfer of grant funding to the new school. But in UC’s view, USC had acted beyond accepted norms by targeting academics based on grant funding and strategizing secretly with those researchers while they were still employed by UC about moving grants to USC. The schools reached a confidential settlement requiring USC to pay UCLA more than $2 million, according to a copy of the agreement obtained through a public records request."

The lawsuit is now in San Diego Superior Court. No trial date has been set.

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. 

Crossing the Two Million Mark: A Dozen Years of Readership on the California Stem Cell Report

Google's page view count for the California Stem Cell
Report as of 11:01 a.m. today 

The California Stem Cell Report this morning hit a readership milestone -- two million page views.

The count was recorded only about 18 months after chalking up one million page views, a number that took 10 years to reach. The blog began publication in January 2005, just as the Golden State's stem cell agency was getting underway. Since then 4,492 items have appeared. 

For those not familiar with Internet terms, a page view is recorded by Google each time a person opens his or her Internet browser on a particular page. It is an industry standard that it is used to help define readership, something akin to circulation numbers for newspaper.

The California Stem Cell Report (CSCR) is somewhat unique. It is the only independent web site devoted to the $3 billion ($6 billion if you count interest costs) California Institute for Regenerative Medicine (CIRM), as the agency is formally known. The report was created to dig deeply into the agency, focusing largely on public policy and economic issues and recording the agency's activities.

David Jensen, Mazatlan, Mexico

The blog is published and written by David Jensen, a retired editor and journalist who spent most of his career at The Sacramento Bee, but who also worked seven years for United Press International and two years as a press aide to Gov. Jerry Brown (1974-76). Over the last 12 years, Jensen has covered the agency while living on a sailboat as it navigated the west coasts of Mexico and Central America. He traveled back to California from time to time for meetings of the agency and interviews with its leaders.

As reported in 2015, the one-million figure then and the two-million figure now are both large and small. The figures are picayune compared to the readership for major news sites. But they are relatively large given the size of the potential audience.

The report's long-time estimate has been that only about 3,000 to 4,000 persons worldwide are deeply interested in stem cell matters. When Randy Mills, former president of the stem cell agency, heard the estimate last year, he said he thought the number was even less. 

The readership for the blog is mostly found in the United States, according to Google's statistics. But a significant component comes from Europe as well. Readers range from individuals seeking information about stem cell therapies to folks at such places as the National Institutes of Health, major research institutions in California and elsewhere including Harvard, Cedars-Sinai, Sanford-Burnham, Stanford, UC San Francisco, UC Irvine. 

The most highly read article during the past 12 years deals with the cost of a stem cell therapy. It has had 23,498 page views, far beyond the second best-read piece that counted 2,754 page views. Presumably the "cost" piece drew considerable attention from persons considering a stem cell treatment. The No. 2 article dealt with a call by the state controller for online posting of the economic interests of members of the CIRM governing board.

The blog has also served as a starting point or helpful reference for many journalists looking into the agency and has been described as "indispensable" by Los Angeles Times columnist Michael Hiltzik. 

The blog began shortly after the passage of the 2004 ballot initiative that created the agency and provided the bond funding for the program. CIRM is unique in California history and is one of the largest, if not the largest, single source in the world of funding for stem cell research, especially involving human embryonic stem cells. CIRM has had a major impact on stem cell science in California and has helped to sustain research interest in the field at a time when others were wary of involvement.

Its birth was unusual, probably the only scientific research effort ever triggered by the use of petitions signed by more than one million voters and then placed on the ballot for further voter approval. It additionally represents a rare confluence of big science, big business, big academia, big government, big politics, religion, morality and life and death. 

The blog itself is financed personally by Jensen, who has no financial ties to biotech, academia or industry or the agency. Google does place ads on the site, which generate about $150 every six months or so based on the number of people who click on an ad. A crowd funding pitch awhile back was unsuccessful. However, the blog does spin off occasional freelance pieces to The Sacramento Bee and Capitol Weekly. 

The Demise of California's Stem Cell Agency: Gone in Three Years or Perhaps Some Other Date?

The $3 billion California stem cell agency goes out of business in less than three years: True or false?

For those of you seeking certainty, the "definite" answer is maybe. The agency has been saying for a couple of years now that it will run out of funds for new awards by roughly the middle of 2020. However, prior to that estimate, the death knell for the research program was forecast for much earlier. In fact, it would have come this year, 2017.

The difference is the result of different projections at different times by different leadership of the California Institute for Regenerative Medicine (CIRM), as the Oakland-based agency is formally known. When Alan Trounson, an internationally known scientist, was president of CIRM, it produced  the 2017 figure. When Randy Mills, a longtime biotech business executive, took over three years ago, he redid the estimate and came up with 2020.

The difference is based on assumptions. And they involve the "burn rate" of CIRM's cash. With the support of the board, Mills reduced the rate at which money would be awarded thus extending its effective life.

Steve Juelsgaard, Iowa State photo

CIRM board member Steve Juelsgaard, a former top executive with Genentech, in June briefly highlighted the vagaries of CIRM's possible demise. According to the transcript of the board meeting, he told CIRM directors:

"So there are ultimately three possibilities, right? The one that's most looming is the ending of current funding at some point in the future. Right now we're targeting 2020..... However, we're the ones who can determine when that funding will end. If we think it's better to run past 2020 to give ourselves more runway, then we should formulate a plan that would allow us to go to 2021 or even a little bit beyond that to see what happens. So nothing is cast in stone yet (concerning) exactly when we're going to end up with our funding.

"The second one would be the opportunity to have a new bond measure passed, let's say, in 2020.  So what's the plan? If that were to happen, then the third one is going back to the old private-public partner approach which, as I understand it, is still on the table.

"So, in any event, I think what we need are side-by-side plans that look at all of those, that as time goes on and it becomes clear which of those is likely to occur, we can just put it into play. The one that's most likely to be put into play is the one that ends the organization. And then if one of the others comes in after the fact, we can then plug it in and continue on."

Later this week, the California Stem Cell Report will look at a new governing board committee that is examining the various end-of-life, CIRM scenarios. As an aside, during the 2004 ballot campaign that created CIRM, it was widely and erroneously believed that CIRM would have only a 10-year life. The 10-year figure dealt with the agency's bonding authority from the date when bonds were first issued.

'A Reliable Voice of Reason:' A Look at a California Stem Cell Researcher/Blogger

Paul Knoepfler's TED talk has drawn more than one million views

The journal Science this week profiled UC Davis stem cell scientist and blogger Paul Knoepfler, describing him both as a consumer watchdog and a "dogged voice of caution."

In the article by Kelly Servick, George Daley,  dean of the Harvard Medical School, also called Knoepfler a "reliable voice of reason."  Daley noted that academics are "often more comfortable being provincial and insular, and not … mixing it up in the public debates."

Knoepfler began blogging seven years ago after -- at the age of 42 -- he was diagnosed with prostate cancer and given a roughly 50-50 chance of survival. He told Servick that he wanted to "expand how I had impact, beyond just the pure science." From the start, his blog went beyond science to patient advocacy.

Readers of the California Stem Cell Report are likely to be familiar with Knoepfler's blogging efforts, which are often reported here. We have followed his efforts since their inception. Over the years, his voice has grown to be heard in publications across the country. Just this week, he was widely quoted in coverage of the ground-breaking research into gene editing of human embryo.

(An aside from this writer, who is quoted in the Servick piece: One of the reasons that Knoepfler is quoted widely is that he returns media phone calls and can "speak English" -- meaning that he can explain science in terms that most persons can understand, at least those who read newspapers. That could have something to do with having an undergraduate degree in English.)

The Science article focused heavily on Knoepfler's writing about unregulated stem cell clinics, including research by him and Leigh Turner of the University of Minnesota that documented for the first time the size of that particular industry in this country. Their work counted 570 clinics with the most in California.

Why the focus on the unregulated treatments? Knoepfler told Science:

"'They were just saying, ‘Screw the rules, we're just going to set up shop and put up a website and start injecting people with stem cells....I saw that as a threat, first to patients, but to the field as well.'"  

California Stem Cell CEO Search: Lid Still on Until Late September

The  governing board of the $3 billion California stem cell agency, which is seeking a new president, does not plan to have another meeting of its presidential search committee until possibly this fall.

The committee has held only one meeting since May 2, when Randy Mills announced he would be leaving at the first of July.  Maria Millan, formerly vice president for therapeutics, has been serving since July 1 as interim president. She has the backing of Mills to fill the slot permanently. 

The meeting of the search committee occurred July 17. And the agency has remained virtually mum on the process of selecting a new president to oversee what some call the final stage of its life. It is scheduled to run out of cash for new awards in about three years. 

Last Monday (July 31) , the California Stem Cell Report carried an item on the dearth of information about the process of selecting a new president, including the lack of a public timetable and addressing such questions as whether a search firm would be involved. The position carries a salary of up to $575,000.

Following publication of the item, Kevin McCormack, senior director for communications at the agency, sent the following email. 

"Just to be absolutely clear, this is exactly the same process we followed when we were looking for a replacement for Alan Trounson. Then, as now, we did not disclose the results of the closed session meetings of the Presidential Search Subcommittee nor described the contents or outcomes.  From the very beginning of this process, and we mentioned this at the last board meeting, the intention was for the subcommittee to meet and evaluate the options for finding a replacement for Randy and then for the matter to be taken up at the very next meeting of the full ICOC (the governing board). There is no 'lack of information' nor is there any intention of holding another Presidential Search Subcommittee meeting before the full board meeting in September."

The agency, however, has a record of difficulty in recruiting new presidents, including rejected offers and board discord on the desired qualities in a CEO.  It also has in the past disclosed such things as timetables and search firms and more. (See here, here and here.)

The Smell of Money and Gene Editing of Human Embryos -- Not to Mention the Breakthrough Science

"Horror to be avoided," "superbabies" and "what it means to be human" -- Just some of the language that turned up today concerning the news about the first human embryo editing experiment in the United States. 

Publications ranging from Wired to the Financial Times all had pieces discussing the work led by Shoukhrat Mitalipov of the University of Oregon in collaboration with researchers from California's Salk Institute, China and Korea. A search on Google news this afternoon turned up more than 1,000 citations dealing with the work.

Details of the science can be found in the journal Nature with a critique by UC Davis stem cell scientist Paul Knoepfler on his blog. He praised the research and said it "raises the stakes on future CRISPR use in humans." Elsewhere, the implications of the work also generated both heat and caution.

 The headline on a commentary in the Chicago Tribune said,

"Don't fear the rise of super babies. Worry about who will own genetic engineering technology."

The piece was written by bioethicist Arthur Caplan. He said,

"Freaking out over impending super babies and mutant humans with the powers of comic book characters is not what is needed....How close are they to making freakish super people using their technology? About as close as we are to traveling intergalactically using current rocket technology."

Caplan continued,

"We need to determine who should own the techniques for genetic engineering. Important patent fights are underway among the technology's inventors. That means people smell lots of money. And that means it is time to talk about who gets to own what and charge what, lest we reinvent the world of the $250,000 drug in this area of medicine."

Pam Belluck of the New York Times reported that the findings are "sure to renew ethical concerns that some might try to design babies with certain traits, like greater intelligence or athleticism."

She interviewed Hank Greely, director of Stanford's Center for Law and Biosciences. 

"'If you’re in one camp, it’s a horror to be avoided, and if you’re in the other camp, it’s desirable,' Dr. Greely said. 'That’s going to continue to be the fight, whether it’s a feature or a bug.'

"For now, the fight is theoretical. Congress has barred the Food and Drug Administration from considering clinical trials involving germline engineering. And the National Institutes of Health is prohibited from funding gene-editing research in human embryos."

Marcy Darnovsky, executive director of the Center for Genetics and Science in Berkeley, said in a news release,

"We have not yet engaged in processes that would promote the`broad societal consensus’ about human germline modification that the National Academies of Sciences and other prominent advocates of gene editing have recommended. Until that is achieved, we call on scientists around the world to refrain from research aimed at refining gene editing for use in human reproduction."

Bradley Fikes of the Union-Tribune in San Diego, a hotbed of biotech activity and the home of Salk, wrote that the study

"...brings to a head fundamental questions about what it means to be human, and whether changing the human genome would also change the human identity. And scientists — including those involved in the study — say it’s time for the public to speak up."

Given that this type of research is not funded by the United States government, just where the money came from is of interest. The Salk Institute had the answer. It said in a news release that the funding was provided by the "Oregon Health and Science University, the Institute for Basic Science, the G. Harold and Leila Y. Mathers Charitable Foundation, the Moxie Foundation, the Leona M. and Harry B. Helmsley Charitable Trust, and Shenzhen Municipal Government of China."

Some of the money "compensated" the women who provided the eggs, according to an article by Kelly Servick in the journal Science. Compensation, as opposed to expense reimbursement, is problematic in some areas of research. For example, it is banned in research that is funded by the $3 billion California stem cell agency.

The stem cell agency wrote about the research last week after the findings leaked out early. In February 2016, the agency convened a day-long session to examine issues involving gene editing. Last summer it issued new regulations that say that consent forms involving CIRM research must be modified to include a mention of genetic research. Added was the following phrase: "donated embryos [blastocysts], derived cells or cell products may be used in research involving genetic manipulation."

Regarding the future of the research, Mitalipov told the Financial Times that he wanted to perform regulated clinical trials at some point in the U.S. Unless something changes, he said that “unfortunately this technology will be shifted to an unregulated place."

Zipped Up in Oakland: California Stem Cell Agency Mute on Search for New CEO

More than mum -- a good description for the $3 billion California stem cell agency this morning as it wrestles with what is likely its most important decision of 2017.

And that is finding a new president to oversee what some call the "last stage" of its life and its search for a stem cell therapy that will fulfill the expectations of the voters who created the research program in 2004.

The governing board of the California Institute for Regenerative Medicine (CIRM), as the Oakland-based agency is formally known, has held one meeting of its presidential search committee since Randy Mills announced his resignation May 2.

No public utterances emerged, however, from the July 17 session. Did the panel set a timetable for selecting a new president? No response. Will the board hire a search firm to help recruit? No response. Is the search committee going to meet again? No response. Simple questions that have been dealt with openly in past presidential searches at CIRM.

The search for a replacement for Mills has special significance. The agency expects it will run out of cash for new awards in three years or less. In the world of stem cell research, that may not be a nanosecond but it is a very short period of time.

Maria Millan, CIRM photo

It raises the likelihood of an exodus of staff from the program, which has also lost another linchpin in the organization, general counsel James Harrison. Without some certainty and confidence about the next three years, some CIRM employees, of which there are only about 50, may look to other enterprises for their professional futures. The likelihood of more departures could increase unless the board moves to shore up stability and to help retain the energy that Mills brought to the program.

Maria Millan, formerly the vice president for therapeutics, is interim president. Mills publicly endorsed her to fill his slot, which carries an annual salary of up to $575,000. She has been in place for one month. She too may be wondering about the stability of her position and whether she should be looking elsewhere for a position.

The next meeting of the governing board of the agency is set for Aug. 24. CIRM Chairman J.T. Thomas usually gives a report to the board at many meetings. He skipped that at the board meeting in July. Will he will brief the board at the August meeting on the presidential search? That has not yet been publicly disclosed.

An FDA Signal: Good News for California's Stem Cell Agency's Search for Therapies

The California stem cell agency this week highlighted a couple of milestones that it suggests may be creating a trend towards wider application of its research.

The springboard was an announcement that the Food and Drug Administration (FDA) had granted a "rare pediatric disease designation" to a therapy that the agency has backed with  nearly $52 million.

The FDA action comes as the agency is in what some call its "last stage." The agency, formally known as the California Institute for Regenerative Medicine (CIRM), expects to run out of cash for new awards in about three years. No additional funding appears readily available for the agency, which was created by voters in 2004. It has yet to fulfill voter expectations that it would produce a stem cell therapy that is widely available.

The agency this week, however, touted the FDA designation, which involves a treatment for what is commonly known as "bubble baby syndrome." The treatment is called OTL-101 and is being developed by Orchard Therapeutics Ltd, which is based in the United Kingdom The firm is working with Donald Kohn of UCLA, who has been researching in the area for decades.

Writing on the $3 billion agency's blog, The Stem Cellar, Kevin McCormack, senior director for communications, said,

"The treatment) involves taking the patient’s own blood stem cells, genetically modifying them to correct the SCID mutation, and then returning the cells to the patient. Those modified cells create a new blood supply, and repair the child’s immune system."

He wrote,

"The importance of the rare pediatric disease designation is that it gives the company certain incentives for the therapy’s development, including priority review by the FDA. That means if it continues to show it is safe and effective it may have a faster route to being made more widely available to children in need."

McCormack continued,

"This is the second time in less than two weeks that a CIRM-funded therapy has been awarded rare pediatric disease designation. Earlier this month Capricor Therapeutics was given that status for its treatment for Duchenne muscular dystrophy. 

"Two other CIRM-funded clinical trials – Humacyte and jCyte – have been given regenerative medicine advanced therapy designation (RMAT) by the FDA. This makes them eligible for earlier and faster interactions with the FDA, and also means they may be able to apply for priority review and faster approval. 

"All these are encouraging signs for a couple of reasons. It suggests that the therapies are showing real promise in clinical trials. And it shows that the FDA is taking steps to encourage those therapies to advance as quickly – and safely of course – as possible."

McCormack added, however,

"Getting these designations is, of course, no guarantee the therapies will ultimately prove to be successful. But if they are, creating faster pathways means they can get to patients, the people who really need them, at a much faster pace."

USA Today Reports on Financial Complaints Involving Stemedica

The San Diego stem cell company that received national attention for treatments of sports heroes such as Gordie Howe and Bart Starr is now facing legal complaints involving its financial affairs, USA Today reported this morning. 

The story by sports writer Brent Schrotenboer said, 

"The company, Stemedica Cell Technologies, had drawn praise from the families of Bart Starr, the legendary former NFL quarterback, and Gordie Howe, the hockey legend. Both families credited the firm’s stem cells for helping the two bounce back after suffering debilitating strokes. John Brodie, another stroke victim and former NFL MVP quarterback, also praised the company’s stem cell products after being injected with them in foreign countries.

"But even after that boost from big names, a spate of recent legal and financial issues has challenged the company, whose business relies on selling hope in the form of new but unproven regenerative medicine."

The lengthy article went on to discuss lawsuits involving misuse of funds and unpaid bills, including the alleged failure to pay a $500,000 loan despite numerous extensions. 

The company told USA Today that the misuse of funds allegations are "completely false" and has contested the other allegations in court. 

Former USC Med School Dean Loses Board Seat at $3 Billion California Stem Cell Agency

Former USC medical school dean Carmen Puliafito, who reportedly led a secret life involving drugs and prostitution, is no longer a member of the governing board of the $3 billion California stem cell agency.

In response to a query last week from the California Stem Cell Report, Evan Westrup, press secretary to Gov. Jerry Brown, said,

"This individual is no longer on the board."

Carmen Puliafito
Photo by Tibrina Hobson, FilmMagic

However, as of this writing, the web site for the agency listed Puliafito as a member of the governing board, carrying a short biography and a photo.

In response to a question this morning, Kevin McCormack, senior director for communication for the agency, said,

"If the governor says he is not in the board then he is not on the board. We will change the web page."

The governor's office did not respond to requests last week for more details concerning Puliafito's departure. But his term expired last December. Agency board members may continue to serve until a replacement is named.

The position that Puliafito held on the board of the California Institute for Regenerative Medicine(CIRM), as the agency is formally known, is required to be filled by an executive from a California university. Since the inception of the agency in 2004, the seat has been filled by the dean of the USC School of Medicine.

Puliafito (far left) at ceremonies opening stem cell center at
USC. CIRM provided $27 million for the $80 million project.
 Then CIRM board chairman Bob Klein is second from right.
Then Gov. Schwarzenegger stands next to Puliafito, who he
appointed to the CIRM board. 

It is not clear whether the governor will replace Puliafito with another representative from USC. Brown may look askance at the school in the wake of reports about how USC handled the Puliafito affair over a period of more than a year. 

A headline on a column last week by Los Angeles Times columnist Steve Lopez said,

"USC bosses flunk the leadership test amid shocking allegations about former medical school dean"

USC ranks 6th among California institution in the amount of awards it has received from CIRM, collecting a total of $110 million.

NY Times: The Race to Create 'Transformative' Cellular Treatments for Cancer

Cellular treatments of cancer received a big media boost this morning with a front page story in the New York Times that said the door is opening on a radical new class of therapy.

The headline on the piece in the print version of the Times in California said,

"Racing to Alter Patients' Cells to Kill Cancer"

The article by Denise Grady was also high on the Internet home page this morning of the Times.

The peg for the lengthy story was the expected approval of gene therapy for leukemia in the next few months. Grady wrote,

"Companies and universities are racing to develop these new therapies, which re-engineer and turbocharge millions of a patient’s own immune cells, turning them into cancer killers that researchers call a 'living drug.' One of the big goals now is to get them to work for many other cancers, including those of the breast, prostate, ovary, lung and pancreas. 

"'This has been utterly transformative in blood cancers,' said Dr. Stephan Grupp, director of the cancer immunotherapy program at the Children’s Hospital of Philadelphia, a professor of pediatrics at the University of Pennsylvania and a leader of major studies. 'If it can start to work in solid tumors, it will be utterly transformative for the whole field.;'"

High in the story (the fifth paragraph), Grady mentioned that cellular treatments are also being studied in connection with glioblastoma, the type of brain cancer afflicting Sen. John McCain. 

The Times carried a host of caveats about the likely new therapy, its dangers and even deaths that have occurred during the research. But "studies are forging ahead," Grady reported, despite the fact that they are expected to cost hundreds of thousands of dollars. 

The article did not mention the research that has been financed by California stem cell agency, which has pumped $90 million into developing cellular-connected treatments for cancer. The California Stem Cell Report wrote about that effort last week and filed a freelance story on the subject for The Sacramento Bee.