The Valley of Death and the California Stem Cell Agency: Luring Deep Pocket Investors

The California stem cell agency this week is tooting a $150 million horn and heralding its efforts to assist stem cell businesses with development of therapies that could ease the travails of everything from cancer to blindness.

It is all about a financial "valley of death" that can imperil biotech firms as they seek to turn research into an actual product that can be used by patients. The latest poster child for the California Institute for Regenerative Medicine (CIRM), as the agency is formally known, is a San Diego firm called ViaCyte. 

The enterprise has received more cash -- $72 million -- from CIRM than any other business. CIRM is facing its own valley of death next year, when its taxpayer cash will run out.

Writing yesterday on the CIRM blog, the agency's communications director, Kevin McCormack, said,

"CIRM was created, in part, to help...great ideas get through the valley (of death). That’s why it is so gratifying to hear the news today from ViaCyte – that is developing a promising approach to treating type 1 diabetes – that they have secured $80 million in additional financing.

"The money comes from Bain Capital Life Sciences, TPG and RA Capital Management and several other investors. It’s important because it is a kind of vote of confidence in ViaCyte, suggesting these deep-pocket investors believe the company’s approach has real potential."

McCormack continued,

"CIRM has been a big supporter of ViaCyte for several years, investing more than $70 million to help them develop a cell therapy that can be implanted under the skin that is capable of delivering insulin to people with type 1 diabetes when needed. The fact that these investors are now stepping up to help it progress suggests we are not alone in thinking this project has tremendous promise.

"But ViaCyte is far from the only company that has benefitted from CIRM’s early and consistent support. This year alone CIRM-funded companies have raised more than $1.0 billion in funding from outside investors; a clear sign of validation not just for the companies and their therapies, but also for CIRM and its judgment.

"This includes:

• Humacyte raising $225 million for its program to help people battling kidney failure
• Forty Seven Inc. raising $113 million from an Initial Public Offering for its programs targeting different forms of cancer
• Nohla Therapeutics raising $56 million for its program treating acute myeloid leukemia"

One could argue that these companies could have found backing from other sources than the stem cell agency. One could argue that state government should not be in a business that is too risky for even the vaunted world of venture capitalists.

Nonetheless it is an important part of the CIRM story, one that will be tested perhaps in November 2020. That's when the $3 billion agency hopes to see a measure on the ballot that will give it another $5 billion. So far the agency, created in 2004 by a ballot initiative, has not fulfilled voter expectations that it would produce a stem cell therapy that is widely available. And it will need a good yarn to inspire voters once again in 2020. 

The Genetically Altered Babies Story: More Information Surfaces on Researcher's California Links

More details are emerging this week concerning the California connections of the man behind what are being described as the world's first gene-edited babies. 

The scientist is He Jiankui, who spent two years in a lab at Stanford University, according to the lab's web site.

Lisa Krieger of the San Jose Mercury News has produced a roundup of the information about the researcher's activities in the Golden State. They include the connections with Stephen Quake of Stanford, who heads the lab where He Jiankui worked from 2010 to 2012.

She reported that Quake is declining any comment on He Jiankui.

Also mentioned in Krieger's piece are Mark Dewitt of UC Berkeley, William Hurlburt of Stanford and Jennifer Doudna, also of Berkeley.

Another useful piece exploring He Jiankui's training was produced by Sharon Begley, Andrew Joseph and Rebecca Robbins at STAT. The article takes a broad look at the researcher's training and background.

One cautionary note: The "facts" in this ongoing tale sometimes seem in conflict and sometimes murky. UC Davis' Paul Knoepfler raised the matter on his blog yesterday in an item headlined, 

"Trying to connect the dots on CRISPR baby story paints a dark, cloudy picture."

Even determining the number of years He Jiankui worked at Stanford is in question. Quake's lab clearly reports two years. STAT reports that it was "about a year" without identifying a source. A relatively minor point, but if that can't be nailed down, what else is missing? As Knoepfler wrote, much murkiness exists in the morass of stories and commentary that has emerged this week.

The caveat for those who follow this matter? As the old adage goes,

"Even if your mother says it's true, check it out."

The California Stem Cell Agency Speaks Out on Raelians and New Types of Human Beings

The California stem cell agency this morning is asking us all whether we remember the Raelians?

The agency, however, is not offering a $64,000 prize for the answer. No quiz show contest at the Oakland headquarters of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known.

Instead the Raelian recollection is the lead-in to a cautionary note about the reports out of China that a researcher, who once worked at Stanford, has genetically altered two babies in embryo. The news has triggered an international flap about the ethics involved along with warnings about gene editing that results in "new kinds of human beings."

Writing on the agency's blog, Kevin McCormack, senior director for CIRM communications, said,

"Remember the Raelians? Probably not. But way back in 2002 the group, some described them as a cult, claimed it had created the world’s first cloned baby. The news made headlines all around the world raising fears we were stepping into uncharted scientific territory. Several weeks later the scientist brought in by the Raelians to verify their claims called it an 'elaborate hoax.'"

McCormack cautioned that ultimately the news out of China could amount to the same sort of thing. 

He noted the use of the CRISPR gene editing technique which has made it much easier to dip into the genetic process. McCormack wrote,

"CRISPR has been making headlines all of its own in the last few years as a fast, cheap and efficient way of editing genes. CIRM supports research using CRISPR for problems such as sickle cell disease. The difference being that our research works with adults so any changes in their genes are just for them. Those changes are not passed on to future generations.

"The work making headlines around the world used CRISPR on embryos, meaning a child born from one of those embryos would pass those changes on to future generations. In effect, creating a new kind of human being."

McCormack picked up a sample of reaction around the world, including a comment from Stanford bioethicist Hank Greely on CNBC. Greeley said that that if the report is accurate, the research is "criminally reckless, and I unequivocally condemn the experiment.”

McCormack concluded,

"Our best hope right now is that this is just a repeat of the Raelians. Our worst fear, is that it’s not."

Genetically Altered Babies: A Bit of a California Connection

This You Tube video produced by He Jiankui had drawn 19,723 views at the time of this posting along with nearly 300 comments, pro and con.  The number of views jumped about 5,000 during one hour this morning.

The startling news about what is being described as the world's first gene-edited baby has a something of a California tie.

The scientist behind the work, He Jiankui, worked from 2010 to 2012 in the lab of Stephen Quake at Stanford University, who is participating in a $40 million genomics program backed by California's $3 billion stem cell agency.  

Like many other scientists, He Jiankui was trained in the United States, receiving his Ph.D. from Rice University. 

A statement on the web site of Direct Genomics, a company He Jiankui founded, said,

"He was working on genome sequencing research during his postdoc training in the lab of Stephen Quake at Department of Bioengineering, Stanford University. Dr. He has multidisciplinary research background, such as in physical theory of network evolution, influenza virus, immune repertoire sequencing, single cell genomics and bioinformatics."

Quake's lab is currently dealing with ultra high throughput DNA sequencing. On the lab's web site, a mission statement by Quake said,

"My work in single molecule biophysics led to the first demonstration of single molecule sequencing, and my research in this field has led me to become deeply involved in human genetics, immunology, and the development of new clinical diagnostics."

Quake has not yet responded to a query concerning He Jiankui's work at Stanford.

In the stem cell agency's genomics project, Quake is the lead on a project dealing with cell differentiation.

California's Center for Genetics and Society in Berkeley released a statement on the news about the gene editing. Executive Director Marcy Darnovsky, said, 

“If true, this amounts to unethical and reckless experimentation on human beings, and a grave abuse of human rights. We wish the best for the health of these babies, but strongly condemn the stunt that threatens their safety, and puts the rest of us at risk. Throwing open the door to a society of genetic haves and have-nots undermines our chances for a fair and just future.”

California Kicks Off Major, New Foray into Gene Therapy: First by Any State in the Country

California today became the first state in the nation to launch itself into the sizzling field of gene therapy, backed by tens of millions of dollars and with the hope of creating treatments that could permanently cure afflictions ranging from hemophilia to cancer.

The move came today as the board of the $3 billion California stem cell agency opened its doors to funding gene therapy research that has reached the most advanced stage, clinical trials. The agency said that gene therapy -- minus stem cells -- is "valuable and worthy of pursuit."

"This is where the science is going," said Jeff Sheehy, chairman of the CIRM board's Science Subcommittee, at hearing earlier this month,

The state stem cell program has allocated $143 million for research programs next year that could include gene therapy.

A document prepared by the leadership of the agency, formally known as the California Insitute for Regenerative Medicine (CIRM), said, 

"For CIRM and the patients it aims to serve, it is vital to support technologies which prove to be highly complementary and augmenting to stem cells, such as gene therapy."

Gene therapy treatments are expected to be quite expensive, with some forecasts running in the $1 million to $2 million range. Supporters of gene therapy argue that the cost is justified because gene therapy can be a total cure that would eliminate the need for also very expensive lifelong treatments of chronic diseases. 

In its action today, the stem cell agency did not announce any specific research awards. Rather it created a procedure for declaring that a gene therapy project with a regenerative element is a "vital research opportunity."  That would allow CIRM to fund such a project under the terms of the ballot initiative that created the agency in 2004. Today's action is the first time that the agency has acted to use the "vital opportunity" provision. 

CIRM has budgeted $143 million for next year in two areas where the new gene therapy initiative could come into play, clinical trials along with translational research that is intended to advance basic research into clinical stages. 

The agency's new foray comes as its cash is running out. By the end of next year, it expects to have no more funding for new research. The agency is pinning its hopes of survival on a $200 million plus private fundraising effort this year and voter approval of a yet-to-be-written ballot initiative on the November 2020 ballot. 

The gene therapy field is moving swiftly and could generate a result that would resonate with voters and help to win approval of an additional $5 billion for CIRM.

CIRM board members have acknowledged that its new gene therapy effort will mean more competition for the state's research dollars, including possibly less for stem cell research, which is the agency's fundamental reason for being.

The agency, however, has already awarded millions of dollars for gene therapy research that has a stem cell link, including a program at UCLA that has led to a successful treatment for what is known as the "bubble boy syndrome." However, that research has not yet moved into the marketplace.

The target of the UCLA treatment is an immune deficiency that is fatal and for which there is no successful treatment outside of the experimental trials that are still underway. 

Bloomberg News has reported that Scott Gottlieb, head of the federal Food and Drug Administration(FDA), has described the field as "somewhat breathtaking." More than 500 experimental treatments are in the pipeline. 

Gottlieb has said that he expects the FDA to approve 40 gene therapies by 2022 and possibly a cure for sickle cell anemia within 10 years. CIRM is deeply involved in a major national push on sickle cell supported by the National Institutes of Health.

Combating Stem Cell Snake Oil: A Primer From a California Researcher

Hundreds of dubious, unregulated stem cell clinics exist throughout the country with the most in California. Desperate people seeking help have been maltreated and fleeced. What to do?

UC Davis stem cell research Paul Knoepfler has produced a useful guide to reporting dubious
activities along with a list of state and federal agencies that could have a role.

In an item on his blog last week, Knoepfler wrote,

"I would emphasize concrete reasons for concern such as the use of an unapproved stem cell drug product by the clinic, a physician practicing outside their area of expertise so putting their patients at risk, false marketing, and potential or documented (if they’ve already happened) patient harms.

"For some clinics that aren’t led by physicians, I would also emphasize the risks of non-physicians such as chiropractors or Ph.D.s doing procedures for which they aren’t trained or licensed. I think patients (or people communicating on their behalf) making complaints about clinics and their personnel will have the greatest impact."

Knoepfler continued,

"We can make a difference by pushing back on the worst clinics. Of course, not every action by those of us in the stem cell arena who are concerned about predatory clinics will hit a bullseye to make real change, but sometimes it has happened in the past and will happen again in the future too."

I would add that the activities and stories that emerge from these dubious enterprises damage the reputation of the field as a whole. Indeed, when I talk to folks in the general public, the clinics' offerings are the most often mentioned reference they have.

As California's stem cell agency moves closer to seeking more billions from voters in 2020, fraudulent stem cell activity could create much confusion about the legitimacy of the entire field. Supporters might want to keep that in mind. But critics should as well. Fleecing the public with unproven therapies is unhealthy for those who are swindled but also for society in general.

California's Stem Cell Agency Opening Door to Pumping More Millions into the Sizzling Gene Therapy Market

Gene therapy graphic from FDA

The California stem cell agency today crossed a key threshold into the "somewhat breathtaking" and potentially multibillion-dollar world of gene therapy, a field that it has skirted previously. 

The action came when a key panel of the agency's governing board this morning approved its first-ever procedure for awarding millions of dollars for research not connected to stem cells. 

"This is where the (regenerative) science is going," said Jeff Sheehy, chair of the Science Subcommittee of the board of the California Institute for Regenerative Medicine (CIRM), as the Oakland-based agency is formally known. 

Under Prop. 71, the ballot initiative that created the $3 billion agency in 2004, CIRM is limited to financing research involving stem cells in some fashion. However, a provision of the measure also allows the support of a "vital research oppportunity" under certain conditions. Today's action formalizes the process for making that finding. 

CIRM said in in a document that it is "vital" that the agency expand its horizons.

"CIRM has supported projects that combine stem cell and gene therapy technologies, such as the gene-corrected stem cell transplants at UCLA that essentially cured 5-year old Evangelina Padilla Vaccaro and several CAR-T cell approaches using stem memory T cells that aim to tackle various cancers. 

"The support of stem cell research that contributes to these treatments is and will continue to be the core of CIRM funding. However, treatment opportunities in regenerative medicine that utilize gene therapy technologies but not necessarily stem cells are also valuable and worthy of pursuit."

The agency's statement continued,

"The field of regenerative medicine brings together technologies that include stem cells, gene therapy, and tissue engineering that in many cases combine to produce a therapeutic product. In some cases, one technology leads the way. For CIRM and the patients it aims to serve, it is vital to support technologies which prove to be highly complementary and augmenting to stem cells, such as gene therapy."

Several directors noted during today's meeting that the change could lead to less cash for purely stem cell projects. 

The field of gene therapy has attracted widespread interest within the regenerative medicine industry and among federal medical regulators. Scott Gottlieb, commissioner of the Food and Drug Administration, earlier this year announced steps to speed development of the therapies. 

Bloomberg News reported:

"'The pace of progress in gene therapy has been somewhat breathtaking,' he (Gottlieb) said, with more than 500 experimental drugs now in development. 'The promise is becoming very much a reality.'"

In April, Novartis AG ponied up $8.7 billion to buy AveXis Inc., of Illinois to strength its efforts to produce a marketable gene therapy.

Gottlieb has said that he expects the FDA to approve 40 gene therapies by 2022 and possibly a cure for sickle cell anemia within 10 years. 

CIRM's new gene therapy policy will go before the full CIRM board one week from today where it is expected to be approved. Additional information on the policy can be found on the Science Subcommittee agenda. 

An FDA High Sign for a California Stem Cell Agency Bet: San Diego Biotech Business Earns FDA Speed-Up Approval

A San Diego firm backed by nearly $24 million from the California stem cell agency scored this week with a special designation from the federal government that could help speed approval of its therapy for a type of blood cancer. 

The firm is Poseida Therapeutics, Inc., which is testing the safety of a therapy for a type of blood cancer in a phase one clinical trial. 

The firm announced yesterday that the Food and Drug Administration (FDA) had granted Regenerative Medicine Advanced Therapy (RMAT) status for the adult stem cell-connected treatment. The designation is intended to expedite development of the multiple myeloma therapy. 

Eric Ostertag, CEO of the firm, said in a news release, that Poseida's potential treatment, P-BCMA-101, "is the first anti-BCMA CAR-T therapy to receive RMAT designation from the FDA and underscores the urgent need for new treatment options for multiple myeloma." 

He continued, 

“Initial Phase 1 data presented at the CAR-TCR Summit earlier this year included encouraging response rates and safety data, including meaningful responses in a heavily pretreated population...."

Ostertag said the firm expects to have more data by the end of the year. 

The stem cell agency, known formally as the California Institute for Regenerative Medicine (CIRM), has invested in 49 clinical trials. Five have garnered RMAT designation, which can significantly speed development of a commercial product. As of September, the FDA had granted only 24 RMAT designations nationally. 

Last Sepetember, Geoff Lomax, CIRM senior officer for medical affairs and strategic centers, wrote in cell&gene that the two-year-old, RMAT program streamlines therapy development by enabling possible priority FDA review and accelerated federal approval. 

Longitude Capital of Menlo Park, Ca., is a major investor in the firm, pumping in tens of millions of dollars.  

California Stem Cell Agency Moving to Expand its Reach into Big Market for Gene Therapy

The definition of gene therapy under proposed changes for
 research funding by the California stem cell agency. CIRM chart

California's $3 billion stem cell research program is set to add gene therapy -- minus stem cells -- as research that it will be able to legally finance. 

The change comes as the stem cell agency is looking to generate results that are likely to resonate with voters in November 2020 who may be asked to provide an additional $5 billion in funding for the program. The agency expects to run out of cash by the end of next year. 

Gene therapy has received considerable attention in the last few years. Yesterday, Orchard 
Therapeutics, a British gene therapy firm that has links to CIRM (also see here) and research by Donald Kohn of UCLA, raised $200 million in an initial stock offering. The company said in its prospectus that the total market potential "in the diseases areas underlying our five lead programs could be greater than $2 billion annually."

Donald Kohn, UCLA photo

Kohn has received nearly $31 million in backing from the stem cell agency, which is formally known as the California Institute for Regenerative Medicine (CIRM).

The Science Subcommittee of the agency is expected to approve extension of its gene therapy efforts next Wednesday in a teleconference meeting that will be available globally through the Internet. 

Under the provisions of the ballot measure that created the agency in 2004, the agency is limited in scope. But exceptions are possible if a finding is made that a "vital research opportunity" exists. 

Next week's meeting is expected to formalize the process of making that determination in regards to gene therapy that does not involve stem cells. It will require a 2/3 vote of CIRM's grant review group, among other things. 

Members of the public can participate in the hearing remotely via the Internet or at locations in Oakland, San Francisco, La Jolla, Riverside and Napa. Directions can be found on the agenda.

A $59 Million Matter of Fraud and Hubris: The Anversa Stem Cell Story and Its Fallout

Piero Anversa -- NYTimes photo by Annie Tritt

Fabricated stem cell research and its fallout are back in the news this morning with excellent pieces from the New York Times and the Washington Post involving talk of "temptation" and the weakness of prestigious institutions.

First the piece by Gina Kolata in the New York Times,which includes the first substantial interview with Piero Anversa, the former Harvard researcher now identified as having produced more than 30 studies containing falsified or fabricated data dealing with heart research. Kolata wrote,

"Dr. Anversa’s story has laid bare some of the hazards of modern medical research: the temptation to embrace a promising new theory, the reluctance to heed contrary evidence and the institutional barriers to promptly stopping malfeasance. Even after three independent researchers were unable to reproduce his findings in 2004, Harvard hired him in 2007 and his lab continued to churn out studies upholding his theory."

Anversa, 80, is now living in New York. He told Kolata in an interview in his apartment that he did nothing wrong and that he was "betrayed by a rogue colleague who altered data in paper after paper."

Kolata has more from Anversa, but also dives into the history and ramifications of the scandal and its implications involving the culture of science. She described the case as "a particularly acrid cautionary tale of scientific hubris."

A couple of highlights from the piece.

• "'Science at this level is like a battleship, and it’s really hard to turn it around,' said Dr. Jonathan Moreno, a professor of bioethics at the University of Pennsylvania.'People get emotionally invested, financially invested, professionally invested.'" 

• “'This was a perfect storm of ego, wishful thinking and lack of accountability,' said Dr. Jil C. Tardiff, a professor of medicine at the University of Arizona, and a heart-muscle cell researcher."'

 Kolata concluded:

"It did not surprise some in academia that the bold promises of the research persisted despite the contested evidence. 

 "There was an argument in the philosophy of science about whether there is such a thing as a ‘crucial experiment,' said Dr. Moreno, the ethics professor, referring to a study that answers a question once and for all. 

"'It turns out there isn’t. People can see what they want to see.'"

Carolyn Johnson of the Washington Post covered much of the same ground but has more on suspension of a clinical trial related to Anversa's work. Johnson also pointed out that Anversa received $59 million from the federal government for his research. Harvard has since been fined $10 million by the federal government.  

The trial is in the midst of recruiting patients. Johnson wrote,

"The decision to temporarily pause the trial came 'out of an abundance of caution,' said David Goff, director of the Division of Cardiovascular Sciences at the National Heart, Lung and Blood Institute, who said the trial’s scientific rationale is largely based on animal studies not conducted by Anversa.... 

"Goff said the board charged with overseeing the safety and integrity of the trial was convened last week and NIH leadership made the decision to pause the trial, which has enrolled 125 of 144 patients, to allow a thorough review.

"'Our commitment, first and foremost, is to patient safety. We haven’t seen any safety signals related to the cell treatment, but we can’t do any of our research without the partnership of our participants, and we make a commitment to our participants that their safety is our highest priority,' Goff said. The pause will allow the board to examine the trial and 'assure that it continues to meet the highest levels of adherence to participant safety and scientific integrity.'"

Tax Breaks and $220 Million for California Stem Cell Agency

The California stem cell agency, which is facing its financial demise, is seeking assurances of "continued tax breaks" for private donors who are being courted for $220 million to support the enterprise, Bloomberg Law reported this week. 

The article by Joyce Cutler referred to the effort to bridge a looming and major stem cell funding gap. The agency says it will run out of cash for new awards at the end of next year. But it does not see additional public funding until November 2020, when the agency hopes that California voters will refinance it with $5 billion from a yet-to-be written ballot initiative. 

Cutler wrote,

"Closing the deal, however, involves getting assurances from elected officials of continued tax breaks to get donors to open their checkbooks and keep CIRM operating until another bond measure can be passed." 

CIRM is the abbreviation for the California Institute for Regenerative Medicine, the formal name of the stem cell agency. It was created in 2004 by voters who provided it with $3 billion in state bonds, but no more. 

Asked for comment by the California Stem Cell Report, Kevin McCormack, senior director for communications at CIRM, said,

"With regard to the tax deductibility issue, that’s really out of our hands but, of course, we’re hopeful that all incentives to potential donors are preserved going forward."

Cutler wrote, 

"Contributions to state agencies currently are deductible from income under state and federal law, H.D. Palmer, state Department of Finance spokesman, told Bloomberg Law in an email.

"'Going forward, that’s going to fall to the next folks who get the keys to the car' in the governor’s office and Legislature, who will decide whether the California deductions remain.

"But the federal Internal Revenue Service is considering regulations to disallow deductibility if the tax credit is for more than 15 percent of the contribution. The Tax Cuts and Jobs Act of 2017 limits the amount of state and local taxes (SALT) an individual can deduct on taxes to $10,000 a year. The proposed regulations crack down on state workarounds to the SALT deduction cap."

Jonathan Thomas, chairman of the CIRM board, is leading the effort to raise funds privately. Bob Klein, who preceded Thomas as chairman, has a role but the agency has declined to go into details. Klein is a real estate investment banker and founder and chairman of Americans for Cures, a nonprofit organization supporting stem cell research. 

Klein has said he has a poll that shows that more than 70 percent of Californians support refinancing the agency. But he has declined to release the poll or identify the firm that provided it when asked by the California Stem Cell Report.  

Klein oversaw the writing of the ballot initiative that created the stem cell agency in 2004 and led the electoral campaign on its behalf. He has said he will try again in 2020 if polls show sufficient support. 

At last week's CIRM board meeting, Thomas gave a short report on the private fundraising effort, which has been underway for many months. He did not announce any contributions or discuss the tax break issue. 

At the meeting, board member Jeff Sheehy expressed concern about progress on a possible 2020 bond measure, noting that there is a relatively short amount of time to mount a major political effort.

Art Torres, vice chairman of the board and a former state legislator, said no real effort can be mounted until after the elections next month. Torres and CIRM general counsel Scott Tocher also noted there are legal limits on what the agency can do in terms of a ballot campaign. 

Fabrication and Stem Cell Research: A Tale of 31 Retractions (Maybe), $63 Million and Heavy News Coverage

Stem cell research fraud was big news this past week. It involved millions of dollars, the reputations of researchers and prestigious institutions, lots of wasted work and damage to the entire field. 

The case, which attracted international attention in the mainstream media, involves a prominent heart researcher, Piero Anversa, formerly of  Harvard, and requests for 31 retractions.  STAT/Retraction Watch broke the story in a piece written by Ivan Oransky and Adam Marcus. The New York Times, the Washington Post and other publications followed. 

As the New York Times summarized, Anversa "fabricated or falsified data in 31 published studies that should be retracted, officials at the institutions have concluded." Harvard has been fined $10 million by the federal government.  

Carolyn Johnson of the Washington Post quoted a California stem cell researcher:

"'This body of work has, for better or worse, been hugely influential,' said Eduardo Marbán, director of the Smidt Heart Institute at Cedars-Sinai Medical Center. 'Despite the fact that several prominent laboratories failed to confirm key findings, c-kit positive heart cells were rapidly translated to clinical testing in heart failure patients. … One can only hope that no patients have been placed at risk in clinical trials based upon fraudulent data.'"

Another California researcher, Benoit Bruneau, was quoted by the New York Times. 

"A couple of papers may be alarming, but 31 additional papers in question is almost unheard-of,' said Benoit Bruneau, associate director of cardiovascular research at the Gladstone Institutes in San Francisco. 'It is a lab’s almost entire body of work, and therefore almost an entire field of research, put into question.'"

Gina Kolata of the New York Times wrote, 

"Despite the troubling questions that had been raised about the stem cell work, the National Heart, Lung and Blood Institute began a clinical trial of injected stem cells for patients with heart failure.... 

"In the past few years, however, skeptical researchers moved on to other prospects for heart treatment. 'The field has backed off a lot,' (Jeffery) Molkentin (a professor at the Howard Hughes Medical Institute) said.

"Some scientists wondered how a questionable line of research persisted for so long. Maybe, Dr. Molkentin said, experts were just too timid to take a stand."

Some researchers have called for suspension of the $63 million clinical trial, including Deepak Srivastava, president of the Gladstone Institutes and president-elect of the International Society for Stem Cell Research.

Here are links to other coverage of the matter, which is been brewing for several years: The Niche, The Scientist, Medscape, Biospace and the  Harvard Crimson.

Autism to Bladder Cancer: California Awards $25.2 Million For Stem Cell Research

The California stem cell agency yesterday approved $25.2 million for research involving a spate of diseases, ranging from HIV and autism to hearing loss and bladder cancer.

The only application involving clinical stage work was submitted by Xiuli Wang of the City of Hope in Duarte, Ca., for her research on a CAR-T treatment to achieve a functional cure for HIV infection without the need for antiretroviral drug therapy.

The application (CLIN1-11223) sought $3.8 million to take her proposed therapy to the point where it can win approval to begin clinical trials. Here is a link to the summary of the review of her application. 

Directors of the California Institute for Regenerative Medicine(CIRM), as the agency is formally known, also approved $13.5 million in awards to translate basic research into clinical work and $7.9 million for more basic research. 

Here is a list of the principal investigators in the translation round. Summaries of the reviews can be found in this document. Translation refers to research that is moving from the basic stage to clinical.

• Steven Schwartz of UCLA, $5.1 million, TRAN1-11265, clinical translation of autologous regenerative cell therapy for blindness
• Karin Gaensler of UCSF, $4.2 million, TRAN1-11259, development of engineered autologous leukemia vaccines to target residual leukemic stem cells
• Ted Leng of Stanford, also $4.2 million, TRAN1-11300, a purified allogeneic cell therapy product for treatment of dry age-related macular degeneration

Here is a list of awards whose approval was stalled in July for financial reasons. The review summaries with scores can be found in this document.

• Tracy Grikscheit of Children's Hospital Los Angeles, $1.3 million, DISC2-10979, Universal Pluripotent Liver Failure Therapy (UPLiFT)
• Philip Beachy of Stanford, $1.4 million, DISC2-11105, pluripotent stem cell-derived bladder epithelialprogenitors for definitive cell replacement therapy of bladder cancer
• Jonathan Lin of UC San Diego, DISC2-10973, $1.2 million, small molecule proteostasis regulators to treat photoreceptor diseases
• Stuart Lipton of Scripps, DISC2-11070, $1.8 million, drug development for autism spectrum disorder
• Neil Segil of USC, DISC2-11183, $833,971, A screen for drugs to protect against chemotherapy-induced hearing loss, using sensory hair cells derived by direct lineage reprogramming from hiPSCs
• Alan Cheng of Stanford, DISC2-11199, $1.4 million, modulation of the Wnt pathway to restore inner ear function

$144 Million California Stem Cell Research Program Set for 2019

Directors of the California stem cell agency this morning approved a $144 million research budget for next year, which could well be its last for dispensing any major cash in its search for stem cell therapies.

The amount compares to $148 million expected to be awarded this year.  At its peak, the agency was handing out close to $300 million a year in research awards, but the amount varied from year to year.

Most of the funds for the next year will be devoted to clinical stage work. The agency, formally known as the California Institute for Regenerative Medicine (CIRM), is already backing 49 clinical trials, the last stage before a therapy is approved for widespread use. But it has yet to help finance a therapy that can be used by the population at large, despite expectations of voters who approved creation of the $3 billion agency in 2004.

CIRM expects to run out of cash for new awards next year. Possibilities exist for continued funding of research in 2020, but the agency is budgeting conservatively. CIRM Chairman Jonathan Thomas is attempting to raise privately $220 million to maintain the agency's funding. Thomas briefed directors today on that effort but notably did not report that specific additional funding had been secured.

CIRM also expects to recover possibly as much as $30 million in 2019 from projects that do not meet their milestones and possibly use the funds for awards next year or in 2020.

The agency is pinning its hopes for ultimate survival on a yet-to-be-written $5 billion bond measure on the November 2020 ballot.

Where Has The Money Gone? A 10-cent Look at $3 Billion in California Stem Cell Spending

CIRM graphic

California has spent about $2.6 billion on stem cell research over the last 14 years. It has roughly $144 million left for new awards. Here is a quick overview of where cash has gone, based on the agency's records.

Keep in mind that an examination of the state stem cell agency's spending can be like the blind men and the elephant. A lot depends on what you grab.

And tomorrow directors of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known, will  be grabbing a piece of the program to determine what is going to be handed out in 2019.

Since 2004 when the agency was created with $3 billion in funding, CIRM reports that it has spent $898 million on various stages of basic research, which it generally calls "discovery," the largest single category.

It has plowed $632 million into clinically connected research dealing with afflictions ranging from cancer to blindness. The amount involves both more recent clinical research and CIRM's earlier disease team programs. Kevin McCormack, senior director for communications, said the money went for late stage research leading to a clinical trial as well as the trials themselves.

The agency's clinical trial dashboard shows that it has supported 49 clinical trials. The dashboard provides more detail on the status of each trial. (Here is a link to a June CIRM spreadsheet on the trials. Here is a link to a table on the trials released in connection with this week's directors' meeting.) 

CIRM has sunk $482 million into "infrastructure," a term that includes a $271 million building program for new facilities at institutions ranging from Stanford to UC Davis.  (See here and here for more on the infrastructure program.

The agency spent $219 million on education, which probably does not include a more than $40 million program to lure star scientists to the Golden State academic institutions. Those awards were specifically for research projects.

In terms of diseases, CIRM research covers 24 disease areas, ranging from Alzheimer's to strokes. A third of the clinical trial money has gone for cancer. Nineteen percent has targeted blood diseases and 12 percent neuro afflictions.

For a full list of institutions, see here.

Stanford, an already well-endowed institution in 2004, was the top institutional recipient with $360
million. UC Davis was the over-achiever in the top 10 recipient list with $138 million. In 2004, it had what could only be described as a tiny stem cell program.

ViaCyte, Inc., of San Diego, is the only business to make the top ten list, snagging $72 million. With the exception of ViaCyte, all of the institutions in the top ten had or have representatives on the CIRM governing board who are not permitted to vote on awards to their institutions.

As mentioned at the beginning of this item, this was the 10-cent tour of CIRM spending, which may tweak your interest. The high-priced excursion will come another day.

California Stem Cell Agency's Latest Awards: Total of $17 Million for Cancer, Blindness, HIV

The California stem cell agency is set this Thursday to award $3.8 million for research aimed at development of a major improvement in treatment for HIV and another $13.5 million to deal with leukemia and problems that can lead to blindness. 

The proposals have already been approved by the $3 billion agency's reviewers in a closed door session. The governing board of the agency is expected to ratify those decisions at a public meeting on Thursday. 

Xiuli Wang, COH photo

The HIV award is scheduled to go to Xiuli Wang of the City of Hope in the Los Angeles area for work leading to a clinical trial. Wang told the board in a letter, 

"(O)ur approach has the potential to be a single delivery therapy that releases patients from the ART (antiviral drug therapy) regime for the rest of their lives. This strategy could also alleviate the cumulative financial burden that represents life-long medication."

In response to a query from the California Stem Cell Report, Jeff Sheehy, an HIV patient advocate on the CIRM board, said that the proposal (CLIN1-11223) would use a vaccine to "to stimulate one's immune system to proliferate and maintain the engineered anti HIV CAR T cells that are the therapy.

"What makes this especially exciting is that 'the approach of using the CMV vaccine to expand CMV specific T-cells may eliminate the current use of preconditioning chemotherapy that is widely adopted for T cell therapies.'  In short, if successful, this approach would not only give people with HIV the ability to control the virus long term with needing antiretroviral therapy but could also make CAR T therapies in general more efficient and effective as well as safer, plus lead to other uses of CAR T technology."

Theodore Leng, Stanford photo

Karin Gaensler, UCSF photo

Karin Gaensler of UC San Francisco is slated to receive $4.2 million to develop a vaccine that will attack residual leukemia cells.   (Application number TRAN1-11259)

Theodore Leng of Stanford is scheduled to be awarded $4.2 million to develop a "purified allogeneic cell therapy product (called NeuBright) for treatment of dry age-related macular degeneration."  (Application number TRAN1-11300)

The board is also expected to approve $5.1 million for an "autologous regenerative cell  therapy for blindness." The identity of that investigator has not yet been released by the stem cell agency. (Application number TRAN1-11265)

Summaries of the application reviews and scores can be found in this document.

Correction

Based on inaccurate figures on the stem cell agency web site, the NIH/CIRM sickle cell item on Oct. 9,2018, incorrectly reported that the agency had committed more than $200 million to sickle cell research. The correct amount is $38.8 million. CIRM said that the error was created by a computer glitch and that it has corrected the figures on its site. The item has also been corrected.