Mom to California: Thanks for 'Keeping My Family Complete' with Life-Saving Stem Cell Therapy

CIRM graphic

In an emotion-choked session this morning, the mother of a four-year-old girl thanked California's stem cell agency for saving the life of her daughter.

"Thank you for keeping my family complete," said Alysia Padilla-Vaccaro, her voice cracking as she spoke to the governing board of the $3 billion California Institute for Regenerative Medicine (CIRM), as the agency is formally known.

Her daughter, Evangelina, also whispered a soft "thank you"to the board and CIRM staff at the Oakland meeting. She had suffered from what is known as the "bubble baby syndrome."

Evangelina was one of two persons cured by treatments developed with the help of financing from the stem cell agency, created by voters in 2004 and supported by state bonds.

Brenden Whittaker, 22, was the second person. He was near death twice and lost parts of his lungs and liver as the result of another, rare, immune deficiency disease. He said,

"My experience has truly been life-changing...I hope you continue to push the boundaries and help as many people as you can."

Randy Mills, president of the agency, presented Whittaker and Evangelina to the board during a review of the progress of the agency. He said they were "the first two patients to be cured by CIRM programs."  Mills also introduced two other patients who have been helped by the agency's research: Jake Javier, who suffered a paralyzing spinal cord injury, and Karl Trede, a cancer patient. The agency has not developed a therapy for widespread use.

Mills hailed their courage and the courage of their families for taking part in the risky clinical trials. Mills told the 29-member CIRM board that in pursuit of stem cell cures that the agency had to be "Jake-strong," a term originating with Javier's mother after his injury.

The stem cell agency estimates it has $692 million left for new awards between now and 2020, when it expects to run out of cash. The research budget for next year was approved at $328 million with most of it going for clinical programs. Clinical trials represent the last stage for a proposed therapy before it reaches the market.

The CIRM board has approved a goal of 40 more clinical trials between now and 2020. Currently it has 22 underway. Only one out of 10 conventional treatments that begin trials wind up as commercial products. Often the trial process can take many years even with conventional therapies. No stem cell treatments have yet been approved by the Food and Drug Administration in this country.

Here is more on the patients featured at today's meeting:

Evangelina, of Corona, Ca., was diagnosed shortly after birth with "bubble baby" disease and no functioning immune system. Her blood cells were genetically altered to create a new blood and immune system. The therapy was developed by Donald Kohn of UCLA. CIRM has backed his work, which goes beyond the bubble baby affliction, with nearly $52 million. (See here, here and here.)

CIRM graphic

Whittaker, of Columbus, Ohio, almost died twice as a result of a rare immune system disease. Parts of his lung and liver were removed due to repeated infection. His blood stem cells were genetically modified to create a new blood system and a healthy immune system. The treatment was also developed by Kohn at UCLA.

Javier, 19, of San Ramon, Ca., was paralyzed as the result of a swimming pool accident. He received 10 million stem cells,the first person to have such an injection, and has since regained the use of his arms. His treatment grew out of the trial that Geron Corp. abandoned in 2011. Asterias Therapeutics of Menlo Park, Ca., has continued the work. Between the two companies, CIRM has invested nearly $21 million in the project. Jane Lebkowski has led the research at both companies.

Karl Trede, CIRM graphic

Trede, 70, of San Jose, Ca., lost his vocal cords, removed because of cancer of the throat.  The cancer nonetheless spread but was treated with the "eat me" protein therapy fromStanford University. As a result, his cancer has stopped growing. CIRM invested $40 million in the project, initiated by Irv Weissman of Stanford, who developed the CD47 treatment. It has led to the formation of a new company in Palo Alto called Forty Seven, Inc. (See here for a CIRM item on Trede.)
(For the text of CIRM summaries on the four, see here.)

(Editor's note: The earlier graphics in this item were replaced later with the ones that actually were displayed the day of the meeting. An earlier version also misstated Evangelina's age.)

The California Stem Cell Four: Text of Short Bios

Here is the text of the information provided by the California stem cell agency on the individual patients featured at today's meeting of its governing board. 

Brenden Whittaker 

Diagnosed with X-linked chronic granulomatous disease (X-CGD), a rare disease that causes the immune system to malfunction leaving it unable to fight off certain bacterial and fungal infections which, over time, can be life-threatening. Hospitalized hundreds of times over the years Brenden almost died on a couple of occasions and had part of his lung and liver removed due to repeated infection.
Brenden was cured thanks to an experimental procedure, developed by Dr. Don Kohn, that removed some of his own blood stem cells; they were then genetically modified to remove the gene that causes the problem, and then re-infused to him. The modified blood stem cells created a new blood system and a healthy immune system capable of fighting off infections. 

Evangelina Padilla-Vaccaro 

Evangelina was diagnosed shortly after birth with severe combined immunodeficiency (SCID); it’s also known as “bubble baby” disease because in the past children were kept in a sterile plastic bubble to protect them. It’s a rare – and often deadly -- genetic disorder that meant she had no functioning immune system, leaving her vulnerable to infections. Many children with this condition die within the first year of life.
Evangelina was cured as part of a clinical trial at UCLA run by Dr. Don Kohn. She underwent a stem cell transplant that took her own blood stem cells, genetically re-engineered them, and returned them to her body.  These re-engineered stem cells created a new blood and immune system.
(Evangelina’s parents are Alysia and Christian, her twin sister is Annabella) 

Jake Javier
An accident at a friend’s pool party on the eve of Jake’s high school graduation left him paralyzed from the chest down with no ability to use either his arms or hands.
On Thursday, July 7th, Jake Javier became a member of a very select group. Jake underwent a stem cell transplant, getting 10 million stem cells transplanted into his neck at Santa Clara Valley Medical Center in San Jose. Since then Jake has regained use of his arms and is working hard to regain even more use.

Karl Trede 

In 2006 Karl was diagnosed with cancer of the throat, he had the tumor and his vocal cords removed. Several years later they found the cancer had spread to his lungs so Karl became patient #1 in a clinical trial at Stanford.
The trial used a monoclonal antibody to target a specific protein on a cancer cell called CD47. This protein tricks the immune system into not attacking the cancer, earning CD47 the nickname from the Stanford researchers as the “don’t eat me” protein. The monoclonal antibody disables CD47, leaving the cancer vulnerable to being attacked by the patient’s own immune system. The therapy stopped Karl’s cancer from growing. 

California's Stem Cell Research Pot Shrinking to Only $692 Million

Highlights
$328 million for 2017 awards
Clinical research to jump to $215 million
New award cash runs out in 2020

The California stem cell agency is now down to its last $692 million after starting out 12 years ago with $3 billion and the promise of generating therapies that could help as many as nearly half of the state's families.

As of today, the agency -- formally known as the California Institute for Regenerative Medicine (CIRM) -- has yet to produce a widely available therapy.  But it has helped to fund treatments that have saved individual lives during the research process, and it is backing 22 clinical trials.

The state of the stem cell agency's finances was reported as part of the agenda for today's governing board meeting in Oakland. On tap is a recommendation from Randy Mills, president of CIRM, that the board approve spending $328 million for research awards in 2017.

Also expected to be discussed are some of the success stories of CIRM, which was created through a ballot initiative in 2004. Voters were promised during the $34 million campaign that "cures will be coming soon."  Backers of the initiative said that nearly half of all California families include a person who suffers from a condition that could be treated with stem cell therapies.

CIRM documents prepared for today's meeting showed that this year the agency awarded nearly $262 million for research. The largest amount -- $87.1 million -- went for clinical level programs.   Basic research, called "discovery" by CIRM, received nearly $47 million, slightly above the $43 million for education. Translational research received nearly $55 million while an infrastructure program chalked up $30 million.

For 2017, clinical programs would jump to as much as $215 million under Mills' proposal. Discovery would come in at $52 million, translation at $45 million, infrastructure at $16 million (two new Alpha stem cell clinics) with no awards for education. None of the awards are for buildings or labs.
The total would be $328 million.

That would leave $364 million in awards for 2018 through 2020, assuming the agency's budget projections come in as expected.

The agency has about $528 million in uncommitted funds. However, "returns" from awards are expected to raise the available amount for awards to $692 million. Returns of cash are generated when researchers do not meet funding benchmarks or when an award is terminated early for whatever reason.

The agency is funded through state bonds. Those will run out for new awards in 2020, according to CIRM estimates.

As of the end of the year, the agency projects it will have 255 awards under active management with a value of $406 million.

California's Stem Cell Year: 70 New Projects, 10 New Clinical Trials Plus a 'Stem Cell Pitching Machine'

The California stem cell agency weighed in today with an upbeat prelude to a review of its performance in 2016, declaring it a "very productive year" that is counting 10 new clinical trials.

And Gov. Jerry Brown, in a short note to the agency, said that he looked "forward to its continuing success."

Brown, who is famously careful with words, made his very brief comment in a letter renominating Jonathan Thomas as chairman of the $3 billion agency, formally known as the California Institute for Regenerative Medicine or CIRM.

Karen Ring, website and social media manager for CIRM, had a little more to say in a piece today on the agency's blog, The Stem Cellar. Her comments came on the eve of the CIRM board meeting in Oakland tomorrow, which includes a self-assessment of the state of the 12-year-old research effort. 

Ring noted that the agency is on target to meet its ambitious goal of helping to fund 50 new clinical trials through 2020. The board has backed eight trials so far this year and is virtually certain to add two more tomorrow at a cost of $14.9 million. In all, the agency is currently supporting 22 clinical trials, which are the last stage of research prior to bringing a therapy to market. Trials, however, can take years.

Declaring 2016 a "very productive year," Ring wrote that this year CIRM funded "70 promising stem cell projects ranging from education to discovery, translational and clinical projects."  She said that the eight board-approved trials include potential therapies for muscular dystrophy, kidney disease, primary immune diseases, and multiple types of cancer and blood disorders.

She also singled out a $30 million effort this year that Randy Mills, president of the agency, believes could be its most significant achievement. Mills sometimes calls it a stem cell "pitching machine."

Ring said,

"Collectively called The Stem Cell Center, the goal of this new infrastructure is to increase efficiency and shorten the time it takes to get human stem cell trials up and running."

No other state has mounted such an effort. The agency predicts that it could make California the world leader in the stem cell field, which is predicted to generate hundreds of billions of dollars globally by 2020 by some, perhaps optimistic accounts.

Regarding the two new clinical trials, already approved by the agency's reviewers, Ring said,

"The first trial is testing a stem cell treatment that could improve the outcome of kidney transplants. For normal kidney transplants, the recipient is required to take immunosuppressive drugs to prevent their body from rejecting the donated organ. This clinical trial aims to bypass the need for these drugs, which carry an increased risk of cancer, infection and heart disease, by injecting blood stem cells and other immune cells from the kidney donor into the patient receiving the kidney. You can read more about this proposed trial here.

"The second clinical trial is a stem cell derived therapy to improve vision in patients with a degenerative eye disease called retinitis pigmentosa. This disease destroys the light sensing cells at the back of the eye and has no cure. The trial hopes that by transplanting stem cell derived retinal progenitor cells into the back of the eye, these injected cells will secrete factors that will keep the cells in the eye healthy and possibly improve a patient’s vision. You can read more about this proposed trial here."

Names of the recipient researchers have been withheld by the agency until the board tomorrow ratifies the decisions by its reviewers.

Upcoming: Full Coverage of California Stem Cell Agency Meeting Tomorrow

Check in here tomorrow with the California Stem Cell Report for gavel-to-gavel coverage of the meeting of the governing board of the $3 billion California stem cell agency -- a day-long session that will include a review of its performance this year and its path for 2017.

The meeting will be based in Oakland and will be covered live  by the California Stem Cell Report from Mexico via the agency's audiocast and online accessibility.

The session is expected to lay out upcoming rounds of awards of interest to both researchers and patients. Stories will be filed as warranted throughout the day.

For those interested in attending and participating in the session either in Oakland or at three teleconference locations in Los Angeles and the San Diego area, addresses can be found on the agenda. It also contains instructions for logging into the audiocast and Internet to see the slides being used.

FDA Stem Cell Regulation: A Pitch for 'Not Too Hot and Not Too Cold'

Members of the California stem cell agency team last week were at the World Stem Cell Summit in Florida, telling the story of the Golden State's research effort.

Something like 1,000-plus people were in attendance at the conference, and Kevin McCormack, senior director of communications for the stem agency, was one.

McCormack filed a report about FDA regulation of stem cell research for the agency's blog, The Stem Cellar. 

He quoted Martin McGlynn, former CEO of StemCells, Inc., of San Leandro, Ca., as saying the rest of the world is moving more rapidly to bring stem cell therapies to the marke, citing Japan, China and Australia.

They are not exactly the three bears of the childhood story. But Goldilocks did come up at the meeting a little later. McCormack wrote,

"Marc Scheineson was the final speaker. He heads the food and drug law practice at Washington, DC law firm Alston & Bird and is a former associate commissioner for legislative affairs at the FDA.... 

"Scheineson says part of the problem is that the FDA was created long before cell therapy was possible and so it is struggling to fit its more traditional drug approval framework around stem cell therapies. As a result, this has led to completely separate regulatory processes for the transplantation of human organs and blood vessels, or for the use of whole blood or blood components. 

"He says it’s like the fable of Goldilocks and the Three Bears. Some of the regulation is too hard- resulting in a lengthy regulatory process that takes years to complete and costs billions of dollars – and some of the regulation is too soft allowing clinics t open up around the US offering unproven therapies. He says we need a Goldilocks approach that blends the two into regulations that are just right."

California's Stem Cell Research Spending Up for Review Next Week

If you are interested in how the state of California is going to spend its final $800 million or so on stem cell research, you should catch a key meeting next Tuesday in Oakland, which also can be heard online.

The session involves the 29-member, governing board of the $3 billion California Institute for Regenerative Medicine (CIRM), as the state stem cell agency is formally known.

The agency was created by California voters in 2004 with voters' expectation that stem cell therapies were all but just around the corner. So far, no therapies have been developed by the agency that are available for widespread use.

Nonetheless, the agency, which runs out of money in 2020, is pushing hard. It has more than 20 clinical trials underway, which is the last step in bringing a therapy to market. However, those trials can take years with no guarantee that a proposed product will emerge successfully.

On tap on Tuesday will be a look at the agency's research plans for the next three years with a review of how it has performed so far in 2016. The agency's proposal for research spending in 2017 is likely to have a significant impact on the hundreds of stem cell researchers in California. The proposal is not yet available online, however, with only two business days left before the meeting.

CIRM is also hinting that there will be some surprises at the meeting, but it is unlikely that a product announcement will be forthcoming.

Additionally on tap are applications for a total of $14.9 million for two early-stage clinical trials. One is for $6.7 million (CLIN2-09439) to test using stem cells and T cells to eliminate the life-long need for immunosuppresive drugs by kidney transplant recipients. The other (CLIN2-09698) is for $8.3 million for a mid-stage trial (2b) for a therapy for retinitis pigmentosa.

The applications were approved for funding by the agency's grant reviewers, who meet behind closed doors and do not publicly disclose their economic or professional interests. Ratification of the reviewer decisions is a formality for the agency. although the names of the recipients are not generally disclosed prior to board action.

The board is expected to re-elect Jonathan Thomas as chairman of the panel. Thomas was elected to the position in 2011. He has sent a  two-page letter to the board detailing his work during the last five years. Also scheduled to be re-elected is Art Torres as vice chairman.

Thomas receives $400,000 annually for his "80 percent effort" in the part-time position. Torres, a former state lawmaker, receives $225,000, also for an "80 percent effort."

Instructions for listening to the meeting online can be found on the agenda. In addition to main meeting site in Oakland, public telephonic locations exist in San Diego and La Jolla. Specific addresses can be found on the agenda.

Voting Underway for Stem Cell Person of 2016

The latest tally of voting for the stem cell person of the year shows that patient advocate Ted Harada, who died in October, is leading with 47 percent of the vote with the nearest contender at 11 percent.

However, only one vote counts since this is not a democratic election. The sole individual choosing the stem cell person of the year is Paul Knoepfler, a stem cell scientist at UC Davis.

Knoepfler originated the award a few years back and personally puts up $2,000 in prize money. He has compiled a list of 20 possible honorees, ranging from patient advocates to researchers. Voting is advisory only. Deadline for the ballot is 11:59 p.m. Dec. 15.

Knoepfler wrote on his blog last month about Harada, who was an ALS patient advocate. Knoepfler said,

"Ted approached all that life threw at him, whether it was ALS or a brain tumor, with a characteristic passion, sense of humor and classiness. I don’t recall anyone dealing with adversity as well as Ted did and I never heard him say anything like, 'why me.' Instead there was always kindness and grace."

Distant second to Harada this morning was Randy Mills, president of the $3 billion California stem cell agency.

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

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

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

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

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

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

Thomas wrote,

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

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

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

Robert Klein, Americans for Cures
photo

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

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

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

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

California Approves $15 Million for Stem Cell Research Ranging from Arthritis to Alzheimer's, But Not Without a "Hair-Cut"

Highlights
Snafu in November
Ankasa whacked
Across-the-board cuts rejected

After a hiccup last month, the California stem cell agency today coughed up $15 million for a quartet of researchers looking into Alzheimer's disease, cartilage repair, arthritis and sickle cell disease, but not before lopping off a big chunk of one proposal.

Action by the governing board of the $3 billion agency came after a snafu at its Nov. 17 meeting. The proposals, all previously approved by the agency's reviewers, hit a roadblock when the budgeted cash was not enough to fund all four. The session last month also stalled as a result of quorum problems and research priorities.

Normally applications approved by reviewers during their closed-door sessions slip through the later public meetings of the agency board with no discussion. But this time around, reviewers approved the four applications, but gave one of the researchers a sizable, financial "hair cut."

Despite concerns about fairness and imposing new conditions on applicants, the board stripped $1.6 million from a $3.7 million application to develop a stem cell therapy for osteoarthritis by Ankasa Regenerative Therapeutics of La Jolla.

The action came after the lead researcher, Jill Helms of Stanford, said her company would make up the shortfall.  She made the comment after being told she could re-submit the application, which was the last to come up for a vote. She indicated that she would prefer to pursue that route rather attempting a problematic and "onerous" re-application with a new set of reviewers early next year.

The other three applications were approved with full funding after a motion to cut all four by about 10 percent failed on a 1-9 vote with one board member abstaining. Board members used the term "hair cut" to describe the reductions, which the applicants would have to make up.

Helms' application was the only one in this round from a business. The others came from non-profit institutions.

Randy Mills, president of the California Institute of Regenerative Medicine or CIRM as the stem cell agency is formally known, opposed the 10 percent cuts on all four awards. He said he and his staff did not want to see programs cut "on the fly." He said applicants were not told that they would have to come up with matching funds when they originally applied.

The other three researchers winning awards are Yadong Huang of the Gladstone Institutes, $6 million for Alzheimer's;  Mark Walters of Children's Hospital, Oakland, $4.5 million for sickle cell, and Denis Evseenko of USC, $2.5 million for cartilage repair.

All the awards went to researchers or institutions that have links to persons who sit on the 29-member board. Overall, about 90 percent of the money awarded by CIRM since 2004 has gone to institutions with ties to past or present board members. While board members set rules for funding and the scope of awards, they are not allowed, however, to vote on specific applications from institutions with which they are connected.  

Summaries of reviewers comments, scores and more can be found on this document from CIRM, which is based in Oakland.  Here is a link to the CIRM press release.

Dubious Stem Cell Therapies Attract Coverage in California's Capital

The leading newspaper in California's state capital this weekend published a lengthy piece exploring the world of unproven stem cell therapies, including one being offered in its own backyard. 

Reporter Claudia Buck of The Sacramento Bee wrote,

"For long-suffering patients...stem cells offer tantalizing hope. In the last few years, more than 570 stem cell clinics have popped up nationwide, advertising treatment for a range of maladies, from autism and Alzheimer’s to neuropathy and Parkinson’s disease, according to a recent UC Davis study. About 113 of those are operating in California. 

"But do they really work? According to most stem cell experts and the federal government, there’s no way to know yet."

Buck quoted Kevin McCormack, spokesman for the California stem cell agency, as saying,

“It’s quite clear that these people are offering treatments that haven’t been tested in clinical trials. It’s a little concerning,”

Buck wrote,

"'My view is that it’s a giant human experiment that doesn’t have FDA approval,' said Paul Knoepfler, a UC Davis stem cell expert, who co-authored the study identifying the 570 clinics. 'I don’t know how much patients are aware of how uncertain the benefits and risks are. As a scientist, it’s worrisome.'"

Knoepfler, who publishes a blog on stem cell matters, has written in the past about advertising in The Bee by a stem cell business called Nervana. The firm was mentioned in Buck's article, which, however, did not note that Nervana has taken out full page advertisements in the past in The Bee.

Knoepfler's most recent piece on Oct. 21 also noted that the firm had taken out a full page ad in the San Diego Union Tribune as well.  The UC Davis researcher said at the time,

"I don’t believe there is a solid, medical or scientific basis for what they are selling."

Stem Cell Suspense to End Dec. 5 for Four California Researchers

Four California stem cell researchers could well receive a total of $16.6 million in awards next week from the Golden State's 12-year-old stem cell program.

The researchers were caught in a bit of a snafu earlier in November when the $3 billion agency appeared to come up $1.6 million short. The story about the snag also involved quorums, priorities and fiscal discipline, more than is necessary to discuss right here in this item. But you can read all about it here. 

The two researchers identified so far are Yadong Huang of the Gladstone Institutes, Jill Helms of Stanford and Ankasa Regenerative Therapeutics of La Jolla.  The identities of the others are being withheld by the stem cell agency.

Whether all four will receive funding will be determined on Monday Dec. 5 when the stem cell agency's board will hold a telephonic meeting out of its base in Oakland. The agenda gave no indication of how the agency plans to overcome the difficulties that stymied it on Nov. 17.

The public can attend the meeting at the agency's headquarters in Oakland or from telephonic locations in Napa, Beverly Hills, Elk Grove, Los Gatos, Irvine, Sacramento and two each in South San Francisco and San Diego.

The session is also expected to be audiocast on the Internet. More information and addresses can be found on the agenda.

Quartet of Researchers Snagged in Budgeting, Parliamentary Web at $3 Billion California Stem Cell Agency

Highlights
Fiscal discipline at CIRM
The 10 percent solution
A quorum shortage pops up

Four California scientists who are ready to kick off highly rated projects to treat everything from Alzheimer's to rotting jaw bones became tangled last week in a financial and procedural briar patch involving the directors of the $3 billion California stem cell agency.

The basic problem, however, was simple. Money.

The agency had budgeted only $15 million for this latest round of awards last Thursday. But the four applications -- already approved by the agency's reviewers -- totalled $16.6 million. Typically, the agency's full board rubber stamps in public the decisions of its reviewers, who act behind closed doors without disclosing their economic or professional interests. The board has reversed approvals by reviewers on only four occasions out of hundreds of awards over the past 12 years, according to the agency.

Last week, the chairman of the agency, Jonathan Thomas, began the public discussion by declaring that the board should go through the applications one by one and vote on them. When the money ran out, that would finish action on funding for November.

Fiscal discipline was cited as the main reason for such a course.

Steve Juelsgaard 

Wait a minute, said Steve Juelsgaard, a member of the board of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known. He asked for the amount of
funding already being provided for the afflictions targeted by the proposals. If research in a particular area was already heavily supported, perhaps approving another award in that area was not necessary, Juelsgaard reasoned. However, the agency staff could not provide those figures at the time of the meeting.

A lengthy discussion followed involving several scenarios. One would have cut each award by 10 percent but approve all four.  But that could mean that the proposals would be altered from the versions that were approved by the reviewers. (However, the board is not legally required to accept what the reviewers decide.  Under the terms of the ballot initiative that created the agency, the board has the final say, which is part of the justification for not publicly disclosing the economic interests of reviewers.)

Another proposal would have simply increased the funding for the round. That could not be acted on because it required 10 days advance public notice.

The board ultimately approved a Juelsgaard motion to slice roughly 10 percent from each award with the condition that applicants come up with matching funds to bring the total to the level approved by reviewers.

Yadong Huang, Gladstone photo

One applicant, Yadong Huang from the Gladstone Institutes, said, however, that non-profit research organizations were already hard-pressed and could not necessarily come up additional cash. His $5.9 million application (TRAN1-09394) was top-ranked by reviewers and targeted Alzheimer's.

Jill Helms, Linked In photo

Another applicant, Jill Helms, chief scientific officer of Ankasa Regenerative Therapeutics, Inc., of La Jolla, spoke on behalf of the company's application (TRAN1-09270) to target osteonecrosis, an affliction that "causes jaw bones to rot and thigh bones to snap." She urged the board to give priority to applications that already had co-funding. Her $3.7 million application contained a 20 percent co-funding component.

Helms, who is also a Stanford University medical school professor, unsuccessfully asked the CIRM board in 2015 to overturn a negative recommendation by reviewers.

During the two-hour telephonic meeting, the board did approve conditionally two awards under the matching-fund requirement. They were for the Alzheimers proposal and one dealing with sickle cell disease (TRAN1-09292).  The identity of the chief scientist on the sickle cell proposal was not disclosed by the agency under its longstanding policy and tradition within the research field.

Jeff Sheehy, Science photo

The board failed to complete action on the two others because it  lost the quorum that is required to do business legally. That came after a motion by board member Jeff Sheehy to reject one of the four applications failed on a 3-8 vote. Sheehy said another related proposal was already being funded by the agency and that the time to translate the research into a therapy  "would be enormous." The $2.5 million application  (TRAN1-09288) up for consideration last week involved cartilage repair.

Thursday's meeting was being conducted telephonically. After Sheehy lost his motion, he did not respond to telephonic queries from the board. The meeting was nearing its scheduled end at noon. Other board members also failed to respond, and the meeting was adjourned minutes later.

Juelsgaard and some other members said it was important for board members to stick around for the full meetings. Juelsgaard said,

"For gosh sakes, this is something that you signed up to do."

Termination of CIRM board business because of quorum problems regularly occurred some years ago. (See here, here and here.) But since Thomas has been chairman the issue has rarely popped up.

Thomas indicated the board would try to schedule a special telephonic meeting to deal with the four applications. It also has a face-to-face meeting scheduled for Dec. 13 in Oakland. Both meetings legally require 10 days advance notice.

The review summaries on the applications are consolidated in this CIRM document along with their scores and more information.

$3 Billion California Stem Cell Agency Now Involved in 23 Clinical Trials

The California stem cell agency yesterday pumped $38 million into three clinical trials with the hope that it will lead to therapies for colorectal cancer, "bubble boy" syndrome and a form of high blood pressure.

The action brought to 23 the number of current clinical trials in which the $3 billion agency is participating via funding in whole or in part, according to information on its Web site. It is hoping that one of those trials will produce its first widely available stem cell therapy.

The trials deal with afflictions ranging from HIV and Huntington's Disease to blindness and skin cancer.

The agency's cash for new awards will run out in about three years. The California Institute for Regenerative Medicine (CIRM), as the agency is formally known, has been in business since 2004 when voters created the agency through a ballot initiative.

Yesterday's funding was expected and largely reported earlier this week by the California Stem Cell Report (see here and here). Yesterday, the agency's board simply ratified -- in a matter of minutes -- decisions in October by its grant review group, which makes the de facto decisions on awards behind closed doors and without publicly disclosing the economic and professional interests of reviewers.

Here is a link to the press release from the agency and a link to its blog item. Here are links to the review summaries of each proposal: colorectal, bubble boy and blood pressure.

The summaries were the only information that the board had in approving the three grants.

During its telephonic meeting yesterday, the board also became entangled in a budgeting and priorities debate involving four translational research proposals, all of which the agency now says are hanging fire. An effort is being made to schedule a special board meeting soon to deal with the issue, but it requires 10-days advance public notice. The California Stem Cell Report will have a full report later on the situation.

Correction

The $20 million "bubble boy" item on Nov. 16, 2016, incorrectly reported that co-funding on the award totalled $8.9 million. The correct figure is $18.2 million.

California Pumping $20 Million into Stem Cell/Gene Therapy for 'Bubble Boy' Syndrome

June 2016 video from UCLA

Highlights
30 out of 30 cured
$18.2 million in matching funds
Cells to be frozen
UK's Orchard Therapeutics partnering

California's stem cell agency is ready to award $20 million on Thursday to a UCLA researcher to assist in his 30-year search for a widely available cure for what has come to be known as the "bubble boy" syndrome-- severe combined immunodeficiency (SCID).

The California scientist is Donald Kohn, of the Broad Stem Cell Research Center at UCLA, who said today that 30 out of 30 babies have already been cured using his type of therapy. Kohn said that the research involving the extremely rare disease could lead to progress in treating other afflictions ranging from sickle cell disease to cancer.

The progress in treating the "bubble boy" disease is much changed from decades ago when the case of David Vetter captured the nation's attention as the boy who was "born into a world he could not touch."  He ultimately died at the age of 12. (This item continues below video.)

Kohn's proposal for an early stage clinical trial would be co-funded with $18.2 million and would test a stem cell and gene product known as OTL-101. It could replace what the stem cell agency said were the "suboptimal," current treatments for  Adenosine Deaminase Severe Combined Immunodeficiency.

The affliction is extremely rare and occurs in less than one in 100,000 births worldwide, according to Wikipedia. Without treatment, children can die before the age of two.

The agency's application review summary said that reviewers were "highly enthusiastic" about Kohn's proposal during their closed-door session last month. The summary said that reviewers, who are from out-of-state and do not publicly disclose their economic interests, "applauded the move to a cryopreserved product that will allow improved patient access to the therapy." They also noted that the costs of the trial are "exceedingly high."

In response to a query by the California Stem Cell Report, Kohn said today via email, 

"Building upon the previous success of our single-site trials for ADA SCID, which have resulted in 30 out of 30 babies cured, our next trial will focus on developing a cryopreserved formulation of the cell product. 

"This has several potential advantages. It will allow the cell product to undergo full testing before the transplant is performed, whereas currently we only have stat viability, sterility and endotoxin assay results, with gene transfer efficiency measurements coming later.

"Additionally, it provides more time to split up the dosing of the conditioning chemotherapy and individually adjust the total dose based on measurement of the individual patient's unique drug clearance activity.

"Finally, this will allow centralization of cell processing, allowing patients to remain at their local hospital for the treatment, with the stem cells traveling to a commercial cell processing site, gene-corrected, frozen and shipped back to their hospital for infusion."

The agency's board is virtually certain to ratify the decision of reviewers at its telephonic meeting on Thursday. It has almost never overturned a positive recommendation by reviewers. 

The agency, formally known as the California Institute for Regenerative Medicine (CIRM), did not release Kohn's name in advance of the Thursday meeting. Its policy, with some notable exceptions, is to withhold that information until the pro forma vote by its governing board. The California Stem Cell Report identified Kohn as the recipient through a number of public documents. The UCLA researcher has already received $32 million from CIRM for his work. 

Kohn has teamed with Orchard Therapeutics Ltd. of Britain, a firm that began operations last May with a $33 million war chest. Kohn is one of the scientific advisors to the company. He said today: 

"This study is being done at the UCLA Broad Stem Cell Research Center in partnership with Orchard Therapeutics Ltd., who have licensed this stem cell gene therapeutic from UCLA and University College London, UK. The general approach of stem cell gene therapy was first done for ADA SCID, which is a highly favorable disease for this treatment. Findings and advances made for this disorder are being applied to many other inherited diseases, such as Sickle Cell Disease, other Primary Immune Deficiencies, Storage and Metabolic Diseases, as well as HIV/AIDS, cancer and leukemia."

The process uses a patient’s own stem cells. Earlier this year, the company said that the cells are "modified with a functioning copy of the missing or faulty gene before being transplanted back into the patient’s body. The use of the patient’s own cells (autologous) removes the need to search for a matching stem cell donor, which can take months or even years," the company said.

Should the treatment emerge successfully from the clinical trials, it will face competition from a rival developed by GlaxoSmithKline that has been approved for use in Europe at a reported cost of $665,000 per patient. Glaxo is expected to seek approval next year for use of the treatment in the United States, which has only about 12 new cases a year, according to the STAT health science news service. However, a document from the U.S. Center for Disease Control places incidence at 40 to 100 new cases each year. 

The public can participate in Thursday's meeting at locations in Oakland, San Francisco, San Diego, Napa, South San Francisco, San Francisco, Beverly Hills, Fresno, Elk Grove, Los Gatos, Sacramento, and Irvine.  It is also being audiocast on the internet. Instructions and addresses can be found on the agenda.

(Editor's note: An earlier version of this item incorrectly reported that co-funding on this award totalled $8.9 million. The correct figure is $18.9 million.)

$10 Million 'Eat Me' Award: California Stem Cell Agency to Firm Called Forty Seven

The California stem cell agency is set this week to award $10 million to a Menlo Park firm to help finance a clinical trial for a therapy for colon cancer, which is the second leading cause of cancer death in this country.

The cash will go to Forty Seven, Inc., an enterprise using an immune system, "eat me" technology developed at Stanford University by stem cell scientist Irv Weissman. The firm is adding $6.8 million of its own cash to the project. Weissman has received $30 million over the years from the state agency.

The application to help with an early stage clinical trial was unanimously approved by the agency's scientific reviewers during a closed-door meeting last month. The full board will ratify the action at its telephonic meeting this Thursday. 

The agency, formally known as the California Institute for Regenerative Medicine(CIRM), has almost never overturned a positive decision by its reviewers.

The $3 billion agency does not release the names of successful applicants prior to board action. Forty Seven was identified through the use of public records.

According to a federal Web site,

"This trial will evaluate Hu5F9-G4 in combination with cetuximab. Hu5F9-G4 is a monoclonal antibody which is designed to block a protein called CD47, which is widely expressed on human cancer cells. Blocking CD47 with Hu5F9-G4 may enable the body's immune system to find and destroy the cancer cells. Cetuximab is a monoclonal antibody drug that is used for treatment of certain types of colorectal cancer as well as head and neck cancer."

The idea is to override a tumor's "don't-eat-me" signal and instead trigger the body's "eat-me" response.

California's scientific reviewers expressed high praise for the project. However, they also said,

"The design of the trial itself is fine, but the decision-making process is sub-optimal. It is critical to include clear go/no go criteria for the second phase of the trial and for the data to be evaluated by an independent, objective third party for a decision as it is unclear what toxicities are expected given the proposed new mechanism of action and use of a combination therapy." 

Forty Seven announced last February that it is backed by $75 million from a variety of partners including Google. Others in the venture capital group are Lightspeed Venture Partners, Sutter Hill Ventures (the two leaders on the financing) and Clarus Ventures.

In August, Karen Tkach wrote in BioCentury:

"With companies lining up to block CD47 for cancer, the cell surface protein is emerging as one of the top new targets in oncology. But the list of suitors could be about to get a lot longer as the target could have uses in a much broader range of indications, according to two studies from Stanford University that extend its prospects to cardiovascular disease and transplant biology, and hint at roles in several more diseases."

According to the clinical trial information on a federal Web site, Forty Seven will have clinical trial locations in Grand Rapids, Mich.; San Antonio, Texas, and Nashville, Tenn.  The California stem cell agency is limited to spending its award for work done in California. 

The federal information has conflicting indications on whether patients are currently being recruited for enrollment in the trial.

(In response to a query following publication of this item, Mark Chao, a co-founder and medical

Mark Chao, Stanford photo

director of Forty Seven and co-PI on the trial, said,

"We have been excited about the positive reviews by the CIRM committee and hope to hear good news on Thursday. Thank you for sending this article. With regards to initiating California clinical sites on the trial, this is a very big point of emphasis for us, in particular with CIRM’s mission and are currently working to activate two sites in California (Stanford University and UCLA) for the trial. One of our goals are to bring this therapy to patients within California and have designed our trials with this in mind. Please let us know if there are any further questions we can address. We look forward to a long relationship with CIRM.")

The chair of the study is Chris Takimoto of Forty Seven. The CIRM application number is CLIN2 -09577.

Trump's 'Ouija' Stem Cell Policy Is Making Scientists Anxious

One of the bulwarks of the mainstream media today weighed in with a hefty assessment of Trump and stem cells, declaring that researchers are "anxious" about what is likely ahead.

Prominently mentioned by ABC News was Vice President-elect Mike Pence, who supported legislation in Indiana banning donation of fetal tissue for research. That law, signed by Pence as governor of Indiana, was temporarily halted by a judge, who questioned its constitutionality.

Alta Charo, a bioethicist and law professor at the University of Wisconsin, was quoted as saying that trying to determine what Trump's stem cell policy might be is a "little bit like using a Ouija board." But she did point to Pence's fetal tissue position.  Additionally, Trump has taken a pro life position on abortion.

Also cited in the article at some length was a spokesman for the $3 billion California stem cell agency, which owes its existence to presidential restrictions on human embryonic stem cell research. ABC reporter Gillian Mahoney wrote,

 "Kevin McCormack, communications director at California Institute for Regenerative Medicine, said reintroducing a funding ban to stymie research would likely be more difficult than it was in the early 2000s when stem cell research was a new field.

"'It would be like putting a genie back in the bottle,' said McCormack.

"Pointing to one case at the University of Southern California, where a paralyzed man regained hand movement after an experimental stem cell therapy, McCormack said any measures that would halt funding or restrict stem cell research wholesale, 'would be like going up to someone and say you can't have that treatment.'

"McCormack did note that more states have provided stem cell funding, including California, which provides grants for the California Institute for Regenerative Medicine. While state funding could help, the NIH provides a huge amount of funding for U.S. medical research, spending approximately $32 billion on medical research annually."

(Editor's note: The state does not provide grants for the stem cell agency. The agency uses state bonds to provide grants to researchers.  The agency's funding flows straight to it without intervention by lawmakers or the governor.)

Trump on Science and Biotech: Wild Card, Chilling or NIH Slasher?

Reaction today from the world of science, stem cells and biotech to the election of Donald Trump as president ranged from "party time" to "chilling" impact.

Here is a sampling of articles today that dealt with the implications of the billionaire's victory.

Dylan Scott wrote in Stat:

"Should President Donald Trump make drug makers relieved? Or anxious? They’re not sure."

Stat also carried a related piece by Damian Garde who said that Trump is a wild card who could side with those who want to cut back on federal funding of research.

An article in Science by Jeffrey Mervis quoted Robert Cook Deegan, a research scientist at Arizona State University, as saying,

"Science won't get much attention, except when it gets in the way or bolsters support for a political priority."

Adam Feuerstein wrote in The Street:

"Half the country woke up Wednesday depressed about President-elect Donald Trump. That group doesn't include investors in biotech and drugs stocks. They are partying like a giant drug-pricing cloud has been lifted from their shoulders."

An article in Nature by Jeff Tollefson, Lauren Morello and Sara Reardon had this:

"'I think at the very least it would put a chilling effect on the interest of scientists from other countries in coming here,' says Kevin Wilson, director of public policy and media relations at the American Society for Cell Biology in Bethesda, Maryland. Some researchers are already thinking about leaving the United States in the wake of the election."

An overview piece by Sarah Kaplan in the Washington Post had this line:

"Last year, Trump told conservative radio host Michael Savage, 'I hear so much about the NIH, and it’s terrible.'"

Yours truly wrote earlier today that Trump's victory could translate to good news for California's $3 billion stem cell agency. (That piece can also be found on Capitol Weekly.)

Trump: Helpmate to the $3 Billion California Stem Cell Agency?

Donald Trump's victory last night, oddly enough, could be good news for the future of the California stem cell agency. 

It could be George Bush all over again.

How does that work, you may ask? Trump is a bit of a blank slate on stem cell issues. He has not addressed them directly. But he is pro-life, a fact being celebrated this morning in the usual pro-life venues.

Given that stance, he is likely to reverse the federal government's current funding of human embryonic stem cell research. It would be easy to do, basically nothing more repealing an executive order or issuing a new one.

Such a move would echo the Bush restrictions on human embryonic stem cell research that provided the justification for the 2004 ballot initiative that created California's $3 billion stem cell research effort. Bush's opposition energized the scientific and patient communities on behalf of the initiative.

His opposition also helped to raise the $34 million for the electoral campaign that spawned the California Institute for Regenerative Medicine (CIRM), the official name of the stem cell agency.

Bush provided a big target for supporters of stem cell research. (See here and here.) He embodied the essence of the "anti-science" crowd. And in politics it is good to have a "demon" that can easily be understood. It simplifies issues, sharpens the focus and stimulates voters.

The stem cell agency is now on track to run out of money in 2020 for new awards. CIRM relies on state bonds for its cash but its ability to issue them is coming to an end. No additional source of funding has been identified.

Assuming Trump bans federal research on human embryonic stem cell research, it would bring new life to the possibility of another multi-billion dollar bond issue in the next few years. A new "demon" would surface. All the agency needs to do now is to come up with a high-impact therapy that would resonate with California voters.