Monday, August 20, 2018

CEO Millan Makes the Case for California's $3 Billion Stem Cell Research Program

Maria Millan, CEO of CIRM, at state Assembly hearing last week
The top executive at California $3 billion stem cell agency, which expects to run out of cash for new awards next year, outlined for state lawmakers last week the benefits of the nearly 14-year-old program.

Maria Millan, president and chief executive officer of the California Institute for Regenerative Medicine (CIRM), as the agency is officially known, laid out how the agency funds "the most innovative, high risk but high reward" stem cell research in the state.

Millan highlighted some of the 49 clinical trials backed by CIRM. She said,
"Every single trial represents a tremendous breakthrough approach that was unimaginable and even the subject of science fiction just years ago."
She also discussed the agency's relationship with the stem cell industry in backing research during a risky financial stage called "the valley of death." She said,
"CIRM supports and de-risks through this stage, where industry and traditional investors are not yet ready to come in. By accelerating development and allowing these early stage trials to proceed with CIRM funding, we have enabled the projects to gain visibility and interest leading to an increase in industry investments."
Her presentation was generally well received by the five lawmakers who were in attendance at various times during the meeting of the Assembly Select Committee on Biotechnology, chaired by Kevin Mullin, D-San Mateo.

The full hearing can be seen here and downloaded with closed captioning. An audio file is also available at the same URL. Tomorrow the California Stem Cell Report will carry the text of remarks by Art Torres, vice chairman of the agency and a former state legislator.  This writer was also invited to appear at the session. My remarks can be found here.

Here is the full text of Millan's comments.
Remarks by Maria Millan, President of CIRM, To California Assembly's Select Committee on Biotechnology 2018... by DavidJensen on Scribd
Sphere: Related Content

Friday, August 17, 2018

A California Stem Cell Tale: The Search for a Treatment for Paralyzing Spinal Injuries

Ed Wirth of Asterias, photo by Gabrielle Luri, SF Chronicle 
The San Francisco Chronicle, in a lengthy and dramatic article this week, reported on the story of the first clinical trial in the United States for a human embryonic stem cell treatment, a tale that continues today and well into the years ahead. 

The story involves paralyzing spinal injuries, incurable afflictions, walking rats, Geron, Asterias Biotherapeutics and BioTime and the economics of development of a stem cell therapy. That is not to mention the California stem cell agency, which has pumped more than $20 million into the effort.

The story was written by Erin Allday and is the third installment in a series involving stem cell research and treatments, both legitimate and illegitimate.

Her story began like this:
"Amid the controlled chaos of the operating room, Edward Wirth stood to the side, watching the surgeon slice open the back of the young man on the table....
"The surgeon nudged aside skin and a thin layer of muscle and clamped them out of the way. He chipped away bony vertebrae, exposing the shiny, smooth rope of the spinal cord. His scalpel slid into the membrane surrounding it.
"Wirth stepped forward, just beyond the surgeon’s shoulder, close by for these last steps. The surgical team moved a robotic arm holding a syringe into place. It was loaded with millions of immature support cells that had been meticulously crafted from stem cells, the cells that are the foundation of the human body, able to transform and reproduce indefinitely."
Wirth is a scientist who has been involved with the research since its early days at Geron of Menlo Park, Ca.. He has put in more than 20 years on the effort. Asterias Biotherapeutics of Fremont, Ca., which is associated with BioTime of Alameda, is currently handling the effort to create a treatment for spinal cord injuries.

The $3 billion California Institute for Regenerative Medicine (CIRM), as the agency is formally known, has provided a total of $20.7 million for the effort, first with Geron and now with Asterias.

Allday detailed the ups and downs, financial and scientific, of the research. She peered into the future and wrote that "it will take years to produce a marketable, federally approved therapy -- assuming their research makes it that far."

Nonetheless, she reported,
"Clinical trials like the one run by Asterias are scientists’ most ambitious attempts to harness the potential of what remains an elusive medical marvel. And the work at Asterias exemplifies both the incredible progress that’s been made in stem cell research and the great distance the field has yet to go before life-changing therapies are widely available.
"Riding on Asterias’ success isn’t just the fate of a single company or the careers of scientists like Wirth. Potentially, tens of thousands of patients every year could benefit directly from its therapy — and millions more if its research leads to further advances."
The fourth and final article in the Chronicle series is now scheduled to appear on Sept. 6  and will take a look at the California stem cell agency. Sphere: Related Content

Wednesday, August 15, 2018

California's Stem Cell 'Gold Rush:' Nearly 14 Years of Prospecting

A committee of the California Legislature today examined the state's $3 billion stem cell agency. Officials of the agency and others presented their perspective. Here is the text of prepared remarks by David Jensen, publisher of this blog, who appeared at the invitation of the Legislature.
Sphere: Related Content

Thursday, August 09, 2018

ACT to Astellas: A 'Looping' Tale of the Stem Cell Industry and Research

Ever wonder what happened to Advanced Cell Technology, Inc. (ACT), the Massachusetts stem cell company that migrated -- with some considerable ballyhoo -- to California in the wake of the creation of the Golden State's $3 billion stem cell agency?

ACT landed in the San Francisco Bay area in 2006 with hopes of snagging millions from the agency, which had been created two years earlier. At one point in the company's life, Gov. Jerry Brown even approvingly toured the company's operation in Alameda. But little has been heard from the company in recent years.

Now comes UC Davis stem cell researcher and blogger Paul Knoepfler. Last week, he published a brief update on the doings of the company once known as ACT and its changing corporate identities.

Michael D. West, AgeX photo
But first a little more on ACT's history and the company's not-so-good times in California. It is a tale  that loops around Geron, Inc., which launched and then abandoned the first U.S. clinical trial involving human embryonic stem cells, and companies called
Asterias and BioTime. One thread that strings them all together is a stem cell pioneer named Michael D. West.

When ACT announced its move to the Bay Area, visions of millions of research dollars danced in the heads of its executives. The move was heralded by the state's governmental leaders, Then State Treasurer Phil Angelides said,
"California voters overwhelmingly approved Proposition 71 (which created the stem cell agency) to ensure that California remains the hub of groundbreaking scientific innovation that has the potential to cure and treat debilitating and life-threatening ailments. Advanced Cell Technology's move to California sends a powerful message that this promise can be realized - bringing high-skilled jobs and revenues to our state, and most importantly, offering hope to millions of patients and their families."
West, then president of ACT, said the company was committed to being a world leader in regenerative medicine.

That was in 2006.  Eight years later, ACT, once the only company in the United States with an ongoing clinical trial involving human embryonic stem cells, changed its name to Ocata Therapeutics In 2016 it was purchased by Astellas Pharma of Japan for $379 million. By then, ACT had abandoned its then nominal operations in California after its multiple applications for California state funding failed to win approval (see here and here).

West left ACT in 2007. He is now co-CEO of BioTime, Inc., of Alameda, and is a member of the board of directors of Asterias Therapeutics, Inc., of Fremont, Ca. Both companies are faring much better with the state stem cell agency, formally known as the California Institute for Regenerative Medicine (CIRM).

In 2013, Asterias picked up the human embryonic stem cell trial that Geron gave up on in 2011. West founded Geron in 1990 but left the company in 1998. Asterias has received $14.3 million to support the spinal injury trial that Geron abandoned.

BioTime also had better luck than ACT. It received a $4.7 million award from CIRM for work on human pluripotent stem cells. 

Last week's report from UC Davis scientist Knoepfler said that Astellas began a phase 1B trial in July to continue the macular degeneration work of ACT/Ocata. Knoepfler described the latest effort as a "small bit of encouraging news." Sphere: Related Content

Tuesday, August 07, 2018

California Lawmakers Schedule Update Next Week on the State's $3 Billion Stem Cell Agency

The parents of this child will be testifying next week at a state legislative hearing

For the first time in many years, a California state legislative committee is going to take a look at the state's $3 billion, 13-year-old stem cell research program.

An informational hearing is scheduled for next week, Aug. 15, by the Assembly 
Select Committee on Biotechnology, chaired by Kevin Mullin, D-San Mateo. His district includes a number of biotech firms. No legislation is up for action, and the hearing is not intended to necessarily lead to legislation.

Scheduled to appear before committee are Jonathan Thomas, chairman of the governing board of the agency, and Maria Millan, president and CEO of the agency, formally known as the California Institute for Regenerative Medicine (CIRM).  

The last time a CIRM CEO appeared before a state legislative committee was in 2005 when Zach Hall, then interim CEO testified. 

Also on tap is Jan Nolta, head of the stem cell program at UC Davis, which now stands as the No. 5 recipient of CIRM funds with $138 million. From Folsom will come a couple, Pawash Priyank and Upsana Thakur, whose infant child is now alive as the result of experimental research backed by the agency. The publisher of the California Stem Cell Report, David Jensen, is also scheduled to appear.

The stem cell agency is unique in California history and is a global leader in funding of stem cell research. It operates outside of the normal state budgetary process with its state bond funding flowing directly to it without the usual state budgetary oversight exercised by the governor and the legislature. That is all due to the ballot initiative that created the agency in 2004 and altered the state constitution.

The agency is scheduled to run out of cash next year. It is hoping that voters will approve $5 billion more for it in November 2020.

Next week's hearing, which will be in room 444 in the Capitol, will be available live on the Internet on the day of the  hearing via this page.  It will be archived as well and will be found via this link.

(Editor's Note: An earlier version of this item misspelled the last name of Kevin Mullin.) Sphere: Related Content

Thursday, August 02, 2018

The 'Renegade Outposts' of the Stem Cell Industry: A Sweeping Examination by the SF Chronicle

Chronicle graphic

"Merchants of hope" was the headline today on a lengthy look by the San Francisco Chronicle at what it called the flourishing but costly, unproven and largely unregulated stem cell clinics in the United States and California.

Written by Erin Allday, the piece said,
"They are renegade outposts operating with little legitimacy and oversight at the frontier of what is otherwise a highly promising field of medicine."
It was the second installment in the Chronicle's look at stem cell treatments, both dubious and not-so-dubious. The first was published last month.

Today's piece took a lengthier look at the dubious efforts than has been done in other recent,  mainstream media examinations of the field, which is drawing increasing scrutiny from federal regulators. Allday wrote,
"None of the treatments the clinics offer have been shown to be safe or effective. None have been approved by the FDA. They’re not backed by decades of laboratory and animal studies or by rigorous testing in humans.
"Yet for many patients desperate for care, these clinics fill the void between the long-anticipated potential and the real-world limitations of stem cells. They cater to people whose needs reach beyond the powers of current medicine — people who want to believe in the almost mythic powers of stem cells, who feel corporate health and science have forsaken them.
"People who turn instead to these merchants of hope."
The article also touched briefly on the $3 billion California stem cell agency. Allday said, 
"The California Institute for Regenerative Medicine (CIRM) — the state agency created by Proposition 71 in 2004 to fund stem cell research — has raised concerns about the thriving consumer therapy market. CIRM officials and many of the scientists they fund worry that the selling of unproven treatments could undermine their own work and cast doubt on the enormous potential of regenerative medicine."
Allday continued,
"'It really hurt our recruitment,' said Jane Lebkowski, president of research and development at Regenerative Patch Technologies in Portola Valley. 'We got a lot of questions: What happened in Florida? Am I going to go blind too?'
"Most patients, Lebkowski noted, don’t understand the difference between the fat stem cells that a for-profit clinic is using and the complex product her company is developing, which uses embryonic stem cells to develop a kind of retinal cell that’s damaged in macular degeneration.
"That’s part of the reason why scientists like Lebkowski and organizations like CIRM, which gave $17 million to the Regenerative Patch trial, have pressured the FDA to crack down on the consumer market."
The next installment in the series will deal with stem cell research and is scheduled for publication Aug. 16.
Sphere: Related Content

Tuesday, July 31, 2018

California Stem Cell Cybercast: Multiplying the CIRM Story


Here is today's CIRM Facebook event. The number in the lefthand corner is not static.
It changes as more people view the cybercast.

California's 13-year-old stem cell research agency staged another event in cyberspace today, chalking up more than 1,200 online views for its exploration of the search for cures and therapies for Lou Gehrig's disease.

It was the second go at Facebook Live for the California Institute for Regenerative Medicine (CIRM), as the agency is formally known.

The online event, which features disease experts and questions from viewers, bypasses traditional media and features a concrete way of measuring the event's reach both today and two weeks from today. It could be a significant communications tool for the $3 billion agency, which expects to run out of funds for new awards by the end of next year. The agency is hoping voters will approve another $5 billion in funding in November 2020.

Today's event garnered 819 viewers during its initial hour. By the time of this writing that figure had climbed to 1,262 as others found the event on Facebook.

The first Facebook event for CIRM, which discussed stroke therapy, has now recorded more than 7,500 views. Sphere: Related Content

Monday, July 30, 2018

Live Online Event Tomorrow from California Stem Cell Agency: Ask the Experts about ALS

California's $3 billion stem cell agency tomorrow will offer up a live, online and interactive look at ALS and the research it is financing to help find a cure for the affliction.

The agency has pumped more than $79.4 million into efforts aimed at ALS, which is often referred to Lou Gehrig's disease. Three researchers funded by the agency will be online tomorrow and will address questions from viewers. Here are more details here about the agency's FaceBook Live event at noon PDT, including instructions on how to view it and take part.  Sphere: Related Content

Solomon and Stem Cells: California's Stem Cell Agency Is Slicing and Dicing Cash and Research Decisions


California's stem cell agency gave away $14 million this month, which could be described as less than a drop in its $3 billion bucket.

But the talk at the agency's awards meeting July 19 was not about largess. Instead it was about the lack of cash, lack of time and the need to split "babies" and "buckets."

"We are going to have to make some hard choices today," said one member of the agency's governing  board, Jeff Sheehy, a patient advocate member of the board for HIV.

"We are coming to the end," said another, Oswald Steward, director of the Reeve, Irvine Research Center at UC Irvine.

Sheehy and Oswald and others referred to the shrinking finances of the California Institute for Regenerative Medicine (CIRM), as the Oakland-based agency is formally known. It expects to run out of cash for new awards by the end of next year. Its leaders are trying to raise more than $200 million privately to tide it over until November 2020. That's when they hope another ballot initiative/bond measure will be approved by California voters and pump an additional $5 billion into the 13-year-old enterprise.

That was the backdrop at the session earlier this month. It was a meeting that illuminated the changing criteria that the agency is beginning to use  -- as the cash squeeze tightens -- to make decisions on who and what to finance. No longer will patient advocates or researchers be able to assume that an excellent scientific score assures that an application will be ultimately approved. Instead, "programmatic" considerations will play an important and perhaps definitive role.

Those considerations range from whether a researcher has received past funding from the agency, whether the application fits well within the agency's mission, whether an application fills a void in the agency's portfolio and just how innovative the research is, plus much more.

The discussion about diminishing resources arose when directors were given the usual list of applications that were approved for funding by its reviewers, who met earlier behind closed doors.  Normally, the reviewer decisions are rubber-stamped. This time, however, the 14 reviewer-approved applications totaled $19 million, but only $10 million was budgeted. That's when some directors brought up the need for Solomon-like decisions that would "split" the babies and the "buckets" of cash.

One upshot was that two applicants, James Hagood of UC San Diego and  Vittorio Sebastiano of Stanford, received only partial funding with the expectation that the board would approve a revision in the budget in late October. Nonetheless, those researchers were better off than six applicants who were also approved for funding by reviewers, but not by the CIRM directors. Final action on their applications was put off, probably also until late October.

The $10 million round involved basic types of research, but with a two-year time table. Directors also took action in another, separate round involving preclinical work. It dealt with only one application for $3.99 million, which was approved with no discussion. It went to Poseida Therapeutics, Inc., of San Diego for research aimed at supercharging  "a patient’s own immune system cells to attack and kill a treatment-resistant form of prostate cancer," according to the CIRM news release on all the awards. Poseida matched the award with $998,023.

It was the second CIRM award for Poseida, bringing its total from the agency to $23.8 million.  Here is a link to the summary of comments from reviewers on the Poseida application.

Below is a list of the other approved awards, all of which went to institutions that have links to a CIRM governing board member. Those members were not allowed to vote on those applications. Here is a link to a document which contains summaries of the reviewer comments on each application as well as ones that were not funded on July 



Application number
Title
Institution

Amount
Principal
Investigator
DISC2-11131
Genetically Modified Hematopoietic Stem Cells for the Treatment of Danon Disease
UC San Diego
$1,393,200
DISC2-11157
Preclinical Development of An HSC-Engineered Off-
The-Shelf iNKT Cell Therapy for Cancer
UCLA
$1,404,000
DISC2-11036
Non-viral reprogramming of the endogenous TCR╬▒
locus to direct stem memory T cells against shared
neoantigens in malignant gliomas
UC San Francisco
$900,000
DISC2-11175
Therapeutic immune tolerant human islet-like
organoids (HILOs) for Type 1 Diabetes
Salk Institute
$1,637,209
DISC2-11107
Chimeric Antigen Receptor-Engineered Stem/Memory
T Cells for the Treatment of Recurrent Ovarian Cancer
City of Hope
$1,381,104
DISC2-11165
Develop iPSC-derived microglia to treat progranulin-
deficient Frontotemporal Dementia
Gladstone Institutes
$1,553,923
DISC2-11192
Mesenchymal stem cell extracellular vesicles as
therapy for pulmonary fibrosis
U.C. San Diego
$865,282
DISC2-11109
Regenerative Thymic Tissues as Curative Cell
Therapy for Patients with 22q11 Deletion Syndrome
Stanford University
$865,282
Sphere: Related Content

Wednesday, July 25, 2018

California Stem Cell Agency's Latest Online Event to Highlight ALS and Challenges to Research

California's $3 billion stem cell agency will mount its second Facebook Live event next Tuesday, featuring ALS researchers from Cedars-Sinai discussing their work and the challenges confronting the field.

The noon PDT cybercast will feature Clive Svendsen, director of the Regenerative Medicine Institute at Cedars, Robert Baloh, director of neuromuscular medicine at Cedars, and Ralph Kern, chief medical officer of Brainstorm Therapeutics, Inc., of New York City.

Viewers will be able to pose questions to the participants during the event, which has been dubbed "Ask the Experts.".

The stem cell agency, known formally as the California Institute for Regenerative Medicine (CIRM), has awarded Brainstorm $15.9  million to support a phase three clinical trial work in California dealing with ALS. Svendsen has received $24.9 million from CIRM, including $6.2 million for a phase one/two trial also involving ALS.  Baloh has received a $3 million CIRM award for research involving peripheral nerve disease.

CIRM's first Facebook Live event has drawn nearly 7.500 viewers since it was staged two months ago, a performance that makes it a useful tool in reaching large numbers of people. Sphere: Related Content

Media Series on California Stem Cell Agency Has New Publication Dates

The San Francisco Chronicle has changed the publication dates for its series on stem cells and the California stem cell agency.

The second installment, dubbed "clinics,"  was scheduled to appear today. However, the publication date is now set for Aug. 2, one week from tomorrow. The rest of the schedule calls for the "research" installment on Aug. 16 and "progress" on Aug. 30.

Here is a link to an item on the beginning of the series earlier this month.
Sphere: Related Content

Tuesday, July 17, 2018

California Parkinson's Group Strikes Out on Path to Stem Cell Therapy; Clinical Trial, For-profit Company Goals

A San Diego patient advocate group for Parkinson's Disease is making a major financial move as it heads toward creation of a for-profit company to develop a stem cell therapy for an affliction that affects about one million people in the United States.

The group is the Summit for Stem Cell Foundation, which has been deeply involved in seeking funds from the $3 billion California stem cell agency. The Summit organization supports research being conducted by Jeanne Loring, director of the Center for Regenerative Medicinat the Scripps Research Institute.

Summit says it has raised $5 million as of this spring from a variety of sources. It estimates it will need $8 to $10 million to reach the stage where the federal government approves the beginning of a clinical trial. It also expects to raise more cash by avoiding the high administrative charges involving many research organizations.

Reporter Bradley Fikes of the San Diego Union Tribune wrote yesterday about the latest developments. He said Summit is moving out of its space at Scripps as it prepares to apply for funds for clinical research. Fikes wrote,
"The group has leased about 5,000 square feet, doubling its space, and as a parting gift Scripps Research is donating equipment from its stem cell center, saving the foundation nearly $1 million in start-up costs. At the same time, its overhead is dramatically reduced, said Jeanne Loring, the group’s lead scientist and professor at Scripps Research. (Loring is serving as the unpaid director of research for Summit.)
"A $2.4 million grant the group received from California’s stem cell agency ran out earlier this year, Loring said. Now the group can step up fundraising and add staff. It’s also soliciting more donated equipment."
Fikes continued,
"The group also plans to establish a for-profit company to get funding from investors interested in generating returns, Loring said. By drawing investments as well as philanthropy, the project gains access to capital not otherwise available.
"The group was inspired by the example of the Cystic Fibrosis Foundation, Loring said. In 2000, the foundation gave San Diego’s Aurora Biosciences $40 million to develop a cystic fibrosis drug."
Fikes reported that separation from Scripps has financial advantages dealing with what called "indirect costs." 
"Raising (donations) has been difficult, in large part because of the overhead issue, Loring said.
"Scripps Research imposes overhead of up to 94 percent, meaning that every dollar donated to the group required an additional 94 cents for the institute, Loring said. At the new location close by on Torrey Pines Mesa, overhead is roughly 10 percent.
"Lower overhead means the group can now apply for philanthropic grants that previously weren’t practical, she said, because donors prefer as much as their money as possible go directly to the cause."
Here is a video of Loring describing her work. 

Sphere: Related Content

Sunday, July 15, 2018

A Good Sign for California's Stem Cell Agency? Californians Like to Say Yes to More Bonds

An ambitious campaign to stave off the death of the California stem cell agency with a $5 billion jolt of state borrowing could have an easy ride in a couple of years. 

At least that would seem to be the case if one bets on the odds as perceived in a column carried today in the Los Angeles Times. 

The headline on the piece by John Myers, the Times' Capitol Bureau chief in Sacramento, said,
"California voters almost always say yes to bonds..."
Myers wrote, 
"It’s the closest thing to a sure bet that exists in statewide campaigns, with an approval rate hovering around 90%."
Myers, however, focused mainly on this November's ballot -- not 2020. And he did not comment directly on the plan to present a $5 billion bond measure to voters in November 2020 to keep the stem cell agency alive.

The agency, formally known as the California Institute for Regenerative Medicine (CIRM), expects to run out of cash for new awards by the end of next year. Its only significant source of funding is money that the state borrows (bonds), which roughly double the costs of its operations because of interest expense. The borrowing was approved by 59 percent of the voters in 2004.

Myers related the current condition of the Golden State's indebtedness:
"State general obligation bond measures approved since 1986 total more than $167.7 billion. Lenders must be repaid with interest, averaging about 5% a year, over a span of several decades. Most general obligation bond payments come from the same bank account that provides cash for services such as education, healthcare and prisons." 
He continued, 
"A recent report by the nonpartisan Legislative Analyst’s Office estimated that California’s general fund is currently paying off $83 billion in bond obligations. Annual debt payments total about $6 billion. That’s roughly equal to a year and a half in general fund spending on the University of California system, or about triple what the state spends on firefighting."
"'When we make these decisions, we have to look at the big-picture context,' state Sen. Bob Hertzberg (D-Van Nuys) said during a legislative hearing last month on November’s slate of bond measures."
State Sen. Bob Hertzberg, News Growl photo
Hertzberg zeroed in on backers of a clean water measure on the fall ballot. The Times piece reported,
"'You’ve got to tell the truth,' he said to the measure’s proponents. 'You back up an armored car to the treasury, and you can take $430 million out of the back door because you can poll [on] something, spend a few million dollars because it’s an issue that looks sexy to voters, and draw the dough.'"

Myers continued,
"Voters are rarely asked to think about which needs government should meet. In 2004, they agreed to borrow $3 billion for stem cell research. In 2008, voters said yes to $9.9 billion in seed money for high-speed rail. Even though the (rail) bonds have only recently begun being sold to Wall Street investors, it’s debatable whether voters would make the same choice if asked again.
"And campaigns rarely offer enough information to fully consider the pros and cons of a bond measure. Voters must do their own homework, beginning with the understanding that a bond is a mandatory expense, an investment decision that can have profound impacts for more than a generation."
Sphere: Related Content

Thursday, July 12, 2018

Expansive Media Series on California's Stem Cell Agency as It Nears Cash Cutoff

Lead photo on Chronicle stem cell series, photo by Gary Wathen
The San Francisco Chronicle today kicked off a major look at California's $3 billion stem cell agency with a multimedia presentation that covered everything from stem cells and how they work to the desperation and hope of patients with all-but-untreatable afflictions..

The four-part series will roll out over the next six weeks in the Chronicle, which says it reaches 1.7 million persons weekly in the San Francisco Bay Area via both print and electronic means. The series looks to be the most expansive look ever at the agency, which is formally known as the California Institute for Regenerative Medicine (CIRM).

The Chronicle effort, which has been many months in the making, comes as the agency is facing its lingering demise unless efforts to raise more billions are successful. CIRM expects to run out of cash for new awards by the end of next year. It is attempting to raise privately more than $200 million to bridge a financial gap with the hope that voters will approve a yet-to-be-written, $5 billion bond measure in November 2020.

The series is likely to have a significant foundational role in more news coverage of the agency as it nears its cash cutoff. As a starting point, reporters will be examining the Chronicle's work and other previous coverage of CIRM, which has all but vanished from news pages and news screens of California readers.

Patient Hopes and Unregulated Treatments

The initial installment in the Chronicle series, written by Erin Allday, had little specific to say about the agency, but dwelt on patients' hopes of finding unregulated stem cell therapies both within California and outside of the state. One piece served as a primer and was called "What Are Stem Cells and How Do They Work." The other two major pieces were headlined,
"In Search of a Miracle: She Tried Everything to Heal Her Son; Stem Cells Were Her Last Hope"
and
"Driven by Desperation: Out of Options, Six Patients Turn to Stem Cells."
An editor's note tied to the series said,
"'The Miracle Cell' explores the hope and reality of the revolutionary science of stem cell therapy. It focuses on what has transpired since 2004, when California voters approved a $3 billion bond measure to fund stem cell research with the promise that it soon would produce new treatments for incurable diseases.
"In four parts, it follows the stories of patients desperately seeking remedies; probes the for-profit clinics where unproven and unregulated treatments are being offered; takes you into the labs and hospital rooms where scientists are testing new therapies; and provides a comprehensive accounting of what California’s multibillion-dollar bet on stem cells has achieved."
The main piece today dealt with a nine-year-old boy from Scott's Valley, Ca., who received stem cell treatments in Tijuana. The story also documented the "powerful allure" of the therapies. Allday wrote,

"In 2004, California voters were so convinced that cures from stem cells were close at hand that they approved Proposition 71, a $3 billion bond measure to pay for research that the federal government would not.
"Nearly 15 years later, no proven therapy has emerged. But some doctors already claim to have tapped stem cells’ potential. And some patients refuse to wait any longer to seek treatment."

Asterias and Paralysis 

One of the six profiles of patients involved Mary Ambery, 59, who was paralyzed from the neck down in a fall in 2017. She is now engaged in a clinical trial run by Asterias Biotherapeutics, Inc., of Fremont, Ca.  The Chronicle reported, 
"Before the transplant, she had almost no movement in the muscles that allow her to bend her arms at the elbows and rotate her wrists. She couldn’t pinch her thumb and forefinger together. She couldn’t feed herself or comb her hair, couldn’t use a smartphone or a pen.
"More than a year after the surgery, she can do her own makeup and hair. She can use a fork, but needs help cutting up her food. She can text with her friends, she can write 'pretty legibly.'"
The story did not mention that Asterias' work has been supported by $21 million from the California stem cell agency.  

The next installments in the series are likely to contain more details on the Golden State's stem cell program. Here are the one-word topics and expected dates of publication: Clinics, July 25; Research, Aug. 8, and Progress, Aug. 22.
Sphere: Related Content

Monday, July 09, 2018

Stanford's Weissman Lauds California Stem Cell Agency For Innovation, Critical Financing

The California stem cell agency has chalked up hearty praise from an internationally known Stanford researcher for its 13-year, $3-billion search for stem cell therapies and cures.

Irv Weissman, Stanford photo
The scientist is Irv Weissman, director of the Institute of Stem Cell Biology and Regenerative Medicine at the Stanford University School of Medicine.  His laudatory reflections on the California Institute for Regenerative Medicine (CIRM), as the stem cell agency formally known, recently found their way to the Oakland-based enterprise. And last Monday the agency posted an item on Weissman's remarks on its blog, The Stem Cellar.  The article began,
"When you get praise from someone who has been elected to the National Academy of Sciences and has been named California Scientist of the Year you know you must be doing something right."
Weissman said the agency has provided the financial support that allows research to bypass "the valley of death," short hand for the stage in which promising research can often die. Plus, he said, CIRM allows the discoverers to guide early stage development rather than diverting it into commercial arena.

Weissman's comments spoke to what the agency calls its "value proposition," a term that is becoming increasingly important as the agency faces its possible demise. The agency expects to run out of cash for new awards by the end of next year. It is trying to raise more than $200 million privately to continue operations until November 2020, when it hopes voters will approve $5 billion more for stem cell research.

CIRM's blog item was authored by Kevin McCormack, CIRM's senior director of communications,  in the context of a $115 million initial public stock offering by Forty Seven, Inc., of Menlo Park, Ca., a company founded on the basis of Weissman's work. Weissman is currently a member of the company's board.

Forty Seven has received $15.2 million from CIRM. Weissman has received $32.4 million.

Weissman said in the statement that CIRM carried,
"The major support (for Forty Seven) came from the California Institute of Regenerative Medicine (CIRM), funded by Proposition 71, as well as the Ludwig Cancer Research Foundation at the Ludwig Center for Cancer Stem Cell Research at Stanford. CIRM will share in downstream royalties coming to Stanford as part of the agreement for funding this development.
"This part of the state initiative, Proposition 71, is highly innovative and allows the discoverers of a field to guide its early phases rather than licensing it to a biotech or a pharmaceutical company before the value and safety of the discovery are sufficiently mature to be known. Most therapies at early-stage biotechs are lost in what is called the ‘valley of death’, wherein funding is very difficult to raise; many times the failure can be attributed to losing the expertise of the discoverers of the field.”
In response to a question from the California Stem Cell Report, McCormack said Weissman's statement came "unbidden" by the agency.  We asked Weissman about what led him to issue the remarks. Weissman said he said he had not seen the CIRM piece, but responded after reading it.
He said in an email, 
"Now that I’ve seen the quote, it is close to what I sent to colleagues at Stanford. I did it so that my colleagues understood the nature of the CIRM experiment in funding research and its translation. One of these colleagues sent it on to CIRM, and I didn’t object.
"I think its very important to know how the original Prop 71 was designed not only to fund stem cell related research, but also to take selected projects competitively reviewed by expert referees to and through phase 1 trials if warranted. The therapy that was developed at Stanford by the team led to the discovery team forming a disease team of experts usually only found in biotechs and pharma, but here led by the discoverers of the leukemia stem cell overexpressed molecule, CD47, which by its ‘don’t eat me’ actions protects the leukemia from removal by scavenger macrophages. The CIRM oversight team helped guide selection of outside advisors, and met frequently with us to monitor our progress, and most importantly, give us advice that led to Stanford filing two INDs on time in the US [FDA] and the UK[MHRA]. The importance of doing high level preclinical testing and toxicity etc without a profit motive allowed the team to keep going when surprising events came up. Many biotechs fail at that point, as the risk starts to worry investors and shareholders. But this went through, and in addition to getting into important phase 1 trials that broadened the potential cancer targets to cancers beyond myelogenous leukemia, the group could see how the therapy needs to be administered to avoid toxicity in patients. By the time Stanford informed us it was time for them to license the ip, many independent companies had formed around the concept discovered by the team, a validation that this could become the second type of checkpoint inhibitor therapy for human cancers, this time for macrophages instead of inhibited T cells. 
"I felt it was equally important to try to get the agency that funded these stem cell related efforts to share royalties with the academic institution that held and licenses the intellectual property; I first raised this issue in 1994 when I was President of the American Association of Immunologists; my article is attached here.
"Most of us hope the discoveries we make can have the potential to help patients with diseases that are only incompletely treated by current medical practice. Very early results of clinical trials reported in the ASCO meeting in early June are consistent with that possibility. 
"I need to make clear that the statement in the blog was written by me, and was not an official document of Stanford University, of Forty Seven, Inc, or from others from the discovery team. If you decide to publish this answer to your question, please either publish it in full, unedited, or don’t publish it at all. I didn’t write this for you to publish, but for you to understand from your question the reason I wrote the original document to colleagues at Stanford."
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Friday, July 06, 2018

Now Official: California Stem Cell Scientist Loses Congressional Race

For those of you who may have missed the news, Hans Keirstead, the former UC Irvine stem cell researcher, has officially lost his bid to become the first stem cell scientist elected to Congress.

He had a close finish in a primary race that went to Harley Rouda, a former Republican, who will be attempting to oust Republican Rep. Dana Rohrabacher this fall. The final vote count showed Keirstead with 125 votes less than Rouda. Both Rouda and Keirstead are Democrats.

Keirstead was a proponent backer of the ballot initiative that created the $3 billion California stem cell agency.

Here are links to stories about the race, which delved into Keirstead's time at UC Irvine, and the results: Voice of OC, Mother Jones. Sphere: Related Content

Thursday, June 28, 2018

California Backs Research for Brain Cancer and Parkinson's with $9.5 Million

OAKLAND, Ca. -- The California stem cell agency today awarded $9.5 million for two late stage preclinical projects for development of therapies aimed at brain cancer and Parkinson's Disease.

A $5.8 million award for Parkinson's went to Krystof Bankiewicz of UC San Francisco and Clive Svendsen of Cedars-Sinai. A $3.7 million award for glioblastoma, a form of brain cancer, went to John Zaia of the City Of  Hope. Glioblastoma is the form of cancer that has afflicted U.S. Sen. John McCain.

In a news release from the agency, known formally as the California Institute for Regenerative Medicine (CIRM), its CEO, Maria Millan, said,
“Glioblastoma is the most common, and the most aggressive, form of brain cancer that led to the death of U.S. Senator Ted Kennedy and former Vice President Joe Biden’s son Beau Biden. 
"CIRM has supported a variety of stem cell-based approaches to target this devastating and currently untreatable condition.  The project approved by our board today is unique in that it seeks to use gene modified stem cells to allow patients to tolerate the high doses of chemotherapy while also making these tumors more susceptible to the chemotherapy.”
Regarding the Parkinson's award, the agency has already pumped $22.3 million into a phase one clinical trial being conducted by Svendsen for treatment of ALS with the same neural progenitor cell product that will be used in the Parkinson's research.

Here are links to the review summaries on the Parkinson's application and the glioblastoma application, plus additional information.

Application Number
Principal Investigator
Institution
Target
Amount
Awarded
Public Summary
of Review
CLIN1-10967
John Zaia
City of Hope
Glioblastoma
3,684,259
CLIN1-11059
Krystof Bankiewicz/
Clive Svendsen
UC San Francisco/
Cedars-
Sinai
Parkinson’s
Disease
5,811,340

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