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. 

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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."
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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"
"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.
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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
Public Summary
of Review
John Zaia
City of Hope
Krystof Bankiewicz/
Clive Svendsen
UC San Francisco/

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Wednesday, June 27, 2018

California Stem Cell Agency Eyes Changes in Funding Decisions; Possible Impact on Bond Election, Development of Different Therapies

A CIRM slide outlining current programmatic criteria. GWG
refers to the group that reviews applications.  The
 subcommittee reference is to the panel of directors  who
ratify reviewers' decisions. ICOC is the abbreviation for
the name of the governing board.

The $3 billion California stem cell agency is re-examining its criteria for awarding hundreds of millions of dollars with an eye to placing more emphasis on what could be called non-scientific criteria.

The move could have an impact on hundreds of researchers in the state and the development of stem cell therapies that could benefit untold numbers of patients afflicted with a host of deadly and debilitating diseases. It could also have an impact on a possible ballot measure to provide an additional $5 billion for the 13-year-old stem cell program.

The changes could be acted on as early as tomorrow at a meeting of the governing board of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known. The meeting is in Oakland, but Internet access is available for those who wish to comment and hear the proceedings.

The move comes under the rubric of "programmatic review" of applications for funding. It has been an ill-defined term for years at the agency. But more specificity was disclosed yesterday in a series of 20 slides scheduled to be shown at tomorrow's meeting of the agency's 29 directors. The posting of the slides came less than two days prior to the meeting.

The agency's staff has laid out seven possible areas where changes might be made:

  • "Annual Program Budget and Goals
  • "Value Proposition of Proposed Project
  • "Patient population, competitive landscape
  • "Relevance of Project to Stem Cells
  • "Contribution to CIRM Portfolio
  • "Disease area, current award overlap
  • "Previous CIRM Support of Project"

The full impact of increased use of any or all of those criteria was not clear from the slides provided by the agency. But it could mean that an application that received a high scientific score could be sidelined in favor of one that fills a void or bolsters a weak spot in the CIRM award portfolio.

CIRM slide on possible new award criteria 
Over the years, many CIRM board members have expressed frustration with how the scoring on some applications works. In the case of some applications, only one point separates those receive millions and those who receive none. The concern has been that a one point difference is less than meaningful.

The slides do not flesh out all the likely reasons for putting more emphasis on non-scientific issues, but the agency is approaching the end of its life. It expects to run out of cash for new awards at the end of next year.

A private fundraising effort is underway to tide the agency over until, it is hoped, voters approve $5 billion more for the agency in November 2020.

Changes in award criteria could lead to approval of research whose results are more likely to resonate with voters in time for a ballot measure campaign in two years.

CIRM was created in 2004 by voters who were swayed by a campaign that raised expectations that stem cell cures were just around the corner. The agency has yet to produce a therapy that is available for widespread use. However, it has helped to fund 49 clinical trials, which are the last stages before a therapy is approved by the federal government for general use. Sphere: Related Content