California Stem Cell Agency Scores 50 Clinical Trials, Says It "Just Getting Started"

OAKLAND, Ca. -- California's ambitious stem cell agency this morning chalked up involvement in 50 clinical trials, an achievement that was regarded by some as unattainable 10 years ago.

The watershed event came when directors of the agency approved a $6.2 million proposal to help fight lymphoma.
Following the action, the first person ever to participate in a CIRM human embryonic stem cell trial, Richard Lajara, praised the efforts of the agency, which is running out of cash. 

He said the people of California have a responsibility to move forward with stem cell research and to continue to fund the agency. Lajara's appeal followed a statement from the agency that 35 persons are alive today because of clinical trials that it has helped to finance.

Lajara, who is paralyzed from the waist down, was enrolled in 2011 in the spinal injury trial initiated by Geron, Inc.,  and backed by the agency. 

Jonathan Thomas, chairman of the agency, which is formally called the California Institute for Regenerative Medicine(CIRM), said in a statement,

"We have come a long way in the past seven and a half years, helping advance the field from its early days to a much more mature space today, one capable of producing new treatments and even cures. 

 "But we feel that in many ways we are just getting started, and we intend funding as many additional clinical trials as we can for as long as we can."

In the early days of the agency, Robert Klein, its first chairman, and others widely regarded major participation in clinical trials, especially phase three, as largely beyond the financial capability of the agency. The cost was prohibitive, they said.

The cost of trials varies widely but can run into hundreds of millions of dollars, which could rapidly devour the $3 billion the agency had to spend, the reasoning went. Clinical trials are the last stage before a treatment is approved for widespread use by the federal government.

CIRM's first strategic plan in December 2006, which covered a 10 year period, anticipated some involvement in phase one and two trials. But it said,

"Because of their expense and because of the time required to reach this stage of clinical development, CIRM is unlikely to fund Phase III trials over the time span of the strategic plan."

The first patient to enroll in a CIRM clinical trial did not come until late 2011. 

Today, the agency has committed $541 million to clinical trials, including four that are in phase three, the ultimate trial hurdle to clear before a treatment wins approval. The phase three trials involve kidney disease and ALS.

The 14-year-old agency is now down to its last $144 million. Money for new awards will run out at the end of next year. CIRM is pinning its hopes for continued life on a proposed $5 billion ballot measure on the November 2020 ballot.

Key to winning approval would be a favorable result from its clinical trials -- one that would resonate with the voters. Their expectations were raised in 2004 by the ballot campaign that led to creation of the agency. However, the agency has yet to produce a stem cell treatment that is widely available.

Trump, Fetal Tissue and the California Stem Cell Agency

The California stem cell agency says the Trump Administration moves against research involving fetal tissue have had no impact on the projects that it is financing, at least so far.

The agency, formally known as the California Institute for Regenerative Medicine (CIRM), was responding to a question originally raised by a reader of the California Stem Cell Report.

The inquiry was triggered by a number of reports over the last few months concerning the federal direction away from fetal tissue, a move that one researcher, Warner Greene of the Gladstone Institutes in California, called "scientific censorship of the worst kind."

The California Stem Cell Report queried CIRM yesterday about the federal actions, asking whether they have had "any impact, direct or indirect, on CIRM awards, existing or likely in the future."

Kevin McCormack, senior director for CIRM communications, replied, noting that the federal move is relatively recent.

"It could mean an increase in applications that use fetal tissue but it’s too soon to tell. Regardless, this is why the people of California created CIRM, so we don’t have to worry about federal funding for potentially life-saving research. Because we are independent, we can fund what we think is the best science."

McCormack alluded to the ballot initiative in 2004 that established the agency. The campaign was largely based on the need to bypass the Bush administration's restrictions on stem cell research. The anti-fetal tissue effort is likely to be the first step towards resurrecting similar restrictions on stem cell research. 

Politically and ironically speaking, new federal restrictions on human embryonic stem cell research could build support for continued funding of CIRM, which is hoping for passage of a proposed $5 billion bond measure on the November 2020 ballot.

While fresh restrictions are not good for the field overall, their imposition could help to preserve the stem cell agency. Any ballot campaign needs a nasty villain to campaign against.

And without Bush to campaign against in 2004, the stem cell agency probably would never have come into existence.

Here are links to a few of the recent stories on the Trump fetal tissue move: Washington Post, Science, STAT.

Walking a Thin Line at the California Stem Cell Agency

California's stem cell agency has a delicate dance to perform as it edges closer to seeing a $5 billion measure on the ballot to provide more funding for its efforts.

The dance involves a prohibition on state agencies spending public money on behalf of bond measures. The $3 billion agency has a legitimate responsibility to keep the public informed about its activities, but when does that task step over a legal line? 

CALmatters, an online news site devoted to state government matters, touched on the issue this morning. Dan Morain, the site's senior editor, wrote about a couple of cases in the last election.

In his morning newsletter "What Matters," he cited a tiny fine imposed on the Bay Area Rapid Transit District and another case involving an $800,000 expenditure by Los Angeles County board of supervisors, which is unresolved.

As for the stem cell agency, it is certain to be accused of using public money to support any ballot measure that may emerge in 2020. 

That would be part of the political tactics of opponents to the measure -- a portrayal of the stem cell agency as unworthy of voter trust.

The agency is treading lightly in this area right now, a position that will serve it well as more clarity emerges on whether a ballot initiative will actually surface on the November 2020 ballot. 

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

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

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

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

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

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

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

McCormack continued,

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

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

"This includes:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

$144 Million California Stem Cell Research Program Set for 2019

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

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

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

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

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

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

SF Chronicle Backs Away From More Cash for California's Stem Cell Agency

The San Francisco Chronicle, which has the largest circulation of any newspaper in Northern California, today said the results generated so far by state's $3 billion stem cell agency "don’t argue for expanded public spending."

The California Institute for Regenerative Medicine (CIRM), as the agency is formally known, expects to run out of cash for new awards at the end of next year. It is seeking to raise privately $220 million to tide it over until November 2020, when it hopes that voters will approve a $5 billion bond measure for continued stem cell research.

However, in a formal unsigned editorial published on its website, the Chronicle said,

"The results to date don’t argue for expanded public spending. The science of stem cell work will need to evolve before more money is provided."

The editorial followed a four-part series  in the Chronicle looking into the state of stem cell research. The final installment last week said the agency had fallen short of the high voter expectations when they approved creation of the agency in 2004. The agency has not yet backed development of a therapy that is available for widespread use, although it currently has investments in 49 clinical trials.

The Chronicle, which says it has a readership of more than 500,000, said,

"California’s pioneering decision to spend $3 billion on stem cell research isn’t producing cures after 14 years of work. Instead, it’s generating a widening scientific field that shows potential but not results.

"It’s a frustrating shortcoming, especially as supporters of the state-sponsored research weigh another bond measure to continue the work. Promised breakthroughs used to sell Proposition 71 in 2004 aren’t panning out, a Chronicle investigation found."

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."

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."

California Stem Cell 'Renewal:' The Search for More Billions -- And Credit for Results

A KTVU video connected to CIRM's research support

California's 13-year-old stem cell agency, which is facing its demise as it lingers in a dim media shadow, last week snagged some credit for the work it has helped to finance in saving the life of a five-year-old girl. 

The news story appeared on San Francisco Bay Area television station KTVU. The piece involved Evangelina “Evie” Padilla Vacarro, who was born with what is known as the "bubble baby" disease. That is a genetic affliction that compromises the immune system so severely that it is nearly impossible for a person to survive.

Evie's story is powerful and well-known among those who closely follow the $3 billion California Institute for Regenerative Medicine (CIRM), as the stem cell agency is formally known. But it has not seeped in the consciousness of California voters, who are likely to be asked to cough up $5 billion more for CIRM.

The agency expects to run out of cash by the end of next year. It is pinning its survival hopes on a private fundraising drive underway this year and passage of a proposed bond measure in November 2020. However, many competing priorities exist for that sort of funding. Plus the agency has yet to fulfill voter expectations that creation of the agency would lead to a stem cell treatment that would have widespread use.

In Evie's case, the treatment is available under exceedingly limited circumstances, like other treatments that the agency is supporting. They are still being tested before the federal government approves them for wider use.

The positive results that are, in fact, surfacing often do not mention CIRM's substantial backing, or they bury that fact so deeply it is all but invisible. (See here, here and here.) That is occurring despite the fact that many of those stories emerge from institutions that have received tens and tens of millions of dollars from the agency.

The fresh news peg for the KTVU story last week was the launch of a book, “California Cures: How the California Stem Cell Program is Fighting Your Incurable Disease," by longtime stem cell patient advocate Don Reed. The station reported,

"'Lives have been saved, and suffering eased, because California stood up for stem cells in 2004,' Reed said. 'Now as we approach the end of that (2004) voter-approved program, it is vital that everybody knows the story of (the institute) and why we must renew its funding.'"

Whether that "renewal" actually takes place may depend on whether the researchers and institutions that have benefited from CIRM's largess do a much better job of selling what they believe are the benefits and importance of the agency's programs and cash.

CIRM Board Member Sheehy Exiting as San Francisco Supervisor; Says SF Voters Favorable on Stem Cell Work

Jeff Sheehy, a member of the governing board of the $3 billion California stem cell agency, will be leaving his fulltime post as a member of the San Francisco board of supervisors later this year, but he says his unsuccessful election campaign disclosed favorable perceptions of stem cell research.

Sheehy disclosed his plans not to seek re-election in the media in the Bay Area. In a statement, he said it was "immensely rewarding" to have served the city. He also had this to say yesterday to the California Stem Cell Report,

"I have been asked about the implications for CIRM (the stem cell agency) and, based on polling around my bio that my campaign conducted, stem cell research remains very popular.

"When we asked voters about what prior work of mine resonated with them, the tagline, 'Fights for stem cell cures for deadly diseases and conditions as a founding board member of the California Institute for Regenerative Medicine,' was one of, if not the most popular items listed in my background.

"I had multiple conversations with voters about our work at CIRM and they were very supportive and very impressed with the what we have accomplished."

Sheehy is a patient advocate member of the stem cell board and has served on it since its inception in 2004. He is also chair of the Science Subcommittee of the board, participates in closed door reviews of applications for funds by scientists and oversees board discussion of the reviewers' decisions.

Sheehy's term on the 29-member board expires in 2020. The agency expects to run out of cash for new awards by the end of next year, 2019.

Fire, Fury and $5 Billion: A Mini Preview of a Ballot Campaign for the California Stem Cell Agency

California's stem cell research effort, which is pinning its survival hopes on a proposed $5 billion bond measure in a couple of years, was slammed in a national publication last week as a "multi-billion dollar money suck."

The column in the conservative magazine National Review, which has about 90,000 circulation and a significant online presence, was a tiny preview of the fire and fury that is likely to erupt around the likely pitch to California voters in 2020 to give more cash to the agency.

Formally known as the California Institute for Regenerative Medicine (CIRM), the agency was created by a ballot initiative in 2004 and backed with $3 billion in state funds. It expects to run out of money for new awards by the end of next year.

Wesley J. Smith, a longtime critic of the agency, wrote in the National Review piece,

"The mendacious (2004) campaign promised Cures! Cures! Cures! with embryonic stem cells and therapeutic human cloning — even promising that disabled children would get out of their wheel chairs and walk. Good grief, campaigners also claimed that the money earned from all the coming cures would reduce California’s health-care budget.

"Some $2 billion later, none of it came to pass. Tens of millions were spent on a fancy-dancy building. Conflicts of interested have abounded. But the supposed point of the CIRM was not achieved. There have been extremely few human trials with embryonic stem cells — mostly dealing with eye conditions — and not all were CIRM-funded."

It is fair to say that Smith's characterizations omit much information about what CIRM calls its value proposition. Nonetheless, his points are likely to resonate with a substantial portion of California voters, who have seen little mainstream media coverage of CIRM. 

Even the institutions and recipients of multi-million dollar research awards regularly fail to note CIRM's contributions in their news releases about state-backed scientific discoveries. (See here and here.)

As of today, the agency has invested in 49 clinical trials, the last stage before a therapy is approved for widespread use. A discovery or treatment that would captivate the public could emerge from those trials between now and the election in November 2020. Meanwhile, given the nature of today's financially struggling media and limited science coverage, the agency and its backers are likely to find it tough to break through the news clutter and convince voters to cough up more cash.   

Viral Power: California Stem Cell Agency Hits 6K with Cyberspace Event on Stroke Therapy

Here is the Facebook Live event produced by CIRM. The number in the left hand 

corner is not static. It changes as the video is viewed by more persons. 

The $3 billion California stem cell agency last week mounted its first "Ask the Experts" session on Facebook, a look at a stroke therapy that left one patient crying with joy and  researchers "shocked" at the initial, beneficial results.

The Facebook Live event dealt with a stem cell treatment for the most common form of strokes, which claim 750,000 victims annually. It is the leading cause of disability in this country and third leading cause of death.

The webcast at noon last Thursday drew only about 80 viewers, the agency reported. But by late Monday, Facebook statistics showed that it had been viewed more than 6,400 times (more than 6,500 by this morning). The figures demonstrated the viral power of Internet communications in spreading the stem cell agency's message. Not to mention that it could help to stave off the agency's financial demise.

Featured on the webcast were researcher Gary Steinberg of Stanford University, whose work has been supported by $24 million from the agency, and Sonia Coontz of Long Beach, Ca., who said she wept after treatment in the clinical trial as she experienced immediate improvements. Steinberg said his team was "shocked" by the rapidity with which some patients improved from their ischemic strokes.

More than 172 comments were made during the session. Some simply sought more information. Others waxed euphoric. Lisa Bayha Deck, wrote on Facebook,

"I’m a patient of Dr. Steinberg’s and so thankful for his professionalism. He gave me my life back after four strokes and Moyamoya Disease."

The Facebook event was the latest effort by the agency, formally known as the California Institute for Regenerative Medicine (CIRM), to educate the public about the work it is financing. However, the agency expects to run out of cash for new awards by the end of next year. It hopes that voters will provide it with $5 billion more in state bond funding via a ballot measure in November 2020. 

During the event, Lila Collins, a senior scientist at CIRM, provided an overview of key stem cell trials around the country. Kevin McCormack, senior director of communication at CIRM, moderated and produced the session.   

Following the event, McCormack said he thought it went well for an initial effort, although he said he was caught up in the mechanics of handling the session. On Monday, McCormack said, 

"We are going through the stats now and plan on putting together a roundup of views, comments, etc. We are also planning on posting a blog about the event – with answers to questions we didn’t get around to during the hour – so that should be coming in the next few days."

Prior to the webcast, the California Stem Cell Report asked McCormack to elaborate on the agency's Facebook effort. Here is a lightly edited version of that email interview. 

Q: Is this the first such event for CIRM? 

A: It’s the first Facebook Live event we are doing. A few years ago we did a similar series using Google Hangout. We featured a number of our experts in ALS and cancer, heart disease etc. but that wasn’t as easy to do technically. Facebook Live is simpler and because so many more people are on Facebook on a regular basis it will hopefully allow us to reach a wider audience. 

Q: Why is CIRM doing this event? 

A: It’s just part of our outreach efforts to let people know how stem cell research is progressing and the role that CIRM is playing in advancing that. We have been doing similar things for years, reporting back to the people of California on the work we are doing. We do it regularly with in-person patient advocate meetings, and with talks and presentations all around the state so we just wanted to take advantage of this technology to see if we could reach a wider audience.

Q: Will it be saved on the CIRM web site for future viewing?

A: One of the great features of Facebook Live is that it is automatically saved at the end and you can watch them on Facebook again and again. And yes, we’ll be putting links to them on our website but the easiest way to find them is to just go to our Facebook page.

Q: How did this originate?

A: We are always looking for new ways to reach out to a wider audience and let people know about CIRM’s help in advancing stem cell research. We looked at Facebook Live and thought it could be a great tool for us. We are already on Facebook anyway so this was a natural extension.

Q: And, finally, is there anything else you want to say about this event and its significance? 

A: Earlier this year we held a patient advocate event at UC Riverside. It was our first excursion to the Inland Empire and we had a great crowd, more than 100 people showed up on a weekday. But our goal is always to reach as many people as possible, and so we are always exploring new ways, new tools to do that. 

Much as we would like to, we don’t have the staff or budget to travel constantly around the state doing in-person meetings so this is a great way of achieving the same goal in a much more efficient manner. The people of California put a lot of faith in us when they approved $3 billion in funding for stem cell research. As we see that funding really help accelerate the field – we have 49 projects that we funded in clinical trials, we are seeing patients cured of life-threatening diseases – we want to share that news with as many people as possible.

California Stem Cell Agency and First-of-Kind Fetal Transplant for Fatal Affliction

Nichelle Obar and her daughter, Elianna, at three weeks. NYT photo by Bryan Meltz

A uniquely California medical treatment -- the first of its kind in the world -- won national attention today with reports that it could open the door to similar operations before birth for such diseases as sickle cell and hemophilia.

The therapy was developed by a UC San Francisco researcher who treated "the first patient enrolled in the world’s first clinical trial using stem cells transplanted prior to birth," according to a UCSF news release.

Fetal surgery was also invented in California. And the transplant was backed by $11 million from the state's stem cell agency, a $3 billion enterprise that is unique among states in its size and scope.

Missing from the news, however, was any mention of the agency's multimillion-dollar contribution -- a not insignificant matter since the agency is facing its own financial demise in less than two years. The agency hopes voters will keep it alive and approve $5 billion more for stem cell research in 2020. The agency, however, is laboring under a lack of public awareness for its "value proposition." (See here and here.)

The research is being conducted by Tippi MacKenzie, a pediatric and fetal surgeon who has received a total of nearly $15 million from the agency. Her employer, UC San Francisco, has received $169 million in 81 awards.  Various deans of its medical school have also served on the agency's governing board since the inception of the agency, known formally as the California Institute for Regenerative Medicine (CIRM).  

A spokeswoman for UCSF said omission of the CIRM funding in its news release was not intentional. 

The agency was not mentioned also in a lengthy article on MacKenzie's research in the New York Times this morning. The piece was displayed on the front page of the weekly Science section of the Times, a prestigious position available only 52 times a year.

MacKenzie's work involved a family from Hawaii and their child, who was treated in utero for a nearly always fatal affliction. 

In the article by Denise Grady, the Times reported, 

"Elianna, born Feb. 1 with a robust cry and a cap of gleaming black hair, has a genetic disease that usually kills a fetus before birth. The condition, alpha thalassemia major, leaves red blood cells unable to carry oxygen around the body, causing severe anemia, heart failure and brain damage.

"The transfusions in the womb kept her alive, but only treated her illness. The bone-marrow transplant has the potential to cure it. Whether it will succeed is still too soon to tell.

"Elianna and her mother, Nichelle Obar, were the first patients in an experiment that pushes the limits of fetal therapy, a field already known for its daring."

The Times continued, 

"If the treatment works, it could open the door to using bone-marrow transplants before birth to cure not just Elianna’s blood disease but also sickle cell anemia, hemophilia and other hereditary disorders, some so severe that the prenatal diagnosis may lead parents to end the pregnancy.

"Bone marrow is considered a potential cure because it teems with stem cells, which can create replacements for cells that are missing or defective as a result of genetic flaws."

Asked for comment by the California Stem Cell Report, Maria Millan, president of CIRM and a pediatric surgeon, said in an email, 

“The New York Times picture of Nichelle Obar with her 3 week old daughter Elianna shows us something that’s hard to capture in a billion words.(See photo above.)  Elianna is afflicted with alpha thalassemia major, a fatal condition that usually ends up in death before birth.

"It is extremely gratifying to know that CIRM has been instrumental in supporting Dr. McKenzie’s research to develop a treatment for this severe unmet medical need. Dr. McKenzie’s approach combines surgical advances that allow her to treat the baby while still in the mother’s womb; transplantation with the mother’s blood stem cells provides healthy blood cells that the baby needs to survive. 

"We have supported Dr. McKenzie’s research from the early years when she was a new faculty working out the basic science and immunology in the laboratory and we helped her to develop her clinical plan. Most recently, we have partnered with Dr. McKenzie to bring this research to clinical trials. To see Ms. Obar take their child home from the hospital is encouraging. We know that this is just the beginning. This is what the people of California voted for when they approved Proposition 71. They depend on us to boldly partner with Dr. McKenzie to translate the promise of stem cell treatments to patients with unmet medical needs."

The phase one clinical trial, which is aimed primarily at safety, is scheduled to release its preliminary results by February 2022 and hopes to treat another nine patients. The treatment would then face another two phases of clinical trials for efficacy. 

As for the baby, her mother told the Times, 

“Elianna’s doing great. I’m not disappointed at all. If it works, great. If it didn’t, we’re O.K. with it. We’ll celebrate all the little accomplishments. I’m glad we did it."

Here is a UCSF video on the trial.

Stem Cell 'Hotbed:' A CIRM Roadshow in Riverside

California's $3 billion stem cell agency took its message of hope for possible therapies to Riverside this week, part of its continuing outreach program that is increasingly taking on additional importance.

Why? Because the agency is scheduled to run out of cash for new awards by the end of next year. It is hoping to raise $220 million to stave off its demise until November 2020 when the plan is to ask state voters to approve an additional $5 billion in funding.

Writing on the agency's blog, Kevin McCormack, senior director of communications for the agency, was enthusiastic. His headline said, 

"A road trip to the Inland Empire highlights a hot bed of stem cell research"

McCormack wrote,

"It was a packed event, with an overflow group watching on monitors outside the auditorium. The questions asked afterwards didn’t just focus on the research being done, but on research that still needs to be done.
"One patient advocate couple asked about clinics offering stem cell therapies for Parkinson’s disease, wondering if the therapies were worth spending more than $10,000 on....
"The visit was a strong reminder that there is exciting stem cell research taking place all over California and that the Inland Empire is a key player in that research, working on projects that could one day have a huge impact in changing people’s lives, even saving people’s lives."

The stem cell agency, formally known as the California Institute for Regenerative Medicine (CIRM), is not exactly a household word among most Californians. Events such as the one in Riverside help to spread the word about its activities to voters who might be considering another funding initiative for the agency. However, these type of CIRM events rarely generate news coverage that can amplify their reach. 

The Riverside event was a case in point. A UC Riverside press release earlier this month led to a four-paragraph item in the Riverside Press Enterprise announcing that the event was upcoming. But no news story has yet emerged from the actual event itself. Indeed, the only news story in the newspaper this month about the benefits of stem cell research involved the Vatican, a Riverside girl and, indirectly, a company, Caladrius Biosciences (formerly Neostem) that was awarded $11.6 million from CIRM. The agency, however, was not mentioned.

Tomorrow, another CIRM event will be held at UCLA to highlight the agency's  $50 million, Alpha Clinic program that brings resources together to focus intensely on stem cell therapies and patient treatment.

Fleshing Out the Details: Inside the California Stem Cell Agency's Fledgling Industry Partnership Program

 California's $3 billion stem cell agency has released details on just what is involved in its new collaboration with industry, giving select companies "direct access" to the hundreds of millions of dollars in research that the state has financed. 

The effort involves creation of "robust data rooms," nondisclosure agreements and licensing templates, among other things, and owes a debt to the agency's moribund, $150 million public-private partnership proposal (ATP3).  The new program is aimed at speeding development of stem cell therapies as the agency faces its possible demise in the next couple of years. 

The California Institute for Regenerative Medicine (CIRM), as the agency is formally known, has dubbed the collaboration as the Industry Alliance Program (IAP). It  already has two partners from the private sector, BlueRock Therapeutics of Cambridge, Mass., and Vivo Capital of Palo Alto, and the agency is looking for more. 

Q & A: Data Rooms and More

Neil Littman, CIRM photo

CIRM disclosed more information about the program in response to questions from the California Stem Cell Report (CSCR). Here is the agency's reply from Neil Littman, CIRM's business development officer. It includes a response to a comment filed last week on the original article by an anonymous reader concerning access to research.

CSCR: "What does 'direct access' to CIRM’s growing stem cell portfolio' mean? Will grantees be asked to share their results with these companies....or will CIRM just give out grantees' proprietary information to these companies?"

Littman:  "CIRM will never share proprietary information without the consent of the awardee and the awardee’s institution. In addition, in order to access non-public information, IAP partners (just like everyone else) will need to execute a confidentiality agreement with the awardee’s institution. 'Direct access' implies CIRM’s role in helping IAP partners navigate CIRM’s large and growing portfolio and facilitating introductions when it is mutually agreed upon by the awardee and IAP partner."

CSCR: "It would be useful to discuss with more specificity this language from the IAP agreements: "...diligence process through template legal agreements, such as non-disclosure agreements and licensing templates, and robust data rooms."

Littman: "What does CIRM mean by diligence process? The term due diligence refers to the process of how a company evaluates technology before making an investment. This is often a lengthy review process where the company evaluates items such as preclinical clinical and clinical data, CMC information, and regulatory correspondence. CIRM will help streamline this process by working with the awardee and awardee’s institution to gather all the information in one place for the collaborator to review (this is commonly referred to as a 'data room').

"Why are template agreements useful to collaborators? The template legal agreements provide standardized language which help save time for both the collaborator and the awardee institution. Many features of the agreements will still need to be negotiated, such as the economics of a specific deal, but the templates serve as a starting point."

Son of ATP3

CSCR: These arrangements appear to be descended from CIRM's ATP3 proposal. How did the partnership program emerge? How did those two companies come to be the first to be involved? 

Littman: "Yes, the IAP is descended from ATP3 and is meant to achieve the same goal: increasing the pull from industry in order to increase the number of partnerships. BlueRock and Vivo Capital were selected for a variety of reasons, including: 1) Demonstrated commitment to advancing stem cell treatments to patients (i.e. they have already made investments in the space) 2) Continued commitment to investing in stem cell programs in the future, 3) They are well capitalized with the ability to invest in CIRM-funded programs."

Text of IAP Agreement

Here is the text of the signed agreement with BlueRock, which was requested by the California Stem Cell Report. The agreement with Vivo is identical.

   California stem cell agency agreement with BlueRock Therapeutics by DavidJensen on Scribd

California's $3 Billion Stem Cell Program Partners with BlueRock and Vivo Capital, Looks for More Industry Collaborators

California's drive to produce a stem cell therapy is ratcheting up a notch with announcement of  two new, global industry partners along with a plan to engage more companies and give them "direct access" to hundreds of millions of dollars in state-funded research.

The California Institute for Regenerative Medicine (CIRM), as the $3 billion state stem cell agency is formally known, said the program represents an opportunity "to bring the most promising stem cell, gene therapy and regenerative medicine programs to market where they can help people with unmet medical needs."

The first two participants are BlueRock Therapeutics of  Cambridge, Ma., with offices in Toronto and New York City, and  Vivo Capital of  Palo Alto, Ca., which has offices in Bejing, Shanghai and Tapei. BlueRock was founded in 2016 with $225 million in backing from Versant Ventures and Bayer AG. Vivo has more than $1.7 billion under management, according to the firm's web site.

In addition to venture capital firms, the agency said its Industry Alliance Program (IAP) is looking for pharmaceutical and biotech partners to give them "direct access to CIRM’s growing stem cell portfolio."

Maria Millan, CEO and president of CIRM, said in a news release,

Maria Millan

"The goal of the IAP is to secure industry partnerships and funding for CIRM’s translational and clinical-stage projects. Our agency provides researchers the initial funding to advance promising projects towards the clinic. Now, we’re going a step further by offering a program that facilitates connections between industry partners and our grantees. These companies can offer the support or additional funding needed to give these promising projects the best chance for success and the best chance of helping patients.”

The stem cell agency is nearing its final days and is looking to fulfill promises to California voters who created it 13 years ago through a ballot initiative. The measure provided $3 billion in state bond funding, but no more. The campaign also generated expectations that stem cell cures were just around the corner. The agency has yet to back a therapy that is widely available.

The agency expects to run out of cash for new awards by the end of next year. A $220 million private fundraising effort is being waged to help the agency along until November 2020. That's when CIRM backers hope that the agency's efforts will excite California voters enough for them to approve $5 billion more in funding via another citizen-based initiative.

Deeper involvement with industry is one way to produce quicker results. Venture capital firms are willing to move fast and bet big on research that they deem likely to produce handsome profits.

BlueRock focuses on cell therapies that target severe brain and heart conditions.  According to Biospace, the company expects its most advanced lead therapeutic, a compound for Parkinson’s disease, to begin clinical trials this year.

Vivo focuses on high quality companies in the United States and China but includes building companies from scratch. 

California also brings something to the game.  Karen Ring, the agency's Internet majordomo, noted last week on the agency's blog,

"CIRM is the world’s largest stem cell research funding institution dedicated to helping patients by accelerating the development of quality stem cell treatments. We’re currently funding 244 active stem cell research programs including 39 ongoing clinical trials."

Neil Litman, the agency's director of business development, said CIRM has a "unique vantage point" because of its broad scope. He said the new program is "essentially a built-in concierge service for the stem cell space."

Media Coverage of Stem Cell Therapy for Blindness Loses Sight of California's $36 Million in Support

Dennis Clegg of UC Santa Barbara, one of the leaders in developing a new stem cell treatment for AMD, speaks broadly about the approach in this 2016 video.

The news this week was good for the $3 billion California stem cell agency, which is facing its possible demise in less than two years.

The stories demonstrated what the CEO of the agency, Maria Millan, calls the "value proposition" of the agency's work for the people of California. But only if the agency is mentioned in the news coverage.

Public perceptions are no small matter for supporters of the research agency, formally known as the California Institute for Regenerative Medicine (CIRM).  They wonder as does Millan: How does the agency get real and robust credit for its work, a likely life-or-death question given the agency's hopes to win voter approval of $5 billion more in funding in 2020?

CIRM says it is on track to run out of cash for new awards by the end of 2019 unless its ambitious fundraising plans are successful. And those are only a partial solution until billions more are provided by California citizens.

This week's "good news" stories generated national attention, albeit relatively modest, about CIRM-funded research that has led to to the first-in-human clinical trial for dry, age-related macular degeneration. The treatment uses technology that was described as "very exciting" by one researcher not connected with trial.

The headline on the New Scientist story on Wednesday said,

"Eye implant improves vision in people with age-related blindness"

Reporter Andy Coghlan wrote, 

"A patch implanted at the back of the eye has improved or stabilised sight in four people with severe age-related macular degeneration. The treatment enabled one 69-year-old woman to read 24 letters on a standard eye chart, when she could previously manage only seven.
"The patch is made of eye cells made from human embryonic stem cells, and it has been designed for treating the 'dry' form of macular degeneration, which accounts for 90 per cent of all cases, and affects 1.7 million people in the US."

Nowhere in the New Scientist story was it mentioned, however, that the state of California, through its stem cell agency, has pumped $36 million into the work. 

Likewise for the Los Angeles Times, whose story also did not mention the agency.  And likewise for articles on MIT Review, MedicalXpress, HealthDay, WebMD, US News and World Report, Futurism and FierceBiotech. The list could go on, but you get the idea.

Even the press release from Regenerative Patch Technologies LLC of Portola Valley, Ca., which holds the exclusive license for the implant, buried the Golden State's contribution in the next-to-last paragraph of a nine-paragraph press release.   Plus the company failed to note that the funding was a not insignificant $36 million.

FierceBiotech did mention some private money that was involved in other AMD research, but ignored California's cash.

Readers not familiar with the traditions surrounding news stories about medical research might wonder why the California support received almost no attention. Generally speaking, the amount of cash and the funding source are all but ignored in such stories with some notable exceptions. How that has come about is not clear, but money talks in most circles. The scientist who has lost his or her appointment by failing to bring in sufficient grants can speak to that.

For the California stem cell agency, it is also likely to be a matter of survival. If it fails to receive the widespread public credit for what it believes is a strong and important body of work, it is likely to wither away in very short order. 

Sacramento Bee, Royalties and California Stem Cell Payoff

The Sacramento Bee this morning carried an article by this writer on the California stem cell agency and its first $190,345.87, royalty check. The article is aimed at a more general audience including policy makers in the state Capitol. Here is a link to the piece, which carries this headline on The Bee web site:

 "Will California's $3 billion in stem cell spending pay off? First royalty check arrives"

The full text of comments summarized in the piece will be carried later today on the California Stem Cell Report. 

A Look at Whether California's Stem Cell Agency Can Carry the Day Two Years From Now

One of California's more respected news operations today posted an overview of the state's $3 billion stem cell research agency, asking the question:

"Should California Voters OK $5 Billion More for Stem Cell Research?"

The piece by David Gorn on KQED's web site recapped the history of the program, its current condition and included comments from Robert Klein, the man behind the $5 billion proposal and who is often regarded as the father of the agency.

Barbara Koenig
 UCSF photo

Also included were comments from folks not always heard from publicly in the discussions about the agency. Quoted was Barbara Koenig, head of the bioethics program at UC San Francisco, who said she supports stem cell research but voted against the ballot measure that created the agency in 2004. She said,

“I didn’t like the overhyping of the immediate idea that there were cures around the corner.  I think we need to be honest about how we’re investing in research.”

Gorn continued,

"Ask Koenig how she might use that proposed $5 billion differently, and she responds with a moment of stunned silence.

"'Oh my, so many things,' she said. 'I would try to figure out how to make sure every child in California has access to basic health services, nutrition, clean water . . . not just make high-priced products, but to improve public health.'

"She said stem cell research privileges these quick-fix biotech approaches, which may make a lot of money but may not benefit the general public.'". 

Gorn's piece had some reach into the general public in the Golden State. In addition to its online news site, the San Francisco-based KQED operates a public TV station including news and  a public radio station with syndicated programming throughout the state. A version of today's story is expected to run next week on KQED's California Report, which the station says reaches 775,500 persons each week.

Gorn's report was pretty much down the middle, exploring the expectations for cures that emerged from the 2004 campaign directed by Klein, who also oversaw the writing of the initiative. His view is that that agency has "out-achieved" the promises of the campaign. Gorn wrote that Klein said that the campaign "never promised cures during the lifetime of the stem cell agency, only progress toward attaining them."

The governing board of the California Institute for Regenerative Medicine, as the agency is formally known, has all but endorsed Klein's current plan to place another initiative on the 2020 ballot, a presidential election year that will generate the large turnout that tends to favor bond measures.

Bonds -- money that the state borrows -- are the only significant source of cash for the agency. Ironically, the measure that created the agency -- also provided the seeds of its death by terminating its bonding authority after a specified period. Today the agency is down to its last few hundred million.

Zev Yaroslavsky, UCLA photo

Bonds additionally are usually used for long-lived assets such as roads and buildings and roughly double the cost of the research to taxpayers because of the interest expense. 

Gorn concluded with a comment from Zev Yaroslavsky, an authority on state politics and government at UCLA, as saying  that even if voter attitudes are highly favorable toward stem cell research that may not be enough to carry the day.

Yaroslavsky said,

"People do see stem cell research as something they have a stake in, but you’re going to have to explain what we got with the first $3 billion. I suspect their case with the voters will be that we need to keep momentum going. But the question is, ‘Will they buy it?’"