Hope and the 'Helping Patients Part': The Uncertain Future of California's Stem Cell Program

One of the big selling points of the $3 billion California stem cell agency has always been hope. And it still is. 

It is a difficult matter to argue with. Hope underpins all our lives. But no more so than with persons suffering from terrible and incurable diseases. And those are precisely the targets of the 13-year-old stem cell research effort financed by the people of California. 

Currently the agency is on a course to run out of cash for new awards in 2019, ironically a fate dictated by Proposition 71, the ballot initiative that also created the agency in 2004. The measure provided $3 billion but no further stream of income. The agency is now wrestling with a variety of possibilities to extend its life for another decade or so, including mounting a $5 billion bond measure on the November 2020 ballot. 

A stem cell researcher at UC Davis, Paul Knoepfler, today addressed those critical matters -- and hope -- in a post on his blog, The Niche. He wrote, 

"The California Institute for Regenerative Medicine, more widely known as CIRM, has accomplished big things over the course of its history of about a decade and sparked a great deal of innovation, but what does the future hold for our stem cell agency?"

Knoepfler mentioned coverage of CIRM meeting last week by the California Stem Cell Report, noting that last week's item included the phrase "withering death." Knoepfler wrote,

"I don’t see things as so bleak and remain hopeful on the agency’s future. It’s unclear how California voters will be feeling about all this in 2020, but with our stem cell agency we are just now getting to the exciting part. The helping patients part. As a past grantee myself, I know how much the funding can make impact to advance science, whether basic, clinical, or somewhere in between. 

"At the recent brainstorming meeting on the agency’s future, there were apparently some upbeat reports of voter sentiment as described by (David) Jensen (producer of the California Stem Cell Report):

"'Robert Klein, a Palo Alto real estate investment banker who ran the 2004 campaign that created the agency, told the CIRM directors of a private poll that he said showed 70 percent of Californians supported stem cell research and continued funds for the stem cell agency.'

"What do you think about our stem cell agency’s future? 

"In terms of clinically relevant science, it is at the most promising point in its history with support for loads of clinical trials. Not all of them will work out, but I’m convinced that some will and other fresh trials that could be initiated with CIRM’s new funding in the future beyond 2020 would bring more hope."

The  California Stem Cell Report welcomes your thoughts on the agency's future and its strategy for getting there. You can submit them either by clicking on the word "comments" at the end of the item or by emailing them to djensen@californiastemcellreport.com.

California Researchers Score $16 Million Plus in State Stem Cell Awards

The California stem cell agency today handed out $16.4 million in research grants seeking therapies for afflictions ranging from gum disease and cancer to vision loss and Parkinson's Disease.

The award for Parkinson's was relatively tiny -- only $150,000 -- but represented a rare case in which the agency's governing board overturned its reviewers, who make the de facto decisions on awards.

The reversal came after one board member, David Higgins, of San Diego, who has Parkinson's, noted that the most common drug that Parkinson's patients take is 70 years old. He told the board.

David Higgins, CIRM photo

“I’m a fourth generation Parkinson’s patient and I’m taking the same medicine that my grandmother took. They work but not for everyone and not for long. People with Parkinson’s need new treatment options and we need them now. That’s why this project is worth supporting. It has the potential to identify some promising candidates that might one day lead to new treatments.”

The award went to Zenobia Therapeutics, Inc., of San Diego, whose president and co-founder, Vicki Nienaber, had filed an appeal on the reviewers' decision.  Another applicant rejected by reviewers, Toshio Miki of USC, also filed an appeal with the board. His appeal was not discussed. Miki's application sought $5.9 million for research involving metabolic disorders.

The largest award today, $5.6 million, went to Anthony Oro of Stanford, who will be testing a therapy to treat an affliction that creates wounds that will not heal. Dan Kaufman of UC San Diego received $5.5 million to produce "killer cells" to help people with a form of leukemia. Catriona Jamieson, also of UC San Diego, received $2.7 million for leukemia research.

Here is a link to summaries of reviewer remarks, including scores, on the three winners and the 11 other applications that were rejected in the translational awards category. (Scroll down on the page to see the reviews.)

In addition to the "discovery" award for Parkinson's, here are the names of the other winners in that category:

•  DISC1-10603, Ngan F Huang, iPSC-Derived Smooth Muscle Progenitors for Treatment of Abdominal Aortic Aneurysm, Palo Alto Veterans Institute for Research, $172,621
• DISC1-10475, Semil P Choksi, Generation of human airway stem cells by direct transcriptional reprogramming for disease modeling and regeneration, U.C. San Francisco, $238,408
• DISC1-10643, Dmitriy Sheyn, IVD rejuvenation using iPSC-derived notochordal cells, Cedars-Sinai, $241,992 
• DISC1-10598, Alice F. Tarantal, Enhanced Branching Morphogenesis and Pluripotent Cell Lineage Differentiation for Pediatric Regenerative Therapies, U.C. Davis, $235,80
• DISC1-10583, John R Cashman, Human Pancreatic Cancer Stem Cells: Developing a Novel Drug for Cancer Eradication, Human BioMolecular Research Institute, $303,894 
• DISC1-10555, Hiromitsu Nakauchi, Optimizing self-renewal signaling kinetics to stabilize ex vivo hematopoietic stem cell expansion, Stanford, $235,836 
• DISC1-10620, David J. Baylink, Bone Marrow Targeting of Hematopoietic Stem Cells Engineered to Overexpress 25-OH-VD3 1-α- hydroxylase for Acute Myeloid Leukemia Therapy, Loma Linda University, $178,967 
• DISC1-10513, Guillem Pratx, Novel metabolic labeling method for tracking stem cells to irradiated salivary glands using PET, Stanford, $235,613 
• DISC1-10522, Gerald P Morris, Identification of antigenic neo-epitopes from in vitro reprogrammed human tissue precursors for regenerative therapy, U.C. San Diego, $193,500
• DISC1-10588, Julia J. Unternaehrer-Hamm, Targeting cancer stem cells with nanoparticle RNAi delivery to prevent recurrence and metastasis of ovarian cancer, Loma Linda University, $172,870 
• DISC1-10721, Karl J. Wahlin, An IPSC cell based model of macular degeneration for drug discovery, U.C. San Diego, $232,200 
• DISC1-10516, Alyssa Panitch, Development of treatments to improve healing of ischemic wounds, U.C. Davis, $235,800 
• DISC1-10718, Alireza Moshaverinia, Gingival mesenchymal stem cells as a novel treatment modality for periodontal tissue regeneration, U.C. Los Angeles, $194,483

Here is a link to all the review summaries and scores in the round, including the 28 rejected applications.  Here is a link to the CIRM press release. 

Balloting on Stem Cell Person of the Year: Cast Your Vote Now

The countdown has begun for selection of the Stem Cell Person of the Year. You can vote online for your preference at The Niche, a blog operated by UC Davis researcher Paul Knoepfler.

He has put together a list of 20 nominees ranging from a California state legislative aide to the CEO of the New York Stem Cell Foundation, Susan Solomon. Also included is a host of researchers, including Shoukhrat Mitalipov and Alexey Bersenev. The full list can be found here.

Knoepfler is the sole judge of the winner and personally provides a prize of $2,000.

The current voting, which ends Dec. 12, will whittle the list down to 10 from which Knoepfler will pick the winner. Earlier this month, he had this to say about the award,

"Unlike some other science awards out there that shall remain nameless, the Stem Cell Person of the Year prize is not an insider kind of thing, but more of an anti-old boy’s club award. It’s not about who you know, but what you do to help science, medicine, and other people."

Personally, I think the team at the California stem cell agency should be on the list. The folks, past and present, at the agency have labored mightily since 2004 to advance stem cell research. Sometimes the circumstances have been difficult and challenging, but the work continued nonetheless. Maybe next year, as they say in the sports world.

"Cuts," Private Fund-Raising, $5 Billion Bond Measure: Answers to the Critical State of California Stem Cell Finances?

Bob Klein explored a $5 billion bond measure at today's stem cell meeting. 
California Stem Cell Report photo

OAKLAND, Ca. -- Facing the likelihood of a slow and withering death, the California stem cell agency today edged gingerly forward on a path of "cuts" and risky fund-raising in hopes that its research results will soon generate voter support for more billions of dollars.

Two governing board committees of the $3 billion agency, formally known as the California Institute for Regenerative Medicine (CIRM), this afternoon recommended that the full board "entertain" the proposals at its Dec. 14 meeting.

The agency is down to its last $269 million and expects to halt new awards in 2019 unless additional funds are raised between now and the beginning of 2020. It has been running at a $300-million-a-year pace recently and has pumped out about $25,000 an hour, 24 hours a day, seven days a week since it started making awards in 2005, according to calculations by the California Stem Cell Report.

Today's meeting focused on both short and long term finances. The committees examined a proposal to cut its planned clinical awards by $68 million over the next two years by limiting their size. The committees also indicated support for an ambitious effort to raise $222 million privately between now and early 2020.

Longer term, directors staked their hopes on voter approval of a ballot initiative in November 2020 that could total $5 billion. Development of a stem cell therapy that would resonate with voters would be a major key to the success of that effort. The 2004 campaign raised expectations that stem cell cures were right around the corner, but so far the agency has not backed one for widespread use.

Robert Klein, a Palo Alto real estate investment banker who ran the 2004 campaign that created the agency, told the CIRM directors of a private poll that he said showed 70 percent of Californians supported stem cell research and continued funds for the stem cell agency.

Following the meeting, the California Stem Cell Report asked him for a copy of the poll. He declined to provide it or identify the firm that conducted the survey.

Klein told the CIRM board members that the agency has made "remarkable progress" and has created a "moral imperative" to continue the search for stem cell cures. He said,

"The bridge to the future is CIRM and stem cell therapies."

The now less-than-robust finances of CIRM are a product of the ballot initiative, Proposition 71, that created it. CIRM is not funded through the customary process used by most state agencies. The initiative  stipulated that CIRM would be supported by $3 billion in state bonds whose funds would flow directly to the agency and bypass the legislature and the governor. When that cash runs out, the agency is left with no other source of state funding.

Raising $222 million privately over the next two years is no small task, but deep pockets exist that may well be tapped. The Eli and Edythe Broad Foundation, for example, has donated nearly $80 million to stem cell research centers at UCLA, UC San Francisco and the University of Southern California. All three are linked to CIRM. In San Diego, the Sanford Stem Cell Consortium was given $100 million in 2013 by Denny Sanford, another billionaire. The consortium came into being after it was backed by $43 million from CIRM.

Nonetheless, competition for philanthropic cash is heated. Thomas and Klein, however, both indicated that they would collaborate on raising the $222 million, which would allow the agency to add eight new clinical awards in 2020, among other things.

The risk lies in the timetable for bringing in the cash. The agency has a relatively tight schedule for making awards --- a schedule that a major philanthropist may or may not be ready or willing to comply with.

Without more cash, the stem cell agency projected that it would wither away by 2023 as it managed a declining number of old research grants.

For more, recent articles on CIRM's current critical funding situation, see here, here, here and here.

California Stem Cell Agency Examines its Financial Options Long-Term and Short-Term

OAKLAND, Ca. -- A key group of directors of the $3 billion California stem cell agency this afternoon opened a discussion dealing with its short and long-term financial future at 1:04 p.m. The meeting is scheduled to last until 4 p.m. The California Stem Cell Report will file stories as warranted.

California Tightening Stem Cell Research Belt; Size of Research Awards Targeted

The stem cell agency outlined its assessment of its current position
 in this slide prepared for today's meeting. 

OAKLAND, Ca. -- California's $3 billion stem cell agency is preparing to put the squeeze on its research awards over the next two years, cutting the caps on new grants in some areas by 50 percent or more.

It is all part of a strategy to prolong the life of the 13-year-old research effort as it fights to fulfill the expectations of voters who created it when they approved a ballot initiative in 2004. Voters provided only $3 billion in funding, however, and the agency is now expected to run out of cash for awards in 2019 unless it changes its financial ways.

Meeting here today are two key groups, the Transition and Science subcommittees of the governing board of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known.

They are scheduled to wrestle with both the agency's short-term finances and the longer term effort to extend CIRM's life for perhaps an additional 10 years or more via another ballot initiative in 2020. As for next year, based on past discussions and practices it appears certain that the agency's directors will reduce the size of awards to the scientists and businesses who are often hard-pressed to find non-governmental support.

A proposal by the president of CIRM, Maria Millan, calls for reducing clinical program awards by a total of $68 million over the next two years. Here is how the cuts would work compared to the average award this year in each category.

• Phase 1 and phase 1/2 clinical trial grants would see their caps reduced from $20 million to $12 million for nonprofits and $8 million for for-profit enterprises. The average award in 2017 in these categories was $10.3 million. 
• Phase 2 trials would see their caps cut from also $20 million to $15 million for both non-profit and for-profit enterprises. The 2017 average award was $15.3 million. 
• Phase 3 trial awards, which averaged $16.7 million in 2017, would have their caps cut from $20 million to $10 million for both types of enterprises.

Millan's presentation indicated that would her proposals would allow the agency to support 24 new trials and eight trial candidates over the next two years, in keeping with a strategy of taking "more shots on goal" as the agency tries to develop a stem cell therapy for widespread use. Clinical trials, which can take years, are the last stage before a therapy is approved by the federal government. 

Millan's plan would also allot only $10 million for what the agency calls "Discovery" awards (basic research) next year (10 projects) and $9.25 million in 2019 (nine projects). Discovery awards are expected to hit $46 million this year. Education awards are expected to total $1 million this year. Next year they  would receive $750,000 and nothing in 2019. 

Key to the spending plan is the assumption that the agency could raise an additional $220 million from a variety of sources between the end of next year and early 2020. The goal of the fund raising is to bring in $55 million by the final quarter of next year. The rest would be raised between then and the first quarter of  2020. 

CIRM did not release details of its strategy for raising the $220 million. CIRM Chairman Jonathan Thomas, however, has already been on the fundraising trail and reports that he has identified a number of potential donors.

The financial plans and any changes will go to the full board for ratification at a meeting Dec. 14 here at CIRM headquarters.

The California Stem Cell Report will cover today's meeting and file reports as warranted on this web site. Below is another presentation slide from the stem cell agency. 

California Stem Cell Agency Faces Rising Cash Burn Rate; Readying for New, Multibillion Dollar Bond Attempt

Cash is flowing out the door fast at California’s $3 billion stem cell agency, which now expects money to run out for new research awards by the end of 2019 instead of the middle of 2020.

The California Institute for Regenerative Medicine (CIRM), as the agency is formally known, expects to be down to its last $269 million in uncommitted funds by end of this year. And it is working on a new plan to raise $200 million in private funds to sustain its operations through 2020.

The financial projections -- crafted as the agency faces what its leaders call a "critical stage" -- are online this week on the CIRM web site and include proposed lower caps on the size of awards in 2018 and 2019. The agency said the increase this year in the pace of funding was generated by more, higher quality research applications.

Maria Millan, CIRM photo

In documents prepared for a key CIRM meeting next Monday, Maria Millan, CEO of the agency, said her budget scenario would maintain CIRM’s “value proposition as intact as possible” while work moves forward on a proposed, multibillion dollar bond measure in November 2020. She also said enough funds would be available to “wind down” the agency if the bond measure fails.

(See here for Millan's plan and here for longer term bond funding.)

The agency was created by a ballot initiative in 2004, Proposition 71, which financed it with a $3 billion bond measure. No other significant funding was provided. The ballot campaign raised rosy expectations among voters that stem cell therapies were right around the corner.

So far the agency has not backed a therapy that has been approved for widespread use. But it is helping to support 38 clinical trials, the last stage before a therapy is approved by the federal government for widespread use. Many more trials, which can take years, are expected to be funded prior to 2020,

CIRM Chairman Jonathan Thomas, in a presentation prepared for next week’s meeting, pointed to “early successes” such as those involving work by Donald Kohn at UCLA. Thomas also cited “promising early returns” with Asterias Therapeutics’ work on spinal cord injuries.

Thomas’ proposal, in addition to private fundraising, calls for a “citizen-led” bond measure in the fall of 2020 to sustain CIRM on a more long-term basis. During next week's meeting, Robert Klein, the Palo Alto real estate investment banker who led the 2004 ballot initiative campaign, is expected to address the prospects for another initiative measure, possibly as large as $5 billion.

As back-up options, Thomas identified the possibility of asking the legislature and governor to place a bond measure on the 2020 ballot along with seeking donor funds for co-funding of specific projects.

In Millan's presentation, she said it is “essential to preserve CIRM’s value proposition to increase the probability of and the speed by which stem cell treatments can reach patients.”

The session on Monday involves the Transition and Science subcommittees of the CIRM board. The committees are expected to recommend budget and fundraising plans to be ratified by the full board at its meeting Dec. 14.

In September, the Transition group took a crack at a wider range of possibilities. The latest proposals are a refinement of what was discussed then.

Next week's meeting will be based at CIRM’s headquarters in Oakland with telephonic sites where the public can participate in La Jolla, Duarte, South San Francisco, Los Angeles and San Francisco. Public comments can be emailed to mbonneville@cirm.ca.gov. The session will also be audiocast on a listen-only basis. Instructions can be found on the agenda along with addresses for the telephonic locations. 

Correction

In the Parkinson’s therapy item on Nov. 17, 2017, the California Stem Cell Report incorrectly described the amount of funding involved in the GForce Parkinson’s initiative. The backing includes $52.3 million plus substantial support from BlueRock Therapeutics, which is financed with $225 million from Bayer AG and Versant Ventures. BlueRock, a Cambridge, Mass., firm, says on its web site, “Our most advanced therapeutic candidate, for Parkinson’s disease, will enter the clinic in 2018.”

More California Millions Sought to Support the 'New Era' of Parkinson's Therapy Research

A "new era" in the search for a cure for Parkinson's disease was heralded this month in an article in a prominent scientific journal that explored research involving more than $52 million and an organization called GForce-PD.

The news was accompanied by a cry for more support for Parkinson's research from the $3 billion California stem cell agency, which has pumped $49 million in Parkinson's studies over the last 13 years.

Jeanne Loring, director of the Scripps Center for Regenerative Medicine in La Jolla, Ca., and also a participant in the GForce initiative, said this week that CIRM has not supported Parkinson's research at the level of the other enterprises involved in GForce.

In an item she wrote for The Niche, a blog published by UC Davis researcher Paul Knoepfler, she listed $52.3 million in support plus substantial backing from BlueRock Therapeutics, which is financed with $225 million from Bayer AG and Versant Ventures. BlueRock, a Cambridge, Mass., firm, says on its web site, “Our most advanced therapeutic candidate, for Parkinson’s disease, will enter the clinic in 2018.

Parkinson's is a devastating disease that afflicts 10 million people in the world and 125,000 in California. One of those persons, David Higgins of San Diego, currently serves on the board of the stem cell agency, formally known as the California Institute for Regenerative Medicine (CIRM). Another, Joan Samuelson, was one of the original board members in 2004 and a fervent but often frustrated voice for Parkinson's research at many CIRM board meetings.

Actor Michael J. Fox, who made TV ads for the 2004 ballot initiative that created the stem cell agency, is also among the those living with the disease. Others with the affliction included the late boxing champion Muhammad Ali and famed semiconductor pioneer Andy Grove. 

Loring wrote on The Niche about a meeting in Japan earlier this year dealing with the research teams in the GForce project. She said,

"The Kyoto meeting was unprecedented in my experience.  Instead of competing, the four groups cooperated and shared plans for their proposed clinical trials.  We agreed to harmonize our trials and stay in communication about our progress.  All of us plan to start clinical trials within two years."

Loring continued,

"Since my team has been recognized by the international GForce initiative devoted to safe effective therapy for PD, we hope that CIRM will follow the example of New York, the EU, and Japan, and invest more in our project to provide neuron replacement therapy for Californians with Parkinson’s disease.

"While we hope to gain more support from CIRM, we are determined to follow through with our clinical trial, with or without CIRM.  It will just be more difficult without their help. The patients and their advocates inspire us, and we won’t let them down."

Loring added more information on Sunday (Nov. 19) concerning CIRM funding. She told the California Stem Cell Report. 

"We started our pre-clinical PD studies in 2011, with funding from Summit for Stem Cell. The first and only funding we received from CIRM for PD research was in 2016. 

"Before 2011, CIRM invested $41,838,336. Since 2011, CIRM has invested $7,357,468. This means that the majority of the funding went to projects that didn’t lead to any translational or clinical applications.  

"There are currently three active grants working on Parkinson’s disease, for a total of $4.9 million. We have the only translational grant, and it will expire in March 2018. All but $650,000 runs out by the spring of 2018. 

"There are no more grants forthcoming for our work. The Scaled Biolabs grant awarded this year is a partnership with us. Birgitt Schuele’s grant is basic research, not a cell therapy. (Below are the three active grants identified by Loring.) 

"Parkinson's Institute, Birgitt Schuele, Quest - Discovery Stage Research Projects, CRISPR/dCas9 mutant targeting SNCA promoter for downregulation of alpha-synuclein expression as a novel therapeutic approach for Parkinson’s disease, $1,931,495 

"Scripps Research Institute, Jeanne Loring, Quest - Discovery Stage Research Projects, Autologous cell therapy for Parkinson’s disease using iPSC-derived DA neurons, $2,354,226 and later $4,285,721  

2017
"Scaled Biolabs Inc., Justin Cooper-White, Quest - Discovery Stage Research Projects, A tool for rapid development of clinical-grade protocols for dopaminergic neuronal differentiation of Parkinson’s Disease patient-derived iPSCs, $657,528 "

(Editor's note: An earlier version of this item contained incorrect figures on the GForce initiative.) 

'Critical Stage' for $3 Billion California Stem Cell Effort and its Search for More Cash

California's $3 billion stem cell research program later this month is expected to unveil detailed plans for extending its life beyond the middle of 2020 in hopes of avoiding a lingering death.

The latest proposals, which are not yet public, are scheduled to be discussed Nov. 27. Possibilities range from another multi-billion dollar bond measure to private fundraising to possible merger with some sort of private entity.  

The stem cell agency, known formally as the California Institute for Regenerative Medicine (CIRM), projects its cash for new awards will run out in about 2 1/2 years. At that point, unless more money is forthcoming, CIRM will only be overseeing the dwindling number of awards whose terms extend beyond June of 2020.

The agency's fate was dictated by Proposition 71, which created CIRM in 2004. It also provided $3 billion in state bond funding, which flows directly to CIRM without oversight by the governor or the legislature. No additional, significant resources were contained in the ballot initiative.

CIRM's future has been an occasional topic for its board for some time. But the issue has taken on more urgency this year. At a meeting in September of a newly formed Transition Subcommittee of the governing board, CIRM Chairman Jonathan Thomas said in what may have been an understatement,

"CIRM, as we know, is at a critical stage of its mission here." 

The meeting on Nov. 27 will additionally involve the board's Science Subcommittee. What emerges from the session will go to the full, 29-member board in December for ratification.

Options in September included a multi-billion dollar bond ballot measure in 2020 and a possible merger, which was described as something of a last resort. Whatever path is chosen, it likely would lead to changes in the agency, which has been criticized for conflict of interest issues and its dual executive arrangement, among other matters.

The agency has awarded $2.3 billion in 919 grants during its 13-year history. About 90 percent of the awards has gone to institutions with links to members of the governing board, past and present, according to calculations by the California Stem Cell Report.

So far the agency has not fulfilled expectations of voters that it would generate a widely available therapy. Something may emerge in the next couple of years from the 38 clinical trials currently backed by the agency. (Forty-three have been funded but five were terminated.) The trials, which can take years, are the last stage before a therapy is approved by the Food and Drug Administration for widespread use. CIRM plans to add more trials in the next couple of years.

This month's meeting will be based at CIRM's Oakland headquarters with teleconference locations elsewhere in the state where the public can take part. It is scheduled to begin at 1 p.m. PST and run until 4 p.m.

The California Stem Cell Report will provide full coverage of the meeting that day with advance information as it is posted on the CIRM web site.

(Here is a link to the transcript of the September meeting. Here is a link to Thomas' slide presentation.)

Financial Examination of California Stem Cell Agency: Fireworks Not Expected

The only state panel that has formal oversight of the $3 billion California stem cell agency meets this Thursday in Los Angeles for what is expected to be a routine meeting.

The body is the Citizens Financial Accountability Oversight Committee, chaired by the state controller, Betty Yee.  The 10 a.m. meeting in Los Angeles City Hall has nothing on the agenda that appears to raise a red flag. However, some past sessions have been lively.

Leaders of the agency are expected to brief the committee, which was created by Proposition 71 in 2004, which also created the research effort itself.

The ballot initiative specifically exempted the agency, known formally as the California Insitute for Regenerative Medicine, from control by the governor and legislature.

Here is a link to names of the members of the committee.

The session will be available on a listen-only basis via the internet or an 800 number. Here are instructions:
Public call-in number (listen only): (877) 260-8900
Confirmation number: 433267

Listen to the meeting online: https://im.csgsystems.com/cgi-bin/confCast
Enter conference ID number 433267, then click “Go.”

The California Stem Cell Story: Key to Extending the Life of a $3 Billion Agency

An Asterias video carried by KQED as part of its story on a CIRM-backed stem cell therapy. 

Just before Halloween, the $3 billion California stem cell agency chalked up another PR score with a long, favorable piece on a public television station that covers the San Francisco Bay area.

The story focused on a potential therapy for spinal cord injury developed by Asterias Therapeutics, Inc., of Menlo Park, Ca. The audience for the story was also critically important -- millions of voters who may well be asked to provide more billions for the stem cell agency, which is slated to run out of cash in mid 2020.

The piece by David Gorn carried caveats, but it also used quotations such as "incredibly exciting" and phrases such as "truly remarkable." And it noted -- relatively high in the story -- that the research is backed by the California Institute for Regenerative Medicine (CIRM), as the stem cell agency is formally known.

Gorn wrote,

"The trial is legitimate. It’s partially funded by the California Institute for Regenerative Medicine, the state’s stem cell agency; well-known spinal experts are participating; and the FDA has certified the treatment as one that preliminary clinical evidence indicates has the 'potential to address unmet medical needs' related to a 'serious or life-threatening disease or condition.'"

The good news about the Asterias therapy has been written about before. But it is far from a topic that is talked about at California breakfast tables. 

The agency's activities -- good, bad or indifferent -- are well out of the coverage of the mainstream media, a sharp change from its early days in 2005 and 2006. Raising its profile -- favorably -- is a daunting task given that science writers have virtually vanished from the mainstream media -- all part of the shrinking world of today's journalism. 

In the last couple of years, however, the agency has stepped up its funding of clinical trials, which are the last stage before a therapy is approved for widespread use. Although clinical trials can take years to complete, their initial results can resonate with the public in a way that basic research does not. Seeing a person overcome an affliction is far more compelling than watching a mouse recuperate. 

CIRM's efforts are additionally hampered by a convention in science journalism that tends to minimize the importance of sources of funding. In most cases, it is mentioned only at the end of articles. Sometimes it is omitted entirely. 

CIRM, however, is a grand, California experiment that took up the cause of stem cell research when it was suffering from a lack of attention from risk averse companies and a lack of support from the federal government. Many of the 921 projects that the agency has funded may have never gotten off the ground without support from the voters of California, who created the agency in 2004 through a ballot initiative. 

CIRM additionally carries policy implications that go beyond bench science. It is the first such effort in state history, marrying big science, big academia, big business  and big politics in a unique way in California.

If the agency is to continue financing research to the tune of $300 million a year, it is almost certain to need another ballot measure. And to win voter approval once again, CIRM will need a vault filled with stories of accomplishment and human emotion that will resonate with the voters of the Golden State.

(Editor's note: The next to last paragraph is slightly rewritten from an earlier version of this item.)

CEO Millan on the Prospects for California's $3 Billion Stem Cell Research Effort

Maria Millan, the president of the $3 billion California stem cell agency, this week discussed the future of the nearly 13-year-old effort, which expects to run out of cash for new awards in 2020.

Her remarks are contained in a Q&A interview on RegMedNet, "a networking site that unites all members of the diverse regenerative medicine community," according to a statement on the site.  

The piece contains no big surprises but is worth examining if you want to get a sense of her background and where she is headed. Here are two excerpts.

Question: "What will happen once CIRM has given out all $3 billion allocated to it by Proposition 71?"

Answer: "We are working with our board to pursue sustainability options to ensure that the products of the Proposition 71 investment have the best chance of reaching the patients.  CIRM has played an essential role in growing the stem cell/regenerative medicine field by bringing in the critical mass of resources, top notch researchers, rigorous basic and translational research and building the most robust late development and clinical stage portfolio to accelerate novel treatments to patients with unmet medical needs. With the CIRM 2.0 processes that drove operational excellence and acceleration, there is incredible potential to build upon the recent early successes that led to projects that are nearing FDA marketing approval and to drive more of these successes to the benefit of healthcare and patients."

Question: "What are your plans for CIRM over the next few years?" 

Answer: "We are fully committed and motivated to executing on the 5 year strategic plan that we launched in January 2016. When we proposed these strategic goals, they were 'stretch' goals and now it looks like we will achieve these goals. This strategic plan is driven by our mission 'to accelerate stem cell treatments to patients with unmet medical needs.'"

'Invisible Work' and the California Stem Cell Agency

At one point in its history, the $3 billion California stem cell agency had only about as many employees as a 24-hour Burger King, probably fewer.

Today it is has 46 workers, most of whom labor behind the scenes, rarely visible to the public. They do what I call "invisible work." That means you only see it when it goes away. Then the job that once was performed very well with little notice draws great and sometimes anxious attention because the work -- all of a sudden -- is not getting done.

Last week the California Institute for Regenerative Medicine (CIRM), as the agency is formally known, to its credit moved to recognize some of those workers, which the agency calls team members.

Todd Dubnicoff, CIRM's multimedia editor, posted an item on the agency blog, The Stem Cellar, headlined,

"Meet Team CIRM: The People Behind the Mission to Save Lives."

Dubnicoff wrote,

"I don’t have the word space in this blog to introduce you to them all so, for today, say hello to a few of our 2017 CIRM Game Ball winners. At our quarterly Team meetings, we honor and celebrate members whose efforts reflect our 'All In' culture with this award."

They ranged from Lilia Leal, a finance officer, to Paul Webb, a senior science officer. Webb received his game ball for completing 40 of the important clinical advisory panel sessions in less than six months. Leal won her ball for reducing grant payment time by 30 days. 

We recommend the Dubnicoff item if you want to improve, however slightly, your understanding of CIRM and how it tries to make science happen. And congratulations to all the Game Ball winners. 

Research for Arthritic Knee Treatment Survives Challenge at California Stem Cell Agency

The California stem cell agency today awarded $33 million for clinical trial research, but not before some governing board members questioned the appropriateness of backing an effort to treat osteoarthritis of the knee.

The awards today bring to 43 the number of clinical trials funded by the stem cell agency, formally known as the California Institute for Regenerative Medicine (CIRM). The agency is pushing hard to fulfill the promise of the 2004 ballot campaign that created the $3 billion effort. Clinical trials are the last stage before a treatment can win federal approval.

The agency expects to run out of money in mid 2020, but so far has failed to back research that has resulted in a therapy that is available for widespread use. 

At today's telephonic CIRM board meeting, the arthritis research by La Jolla's California Institute for Biomedical Research encountered opposition from some members of the board who expressed concern that it did not square with the mission of the agency. 

At issue was the use of a small molecule drug, KA34, to stimulate stem cells to create new cartilage in knees. Jeff Sheehy, a board member and San Francisco county supervisor, said small molecule development is widely done already by the pharmaceutical industry. Noting that the research is a treatment and not a cure, he said funding the arthritis award would mean not funding other research that would be more focused on direct stem cell cures.

Art Torres, vice chairman of the board and a former state senator, supported the application, declaring that "if we can show we are finding some treatment we may be moving forward to getting support in other ways."

Both men have suffered from severe knee problems.  About one in five persons over 45 are afflicted with arthritis of the knee.

The vote by the board on the application, which involves a phase one safety trial, was 9-5. Last month, the agency's grant reviewers, meeting behind closed doors last month, approved the award following a more detailed examination of the proposal.

It was the third CIRM award for the San Diego not-for-profit firm, which has already received $4 million for work on arthritis. 

The largest award, $19.8 million, went to another San Diego area firm, Poseida Therapeutics.  A CIRM news release on today's action said the research will test "the safety of a gene modified cell therapy to treat multiple myeloma, the abnormal growth of malignant plasma cells of the immune system."

Maria Millan, president of the stem cell agency, said, 

“Multiple myeloma disproportionately affects people over the age of 65 and African Americans, and it leads to progressive bone destruction, severe anemia, infectious complications and kidney and heart damage from abnormal proteins produced by the malignant plasma cells. Less than half of patients with multiple myeloma live beyond 5 years.”

About 12,590 deaths are expected from multiple myeloma this year in the United States, according to the American Cancer Society. The award was the first for Poseida from CIRM. The company is providing $8.6 million in co-funding.

Like all the awards today, the Poseida award was approved earlier in a closed door meeting by reviewers who do not have to publicly disclose their economic or professional conflicts of interest.

There was no board discussion today of the Poseida award nor of the third award, $4.8 million to Childrens' Hospital of Los Angeles. Its phase one trial involves testing the feasibility of using engineered T-cells to fight viruses that can kill patients with weakened immune systems. Those patients include persons undergoing chemotherapy, bone marrow or cord blood transplants.

Childrens' Hospital Los Angeles earlier had received $26.3 million from the agency.

The agency has helped to finance 16 clinical trials in 2017 alone. Whether it will continue at this pace in 2018 is expected to be discussed at its December board meeting.  Some board members have indicated it would be of some benefit to slow the pace of funding to extend the life of the agency.

Here is a link to the overall staff presentation on the applications. Here are links to the summaries of the grant reviewers comments:  California Institute for Biomedical Research application CLIN2
-10388, Poseida application CLIN2-10392, and Childrens' Hospital application CLIN2-10392.

More information on the Poseida clinical trial, which is now recruiting, can be found here.

More information on all the agency's clinical trials can be found on CIRM’s Clinical Dashboard.

Stem Cells, Anonymous Commentary and Silence Dogood

What do Benjamin Franklin and Mrs. Silence Dogood have to do with the affairs of the $3 billion California stem cell agency?

Very little -- directly -- is one answer. The other answer is that Ben and the publicly spirited Mrs. Dogood had a lot to do with the publication of strong views that run afoul of the established order.

Ben Franklin, Getty Images

Silence Dogood, you see, was a pen name for Ben early in his career. He used it successfully to get his thoughts into print. It made Franklin, as a writer, anonymous -- thus overcoming the barrier that use of his own name posed.

All of which raises the topic of the day -- publication of anonymous comments concerning articles on the California Stem Cell Report -- more particularly the comment this morning on the ViaCyte item earlier this week.

In advance of today's publication of the comment, ViaCyte was offered, in the spirit of fairness, an opportunity to respond to the anonymous writer. Declining on behalf of the San Diego company was Jessica Yingling, president of Little Dog Communications Inc., of San Diego. She also asked whether “it is normal to have comments like this.”

My email reply to her earlier this week said, yes, it is relatively common to permit anonymous comments on the California Stem Cell Report. As I replied, I thought others were likely to have similar questions. Thus this piece came about.

But first, it is helpful to understand just how anonymous comments work on Blogger, the Google-owned platform for the California Stem Cell Report.

Google allows readers, at the option of the blog publisher, to make comments anonymously. Google controls the method that protects the anonymity of the writer. When I receive an anonymous comment, I do not and cannot know the names of persons who file them. But I do moderate them.

I permit anonymous comments because of the nature of the scientific community, the stem cell agency and the biotech industry. Of particular importance is that the agency is, in fact, a state government body and is spending public money. However, it is not answerable to the governor or the legislature because of the terms of the ballot measure that created it, Prop. 71. That is not the case for nearly all other state agencies. Currently the agency, formally known as the California Institute for Regenerative Medicine (CIRM), also functions almost invisibly with little attention from any media, mainstream or otherwise.

Over the past 13 years of writing about this rather large source of public funding for stem cell research, I have found that many persons in the field are reluctant to comment with complete candor, sometimes because it may appear to others in the field that their comments are unseemly. In other cases, people in the field are simply afraid of possible financial or professional repercussions if they make comments that some may find objectionable, no matter how well founded. If anonymous comments were barred entirely, it would mean a loss of a certain perspective about the agency and sometimes useful information about how the stem cell industry and the agency works. That said, not all anonymous comments satisfy that criteria.

I do not publish all anonymous comments. Some have been libelous. A few have been deranged. Others are nothing more than spam.

Reasonable people can and do differ about the use of anonymous comments on blogs or in the mainstream media, which are very different animals. During my decades of covering and editing news as well as directing coverage, use of anonymous sources has always been a matter of debate and controversy. I acknowledge that some, perhaps many, anonymous writers may be grinding a particular axe. On the other hand, the targets of such comments are not always forthright. It is not necessarily in their interests to disclose bad news. The media can also be easily manipulated by "official" sources, something I have seen occur widely over the past five decades.

Indeed, the backers of Prop. 71 in 2004 were less than forthright during ballot campaign that created the stem cell agency. But such is the nature of such political activities.

Ben Franklin was an adroit politician as well as a clever writer and advocate. He also hid his identity under many pen names during his life in the 18th century. Today I have no doubt that Silence Dogood would have no difficulties with our judicious posting of anonymous comments on the California Stem Cell Report.

For those of you would like to comment on this topic, please feel free. Just click on the word “comments” at the end of this item. Perhaps we will hear from some of Mrs. Dogood’s descendants.

Public Welcome: California Stem Cell Agency Holding Show-and-Tell Session Next Monday

California's $3 billion stem cell agency is inviting the public to a road show next Monday in Los Angeles that will feature the chairman and president of the research effort.

The agency says the public will learn about the "exciting progress being made in stem cell research and what it could mean for you, your family and loved ones."

The one-hour session will be at the Cedars-Sinai Medical Center from noon to 1 p.m. In addition to Jonathan Thomas, chairman of the California Institute for Regenerative Medicine (CIRM), and Maria Millan, CEO of CIRM, three speakers from Cedars are scheduled.

They are Shlomo Melmed,  Cedars-Sinai executive vice president and a member of the CIRM board; Eduardo Marbán,  director of the Cedars Heart Institute, and Clive Svendsen,  director, Cedars Board of Governors Regenerative Medicine Institute.

ViaCycte Update: Clinical Trials for a Diabetes Device Plus the Rain Gear Connection

ViaCyte, Inc., is a San Diego stem cell firm working on what could be a virtual cure for diabetes -- one that the $3 billion California stem cell agency has supported handsomely for years. 

UC Davis researcher Paul Knoepfler last week carried a piece on his blog on ViaCyte's progress. The article came in the form of a Q&A with the firm's president, Paul Laikind.

Paul Laikind, CEO Viacyte

The interview covered a lot of scientific ground as well as some financial matters dealing with the firm and its clinical trials. Perhaps a good part of the bottom line was contained in this paragraph from Laikind.

"Near term, as the PEC-Direct clinical trial advances into Cohort 2, full enrollment is expected in the second half of 2018 with evaluation of efficacy about 6 months later. The primary efficacy endpoint is clinically relevant insulin production, as measured by C-peptide 6 months after implantation. While the efficacy analysis is expected to occur in 2019, patients will remain in the study for two years, thus the expected completion date for the Phase 1/2 study is December 2020."

Also of interest is the use of a product from the company that produces Gore-Tex, a fabric that took the rain gear industry by storm, so to speak, decades ago. The fabric is now used in a wide variety of medical applications. Here is what Laikind said about the Gore-Tex connection.

"The goal of the research agreement with W.L. Gore & Associates is to cooperatively establish new methods of effectively delivering cell therapies, specifically with improvements in the Encaptra Cell Delivery System used in PEC-Encap. The semipermeable membrane that is a key component of the Encaptra device is made of the same material that makes up Gore-Tex. The Gore team are the world’s leading experts for manipulating and engineering this material.

"Gore has expertise in medical device development and drug delivery technologies, as well as previous research and development experience on cell encapsulation and implant programs for diabetes. Gore’s contribution to the material and design improvements of the Encaptra Cell Delivery System is expected to support the reliable and robust long-term engraftment that is required for the PEC-Encap product to be most effective.

"Gore’s participation in ViaCyte’s financing announced in May 2017 represents another external validation of the company and its technologies. It also reflects Gore’s great interest in, and commitment to, the development of a successful implantable cell therapy for all patients with diabetes who use insulin."

LA Times: Does California's New Stem Cell Law Do Enough to Regulate Exploitation of Desperate Patients?

The Los Angeles Times this morning carried a piece that praised the state's first-in-the-nation disclosure law concerning unregulated stem cell treatments, but the article also questioned whether the law is tough enough for the task.

Business columnist Michael Hiltzik wrote that the law, which goes into effect in January, is "a major step to address an emerging public health crisis."  But, he continued,

"(T)here’s reason to ask whether California’s law goes far enough to regulate businesses exploiting the desperation of patients with intractable diseases."

The law targets the more than 100 clinics in California that sell what Hiltzik described as  "unlicensed, unproven — and sometimes disproven — stem-cell 'treatments.'" For the first time, such California clinics will be required to disclose to their customers that the treatments are not approved or regulated by the federal government. The notices will advise the customers to consult with their physicians prior to treatment.

Hiltzik,  however, questioned the optimistic wording of the disclosure which says that the treatments have "not yet" been approved by the Food and Drug Administration (FDA). He said,

"This suggests that FDA endorsement may only be a matter of time — that the treatments may be premature, but not fictitious. That’s wildly optimistic and may itself foster a false hope for the treatments."

Hiltzik, a Pulitzer Prize winner,  said the state's Medical Board, which is charged with enforcement, has not been provided with funding to take on the clinics. Plus, he said the board, at best, is a "reluctant regulator."

State Sen. Ed Hernandez, D-Azusa, authored the law. He told Hiltzik the measure is a first step. Hiltzik quoted the legislator as saying,

 “Because it’s so new, we’re trying to figure out the best way to start the conversation.”

Hiltzik concluded,

"But lawmakers and regulators may need to move faster. What will make a difference in California may not be how the conversation starts, but where it leads."

CIRM-funded ALS Trial Enrolls First Patients; Therapy Produced by Israeli Firm

An Israeli firm backed with $16 million from the California stem cell agency today announced that it has enrolled the first patients in its phase three trial for a treatment for ALS, sometimes known as Lou Gehrig's disease.

The trial, the final one before possible approval for widespread use of the therapy, is expected to include about 200 patients. The California component is being conducted at UC Irvine for the firm, BrainStorm Cell Therapeutics. 

The $3 billion California stem cell agency, known formally as the California Institute for Regenerative Medicine (CIRM),  awarded the cash to BrainStorm last July. The agency's reviewers said of the application:

"Overall, the proposed phase 3 study is well-designed. If executed successfully, it will provide a very meaningful outcome, generating data to define the overall value of the program and the path to regulatory approval and marketing. 

"The investigators have now included slow vital capacity as a clinical measure in the revised clinical trial per (earlier reviewer) recommendations . 

"The current protocol will still not answer the question of whether the product is better than untreated autologous bone marrow-derived MSCs. However, reviewers felt this is not critical for the current study as a positive outcome in this trial may allow a demonstration of superiority over MSC alone in a future study."

The firm has matched the California award with another $16 million. Completion date of the trial is 2019.  The trial is one of two phase three trials backed by CIRM that are currently recruiting. The principal investigator at UC Irvine is Namita A. Goyal. More information on the trial can be found here. 

About 5,600 people in the United States are diagnosed annual with ALS, which has severely disabled British physicist Stephen Hawking.