No. 54: Counting California Stem Cell Agency's Clinical Trials, This One for Diabetes

The California stem cell agency has awarded $11 million to help treat type one diabetes, an affliction that affects 1.25 million persons nationally.

The award brings to $194.6 million the amount given to UC San Francisco (UCSF) since 2005 by the California Institute for Regenerative Medicine (CIRM), as the agency is formally known. 

UCSF has held a seat on the governing board of the $3 billion agency since it was created by voters in 2004. About 90 percent of its funding has gone to institutions with ties to board members. They are not allowed to vote on awards involving their institutions, but the board can create or eliminate funding programs. 

The $11 million phase one clinical trial award last week went to Peter Stock of UCSF and was his first for a trial from the agency.  It is the 54th investment by the agency in a clinical trial. CIRM said in a news release:

"Transplantation of beta cells, contained in donor pancreatic islets, can reverse the symptoms of diabetes. However, due to a poor islet survival rate, transplants require islets from multiple donors. Furthermore, since islet cells are transplanted directly into the vessels that enter the liver, it is extremely difficult to monitor and retrieve these cells should the need arise.

"Dr. Stock’s clinical trial at UCSF aims to address these limitations. The trial will be using parathyroid glands to aid in the success and viability of the transplant procedure."

CIRM's review of Stock's application (CLIN2-11437) noted that questions had been raised about commercialization of his research. It said, 

"If efficacious, the proposed therapy could lead to US regulatory approval for islet transplantation and clear the commercialization path for this and future diabetes treatments in a field that needs innovation. Overall, the enthusiasm from clinical experts for the potential of a new approach outweighed commercialization concerns and the panel recommended the application for funding."

Looking Back and Forward at the California Stem Cell Agency: 1,000 Awards, $2.6 Billion, 1,200 Patients in Clinical Trials

A CIRM slide from tomorrow's presentation
on the stem cell agency's work.

The California stem cell agency has whomped up a fulsome presentation on its progress since it was created in 2004 and plans to unveil it at a public meeting tomorrow in Oakland. 

The presentation covers everything from cell therapy to de-risking stem cell investing for biotech companies. Maria Millan, CEO of the $3 billion enterprise, will run through the agency's 1,000 awards and 53 clinical trials during tomorrow's meeting of the governing board of the research effort. 

Her presentation comes at an increasingly critical time for the agency. It expects to run out of cash for new awards later this year. It is attempting to raise $220 million privately to help tide it over until November 2020, when it hopes to persuade California voters to give it another $5 billion. 

The agency, known formally as the California Institute for Regenerative Medicine (CIRM), is making the meeting available to the public through its usual Internet audiocast in addition to teleconference meeting sites in Riverside, La Jolla, South San Francisco, Fresno, San Diego, Palo Alto and two in Los Angeles.  That is in addition to the main meeting site in Oakland. (Full directions are on the meeting agenda.) The public can also ask questions via the Internet or the teleconference locations. 

Also up for tomorrow's meeting is discussion of possibilities of changes in CIRM's operations that might be embodied in a ballot initiative in 2020. Two governing board committees mulled over a wide range of options at a session last week, but no decisions were made. The measure is yet to be written but will need to be officially filed later this year. 

California Stem Cell Funding Flap: Stanford Ponies Up $1.8 Million

Stanford University has come through on matching funds for state-financed stem cell research, coughing up $1.8 million after California's stem cell agency applied a little financial pressure.

The matter involves Stanford  researcher Judith Shizuru, who is conducting a clinical trial that is aimed at treating the "bubble boy" genetic affliction without requiring high-risk chemotherapy or radiation. Her work has implications for reducing the need for the dangerous treatments in other diseases. 

In 2012, Shizuru was awarded $19 million by the stem cell agency for her trial. Late last year, she applied for $6 million more. 

Sharp questions arose, however, from the governing board of the $3 billion California Institute for Regenerative Medicine (CIRM), as the stem cell agency is formally known. It was the first time that the CIRM board had publicly rebuked a grantee and an institution on co-funding.

The board noted that the $19 million grant required $1.8 million in matching funds that had not been forthcoming.  

Directors pointed out that Stanford was well-endowed and should not be hard-pressed to provide cash to help develop a potentially "transformative" product that would eliminate the toxic impact of chemotherapy for a number of diseases. 

That was back in January. The CIRM directors set a May 1 deadline for seeing the cash. 

Last month the agency, which expects to run out of funds for new awards later this year, received a letter from Robert Harrington, the chairman of the Department of Medicine at Stanford. 

The letter said, 

"This letter is to confirm that the Department of Medicine will provide funding in the amount of $1,784,953 to meet the required co-funding for Operational Milestones #3 and #4 disbursements as referenced in your email dated 3/14/19 for the above referenced grant. These funds are available immediately to Dr. Shizuru for the study."

The flap also led to an inside look at how research funding works at the stem cell agency in a case involving a rare affliction, delays in clinical trials and the financial pressures now facing CIRM. 

Over its 14-year life, the agency has awarded $2.6 billion. Stanford is the No. 1 recipient with $383 million. Its total far exceeds the No. 2 recipient, UCLA, which has chalked up $284 million. 

Nine out of the top 10 recipient institutions, including Stanford and UCLA, have members on the CIRM governing board. They are not allowed to vote on awards to their institutions, but they establish the research award programs and their rules. 

Legislation to Regulate 'Snake Oil' Stem Cell Clinics in California Hits Fiscal Speed Bump

California legislation to crack down on "snake oil" stem cell clinics has stalled after a cost of $100,000 was assigned to the measure, which is backed by the state's stem cell research program. 

The bill was sent last week to a "suspense" file, which holds fiscal legislation while lawmakers juggle priorities in the Golden State's yet-to-be-approved, $213 billion budget.

If all goes well, the measure could clear the Assembly Appropriations Committee in the next month or so and be sent to the floor of the Assembly. It would then go to the Senate for more committee hearings and a Senate floor vote.

No public opposition has yet surfaced to the measure (AB617), authored by Assemblyman Kevin Mullen, D-San Mateo. It would not take effect any earlier than 2020.

The bill would require California's Medical Board to move on the clinics, which have proliferated across the country in recent years. California has more than 100, according to the latest estimates. 

The clinics charge thousands of dollars for treatments using substances that they describe as stem cells. However, in virtually all cases, the treatments have not been tested scientifically. Some have led to serious injuries. 

The state Medical board would be required to create a stem cell advisory group by February 2020 that would make recommendations by July 2020 for regulation of the dubious clinics.

The new group would have nine members. Three would be appointed by the California stem cell agency, three by state Medical Board, two by the state osteopathic medical board and one by the state nursing board. 

The group could also recommend emergency regulations that could be adopted by the state Medical Board with a 90 day notice. 

Last week, a committee of directors of the California Institute for Regenerative Medicine (CIRM), as the stem cell agency is formally known, endorsed the bill. The full board is expected to ratify that endorsement on Thursday. An analysis prepared by the legislative staff already lists CIRM as a supporter. 

Exploring California's Stem Cell Future: A Start Today on the 16th Floor in Oakland

OAKLAND, Ca. -- "Phantom equity," the affordability of $1 million cures, maximizing returns to the state and conflicts of interest -- all that and more was on the table today at the $3 billion California stem cell agency.

The occasion was a discussion of "ideas for enhancement" by some of the directors of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known. 

This was more than simply kicking around possibilities. The meeting was called because the agency expects to run out of money for new awards later this year.

Its hopes for financial survival rest largely on a possible $5 billion bond initiative on the November 2020 ballot. Writing an initiative also means an opportunity to improve agency operations. To pass an initiative, California voters would also need to be inspired by the work the agency has done and how it will do even better in the future. 

So the governing board put together today's session to hash over ideas, starting with a 10 page list of initial thoughts. No decisions were reached, however. The discussion will carry on next Thursday at a meeting of the full board, which will also be held in CIRM's 16th floor offices here. But internally the agency plans to begin to explore some of the areas in more depth.

The implications of changes could have a major impact not only on California researchers but biotech businesses looking for possible products that could generate profits, preferably large ones.

One area of concern by CIRM directors was maximizing the return to the state for its $6 billion investment, which includes the interest on the $3 billion borrowed for the CIRM program. One of several suggestions included the use of "phantom equity," a loose term that implies having an investment but not ownership in a company that is tied to the value of its shares.  (CIRM is barred from actually owning stock.)

At the same time, directors also said they did not want to raise financial obstacles that would stop biotech firms from turning CIRM research into cures.

CIRM Director Jeff Sheehy, who has served on the board since its inception in 2004, brought up affordability and access suggestions by the man who led the 2004 campaign, Robert Klein. 

In a recent interview with the California Stem Cell Report, Klein said he was interested in seeing more stringent requirements to assure that state-backed therapies are available to all.  Esimates of costs of some legitimate stem cell treatments have ranged up to $1 million or more. 

Another subject of some discussion was the matter of perceived conflicts of interest involving the current structure of the CIRM board. About 90 percent of the awards made by CIRM have gone to institutions with links to members of the board. While some board members acknowledged the importance of perceptions, they said no conflicts of interest have actually occurred. 

A proposed initiative will have to be filed late this year in order to qualify for the November 2020 ballot. In the interview with Klein, he said he was looking at filing around the middle of September.