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.

Correction

An item earlier today said incorrectly that this week's Internet outage at the California stem cell agency was the first such significant occurrence. The agency, in fact, had another outage in September.

Internet Outage for California Stem Cell Agency Earlier This Week: Cause Unknown

California's $3 billion stem cell agency went dark on the Internet earlier this week, the second time it has had a significant Internet outage in recent months.

The outage began on Monday afternoon. The agency was back up by Tuesday at about 7 p.m. The California Institute for Regenerative Medicine (CIRM), as the agency is formally known,. reported that the problem did not affect internal work but did affect public access to agency information. It also blocked any incoming email or outgoing email. However, all of the email went through after the problem was solved. 

In response to a question from the California Stem Cell Report, Kevin McCormack, senior director for communications, said,

"At about 1 p.m. on Monday 10/9/2017 our external Domain Name System (DNS) provider dropped our DNS records, that meant people looking for our website, blog, GMS(grant management system), and email servers were unable to access them as DNS converts names (like www.cirm.ca.gov) into an IP (internet protocol) address (like 192.168.2.3) so that the appropriate server may be accessed by your browser. 

"We are working with our DNS provider to find out the root cause of that event.  In the meantime, we brought up a new external DNS server with another provider to restore name resolution.

"The servers for www.cirm.ca.gov and grants.cirm.ca.gov were themselves unaffected in that they continued to operate as normal awaiting requests - but without external DNS converting names into IP addresses, no requests would come to those servers from outside of CIRM.

 "CIRM staff and the GWG (grant application reviewers) then meeting at CIRM were still able to continue as usual accessing the GMS since they were using internal DNS servers.  Similarly, all purely internal email within CIRM was unaffected - however, because we were without external DNS, any email coming into or out of CIRM was not delivered."

Editor's note: An earlier version of this incorrectly stated that the problem was the first significant outage for the agency.

Probing California's Stem Cell Trials: New Tool Helps Public Navigate the Multi-Million Dollar Maze

Here's how the new clinical trial dashboard looks. You can slice and dice
the information by clicking on the black and blue boxes on the CIRM
website at the top of the page.

California's $3 billion stem cell agency this week is debuting a new, online guide to its burgeoning network of clinical trials aimed at  developing therapies ranging from acute myeloid leukemia to X-linked severe combined immunodeficiency (X-linked SCID).

The new tool is called the clinical trials dashboard. It is a major improvement in making information on the all-important trials more easily available to the public, patients, researchers and policy makers.

Clinical trials, which have three stages and can last years, are the final step before a therapy can be approved for widespread use by the Food and Drug Administration. The agency plans to spend about $400 million on clinical ventures from 2017 to 2020.

The new dashboard cuts through the online maze and allows readers to sort by disease areas, investigator and institution, among other things. It also shows quickly the status of each trial, whether it is recruiting and takes the reader to a contact if he or she is interested in participating in a trial.

As the main dashboard page shows, the agency, formally known as the California Institute for Regenerative Medicine (CIRM), has funded 40 trials. The dashboard allows you to see which are still active and which are still recruiting. If you are interested in cancer and solid tumors, filtering them out is simple. Just click on the blue box on the dashboard.

Want to know which institution has the most CIRM-backed trials? The answer is UCLA with five, a figure easily arrived at by using the new CIRM tools. That goes for investigators as well. The dashboard can show you that Donald Kohn of UCLA has the highest number of trial awards with three. A bunch of others have two each.

CIRM has long had a vast array of information on its website. As with any website, that presents a challenge in terms of making the information available to public. First, the public needs to know it is there. Next, they need to be able to actually find the relevant information and find it relatively easily. Removing barriers to online access is critical. The online tools also must fill a wide range of information needs.  A cancer patient or researcher is not likely to be interested in plowing through reams of eye disease information in order to gain access to the relevant cancer data.

The clinical trial dashboard was built by Karen Ring, CIRM's website manager and a former stem cell researcher, along with contributions from numerous others on the agency's team. It is a major step forward in the agency's effort to tell the CIRM story and how it has spent the billions provided by California taxpayers.

Here is a video that turned up this morning as I navigated my way through the clinical trial dashboard. Another note: I did not encounter any bugs this morning, but Ring says she will be tweaking the dashboard and improving it in the next couple of weeks.

Preview of Bond Campaign: California Stem Cell Agency Described as 'Dismal,' 'Disappointing' and a 'Waste'

A couple of die-hard opponents of the $3 billion California stem cell agency minced no words this weekend. In an op-ed piece in the Orange County Register, they described the agency as nothing more than an "advanced high school science project."

The article was written by Jon Coupal, president of the Howard Jarvis Taxpayers Association in Sacramento, and state Sen. John Moorlach, R-Costa Mesa. 

They described the agency's efforts as "dismal" and declared that "this disappointing abuse of taxpayer dollars" should be terminated.

The print version of the article appeared in Sunday's paper, which has a circulation of about 312,000. Both the print and online version carried photographs involving stem cell research. But neither was from UC Irvine, which has received $108 million from the agency and has a member on the board of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known.  UC Irvine is located only 17 minutes away from the offices of the newspaper. 

The piece is a relatively tame preview of the rhetoric that will confront CIRM if it goes to the ballot in 2020 for more billions from California taxpayers. The article cited arguments from the 2004 Prop. 71 ballot measure campaign that created the agency. 

Coupal and Moorlach said, 

"According to the ballot pamphlet mailed to voters, proponents promised the bond proceeds would advance the 'cure and treatment' of  'cancer, diabetes, heart disease, Alzheimer’s, Parkinson’s, spinal cord injuries, blindness, Lou Gehrig’s disease, HIV/AIDS, mental health disorders, multiple sclerosis, Huntington’s disease, and more than 70 other diseases and injuries.' 

"But actual outcomes for these promised advances are speculative at best and nonexistent at worst. Similar benefits were promised to the California economy to 'generate millions of new tax dollars.' 

"With such a dismal record, this would be a good time to shut the spigot on issuing the remaining $345 million — meaning some $690 million would be saved by state taxpayers. That money could be better spent on pensions, schools, roads, housing or better basic medical care for our residents."

As for the high school project business, the article said CIRM "continues to operate as a kind of advanced high-school science project, instead of moving toward the cures promised to voters in Prop. 71."

Forty-three Percent Jump in Interest in California Stem Cell Internet Information

Interest in California stem cell matters spiked in mid-week but still is well below the interest in broader matters, such as stem cell therapies, according to Google search data this morning.

Searches using the term "California stem cells" shot up 43 percent in midweek, Google reported. Just exactly why more people were searching on the term is not clear, but the Google data shows a definite high point.

The scale of 1 to 100 on the charts with this item reflects the level of interest -- not numbers of readers or page views. One-hundred shows the peak interest level only.  Actual numbers were not disclosed by Google.

Readers can see the trends in the two Google-generated charts attached to this item, which have an important caveat. The charts are live and updated automatically by Google as long as they are posted.

My take on the information is that at this point it is more of a curiosity than of any major signficance. However, in the event of major stem cell news, the data might have more value.

California Moves to Protect Patients Seeking Unregulated Stem Cell Treatments

Beginning next year, California will have a new law that imposes the first-ever disclosure requirements on currently unregulated stem cell clinics that offer therapies that have not been approved by the Food and Drug Administration.

UC Davis stem cell scientist Paul Knoepfler, who for years has raised concerns about such clinics, wrote an item yesterday about the new law for his blog. It was headlined:

"Groundbreaking new California stem cell law gives consumer protections on clinics"

Ed Hernandez, Daily News photo

The measure is the first of its kind in California and probably the entire nation.  Authored by state Sen. Ed Hernandez, D-West Covina, it will require clinics to specifically notify its customers that he or she is about to undergo a treatment not approved by the FDA. The notification also must include advice encouraging customers to consult their primary care physician prior to undergoing a stem cell therapy.

A legislative analysis of the bill, SB512, cited a statement from the Center for Public Interest Law that said, 

"It is critical to patient safety that these individuals are not misled into believing they are partaking in an FDA-approved clinical trial and assuming serious health and financial risks in the process. The disclosure notices required by this bill are an important step in ensuring that patients have the information they need before making such monumental decisions about their treatment."

Paul Knoepfler, UC Davis photo

Knoepfler co-authored a research paper in 2015 that documented  the presence of nearly 600  unregulated clinics nationwide with California leading the way. He wrote on his blog, 

"Taken together, the provisions of this law will help consumers learn more about the stem cell clinic industry, make better decisions about their health and that of their loved ones, and delineate the difference between stem cell clinics versus compliant researchers conducting stem cell clinical trials with FDA approval.

"In the big picture, this new California law plus a more active FDA on the stem cell front together give me more hope that the wild west of stem cell clinics can be reined in sooner rather than later! Perhaps other states will follow suit with new laws and state medical boards will get more involved in overseeing stem cell therapies. With more 570 stem cell clinics in the US and more than 100 here in California alone, more efforts like these are needed on the consumer protection and educational outreach front."

Knoepfler deserves great credit for his efforts regarding unregulated clinics. It is fair to say that without his work, California would not have seen this law at this time. He was the first to document the size of the industry with the 2015 article, co-authored by Leigh Turner of the University of Minnesota.  Their work makes it abundantly clear that scientists can make a real difference on public policy issues if they are persistent and effective. One of Knoepfler's key tools was blogging, a practice that some scientists think is less than dignified. Nonetheless, his blogging helped to elevate the issue and served as a source for the news media as they looked into the matter. 

Like most new state laws, the law takes effect Jan. 1, 2018.

Asterias Biotherapeutics: Sizzling Superlatives on California Stem Cell Trial for Spinal Cord Injuries

A California stem cell trial backed with $21 million in state cash has generated "super, super-exciting" results involving patients who were paralyzed as the result of  severe spinal cord injuries.

A story today by Erin Allday in the San Francisco Chronicle said,

"Four out of six paralyzed patients who had 10 million stem cells transplanted into their spinal cords have shown striking improvement a year after treatment, including increased ability to move their hands and arms and to perform basic functions like feeding and bathing themselves, according to research results being released Monday. 

"All six patients in the early-stage clinical trial, conducted by Fremont’s Asterias Biotherapeutics, reported at least some recovery after the stem cell transplant. The trial is among the first to use embryonic stem cells in human subjects. 

"It’s too soon to know for sure that the stem cells were solely responsible for the patients’ improvement. The patients could have experienced a spontaneous recovery, which is not unheard of in spinal cord injury victims, or their improvement could be the result of intense rehabilitation. 

"But compared to a large group of people with similar injuries, the results among patients treated with stem cells were remarkable, said doctors and scientists involved with research.

Allday also wrote,

“Scientifically, I have to say we don’t know for sure if it’s the stem cells. But I’ve been treating these kinds of patients for 30 years, and I’ve never seen anything like this before,” said Dr. Richard Fessler, lead investigator of the Asterias trial and a professor in the department of neurosurgery at Rush University Medical Center in Chicago."

The Chronicle story continued,

"'The bottom line is super, super exciting. Well beyond anything I thought we could have achieved at this point,' said Dr. Edward Wirth, chief medical officer with Asterias."

The story was good news for the California Institute for Regenerative Medicine (CIRM), as the $3 billion, state stem cell agency is formally known and which has pumped the $21 million into the work. However, the bad news was that the agency's support of the research was not mentioned until the last paragraph of the Chronicle story. Most readers are not likely to get that far.

CIRM has backed Asterias with $14.3 million. The agency also funded the research with $6.4 million to Geron Corp.,which abandoned the trial for financial reasons. Asterias later acquired the research from Geron.

The agency has had a tough time getting its successes into the mainstream media for a number of years. But its story is now more important for the agency and will be for the new next three years. It is scheduled to run out of money for new awards in mid 2020. It is currently examining funding options including the possibility of asking voters for another multi-billion dollar bond issue. The nearly 13-year-old effort has not yet fulfilled voter expectations of development of a widely available therapy. Without something dramatic to show voters, a bond issue is likely to have heavy going.

The agency also put out a news release on the developments as did Asterias. However, a check with Google at 4 p.m. Monday showed that no other newspapers or other major mainstream outlets have picked up the story yet.

The news seemed to benefit the price of Asterias stock. It rose nearly 6 percent today, closing at $3.20. Its 52-week high is $5.80 and its 52-week low is $2.83.super

$75 Million For California Stem Cell Research: Brain Cancer, Sickle Cell, Alpha Clinics and More

OAKLAND, Ca. -- The California stem cell agency yesterday handed out $75 million, doubling down on a couple of efforts to develop a stem cell therapy and a stem cell tool, plus funding an expansion of its Alpha Clinic network with two new, Northern California sites.

The awards bring to $2.34 billion that the nearly 13-year-old agency has committed to stem cell research. The awards also leave the agency with $414 million in uncommitted funds. The state research program, formally known as the California Institute for Regenerative Medicine (CIRM), expects to run out of cash for new awards in less than three years.

The clinical program awards yesterday targeted such afflictions as diabetes, brain cancer and sickle cell anemia. One award of $20 million set a new mark for one CIRM-funded project.

That award went to Viacyte, Inc., of San Diego, bringing to more than $71 million that the agency has pumped into the firm, the largest amount provided to any single project. The firm is seeking to create an implant that would basically be a virtual cure for diabetes.

Also reinforced with more millions was Humacyte, Inc, of North Carolina. It received $14.1 million for its stem cell tool on top of the $10 million it has already received.  The firm is working on a new type of "lifeline" for kidney disease patients undergoing hemodialysis.

The agency's Alpha Clinic Network received a $16 million infusion, split between two new sites, one in Sacramento and the other in the Bay Area. The latter is a joint effort involving pediatric work and UC San Francisco and Childrens' Hospital Oakland. The other award went to UC Davis, whose stem cell program is located in neighboring Sacramento. The Alpha network already has three sites in Southern California at City of Hope, UC San Diego and UCLA/UC Irvine. 

In a CIRM news release,  Abla Creasey, CIRM’s senior director of Strategic Clinical, Regulatory, and Infrastructure Programs, said,

“The Alpha Clinics are a one-of-a-kind network that gives patients access to the highest quality stem cell trials for a breadth of diseases including cancer, diabetes, heart disease and spinal cord injury.” 

Cedars-Sinai in Los Angeles lost out on its bid to be added to the Alpha network. The agency had allotted only $16 million to the expansion under its strategic plan. Directors have been loathe to add more funding to the plan. 

Other clinical stage funding included:

• City of Hope, $12.8 million, PI Christine Brown, a Phase 1 CAR-T trial targeting an aggressive brain cancer called malignant glioma.
• Nohla Therapeutics Inc., Seattle, Wa.,$6.9 million, a Phase 2 trial dealing with neutropenia, a condition that leaves people susceptible to deadly infections after receiving chemotherapy for acute myeloid leukemia.
• Forty Seven Inc., Menlo Park, $5 million, a Phase 1b clinical trial treating acute myeloid leukemia. 
• Stanford, $5.2 million, PI Matthew Porteus, preparatory work for a clinical trial on a genome editing technology to correct the sickle cell disease mutation.

Here are links to summaries of the reviews of each application: UC Davis, UCSF/Childrens' Hopsital, Cedars-Sinai, Viacyte, Humacyte, City of Hope, Nohla, Forty Seven, Stanford.

'Right Person at Right Time:' Maria Millan Named as CEO of California Stem Cell Agency

Maria Millan at CIRM board meeting today, following her appointment as new president.
CIRM photo by Todd Dubnicoff

OAKLAND, Ca. -- Maria Millan, who joined the California stem cell agency five years ago, this morning was named as president of the $3 billion enterprise as it moves into what may well be its last three years.

Millan, who was serving as interim president,  was unanimously approved by the governing board of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known.

CIRM Chairman Jonathan Thomas said he was enthusiastic about Millan when she was named interim president in June, when Randy Mills left. Thomas said he was "doubly enthusiastic" today and  described Millan as the "right person at the right time."

Millan was vice president for therapeutics and her appointment was expected. She will preside over  the agency in what some have called the "final stage" of the organization. It has projected it will run out of funds for new awards in mid 2020.  The agency is looking at various alternatives for future funding ranging from another bond issue, the agency's current financing, to possible some sort of merger or acquisition.

Millan this morning said the agency had $414 million in uncommitted funds after awarding $2.34 billion.

Millan's salary will be $550,000 retroactive to the beginning of July, when she assumed her new duties.

California Stem Cell Board in Executive Session on New President

OAKLAND, Ca. -- Directors of the $3 billion California stem cell agency this morning opened their meeting at  9:07 a.m. as they were set to award roughly $80 million and name a new president. 

David Martin was introduced as the latest member of the 29-person board.  Martin is chairman and  CEO of  AvidBiotics Corp . of South San Francisco. 

The board immediately moved into executive session to consider the appointment of a new president who left the agency at the end of June.

Tap into Stem Cell Agency's Meeting Tomorrow

Several new, teleconference locations have been added to the list of those where the public can take part in tomorrow's meeting of the governing board of the $3 billion California stem cell agency.

On the agenda is appointment of a new president for the agenda and the award of roughly $80 million to California researchers.

Here is the latest list of locations apart from the meeting site at the agency's headquarters in Oakland. The agenda has more information regarding internet and audiocast access on a listen-only basis.

1. 1156 High Street, 200 Kerr Hall, Santa Cruz CA 95064 - Location available 9:00 to 11:30
2. 291 Campus Drive, Stanford, CA 94305 - Location available 9:15 to 11:00
3. 500 Hayes Street, San Francisco, CA - Location available 9:00 to 12:00
4. 9500 Gilman Drive and Meyers Leichtag Bldg. Room 284 La Jolla, CA 92093
5. 8700 Beverly Blvd 2015, Los Angeles, CA 90048
6. 700 Tiverton Avenue, Los Angeles CA 90095
7. 10996 Torreyana Road, Suite 200 San Diego, CA 92121

Alpha Clinic Expansion: California Stem Cell Agency to Award $7.9 Million to UC Davis

UC Davis to land millions of dollars for stem cell clinic http://www.sacbee.com/news/local/health-and-medicine/article175470856.html

$80 Million Stem Cell Infusion Coming Up in California

The state of California is expected to plunk down roughly $80 million this week for stem cell research and clinical trials as it moves to widen their access and develop a therapy that fulfills promises to voters nearly 13 years ago.

The awards are scheduled to be ratified Thursday during a meeting of the governing board of the California Institute for Regenerative Medicine (CIRM), as the $3 billion state stem cell agency is known.

The largest chunk of cash consists of $64 million for six applications for help in clinical trials, the last stage before a therapy is approved for widespread use.

Another $16 million is slated to go to expand the Alpha Clinic stem cell program, especially in Northern and Central California. NoA $7.9 million award is set to go to UC Davis, which won unanimous approval earlier from CIRM reviewers. Cedars-Sinai and UC San Francisco/Children's Hospital Oakland are likely to be competing for remaining $8 million.

Three Alpha Clinics, which are aimed at conducting clinical trials,  already exist in Southern California. This week's action will bring them north for the first time with an emphasis on the 33-county area served by UC Davis. (See here, here and here for more on the Alpha network.)

The stem cell agency was created in 2004 when voters approved a ballot initiative in a campaign that led voters to believe that cures were right around the corner. The agency has yet to help finance a therapy that has widespread application.

CIRM is also down to its last $600 million or so and projects that it will run out of cash for new awards by mid 2020. The agency's governing board is examining its financial options. Action on the issue is scheduled to be taken in December.

Also on the table Thursday is the approval of a new president for CIRM. Maria Millan, the interim CEO, is likely to get the job.

The session will take place in Oakland but teleconference locations will be in the Los Angeles area, Stanford, La Jolla and San Diego where the public can also participate. The meeting can also be heard in an audiocast. Details and addresses can be found on the agenda.

The California Stem Cell Report will provide gavel-to-gavel coverage of the Thursday meeting from CIRM headquarters in Oakland, filing updates as warranted throughout the day.

New President Coming Up for California Stem Cell Agency: Maria Millan Likely Choice

By this time next week, California's $3 billion stem cell research agency is expected to have a new president to preside over what may be the last act for the nearly 13-year-old effort.

Item Five on the agenda for this Thursday's meeting of the governing board of the agenda says:

"Consideration of appointment of new president, including compensation package."

Preceding that is an executive session of the board to discuss the matter behind closed doors. 

The California Stem Cell Report is predicting that Maria Millan, currently interim president, is likely to get the job. Millan was named as the interim CEO after Randy Mills left the agency at the end of June. Mills publicly recommended Millan to replace him as head of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known. 

A subcommittee of the governing board has met only once -- also behind closed doors -- to consider a replacement for Mills. The board made no public comment about the outcome that July meeting.

Millan was vice president for therapeutics for the agency.  A news release from CIRM said in May that Millan "was instrumental in developing and implementing the current strategic plan."

The news release continued, 

"She received her general surgery training and transplant immunology postdoctoral fellowship at Harvard Medical School and trained in solid organ transplantation at Stanford University School of Medicine, where she went on to serve as associate professor of surgery and ultimately director of the Pediatric Organ Transplant Program. Maria received her bachelor’s degree from Duke University and her M.D. from the University of Medicine and Dentistry of New Jersey."

She joined the agency in 2012 after leaving a position as vice president at StemCells, Inc., which has received $9 million from the agency. 

CIRM has projected that it will run out of cash in mid 2020. Its governing board is currently studying a wide range of options for life after 2020.

Ballot Measures to Mergers: California Stem Cell Agency Examines Alternatives to Its Demise

Discussing the future of CIRM on Monday: Left to right, Chair Jonathan 

Thomas,  Vice chair Art Torres, Director Diane Winokur. Photos behind

 them are  of  persons helped by the agency's clinical trials. 

Photo by The California Stem Cell Report.

OAKLAND, Ca. -- Directors of California's $3 billion stem cell research effort are looking at ways to stave off the agency's death ranging from asking voters for billions more to being acquired by some sort of private entity.

The choices came before a new Transition Subcommittee of the agency's governing board last Monday. It is considering options as the money runs out for the California Institute for Regenerative Medicine (CIRM), as the agency is formally known.

Current projections estimate that cash for new awards will end in mid 2020. However, directors could alter the award rate and survive longer. That would shrink the flow of cash to possibly hundreds of researchers from Sacramento to San Diego.

CIRM's funds come from money that the state borrows. The ballot initiative that created it in 2004 provided for $3 billion in state bond funding but no other significant revenue. The agency has roughly $650 million remaining.

No directors at the meeting expressed support for simply letting financial nature take its course and permitting the agency to slowly expire.

One option that seemed to attract significant interest would call for the agency to ask the legislature and the governor to place another multi-billion dollar ballot measure before voters in 2020. That option would involve the governor who succeeds Jerry Brown in 2019.  Brown is wary of adding any height to what he calls California's "wall of debt."

Such an option requires a two-thirds vote of both houses of the legislature and the signature of the governor. (A CIRM memo on legislative options incorrectly said that only a majority vote was needed. It was corrected during the meeting.)

One possibility would involve another ballot initiative, a process that would not need approval of the legislature. However, under new state law provisions, the legislature is required to hold hearings on ballot initiatives. Such a process could result in changes in a proposed initiative.

CIRM directors seemed to acknowledge that either going to the legislature directly or using a ballot initiative would likely mean significant changes involving the agency. Director Steve Juelsgaard said the result could be a "very different CIRM."

The options considered this week also included private fund-raising. Some directors indicated that raising $200 million to $300 million a year was not entirely realistic. However, some combination of fund-raising and public support was also a possibility.

The last-ditch option involved acquisition of the agency by another enterprise including possibly a venture capital driven entity.  CIRM Chairman Jonathan Thomas said a possibility could involve an organization such as the Gates Foundation or the Wellcome Trust. He said California has a "tremendous asset" in CIRM and a "ton of IP(intellectual property)."

Director Jeff Sheehy said he had "never heard of a state agency that was merged or acquired."
"I wouldn't put my head in that noose," Sheehy said.

Thomas said the next step will be to hold a joint meeting of the directors' Science and Transition Committees in November and take the resulting recommendations to the full board in December.

California Stem Cell Agency: $20 Million Cancer Award from 2012 Bears Clinical Trial Fruit

California's stem cell agency this week took the relatively unusual step of a firing off a double-barreled salute to the beginning of one of its clinical trials -- a $20 million effort based out of UCLA.

Antoni Ribas, UCLA photo

The press release and blog item heralded research by Antoni Ribas, who received the award in 2012 from the California Institute for Regenerative Medicine (CIRM), as the agency is formally known.

The potential treatment deals with the spread of cancer to other
parts of the body, which the agency said is responsible for 90 percent of cancer deaths. Ribas' trial will test a stem cell-based treatment that is better at tracking down and destroying hard-to-treat cancer stem cells. In a news release from UCLA, which is also funding the research, Ribas said,

"(F)ew options exist for the treatment of patients whose cancers have metastasized due to resistance to current therapies. This clinical trial will allow us to try a new approach that engineers the body’s immune system to fight metastasized tumors similar to how it fights germs and viruses.”

Siwen Hu-Lieskovan,
co-investigator, UCLA photo

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

“Backed by rigorous science, the stem cell derived T cell immunotherapy being developed by Dr. Ribas and his team has the potential to address advanced cancers that have spread beyond the primary tumor and which are associated with very low survival.

"This trial is the first step in developing a therapy that could alleviate the complications resulting from cancer metastases as well as potentially improving outcomes in cancer patients where there are currently no effective treatment options. We are confident that CIRM’s funding and partnership, in combination with the expertise provided by our Alpha Stem Cell Clinic network, will give provide critical support for the successful conduct of this important clinical trial.”

The $3 billion stem cell agency is actively supporting 33 clinical trials (five involving cancer), which are the last stage prior to approval of a therapy for widespread use. Why the CIRM salute in this case?  The blog item by Todd Dubnicoff said,

"The reality is this: the launch of a clinical trial isn’t a beginning. It represents many years of effort by many researchers and a lot of funding to take an idea and develop it into a tangible product that has been given clearance to be tested in people to potentially save their lives. That’s why this important milestone deserves to be recognized.

More information on the award (DR2A-05309) can be found here. Persons interested in participating in the trial can contact Clinical Research Coordinator Justin Tran by email at justintran@mednet.ucla.edu or by phone at 310-206-2090.

Curtailing Research Awards and Other End-of-Life Matters at California Stem Cell Agency

If you are interested in whether the $3 billion California stem cell agency is going to live or die, you may want to check in on a meeting one week from today.

A new committee of the agency's directors that was formed to deal with transition issues is scheduled to meet for three hours next Monday to consider various scenarios and how the agency might deal with them.

The impetus for the meeting is a projection that it will run out of cash for new awards in mid 2020 with no funding  in realistic sight.

One of the possibilities for extending the life of the agency is to curtail its award programs, which could possibly give the agency another one or two years of existence. The California Institute for Regenerative Medicine, as the agency is formally known, has roughly $650 million left but has been taking on clinical trials, some of which have been running $20 million a pop.

The session will be based out of the agency's headquarters, but teleconference locations are listed in Los Angeles, Duarte and La Jolla. The public can ask questions or make statements from those locations in addition to the main site in Oakland. Listen-only access is also available on the Internet. Full instructions and addresses can be found on the meeting agenda.

San Francisco Business Times: Can Clinical Trials Save California's Stem Cell Agency?

Tippi McKenzie on front page of San Francisco Business Times

Long, difficult and expensive -- that's how the San Francisco Business Times describes stem cell therapy development in an article about the 33 clinical trials currently backed by the $3 billion California stem cell agency.

Will it all prove to be worthwhile? Reporter Ron Leuty addressed the matter in an Aug. 25, front-page piece that featured Tippi McKenzie of UC San Francisco. She recently received a $10.9 million award from the California Institute of Regenerative Medicine (CIRM), as the agency is formally known, to test her possible therapy on 10 pregnant women.

In what will be the first clinical trial of an in-utero blood stem cell transplant, McKenzie will transplant a mother's own stem cells into her fetus. Leuty wrote that it could be a precursor to pre-birth cures for other blood diseases, such as sickle cell disease.  He continued,

"It’s also the sort of high-profile medical breakthrough that could give the state stem cell funding research agency momentum as it prepares to (possibly) seek billions in fresh money to extend its life beyond 2020."

Leuty wrote,

"Still, any potential treatments are years into the future. Are trials such as MacKenzie’s too little, too late to help CIRM? "  

"It’s all an illustration of the long, difficult and expensive path for bringing any drug to market. Only four of every 10 late-stage trials succeed, according to a 2016 Biotechnology Innovation Organization study of clinical trials from 2006 to 2015. As a relatively new field, in which regulators and companies are seeking a new pathway to Food and Drug Administration approval, stem cell therapies take eight years to translate into clinical trials; non-stem cell therapies take 3.2 years, according to CIRM Chairman Jonathan Thomas. That’s a potentially awkward narrative as efforts ramp up to keep CIRM alive longer. "

Leuty said,

"CIRM can point to 33 projects that have reached clinical trials. For example, an $11.9 million grant to UCSF and St. Jude Children’s Research Hospital is paying for a mid-stage study in 'bubble boy disease.' The agency wants to fund another 40 clinical trials over the next four years, and it is pitching that scale and scope as a reason to keep CIRM going."

The article continued,

 "If anyone has a chance of showing CIRM’s value, it may be MacKenzie, an associate professor of surgery at UCSF’s pediatric surgery unit and head of its Fetal Treatment Center. Her lab since 2010 has been awarded $14.9 million in grants, including cash for basic research, translational research and now in the clinic. 

"CIRM is about more than funding for studies, MacKenzie said. Agency staff has provided advice about how to translate animal studies into work in humans, she said, as well as hiring an FDA consultant, writing an investigational new drug application and setting up a clinical protocol. 'I’m a clinician, but running a clinical trial is different,' MacKenzie said. 'CIRM’s been incredibly helpful in helping me navigate that.'"

The Dual Images of Stem Cell Medicine Highlighted in the Headlines

Google news stem cell headlines this week

A couple of notable headlines surfaced this week dealing with stem cell matters, capturing something of the dichotomy in a field that has been heralded for its possible production of miracle cures. 

One story told of a person who plays football for a living, Doug Baldwin, who is known as the $46 million man.  He decided to spend some time in England this summer receiving what he believes was a stem cell treatment to prevent his knees from deteriorating. It was the type of story that gives many others hope that some sort of stem cell therapy could cure a serious or fatal condition despite the fact that no such cure has been approved for widespread use in this country. 

The other story told of a modest crackdown by the Food and Drug Administration (FDA) on a couple of unregulated stem cell clinics in this country, a move that many believe was long overdue. More than 500 such clinics exist in the United States.  One of the California clinics identified by the FDA was using a restricted small pox vaccine as part of its treatment. 

Your average health care consumer could justifiably wonder, "What in the world is going on? Is this stuff safe or what?" Some scientists have been long frustrated by the dueling public faces of stem cell medicine. On one hand, stories of miracle cures involving professional athletes generate great attention and tend to create faith in the efficacy of stem cell treatments, although the therapies involved do not measure up to scientific standards. On the other hand, the FDA is now taking a more active role in policing dubious actors in this business.

Our average medical consumer might believe that the FDA action signals a new assurance of stem cell safety or is it the other way around? Is the stem cell glass half full or half empty?

Paul Knoepfler, a stem cell researcher at UC Davis, has been the bellwether for seven years regarding news about unregulated and dubious stem cell clinics. He once even went sort of undercover to attend a public marketing session produced by one clinic in the Sacramento area. 

Knoepfler wrote this week on his blog about the FDA action, its implications and the questions that remain. He said the FDA action was a "very big deal." 

But Knoepfler said six important questions remain:

• "How much further will the FDA go with actual enforcement actions?
• "Will the FDA define fat stem cells as a drug (or not) in upcoming guidances?
• "How will the FDA handle non-homologous use of bone marrow cells in the commercial sector?
• "Will the FDA work to deal with the growing problem of unapproved, amniotic stem cell offerings? 
• "What about networks of stem cell businesses?
• "Will other entities like state medical boards use this FDA action as a spring-board to get off the sidelines and take positive action too?"

Meantime, patients will continue to have to wade through conflicting claims, hype and the possibility of serious medical harm or death as they ponder whether they should undergo a stem cell treatment. 

Calimmune's HIV Clinical Trial and the California Stem Cell Agency: Decisions Looming on the State-backed Research

The HIV clinical trial involving Calimmune and the California stem cell agency appears to be headed today for several major decision points following the purchase of the company in a deal that could total more than $400 million. 

CSL Behring announced yesterday that it was acquiring the company. One published report said that CSL was not interested in the Calimmune HIV research, which has been funded with $8.3 million by the California Institute for Regenerative Medicine (CIRM), as the agency is formally known. 

Responding to a query from the California Stem Cell Report, Natalie deVane, a spokeswoman for CSL, said today, 

"Our only comment regarding (the trial) was the following – 'We are currently evaluating our options for developing this pipeline candidate, which could include licensing or partnering. Given our areas of focus, it is unlikely that we will develop this candidate on our own.'

"We made no comments regarding timing, and at this point is would be premature to comment further."

Asked for a comment, Kevin McCormack, a CIRM spokesman said yesterday,

"Calimmune plans to complete the clinical trial that CIRM is funding, and CIRM has every intention of continuing the partnership with Calimmune in funding this essential research. Based on the findings of the trial, Calimmune hopes to make a decision as to whether or not it is feasible to move ahead with the next phase of this work."

The trial is scheduled to be completed in October.

$400 Million Deal Leaves California-backed HIV Trial Hanging

A California-financed clinical trial testing a promising stem cell therapy for HIV is up in the air this morning following the purchase of its California backer by an Australian corporation in what could be a more than $400 million deal.

The firm being acquired is Calimmune, which has an $8.3 million award from the California Institute of Regenerative Medicine (CIRM), as the state stem cell agency is formally known. 

CSL Behring announced this morning that it is buying Calimmune for $91 million and as much as $325 million more depending on whether its research meets success milestones. 

However, CSL is not interested in the early phase Calimmune trial, which began in 2013 and was scheduled to be completed by this October. John Carroll, writing on the Endpoint News web site, reported this morning, 

"CSL, though, plans to let go of control of Calimmune’s lead, clinical program on HIV as soon as possible. In a follow-up to a query, a company spokesperson replied:
'We are currently evaluating our options for developing this pipeline candidate, which could include licensing or partnering. Given our areas of focus, it is unlikely that we will develop this candidate on our own.'"

The California stem cell agency had no immediate comment on the potential impact of the deal. In response to a query this morning, Ronald Mitsuyasyu of UCLA, listed by the NIH as the principal investigator, said he had no comment.

The latest CIRM progress report on the research indicated that the trial had been advancing. A notice on the NIH clinical trials web site said, however, that it is no longer recruiting patients. The CIRM progress report said,

"The objective of the Cal-1 therapy is to increase the number of protected cells in the body of an individual infected with HIV to the point where the virus is incapable of causing harm. This would potentially reduce or eliminate the need for a lifetime of antiretroviral therapy."

Calimmune was co-founded by David Baltimore, a Nobel Prize winner and former member of the governing board of the state stem cell agency.

California Stem Cell Agency's First Royalty Payment: Beginning of a $1 Billion Flood? No One is Saying

The check is in the mail for California's $3 billion stem cell research effort. But it is something of a secret.

So reports Ron Leuty of the San Francisco Business Times concerning the expectation that the agency, formally known as the California Institute for Regenerative Medicine (CIRM), would generate $1 billion in royalties. In an article online yesterday afternoon, Leuty said,

"We are expecting the first check to be delivered to the state very soon," CIRM spokesman Kevin McCormack said in an email.

"Yet even as a public state agency, CIRM officials are holding tight to key information about the first royalty check: How large (or small) is the check? When will the check actually be forwarded to the general fund? And from which CIRM-funded project did it spring?

"'The royalty check is something that is still being worked out so it’s premature to say anything at the moment,' McCormack said in a followup email. 'Sorry to sound so secretive but it is a big deal, the first of what we hope will be many such repayments for the state’s investment.'"

During the ballot initiative campaign that led voters in 2004 to create the stem cell agency, supporters said that the agency's research could generate up to $1.1 billion in royalties. None have yet surfaced. And at least one description of the royalty promise has called it a "cynical ruse."

California Stem Cell Agency Pushes $23 Million into Clinical Trials for Leukemia, Bone Marrow Transplants

California's 12-year-old stem cell research program this morning popped for $23 million to help finance clinical trials to "confuse and kill" leukemia cells and to develop a better alternative to bone marrow transplants.

The two awards are part of the stem cell agency's effort to produce a widely available stem cell therapy before its money for new awards runs out in less than three years. So far, the agency, known formally as the California Institute for Regenerative Medicine (CIRM), has not been successful in producing such a therapy.

CIRM has now funded 35 clinical trials, which are the final stage of testing before a therapy is approved by the federal government for widespread use.  Thirty-one of the trials are still active.

Today's largest award, $18.3 million, will go to Thomas Kipps of UC San Diego. An additional Oncternal Therapeutics, also of San Diego.  Kipps is a scientific advisor to the firm. The other award, $5 million,  goes to Angiocrine Bioscience, Inc., of San Diego. The company will add $2.7 million to the effort.

Thomas Kipps, Oncternal photo

$13.3 million will be provided by

The Kipps project targets the most common form of lymphoma, chronic lymphocytic leukemia (CLL) the agency said in a news release. The agency said Kipps is "using a combination strategy to kill the cancer stem cells that help CLL – and other cancers – survive traditional therapies, such as chemotherapy, and cause a relapse."

Every year, about 20,000 people nationwide are diagnosed with CLL.

The Angiocrine research is aimed at increasing the supply of cord blood for bone marrow transplants, when no matched donor is available.  Its product is called AB-110.

Maria Millan, interim CEO of the stem cell agency, said,

 "This (Phase 1) clinical trial will be the first step in determining if AB-110 is able to provide a way to improve the results of cord blood transplants."

Today's award appears to advance work previously funded by CIRM at a cost of $4 million.  Paul Finnegan was listed as the principal investigator on that work.

Angiocrine's key technology  is licensed from Weill Cornell Medical College and was invented and developed by Shahin Rafii.

The awards were approved in less than 10 minutes this morning with no discussion by the CIRM governing board, which simply ratifies the decisions of its out-of-state, grant reviewers, who considered the applications in July behind closed doors.

A summary of the reviewers' comments can be found here for Kipps' application, CLIN2 -101, and here for Angiocrine's, CLIN2-10386. Information on the Kipps trial can be found here on clinicaltrials.gov. Catriona Jamieson of UC San Diego is listed as the principal investigator on the Kipps' award.

The Angiocrine trial was not yet listed on clinicaltrials.gov at the time of this writing.