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.

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.