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

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

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

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

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

Gorn wrote,

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

'Invisible Work' and the California Stem Cell Agency

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

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

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

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

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

Dubnicoff wrote,

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Stem Cells, Anonymous Commentary and Silence Dogood

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

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

Ben Franklin, Getty Images

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Paul Laikind, CEO Viacyte

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Hiltzik concluded,

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

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

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

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

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

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

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

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

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

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