Update on California's $72 Million Bet on a Diabetes Cure: Gene Editing Holds Promise

Viacyte video

A San Diego stem cell firm fueled by $72 million from the state of California this week announced an "important step" in its search for a diabetes cure in collaboration with a Massachusetts gene-editing enterprise.

The California business is ViaCyte, Inc., a privately held company that has received more funding from the California stem cell agency than any other business. 

It ranks 9th on the list of all recipients of cash from the California Institute for Regenerative Medicine (CIRM), as the agency is formally known. The ranking places it ahead of such highly regarded research institutions as Salk in La Jolla and Gladstone in San Francisco.

The East Coast firm is CRISPR Therapeutics, AG, a publicly traded firm that aims at "developing transformative gene-based medicines for serious human diseases."

CRISPR and Viacyte announced on Tuesday that their research is now showing that ViaCyte's "CyT49 pluripotent stem cell line, which has been shown to be amenable to efficient scaling and differentiation, can be successfully edited with CRISPR. The CyT49 pluripotent stem cell line is currently being used to generate islet progenitors for clinical trials."

Paul Laikind, CEO of ViaCyte, said in a news release that the latest news brings the firms "potentially one step closer to a transformational therapy for patients with insulin-requiring diabetes through the development of an immune-evasive gene-edited version of our technology."

Laikind described the gene editing result as "an important step" in achieving "yet another first, the development of an immune-evasive cell replacement therapy as a potential cure for type one diabetes."

In 2017, CIRM gave ViaCyte $1.4 million for work on the CyT49 line. Maria Millan, president of CIRM, said at the time,

“Development of an immune-evasive cell therapy would increase the chances of engraftment and durable effect of a cell replacement therapy for diabetes."

Investors were not energized by the CRISPR/ViaCyte announcement. CRISPR's stock price closed at $49.40 today, down from a $49.67 close on Monday, the day prior to the announcement. The 52-week high for the firm is $53.97. The low is $22.22. 

CRISPR and ViaCyte announced their $15 million collaboration a year ago. Here is a 2018 overview of Viacyte by Bradley Fikes of the San Diego Union Tribune.  

'Regulated, Reputable, Reliable:' A California Call for More Regulation of Dubious 'Stem Cell' Clinics

The president of the $3 billion California stem cell agency, Maria Millan, this week is recommending a new approach to state regulation of rogue "stem cell" clinics that are preying on desperate patients.

In a presentation prepared for a meeting Wednesday of the

Maria Millan
CIRM photo

stem cell task force of the State Medical Board, Millan listed standards for patient care, declaring that the field should be "regulated, reputable and reliable."

Millan said patients are being harmed by unproven treatments at clinics in California and elsewhere. The chairman of the board of her agency, Jonathan Thomas, has called the treatments "snake oil." (The agency is formally known as the California Institute for Regenerative Medicine (CIRM).)

A small task force of the State Board is laying the groundwork for additional regulation of the industry, which has grown rapidly in recent years. Estimates are that 1,000 clinics exist across the country with the largest number in California. 

Earlier this year, a measure to set standards for the clinics died in a legislative committee. The board itself initiated its task force more than a year ago. This week is its first public hearing. 

Millan's slide presentation for the meeting did not go into details. But she called for improved informed consent from patients and raised the following considerations:

• Creation of publicly available registries of stem cell treatment options  
• Creation of a method for patients to self-report outcomes or harm from unregulated regenerative medicine treatments 
• Requiring "clear visibility" for patients of the treatment team's credentials
• Creation of a "mechanism for investigating those holding healthcare  licenses suspected of violating professional        standards when providing unproven stem cell interventions,  particularly those outside their scope  of training" 
• Registration of treatments that involve human cellular and tissue products along with a clear distinction between federallly authorized treatments and practice of medicine

The public can file comments on the matter by emailing them to April.Alameda@mbc.ca.gov.  Check here for details on Internet access to the meeting.

$1 Million StemGenex Bankruptcy: Only $300 in the Bank

The tale of a La Jolla firm called StemGenex appears to be winding down with a bankruptcy filing that says it owes more than $1 million and has assets of less than $156,000.

The current state of the "stem cell" enterprise, which is facing a patient lawsuit and federal scrutiny, was disclosed this week in the Los Angeles Times and on the blog of UC Davis stem cell researcher Paul Knoepfler. 

Knoepfler has followed the firm for years. In his posting Wednesday, he said the company's bankruptcy filing shows that it owes money to its landlord, some former employees, some of its attorneys and has only $300 in the bank. 

Yesterday, Michael Hiltzik of the Los Angeles Times, who also has followed the company for some time, wrote, 

"The filing opens a window into the scale of StemGenex’s business. It discloses revenues of more than $8.2 million dating back to Jan. 2, 2017. Based on the firm’s standard fee of about $14,900 per treatment, suggesting it may have had as many as 550 customers over that period; some have said they had more than one treatment, for which they were charged separate fees."

Hiltzik said that company officials could not be reached for comment and that the firm's attorney did not respond to a query. The company's web site no longer shows a phone number and identifies the firm as only an "educational stem cell resource."

Hiltzik reported that the lead attorney in the patient class action lawsuit says he will continue to press the company, including physicians formerly associated with it. 

A task force of California's state Medical Board next Wednesday is scheduled to begin hearings in Sacramento on possible regulations dealing with operations of dubious stem cell clinics and physicians associated with them.   

Meeting Delays and the California Stem Cell Agency: A Matter of Many Millions of Dollars

For the second time in two months, the governing board of the $3 billion California stem cell agency has postponed important meetings which had been expected to deal with its final research awards and its declining finances. 

The latest postponement involved a Sept. 25 meeting. On the table would have been redirection of tens of millions of dollars and the question of financing awards already approved by the agency's reviewers.

Last month, an Aug. 22 session involving major awards was  cancelled. As of today, the next meeting of the agency's board will not come until Oct. 31.

The governing board of the agency, known formally as the California Institute for Regenerative Medicine (CIRM), has before it far more reviewer-recommended awards than it can fund. Agency officials hoped that funds received from cancelled research projects would help fill the gap.

CIRM is financed with $3 billion in state bonds but has no source of significant cash beyond that. It expects to run out of money for new awards -- most likely by the end of next month -- depending on how it deals with the applications in its award pipeline. Those decisions are now likely to be made at the meeting currently scheduled for Oct. 31. 

Queried about the reason for delaying this month's meeting, Maria Bonneville, executive director of the board,  replied, 

"There were some scheduling issues and, as you know, getting the whole board together isn’t easy. (The) soonest I could get a quorum was Oct 31."

CIRM's future depends on a proposed, $5.5 billion ballot measure in November 2020 that would allow it to continue at the pace of the last 14 years. The agency also has been engaged for some time in an effort to raise privately more than $200 million to bridge the funding gap between now and the 2020 election. 

No specific progress has been publicly announced concerning that effort. However, the financial plight of the agency has received more public attention in recent months. That attention may have generated the loosening of the purse strings of some potential donors. 

The agency also may well have made a pitch to California Gov. Gavin Newsom for some sort of interim funding, possibly payable back with 2020 bond proceeds. Newsom was an important supporter of the agency in 2004-05 and engineered a $17 million package to lure its then headquarters to San Francisco when he was mayor of that city.

$5.5 Billion Stem Cell Ballot Measure: California Backers Taking First Formal Step This Month

CIRM graphic

Backers of a California ballot initiative to provide $5.5 billion more for the state's cash-strapped stem cell agency say they will take their first official step by the end of this month. 

That's when they will submit the proposed measure to California election officials and trigger a many-months-long process. The effort is aimed at ensuring that the nearly 15-year-old research effort survives in a meaningful way beyond next year.

The stem cell agency, officially known as the California Institute for Regenerative Medicine (CIRM), expects to  run out of money for new awards as early as late October.  It has already cut off grant applications except for a joint sickle cell effort involving the National Institutes of Health. 

Robert Klein, a Palo Alto real estate investment banker, and his stem cell advocacy group, Americans for Cures, are leading the way on the initiative. Melissa King, executive director of the organization, told the California Stem Cell Report last week that the wording of the initiative is still being crafted.

King said, however, that she expected the measure to be submitted to the California secretary of state before October. She said that one area still being drafted involves providing assistance for low income patients and their families in rural areas who do not have the wherewithal to travel to and participate in clinical trials.  

The initiative filing will trigger a lengthy process to gather the  633,212 signatures of registered voters necessary to qualify the  proposal for November 2020 ballot. Gathering those signatures is a task performed by specialized firms. It could cost something in the neighborhood of $5 million or more, which Klein will have to raise on his own.

Many more signatures than the minimum are gathered because significant numbers of the signatures are commonly determined not be valid.

The ultimate deadline for qualification is June 25 of next year, 131 days before the Nov. 3 election. But the signatures will have to be submitted well before then.

The stem cell agency was created in 2004, also by a ballot initiative, with $3 billion in state bond funding. The new initiative will likewise use bond funding, which roughly doubles the cost to taxpayers because of interest expense on the borrowed cash.

The 2004 ballot campaign was supported by Hollywood stars and Nobel Prize-winning scientists. It generated grand expectations that stem cell therapies were right around the corner. While CIRM is currently involved in 56 clinical trials, it has yet to back a therapy that is widely available. Clinical trials are the last step before a medical treatment is approved for widespread use and have a high failure rate. 

Klein led the campaign in 2004 and became the first board chairman of the agency. Klein has been gathering information, statistics and support for the effort at his Palo Alto offices. 

In June, he told the California Stem Cell Report:

"This medical revolution holds the promise of restoring health and quality of life for many of California’s individuals and families suffering from chronic disease and injury.

"However, the last tactical mile to bring this broad spectrum of therapies to patients will require more funding and the thoughtful support of California’s public as the human trials and discoveries are refined and tested, overcome numerous obstacles or complications, and ultimately serve to improve the life and reduce the suffering of every one of us."

Google to Halt Advertising by Dubious Stem Cell Clinics, Cites 'Bad Actors'

Google says it is cracking down on advertising by rogue "stem cell" clinics, which it characterized as a rising tide of "bad actors" who are fleecing patients yearning for cures. 

The announcement came Friday and was quickly picked up by the Washington Post and then numerous other outlets, ranging from Yahoo to the MIT Technology Review. 

Google's move, which takes effect next month, would seem to add impetus to a growing cry for more and faster regulation of the dubious clinics by state and federal regulators. Both the Food and Drug Administration and California have been slow to act although the problem has been known for years. (See here, here and here.)

Injuries, blindness and deaths have been reported globally as the result of the so-called stem cell treatments. No assurances exist that the substances being used are, in fact, stem cells. 

The MIT article by Antonio Regalado noted that Google hauls in more than $110 billion annually in advertising revenue. The first sentence of his piece said, 

"After brazenly taking ad money from health-care scammers, Google is finally saying no to ads for unproven stem-cell treatments."

A UC Davis researcher, Paul Knoepfler, a national leader and pioneer in documenting the reach of the rogue clinics, said on his blog,

"I see the new policy by Google as a positive step and support them taking it. Perhaps some mainstream media outlets will follow suit and also adopt policies whereby they do not run these risky biomedical ads."

He also noted, 

 "These ads and certain particularly risky clinics also are a real threat to the legitimate stem cell and gene therapy fields."

Deepak Srivastava, president of the International Society for Stem Cell Research and head of the Gladstone Institutes in San Francisco, said in a statement, 

“Google’s new policy banning advertising for speculative medicines is a much-needed and welcome step to curb the marketing of unscrupulous medical products such as unproven stem cell therapies.”

The California State Medical Board has scheduled a Sept. 18 hearing into the clinics with an eye to strengthening regulation of treatments at the clinics. 

California Regulators Fleshing Out Details of Hearing on Regulation of Rogue Stem Cell Clinics

California state regulators have posted the line-up for a meeting later this month to deal with rogue stem cell clinics that peddle "snake oil" treatments that have led to injury and financial loss.

The meeting comes as Google announced this week that it is cracking down on advertising involving the dubious clinics. Also this week, the president of the largest group of stem cell researchers in the the world warned of the dangers of unproven treatments. 

Deepak Srivastava, president of the Goldstone Institutes in San Francisco and leader of the International Society for Stem Cell Research, said the promises of the largely unregulated clinics "aren’t true--they’re propagated by people wanting to make money off of a desperate and unsuspecting or unknowing public."

The state Medical Board scheduled its meeting for Sept. 18 in Sacramento as a precursor to possible regulation of the activities of medical professionals at the clinic.

Scheduled to testify are Maria Millan, president of the $3 billion state stem cell agency, formally known as the California Institute for Regenerative Medicine (CIRM), and Mehrdad Abedi of UC Davis, a physician, cancer specialist and stem cell researcher. 

Abedi is a key figure in UC Davis' Alpha Clinic, which is designed to coordinate and sharpen the focus of clinical stem cell research and treatment. 

Also scheduled to appear are representatives of the State Department of Public Health. The meeting is scheduled to be available via the Internet. The public can attend and comment at the session. 

The medical board said earlier that another session may be scheduled later this fall. Recommendations for regulations could come to the full medical board in January. See here for more details on the board's plans.

New Warning on Shady Stem Cell Clinics that Prey on Desperate Patients; California Hearing Coming Up

The head of the largest organization of stem cell scientists in the world this week spoke out about rogue stem cell clinics that are fleecing and endangering desperate patients. 

Deepak Srivastava
Gladstone photo

Deepak Srivastava, president of the International Society for Stem Cell Research and president of the Gladstone Institutes in San Francisco, said advertisements and pseudo news articles are promising cures for everything from autism to cerebral palsy.

"The claims simply aren’t true--they’re propagated by people wanting to make money off of a desperate and unsuspecting or unknowing public," Srivastava wrote on the web site of the Scientific American.

The headline on his article said, 

"Don’t Believe Everything You Hear about Stem Cells

"The science is progressing rapidly, but bad actors have co-opted stem cells’ hope and promise by preying on unsuspecting patients and their families"

The piece comes as California is preparing to take another step in regulation of the clinics, which have burgeoned across the nation.  Estimates are that the number of clinics exceeds 1,000 with the California having the largest share. 

The state Medical Board has scheduled a hearing on the clinics Sept. 18. The head of the state's $3 billion stem cell agency, Maria Millan, is slated to testify among others. Members of the public may testify as well. The Sacramento hearing will be broadcast on the Internet. 

(About eight hours after this item was published, the Medical Board board posted its agenda for the meeting.)

UC Davis stem cell scientist Paul Knoepfler and Leigh Turner of the University of Minnesota were the first to chronicle the scope of the dubious clinics. Knoepfler wrote this week about a follow-up study that he has published that showed that regulators have a whack-a-mole problem. 

Knoepfler said that his study "indicates that stem cell clinics are in general a fairly rapidly-changing type of business and many disappear or change over a few years. This makes overseeing this clinic industry harder for (regulators)." 

Both state stem cell agency and the international stem cell  group, which has more than 4,000 members in 60 countries,  provide information aimed at helping patients separate legitimate stem cell activities from bogus ones. Here is a link to the ISSCR advice. Here is a link the state stem cell agency's information. 

Kaiser Healthline: California's Stem Cell Program Short on Cash and Cures

An overview by Kaiser Healthline of California's nearly 15-year-old stem cell research program received attention in California and nationally last month. 

"Despite Failed Promises, Stem Cell Advocates Again Want Taxpayers To Pony Up Billions" said the headline on the article by Ana Ibarra.

Her piece carried both positive and negative comments on the performance of the $3 billion agency, which is running out of cash for new awards. The enterprise hopes voters will approve in November 2020 another $5.5 billion to continue its work.

The article quoted Marcy Darnovsky, executive director of the Berkeley-based Center for Genetics and Society, a longtime critic of the agency, which was created through a ballot initiative campaign in 2004. 

Darnovsky said that if the agency, known formally as the California Institute for Regenerative Medicine (CIRM), is measured against the campaign promises, “then CIRM has been a flop.”  

The agency, however, pointed to its 56 clinical trials, along with the stories of patients who have benefitted from that research, ranging from children who are alive today as the result of experimental treatment to spinal cord injury victims who are seeing their lives improve. 

Ibarra's article was picked up nationally by Salon. Politico noted it in its California newsletter.  The Sacramento Bee, the only daily newspaper in the state capital, published it as well.  

Webinar on Navigating FDA Stem Cell and Regenerative Regulations

Confused about federal regulation of stem cell therapies? That is the question being asked this morning by a Washington, D.C., law firm that plans to try to provide answers later this month.

The firm, Buchanan Ingersoll & Rooney, said it will stage a webinar on Sept. 17 to explain Food and Drug Administration "regulations and enforcement, and how stem cell stakeholders (pharma/biotech companies, healthcare providers) can best comply."

Fees for the session range from $287 to $487. More information can be found here.  

Brain Cells in Space Backed by Millions from the California Stem Cell Agency

UC San Diego video

The New York Times is carrying a piece today about a San Diego stem cell scientist and a project that involves "brain cell blobs" growing "like crazy" in space.  

The researcher is Alysson Muotri of the University of California, San Diego, who is trying crack some of the mysteries of brain development and mental disorders. His space cell project has been supported by $2.1 million from California's $3 billion stem cell agency along with other funding. 

Muotri is a brain organoid man, so to speak. Muotri and his team grew clusters of cells called brain organoids and sent them into space in July with the help of NASA to see how they would develop in zero gravity. 

Carl Zimmer of the New York Times wrote 1,000 words about the experiment. This morning his piece was on the front page of the Times website with this headline: "These brain cell blobs are growing 'like crazy' in space." 

"What, exactly, are they growing into?" Zimmer's article asked. "That's a question that has scientists and philosophers alike scratching their heads."

"As the organoids mature," Zimmer wrote, "the researchers also found, the waves change in ways that resemble the changes in the developing brains of premature babies."

Zimmer quoted Giorgia Quadrato, a neurobiologist at USC who was not involved in the study, on the subject:

“It’s pretty amazing. No one really knew if that was possible.”

The Times piece continued,

"But Dr. Quadrato stressed it was important not to read too much into the parallels. What she, Dr. Muotri and other brain organoid experts build are clusters of replicating brain cells, not actual brains.

“People will say, ‘Ah, these are like the brains of preterm infants,’ she said. 'No, they are not.'"

California's stem cell agency, formally known as the California Institute for Regenerative Medicine (CIRM), has plowed a total of $5.2 million into Muotri's research, which investigates fundamental mechanisms of brain development and mental disorder. 

In response to a query, Muotri told the California Stem Cell Report:

"CIRM funding was used on this last work to optimize the brain organoid protocol. We used this tool in our last two grants, including the one on Zika virus. So, thankfully to CIRM we now have a reproducible and more robust protocol.

"I think the importance and potential impact of this study is quite significant. We can now model neurological and psychiatric conditions that are caused by defects in the network. All previous brain organoid protocols couldn’t get to this level of activity."

Of Muotri's four CIRM grants, two totalling $2.1 million came into play in connection with the space organoids. One of the awards, DISC2-09649, involved Zika and human neurodevelopment. The other, DISC1-08825, dealt with neuroinflammation, a significant component of neurological disorders, including autism, ALS, Parkinson, Alzheimer, lupus, multiple sclerosis and aging.

Muotri's work has led him to co-found a firm called Tismoo, which is developing therapies involving autism spectrum disorder and other neurological disorders with genetic origins.

Muotri's space organoids also triggered a number of news articles. One by Sharon Begley of STAT carried this headline,

"In a first, cerebral organoids produce complex brain waves similar to newborns’, reviving ethical concerns."

Here is a link to a lengthy release from the UC San Diego wth a headine saying,

"AI Algorithm Can’t Distinguish These Lab Mini-Brains from Preemie Babies"

Here is what CIRM had to say this morning about Muotri's research on the agency's blog, The Stem Cellar. 

"These new organoids allow us to explore how new therapies might work in the human brain, and hopefully increase our ability to develop more effective treatments for conditions as varied as epilepsy and autism."

How Muotri might translate brain cells in space into therapies for such things as autism is yet to be determined. But there is little doubt that his latest results will draw increased attention nationally and internationally in the coming months.

(Editor's note: The information about CIRM's blog was not contained in earlier versions of this item.)

Pressures for Stem Cell Profits and Cures: A Case from Japan with Implications for California

A stem cell treatment in Japan for spinal cord injury is raising a ruckus about ethics, efficacy and billion-dollar searches for cures and profits.

The matter involves a therapy called Stemirac and Sapporo Medical University. The treatment is now available to the public in Japan with most of its $140,000 cost covered by Japan's national health insurance program. 

The most recent overview of Stemirac came yesterday on a site called "Undark" in an article written by Amos Zeeberg. In the piece, Arnold Kriegstein, director of the stem cell program at UC San Francisco, called Stemirac  "essentially an unproven therapy."  Bruce Dobkin, a UCLA neurologist, was reported as saying "the results briefly reported in the media may suggest the treatment doesn’t even work."

(Undark's site says it is a "is a non-profit, editorially independent digital magazine exploring the intersection of science and society."  Its publisher is Deborah Blum, a former colleague of this writer at The Sacramento Bee. Blum is now director of the Knight Science Journalism Program at MIT.) 

In the piece yesterday about Stemirac, Zeeberg wrote, 

"It’s arguably the world’s most ambitious approved stem cell treatment and should have been a cause for celebration: a long-awaited breakthrough for the field of regenerative medicine — using modern biological tools to repair the body — and a harbinger of more impressive medicines."

He continued, 

Arnold Kriegstein
UCSF photo

"Instead, the therapy has been met with a heated debate. On one side, many experts have slammed Stemirac’s approval in uncommonly direct terms, saying there isn’t enough evidence to show it is effective or even safe. The treatment went through an expedited approval unique to Japan: After short, small clinical trials that suggest safety and efficacy, regulators can approve stem cell treatments on a conditional basis — allowing use of the treatments for seven years, while sponsors gather additional evidence to support a full approval.

"Critics also say Japan’s approach is far too soft — that early approvals allow patients to take experimental therapies that could be ineffective or dangerous, at a high cost to both patients and insurance providers. 'This is essentially an unproven therapy,' said Arnold Kriegstein, a stem cell researcher at the University of California, San Francisco. 'I’m very surprised this is happening in a country like Japan.'..."

The Undark article continued, 

Bruce Dobkin
UCLA photo

"What’s more, UCLA neurologist Bruce Dobkin told Undark, the results briefly reported in the media may suggest the treatment doesn’t even work. Dobkin pointed to previous trials testing other potential treatments for spinal cord injuries, and the Stemirac findings 'are exactly the results we found in patients in randomized controlled trials — in the control groups,' he said. That is, patients injected with Stemirac seemed to do as well as patients who got placebos in these earlier trials. He says people who have recently suffered spinal cord injuries, like Kusachi, the injured high diver (mentioned in Zeeberg's piece), and the others in the Stemirac trial, often have significant natural improvement over the next several months — exactly the period covered by the trial. It’s possible the patients were simply healing naturally, he says, but without a control group and double-blinding, it is hard to tell."

Undark's article captures many of the issues surrounding the development of stem cell therapies including the pressure to generate results for patients and profits for companies -- not to mention prestige and praise for researchers.

California's $3 billion stem cell program feels that pressure as well. It is running out of cash and would more than welcome a breakthrough in one of its 56 clinical trials -- one that would stimulate California voters to provide more billions for the state's nearly 15-year-old stem cell research effort.

The Search for a Cure for the Bubble Boy Disease: Orchard Therapeutics and the California Stem Cell Agency

Alliance for Regenerative Medicine video

Orchard Therapeutics, a British firm in which the California stem cell agency is directly supporting with $8.5 million, reports that it is "well underway" with its plans for a major facility in the San Francisco Bay area. 

Orchard says that it is on schedule to open the 150,000-square-foot plant in Fremont, Ca., in 2021, according to an article on BioProcess International.  

The move is part of a broad effort by Orchard to commercialize genetic therapies based on research pursued for decades by Donald Kohn of UCLA. California's stem cell research program has pumped $52 million into Kohn's research, which has saved the lives of more than 50 babies in (ADA-SCID) clinical trials.

Kohn has targeted what is often known as the bubble boy syndrome, a rare, fatal immune deficiency disorder (adenosine deaminase-deficient severe combined immunodeficiency -- ADA-SCID).  

UCLA has licensed Kohn's work to Orchard and will receive compensation at some point. CIRM is also slated to receive compensation should a product be developed. Kohn is one of the scientific founders or the Orchard and is a scientific adviser to the firm. 

The BioProcess article last week by Dan Stanton quoted Ran Zheng, Orchard's chief technical officer, as saying, 

“The diseases we target affect patients around the world, which require us to have the infrastructure to deliver gene therapies globally. We are therefore building a commercial-scale manufacturing infrastructure and leveraging technologies that will allow us to deliver our gene therapies globally and in a fully-integrated manner.”

The Fremont facility represents only part of Orchard's presence in California. Ron Leuty of the San Francisco Business Times reported that the firm leases 14,138 square feet in Menlo Park for labs and offices and 4,472 square feet for development labs and offices in Foster City. 

Orchard's stock price closed at $13.67 yesterday. Its 52-week high was $21.64 and the 52-week low was $8.65.

(Editor's note: This item has been altered from an earlier version to be more specific about the number of babies whose lives have been saved in clinical trials involving Kohn's work. The number now exceeds 50.) 

'Tough Lesson' and Stem Cells: More Time, More Money Urged -- Indirectly -- for California's Research

BioInformant graphic

Time and money, hope and hard work -- not to mention death -- were the topics today on the blog of the $3 billion California stem cell agency. 

The blog item involved more than the demise of patients waiting for a stem cell therapy but also the possible demise of the nearly 15-year-old program, unique in California history. 

The research effort, formally known as the California Institute for Regenerative Medicine (CIRM), is running out of cash. By the end of this year, it expects to have no funds for new awards. 

That situation led to a piece this morning on CIRM's  blog, The Stem Cellar. It was a bit of indirect pitch for continued funding by California taxpayers.

"Time and money are always going to be challenging when it comes to advancing stem cell research and bringing treatments to patients. With greater knowledge and understanding of stem cells and how best to use them we can speed up the timeline. But without money none of that can happen."

The article by Kevin McCormack, senior director of communications for CIRM, recapped the history of the agency, created by voters in 2004 through a ballot initiative that set the state off on the largest scientific research effort of any state in the nation. Indeed, as McCormack pointed out, the funding surpassed research budgets of some nations. The catch in California was that no source of funding for the agency was provided beyond the initial $3 billion. 

CIRM noted the high hopes for quick therapies back in 2004. 

"In the early days there was a strong feeling that this was going to quite quickly produce new treatments and cures for diseases ranging from Parkinson’s and Alzheimer’s to heart disease and stroke. Although we have made tremendous strides we are still not where we hoped we’d be. 

"It’s a tough lesson to learn, but an important one: good scientific research moves at its own pace and pays little heed to our hopes or desires. It takes time, often a long time, and money, usually a lot of money, to develop new treatments for deadly diseases and disorders."

McCormack briefly catalogued some of CIRM's progress and the 56 clinical trials in which it has invested, some of which are in the final stage before federal approval of a treatment. 

But CIRM said, 

"The simple truth is that unless we, as a nation, invest much more in scientific research, we are not going to be able to develop cures and new, more effective, treatments for a wide range of diseases." 

The agency is hoping that voters will approve a ballot initiative in November 2020 that will provide $5.5 billion more for stem cell research. In the meantime, it has $71 million to hand out.

Coming Up Next Month: Final Award Decisions by California's $3 Billion Stem Cell Agency?

The California stem cell agency, which is running out of cash for new awards, has cancelled a meeting this week at which it was scheduled to approve funding for more clinical stage research.

The action sets the stage for a full discussion and decisions by the agency board in late September on its last likely research awards unless it receives a substantial infusion of cash. Known formally as the California Institute for Regenerative Medicine (CIRM), the agency was created by voters in 2004 with $3 billion. That has dwindled to $71 million, although $28 million is committed to sickle cell anemia.

CIRM is pinning its hopes for survival on a possible ballot initiative in November 2020 to provide it with another $5.5 billion. 

In response to a question about the status of the meeting once scheduled for this Thursday, Kevin McCormack, CIRM senior director of communications, noted that the last of the clinical stage applications are being reviewed this month. He said,

"There may be more projects to fund than money."

McCormack said,

"We will be bringing all meritorious projects to the board in September to make funding decisions.  In addition, the full board (not the Application Review Subcommittee) must decide whether or not to redirect money to the Translation bucket in order to fund  those that were not funded last month."

CIRM's funding squeeze generated considerable discussion at the July meeting, including appearances by scientists seeking awards. The full transcript of that session can be found here. 

The application review subcommittee is a subset of the full 29-member board, which includes a number of representatives from institutions that receive awards. The subcommittee was created to avoid the appearance of conflicts of interests on the part of the CIRM board. 

September's meeting will be based at the Oakland headquarters of the agency. It is also scheduled to be audiocast live with Internet access. Additional physical locations are expected to be announced for teleconference access. The public can participate in the meetings via the Internet and at the teleconference locations. 

California's $76 Million Bet: Something Called CAR-T, Cancer and Promises

CIRM-funded researcher Saul Priceman of the City of Hope discusses the CART-T frontier, April 2019. Video by American Association for Cancer Research

California's state stem cell agency has now invested $76 million in treatments sometimes described as "miraculous," whose costs can run upwards of $1.5 million. 

The push into the much-heralded CART-T therapy field is part of the agency's effort to fulfill its 15-year-old campaign promise to state voters to turn stem cells into cures. 

The California Stem Cell Report this week took a look at the  CAR-T slice of the agency's $3 billion research pie in the wake of news that Medicare would now cover major portions of the cost of the cancer-fighting technology.

The decision applied to only two specific therapies. But Seema Verma, the top Medicare executive, said CAR-T was
"an important scientific advancement" and would provide help for "some patients who had nowhere else to turn."

Maria Millan, president of the stem cell agency, called the announcement a big step forward. In an email to the California Stem Cell Report, she said,

“We are encouraged by the announcement that the Centers for Medicare and Medicaid will provide coverage for hospital costs related to CAR-T therapies. This is a major step to providing access to these life-saving treatments for patients in need.”

The CAR-T therapies approved by Medicare can run close to $500,000 plus hundreds of thousands more for related costs. One estimate is that total cost of a CAR-T treatment could hit $1.5 million. 

Their medical promise of CART-T is that it's a cure -- not an ongoing treatment, which also can raise total costs exponentially. The idea behind the therapy is that it powers up a patient's immune system to destroy cancer cells in a targeted fashion.  

"Drugmakers note CAR T-cell therapy is designed to be given just once and to be a potential cure for patients who have run out of other options. But not all patients benefit from it and because it is so new, it’s too soon to know whether it will deliver long-term cures," Laurie McGinley wrote in the Washington Post last week. 

California's stem cell agency, formally known as the California Institute for Regenerative Medicine(CIRM), has approved 11 awards involving CAR-T therapies ranging from basic research to clinical trials. The amounts of the awards run from less than $2 million to nearly $20 million, which went to Poseida Therapeutics, Inc., of San Diego, Ca.

The company has received a total of nearly $24 million from CIRM for its CAR-T work. In May, the Food and Drug Administration approved Poseida's CIRM-backed product as an orphan drug treatment for multiple myleoma, a disease that affects 300,000 Americans every year. The company reports that its Phase Two clinical trial for the treatment is now underway.

Poseida's work has attracted the interest of Big Pharma. In March, Novartis pumped $75 million into the company in a fund-raising round that totalled more than $142 million.  (See here for more information on Poseida.)

Last month, in another CART-T venture, the stem cell agency added more millions to an effort at the City of Hope by Saul Priceman, a breast cancer researcher. He told the CIRM board,

"For the past 20 years, City of Hope has focused intensely on developing CAR-T cell approaches for treating the most intractable solid tumors. In the early 2000s, we were the first to demonstrate solid tumor CART-T cell therapy treatment in patients. And recently we were the first to report our remarkable response for patients with glioblastoma."

CIRM directors added more than $9 million to the $1.4 million already provided to Priceman.

In announcing the award, CIRM CEO Millan said, 

“When a patient is told that their cancer has metastasized to other areas of the body, it can be devastating news. There are few options for patients with breast cancer brain metastases (the target of Priceman's research).

"Standard of care treatments, which include brain irradiation and chemotherapy, have associated neurotoxicity and do little to improve survival, which is typically no more than a few months.  CAR-T cell therapy is an exciting and promising approach that now offers us a more targeted approach to address this condition.”

CAR-T is a gene therapy, which has raised some questions about whether it fits within the scope of the stem cell agency, which was created by a ballot measure in 2004, Proposition 71.  

Kevin McCormack, senior director of CIRM communications, said in response to a query, 

"The programs we’ve funded fit into Proposition 71 because (1) HSC (hematopoietic stem cell) derived CAR-T, (2) CAR T’s enriched for TSCM (stem cell) or gene-engineered T cells qualify as a 'vital research opportunity' as outlined in the proposition." 

Here are links to the CAR-T awards by their CIRM application number, which is very useful in searching for additional information on each grantee's research.

Tran1-10258, $5.6 million, Ezra Cohen, UC San Diego; Clin2-10395, $19.8 million, Matthew Spear, Poseida; Clin1-10999, Devon Shedlock, Poseida; Clin2-10248, $12.8 million, Christine Brown, City of Hope; Clin2-10846, $11 million, Crystal Mackall, Stanford; Clin1-11223, $3.8 million, Xiuli Wang, City of Hope; Disc2-11107, $1.4 million, Saul Priceman, City of Hope; Clin2-11574, $9.3 million, Priceman, City of Hope; Disc2-10748, $1.7 million, Scott Kitchen, UCLA; Disc2-11157, $1.4 million, Lili Yang, UCLA, and Clin2-11380, $4.7 million, Theodore Nowicki, UCLA.

City of Hope video

WebMD and the Rising Framework for a $5.5 Billion Stem Cell Request in California

USC researchers Mark Humayun (right) and Amir Kashani,
CIRM-funded scientists. Click here to go to their research video.

WebMD, a heavily used Internet health and medical site, this week assessed the state of the stem cell field in a two-part series that highlighted much of the clinical work backed by California's $3 billion stem cell agency.

The first installment by Kathleen Doheny offered a national overview, declaring that stem cell research has been underway in significant way for three decades. "Where are we now?" was the headline on the article. Perhaps the key sentence declared,

"While proponents say all this groundwork is finally coming to fruition, others call progress slow and plodding."

WebMD is a go-to site for the public when it looks for medical information. In 2016 it reported that it had nearly 180 million unique visitors per month. Today, it says one out of every four Americans uses its site every month.

The series led with work at USC that is being assisted with millions from the California Institute for Regenerative Medicine(CIRM), as the stem cell agency is formally known. It also noted CIRM's 56 clinical trials and its clinical dashboard. 

CIRM grantees were mentioned, including Andy McMahon, Amir Kashani and Mark Humayun, all of USC and recipients of CIRM awards.

The second part of the series, authored by Karen Weintraub, focused on the unregulated and dubious "stem cell" treatments that are the target of both federal and California state regulators.  The headline said, 

"Stem Cell Clinics: Effective or Pricey False Hope?"

One might ask whether readers of the piece are distinguishing between those sorts of sketchy clinics and California's Alpha stem cell clinics, which are very much the pride of the state research effort. 

The WebMD coverage is part of the framework that is taking shape as the California stem cell agency sees its funds coming to an end. It is hoping for a $5.5 billion infusion from voters via a ballot measure in November 2020. How the public perceives stem cell treatments overall and how voters perceive the success of the state effort are likely to be critical in winning approval of more stem cell cash in California.