Whoopee Time at the California Stem Cell Agency: Celebrating a $4.9 Billion Deal

The California stem cell agency this afternoon burst out with an exuberant cheer, declaring that a huge financial deal announced just yesterday gave its research program a $4.9 billion seal of approval. 

If you missed it, the deal involves the $4.9 billion purchase of Forty Seven, Inc., by Gilead Sciences, Inc., two companies nestled only 20 minutes apart on the San Francisco Bay peninsula. 

Writing on its blog, The Stem Cellar, the agency all but said, "WHOOPEE!"  Not that that would have been inappropriate. The agency declared, 

"It’s not every day that a company and a concept that you helped support from the very beginning gets snapped up for $4.9 billion...CIRM has supported this program from its very earliest stages, back in 2013, when it was a promising idea in need of funding."

CIRM, of course, is the official name of agency, the California Institute for Regenerative Medicine. 

Maria Millan, CIRM photo

The blog item continued with this from Maria Millan, CEO of CIRM:

“To say this is incredible would be an understatement! Words cannot describe how excited we are that this novel approach to battling currently untreatable malignancies has the prospect of making it to patients in need and this is a major step. Speaking on behalf of CIRM, we are very honored to have been a partner with Forty Seven, Inc., from the very beginning."

The Forty Seven tale originated in the Stanford University lab of Irv Weissman. CIRM quoted him as saying,

Irv Weissman, Stanford photo

"The story of the funding of this work all of the way to its commercialization and the clinical trials reported in the New England Journal of Medicine is simply this: CIRM funding of a competitive grant took a mouse discovery of the CD47 ‘don’t eat me’ signal through all preclinical work to and through a phase 1 IND with the FDA (Food and Drug Administration). Our National Institutes of Health (NIH) did not fund any part of the clinical trial or preclinical run up to the trial, so it is fortunate for those patients and those that will follow, if the treatment continues its success in larger trials, that California voters took the state’s right action to fund research not funded by the federal government.”

Ingrid Caras, CIRM photo

Ingrid Caras, CIRM senior science officer, who was on the agency team that provided assistance to the academic researchers, said,

“I had the pleasure of working with and helping the Stanford team since CIRM provided the initial funding to translate the idea of developing CD47 blockade as a therapeutic approach. This was a team of superb scientists who we were fortunate to work closely with them to navigate the Regulatory environment and develop a therapeutic product. We were able to provide guidance as well as funding and assist in the ultimate success of this project.”

McCormack concluded, 

"Forty Seven Inc. is far from the only example of this kind of support and collaboration. We have always seen ourselves as far more than just a funding agency. Money is important, absolutely. But so too is bringing the experience and expertise of our team to help academic scientists take a promising idea and turn it into a successful therapy."

CIRM did not mention the amount of money provided to support the research. But it has awarded $15 million directly to Forty Seven. Weissman has received $30 million, much of which has played a role in Forty Seven's products.  

'Perfect Example' and 'Broader Utility:' Pieces of the Forty Seven-Gilead-California Stem Cell Story

The history of the stock price of Forty
Seven, Inc., since it went public in 2018.
Google graphic

The stock price of Forty Seven, Inc., California's "don't eat me," cancer therapy firm, today closed at $$93.91 as the state's stem cell agency hailed the firm's performance as "perfect example" of the agency's value to the field and to the people of California. 

The closing price represented a stunning increase over the firm's record low of $5.53 last October. It came as Gilead Sciences, Inc., and Forty Seven announced this morning that the firm would be purchased by Gilead for $4.9 billion. 

Maria Bonneville, a spokeswoman for the agency, said, 

"Forty Seven, Inc., is the perfect example of CIRM’s value to the field of regenerative medicine.  We take pride in our ability to work with our grantees to make them as successful as possible and get them ready to partner in order to fulfill our mission."

Mathew Herper of Stat news interviewed Daniel O'Day, CEO of Gilead, today about the deal. Here is what Herper wrote, 

"So why purchase Forty Seven?

"'Because it’s novel,' O’Day said, referring to the company’s lead medicine, magrolimab, an antibody against CD47, a protein that cancer cells use to tell white blood cells 'don’t eat me.' The idea is that blocking this protein will allow the body’s immune system to attack cancer cells.

"'We had our eyes on Forty Seven for a while,' O’Day said. Data presented in two malignancies, myelodysplastic syndrome and acute myeloid leukemia, at last year’s annual meeting of the American Society of Hematology showed that the drug was doing 'some pretty special things,' he said. He said Gilead scientists believe that magrolimab could have 'broader utility' because it could be relatively safe and could be combined with other medicines relatively easily." 

The stem cell agency, formally known as the California Institute for Regenerative Medicine (CIRM), publishes anonymized summaries of what grant reviewers have to say about the applications from researchers. Here is the review summary for one application for $5 million in 2017. Here is the summary for a $10.2 million application in 2016.

$4.9 Billion Dollar Buyout of Firm Backed by California's Stem Cell Program; Good News for Agency Supporters

California's "eat-me," cancer-fighting firm Forty Seven, Inc., is being purchased in a $4.9 billion deal this morning that appears to validate the state's multimillion-dollar investment in the enterprise.

Forty Seven has received $15 million directly from the California stem cell agency. One of Forty Seven's co-founders, Irv Weissman of Stanford University, has received an additional $30 million for research, much of which underpins the company's approach. 

Gilead Sciences, Inc., of Foster City, Ca., is purchasing Forty Seven for $95.50 a share. Just last October, Forty Seven's stock was cratering at $5.53 a share. 

California will not benefit directly from the huge jump in the stock price. The state Constitution bars state agencies from holding stock in companies. However, if CIRM funded-research helps to create a profitable therapy, the state could receive royalties. See here for a look at the agency's intellectual property regulations.  

The purchase is good news for supporters of a proposed ballot initiative to give the agency an additional $5.5 billion, which would save CIRM from financial extinction. The backers of the proposal are currently gathering 600,000-plus signatures to place it on the Nov. 3 ballot. 

The agency was created in 2004 in a ballot campaign that provided $3 billion in state bond funding to help stimulate creation of stem cell therapies. So far the agency has not backed a stem cell therapy that is approved for use by the general public. But the Gilead purchase is a strong indicator that such a treatment is getting much closer. 

In its news release, Gilead highlighted Forty Seven's lead product candidate, magrolimab, and said, 

"The acquisition will strengthen Gilead’s immuno-oncology research and development portfolio. Magrolimab is a monoclonal antibody in clinical development for the treatment of several cancers for which new, transformative medicines are urgently needed, including myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) and diffuse large B-cell lymphoma (DLBCL).

The stem cell agency, known formally as the California Institute for Regenerative Medicine(CIRM), has backed part of the work on magrolimab.  Last fall, Mark Chao, vice president of clinical development at Forty Seven, said, 

“CIRM’s support has been instrumental to our early successes and our ability to rapidly progress Forty Seven’s CD47 antibody targeting approach with magrolimab. CIRM was an early collaborator in our clinical programs, and will continue to be a valued partner as we move forward with our MDS/AML clinical trials.”

At the time, CIRM said the awards to Forty Seven and several other companies amounted to important deal-flow funding. CIRM quoted a USC study of the agency as saying, 

 “Deal-flow funding usually involves several waves or rounds of capital infusion over many years, and thus is it expected that CIRM’s past and current funding will attract increasing amounts of industry investment and lead to additional spending injections into the California economy in the years to come.”

Forty Seven's "eat me" expression involves enabling a person's immune system to overcome and devour cancer stem cells. The company's web site says, 

"Blocking CD47 'don’t eat me' signals while releasing and boosting 'eat me' signals is the core focus of our research to enable the patient’s own immune system to attack and destroy their cancer."

Rich Day on the Stock Market for California "Eat Me" Cancer Therapy Firm

Forty Seven went public in June 2018. Here is how its stock has performed.
Google graphic

The stock price of Forty Seven, Inc., the high-flying company with a $15 million link to the California stem cell agency, today closed nine times higher than its all-time low just last October. 

The stock hit $50.00, 19 percent above its close yesterday. Its low last fall was $5.53. The stock took off this morning on the basis of news reports that Gilead Sciences, Inc., was in talks with the company about a possible purchase. Forty Seven is one of the few companies showing gains today as the stock market continued to plummet. 

Forty Seven was identified as "pivotal" investment earlier this month by the stem cell agency. It is one of 60 companies whose clinical trials the $3 billion agency is supporting. Forty Seven aims at fighting cancer by triggering the body's immune system and is known for its "eat me" therapeutic approach.  

The company's web site says, 

"The therapeutic potential of the innate immune system, the first line of defense against cancer, was not well understood and appreciated when Irv Weissman and his colleagues at Stanford University identified CD47-SIRP-alpha as a novel immune pathway. This discovery has the potential to lead to new therapies and empower patients to fight cancer with their own immune cells, in the hopes of one day saving lives."

No new details have emerged as of this writing on a possible Gilead-Forty Seven deal. 

CIRM, as a state agency, cannot profit directly from an increase in the company's stock price. California's state constitution bars the state from owning stocks. However, the state could benefit from royalties from Forty Seven if the company's CIRM-financed work results in profits. 

So far, CIRM-backed investments have generated few royalties despite expectations raised by agency supporters. During the 2004 ballot campaign that created the agency a potential of more than $1 billion in royalties was bandied about. 

The stem cell agency, known formally as the California Institute for Regenerative Medicine (CIRM), declined to comment on the Forty Seven news. But the agency has previously touted the significance of its role in funding the firm with $15.2 million and also backing underlying research by Weissman, who has received $30 million from CIRM. Weissman sits on the company board. 

Also not commenting was Forty Seven and the campaign organization pushing a November ballot proposal that would give financially strapped CIRM an additional $5.5 billion. CIRM is running out of cash and will begin to shut down if the measure fails to make the ballot or win voter approval.  

CIRM points to companies like Forty Seven as evidence of the value that the agency has provided for the people of California and the state's business climate. Forty Seven and other CIRM success stories are likely be ballyhooed often in the upcoming campaign.  

Readers who are not familiar with northern California may be interested in how the stem cell geography works in the Golden State. 

• CIRM is headquartered in Oakland, It is only 42 driving minutes away from Gilead.
• Gilead is located in Foster City, only 20 minutes from Forty Seven.
• Forty Seven is located in Menlo Park, only 19 minutes from Irv Weissman's office at Stanford. 

One caveat on those times and distances: They are only good when the traffic is not too bad.  But the physical proximity does have something to do with the building of a "critical mass" of stem cell enterprises in the Golden State, something that researchers and CIRM find valuable. 

Here is a Forty Seven video discussing the company's "eat me" approach.

Booming Stock Price This Morning for Firm Backed by California Stem Cell Agency

Google chart

California's more than $15 million investment in a San Francisco Bay area company could be paying off more than handsomely this morning -- for the company.

The firm is called Forty Seven, Inc. Its stock skyrocketed overnight and was up 24 percent this morning at the time of this writing.  The jump occurred as the rest of the market continued its deep slump.

The trigger for Forty Seven was a report from Bloomberg News that Gilead Sciences, Inc., had approached the Menlo Park, Ca., company with a takeover bid.

This morning's stock price of $60,34, however, was still below the company's 52-week high of $65. That compares to the 52-week low of $5.53.

The hike in Forty Seven's stock price will not necessarily directly benefit the stem cell agency, which is formally known as the California Institute for Regenerative Medicine (CIRM).  The California state constitution bars the state from holding stock in companies, which has rankled some of CIRM's top officials.

Any financial return on the two CIRM awards made directly to Forty Seven would come through possible royalties from use of research that the agency has helped to finance. 

CIRM's support for the firm's research actually exceeds the $15.2 million in direct awards. The $3 billion agency, which is running out of cash, has financed other awards that laid the ground work for Forty Seven. They  went to Irv Weissman at Stanford University, who is on the company's board of directors and a co-founder of the firm. Weissman has received $30 million from CIRM.  

Last October the agency cited its investment with Forty Seven as part of the economic benefits chalked up by CIRM and provided this quote from the company.

"'CIRM’s support has been instrumental to our early successes and our ability to rapidly progress Forty Seven’s CD47 antibody targeting approach with magrolimab,” says Mark Chao, M.D., Ph.D., Founder and Vice President of Clinical Development at Forty Seven Inc. 'CIRM was an early collaborator in our clinical programs, and will continue to be a valued partner as we move forward with our MDS/AML clinical trials.'"

Earlier this month, CIRM President Maria Millan highlighted Forty Seven as a "pivotal" clinical trial in a briefing for CIRM directors, producing the slide below. 

Look for more coverage involving the Forty Seven-Gilead news later today right here on the California Stem Cell Report. 

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.)

The California Stem Cell Agency: 'Envy of the World, ' Hopes Too High?

The prestigious journal Nature yesterday published a piece about California's $3 billion stem cell agency that spoke of voids, envy and "double-edged swords."

The opinion piece was written by Jeanne Loring, a San Diego area

Jeanne Loring

researcher who has followed the agency for years and has been one of its beneficiaries($17 million in awards).

Reflecting on the agency's importance, she wrote,

"For the past dozen or so years, stem-cell researchers in California have been the envy of the world."

Creation of the agency, known formally as the California Institute for Regenerative Medicine (CIRM), "essentially guaranteed that the state would become the center of innovation in the field," Loring declared. Its demise would leave a major void, she said.

Loring continued,

"Although its intentions were laudable, CIRM raised the hopes of the public too high. It needed catchy advertising to gain voters’ support. One of its campaign slogans was 'Save lives with stem cells.' Effective advertisements often focus on a promise and downplay shortcomings, such as the time and resources required to advance a stem-cell therapy through clinical trials to market approval. No CIRM-supported therapy has been approved by the US Food and Drug Administration (FDA), resulting in dashed expectations.... 

"Still, fulfilment of the campaign promise is under way. CIRM has granted funding for 56 stem-cell-based clinical trials."

At the same time, dubious and unregulated clinics that peddle stem cell "snake oil" have proliferated across the country, leading the FDA to attempt a belated takedown of some of the enterprises.

The growth of those clinics is part of "the double-edged sword that is CIRM’s legacy,"  Loring said.

"The agency has enabled fundamental science and helped to establish know-how for rigorous assessment of stem-cell therapies. Earlier this year, my colleagues and I started a biotechnology company, Aspen Neuroscience in La Jolla, California, and are raising funds for a clinical trial of a neuron-replacement therapy for Parkinson’s disease. Without the work that CIRM has done to educate investors and researchers, this would have been very difficult. 

"But the agency’s work has inadvertently helped to boost unregulated, for-profit ‘clinics’ claiming, without sound evidence, that cells derived from fat, bone marrow, placenta and other tissues can cure any disease."

Loring said,

"CIRM has regularly denounced these clinics, which existed before the institute’s creation and will persist as long as they can make money. Still, it is easy to understand how public enthusiasm would spill over to those offering quackery."

Loring noted that the agency, which expects to run out of cash for new awards this year, is hoping that voters will give provide $5 billion more via a ballot initiative in November 2020. 

Loring urged rhetorical caution in the ballot campaign.

"We must strike a balance between future potential and current reality when we talk to the public. Researchers should emphasize that even when therapies show promise in mice, they often fail to work in humans. The only way to find out — and to check for safety — is rigorous scientific testing in clinical trials."

"We need to temper public hope," Loring wrote, while regulators, including the FDA and the California State Medical Board, bring the bad actors under control. 

Leader of Global Research Group: California is 'Hotbed' of Stem Cell Activity

The man slated to be president of the world's largest group of stem cell scientists this week declared that California's stem cell agency has "really accelerated" the work that has made the  state a "hotbed" in the field.

In an interview in the Los Angeles Times, Deepak Srivastava,

Deepak Srivastava
Gladstone photo

also president of the Gladstone Institutes in San Francisco, provided a primer on stem cell research. He said,

"California is a hotbed of activity in the stem cell research world. The California Institute for Regenerative Medicine(CIRM) has really accelerated so much of this. We thought this international community of leaders ought to converge at this major hub in L.A.

"Many people talk about the semiconductor being the dominant discovery in the last 50 years. Now, many think biotech will be the major driver of advancements in the coming 50 years. California promises to be an epicenter for that."

Srivastava has received $17.8 million in research funding from CIRM. Gladstone has received 32 grants totaling $56.4 million.

The occasion for Srivastava's remarks is the annual meeting this week of the International Society for Stem Cell Research in Los Angeles. Srivastava is the incoming president of the organization. The meeting has drawn about 4,000 participants but little major news coverage so far. 

The light coverage is not surprising given that much of meeting deals with quite technical issues. The Los Angeles Times piece was an attempt to demystify the field for the general reader. 

For the $3 billion state stem cell agency, the session was an opportunity to tell its story to a broader research community, including the fact that expects to run out of cash for new awards this year. CIRM is hoping that voters will re-fund it with $5.5 billion in November 2020. Next week it is closing off applications for any further awards this year.

One of ISSCR's concerns is the need for strong funding for stem cell research.

CIRM Application Shutdown: Text of Robert Klein's Comments

Here is the text of comments by Robert Klein, chairman of Americans for Cures, on the shutdown of applications at the California stem cell agency. Klein was responding to questions from the California Stem Cell Report.

"When Californians learn of the remarkable progress from the California funded stem cell and genetic therapies FDA approved human trials in restoring major function to paralyzed patients, to save the lives of children with severe immune diseases, to restoring sight to patients that are blind, the support for stem cell research and therapy development exceeds 70% in recent polls.

"California’s leadership in cellular and genetic therapies, through its state funded research and human trials, currently supports 51 human trials for a range of chronic disease and injuries, and 24 more human trials are in progress by biotech companies based upon California’s funded research.

"The life-changing and life-restoring work of California’s scientists and physicians will predictably earn the chance for renewed funding. Polls indicate that California voters want the opportunity to vote in 2020 on continuing this visionary California initiative, originally funded in 2004 through Proposition 71, the California Stem Cell Research and Cures Act. The gap in available state funding from the fall of 2019 through November 2020 will hold back additional critical human trials for new life saving and/or disease mitigating therapies; but, I have faith that Patient Advocates and California voters will back new funding at the polls in 2020 and continue California’s remarkable contribution to this medical revolution that effects every one of our lives.

"In advancing the research and therapies, the California research funding agency has also gained broad financial support for its portfolio of research and human trials based on the strength of more than 2850 peer reviewed published medical discoveries and the 75 human trials directly funded or separately funded supporting the California funded discoveries. The matching funds from donors, institutions, private companies and non-profit organizations have already exceeded $3,250,000,000, more than a 100% match on the $3,000,000,000 originally approved in state funding.

"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."

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

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

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

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

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

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

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

Major Sickle Cell Surge: Feds and California Collaborate on Cell Therapies for the Disease

In August, the stem cell agency staged a live event on Facebook dealing  with 

the current state of sickle cell research. It has since received  more than 2,200

 page views. Here is a link to the event, which featured  Don Kohn of  UCLA  and 

Mark Walters of UCSF Benioff Children’s Hospital. 

California's stem cell agency has embarked on what it calls a "remarkable" collaboration with the federal government aimed at developing cell-based and gene-based therapies for sickle cell disease, which affects 100,000 persons nationwide.

The partnership marks the first time that the state agency has partnered directly with the National Institutes of Health(NIH), which spend $100 million a year on sickle cell research. 

The NIH has committed an additional $7 million to jump start its new effort, dubbed "The Cure Sickle Cell Initiative."   The California stem cell agency has already pumped nearly $39 million into sickle cell research. 

The affliction is caused by a genetic defect that deprives the body of oxygen, "wreaks havoc on the body, damaging organs, causing severe pain, and potentially leading to premature death," says the NIH. 

In the agreement (see below) with California's $3 billion stem cell agency, the NIH said that the agency is "a recognized leader in the development and funding of clinical trials focused on cell-based therapies and is now working to accelerate support for clinical stage candidate treatments that demonstrate scientific excellence."

Millan told directors in in June that the arrangement amounted to a "quite remarkable" recognition of CIRM's capabilities. She said the NIH "made a decision that they needed to partner with us in order to have the best shot at accomplishing what they want to do with this 'cure sickle cell initiative.'"

On Thursday, directors of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known, will receive a more complete briefing about the full range of CIRM's involvement.

CIRM will handle the funding processes for the applications for the late stage research program, making funding decisions in as little as 85 days. The agency's work will include scientific peer review, contracting and post-award management, according to CIRM documents. (The documents are part of the presentation that can be found here.)

Millan said that the NIH has recognized the agency's value in terms of accelerating development therapies, building late development research and translating basic research into clinical use. 

The agency said it will provide funding on approved awards for work done in California, according to CIRM rules. It will have the ability, in consultation with the NIH,  to suspend or terminate research if milestones are missed, including taking back unused funds. Kevin McCormack, a spokesman for the agency, said that it will be compensated by the NIH for additional work that it has to perform but that details are yet to be worked out.. 

Last month, the NIH said in a news release:

"Currently, the only cure for sickle cell disease is a bone marrow transplant, a procedure in which a sick patient receives bone marrow from a healthy, genetically-compatible sibling donor. However, transplants are too risky for many adults, and only about 18 percent of children with sickle cell disease have a healthy, matched sibling donor.

"The Cure Sickle Cell Initiative seeks to develop cures for a far broader group of individuals with the disease, and it is initially focusing on gene therapies that modify the patient’s own hematopoietic stem cells (HSCs), which make red and other blood cells. These modified HSCs can then be given back to the patient via a bone marrow transplant, making a cure available to more patients who lack a matched donor."

Below is a CIRM video on sickle cell disease and a copy of the agreement between the stem cell agency and the NIH. 

(Editor's note: An earlier version of this item incorrectly reported that the agency had committed more than $200 million to sickle cell research, based on inaccurate figures on the CIRM web site. The correct amount is $38,8 million. CIRM said the error was created by a computer glitch and that it has corrected the figures on its site.)

Sickle Cell Cirm-nhlbi Mou ... by on Scribd

Stanford's Weissman Lauds California Stem Cell Agency For Innovation, Critical Financing

The California stem cell agency has chalked up hearty praise from an internationally known Stanford researcher for its 13-year, $3-billion search for stem cell therapies and cures.

Irv Weissman, Stanford photo

The scientist is Irv Weissman, director of the Institute of Stem Cell Biology and Regenerative Medicine at the Stanford University School of Medicine.  His laudatory reflections on the California Institute for Regenerative Medicine (CIRM), as the stem cell agency formally known, recently found their way to the Oakland-based enterprise. And last Monday the agency posted an item on Weissman's remarks on its blog, The Stem Cellar.  The article began,

"When you get praise from someone who has been elected to the National Academy of Sciences and has been named California Scientist of the Year you know you must be doing something right."

Weissman said the agency has provided the financial support that allows research to bypass "the valley of death," short hand for the stage in which promising research can often die. Plus, he said, CIRM allows the discoverers to guide early stage development rather than diverting it into commercial arena.

Weissman's comments spoke to what the agency calls its "value proposition," a term that is becoming increasingly important as the agency faces its possible demise. The agency expects to run out of cash for new awards by the end of next year. It is trying to raise more than $200 million privately to continue operations until November 2020, when it hopes voters will approve $5 billion more for stem cell research.

CIRM's blog item was authored by Kevin McCormack, CIRM's senior director of communications,  in the context of a $115 million initial public stock offering by Forty Seven, Inc., of Menlo Park, Ca., a company founded on the basis of Weissman's work. Weissman is currently a member of the company's board.

Forty Seven has received $15.2 million from CIRM. Weissman has received $32.4 million.

Weissman said in the statement that CIRM carried,

"The major support (for Forty Seven) came from the California Institute of Regenerative Medicine (CIRM), funded by Proposition 71, as well as the Ludwig Cancer Research Foundation at the Ludwig Center for Cancer Stem Cell Research at Stanford. CIRM will share in downstream royalties coming to Stanford as part of the agreement for funding this development.

"This part of the state initiative, Proposition 71, is highly innovative and allows the discoverers of a field to guide its early phases rather than licensing it to a biotech or a pharmaceutical company before the value and safety of the discovery are sufficiently mature to be known. Most therapies at early-stage biotechs are lost in what is called the ‘valley of death’, wherein funding is very difficult to raise; many times the failure can be attributed to losing the expertise of the discoverers of the field.”

In response to a question from the California Stem Cell Report, McCormack said Weissman's statement came "unbidden" by the agency.  We asked Weissman about what led him to issue the remarks. Weissman said he said he had not seen the CIRM piece, but responded after reading it.

He said in an email, 

"Now that I’ve seen the quote, it is close to what I sent to colleagues at Stanford. I did it so that my colleagues understood the nature of the CIRM experiment in funding research and its translation. One of these colleagues sent it on to CIRM, and I didn’t object.

"I think its very important to know how the original Prop 71 was designed not only to fund stem cell related research, but also to take selected projects competitively reviewed by expert referees to and through phase 1 trials if warranted. The therapy that was developed at Stanford by the team led to the discovery team forming a disease team of experts usually only found in biotechs and pharma, but here led by the discoverers of the leukemia stem cell overexpressed molecule, CD47, which by its ‘don’t eat me’ actions protects the leukemia from removal by scavenger macrophages. The CIRM oversight team helped guide selection of outside advisors, and met frequently with us to monitor our progress, and most importantly, give us advice that led to Stanford filing two INDs on time in the US [FDA] and the UK[MHRA]. The importance of doing high level preclinical testing and toxicity etc without a profit motive allowed the team to keep going when surprising events came up. Many biotechs fail at that point, as the risk starts to worry investors and shareholders. But this went through, and in addition to getting into important phase 1 trials that broadened the potential cancer targets to cancers beyond myelogenous leukemia, the group could see how the therapy needs to be administered to avoid toxicity in patients. By the time Stanford informed us it was time for them to license the ip, many independent companies had formed around the concept discovered by the team, a validation that this could become the second type of checkpoint inhibitor therapy for human cancers, this time for macrophages instead of inhibited T cells. 

"I felt it was equally important to try to get the agency that funded these stem cell related efforts to share royalties with the academic institution that held and licenses the intellectual property; I first raised this issue in 1994 when I was President of the American Association of Immunologists; my article is attached here.

"Most of us hope the discoveries we make can have the potential to help patients with diseases that are only incompletely treated by current medical practice. Very early results of clinical trials reported in the ASCO meeting in early June are consistent with that possibility. 

"I need to make clear that the statement in the blog was written by me, and was not an official document of Stanford University, of Forty Seven, Inc, or from others from the discovery team. If you decide to publish this answer to your question, please either publish it in full, unedited, or don’t publish it at all. I didn’t write this for you to publish, but for you to understand from your question the reason I wrote the original document to colleagues at Stanford."