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

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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. 

The Valley of Death and the California Stem Cell Agency: Luring Deep Pocket Investors

The California stem cell agency this week is tooting a $150 million horn and heralding its efforts to assist stem cell businesses with development of therapies that could ease the travails of everything from cancer to blindness.

It is all about a financial "valley of death" that can imperil biotech firms as they seek to turn research into an actual product that can be used by patients. The latest poster child for the California Institute for Regenerative Medicine (CIRM), as the agency is formally known, is a San Diego firm called ViaCyte. 

The enterprise has received more cash -- $72 million -- from CIRM than any other business. CIRM is facing its own valley of death next year, when its taxpayer cash will run out.

Writing yesterday on the CIRM blog, the agency's communications director, Kevin McCormack, said,

"CIRM was created, in part, to help...great ideas get through the valley (of death). That’s why it is so gratifying to hear the news today from ViaCyte – that is developing a promising approach to treating type 1 diabetes – that they have secured $80 million in additional financing.

"The money comes from Bain Capital Life Sciences, TPG and RA Capital Management and several other investors. It’s important because it is a kind of vote of confidence in ViaCyte, suggesting these deep-pocket investors believe the company’s approach has real potential."

McCormack continued,

"CIRM has been a big supporter of ViaCyte for several years, investing more than $70 million to help them develop a cell therapy that can be implanted under the skin that is capable of delivering insulin to people with type 1 diabetes when needed. The fact that these investors are now stepping up to help it progress suggests we are not alone in thinking this project has tremendous promise.

"But ViaCyte is far from the only company that has benefitted from CIRM’s early and consistent support. This year alone CIRM-funded companies have raised more than $1.0 billion in funding from outside investors; a clear sign of validation not just for the companies and their therapies, but also for CIRM and its judgment.

"This includes:

• Humacyte raising $225 million for its program to help people battling kidney failure
• Forty Seven Inc. raising $113 million from an Initial Public Offering for its programs targeting different forms of cancer
• Nohla Therapeutics raising $56 million for its program treating acute myeloid leukemia"

One could argue that these companies could have found backing from other sources than the stem cell agency. One could argue that state government should not be in a business that is too risky for even the vaunted world of venture capitalists.

Nonetheless it is an important part of the CIRM story, one that will be tested perhaps in November 2020. That's when the $3 billion agency hopes to see a measure on the ballot that will give it another $5 billion. So far the agency, created in 2004 by a ballot initiative, has not fulfilled voter expectations that it would produce a stem cell therapy that is widely available. And it will need a good yarn to inspire voters once again in 2020. 

State of Stem Cells: Three-day Conference Opens Today, Includes Japanese Research, Affordability and More

A three-day session to kick around business and scientific developments involving genes and stem cells begins today in La Jolla with live Internet video casts of many of the presentations and panels.

The state of Japanese research, therapies for stroke, commercialization pathways, affordability and much, much more are available. Some samples and times for today for the Cell and Gene Meeting on The Mesa:

7:15am – 8:45am -- Learning Theater, Readiness strategies for cell therapy commercial manufacturing workshop

7:20am – 8:00am -- Ballroom 2, Panel, Session 1: U.S.-based Clinical Programs

7:50am – 8:05am -- Magnolia Room, Development of an “off the shelf” cell therapy for ischemic stroke and other indications under the regenerative medicine regulatory framework in Japan
Speaker: Gil Van Bokkelen, Ph.D., Chairman and CEO, Athersys

1:15pm – 2:15pm -- Ballroom 1, Panel, Navigating acceptance, uptake and affordability across the life cycle 

The full agenda can be found here. The webcasts are available here.  Webcasts can be found by room location. 

ACT to Astellas: A 'Looping' Tale of the Stem Cell Industry and Research

Ever wonder what happened to Advanced Cell Technology, Inc. (ACT), the Massachusetts stem cell company that migrated -- with some considerable ballyhoo -- to California in the wake of the creation of the Golden State's $3 billion stem cell agency?

ACT landed in the San Francisco Bay area in 2006 with hopes of snagging millions from the agency, which had been created two years earlier. At one point in the company's life, Gov. Jerry Brown even approvingly toured the company's operation in Alameda. But little has been heard from the company in recent years.

Now comes UC Davis stem cell researcher and blogger Paul Knoepfler. Last week, he published a brief update on the doings of the company once known as ACT and its changing corporate identities.

Michael D. West, AgeX photo

But first a little more on ACT's history and the company's not-so-good times in California. It is a tale  that loops around Geron, Inc., which launched and then abandoned the first U.S. clinical trial involving human embryonic stem cells, and companies called
Asterias and BioTime. One thread that strings them all together is a stem cell pioneer named Michael D. West.

When ACT announced its move to the Bay Area, visions of millions of research dollars danced in the heads of its executives. The move was heralded by the state's governmental leaders, Then State Treasurer Phil Angelides said,

"California voters overwhelmingly approved Proposition 71 (which created the stem cell agency) to ensure that California remains the hub of groundbreaking scientific innovation that has the potential to cure and treat debilitating and life-threatening ailments. Advanced Cell Technology's move to California sends a powerful message that this promise can be realized - bringing high-skilled jobs and revenues to our state, and most importantly, offering hope to millions of patients and their families."

West, then president of ACT, said the company was committed to being a world leader in regenerative medicine.

That was in 2006.  Eight years later, ACT, once the only company in the United States with an ongoing clinical trial involving human embryonic stem cells, changed its name to Ocata Therapeutics.  In 2016 it was purchased by Astellas Pharma of Japan for $379 million. By then, ACT had abandoned its then nominal operations in California after its multiple applications for California state funding failed to win approval (see here and here).

West left ACT in 2007. He is now co-CEO of BioTime, Inc., of Alameda, and is a member of the board of directors of Asterias Therapeutics, Inc., of Fremont, Ca. Both companies are faring much better with the state stem cell agency, formally known as the California Institute for Regenerative Medicine (CIRM).

In 2013, Asterias picked up the human embryonic stem cell trial that Geron gave up on in 2011. West founded Geron in 1990 but left the company in 1998. Asterias has received $14.3 million to support the spinal injury trial that Geron abandoned.

BioTime also had better luck than ACT. It received a $4.7 million award from CIRM for work on human pluripotent stem cells. 

Last week's report from UC Davis scientist Knoepfler said that Astellas began a phase 1B trial in July to continue the macular degeneration work of ACT/Ocata. Knoepfler described the latest effort as a "small bit of encouraging news."

California's $30 Million Bet On a Cancer Treatment: New Company Formed to Bring the Therapy to Market

Highlights

Stanford, Weissman involved

Good news for CIRM

Google hooked in

A new stem cell company that targets cancer by unleashing an “eat me” trigger has emerged from a $30 million investment by the state of California.

Creation of the Palo Alto firm, which is called Forty Seven, Inc., was announced this week by its backers and its key researcher, Irv Weissman, director of Stanford University’s stem cell program.

Venture capitalists, including Google, are supporting the enterprise with $75 million. The effort

has two phase one clinical trials underway, the first step in a years-long process of testing potential therapies before the federal government approves their widespread use.

Forty Seven, named after the molecular target of the “eat-me” trigger, is not the first firm to emerge from research funded by the California Institute for Regenerative Medicine (CIRM), as the state stem cell agency is formally known. At least eight others have surfaced over the years.

But this week’s announcement attracted some national attention in a story by Alex Lash on Xconomy, an online technology information service. Lash wrote,

“This is the kind of news CIRM has yearned for in recent years: significant private cash that gives CIRM-funded projects a push to become actual products and to return value to the state…. After a decade of funding buildings, salaries, and early stem-cell related research—not to mention conflict of interest problems that included a past CIRM president and a different company (StemCells, Inc.) with Weissman’s imprimatur—CIRM and its new president acknowledged it needed to show results for the $6 billion taxpayers committed to the agency in 2004.

“This type of follow-on funding is what we’re looking for,” says CIRM spokesman Don Gibbons, who adds that the big financial awards for Stanford were in line with the agency’s mission “to get things moving early when others won’t invest.”

(See here, here and here for more on the conflicts of interest.)

Voters approved the creation of the $3 billion agency in 2004. But no therapies have emerged for widespread use despite the optimism of its early backers and campaign promises. The agency expects to run out of funds for new awards in 2020. One of the possibilities for new funding is another multi-billion dollar state bond issue. State bonds are the only significant source of cash for the Oakland-based agency.

Xconomy reported that CIRM has yet to provide its final $5.1 million to Weissman. And Lash wrote that “Forty Seven is in the process of taking charge of the grant-funded programs.” Asked this morning by the California Stem Cell Report whether the funds would be going directly to the firm, Kevin McCormack, senior director of communications, replied,

“Our grant goes to the principal investigator on the project, in this case it’s both Irv Weissman and his co-PI Ravi Majeti. Both are at Stanford.”

Weissman’s technique uses a monoclonal antibody that attaches to the CD47 protein on cancer cells them from hiding from the patient’s immune system. Lash wrote,

“But cancer cells also produce what Weissman and colleagues call an ‘eat me’ signal from a protein called calreticulin. Normal, healthy cells don’t. By cutting off the CD47 ‘don’t eat me’ signal, Hu5F9-G4 should in theory allow the calreticulin signal to prevail.”

Stanford, which has a member on the CIRM board of directors, is the No. 1 recipient of funds from CIRM. It has chalked up 98 awards totalling $308 million. Weissman has received five awards totalling $36 million. StemCells, Inc., which was co-founded by Weissman, has been awarded $9 million in for three projects.

The StemExpress Controversy and Collateral Damage

Back in July, after the Planned Parenthood, anti-abortion controversy erupted and entangled a California firm, one Internet headline read,

“Fetus Miner’s Friends in High Places”

The site that posted the headline was the American Conservative. The item referred to Charlotte Ivanic, the older sister of Cate Dyer, CEO of StemExpress LLC of Placerville. It is the stem cell and human tissue firm that was named in the videos involving Planned Parenthood.

In July, Ivanic was the highly regarded top health policy aide to House Speaker John Boehner, who denounced Planned Parenthood and approved House committee investigations into Planned Parenthood and StemExpress.

Dyer once said that her sister is “one of her biggest inspirations.”

Now she is gone from public service. She left on Aug. 5 and has become a Capitol Hill lobbyist. In a press release, Boehner said, 

“Charlotte has spearheaded some of our most significant accomplishments on behalf of the American people. She is one of the best I’ve seen at bringing people together to find common ground, and she leaves Boehnerland with the deepest respect — and best wishes — of her peers as well as lawmakers from both parties.” 

The news about her resignation was slow to ripple out. It was only yesterday that one anti-abortion Web site caught up with the news. Fireandreamitchell.com had this to say, 

“It took three weeks for Charlotte Ivancic to resign from John Boehner’s staff after the videos went public. This yet again shows that John Boehner is just a progressive like liberal Democrats. Why else would he have a leftist like Charlotte Ivancic on his staff in the first place? John Boehner is not only mentally unstable but a progressive hack too. Boehner has to go, NOW!”

StemExpress: Anti-Abortion Activists Telling "Long Series of Lies"

A beleaguered California company caught in the national, anti-abortion controversy involving Planned Parenthood late today said its foes were engaged in a “long series of lies.”

The company, StemExpress LLC of Placerville, made the charge in a statement that included the unedited portions of the latest anti-abortion video along with a transcript of what was said.
(If you would like the video, please email djensen@californiastemcellreport.com. It is a large file.)

The firm said,

“David Daleiden and the Center for Medical Progress today released their latest heavily edited, highly-deceptive video in which they claim StemExpress “admitted” to receiving fully intact fetuses from Planned Parenthood….

“During the video, the parties refer to 'cases,' which is a term of art referring to livers in this conversation. CMP’s accusations that this conversation somehow refers to 'intact fetuses,' which were never mentioned at any point during the entirety of the illegally recorded conversation, are false.

“StemExpress has never requested, received or provided to a researcher an “intact fetus.” CMP’s and Daleiden’s claims to the contrary are unequivocally false.”

The statement and release of the transcript reflected a more aggressive posture on the part of StemExpress, which has lost business as a result of the activists’ efforts. Its employees have also been threatened with violence.

Here is the full text of the StemExpress statement.

“StemExpress today released the following concerning CMP’s 8th video:

“David Daleiden and the Center for Medical Progress today released their latest heavily edited, highly-deceptive video in which they claim StemExpress ‘admitted’ to receiving fully intact fetuses from Planned Parenthood. Accompanying this document is a link to the unedited part of that video where this supposed admission discussion occurred, as well as a transcript of what was actually said.

“As anyone can see and read, the entire discussion was in fact about ‘intact livers.’ Livers are among the most urgently needed of medical tissues by scientists and medical researchers working to cure cancer, diabetes and Alzheimer’s disease.

“During the video, the parties refer to ‘cases,’ which is a term of art referring to livers in this conversation. CMP’s accusations that this conversation somehow refers to ‘intact fetuses,’ which were never mentioned at any point during the entirety of the illegally recorded conversation, are false.

“StemExpress has never requested, received or provided to a researcher an ‘intact fetus.’ CMP’s and Daleiden’s claims to the contrary are unequivocally false.

“Earlier today, a court found that this footage was likely obtained in violation of California criminal law prohibiting the illegal recording of private conversations. In a different court later this afternoon, Daleiden and his CMP co-defendants invoked the 5th Amendment rather than answer questions about their ongoing illegal activities in a related case in federal court. The release of today’s video and CMP’s claims about it are just another in a long series of lies.”

California's StemExpress Loses Bid to Block Anti-Abortion Videos; Appeal Being Considered

A Los Angeles judge today rejected a bid by a California stem cell/human tissue firm to halt the release of an anti-abortion video that the firm said is harming its business and endangering the lives of its employee.

The firm, StemExpress LLC of Placerville, said, however, it is considering appealing the ruling.

Brian Melley of The Associated Press wrote,

“Los Angeles Superior Court Judge Joanne O'Donnell rejected efforts by StemExpress to block the videos, though she said the company likely will prevail in its lawsuit claiming its privacy was violated by an anti-abortion activist posing as a biomedical company employee.”

Melley continued,

“StemExpress won a temporary restraining order last month, but O'Donnell said Friday that the center's First Amendment rights to release the videos trumped the company's right to block them under their privacy claims.

“The judge said she couldn't tell who was telling the truth about how confidential the May meeting was, but she said the fact (David) Daleiden concealed his identity and secretly recorded the conversation made his account less believable.

“O'Donnell rejected the center's argument that the secret recordings were legal under an exemption that allows such subterfuge if someone believes they are gathering evidence of a crime.

"'Defendants' apparent ideological conviction that fetal tissue procurement is a violent felony does not, without more (evidence), rise to the level of a 'reasonable belief,' O'Donnell wrote.”

Text of StemExpress Statement on Cutting Ties to Planned Parenthood

Here is the text of the full statement from StemExpress as provided to the California Stem Cell Report by a spokesman for the firm. 

"StemExpress statement Regarding Termination of Agreements With Planned Parenthood

"StemExpress at its core is a small life sciences company committed to accelerating research, advancing medicine, and saving lives. We partner with organizations also seeking to help researchers find solutions to some of life's most significant medical conditions and diseases. Our commitment to quality defines us and is demanded by our customers in the research community. 

"We value our various partnerships but, due to the increased questions that have arisen over the past few weeks, we feel it prudent to terminate activities with Planned Parenthood. While we value our business relationship with Planned Parenthood, that work represents a small percentage of our overall business activity and we must focus our limited resources on resolving these inquiries.

"StemExpress works tirelessly to accelerate the speed of helping patients globally: 7.6 million people die of cancer each year, another 7.4 million of heart disease, over 4.6 million from lung cancer, AIDS and diabetes and every 12 minutes another name is added to the national transplant waiting list. These numbers drive our work and the research community. StemExpress looks forward to the swift resolution of all inquiries and audits so we can focus our full attention on helping the medical and research community improve and save lives."

Three California Human Tissue Firms Targeted by House Committee

A Republican-dominated Congressional committee today zeroed in on three California human tissue firms entangled in the national flap over abortion and the Planned Parenthood Association.

All three were sent letters today seeking to determine whether the companies were in compliance with laws dealing with the distribution of fetal material.  They were given a deadline of Aug. 21 to provide a briefing to the House Energy and Commerce Committee.

Questions include procedures involving informed consent from donors, fees for fetal tissue, the amount of revenue from fetal tissues in 2014 along with policies and practices for handling fetal tissue.

StemExpress of Placerville, east of Sacramento, and its president Cate Dyer, received one of the letters. The stem cell and tissue firm has been much in the news about the controversy. The flap was triggered by Internet videos with Planned Parenthood officials that were taped surreptitiously by anti-abortion activists using false identities and false company credentials.

Both the federal and California departments of justice are investigating whether the anti-abortion activists violated the law when they made the undercover videos. 

The other two letters went to Linda Tracy, president of Advanced Bioscience Resources, Inc., of Alameda, and Ben Van Handel, executive director of Novogenix Laboratories, LLC, of Los Angeles. (See the letter to Advanced here, the letter to Novogenix here.)

The letters to StemExpress and the Advanced Bioscience referred to a July 27, New York Times article that included them. The House committee letter quoted from the piece.

The article by Denise Grady and Nicolaus St. Fleur said, 

"(F)etal tissue is a uniquely rich source of the stem cells that give rise to tissues and organs, and that studying how they develop can provide clues about how to grow replacements for parts of the body that have failed.

“'Think of fetal tissue as a kind of instruction booklet,' said Sheldon Miller, the scientific director of the intramural research program at the National Eye Institute.

"Stem cells derived from adult tissue may eventually replace fetal ones, researchers say, but the science is not there yet."

All three companies were told by the House committee,

“Under the NIH Revitalization Act of 1993, it is "unlawful for any person to knowingly acquire, receive, or otherwise transfer any human fetal tissue for valuable consideration if the
transfer affects interstate commerce." While this provision prohibits the sale or purchase of fetal
tissue itself, the term "valuable consideration" does not include reasonable payments associated
with the transportation, implantation, processing, preservation, quality control, or storage of
human fetal tissue. As the committee with legislative jurisdiction over the NIH Revitalization
Act of 1993, we have an oversight responsibility and interest in determining whether there is
adequate compliance with the law, and/or whether the law is adequately meeting ethical and
moral concerns." 

A Reuters story said that none of the companies has responded to a request for comment.

Text of Court Documents in the StemExpress-Daleiden Case

Coming up on Aug. 19 in Los Angeles will be the next court hearing on the temporary restraining order obtained by StemExpress against David Daleiden. (See here for a related story.)

Here is the text of the July 2015 request by StemExpress for the order.

  StemExpress Filing for Restraining Order Against David Dalaiden by DavidJensen

Here is the actual text of order that was granted.

   Temporary Restraining Order Obtained by StemExpress Against David Daleiden by DavidJensen

The Hard Business of Stem Cell Economics and Patient Needs

Premature clinical trial shutdown?

Implications for California stem cell agency

The vagaries of Big Pharma and development of stem cell therapies -- plus the frustrations of a prominent Stanford researcher -- were the topic this week in a major California newspaper.

Irv Weissman, Stanford photo

The researcher is Irv Weissman, head of the stem cell program at the Palo Alto university. The companies are Sandoz Pharma, Ciba-Geigy and Novartis. The story also includes a $392 million deal involving Weissman.

The basic storyline, as reported June 14 by Lisa Krieger of the San Jose Mercury News, is that years ago Weissman developed a “unique way to grow and deliver blood stem cells to desperate patients with aggressive cancers, boosting survival rates.”

According to Krieger, Weissman in effect sold the potential stem cell therapy to Sandoz in 1991 for $392 million in an effort to place “his innovation into the hands of a company large and prosperous enough to accelerate research.”

Sandoz then “merged with Ciba-Geigy and became Novartis, which bought the remainder of Weissman's company (Systemix) for $76 million in 1997 -- and, with it, all patents,” according to Krieger.

Novartis shut down the trials in 2000 along with Weissman’s company. Krieger reported that the firm “ended the program because it couldn't produce blood stem cells in large enough numbers to develop a commercial market -- and it was not in the business of producing personalized ‘custom-made’ therapies.”

Krieger continued,

Karuna Jaggar, BCA photo

"'Well before the launch of the War on Cancer, the corporate profit motive has driven the cancer research agenda,' said Karuna Jaggar, executive director of the Breast Cancer Action, a San Francisco-based patient advocacy group. 'Time and again, history has shown that it is not only the possibility of saving lives but the potential of making money that has steered the research agenda toward some areas -- and away from others.

"'As long we have a health care system that puts profits before patients we will always be at the mercy of corporations looking to make profits. Any new innovation needs to be evidence-based and proven safe and effective no matter what money is to or is not to be made,' she said.”

Krieger wrote,

“Now, a quarter-century after it was conceived, the technique is finally back in Weissman's hands at Stanford -- although Novartis still holds the patent.” 

She reported that Weissman hopes to take the potential therapy forward in a non-profit setting.

Krieger has much more in her story, which offers considerable food for thought, particularly in connection with California’s $3 billion effort to bring a stem cell therapy into widespread use. It has not done so yet after nearly 11 years of trying and the expenditure of roughly $1.9 billion.  The agency also suffered a significant blow at the hands of one company, Geron, that dropped -- for financial reasons -- the first-ever clinical trial  for a hESC stem cell therapy, which the agency had backed with a $25 millon loan. 

The agency is currently revising its strategic plan. Randy Mills, president of the agency, says he is serious about developing a solid plan that will be followed assiduously with measurable benchmarks along the way.  

Our view: One important element in the new plan should focus on avoiding situations such as those involving Geron (see here and here) and the morass that Weissman fell into.

Whether one likes it or not, the facts of life in the biomedical world – pleasant or unpleasant – mean that business must be firmly engaged if a stem cell therapy is to be widely available to the public. Government agencies, however, often fall short in their dealings with private firms. For the stem cell agency, that means it needs a keen eye and clear goals when it deals with Big Pharma and stem cell firms. And if the California’s stem cell agency is to deliver on the promises made to the people of California, it must be willing to walk away from a deal if the terms aren’t right.

Researcher Takahashi Honored as Stem Cell Person of the Year

Riken photo

Masayo Takahashi, the scientist in Japan who is leading the first clinical trial involving reprogrammed adult stem cells, today was named the stem cell person of the year.

The announcement was made by Paul Knoepfler, the UC Davis stem cell researcher who sponsors the award and personally funds its $2,000 prize.

Knoepfler said,

“In an astonishing feat, Takahashi's team transplanted its first macular degeneration patient recently on September 12, only 7 years after human IPSCs (induced pluripotent stem cells) were first ever published.”

The development of IPS cells, which also originated in Japan, has been hailed because they remove the moral objections that some persons have concerning the use of human embryonic stem cells. Many scientists, however, continue to consider the human cells as the gold standard.

Takahashi is a physician-scientist and a faculty member and project leader at the Laboratory of Retinal Regeneration at the Center for Developmental Biology at RIKEN.

Last December, Takahashi said she was wary of the high economic expectations surrounding potential stem cell therapies. In an article in the Financial Times by Jonathan Soble, she said, 

“Start-up companies are already involved and the road to commercialization is there, but to assume that the concept of iPSCs and regenerative medicine will yield a lot of money is naïve. Only parts of the field will become industries. It’s dangerous to think that all of regenerative medicine will.”

Takahashi was introduced to the field of stem science in 1995 when she followed her husband to the Salk Institute in the San Diego area in California.

Soble wrote,

“Paradoxically, because she had chosen clinical research, academia’s mix of glass-ceiling sexism and disdain for applied science worked in her favor. ‘I could do what I wanted because I was a woman,’ she says. ‘I didn’t think about career advancement.’”

She said barriers to women in science have largely disappeared in Japan although the comment was made before the STAP scandal that involved Riken. A key figure in the STAP research was a woman scientist, and persons prejudiced against women in science may well to use it to justify their biases.

Takahashi did say last year that traditional cultural values remain a problem in Japan. She said,

“'Japanese women don’t want to stand out, they don’t want to be leaders. They don’t think, ‘I want to have my own lab and reach the top in my field.’ I certainly didn’t until Salk.’ But Dr. Takahashi believes things are changing, in part because of the growing number of role models such as herself. ‘Sometimes,’ she says, ‘I meet young women who tell me, ‘You’re cool.’”

$55 Million California Investment: First Patient Receives Viacyte Diabetes Device

Viacyte's diabetes device
San Diego U-T photo

The California stem cell agency and Viacyte, Inc., today marked a diabetic and stem cell first.

The first of about 40 patients has received the San Diego firm’s human embryonic stem cell device as part of a clinical trial testing what could be a virtual cure for type 1 diabetes.

The stem cell agency, which has invested $55 million in Viacyte, carried the news on its blog, The Stem Cellar. Kevin McCormack, a spokesman for the agency, wrote,

Viacyte graphic

“The beauty of the VC-01 is that while it lets cells secrete insulin out, it prevents the body’s own immune system from getting in and attacking the device. The device is about the length and thickness of a credit card but only half as wide which makes it easy to implant under the skin.”

The $55 million is believed to the be largest amount that the state has invested in a single company.  

Paul Laikind, president of Viacyte, said in a press release, 

“To our knowledge, this is the first time that an embryonic stem cell-derived cell replacement therapy for diabetes has been studied in human subjects, and it represents the culmination of a decade of effort by the ViaCyte team, our collaborators, and our supporters at the California Institute for Regenerative Medicine (the stem cell agency)  and at JDRF (Juvenile Diabetes Research Foundation).”  

The trial is being led by Robert Henry at the UC San Diego Health System with the support of the UC San Diego Sanford Stem Cell Clinical Center.

The initial testing involves the safety of the device. It could take years before it might reach the marketplace. 

Knoepfler and Capricor Score Big This Week

Capricor's stock price has soared since Monday.
Chart from Google Finance

With the new year hardly begun, UC Davis stem cell researcher and blogger Paul Knoepfler has fulfilled one of his 10 predictions for the stem cell world in 2014.

On Dec. 29, Knoepfler predicted a “big announcement from Big Pharma” in 2014. He did not have to wait long to add some shine to his crystal ball.

On Monday, he wrote about the news that Johnson&Johnson was pumping $12.5 million into Capricor Therapeutics' stem cell therapy for heart disease. Capricor could see another $325 million from J&J if all goes well in its stage two clinical trial, which is being supported by $20 million from the California stem cell agency.

“I'd call that big money,” Knoepfler wrote. He also noted in his blog he has no financial interest in either company.

Investors liked the news as well. Capricor's stock closed at $7.05 today, more than double its $3.40 close on Friday, the business day just prior to J&J announcement. 

Inside the Business in California's $70 Million Alpha Stem Cell Clinic Proposal

Want to know more about the business aspects of a $70 million proposal to create a chain of “Alpha” stem cell clinics in California?

More details can be found in a report from the California stem cell agency titled “Alpha Stem Cell Clinics: Delivering a New Kind of Medicine.”

Among other things, the 23-page report discusses how the plan would guide efforts to build profits into stem cell therapies and to develop strategies to attract investors and philanthropists. Not all of the business questions are answered. However, the report does paint a more complete picture of how the clinics would lead to actual production and marketing of a therapy. Overall, the proposal is aimed at creating a sturdy foundation for the stem cell industry in California, one that surpasses anything found elsewhere in the world.

The stem cell agency's governing board is set to move forward on the Alpha clinics at its meeting on Thursday. This week's action involves approval of the concept with an RFA coming in October. Awards to six recipients could be made as early as July of next year.

The business aspects of the proposal are critical because without a clear pathway to profits no stem cell therapies will be available on anything approaching a significant scale. 

CIRM President Alan Trounson first advanced the Alpha concept two years ago. Last fall the $3 billion agency brought together 70 folks from the stem cell world to ponder the idea and to make suggestions. CIRM's report on the discussions at the workshop served as the basis for the proposal to be considered by its governing board this week. Here are excerpts from the report.

“Workshop participants...emphasized the need for engaged experts who can consider and implement strategies for reimbursement (i.e.generating profits) for stem cell therapies, and to gather evidence for their value and effectiveness that will be important for coverage by payers. Having clear pathways in place will help in building financially sustainable clinics as stem cell therapies gain approval and are implemented as standard medical practice. The Alpha Coordinating Center (funded at $15 million) would work with Accountable Care Organizations (funding gouprs that tie performance to payment) and multi-stakeholder collaborations to generate evidence for informing coverage and payment policies.”

“Incentivizing company sponsors of clinical trials to participate in data sharing will be challenging, and it will be important to protect their interests as appropriate, by respecting confidentiality of proprietary information, while at the same time requiring an appropriate degree of data sharing to advance the mission of the Alpha Stem Cell Clinics Network(five clinics funded at $11 million each). It is interesting to note that at this time, the landscape of disclosing clinical trial results is in flux, and there is increasing international pressure for companies to disclose information on safety and efficacy to the research and medical communities.”

“Alpha Stem Cell Clinics will create unique models for assessing the financial viability of stem cell therapies in a clinical setting. Cost and revenue data may serve as the basis for developing reimbursement options among the public and private sector as therapies accumulate. Identification of reimbursement options can reduce investor uncertainties and encourage further investment by pharmaceutical companies, investors, funding agencies and philanthropists.
“The elements of the Alpha Stem Cell Clinics Network, namely the clinical sites and central coordinating center, will interact with external entities to generate revenue streams that would ultimately ensure financial sustainability independent of CIRM funding (Figure 3).”

“The Coordinating and Information Management Center could develop a fee for service model for its consulting services, and operate like a CRO. Sponsors could choose whether to use the consulting services and whether to use the Alpha Stem Cell Clinics Sites. The Alpha Stem Cell Clinics Sites would generate operating revenue by running the clinical trials and could perhaps support the Center with revenues, as the volume of trials grows and the Network builds steam.

“In a second model, clinical trial sponsors would all contract with the Coordinating and Information Management Center, which would then set prices according to services needed. From this revenue, the Center would pay the Alpha Stem Cell Clinics Sites for costs associated with the clinical trials.

“By the time the CIRM seed money is depleted, the clinics should have established a strong track record and brand for excellence in conducting clinical trials in stem cell therapies, which would attract more clinical trial sponsors, including companies. To have the largest possible impact on healthcare, it will be desirable to increase industry involvement for cell therapies. However engaging corporate involvement could be challenging, given that many cell therapies are not considered patentable, and many of the ongoing trials are conducted in academic settings. It was suggested that the Alpha Stem Cell Clinics Network align as much as possible with corporate “mentality” to maximize corporate participation.

“Overall, the Alpha Stem Cell Clinics Network will help companies increase their 'bandwidth' and run stem cell therapy clinical trials more effectively and successfully. Many companies will already have sufficient in-house expertise for administration and regulatory guidance, and may not need to engage the Center’s consulting services. They would be attracted to the Alpha Stem Cell Clinics Network because of advantages for clinical trials such as benefiting from the collective databases, know-how and experience of the 'brain trust,' positive interactions and lines of communication with the FDA and regulatory experts, positive branding, quality control, accreditation for their trials, access to patient registries for outreach and patient recruitment and, through its clinical trial management resources, help with enrollment.

“Workshop participants also emphasized that attaining reimbursement for stem cell therapies will be necessary for delivering approved therapies into medical practice. It is likely that the business models for at least some of the clinics will resemble bone marrow/HSC transplant clinics, where for stem cell therapies that are proven superior to the standard of care, the clinic will directly receive reimbursement from insurers for the procedure and follow-up care.

“Reaching this point will require advance advocacy and preparation, and the engagement with the CMS at an early stage of product development. It was recommended that the Alpha Stem Cell Clinics Coordinating and Information Management Center should employ experts in reimbursement methodologies to facilitate entry of approved products into healthcare delivery. One workshop participant, Jeff Sheehy(a stem cell agency board member), suggested that early engagement with Accountable Care Organizations (ACOs) could be helpful, given that stem cell therapies offer the promise of cures, which in the long run will offer high value and effectiveness, albeit with ' high front end costs and the necessity of developing the appropriate infrastructure for delivering complex cell based procedures.' Consortiums such as the Green Park Collaborative are being established to develop methodological standards to demonstrate the effectiveness and value of new technologies. These data could be used to inform healthcare payers of the overall benefits of cell therapies and their long-term value, as compared with existing therapies."

“In 2016 and beyond, CIRM will initiate the 'Delivery' phase, in which priorities will be 'facilitating commercialization (and non-commercial adoption, where appropriate) of therapies, advancing therapies to patients, and enabling business models for stem cell-based therapies.' Connecting this network to other networks and centers with a similar mission outside of California will further accelerate the development and delivery of stem cell therapies, through the global exchange of information and expertise. International testing of experimental therapies developed in California will be essential for ensuring their sustainability, as regulatory approval and widespread delivery of these products in major markets throughout the world will ensure commercial viability and sustainability of companies and universities that produce them, which will in turn help deliver returns to investors. Ultimately, establishing a solid foundation for investor engagement will ensure the viability of stem cell therapies as they move into clinical practice.'”

Multimillion Dollar Carrots for Stem Cell Research in California

Directors of the California stem cell agency approved an $80 million business-friendly plan that will dangle multimillion dollar carrots before biotech firms in an effort to push therapies into the marketplace.

The upfront payment effort will allow CIRM to take part in early stage clinical trials at no risk and could generate a list of achievements that will be useful in creating support for fresh funding after CIRM's money runs out in 2017.

The proposal is the first-ever from CIRM that involves no upfront payments. Instead, recipients will have to meet agreed-upon criteria to receive either grants or loans.

A CIRM staff document said,

“The major development milestone and success criteria will be mutually agreed upon between CIRM and the applicant at the beginning of the project(s) and at a minimum will require completion of a clinical trial that shows some level of biological activity/clinical efficacy and safety. The advantage to CIRM of this...is that CIRM funds will only be applied to projects that are successful.”

The proposal was wrapped into what the agency calls its strategic partnership plan, which also has a more conventional aspect, providing loans and grants in advance.

As part of the program, the CIRM board also today approved a $6.4 million award to Sangamo BioSciences of Richmond, Ca., to help develop a therapy for beta-thalassemia. The firm will have to match the amount of the award.

StemCells, Inc., Nails Down Controversial, $19 Million Award from California Stem Cell Agency

The stock price of StemCells, Inc., price today jumped as much as 9 percent after the company disclosed it had finally concluded an agreement with the California stem cell agency for a $19.3 million forgivable loan for research twice rejected by the agency's scientific reviewers..

The stem cell agency governing board seven months ago approved the loan to the Newark, Ca., firm. But the cash was withheld until the financially strapped company could demonstrate that it could match the size of the loan, as promised in its application.

The StemCells, Inc., (SCI) application was nixed two times in 2012 by the agency's scientific reviewers who gave it a score of 61. In a controversial move, the 29-member board approved the award in early September on a 7-5 vote after former agency chairman Robert Klein intervened publicly on behalf of the firm. It was the first time that Klein had lobbied the board publicly on behalf of an application. It was also the first time that the board approved an application that was rejected twice by its reviewers, a panel of internationally recognized stem cell scientists.

In a press release, Martin McGlynn, CEO of StemCells, Inc., said,

"With CIRM's support, we are now able to lay the groundwork that could result in the world's first neural stem cell trial in Alzheimer's patients."

Both the company and the $3 billion state research agency were tight-lipped about the nature of the matching funds from the company, which reported losses of $28.5 million in 2012 on revenues of $1.4 million.

In a brief response to questions from the California Stem Cell Report, McGlynn said, 

 “At this time, we do not intend to elaborate any further on the contents of our press releases or public filings pertaining to the SVB (Silicon Valley Bank) or CIRM(the stem cell agency) loans.”

Earlier this week, the company reported receiving a $10 million loan from Silicon Valley Bank. Both McGlynn and the stem cell agency did not answer a question about whether those funds are being used to back the award from California taxpayers.

The agency confirmed that the firm was providing $19.3 million in matching resources. But Kevin McCormack, senior director of public communications, did not provide any specifics on the nature of the match. He only said,

“The matching  requires them to demonstrate they have enough funds necessary to fund SCI’s share going forward as well as their own operations and other commitments.”

The award was originally for $20 million. We have queried the agency about the smaller figure announced today.

The company's stock price rose as high as $1.87 earlier today after closing at $1.71 yesterday. It stood at $1.77 at the time of this writing. Its 52 week high is $2.67, and its 52 week low is $0.59. The loan from Silicon Valley Bank gives the bank warrants to purchase 293,531 shares of the company at $1.70 over the next 10 years.

The 10-year loan from CIRM is low risk for the company, which said its “obligation to repay the loan will be contingent upon the success” of the research. If a product is developed, it will take years before it could hit the market.

The award to StemCells, Inc., put the stem cell agency in a touchy situation involving the company's decision last month to reject an additional $20 million award from the agency.( It was the first time a recipient has rejected an award.) Neither the company nor the agency would give a reason for the rejection of the loan for a spinal injury project . However, the award also required a $20 million match, which undoubtedly tested the company's resources.

The spinal injury application was scored at 79 by agency reviewers and was routinely approved by the board. With its withdrawal by the company, the agency, which prides itself on funding only the best science, was left supporting research (StemCells, Inc.'s Alzheimer's project) judged significantly inferior by reviewers with its score of 61.

In response to a question about that situation, CIRM's McCormack said,

“Our goal is to always fund the best, most promising science. This is not the first time that our board has voted to fund a project that the Grants Review Group had not recommended (this has happened in around 2% of cases) The board did so for a number of reasons, not the least of which is that this was the first disease team application that had a goal of  moving a promising stem cell therapy for Alzheimer's towards clinical trials.”

The round in question, however, had another application dealing with Alzheimer's which was scored at 63, two points higher than the one from StemCells, Inc. Reviewers also did not recommend funding that application.

The action last September by the agency board came only after it publicly said the funds would not be distributed until the StemCells, Inc., could show it could provide the match, still another first for the agency.

The award triggered a column in the Los Angeles Times by Pulitzer Prize winning writer Michael Hiltzik, who said in October that  the process was “redolent of cronyism.” He said a “charmed relationship” existed among StemCells, Inc., its “powerful friends” and the stem cell agency.

StemCells, Inc., was founded by Stanford researcher Irv Weissman, who was a major fundraiser for Proposition 71, which created the stem cell agency in 2004. Klein headed the ballot campaign, which spent more than $30 million to win voter approval. Weissman sits on board of directors of StemCells, Inc., and holds 124,608 shares in the firm, including 8,630 he reported this month receiving.

BioTime Makes Bid for Geron's Stem Cell Assets

Biotime, Inc., and two men who were leading players in history of Geron Corp. today made a surprise, public bid for the stem cell assets of their former firm.

Michael West
West photo

Tom Okarma
AP file photo

The men are Michael West and Thomas Okarma. West founded Geron in 1990 and was its first CEO. West is now CEO of Biotime. Okarma was CEO of Geron from 1999 to 2011. Okarma joined Biotime on Sept. 28 to lead its acquistion efforts. Both Geron, based in Menlo Park, Ca., and Biotime, based in Alameda, Ca., are publicly traded.

West and Okarma sent an open letter this morning to Geron shareholders and issued a press release making a pitch for the Geron's stem cell assets. Geron jettisoned its hESC program nearly a year ago and closed its clinical trial program for spinal injuries. The move shocked the California stem cell agency, which just a few months earlier had signed an agreement to loan the firm $25 million to help fund the clinical trial. The portion of the loan that was distributed was repaid with interest.

At the time, Geron said it would try to sell off the hESC program, but no buyers have surfaced publicly. Personnel in the program have been laid off or found employment elsewhere.

The West-Okarma letter to shareholders said that under the deal,

“Geron would transfer its stem cell assets to BAC(a new subsidiary of Biotime headed by Okarma), in exchange for which you along with the other Geron shareholders would receive shares of BAC common stock representing approximately 21.4% of the outstanding BAC capital stock. BioTime would contribute to BAC the following assets in exchange for the balance of outstanding BAC capital stock:

• “$40 million in BioTime common shares;
• “Warrants to purchase BioTime common shares (“BioTime Warrants”);
• “Rights to certain stem cell assets of BioTime, and shares of two BioTime subsidiaries engaged in the development of therapeutic products from stem cells.”

The letter asked Geron shareholders to write the firm's board of directors to urge them to approve the offer.

Geron had no immediate response to the proposal. Asked for comment, Kevin McCormack, spokesman for the California stem cell agency, said the deal “had nothing to do with us.” However, in the past, CIRM has indicated that it could find a way to transfer the loan to an entity that would continue spinal injury clinical trial. CIRM President Alan Trounson was also involved at one point in trying to assist in a deal.

Geron's shares rose 12 cents to $1.54 today while Biotime's shares lost four cents to $3.95.

Here are links to the two news stories that have appeared so far on the proposed deal: Associated Press, Marketwatch.