Possible Federal Restrictions on Stem Cell Research and the Multi-Billion Dollar California Angle

The recent federal crackdown on the use of fetal tissue in scientific research could well be a harbinger of an effort to revive restrictions on the use of human embryonic stem cells, placing a roadblock in the way of creation of therapies to treat often deadly afflictions that affect millions of Americans.

And it could have an impact on the fate of California's $3 billion stem cell program, which expects to run out of money for new awards by the end of next year.

A leader of the pro-life movement signalled today that anti-abortion groups' next target is likely to be the National Institutes of Health(NIH), which provide billions of dollars in research funding, including use of embryonic stem cells (hESC).

Writing on The Hill web site, Tom McClusky, president of March for Life Action, denounced current federal research practices. His opinion piece was headlined.

"Trump's move on unethical fetal tissue experimentation isn't enough"

McClusky wrote,

"The head of NIH, Frances Collins, has been a long-time supporter of unethical research and has a reputation of disinterest for the countless lives lost as long as it produces results.
"His track record not only includes support for fetal tissue research but also human-embryonic stem cell experimentation, human-animal chimeras and even human cloning. Of the many great nominations made by President Trump, Frances Collins sticks out as a counter to his stated pro-life agenda."

This is a bit of deja vu for the California stem cell agency, whose $3 billion program was approved by voters in 2004. The impetus for creation of the agency, known formally as the California Institute for Regenerative Medicine (CIRM), was generated by then President Bush's restrictions on federal funding for hESC research. State cash, however, was not similarly restricted.

Trump has not yet revived Bush's restrictions, but the issue seems to be increasing in importance for Trump's evangelical political base and at least 102 congressmen. The opposition is based on the belief that using human embryonic stem cells for research is tantamount to murder.

The stem cell agency is hoping that California voters will extend its life in November 2020 by approving $5 billion more for the research. However, the agency has not delivered on 2004 expectations that stem therapies were right around the corner. The agency has yet to finance a therapy that is widely available.

Overcoming voter disenchantment could be difficult. But a Trump crackdown could energize stem cell supporters much as Bush's did in 2004. Scientists, patient advocate groups, venture capitalists and others banded together to win approval of the ballot initiative that created the state stem cell program, using Bush as a handy villain in the argument for more stem cell research.

Ironically, the article by the pro-life group came almost exactly one year after the then president of the International Society for Stem Cell Research,  Hans Clever, wrote on the Stat website that fetal tissue is absolutely necessary to produce cures and therapies. He said,

"The development of vaccines against polio, rubella, measles, chickenpox, adenovirus, rabies, and treatments for debilitating diseases such as rheumatoid arthritis, cystic fibrosis, and hemophilia all involved fetal tissue."

"Fetal tissue has been essential in research used to develop therapies that have saved millions of lives, and it continues to be necessary for the future of medicine."

'Paying for Miracles:' the Vatican and California's Stem Cell Research Program

California's $3 billion stem cell program owes its life to human embryonic stem cells. The state's research effort was created in 2004 to finance scientific inquiries involving such cells, long a matter a major controversy and banned at the time from federal funding by then President Bush.

Last week, Randy Mills, the president of the California agency, took part in a conference at the Vatican, which is adamantly opposed to hESC research as "gravely immoral" because it involves the destruction of embryos.

UC Davis stem cell researcher Paul Knoepfler wrote about the appearance on his Niche blog. He quoted Mills as saying,

“We are committed to accomplishing our mission of accelerating stem cell treatments to patients with unmet medical needs. We are encouraged that the Vatican is taking a leadership role by bringing together an outstanding collection of voices from the stem cell community to try to find common solutions to some very real problems. We are honored to participate.”

The California stem cell agency's position on adult stem cells has evolved over the years. In 2008, the agency fought an effort (see here and here) in the California legislature to make it easier for the agency to support adult stem cell research. The agency opposed the measure with Bob Klein, then chairman of the agency, indicating the move was attempt to sabotage the research program.

In 2010, an academic study showed that through 2009 only 18 percent of California's dollars went for grants that were "clearly" not eligible for federal funding under the Bush restrictions. In 2013, the agency's web site showed that that about 240 of the 595 awards that it had handed out went for hESC research. At the time, such funding amounted to $458 million out of the $1.8 billion it had awarded.

Updates to the 2013 figures could not be found on the agency's web site as of this writing. We are querying the agency for fresh figures.

The Vatican conference last week involved theology as well as science. The topic of Mills' panel, however, was "a look at who is paying for miracles."

Mills also often says he is "agnostic" about the sorts of cells to be used to develop therapies. But "agnostic" is probably not a word that he used last week at the Vatican.

Pay-for-Eggs Legislation Up Again in California: Fertility Industry Trying to Repeal Ban on Compensation for Human Eggs in Research

The industry that deals in human eggs is once again pushing forward with California legislation to allow it to pay women thousands of dollars to harvest their eggs for research purposes.

The measure (AB2531) by Assemblywoman Autumn Burke, D-Inglewood, is now on the Assembly floor after clearing the Assembly Health Committee on a 17-0 vote. (See the March 31 legislative analysis of the measure here.)

The bill is essentially the same as the one vetoed by Gov. Jerry Brown in 2013. It is not clear whether the current author of the measure has been successful in removing Brown’s opposition.

The legislation is sponsored by American Society for Reproductive Medicine, the dominant trade group in the largely unregulated fertility industry.

When she introduced her bill in February, Burke said in a press release,

Autumn Burke on Assembly floor
Sacramento Bee photo

"It's perfectly legal for a woman to get paid when advertising through Craigslist to provide eggs for infertile couples, but she can't get paid for a donation in medical research. It's insulting to women, and it keeps California's research institutions in the dark ages. Instead of leading the way on women's health, we're stuck behind 47 other states all because of a misguided ban that assumes women shouldn't be allowed to make their own decisions."

Burke and the industry organization have an array of groups backing the legislation, ranging from California's district nine of  the American Congress of Obstetricians and Gynecologists to California Cryobank.

The bill is opposed by the Center for Genetics and Society in Berkeley along with groups ranging from the Catholic church to "We Are Egg Donors."

Marcy Darnovsky, NBC photo

Earlier this month, Marcy Darnovsky, executive director of the Center for Genetics and Society, wrote:

"The health risks of egg harvesting are significant, but they’re woefully under-studied. A well-known and fairly common short-term problem is ovarian hyper-stimulation syndrome (OHSS), but no one is sure how many women get the serious – sometimes life-threatening – version of it. Data on long-term outcomes, including follow-up studies on reports of cancers and infertility in egg providers, are notoriously inadequate.

"It is impossible for women to give truly informed consent if adequate health and safety information can’t be provided.

"Offering large sums of money encourages women in need to gamble with their health. It’s what bioethicists call 'undue inducement.'"

California's $3 billion stem cell agency bans compensation for women who provide eggs for research that the agency finances but it does allow reimbursement of expenses. The legislation would repeal a state law banning compensation.

(Editor's note: The original version of this story said that Brown vetoed an egg compensation bill last year instead of 2013.)

CRISPR and Anti-HESC Updates from UC Davis Researcher

UC Davis stem cell scientist and blogger Paul Knoepfler has been busy this week, posting updates on CRISPR and two persons who have been behind the drive against the research use of human emrbryonic stem cells.

First, the information about the embryonic stem cell opponents, James Sherley and Theresa Deisher.

Sherley is running Asymmetrex, Inc., an adult stem cell firm in Boston. Knoepfler reported,

"I haven’t really seen Sherley out there in the public domain as an activist that much ever since the ES cell court ruling."

The negative ruling came in a federal court case challenging federal financing of human embryonic stem cell research.

Knoepfler cited a piece in Mother Jones magazine for his description of continuing activism on the part of Deisher. She was involved in the secretly recorded video tapes of Planned Parenthood officials. Among others, employees of Stem Express of Placerville, Ca., were also taped without their permission, and the California Department of Justice is investigating whether state laws were broken.

On the CRISPR front, Knoepfler has a series of links to good articles on the ongoing discussion involving the genetic modification technique. The debate continues unabated, although not in the mainstream media.

California's $3 billion stem cell agency held a daylong session on the matter some months ago. The agency is scheduled to take another look at it, but no date has been announced yet.

National Controversy Snares California Stem Cell Firm; Congressional Investigation, Presidential Politics Involved

A California stem cell firm is enmeshed today in a national flap linked to abortion, buying and selling body parts and the 2016 presidential race.

The firm is StemExpress of Placerville, just east of Sacramento in the Sierra Nevada foothills. It was mentioned in a YouTube video that was recorded secretly by abortion foes who were posing undercover in a discussion with Planned Parenthood officials.

The video has been viewed nearly two million times as of this writing. The New York Times, the Washington Post and other major news outlets are covering the story.  It has triggered virulent headlines on anti-abortion and conservative web sites.

One headline on inquisitor.com said in red type,

“Buying And Selling Aborted Fetus Body Parts For $30 To $100? ‘Stem Express’ Website Down After Undercover Video Exposes Planned Parenthood” 

StemExpress provides researchers with “high-quality stem cells they need for their research,” an employee of the firm told the California Stem Cell Report in an email last May.  The firm also supplies “human blood, tissue products, primary cells and other clinical specimens to biomedical researchers around the world,”

Reporter Sammy Caiola wrote today in The Sacramento Bee,

“The eight-minute undercover clip, which has garnered over 1 million views (as of yesterday) and inspired the popular anti-abortion Twitter hashtag ‘#PPSellsBabyParts,’ is edited in a way to suggest Planned Parenthood and its affiliates profit from fetal tissue and organs procured during abortions, which is against federal law.”

Caiola said that the video contains “a supposed image of the StemExpress website (that) shows an order form, where users can designate type of order, number of specimens, tissue type and shipping options.”

Caiola continued,

“In a statement released by Planned Parenthood, spokesman Eric Ferrero said that while many women who undergo abortions choose to donate fetal tissue to scientific research, there is no financial benefit for either the patient or Planned Parenthood. Sometimes, Planned Parenthood is reimbursed for the cost of transporting the tissue to labs, he said.

“’We do this just like every other high-quality health care provider does – with full, appropriate consent from patients and under the highest ethical and legal standards,’ Ferrero said.” 

The California Stem Cell Report this morning asked StemExpress for comment and will carry it verbatim when it is received. However, all of the news stories so far say that the company has not responded to similar requests.

(The company responded -- see here for full text -- just as this item was posted and said,

"StemExpress prides itself on complying with all laws. Our compliance protocols and donor consents have been established by an FDA-compliant Independent Review Board. Written donor consent is required for any donation, including bone marrow, tissue of all types or blood."

(The company also said,

"Everything we provide is solely at the request of the nation’s and the world’s great research institutions. Producing the isolated cells researchers need from donated tissues requires the development of complicated, often unique, research techniques using millions of dollars of scientific equipment. We are hopeful the events of the last few days will not diminish our efforts to support the research community or hinder our partners from continuing their important work.")

The company was founded in 2010 by Cate Dyer.  Inc. magazine ranked the firm 363rd on Inc. magazine’s list of the fastest-growing private companies in America last year.

Ariana Eunjung Cha of the Washington Post wrote that GOP presidential hopefuls Ted Cruz, Jeb Bush, Ben Carson and Bobby Jindal all have spoken out on the controversy.

In Congress, Republican leaders have ordered an investigation. Jackie Calmes and Nicholas St. Fleuer of the New York Times said,

"House Republican leaders on Wednesday announced a congressional investigation of Planned Parenthood, a day after anti-abortion activists released a video of an unsuspecting official from the organization explaining how it provides fetal tissue to researchers.
 "Echoing the activists’ allegation, Speaker John A. Boehner and other top Republicans suggested that Planned Parenthood was selling fetal parts, which is illegal if done for profit. But Planned Parenthood said that while it charges for expenses such as processing and transporting, it makes no money from the fetal tissue donated by women who get abortions. The official shown in the video repeatedly says something similar to two activists posing as biotechnology representatives."

ViaCyte's hESC Diabetes Effort Examined, Critiqued in MIT Publication

The ViaCyte device -- photo San Diego U-T

The state of California has invested $55 million in a San Diego firm that last week attracted some East Coast attention for its efforts to develop a “virtual” cure involving Type 1 diabetes.

The firm is Viacyte, which is in a stage one clinical trial involving its therapy. The MIT Technology Review looked at the potential product on Feb. 12.

In a piece headlined “A Pancreas in a Capsule,” writer Brian Alexander said,

“In October, a San Diego man had two pouches of lab-grown pancreas cells, derived from human embryonic stem cells, inserted into his body through incisions in his back. Two other patients have since received the stand-in pancreas, engineered by a small San Diego company called ViaCyte.

“It’s a significant step, partly because the ViaCyte study is only the third in the United States of any treatment based on embryonic stem cells.” 

All three of those trials involve California. A spinal cord injury treatment is being tested by Asterias Biotherapeutics of Menlo Park, Ca. It has received $14.3 million from the California stem cell agency. The other trial is for macular degeneration and is being conducted at UCLA by Steven Schwartz for Ocata Therapeutics of Massachusetts, formerly known as Advanced Cell Technology. The firm applied multiple times for California funding but was rejected.

Viacyte, which has received more funding from the stem cell agency than any other company, began its efforts optimistically years ago. Alexander wrote,  

“'When I first came to ViaCyte 12 years ago, cell replacement through stem cells was so obvious. We all said, ‘Oh, that’s the low-hanging fruit,’” says Kevin D’Amour, the company’s chief scientific officer. 'But it turned out to be a coconut, not an apple.'” 

 (Robert Henry at UC San Diego is conducting the  trial on behalf of ViaCyte.)

  

Alexander continued, 

“Douglas Melton, a biologist at Harvard University who has two children with type 1 diabetes, worries that the ViaCyte system may not work. He thinks deposits of fibrotic, scarlike tissue will glom onto the capsules, starving the cells inside of oxygen and blocking their ability to sense sugar and release insulin. Melton also thinks it might take immature cells up to three months to become fully functional. And many won’t become beta cells, winding up as other types of pancreatic cells instead. 

Doug Melton -- Harvard photo

“Melton says the ‘inefficiency’ of the system means the company ‘would need a device about the size of a DVD player’ to have enough beta cells to effectively treat diabetes. ViaCyte says it thinks 300 million of its cells, or about eight of its capsules, would be enough. (Each capsule holds a volume of cells smaller than one M&M candy.)  Last October, Melton’s group announced it had managed to grow fully mature, functional beta cells in the lab, a scientific first that took more than 10 years of trial-and-error research. Melton thinks implanting mature cells would allow a bioartificial pancreas to start working right away.”

The piece in the MIT Technology Review is a plus for the California stem cell agency, which is seeking to raise its profile.  The agency's president, Randy Mills, is making a push to draw interest from non-California enterprises that might find funding from California attractive even with restrictions that it be used in the Golden State.

A Look at Spinal Cord Injury Treatments from California's Stem Cell Agency

The California stem cell agency today took to the Internet to conduct a nearly hour-long video briefing concerning the state of stem cell treatments for spinal cord injury.

The Google Hangout event featured Jane Lebkowski, president of research and development for Asterias Biotherapeutics of Menlo Park, Ca., which is involved in an early stage clinical trial for a human embryonic stem cell therapy.

The firm is backed by $14.3 million from the stem cell agency. Asterias is carrying forward the Geron spinal cord trial, which that company abandoned for financial reasons. Asterias expects to enroll more patients next year.

She and Kevin Whittlesey, a science officer with the state agency, discussed the multiple stem cell approaches involving spinal injuries that have surfaced since Geron began the first trial with human embryonic stem cells in 2010.

Lebkowski said that first stage of her firm’s trials demonstrated the initial safety of the treatment. She also said it showed some evidence of “preferential restoration” and “prevention of further deterioration.” The patients involved were treated less than a month after their injuries.

Whittlesey gave an overview of other research around the country. He commented on a case in Poland in which one paralyzed man is reportedly now walking with the help of a walker following treatment with cells from his nasal cavity. The cells were extracted by going in through his skull.

Whittlesey said that it is “hard to draw any conclusions from this one patient.” He said the man “enjoyed significant benefit.” However, he said that it is not possible to attribute the benefits entirely to the cell treatment because the experiment was not scientifically controlled.

California’s stem cell agency has put together a healthy portfolio of Webinars, You Tube videos and Google Hangouts involving a wide range of issues. It is all part of its effort to inform the public and spread good news about its $3 billion program.

However, today’s effort demonstrated the difficulty in drawing an audience. Spinal cord injuries affect as many as an estimated 332,000 persons in this country.  Despite promotion online, in the social media and notices in some publications, only 39 persons checked in for today’s Hang Out.

Kevin McCormack, who hosted the event and who is the director of communications for the agency, said that it is pretty much the pattern for these sort of events. The payoff, he said, is the 1,000 or more viewers that are picked up as people go to You Tube to view the video event.   We might add that the information is current, authoritative and useful, although at times a tad technical for non-scientists.

Asterias Stock Price Jumps Nearly 13 Percent Today Following hESC Therapy News

The California stem cell agency and Asterias Biotherapeutics today picked up a modicum of news coverage in connection with an advance on a spinal injury therapy that was once hailed as historic.

The news about the Menlo Park, Ca., firm’s clinical trial received major attention in the San Francisco Chronicle and more modest coverage in the San Francisco Business Times and on the ipscell.com blog.  

The news also helped to push the Asterias stock price up nearly 13 percent since yesterday to close at $3.08 today. The stock closed at $2.43 Tuesday, the day before the company released the clinical trial news, according to Google Finance.

Stephanie Lee’s piece in the Chronicle contained some history about the potential therapy, dating back to when it was developed by Geron and then abandoned. Geron was the first firm to win approval of a clinical trial for a human embryonic stem cell (hESC) treatment.

Lee also had a couple of interesting tidbits, including the fact that the stem cell agency’s $14.3 million award to support the trial will cover half its costs. Lee also reported,

“Geron treated severe injuries in the thoracic region of the spinal cord, which runs along the back. Asterias is targeting injuries that originate in the neck, citing an outside study that suggests injuries in this area are easier to treat.”

Enal Razvi
Select Biosciences photo

Lee additionally quoted Enal Razvi, managing director of Select Biosciences U.S., an international life sciences consulting firm with its U.S. headquarters in Fremont, Ca.,  as saying,

"This is just the start of a trial, not the approval of a drug, which are two very, very different things in this space…(but) this helps things go to the next level." 

The Chronicle story was the No. 1 story late afternoon today in Google news search results using the term "stem cell," ranking ahead of the STAP news out of Japan.

Paul Knoepfler, a UC Davis scientists who writes the ipscell blog, carried a Q&A with Jane Lebkowski, president of research and development at Asterias, who discussed another hESC product. She said,

“A second Asterias product is AST-VAC2, which are human embryonic stem cell derived dendritic cells. These cells are modified to express telomerase, a protein typically expressed in cancer cells. The aim is to use these telomerase expressing dendritic cells to stimulate immune responses against cancer cells. We are now preparing for clinical trials with this product.” 

That effort could well find its way to additional funding from the California stem cell agency if it meets the four-point criteria of the new president, Randy Mills, of the $3 billion research program.

In the San Francisco Business Times piece, Ron Leuty noted that the initial five-patient safety trial showed that “spinal cord injuries in four the patients had shrunk.” Leuty wrote,

“Whether that means Geron’s treatment is working in those patients is an open question. Geron’s study looked only at acute, or new, spinal cord injuries, so some of the results could be connected to normal healing over time.”

California's Stem Cell Trial for Spinal Cord Injury Moves Forward

A California firm, backed by $14.3 million in state cash, today announced that it has received a federal go-ahead to advance its clinical trial involving a human embryonic (hESC) therapy for cervical spinal cord injury.

Asterias Biotherapeutics, Inc., of Menlo Park, said in a press release that it is currently selecting clinical trial sites and expects to enroll patients beginning early next year. The trial is the continuation of an effort that Geron abandoned in 2011 for financial reasons.

Pedro Lichtinger, president and CEO of Asterias, said,

  “We are especially enthusiastic about working with our new partner, (the California Institute for Regenerative Medicine or CIRM), in executing this clinical trial. The FDA clearance provides Asterias with imminent access to the previously announced $14.3 million CIRM grant, which provides non-dilutive funding to support both the clinical trial and other product development activities for AST-OPC1.”

The phase 1/2a trial will involve doses of up to 10 times higher than what was used earlier. Up to 13 patients will be treated within 14 to 30 days after their injury occurred. The hope is that it will be easier to detect the efficacy of the treatment with such dosages.

As for the early stage trial involving five patients, the company said,

“These five patients were administered a low dose of two million AST-OPC1 cells and have been followed to date for 2 to 3 years. No serious adverse events were observed associated with the delivery of the cells, the cells themselves, or the short-course immunosuppression regimen used.  There was no evidence of expanding masses, expanding cysts, infections, cerebrospinal fluid leaks, increased inflammation, neural tissue deterioration or immune responses targeting AST-OPC1 in these patients.  In four of the five subjects, serial MRI scans performed throughout the 2 to 3 year follow-up period indicate that reduced spinal cord cavitation may have occurred and that AST-OPC1 may have had some positive effects in reducing spinal cord tissue deterioration.”

Asterias was awarded the cash by the California stem cell agency in May. (See here and here.)

Randy Mills, president of the stem cell agency, said today,

“This is exactly the type of treatment, focusing on an unmet medical need, that CIRM was created to address.”

Katie Sharify, one of the patients involved in the trial when it was started by Geron, said in the CIRM press release,

“A lot remains unknown about human embryonic stem cells and that's exactly why this research is so important. The scientific community is going to have a much greater understanding of these stem cells from the data that will be collected throughout the study and I'm glad to have been a part of this advancement."

Stem Cell Blowback on the Ice Bucket Challenge

Virulent opposition to research involving human embryonic stem cells is surfacing anew in the wake of the vast attention attracted by the Ice Bucket Challenge.

Sarah Pulliam Bailey wrote on Religion News Service that the objections have “gone viral” on the Internet because the beneficiary of the watery fundraising, the ALS Association, finances research involving human embryonic stem cell (hESC) lines.

For those of you who are not tuned into the icy effort, it involves celebrities and others pouring frigid water over themselves and challenging others to do likewise and donate to the ALS Association.  About $16 million has been raised so far and is still growing. Photos, news stories and blogs all chronicle the challenge on the Web.  A search this morning on the term “ice bucket challenge” turned up 57.2 million hits.

Our readers might ask how this involves the $3 billion California stem cell agency. The answer is that hESC research is the primary reason for the existence of the agency. It was created in 2004 by California voters after former President Bush restricted federal funding for research involving hESC.  Ironically Bush has participated in the challenge(see video above).

Bush’s restrictions, since lifted by President Obama, generated major controversy in the scientific community and raised fears that efforts to develop what seemed to be nearly magical therapies would wither and die. Without that concern, voters would have been unlikely to approve the measure, Proposition 71, and campaign contributors would have been unwilling to open their checkbooks.

The stem cell agency, however, has turned away from hESC research. Less than 250 of its 622 awards have gone to that field, according to the agency. Instead the agency is backing adult stem cell research, once an anathema to the organization, along with experiments involving reprogrammed adult stem cells. Leaders in the stem cell field, however, say human embryonic stem cells remain the scientific gold standard. (No figures were immediately available on the dollar value of the hESC awards.)

Continued funding of hESC research is linked to the agency’s search for alternative sources of cash as its current financing winds down. Efforts to develop a fresh stream from public sources will run up against the controversy involving hESC experiments, one of the reasons for the lack of interest by Big Pharma. The hESC opposition could also have an impact on development of private sources of funding who may not want to become embroiled in the flap, which can lead to picketing and public protests involving entities that support hESC research.

Kevin McCormack, senior director for the stem cell agency’s public communications, wrote about the ice bucket fad last week on the agency’s blog. He said it “shows how a little bit of creativity can create so much more interest in a disease, and the people suffering from it, than any amount of well-meaning, more traditional attempts at education.” And he poured a bucket of water over his head.

Nonetheless, the opponents hold their views with great passion and zeal and have little respect for hESC science. Here is what one person said today in a comment posted on the Religion News Service article. The individual was identified only as “jamadan.”

“My father died of ALS 6 years ago. My father was and my family is ‘pro-life’, meaning we believe abortion to be murder and embryonic research akin to Nazi medical testing on dead camp victims. Nothing can make us ‘accept’ abortion or anything that benefits from it. Not even our own lives. I think you’ll find that true for all Christians, who by definition, must be pro-life.” 

For other commentary involving objections to the Ice Bucket Challenge, see here, here and here.

(A footnote: This item marks the first video appearance of former President Bush and Kevin McCormack on this blog.)

California Stem Cell Agency Approves $14 Million for Landmark hESC Clinical Trial

Above is a CIRM video involving one of the participants in the original Geron trial.

LA JOLLA, Ca.  – The state of California today pumped $14.3 million into an historic clinical trial for a stem cell therapy that was once abandoned because it was deemed too risky financially by the firm that devised the treatment.

The action came when the governing board of the California Institute for Regenerative Medicine (CIRM) approved the award to Asterias Therapeutics of Menlo Park, Ca., a subsidiary of BioTime, Inc., of Alameda, Ca. The firms purchased the spinal cord injury treatment along with the human embryonic stem cell assets of Geron Corp., also of Menlo Park, in 2013.

The scientists who reviewed the Asterias application said the therapy could have a “highly significant impact” on the spinal cord injury, which afflicts more than 200,000 people nationwide. According to a CIRM review summary, the reviewers said a successful result from the trial would be a “high visibility achievement for the entire field of stem cell-based/regenerative medicine.”

The Geron clinical trial was the first ever in the United States for a therapy based on human embryonic stem cells, an area of research roiled by controversy. Some persons believe that deriving such cells is tantamount to killing a human being.

Geron submitted nearly 28,000 pages of material to the FDA in its years-long bid to start the trial, which began in 2010. However, in November 2011, the company stunned the stem cell world by giving up on the trial, citing business reasons.

The action also shocked the stem cell agency, which less than four months earlier had signed an agreement loaning the company $25 million. The agency's governing board gave the go-ahead on the loan during a process that involved major departures from its normal procedures. Geron repaid the loan with interest.

Approval of the funds for Asterias was not unexpected. The California Stem Cell Report carried an item on the matter May 22.

Today, Jonathan Thomas, chairman of the CIRM board, said in a statement,

“This new investment means we have a chance to build on the lessons we learned first time around. If this therapy can achieve even very modest improvements for patients, it could have an enormous impact on the quality of their life, and the lives of their families."

CIRM's scientific grant reviewers, all of whom are from out-of-state, gave the Asteria application a score of 76 out of 100 during their closed-door review of the proposal. Asterias, which currently has 17 employees including some from Geron, said in its application,

“Initial clinical safety testing was conducted in five subjects with neurologically complete thoracic injuries. No safety concerns have been observed after following these five subjects for more than two years. The current project proposes to extend testing to subjects with neurologically complete cervical injuries, the intended population for further clinical development, and the population considered most likely to benefit from the therapy.

“Initial safety testing will be performed in three subjects at a low dose level, with subsequent groups of five subjects at higher doses bracketing the range believed most likely to result in functional improvements. Subjects will be monitored both for evidence of safety issues and for signs of neurological improvement using a variety of neurological, imaging and laboratory assessments.”

Asterias' application continued,

“By completion of the (Phase 1/2a) project, we expect to have accumulated sufficient safety and dosing data to support initiation of an expanded efficacy study of a single selected dose in the intended clinical target population.”

The complete application is not available. CIRM released only selected excerpts on its Web site. See here for the text of the CIRM review summary.

While reviewers praised the bulk of the proposal they also raised concerns. They “questioned the strength of the preclinical efficacy data.” They “expressed concern regarding the manufacturing plan and strategy to support future development, which they viewed as risky.” They also said the budget “may be high.”

BioTime, which is headed by the founder of Geron, Michael West, is a publicly traded firm. Its stock price closed at $2.73 yesterday. Its 52-week price range runs from $2.21 to $4.82.

Here is a link to the CIRM press release on the grant. 

Text of the CIRM Review Summary of the Asterias hESC Clinical Trial Proposal

Here is a copy of the summary of the review of Asterias application 

for funding for its hESC clinical trial involving spinal cord injury. 

Asterias-Geron hESC Trial and Funding Reported in The Scientist

The Scientist magazine today picked up on the item on the California Stem Cell Report that said that Asterias Therapeutics would receive $14.3 million to continue the human embryonic stem cell trial that was abandoned by Geron.

The Scientist article by Jef Akst was headlined, “Geron hESC Trial to Resume? Nearly three years after Geron shuttered its stem cell program, BioTime receives funding to relaunch a Phase 1 trial for spinal cord injury.”

The brief piece largely cited information contained in our May 22 item. Akst also said that Asterias, a subsidiary of Biotime, and the California stem cell agency, which is expected to provide the cash, declined to comment.

Asterias also has reported successful results from the first phase of the trial. 

$37 Million Slated for California Stem Cell Research

Directors of the California stem cell agency this week are expected to hand out $37 million to businesses and scientists for projects involving human embryonic stem cells(hESC), spinal injury and urinary incontinence.

About $20 million will go to enterprises involved in later stage research. A $14.3 million award is expected to go to Asterias Therapeutics of Menlo Park, Ca., which has purchased the stem cell program that originated with Geron Corp. Asterias plans to move forward with the hESC clinical trial that Geron began amid much ballyhoo. However, Geron abandoned the effort in 2011 for financial reasons. (See here and here.)

A $5.6 million award is expected to go a previous but unidentified grant recipient for work involving HIV/AIDS. (Late today, an anonymous reader said in a comment at the end of this item that the award is for Sangamo Biosciences in Richmond, Ca.)

At their meeting Thursday in San Diego, directors of the agency are also expected to approve $16.2 million to help recruit three out-of-state scientists. The academic recruitment program was created to help California lure star scientists to the Golden State. The awards range from $6.4 million to $4.6 million. Two additional applicants were classified as by reviewers as additional possibilities for funding depending on the druthers of the board. The names of the applicants are being withheld by the agency

The recruitment program was originally budgeted some years ago for $44 million. Twenty-three million dollars was added in 2013. Prior to this week, the awards helped to finance the recruitment of seven scientists.

Information about the $900,000 urinary incontinence award can be found here. 

California Stem Cell Agency Expected to Pump $14 Million into Revival of hESC Clinical Trial Dropped by Geron

Geron's abandoned clinical trial for a spinal cord therapy based on human embryonic stem cells appears to be back on again but at a different company and with $14.3 million in help from the California stem cell agency.

An eagle-eyed anonymous reader of the California Stem Cell Report pointed out the upcoming award to Asterias Biotherapeutics/Biotime, which purchased the stem cell operations of Geron Corp. Geron ditched the trial in November 2011 for what it said were financial reasons.

Here is what the reader said in a comment posted on the “Trounson" item that appeared recently on this blog.

“The Strategic Partnership III Award reviews are in: Asterias Biotherapeutics / BioTime will get $14 million to restart spinal cord injury trial with GRNOPC1.”

The reference is to an item on the agenda for the May 29 meeting of the governing board of the $3 billion agency.

The exact title of the application is “A Phase I/IIa Dose Escalation Safety Study of [REDACTED] in Patients with Cervical Sensorimotor Complete Spinal Cord Injury.”

The information provided by the anonymous reader goes beyond what is currently available on the CIRM Web site, and he or she seems to have special knowledge of the nature of the application. That includes the names of the applicants, normally kept secret by CIRM, and the nature of the material involved in the proposal, GRNOPC1.

The staff recommendation is virtually certain to be approved by the CIRM governing board, which rarely rejects such positions.

Another $9.8 million proposal for a spinal cord therapy project was rejected by the staff. The applicants, however, may make an appeal directly to the board on May 29.

CIRM was also involved with the original Geron proposal, which was the first clinical trial for a therapy based on human embryonic stem cells. The stem cell agency loaned the company $25 million only three months before Geron bailed out on the project. It was an unpleasant surprise for the agency and shock to many patients. Geron paid back the loan with interest.

Asterias was headed by Tom Okarma, once the CEO of Geron, and BioTime is headed by Michael West, who founded Geron many years ago.

Our thanks to the anonymous reader for pointing out the information on the award.

(The day following publication of this item, Asterias reported clearing the first safety hurdle on the trial.)

(Okarma left Asterias in April. An earlier version of this item said Okarma was still head of the company.)

hESC Research Totals $458 Million out of $1.8 Billion from California Stem Cell Agency

The California stem cell agency today said that it has awarded $458 million to fund research involving human embryonic stem cells (hESC) out of a total of $1.8 billion it has given away during the past eight years.

The amount is of some interest because the key reason that the agency now exists is the perceived need in 2004 to fund hESC research in the wake of the Bush Administration restrictions on federal funding in that area. The restrictions created a national uproar in the scientific and patient advocate community, which feared that promising therapies would never be developed.

The $35 million ballot campaign to create the agency focused hard on hESC research to the virtual exclusion of any mention of adult stem cell research. Opposing the effort were such forces as the anti-abortion movement and the Catholic church. But this month LifeNews.com carried a mildly approving item that pointed to the agency's turn towards adult stem cell research.

When the Obama administration lifted the Bush restrictions, some questions were raised about the need for the California effort, which is costing state taxpayers $6 billion, including interest. But those concerns received little public attention and quickly died out.

Funding for the agency comes through state bonds. Cash for new awards is scheduled to run out in 2017. The agency is looking at developing a public-private effort for thefuture that would need a $50 to $200 million “public investment” and major private funding.

Amy Adams, CIRM's communications manager, provided the $458 million figure following publication of this item yesterday on the California Stem Cell Report.

'Praise' for California Stem Cell Agency from Unlikely Corner

The California stem cell agency this month received what some might consider a gesture of approval from a longtime foe – LifeNews.com.

LifeNews is a site devoted to anti-abortion efforts and information and is sharply opposed to research involving human embryonic stem cells.

So it was with some surprise that we read a tacit endorsement of recent CIRM activities in an April 22 piece written by Gene Tame out of Sacramento. It said the most recent $32 million grant round from CIRM “demonstrates – again – where the future of stem cell reserch lies.”

Tame wrote,

“CIRM has been steadily moving away from its original mission to give preferential treatment to funding for human embryonic stem cell research (hESCR). Instead, after adopting a renewed emphasis on translating research into clinical trials, CIRM has more and more shifted the bulk of its grants towards funding research utilizing adult stem cells and other alternatives to hESCR, such as induced pluripotent stem cells (iPSCs).”

Tame continued,

“(T)he lack, once again, of funding for hESCR only serves to highlight how old and dated that approach to finding treatments and cures increasingly seems.”

Tame is correct in his assertion that the stem cell agency has moved a considerable distance from its reason for being – research involving human embryonic stem cells. In 2004, the ballot campaign to create the agency pitched voters hard on hESC research and made no real mention of adult stem cells. Instead, it focused on the threat from the Bush Administration with its restrictions on hESC research, which have been lifted by the Obama Administration. .

In 2010, a study by a Georgia Tech academic, Aaron Levine, reported that through 2009 only 18 percent of California's dollars went for grants that were "clearly" not eligible for federal funding under the Bush restrictions. 

At the date of the study, CIRM had not publicly disclosed statistics on its funding of hESC research.

Today, however, its web site shows that only about 240 of the 595 awards that it has handed out are going for hESC research. CIRM has not made public the dollar value of those 240 awards, but it has given away a total of $1.8 billion. (Following publication of this item, the agency told the California Stem Report that it has funded $458 million in hESC research.) 

A footnote: Levine was a member of the blue-ribbon Institute of Medicine panel that recommended sweeping changes at CIRM.  

BioTime Will Have to Compete for California Cash for Geron's Dormant Clinical Trial

The California stem cell agency said today it does not plan to reactivate the $25 million loan to assist in Geron's spinal injury clinical trial despite an impending deal that would turn the effort over to BioTime, Inc.

Kevin McCormack, senior director for public communications for the agency, said BioTime will have to compete in an upcoming award round if it wants to win California dollars.

Responding to a question from the California Stem Cell Report, McCormack said,

“That (earlier) loan was specific to Geron and when the trial was ended the loan ended too. Of course if Biotime and Geron do complete their deal then Biotime would be free to apply to us for a new disease team grant.”

McCormack later added that BioTime could also compete in other appropriate rounds, including the strategic partnership round just posted by CIRM. It provides for four awards of up to $15 million. Funding could come as early as October of next year. The strategic partnership round is a business-friendly effort that is aimed at attracting “industry engagement and investment.” The deadline for letters of intent is Dec. 18.

The stem cell agency made its $25 million loan to Geron in 2011 just a few months before the Menlo Park firm abandoned its human embryonic stem cell trial for financial reasons. (The full text of the loan agreement can be found here.) The company has repaid the loan with interest.

The company has tried to sell the assets associated with the clinical trial since last November. The only public interest that has surfaced has come from BioTime, Inc., of Alameda, Ca. Michael West, founder of Geron, is the CEO of BioTime. Tom Okarma, CEO of Geron from 1999 to 2011, is CEO of the BioTime subsidiary that would assume the clinical trial.

News from clinical trial is expected to be published soon, according to a story in the San Francisco Business Times by Ron Leuty. He quoted CIRM President Alan Trounson as saying that “some findings” from the trial would be published next month in a medical journal.

Geron's stock traded at $1.24 at the time of this writing today, up from $1.21 yesterday. BioTime's stock stood at $2.99, up from $2.97.

Biotime-Geron Deal Attracts Interest from Brit Investor

A British investment trust that has invested in Geron says it is going to take an advantage of an offer by an Alameda firm that is seeking to acquire Geron's human embryonic stem cell assets.

Jonathan C. Woolf, managing director of British & American Investment Trust PLC, said last week in a letter to its shareholders that it is disappointed in Geron's performance and the abandonment of its hESC program last November. The sudden halt to the program and its historic clinical trial also surprised the California stem cell agency, which had loaned Geron $25 million just a few months earlier. The agency has expressed an interest in continuing the trial.

Woolf said,

“We have been highly critical of Geron management's decisions and strategy over the past 20 months, in particular the decision in November 2011 to abruptly exit Geron's regenerative medicine (stem cell) business in which it was the acknowledged world leader. Since that time, Geron management has attempted to sell or partner this business but to date has been unable to announce any progress on this.”

Woolf's trust is not listed as a major Geron shareholder by Morningstar, but Woolf said 17 percent of his firm's investments are in the Menlo Park, Ca., company. The specific size of the trust's holdings in Geron was not immediately known.

Woolf pointed to the offer by Biotime, Inc., of Alameda, Ca., as a way for Geron shareholders to benefit. On Oct. 18, Biotime proposed a complicated deal in which it would acquire Geron's hESC program. Biotime's president, Michael West, founded Geron in 1990. The head of the Biotime subsidiary that would acquire the Geron assets is Tom Okarma, who was CEO of Geron from 1999 to 2011. (Here are links to brief stories on the offer: Fiercebiotech, New Scientist.)

In his letter, Woolf noted Geron's declining stock performance. He said he is “seriously concerned” that Geron has failed to find a buyer for the assets. Woolf said,

“These now dormant and untended assets are inevitably losing value as competitors make progress in Geron's absence from the field and patent protection periods decline.”

Woolf continued,

“We believe BioTime's proposals would make Geron's stem cell assets in combination with those of BioTime once again the world's leading stem cell business with sufficient resources to recommence the discontinued programmes and develop the business further into the medium term.”

Woolf urged Geron directors and other Geron shareholders to work with Biotime to complete the deal. Geron has not commented on the offer.

ACT and CIRM: Fresh Life in a Troubled California Stem Cell Courtship?

Advanced Cell Technology, which has unsuccessfully sought funding several times from the $3 billion California stem cell agency, drew some attention today in a piece in a Massachusetts newspaper.

The Worcester Telegram took a look at the firm, headquartered in Santa Monica, Ca., with labs in Marlboro, Mass., in the wake of Geron's departure from hESC research. The move left ACT as the only firm in the country with an hESC trial and perhaps with a better shot at CIRM funding.

Reporter Lisa Eckelbecker wrote,

"Advanced Cell, publicly traded since 2005, has spent years developing its technologies. The company brings in little revenue and has an accumulated deficit of $180.9 million. About 1.6 billion shares of Advanced Cell common stock is outstanding, a result of numerous financings over the years. It trades for about 10 cents a share on the Over-the-Counter Bulletin Board, an electronic exchange for small companies. No analysts from major Wall Street banks report on the company.

"The company's treatment for Stargardt's macular dystrophy and dry age-related macular degeneration — the treatment that required (a) mountain of paperwork before the FDA — first went into the eyes of patients in July in Los Angeles. The retinal pigment epithelial cells, generated from embryonic stem cells, were developed to slow the progression of the eye disorders, which can lead to blindness."

ACT moved its headquarters to California following the passage of Prop. 71 in 2004, the ballot initiative that created the California stem cell agency. The company said at the time it expected to "gain significant momentum by being able to take advantage of a favorable environment for funding."

ACT initially landed in Alameda, Ca., but has since moved to Southern California. Its official opening in 2006 in Alameda was attended by the state treasurer and at least one CIRM official, according to the company. The firm has never secured funding from the stem cell agency, which does not release the names of rejected applicants. However, the California Stem Cell Report carried an item in 2008 that pointed out that a researcher for ACT complained publicly about a reviewer's conflict of interest in connection with an ACT application(see here and here). At the time, Robert Klein, then CIRM chairman, brushed off the complaint. The journal Nature has also reported that ACT has applied unsuccessfully several times for CIRM awards.

It is a fair bet that ACT was an initial applicant in the round that provided funding to Geron last spring. However, by the time Geron's application went to the full CIRM board, the other applicants had withdrawn – the first time such an event had occurred at CIRM.

Since Geron pulled out of the hESC business last month, it is likely that ACT and CIRM have opened fresh discussions, given their mutual interest in producing a stem cell therapy. CIRM also has a new chairman who is familiar with ACT. After Geron was awarded its $25 million loan from CIRM last May, the agency's board elected as chairman a Los Angeles bond financier, Jonathan Thomas, who led an early round of financing for ACT in 2000. Thomas last summer sold his remaining 17,046 shares in ACT for $3,239. Thomas said he had a "significant loss" on the sale but did not disclose the amount.

Geron's flight from hESC and ACT's perserverance come as the stem cell agency is pushing aggressively to drive research into the clinic. Plus CIRM needs tangible results that voters can understand if CIRM is win ballot-box approval for continued funding in the next few years. The agency will run out of cash in about 2017 and is considering mounting a campaign for another multibillion bond issue.