The ViaCyte Diabetes Trial: Clarifying a Patient Matter

The ViaCyte clinical trial is aimed at producing a “virtual” cure for Type 1 diabetes among children, but the first implantation of the device involved an adult man.

That information was reported by the MIT Technology Review and raised a question about whether the article was in error or whether something else was involved.

The California Stem Cell Report queried Paul Laikind, CEO of ViaCyte, which is based in San Diego, about the matter.

Laikind replied,

“This first clinical trial of VC-01, called STEP ONE*, requires patients to be 18 to 55 years old (see https://clinicaltrials.gov/ct2/show/NCT02239354?term=viacyte&rank=1).  Once we have gained experience with VC-01 and assuming that it is shown to be safe and effective in the adult population we would expect a follow up protocol to include children with T1D.”  

The Sagan Effect and Public Support for Research

The media chief at the $3 billion California stem cell agency yesterday put together a first-rate piece that invoked Meryl Streep, Carl Sagan and Lindsay Lohan and said that scientists can learn something from them.  

The item by Kevin McCormack, senior director of communications for the stem cell agency, dealt with telling the story of the facts and the romance of science. Not to be too crass about it, but his item piece also dealt with generating the public enthusiasm that will lead to more cash for researchers’ labs. Maybe even do some public good.

McCormack, who has labored both in public relations and in the grimy trenches of journalism, wrote about the American Association for the Advancement of Science conference last week in San Jose on science communications. The session explored ways to get the public to both understand and care more about science and technology and to get scientists to do a better job of explaining both to them.

A number of problems have plagued science communications for decades. One is that science is sometimes difficult for the general public and reporters to understand. It is also difficult to find researchers who can “speak English” – explain what they are doing and why it is important in ways that resonate with the media and their readers and viewers.

Another problem is that sometimes scientists who are good at explaining are dismissed by their colleagues as less than professional or as not really good scientists.

One rendering of invidia at work

McCormack said there is a risk. He wrote,

“Some scientists reported facing a backlash from colleagues who felt they were trying to hog the limelight. They fell victim to what is called the ‘Carl Sagan’ effect, which holds that if someone is spending that much time and effort communicating science to the public they must not be a very good scientist to start with.” 

From what I have seen over the last decade of watching the stem cell agency, such a reaction also often seems a case of invidia at work. Seeing another researcher’s name in print can trigger a serious case of irritation.

McCormack quoted Stanford’s Noah Diffenbaugh on reasons for taking his science to the public.

“I feel it is my responsibility to answer questions from the public when asked, because my research group is publicly funded by taxpayer dollars through agencies like the NSF. And as a public citizen I feel responsible that if we are having a public dialogue about climate change that I should be part of that dialogue.” 

McCormack’s piece on the stem cell agency’s blog, The Stem Cellar, is a good reminder that the science community cannot take for granted public support for science and research funding. Most people are heavily focused on other matters that they believe are more relevant to their lives, such as their jobs and getting their children off to school.

It is up to researchers to make building support and educating the public and the media about the benefits of their efforts a regular part of their profession. Perhaps the stem cell agency could even encourage it by adding a communications component to their awards.

As for Meryl Streep and Lindsay Lohan, it is best to go directly to McCormack’s piece to see how their communication works. It could be inspirational.

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.

Stem Cell Ethics: An Overview from UC Davis Event

Alison Sorkin -- Knoepfler photo

California scientist Paul Knoepfler yesterday posted a synopsis of the recent stem cell ethics session at UC Davis that touched on topics ranging from Right to Try laws to hype about hype in stem cell research. 

Writing on his blog, Knoepfler estimated the attendance at 70 to 80 persons including patient advocates as well as scientists, attorneys and institutional compliance officers.

One presenter was Alison Sorkin, deputy general counsel for University of Colorado Health, who dealt with her state’s Right to Try law. Knoepfler wrote that she said that the law is actually quite limited. Knoepfler wrote,

“She also discussed problematic issues with the specifics of the law such as that patients would be responsible for paying for all of their own healthcare for 6 months after treatment under Right To Try as insurers would be exempt from having to provide ANY coverage. There seems to be a growing sense that Right To Try in Colorado may not actually lead to any patients getting non-FDA approved drugs.” 

Tim Caulfield, a professor, Faculty of Law and School of Public Health at the University of Alberta, dealt with hype. Knoepfler wrote,

“Tim focused on hype in the stem cell field and in particular hype involving scientific publications. He even talked about hype about hype. In the current environment there are strong pressures for scientists to hype their work, including in particular in abstracts. What is the relationship between hype in science articles and in the media?” 

The session was the second annual such event for UC Davis, which will presumably stage another next year.

Stem Cell Researchers Face Tighter Scrutiny in Quest for California Millions

Attention stem cell scientists: Want to know who is going to be scrutinizing your budget in your next application for financing from the $3 billion California stem cell agency?

The California Institute for Regenerative Medicine (CIRM), the formal name for the agency, is hiring outside firms to examine the budgets currently being submitted in a $50 million clinical stage award round.  

The two firms that are  being considered have a host of other clients, some of whom might be competitors with California scientists applying for state funding.  CIRM plans to require the experts to self-report any conflicts of interest, basically excusing themselves if such a situation occurs during their work.

It is all part of CIRM 2.0, a radical and ambitious plan to speed funds to researchers and improve quality of applications.  The budget review is a new and critical step for researchers. If their financial plans, including a new financing contingency requirement, do not pass muster, the applications will not even be sent to the agency’s blue-ribbon reviewers.

Here is what the agency says about the budget review,

“An external team of budget professionals will review the proposed budget to provide information to CIRM regarding how the proposed costs compare with established market rates for similar activities (or how well the costs are justified when market rates are not established).

 “When a proposed budget differs significantly from market rates, adjustments to the budget will be required by CIRM prior to further review of the application. Applicants will be notified of the specific discrepancies and applications will not be forwarded for scientific review until an amended budget has been submitted and approved by CIRM.” 

Last month the agency posted a 37-page request for proposals on its Web site. It contained details of how the work is to be performed, budget templates and much more material that offers insights into the agency’s new, CIRM 2.0 thinking. 

The firms that responded to the RFP are Amarex Clinical Research of Germantown, Md., and Integrium Clinical Research of Tustin, Ca.

Integrium said in its proposal,

“Integrium does not have experience in providing the type of service required in the RFP. However, we have many years of experience in which we have internally reviewed budgets that we prepared for our clients.”

 It appears to have offered to review each application’s budget for $2,740 each.­­­­­­­­­

Amarex said,

“Amarex has experience in conducting budget negotiations for services across all types of clinical sites, and knows what appropriate market rates are.  Our clients are both privately funded, and government funded, so we are also aware of the difference in budgeting requirements for both types of clients.”

The Amarex proposal appears to have a cost of $703 for each budget, with expenses such as travel billed to CIRM plus a 10 percent fee.

The agency’s RFP said,

“CIRM anticipates selecting multiple budget review firms pursuant to this RFP and will alternate work among them based on relative expertise in specific areas, timelines, and the avoidance of potential conflicts of interest.”

Both of the firms are well-established organizations and have a considerable history of work with a variety of clinical trials. Their clients are not identified but could be competitors with the organizations that apply for California funding.

The RFP does not speak directly to those sorts of conflicts although it is more specific about financial ties with CIRM employees.  Regarding the budget review consultants, the proposed CIRM contract said,

“The (budget review) firm must be free from actual conflicts of interest not only at the time of selection, but also throughout the term of the contract.”

The agency has a substantial number of outside contractors. On at least one occasion, a conflict has arisen in public. The case was first reported by the California Stem Cell Report in 2012 and involved a “special advisor” to CIRM who was elected to the board of directors of Sangamo, Inc. At the time, Sangamo was the recipient of $5.4 million from the agency as a co-participant on an award. In 2013, the Richmond, Ca., firm received another $6.4 million directly from CIRM. (See here and here for details.)  In January 2014, the firm’s president told CIRM,

“We wouldn't be where we are today without you.” 

The RFP requires that the firms sign a contract that states, 

“The consultant affirms that to the best of his/her knowledge there exists no actual or potential conflict between the consultant's family, business or financial interest and the services provided under this Agreement, and in the event of change in either private interests or service under this Agreement, any question regarding possible conflict of interest which may arise as a result of such change will be raised with CIRM.”

The RFP also states that the firms may be required to “execute” a form 700, a state document that is aimed at disclosing financial conflicts of interest. However, the form is most commonly filed by individuals -- not commercial interests -- and has major limitations in providing full disclosure.

The RFP does not make it clear whether the form 700s would be publicly disclosed or simply held privately by CIRM. However, the agency has never disclosed any reports involving conflicts of interests of its consultants.

Here are the proposals, which are public records, from the two companies.

   Amarex CIRM Budget Prep Proposal January 2015

  

   Integrium Budget Review Proposal for CIRM January 2015

Update on the Search for New Execs at the California Stem Cell Agency

California’s $3 billion stem agency no longer lists on the Internet job openings for a director of medical affairs and director of administration but reports that the positions remain vacant.

The new, top level posts were created in a reorganization of the enterprise, which has less than 60 employees, by its president Randy Mills, who took over last May. He made the move as part of his CIRM 2.0 effort.

In the initial postings last month, the agency said the positions would remain open until they were filled. Three other openings for directors in the areas of blood and cancer, neuro/ocular and organ systems continue to remain up on the CIRM Web site.

No explanation was offered for removal of the medical affairs and administration openings. Kevin McCormack, a spokesman for the agency, said the positions have not been filled.

Here are job posting documents as they originally appeared.

   Director of Administration, California Stem Cell Agency

   Director Medical Affairs, California Stem Cell Agency

Crossing the One-Million Mark: A Decade's Worth of Stem Cell Readership

Google message on page views from last Friday.

The California Stem Cell Report last week chalked up its one millionth page view, a large and fancy readership score that came after more than 10 years of writing about the Golden State’s $3 billion stem cell research program.

Google reported the seven-digit figure at 10:50 a.m. PST on Friday.  No bells rang, however, and no whistles sounded. The tumbler on “dashboard” of the blog just simply and silently clicked over from 999,999.

For those not familiar with Internet terms, a page view is recorded by Google each time a person opens his or her Internet browser on a particular page. It is an industry standard that it is used to help define readership, something akin to circulation numbers for newspaper.

The one-million figure is both large and small. It is tiny in comparison to most general news sites, which may gather millions of page views in a week. It is large in comparison to the potential audience. This writer estimates that no more than 3,000 or 4,000 persons worldwide are deeply interested in stem cells. Considerably fewer are deeply interested in the affairs of the California stem cell agency.

There is also the “so what” question that comes up when evaluating readership. Have any of the more than 4,000 items published since January 2005 had a significant impact? That is always hard to judge, but bumps in readership tend to indicate that certain themes are resonating.  The scope of the audience also indicates that many individuals find frequent value in what is carried here. 

Regular readers of the California Stem Cell Report range from the general public to the folks at the National Institutes of Health. Readers check in from Harvard, UC San Francisco, Stanford, UCLA, UC San Diego, France, Germany, Russia, the United Kingdom and many other locations. Occasionally, a member of the stem cell agency governing board will comment favorably and privately about the value of the blog. Journalists read it, using it as a springboard for their own stories.

The article with the highest views by far deals with the potential cost of stem cell therapies and discussed a report from Japan that contained the figure $512,000.  Earlier today, the item recorded 10,303 page views since it was published less than two years ago. Also today, the article ranked No. 6 out of 2.5 million results in a Google search using the term “stem cell therapy cost.” The piece seems to have attracted a great deal of interest from the public with many onetime hits, probably coming from people who are considering such a treatment.

The second most read item on the California Stem Cell Report is a 2009 item headlined, “Controller Calls for Online Posting of Financial Holdings of CIRM Officials.” It had 2,748 page views. Third is a “pay-for-eggs” item from 2013 that hit 2,487.  That piece involved a commentary in Forbes, which undoubtedly generated abnormally high traffic for the subject.

Our continuing intent has been to delve deeply into a single subject, the California stem cell agency. It is an important experiment in stem cell research funding. Its work has already had a major impact on the field in California. The agency’s success or failure could have major implications for the field and is worthy of considerable attention.

The California Stem Cell Report brings an independent focus to information about the agency. The Report is the only news site devoted exclusively to coverage of the agency and related matters, including analysis and commentary.  The blog provides on-the-scene coverage of the agency's most important public events, either via the Internet or from the sites of the sessions. The blog also explores in more depth California stem cell issues ignored by both the scientific press and the mainstream media. It provides information that can be nowhere else. 

The Internet is well-designed for such a relatively narrowly focused effort as opposed to the mainstream media, which must pursue mass audiences.  Blogs are especially useful in dealing with narrow subjects because of their relatively low production costs, timeliness and lack of space limitations. Newspapers and other mass media, on the other hand, have high costs and extraordinary space limitations as to do all print products. Timeliness can also be issue with some Web sites associated with print.

As for our costs, this blog is produced by one person, David Jensen (yours truly). He is a retired journalist who finances it personally and who has no financial ties to biotech academia or industry,
or the agency. Google does place ads on the site, which generate about $150 every six months or so based on the number of people who click on an ad.

But beginning today this blog is boosting its efforts to cover the costs of the California Stem Cell Report and adding a way to contribute directly to the effort. On this page, you can find a PayPal “donate” button in upper left hand corner. Donate today. It is a way to help keep independent, California stem cell news flowing vigorously. As the California stem cell agency noted last week, “Money matters.”

And thanks to all who are moved to contribute.

A California Stem Cell Plus: Cash Counts on Research Publications

“Money matters,” says the $3 billion California stem cell agency. And it is right.

The agency was commenting yesterday on a study published this week that indicated that the Golden State has “over-performed”in terms of publication of research findings as the result of the agency’s efforts.

The comment appeared on The Stem Cellar, the agency’s blog. Kevin McCormack, senior director of communications, wrote,

“The question the researchers posed was; have the states that fund stem cell research seen an increase in their share of scientific publications in the field? The answer, at least in California’s case, is absolutely yes.” 

The study by Aaron Levine of Georgia Tech said its findings “suggested” that the increase was due to 667 awards totaling $1.9 billion made by the stem cell agency over the last 10 years.

As Levine’s article noted, many other factors need to be examined to determine whether the agency has met the goals of the 2004 ballot campaign that created the stem cell research effort. But for now, the piece by Levine is a significant plus for the California Institute for Regenerative (CIRM), as the agency is formally known. And it comes from an independent source, one that is not financed by the agency, as some other studies have been.

The California Stem Cell Agency and "Over-Performance' -- Study Cites Hefty Publication Record

The trajectory of CIRM-funded research publications in two areas: The blue
line involves U.S. hESC research articles, green represents iPSC. The black
 and grey lines involve non-CIRM funded research from California in cancer
and RNAi. The vertical bars indicate the general date when each of the four
 states studied began their state-funded efforts. Levine chart.

A study by a Georgia Tech researcher today indicated that California state funding has “played an important role” in creating “over-performance” in the Golden State’s stem cell research efforts.

The article in Cell Stem Cell by Aaron Levine, an associate professor of at Georgia Tech’s School of Public Policy,  was titled "Assessing State Stem Cell Programs in the United States: How Has State Funding Affected Publication Trends?"

It dealt with publication of human embryonic (hESC) and induced pluripotent stem cell (iPSC) research from 2006 to 2013 from four states with stem cell programs. He and his students counted the frequency of articles that cited some funding from each of the state agencies involved.  

Levine wrote,

“In both California and Connecticut, state funding programs appear to have contributed to over-performance in the field.”

 He also said,

“Between 2010 and 2013, approximately 55 % of hESC-related articles published with at least one California author acknowledged state funding, suggesting that this funding program played an important role as California maintained and built upon its early leadership in the field.” 

Levine noted that other measures are important in assessing the impact of the state efforts, including New York and Maryland. In an email, he said,

“There are many possible measures of impact. These could include measures of research output (i.e. publications or patents), research quality (i.e. citations to publications or patents or measures of journal quality), scientist training, scientist recruitment, commercialization of research, etc.  The hope for this article is to provide one data point in an ongoing effort to better understand the impact of CIRM and other state stem cell funding programs.  It's always hard to know how a research program will unfold, but I certainly hope to conduct additional analyses of state funding efforts and contribute to our understanding of the impact these programs have had on the field.” 

Levine examined hESC articles because that area of research was critical to California voter approval of Proposition 71 in 2004. The ballot measure created the $3 billion California Institute for Regenerative Medicine (CIRM), the formal name of the stem cell agency. The initiative was mounted in response to the Bush Administration’s restrictions on hESC research.

The agency says that about 240 of its 667 awards involve human embryonic stem cells. A little more than 100 involve iPSC. CIRM has awarded $1.9 billion so far and is expected to run out of money in 2020 at the current pace.

Aaron Levine
Georgia Tech photo

Levine, who served on the Institute of Medicine panel that evaluated the California agency, also published a piece in 2010 that said through 2009 only 18 percent of California's dollars went for grants that were "clearly" not eligible for federal funding.

Here are some excerpts from Levine’s article today.

“After the California Institute for Regenerative Medicine (CIRM) issued its first grants in April 2006, the share of articles acknowledging California funding increased rapidly from approximately 3% in 2006 to 2007 to more than 20% in 2010 to 2011 and 2012 to 2013. 

“Overall, California state funding was acknowledged in nearly 19% of all hESC-related articles in our data set published between 2006 and 2013, compared with 1.8% of articles in a comparable set of RNAi-related research (t test, p < 0.01). 45% of the hESC-related articles published between 2006 and 2013 in our data set with at least one author from California acknowledged funding from the state.”
 “Our comparative analysis provides some of the first evidence that the distribution of stem-cell-related publications in the United States differs from the distribution of publications in fields not targeted by specific state funding policies, and our analysis of the funding sources acknowledged in many of these articles strongly suggests that state funding is responsible, in part, for these differences.

"The share of hESC-and iPSC-related publications produced in each of the four states examined depends on a variety of considerations, including the size, strengths, and interests of the scientific community and the specifics of the policy itself (i.e., its timing, its size, and its focus). In addition, it depends on the competitive environment within the United States, as over-performance in one state must be balanced by under-performance in others. In both California and Connecticut, state funding programs appear to have contributed to over-performance in the field. In California’s case, the state was already a strong performer in hESC related research before its state funding policy was adopted in 2004, and funding began flowing in 2006. This may reflect a generally supportive state environment or a first-mover advantage, as Geron Corporation, a key funder of early hESC research, is based in the state.

“Following passage of Proposition 71 in November 2004 and the creation of CIRM in the ensuing years, the state’s share of hESC-related research grew from approximately 25% in 2002 to 2003 to more than 40%, and the state maintained this position of strength in both hESC-and iPSC-related research from 2008 through the end of our data in 2013. Between 2010 and 2013, approximately 55% of hESC related articles published with at least one California author acknowledged state funding, suggesting that this funding program played an important role as California maintained and built upon its early leadership in the field." 

“In addition, publications are only one measure of the impact of state science funding programs, and examining other outcomes (e.g., patents awarded, clinical trials initiated, etc.) is an important topic for future investigation. Indeed, more thorough efforts to evaluate these state stem cell programs, ideally drawing on the initial goals of the programs and a wide range of relevant outcomes, would be an important step to help assess their impact on the field and the value of field specific state science funding programs more generally.”

The students listed on the article include Hillary Alberta, Albert Cheng, Emily L. Jackson and Matthew Pjecha.

Trounson Named as Advisor to California Cord Blood Firm

A California cord blood firm yesterday appointed Alan Trounson, the former president of the $3 billion California stem cell agency, to its newly formed scientific advisory board.

Cord Blood Registry of San Bruno, which says it is the largest “family bank” in the world, announced yesterday that Trounson is one of four members of its science board. It said the panel would help expand the scope of therapies that it is developing.

Alan Trounson, UCSD photo

Trounson last year left his post as president of the agency, formally known as the California Institute for Regenerative Medicine(CIRM). Seven days later, he joined the governing board of StemCells, Inc., a firm that had received $19.3 million in funding from CIRM. The move surprised the agency and generated a flap over revolving-door conflicts of interest.

Cord Blood Registry has not received any funding from the stem cell agency. In response to a question, Kevin McCormack, senior director for CIRM communications, said today the firm has “no connections whatsoever” with the agency.

It is not clear whether the firm plans to seek financing from CIRM in the future. Cord Blood announced last month that it is involved in an effort with a CIRM-funded, Cellular Dynamics International of Madison, Wisc., to reprogram cord blood and umbilical tissue into reprogrammed pluripotent cells.

Cellular Dynamics, founded by famed researcher Jamie Thomson, has a a facility in Novato, Ca., and was awarded more than $16 million from CIRM in 2013.

Heather Brown, vice president of scientific and medical affairs at Cord Blood (CBR), said in a press release,

"The (scientific board) will provide strategic guidance on current issues that will contribute greatly to CBR's continued progress in research and clinical development."

The company’s press release said,

“CBR is dedicated to advancing the clinical application of newborn stem cells by partnering with leading research institutions to establish FDA-regulated clinical trials, requiring CBR processed cord blood….” 

The company has been in business since 1992 but yesterday’s announcement marked the formation of its first scientific advisory board. It is headquartered in the San Francisco Bay Area, but it stores its cord blood in an 80,000-square-foot facility in Arizona.

Last month, Geoffrey Crouse, CEO of the firm, told Karen Garloch of the Charlotte Observer that some private cord blood banks have“overstated the state of the research” involving cord blood.

He made the comment in connection with the formation of the national Cord Blood Association. He said that he expects the association to “bring the industry to a higher standard.”

According to an April 25, 2014, article in the Wall Street Journal, the blood cord banking business globally runs about $4 billion a year and has had its share of problems. The piece by Dionne Searcy and Christopher Stewart said,

“A Wall Street Journal analysis of government inspections and a review of lawsuits in the U.S. found problems in the loosely regulated cord-blood-banking business, including dirty storage conditions, leaky blood samples and firms going out of business. 

“Some private cord-blood banks are essentially marketing websites that lure customers, collect fees, then outsource the processing and storage of what is touted as biological life insurance for children.”

California's Stem Cell Agency Receives Two Applications in Kick-off of Fast-track Program

The California stem cell agency said today that its new, $50 million CIRM 2.0 program has attracted two applications from businesses for funding of clinical stage work.

The $3 billion agency refused to reveal any further information about the applications, which are part of a radical overhaul of its grant-making efforts.

The next applications in the round are due on Feb. 27.  End-of-the month, rolling deadlines for applications will continue through the middle of this year. The agency did not expect to see a rush of applicants last month because the new, rolling deadlines allow researchers greater flexibility on when they can seek financing.

The goal of the CIRM 2.0 program, which was devised by Randy Mills, president of the agency, is to fast-track funds to researchers and improve the quality of applications.

If the applications that were filed last Friday are approved, the companies should receive their cash before the beginning of May. That compares to an average of about 22 months under former agency President Alan Trounson.

The agency, formally known as the California Institute for Regenerative Medicine or CIRM, has yet to officially promulgate the rules for the grant rules as well as revised loan policies.

Both items were on tap for last week’s board meeting. They were put off until the March meeting while unspecified revisions are being made. A draft is available for the new grant administrative process.

The agency has declined to disclose the draft of the new loan regulations. The loans have been attractive to businesses in the past because they are forgivable if no commercial product results. It is not clear whether the agency intends to continue with that policy.

The California Stem Cell Report has asked the agency for the amount being sought on each application, the general nature of the research being proposed and which of the three CIRM 2.0 programs the applications address.

Correction

The Stem Cellar item on Saturday said that Anne Holden wrote the piece in question on the CIRM blog. It was actually written by Don Gibbons. The attribution to Holden was based on information on the CIRM blog item that incorrectly indicated she wrote it.

Ethics and Stem Cell Research Symposium Feb. 12: Gordie Howe to Right to Try

The public and other interested parties are invited to a UC Davis bioethics symposium Feb. 12 that is likely to deal with some high profile issues involving stem cell research.

Davis researcher Paul Knoepfler is helping to organize the event which he said will include stem cell tourism (think former hockey great Gordie Howe), Right to Try laws and much more. The panelists include Timothy Caulfield of the University of Alberta and Leigh Turner of the University of Minnesota.

A blogger by the name of HappyAnise wrote on the StemcellPromise blog,

“What it makes this so exciting is that they’re apparently going to be talking about some REAL, GENUINE ethical issues. To wit… what on earth are we going to do about all of those stem cell clinics popping up in various and assorted countries? You know, the ones with the weird, dubious, expensive treatments that the FDA would never approve in a gazillion years? And while we’re on the subject, when is the FDA going to do anything about regulating, say, $10,000 stem cell creams? And what about those “Right to Try” laws? They passed in four states in November, but what is the federal government going to do, if anything? What should they do?”

You can register with at 916-734-6181 or julie.bechtel@ucdmc.ucdavis.edu.

California's New, Fast-Track Stem Cell Program Draws Applications But Details Missing

California’s new and ambitious effort to speed stem cell therapies into widespread use drew “multiple” applications as it closed out its first round on Friday.

January is the first month of what the agency calls a radical move in its grant-making. Its initial foray is a $50 million clinical stage round that will be accepting applications for funding at the end of each month until the middle of the year.

The promise for those filing Friday is to put money in their hands in roughly four to five months. That compares to an average of 22 months under the agency’s previous grant rounds.

Randy Mills, the president of the agency, devised the fast-track effort and dubbed it CIRM 2.0. He told agency directors on Thursday that “multiple applications” had been received. (See here and here for more on CIRM 2.0.)

The California Stem Cell Report on Thursday and Friday asked for the specific number that Mills referred to. The agency, formally known as the California Institute for Regenerative Medicine(CIRM), however, did not provide a figure. 

The requests from the California Stem Cell Report also sought the following, all of which is public information: the total number of applications, the number from academic institutions, number from nonprofits, number from businesses, figures on the amount being sought on each application and the general nature of the research proposed.

Applications were due by 5 p.m. PST Friday. Presumably the agency will have the complete information assembled by early Monday and will provide it then. 

The Stem Cellar: California Stem Cell Agency on Gordie Howe and Human Tissue Donations

The Stem Cellar is the blog of the California stem cell agency, and it is consistently worthy of attention.

For the most part it deals with scientific issues, only occasionally touching on other matters. Of course, it does serve as a vehicle for selling the agency’s programs and informing readers about their benefits.

On Friday, the Stem Cellar dealt once again with the Gordie Howe stem cell treatment situation, which received a fair amount of attention over the holidays in December.

The case involved a San Diego firm and treatment of the famed hockey star in Tijuana. Most of the coverage in the mainstream media has largely accepted the claims that the treatment has been wildly successful.  

Don Gibbons, senior science and education officer, wrote on Friday, 

“Finally some healthy skepticism has arrived. Hockey legend Gordie Howe’s recovery from a pair of strokes just before the holidays was treated by the general media as a true Christmas miracle. The scientific press tried to layer the coverage with some questions of what we don’t know about his case but not the mainstream media. The one exception I saw was Brad Fikes in the San Diego Union Tribune who had to rely on a couple of scientists who were openly speaking out at the time. We wrote about their concerns then as well.

"Now two major outlets have raised questions in long pieces back-to-back yesterday and this morning. The Star in hockey-crazed Canada wrote the first piece and New York Magazine wrote today’s. Both raise serious questions about whether stem cells could have been the cause of Howe’s recovery and are valuable additions to the coverage."

Gibbons also wrote on another subject.

“A University of Michigan study suggests most folks don’t care how you use body tissue they donate for research if you ask them about research generically. But their attitudes change when you ask about specific research, with positive responses increasing for only one type of research: stem cell research.

“On the generic question, 69 percent said go for it, but when you mentioned the possibility of abortion research more than half said no and if told the cells might lead to commercial products 45 percent said nix. The team published their work in the Journal of the American Medical Association and HealthCanal picked up the university’s press release that quoted the lead researcher, Tom Tomlinson, on why paying attention to donor preference is so critical:

“'Biobanks are becoming more and more important to health research, so it’s important to understand these concerns and how transparent these facilities need to be in the research they support.'

“CIRM has begun building a bank of iPS-type stem cells made from tissue donated by people with one of 11 diseases. We went through a very detailed process to develop uniform informed consent forms to make sure the donors for our cell bank knew exactly how their cells could be used. Read more about the consent process here.” 

We should also note that The Stem Cellar is several notches above what the agency used to produce several years ago for a blog. It is informative, explanatory and accessible and improving.

(Editor's note: An earlier version attributed The Stem Cellar item to Anne Holden based on incorrect information on the CIRM blog that indicated that she had written the piece.) 

Winners Revealed for $30 Million in California Stem Cell Awards

The California stem cell agency today revealed the identities of the winners of $30 million in awards aimed at removing bottlenecks in stem cell research.

The 20 names were added to the news release posted yesterday afternoon on the agency’s Web site. All the recipients work at institutions that have representatives on the agency’s governing board. Those representatives are not allowed to vote on the applications from their institutions, but they set the rules for and the scope of the research that is being funded.

Today’s posting of the names is a departure from past practices. Previously the agency would release the names on the day when the agency board approved the grants. Yesterday, the agency moved quickly to publish the main body of the news release on the action, minus the names.

The list contains the number of each application, but without a link to the summary of reviewer comments on the proposals.  The reviewer comments cannot be found by searching on the application number on the CIRM Web site.

Instead, a search on application numbers on the CIRM Web site will turn up only an abstract and statement of public benefit prepared by the researcher.

The review summary, which contains more details and something of a critique, can only be found in a 162-page, omnibus document given to board members and posted on the meeting agenda. It encompasses all the application review summaries along with scores and staff comments.  That document, which is much more valuable to the public and the scientific community than the abstract and benefit statement, can be found here.  

(Editor's note: Following publication of this item, Kevin McCormack, senior director of communications for CIRM, sent the following concerning the statement that representatives of institutions receiving awards are not allowed to vote on applications from their institutions.

("That's not quite right. In fact, it's not right at all. Representatives of institutions are not allowed to vote on any applications at all, not just those that involve their own institutions. They can't vote on any funding or award.")

Evaluation of California's Stem Cell CEO Caps Today's Board Meeting

Directors of the California stem cell agency have gone into executive session to discuss evaluation of its new president, Randy Mills, who has been on the job since last May. No major additional action is expected from the board. The California Stem Cell Report does not expect to file additional items later today. But check the articles below for earlier board action today on $30 million in grants, sweeping proposed rules for stem cell grants and termination of the $131 million CIRM scholars program.

From Fraud Checks to Unspent Funds: California's Proposed Rules for Stem Cell Researchers

The California stem cell agency today put off adoption of  new rules for the way it will hand out its last $1 billion, speeding the money to researchers and attempting to improve the quality of research proposals.

The agency's staff deferred action on the proposal in order to spend more time refining it prior to action in March. The interim grant administration rules are designed to implement the CIRM 2.0 plan laid out by agency president Randy Mills, who has been on the job since last May. 

The rules will apply to the initial phase of CIRM 2.0, which closes the first of its new, rolling application rounds tomorrow, and is subject to adjustment. CIRM (the California Institute for Regenerative Medicine) expects to extend the new rules in one form or another to all upcoming award rounds.

The agency calls the fast-track effort a radical change from previous years. It is certain to have a major impact on many scientists.

The agency is funded by money that the state borrows (bonds). It has handed out roughly $2 billion and figures its remaining $1 billion will last until about 2020 when it will need additional financing.

The new regulations talk about such things as “real-time course corrections,” background fraud checks, early and stringent budget review, restrictions on appeals by rejected applicants and elimination of paper work.

Here are some excerpts from an agency memo identified as coming from the “legal team.”  It unfortunately does not contain a marked-up version showing language that has been deleted from the previous grant administration policy along with the new language.

Money

“Prior to CIRM 2.0, payments to grantees were made primarily based on the calendar – disbursements keyed off the start date of the project and were periodically made based on some given period of time following that date. Under the proposed GAP(grant administration policy), however, for clinical stage projects, CIRM will shift to a milestone-based payment schedule. Thus, this section of the GAP describes the importance of the milestones and how payments on the grant will only be made upon successful completion of the milestones.

“Additionally, in many circumstances the grantee will be allowed to keep unspent CIRM funds upon successful completion of the project, to be spent on any other project of the grantee’s that is consistent with advancing CIRM’s mission. This new process will incentivize grantees to advance the project in the most efficient and shortest time possible, fulfilling CIRM’s goal to accelerate such projects.”

Background checks

“The eligibility section has been drafted to reflect that applicants will undergo a background check to ensure no prior or pending records of fraud or misuse of funds.” 

Budgets

“This new review will examine the proposed budget to identify where proposed costs diverge from established market rates and where opportunities for budget tightening may be found. To incentivize efficient budgeting, where CIRM determines that a budget differs significantly from market rates, conforming adjustments will have to be made before the application will be brought forward for review by the GWG (the grant review group).” 

Fast-track

“Rather than require submission of extensive documentation regarding compliance with myriad protocols and processes – some CIRM-imposed and others external – the proposed process will rely on certification of compliance by the applicant, with the ability for CIRM to request supporting documentation if cause to do so arises.” 

Elimination of paper work

“Because most prior approval requests were routinely granted, and therefore added little value to the process, prior approval requests for rebudgeting and carryforward have been eliminated. We have also eliminated prior approval requests for no-cost extensions because our new CIRM awards will have project end dates that will be extended automatically as needed to complete the final Operational Milestone. CIRM intends to increase the latitude for grantees to pursue their research, while maintaining visibility into and approval of any changes to key components of clinical trials, manufacturing processes, or any other activities that meaningfully impact milestones or suspension events.” 

Clinical advisory panels (CAP)  for each award

“CAPs will provide real-time course correction and will focus more on acceleration opportunities than pure evaluation. CAPs will be tailored for the needs of each project and will consist of CIRM and external members, more nimbly sized than prior CDAP panels. CAPs will meet on a quarterly basis (instead of annually with CDAP) and examine all relevant information regarding project progression, possible roadblocks, and avenues for progression.” 

Appeals from rejected applicants

“Finally, in light of the rolling nature of the programs which will allow unsuccessful applicants in many instances to reapply with improvements to their applications, CIRM will limit the grounds for appeal of Scientific Review to those based on demonstrable conflicts of interest (as defined in the conflict of interest policy applicable to GWG members).”

Stem Cell Research Training Program Terminated by California

The California stem cell agency today scuttled its first grant program, a $131 million effort to train stem cell scholars at time when researchers were backing away from the field.

The 29-member governing board voted, 14-5, to end the program that began in 2005 as an effort to demonstrate that the research effort was still kicking while legal challenges threatened its existence. The vote came on a recommendation by the agency's staff.

Arlene Chiu, who is now with the City of Hope, was the chief scientific officer for the agency when the program was launched. She told agency directors said it was time to rethink the program, which was aimed at bringing more scientists into the field. She said,

"Its success has removed its necessity."

Chiu said stem cell research is currently attracting a growing wave of interest among younger scientists. The agency said some training would be included in future research programs.

(Editor's note: The chart on the training program was added to this item after it was initially posted.)

CIRM Press Release on $30 Million in Awards

The California stem cell agency has posted a news release on approval of $30 million for 20 projects to clear out roadblocks hampering the development of stem cell cures. A list of recipients will be forthcoming later, the agency said.

California Okays $30 Million in Awards to Help Remove Stem Cell Roadblocks

Directors of the California stem cell agency today approved $30 million to help eliminate bottlenecks in turning stem cell research into cures.

The action gave the go-ahead to awards that were backed by either its blue-ribbon reviewers from outside of California or the agency’s own staff, plus three additional proposals moved forward by the board.  The agency has already spent $52 million to develop stem cell research tools. Today's round was originally budgeted for $35 million.

After a brief discussion, the 29-member board approved, 9-2, an award to UC Davis researchers who had appealed rejection of a $1.8 million proposal by the staff of the California Institute for Regenerative Medicine (CIRM), as the $3 billion agency is formally known.

The agency did not immediately release the names of the winners. It keeps the names of all applicants secret until after the board ratifies the actions of its reviewers, who make the de facto award decisions for the agency behind closed doors.  The agency is expected to issue a press release on the awards later today. (Here is the link to the press release. It does not include a list of recipients.)

The board did not vote on two applications on which appeals were filed involving material misstatement of facts. Those were deferred  until the March board meeting. The final four numbers of those applications are 7836 and 7678.

Here is a link to the document on this "tools and technology" round submitted to the board by its staff. Summaries of the reviews can be found with the document along with the scores on the winners.

Discussion Underway in $35 Million in California Stem Cell Grant Round

Directors of the California stem cell agency have begun discussion of awards in a $35 million round to remove bottlenecks in stem cell research. Here is a CIRM list of board members that have conflicts on specific applications. Those board members are not allowed to discuss those applications or vote on them.

  Voting Conflict List CIRM Board Meeting 1-29-15 by DavidJensen

California Stem Cell Directors Open Meeting Today in California

Directors of the California stem cell agency opened their meeting today in Burlingame, Ca., at 9 a.m. PST with introduction of new board members.

Former Top Exec at Stem Cell Agency Appointed President of Huntington Medical

The former chief scientific officer of the California stem cell agency, Marie Csete, yesterday was named the president of the $53 million Huntington Medical Research Institutes in Pasadena, Ca.

Marie Csete, Huntington photo

Csete left the stem cell agency in 2009, after serving for a little more than a year. Her departure involved tension between her and former agency President Alan Trounson.  She told the journal Nature,

"When it became clear to me that my considered clinical advice was not respected, I concluded that it made no sense for me to stay at CIRM.”

Csete was the last person to hold the position of chief scientific officer at the agency. Trounson left the agency in July last year.

Huntington reported assets of $53 million in late 2013 and funds a wide variety of research. 

California Stem Cell Appeal: $1.8 Million Needed for Removing Bone Replacement Bottleneck

A UC Davis researcher is making a strong pitch to the California stem cell agency to finance a $1.8 million effort to “resolve bottlenecks in engineering replacement bone and cartilage.”

J. Kent Leach, UC Davis photo

J. Kent Leach, an associate professor in the departments of biomedical engineering and orthopedic surgery, said his proposal addresses “a major hurdle in regenerative medicine of the musculoskeletal system (that) impairs the inherent personalized medicine component of stem cell-based methods.”

In a letter to the agency’s board for its meeting tomorrow, Leach said the research team involved is “arguably the most qualified team in the nation to conduct these studies.” 

Other scientists participating are Laura Marcu and Kyriacos Athanasiou.

Kyriacos Athanasiou
UC Davis photo

Reviewers for the $3 billion agency, who make the de facto decisions on awards, scored the application at 72 and did not approve it for funding. The agency’s staff also nixed the proposal, declaring,

“There is another application recommended for funding in Tier 1 that proposes to optimize and apply the same imaging technology platform to a different test system. In addition, the scientific leadership of the two applications is the same.”

Leach said,

“The co-PI (Dr. Marcu) of this proposal is also PI (principal investigator) on RT3-07879, which is focused on assessing stem cell repopulation and remodeling of engineered vascular tissue constructs. 

Laura Marcu, UC Davis photo

"However, the use of this technology for monitoring the maturation of engineered bone and cartilage, tissues composed of dense matrix reflective of the differentiation of contributing stem cell populations, is substantially different from cardiovascular applications. Of course, both applications involve instrumentation based on optical spectroscopy and ultrasound principles, but the implementation and subsequent commercial hurdles for this technology is very different.”

 (For the summary of reviewer and staff comments, see application RT3-07981 in this document.)

Leach noted that another competing application in the round received an identical 72 score and was approved by the agency’s staff.

The grant round was budgeted for as much as $35 million. Reviewers and CIRM staff recommended approval of awards totaling $29.2 million.

Scientists making appeals directly to the board have not been successful in the last 12 months or so. The board has been more reticent about overturning reviewer and staff recommendations since it changed review and appeal procedures in 2013.

Follow Complete Coverage of Tomorrow's California Stem Cell Meeting

Keep track of all the “thrills and chills” at tomorrow’s meeting of the governing board of the $3 billion California stem cell agency with gavel-to-gavel coverage from the California Stem Cell Report.

This blog will monitor the session via the Internet from our perch in Banderas Bay in Mexico and file stories as warranted. On tap is as much as $35 million in awards. Reviewers and agency staff have approved only $29 million. But three UC Davis researchers are seeking another $1.8 million.  

Also up for action are major changes in the administration of grants – all part of the CIRM 2.0 effort designed to fast-track cash and beef up the quality of applications.

The session, scheduled for eight hours, can also be heard via a listen-only audiocast and Webcast for the slides being used.  Teleconference locations where the public can attend and comment are also available in Sacramento, Irvine and two in La Jolla.  Specific locations and directions for the Internet access are available on the agenda.  

The meeting begins at 9 a.m. PST in Burlingame.

Bump on CIRM 2.0 Speedway: California's Missing Stem Cell Loan Rules

When the applications come in this Friday for the California stem cell agency’s new, $50 million stem cell research round, business applicants will not be seeing a substantial portion of key financial rules for the awards.  

Missing will be the terms of loans that the agency expects to offer to for-profit enterprises. Loans -- rather than grants -- have been the favored method of businesses for receiving awards. The reason is that the agency’s loans have been forgivable if the research does not generate an appropriate amount of cash for the company. Grants, on the other hand, carry requirements for royalty payments. (None have been generated.)

Under the terms of the fast-track, CIRM 2.0 applications, businesses will have the choice of grants or loans. New grant terms are expected to be approved at Thursday’s meeting of the governing board of the $3 billion agency, one day before the deadline for applications for the first round of CIRM 2.0.

Action on new loan rules was originally scheduled for this week but postponed a few days ago after the agenda was posted Jan. 17. The specific reasons are not entirely clear.  The California Stem Cell Report yesterday asked about the delay and for a copy of the latest loan proposal. Kevin McCormack, senior director for communications, replied, 

“We are in the process of revising the (loan policy) and nAeeded additional time to ensure alignment with CIRM 2.0 and the other policy changes so we postponed the meeting.  It will be rescheduled before the March board meeting.
 “And as we are still working on the loan policy it would be premature to share that with you right now, it's still a work in progress.”  

Given that businesses have amounted to a tiny percentage of awards in the past, the delay in the loan rules question may not be significant. But this round is aimed at clinical stage projects, which are more likely to involve businesses and could generate more applications from the private sector.

Some time is available to adopt new rules before CIRM board action on the awards, possibly during an April 23 telephonic meeting. But one of the main points of CIRM 2.0 is to put cash in the hands of recipients significantly faster than in the past. This is especially important for stem cell companies, which are always pretty much cash starved.

Delays in any portion of the aggressive timetable for CIRM 2.0 could mean delays in handing out money.

It is not surprising that some difficulties have arisen in the new award procedures. Randy Mills, CEO of the stem cell agency, last week told an Internet audience of about 200 there would be “some bumps.” He said,

“This is going to be one wild ride.”  

To help smooth it out for both the agency and applicants, it would behoove the agency to post the proposed loan terms in a timely fashion. That means that they should be available to the public when a meeting agenda involving the rules – be it for a subcommittee or full board meeting -- is posted on the CIRM Web site. That is normally 10 calendar days ahead of the session.  The agency, which is costing taxpayers $6 billion including interest, doesn’t need any more mysteries.