Friday, July 22, 2016

Tracking California Stem Cell Awards: Diabetes to Dialysis

The California stem cell agency, as expected, yesterday pumped $10 million into a North Carolina firm for a kidney dialysis device and upped its stake in a San Diego diabetes therapy firm to $60 million.

The awards were first reported (see here and here) by the California Stem Cell Report last week, which will have more on the subject and other awards in the next day or two. Here is a link to the press release from the $3 billion agency.  Sphere: Related Content

Thursday, July 21, 2016

California Stem Cell Appeals: Zika, Parkinson's and 'Heart-on-a-Chip'

Three California researchers are asking the directors of the state's stem cell agency today to reject the decisions of its blue-ribbon scientific reviewers and grant them awards ranging up to $2 million.

The scientists are Alysson Muotri, director of the UC San Diego stem cell program; Birgitt Schuele, director of gene discovery and stem cell modeling at the Parkinson's Institute in Sunnyvale, and Kevin Healy, professor in the department of bioengineering at UC Berkeley.

Muotri is seeking $1 million from the California Institute for Regenerative Medicine (CIRM), as the stem cell agency is known. Schuele has applied for $2 million and Healy $1 million.
Alysson Muotri, UCSD photo
In a letter to CIRM's board, Muotri said he is attempting to "set up a human stem cell platform to measure the impact of the Zika virus in the nervous system and to screen potential drugs to alleviate the neurological problems associated with the infection." His application (DISC2-09095) is aimed at filling "fundamental gaps" in Zika knowledge. Muotri, who is from Brazil, wrote,
"I never debated over a grant fund decision before . However, in this case I feel I have the responsibility to alert the ICOC (the CIRM board) about neglecting studies on what we call now the ' Zika virus syndrome.' I can tell by personal experience dealing with this virus in my own lab that this is one of the most dangerous infectious agent I (have) ever seen – one can witness the virus killing brain cells in less than a day."

Birgitt Schuele, TSN photo
Schuele's letter pointed out a new study that she said demonstrated the feasibility of her research (DISC2-08953) involving a therapy for Parkinson's disease. She also included additional information that she hoped would be persuasive to the CIRM board.

Kevin Healy
photo by Laura Peterson, AAAS
In his letter, Healy said his research is aimed at developing "patient specific ‘heart-on-a-chip’ diagnostics that will have a significant impact on the early screening of drugs used to manage hypertrophic cardiomyopathy . Currently, there are no drugs that target specific disease alleles of hypertrophic cardiomyopathy."

He said the main criticism of CIRM reviewers involved the "level of maturity of cardiomyocytes" in his proposed study (DISC2-08990). But he said he proposed using the same protocol as already used by a number of currently funded CIRM researchers.

All three applications were ranked below the cutoff line for funding, which was 85. The score for Healy was 83, Muotri 77 and Schuele 72.

CIRM has funded some applications in the past with lower scores than 85. But in the last two years, it has revised its review and scoring protocols. Since then it has not overridden reviewers' negative recommendations.

The board is scheduled to act on about $30 million in awards today in a telephonic meeting with public locations throughout the state. (See here and here. ) The public can participate in the meeting at those locations, whose addresses can be found on the meeting agenda. The session will be audiocast on the Internet and through an 800-number. Complete information about the Internet access and phone number can be found on the agenda. Sphere: Related Content

Thursday, July 14, 2016

Search for a Diabetes Cure: California Stem Cell Agency Hits $60 Million Mark with ViaCyte

The California stem cell agency next week is slated to award  an additional $4 million to ViaCyte, Inc., a San Diego firm that is working with the agency to develop a "virtual" cure for diabetes.

ViaCyte has already received $56 million over the years from the California Institute for Regenerative Medicine(CIRM), as the agency is formally known. The latest award will be used to help prepare for a clinical trial for a new treatment for the highest risk diabetes patients.

In response to a query this morning from the California Stem Cell Report, Paul Laikind, president and CEO of ViaCyte, said that the new product, PEC-Direct, will deliver the same biologic component as used in the firm's current product, which is now in a clinical trial.

Laikind said PEC-Direct will allow direct vascularization, which "is expected to allow for a very robust engraftment and cellular performance."

Because the new device will require chronic immune suppression, Laikind said,
"It is being developed to treat patients with type 1 diabetes that are at high risk for acute complications such as severe hypoglycemic events associated with hypoglycemia unawareness syndrome."
(The full text of Laikind's remarks and research update can be found here.)

The agency's summary of the closed-door review of the Viacyte proposal said,
"There are over 100,000 people in the U.S. with type 1 diabetes so severe that they are at constant risk of hospitalization and/or death. Within months after administration, this product could naturally restore those patients’ blood sugar to normal healthy levels and save their lives." 
In addition to the $4 million, ViaCyte is putting up $994,343 of its own cash.

CIRM's blue-ribbon panel of scientific reviewers has already approved the award, which is part of a $30 million package of applications coming up next Thursday.  The governing board of the agency will ratify the approvals at its meeting next Thursday during a one-hour telephonic meeting.

The largest award, $10 million, will go to Humacyte, Inc., of North Carolina,  to produce an artificial vein for use in hemodialysis as reported yesterday on the California Stem Cell Report. More details of all the applications and review summaries can be found on the meeting agenda.

The session will be audiocast and carried on the Internet on a listen-only basis. Interested parties can participate in the meeting from telephonic locations throughout the state.

The main site for the meeting will be at the Sanford consortium in San Diego. Other locations include the agency's headquarters in Oakland and sites in Davis, South San Francisco(2), Napa, Los Gatos, Sacramento, Irvine, San Francisco and Los Angeles. For specific addresses and instructions for online access, see the agenda.
Sphere: Related Content

Text of ViaCyte's Statement on its New Proposed Diabetes Product

The California Stem Cell Report this morning queried Paul Laikind, the CEO of ViaCyte, Inc., of San Diego, about the company's upcoming $4 million award from the California stem cell agency and the award's relationship to the ViaCyte product known as VC-01. Here is the text of his response.
"ViaCyte is continuing development of VC-01 (what we now call PEC-EnCap).  PEC-EnCap is the first encapsulated allogeneic cell therapy to enter the clinic where the device is designed to protect the cells from the host adaptive immune system.
 "We have early clinical demonstration of the feasibility of the PEC-EnCap approach; the Encaptra Drug Delivery Device appears to be functioning as designed and we have shown engraftment and differentiation to beta cells is achievable at 12 weeks.  However, work is continuing to ensure a robust and consistent engraftment before we move to the second cohort of patients and seek to demonstrate efficacy.
 "We can’t overemphasize enough the importance the clinical results we are obtaining, not only for the further development of PEC-EnCap but for the stem cell-derived cell therapy field in general. This important work has, of course, received important support from CIRM. "In parallel with the development of PEC-EnCap we are preparing to initiate clinical development of VC-02 (PEC-Direct).  PEC-Direct delivers the same biologic component as PEC-EnCap, PEC-01 pancreatic progenitor cells, but does so in a device that allows direct vascularization.  This direct vascularization, based in part on what we have learned with PEC-EnCap during the clinical evaluation, is expected to allow for a very robust engraftment and cellular performance.
"Given the open nature of the device, patients implanted with PEC-Direct, as with other transplants, would require chronic immune suppression.  Thus it is being developed to treat patients with type 1 diabetes that are at high risk for acute complications such as severe hypoglycemic events associated with hypoglycemia unawareness syndrome.
 "This high risk patient population is the same population that would be eligible for cadaver islet transplants, a procedure that has been demonstrated as very effective but suffers from a severe lack of donor material and high cost.  PEC-Direct is expected to overcome these limitations by providing an unlimited supply of cells for transplant and a safer more optimized route of administration.
"ViaCyte remains committed to the development of PEC-EnCap which we view as a potentially transformational therapy for the majority of insulin utilizing patients with diabetes, both type 1 and type 2.  PEC-Direct represents a potentially nearer term therapy for the patients at the highest risk."
Sphere: Related Content

Wednesday, July 13, 2016

$10 Million California Stem Cell Award for Creation of a New 'Lifeline" for Kidney Disease Patients

A 2014 interview with Laura Niklason, whose firm, Humacyte, will receive a $10 million award from California. The interview was conducted at the Stem Cells Meeting on the Mesa in La Jolla, Ca.

$10 million matched by Humacyte
Three clinical trial locations in California
Humacyte raised $150 million last year

The California stem cell agency is set to award nearly $10 million for a phase 3 clinical trial to produce a new type of "lifeline" for kidney disease patients undergoing hemodialysis.

The $10 million award to Humacyte, Inc., of Morrisville, N.C., will go for final testing and development of an artificial vein that is critical for kidney disease patients who need hemodialysis.

The $10 million will be matched by the privately held firm. The state funds can only be spent for work performed in California to test the vascular access device. Humacyte plans clinical trial sites in Sacramento, Long Beach and Irvine.  

Formal approval of the award is expected to come July 22  at a telephonic meeting of the $3 billion agency's board of directors.

The stem cell agency traditionally does not identify recipients of awards until its board formally ratifies the decisions of its reviewers, which it almost never overturns. The California Stem Cell Report determined the identity  of the recipient using public sources.

According to the National Institute of Diabetes and Digestive and Kidney Diseases,
"A vascular access is a hemodialysis patient’s lifeline. A vascular access makes life-saving hemodialysis treatments possible. Hemodialysis is a treatment for kidney failure that uses a machine to send the patient’s blood through a filter, called a dialyzer, outside the body. The access is a surgically created vein used to remove and return blood during hemodialysis."

The Humacyte device, photo Humacyte
A summary of the closed-door review of the application described the product as a "human acellular vessel" that "has the potential for less frequent clotting, abandonment and infection." The summary said current technology is "fraught with complications."

Humacyte was founded in 2004 and raised $150 million last year in venture capital, according to an article last month by Meghana Keshavan on the STAT online biomedical news service. 

In the piece, Keshaven described the process of growing the vessels. She said each has "its own little plastic sack, which serves as a sort of womb for the vessel as it grows. Each bag’s connected to a central bioreactor tank that pumps out all the nutrients it needs — a carefully crafted 'soup' of vitamins, amino acids, and chemicals called cytokines that feed cells directions about how they’re supposed to grow."

Keshaven continued,    
"The lab-grown blood vessels are currently being studied in hemodialysis, a procedure that uses implanted veins as a conduit to remove waste from the blood of patients with kidney failure. Last month, promising results from a 60-patient midstage trial of Humacyte’s product were published in The Lancet."
Humacyte currently is recruiting 350 patients and expects to have preliminary results by July of next year. In response to a question this morning, Jeffrey Lawson, chief medical officer of the firm, said, 
Shannon Dahl,
co-founder Humancyte
Juliana Blum,
co-founder Humacyte
"We currently are engaged on using at least 3 clinical sites in California that should start enrolling patients (Sacramento, Long Beach and Irvine). We also have a number of manufacturing support programs based in California."
Founders of the firm include  Laura Niklason, professor of biomedical engineering and Yale, and Shannon Dahl and Juliana Blum, vice president of the firm.
Sphere: Related Content

Monday, July 11, 2016

More Than a Minor Headache: The Stem Cell Snake Oil Problem vs. Legitimate Research

Just two weeks ago, the headlines from Bloomberg News offered a glowing view of the prospects for stem cell therapies and the industry. The story in the online publication, which counts nearly 9 million readers monthly, said,
"Stem cell crusader sparks new hope....Regenerative medicine could be a $120 billion industry by 2030"
But only three days later, that article was overwhelmed by a wave of stories with a much different flavor. They carried reports of unproven therapies, possibilities of fraud, lack of regulation and fearful, expensive consequences for desperate patients.

That theme continued even as recently as this past weekend as The Economist carried a piece headlined,
"A dish called hope: The flourishing, unregulated industry in expensive, experimental treatments"
So which is it? Hope for legitimate cures and oodles of cash for stem cell companies? Or "hope" for treatments that do not work and have sometimes damaged both the bodies and wallets of the patients?

The situation is more than a minor public relations headache for the supporters of stem cell research, be they patients, stem cell companies or the $3 billion California stem cell agency, which is on a campaign to ease federal regulation of stem cell clinical trials.

For all practical purposes, the public generally does not make much of distinction between the legitimate research conducted by institutions such as Stanford and the so-called "miracles" reported about the late hockey great Gordie Howe and others. It all goes into the same cognitive bag. The stories about mysterious and fearsome tumors found in little-known patients attract little widespread attention.

But UC Davis scientist Paul Knoepfler and bioethicist Leigh Turner of the University of Minnesota ripped open that bag with their study last month that reported for the first time that nearly 600 dubious stem cell clinics are peddling their unproven therapies across the country.  Their report supported the view that the stem cell field is rife with snake oil merchants. For the general public, which does not delve deeply into medical research, the perspective could well be described as, "You seen one stem cell therapy, you seen 'em all."

Does this mean that these clinics should be ignored and shoved quietly off into a corner in order to avoid besmirching legitimate efforts? Of course not. It certainly appears that the FDA and other  state regulatory bodies can do a better job. But stiffer regulations are not going to come anytime soon, despite an FDA hearing on the topic in September.

However, the situation DOES mean that folks like Knoepfler and Turner should continue to speak out along with many other scientists who do not want their efforts blackened by the snake oil men. Researchers can work with their institutions' PR departments to place op-ed pieces, find speaking engagements and gin up TV and radio interviews. Blogs, like the one produced by Knoepfler, can be started. The International Society for Stem Cell Research should revive its public education efforts to help patients and the general public understand the facts about stem cell research. It should also reinvigorate its warnings about dubious therapies, which were throttled back a few years ago, reportedly after legal threats were made.

California's stem cell agency has a special concern. It is trying to "de-risk" development of therapies  by a variety of means and lure biotech and Big Pharma into the stem cell game in a bigger way. This summer the agency is offering $75 million to entice a private partner into the state's first-ever, public-private partnership to create a stem cell cure.

The private sector has shied away from the stem cell business, as the stem cell agency's CEO, Randy Mills, has remarked on multiple occasions. One of the reasons involves the public climate and perception of the field. It is hard for companies to invest hundreds of millions of dollars or billions when the stem cell field is burdened with public perception and regulatory obstacles.

Selling the stem cell story in a realistic way is not necessarily an easy task. Nuances must be respected, but excitement is also needed. Balancing it all is a challenge for the men and women in the trenches. But without a good push, development of therapies will be slower, and, as Mills has noted, people will undoubtedly die who likely would have benefited from a more timely treatment. Sphere: Related Content

Sunday, July 10, 2016

A Scientist's Comment: Deal Directly with FDA Rather Criticizing It in the Media

The following comment on FDA regulation of stem cell research was submitted via email by a longtime scientist in the field, who asked to remain anonymous. 
"Many advertised  'stem cell' treatments use hematopoietic or blood stem cells which are run under a different set of regulations from pluripotent stem cells since they are umbrella-ed under regulations designed to cover blood transfusions and bone marrow transplants.  Pluripotent stem cells are very new, with many unknowns and the potential for triggering tumor growth.   In contrast, clinical use of blood stem cells has been ongoing for over 50 years with special regulations (or lack thereof) grandfathered in.   Unfortunately, the newly touted 'treatments' are not for homologous use of blood stem cells, are unlikely to be therapeutic and may even be dangerous. 
"The FDA has published new draft guidances addressing these issues that will be discussed in open forum this September.  I think it best to bring concerns about FDA regulations to these meetings and to initiate change by talking directly with the agency rather than criticizing them in the press or through Congress.  Like their oversight over the IRS and other federal agencies, Congress’s actions are counterproductive when they add broad, unfunded mandates while cutting funding at the same time.  But perhaps this is their way of shrinking the government and simultaneously dinging them for not doing their work.  A sure route to failure."
Sphere: Related Content

Thursday, July 07, 2016

Monty Python, $3 billion and Stem Cells in the Golden State

Inquisition scene from Monty Python, photo CIRM/Daily Mail
The headline today from California was nearly irresistible:
"The Spanish Inquisition and a tale of two stem cell agencies"
Not only that, but the headline appeared over an article involving Monty Python, the $3 billion California stem cell agency and the lesser,  $38 million United Kingdom's Regenerative Medicine Platform(UKRMP)

The "Inquisition" article ran on the California agency's blog. The author was Kevin McCormack, senior director of communications for the California Institute for Regenerative Medicine(CIRM), as the agency is formally known. 

His topic? How the UK and California efforts have performed, according to an article by Stanford's Irv Weissman and Fiona Watt of King's College London, who is a member of the CIRM scientific advisory board, currently "on hold," according to McCormack.  The Watt-Weissman piece was recently published and buried behind a paywall in Cell Stem Cell.

McCormack noted that the article cited location and politics as important in both operations. He wrote, 
"CIRM was created by the voters of California in 2004, largely in response to President George W. Bush’s restrictions on the use of federal funds for embryonic stem cell research. UKRMP, in contrast was created by the UK government in 2013 and designed to help strengthen the UK’s translational research sector....
"Inevitably the two agencies took very different approaches to funding, shaped in part by the circumstances of their birth – one as a largely independent state agency, the other created as a tool of national government.
"CIRM, by virtue of its much larger funding was able to create world-class research facilities, attract top scientists to California and train a whole new generation of scientists. It has also been able to help some of the most promising projects get into clinical trials. UKRMP has used its more limited funding to create research hubs, focusing on areas such as cell behavior, differentiation and manufacturing, and safety and effectiveness. Those hubs are encouraged to work collaboratively, sharing their expertise and best practices."

Irv Weissman, photo wapiti-waters
Weissman and Watt said it was "not unexpected" that CIRM still has not produced a therapy for widespread use. They cited the sometimes decades-long time frame for transforming basic research into a therapy.

Which is where Monty Python comes in, said McCormack. The two scientists picked up a famous line from the British comedy series:
“Nobody expects the Spanish Inquisition – because our chief weapon is surprise.”
Fiona Watt, photo Watt Lab
McCormack wrote,
"They use that to highlight the surprises and uncertainty that stem cell research has gone through in the more than ten years since CIRM was created. They point out that a whole category of cells, induced pluripotent stem (iPS) cells, didn’t exist until 2006; and that few would have predicted the use of gene/stem cell therapy combinations. The recent development of the CRISPR/Cas9 gene-editing technology shows the field is progressing at a rate and in directions that are hard to predict; a reminder that that researchers and funding agencies should continue to expect the unexpected."

Sphere: Related Content