California Pumping $20 Million into Stem Cell/Gene Therapy for 'Bubble Boy' Syndrome

June 2016 video from UCLA

Highlights
30 out of 30 cured
$18.2 million in matching funds
Cells to be frozen
UK's Orchard Therapeutics partnering

California's stem cell agency is ready to award $20 million on Thursday to a UCLA researcher to assist in his 30-year search for a widely available cure for what has come to be known as the "bubble boy" syndrome-- severe combined immunodeficiency (SCID).

The California scientist is Donald Kohn, of the Broad Stem Cell Research Center at UCLA, who said today that 30 out of 30 babies have already been cured using his type of therapy. Kohn said that the research involving the extremely rare disease could lead to progress in treating other afflictions ranging from sickle cell disease to cancer.

The progress in treating the "bubble boy" disease is much changed from decades ago when the case of David Vetter captured the nation's attention as the boy who was "born into a world he could not touch."  He ultimately died at the age of 12. (This item continues below video.)

Kohn's proposal for an early stage clinical trial would be co-funded with $18.2 million and would test a stem cell and gene product known as OTL-101. It could replace what the stem cell agency said were the "suboptimal," current treatments for  Adenosine Deaminase Severe Combined Immunodeficiency.

The affliction is extremely rare and occurs in less than one in 100,000 births worldwide, according to Wikipedia. Without treatment, children can die before the age of two.

The agency's application review summary said that reviewers were "highly enthusiastic" about Kohn's proposal during their closed-door session last month. The summary said that reviewers, who are from out-of-state and do not publicly disclose their economic interests, "applauded the move to a cryopreserved product that will allow improved patient access to the therapy." They also noted that the costs of the trial are "exceedingly high."

In response to a query by the California Stem Cell Report, Kohn said today via email, 

"Building upon the previous success of our single-site trials for ADA SCID, which have resulted in 30 out of 30 babies cured, our next trial will focus on developing a cryopreserved formulation of the cell product. 

"This has several potential advantages. It will allow the cell product to undergo full testing before the transplant is performed, whereas currently we only have stat viability, sterility and endotoxin assay results, with gene transfer efficiency measurements coming later.

"Additionally, it provides more time to split up the dosing of the conditioning chemotherapy and individually adjust the total dose based on measurement of the individual patient's unique drug clearance activity.

"Finally, this will allow centralization of cell processing, allowing patients to remain at their local hospital for the treatment, with the stem cells traveling to a commercial cell processing site, gene-corrected, frozen and shipped back to their hospital for infusion."

The agency's board is virtually certain to ratify the decision of reviewers at its telephonic meeting on Thursday. It has almost never overturned a positive recommendation by reviewers. 

The agency, formally known as the California Institute for Regenerative Medicine (CIRM), did not release Kohn's name in advance of the Thursday meeting. Its policy, with some notable exceptions, is to withhold that information until the pro forma vote by its governing board. The California Stem Cell Report identified Kohn as the recipient through a number of public documents. The UCLA researcher has already received $32 million from CIRM for his work. 

Kohn has teamed with Orchard Therapeutics Ltd. of Britain, a firm that began operations last May with a $33 million war chest. Kohn is one of the scientific advisors to the company. He said today: 

"This study is being done at the UCLA Broad Stem Cell Research Center in partnership with Orchard Therapeutics Ltd., who have licensed this stem cell gene therapeutic from UCLA and University College London, UK. The general approach of stem cell gene therapy was first done for ADA SCID, which is a highly favorable disease for this treatment. Findings and advances made for this disorder are being applied to many other inherited diseases, such as Sickle Cell Disease, other Primary Immune Deficiencies, Storage and Metabolic Diseases, as well as HIV/AIDS, cancer and leukemia."

The process uses a patient’s own stem cells. Earlier this year, the company said that the cells are "modified with a functioning copy of the missing or faulty gene before being transplanted back into the patient’s body. The use of the patient’s own cells (autologous) removes the need to search for a matching stem cell donor, which can take months or even years," the company said.

Should the treatment emerge successfully from the clinical trials, it will face competition from a rival developed by GlaxoSmithKline that has been approved for use in Europe at a reported cost of $665,000 per patient. Glaxo is expected to seek approval next year for use of the treatment in the United States, which has only about 12 new cases a year, according to the STAT health science news service. However, a document from the U.S. Center for Disease Control places incidence at 40 to 100 new cases each year. 

The public can participate in Thursday's meeting at locations in Oakland, San Francisco, San Diego, Napa, South San Francisco, San Francisco, Beverly Hills, Fresno, Elk Grove, Los Gatos, Sacramento, and Irvine.  It is also being audiocast on the internet. Instructions and addresses can be found on the agenda.

(Editor's note: An earlier version of this item incorrectly reported that co-funding on this award totalled $8.9 million. The correct figure is $18.9 million.)

$10 Million 'Eat Me' Award: California Stem Cell Agency to Firm Called Forty Seven

The California stem cell agency is set this week to award $10 million to a Menlo Park firm to help finance a clinical trial for a therapy for colon cancer, which is the second leading cause of cancer death in this country.

The cash will go to Forty Seven, Inc., an enterprise using an immune system, "eat me" technology developed at Stanford University by stem cell scientist Irv Weissman. The firm is adding $6.8 million of its own cash to the project. Weissman has received $30 million over the years from the state agency.

The application to help with an early stage clinical trial was unanimously approved by the agency's scientific reviewers during a closed-door meeting last month. The full board will ratify the action at its telephonic meeting this Thursday. 

The agency, formally known as the California Institute for Regenerative Medicine(CIRM), has almost never overturned a positive decision by its reviewers.

The $3 billion agency does not release the names of successful applicants prior to board action. Forty Seven was identified through the use of public records.

According to a federal Web site,

"This trial will evaluate Hu5F9-G4 in combination with cetuximab. Hu5F9-G4 is a monoclonal antibody which is designed to block a protein called CD47, which is widely expressed on human cancer cells. Blocking CD47 with Hu5F9-G4 may enable the body's immune system to find and destroy the cancer cells. Cetuximab is a monoclonal antibody drug that is used for treatment of certain types of colorectal cancer as well as head and neck cancer."

The idea is to override a tumor's "don't-eat-me" signal and instead trigger the body's "eat-me" response.

California's scientific reviewers expressed high praise for the project. However, they also said,

"The design of the trial itself is fine, but the decision-making process is sub-optimal. It is critical to include clear go/no go criteria for the second phase of the trial and for the data to be evaluated by an independent, objective third party for a decision as it is unclear what toxicities are expected given the proposed new mechanism of action and use of a combination therapy." 

Forty Seven announced last February that it is backed by $75 million from a variety of partners including Google. Others in the venture capital group are Lightspeed Venture Partners, Sutter Hill Ventures (the two leaders on the financing) and Clarus Ventures.

In August, Karen Tkach wrote in BioCentury:

"With companies lining up to block CD47 for cancer, the cell surface protein is emerging as one of the top new targets in oncology. But the list of suitors could be about to get a lot longer as the target could have uses in a much broader range of indications, according to two studies from Stanford University that extend its prospects to cardiovascular disease and transplant biology, and hint at roles in several more diseases."

According to the clinical trial information on a federal Web site, Forty Seven will have clinical trial locations in Grand Rapids, Mich.; San Antonio, Texas, and Nashville, Tenn.  The California stem cell agency is limited to spending its award for work done in California. 

The federal information has conflicting indications on whether patients are currently being recruited for enrollment in the trial.

(In response to a query following publication of this item, Mark Chao, a co-founder and medical

Mark Chao, Stanford photo

director of Forty Seven and co-PI on the trial, said,

"We have been excited about the positive reviews by the CIRM committee and hope to hear good news on Thursday. Thank you for sending this article. With regards to initiating California clinical sites on the trial, this is a very big point of emphasis for us, in particular with CIRM’s mission and are currently working to activate two sites in California (Stanford University and UCLA) for the trial. One of our goals are to bring this therapy to patients within California and have designed our trials with this in mind. Please let us know if there are any further questions we can address. We look forward to a long relationship with CIRM.")

The chair of the study is Chris Takimoto of Forty Seven. The CIRM application number is CLIN2 -09577.

Trump's 'Ouija' Stem Cell Policy Is Making Scientists Anxious

One of the bulwarks of the mainstream media today weighed in with a hefty assessment of Trump and stem cells, declaring that researchers are "anxious" about what is likely ahead.

Prominently mentioned by ABC News was Vice President-elect Mike Pence, who supported legislation in Indiana banning donation of fetal tissue for research. That law, signed by Pence as governor of Indiana, was temporarily halted by a judge, who questioned its constitutionality.

Alta Charo, a bioethicist and law professor at the University of Wisconsin, was quoted as saying that trying to determine what Trump's stem cell policy might be is a "little bit like using a Ouija board." But she did point to Pence's fetal tissue position.  Additionally, Trump has taken a pro life position on abortion.

Also cited in the article at some length was a spokesman for the $3 billion California stem cell agency, which owes its existence to presidential restrictions on human embryonic stem cell research. ABC reporter Gillian Mahoney wrote,

 "Kevin McCormack, communications director at California Institute for Regenerative Medicine, said reintroducing a funding ban to stymie research would likely be more difficult than it was in the early 2000s when stem cell research was a new field.

"'It would be like putting a genie back in the bottle,' said McCormack.

"Pointing to one case at the University of Southern California, where a paralyzed man regained hand movement after an experimental stem cell therapy, McCormack said any measures that would halt funding or restrict stem cell research wholesale, 'would be like going up to someone and say you can't have that treatment.'

"McCormack did note that more states have provided stem cell funding, including California, which provides grants for the California Institute for Regenerative Medicine. While state funding could help, the NIH provides a huge amount of funding for U.S. medical research, spending approximately $32 billion on medical research annually."

(Editor's note: The state does not provide grants for the stem cell agency. The agency uses state bonds to provide grants to researchers.  The agency's funding flows straight to it without intervention by lawmakers or the governor.)

Trump on Science and Biotech: Wild Card, Chilling or NIH Slasher?

Reaction today from the world of science, stem cells and biotech to the election of Donald Trump as president ranged from "party time" to "chilling" impact.

Here is a sampling of articles today that dealt with the implications of the billionaire's victory.

Dylan Scott wrote in Stat:

"Should President Donald Trump make drug makers relieved? Or anxious? They’re not sure."

Stat also carried a related piece by Damian Garde who said that Trump is a wild card who could side with those who want to cut back on federal funding of research.

An article in Science by Jeffrey Mervis quoted Robert Cook Deegan, a research scientist at Arizona State University, as saying,

"Science won't get much attention, except when it gets in the way or bolsters support for a political priority."

Adam Feuerstein wrote in The Street:

"Half the country woke up Wednesday depressed about President-elect Donald Trump. That group doesn't include investors in biotech and drugs stocks. They are partying like a giant drug-pricing cloud has been lifted from their shoulders."

An article in Nature by Jeff Tollefson, Lauren Morello and Sara Reardon had this:

"'I think at the very least it would put a chilling effect on the interest of scientists from other countries in coming here,' says Kevin Wilson, director of public policy and media relations at the American Society for Cell Biology in Bethesda, Maryland. Some researchers are already thinking about leaving the United States in the wake of the election."

An overview piece by Sarah Kaplan in the Washington Post had this line:

"Last year, Trump told conservative radio host Michael Savage, 'I hear so much about the NIH, and it’s terrible.'"

Yours truly wrote earlier today that Trump's victory could translate to good news for California's $3 billion stem cell agency. (That piece can also be found on Capitol Weekly.)

Trump: Helpmate to the $3 Billion California Stem Cell Agency?

Donald Trump's victory last night, oddly enough, could be good news for the future of the California stem cell agency. 

It could be George Bush all over again.

How does that work, you may ask? Trump is a bit of a blank slate on stem cell issues. He has not addressed them directly. But he is pro-life, a fact being celebrated this morning in the usual pro-life venues.

Given that stance, he is likely to reverse the federal government's current funding of human embryonic stem cell research. It would be easy to do, basically nothing more repealing an executive order or issuing a new one.

Such a move would echo the Bush restrictions on human embryonic stem cell research that provided the justification for the 2004 ballot initiative that created California's $3 billion stem cell research effort. Bush's opposition energized the scientific and patient communities on behalf of the initiative.

His opposition also helped to raise the $34 million for the electoral campaign that spawned the California Institute for Regenerative Medicine (CIRM), the official name of the stem cell agency.

Bush provided a big target for supporters of stem cell research. (See here and here.) He embodied the essence of the "anti-science" crowd. And in politics it is good to have a "demon" that can easily be understood. It simplifies issues, sharpens the focus and stimulates voters.

The stem cell agency is now on track to run out of money in 2020 for new awards. CIRM relies on state bonds for its cash but its ability to issue them is coming to an end. No additional source of funding has been identified.

Assuming Trump bans federal research on human embryonic stem cell research, it would bring new life to the possibility of another multi-billion dollar bond issue in the next few years. A new "demon" would surface. All the agency needs to do now is to come up with a high-impact therapy that would resonate with California voters.

Millions More on the Way: California Stem Cell Agency Beefing Up Fight to Reverse Arthritis

California's $3 billion stem cell agency appears ready to back with millions of dollars a proposed therapy intended to reverse arthritis -- an affliction that affects 40 million Americans --  and push the treatment into clinical trials.

It would be the first ever disease-modifying therapeutic for osteoarthritis if it clears clinical trials, which could take years.

Peter Schultz, chief executive officer of the Scripps Research Institute, last month indicated that the therapy was all but assured of funding by the California Institute for Regenerative Medicine (CIRM), as the stem cell agency is formally known.

Shultz' disclosure came at the end of an Oct. 20 article by Bradley Fikes in the San Diego Union Tribune. Schultz said,

"We’re just finishing (toxicology studies) with a regenerative medicine for osteoarthritis that [the California Institute for Regenerative Medicine] wants to fund. That’ll be dosed in patients probably in the first quarter of next year."

Schultz did not respond to a request for additional comment from the California Stem Cell Report. The stem cell agency itself does not identify applicants, with a few notable exceptions, for funding unless they actually receive awards.

Schultz, however, has already received about $10 million for a therapy (see here and here) aimed at tweaking cells to reverse the course of arthritis, which would be the basis for a clinical trial.

In an undated progress report filed with CIRM, Schultz said,

 "A unique and unexplored therapeutic opportunity exists to induce somatic stem cells to regenerate the damaged tissue and reverse the chronic destructive process. Because limited joints are affected in most (osteoarthritis) patients, intra-articular (IA) drug injection is an attractive treatment approach that allows high local drug concentration with limited systemic exposure. Targeting resident stem cells pharmacologically also avoids the risks and costs associated with cell-based approaches."

Schultz also said in the CIRM document,

"The primary objective of this project is to develop a non-invasive, therapeutic for the regeneration of cartilage in OA. This new therapy will target the resident MSCs in the joint, stimulate production of new cartilage matrix, promote repair and thus limit additional joint damage and improve joint pain and function."

The CIRM document included an accounting of achievements in the research involving animals. The document said,

"We have demonstrated efficacy in preclinical in vivo models of a potential drug candidate for the treatment of osteoarthritis. The small molecule functions by selectively differentiating meschenchymal stem cells to chondrocytes to repair damaged cartilage."

In another CIRM document, Schultz reported that "a scale-up manufacturing process has been developed and confirmed feasible" and would be used in the initial clinical trials.

An award could be made publicly to Schultz before the end of the year at meetings of the full board of the stem cell agency in 10 days or in December.

California's $150 Million Public/Private Plan to Commercialize Stem Cell Therapies: An Update

California's plan to create an ambitious, $150 million public/private partnership to commercialize state-funded stem cell research edged forward this week as the deadline for applications closed on Monday afternoon.

Little is known about the nature of the applications -- not even the number received. The state's stem cell agency yesterday declined to reveal the figure, declaring that the proposals needed to be examined to determine eligibility.

Traditionally the $3 billion agency does not disclose the names of applicants for its funding or details of their applications, although there have been exceptions. Their proposals are reviewed behind closed doors by scientific grant reviewers whose names are not disclosed. Nor are the reviewers' statements of economic interest publicly revealed.

A CIRM document calls for the proposal to be evaluated by reviewers during the first quarter of next year with final board action also coming during that period. The recommendations of reviewers are almost never overturned by the board.

The public/private partnership could well be one of the landmark legacies of the stem cell agency, formally known as the California Institute for Regenerative Medicine(CIRM). The project would be unique in California history and nationally.

The eligibility requirements include the following:

• A California location for the work
• Documentation of an "upfront financial commitment" of $75 million(no in-kind services)
• Readiness to begin work as required by CIRM
• Incorporation by the date of the application

The recipient must begin work on the project within 45 days of the award, which translates to before the middle of next year.

New Stem Cell Trial for ALS at Cedars-Sinai in Los Angeles; California Invested $17 Million

You might say it is a case of "self-control" involving the test of a stem cell therapy for an infamous and terrible disease.

Not self-control in the usual sense, but in the sense of controls during a clinical trial for a treatment prior to its release to the general public.

Clive Svendsen (left) during 2013 visit to Cedars-Sinai
by famed physicist Stephen Hawking (seated), who .
 has ALS. Photo Eric Reed/Cedars-Sinai

The key scientist involved in the trial is Clive Svendsen  at Cedars-Sinai in Los Angeles. He and his team have just received the federal go-ahead for the test of a therapy for amyotrophic lateral sclerosis, commonly known as Lou Gehrig's disease. Approval came after a 4,600-page application was submitted.

Research leading to the trial has been heavily funded by California's $3 billion stem cell agency. About $17 million has been awarded to Svendsen related to the project, which is tackling what is a truly frightful affliction.

As Kevin  McCormack, senior communications director for the stem cell agency, put it this morning in an item on the agency's blog:

"People with ALS lose the ability to speak, eat, move and finally, breathe. The average life expectancy after diagnosis is just 3 – 4 years. It’s considered an orphan disease because it affects only around 30,000 people in the US; but even with those relatively low numbers that means that every 90 minutes someone in the US is diagnosed with ALS, and every 90 minutes someone in the US dies of ALS."

Normally in clinical trials, a treatment is tested on two groups of patient. One group receives the treatment. The other, control group does not,. McCormack explained how Svendsen's trial will work.

"In this clinical trial the patients will serve as their own control group. Previous studies have shown that the rate of deterioration of muscle movement in the legs of a person with ALS is the same for both legs. So Svendsen and his team will inject specially engineered stem cells into a portion of the spine that controls movement on just one side of the body. Neither the patient nor the physician will know which side has received the cells. This enables the researchers to determine if the treated leg is deteriorating at a slower rate than the untreated leg."

The agency, formally known as the California Institute for Regenerative Medicine (CIRM), quoted its chairman Jonathan Thomas in news release as saying,

“The disease affects around 30,000 people in the US, too small a number to make it economically viable for many companies to develop a treatment. Fortunately, the people of California created CIRM to get around problems like that. Our goal is not to make money. Our goal is to save lives."

Cedars said in its press release:

"The stem cell implantations for ALS patients involved in the clinical trial could begin by the end of the year, Svendsen said. Participants will come from the ALS Clinic at Cedars-Sinai, and the trial will be led by Robert Baloh, MD, PhD, and Peggy Allred, PT, DPT. The neurosurgical team will be led by J. Patrick Johnson, MD, MS."

Patients interested in the trial should call Cedars at 310-423-1791.

QuintilesIMS Driving $30 Million, California, Stem-Cell Pitching Machine

(Editor's note: The following article by yours truly appeared in The Sacramento Bee yesterday afternoon.j

BY DAVID JENSEN

Special to The Bee

The California stem cell agency on Wednesday completed creation of a $30 million effort to dramatically speed approval of stem cell therapies and establish the Golden State globally in the much-heralded regenerative medicine field.

Dubbed the “pitching machine,” the two-part program is designed to pick up where basic stem cell research leaves off and to accelerate it through the all-important clinical trials involving humans. Such trials are required prior to widespread use of a therapy by the public and generally take years.

With no debate, no questions and no discussion Wednesday, the governing board of the stem cell agency unanimously approved a $15 million award to QuintilesIMS in San Diego to help move basic research into clinical trials. The effective decision, however, was made Oct. 4 during a closed-door meeting of the agency’s scientific reviewers, who gave the proposal a score of 89 out of 100.

The other half of the pitching machine was an additional $15 million award to Quintiles, which formally began operations this month. Quintiles is a publicly traded, multinational firm based in Durham, N.C., that deals with “information and technology solutions” in health care.

C. Randal Mills, president of the $3 billion stem cell agency officially known as the California Institute for Regenerative Medicine, said the pitching machine is likely to be the most significant achievement of the state’s 12-year-old research effort.

CIRM’s contracts with Quintiles call for the $30 million to be spent in California.

California voters created the state’s stem cell agency in 2004 following a ballot initiative in which voters were told that stem cell cures were nearly at hand. The agency has yet to finance research that has produced a therapy that is available for widespread use.

Quintiles’ responsibilities will include pharmacology and toxicology studies along with manufacturing stem cell and gene-modified stem cell products. The company will also provide clinical trial operations and management services as well as data management, and biostatistical and analytical services.

CIRM’s contracts with Quintiles are for five years. The effort will also feed into the agency’s Alpha Clinics, a $34 million program to intensify focus on stem cell treatments and to contribute to California’s global position in the stem cell field.

The agency said Wednesday’s action will create “the first center in the world designed specifically to overcome the unique challenge of manufacturing, safety testing and other activities needed to successfully apply” to start a stem cell clinical trial. One clinical trial that launched in 2010 required submission of 22,000 pages of information to the FDA.

CIRM said Quintiles’ expertise will create “a standardized, uniform approach that best meets the needs of the FDA, making it easier for the agency to evaluate projects in a timely manner.”

Mills said that with the $30 million Quintiles deal, “we are doing a lot more than just funding research. We have created an entire infrastructure, unique to California, that will help us increase the volume, speed and quality of projects moving into clinical trials.”

CIRM is involved in 19 active clinical trials. It is projecting its participation in about 50 more before 2020, when its funding is scheduled to run out. No additional source of funding has been secured.

(Editor's note: On Oct. 21, the agency said its list of active clinical trials had now reached 22. The agency's web page on the list of clinical trials should be updated soon. )

Read more here: http://www.sacbee.com/news/local/article109286937.html#storylink=cpy

From California to Spain: Growing Human Organs in Pigs

Juan Carlos Izpisúa Belmonte in Murcia, Spain, in 2015
El Mundo photo

The ongoing tale of pigs, people and their organs moved along during the weekend with a fresh chapter about a Spaniard and the Salk Institute in La Jolla, Ca.

Reporter Bradley Fikes wrote a lengthy piece in the San Diego Union-Tribune dealing with Juan Carlos Izpisúa Belmonte and his quest to grow human organs in pigs.

Izpisúa Belmonte has a lab at Salk and another in Spain. Fikes reported that the researcher received a $2.5 million award from the National Institutes of Health last week "to advance his research with monkey cells implanted into pig embryos."

Fikes wrote,

"Since monkeys are biologically similar to humans, analysis of pig-monkey chimeras should yield insights that can be applied to eventual production of human organs, he said. And unlike mice, pigs are large enough to grow usable human organs."

In Spain, Fikes said, Izpisua Belmonte is forging ahead at the same time with human-pig work.

The research is touchy for obvious reasons. But Fikes wrote that "the shortage of organs that causes nearly two dozen Americans — and many others around the world — to die each day while awaiting a transplant."

Izpisúa Belmonte is making progress, according to the newspaper report. Fikes wrote,

"After years of experiments, in 2015 his team reported success in coaxing a newly identified type of human stem cell to not only live in mouse embryos, but also integrate into the embryos’ structure. Those embryos weren’t allowed to develop further because of U.S. regulations."

Izpisúa Belmonte has received $6.5 million in three awards from the California stem cell agency, but none of those grants are currently active.  

Trimming Time on Stem Cell Therapies -- A $30 Million Push in the Golden State

CIRM graphic and text on its pitching machine, consisting of the translating
and accelerating centers. Discovery is basic research. 

Highlights
Application scored at 89
Dramatic reductions in time expected
Unusual 'trinity' support

California's stem cell agency next week is set to approve the second part of a $30 million "pitching machine" aimed at accelerating stem cell research and translating it into therapies that can save people's lives.

An as yet-to-be-identified organization will receive $15 million under the proposal (INFR2-09298) to be considered publicly by the full board of the California Institute for Regenerative Medicine (CIRM), as the Oakland-based state agency is formally known.

The plan has already been enthusiastically endorsed by CIRM's out-of-state scientific reviewers who gave it a score of 89 out of 100 in a closed-door session, according to a CIRM summary of the review. The CIRM board almost never overturns a decision by its reviewers.

A competing proposal (INFR2-09233), also considered behind closed doors, was rejected by reviewers. They gave it a score of less than 60, declaring that the application did not focus on the agency's objectives but rather on the unidentified applicant's proprietary technology.

The "pitching machine" description came from Randy Mills, president of the stem cell agency, who last December told the CIRM board last December that the agency should dramatically reduce the number of years it takes for a stem cell therapy to reach patients.

CIRM photo and text

One-half of the machine -- the accelerating center -- involves a $15 million contract with QuintilesIMS.  Last week, the company formally kicked off its new operations on behalf of CIRM in
San Diego. Speaking at the ceremonies for the opening, Mills said the intent was to create "a center for the world’s most brilliant researchers and innovators in cell therapy that gives them the tools they need to successfully navigate this regulatory system."

The agency said Quintiles will provide support and management services that scientists need to boost the chances that their clinical trials will be successful. Conventional clinical trials can have a 90 percent failure rate. The presumption is that stem cell clinical trials, which are relatively new, are likely to have a higher failure rate. 

The $15 million award next week will create a translating center to work with the accelerating center being run by Quintiles.

In December, Mills said,

"There's a lot of opportunity in this translational phase for us to go after. We can literally cut this phase in half. So the research centers are excited about it, and the FDA was excited about it, and I was excited about it. And that's a very, very unusual trinity to have." 

CIRM said in the review summary,

"Our ultimate goal is to empower the translating center and other elements of CIRM infrastructure to become the premier enabler of cell based therapies to patients in California and worldwide."

The winner of the translating center award will have to start work by early December under the terms of the award. 

Next week's one-hour board meeting will be held telephonically with locations from which the public can participate in Oakland, San Diego, Napa, Fresno, Santa Barbara, Los Gatos, Sacramento, Irvine and San Francisco. The session will be audiocast online and via an 800 number. Addresses and directions can be found on the agenda.

The National Curse of Not-So-Special Days: Stem Cells, Briskets, Fossils and Free Thought

One of the great abominations of our time -- at least in the view of this curmudgeonly writer -- is the nearly endless list of "special days" that seem to parade without stop throughout the year.

I take that back. The list is not nearly endless. A web site called Track Maven has counted something like 2,300 "special" or "national" days. And -- most importantly -- the list does not include today, Oct. 12, as Stem Cell Awareness Day.

This year, according to the quasi-official list, today, Oct. 12, is actually limited to marking the following occasions: National Free Thought Day, National Farmer’s Day, National Gumbo Day, National Fossil Day (Wednesday of second full week in October), National Emergency Nurse’s Day (second Wednesday in October),  National Bring-Your-Teddy Bear-to-Work/School Day (second Wednesday in October) and National Stop Bullying Day (second Wednesday in October).

Stem cells are quite clearly missing from the entire Track Maven list. There is a National Brisket Day (May 28), National Cabbage Day (Feb. 17),  National Public Sleeping Day (Feb. 28), National Absinthe Day (March 5) and National Get-Over-It Day (March 9). But definitely no stem cell day.

So why is the California Stem Cell Report writing about this when there are so many more important things to discuss? Because California's $3 billion stem cell agency conjured up its Stem Cell Awareness Day a few years back and can't seem to shake loose of the concept.

The reality of these not-so-special days is that they originate as a feeble tool of public relations practitioners to appear to gin up some attention for the clients and pad out an invoice. The most effective thing the special days do is fill the mail boxes of the running dogs of the media, who pitch them in the trash without even opening the envelope or the email.

That said, UC Davis stem cell researcher Paul Knoepfler bit on the ploy. He actually put together a useful overview on his blog of the state of the stem cell arena, albeit tilted toward the optimistic.

Meanwhile, today this curmudgeon is going to celebrate National Grouch Day, which is supposed to be on this Saturday but is going to be extended this year to a four-day holiday by unanimous consent.

(Late-breaking development: As per my usual practice with organizations, I notified Track Maven that it was mentioned in an item today on the California Stem Cell Report. Here is their response, and Stem Cell Awareness Day is now officially quasi-official: "Thanks for bringing National Stem Cell Awareness Day to our attention. You'll see I've updated our post to include it.  Appreciate the feedback.  Warmly, Kara")

A Half Full Stem Cell Cocktail on Twitter

From a Twitter feed today

It was an interesting juxtaposition today on Twitter -- a vision of stem cell hope vs. a reality check.
The apparent contradiction is not uncommon in health science news.

It is a variation of the glass half-full or half-empty expression. But the stakes are not trivial. They involve deep emotions and the finances of the patients who face decades of impairment and death.

The perspectives also involve the mindsets of researchers and entities such as the $3 billion California stem cell agency. It has been wrestling for 12 years with the problem of producing a viable stem cell therapy for any sort of affliction. Its funds could well run out -- as expected in about three years -- with no cure to demonstrate for California voters who created the program in 2004.

Should the agency and researchers surrender because the task is enormous and is likely not to bear real fruit during their lifetimes? Should they move on -- if they could -- to something that would provide a more immediate, major public health benefit.

Can or should taxpayers support what some might call dreamy scientific aspirations while the state could use the billions to improve education and daily medical care for the poor?

Some may be able to come up with firm, black-and-white answers to these sort of policy and personal -- at least for researchers -- questions. This writer cannot.

As for the agency, its funds are legally locked for stem cell research or something akin to it. All the agency can do is spend the money well in that area -- a restriction approved by voters in the ballot initiative process.

Meantime, the public is hit with contradictory messages, becomes cynical and less ready to back research. All part of the challenge that faces patient advocates, researchers and drug companies today.

'Hands Off My Cells' -- Reaction to Proposals to Change FDA Stem Cell Research Rules

A California scientist has plunged into the jungle of 4,000-plus comments dealing with the federal government's proposal to change regulation of stem cell research and has discovered an intense sense of ownership on the part of many. 

Paul Knoepfler of UC Davis yesterday wrote on his blog,

"In fact more than 700 use the exact same phrase 'My cells are MY cells' and it looks like hundreds more comments have the exact same or similar language is used in more extensive forms. 'My cells are my property.'  'My cells are mine.'" 

In all, Knoepfler said that the Food and Drug Administration(FDA) had received 4,251 comments by the time the comment period closed. The comments showed a clearly organized effort by one segment of the public. He said the general sense of many was:

"Keep your hands off my cells!"

Knoepfler wrote,

"It would seem the point is that these particular commenters believe that cells taken from their bodies should not be regulated as drugs under any circumstances.

"Everyone is of course entitled to their own opinion, but cells can be drugs if they are changed or used in ways that are not homologous because these factors make them have higher risk to patients. To ask for cells to never be regulated as drugs is asking for chaos and many harms to patients, but people may not realize that."

California's $3 billion stem cell agency is among those seeking changes in the FDA guidelines. The FDA has not set a public timetable for action on new rules, which Knoepfler and others have said are needed to deal with "an out-of-control, direct-to-consumer stem cell clinic industry."

Knoepfler surveyed the industry earlier this year and reported nearly 600 unregulated clinics operating nationwide. It was the first time that the size of the industry has been documented.++

Correction

The Semma-Melton diabetes item on Sept. 29, 2016, contained an inaccurate and incomplete description of the roles of institutions involved in the work being funded by the California stem cell agency. The item has been corrected. Here is the now accurate paragraph in question.

"Peter Butler, chief of Endocrinology, Diabetes and Hypertension at UCLA, will be dealing with patient selection. Dhruv Sareen of the Induced Pluripotent Stem Cell Core Facility at Cedars-Sinai will direct derivation and analysis of pluripotent stem cells from each patient’s blood. The cells will be transferred to the City of Hope for manufacture of products for clinical trials."

The $50 Million, Semma-Melton Quest: Looking for a Cure for Diabetes

An eminent Harvard stem cell researcher who is searching for a cure for an affliction that plagues 29 million Americans stood on a San Francisco stage this week and spoke of "things we don't understand."

Doug Melton, photo Harvard Gazette/B.D. Colen

The scientist is Doug Melton, who is on a deeply personal quest for a cure for diabetes. Both of his children have the disease. And the state of California is helping out on his search with $5 million.

The occasion for Melton's remarks was the presentation of the Ogawa-Yamanaka Stem Cell Prize, a $150,000 award for his work in cellular reprogramming.

Here is how Hannah Robbins of the Harvard Gazette described the results of Melton's research:

"As a pioneer in programming insulin-producing beta cells from stem cells, Melton’s lab can now generate therapeutic quantities of functional, stem cell-derived beta cells, which Melton hopes will someday soon replace the life-saving yet painful daily insulin injections for diabetics."

The $5 million from California is a grant made last March by the state's $3 billion stem cell agency, formally known as the California Institute for Regenerative Medicine (CIRM).

The cash is going to a firm in Cambridge, Ma., called Semma Therapeutics, Inc., which Melton co-founded and which is named after his two children, Sam and Emma. Melton now serves on the firm's board of directors. The business is only two years old, but has raised roughly $50 million to translate Melton's work into actual treatments.

His grant application to CIRM in March was titled simply "Personalized Cell Therapy for Diabetes." The proposal (application number TRAN1-08561) received a score of 90 out of 100 from the agency's scientific reviewers who are from out-of-state. A summary of the closed-door review said the proposal was "strong, well-­designed, feasible. and high impact." The research "has excellent product development plans and great regulatory support," reviewers said.

The stem cell agency is limited to funding only work that is done in California. Semma announced earlier this month that it has set up arrangements with UCLA, Cedars-Sinai and the City of Hope in the Los Angeles area to generate "suitable clinical grade" cells from patients and "to establish a path leading to the transplantation of these cells back into patients in a clinical trial."

Peter Butler, chief of Endocrinology, Diabetes and Hypertension at UCLA, will be dealing with patient selection. Dhruv Sareen of the Induced Pluripotent Stem Cell Core Facility at Cedars-Sinai will direct derivation and analysis of pluripotent stem cells from each patient’s blood. The cells will be transferred to the City of Hope for manufacture of products for clinical trials.

Overseeing the entire project is Felicia Pagliuca, principal investigator on the CIRM grant. She is also scientific co-founder of the firm, the vice president of Cell Biology Research and Development and a lead on the original research in Melton's lab.

Felicia Pagliuca and Robert Millman
 photo Boston Globe/Dina Rudick

The financial backers are led by MPM, a venture capital firm with offices in South San Francisco and Cambridge, Mass. Robert Millman, formerly of MPM, is CEO of Semma. Other investors include Medtronic, Novartis, Fidelity Biosciences, Arch Venture Partners and the Juvenile Diabetes Foundation.

Semma is still hiring and has openings listed for five positions on its web site, ranging from scientists to a director of device development and manufacturing.

Here is a video recording of the award ceremony in which Melton discusses his research and "the things we don't understand" in the science.

(Editor's note: An earlier version of this story contained an inaccurate description of the roles of Cedars-Sinai and the City of Hope involving the CIRM-funded work.) 

A Nearly Three-Decade-Long Stem Cell Tale in California

Kris Boesen, patient in Asterias trial -- photo from CIRM

One could say that the latest news involving human embryonic stem cell research and the California stem cell agency stretches back nearly 27 years. 

It was then -- in 1990 -- that Geron, Inc., was incorporated by Michael West who began what eventually turned into a quest for a stem cell therapy for treatment of spinal cord injury.

Yesterday, the Golden State's stem cell research effort carried an item on its blog, The Stem Cellar, dealing with the latest chapter in that quest. The headline said,

"Full Steam Ahead: First Patient is Dosed in Expanded CIRM Spinal Cord Injury Trial"

In the piece, Karen Ring, website manager for the stem cell agency, celebrated the latest patient news concerning the trial which is backed by a Menlo Park, Ca., company called Asterias Biotherapeutics.  Ring said,  

"Inspiring stories like that of Kris Boesen, who was the first AIS-A patient to get 10 million cells in the Asterias trial and now has regained the use of his arms and legs, are the reason why CIRM exists and why we are working so hard to fund promising clinical trials. If we can develop even one stem cell therapy that gives patients back their life, then our efforts here at CIRM will be worthwhile."

Michael West, Biotime photo

The tale of  Michael West, his research and his companies is long and convoluted. The short version is that he is now co-CEO of Biotime, Inc., of Alameda, Ca., which spawned in 2012 Asterias Biotherapeutics, Inc., of  Menlo Park, Ca. 

Geron is out of the business of human embryonic stem cell research. In 2011, it abandoned the nation's first-ever hESC trial for financial reasons. The effort was sold to Asterias in 2013. In 2014, the $3 billion California stem cell agency jumped in with $14.3 million for Asterias. 

 Asterias' stock closed at $4.56 yesterday. Its 52-week high stood at $5.75. Its 52-week low was $2.30. 

A Look at Stem Cell Treatments in Mexico with Ties to California

First part of KBPS' stem cell treatment series

A San Diego television station this week aired a solid series exploring the world of unproven stem cell treatments, including therapies in Mexico and involving a California company.

The work was produced on KBPS by David Wagner and ran as a two-part series(see image above). UC Davis researcher Paul Knoepfler, who earlier this year documented the existent of 570 unregulated stem cell clinics nationally, described Wagner's work as "an important new piece...on for-profit investigational stem cell treatments."

Companies mentioned by Wagner included Stemedica Cell Technologies, Inc., Global Stem Cell Health, Inc., both in the San Diego area, and Hospital Angeles in Tijuana, just south of San Diego in Mexico.

Stemedica is the firm connected to nationally reported treatments of the late hockey great Gordie Howe and former professional quarterbacks John Brodie and Bart Starr. (See here and here.)

California Stem Cell Research: $639 Million Left in the Golden State's "Big Bucket"

Randy Mills, head of the California stem cell agency, calls the cash
available for research awards "the big bucket." CIRM graphic

California's ambitious stem cell research agency has $639 million remaining in uncommitted cash as it continues to seek therapies and perhaps cures for afflictions ranging from spinal injury to diabetes.

Randy Mills, president of the 12-year-old program, announced the figure today at a San Diego meeting of the agency's governing board. He also said the program, formally known as the California Institute for Regenerative Medicine (CIRM), is expected to run out of funds in June 2020.

CIRM is financed by money that the state borrows -- $3 billion in bonds approved by California voters in 2004. Using borrowed money also leads to interest costs, increasing the ultimate taxpayer expense to roughly $6 billion. However, that estimate dates back to 2004 and no fresher figure has been produced by the state.

Mills reminded his directors that the agency is allowed only $180 million for operational expenses over the life of the program. About $61 million remains for those expenses.The current annual operational budget of $16 million pays for the roughly 55-person staff  to oversee $900 million in active awards and to make new awards.

The agency has handed out $2.1 billion over its life but many of those research efforts are finished. No therapies have been developed for widespread use.

The agency also has a "return rate" of 3 percent to 5 percent on awards.  The "return" is cash that is left over from an award or that is returned to the agency when a researcher does not meet research milestones, and the award is cancelled.  The returned cash is running at about $40 million annually.

Just what will happen to the agency come 2020 is unclear. Mills today said he and his team are monitoring the funds carefully so that awards and the operational funds run out at the same time.

The agency also may begin lose key staff as time passes and no plan for 2020 emerges, a possibility that Mills has publicly discussed, albeit briefly.

As for future funding, thoughts about another bond issue, public-private partnerships and more legislative funding have been bandied about. But nothing concrete has yet emerged.

Operational funds are described as "the little bucket" by Mills. CIRM graphic

Time to Crank Up the Stem Cell Comment Machine and Weigh in on Proposed Federal Regulation

Folks interested in seeing more or less or different federal regulation of stem cell treatments and research have until Sept. 27 to file their arguments with the Food and Drug Administration (FDA) following two days of public hearings earlier this week. 

Patients, researchers and representatives of regulated and unregulated companies turned out personally Monday and Tuesday for FDA hearings on its new proposals. Witnesses included Randy Mills, president of the California stem cell agency. Questions were asked by an FDA panel but no conclusions reached. 

For those who missed the marathon sessions, they are recorded and are available online. One big advantage of watching them in a recorded format is the ability to skip through the content rapidly instead of having to sit and wait for the whole process to unwind. The first day can be found here and the second here. 

The live, online Internet broadcast chalked up about 770 views on the first day. On the second day, only about 550 were reported.  The numbers seem low to this writer based on the intense, emotional interest on the part of many patients. Industry also does not seem overly interested despite forecasts of the billions of dollars to be made from regenerative medicine, which may say something about the likelihood of handsome profits.

Only 15 written comments have been filed so far, mostly from patients. That number is likely to increase as industry and academia weigh in with more details. 

The FDA has not released a timetable for action which could affect many of the 570 unregulated stem cell clinics operating across the country. 

The hearings generated almost no media coverage. However, the Washington Post and Stat published good pieces (see here and here) that provided an overview of the issues ahead of this week's hearing. You can find coverage by the California Stem Cell Report here, here, here and here.

California Healthline carried a piece Monday with comments from Mills that basically summarized his presentation to the FDA. Today, the agency's blog carried an item with the text of the Healthline comments. The item by Kevin McCormack, senior director of communications, also said that Mills believes that "the rules the FDA is proposing will not fix the problem, and may even make it worse."

UC Davis stem cell researcher Paul Knoepfler summed up the second day of the hearings in a blog item yesterday. He quoted Leigh Turner, a University of Minnesota bioethicist, as saying, 

“The out-of-control marketplace for stem cell interventions needs effective regulatory oversight. I therefore hope the draft guidances are more than stage props and this hearing is more than public theater. When patient safety and public health are at stake, the FDA must do more than function as a paper tiger. It is time for action.”

Here is a link to the key Federal Register document laying out the process. Here is a link to the site for filing a comment electronically.