Showing posts with label cirm 2.0. Show all posts
Showing posts with label cirm 2.0. Show all posts

Thursday, July 27, 2017

An FDA Signal: Good News for California's Stem Cell Agency's Search for Therapies

The California stem cell agency this week highlighted a couple of milestones that it suggests may be creating a trend towards wider application of its research.

The springboard was an announcement that the Food and Drug Administration (FDA) had granted a "rare pediatric disease designation" to a therapy that the agency has backed with  nearly $52 million.

The FDA action comes as the agency is in what some call its "last stage." The agency, formally known as the California Institute for Regenerative Medicine (CIRM), expects to run out of cash for new awards in about three years. No additional funding appears readily available for the agency, which was created by voters in 2004. It has yet to fulfill voter expectations that it would produce a stem cell therapy that is widely available.

The agency this week, however, touted the FDA designation, which involves a treatment for what is commonly known as "bubble baby syndrome." The treatment is called OTL-101 and is being developed by Orchard Therapeutics Ltd, which is based in the United Kingdom The firm is working with Donald Kohn of UCLA, who has been researching in the area for decades.

Writing on the $3 billion agency's blog, The Stem Cellar, Kevin McCormack, senior director for communications, said,
"The treatment) involves taking the patient’s own blood stem cells, genetically modifying them to correct the SCID mutation, and then returning the cells to the patient. Those modified cells create a new blood supply, and repair the child’s immune system."
He wrote,
"The importance of the rare pediatric disease designation is that it gives the company certain incentives for the therapy’s development, including priority review by the FDA. That means if it continues to show it is safe and effective it may have a faster route to being made more widely available to children in need."
McCormack continued,
"This is the second time in less than two weeks that a CIRM-funded therapy has been awarded rare pediatric disease designation. Earlier this month Capricor Therapeutics was given that status for its treatment for Duchenne muscular dystrophy. 
"Two other CIRM-funded clinical trials – Humacyte and jCyte – have been given regenerative medicine advanced therapy designation (RMAT) by the FDA. This makes them eligible for earlier and faster interactions with the FDA, and also means they may be able to apply for priority review and faster approval. 
"All these are encouraging signs for a couple of reasons. It suggests that the therapies are showing real promise in clinical trials. And it shows that the FDA is taking steps to encourage those therapies to advance as quickly – and safely of course – as possible."

McCormack added, however,
"Getting these designations is, of course, no guarantee the therapies will ultimately prove to be successful. But if they are, creating faster pathways means they can get to patients, the people who really need them, at a much faster pace."

Tuesday, May 02, 2017

California's $3 Billion Stem Cell Agency Loses CEO Randy Mills

C. Randal Mills
CIRM photo
In a surprise move, the president of California's $3 billion stem cell research effort this morning announced his resignation as the program enters what some are calling its "final test."

C. Randal Mills said that he has taken a position as president of the National Marrow Donor Program in Minneapolis, Minn. He said he will leave the California Institute for Regenerative Medicine (CIRM), as the stem cell agency is formally known, at the end of June.

Maria Millan, CIRM photo
Maria Millan, vice president of therapeutics, will become interim president of the 12-year-old agency in July. The governing board of the agency plans a meeting of its search committee in July to consider its options regarding the appointment of a permanent president for CIRM, which expects to run out of cash for new awards in three years.

Just last week, the prestigious journal Nature described the Oakland-based agency as entering its "final test" and "last stage."

Mills, 45, joined the agency almost exactly three years ago and promptly launched a more focused effort than previously existed to fulfill the promises and expectations created by the 2004 ballot initiative campaign that created the agency.

Jonathan Thomas, CIRM chairman and who recruited Mills, said in a press release,
“CIRM has experienced a remarkable transformation since Randy’s arrival. He has taken the agency to a new level by developing and implementing a bold strategic plan, the results of which include an 82 percent reduction in approval time, a 3-fold increase in the number of clinical trials, and a 65 percent reduction in the time it takes to enroll those trials.

"CIRM’s mission is to accelerate stem cell treatments to patients with unmet medical needs, and under Randy’s leadership, CIRM has done just that. The opportunity for Randy to lead a tremendously important organization such as NMDP is consistent with the values he demonstrated at CIRM, which put the well-being of patients above all else."
In an interview with the California Stem Cell Report, Mills said the offer to lead the donoro program "came out of the blue." He said the opportunity to join the world's largest bone marrow effort was unique. The organization, he said "does not do anything that doesn't save lives."

Mills said in the interview that Millan was an obvious choice to succeed him on a permanent basis. In the agency's press release, Mills said,
"What this team has been able to accomplish in that time is remarkable by any objective measure and I thank them for their 'All In' attitude and effort. As a trailblazing institute, CIRM is setting new highs in productivity and efficiency and will continue to deliver on its mission under the leadership of Dr. Millan."
Millan, a physician, has been with the agency since 2012, joining it from StemCells, Inc., where she was acting medical officer and vice president. Prior to that, she was an associate professor of transplant surgery for eight years at Stanford University.

Thomas said,
“One of the most valuable contributions Randy has made at CIRM is the strength of the team he has assembled. Maria is exceptionally well qualified and completely engaged in the operations of CIRM, having worked with Randy as member of the leadership team that created and is executing the strategic plan. With her leadership, we are well positioned for continued success,
Millan was paid $281,000 last year, according to The Sacramento Bee's state worker database. Mills was paid $573,000.

Mills' departure comes as supporters of the agency are concerned about whether its work will effectively end in 2020. However, its first chairman, Bob Klein, is talking about asking California voters for another $5 billion. Klein also led the $34 million ballot campaign.

Klein's organization, Americans for Cures, is planning to conduct a poll this fall to determine the level of public support for CIRM. He has said that if support is in the 70 percent range he would mount a bond issue in 2018. Otherwise, he might try in 2020, a presidential election year, with a larger voter turnout.

The organization that Mills is joining is "the world's largest the world's largest registry of unrelated adult donors and umbilical cord blood (UCB) units," according to Nature. It has been heavily funded by the federal government with an annual budget of $383 million, according to 2014 figures, and has about 1,000 employees. CIRM currently has 46 employees and has ranged up into the middle 50s.

Accompanying Mills in the move to Minneapolis will be his wife, Anna, and two children, Elise, 13, and Chase, 10.

(The agency posted an item on its blog, The Stem Cellar, dealing with Mills' resignation shortly after this item was posted.)

Friday, March 10, 2017

California's Alpha Clinics: A Unique, Stem Cell 'Clincher' for Patients, Doctors and Researchers

California's $3 billion stem cell agency this week explored the status of its ambitious Alpha Clinic network, touting its impact and progress over the last two years involving hundreds of patients.

The network, which now has bases only in Southern California, is slated to add two more this year in what will be a $40 million investment by the state of California. It is likely to be a major part of the legacy of the California Institute of Regenerative Medicine or CIRM, as the Oakland-based stem cell agency is formally known. The agency runs out of cash for new awards in 2020.

Geoff Lomax, senior officer for CIRM's strategic initiatives, yesterday wrote about the Alpha network in an item on the agency's blog, The Stem Cellar.

He noted the state’s position as a world leader in stem cell research, helped mightily by the efforts of the 12-year-old agency. He wrote,

“But the real clincher is that California has something that no one else has: a network of medical centers dedicated to stem cell-based clinical trials for patients.”

Lomax, who was one of the first employees at the agency in 2005, said,

“So far, hundreds of patients have been treated at our Alpha Clinics. These top-notch medical centers use CIRM-funding to build teams specialized in overseeing stem cell trials. These teams include patient navigators who provided in-depth information about clinical trials to prospective patients and support them during their treatment. They also include pharmacists who work with patients’ cells or manufactured stem cell-products before the therapies are given to patients. And lastly, let’s not forget the doctors and nurses that are specially trained in the delivery of stem cell therapies to patients.

“The Alpha Clinics Network also offers resources and tools for clinical trial sponsors, the people responsible for conducting the trials. These include patient education and recruitment tools and access to over 20 million patients in California to support successful recruitment. And because the different clinical trial sites are in the same network, sponsors can benefit from sharing the same approval measures for a single trial at multiple sites….

“This collective expertise has resulted in a 3-fold (from 12 to 36 – two trials are being conducted at two sites) increase in the number of stem cell clinical trials at the Alpha Clinic sites since the Network’s inception.”

The agency is seeking applications to open two more Alpha Clinics this year, funding them with $8 million each. One of the criteria is geographic diversity. The application deadline is May 15.

In just 13 days, folks interested in Alpha Clinics can take part in a one-day symposium at the City of Hope in the Los Angeles area, which is one of the current Alpha sites. Advance registration is requested for the free event.

The other Alpha sites are at UC San Diego and UCLA/UC Irvine.

Thursday, March 02, 2017

'Pressure testing' a $150 Million California Plan to Lure Business into Development of Stem Cell Therapies

The California stem cell agency's far-reaching plan to crate a $150 million, public-private partnership to speed development of stem cell therapies remains on hold as the agency looks for ways to lure in private enterprises.

In an interview last week with the California Stem Cell Report, Randy Mills, president of the $3 billion agency, said he had nothing fresh to report on the project, which did not draw any eligible applicants last fall.

Mills said his team is "pressure testing (the project) to make sure people really understand the terms."

In December, Mills said that the firms that responded to the request for applications in October were seeking to make a "better deal" than the agency had offered. Under the proposal, a new company would be created to develop therapies. It would be backed by a $75 million state loan (discounted to 50 percent payback)  with a matching $75 million coming from a successful applicant. The company would have the pick of agency research that did not already have a commercial partner.

Mills said that the unusual nature of the proposal posed challenges for the company and the agency.

In the interview last week, Mills said the agency is seeking to determine if having more time to prepare proposals will trigger more applications. Another factor is whether the terms do not meet the needs of potential applicants.

Thursday, December 22, 2016

California Stem Cell Agency Says Companies Seeking "Better Deal" in Unique, $150 Million Plan

Highlights
Five responses to plan
Application process is not a negotiation
Protection of state taxpayers paramount
More talks with companies planned

The president of the California stem cell agency, Randy Mills, yesterday said that the firms that responded to an ambitious proposal to create a $150 million public/private partnership were seeking to make a "better deal" than the agency had offered.

Mills said that the agency was "not going to give away something that is not in the best interests of the people of California."

Randy Mills, FDA photo
Mills was responding to questions raised earlier this week as a result of a report on this web site that
the proposal has hit a significant snag. The plan is aimed at creating a unique enterprise to speed development of stem cell therapies and to help establish California as a global stem cell powerhouse. The new company would be backed by a $75 million state loan (discounted to 50 percent payback)  with a matching $75 million coming from a successful applicant. The company would have the pick of agency research that did not already have a commercial partner.

The deadline for applications was Oct. 31. Up until yesterday, the agency had not even disclosed the number of responses to the request for applications(RFA). Nor had it gone beyond vague expressions of the issues troubling the proposal.

In a telephone interview with the California Stem Cell Report, Mills said that five responses were received on Oct. 31. But he said none were eligible for consideration because they did not meet the requirements of the RFA. He said the responses indicated that the companies viewed the application process as a "negotiation." Mills said "all kinds of terms" were proposed that were "different than in the RFA." He said,
"We put forward what we thought was a very good deal. The heads of the companies wanted to make a better deal."
Mills added,
"The deal is as good as the deal is going to get."
He said the $3 billion agency, known formally as the California Institute for Regenerative Medicine (CIRM), has to be willing to walk away if the deal is not appropriate.  He said the agency had a fiscal responsibility to taxpayers. "My investors are the people of California," Mills said.

Mills said, however, he was going to discuss the proposal further with those who responded to determine whether it was a matter of "terms or time." He said the proposal was innovative and unusual, posing challenges for both the companies and the agency.

Mills comments came as he was responding to questions raised by a reader of the California Stem Cell Report, Ed Snively, of El Centro, Ca. Snively is a longtime participant in local affairs in his area in Imperial County and has long followed stem cell agency matters.

He wrote in an email to California Stem Cell Report,
"Thank you, David, for this interesting observation on selective transparency by the agency. The comments by Mills regarding state regulatory compliance and taxpayer procedure acceptance were curious to me. I think Mills owes an explanation of his remarks to taxpayers. If this 'bold' plan violates the terms of the agency contract with the state and stakeholder/taxpayers then Mills needs to explain why that is. What he has done is make me think that something right on the legal edge is going on behind closed doors. I hate that in public agencies."
The California Stem Cell Report emailed the comments to the agency, asking if it would like to respond.

In the subsequent telephone interview, Mills said that he did not want the agency to be perceived as selectively transparent and that he had "no problem" in answering any questions.  He said that if his earlier comments were not clear that it was his fault, and he elaborated on the issues involved.

But under the agency's longstanding rules, it does not disclose the names of applicants nor does it disclose their applications -- only a review summary when they come before the agency's governing board for final action.  However, the terms of contracts with successful applicants are a public record.

Monday, December 19, 2016

Ambitious, $150 Million, California Plan for Stem Cell 'Powerhouse' Stalls

Highlights
$75 million state loan
Pick of stem cell research
Agency vague on problems

The California stem cell agency's bold plan to create a unique, $150 million, public-private company to speed development of stem cell therapies has hit a significant snag, stalling its progress indefinitely.

The agency, however, says it hasn't given up and will try to find solutions to the undisclosed problems.

Under the proposal -- first advanced a year ago -- California would provide a $75 million loan to a partner that would also provide $75 million. The goal would be to create a "powerhouse" that would likely be one of the landmark legacies of the $3 billion agency. The partner would be expected to pay back only 50 percent of the loan plus interest. The new company would also have the pick of the 94 percent of the agency research that doesn't already have a business partner. 

The public-private biotech partnership  -- dubbed ATP3 -- would be the first in state history and the first of such magnitude nationally.

The agency has been working for much of 2016 to recruit applicants and to address potential concerns. The difficulties began to surface last fall at the Oct. 31 deadline for applications. The agency declined to disclose to the California Stem Cell Report even the number of applications it had received. A spokesman said only that the agency was checking to see if they were "eligible."

The chairman of the agency, Jonathan Thomas, went public with slightly more information at last week's meeting of the agency's governing board.

He referred to a "number of applicants" that were involved. He said that issues still exist and that the application(s) that were submitted to the agency will not be given to the agency's reviewers as scheduled. Thomas said the request for applications may extended and some criteria adjusted.

Randy Mills, president of the agency, said later in the meeting that an effort would be made to make the plan "compliant with state requirements and palatable to taxpayers." He described it as an "ongoing challenge."

Mills said,
"We haven’t given up but we haven’t nailed it yet."
No public questions were raised at the meeting by 29-directors of the agency, which is officially known as the California Institute for Regenerative Medicine (CIRM).

It was created 12 years ago by a ballot initiative approved by voters and relies on money borrowed by the state(bonds). The ballot campaign indicated that stem cell therapies were close on the horizon. However, the agency has not developed a therapy for widespread use.

It estimates that it has about $692 million left for awards. The agency's funds are projected to run out in 2020. No additional funding is in sight.

Tuesday, December 13, 2016

Mom to California: Thanks for 'Keeping My Family Complete' with Life-Saving Stem Cell Therapy

CIRM graphic
In an emotion-choked session this morning, the mother of a four-year-old girl thanked California's stem cell agency for saving the life of her daughter.

"Thank you for keeping my family complete," said Alysia Padilla-Vaccaro, her voice cracking as she spoke to the governing board of the $3 billion California Institute for Regenerative Medicine (CIRM), as the agency is formally known.

Her daughter, Evangelina, also whispered a soft "thank you"to the board and CIRM staff at the Oakland meeting. She had suffered from what is known as the "bubble baby syndrome."

Evangelina was one of two persons cured by treatments developed with the help of financing from the stem cell agency, created by voters in 2004 and supported by state bonds.

Brenden Whittaker, 22, was the second person. He was near death twice and lost parts of his lungs and liver as the result of another, rare, immune deficiency disease. He said,
"My experience has truly been life-changing...I hope you continue to push the boundaries and help as many people as you can."
Randy Mills, president of the agency, presented Whittaker and Evangelina to the board during a review of the progress of the agency. He said they were "the first two patients to be cured by CIRM programs."  Mills also introduced two other patients who have been helped by the agency's research: Jake Javier, who suffered a paralyzing spinal cord injury, and Karl Trede, a cancer patient. The agency has not developed a therapy for widespread use.

Mills hailed their courage and the courage of their families for taking part in the risky clinical trials. Mills told the 29-member CIRM board that in pursuit of stem cell cures that the agency had to be "Jake-strong," a term originating with Javier's mother after his injury.

The stem cell agency estimates it has $692 million left for new awards between now and 2020, when it expects to run out of cash. The research budget for next year was approved at $328 million with most of it going for clinical programs. Clinical trials represent the last stage for a proposed therapy before it reaches the market.

The CIRM board has approved a goal of 40 more clinical trials between now and 2020. Currently it has 22 underway. Only one out of 10 conventional treatments that begin trials wind up as commercial products. Often the trial process can take many years even with conventional therapies. No stem cell treatments have yet been approved by the Food and Drug Administration in this country.

Here is more on the patients featured at today's meeting:

Evangelina, of Corona, Ca., was diagnosed shortly after birth with "bubble baby" disease and no functioning immune system. Her blood cells were genetically altered to create a new blood and immune system. The therapy was developed by Donald Kohn of UCLA. CIRM has backed his work, which goes beyond the bubble baby affliction, with nearly $52 million. (See here, here and here.)
CIRM graphic

Whittaker, of Columbus, Ohio, almost died twice as a result of a rare immune system disease. Parts of his lung and liver were removed due to repeated infection. His blood stem cells were genetically modified to create a new blood system and a healthy immune system. The treatment was also developed by Kohn at UCLA.

Javier, 19, of San Ramon, Ca., was paralyzed as the result of a swimming pool accident. He received 10 million stem cells,the first person to have such an injection, and has since regained the use of his arms. His treatment grew out of the trial that Geron Corp. abandoned in 2011. Asterias Therapeutics of Menlo Park, Ca., has continued the work. Between the two companies, CIRM has invested nearly $21 million in the project. Jane Lebkowski has led the research at both companies.

Karl Trede, CIRM graphic
Trede, 70, of San Jose, Ca., lost his vocal cords, removed because of cancer of the throat.  The cancer nonetheless spread but was treated with the "eat me" protein therapy fromStanford University. As a result, his cancer has stopped growing. CIRM invested $40 million in the project, initiated by Irv Weissman of Stanford, who developed the CD47 treatment. It has led to the formation of a new company in Palo Alto called Forty Seven, Inc. (See here for a CIRM item on Trede.)
(For the text of CIRM summaries on the four, see here.)

(Editor's note: The earlier graphics in this item were replaced later with the ones that actually were displayed the day of the meeting. An earlier version also misstated Evangelina's age.)


Monday, December 12, 2016

California's Stem Cell Year: 70 New Projects, 10 New Clinical Trials Plus a 'Stem Cell Pitching Machine'

The California stem cell agency weighed in today with an upbeat prelude to a review of its performance in 2016, declaring it a "very productive year" that is counting 10 new clinical trials.

And Gov. Jerry Brown, in a short note to the agency, said that he looked "forward to its continuing success."

Brown, who is famously careful with words, made his very brief comment in a letter renominating Jonathan Thomas as chairman of the $3 billion agency, formally known as the California Institute for Regenerative Medicine or CIRM.

Karen Ring, website and social media manager for CIRM, had a little more to say in a piece today on the agency's blog, The Stem Cellar. Her comments came on the eve of the CIRM board meeting in Oakland tomorrow, which includes a self-assessment of the state of the 12-year-old research effort. 

Ring noted that the agency is on target to meet its ambitious goal of helping to fund 50 new clinical trials through 2020. The board has backed eight trials so far this year and is virtually certain to add two more tomorrow at a cost of $14.9 million. In all, the agency is currently supporting 22 clinical trials, which are the last stage of research prior to bringing a therapy to market. Trials, however, can take years.

Declaring 2016 a "very productive year," Ring wrote that this year CIRM funded "70 promising stem cell projects ranging from education to discovery, translational and clinical projects."  She said that the eight board-approved trials include potential therapies for muscular dystrophy, kidney disease, primary immune diseases, and multiple types of cancer and blood disorders.

She also singled out a $30 million effort this year that Randy Mills, president of the agency, believes could be its most significant achievement. Mills sometimes calls it a stem cell "pitching machine."

Ring said,
"Collectively called The Stem Cell Center, the goal of this new infrastructure is to increase efficiency and shorten the time it takes to get human stem cell trials up and running."
No other state has mounted such an effort. The agency predicts that it could make California the world leader in the stem cell field, which is predicted to generate hundreds of billions of dollars globally by 2020 by some, perhaps optimistic accounts.

Regarding the two new clinical trials, already approved by the agency's reviewers, Ring said,
"The first trial is testing a stem cell treatment that could improve the outcome of kidney transplants. For normal kidney transplants, the recipient is required to take immunosuppressive drugs to prevent their body from rejecting the donated organ. This clinical trial aims to bypass the need for these drugs, which carry an increased risk of cancer, infection and heart disease, by injecting blood stem cells and other immune cells from the kidney donor into the patient receiving the kidney. You can read more about this proposed trial here.
"The second clinical trial is a stem cell derived therapy to improve vision in patients with a degenerative eye disease called retinitis pigmentosa. This disease destroys the light sensing cells at the back of the eye and has no cure. The trial hopes that by transplanting stem cell derived retinal progenitor cells into the back of the eye, these injected cells will secrete factors that will keep the cells in the eye healthy and possibly improve a patient’s vision. You can read more about this proposed trial here."
Names of the recipient researchers have been withheld by the agency until the board tomorrow ratifies the decisions by its reviewers.

Monday, November 21, 2016

Quartet of Researchers Snagged in Budgeting, Parliamentary Web at $3 Billion California Stem Cell Agency

Highlights
Fiscal discipline at CIRM
The 10 percent solution
A quorum shortage pops up

Four California scientists who are ready to kick off highly rated projects to treat everything from Alzheimer's to rotting jaw bones became tangled last week in a financial and procedural briar patch involving the directors of the $3 billion California stem cell agency.

The basic problem, however, was simple. Money.

The agency had budgeted only $15 million for this latest round of awards last Thursday. But the four applications -- already approved by the agency's reviewers -- totalled $16.6 million. Typically, the agency's full board rubber stamps in public the decisions of its reviewers, who act behind closed doors without disclosing their economic or professional interests. The board has reversed approvals by reviewers on only four occasions out of hundreds of awards over the past 12 years, according to the agency.

Last week, the chairman of the agency, Jonathan Thomas, began the public discussion by declaring that the board should go through the applications one by one and vote on them. When the money ran out, that would finish action on funding for November.

Fiscal discipline was cited as the main reason for such a course.

Steve Juelsgaard 
Wait a minute, said Steve Juelsgaard, a member of the board of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known. He asked for the amount of
funding already being provided for the afflictions targeted by the proposals. If research in a particular area was already heavily supported, perhaps approving another award in that area was not necessary, Juelsgaard reasoned. However, the agency staff could not provide those figures at the time of the meeting.

A lengthy discussion followed involving several scenarios. One would have cut each award by 10 percent but approve all four.  But that could mean that the proposals would be altered from the versions that were approved by the reviewers. (However, the board is not legally required to accept what the reviewers decide.  Under the terms of the ballot initiative that created the agency, the board has the final say, which is part of the justification for not publicly disclosing the economic interests of reviewers.)

Another proposal would have simply increased the funding for the round. That could not be acted on because it required 10 days advance public notice.

The board ultimately approved a Juelsgaard motion to slice roughly 10 percent from each award with the condition that applicants come up with matching funds to bring the total to the level approved by reviewers.

Yadong Huang, Gladstone photo
One applicant, Yadong Huang from the Gladstone Institutes, said, however, that non-profit research organizations were already hard-pressed and could not necessarily come up additional cash. His $5.9 million application (TRAN1-09394) was top-ranked by reviewers and targeted Alzheimer's.

Jill Helms, Linked In photo
Another applicant, Jill Helms, chief scientific officer of Ankasa Regenerative Therapeutics, Inc., of La Jolla, spoke on behalf of the company's application (TRAN1-09270) to target osteonecrosis, an affliction that "causes jaw bones to rot and thigh bones to snap." She urged the board to give priority to applications that already had co-funding. Her $3.7 million application contained a 20 percent co-funding component.

Helms, who is also a Stanford University medical school professor, unsuccessfully asked the CIRM board in 2015 to overturn a negative recommendation by reviewers.

During the two-hour telephonic meeting, the board did approve conditionally two awards under the matching-fund requirement. They were for the Alzheimers proposal and one dealing with sickle cell disease (TRAN1-09292).  The identity of the chief scientist on the sickle cell proposal was not disclosed by the agency under its longstanding policy and tradition within the research field.

Jeff Sheehy, Science photo
The board failed to complete action on the two others because it  lost the quorum that is required to do business legally. That came after a motion by board member Jeff Sheehy to reject one of the four applications failed on a 3-8 vote. Sheehy said another related proposal was already being funded by the agency and that the time to translate the research into a therapy  "would be enormous." The $2.5 million application  (TRAN1-09288) up for consideration last week involved cartilage repair.

Thursday's meeting was being conducted telephonically. After Sheehy lost his motion, he did not respond to telephonic queries from the board. The meeting was nearing its scheduled end at noon. Other board members also failed to respond, and the meeting was adjourned minutes later.

Juelsgaard and some other members said it was important for board members to stick around for the full meetings. Juelsgaard said,
"For gosh sakes, this is something that you signed up to do."
Termination of CIRM board business because of quorum problems regularly occurred some years ago. (See herehere and here.) But since Thomas has been chairman the issue has rarely popped up.

Thomas indicated the board would try to schedule a special telephonic meeting to deal with the four applications. It also has a face-to-face meeting scheduled for Dec. 13 in Oakland. Both meetings legally require 10 days advance notice.

The review summaries on the applications are consolidated in this CIRM document along with their scores and more information.

Tuesday, November 15, 2016

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.)

Monday, November 07, 2016

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.

Wednesday, November 02, 2016

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.

Monday, October 24, 2016

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.

Thursday, October 20, 2016

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

Thursday, October 13, 2016

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.

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.

Highlights
$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.

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