Monday, July 27, 2020

California's Stem Cell Covid Round Ends: Three Clinical Trials, 17 Awards

The California stem cell agency has finished its special round of Covid-19 awards, adding three clinical trials to bring its total to 64 plus 14 other awards totaling in all $5.3 million. 

The final awards were made on Friday in the emergency, fast-track round. However, the agency noted that additional Covid awards are possible through its existing awards process and today issued a "special call" for applications in its Quest awards program.  The deadline is Aug. 31.

The agency said in an email, 
"For this special edition of DISC2, the overall timeline and award amount have been capped at 12 months and $250,000, respectively. The expected outcome, at the end of the award, is a candidate therapeutic, diagnostic, medical device, or tool that can immediately progress to translational stage activities."
Last week's awards of $250,000 each went to Karen Christman at UC San Diego and Lili Yang at UCLA.

Christman hopes to develop a treatment for acute respiratory distress syndrome, the agency said, a life-threatening lung injury that occurs when fluid leaks into the lungs and is prevalent in COVID-19 patients.  Her research involves extracellular matrix hydrogels, a structure that provides support to surrounding cells.

Yang is seeking to use blood stem cells to create invariant natural killer T (iNKT) cells, a powerful type of immune cell with the potential to clear virus infection and mitigate harmful inflammation.

For more details, the agency's review summary for Christman's application (DISC2COVID19-12007 #2 ) can be found here. The summary of Yang's review (DISC2COVID19-12020) can be found here. Yang also sent a letter to the agency board as did Christman.

Quote of the Day

"In science, true hope is clear-eyed and brings a tight focus on the barriers and potential setbacks that exist along the path to desired results." 

-- , in his New Yorker article titled "The Long Game of Coronavirus Research."

Friday, July 17, 2020

Covid Clinical Trial Location Still Missing on $750,000 California Stem Cell Grant

The California stem cell agency stipulates that winners of research awards in its fast-track, Covid-19 round must be ready to start work within a month of approval, but a New Jersey firm that snagged $750,000 three weeks ago has yet to report the location of its California work.

The  firm is Celularity, Inc. Its proposed therapy is backed by Rudi Giuliani, the president's personal lawyer, who has also touted other possible Covid therapies, including one that has been rejected by the Food and Drug Administration.

The $750,000 is intended to finance a clinical trial someplace in California. The stem cell agency funds only California work.

In creating the Covid round, CIRM said award winners must be "ready to start work within 30 days of approval and propose achieving a clear deliverable within six months." It has been 21 days since the Celularity award was approved. 

The California Stem Cell Report has asked the firm repeatedly for the location of the California site but it has not responded with this routine information. The agency itself also has not disclosed the location and defers to the company.  

Celularity updated the information today that it files with the National Institutes of Health on the trial. However, the locations of the trial still did not show any in California. 




Thursday, July 16, 2020

California's $40 Million Stem Cell Genomics Center: Its Fate and Outcomes

California's stem cell agency hit something of a milestone six years ago when it approved $40 million to create a genomics center that was aimed at positioning the state as a global leader in stem cell genomics. 

The round triggered complaints about irregularities, unfairness, score manipulation and the role of its then president, Alan Trounson. The $40 million, at the time the largest single research award by the agency, was ultimately divided three ways and now has been spent. 

The California Stem Cell Report queried the agency this week about the award, its status and results. Here is the response in Q&A format.

Q: How was the $40 million shared and with which institutions?
A: The genomics grant was split into three awards: $22.7M to Stanford (GC1R-06673-A), $13.2M to the Salk Institute (GC1R-06673-B), $4M to UC Santa Cruz (GC1R-06673-C). (The application numbers carry links to the progress reports on the CIRM website.) 

Q: Is there any requirement for the grantees to come up with a plan for continued funding? 
A: There was no requirement for the grantees to come up with a plan for continual funding in the concept RFA.  Stanford and Salk provided co-funding to support the centers during the award period.

Q: If not, what prevents the doors from closing at the genomics center(s) in the next couple of years?
A: The Stanford sequencing center established by the genomics awards continues to operate with other sources of funding.  The Stem Cell Data Hub established by UCSC continues to be supported.  UCSC has no plans to shut down the site even though its CIRM award has ended. 

Q: How much time remains on the grant(s)? I See there was at least one extension given, but it is unclear why there was delay.
A: All three genomics grants have ended as of May 31st.  The sequencing centers at Stanford and the Salk were given six month award extensions to continue supporting projects with technical delays in sequencing activities.  The data hub at UCSC was given a 12 month extension to process data generated by the sequencing centers.

Q: What else do readers need to know about this award? 
A: A number of outputs were generated from genomic center projects, including:
  • 60 publications connected to CESCG funding
  • 10 data analysis/visualization tools created
  • 1 new sequencing technique developed
  • 300 new iPSC lines created
  • Central online data hub created with standard metadata, analysis pipelines, restricted access
  • Data repository of human single cell global transcription in heart, pancreas, blood, brain, brain
  • 84TB data generated from sequencing activities across projects

Tuesday, July 14, 2020

Former Chief of California Stem Cell Agency Returns to California as Head of Sanford Burnham

C. Randal Mills, who led California's $3 billion stem cell agency for three years, this afternoon was named as chief executive officer of the Sanford Burnham Prebys Medical Discovery Institute in La Jolla, Ca.


Randy Mills
Sanford Burnham photo
The institute said in a news release that Mills brought to Sanford "decades of experience as an entrepreneur and transformational leader in the biomedical industry."

Most recently, Mills was president of the National Marrow Donor Program/Be The Match nonprofit, an international leader in facilitating and supporting bone marrow transplantation.

Mills left Be The Match in February of this year, citing personal reasons.

Mills, who goes by Randy, was  president and CEO of the California stem cell agency from May 2014 until July 2017. 

During his time at the agency, which is formally known as the California Institute for Regenerative Medicine (CIRM), Mills instituted something he called CIRM 2.0. It streamlined and sped up the work of the agency, sharpening its focus with an emphasis on performance metrics. The structure of the effort remains in place today. 

When Mills left the agency, CIRM Chair Jonathan Thomas, who recruited Mills, said his efforts had created 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."

Sanford Burnham has received $39.4 million from CIRM over the years. Its president, Kristiina Vouri, sits on the governing board of the stem cell agency, which has included a Sanford representative since 2004. 

Vouris said in the news release that Mills "comes to us with extensive organizational and executive leadership experience. His diverse background and knowledge of translational research and drug discovery will help us propel the Institute into a bright and successful future.”

Mills will begin his work immediately at Sanford Burnham, which has 700 employees in the San Diego area.  

Monday, July 13, 2020

Covid Research Backed by California's Stem Cell Agency: 15 Awards, Including Help with Three Clinical Trials

The California stem cell agency is down to its last $272,357 in its special, $5 million effort to help finance research involving Covid-19.

The research round began in May and has approved 15, fast-track research projects, including participation in three clinical trials. The latest awards were approved last Friday by agency directors. 

  • Evan Snyder of Sanford Burnham Prebys Medical Discovery Institute received $250,000  to create lung organoids to test two drug candidates for treatment of the virus.
  • John Zaia of the City of Hope received an additional $250,000 for his previously approved study dealing the use of convalescent plasma treatments. 
  • Steven Dowdy at UC San Diego was awarded $150,000 to study a more effective way of delivering a genetic medicine, called siRNA, into the lungs of infected patients.

Summaries of the CIRM application review on the grants can be found here, including the six rejected.  

Approval of the latest awards came as a New Jersey firm that two weeks ago received a $750,000 award still has not disclosed the location of its clinical trial site in California. By law, the stem cell agency can only finance work within California.

The awardee is Celularity, Inc., a business whose proposed therapy is backed by Rudi Giuliani, the president's personal lawyer, who has also touted other possible Covid therapies, including one that has been rejected by the Food and Drug Administration.

In creating the Covid round, CIRM said award winners must be "ready to start work within 30 days of approval and propose achieving a clear deliverable within six months." It has been 16 days since the Celularity award was approved. 

The California Stem Cell Report has asked the firm repeatedly for the location of the California site but it has not responded. The agency itself also has not disclosed the location and defers to the company.

Sheehy Steps Back from Stem Cell Agency Positions; Cites His Opposition to Prop. 14

A longtime member of the governing board of the $3 billion California stem cell agency has stepped away from two leadership roles in the wake of his vote against the ballot measure that would refinance the research enterprise, which is running out of money. 

Jeff Sheehy, an HIV/AIDs patient advocate on the board since 2004, made the moves after becoming the only member of the 29-member board to vote against endorsing Proposition 14, which would provide $5.5 billion for the California Institute of Regenerative Medicine (CIRM), as the agency is formally known. 

The proposal would also make significant changes in the operations of the agency, enlarge its scope, lock up money for certain purposes and expand the size of its board from 29 to 35.

Sheehy voted against the endorsement on June 26 and released a statement to the California Stem Cell Report which cited a wide range of reasons for his negative vote. 

The actual vote on Proposition 14 was 21-1. Some members of the board were not present. Two vacancies also exist on the board. 

Sheehy was chairman of the board's science subcommittee. He was also a member of CIRM's grant working group and for years directed the evaluation by the full board of the billions of dollars in grant applications. 

Responding to a question last week, Sheehy said,
 "I instigated the change. I believe that it doesn't make sense for me to have any leadership roles given that I do not support Proposition 14.  I can imagine a scenario where the reality of my opposition becomes stark, and I don't want to drag the functionality of the board or the agency into any potential, campaign back-and-forth."
The changes in Sheehy's role became apparent last Friday when another board member led the evaluation of the Covid-19 applications. It came as a surprise to at least one board member, Vice Chairman Art Torres, who inquired at the beginning of the Friday meeting about the change. 

"What happened to Mr. Sheehy? He's not running these things anymore?" Torres asked.

Chairman Jonathan Thomas replied briefly, "Mr. Sheehy is is not going to be running the application review."

Torres replied, "Sorry to hear that."

Friday, July 10, 2020

Saving CIRM: $5.5 Billion Ballot Campaign, Rhetoric and Winning

The campaign to save California's financially strapped stem cell research agency said this week that voter approval of a $5.5 billion rescue measure "has never been more important to the future of California’s health care, for the patients and their families, than it is now."

The pitch came in an opinion piece carried on the Capitol Weekly online news service. The article appears to be the first "op-ed" piece that the campaign has placed since qualifying the ballot initiative, Proposition 14

The article carried the byline of Robert Klein, chairman of the campaign effort, Californians for Stem Cell Research. Klein is the Palo Alto real estate developer who led the 2004 ballot campaign and directed the writing of the original initiative as well as the current one. He also was the first chairman of the agency, known officially as the California Institute for Regenerative Medicine (CIRM). 

Klein's article echoed rhetoric from the campaign web site, in some cases using identical phrasing, which is to be expected.  He wrote,
"CIRM funding has advanced research and therapy development for more than 75 different diseases and conditions, more than 90 clinical trials, more than 1,000 medical projects at 70 institutions across California and nearly 3,000 published medical discoveries. This investment has already saved and improved lives, including a high school student who was paralyzed in a diving accident and was able to regain function in his upper body and go on to college, a mother who went blind from a genetic disease has had some of her eyesight restored, two FDA-approved cancer treatments are already saving lives, and many more."
Klein's campaign piece pushed the envelope in some cases. One example is the mention of "more than 90 clinical trials." The agency itself only claims 64. The key to Klein's figure of 90 is the phrasing "CIRM funding has advanced ... more than 90 clinical trials." That is a different criteria than used by the agency. Klein is basing his figure on any kind of research connected in any way to any kind of trial. 

Klein's number of 90 has also climbed from 80 just 16 days ago.  

Additionally, Klein's claims in his article for the agency's economic benefits are based on studies that the agency itself has paid for as opposed to independent, third party analyses. The most recent example came last fall; the study cost CIRM $206,000. 

The 2004 campaign that established the agency was widely criticized for its hype. Most ballot campaigns can be criticized on the same grounds. However, none have dealt with science in the way that Proposition 14 does. But Klein's job is to win approval of the proposal. Without a victory in the fall, CIRM will begin to close its doors. 

California voters can expect to see more rhetoric like Klein's over the next three months or so, intensifying significantly in October. The same sort of rhetoric is  already coming from the opposition and can be more extreme. As the ChurchMilitant web site said on June 29
"California state officials have confirmed a ballot initiative that, if approved, would give a state biomedical agency $5.5 billion to kill human embryos in order to extract their stem cells."
All this -- Klein's envelope-pushing and opponents' emotional, religious screeds -- is part of the way ballot campaigns work in California. Cautious, deliberative discussions cannot be expected to carry the day for the partisans on both sides. It is war with a deadline. 

Sunday, July 05, 2020

Quote of The Day: Noah's Ark and the California Stem Cell Agency

'''CIRM operates at the nexus of the Political (with a capital P), scientific, institutional, and business forces of an aggressive state that views economic development as a priority.' Its organization, (Hamilton Moses) adds, doesn't help. ' 'Noah's Ark' boards, where each member is appointed to represent a constituency, rarely work.'"
 --  Hamilton Moses is a biomedical consultant in Virginia who focuses on non-profit governance, quoted in Nature Reports Stem Cells, from article Sept. 13, 2007, by Monya Baker

Thursday, July 02, 2020

Bert Lubin: A Memory from a Sickle Cell Moment in 2008



Bert Lubin died last week. He was a member of the board of the California stem cell agency for a number of years, but what I remember him for was an appearance he made before the agency's governing board in 2008. 

Back then he was not serving as a member of the board. Instead he was a supplicant. And he was the first person to appear before the board seeking to reverse a negative decision by CIRM's reviewers.  

Lubin lost but not without raising a not-so-discreet ruckus. 

One board member, Gerald Levey, then dean of the UCLA School of Medicine, was more than irritated by Lubin's appeal of the reviewers' decision. I wrote at the time, 

"Levey said, "I don't think we can run a board this way. If we do, it would be chaos." 

"Levey was responding to a request by Lubin for a 10 minute presentation...of Childrens' case. Levey warned that allowing the presentation would lead to 50 other rejected applicants coming to the board.

"Director Joan Samuelson said that even 100 persons would be okay with her. She provoked laughter when she declared that the number would show more interest than at any other board meeting," the California Stem Cell Report wrote.


Ironically, the application involved sickle cell disease, a program that Lubin pioneered at Children's Hospital Oakland. In 2008, sickle cell was receiving little or no attention from CIRM. Today the agency is more than proud of its sickle cell arrangement with the National Institutes of Health.

Earlier this week, Kevin McCormack, senior director of communications for CIRM, wrote an item on Lubin for the agency's blog, The Stem Cellar. McCormack quoted Lubin as saying, 
"When I became the director of the research program we had $500,000 in NIH grants and when I left we had $60 million. We just grew. Why did we grow? Because we cared about the faculty and the community. We had a lovely facility, which was actually the home of the Black Panther party. It was the Black Panthers who started screening for sickle cell on street corners here in Oakland, and they were the start of the national sickle cell act so there’s a history here and I like that history. 
"Then I got a sense of the opportunities that stem cell therapies would have for a variety of things, certainly including sickle cell disease, and I thought if there’s a chance to be on the CIRM Board, as an advocate for that sickle cell community, I think I’d be a good spokesperson. So, I applied. I just thought this was an exciting opportunity."I thought it was a natural fit for me to add some value, I only want to be on something where I think I add value.” 
"Bert added value to everything he did."

Wednesday, July 01, 2020

Celularity and $750K from California Stem Cell Agency: Where is the Money Being Spent?

The New Jersey firm that was awarded $750,000 by the California stem cell agency to help finance a Covid-19 clinical trial has four trial sites in two states, but has not identified any in California. 

State law requires that awards from its taxpayer-funded stem cell agency be spent for work in California. 

The firm is Celularity, Inc., which is developing a product that has been fast-tracked by the federal government and which has the support of President Trump's personal attorney, Rudy Giuliani. 

According to the National Institutes of Health website this morning, Clinicaltrials.gov, Celularity has three clinical trial sites in its home state of New Jersey and one in Washington state for the Covid therapy. The information shows that all of those sites are currently recruiting patients. The estimated primary completion date of the work is Nov. 30, 2020.

Although the stem cell agency said on Sunday that a trial site existed in California, it declined to disclose the location. The agency referred questions about a site in California to the company, which has not responded to three requests yesterday and today for information.

Corey Casper, interim president of the Infectious Disease Research Institute in Seattle, is listed as the principal investigator for the trial by Celularity. Casper spoke to stem cell agency directors on May 15 on behalf of the application. Casper also did not respond to inquiries about the location of the California work. 

Six weeks ago, when Celularity's application first came before directors of the California Institute for Regenerative Medicine (CIRM), Casper said the treatment "has a biologic plausibility for being very important and very unique in its treatment for Covid disease."

He continued,
"I think that we have adequate safeguards that have been put into the trial to really assure the safety of the participants."
Safety concerns have been raised by CIRM's grant reviewers as well as by other scientists. The reviewers, who are from outside California, originally rejected the application, giving it a score of 84, one below the cutoff point. After Celularity addressed reviewers' concerns, it scored 85 and was sent to directors who approved it last Friday with no debate.

It is CIRM's 64th clinical trial.