Guest Posting: "Stem Cell Options Should be on the Table"

(Editor's note: The following is a guest posting from Joseph Rodota and Bernard Munos, both of whom have been active in California policy matters for some time. More biographical information can be found at the end of the item. The California Stem Cell Report welcomes diverse, well-considered views on California stem cell issues. If you have something that you think should see the light of day, please send it to djensen@californiastemcellreport.com.)

By Joseph Rodota and Bernard Munos

The sponsors of Proposition 71, the 2004 initiative that provided $3 billion in bonds to support stem-cell research, are readying a proposal to keep the agency alive after the last of these funds have been given out. According to recent news reports, a new $5 billion bond could be on the California ballot as early as November 2018.

Researchers supported by the California Institute for Regenerative Medicine (CIRM) have published hundreds of academic articles, but placed fewer than 30 drugs in clinical trials.

Even if all of these clinical trials resulted in drug candidates, they would still come up against the so-called “Valley of Death”—the well-documented shortage of funding for early-stage translational research.

California needs to move regenerative medicine from an academic timeline to a business timeline. The skills needed to turn an academic discovery into a commercial product are very different from the skills needed to be a successful academic scientist.

We proposed an alternative to continuing the current approach -- a state bond with three distinctive features:

A Focus on Entrepreneurs: Funds would be available only to companies, not academics (who would still be able to tap into billions in NIH funding for stem cell research);

A Focus on California: Only companies with a headquarters and a majority of employees in California, the nation’s center of overall innovation, or willing to relocate here; and

A Focus on Breakthrough Medicine: Only companies working on projects that have the potential to greatly impact patient health would qualify.

The University of California is well-qualified to administer this bond and report on its operations to the Legislature and the Governor, without the need for the cumbersome and controversial governance structure put in place by Proposition 71.

In exchange for the funds they receive, companies would tender to the University of California shares of their common stock, with an estimated value as determined by the most recent outside valuation or price set by investors. These shares would become part of the UC endowment -- and the University of California be free to sell or leverage these shares, or acquire additional shares, as it sees fit.

CIRM has over-invested in academic research, and under-invested in translating that research into therapies that cure diseases and prolong heathy lives. California needs to right that balance.

(Joe Rodota served as Cabinet Secretary to former California Governor Pete Wilson and director of policy for Arnold Schwarzenegger’s 2003 recall campaign. Munos is a senior fellow with FasterCures and the founder of the Innothink Center for Research in Biomedical Innovation.).

Here is a summary of the bond proposal.

SUMMARY -- California Next Generation Cures Bond -- June 2017 uploaded by DavidJensen on Scribd

California Stem Cell Agency Reports 'Streak of Good News' on Asterias Spinal Therapy

Asterias video

California's $3 billion stem cell program today reported ongoing rosy results in a clinical trial involving a therapy for severe spinal cord injury.

The treatment is being developed Asterias Biotherapeutics, Inc., of Fremont, Ca., with $14.3 million from the state research program, which is now in its 12th year.

The latest news was reported on The Stem Cellar, the agency's blog, and was based on a news release from Asterias, which is publicly traded. 

Todd Dubnicoff, the agency's multimedia editor, wrote the item which discussed nine-month results for the trial involving six patients paralyzed from the neck down. He said,

"In a nut shell, their improvements in arm, hand and finger movement seen at the earlier time points have persisted and even gotten better at 9 months."

Dubnicoff said that the level of improvement "can mean the difference between needing 24-hour a day home care versus dressing, feeding and bathing themselves."

He said,

"The impact of this level of improvement cannot be overstated. As mentioned in the press release, regaining these abilities, 'can result in lower healthcare costs, significant improvements in quality of life, increased ability to engage in activities of daily living, and increased independence.'"

In the Asterias press release, Edward Wirth, chief medical officer for the company, said,

“The new efficacy results show that previously reported meaningful improvements in arm, hand and finger function in the 10 million cell cohort treated with AST-OPC1 cells have been maintained and in some patients have been further enhanced even 9 months following dosing. We are increasingly encouraged by these continued positive results, which are remarkable compared with spontaneous recovery rates observed in a closely matched untreated patient population.”

The company also reported that no "serious adverse events" have surfaced that could be attributed to the therapy, which was initially developed  by Geron, Inc., which received $6.4 million from the stem cell agency. Geron abandoned the trial for financial reasons, and Asterias acquired the technology.

Aserias' stock price jumped nearly 13 percent today, hitting $3.55. Its 52 week high is $5.80 and its 52-week low is $2.30.

California Stem Cell Report Going Dark for a Few Days

The California Stem Cell Report expects to be offline for perhaps the next five to seven days.

The moving home of this web site, the sailing vessel Hopalong, will be making a passage north from Mazatlan into the Sea of Cortez, formally known as the Gulf of California. We will not have access to cellular or Internet coverage during that time.

A Longer Look at the Golden State's Stem Cell Research Efforts

Here is the overview of the California stem cell agency, published May 23, 2017, on Capitol Weekly and written by yours truly.

  California's Stem Cell Agency Confronts Uncertain Future: Capitol Weekly by DavidJensen on Scribd

Full Text: The California Stem Cell Agency's Response on its Accomplishments

  Stem Cell Agency's Response to Questions About Its Performance From Capitol Weekly_ the Newspaper of Califo... by DavidJensen on Scribd

California's 'Great Ideas,' Stem Cell Awards Target Universal Blood Supply, Alzheimer's and Much More

The California stem cell agency this week awarded a total of $1.4 million to six scientists to jump start their work in what it calls its "great ideas" program.

The awards went for research ranging from creation of a universal blood supply with human stem cells to mitigating Alzheimer's disease, which has seen an increase of 55 percent in its death rate from 1999 to 2014, according to results of a new study released yesterday

The agency said in a press release that the "Inception" program  "provides seed funding for great ideas that have the potential to impact human stem cell research, but need some initial support. It’s hoped this will enable the researchers to test their ideas, and give them the data they need to compete for more substantial funding."

Jonathan Thomas, chairman of the agency's governing board, said,

"This is a high risk, high reward program. We feel that a small investment now could produce enormous benefits later.”

The funding is small indeed. The California Institute for Regenerative Medicine(CIRM), as the agency is formally known, finances some clinical trials at $20 million a crack. The largest award in the "great ideas" program was $265,500.

The blood supply award was a reminder of another program that the agency used to entice star researchers to California. The blood grant went to Tannishtha Reya of UC San Diego. She came to California with her spouse, Robert Wechsler-Reya. He was lured by CIRM in 2010 with $5 million in funding to work at the Sanford-Burnham Medical Research Institute in La Jolla.. He has not received any further funding from the agency. This is the first CIRM award for Reya.

Another round of the Inception program is scheduled to open up in January 2018. Here is a link to the most recent request for applications. 

Here is a list of the winners with their application numbers. The summaries of reviewer comments on each application and their scores can be found here.  All of the institutions have ties to CIRM board members, who are not permitted to vote on applications involving their institutions. However, they can vote on creation of the research grant programs, establishment of their scope and rules.

DISC1-10074

Reprogramming human stem cells for blood cell generation

T. Reya – U.C. San Diego

$232,200

DISC1-10036

Prodrug innovation to target muscle stem cells and enhance muscle regeneration

H. Blau – Stanford University

$235,834

DISC1-10079

An exosome-based translational strategy to mitigate Alzheimer’s disease neuropathology

J. Baulch – U.C. Irvine

$179,911

DISC1-09912

A novel tissue engineering technique to repair degenerated retina

B. Thomas – University of Southern California

$215,133

DISC1-09999

Generation of expandable, self-renewing muscle stem cells for Duchenne Muscular Dystrophy

A. Sacco – Sanford-Burnham Medical Research Institute Letter to board

$265,500

DISC1-09984

Hypo-immunogenic cardiac patches for myocardial regeneration

S. Schrepfer – U.C. San Francisco Letter to board

$238,500

A Look at the California Stem Cell Agency: Its Origins, Its Accomplishments and Its Future

The Capitol Weekly online news and information service this afternoon posted a major overview of the $3 billion California stem cell agency.

The piece covered the agency's origins, recent high water marks and discussed its future. Here is the beginning of the freelance article by yours truly.

"C. Randal Mills, the 45-year-old CEO of California’s $3 billion stem cell research program, is a man who loves his milestones. 

"A private pilot, he charts his course in the air from one specific point to the next. Three years ago, Mills brought that same sort of navigation to the state stem cell agency. Miss one of the agency’s milestones, and — if you’re a stem cell scientist — you may not crash and burn, but you could lose millions of dollars in research funding from the state. 

"Mills has left an indelible stamp on the agency with his emphasis on concrete, measurable results. But he is resigning from the research program at the end of June in the midst of what some say is its “last stage.” His surprise departure to head the world’s largest bone marrow donor organization shocked many in California’s stem cell community. And it added to the unease about its future along with the future of possible stem cell therapies."  

(For those of you who read a brief item this morning about how this blog was going to go dark for a few days while it was on an ocean passage in the Sea of Cortez, we had a minor setback. Our floating home, the sailing vessel Hopalong, suffered a mechanical problem that we could not fix at sea, so we returned to port for repairs. The voyage begins anew tomorrow morning.)

Major Overview of California Stem Cell Upcoming This Afternoon

Look for a major overview of the $3 billion California stem cell agency later today on Capitol Weekly, a well-respected online news and information service that focuses on state government and politics.

The piece was written by yours truly on a freelance basis for Capitol Weekly and includes the latest developments at the agency, including what departing president Randy Mills leaves behind.

Given the vagaries of the Internet and news, publication of the article cannot be totally guaranteed this afternoon. So if it doesn't pop up today, try again later this week.

Meanwhile, the California Stem Cell Report is going dark for a number of days while it makes an ocean voyage in its maritime home, the sailing vessel Hopalong, in the Sea of Cortez.  Coverage of the agency is expected to resume perhaps by this weekend when an Internet connection can be found in Baja California.

California Stem Cell Agency Has Opportunity for 'All-in" Executive Assistant

Looking for a great job with a $3 billion operation headquartered in downtown Oakland? You will be able to share in the progress of one of the hottest biomedical fields in the country and perhaps help save some lives.

The job is executive assistant to the president of the California stem cell agency. The current president, Randy Mills, is leaving at the end of June. Maria Millan, now vice president for therapeutics, is taking over as the interim CEO. She is line to succeed Mills, but there is no guarantee on that.

The job is no walk-in-the-park. The agency is small -- only 46 employees -- despite its reach. Long hours could be the order of the day.

The job posting on the agency's web site says the position requires an "all-in" commitment to the goals of the agency. Salary can range up to $10,433 a month.

Bones, Stem Cells and Bridging the Gap

California's $3 billion stem cell research effort chalked up a small score yesterday with the announcement that a $5.2 million investment is making progress towards development of a therapy to regenerate broken bones. 

Writing on the the state stem cell agency's blog, Karen Ring, social media manager for the agency, said,

"Scientists from Cedars-Sinai Medical Center have developed a new stem cell-based technology in animals that mends broken bones that can’t regenerate on their own. Their research was published today in the journal Science Translational Medicine and was funded in part by a CIRM Early Translational Award."

The award went to Dan Gazit and Hyun Bae at Cedars. Their year one and two progress reports involving the adult stem cell therapy can be found at the link in the above paragraph. 

Ring's  blog item also carried a nifty graphic on the work and a link to a video on the research. 

Ring wrote,

 "Over two million bone grafts are conducted every year to treat bone fractures caused by accidents, trauma, cancer and disease. In cases where the fractures are small, bone can repair itself and heal the injury. In other cases, the fractures are too wide and grafts are required to replace the missing bone.

"It sounds simple, but the bone grafting procedure is far from it and can cause serious problems including graft failure and infection. People that opt to use their own bone (usually from their pelvis) to repair a bone injury can experience intense pain, prolonged recovery time and are at risk for nerve injury and bone instability."

Read All About It! Bad News for The Stem Cell 'Other'

It is a sad day for the stem cell "other."

Only 11 percent of the readers of one stem cell blog say they fit that category. That was a big drop from the early returns that showed the "other" with 21 percent.

(Never mind that we don't know the precise number of eyeballs actually represented by that 11 percent.)

All of this is the product of The Niche, the blog of UC Davis stem cell researcher Paul Knoepfler. He mounted a poll last week for readers to determine both their interests and general identity.

Initially "other" sprang into the lead. But as more readers responded, the reader category of academic scientists moved to the top with 32 percent. Industry scientists followed with 19 percent and patient or patient advocates with 17 percent.

What were they interested in? Investigations, 25 percent, newsy items, 20 percent, and journal club-like paper reviews, 18 percent.  Less than four percent of readers identified themselves as interested laypersons.

If you are feeling left out, there is still time to respond by going to this link. A chance at free stem cell swag is being offered. And the swag is better than a used petri dish.

$20 Million, California-backed Stem Cell Trial Discloses Disappointing News

Capricor Therapeutics, Inc., today announced some bad news about its state-of-California financed clinical trial for a cardiac, stem cell therapy and said that it planned to lay off an unspecified number of employees.

Capricor's stock price plummeted 62 percent following what the company called the "unexpected" news, dropping from $1.89 to $1.16. California's stem cell agency has backed the trial with $20 million, plus an additional $7 million for earlier, related research.

The agency, formally known as the California Institute for Regenerative Medicine (CIRM), said on its blog,

"Obviously this is disappointing news for everyone involved, but we know that not all clinical trials are going to be successful. CIRM supported this research because it clearly addressed an unmet medical need and because an earlier Phase 1 study had showed promise in helping prevent decline in heart function after a heart attack."

In response to a question, Kevin McCormack, senior director of communications, said the agency is talking to Capricor about the next steps. The agency regularly halts funding of awards when recipients do not meet milestones. McCormack did not respond to a question about how much money the firm had already received from CIRM.

Capricor, which is headquartered in Beverly Hills, said in a press release that an interim analysis on the phase two trial has "has demonstrated a low probability (futility) of achieving a statistically-significant difference in the 12-month primary efficacy endpoint." The company said there was "no notable difference" between treatment groups.

The company said it would cut its workforce to focus more sharply on its treatment of Duchenne muscular dystrophy, which the stem cell agency is also backing with $3.4 million. The Duchenne treatment had better news the last month, clearing its phase one trial with no adverse effects.

Timothy Henry and Rajenda Makkar of the Cedars-Sinai Heart Institute in Los Angeles are the principal investigators for the clinical trial.

The highest price for Capricor stock over the last 12 months was $5.40 and the lowest was $1.13.

Here are links to additional news stories today on Capricor: BiopharmaDive, MarketWatch, Genetic Engineering News, 

The "Other" and Stem Cell Blogs

Ever wonder who reads stem cell blogs? The "other" are the predominant readers of the one produced by a UC Davis stem cell researcher. At least that is the latest result from a survey that Paul Knoepfler is conducting about his cyberspace effort.

Knoepfler posted the survey request today. The results are still coming as you read this item. The initial tally this afternoon showed that 21 percent of respondents placed themselves in the "other" category when asked about their background. Next were academic and industry scientists, both with 18 percent, and physicians, 15 percent.

Most liked posts? Investigations, 33 percent; opinion pieces, 21 percent; newsy items, 17 percent.

The results are ever-changing as more readers respond. You can express your own preferences by going to this item. Respondents will be entered in a drawing for a stem cell T-shirt and signed copies of Knoepfler's two books.