California Awards $37 Million for Stem Cell Research; Parkinson's Grant Deferred After Emotional Session

Directors of the California stem cell agency today approved nearly $37 million for translational stem cell research into possible therapies for afflictions ranging from cancer to Canavan disease.

The vote came routinely after a lengthy and sometimes emotional discussion involving an $8 proposal for Parkinson's disease from Scripps Institute in La Jolla that was rejected by the agency's grant review group.

Their voices cracking and tears welling up, persons with the disease appealed to the agency's directors to provide "a future without fear, a future with hope."

Cassandra Peters, who was diagnosed with Parkinson's 15 years ago, told stem cell agency president, Randy Mills, via a phone link to San Diego,

"I hope that I have the opportunity to kneel in front of you and say thank you."

On an 8-4-2 vote, the board ultimately sent the application from Jeanne Loring, head of the stem cell program at the Scripps Institute, back to reviewers for an accelerated re-examination of her proposal, which was submitted last Nov. 20. It was reviewed on Feb. 11 behind closed doors and given a score of 70, well below the cutoff of 85.

This week, Loring said in a letter to the board that new information, including comments from the FDA, has emerged since November that will satisfy the concerns of reviewers. CIRM officials estimated it would take about two months to have the proposal re-examined. Then it would have to come back to the board for final action.

Loring's proposal and the others were reviewed under new procedures that are aimed at providing more, regular opportunities for researchers to apply for funding. Old procedures for appeals have been scrapped after failing to deal with the emotional appeals that have been generated for awards over the last decade.

Some board members were concerned that the exception granted for Loring today would stimulate a fresh wave of public pitches by scientists and patients whose proposals have not fared well with reviewers. The board is reluctant to second-guess its reviewers. Agency directors do not see the full applications for cash, just the same review summaries seen by the public, with the exception of proprietary information, which the board can see during executive sessions.

While seven other translational awards were approved, the board rejected another effort to fund research that was rejected by reviewers. In this case, the application scored only two points below the cutoff.

Speaking after the long debate on Loring's proposal, Thomas Kremen of Cedars-Sinai and Olympic gold medalist Jason Lezak appeared to appeal to the board to overturn the rejection. The board, however, did not discuss the application or respond to their comments.

All seven winning institutions in this round all had ties to members of the governing board of the agency, formally known as the California Institute for Regenerative Medicine (CIRM). However, those board members are not allowed to vote on such applications. About 90 percent of the $1.98 billion in CIRM awards has gone to institutions with links to past or present CIRM board members.

Randy Mills, president of the agency, said in a press release,

“Many of the programs we are funding today are focused on helping find treatments for diseases that affect children, often in infancy. Because many of these diseases are rare there are limited treatment options for them, which makes it all the more important for CIRM to focus on targeting these unmet medical needs.”

Here is a link to the agency's press release on today's meeting, which includes the names of the recipients.

California Okays $7.3 Million for Stem Cell Research Related to Duchenne's and Immunodeficiencies

Directors of the California stem cell this morning awarded $4.3 million to researchers at UC San Francisco and $3 million to Capricor, Inc., of Beverly Hills for clinical trial-related research for therapies connected respectively to an extremely rare immunodeficiency affliction and Duchenne's disease.

The larger award was ratified on a 10-3 vote after questions arose about whether sufficient patients could be recruited for a clinical trial, additionally a concern of the agency's grant reviewers who earlier approved the application, also on a split vote.

The agency has already provided $3.9 million for the UCSF research. The lead scientists on that effort were Morton Cowan and Jennifer Puck. The treatment is aimed at the "bubble boy" immunodeficiency disease. The agency's summary of the application review said that the research "could lead to a lasting cure" for that version of the affliction.

The Capricor award was approved on a 13-0 vote after Jeff Sheehy, a member of the governing board, said it was "pretty much a pure CIRM product," referring to the initials of the stem cell agency, formally known as the California Institute for Regenerative Medicine.

Capricor, a publicly traded firm, has already received $19.8 million from the agency to develop stem cell heart treatments, The $19.8 million came on top of earlier, related funding for research at Cedars-Sinai that hit $7 million.

The treatment is aimed at Duchenne muscular dystrophy cardiomyopathy using a Capricor product called CAP-1002.

California's expected action on the two awards was first reported by the California Stem Cell Report on March 8.

Directors of the California Stem Cell Agency Open Meeting

The meeting of the governing board of the California stem cell agency began at 9:10 a.m. PDT this morning with the roll call and pledge of allegiance.

Ethics to Eye Disease: Presentations This Morning at California Stem Cell Agency Meeting

Here are links to a couple of presentations on the agenda for today's meeting of the governing of the $3 billion California stem cell agency.

Ethics presentation by James Harrison, general counsel to the agenda: Topics include conflicts of interest and financial disclosure requirements.

Briefing on eye disease, clinical trial projects backed by the agency.

Read All About It! Gavel-to-gavel Coverage of Today's California's Stem Cell Agency Session, Researchers to Receive $44 Million

Check in right here all day-long on the California Stem Cell Report for all the news and information out of the meeting this morning of the governing board of the $3 billion California stem cell agency.

Directors are slated to give away $44 million for a variety of research projects, maybe more if two researchers are successful in overturning rejections of their proposals by the agency's reviewers.

Also on tap is examination of the agency's eye disease clinical portfolio, the first such thorough-going review. An ethics presentation is scheduled as well, dealing with public disclosure of  board member's financial interests and conflict-of-interest rules.

Going for the Gold: Pitches for $12.5 Million in Rejected Stem Cell Research Applications

Highlights

New scoring system

IOM team member appeal

New information on application

Olympic gold medalist, one of “America’s Top Doctors” and the head of the Scripps Institute’s stem cell program are lobbying the California stem cell agency this week to fund requests for $12.5 million in research grants. 

The two different grants have been rejected by the agency’s blue-ribbon reviewers, who meet behind closed doors and and make decisions without disclosing publicly their financial and professional interests. However, the proposals will come before a public meeting tomorrow of the governing board of the $3 billion agency for official ratification of reviewer actions.

Directors of the agency, officially known as the California Institute for Regenerative Medicine(CIRM), have been loath to override reviewers’ decisions, especially in the past couple of years. Plus this week's applications were considered under a new scoring system, which cuts off funding at a scientific score of 85. In the past, the agency has approved awards that were scored as low as 61.

Jeanne Loring, director of the Center for Regenerative Medicine at Scripps, wrote the board to seek funding for her $8 million application (TRAN1-08468) for a treatment involving Parkinson's disease. The proposal was scored at 70.

But first, here are details on the other application (TRAN1-08527). It seeks $4.5 million for research on a treatment for tendon and ligament injuries, something that the agency has not yet funded, according to the three letters supporting the application. The proposal was scored at 83, two points below the cut off. In the past, board members have noted that such small scoring definitions are statistically insignificant.

The identity of the applicant has not been released by the agency. Its practice is to withhold that information until the board acts, although there are notable exceptions to that policy.

Cato Laurencin, UConn photo

One of the letters of support came from Cato Laurencin, an eminent orthopedic surgeon at the University of Connecticut and who is listed as one of “America’s Top Doctors.” Laurencin also served on the Institute of Medicine’s team that conducted a $700,000 study of the California stem cell agency. 

In the letter dated yesterday, he said hundreds of thousands of persons suffer from tendon and ligament injuries. (All letters are clumped under the same URL.)  Laurencin wrote, 

"This seems to me like a marvelous opportunity to support an excellent study with tremendous potential clinical impact on patients in California and throughout the United States."

Jason Lezak, an Olympic swimmer with four gold medals, said in his letter that there is a "clear need" for legitimate research and treatment for such injuries, given the appeal of untested stem cell treatments attracting patients here and abroad.

 

A CIRM document shows that while the application had an overall score of 83, its median score was 85 with scoring ranging from 75 to 92. 

In her March 11 letter, Loring focused on "signicant new information" concerning her application that

Jeanne Loring, Scripps photo

was submitted Nov. 20 of last year. The proposal was not reviewed until Feb. 11.

Loring said, 

"Between November and February, we generated new information that was not available to the GWG(grant review group). Importantly, we also received guidance from the FDA that alleviates the major concerns of the reviewers."

Her nine-page letter itemized reviewer concerns and provided her responses. She wrote, 

"In summary, based on our new data, our DNA sequencing publication, the recent approvals of two of our quality control-focused CIRM grants, and feedback from our meeting with the FDA, we believe that we are ready to proceed on our pilot studies to inform our IND-enabling studies. Some of the GWG concerns conflict with the guidance given by the FDA, and had the GWG been aware of the feedback we had received from the FDA, many of their concerns would have been addressed."

Loring's scientific and median scores were identical: 70. Scoring ranged from 60 to 80. 

David Higgins
 Parkinson's Association photo

The San Diego-based Summit4StemCell group has strongly supported Loring's research and raised funds for it. Representatives from the group have attended a number of CIRM board meetings, laying out the urgency of their needs. One meeting last year became emotional and left some CIRM representatives uneasy and irritated. (See here and here.)

The 29-member CIRM board includes one patient advocate from the Parkinson's community, David Higgins of San Diego. 

Of the $1.9 billion that the agency has handed out, $44 million has gone for Parkinson's. The relatively meager rate of funding was a long a sore point for the first Parkinson's patient advocate on the CIRM board, Joan Samuelson, who has since left the board as her affliction advanced. 

Listen in on the $3 Billion California Stem Cell Agency; $44 Million Meeting Available on the Internet

People around the world will have a chance to follow every minute this week of the meeting of the governing board of the $3 billion stem cell agency, which is expected to give away $44 million to chase therapies for everything from cancer to Canavan disease.

The session in Millbrae near San Francisco International Airport will be available on the Internet and by phone, including display of the charts and presentations being used during the day-long session. The phone link is audio only and is available toll-free. Full directions for listening are available on the agenda. 

For those who want to comment live on Wednesday, they will have to be on the scene or at one of three remote locations, all of which are located in La Jolla. Specific addresses again are available on the agenda. 

In addition to the research awards, the board is scheduled to be briefed on the agency's ambitious clinical trial effort, which could be interesting. However, the agency has not posted any background material on the briefing as of this writing. Here is a link to what the agency has on its Web site concerning the clinical effort.

Also on the agenda is a closed-door evaluation of the agency's president, Randy Mills, who was hired in April 2014.

Update on California's Bob Klein: Former Chair of Stem Cell Agency at White House dinner, in Reno Apartment Construction Deal

Robert Klein, who is regarded by some as the father of California’s $3 billion stem cell research effort, surfaced in the news this week both in the White House and Reno.

Robert Klein, White House
news pool photo

The occasion in the White House was a state dinner last night honoring Canadian Prime Minister Justin Trudeau. The Reno event was approval of a $90 million bond issue to finance an apartment development in Nevada backed by Klein, who is a Palo Alto real estate developer and the first chairman of the California stem cell agency.

The Web site, thisisreno.com, said in a "sponsored post" March 8 about the bond financing:

"Robert Klein, the Co-Managing Partner of Sierra Summit LLC and President of Klein Financial Corporation, emphasized, “The project will bring high-quality architecture and a village design with the apartments developed in 12-, 18-, and 26-unit buildings, and courtyards, greenways, and recreational centers built into the project site plan.”

No news involving Klein emerged from the White House dinner, attended by about 200 persons, with the exception of his name on a list of guests.

Klein's stem cell visibility has diminished substantially since he left his post in 2011, replaced by the current chairman, Jonathan Thomas. Occasionally, Klein is mentioned in the media as promoting another bond issue for the stem cell agency that could total as much as $5 billion.

The agency subsists on money borrowed by the state (bonds), which roughly doubles the cost of the research because of interest expenses. The agency expects to run out of cash for new awards in 2020. It has no source of funding beyond that date, but is exploring possibilities.

California Stem Cell Researchers Expect $44 Million in Awards from the State Next Week

California's stem cell research agency next week is expected to hand out more than $44 million for attempts to find therapies for everything from cancer to diabetes.

Scheduled to be approved at the $3 billion agency's board meeting next Wednesday are nine applications, most of which are termed translational, meaning that they are attempting to move from basic research to a level where they might be suitable for clinical trials.

Two of the awards are more advanced, and are discussed in an item on the California Stem Cell Report yesterday. They total $7.4 million. Seven translational awards are up for action, totalling $36.8 million. All were approved earlier behind closed doors by the agency's reviewers.

An eighth application for $2.9 million to study a 2nd generation vaccine for the treatment of glioblastoma was also approved by reviewers. However, an agency document said board action is being deferred "to review material new information."  Asked whether questions had been raised "about the nature of the action by the grant review group," Kevin McCormack, senior director of communications, replied, 

"No, this has to do with information that has come to us that might affect the recommendation" of the review group.

Twenty-two applications seeking a total of $59 million were rejected.

None of the applicants was identified by the agency, which withholds that information until the board acts.

However, the agency posted more detail about the review process, scoring and voting than it has in the past. The review summaries and the additional material consumed 85 pages for all of the applications, including those rejected.

The review also marked the first use of new procedures that cut off awards on applications that received a scientific score of less than 85. In the past, awards were made for some applications that ranked in the 60s, including this one that was scored at 61.

In the past, some of the researchers whose applications have been rejected have appeared before the board to request that reviewer decisions be overturned. It was not clear whether that would occur under the new procedures.

Formal appeals are limited to demonstrable conflicts of interest and are pursued in private,  under the agency's rules. However, applicants are not told the names of persons who review their applications, making it difficult to determine whether conflicts exist.

California Stem Cell Agency to Award More Than $7 Million for Duchenne and 'Bubble Boy' Afflictions

Highlights
Capricor, UCSF win
Duchenne, "bubble boy" affliction targeted
Board linkage to recipient enterprises

The California stem cell agency is set next week to make two awards totaling $7.4 million to a Beverly Hills stem cell firm and to scientists at UC San Francisco for late stage research into therapies for rare diseases.

The largest award, $4.3 million, appears to be going to a team in San Francisco that has already received $3.9 million for its research. The lead scientists on that effort were Morton Cowan and Jennifer Puck. 

The latest award involves the "bubble boy" immunodeficiency disease. The agency's summary of the application review said that the research "could lead to a lasting cure" for that version of the affliction. 

The review said the treatment would modify a gene "to become normal by addition of a correct copy of the Artemis/DCLRE1C DNA repair gene (Art)." The goal of the grant is to complete nonclinical efficacy studies and set the stage for a clinical trial in 18 months.

Meeting behind closed doors earlier this year, the agency's blue-ribbon, out-of-state grant reviewers narrowly approved the application on 8-6-1 vote, meaning eight favored the award,  six thought the application needed improvement and one voted for denial. The governing board of the agency, formally known as the California Institute for Regenerative Medicine (CIRM), has a decade-long record of going along with its reviewers' positive funding decisions. Reviewers are not required to publicly disclose their economic or professional interests.

Also approved by reviewers was a $3.4 million award to Capricor, Inc., a firm that has already received $19.8 million from the agency to develop stem cell heart treatments, The $19.8 million came on top of earlier, related funding for research at Cedars-Sinai that hit $7 million. The lead scientist on those efforts was Eduardo Marban, who co-founded the firm with his wife, Linda. She is now president of the firm. He is chairman of the scientific advisory board.  

Capricor will add $2.3 million in matching funds to what CIRM provides to finance a clinical trial of the firm's treatment for Duchenne muscular dystrophy cardiomyopathy using a product called CAP-1002. The review summary said the treatment is "intended to stop fibrosis and potentially initiate regeneration following administration."

No therapies exist for treatment of cardiomyopathy for persons with Duchenne, according to the review summary.

The reviewers voted 12-1-0 to approve the award. 

Capricor is publicly traded. Its stock closed today at $2.18. Its 52-week high was $10.68 and its low was $1.88.

CIRM's governing board includes representatives from Cedars-Sinai and UC San Francisco. About 90 percent of the $1.9 billion awarded by CIRM has gone to enterprises with links to past or present board members.

CIRM does not disclose the names of award recipients until after the full board acts. The California Stem Cell Report identified the applicants on the basis of publicly available information. 

Ten Days in March: Is the $3 Billion California Stem Cell Agency Measuring Up?

Highlights

'Success metrics'

Next week's board meeting

Discouraging public attendance

But amply open in many ways

One of the more admirable aspects of the California stem cell agency’s plan for spending its last $900 million is its attention to careful measurement of the agency’s own performance.

The “success metrics” are tucked away at the end of the agency’s new, 47-page strategic plan. They lay out the criteria for determining how well each team at the agency is doing. The metrics range from the number of conflict of interest appeals to the number of clinical trials completed at Alpha clinics. Based on decades of experience with state agencies, the California Stem Cell Report can attest that such attention to performance is rare among state departments.

The agency's measurements also include the “number of board meeting documents posted with ten-day lead time.” Which is where the March 16 meeting of the governing board of the stem cell agency comes in.

On Saturday, the agency posted on its Web site the agenda for the meeting, a good 11 days ahead of the session in Millbrae, near San Francisco International Airport. The agency plans to give away millions of dollars, perhaps tens of millions. It will review the status of its ambitious and risky clinical trial program, which has seen a sharp upsurge in the last year or two. At least that is what can be deduced from the cryptic agenda items, the longest of which consists of only 26 words.

Total missing, as of this writing, are any documents supplying the details essential for understanding what the agency is actually doing.

The board meetings are the single most important public events of the agency. The agency professes to want to see greater public turnout at the sessions. But without adequate notice and some sort of meaningful information, the public, stem cell firms, scientists and patient advocates cannot make plans to attend the meetings even if they might have a deep impact on their lives.

On Feb. 9, Kevin McCormack wrote on the agency's blog about a CIRM meeting dealing with gene editing. He said,

“(Bioethicist) Alta Charo said this is not just a question for scientists, but something that could potentially affect everyone and so there is a real need to engage as many groups as possible in discussing it

"‘How and to what extent do you involve patient advocates, members of the disability rights community and social justice community – racial or economic or geographic.  This is why we need these broader conversations, so we include all perspectives as we attempt to draw up guidelines and rules and regulations.’”

Those sentiments pretty much apply to all that the agency does. It is spending $6 billion of California taxpayers’ money, including interest, on research that is yet to produce a commercial therapy, despite the facile promises of the ballot campaign that created it in 2004. It is financing experiments in areas that are new to medicine, some of which involve serious risk and ethical considerations.

All of which might seem to be issues that would engage many persons and enterprises. But the best way to discourage involvement by those not embedded in the agency is to withhold information until it is too late to respond. If interested parties don’t know what is going on, how can they offer suggestions and criticism, some of which might be useful and help the agency succeed in its endeavors? Not to mention helping to build support for continued funding beyond 2020, when the agency expects to run out of cash.

Additionally, the agency basically hides the schedule of its public meetings on its Web site. They are virtually invisible on the agency’s home page, buried at the bottom in teeny lettering under a heading of “about CIRM” -- one of 11 subjects such as “mission” and “history.”

In many ways, CIRM is more than amply open and transparent. Its board meetings are audiocast on the Internet and by phone. Its committee sessions are now available live online as well, an improvement that began during the last few months. Transcripts of the sessions are also available online, albeit sometimes months after the sessions.

The CIRM Web site is laden with a variety of material. The agency’s excellent blog, The Stem Cellar, produces daily reports that chronicle CIRM affairs as well as research developments elsewhere.  Interested persons can sign up for email alerts on various CIRM matters. Eventually, most of background information on board meeting agendas is posted online, although sometimes only a day or two ahead of the session.

Nonetheless, CIRM can and should do a better job of telling California what its governing board is up to and what the agency is thinking and doing. One key and long neglected tool is to provide more detailed information -- well in advance -- about the issues that come before the 29-member board that hands out the cash and establishes the priorities for one of the most ambitious stem cell programs in the world.

Champion of Stem Cell Research: Nancy Reagan Hailed by California Stem Cell Leader

The chairman of California’s $3 billion stem cell research effort yesterday weighed in with a tribute to Nancy Reagan and her support for human embryonic stem cell research.

Jonathan Thomas said,

“With the passing of former first lady Nancy Reagan the California Institute for Regenerative Medicine has lost a good friend and a champion of stem cell research. Mrs. Reagan was an advocate for stem cell research for many years and her voice was an important one in helping ensure the passage of Proposition 71. Her call to protect the ability of scientists to ‘pursue medical miracle possibilities’ echoed the feelings of millions of Americans looking to stem cell research for help in battling deadly diseases. We, and patients everywhere, were fortunate to have such a great champion for the work that we do.”

Nancy Reagan’s backing of hESC research began in the spring of 2004 with an unsuccessful effort to convince former President Bush to rescind his restrictions on federal funding of hESC research.

An Associated Press story said at the time,

"'It's hard to overstate or overestimate the power of her impassioned plea for the Bush administration to reform its stem cell policy,' said Daniel Perry, president of the Coalition for the Advancement of Medical Research. "She's given permission for very conservative, anti-abortion Republicans to disagree with Bush. It's a courageous stance against a president of her own party."

Newsweek magazine also carried a piece about her efforts.

Royalties and California Stem Cell Research: $1.1 Billion Promise Still to be Fulfilled

California’s 11-year-old stem cell research effort was born with the extravagant promise that it would generate something like  $1.1 billion in royalties that would flow into the Golden State’s coffers.

None of that bonanza has yet surfaced, but there is no doubt that scientific research generally has the potential to generate economic value for state entities. A case in point was news this morning in the Los Angeles Times that the sale of drug rights (intellectual property or IP) held by UCLA will generate “hundreds of millions of dollars.”

The story by Teresa Watanabe said the deal involved a prostate cancer drug developed at the campus. She reported,

“Royal Pharma, a New York-based pharmaceutical company, paid $1.14 billion for royalty rights to the drug known as Xtandi. It was the largest-ever technology transfer deal involving a University of California invention.”

 California’s $3 billion stem cell agency is not involved in the UCLA-Royal Pharma arrangement. However, the agency, known formally as the California Institute for Regenerative Medicine (CIRM), has acquired other bits and pieces of IP as the result of the $1.9 billion that it has given to researchers over the last decade.

So far the agency has not been able to turn that IP into cash largely because no therapies have reached the marketplace, although the agency has a number of clinical trials underway.

Back in 2005, the royalty promises made during the ballot campaign that created the stem cell agency came under fire as the result of actions by the man who headed the campaign, Robert Klein. He also served as the agency’s first chairman.

Bernadette Tansey, writing in the San Francisco Chronicle, reported,

“The billion dollars in royalties that voters were told could flow to the state if they passed California's $3 billion stem cell research funding initiative in 2004 may turn into an empty promise.”

Stuart Leavenworth, then editor of The Sacramento Bee’s editorial pages, wrote,

“In marketing this initiative, proponents said the state would receive not only miracle cures and reduced medical costs, but also up to $1.1 billion in royalties from new stem cell innovations.

“Now we are learning that this promise, at best, was misleading. At worst, it was a cynical ruse.”

The issue turned on whether tax-exempt bonds would be used to finance the agency, which depends solely on state borrowing. Federal tax laws restrict the use of such bonds. To date, however, no tax-exempt bonds have been used to support CIRM, according to last report.

The use of taxable bonds, however, raises the cost of borrowing and the cost of the research. Estimates in 2004 were that that the total cost of the agency would exceed $6 billion, including the interest on the borrowed $3 billion. No revised, upward estimate has been made public, if it exists.

The issue of the agency’s IP, its possible value and protection has surfaced only intermittently over the years. The most recent mention came last November in the agency’s plan for spending its last $900 million. (The agency expects to run out of cash for new awards in less than four years.)

The agency’s five-year plan said that it would “demand creation (from universities)  for the out-licensing of CIRM-funded technologies with a greater opportunity to achieve a financial return.” Aligned with that is a $75 million proposal to partner with specific enterprises and give them pick of the agency’s best research that does not currently have a partner. (See here and here.)

Relationships with universities can be touchy at the agency because its governing board includes top executives from virtually all of the major, academic stem cell research centers in California. Sometimes those board members can be protective of the interest of their institutions, which have received hundreds of millions of dollars in agency cash over the years.

For those who want to dig more deeply into CIRM’s IP policy, the regulations can be found here and here.

Scientists to Executive Assistants: California Stem Cell Agency Seeking to Fill Four Positions

Looking for stem cell work in warm and dry California?

The state’s $3 billion stem research effort is seeking four persons to fill slots as an executive assistant to the vice president of therapeutics, project manager for medical affairs and centers and two science officer positions, one on the discovery team and another in therapeutics.

The job descriptions and requirements, along with salary ranges, can be found on this Web page.

The agency is headquartered in new offices in downtown Oakland, overlooking Lake Merritt, close to public transportation. The offices are also only a 30-minute walk from the waterfront saloon where author Jack London misspent a portion of his youth.

California's $30 Million Bet On a Cancer Treatment: New Company Formed to Bring the Therapy to Market

Highlights

Stanford, Weissman involved

Good news for CIRM

Google hooked in

A new stem cell company that targets cancer by unleashing an “eat me” trigger has emerged from a $30 million investment by the state of California.

Creation of the Palo Alto firm, which is called Forty Seven, Inc., was announced this week by its backers and its key researcher, Irv Weissman, director of Stanford University’s stem cell program.

Venture capitalists, including Google, are supporting the enterprise with $75 million. The effort

has two phase one clinical trials underway, the first step in a years-long process of testing potential therapies before the federal government approves their widespread use.

Forty Seven, named after the molecular target of the “eat-me” trigger, is not the first firm to emerge from research funded by the California Institute for Regenerative Medicine (CIRM), as the state stem cell agency is formally known. At least eight others have surfaced over the years.

But this week’s announcement attracted some national attention in a story by Alex Lash on Xconomy, an online technology information service. Lash wrote,

“This is the kind of news CIRM has yearned for in recent years: significant private cash that gives CIRM-funded projects a push to become actual products and to return value to the state…. After a decade of funding buildings, salaries, and early stem-cell related research—not to mention conflict of interest problems that included a past CIRM president and a different company (StemCells, Inc.) with Weissman’s imprimatur—CIRM and its new president acknowledged it needed to show results for the $6 billion taxpayers committed to the agency in 2004.

“This type of follow-on funding is what we’re looking for,” says CIRM spokesman Don Gibbons, who adds that the big financial awards for Stanford were in line with the agency’s mission “to get things moving early when others won’t invest.”

(See here, here and here for more on the conflicts of interest.)

Voters approved the creation of the $3 billion agency in 2004. But no therapies have emerged for widespread use despite the optimism of its early backers and campaign promises. The agency expects to run out of funds for new awards in 2020. One of the possibilities for new funding is another multi-billion dollar state bond issue. State bonds are the only significant source of cash for the Oakland-based agency.

Xconomy reported that CIRM has yet to provide its final $5.1 million to Weissman. And Lash wrote that “Forty Seven is in the process of taking charge of the grant-funded programs.” Asked this morning by the California Stem Cell Report whether the funds would be going directly to the firm, Kevin McCormack, senior director of communications, replied,

“Our grant goes to the principal investigator on the project, in this case it’s both Irv Weissman and his co-PI Ravi Majeti. Both are at Stanford.”

Weissman’s technique uses a monoclonal antibody that attaches to the CD47 protein on cancer cells them from hiding from the patient’s immune system. Lash wrote,

“But cancer cells also produce what Weissman and colleagues call an ‘eat me’ signal from a protein called calreticulin. Normal, healthy cells don’t. By cutting off the CD47 ‘don’t eat me’ signal, Hu5F9-G4 should in theory allow the calreticulin signal to prevail.”

Stanford, which has a member on the CIRM board of directors, is the No. 1 recipient of funds from CIRM. It has chalked up 98 awards totalling $308 million. Weissman has received five awards totalling $36 million. StemCells, Inc., which was co-founded by Weissman, has been awarded $9 million in for three projects.

Chinese Cloning Firm Pumps $15 Million into California Stem Cell Business

A Chinese firm that says it has the technology to clone human beings has invested $15 million in a stem cell company in Northern California.

The American firm is Cesca Therapeutics of Rancho Cordova, a suburb of Sacramento. The Chinese enterprise is BoyaLife Group, which has plans to clone one million cattle a year by 2020. In December, Rebecca Davis of Agence France-Press interviewed Xu Xiaochun, CEO of BoyaLife, and wrote:

“The Chinese scientist behind the world's biggest cloning factory has technology advanced enough to replicate humans, he told AFP, and is only holding off for fear of the public reaction.”

BoyaLife has a South Korean partner, Sooam, which was founded by Hwang Woo-Suk, the researcher who generated a global scandal in 2005 by falsly claiming to have cloned a human embryo. Sooam is involved currently in cloning pet dogs at $100,000 a pop, according to AFP.

Last year, Cesca lost a bid for $11 million from the California stem cell agency. The president of the firm, Robin C. Stracey, told this writer at the time that it expected to partner with another enterprise rather than try again for California stem cell agency funding.

The company’s application to the state research agency sought funds for a phase three clinical trial for a process to treat critical limb ischemia, which can lead to the loss of limbs.

Dale Kasler of The Sacramento Bee reported today that financially strapped Cesca could be taken over by BoyaLife. He reported that the company said this week that BoyaLife intended “to become a majority shareholder” in Cesca.

Kasler wrote,

“However, a change in control isn’t imminent, and Cesca officials said they welcome BoyaLife’s investment as a vote of confidence in their company.”

The New York Times reported last November that BoyaLife is planning the world’s largest animal cloning center in China this year. It quoted Xu as saying,

“And I can tell you all that cloned beef is the tastiest beef I have ever had.”

It was not clear, as of this writing, what role, if any, Cesca would have in cloning animals.

Cancer and Stem Cells: A Look at the Safety of iPS cells

The safety of reprogrammed adult stem cells was much in the news during the past few days as a result of work at the Scripps Research Institute that was funded by California’s $3 billion stem cell agency.

The press release from Scripps triggered a spate of stories quoting Jeanne Loring, who led the work. The Scripps release said,

“A new study led by scientists at The Scripps Research Institute (TSRI) and the J. Craig Venter Institute (JCVI) shows that the act of creating pluripotent stem cells for clinical use is unlikely to pass on cancer-causing mutations to patients.

“The research, published February 19, 2016, in the journal Nature Communications, is an important step in assessing patient safety in the rapidly developing field of stem cell therapies.”

The stem cell agency took a deep dive into the research today on its blog, The Stem Cellar, by Karen Ring, a former stem cell researcher who is the agency’s web site and social media manager. Ring wrote,

“It’s good news that reprogramming methods are relatively safe, but the fact that maintaining and expanding iPS cells in culture causes cancerous mutations is still a major issue that scientists need to address.

“Jeanne Loring recognizes this important issue and says that the next steps are to use similar genomic analyses to assess the safety of reprogrammed iPS cells before they are used in patients.”

Scripps’ press release reported that funds from five different stem cell agency grants were used in the research. Additional funds were also provided by a variety of sources.

Inside STAP: New Yorker's Long Look at the Flap and its Implications

Over the weekend, the New Yorker published online a bang-up and thorough account of the STAP stem cell scandal of 2014. which stretched across the Pacific from Japan to Boston.

The subhead on the story said,

“Rivalries, intrigue, and fraud in the world of stem-cell research”

The piece was authored by Dana Goodyear, a writer for the New Yorker who also teaches writing at the University of Southern California.

UC Davis stem cell researcher Paul Knoepfler, who carried on his blog early and lengthy pieces on the STAP flap, today said of the article:

“It’s a long, fascinating look inside of STAP, the tangled and ultimately tragic scientific implosion that created and then brought down two Nature papers and some careers.”

Goodyear’s article brought out much fresh material, including a more detailed look at the history of the STAP research than has been previously published. The piece also contained probably enough scientific detail to satisfy the experts in the field.

But Goodyear also included thoughts on the stem field in general, issues related to scientific journals, hyper-competitiveness among researchers, replication of research and more. Here are a couple of excerpts from the article, which we highly recommend:

“The promises of stem-cell research lie at the core of human desires—to understand our origins and to cheat death—and there is a great deal of money and prestige at stake. It is a ruthlessly competitive field, susceptible to fantasy and correspondingly sensitive to bunglers. Human embryonic stem cells were first cultured in 1998; nearly twenty years later, basic assumptions about cell behavior are still routinely overturned. Andrew McMahon, a top researcher at the Broad Center for Regenerative Medicine and Stem Cell Research, at the University of Southern California, told me, “It’s not unusual to see something and not be able to explain it.” In reporting results, researchers must often craft a narrative to make sense of mysterious phenomena. What to ignore and what to privilege—that discernment can be the difference between brilliance and quackery, and between fame and obscurity.”

On the difficulties in replicating research findings:

“Many people believe this is partly the fault of the scientific journals. Along with the influential role that Nature has in shaping the trajectories of ideas, technologies, and careers, it is essentially a commercial enterprise. The editors like big stories, and for the right ones they take risks. Some observers complain that incentives to publish have a distorting effect, causing scientists to oversell data; a cutthroat culture sometimes leads researchers to publish intentionally incomplete or vague protocols. The perceived conflict between good science and prestige has become so pointed that, two years ago, Randy Schekman, a Nobel Prize-winning biologist, announced in the Guardian that he would no longer publish in Nature, Cell, or Science, which, he wrote, ‘aggressively curate their brands, in ways more conducive to selling subscriptions than to stimulating the most important research.’”

Leukemia Treatment: California Stem Cell Agency Awards $3.8 Million to San Diego's Angiocrine Bioscience

CIRM graphic

The California stem cell agency today approved a $3.8 million award to a San Diego firm to help develop a better way to treat such afflictions as leukemia with cord  blood transplants despite concerns that the effort was too complex.

Shahin Rafii, Cornell photo

The funds will go to Angiocrine Bioscience, Inc., whose key technology is licensed from Weill Cornell Medical College and was invented and developed by Shahin Rafii, a professor of medicine at the New York school. He remains on the company's scientific advisory board.

Directors voted 13-0 to approve the award, but not before two directors raised questions. Joe Panetta, president of the San Diego-based industry group, Biocom, wondered about difficulties with the manufacturing process raised by the agency’s blue-ribbon reviewers, who earlier approved the application behind closed doors.

Steve Juelsgaard, former executive vice president of Genentech, also raised questions. If the effort flounders, he said, 

“We need to be able to put the brakes on.”

CIRM officials said that the research would be closely monitored with clear milestones that needed to be achieved before cash continued to flow to the company.

The agency’s press release said Angiocrine

“plans to develop a product called AB-110, which blends an expanded mix of stem cells from cord blood with genetically modified endothelial cells, the kind of cell that forms the lining of blood vessels, to improve the success rate of cord blood transplantation.

“The hope is that AB-110 will reduce the complications that can occur with a cord blood transplant – such as viral infections or pneumonia – and increase the likelihood the transplanted cells will successfully engraft, meaning they start growing and creating new, healthy, blood cells.”

No members of the public spoke at the teleconference meeting which had 12 public locations around the state. The next meeting of the agency’s directors will be March 16 near San Francisco International Airport and will be a face-to-face session with likely a handful of remote public locations.

Speak Up! A Chance to Sound Off to California Stem Cell Agency

If you would like to speak directly to the governing board of the $3 billion California stem cell agency, here’s your chance on Thursday.

The  directors are holding a teleconference meeting at 11 a.m. PST with public locations at 12 different sites around the state. The purpose of the meeting is to approve a $3.8 million application for work on process to manufacture a cord blood treatment for such afflictions as leukemia and lymphoma.

Approval is expected to be routine since the agency’s blue-ribbon reviewers, meeting behind closed doors, have already decided the application should be funded. The identity of recipient, as usual, is being withheld until after the board ratifies the decision by reviewers.

Every board meeting has a point at which any person can address the board on any issue. The board sets a three-minute time limit but has been very flexible in the past.

The teleconference locations are in Oakland, Redwood City, Napa, South San Francisco, Beverly Hills, Fresno, San Diego, Elk Grove, Los Gatos, San Francisco (two different locations there) and Irvine. Specific addresses can be found on the meeting agenda,

You may want to double-check in advance with the agency on the addresses. Only one lists a room number. Others may need to include that detail as well.