A USC Researcher's Perspective on the Grant Round Involving StemCells, Inc.

A USC scientist late today sent an email that dealt with the 2012 decisions that resulted in the award of $19.3 million to StemCells, Inc., by the California stem cell agency. The award was made on a close vote (7-5) despite being rejected twice by the agency’s reviewers.

It was the first time that the agency’s 29-member board had approved an application that was turned down twice by its respected reviewers. 

The circumstances surrounding the award were unusual in other respects, and we are providing links to stories carried by the California Stem Cell Report at the time to provide additional context. The links are at end of the scientist’s email.

The author of the note is Lon S. Schneider, a professor of psychiatry, neurology and gerontology at the Keck School of Medicine at USC.  He was co-PI on an application in the same round as the StemCells, Inc., proposal. His application was rejected by the CIRM board despite having a higher score than the StemCells, Inc., application. 

Then-CIRM President Alan Trounson recused himself from the public discussion of the proposal by StemCells, Inc., because of his relationship with Stanford researcher Irv Weissman, who sits on the company’s board.  This month, Trounson was named to the StemCells, Inc., board seven days after leaving the stem cell agency, triggering a flap over conflicts of interest.

Here is Schneider’s note:

“In view of the CIRM’s comment today that they commissioned their own lawyers to investigate and find no conflicts, I thought that I’d share some thoughts with your readers based on my experiences with CIRM.  An investigation of CIRM’s actions during the last month or so would – almost by definition – not reveal a serious conflict because the alleged conflicting behavior would have occurred at the time that the StemCells, Inc. contracts were awarded, if it happened at all.  Bending milestones after a contract is awarded and when one’s foot is out the door is of little concern and can be corrected.

“My interest in Mr. Trounson’s alleged actions is that my colleague and I submitted an Alzheimer's disease grant that was scored higher than StemCells’ Alzheimer’s grant in the same funding cycle. Yet, StemCells’ appeal was funded, while our appeal was not even accepted as an appeal application.  Our recourse was to protest during the public comments part of the CIRM board meeting at which StemCells’ was awarded their contract.  In my opinion, Mr. Trounson and the CIRM staff were clearly antagonistic to us and strongly supportive of StemCells.  Board members were not aware of our appeal.  Indeed, the Alzheimer’s disease advocate on the CIRM board, Leeza Gibbons, who was well-rehearsed in her advocacy for StemCells, Inc, had to be informed during a break on what our grant was about so that she could support it as well.

“StemCell’s sinecure for Mr. Trounson reinforces my opinion that the StemCell/CIRM arrangement was – let’s say -- interesting.  No doubt, others will disagree and point out why our proposal – although rated higher than StemCells – was deficient and should not have been funded while StemCells’ should have been and was.  They, of course, may have a point, and I will continue to believe that the StemCell contract was awarded in no other way than with probity. I thought I would nevertheless share these observations.”

Here are links and excerpts from the 2012 articles.

StemCells, Inc., Wins Another $20 Million From California Stem Cell Agency

Following a second impassioned pitch by its former chairman, Robert Klein, the governing board of the California stem cell agency approved a $20 million award to a financially strapped biotech firm, StemCells, Inc., of Newark, Ca.

An Unseemly Performance: Former Chair of Stem Cell Agency Promotes $20 Million Research Proposal

Bob Klein is nearly an icon in the history of the $3 billion California stem cell agency. And when he appeared before its governing board last month and aggressively touted a $20 million grant proposal already rejected by agency reviewers, his actions raised eyebrows.

Arm-twisting and Emotion: Stem Cell Directors Move to Reform Appeals on Multimillon Dollar Grants

Frustrated with politicking, “arm-twisting,” lobbying and “emotionally charged presentations,” the governing board of the $3 billion California stem cell agency today approved short-term changes in its grant appeal process and ordered up a study to prepare long-term reforms.

California Stem Cell Firsts: From Emotional Appeals to $40 Million Awards

During the last few months, the $3 billion California stem cell agency, which is approaching its eight-year anniversary, has chalked up a number of important firsts.

California Stem Cell Agency Scores on Early Coverage of Today's Trounson Story

Two media outlets were quick today to write about the Trounson Affair and the reaction from the California stem cell agency, but did not note what the agency itself described as the limited nature of its investigation into the matter.

They focused on what Randy Mills, the new president of CIRM, promised regarding his future employment and acceptance of gifts and travel. The upshot was a PR plus for the agency, which has been caught in a “bit of stink” since Alan Trounson, its former president, was named to the board of directors of a firm that has received $19.4 million from the agency.

John M. Simpson of Consumer Watchdog of Santa Monica, Ca., who has been sharply critical of the Trounson appointment, released a statement, declaring,

"CIRM President Randy Mills clearly recognizes the importance of ethics and personal integrity.  His formal agreement to refuse employment with a company CIRM has funded for at least a year after his departure proves he understands the potential for conflict and is committed to maintaining a high standard of integrity.   

"His action helps correct the damage  done to CIRM’s standing by former President Alan Trounson rashly and inappropriately joining the board of StemCells Inc, a mere week after leaving the agency.

 "Meanwhile, CIRM should make public all emails and letters between Trounson, StemCells Inc, and its employees and directors.” 

Ron Luety of the San Francisco  Business Times wrote that Mills’ action stopped short of rebuking Trounson.  Luety also said that Mills’ response seemed like a “no-brainer” but appeared necessary.  Simpson was quoted along with Mills.

Bradley Fikes of the San Diego U-T also quoted Simpson. Fikes additionally wrote,

“Mills made the right decision, said Jeanne Loring, a CIRM-funded stem cell researcher at The Scripps Research Institute.

"’There's a difference between what is legal and what is ethical,’ said Loring, who attended the meeting. ‘And he's going to be pushing the needle a lot more toward the ethical side without worrying whether he can get away with stuff.’"

It was Kevin McCormack, senior director of public communications for the agency, who told CIRM directors late in the meeting that the agency had been caught in a “bit of a stink” this past month as a result of the coverage. 

Law Firm Memo on Trounson Investigation

Here is the memo provided by Remcho, Johansen & Purcell concerning its limited investigation of Alan Trounson and his contact during May and June with StemCells, Inc. It contains additional details and the names of persons interviewed.

 Here is one paragraph that deals with what CIRM might have done had they known Trounson was in contact with the firm concerning employment. The full text follows.

“Dr. Trounson contacted Martin McGlynn, SCI’s President and Chief Executive Officer, on May 1, 2014 to set up a meeting to discuss his future plans. Based on a calendar entry, it appears that Dr. Trounson and Mr. McGlynn met on June 4, 2014. On June 9, 2014, SCI offered Dr. Trounson a seat on SCI’s Board of Directors, subject to the Board’s approval. SCI made the appointment on July 7, 2014. Had SCI notified CIRM at the time of its offer to Dr. Trounson, CIRM would have taken steps to wall Dr. Trounson off from any involvement in decisions relating to SCI.”

  Remcho Memo on Trounson Investigation by DavidJensen

Limited Trounson Investigation Shows No Evidence of Illegal Conflicts

The California stem cell agency said today that its "severely" limited investigation found no evidence that its former president, Alan Trounson, attempted to influence action on behalf of StemCells, Inc., during June of this year.

Randy Mills, the new president of the agency, said the inquiry involved examination of documents, emails and interviews with staffers of the California Institute of Regenerative Medicine(CIRM), as the agency is formally known. But he noted that the investigation was "severely" constrained because it involved only internal CIRM activities and interviews with Trounson. The agency does not have subpoena power or the ability to scrutinize StemCells, Inc.'s internal records.

Mills said that the inquiry covered a period beginning June 9 when Trounson was offered a position on board of StemCells, Inc., a publicly traded firm based in Newark, Ca. The firm has received $19.4 million from CIRM. Trounson's appointment was announced seven days after he left the agency on June 30. The agency was not notified in advance about Trounson's appointment. Directors of StemCells, Inc., were paid up to $99,000 during 2013.

The investigation also disclosed, Mills said, that StemCells, Inc., in June requested and received special funding and other financial benefits from the agency despite its failure to meet the milestones specified under its contract with CIRM.

Mills said a full report on the investigation would be made available to the public. The inquiry was conducted by an attorney, Margaret Prinzing, with the law firm that is the long-time general counsel to the board, Remcho, Johansen&Purcell of San Leandro, Ca.

A number of board members expressed concern about the negative publicity that resulted from the Trounson appointment. Chairman Jonathan Thomas said the probity of the agency was of "paramount importance."

CIRM Director Michael Friedman, CEO of the City of Hope, said that the situation could have been managed better if Trounson and the company had disclosed to the agency the possible hiring at the time it was first discussed.

Another director Jeff Sheehy, a communications manager with UC San Francisco, admonished recipients of CIRM awards to exercise some discretion in connection with conflicts of interest and to respect the people of California.

Mills said that as a result of the inquiry he was going to go beyond state law dealing with conflicts and revolving door employment. He said he would not accepts gifts or travel from enterprises with financial connections to CIRM even when permitted by state law. Mills also pledged not to accept employment with a CIRM award recipient until at least one year after leaving CIRM, another standard that exceeds state law.

Following today's meeting, the agency issued a press release about Mills' decision. The release did not mention the investigation into the Trounson Affair.

Mills said the standards applied only to himself. He said he did not want to block possible employment of CIRM staffers by CIRM grant recipients in the future.

It was not known when the Trounson investigation report would be available. Here are the slides that Mills used for a variety of purposes at today's meeting. His summary of the investigation is contained within the slides, beginning on slide 6. His signed pledge regarding conflicts is also contained in the slides.

   California Stem Cell Agency Slides on Trounson Investigation FINAL by DavidJensen

California Stem Cell Agency Directors Conclude Meeting

Directors of the California stem cell agency adjourned their meeting today at 12:09 p.m. PDT. A story on the discussion of the Trounson Affair will be carried shortly.

$1.2 Million for UC Stem Cell Researchers

Directors of the California stem cell agency today approved $1.2 million for two University of California researchers to continue pursuing their work on Huntington’s Disease and corneal problems.

The awards went to Leslie Thompson of UC Irvine and Sophie Deng of UCLA. Thompson received $505,717 for her work on Huntington’s Disease (see here and here). Deng received $699,983 for her eye research (see here and here).

$5 Million Sliced from California's Ambitious Alpha Stem Cell Clinic Program

Directors of the California stem cell agency today cut $5 million from their $70 million plan to create a series of Alpha stem cell clinics aimed at making the Golden State the leading location in the world for stem cell therapies.

On a 6-1-1 vote, the directors trimmed the effort, much touted by former agency President Alan Trounson. Eliminated was a data/information center whose tasks would have included marketing and patient education. The center also would have worked on strategies to persuade the federal government and insurance companies to pay for what are expected to be enormously expensive treatments.

The board has 29 members. However, only eight were allowed to vote because of conflicts of interest among the others. 

The cut by the board of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known, came after its new president, Randy Mills, recommended scaling back the effort. He told the board the plan was not “clearly justified.”

He said in a memo,

“The proposal as written is too broad and overly complex to be successful. In a word, it lacks focus.”

Mills proposed that a refined RFA be reissued with $10 million in funding, which the board approved. It was the first time that the board had retroactively revised a concept plan and directed that an RFA be reissued.  

The Alpha clinic concept first surfaced publicly in 2011. Trounson and two other CIRM executives promoted the plan in a scientific journal financed by the stem cell agency. (See here and here for more.)

Trounson wrote that the scientific community owes it to persons suffering from diseases “to rapidly implement the best and safest practices for cell therapy clinical trials and move toward fast-tracking in therapies where safety and efficacy has been proven.” Nature Medicine said it would be the first-ever “clinical trials network focused around a broad therapeutic platform.”

Eight institutions have applied for the main portion of the award, which is designed to make California a one-stop shopping center for stem cell therapies. The hope is that patients will be attracted from throughout the world. Up to five awards are scheduled to be made for those clinics.

A separate RFA deals with the data center. Five institutions have applied in that RFA, including some also involved in the main portion.  The agency has already received all of the applications in both categories. Based on testimony today, it appears that UC San Diego, the City of Hope and Stanford have all submitted applications in the data center round. 

Although the applicants have not been identified by the agency, virtually all are likely to be represented by persons sitting on the CIRM governing board because of the nature of the concept plan and the RFA.

Review of the applications is scheduled for this September but was originally scheduled for June. In one of his first public actions, Mills delayed the review. The agency said it needed more time to secure knowledgeable reviewers, who must come from out-of-state.

Reduction of the size of the proposal will free cash for other research efforts. Directors are feeling increasingly pressed by financial issues. The agency is scheduled to run out of cash for new awards in less than three years. It is looking into some sort of public/private combination of financing that will allow it to continue in the same fashion beyond 2017.

The CIRM board approved the original Alpha concept in July 2013. At the time, the plan was hailed by the directors, who spent little time discussing the data center that was revised today.

Earlier items on the California Stem Cell Report incorrectly indicated that the effective reduction proposed totaled $15 million instead $5 million.

CIRM Says No Ilegality in Trouson Affair

The California stem cell agency today said its limited investigation has determined that no laws were violated when the StemCells, Inc., which holds a $19.3 million award from the agency, appointed the agency's former president to the company's board.

More on this later.

Trounson Appointment Comments Begin CIRM Directors Meeting

The governing board of the $3 billion California stem cell agency this morning began its meeting at 9:08 a.m. with an immediate comment on the Trounson Affair.

Board Chairman Jonathan Thomas reiterated the steps taken by the agency so far and said maintaining the public trust in the agency is paramount. CIRM President Randy Mills is expected to make further comments later in the meeting.

Coming Up: Live Coverage of Today's California Stem Cell Meeting

The California Stem Cell Report will provide live, gavel-to-gavel coverage of today's meeting of the 29 members of the governing board of the $3 billion California stem Cell agency, which is expected to lop $15 million from its ambitious Alpha stem cell clinic proposal.

Not on the agenda, however, is the so-called Trounson Affair, although the matter (see here and here)  may well come up at the session, which begins at 9 a.m. PDT. 

Interested parties in Canada will be able to participate in the meeting from the W Montreal Hotel, where one of the CIRM directors is staying. However, the agenda does not mention a room number so our advice is to check with the agency for specifics. The room is public by law for CIRM meeting purposes.

Other teleconference locations are available in Los Angeles, which has two, and one each in La Jolla and Napa.

The meeting, which will be in Millbrae, Ca., can be heard through the Internet via an audiocast. Directions for logging in can be found on the agenda. 

A Brief Look at the $12 Million California Stem Cell Bridging Program

The directors of the California stem cell agency later today are expected to approve $1.2 million for two University of California stem cell researchers as part of what the agency calls a “bridging” program.

The effort has received little attention but could be a key for some research as scientists try to turn more basic efforts into something that could reach the marketplace.

Patricia Olson, executive director of scientific activities , has prepared some slides for today’s meeting in Millbrae, Ca., that lay out a bit of the scope of the effort.

She reported that the goal of the program is to accelerate development of stem cell therapies. She said the bridging program is aimed at providing an “efficient and seamless advancement of promising CIRM-funded translation and development projects towards and through clinical development.”

No RFA is used for the effort. Instead scientists must submit a brief proposal that could lead to further consideration. Up to $12 million has been allotted to the effort. Olson did not present information on how many proposals have been submitted.   

California Stem Cell Agency Director Prieto Defends Agency in Trounson Affair

One of the long-standing directors of the $3 billion California stem cell agency has taken issue with an item earlier today headlined “Fallout From the Trounson Affair: A Taint on the California Stem Cell Agency.”

In an email, Francisco Prieto, a Sacramento physician, said, among other things, that it is “grossly unfair” to say that none of the media coverage and other reaction in the matter reflects well the agency. Prieto, who has served as a CIRM director since 2004, said “the agency had nothing to do with it.”

The item this morning discussed reaction to the news earlier this month that the agency’s former president, Alan Trounson, was appointed to the board of StemCells, Inc., which is the recipient of $19.4 million in funding from the stem cell agency. Concerned about a conflict of interest, the agency has announced a “full review” of all StemCells, Inc., activities. Trounson was appointed seven days after he left the agency.

The item also contained a comment from scientist Jeanne Loring of Scripps that said that the Trounson Affair detracts from the value of CIRM’s good work.

Here is the text of Prieto’s comment, the essence of which is certain to be shared by many CIRM board members,

“I think Jeanne Loring is right: CIRM has been a remarkable driver of this research, and it would be a shame if the actions of Dr. Trounson and StemCells Inc. (What were they thinking?) obscures this.  I think it is grossly unfair to say that ‘none of this reflects well on the agency,’ when the agency had nothing to do with it.  Most of us on the board – and the staff, I think it’s safe to say – felt blindsided by this.  I was gratified to see Randy Mills’ prompt and appropriate response to this, and I expect we’ll hear more from him on the subject.  I think it’s a bit disingenuous of Michael Hiltzik (of the Los Angeles Times) to say that ‘so many members had to recuse themselves that only nine were left to vote,’ when the new voting procedures (that prohibited members from grant-receiving institutions from discussing or voting on those grants) were a direct response to the reform recommendations in the IOM report, and were lauded by most at the time. I don’t think that included Mr. Hiltzik, who I believe has never had anything good to say about the agency or its work. I’m curious whether that will change as stem cell treatments we’ve funded actually start moving into clinical trials, but I won’t hold my breath.”

The California Stem Cell Report has great respect for Prieto and the other 28 members of the agency’s board and its staff.

However, there is no escaping the impact of the news and the resultant commentary, which will be around virtually forever, embedded in every Internet search that is performed about the stem cell agency. Today, for example, a Google search on the term “California stem cell agency” turned up eight hits on the first page of search returns. Five dealt with the Trounson Affair.

Moreover, conflict of interest concerns were aired very early on in CIRM’s history, dating back to 2004, before the ballot proposal creating the agency was even approved by voters. Revolving door issues also came up years ago, including in 2007 when Richard Murphy, a former member of the board, was hired as interim president at a salary of $300,000 for six months work. The Little Hoover Commission mentioned the issue briefly in its 88-page report in 2009.

Additionally, given that financing of the agency was limited to 10 years, revolving door problems were always likely to surface. It was an issue that could have been dealt with by the board years ago, avoiding the situation with Trounson today. Revolving door restrictions could have and should have been part of his conditions of employment.

The IOM’s recommendations for dealing with conflict-of-interest problems at the agency were far-reaching. The steps taken by the agency do little to comply with the IOM recommendations.  The strange case of having only nine out of 29 members eligible to vote is not all that uncommon. Indeed, the agency has worked hard to keep its 12 patient advocate members in attendance at board meetings because sometimes they are the only ones who can vote without legal conflicts-of-interest.

The situation with Trounson is certainly unpleasant.  Whether board members think the reaction is unfair is not the main point. It is up to them to take action to respond to those public concerns and ensure that the agency’s integrity is reinforced and that its work is not impugned by conflicts of interest, real or perceived.

Fallout From the Trounson Affair: A Taint on the California Stem Cell Agency

Directors of the $3 billion California stem cell agency meet tomorrow in the San Francisco Bay Area, but the hottest topic is not on the agenda, and that is the Trounson Affair.

Alan Trounson
SF Business Times photo

The term is shorthand for the host of questions raised by the appointment July 7 of Alan Trounson, former president of the agency, to the board of StemCells, Inc. The company is the recipient of $19.4 million from the agency, cash that was awarded under unusual circumstances on a narrow 7-5 vote.(See here and here.)

Two days after Trounson’s appointment, the agency’s new president, Randy Mills, announced a “full review” of the activities involving StemCells, Inc., a publicly traded firm based in Newark, Ca.

News and commentary about the matter has slowly emerged since the appointment. None of it reflects well on the agency, which is trying to devise some way to secure public or private funding beyond 2017 when the cash for new awards runs out.

The most visible article appeared in the Sunday Los Angeles Times, which has a readership of 4 million in print and online. Michael Hiltzik wrote that cronyism is rife at the California Institute for Regenerative Medicine(CIRM), as the agency is formally known.  He said,

“How bad are the conflicts? When the (29-member) board considered a proposal earlier this year to spend $16 million to attract three star scientists to California, so many members had to recuse themselves that only nine were left to vote. (Six ended up voting in favor.)

“When conflicts of interest are so rife that only one-third of your board can weigh in on a major policy issue, that's tantamount to not having any board at all.”

The tone was echoed in other pieces, including one in the San Francisco Business Times, where the headline said,

 “'Trounson affair' another strike against California stem cell agency.”

Other articles appeared in the San Diego U-T and the San Francisco Chronicle. The Orange County Register published an editorial that said the agency has “operated as a cash cow for a tiny circle of well-connected individuals and institutions.”

The Trounson appointment “reignites charges of cronyism,” said a headline on allgov.com. Pete Shanks of the Biopolitical Times wrote, 

"Let's be blunt: This looks like a pay-off. Technically, what Trounson and (Irv) Weissman (of Stanford) and StemCells, Inc., just did may not be illegal. But it's shameless.”

The Scientist magazine wrapped the Trounson appointment into a piece that included news about a lawsuit against StemCells, Inc., that charged the company was endangering patients in clinical trials. 

The talk ricocheted around California’s stem cell community. One longtime reader of the California Stem Cell Report, who is a patient advocate, said in an email that Trounson’s conflicts of interest are “now even more transparent and make the previous grant decisions even more suspect.” “Self-dealing” is how this supporter of stem cell research described the situation.

Another reader and knowledgeable observer, who also must remain anonymous, described the Trounson appointment as “brazen.” And yet another who is quite familiar with the agency said,

“No one seems to understand what conflict of interest means.  I don't understand how they can even think that it is OK to do this.”

We should note that these remarks come from persons who back stem cell research and the agency.

In some ways, however, public attention to the matter could be described as minimal. The stem cell agency is little known to most people, and the Trounson Affair did not garner front page headlines. But like some sort of immortal cell, the stories will live on. Twenty years ago, the individual stories would have faded, buried in the morgues of the mainstream media. However, today, given Google searches, they will become embedded in all future reporting about the agency – not to mention knife-edged opposition research should another bond measure be placed before voters to fund the agency.

The Trounson Affair also highlights the need for the agency to stiffen its revolving door restrictions – the regulations that would have prevented his immediate appointment to a post at an enterprise that has benefited from the agency’s largess. It is a problem that will grow as the agency nears its financial demise. CIRM staffers will naturally be looking for places where they can find future employment.

The state has some minimal laws restricting future employment by agency personnel. But the agency needs to do more, a difficult task given that such action basically will change the terms of employment for staffers. But failure to confront the issue will only lead to more debacles.

CIRM’s “full review” of the situation is well-taken. However, the agency has not publicly defined even generally what a full review entails nor has it responded to questions from the California Stem Cell Report about the nature of the inquiry. The agency also has not indicated whether it is seeking an outside, independent entity to conduct the review. One possibility would be State Controller John Chiang, who is the chairman of the only state body (the Citizens Finanancial Accountability and Oversight Committee) charged with oversight of the agency. Another would be the state’s Fair Political Practices Commission, the state department charged with enforcing conflict of interest laws.

One California researcher and CIRM grant recipient has noted that the flap obscures the work that the stem cell agency has done. In a comment filed on an item on the California Stem Cell Report, Jeanne Loring, director of the Center for Regenerative Medicine at The Scripps Research Institute, said that despite “the errors in judgment” at the agency, 

“CIRM is at the heart a remarkably effective driver of cutting edge research. By focusing on a narrow area of research and encouraging international collaboration, CIRM has singlehandedly pushed the whole world's stem cell research forward. If CIRM were a drug company, it would be considered miraculous that so many promising treatments are in the pipeline just eight years after it started."

Loring makes a good point. And it would be a shame if the good work of CIRM is discredited because of a failure to deal forthrightly, quickly and publicly with conflict of interest issues at the agency. 

Cloaking Informed Consent in Clinical Trials: A California Stem Cell Case

Patients come first. That’s the rhetoric from biotech companies and agencies like the FDA, which has oversight responsibilities for clinical trials.

But when it comes down to specifics, the doors may close and little revealed publicly.

The case in point involves StemCells, Inc., which was charged last week in a lawsuit with endangering patients involved in its clinical trials. The suit was filed by an unhappy manager who was fired by the Newark, Ca., firm. StemCells, Inc., said the charges lack merit.

But the firm is mum when it comes to the question of whether it has informed its patients about the allegations and its response. Those are the folks whose brains are being injected with what is alleged to be a product that is being manufactured improperly. They are supposed to give informed consent to the treatment and obviously need to know when serious questions are raised about their therapy.

Queried by the California Stem Cell Report about whether the patients in its clinical trials had been informed of the allegations, Ken Stratton, general counsel for StemCells, Inc., said,

“StemCells, Inc. has no further comment on the ongoing litigation or Mr. Williams’ allegations.” 

The FDA and the attorney for the fired manager responded in much the same fashion. Asked whether his client, Rob Williams, or he has notified the FDA about the alleged problems, attorney Daniel Velton said,

“We can't comment on pending cases.”

The FDA said,

“As a matter of policy FDA cannot comment on whether or not we are investigating or have plans to investigate any allegations.”

Questioned further about the federal rules for giving patients the information they need to provide informed consent, Paul Richards, a spokesman for the FDA said,

“Participation in any clinical trial is associated with some level of risk as the safety of investigational products has not been fully assessed. FDA’s primary responsibility is to determine whether the theoretical risks of the proposed study are reasonable and acceptable in order for the study to proceed “It is the responsibility of the study sponsor to conduct an investigation properly, to ensure proper monitoring of the investigation and to ensure that the investigation is conducted in accordance with the general investigational plan and protocols contained in the Investigational New Drug (IND) application.  The sponsor also ensures that FDA and all participating investigators are promptly informed of significant new adverse effects or risks with respect to the product being studied.

 “Additionally, the individual who actually conducts the clinical investigation (i.e. the investigator) is responsible for ensuring that the trial is conducted according to the signed investigator statement, the investigational plan, and applicable regulations.  The investigator is also responsible for protecting the rights, safety, and welfare of subjects under the investigator's care; and for the control of drugs under investigation. 

“In certain situations in which FDA alleges a clinical investigator has violated applicable regulations, FDA may initiate a clinical investigator disqualification proceeding.   FDA does maintain a publicly available database that provides information about disqualification actions.  Further background related to this topic is available at:  http://www.fda.gov/ICECI/EnforcementActions/ucm321308.htm”

No doubt seems to exist that the patients should be informed about the allegations in the lawsuit. However, implementation of the requirement is considerably less than transparent. How does the public know whether patients have actually been informed?  How do the patients themselves know whether they have been adequately informed? Trust us is the operative and dubious response.

One must ask whether these tight-lipped non-responses are in the best interests of patients, biomedical research, the government or even the companies. Patients and the public deserve more than lip-service to the process of informed consent. The parties involved in the StemCells, Inc., litigation, as well as the government, can do better. 

What possible harm could result from simply saying, “Yes, the patients have been told of the lawsuit and the company’s response.” Such a response might help to inspire confidence among persons considering clinical trials and help recruit the patients needed to test possible new therapies.

Coming Up: Live Coverage of Thursday's California Stem Cell Board Meeting

The California Stem Cell Report will provide live, gavel-to-gavel coverage of this Thursday’s meeting of the 29 members of the governing board of the $3 billion California stem Cell agency, which is expected to lop $15 million from its ambitious Alpha stem cell clinic proposal.

Interested parties in Canada will be able to participate in the meeting from the W Montreal Hotel, where one of the CIRM directors is staying. However, the agenda does not mention a room number so our advice is to check with the agency for specifics. The room is public by law for CIRM meeting purposes.

Other teleconference locations are available in Los Angeles, which has two, and one each in La Jolla and Napa.

The meeting, which will be in Millbrae, Ca., can be heard through the Internet via an audiocast. Directions for logging in can be found on the agenda. 

California Stem Cell CEO Randy Mills on Focus and Four-Part Tests

It was a case of CEOs interviewing CEOs.

More specifically, it was Robin Smith, head of Neostem, Inc., “grilling” Randy Mills, the new CEO of the $3 billion California stem cell agency. The venue was the Huffington Post.

It wasn’t exactly hard ball stuff, as one might expect. Nonetheless it was the lengthiest such exchange with Mills, the former president of Osiris Therapeutics of Maryland, since he was named president of the stem cell agency in April.

Neostem, by the way, does not hold any awards from the agency, although it does have operations in Mountain View and Irvine. The Southern California location is the site of the former California Stem Cell, Inc., which was purchased by Neostem for $126 million earlier this year, obviously making Neostem a potential applicant for CIRM funds.

Here are some excerpts from Smith’s interview with Mills.

On leaving Osiris and coming to California, Mills,

“I started discussing with my family what might be next, including taking a break to spend more time with them. However, fate had other plans.

“In February I received a call from CIRM asking if I was interested in the President and CEO position. Having spent the past five years as a grant reviewer for CIRM, I was already quite familiar with the stem cell agency. If you believe in the potential of regenerative medicine and cell therapy as I do, there is no place in the world you could go to have a bigger impact. No company, no other state, not even a country can have the impact California can have in bringing these treatments to patients. And so with that, I accepted the challenge.”

Mills’ four-part test for CIRM projects:

“First, will what we are doing speed up the development of stem cell treatments for patients? Second, will it increase the likelihood of a successful treatment reaching patients? Third, is it for an unmet medical need? And lastly is it efficient?”

Mills’ focus on “focus,” something he mentioned in slicing $15 million from the $70 million Alpha stem cell clinic plan.

“For CIRM to achieve its full potential, I firmly believe we need to remain focused on bringing treatments to patients, fast. Everyone loves that word, ‘focus.’ However, what they may not love is living with its reciprocal, which is everything else we don't do. Without focus, you never have to have the hard conversation. You never have to say ‘no.’ However, without focus, you also tend to not get things done. I came to CIRM to get stem cell treatments to patients in need, and that means focus.”

Mills on funding projects that “otherwise will get done.”

“CIRM exists under the principle of ‘If not for us....’ California stepped up when, and most importantly because, others would not. Funding something here-and-now that will otherwise get done without CIRM is not consistent with what the people of California wanted to accomplish with Proposition 71(which created the agency). It also violates my third rule, because it wouldn't really be an unmet need if it were going to happen in any event.

“We are here to help get stem cell treatments that, if not for us, would take longer to reach patients or might not happen at all. If you look at the projects we support that are now heading into clinical trials, many would never have even gotten off the ground if it hadn't been for us.”­­­­

Mills did not mention this, but funding such projects is also high risk. That’s why they haven’t been funded. So the reasonable expectation is to see a few failures – perhaps more than a few – among the CIRM efforts.

Verastem Bid for Nearly $10 Million from California Nixed

A Massachusetts firm called Verastem, Inc., heard some bad news recently about its pitch for $9.9 million from the $3 billion California stem cell agency.

The Cambridge firm sought the cash from the agency to help out with a clinical trial dealing with breast cancer.

However, the agency’s directors were told in a memo on the CIRM Web site, 

“Weaknesses in the scientific merit of the proposal combined with portfolio considerations led to a staff recommendation NOT to fund.“

By portfolio considerations, the staff seemed to mean that the agency had already awarded funds in the same scientific area.

The agency’s reviewers, who come from outside California, gave the application of score of 74. Formal action will be taken on the application at Thursday’sboard meeting in the San Francisco Bay Area.

Scripps Confirms Marletta's Plan to Leave as President

The Scripps Research Institute has confirmed the departure of Michael Marletta as its president in a 72-word statement, but details about who will replace him and when are yet to emerge.

The move was announced this morning at a meeting at the 2,900-employee institute in La Jolla. Later, Scripps released its terse statement. Not mentioned were any proposals to deal with the financial plight of the renown biomedical research organization, which is the issue at the root of Marletta's resignation.

Bradley Fikes and Gary Robbins of the San Diego U-T have more details and background. Here is the Scripps statement, which is oddly worded, seeming to leave open the possibility of Marletta remaining at Scripps. Fikes and Robbins nonetheless report that four scientists at the morning meeting said Marletta is resigning.

"The Scripps Research Institute (TSRI) Board of Trustees has announced that Dr. Michael Marletta has indicated his desire to leave TSRI and the Board is working with Dr. Marletta on a possible transition plan. Should Dr. Marletta depart TSRI, the Board will work to make any transition to new leadership the highest priority. Any such transition will engage all key constituencies in a dialogue about the future direction of this storied institution."

Scripps Research President Resigns Following Financial Problems at the Institute

Michael Marletta today resigned as head of The Scripps Research Institute, one of nation’s leading biomedical research organizations, in the wake of an aborted, $600 million merger with the University of Southern California.

Bradley Fikes and Gary Robbins of the San Diego U-T reported that the announcement of his resignation came at a meeting this morning at the La Jolla facility. They wrote that no successor has been named.

Marletta joined Scripps in January 2012. His resignation came in the wake of financial problems at the institute, which is operating this year under a $21 million deficit. Leading members of the faculty called for his removal after the proposed merger came to light. 

Scripps has not yet made a formal announcement on its Web Site. 

California's Far-Reaching Alpha Stem Cell Clinic Plan Likely to Take a Hit

The new president of the California stem cell agency today recommended cutting $5 million from the agency’s ambitious Alpha stem cell clinic plan, declaring that the proposal’s $70 million cost is “not clearly justified.”

If the agency’s board goes along with the recommendation at Thursday’s meeting, it will be the first time the $3 billion agency has so radically and retroactively reduced a proposal in its nearly 10-year history.

Randy Mills

In a memo posted early today on the agency’s Web site, Randy Mills, who joined the agency in May, said,  

“While all of the aims of the concept plan are individually laudable, it is my firm belief that the proposal as written is too broad and overly complex to be successful. In a word, it lacks focus. As a result of its overly wide-ranging scope, I also believe that there is a real possibility of incurring significant duplicative costs. Following a thorough review and conversations with senior members of the CIRM team, it is my opinion that the $70 million price tag is not clearly justified in terms of the benefits it will deliver to the people of California.”

The Alpha stem cell clinic program was heavily promoted by the former president of the stem cell agency, Alan Trounson. It is aimed at making the Golden State the world’s “go-to” location for stem cell therapies.

Mills said, however, that a $15 million component creating a data/information center should be stripped from the plan and whittled down to $10 million.

He said the center’s efforts to combine aspects of clinical operations, data sharing, education/marketing and lobbying for insurance coverage of stem cell therapies would create an “unwieldy program.” Instead, he said the Alpha effort should focus on early stage clinical operations  – “efforts directly related to high quality stem cell clinical trials.”

Mills’ proposal comes late in the game for the Alpha awards. Applicants have already submitted their proposals. The review of the applications was originally scheduled to occur last month. However, in one of his first public acts, Mills postponed the review, which is now scheduled for September.  The reason for the delay, the agency said in June, was the difficulty in finding reviewers.

However, the information center component is contained in a separate RFA and could be easily discarded. The only damage would be the time that the five applicants spent on preparing their applications, which is no small task, and the work that the CIRM staff has done so far.

Mills told the board in the memo,

“I realize that making this recommendation after the submission of applications for the CIMC (the data center) is not optimal. However, given the magnitude of the spending proposed, not sharing this critical assessment with the board would be a greater disservice. I believe that these recommendations are not only fiscally responsible, but more importantly, give the program the greatest chance of success to accomplish our mission of getting stem cell treatments to patients in need.”

Mills is also recommending alterations in the clinical portion of the Alpha plan, which involves eight separate applications, all of which are likely to have come from institutions with representation on the stem cell board.  Mills said he wanted  “a staged approach to funding, where we evaluate with proper metrics, the effectiveness of the program in a limited number of sites before expanding.”

Mills’ Alpha memo does not appear to envision modifying the RFA, so presumably the staged funding would be dealt with in negotiations following board action on the applications, which will probably occur later this year.  Up to five awards are scheduled to be made.

Mills’ Alpha cuts are virtually certain to be approved by the board. Rejection of his recommendations would amount to a vote of no-confidence in Mills and would likely result in his resignation. (On Thursday, however, he assured the board he would not quit if it did not go along.)

Even earlier this year, Mills, who has made his career in business, demonstrated his parsimony. Trounson’s proposed operations 2014-15 budget for the agency was submitted in early May at $17.9 million, an increase of 9.5 percent increase over estimated 2013-14 spending. Mills sliced the spending plan to $17.3 million, maintaining it at virtually same level as last year – lower if inflation is factored in.

(An earlier version of this item incorrectly stated that Mills wanted to cut the program by $15 million.)

Creating Critical Mass at a California Stem Cell Consortium

News about the California stem cell agency is dominated by such matters as $70 million Alpha stem cell rounds and clinical trials but other significant activities occur below that high level surface.

One such event is the creation of a state-of-the-art imaging facility at the Sanford Consortium in the San Diego, a facility that was built with the help of a $43 million award from the stem cell agency.

According to Terri Somers, a spokeswoman for the imaging facility,

“It is the only commercial location within California where these high-powered imaging modalities are available to researchers under one roof, along with pharmacology expertise and a deep reference library.”

The facility was opened last fall by Molecular Imaging, Inc., of Ann Arbor, Mich. While it provides services to the stem cell researchers at the consortium, its services are also available to researchers throughout the state, both private and academic.

Edward Holmes, president of the Sanford Consortium, said in a statement,

“We believe that in vivo imaging will play a critical role in tracking the effects of stem cells, and accelerate first-of-their-kind therapies to treat and cure some of the world’s most debilitating diseases.”

The facility includes one of the world’s most powerful MRIs, a PET, SPECT, CT, ultrasound and other molecular imaging technologies. It additionally provides as access to hundreds of disease models and a decades-deep expertise in pharmacology, according to the company.

Somers said,

“These technologies have been developed and leveraged in academic settings. Some global pharmaceutical companies have embraced the technologies as well, creating core-imaging facilities. However, drug companies don’t have this capacity on all their campuses, and none are in Southern California, making access for researchers here problematic.”

With the facility at Sanford, these services are more readily available to cash-strapped biotech companies on the entire West Coast.

Backers of the stem cell agency argue that one of its benefits has been to help build the critical mass in California that is necessary to support and attract stem cell research. The addition of the Molecular Imaging Center at the Sanford Consortium appears to be part that continuum. 

Los Angeles Times: California Stem Cell Agency Rife with Conflicts and Unrealistic Expectations

The Los Angeles Times, California’s largest circulation newspaper, is carrying a piece this weekend about “cronyism,” conflicts of interest and “inflated expectations” at the state’s $3 billion stem cell agency.

The column by Pulitzer Prize-winning writer and author Michael Hiltzik used this month’s Trounson Affair as a starting point to dissect the situation at the California Institute for Regenerative Medicine (CIRM), as the agency is formally known.

Trounson was appointed to the board of StemCells, Inc., of Newark, Ca., on July 7, just seven days after leaving the agency. StemCells, Inc., holds a $19.4 million award from the agency.  CIRM has ordered a full review of the situation and barred its staff from communicating about StemCells, Inc., matters with Trounson. 

But even before Trounson’s appointment, there were issues involving StemCells, Inc.(See here and here.)  Hiltzik said,

 “The relationship already reeked of cronyism.”

Hiltzik wrote,

“Trounson's move comes as CIRM must begin looking to the future, but any discussions about extending the agency's life span will have to address the flaws created by Proposition 71 (the ballot initiative that created the agency in 2004). Among them is the program's very structure, and even its scientific goals.”

Hiltzik continued,

“How bad are the conflicts? When the board considered a proposal earlier this year to spend $16 million to attract three star scientists to California, so many members had to recuse themselves that only nine were left to vote. (Six ended up voting in favor.)

“When conflicts of interest are so rife that only one-third of your board can weigh in on a major policy issue, that's tantamount to not having any board at all.”

Some of the issues at the agency have to do with the ballot campaign that created it in 2004, an election in which California voters were led to believe that miraculous stem cell therapies were imminent.

Hiltzik wrote,

“Programs like CIRM are always susceptible to inflated expectations.

"”Since Big Science needs great public support it thrives on publicity,’ the physicist Alvin Weinberg, a veteran of the Manhattan Project, wrote in a famous 1961 article in "Science" about the drawbacks of big-money scientific research. He added: ‘The inevitable result is the injection of a journalistic flavor into Big Science which is fundamentally in conflict with the scientific method.... The spectacular rather than the perceptive becomes the scientific standard.’"

Hiltzik acknowledged the contributions that CIRM has made to stem cell science.

“CIRM-funded labs have produced genuine achievements. But the agency tends to delineate its progress in buildings built, papers published, and big-name scientists lured to California. But the specific cures promised by the Proposition 71 campaign haven't materialized, which doesn't surprise anyone steeped in the realities of the scientific method.”

Hiltzik concluded,

“Even if one believes the need for California to devote $3 billion to a narrow, extremely speculative field of science, the Trounson case and other CIRM administrative missteps have made clear that Proposition 71 created the wrong framework to manage a complex research effort. The initiative left the public with no way to tell if its money has been well spent, and no accountability if it hasn't.

“Moreover, the program deprived potentially more promising research efforts of resources and contributed to the general impoverishment of California's entire higher-education system. If its sponsors have the audacity to ask taxpayers for even more money under the same terms as Proposition 71, the reply should be a resounding ‘no.’ If the voters are gullible enough to repeat the same mistake they made in 2004, there's no cure for them.”

The Hiltzik column appeared online last night. It is scheduled to appear in the Sunday print edition of the Times, which says it has a combined print and online reach of 4 million readers. 

California-funded Stem Cell Diabetes Treatment Edges Forward

CIRM video

The California stem cell agency’s $39 million investment in a possible therapy for diabetes moved forward this week with the announcement that the treatment could enter clinical trials as early as next month.

ViaCyte, a San Diego, Ca., firm, and the agency announced yesterday that the firm has applied with the FDA to start the testing to determine whether the product is safe in human beings. The Juvenile Diabetes Research Foundation, which is also funding the ViaCyte product, said the therapy was “potentially transformative.”

Randy Mills, president of the $3 billion stem cell agency, said in a press release,

“This is good news for ViaCyte and is a clear sign of the progress they are making. Filing for an IND is a crucial step along the path to bringing a stem cell treatment to patients. CIRM will be working with them and supporting them every step of the way to try and make this happen as quickly, and as safely, as possible.”

The agency described the treatment like this:

“Viacyte’s approach uses a thin plastic pouch, containing an immature form of pancreatic cells that, when implanted under the skin, are designed to mature and become insulin-producing and other cells needed to regulate blood glucose levels. These cells are able to sense when blood glucose is high, and then secrete insulin to restore it to a healthy level. In effect this is designed to mimic the glucose regulating functions of the pancreas, which, in people with T1D(type one diabetes), no longer works. This approach was shown to be effective in extensive preclinical testing in models of the disease.”

Paul Laikind, president of ViaCyte, told Bradley Fikes of the San Diego U-T that if “all goes smoothly” the initial stage of the clinical trials could begin next month or in September. Fikes also quoted the first chairman of the stem cell agency, Robert Klein, whose son has diabetes, as saying,

"This is an exciting day for the father of any son or daughter who has Type 1 diabetes."

The therapy, which is based on human embryonic stem cells, could take years to successfully complete all of the necessary clinical trials. Only one out of 10 possible therapies that enter clinical trials enters the marketplace.

StemCells, Inc., Says Patient Endangerment Charges Lack Merit

StemCells, Inc., said late today that charges that is endangering patients in clinical trials have no merit and that the company’s primary concern is the safety of its patients.

The Newark, Ca., company was responding to a lawsuit filed earlier this week that alleges the firm is manufacturing human cells in a process that puts “patients at risk of infection or death.”

The suit was filed by Rob Williams, a former senior manager at the publicly traded company. Williams said he was unlawfully fired by StemCells, Inc., after bringing the stem cell quality issues to the attention of senior management.

Earlier today, the California Stem Cell Report asked the company for comment. Ken Stratton, general counsel, responded. Here is the text of his reply.

“As you know, StemCells, Inc. is engaged in the research and development of cell-based therapeutics and is currently sponsoring clinical studies of potential therapies for spinal cord injury, AMD and pediatric neurological disorders as well as conducting pre-clinical studies in Alzheimer’s disease.  The pre-clinical AD studies, but none of the clinical studies, are partly funded by CIRM.

“The Company has reviewed the complaint filed by Mr. Williams, a former employee whose employment was terminated for performance deficiencies, and finds no merit to the allegations. The Company has retained Littler Mendelson as its litigation counsel and intends to defend itself vigorously in court.

“You should know, the elements of manufacturing practices that concerned Mr. Williams were immediately and carefully reviewed by the Company.  The Company’s primary concern has always been, and will continue to be, the safety and tolerability of stem cell transplantation in its clinical trials. Over the years, we have consulted with multiple experts in the field and we believe our processes, procedures and controls, as fully described in our regulatory filings, are appropriate for a company at our early stage of clinical development and comport with applicable guidelines and regulations.  To date, no patients participating in the Company’s clinical studies have experienced any product related safety concerns.

“We hope you find this information helpful.”