Tuesday, August 17, 2010

CIRM Hiring of Former Geron Exec Raises Conflict of Interest Questions

The California stem cell agency has hired a former executive of Geron Corp. to serve as a consultant on a $50 million clinical trial award round in which Geron is expected to be an applicant.

He is Laurence Elias, who worked for Geron from March 2006 until October 2009 as vice president for oncology clinical development.

In April, Nature Medicine identified Geron as one of the likely applicants in CIRM's first ever involvement in financing a clinical trial. On May 24, CIRM hired Elias as a $50,000 consultant at a rate of $300 an hour. His contract runs until Dec. 31.

In response to a query, CIRM defended the hiring and said no conflicts of interest were involved. The agency said,
“Dr. Elias is an independent consultant and an accomplished clinical development professional. He was consulted for his technical and regulatory input to ensure that the clinical elements of the RFA were technically complete and accurate.  The concept for the clinical RFA had already been approved and as such Dr. Elias was not in any position to influence the overall scope or structure, nor will he have any role in evaluating applications.  Dr. Elias’s integrity and professionalism are beyond question.  CIRM staff and Dr. Elias complied with all conflict of interest requirements.”
The RFA for the clinical trial round was originally expected to be posted in April or May. It is now scheduled for Aug. 31. CIRM has not responded to repeated inquiries concerning the reason for the delay.

We asked CIRM for Elias' statement of economic interests, which some of its consultants are required to file. CIRM said one was not required in Elias' case.

Geron, in announcing Elias' hiring in 2006, said,
His responsibilities will include the planning, design and execution of clinical trial strategies and protocols as well as the monitoring of these multi–center clinical trials.”
The other two companies expected to be competing in the clinicial trial round are Advanced Cell Technology and iPierian, which is backed by venture capitalists who funnelled about $6 million into the election campaign to create the California stem cell agency.

Our take: The Elias hiring has all the appearances of a conflict of interest. We would not expect iPierian or Advanced Cell Technology to be pleased by the situation. Sphere: Related Content

19 comments:

  1. iPierian is close of clinical (human) trial for its iPS cells? Are you kidding? They just got a 1.5M CIRM grant for 3 years of "basic" research. This implies to me that it will be a few years before it is ready for human (clinical) trials. ACTC's IND is still on hold by the FDA. It is not known when, or whether this year, or if ever the hold will be lifted by the FDA. There is only one company, Geron, to my knowledge that is ready to do ESC/iPS cell human (clinical) trials after the FDA lifted the hold on the Phase 1 human trial.

    ReplyDelete
  2. iPierian is close of clinical (human) trial for its iPS cells? Are you kidding? They just got a 1.5M CIRM grant for 3 years of "basic" research. This implies to me that it will be a few years before it is ready for human (clinical) trials. ACTC's IND is still on hold by the FDA. It is not known when, or whether this year, or if ever the hold will be lifted by the FDA. There is only one company, Geron, to my knowledge that is ready to do ESC/iPS cell human (clinical) trials.

    ReplyDelete
  3. In April, iPierian said it was looking the CIRM clinical trial round. See: http://californiastemcellreport.blogspot.com/2010/04/ipierian-to-seek-multimillion-clinical.html

    ReplyDelete
  4. When to the link and iPierian said that it will be 3 years (at least IMO) before it is ready for human trials:

    "He quoted John Walker(at left), president of iPierian, as saying that CIRM's assistance fits “very nicely” with the company's plans to generate a therapy candidate within three years.

    Ipieran is backed by Kleiner Perkins Caufield and Byers, Highland Capital Partners, FinTech Capital Partners and MPM Capital, which have provided $31.5 million to the firm."

    If it gets a grant under this clinical trial program, it will be because of (IMO) the great power that Kleiner Perkins Caufield and Byers has in California.

    The FDA required Geron to initially use almost three thousand mice to carry out the FDA preclinical safety test (known as Phase 0 of clinical trial.) This took a couple of years alone. As part of FDA Phase 0 clinical trial, the manufacturing plant has to be finalized and approved by the FDA in addition to the mice tests. Because Geron needed to make an improvement to the manufacturing process, the FDA demanded another round of safety tests in mice which took another year. The data for the first round of mice safety test was over 20 thousand pages, which took the FDA near another year to review. That was years of Phase 0 work. Now Geron is finallyy ready to do the Phase 1 FDA human (clinical) trial.

    iPS cells during their initial developments are cancer prone. IMO, the FDA will probable require an extensive Phase 0 preclinical trial in mice to make sure that these cell will not turn cancerous in the following Phase 1 to Phase 3 human trials. It is very difficult to prove that cells will not turn cancerous, and it may take a huge number of mice, and a significant waiting period to see if these iPS cell may turn cancerous. It will be a long time before the FDA will sllow iPS cells to be injected into humans, IMO, unless some scientific break through is achieved to ensure iPS cells will not turn cancerous. All it takes is for a single iPS cell to turn into an aggressive cancerous cell to kill a patient in time.

    This year or early next year, Geron is ready to inject its ESC derived product into patients in a Phase 1 trial. ACTC is still on hold by the FDA, and once the hold is lifted (if) ACTC is ready to treat patients in a Phase 1 trial. To my knowledge, no other ESC or iPS cell company is anywhere near human trials.

    Adult stem cells are a different story. Human trials using "adult" stem cells have been on going already for many years worldwide.

    ReplyDelete
  5. Went to the link and iPierian said that it will be up to 3 years (at least IMO) before it is ready for human trials:

    "He quoted John Walker(at left), president of iPierian, as saying that CIRM's assistance fits “very nicely” with the company's plans to generate a therapy candidate within three years.

    Ipieran is backed by Kleiner Perkins Caufield and Byers, Highland Capital Partners, FinTech Capital Partners and MPM Capital, which have provided $31.5 million to the firm."

    If it gets a grant under this clinical trial program, it will be because of (IMO) the great power that Kleiner Perkins Caufield and Byers has in California.

    ReplyDelete
  6. Anonymous3:29 PM

    The most likely recipient of a grant from a state agency has one of its former VPs (left less than a year ago) design the RFA for the grant round and it's not illegal? Given that there is no Form 700 to examine, how do we know? He worked there and took no options or warrants or other future payouts?

    At the very least there is an appearance problem. It's a stinky, stinky process for an agency that has maintained that it has a clean process by mandating grant reviewers come from outside California and thus be unable to apply for grants. The review process is now tainted for this clinical trial round by allowing a Geron's ex-employee to help write the RFA. And the sad thing is that one could find a clearly unconflicted consultant and Geron would probably still be awarded a grant.

    If I were at Geron, I would be quite unhappy about this. If you are a current or potential investor, would you not appreciate the cleanest, most objective external evaluation of Geron's science? Or do you want to grab some quick CIRM cash under dodgy circumstances? I hope no one is stupid enough to issue a "buy" recommendation on Geron's stock when they get the grant.

    ReplyDelete
  7. Anonymous4:15 PM

    I bought more today. Thank you!

    ReplyDelete
  8. Your right that this is weird that CIRM picked a former employee of a potential applicant. CIRM appears to do a lot of weird things. If I am still living and working in California as a taxpayer of California, I would be advocating a through independent audit of this organization by a reputable independent accounting firm, as it appears to be not using taxpayer money in the most efficient way, and to see why they appeared to purposely chose a potentially controversial referee. It could be that somebody there is trying to set up for an iPS win, event hough the iPS technology to my knowledge is years from human trials. There may appear to be (IMO) a lot of politics there from the actions it takes, even though it may be using the California taxpayers money sensibly.

    ReplyDelete
  9. Anonymous9:45 PM

    From CIRM's statement.

    >>The concept for the clinical RFA had already been approved and as such Dr. Elias was not in any position to influence the overall scope or structure, nor will he have any role in evaluating applications.<<

    If true then I see no potential for Dr Elias to effect the outcome of the grant making process.

    Bob

    ReplyDelete
  10. Anonymous10:49 AM

    Meanwhile, on August 18, as to iPS:

    Advanced Cell Technology, Inc. announced today that it is positioned to obtain significant patents relating to cellular reprogramming and the generation of induced pluripotent stem (iPS) cells.

    ReplyDelete
  11. Anonymous11:25 PM

    I think to suggest that involving oneself in the RFA after the concept phase absolves one from conflict is preposterous.

    In fact, the reason the ICOC itself only approves concepts and NOT THE RFAs themselves is that state law is clear that to participate in the actual drafting of an RFA or RFP that one's entity can benefit from is a prima facie conflict of interest.

    Indeed, the reason for this is that the actual terms of the RFA can be structured to either benefit oneself or to exclude potential competitors. One additional requirement, for instance, can make a competitor's application non-responsive. Or, it can be written to include conditions that play to your strengths. Concepts approved by the ICOC are intentionally broad and non-specific to prevent such shenanigans and protect the Board from an actual conflict or the appearance of one.

    ReplyDelete
  12. CIRM may need to consult an experienced lawyer in this perceived conflict of interest matter to work out a way to get around the problem, if Geron does decide to apply for the grant (or is it a "loan" rather than a grant as mention in the April blog?) Geron may not be interested in applying if the strings attached are onerous, or if the timing is too slow, as after the 7/30/2010 lifting of the hold by the FDA, Geron is going to go as fast as possible to carry out the Phase 1 human trial. Time is of the essence for many reasons. Competition is growing from other companies like Stem Cell Company, which just published positive mice results for treating spinal cord patients with older wounds. The November Congressional election is coming up fast, and if the Republicans win big, they may try to ban all ESC activities as stated in the Republican Party platform of 2008 to ban all ESC research and development. Geron could use a helping hand in funding, as medical development and trials are expensive, but waiting for CIRM could be even more expensive. Plus, if Geron is successful in the upcoming human trial, another state or even another country may offer a lot to get the company to operate there, and Geron may not want to get locked into California, which has not been that helpful so far. It is no time to be playing games. There are too much at stake, and there are too many enemies nipping at the heels.

    ReplyDelete
  13. It would be a loan if a business, grant if nonprofit. However, based on the board discussion, it appears only three enterprises -- all businesses -- are likely to be in a position to apply. Here's a link to the concept proposal approved by the CIRM last March. http://www.cirm.ca.gov/files/meetings/pdf/2010/%238_for_3.11.10_ICOC__8_031010_%20ClinDevConcept_f.pdf

    ReplyDelete
  14. Anonymous10:18 AM

    It seems the implication of ric's last comment is that the current CIRM general counsel is not an experienced lawyer in the area of government contracting and conflict of interest law.

    Intriguing notion considering the individual pulls down 250K per annum.

    He does raise the question of who was minding the store when this apparently dodgy contract was given out.

    ReplyDelete
  15. Thanks for the link Calf Stem Cell Rpt. According to the link there was never a conflict of interest as the proposal is for iPS cells, and Geron is not using iPS cells for the current spinal trial:


    "AGENDA ITEM # 8
    3/11/10 ICOC MEETING
    RFA 10-03 CONCEPT PROPOSAL
    CIRM TARGETED CLINICAL DEVELOPMENT AWARDS


    Purpose: Facilitate the development of novel cell therapies derived from pluripotent
    stem cells for the benefit of persons with disease or serious injury.

    Goal: Completion of early stage clinical trials within three years that: 1) demonstrate
    preliminary safety in humans and 2) provide compelling data for proof of mechanistic
    concept and/or early testing for efficacy that could lead to more definitive efficacy
    studies.

    Eligibility Requirement: IND filed by application deadline on the novel cell therapy
    derived from human pluripotent stem cells proposed for CIRM funding."

    Pluripotent stem cells means iPS cells.

    Geron is using ESC and not iPS cells in the current clinical trial. It may get involved in iPS cells in the future, but there have been no announcements to this intend at present by Geron.

    ACTC's IND for eye treatment, which is on hold by the FDA at present, is also not using iPS cells. ACTC does do research and development of iPS cells among many other types, but it had so far said that its iPS cells were found to be weak so far.

    iPS cells are made by taking an "adult" (skin) (stem?) cell, and turn it back to an embryonic like cell, so that the embryonic-like cell can be differentiated back into an "adult" cell for use in treatments. It has been very difficult, uncertain, and near impossible to turn an "adult" (stem) cell directly into another type of cell without first turning it back to an embryonic-like "pluripotent" cell that can be differentiated to many other types of cells. Thus, the embryonic-like "adult" cell is called pluripotent (adult) cell.

    ReplyDelete
  16. The CIRM concept proposal involving clinical trials does cover human embryonic stem cells, which are, in fact, pluripotent. As Nature noted last April, Geron and ACT both appear to be potential applicants. That is where the conflict problem arises. Here is the link to the Nature item: http://californiastemcellreport.blogspot.com/2010/04/geron-and-act-could-apply-in-50-million.html

    ReplyDelete
  17. Thanks for the link Calf Stem Cell Rpt. You are correct that it appears that the clinical trial funding proposal include ESC.

    According to the link, it will take a few months to have applicants submit their applications. These applicants must have an IND submitted to the FDA (even if the IND is on hold by the FDA.) It will take about another six months for CIRM to select the applicants for awards. At the time of the actual awarding of funds, the IND has to be active (meaning not on FDA hold? and the trial is actively recruiting?)

    According to the blog, for profit companies will be awarded loans rather than grants. It is not clear whether there are other stings attached for the loans (above that the clinical trial has to take place in California.)

    By that time Geron will probably already have treated one or more patients unless another hold takes place. Even though the initial Phase 1 safety-trial dosage is low, the injected cells can multiply giving possible measurable results, specially using sensitive imaging and electronic instruments. The initial results may be large enough to provide increased feelings of the lower body by the patient, or more according to a Q&A response by Geron's CEO in a recent earnings conference call. If these initial positive results do occur, it will be hard pressed to see why Geron would want to take out a loan from CIRM, when Geron will be able to easily go to the capital market to get free money by issuing stocks, unless the economy falls into a severe depression shutting down the capital market.

    CIRM people may know this that its loan offer, and slow timing will decrease interest from companies such as Geron. If it is sincere about giving a hand, it should just provide a grant to the only one or two possible clinical trial(s) that will likely to occur this or early next year to cover its purported function of helping to provide new treatments, and helping to develop new industries for the people of the state.

    It takes over six months to evaluate one, two or even three applications? IMO, a couple of weeks is more than sufficient. It is not like the people at CIRM have never heard of these three companies.

    ReplyDelete
  18. Is there mission creep? While to the taxpayers, it does not matter if new medical treatments are based on adult stem cells, embryonic stem cells, or iPS stem cells, the original rational for the taxpayer contribution was to fill the funding gap created by the Republican Federal government of not funding embryonic stem cell research and development. The former Republican administration did not impede funding of adult stem cell R/D, and it probably encouraged adult stem cell development efforts. Thus, adult stem cells were well funded by the Federal government, and thus did not require state taxpayers to help out. ESC R/D have not been well funded by the Federal government even up to now, and thus the state program was created by advocates, and the program was approved by the state taxpayers via voting. iPS cells, being adult cell derived, are not impeded in Federal funding. iPS R/D ought to be well funded by the Federal government, specially as the Republicans support the use of iPS cells in place of ESC; however, with the current depressed economy, iPS R/D may not be funded by the Federal government as robustly as needed. The mission creep of CIRM to include iPS cell R/D that have no impediments of Federal government funding may be justified on the basis that the taxpayers really don't care whether new medical treatments are based on adult stem cells, ESC, or iPS cells, even though they originally voted on ESC R/D based on the ban on Federal government funding placed by the former Republican administration. But, along this line of reasoning, it would seen that iPS R/D should first apply for Federal support, before applying for CIRM support, IMO. Even though I no longer live in California, my brother and many of my relatives do live and work in the state paying taxes, so that butting into this matter is not completely unreasonable.

    ReplyDelete
  19. While Ric talks about the Republican federal government, note the decision by Judge Royce C. Lamberth blowing away via the Dickey-Wicker Amendment the Obama guidelines. As to iPS cells, they were developed outside the US without Federal funding and have a variety of patents covering use.

    ReplyDelete