Only hours before its directors meet today, the California stem cell agency has posted its proposed policy for handling requests for reconsideration of negative recommendations from reviewers on grant applications.
The proposal is an attempt to deal with a problem that has dogged CIRM since last January when an unhappy applicant asked the board to approve its grant despite a negative decision by reviewers.
The board was clearly uncomfortable with the attempt, both in terms of fairness to other applicants and because of the disruption of its normal procedures. The issue surfaced once again in June, leading to more extended public discussion of the appeal or reconsideration process. CIRM allows "appeals" only in the case of conflicts of interest on the part of reviewers. However, reviewers do not have to publicly disclose their economic or professional interests.
The proposed procedure requires the applicant to file a request for reconsideration five days prior to a directors meeting. CIRM's president will then evaluate it and make a finding on whether it has merit. The proposal is unclear on whether it means calendar days or business days.
The reconsideration requests, which CIRM calls "extraordinary petitions," will be posted on the CIRM website. Presumably the president's findings will be as well, although that is not specified.
The policy does not appear to eliminate an applicant's ability to appear publicly before the board to seek reconsideration. However, with a negative decision from reviewers and a "no merit" finding from the president, a disgruntled applicant is not likely to find a receptive audience.
It is unfortunate, to say the least, that this important proposal, which affects hundreds of scientists in California, has been posted at the very last minute. It deals with an issue that affects CIRM's credibility and the credibility of its reviewers. It is virtually impossible for those affected by this plan to comment intelligently to the board in a timely fashion.
Presumably, they could send an email with their comments at this late hour – if they are aware of the details of the proposal. It is our sense, however, that few scientists spend much time scouring the depths of the CIRM website, which does not even put a notice of its directors meetings on its home page.
For a look at previous items on this issue, search on the label "reconsideration" or "grant appeals."
Showing posts with label reconsideration. Show all posts
Showing posts with label reconsideration. Show all posts
Tuesday, August 12, 2008
Wednesday, July 09, 2008
CIRM Director Sheehy Proposes Changes in Grant Appeals
Jeff Sheehy, a member of the board of directors of the California stem cell agency, offers the following thoughtful perspective on the problems with appeals/reconsideration of grant applications. His comments include suggestions for changes that could ease concerns of some applicants and what he describes as a "muddle."
Sheehy is a member of the Grants Working Group and has participated in the reviews of hundreds of grant applications at CIRM. He has served as its acting vice chairman on a number of occasions. Here is the text of his comments.
Sheehy is a member of the Grants Working Group and has participated in the reviews of hundreds of grant applications at CIRM. He has served as its acting vice chairman on a number of occasions. Here is the text of his comments.
"I think we have gotten into a muddle over the question of appeals by applicants to CIRM and the ICOC(CIRM's board of directors). First, as Don Gibbons has reiterated in this item, objective process complaints such as one involving potential undisclosed conflicts of interest by reviewers are allowed by CIRM and given appropriate consideration with appropriate action if needed.
"However, appeals/comments concerning the content of reviews cannot be considered by CIRM staff. To do so would make CIRM staff effectively reviewers. In addition, CIRM staff could be placed in the position of making decisions regarding the funding of grant applications. Prop. 71 clearly gives the Grants Working Group (GWG) responsibility for reviewing grants and the ICOC takes those reviews as advice and then is solely empowered to make decisions to approve or not approve a grant application.
"CIRM and the ICOC could decide to implement a resubmission process allowing applications with disputed reviews to be re-reviewed by the GWG. I personally am undecided on this approach but think it is unlikely to be adopted.
"What is confusing is that appeals/comments about any item under consideration by the ICOC are expressly allowed. California public meeting laws govern a state agency with a decision-making board that meets in public. That means public comments/appeals are expressly allowed, as the ICOC has already experienced. In addition, letters to the ICOC regarding applications or any matter under consideration are also allowed and we have received them on an application and other matters.
"Instead of obfuscating and stonewalling, CIRM should be direct and forthright about this existing appeal process. In that context, the process could then be properly organized. Those who wish to use public comment can be informed of our current 3-minute limit and advised that the limit could be shortened to 2 or even 1 minute if we get a significant number of individuals who wish to comment. In addition, we could suggest length (hopefully a couple of pages) and format for written appeals (i.e., formats easy to post on CIRM¹s website). We could also inform applicants who wish to use this process that their letters will be made public and the application score and identity will be revealed upon receipt/posting of letters or after public comment.
"From my perspective, written comments/appeals from applicants would be preferable and I would hope to receive them early enough to consider thoughtfully as I review materials prior to ICOC meetings.
"Part of the rationale for the composition of the ICOC is to have on hand scientific expertise to inform decisions around grant applications. I have confidence that my colleagues can digest any additional input from applicants and make appropriate decisions. After all, the ICOC has already considered and made decisions regarding applications appealed to it."
Tuesday, July 08, 2008
CIRM Responds to Cascade Complaints
The California stem cell agency today defended its grant review process in the wake of complaints by an applicant, Cascade LifeSystems of San Diego, concerning the fairness of CIRM's procedures.
We asked CIRM if it had any comments concerning the item we wrote dealing with Cascade's concerns. We also specifically asked CIRM the following question: How can an applicant appeal on the basis of a conflict of interest if it does not know the names of the specific reviewers who evaluated their application?
Here is the text of the response from Don Gibbons, chief communications officer for CIRM.
We suspect that no applicant has performed that sort of due diligence, but we could be wrong. In fact, raising such an issue ahead of a review could have a negative impact on consideration of an application. Few reviewers are likely to be fond of having their integrity questioned. And an accusation of a conflict of interest cannot be fully investigated without informing the reviewer involved.
We asked CIRM if it had any comments concerning the item we wrote dealing with Cascade's concerns. We also specifically asked CIRM the following question: How can an applicant appeal on the basis of a conflict of interest if it does not know the names of the specific reviewers who evaluated their application?
Here is the text of the response from Don Gibbons, chief communications officer for CIRM.
"The company would note anyone on the review panel whom it believes has a potential conflict, then staff would see if that person was a primary or secondary reviewer, or if not, whether they made substantive comments during the review that could have influenced scores.Our comment on the conflict of interest question raised by Cascade: The names of all the scientists on the review panel are public. Only in cases of the names of individuals assigned specifically to a specific application are the names secret, as we understand the process. An applicant can see the names of all reviewers in advance, do some research on the individuals and ask CIRM ahead of the review to bar particular reviewers from evaluating its application.
"You should know that CIRM does not believe that the reviewer citing 0.3 percent instead of 0.66 percent is a substantive error. The latter would still require 150 eggs to get one cell line, and that was a significant weakness in the application. The three percent or one-in-30 number cited elsewhere in the application by the firm is noted to come from preliminary data, something that we felt was not peer reviewed and not substantiated, and therefore outside of the realm of consideration for review. There were several other weaknesses in the application cited by the reviewers.
"CIRM’s success rate for grant applications is already considerably higher than for NIH applicants."
We suspect that no applicant has performed that sort of due diligence, but we could be wrong. In fact, raising such an issue ahead of a review could have a negative impact on consideration of an application. Few reviewers are likely to be fond of having their integrity questioned. And an accusation of a conflict of interest cannot be fully investigated without informing the reviewer involved.
Monday, July 07, 2008
Multimillion Dollar Hooha Over CIRM Grant Reviews
As part of a burgeoning flap over grant reviews at the $3 billion California stem cell agency, one rejected applicant has formally asked for reconsideration of its request for funds, citing errors in fact by reviewers, among other things.
Such a request might seem routine, but for CIRM it is novel and fraught with pitfalls. At stake is the reputation for fairness and credibility of the still young California Institute for Regenerative Medicine.
Created only in 2004 with its first grants approved in 2005, CIRM has struggled with its processes. It has been helped, but also hamstrung by the ballot initiative that created it. The measure, which bypassed the legislature and the governor, also locked in a host of restrictive procedures. One of those involves the grant review process, which is also governed by policies approved by the CIRM board of directors.
The rejected applicant, Cascade LifeSciences of San Diego, was routinely denied funding last month by the CIRM board of directors, based on the decisions of scientific reviewers. The board has almost universally ratified the $500-million-plus decisions of its scientific reviewers, who conduct their sessions in private and whose economic or professional interests are not publicly known.
Rejected applicants do not have the right of appeal except in the case of a conflict of interest. But Cascade says it does not know the identity of reviewers of its grant so it is impossible to know whether a conflict of interest exists. However, the board itself is filled with conflicts of interest -- all legal -- that even Nature magazine has warned about.
Ken Woolcott, chief business officer for Cascade, appeared before the CIRM directors last month to express concern about the grant review process. At the time, he did not seek an appeal or reconsideration of the firm's application. He had been told by CIRM that no appeal was possible. After he left the meeting, another rejected grant, albeit in a slightly higher category, won funding after a CIRM director read a letter from the applicant.
On July 3, Woolcott wrote a letter to CIRM Chairman Robert Klein and CIRM President Alan Trounson that includes a request for reconsideration of his firm's grant. Woolcott's letter does not seek an appeal.
Much of the information in it is contained in an earlier posting on the California Stem Cell Report. But Woolcott has fine-tuned the letter and added important significant details. The entire letter follows as a separate posting. Here is a sample.
Such a request might seem routine, but for CIRM it is novel and fraught with pitfalls. At stake is the reputation for fairness and credibility of the still young California Institute for Regenerative Medicine.
Created only in 2004 with its first grants approved in 2005, CIRM has struggled with its processes. It has been helped, but also hamstrung by the ballot initiative that created it. The measure, which bypassed the legislature and the governor, also locked in a host of restrictive procedures. One of those involves the grant review process, which is also governed by policies approved by the CIRM board of directors.
The rejected applicant, Cascade LifeSciences of San Diego, was routinely denied funding last month by the CIRM board of directors, based on the decisions of scientific reviewers. The board has almost universally ratified the $500-million-plus decisions of its scientific reviewers, who conduct their sessions in private and whose economic or professional interests are not publicly known.
Rejected applicants do not have the right of appeal except in the case of a conflict of interest. But Cascade says it does not know the identity of reviewers of its grant so it is impossible to know whether a conflict of interest exists. However, the board itself is filled with conflicts of interest -- all legal -- that even Nature magazine has warned about.
Ken Woolcott, chief business officer for Cascade, appeared before the CIRM directors last month to express concern about the grant review process. At the time, he did not seek an appeal or reconsideration of the firm's application. He had been told by CIRM that no appeal was possible. After he left the meeting, another rejected grant, albeit in a slightly higher category, won funding after a CIRM director read a letter from the applicant.
On July 3, Woolcott wrote a letter to CIRM Chairman Robert Klein and CIRM President Alan Trounson that includes a request for reconsideration of his firm's grant. Woolcott's letter does not seek an appeal.
Much of the information in it is contained in an earlier posting on the California Stem Cell Report. But Woolcott has fine-tuned the letter and added important significant details. The entire letter follows as a separate posting. Here is a sample.
"The information on the 0.3% efficiency presented to the Study Section by the Reviewer #2 is factually incorrect. Even if the reviewer was mistakenly relying on our Nov. 2007 Nature publication, that efficiency was reported as 0.66%. More importantly, on pages 5 and 8 of this grant application we provided information that the efficiency of SCNT in primates was 3.3% (1 ESC line per 30 oocytes)."We have asked CIRM if it has any comment on the situation. We will carry its response when it provides one. Here is the link to the public summary of the CIRM scientific review of the Cascade application.
Text of Reconsideration Letter From Cascade
Here is the text of the reconsideration letter from Cascade concerning its application for a grant from the California stem cell agency.
July 3, 2008
Mr. Robert Klein, J.D.
Chairman, ICOC Committee
210 King Street
San Francisco, CA 94107
Re: Request for Reconsideration - New Cell Line Development RFA 07-05 Review Process
Dear Committee Member:
Last Thursday evening, 26 June 2008, I had the pleasure of appearing before your Committee, officially on behalf of Cascade LifeSciences (See Exhibit A) and perhaps unofficially as a voice for industry, regarding our expectations and experience with the RFA and Grant Review noted above. To quote Mark Twain, “I apologize for the length of my letter; I did not have time to write a shorter one.” Three minutes to comment on a $1MM decision is remarkably challenging. For the benefit of the Committee and with the luxury of a written response, let me see if I can more clearly articulate our expectations, experience and suggestions going forward.
First, I would like to start at the beginning. Prop. 71 is a very innovative and groundbreaking paradigm shift in the funding of research. We applaud the CIRM mission and the stewardship of the Committee. The mission statement of Prop. 71 makes very clear that although science is a laudable goal it is not the end game. Products that treat, cure, or enhance our lives are the end game. Fast forward 10 to 15 years and I would like to be so bold as to suggest that the ultimate arbiter of the success of CIRM or Prop. 71 will be PRODUCTS. Not research achievements, not publications, not patents, not even Nobel Prizes. All of these are important milestones that will advance our efforts and may even contribute to the economy of California. But “John Q. Public” will only benefit directly by the development of innovative stem cell related PRODUCTS that I believe will change medical approaches to disease in fundamental ways.
In the interest of full disclosure, I prefer to admit my biases up front. I have a bias toward products. I am also a lawyer, the Chief Business Officer of Cascade LifeSciences, and a taxpayer. My product bias has been cultivated over 20 years with two of the San Diego biotech pioneers, Hybritech and IDEC. (See Exhibit B, Background). What I know about Stem Cells I have learned, but what I know about product development, I have lived.
I believe that industry and CIRM share the same goal of enhancing product development. Although funding cutting edge research and academic inquiry are part of the larger goal, I believe that industry will be the ultimate conduit through which products must run the clinical, regulatory and marketplace gauntlet.
RFA 07-05 and Cascade’s Expectations
Upon understanding that CIRM was opening up funding under the RFA process to for-profit entities, we were quite pleased and encouraged. Funding critically important translational research that can neither be funded by the NIH nor is of interest to all but a very few private investors seems prudent and product focused.
The specific language in the Objective of RFA 07-05 perhaps set our expectation too high:
Page 1 -- Somatic cell nuclear transfer (SCNT) , a method for reprogramming that is well-established in several mammalian species, has not yet been achieved with human cells, but recent success has been reported in non-human primates. " [This is Dr. Mitalipov's work published in Nature and exclusively licensed by Cascade]
Page 2. "The needs may in the future be met by derivation of hESC following SCNT..."
Page 2. "CIRM proposes a new program to address the need for new types and sources of human pluripotent stem cell lines and for the optimization of existing methods for their derivation." To be candid, we believed that the translation of our SCNT primate work into the SCNT generation of hESC was right in the "strike zone" of the RFA as written. The alternate non-embryo sourced approach, iPS is a very important scientific avenue of research and should be funded as well. That said, SCNT is a very compelling opportunity to develop genetically matched cell lines that may lead to human therapeutic products.
Cascade’s Grant Review Experience
Our responses to the Reviewers’ comments are beyond the scope of this letter but are attached as Exhibit C for independent review. For the record, we filed a formal request with Dr. Trounson to rebut the conclusions and comments of the reviews but were told by Staff that there was no such process. We were told that the only avenue for rebuttal would be based on conflict of interest. As the reviewers are anonymous, it is unclear how this would ever be realistic. Two additional points are striking in this regard. First, we now understand that after our departure on Thursday evening, Rusty Gage, one of our esteemed colleagues here in San Diego was allowed to rebut reviewer comments and, hence, did receive funding. We are unclear on how this rebuttal process works and why we were denied any opportunity to dialogue on the merits of our grant application. Second, I understand second-hand that an ICOC member believed my discussion at CIRM was flawed, for example, because I did not address the mistake regarding efficiency of our SCNT. This is unfortunate, as we were told our request for rebuttal was rejected and that we were not allowed to discuss the merit or lack of merit of the specific review of our application but our three minutes was limited to expressing our concerns about the process and our suggestions for improvement from an industry perspective.
By way of example, we would like you to better understand the disconnect between our expectations and our experience with this Grant Review. As you will note in Exhibit C, most of the review comments we received on our Grant Application were factually incorrect. We are unable to reconcile the review committees’ comments with the stated objectives of the RFA, the articulated criteria for review and our actual grant submission.
For example, Reviewer #1 comment was:
"Lack of Novelty, pure translation of the non-human primate work into humans."
This seems to defy logic and the mission of human therapeutics. Moreover, this does not seem to be consistent with the objectives published by CIRM in its RFA, which specifically calls out the "hurdle" of human SCNT as a fundable goal. I would venture to suggest that successful application of SCNT to humans will be a scientific achievement and will be an “above the fold” kind of worldwide news story. Finally, at the CIRM ICOC meeting, Dr. Uta Grieshammer, presented the review committees grant criteria and noted specifically that the review team was advised that "novelty" was NOT a priority for these types of grants.
Also at the meeting, Dr. Trounson announced that no SCNT grants had been funded due to some sort of vague policy concern about access to human oocytes and the challenges this had created in other countries. (We are aware of Grant#R31-00404 related to SCNT that was previously funded).
First, this was "moving the goal posts" after we had submitted our grant application. Second, we appreciate the challenge of securing oocytes but we at Cascade had been fortunate enough to secure a collaboration with La Jolla IVF clinic to supply all the oocytes we need to proceed with our cell line development effort. Moreover, if this was truly the reason for flagging our grant application as non-fundable, CIRM should have just told us that in writing and explained how they were going to proceed, if at all, in the area of SCNT.
A factually incorrect assumption about our “efficiency” may have been the fundamental error that doomed our application. The CIRM reviewer commented:
The ability to generate individualized human embryonic stem cell lines using somatic cell nuclear transfer from either healthy individuals or patients with specific disease states is an exciting and yet technically demanding prospect. To date, no one has successfully cloned human embryonic stem cells, although recently, a group at University of Oregon Heath Sciences Center has successfully derived primate embryonic stem cells, with an efficiency of approximately 0.3%
This is factually incorrect at two levels. First, we are unclear where the reviewer got the 0.3% efficiency rate. This is not a number we have used. Our November 2007 Nature paper calls out 0.66% efficiency at page 497. Our grant application (filed Jan 2008) describes in detail at page 8, "These results represent a significant reduction in the number of oocytes required to produce a single ESC line over previously reported efficiency (from 152 to 30) providing the important foundation to conduct the proposed studies in humans." 1 ESC cell line out of 30 oocytes is actually 3.3%.
I am unclear how this fundamental oversight occurred. Mistake? Miscommunication? Pre-existing bias? Misunderstanding? Suffice it to say, we believe that the incorrect information about efficiency was the driving force behind the reviewers’ comments and failure to fund.
Suggestions and Action Items for Consideration.
Our hope is that thru expressing our concerns and our experience we will be able to make industry (For-Profit) a viable partner in the mission of Prop 71. With that in mind, we would like to suggest the following ideas for review and consideration by the ICOC:
Industry representation on CIRM grant review teams
Formal appeal process or ability to respond in writing to reviewer comments. See, for example, SBIR, STTR, NIH funding for models of review cycles.
Holding the review team to the published review criteria--e.g., novelty is not a priority criteria.
One of the review criteria should always be the impact of the research on the advancement of human product development. If the Rusty Gage review reconsideration is as I understand it, it seems that there is one set of rules for a deservingly prominent scientist and a different set of rules for Cascade LifeSciences/Industry. We also filed a letter with CIRM asking for the opportunity to comment on our grant review and were denied. This seems, without more complete information, to be unfair.
Perhaps separate academic/not-for-profit grant application review from for-profit review. Comparing not for profit grants (institutions that are Grant Writing Machines) with the grant applications of fledgling biotech companies is fundamentally unbalanced.
Although I believe that Industry is a key element of Product development and we desire to work with CIRM to advance the cause, if CIRM’s funding criteria or standards are inconsistent with industry participation or pragmatic product development, we need to know that earlier rather than later.
I am personally and professionally committed to assist CIRM in making industry an equal partner in achieving the mission of Prop 71. I would look for guidance from the ICOC on how we can work through some of these administrative and structural challenges.
Although we are disappointed by the CIRM review and admittedly discouraged by the process, I trust that the agency and the applicants will evolve favorably with time and experience.
As our distinguished Governor would say.............."We'll be Back."
Sincerely,
Kenneth J. Woolcott
Chief Business Officer
Cascade LifeSciences Inc
10398 Pacific Center Ct.
San Diego, CA 92121
kjwoolcott@aol.com
858-945-4667
KJW/rrc
cc: Alan Trounson, President CIRM
Howard Birndorf
Sophia Khaldoyanidi
Exhibit A
Cascade LifeSciences
Founded 2004
San Diego, CA
Howard Birndorf, Chairman
Kenneth Woolcott, Chief Business Officer
Sophia Khaldoyanidi, Ph.D, MD, Chief Scientific Officer
Larry Respess, General Counsel
Exclusive Licensee of Novel SCNT technology developed at Oregon Health Sciences University (OHSU) and published in Nature, Nov 2007. (First successfully SCNT in Primates)
Dr. S. Mitalipov, inventor of SCNT patents and consultant on human SCNT effort.
Exhibit B
KENNETH J. WOOLCOTT
6100 La Jolla Scenic Drive South
2000 First Avenue
La Jolla, CA 92037
Suite 2304
858-454-8496 phone/fax
Seattle, WA 98121
kjwoolcott@aol.com
206-795-4667 phone
GENERAL COUNSEL & LICENSING EXECUTIVE
Strategic Advisor . . . Entrepreneurial Counsel . . . Transactional Architect
Summary: Executive with over 20 years of experience and outstanding accomplishment in the Biopharmaceutical Industry, including 12 plus years of key legal and management responsibilities at IDEC Pharmaceuticals Corporation (now Biogen IDEC) through its growth from a market cap of $50M to a company with a valuation of over $10B. Provided counsel and craftsmanship on over $1B in global corporate alliances and public financings. Contributed legal leadership and team influence in the development and FDA approval of two oncology drugs, RITUXAN (first antibody approved for cancer) and ZEVALIN (first radioimmunotherapy approved for cancer), currently generating annual U.S. sales of over $1.9B. Provided leadership in diverse and challenging roles based on the growth and needs of the organization, for example:
Strategic advisor with entrepreneurial zeal and global biopharma perspective.
Counsel with intra-disciplinary experience, scientific background and a proven track-record of incisive legal analysis and problem-solving.
Executive officer with achievement in operational management, strategic planning, business development, team building, and change agent in development of company’s core values as it grew from 70 to over 800 employees.
General Counsel and Corporate Secretary with broad experience in public company matters, corporate governance, SEC compliance, FDA issues, intellectual property strategy, transactional negotiation and crafting, corporate partner management, litigation management, and government relations.
PROFESSIONAL EXPERIENCE AND KEY METRICS
Woolcott Bioscience Strategies 2002-present
Transactional and Business Development Consulting Services
Chief Business Officer, Cascade Lifesciences Inc 2007 to present
Strategic Advisor 2005 to 2007
Nativis, Inc. San Diego, CA
Acting Vice President, Business Development & General Counsel 2004-2005
Imagine Pharmaceuticals, San Diego, CA
IDEC Pharmaceuticals Corp., San Diego, CA 1989-2002
VP, General Counsel, Licensing Executive and Secretary 1994-2002
General Counsel, Licensing Executive and Secretary 1992-1994
Deputy General Counsel and Secretary 1991-1992
Intellectual Property Counsel 1989-1991
Counsel to approximately $700M in IDEC Public Equity & Debt Financings:
Initial public offering (IPO): (1991--$52 M)
Follow-on equity offerings: (1994 – $8M; 1996 -- $50M; 2000 -- $473M)
“LYONS” convertible debt offering: (1999 -- $113M)
Counsel and negotiator for approximately $300M in corporate alliances from 1991-00, including:
Zenyaku/Rituxan – 1991, $10M SmithKline/CD4 – 1992, $60M
Mitsubishi/B7 – 1994, $12M Seikagaku/CD23 – 1995, $26M
Genentech/Rituxan – 1995, $57M Eisai/gp39/CD40L – 1995, $38M
Kirin, BI, and Chugai/ Upjohn/9AC – 1997, $12M
Expression System – 1995-7, $15M
Schering AG/Zevalin –1999, $47M Nordion /Yttrium – 2000, $20M
Member of core team of executives that led turnaround from $50M valuation and six months of cash in 1994 to pivotal Genentech partnership/cash infusion and over 800% increase in stock valuation in 1995.
Managed key patent litigation (IDEC v. Corixa et al), including selection process for lead counsel and development of declaratory judgment strategy over a multi-year period. Strategically, IDEC prevailed in securing venue in San Diego Federal District Court, while actions in Delaware and Northern District of California were dismissed. In October 2003, summary judgment was granted in favor of IDEC declaring invalid and unenforceable all of Corixa’s subject patents. The case was ultimately settled on favorable terms
Executive Committee level advisor on IND, clinical strategy, Advisory Committee meeting, manufacturing subcontracting and inspection, approval and launch of RITUXAN and ZEVALIN.
Early advocate and adopter of Rule 10b-5 executive stock selling plans, including successful initiation of amendment to California State Securities Laws to conform with provisions of new Federal law
Managed preparation and filing of SEC corporate disclosure documents including crafting of numerous sensitive and challenging press releases.
Managed legal aspects of “Poison Pill” adoption and revision
Lead legal analysis and selection of RITUXAN and ZEVALIN trademarks
Coordinated legal and peer analysis for stock splits 2:1 21 Dec ’99 and 3:1 18 Jan ‘01
Built and managed a high-performance Legal Team of thirteen professionals
Managed Corporate Policy on Insider Trading and Stock Trading Windows
Member of Executive Committee, Corporate Secretary and liaison with Board of Directors
Strong presentation skills and recognized public speaker
Christensen, O’Connor, et al., Seattle WA 1987-1989
Associate
Hybritech, Inc., San Diego, CA 1985-1987
Intellectual Property and Licensing Counsel 1986-1987
Patent Counsel 1985-1986
EDUCATION
George Washington University, Washington, D.C.
Juris Doctorate, 1985
Leader, Save the Night Law School Campaign, 1984
President—Evening Division, Student Bar Association, 1984
University of Maryland, College Park, MD
MS candidate/Chemical Engineering, 1980-81
Pacific Lutheran University, Tacoma, WA
B.S,. Biochemistry, Cum Laude, 1980
PROFESSIONAL ORGANIZATIONS
California State Bar Association
Washington State Bar Association
District of Columbia Bar Association
United States Patent Office
Registered Patent Attorney (#30,824)
American Corporate Counsel Association
Founding Director of San Diego Chapter, 1994
American Association of Corporate Secretaries
Biotechnology Industry Organization
Founder of General Counsel Committee, 2001
COMMUNITY AFFILIATIONS
Burnham Institute for Medical Research, La Jolla, CA
Trustee and Chairman of Technology Transfer Committee., 2004 to present
Basketball Club of Seattle, L.L.P.
Partner, 2002 to 2006
The Jimmy V Foundation for Cancer Research
Friends of V Member
The Starlight Foundation for Children
Freshstart , Inc.
Exhibit C
Rebuttal letter & REQUEST FOR rECONSIDERATION
sophia Khaldoyanidi, ph.d., m.d.,
chief scientific officer
cascade lifesciences, inc.
RL1-00656-1: Generation of human ESC lines using SCNT
Executive Summary Comments
Comment #1: The proposal lacks a detailed description of how the resultant cell lines will be assessed and characterized for pluripotency.
Response #1: This concern was raised by the Reviewer #2. However, the description of the pluripotency tests is described on page 5 of the grant application (Step 4 of our protocol). We proposed to evaluate pluripotency of SCNT-ESC lines based on stemness marker expression and both in vivo and in vitro differentiation using standard state-of-the art methods. These methods include immunocytochemistry, flow cytometry, quantitative RT-PCR, embryoid body formation and teratoma assay. All these assays are standard in stem cells biology field and are routinely used by the members of our scientific team (see list of publications provided in Part C of this grant application).
Comment #2: No data is presented suggesting that these assays [for pluripotency] are routinely available in the applicant’s laboratory.
Response #2: Due to the space constrains of the Preliminary Results and Feasibility section (2 pages), we have chosen to present the results supporting the novel and scientifically-challenging aspects of the SCNT technology. The concern regarding our ability to run the pluripotency tests was raised by the Reviewer #2 and the rationale for this concern is not clear to us: the assays for pluripotency are standard techniques used in every stem cell laboratory including laboratories leaded by the members of our scientific team. The fact that we are familiar with the standard techniques used in our field is supported by our publications (Part C of this grant application).
Comment #3: The collaborator with the primate cloning expertise proposes to spend 25% of his/her time in the applicant’s laboratory in California. However, reviewers expressed serious concern that it will be logistically difficult for the out-of-state collaborator to be available at the time when the oocytes are donated.
Response #3: Anyone with experience with IVF understands that the day of oocyte harvesting is predicted in advance based on the rigid hormone treatment schedule for each donor. Based on this well known schedule, the travel for Dr. Mitalipov from Portland to San Diego (2.5 hour duration) can be easily planned in advance.
Comment #4: Regarding the source of the oocytes, which will be obtained from an in vitro fertilization (IVF) clinic, one reviewer felt that the procurement of 100 oocytes per year seems reasonably achievable. However, others felt that not enough information is presented in the application to firmly support that the applicant can obtain the high quality eggs.
Response #4: Due to the space constrains, we did not have an opportunity to explain in the body of the grant as to how human oocytes will be obtained. This information is provided very clearly in the letter of collaboration from Dr. Smotrich of La Jolla IVF Clinic (Part C). Dr. Smotrich established a list of young and healthy volunteers who desire to donate oocytes specifically for this SCNT project. All these donors were pre-tested and demonstrated a high oocyte production (20-25 oocytes per cycle) in response to hormonal stimulation. We do not intent to use oocytes that have been obtained for the purpose of IVF treatment and were not used due to poor quality.
Comment #5: If they [Cascade LifeSciences team] have access to 100 eggs, some reviewers argued that it would not be enough to make a cell line in 1 year, given the primate success rates (0.3%).
Response #5: The information on the 0.3% efficiency presented to the Study Section by the Reviewer #2 is factually incorrect. Even if the reviewer was mistakenly relying on our Nov. 2007 Nature publication, that efficiency was reported as 0.66%. More importantly, on pages 5 and 8 of this grant application we provided information that the efficiency of SCNT in primates was 3.3% (1 ESC line per 30 oocytes)
Comment #6: Reviewers mentioned that there is no consideration of how the resultant cell lines, if any, will be distributed to other research groups and under what conditions as requested in the application.
Response #6: This is factually incorrect. This concern was raised by the Reviewer #2. However, this information has been provided on page 10 of the application (last paragraph).
In summary: Our response demonstrates that the Reviewer #2 provided factually incorrect information to the Study Section. In particular, the efficiency (which is an important parameter) was erroneously reported. Moreover, despite the challenges others may legitimately face in securing oocyte donors, we were able to secure reliable and excellent source of oocytes to advance our work in humans. Finally, to suggest our proposal is not novel is a flawed conclusion as Human SCNT is a stated goal of the RFA and the stated RFA review criteria specifically noted that “novelty” was NOT a measure for funding. As a result of these factual errors and an unknown change in SCNT funding philosophy in mid-review, our project received a non-fundable score. We requested an opportunity to rebut. We were denied.
REQUESTED ACTION: We respectfully request that the ICOC reconsider our grant application for funding.
July 3, 2008
Mr. Robert Klein, J.D.
Chairman, ICOC Committee
210 King Street
San Francisco, CA 94107
Re: Request for Reconsideration - New Cell Line Development RFA 07-05 Review Process
Dear Committee Member:
Last Thursday evening, 26 June 2008, I had the pleasure of appearing before your Committee, officially on behalf of Cascade LifeSciences (See Exhibit A) and perhaps unofficially as a voice for industry, regarding our expectations and experience with the RFA and Grant Review noted above. To quote Mark Twain, “I apologize for the length of my letter; I did not have time to write a shorter one.” Three minutes to comment on a $1MM decision is remarkably challenging. For the benefit of the Committee and with the luxury of a written response, let me see if I can more clearly articulate our expectations, experience and suggestions going forward.
First, I would like to start at the beginning. Prop. 71 is a very innovative and groundbreaking paradigm shift in the funding of research. We applaud the CIRM mission and the stewardship of the Committee. The mission statement of Prop. 71 makes very clear that although science is a laudable goal it is not the end game. Products that treat, cure, or enhance our lives are the end game. Fast forward 10 to 15 years and I would like to be so bold as to suggest that the ultimate arbiter of the success of CIRM or Prop. 71 will be PRODUCTS. Not research achievements, not publications, not patents, not even Nobel Prizes. All of these are important milestones that will advance our efforts and may even contribute to the economy of California. But “John Q. Public” will only benefit directly by the development of innovative stem cell related PRODUCTS that I believe will change medical approaches to disease in fundamental ways.
In the interest of full disclosure, I prefer to admit my biases up front. I have a bias toward products. I am also a lawyer, the Chief Business Officer of Cascade LifeSciences, and a taxpayer. My product bias has been cultivated over 20 years with two of the San Diego biotech pioneers, Hybritech and IDEC. (See Exhibit B, Background). What I know about Stem Cells I have learned, but what I know about product development, I have lived.
I believe that industry and CIRM share the same goal of enhancing product development. Although funding cutting edge research and academic inquiry are part of the larger goal, I believe that industry will be the ultimate conduit through which products must run the clinical, regulatory and marketplace gauntlet.
RFA 07-05 and Cascade’s Expectations
Upon understanding that CIRM was opening up funding under the RFA process to for-profit entities, we were quite pleased and encouraged. Funding critically important translational research that can neither be funded by the NIH nor is of interest to all but a very few private investors seems prudent and product focused.
The specific language in the Objective of RFA 07-05 perhaps set our expectation too high:
Page 1 -- Somatic cell nuclear transfer (SCNT) , a method for reprogramming that is well-established in several mammalian species, has not yet been achieved with human cells, but recent success has been reported in non-human primates. " [This is Dr. Mitalipov's work published in Nature and exclusively licensed by Cascade]
Page 2. "The needs may in the future be met by derivation of hESC following SCNT..."
Page 2. "CIRM proposes a new program to address the need for new types and sources of human pluripotent stem cell lines and for the optimization of existing methods for their derivation." To be candid, we believed that the translation of our SCNT primate work into the SCNT generation of hESC was right in the "strike zone" of the RFA as written. The alternate non-embryo sourced approach, iPS is a very important scientific avenue of research and should be funded as well. That said, SCNT is a very compelling opportunity to develop genetically matched cell lines that may lead to human therapeutic products.
Cascade’s Grant Review Experience
Our responses to the Reviewers’ comments are beyond the scope of this letter but are attached as Exhibit C for independent review. For the record, we filed a formal request with Dr. Trounson to rebut the conclusions and comments of the reviews but were told by Staff that there was no such process. We were told that the only avenue for rebuttal would be based on conflict of interest. As the reviewers are anonymous, it is unclear how this would ever be realistic. Two additional points are striking in this regard. First, we now understand that after our departure on Thursday evening, Rusty Gage, one of our esteemed colleagues here in San Diego was allowed to rebut reviewer comments and, hence, did receive funding. We are unclear on how this rebuttal process works and why we were denied any opportunity to dialogue on the merits of our grant application. Second, I understand second-hand that an ICOC member believed my discussion at CIRM was flawed, for example, because I did not address the mistake regarding efficiency of our SCNT. This is unfortunate, as we were told our request for rebuttal was rejected and that we were not allowed to discuss the merit or lack of merit of the specific review of our application but our three minutes was limited to expressing our concerns about the process and our suggestions for improvement from an industry perspective.
By way of example, we would like you to better understand the disconnect between our expectations and our experience with this Grant Review. As you will note in Exhibit C, most of the review comments we received on our Grant Application were factually incorrect. We are unable to reconcile the review committees’ comments with the stated objectives of the RFA, the articulated criteria for review and our actual grant submission.
For example, Reviewer #1 comment was:
"Lack of Novelty, pure translation of the non-human primate work into humans."
This seems to defy logic and the mission of human therapeutics. Moreover, this does not seem to be consistent with the objectives published by CIRM in its RFA, which specifically calls out the "hurdle" of human SCNT as a fundable goal. I would venture to suggest that successful application of SCNT to humans will be a scientific achievement and will be an “above the fold” kind of worldwide news story. Finally, at the CIRM ICOC meeting, Dr. Uta Grieshammer, presented the review committees grant criteria and noted specifically that the review team was advised that "novelty" was NOT a priority for these types of grants.
Also at the meeting, Dr. Trounson announced that no SCNT grants had been funded due to some sort of vague policy concern about access to human oocytes and the challenges this had created in other countries. (We are aware of Grant#R31-00404 related to SCNT that was previously funded).
First, this was "moving the goal posts" after we had submitted our grant application. Second, we appreciate the challenge of securing oocytes but we at Cascade had been fortunate enough to secure a collaboration with La Jolla IVF clinic to supply all the oocytes we need to proceed with our cell line development effort. Moreover, if this was truly the reason for flagging our grant application as non-fundable, CIRM should have just told us that in writing and explained how they were going to proceed, if at all, in the area of SCNT.
A factually incorrect assumption about our “efficiency” may have been the fundamental error that doomed our application. The CIRM reviewer commented:
The ability to generate individualized human embryonic stem cell lines using somatic cell nuclear transfer from either healthy individuals or patients with specific disease states is an exciting and yet technically demanding prospect. To date, no one has successfully cloned human embryonic stem cells, although recently, a group at University of Oregon Heath Sciences Center has successfully derived primate embryonic stem cells, with an efficiency of approximately 0.3%
This is factually incorrect at two levels. First, we are unclear where the reviewer got the 0.3% efficiency rate. This is not a number we have used. Our November 2007 Nature paper calls out 0.66% efficiency at page 497. Our grant application (filed Jan 2008) describes in detail at page 8, "These results represent a significant reduction in the number of oocytes required to produce a single ESC line over previously reported efficiency (from 152 to 30) providing the important foundation to conduct the proposed studies in humans." 1 ESC cell line out of 30 oocytes is actually 3.3%.
I am unclear how this fundamental oversight occurred. Mistake? Miscommunication? Pre-existing bias? Misunderstanding? Suffice it to say, we believe that the incorrect information about efficiency was the driving force behind the reviewers’ comments and failure to fund.
Suggestions and Action Items for Consideration.
Our hope is that thru expressing our concerns and our experience we will be able to make industry (For-Profit) a viable partner in the mission of Prop 71. With that in mind, we would like to suggest the following ideas for review and consideration by the ICOC:
Industry representation on CIRM grant review teams
Formal appeal process or ability to respond in writing to reviewer comments. See, for example, SBIR, STTR, NIH funding for models of review cycles.
Holding the review team to the published review criteria--e.g., novelty is not a priority criteria.
One of the review criteria should always be the impact of the research on the advancement of human product development. If the Rusty Gage review reconsideration is as I understand it, it seems that there is one set of rules for a deservingly prominent scientist and a different set of rules for Cascade LifeSciences/Industry. We also filed a letter with CIRM asking for the opportunity to comment on our grant review and were denied. This seems, without more complete information, to be unfair.
Perhaps separate academic/not-for-profit grant application review from for-profit review. Comparing not for profit grants (institutions that are Grant Writing Machines) with the grant applications of fledgling biotech companies is fundamentally unbalanced.
Although I believe that Industry is a key element of Product development and we desire to work with CIRM to advance the cause, if CIRM’s funding criteria or standards are inconsistent with industry participation or pragmatic product development, we need to know that earlier rather than later.
I am personally and professionally committed to assist CIRM in making industry an equal partner in achieving the mission of Prop 71. I would look for guidance from the ICOC on how we can work through some of these administrative and structural challenges.
Although we are disappointed by the CIRM review and admittedly discouraged by the process, I trust that the agency and the applicants will evolve favorably with time and experience.
As our distinguished Governor would say.............."We'll be Back."
Sincerely,
Kenneth J. Woolcott
Chief Business Officer
Cascade LifeSciences Inc
10398 Pacific Center Ct.
San Diego, CA 92121
kjwoolcott@aol.com
858-945-4667
KJW/rrc
cc: Alan Trounson, President CIRM
Howard Birndorf
Sophia Khaldoyanidi
Exhibit A
Cascade LifeSciences
Founded 2004
San Diego, CA
Howard Birndorf, Chairman
Kenneth Woolcott, Chief Business Officer
Sophia Khaldoyanidi, Ph.D, MD, Chief Scientific Officer
Larry Respess, General Counsel
Exclusive Licensee of Novel SCNT technology developed at Oregon Health Sciences University (OHSU) and published in Nature, Nov 2007. (First successfully SCNT in Primates)
Dr. S. Mitalipov, inventor of SCNT patents and consultant on human SCNT effort.
Exhibit B
KENNETH J. WOOLCOTT
6100 La Jolla Scenic Drive South
2000 First Avenue
La Jolla, CA 92037
Suite 2304
858-454-8496 phone/fax
Seattle, WA 98121
kjwoolcott@aol.com
206-795-4667 phone
GENERAL COUNSEL & LICENSING EXECUTIVE
Strategic Advisor . . . Entrepreneurial Counsel . . . Transactional Architect
Summary: Executive with over 20 years of experience and outstanding accomplishment in the Biopharmaceutical Industry, including 12 plus years of key legal and management responsibilities at IDEC Pharmaceuticals Corporation (now Biogen IDEC) through its growth from a market cap of $50M to a company with a valuation of over $10B. Provided counsel and craftsmanship on over $1B in global corporate alliances and public financings. Contributed legal leadership and team influence in the development and FDA approval of two oncology drugs, RITUXAN (first antibody approved for cancer) and ZEVALIN (first radioimmunotherapy approved for cancer), currently generating annual U.S. sales of over $1.9B. Provided leadership in diverse and challenging roles based on the growth and needs of the organization, for example:
Strategic advisor with entrepreneurial zeal and global biopharma perspective.
Counsel with intra-disciplinary experience, scientific background and a proven track-record of incisive legal analysis and problem-solving.
Executive officer with achievement in operational management, strategic planning, business development, team building, and change agent in development of company’s core values as it grew from 70 to over 800 employees.
General Counsel and Corporate Secretary with broad experience in public company matters, corporate governance, SEC compliance, FDA issues, intellectual property strategy, transactional negotiation and crafting, corporate partner management, litigation management, and government relations.
PROFESSIONAL EXPERIENCE AND KEY METRICS
Woolcott Bioscience Strategies 2002-present
Transactional and Business Development Consulting Services
Chief Business Officer, Cascade Lifesciences Inc 2007 to present
Strategic Advisor 2005 to 2007
Nativis, Inc. San Diego, CA
Acting Vice President, Business Development & General Counsel 2004-2005
Imagine Pharmaceuticals, San Diego, CA
IDEC Pharmaceuticals Corp., San Diego, CA 1989-2002
VP, General Counsel, Licensing Executive and Secretary 1994-2002
General Counsel, Licensing Executive and Secretary 1992-1994
Deputy General Counsel and Secretary 1991-1992
Intellectual Property Counsel 1989-1991
Counsel to approximately $700M in IDEC Public Equity & Debt Financings:
Initial public offering (IPO): (1991--$52 M)
Follow-on equity offerings: (1994 – $8M; 1996 -- $50M; 2000 -- $473M)
“LYONS” convertible debt offering: (1999 -- $113M)
Counsel and negotiator for approximately $300M in corporate alliances from 1991-00, including:
Zenyaku/Rituxan – 1991, $10M SmithKline/CD4 – 1992, $60M
Mitsubishi/B7 – 1994, $12M Seikagaku/CD23 – 1995, $26M
Genentech/Rituxan – 1995, $57M Eisai/gp39/CD40L – 1995, $38M
Kirin, BI, and Chugai/ Upjohn/9AC – 1997, $12M
Expression System – 1995-7, $15M
Schering AG/Zevalin –1999, $47M Nordion /Yttrium – 2000, $20M
Member of core team of executives that led turnaround from $50M valuation and six months of cash in 1994 to pivotal Genentech partnership/cash infusion and over 800% increase in stock valuation in 1995.
Managed key patent litigation (IDEC v. Corixa et al), including selection process for lead counsel and development of declaratory judgment strategy over a multi-year period. Strategically, IDEC prevailed in securing venue in San Diego Federal District Court, while actions in Delaware and Northern District of California were dismissed. In October 2003, summary judgment was granted in favor of IDEC declaring invalid and unenforceable all of Corixa’s subject patents. The case was ultimately settled on favorable terms
Executive Committee level advisor on IND, clinical strategy, Advisory Committee meeting, manufacturing subcontracting and inspection, approval and launch of RITUXAN and ZEVALIN.
Early advocate and adopter of Rule 10b-5 executive stock selling plans, including successful initiation of amendment to California State Securities Laws to conform with provisions of new Federal law
Managed preparation and filing of SEC corporate disclosure documents including crafting of numerous sensitive and challenging press releases.
Managed legal aspects of “Poison Pill” adoption and revision
Lead legal analysis and selection of RITUXAN and ZEVALIN trademarks
Coordinated legal and peer analysis for stock splits 2:1 21 Dec ’99 and 3:1 18 Jan ‘01
Built and managed a high-performance Legal Team of thirteen professionals
Managed Corporate Policy on Insider Trading and Stock Trading Windows
Member of Executive Committee, Corporate Secretary and liaison with Board of Directors
Strong presentation skills and recognized public speaker
Christensen, O’Connor, et al., Seattle WA 1987-1989
Associate
Hybritech, Inc., San Diego, CA 1985-1987
Intellectual Property and Licensing Counsel 1986-1987
Patent Counsel 1985-1986
EDUCATION
George Washington University, Washington, D.C.
Juris Doctorate, 1985
Leader, Save the Night Law School Campaign, 1984
President—Evening Division, Student Bar Association, 1984
University of Maryland, College Park, MD
MS candidate/Chemical Engineering, 1980-81
Pacific Lutheran University, Tacoma, WA
B.S,. Biochemistry, Cum Laude, 1980
PROFESSIONAL ORGANIZATIONS
California State Bar Association
Washington State Bar Association
District of Columbia Bar Association
United States Patent Office
Registered Patent Attorney (#30,824)
American Corporate Counsel Association
Founding Director of San Diego Chapter, 1994
American Association of Corporate Secretaries
Biotechnology Industry Organization
Founder of General Counsel Committee, 2001
COMMUNITY AFFILIATIONS
Burnham Institute for Medical Research, La Jolla, CA
Trustee and Chairman of Technology Transfer Committee., 2004 to present
Basketball Club of Seattle, L.L.P.
Partner, 2002 to 2006
The Jimmy V Foundation for Cancer Research
Friends of V Member
The Starlight Foundation for Children
Freshstart , Inc.
Exhibit C
Rebuttal letter & REQUEST FOR rECONSIDERATION
sophia Khaldoyanidi, ph.d., m.d.,
chief scientific officer
cascade lifesciences, inc.
RL1-00656-1: Generation of human ESC lines using SCNT
Executive Summary Comments
Comment #1: The proposal lacks a detailed description of how the resultant cell lines will be assessed and characterized for pluripotency.
Response #1: This concern was raised by the Reviewer #2. However, the description of the pluripotency tests is described on page 5 of the grant application (Step 4 of our protocol). We proposed to evaluate pluripotency of SCNT-ESC lines based on stemness marker expression and both in vivo and in vitro differentiation using standard state-of-the art methods. These methods include immunocytochemistry, flow cytometry, quantitative RT-PCR, embryoid body formation and teratoma assay. All these assays are standard in stem cells biology field and are routinely used by the members of our scientific team (see list of publications provided in Part C of this grant application).
Comment #2: No data is presented suggesting that these assays [for pluripotency] are routinely available in the applicant’s laboratory.
Response #2: Due to the space constrains of the Preliminary Results and Feasibility section (2 pages), we have chosen to present the results supporting the novel and scientifically-challenging aspects of the SCNT technology. The concern regarding our ability to run the pluripotency tests was raised by the Reviewer #2 and the rationale for this concern is not clear to us: the assays for pluripotency are standard techniques used in every stem cell laboratory including laboratories leaded by the members of our scientific team. The fact that we are familiar with the standard techniques used in our field is supported by our publications (Part C of this grant application).
Comment #3: The collaborator with the primate cloning expertise proposes to spend 25% of his/her time in the applicant’s laboratory in California. However, reviewers expressed serious concern that it will be logistically difficult for the out-of-state collaborator to be available at the time when the oocytes are donated.
Response #3: Anyone with experience with IVF understands that the day of oocyte harvesting is predicted in advance based on the rigid hormone treatment schedule for each donor. Based on this well known schedule, the travel for Dr. Mitalipov from Portland to San Diego (2.5 hour duration) can be easily planned in advance.
Comment #4: Regarding the source of the oocytes, which will be obtained from an in vitro fertilization (IVF) clinic, one reviewer felt that the procurement of 100 oocytes per year seems reasonably achievable. However, others felt that not enough information is presented in the application to firmly support that the applicant can obtain the high quality eggs.
Response #4: Due to the space constrains, we did not have an opportunity to explain in the body of the grant as to how human oocytes will be obtained. This information is provided very clearly in the letter of collaboration from Dr. Smotrich of La Jolla IVF Clinic (Part C). Dr. Smotrich established a list of young and healthy volunteers who desire to donate oocytes specifically for this SCNT project. All these donors were pre-tested and demonstrated a high oocyte production (20-25 oocytes per cycle) in response to hormonal stimulation. We do not intent to use oocytes that have been obtained for the purpose of IVF treatment and were not used due to poor quality.
Comment #5: If they [Cascade LifeSciences team] have access to 100 eggs, some reviewers argued that it would not be enough to make a cell line in 1 year, given the primate success rates (0.3%).
Response #5: The information on the 0.3% efficiency presented to the Study Section by the Reviewer #2 is factually incorrect. Even if the reviewer was mistakenly relying on our Nov. 2007 Nature publication, that efficiency was reported as 0.66%. More importantly, on pages 5 and 8 of this grant application we provided information that the efficiency of SCNT in primates was 3.3% (1 ESC line per 30 oocytes)
Comment #6: Reviewers mentioned that there is no consideration of how the resultant cell lines, if any, will be distributed to other research groups and under what conditions as requested in the application.
Response #6: This is factually incorrect. This concern was raised by the Reviewer #2. However, this information has been provided on page 10 of the application (last paragraph).
In summary: Our response demonstrates that the Reviewer #2 provided factually incorrect information to the Study Section. In particular, the efficiency (which is an important parameter) was erroneously reported. Moreover, despite the challenges others may legitimately face in securing oocyte donors, we were able to secure reliable and excellent source of oocytes to advance our work in humans. Finally, to suggest our proposal is not novel is a flawed conclusion as Human SCNT is a stated goal of the RFA and the stated RFA review criteria specifically noted that “novelty” was NOT a measure for funding. As a result of these factual errors and an unknown change in SCNT funding philosophy in mid-review, our project received a non-fundable score. We requested an opportunity to rebut. We were denied.
REQUESTED ACTION: We respectfully request that the ICOC reconsider our grant application for funding.
Sunday, July 06, 2008
CIRM's Grant Review Process: Complaints About Errors and Appeals
California's stem cell agency has pumped out more than $554 million in awards for stem cell research, but this year grumbling has emerged about its secretive awards process, which officially does not permit rebuttal in the case of errors and allows appeals only in the case of conflicts of interest. On Sunday, reporter Terri Somers of the San Diego Union-Tribune became the first mainstream media writer to examine the issue in some detail.
Somers used June's meeting of the CIRM board of directors to discuss the subject, including additional interviews with researchers.
Somers wrote that CIRM is
"...basing its funding decisions on recommendations from panels of scientists who sometimes make significant factual errors in their reviews of grant requests, some applicants say.
"Yet there is no way for applicants to point out or rebut the errors – at least not through a formal appeals process, such as the one used by the National Institutes of Health.
"'I cannot tell you how frustrating it is to get turned down for a grant and have no recourse other than to shred it and all the time you spent doing it,' said Jeanne Loring(see photo), a researcher at the Scripps Research Institute in La Jolla.
Somers said CIRM has no plans to change its policies concerning appeals or error. She quoted CIRM Chairman Robert Klein as saying the NIH appeal process is too slow for CIRM. He said an NIH appeal can take as long as two years.
Somers did not raise the closed-door nature of the grant reviews as an issue, but applicants do not have access to the proceedings. Nor do apparently many of them know that they can appear publicly before CIRM directors and ask them to change the recommendations of scientific reviewers or even write a letter to that effect.
Directors have final authority on grant approval but generally ratify decisions of the scientific reviewers, without even officially knowing the identities of the research applicants. Their identities are withheld but in many cases can be discerned through the public summary of reviewers' comments.
Somers quoted one CIRM director, Jeff Sheehy of the University of California, San Francisco, about the review process. Sheehy is also a patient advocate member of the CIRM grant review group and played a role last month in airing concerns by one scientist, Fred Gage of the Salk Institute.
Sheehy told Somers:
"We may have missed some good science, but I don't think we have funded (bad science)."
While CIRM does not plan changes in its review process, Klein did tell Somers about one option for disgruntled applicants. She wrote:
"If a scientist wants to rebut an error of fact of great scientific importance, he or she should point it out to institute President Alan Trounson or Chief Scientific Officer Marie Csete, Klein said.
"Those scientists could then sort out the issue with the reviewers and decide whether it needs to be brought to the board's attention, he said."
Our take: If that is CIRM policy, all applicants should be informed about that possibility as they apply. Fairness and the appearance of fairness are critical to CIRM's credibility.
Here is a link to a detailed critique by one applicant and our report from the June meeting of CIRM directors.
Monday, June 30, 2008
Cascade LifeSciences Critiques CIRM Grant Review Process; Questions Raised about Fairness and Facts
Cascade LifeSciences of San Diego is one of the few companies to appear at a meeting of the board of directors of the $3 billion California stem cell agency in connection with rejection of its grant application.
Kenneth Woolcott, chief business officer of the firm, expressed dismay last Thursday night concerning CIRM's scientific grant review process. Among other things, he said that reviewers appeared not to have read the application very carefully.
Following the meeting, we emailed him and asked if he would like to comment further with an eye to making constructive suggestions for changes in the review process. We are asking CIRM if it has any comment on Woolcott's remarks, the text of which follows:
Kenneth Woolcott, chief business officer of the firm, expressed dismay last Thursday night concerning CIRM's scientific grant review process. Among other things, he said that reviewers appeared not to have read the application very carefully.
Following the meeting, we emailed him and asked if he would like to comment further with an eye to making constructive suggestions for changes in the review process. We are asking CIRM if it has any comment on Woolcott's remarks, the text of which follows:
"We were disappointed by the CIRM review and discouraged by the process. I trust that the agency and the applicants will evolve favorably with experience. As our distinguished Gov would say..............'We'll be Back.'
"Our real hope is that through expressing our concerns we will be able to make industry (For Profit) a viable partner in the mission of Prop. 71.
"The mission statement of Prop. 71 makes very clear that although science is a laudable goal it is not the end game. Products that treat, cure, or enhance our lives are the end game. Fast forward 10 to 15 years and I would like to be so bold as to suggest that the ultimate arbiter of the success of CIRM or Prop 71 will be PRODUCTS. Not research achievements, not publications, not patents, not even Nobel Prizes. All of these will advance our efforts and are important metrics and may even contribute to the economy of California. But John Q. Public will only benefit directly by the development of innovative stem cell related PRODUCTS that I believe will change medical approaches to disease in fundamental ways.
"I am a lawyer and the CBO of Cascade LifeSciences, but I am also a taxpayer. I also have an industry bias cultivated over 20 years with two of the San Diego biotech pioneers, Hybritech and IDEC. What I know about stem cells I have learned, what I know about product development I have lived.
"I believe industry and CIRM share the goal of product development. Although cutting edge science and academic excellence are part of the goal, we believe that industry must be the conduit through which PRODUCT run the clinical, regulatory and marketplace gauntlet.
--------
(Editor's note: Here is a brief sketch of the firm provided by Woolcott.)
"Cascade LifeSciences
"Founded 2007
"San Diego, CA
"Howard Birndorf, Chairman
"Kenneth Woolcott, Chief Business Officer
"Sophia Khaldoyanidi, Ph.D, MD , Chief Scientific Officer
"Larry Respess, General Counsel
"Exclusive Licensee of Novel SCNT technology developed at Oregon Health Sciences University (OHSU) and published in Nature, Nov 2007. (First successfully SCNT in Primates)
"Dr. S. Mitalipov , inventor of SCNT patents and consultant on human SCNT effort.
----------
"Our Expectation
(Editor's note: Woolcott's detailed comments follow.)
"CIRM RFA 07-05: New Cell Line Awards
"Page 1, Program Objectives --'Somatic cell nuclear transfer (SCNT), a method for reprogramming that is well-established in several mammalian species, has not yet been achieved with human cells, but recent success has been reported in non-human primates.' [This is Dr. Mitalipov's work published in Nature and exclusively licensed by Cascade]
"Page 2. 'The needs may in the future be met by derivation of hESC following SCNT...'
"Page 2. 'CIRM proposes a new program to address the need for new types and sources of human pluripotent stem cell lines and for the optimization of existing methods for their derivation"
"Cascades Reasoned Expectation:
"Translation of our SCNT primate work into the SCNT generation of hESC is right in the 'strike zone' of the RFA. We were very pleased the CIRM had seen the wisdom of opening up the grant process to industry to help fund this critically important translational research that can neither be funded by the NIH nor is of interest to all but a very few private investors.
"Cascades Competitive Appreciation.
"iPS is a very important scientific avenue of research but SCNT is a very competitive alternative especially for PRODUCTS that are intended for human use.
"Cascades Experience with the Grant Review
"Grant review comments were factually incorrect. Not a matter of subjective scientific debate. Hence, the conclusions were fundamentally flawed. For example, reviewer #1 comment was 'lack of novelty, pure translation of the non-human primate work into humans.' This seems to defy logic and the mission of human therapeutics. Moreover, this does not seem to be consistent with the objectives published by CIRM in its RFA, which specifically calls out the 'hurdle' of human SCNT as a fundable goal.
"A second example of a reviewer's factual error is the comment 'The ability to generate individualized human embryonic stem cell lines using somatic cell nuclear transfer from either healthy individuals or patients with specific disease states is an exciting and yet technically demanding prospect. To date, no one has successfully cloned human embryonic stem cells, although recently, a group at University of Oregon Heath Sciences Center has successfully derived primate embryonic stem cells, with an efficiency of approximately 0.3[s1] %.' This is factually incorrect at two levels and we are unsure of where the reviewer got the 0.3% efficiency rate. Our November 2007 Nature paper calls out 0.66% efficiency at page 497. Our grant application (filed Jan 2008) describes in detail at page 8, Confidential, non-published information, 'These results represent a significant reduction in the number of oocytes required to produce a single ESC line over previously reported efficiency (from 152 to 30) providing the important foundation to conduct the proposed studies in humans.' One ESC out of 30 oocytes is actually 3.3%.
"As we all know development of therapeutics for the monkey population is a very low margin business. [Sorry could not resist]
"Moreover, at the CIRM IROC meeting Dr. Uta Grieshammer, specifically presented the review committees grant criteria and noted specifically that the review team was advise that 'novelty' was NOT a priority for these types of grants. Also at the meeting, Dr. Trounson announced that no SCNT grants had been made due to some sort of vague policy concern about access to human oocytes and the challenges this had created in other countries. First, this was 'moving the goal posts' after we had submitted our grant application. Second, we appreciate the challenge of securing oocytes but we at Cascade had been fortunate enough to secure commitment from LJ IVF clinic to supply all the oocytes we need to proceed with our effort. Moreover, if this was truly the reason for flagging our grant application as non fundable, CIRM should have just told us that in writing and explain how they were going to proceed, if at all, in the area of SCNT.
"We filed a formal request to rebut the conclusions and comments of the reviews but were told there was no such process. We now understand that after our departure on Thursday, Rusty Gage, one of our esteemed colleagues here in San Diego was allowed to rebut reviewer comments and did receive funding. We are unclear on how this rebuttal process works and why we were denied any opportunity to dialogue on the merits.
"We are now told that my discussion at CIRM was flawed because I did not address the mistake regarding efficiency of our SCNT. This is unfortunate, as we were told our request for rebuttal was rejected and that we were not allowed to discuss the merit or lack of merit of the specific review of our application but our 3 minutes was limited to expressing our concerns about the process and our suggestions for improvement from an industry perspective.
"How did this happen? Mistake? Miscommunication? Misunderstanding? Bias?
"Suggestions and Action Items for Consideration
"Industry representation on CIRM grant review teams
"Formal appeal process or ability to respond in writing to reviewer comments. See, SBIR, STTR, NIH funding for models of review cycles.
"Holding the review team to the published review criteria--e.g., in this RFA, novelty is not a priority criteria.
"One of the review criteria should always be the impact of the research on the advancement of human product development.
"If the Rusty Gage review reconsideration is as I understand it, it seems that there is one set of rules for a deservingly prominent scientist and a different set of rules for Cascade LifeSciences. We also filed a letter with CIRM asking for the opportunity to comment on our grant review and were denied. This seems, without more complete information, to be unfair.
"Perhaps separate academic/not-for-profit grant application review from for profit review. Comparing not-for-profit grants (institutions that are grant writing machines) with the grant applications of fledgling biotech companies is fundamentally unfair. Anyone who knows me will tell you I am a basketball fan. Using that sport as an analogy, this is like the USA basketball team of young college players competing against the Soviet National Team of grown men that had played together for four years. We all know how that worked out.
"Although I believe that industry is a key element of product development, and we desire to work with CIRM to advance the cause, if their funding criteria or standards are inconsistent with industry participation or pragmatic product development, we need to know that earlier rather than later.
"I am personally and professionally committed to assist CIRM in making industry an equal partner in achieving the mission of Prop. 71. I would look for guidance from the ICOC (CIRM's board of directors) on how we can work through some of these administrative and structural challenges.
"Hope this helps. It is a complex issue for industry as well as for CIRM."
Friday, June 27, 2008
More California Dough -- $23 Million -- Rolls Out the Door for Stem Cell Research
BURLINGAME, Ca. -- Directors of the California stem cell agency Thursday night approved $23 million for research grants to develop new cell lines, including reprogramming efforts.
However, they put off until today approval of about $1 million in disease planning grants.
The agency did not announce the names of the 16 winners out of the 50 applicants for new cell line grants. But all of those recommended for funding by scientific reviewers were routinely ratified. Another two grants that reviewers did not think warranted approval for scientific reasons were also approved.
The directors of the $3 billion agency decided to give cash to the two on the basis of "programmatic" and other reasons.
All of the recipients and their grant reviews can be found here, minus their names. The approved applications are color-coded with either white or grey.
The new stem cell round of grants was the first opportunity for businesses to receive research cash from CIRM. Twelve firms applied. But scuttlebutt at the meeting was that none of the businesses won grants. CIRM Chairman Robert Klein declined even to say whether any businesses were in the "recommended for funding" category, when asked by John M. Simpson, stem cell project director for the Consumer Watchdog group.
Ken Woolcott, chief business officer of Cascade Life Sciences of San Diego, Ca., appeared before CIRM directors to express dismay about the grant process. His firm was not recommended for funding. While he did not ask for reconsideration, he said "reviewers simply did not read our application (No. 656) very carefully." He said that with NIH grants, applicants get a chance to respond to reviewers' comments prior to final action – something that CIRM does not formally provide. Woolcott said the firm's "experience was very different from our expectations."
The public review of the Cascade application said the research was "based on a collaboration between the applicant and the only group known to have successfully cloned primate cells." Reviewers expressed concerns that the firm could not get enough human eggs for its work, among other comments.
The two "programmatic" grants won approval after two unusual pitches were made on their behalf. One emotional appeal came from Judy Robertson of Sacramento, Ca., a Huntington's Disease advocate. She has lost four members of her family, including her husband to the disease. The family has donated $500,000 to UC Davis for a Huntington's clinic.
She complained that the review was "factually incorrect." The board discussed the assertion at some length, including comments from audience and staff, without reaching a conclusion on the accuracy of the information. Ultimately, the board approved the grant because it appeared to want to include Huntington's in CIRM's "program."
CIRM Director Jeff Sheehy made an appeal for funding the other of the two "programmatic" proposals. He read a letter from Fred Gage of the Salk Institute, stoutly defending the application. Directors had the letter before them but it was not available to the public, which Klein said was a mistake. Sheehy carried the day, and the Gage grant was approved on a 9-7 vote with one abstention. (The committee officially has 29 members, but only 17 were present and qualified to vote Thursday night.)
Sheehy's reading triggered a discussion not only of the merits of the application but of the sanctity of the review process, which was reminiscent of the flap in January when Childrens Hospital of Oakland Research Institute was the first applicant to publicly appeal a negative decision by scientific reviewers. Childrens was ultimately unsuccessful in that effort
By law, directors have the right to make the final decision on grants. However, they have approved 168 grants since 2004 and rejected only one recommended by scientific reviewers. Any applicant may appear before directors or write an appeal, a fact not well known to applicants. Few have appealed. Presumably they have not done so either out of ignorance or because they do not want to offend an agency which holds the key to their professional lives.
Some CIRM directors were uncomfortable with the Childrens Hospital appeal, and some were still uncomfortable Thursday night.
Oswald Steward, a CIRM director and chairman of the Reeve, Irvine, Resarch Center, UC Irvine, raised the issue of fairness in connection with Sheehy's reading of the Gage letter. Steward said other rejected applicants may not have understood that they could also seek to overturn a negative decision by scientific reviewers.
Marcy Feit, a CIRM director, president of ValleyCare Health Systems of Livermore, Ca.,and a member of the Grants Working Group, said she would "hate to see us redo those reviews." She said was against an "extensive rebuttal process" because it would "undermine" reviewers.
CIRM President Alan Trounson told directors they should accept that reviewers do a "reasonable job" and that disappointed applicants will naturally find fault with the system, which may sometimes include incorrect information. He warned that overturning scientific reviewers decisions could mean the loss of the reviewers, who are already being worked hard.
In January, directors seemed to be looking to CIRM staff for a proposal on how to deal with appeals from applicants. However, other chores, including a $1.1 billion lab building effort, have consumed a great deal of time. We suspect the appeal process may gain more attention in the very near future.
As for the names of the grant recipients and CIRM's take on Thursday night's soirée(It was a thrill a minute!), look for a press release on the CIRM website later today.
However, they put off until today approval of about $1 million in disease planning grants.
The agency did not announce the names of the 16 winners out of the 50 applicants for new cell line grants. But all of those recommended for funding by scientific reviewers were routinely ratified. Another two grants that reviewers did not think warranted approval for scientific reasons were also approved.
The directors of the $3 billion agency decided to give cash to the two on the basis of "programmatic" and other reasons.
All of the recipients and their grant reviews can be found here, minus their names. The approved applications are color-coded with either white or grey.
The new stem cell round of grants was the first opportunity for businesses to receive research cash from CIRM. Twelve firms applied. But scuttlebutt at the meeting was that none of the businesses won grants. CIRM Chairman Robert Klein declined even to say whether any businesses were in the "recommended for funding" category, when asked by John M. Simpson, stem cell project director for the Consumer Watchdog group.
Ken Woolcott, chief business officer of Cascade Life Sciences of San Diego, Ca., appeared before CIRM directors to express dismay about the grant process. His firm was not recommended for funding. While he did not ask for reconsideration, he said "reviewers simply did not read our application (No. 656) very carefully." He said that with NIH grants, applicants get a chance to respond to reviewers' comments prior to final action – something that CIRM does not formally provide. Woolcott said the firm's "experience was very different from our expectations."
The public review of the Cascade application said the research was "based on a collaboration between the applicant and the only group known to have successfully cloned primate cells." Reviewers expressed concerns that the firm could not get enough human eggs for its work, among other comments.
The two "programmatic" grants won approval after two unusual pitches were made on their behalf. One emotional appeal came from Judy Robertson of Sacramento, Ca., a Huntington's Disease advocate. She has lost four members of her family, including her husband to the disease. The family has donated $500,000 to UC Davis for a Huntington's clinic.
She complained that the review was "factually incorrect." The board discussed the assertion at some length, including comments from audience and staff, without reaching a conclusion on the accuracy of the information. Ultimately, the board approved the grant because it appeared to want to include Huntington's in CIRM's "program."
CIRM Director Jeff Sheehy made an appeal for funding the other of the two "programmatic" proposals. He read a letter from Fred Gage of the Salk Institute, stoutly defending the application. Directors had the letter before them but it was not available to the public, which Klein said was a mistake. Sheehy carried the day, and the Gage grant was approved on a 9-7 vote with one abstention. (The committee officially has 29 members, but only 17 were present and qualified to vote Thursday night.)
Sheehy's reading triggered a discussion not only of the merits of the application but of the sanctity of the review process, which was reminiscent of the flap in January when Childrens Hospital of Oakland Research Institute was the first applicant to publicly appeal a negative decision by scientific reviewers. Childrens was ultimately unsuccessful in that effort
By law, directors have the right to make the final decision on grants. However, they have approved 168 grants since 2004 and rejected only one recommended by scientific reviewers. Any applicant may appear before directors or write an appeal, a fact not well known to applicants. Few have appealed. Presumably they have not done so either out of ignorance or because they do not want to offend an agency which holds the key to their professional lives.
Some CIRM directors were uncomfortable with the Childrens Hospital appeal, and some were still uncomfortable Thursday night.
Oswald Steward, a CIRM director and chairman of the Reeve, Irvine, Resarch Center, UC Irvine, raised the issue of fairness in connection with Sheehy's reading of the Gage letter. Steward said other rejected applicants may not have understood that they could also seek to overturn a negative decision by scientific reviewers.
Marcy Feit, a CIRM director, president of ValleyCare Health Systems of Livermore, Ca.,and a member of the Grants Working Group, said she would "hate to see us redo those reviews." She said was against an "extensive rebuttal process" because it would "undermine" reviewers.
CIRM President Alan Trounson told directors they should accept that reviewers do a "reasonable job" and that disappointed applicants will naturally find fault with the system, which may sometimes include incorrect information. He warned that overturning scientific reviewers decisions could mean the loss of the reviewers, who are already being worked hard.
In January, directors seemed to be looking to CIRM staff for a proposal on how to deal with appeals from applicants. However, other chores, including a $1.1 billion lab building effort, have consumed a great deal of time. We suspect the appeal process may gain more attention in the very near future.
As for the names of the grant recipients and CIRM's take on Thursday night's soirée(It was a thrill a minute!), look for a press release on the CIRM website later today.
Wednesday, April 30, 2008
'Nature' Assesses CIRM, Warns of Conflicts of Interest
Nature magazine took a run at the California stem cell agency today, producing a fine overview and an editorial that warned of "cronyism" on its board of directors. The occasion for the coverage is the upcoming approval next week of $262 million in funding for stem cell lab construction, an event that is likely to trigger a number of articles about CIRM in the California media and perhaps nationally.
The article by Erika Check Hayden recapped the history of tiny organization (staff about 26) and said,
"If $3 billion seemed like a dream four years ago, it is now a reality that is changing not only the way science is done in California, but is resonating across the US biomedical landscape."Nature highlighted some of the conflict of interest problems on the Oversight Committee, as CIRM's board of directors is known. Its editorial said,
"Several episodes over the past year have highlighted an inherent problem with the CIRM's structure: the board that distributes its funding is stacked with representatives from the universities that benefit most from those disbursements. The CIRM has enacted rules to try to limit the conflicts of interest posed by this arrangement. They don't go far enough. At one meeting in January, for instance, CIRM board members from institutions that had applied for a facilities grant voted to deny one of these grants to an institution that has no representatives on the CIRM board."The editorial continued,
"For the agency to succeed, patient advocates and other public representatives must fight the tendency of the academic institutions on the board to hoard dollars. As the patient advocates grow into their roles as full partners, and with help from well-intentioned lawmakers such as (State Sen. Sheila)Kuehl, the CIRM must be coaxed into serving its most important constituency — the taxpayers of California. The roles themselves are not unusual in the world of governance, but here the stakes are exceptionally high."Hayden's overview said,
"...(E)ven as the agency is changing California's scientific outlook, it is also facing pressure to prove its worth to voters — and to show that it can deliver the medical and economic benefits it promised in order to convince taxpayers to fund it in the first place. Which raises the biggest question about the CIRM: will scientists be able to deliver the results it promised? This is an urgent concern for the leaders of the CIRM, because it won the hearts of California voters by saying it would produce cures for a number of debilitating diseases."Hayden discussed legislation by Kuehl, D-Santa Monica, as one of the responses to the questions about delivering on Prop. 71 campaign promises.
Hayden also wrote about the recent complaints that CIRM overstated its funding role in UCSD research that has led to clinical trials and about the conflict-of-interest flap involving CIRM director John Reed. Both cases were first reported by the California Stem Cell Report, a fact that Nature did not mention, but media coverage of CIRM was incidental to the article.
Hayden continued:
"...CIRM's structure has, at times, seemed to hamper its own mission. That was painfully evident at a meeting in January, when one doctor found himself begging for funding from 13 board members who were competing directly against him for money."As we reported in January, Bert Lubin(see photo), head of the Children's Hospital Oakland Research Institute, unsuccessfully appealed a negative recommendation by scientific reviewers to the full Oversight Committee, which has final say on grants. (The committee has reversed a positive recommendation for funding once (Sept. 9,2005) and never reversed, as far as we can recall, a do-not-fund decision by scientific reviewers.)
Lubin told Nature,
"We're not in the 'in' crowd. So a project that was really going to go into patients was essentially triaged."The Nature article said,
"The episode is only one in a series of incidents that have raised questions about the wisdom of putting the institutions that benefit from the CIRM in charge of governing it."
(Editor's note: An earlier version of this item incorrectly said the Oversight Committee has never reversed a positive recommendation for funding. In fact, committee rejected, on a 4-20 vote, a recommended training grant proposal (T3-00005) in its first round of grants Sept. 9, 2005. The grant was given a 70 score out of 100 by reviewers. However, some CIRM Oversight members said they were concerned about the lack of appropriate faculty at the unidentified institution and "under developed" lab space. The actual vote tally on the grant was not announced during the meeting nor in the minutes from the session. Our 4-20 vote count was arrived at by going through the 323-page transcript).
Thursday, January 17, 2008
Childrens Hospital Loses Bid for Lab Grant; 12 Survive
In their most heated public session in their short history, directors of the California stem cell agency Wednesday night rejected a bid by Childrens Hospital Oakland Research Institute to overturn a negative recommendation on a grant to build a lab to fight sickle cell anemia.
Childrens' request failed on a 5-10 vote despite an impassioned plea by CIRM director Jeff Sheehy.
"This is a no-brainer," said Sheehy. "This is a very promising area of research."
Other board members argued that Childrens' public appeal, the first ever directed to the Oversight Committee, violated the agency's processes, was unfair to other rejected applicants and needed consideration in some future round of grants.
Sheehy didn't buy the arguments. "Let us study it," he said caustically. "Let another person die."
The board's action came during a session that resulted in the relatively routine approval of 12 institutions to advance to the next round of the $262 million stem cell lab grant program, which will judge the actual building plans. Today's review focused on the research proposed for the facilities. All 12 approved Wednesday night were identified earlier as being recommended for funding following a closed-door session involving scientific reviewers who are not required to disclose publicly their financial interests.
Childrens Hospital received a "do-not-fund" decision by the reviewers. Bertram Lubin, president of the hospital, appeared before the Oversight Committee Wednesday night after sending three letters to the members of the panel. (Two of have appeared on this web site.)
He told directors that the grant reviewers did not appreciate the type of research proposed by Childrens. Sheehy, who participates in the closed-door review sessions, concurred.
Lubin also told directors, "When you report on what CIRM has done, this (funding his program)would be a major accomplishment." He said it could result in actual treatments in a year or two, which is a far cry from almost all of the research financed by CIRM.
Some directors, including Chairman Robert Klein, have pushed aggressively for faster work on therapies. Ironically, earlier in the day, a CIRM Task Force explored details of how it could launch a massive loan program, totaling as much as $750 million, to speed development of therapies.
Gerald Levey, dean of the UCLA School of Medicine, did not agree with Childrens' appeal. "I don't think we can run a board this way. If we do, it would be chaos." He was responding to a request by Lubin for a 10 minute presentation Thursday of Childrens' case. Levey warned that allowing the presentation would lead to 50 other rejected applicants coming to the board.
Director Joan Samuelson said that even 100 persons would be okay with her. She provoked laughter when she declared that would show more interest than at any other board meeting.
CIRM's new president, Alan Trounson, who was attending his first board meeting, expressed concern about whether allowing Lubin to make a 10 minute presentation on Thursday would be fair to the five other rejected applicants. He suggested that they might need to be notified and allowed to make a similar pitch, perhaps by phone.
Ted Love, another director, said, "We can't fund everything. He said that if Childrens' research is "really good," they will find funding elsewhere. Both Klein and Trounson indicated that Childrens research might find favor in another round of grants.
However, the board rejected, on a 3-10 vote with one abstention, Samuelson's motion to permit a 10 minute presentation. Lubin was allowed to make his appeal during the comment period alloted to the general public. Speakers are supposed to be limited to three minute presentations, but enforcement of is sometimes lax.
While Childrens was frustrated in its bid on Wednesday, other applicants are going to be disappointed this spring in the second round of the competition. CIRM staff said that if all 12 were funded at the midrange of the amounts alloted in each category of competition, $320 million would be required. The board has already said it will only spend $262 million.
Following the meeting, CIRM released the following statements:
Klein said,
The 12 institutions that survived Wednesday night's judgments are Buck Institute, the San Diego Consortium for Regenerative Medicine, Stanford, UC campuses in Berkeley, Davis, Irvine, San Francisco, Merced, Santa Barbara, Los Angeles and Santa Cruz and the University of Southern California.
The agency's press release is not likely to be available on its web site until sometime Thursday morning.
Childrens' request failed on a 5-10 vote despite an impassioned plea by CIRM director Jeff Sheehy.
"This is a no-brainer," said Sheehy. "This is a very promising area of research."
Other board members argued that Childrens' public appeal, the first ever directed to the Oversight Committee, violated the agency's processes, was unfair to other rejected applicants and needed consideration in some future round of grants.
Sheehy didn't buy the arguments. "Let us study it," he said caustically. "Let another person die."
The board's action came during a session that resulted in the relatively routine approval of 12 institutions to advance to the next round of the $262 million stem cell lab grant program, which will judge the actual building plans. Today's review focused on the research proposed for the facilities. All 12 approved Wednesday night were identified earlier as being recommended for funding following a closed-door session involving scientific reviewers who are not required to disclose publicly their financial interests.
Childrens Hospital received a "do-not-fund" decision by the reviewers. Bertram Lubin, president of the hospital, appeared before the Oversight Committee Wednesday night after sending three letters to the members of the panel. (Two of have appeared on this web site.)
He told directors that the grant reviewers did not appreciate the type of research proposed by Childrens. Sheehy, who participates in the closed-door review sessions, concurred.
Lubin also told directors, "When you report on what CIRM has done, this (funding his program)would be a major accomplishment." He said it could result in actual treatments in a year or two, which is a far cry from almost all of the research financed by CIRM.
Some directors, including Chairman Robert Klein, have pushed aggressively for faster work on therapies. Ironically, earlier in the day, a CIRM Task Force explored details of how it could launch a massive loan program, totaling as much as $750 million, to speed development of therapies.
Gerald Levey, dean of the UCLA School of Medicine, did not agree with Childrens' appeal. "I don't think we can run a board this way. If we do, it would be chaos." He was responding to a request by Lubin for a 10 minute presentation Thursday of Childrens' case. Levey warned that allowing the presentation would lead to 50 other rejected applicants coming to the board.
Director Joan Samuelson said that even 100 persons would be okay with her. She provoked laughter when she declared that would show more interest than at any other board meeting.
CIRM's new president, Alan Trounson, who was attending his first board meeting, expressed concern about whether allowing Lubin to make a 10 minute presentation on Thursday would be fair to the five other rejected applicants. He suggested that they might need to be notified and allowed to make a similar pitch, perhaps by phone.
Ted Love, another director, said, "We can't fund everything. He said that if Childrens' research is "really good," they will find funding elsewhere. Both Klein and Trounson indicated that Childrens research might find favor in another round of grants.
However, the board rejected, on a 3-10 vote with one abstention, Samuelson's motion to permit a 10 minute presentation. Lubin was allowed to make his appeal during the comment period alloted to the general public. Speakers are supposed to be limited to three minute presentations, but enforcement of is sometimes lax.
While Childrens was frustrated in its bid on Wednesday, other applicants are going to be disappointed this spring in the second round of the competition. CIRM staff said that if all 12 were funded at the midrange of the amounts alloted in each category of competition, $320 million would be required. The board has already said it will only spend $262 million.
Following the meeting, CIRM released the following statements:
Klein said,
"Investment in facilities to extend California’s state-of-the art research capacity is a critical part of CIRM’s Scientific Strategic Plan to sustain and build California’s global leadership in stem cell research. Through the Major Facilities Grants we are leveraging the impact of Proposition 71 funds with contributions from donors and non-profit research institutions. Our goal is to exceed $550,000,000 in research facility investments that will advance critical stem cell research. Achieving this goal would mean that every one dollar of State funding from Proposition 71 would deliver two dollars in research facility investment."Trounson said,
"The facility investments CIRM will make through these grants will continue to propel California as a leader in stem cell research. Providing the necessary infrastructure for research is a critical step in laying the foundation for eventual therapies and cures."The Oversight Committee meeting will continue today with an appeal by the Human BioMolecular Research Institute San Diego of reviewer rejection of its grant application.
The 12 institutions that survived Wednesday night's judgments are Buck Institute, the San Diego Consortium for Regenerative Medicine, Stanford, UC campuses in Berkeley, Davis, Irvine, San Francisco, Merced, Santa Barbara, Los Angeles and Santa Cruz and the University of Southern California.
The agency's press release is not likely to be available on its web site until sometime Thursday morning.
Tuesday, January 15, 2008
CHORI Lab Grant Bid Gets Help
The bid by Childrens Hospital Oakland Research Institute today received added support in its effort to reverse a negative decision on its application for a CIRM grant to build a stem cell facility that could help sickle cell anemia research.
The support came in the form of a letter from the Greenlining Institute of Berkeley, which has lobbied CIRM on minority issues in the past.
Here is the text of the missive to the Oversight Committee:
The support came in the form of a letter from the Greenlining Institute of Berkeley, which has lobbied CIRM on minority issues in the past.
Here is the text of the missive to the Oversight Committee:
January 15, 2008
Dear Members of the ICOC,
The Greenlining Institute is a multi-ethnic public policy and advocacy organization that is dedicated to improving health outcomes for low-income communities of color in California. Our coalition includes civil rights, health, business, and faith-based organizations such as the First AME Church, the California Black Chamber of Commerce, the California Hispanic Chamber of Commerce, the Asian Business Association, the Mexican American Political Association, the Southeast Asian Center, and the La Maestra Community Health Center.
We are disappointed that the application submitted by Children’s Hospital Oakland Research Institute (CHORI) to CIRM for a Facilities Grant was not approved by the CIRM Working Group Committee. As advocates for minority health and the elimination of health disparities, we do not believe that the working group appreciated that a proportion of CIRM funds provided by the vote of citizens of this State should be used to support programs that address the needs of underserved communities. We believe that the work CHORI proposes is likely to benefit a disproportionate number of citizens as a result of the ethnic diversity in this State. We understand that you have the authority to make the final decision on CHORI’s application and encourage you to approve it.
CHORI’s application included a plan to construct a new GMP cellular facility which would perform clinical and translational research using adult stem cells obtained from cord blood and from placenta. CHORI is recognized as a national resource for cord blood and placental cell studies, and in addition to basic research studies, it serves as a core resource for other investigators. CHORI staff have reported that 92% of children with sickle cell anemia have been cured following an HLA matched sibling cord blood stem cell transplantation. This information has previously been presented to ICOC and was enthusiastically supported. As less than 25% of patients with sickle cell anemia have a suitable donor for a stem cell transplant, the research proposed at CHORI has the potential to expand current transplantation practice in our State and throughout the nation. Not only will this impact health and quality of life, it will have an enormous beneficial economic effect. It appears that the working group did not appreciate the need for CHORI’s GMP facility to successfully carry out clinical trials that would benefit our State.
In light of the state’s swelling budget deficit, we cannot afford to ignore any portion of the state’s population—especially its most underserved. To better ensure that California’s diverse communities be included in the implementation of Proposition 71, we urge you to consider applicants for stem cell research grants who have demonstrated a historical commitment to serve the state’s diverse public. The Children’s Hospital of Oakland Research Institute is one such institution. Thus, we urge you to approve the application submitted by the Children’s Hospital Oakland Research Institute at your meeting on
January 16 and 17, 2008.
Respectfully,
Héctor Javier Preciado
Health Policy Director
Joe Araya Tayag
Program Manager, Health
Rejected Grant Applicant Steps Up its Bid for Approval
The Childrens Hospital Oakland Research Institute has beefed up its effort to overturn the initial rejection of its bid for a multimillion dollar stem cell lab construction grant with a second letter that amounts to a "peer review" of the "peer review" of its plan.
The effort by the institute is believed to be the first such appeal by a rejected applicant, although CIRM refuses to confirm that. It also refused to release the letter, saying such an action would be inappropriate. Earlier today, we filed a formal request for the letter under California's public records law. Later, the letter came to us from a source that asked not to be identified (it was not the Oakland institute).
Both letters were sent Monday to all members of the CIRM Oversight Committee, which meets Wednesday to consider the scientific segment of the lab grant proposals.
Grants not approved on Wednesday and Thursday will be knocked out of the running for the second stage of the grant review, which will focus on the building plan. The current stage focuses on the science that is being proposed.
Last fall the CIRM Grants Working Group conducted a "peer review" of all 17 applications. The review was performed behind closed doors with scientists who did not disclose publicly their financial interests -- standard policy for CIRM. Twelve applicants were recommended for funding. Five were rejected, including Childrens Hospital, the University of California at Riverside and Cedars Sinai.
CIRM has identified the 12, in "violation" of its own policy of confidentiality on the names of applicants. UC Riverside and Cedars Sinai confirmed to the California Stem Cell Report that they were rejected. But they have not responded to questions about whether they are appealing the decisions.
The text of the Childrens letter is below.
The effort by the institute is believed to be the first such appeal by a rejected applicant, although CIRM refuses to confirm that. It also refused to release the letter, saying such an action would be inappropriate. Earlier today, we filed a formal request for the letter under California's public records law. Later, the letter came to us from a source that asked not to be identified (it was not the Oakland institute).
Both letters were sent Monday to all members of the CIRM Oversight Committee, which meets Wednesday to consider the scientific segment of the lab grant proposals.
Grants not approved on Wednesday and Thursday will be knocked out of the running for the second stage of the grant review, which will focus on the building plan. The current stage focuses on the science that is being proposed.
Last fall the CIRM Grants Working Group conducted a "peer review" of all 17 applications. The review was performed behind closed doors with scientists who did not disclose publicly their financial interests -- standard policy for CIRM. Twelve applicants were recommended for funding. Five were rejected, including Childrens Hospital, the University of California at Riverside and Cedars Sinai.
CIRM has identified the 12, in "violation" of its own policy of confidentiality on the names of applicants. UC Riverside and Cedars Sinai confirmed to the California Stem Cell Report that they were rejected. But they have not responded to questions about whether they are appealing the decisions.
The text of the Childrens letter is below.
Childrens Hospital's Second Letter
Here is the text of the latest appeal letter from Childrens Hospital Oakland Research Institute. The boldface indicates the criticism of the Oakland proposal. CIRM refuses to release the actual report by CIRM reviewers, who performed their review behind closed doors.
January 14, 2008
Dear Members of the ICOC:
The critique of the Grants Working Group indicates clearly that the intent and aims of our proposal were misunderstood. We think that the reviewers might have overlooked that the goal of Proposition 71 was to cure disease by the innovative use of stem cells, not simply to explore the possibility of curing disease with ES-derived cells. The reviewers imply that we have requested a facility that will be used simply to process and store blood stem cells for conventional transplant procedures. This is not the case: we have proposed to explore the use of a new type of blood stem cell, discovered here, that has the potential to transform blood stem cell transplantation and make it available to far larger numbers of patients.
Achievement of this goal will however require rigorous research. The research must be very strongly clinically oriented if our discovery is to be translated into something that can be used to cure disease. We should also note that the cost of our facility is relatively modest, particularly in light of the probable direct and near-term benefit to the citizens of California.
We would like to respond to the principal criticisms of the application:
1. No collaboration with established stem cell lab/groups to help characterize novel cellular populations; absence of hESC studies. The focus of our research and the purpose of the application is to benefit California citizens affected by hemoglobin disorders, which afflict a disproportionate number of citizens as a result of the ethnic diversity in this State, through innovative applications of stem cell therapy. We are committed to accomplishing these aims in the near-term, and more important, to apply our research in the clinic by using the safest and most reliable methods. Currently, there is a great deal of uncertainty surrounding the clinical applicability of hESC, and their clinical safety has not been sufficiently well characterized to support clinical trials with these cells in the near-term. Thus, we have elected to apply other methods of regenerative cellular therapy, in part because the safety, efficacy, and availability of other sources of cells are better developed, and we have considerable experience with conducting these trials.
2. Institutional collaborations were not carefully described, and corporate partnerships to develop the products were not included in the application. While we have established institutional collaborations with UCSF, UC Berkeley, and UC Davis, and share CIRM funding with UC Berkeley to conduct stem cell biology training for our clinical fellows, none of these institutions has developed expertise in characterizing placental stem cell populations, which are the focus of this application. Thus, we are uncertain about how collaboration on this subject outside our group would be practical or useful. It should be evident that we have extensive established collaborations relating to hematopoietic stem cell transplantation and cord blood collection, processing, and storage.
3. Poor interdisciplinary collaboration of pre-clinical and clinical research projects, with a lack of track record by some PIs. This criticism ignores information that was clearly presented in the proposal: in fact we have an extremely well integrated program of research. Our proposals were prepared as a result of ongoing interactions by laboratory-and clinical-based investigative teams to 1) collect stem cell populations from placenta to investigate a new source of stem cells that might augment and expand the applicability of cord blood transplantation; 2) overcome barriers to histocompatibility by using photochemical treatment of donor lymphocytes before hematopoietic cell transplantation with mismatched donors. These projects were initiated, and are undergoing further development, as collaborations between basic and clinical investigators devoted to discovering medical therapies for hemoglobin disorders. The goal of these interactions is to translate these ideas into readily available applications of cellular therapy, something we believe is strengthened by our strong track record of conducting successful stem cell transplantation clinical trials for hemoglobin disorders.
4. Clinical research/cores proposed were not innovative and were perceived as currently supported by HRSA/Bill Young stem cell bill. Pre-clinical proposals were nnovative but not sufficiently well developed to proceed to a clinical trial in the near future; perhaps more appropriate in an Element Y application. We propose to construct a facility devoted to novel applications of stem cell transplantation for
hemoglobin disorders, not simply to construct a duplicate facility for housing cord blood collections from California families. This research would involve the collection of placentas for cryopreservation, analysis and mobilization of stem cell populations from placenta, and then processing these cells for use in a clinical transplantation trial that will be initiated in the next 1-2 years. We are currently preparing an IND with the FDA for this purpose. It is important to point out that the placenta-derived hematopoietic stem cells are the first new type of stem cell used in this field since the 1970’s, when cord blood was first used. Federal regulations governing this research have changed dramatically since that time, and are now far more complex. This project is thus truly innovative, and it will serve as a model for other attempts to use stem cells clinically. If proof of principle were provided by this initial clinical trial, the technology then would be applied to existing transplantation efforts, with the goal of expanding and improving outcomes after cord blood transplantation, particularly after unrelated donor transplantation. The proposed research is not supported by HRSA or the C. W. Young bill. The primary purpose of this bill is to establish cord blood banks and develop an inventory of 150,000 units for public use. It is not to perform clinical/translational research like that we have proposed. While a small amount of funds are allocated to support sibling banking ($250,000) by the funded cord blood banks, there are none in California who elected to participate in this sibling effort. It is critical that we have a facility for developing, characterizing, and distributing these cells for clinical transplantation trials. Thus, a GMP/GLP cell processing laboratory and a HLA laboratory are key components in support of the proposed clinical and pre-clinical investigations. This work cannot move forward without a facility.
5. A plan to utilize national networks in order to conduct a clinical trial was not detailed. It should be very clear from Dr. Walters’ track record that he is able to utilize, indeed currently is utilizing, such national networks in a highly productive fashion. The proposed pre-clinical investigations will be transitioned to phase I clinical trials in the very near term, responsive to the Element Z category we employed for this application. By providing proof of principle, this research has the potential to expand current clinical transplantation practice that will utilize HLA – mismatched and unrelated stem cell donors for hemoglobin disorders, a practice that is not routinely available. These will be conducted using multi-center networks that we can access for completing these clinical trials and which were detailed in the application. These include the Center for International Blood and Transplantation Research (IBMTR), the Sickle Cell Disease Clinical Research Network (SCD-CRN), and the Blood and Marrow Transplantation Clinical Trials Network. Our investigative team has leadership positions in these organizations and a successful track record of carrying out similar translational clinical trials in human hematopoietic cell transplantation.
We appreciate the opportunity to present our responses to critiques of our application and hope that the ICOC might look favorably on this and future applications to CIRM that we submit for consideration.
Respectfully,
Bertram H. Lubin, MD
President, Director of Medical Research
5700 Martin Luther King Jr. Way
Oakland, CA 94609
Mark Walters, MD
Director, Blood and Marrow Transplant Program
Children's Hospital & Research Center, Oakland
747 -52nd Street
Oakland, CA 94609
Friday, January 11, 2008
FTCR: Rejected Lab Grant Applicants Should Appeal in Public
A CIRM watchdog organization today urged five institutions "rejected" for multimillion dollar state lab construction grants to appear publicly next week and make their case for funding from the California stem cell agency.
John M. Simpson, stem cell project director of the Foundation for Taxpayer and Consumers Rights, said the review process for the $263 million lab grant program "has been flawed and smacks of favoritism that can only be cured by transparency." He said,
"CIRM management decided to reveal (last month) the 12 institutions that will be recommended for an invitation to seek funding so that they could use the information in year-end fundraising efforts. How is that fair to the five who were not anointed in secret by the closed scientific brotherhood?"
The California stem cell agency has declined to say whether any other lab grant applicants – besides Childrens Hospital Oakland Research Institute – are attempting to overturn negative decisions on their grant applications.
Ellen Rose, a spokeswoman for the agency, said,
In response to queries from the California Stem Cell Report last month, two other institutions disclosed that their applications have been rejected. They are the University of California at Riverside and Cedars-Sinai in Los Angeles. However, they have not responded to queries on Thursday about whether they are asking Oversight Committee to reconsider the working group action.
The lab grant program is the first in which the names of applicants have been disclosed by CIRM, which previously said the names of all applicants were confidential even when the applicants themselves disclosed their own identity. The decision to assist the applicants with fundraising is important because CIRM will look more favorably during the two-step approval process on applicants with large matching funds.
The Oversight Committee is scheduled to take up the grants next Wednesday during the scientific portion of the approval process. Only those approved next week will move on to the next step.
John M. Simpson, stem cell project director of the Foundation for Taxpayer and Consumers Rights, said the review process for the $263 million lab grant program "has been flawed and smacks of favoritism that can only be cured by transparency." He said,
"CIRM management decided to reveal (last month) the 12 institutions that will be recommended for an invitation to seek funding so that they could use the information in year-end fundraising efforts. How is that fair to the five who were not anointed in secret by the closed scientific brotherhood?"
The California stem cell agency has declined to say whether any other lab grant applicants – besides Childrens Hospital Oakland Research Institute – are attempting to overturn negative decisions on their grant applications.
Ellen Rose, a spokeswoman for the agency, said,
"Appeals are allowable only if there is demonstrable evidence of a financial or scientific conflict of interest. Differences of scientific opinion among PIs and reviewers are not grounds for appeal. In the past, applicants who have raised questions about their grant applications or sought clarification, which is common in any granting exercise, have been informed of this policy. Thus far we have had no formal appeals to our grant-making process."Simpson said CIRM's statement was "Orwellian double-speak." He said,
"I strongly urge representatives of all five rejected institutions to show up at next week's ICOC meeting and make their case in public directly to the board. It is, they claim, the decision making authority. What's happened so far were merely "recommendations.'"By law, the Oversight Committee is the final authority on grant approval. It can accept or reject – for virtually any reason -- decisions by the working groups. That is one reason CIRM says it is not necessary for grant reviewers to publicly disclose their financial interests.
In response to queries from the California Stem Cell Report last month, two other institutions disclosed that their applications have been rejected. They are the University of California at Riverside and Cedars-Sinai in Los Angeles. However, they have not responded to queries on Thursday about whether they are asking Oversight Committee to reconsider the working group action.
The lab grant program is the first in which the names of applicants have been disclosed by CIRM, which previously said the names of all applicants were confidential even when the applicants themselves disclosed their own identity. The decision to assist the applicants with fundraising is important because CIRM will look more favorably during the two-step approval process on applicants with large matching funds.
The Oversight Committee is scheduled to take up the grants next Wednesday during the scientific portion of the approval process. Only those approved next week will move on to the next step.
Wednesday, January 09, 2008
FTCR on Childrens Hospital Appeal: Fairness v. Secrecy
John M. Simpson, stem cell project director of the Foundation for Tazpayer and Consumers Rights, offered the following comment on the item below dealing with Childrens Hospital Oakland appeal of what amounts to a grant denial.
"CIRM management's now inconsistent penchant for secrecy coupled with news of the Children's Hospital letter of appeal once again demonstrates the importance of complete transparency.
"When institutions ask for public money they should be publicly identified. When they are rejected -- even if it's by members of a closed scientific brotherhood -- they should be identified and the reasons for the rejection should be spelled out.
"In this case CIRM management touted the 'successful' applicants and remained mum about what may, in fact, be excellent programs.
"Anything less than full disclosure leaves CIRM management justifiably open to charges of favoritism. In the long run that inevitably undercuts public faith in an agency whose dedicated staff in fact is attempting to serve the public interest by fostering important scientific research."
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