Friday, August 30, 2013

Tracking the Fruits of California Stem Cell Agency Research

The California stem cell agency yesterday shed some interesting light on the awards in its $41 million round this week and their pathway to actually producing a product that can be used to treat persons who are suffering from diseases.

It is a difficult and long journey to generate usable therapies, a process poorly understood by the public, which was promised in 2004 that the stem cell agency would produce cures for ailments afflicting half the population of the state.

Writing on the agency’s blog, Amy Adams, CIRM communications manager, dealt with the issue indirectly. She said,
“Many scientists who receive our early translation awards first got their idea for a therapy while carrying out research with one of our other awards. In fact, eight of the scientists in this round of funding had previous CIRM funding for an earlier stage of research. If a scientist's early translation award provides good results, the scientists are then able to apply for one of our disease team awards, which fund the effort of compiling data to convince the Food and Drug Administration to allow them to test it in people.  Other organizations fund only early discovery research or only preclinical research. Under those conditions, researchers continually pause their projects to look for new sources of funding as the project moves through the phases toward clinical trial.
One of the virtues of the California stem cell agency is its promise of a continued stream of funding. Former Chairman Robert Klein used to tout that particular aspect of the agency, particularly in light of limited federal resources.

Adams’ comments implicitly raise important questions concerning CIRM’s entire portfolio. How many CIRM grants have led to additional funding from CIRM? How many are basically one-off shots that have not led to research that has advanced the development of stem cell therapies, either via CIRM or other funding. What is the therapeutic and scientific significance of the research that is linked by more than one CIRM award?  What previously funded CIRM research could be fruitfully funded again to advance the science and not necessarily through the traditional grant rounds, which sometimes have awkward timing?

Unmentioned in Adams’ item is an application from a UC Irvine researcher that came up at Wednesday’s meeting of the governing board of the stem cell agency. The woman, whose name was not clearly audible on the Internet audiocast, publicly appealed rejection of her application by reviewers. She noted that it was an extension of work that was previously funded by the agency. She also noted that the score on her review was all but identical to work that was funded. The board, however, turned her appeal aside, which had already been rejected behind closed doors by CIRM staff.

Hers is not the only such case in CIRM history. But they are virtually impossible to track systematically because of the structure of the CIRM grant-making progress. It is also not clear whether the agency itself is tracking its research awards to determine if they result in continuing, fruitful research in a specific area. Nonetheless, the matter deserves some public attention. 

Wednesday, August 28, 2013

UCLA Takes Four of 13 Awards Today; One Business Wins

The California stem cell agency has made it official, sending out its press release on the $41 million in grants approved today for institutions throughout the state. 

Most of the 13 awards, as usual, went to organizations represented on the governing board of the agency. Individual board members, however, are barred from voting on specific grants to their organizations. 

UCLA topped the list with four grants. No other institution received more than one, including only one business, Numerate, Inc., of San Bruno, via John Griffin, the firm's chief scientific officer. The lack of awards to businesses has long been a sore subject in the biotech community.  

The only news story so far was written by Bradley Fikes of the San Diego U-T, which circulates in an area that is a hotbed of biotech research. Institutions there snagged $12.6 million in four grants. Fikes also identified one of the five researchers who lost their appeals on negative grant review decisions. He is Evan Snyder, leader of stem cell research at Sanford-Burnham Medical Research Institute in La Jolla, who had a $5 million request before the agency.

CIRM Board Meeting Adjourns

Today's meeting of the directors of the California stem cell agency concluded at 4:11 p.m. PDT. We do not anticipate posting additional news items today.

Stem Cell Agency Seeks Stronger Ties with Possible Industry Funding Partners

The California stem cell agency today triggered a new program aimed at recruiting major biotech and venture capital firms to assist in providing tens of millions of dollars for research by California enterprises.

The effort, part of an $80 million business-friendly initiative, was approved by the agency's governing board on a voice vote.

Participating companies will have a special relationship with the state agency, according to a staff document. The "industry collaborators" will have early input into concept funding proposals prior to their presentation to the agency's governing board. The companies will also be able to attend agency workshops and meetings involving hundreds of grant recipients. 

Other aspects of the proposal call for special event-hosting arrangements aimed at creating more collaborations along with posting of information from the selected collaborators on the CIRM website.

California Stem Directors Still in Closed Session

Directors of the California stem cell agency today are still huddled behind closed doors, discussing an evaluation of CIRM President Alan Trounson. It is not clear when the public meeting will resume. Normally, little is publicly disclosed about such private personnel sessions, which are permitted under state law.

UCLA Snags $3.6 Million from California Stem Cell Agency

UCLA scored today with at least two grants, totaling $3.6 million, from the California stem cell agency. 

Seeking the cash were Donald Kohn,  application 6823, and Gerald Lipshutz, application 6831. Both of the  grants are for $1.8 million each. 


Their applications were initially in the agency's tier two category, which means that CIRM's reviewers did not approve them outright for funding.  CIRM staff, however, did under a new procedure, and the agency's governing ratified the recommendation. 

Lipshutz also appeared before the board along with several patient advocates who made emotional appeals for funding. Lipshutz's research deals with urea cycle disorders, which occur in one out of 8,200 births. Current treatment is arduous and can involve liver transplants.  

Kohn's research deals with sickle cell disease, which afflicts primarily African-Americans. His efforts are aimed at correcting the sickle gene defect in the blood stem cells before transplanting them back into the patient.

$41 Million in California Stem Cell Grants Virtually Approved

Directors of the California stem cell agency today all but approved about $41 million in early translational grants, rejecting all appeals by applicants and accepting staff recommendations on marginal grants.

The roll call vote was held open this morning to record a vote by one board member who was not present at the time. It is virtually certain that the member will vote in favor of affirmative action on the applications in question.

One member of the board, Joan Samuelson, abstained from voting on any of the applications. She said she did not think the board had adequate information on its total grant portfolio, particularly in view of the declining amount of money available.

The agency has about $600 million in uncommitted funds and is scheduled to run out of cash for new grants in 2017.

The research acted on today is aimed at “proof of concept for development of a therapy candidate and/or studies to select a development candidate. The approved grants can be found on this CIRM website page and are listed in tier one and tier two.  Identities of the applicants are withheld by CIRM to avoid embarrassing rejected candidates and to avoid disclosing the names of applicants to board members before they vote. However, applicants often appear before the board, as they did today, and identify themselves.

Five applicants appealed negative decisions on their applications by grant reviewers. The agency declined to disclose the appeal letters or identify the applicants, information that was a public record under the previous appeal procedures. New processes were put in place this spring that moved the appeals behind closed doors and made them subject to staff instead of board review. Nonetheless, rejected researchers have a legal right to address the board on appeals or any other matters.

At the request of the California Stem Cell Report, the agency provided the numbers of the grants on which appeals were filed. They are: 06787, 06888, 06761, 06793 and 06830. Review summaries on the applications can be found here. 

We have asked the agency to provide its legal and policy justification for now withholding information that was once a public record.


Stem Cell Board Moves into Closed Door Lunch Session

Today's meeting of the California stem cell agency governing board is now in recess for a closed-door lunch session involving the evaluation of CIRM President Alan Trounson. It is not clear when the open session will resume, but probably it will be at least 90 minutes.

UCLA Application for $1.8 Million Moves Ahead at Stem Cell Board Meeting

Directors of the California stem cell agency this morning moved forward on a $1.8 million application from UCLA that the agency's reviewers declined to approve outright.

The application (No. 6831) was moved into a category that will be approved routinely later today by the board. CIRM staff recommended that the application be approved.

Advocates speaking on behalf of the application identified UCLA as the institution involved. A researcher also spoke, but his name was not clearly audible on the Internet audiocast.

California Stem Cell Board Moves Positively on 'Wobbler' Grant Application

Directors of the California stem cell agency this morning ratified a staff recommendation for funding of a $1.8 million application that was a "wobbler" when it was examined behind closed doors by agency reviewers.

The CIRM staff had recommended funding of the application (No. 6823) with the condition that the agency staff be satisfied with the support to be provided by a collaborator. Reviewers had declined to approve the application outright.

The agency has not disclosed the identity of the applicant.

Discussion Begins in $70 Million Grant Round

Directors of the California stem cell agency have begun discussion of applications in its $70 million early translational round. Above is the Power Point presentation to the board of some of the applications including the range on the scientific scores in the round.

Stem Cell Agency Pays Tribute to the Late Duane Roth

The governing board of the California stem cell agency today paid tribute to the late Duane Roth, co- vice chairman of the agency, who died recently as the result of a bicycle accident.

With members of Roth's family present, CIRM Chairman J.T. Thomas characterized Roth, 63, as a "voice of reason" on the 29-member board. The video included testimonials from both staff and board members.

He was described as a "kind person" who could find "common ground" on difficult issues. Roth was deeply involved in San Diego affairs that went well beyond the stem cell agency. More than 1,000 persons attended memorial services for Roth earlier this month in San Diego.

CIRM President Alan Trounson said following the video that he will "miss (Roth) terribly" and expressed  "hope that his memory will lighten and brighten the day for all of us."

Jeanne Loring, a stem cell researcher at Scripps, said Roth "inspired us to do more than we thought we could do." She said he was an unusual kind of businessman who respected science.  "I wish I could thank him one more time," she said.

California Stem Cell Agency Board Opens Meeting

The California stem cell agency today started its meeting this morning at 9:11 a.m. with the announcement that the board is expecting the arrival of a "very important guest." The board began its business by dealing with routine business. The board may have difficulty with maintaining a quorum later in the day, it was announced.

Technical Problems with Stem Cell Audiocast

This morning's meeting of the governing board of the California stem cell agency was scheduled to begin five minutes ago, but technical problems are reported with its Internet audiocast. We will let you know when the audiocast begins.

Skin in California’s Stem Cell Game

The California stem cell agency’s road map to its financial future makes a big, $200 million assumption.

The amount would be the agency’s skin in the game for a new, public-private partnership to continue with the agency’s work after 2017, when its cash basically runs out.

The $200 million figure is contained in the assumptions for development of the proposed partnership, which is now in the very early stages of being crafted by a Marin County consultant, James Gollub. He was told that whatever he comes up with can assume a onetime, $50 million to $200 million public contribution.

The sixty-four-dollar question – to use a term from the 1940s -- is how to raise that sort of cash. Consider two unappetizing possibilities. The 29 members of the agency’s governing board could go to Sacramento and ask lawmakers and the governor to give them the money, a prospect that most of them would not relish. Such a move would open the door to tinkering or more with the agency’s structure and operations.  Or the board could seek more bond financing via a statewide election, requiring an electoral campaign that would cost many millions to mount. In both cases, there is no guarantee that funds would be forthcoming. Money is still tight in California government, and voters may not fancy spending more on stem cell research, especially if the agency has not delivered on the promises of the 2004 ballot campaign that created the $3 billion program.

A third possibility, however, exists, but it also could be difficult considering pressures to spend all that the agency has. The board of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known, has about $600 million in uncommitted cash. It could take $200 million off the table and reserve it as seed money for whatever future plans would involve. Or the board could simply roll back commitments it has made for lower priority grant rounds – ones that have not yet been initiated. Some are in concept stages, and others have not yet been posted as RFAs.

Scrimping on existing efforts is not going to suit the condition of all board members. The question of priorities on spending came up last month in connection with the agency’s generous, $69 million researcher recruitment effort that benefits many institutions represented on the agency’s board. Jeff Sheehy, who is a patient advocate member of the board but also a communications manager at UC San Francisco, and others bridled at adding more money to the recruitment program. Sheehy cited scarcity of funds and said it was a “distraction” from more important efforts. His view, however, did not prevail.

Today the board is scheduled to act on a grant round that is budgeted for $70 million. However, grant reviewers have approved grants totaling only $37 million. Board members, if they wish, could indicate that the surplus $33 million be designated as a down payment on the future of the agency – an organization in which they take great pride.

Tuesday, August 27, 2013

Live Coverage for Tomorrow's California Stem Cell Meeting

The California Stem Cell Report will provide live coverage of tomorrow’s meeting of the governing board of the $3 billion California stem cell agency. Stories will be filed as warranted during the daylong session, which begins at 9 a.m. PDT in La Jolla, Ca. Coverage will be provided via the Internet audiocast.

Those wishing to listen to the event live on the Internet can find instructions on the meeting agenda. Also available is a Webex transmission, which provides viewing access to the many documents that are used during the meeting but have not been made available yet to the public.

In addition to the La Jolla location, those wishing to participate in the meeting can do so at teleconference locations in Menlo Park and Duarte, both in California. Directions for the audiocast and Webex broadcast can be found on the meeting agenda.

Future Financing Plan for California Stem Cell Agency Coming Up in December

The California stem cell agency today released the $150,000 contract and proposal from James Gollub Associates to create a “strategic road map” for the $3 billion state program, which is scheduled to run out of cash for new grants sometime in 2017.

The goal of the road map, according to the contract, is to develop a “preferred model for a public-private sponsored entity to fund the most desirable translational projects in the CIRM portfolio.” That would appear to rule out future funding for basic research and training, which the agency has supported well during its nine-year history.  It would also be an acknowledgement that the agency cannot count on $300 million a year for grants as it has in the past.

Under the terms of Prop. 71, which created the agency in 2004, the effort is currently financed by state bonds, money borrowed by the state of California that flows directly to the agency without oversight by the governor or legislature. Authority to issue the bonds expires in 2017.

The contract calls for an initial report from the Gollub by Nov. 30 with the agency to decide by March 1, 2014, on whether it wants an operations and business plan from the Tiburon, Ca., firm.  Presumably the agency’s governing board would hear recommendations from Gollub at its December meeting.

The contract, signed July 16, specifies that Gollub will conduct at least 20 interviews with stakeholders to evaluate four possible models that it will develop. The stakeholders will include “investment, academic and government groups” and possibly others to be determined later.

The proposal presented by Gollub contains more information on the firm and the persons who will be working on the project. In addition to Gollub, they include Steve Marshall, Amy Rassen and Annika Barnes, all Gollub employees. The contract and proposal can be found below.


Stem Cell Grant Applicants Identities and Secrecy

The California stem cell agency today took issue with a statement in an item yesterday that said the agency withheld the names of grant applicants prior to action on their applications by the agency’s governing board to avoid embarrassing the researchers.

The agency said that the reason was to avoid identifying applicants to members of the governing board prior to its vote on the applications.

The agency’s official practice of withholding the identities of institutions and individuals seeking public funds has a long history.  The agency itself has breached the policy on more than one occasion.  While it also does not officially release the names of applicants denied approval, that practice is also breached when appeals are filed.

Interested readers can find a short discussion of the policy and links to additional material at the end of this item. 

Correction

The "New Procedures" item on Aug. 26, 2013, incorrectly stated, based on information provided by the stem cell agency, that six applicants in this week’s early translational round had filed appeals to overturn negative decisions by grant reviewers.  The agency today said the correct number is five. 

Monday, August 26, 2013

New Procedures at CIRM: California Stem Cell Agency Staff Nixes Grant Application

For the first time in its nine-year history, the staff of the $3 billion California stem cell agency this week  formally and publicly weighed in on grant approval actions by its prestigious reviewers, recommending that one application be rejected and another approved with conditions.

The staff, led by CIRM President Alan Trounson and Patricia Olson, the agency’s executive director of scientific activities, made recommendations to the agency governing board on three applications that can be described as “wobblers.” In other words, the board could go either way on the proposals when it considers them at its meeting in La Jolla on Wednesday.

Trounson recommended that the governing board reject one of the wobblers  (No. 6666),  a $2.0 million proposal, even though it received a higher scientific score – 70 – than the other two applications. Trounson recommended approval of two $1.8 million projects (Nos. 6831 with a scientific score of 66 and 6832 with a scientific score of 69), with staff-imposed conditions on one.

 Trounson said the agency is or 
 "will be funding 2 similar approaches to address photoreceptor degenerative disorders so addi-tional investment in an earlier stage project is harder to justify.”
All three fall into a newly defined category, called tier 2, for ranking of applications. The CIRM web site said tier 2 proposals are now ones that possess “moderate scientific quality, or consensus on scientific merit cannot be reached and may be suitable for programmatic consideration by the ICOC(the governing board).”

A fourth application  (No. 6648) for $4.3 million that scored below all three at 64 was approved, however, by reviewers after they imposed a condition on the proposal.  CIRM staff did not publicly address that application. The application review summary said that the researcher – who was not identified – must “demonstrate, within 12 months, the ability to make the hESC–derived 3-D sheets. This is a go no/go milestone for the project.”

The agency’s standard practice is withhold the identities of applicants prior to board action because they might be embarrassed.

In the other instance where conditions are to be imposed, they appeared to deal with an in-kind contribution of “essential services, technology and expertise.”

The new process for evaluating marginal or wobbler applications was established last March in response to an Institute of Medicine study last year that made a host of recommendations for improvements at the stem cell agency.

The staff recommendations on applications came in a $70 million early translational round that is aimed at “proof of concept for development of a therapy candidate and/or studies to select a development candidate.

In all, including staff and reviewer actions, 13 applications were recommended for funding, although the board has almost never rejected reviewer decisions. The 11 grants initially approved by reviewers total $37 million. With the two more recommended by staff, the figure would be about $41 million. A total of 39 applications were considered for funding.

Five applicants filed appeals of reviewer rejections, a CIRM spokesman said today. The  California Stem Cell Report has asked for copies of those appeals and CIRM staff action on them. Appeals are also being conducted under a new staff-dominated procedure, although all applicants have the right under state law to appear before the board to address any subject.

Budgeted grant funds that are unused are available to the board for future grant rounds in any area they so desire.

(An earlier version of this item incorrectly said six applicants had filed appeals, based on information from the agency. The correct figure is five.)

(Editor's note: Kevin McCormick, CIRM's spokesman, later commented on the agency's practice of withholding the identities of applicants to avoid embarrassment to applicants who are not approved. He said,  "Actually they are withheld so that the board doesn't know the identities of the researchers or the institutions whose applications they are voting on." 
(We should note that official CIRM policy is to withhold all applicant names until board action, but it does not release any of the names of denied applicants even after board action. However, it has in the past released in advance of board action the names of applicants when it suits its purposes . Also, the names of many applicants can be discerned based on information provided in the review summaries of the applications. The identities of applicant institutions can also be determined based on which board members are allowed to participate in discussion of specific applications as well as being allowed to vote. For more on the practice of withholding names, see here, here, here and here. )

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