California Stem Cell Agency Backs Breast/Ovarian Cancer, Brain Injury Research and More with $29 Million; $71 Million Left

Saul Priceman of the City of Hope. Priceman received $9.3 million last month from CIRM for a clinical trial for breast cancer. City of Hope video.

The California stem cell agency last month handed out $29 million to finance efforts to develop treatments for traumatic brain injury, ovarian cancer and more, leaving it with about $71 million for new research awards before its cash runs out. 

The nearly 15-year-old agency, known formally as the California Institute for Regenerative Medicine (CIRM), is hoping that a yet-to-be written ballot initiative for the November 2020 ballot will give it a $5.5 billion infusion. The agency began its life in 2004 with $3 billion. 

Fresh figures from the agency show that it has about $43 million available for new awards, not including those involved in a sickle cell anemia effort with the National Institutes of Health.  CIRM's contribution to that program totals about $28 million. The agency is still accepting applications in that program. 

The amount of funds available overall to CIRM could rise as funds come back to the agency as the result of termination of unsuccessful research.

In last month's two-hour meeting, CIRM's board approved five grant applications, but not without more public discussion than has occurred in some past years when the agency was flush with cash. 

Directors talked about priorities, CIRM's portfolio and the vagaries of the scoring process, which is done behind closed doors by out-of-state researchers/reviewers who do not have to publicly disclose their professional or financial conflicts of interest. 

But the meeting also led to a reflection by CIRM board member Jeff Sheehy on the value that CIRM has brought to the field and California. Sheehy is a patient advocate of the 29-member panel. He has been on the board since its first meeting in December 2004 and leads the board's public discussion during ratification of funding decisions by reviewers.

Sheehy told his fellow board members that he had lost his mother to ovarian cancer and knew the "incredibly painful, difficult road" that she walked.  He said that CIRM is providing a new path to a better future for cancer patients and others with dreadful diseases and urged diligence in supporting renewed funding for the agency.  

In formal action, the board approved a $9.3 million investment in a clinical trial for a treatment of breast cancer, the second most common cancer in women. The trial is the 56th in which the agency is involved. The award went to Saul Priceman of the City of Hope. The review summary of his application (CLIN2-11574) can be found here. 

The CIRM panel also approved awards to the following researchers and institutions. The review summaries for all, including applications not approved, can be found here. 

Mark Tuszynski, $6.2 million, UC San Diego, spinal cord injury (no UCSD news release)
Evan Snyder, $4.9 million, Sanford Burnham, ischemic brain injury (no Sanford news release)
Brian Cummings, $4.8 million, UC Irvine, traumatic brain injury (UCI news release)
Mark Humayun, $3.7 million, USC, age-related macular degeneration (no USC news release)

The CIRM news release on the July meeting and awards can be found here. The transcript of the meeting can be found here. 

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Bones, Stem Cells and Bridging the Gap

California's $3 billion stem cell research effort chalked up a small score yesterday with the announcement that a $5.2 million investment is making progress towards development of a therapy to regenerate broken bones. 

Writing on the the state stem cell agency's blog, Karen Ring, social media manager for the agency, said,

"Scientists from Cedars-Sinai Medical Center have developed a new stem cell-based technology in animals that mends broken bones that can’t regenerate on their own. Their research was published today in the journal Science Translational Medicine and was funded in part by a CIRM Early Translational Award."

The award went to Dan Gazit and Hyun Bae at Cedars. Their year one and two progress reports involving the adult stem cell therapy can be found at the link in the above paragraph. 

Ring's  blog item also carried a nifty graphic on the work and a link to a video on the research. 

Ring wrote,

 "Over two million bone grafts are conducted every year to treat bone fractures caused by accidents, trauma, cancer and disease. In cases where the fractures are small, bone can repair itself and heal the injury. In other cases, the fractures are too wide and grafts are required to replace the missing bone.

"It sounds simple, but the bone grafting procedure is far from it and can cause serious problems including graft failure and infection. People that opt to use their own bone (usually from their pelvis) to repair a bone injury can experience intense pain, prolonged recovery time and are at risk for nerve injury and bone instability."

Quartet of Researchers Snagged in Budgeting, Parliamentary Web at $3 Billion California Stem Cell Agency

Highlights
Fiscal discipline at CIRM
The 10 percent solution
A quorum shortage pops up

Four California scientists who are ready to kick off highly rated projects to treat everything from Alzheimer's to rotting jaw bones became tangled last week in a financial and procedural briar patch involving the directors of the $3 billion California stem cell agency.

The basic problem, however, was simple. Money.

The agency had budgeted only $15 million for this latest round of awards last Thursday. But the four applications -- already approved by the agency's reviewers -- totalled $16.6 million. Typically, the agency's full board rubber stamps in public the decisions of its reviewers, who act behind closed doors without disclosing their economic or professional interests. The board has reversed approvals by reviewers on only four occasions out of hundreds of awards over the past 12 years, according to the agency.

Last week, the chairman of the agency, Jonathan Thomas, began the public discussion by declaring that the board should go through the applications one by one and vote on them. When the money ran out, that would finish action on funding for November.

Fiscal discipline was cited as the main reason for such a course.

Steve Juelsgaard 

Wait a minute, said Steve Juelsgaard, a member of the board of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known. He asked for the amount of
funding already being provided for the afflictions targeted by the proposals. If research in a particular area was already heavily supported, perhaps approving another award in that area was not necessary, Juelsgaard reasoned. However, the agency staff could not provide those figures at the time of the meeting.

A lengthy discussion followed involving several scenarios. One would have cut each award by 10 percent but approve all four.  But that could mean that the proposals would be altered from the versions that were approved by the reviewers. (However, the board is not legally required to accept what the reviewers decide.  Under the terms of the ballot initiative that created the agency, the board has the final say, which is part of the justification for not publicly disclosing the economic interests of reviewers.)

Another proposal would have simply increased the funding for the round. That could not be acted on because it required 10 days advance public notice.

The board ultimately approved a Juelsgaard motion to slice roughly 10 percent from each award with the condition that applicants come up with matching funds to bring the total to the level approved by reviewers.

Yadong Huang, Gladstone photo

One applicant, Yadong Huang from the Gladstone Institutes, said, however, that non-profit research organizations were already hard-pressed and could not necessarily come up additional cash. His $5.9 million application (TRAN1-09394) was top-ranked by reviewers and targeted Alzheimer's.

Jill Helms, Linked In photo

Another applicant, Jill Helms, chief scientific officer of Ankasa Regenerative Therapeutics, Inc., of La Jolla, spoke on behalf of the company's application (TRAN1-09270) to target osteonecrosis, an affliction that "causes jaw bones to rot and thigh bones to snap." She urged the board to give priority to applications that already had co-funding. Her $3.7 million application contained a 20 percent co-funding component.

Helms, who is also a Stanford University medical school professor, unsuccessfully asked the CIRM board in 2015 to overturn a negative recommendation by reviewers.

During the two-hour telephonic meeting, the board did approve conditionally two awards under the matching-fund requirement. They were for the Alzheimers proposal and one dealing with sickle cell disease (TRAN1-09292).  The identity of the chief scientist on the sickle cell proposal was not disclosed by the agency under its longstanding policy and tradition within the research field.

Jeff Sheehy, Science photo

The board failed to complete action on the two others because it  lost the quorum that is required to do business legally. That came after a motion by board member Jeff Sheehy to reject one of the four applications failed on a 3-8 vote. Sheehy said another related proposal was already being funded by the agency and that the time to translate the research into a therapy  "would be enormous." The $2.5 million application  (TRAN1-09288) up for consideration last week involved cartilage repair.

Thursday's meeting was being conducted telephonically. After Sheehy lost his motion, he did not respond to telephonic queries from the board. The meeting was nearing its scheduled end at noon. Other board members also failed to respond, and the meeting was adjourned minutes later.

Juelsgaard and some other members said it was important for board members to stick around for the full meetings. Juelsgaard said,

"For gosh sakes, this is something that you signed up to do."

Termination of CIRM board business because of quorum problems regularly occurred some years ago. (See here, here and here.) But since Thomas has been chairman the issue has rarely popped up.

Thomas indicated the board would try to schedule a special telephonic meeting to deal with the four applications. It also has a face-to-face meeting scheduled for Dec. 13 in Oakland. Both meetings legally require 10 days advance notice.

The review summaries on the applications are consolidated in this CIRM document along with their scores and more information.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Faster Action Approved in California on Stem Cell Therapy for Parkinson's

To cheers and applause, directors of the $3 billion California stem cell agency this morning moved to speed action on a much-lobbied effort to fund research on a therapy for Parkinson's disease.

Randy Mills, president of the agency, said the action would mean that a request for applications would be posted within the next seven days instead of sometime next spring.

He spoke from the Sanford Consortium in La Jolla during a teleconference meeting with 18 locations. Parkinson's advocates at his site cheered and applauded the news.

A giddy Jenifer Raub, one of the leaders of the Summit4StemCells group, told agency directors,

"I feel like a kid at Christmas."

It was a feeling echoed by other members of the group, which had protested the delay at a CIRM board meeting in July and also earlier this month. About 17 were in attendance at Mills' location this morning.

The San Diego Parkinson's group is backing research by Jeanne Loring, head of stem cell research at the Scripps Institute in La Jolla. (See here and here.)

The unanimous vote by the board gave Mills more flexibility in scheduling upcoming rounds of awards involving basic and translational research. Loring's research fits in the translational area. The basic research round will now apparently be put off until next spring.

Openness and Transparency: Backsliding at California Stem Cell Agency

Highlights
$34 million Alpha Clinics involved
Information failure on proposal
Discourages public/researcher participation
California’s stem cell agency this past couple of weeks skidded significantly backwards in its efforts to improve clarity and transparency in its $3 billion operation.

The latest example came this week and involved its ambitious, $34 million Alpha stem cell clinic program at four major California institutions: the City of Hope, UCLA and UC Irvine and UC San Diego. 

A proposed, multimillion dollar project involving the effort was scheduled for action next Tuesday by the Science Subcommittee of the agency’s governing board.  As of early this morning -- only one full business day from the meeting -- the agency had released only nine words about it to the public. Here is the full text:

“Consideration of concept plan for Alpha Clinics Accelerating Center.” 

Opaque is the only way to describe the process. And it was bound to create issues with affected parties, which it has in this case.

Such cryptic notices make it impossible for the public to comment intelligently or otherwise, given the lack of information. The failure to provide the information in a timely fashion also feeds suspicion and distrust.

Clarity is one of the watch words that Randy Mills has invoked in his 15-month tenure at the California Institute for Regenerative Medicine(CIRM), as the agency is formally known. He has done much to sharpen CIRM’s focus and provide additional clarity through his analysis of the agency’s work.  

But failing to provide material in a timely fashion removes more than the shine on his efforts. The meetings of the agency’s directors are CIRM’s most important public events.  They are where patients, advocates, researchers, biotech executives and even the unwashed public can come together to hear and see the board in action and discuss issues informally with directors and the CIRM staff. Attendance should be encouraged – not discouraged. Which is what happens when important information is withheld from the public.

Last Friday the California Stem Cell Report carried an item on another mysterious agenda item, one that involved forgiveness of agency loans and potential royalty revenue, something that was promised in the election campaign that created the agency in 2004. 

That too was a case of missing information until it was much too late for the public or affected parties to make thoughtful comments. (See here and here.)

CIRM can and should do better than this. 

(The California Stem Cell Report this morning asked CIRM for comment on the failure to provide information on the Alpha proposal scheduled for Tuesday.  About ninety minutes later, CIRM spokesman Don Gibbons responded, saying that the item was now being postponed "to allow more time for refinement and consideration.")

(By this afternoon, the agency had also posted the first explanation of another cryptic item on the Tuesday agenda for the Science Subcommittee. This one would eliminate the specific schedule for RFAs in the upcoming basic research (discovery) and translational RFAs. The reason for the change is to provide more flexibility.)

(Editor's note: The last paragraph of this item was added several hours after the original posting.)

Sunlight on California's Stem Cell Loan Effort; Info Missing on Changes in $127 Million Research Programs

Highlights

Some details on loan changes

New Alpha clinic center proposed; no details

Unspecified changes upcoming in $93 million award programs

A little sunshine popped up over the weekend on a bit of fiscal alchemy at the $3 billion California stem cell agency, and a little clarity emerged.

The matter involves the agency’s loan program, which affects multi-million awards to businesses. The awards are called loans but are forgiven if no viable product emerges.

The matter surfaced as a result of a cryptic agenda item for Thursday’s meeting of the agency’s directors’ Intellectual Property Subcommittee. Here is what happened:

About a week ago, the agency posted the agenda for the meeting. The agenda contained a 24-word line that said that it was going to change its policies “to permit existing loan recipient whose loan has been forgiven to convert its award to a grant.”

The need for change and its financial impact on the agency was not discussed. The specific language being changed was not spelled out. The timetable for the changes was not specified. Nor was it discussed whether the move was desired by any recipients of the agency’s largess.

Given the opaque nature of the agenda item, the California Stem Cell Report carried an item Friday morning that said,

“In just four business days, the $3 billion California stem cell agency is going to perform a bit of financial alchemy. But like most alchemists, its methods are less than transparent.” 

Much later that day or possibly early Saturday, the agency posted a brief memo and regulatory language that provided a better look at the loan rule changes, which could have an impact on royalties the state might receive on a successful stem cell therapy.

Based on what is now on the agency’s Web site, the proposal would clarify what happens if a loan-financed therapy is dropped and then revived, leading to actual revenue. Under existing rules, such a situation could trigger an ambiguous financial burden that would have to show on the company books. And business executives and investors do not like ambiguous financial burdens. 

The memo from the California Institute for Regenerative Medicine (CIRM), as the agency is formally known, said,

“To provide clarity regarding future obligations, CIRM proposes giving existing loan recipients whose loan has been forgiven by CIRM the option to convert their loan to a grant and forego reinstatement of a forgiven loan. In this way, loan recipients will be automatically governed by the revenue sharing (and other) principles of the agency’s intellectual property regulations in the event future revenue streams are realized. This will be particularly important in the event future revenues are realized after CIRM has exhausted its funding.” 

The directors’ subcommittee is likely to approve the change on Thursday. It would then go to the full board at its Sept. 24 in San Diego for action before it enters the state’s regulatory process, which will open it to further public comment.

The Thursday meeting will also take up changes in the “loan election policy” for this year’s $100 million clinical award program. Details on that are still not available as of this morning, but one assumption would be that they are an extension of the proposed loan changes to that particular program.

The weekend’s memo on the loan changes was dated  Aug. 20.  One can only assume that it was lingering on some CIRM executive’s desk for eight days until it was made available to the public, researchers and likely affected businesses.  

Problems with timely posting of agenda material are not new to the agency. In the more distant past, they were significant but have diminished. That is, until this case and others earlier this year.

The agency also has another directors’ subcommittee coming up in just five business days. The session involves two significant, multimillion dollar programs. One proposal calls for creation of an “Alpha Clinics Accelerating Center” in connection with the $34 million Alpha clinics effort.

The other proposal before the Science Subcommittee deals with unspecified changes in the agency’s upcoming, $93 million “discovery and translational” award rounds.

This morning, no additional details were available on those two matters.

The Science Subcommittee teleconference session on Sept. 8 will be based in San Francisco. Interested parties can weigh in at public locations in Irvine, La Jolla, Los Angeles and Duarte. Addresses are on the agenda.

The meeting Thursday of the Intellectual Property Subcommittee is also a teleconference session based in San Francisco. Public locations are available in San Diego, Hawaii, Woodside and Redwood City with two in San Francisco.

The only public access to these meetings is at their physical locations. No participation is available via the Internet.  However, comments may be submitted in advance or later by emailing them to mbonneville@cirm.ca.gov.

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.

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.

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. )

California Stem Cell Agency Spending: Where the Money Is Going

Analysis of CIRM funding by Pat Olson, executive director of CIRM scientific activities July 2013

The California stem cell agency will have committed $472 million to translational research – a key to commercializing stem cell therapies – if it awards the full $70 million in new grants and loans slated to come before its governing board next week.

The nearly $500 million will amount to about 17 percent of its funding so far, according to an analysis last month by Pat Olson, the agency's executive director of scientific activities. The largest percentage of the agency's cash, however, will be going for “development” – 35 percent or $970 million. Olson defined “development” as “essentially our IND enabling, our preclinical development programs and our clinical development programs.”

Basic research is to receive 17 percent or about $469 million with buildings and facilities taking up $443 million or 16 percent. Training and career development has consumed about 15 percent or $414 million.

However, those calculations include $577 million in funds that have been allocated but not yet awarded. Another $491 million is “concept approved” but also not awarded. The agency's governing board could change those allocations or withdraw approval of concepts, although it has not yet shown signs that it might do so.

The agency will run out of money for new grants in 2017 and is examining the possibility of generating more cash through some sort of public-private partnership. To develop support for continued funding, the agency is under pressure to generate results that will resonate with the public and potential private funding sources. Those results are most likely to come from a late stage translational/clinical trial effort.

Here is a link to CIRM's translational portfolio as of September 2012.

(An earlier version of this item incorrectly said that the agency would run out of money for new grants in 2013. The correct year is 2017,.)

Reproducing Research Results: Removing a Scientific Roadblock

The California stem cell agency faces no easy task in trying to translate basic research findings into something that can be used to treat patients and be sold commercially.

Even clinical trials, which only begin long after the basic research is done and which involve more ordinary therapeutic treatments than stem cells, fail at an astonishing rate. Only one out of five that enter the clinical trial gauntlet successfully finish the second stage, according to industry data cited last spring by Pat Olson, executive director of scientific activities at the stem cell agency. And then come even more challenges.

But at a much earlier stage of research there is the “problem of irreproducible results,” in the words of writer Monya Baker of the journal Nature. Baker last month reported on moves by a firm called Science Exchange in Palo Alto, Ca., to do something to ease the problem and speed up preclinical research. The effort is called the Reproducibility Initiative and also involves PLOS and figshare, an open science Internet project.

Elizabeth Iorns
Science Exchange Photo

Science Exchange is headed by Elizabeth Iorns, a scientist and co-founder of the firm. She wrote about  test-tube-to-clinic translation issues in a recent article in New Scientist that was headlined, “Is medical science built on shaky foundations?”

Iorns said,

“One goal of scientific publication is to share results in enough detail to allow other research teams to reproduce them and build on them. However, many recent reports have raised the alarm that a shocking amount of the published literature in fields ranging from cancer biology to psychology is not reproducible.”

Iorns cited studies in Nature that reported that Bayer cannot “replicate about two-thirds of published studies identifying possible drug targets” and that Amgen failed at even a higher rate. It could not “replicate 47 of 53 highly promising results they examined.”

The California Stem Cell Report earlier this week asked Iorns for her thoughts on the implications for the California stem cell agency, whose motto is "Turning stem cells into cures." Here is the full text of her response.

“First, I think it is important to accept that there is a crisis affecting preclinical research. Recent studies estimate that 70% of preclinical research cannot be reproduced. This is the research that should form the foundation upon which new discoveries can be made to enhance health, lengthen life, and reduce the burdens of illness and disability. The irreproducibility of preclinical research is a significant impediment to the achievement of these goals. To solve this problem requires immediate and concrete action. It is not enough to make recommendations and issue guidelines to researchers. Funders must act to ensure they fund researchers to produce high quality reproducible research. One such way to do so, is to reward, or require, independent validation of results. The reproducibility initiative provides a mechanism for independent validation, allowing the identification of high quality reproducible research. It is vital that funders act now to address this problem, to prevent the wasted time and money that is currently spent funding non-reproducible research and to prevent the erosion of public trust and support for research.”

'Sun Never Sets on CIRM' – California Agency Awards $69 Million to Researchers

The California stem cell agency today awarded $69 million in grants, including the first involving a collaboration with researchers in China, but none of the awards went to California biotech businesses.

The awards were made in the agency's third translational round, which funds projects that are in the initial stage of identifying drugs or cell types that could become drug therapies.

CIRM originally allocated $95 million for the round, but CIRM spokesman Kevin McCormack said that grant reviewers determined that no applications beyond $69 million were worthy of funding.

The CIRM governing board overturned a negative reviewer decision on one grant after the scientist – W. Douglas Boyd of UC Davis -- filed an appeal. The appeals of two other researchers, including one from a San Diego business, were not successful (see here and here).

CIRM did not disclose the number of applications from businesses. The agency has been sharply criticized for failing to fund businesses in a substantial way.

The approved grants involve collaboration with researchers in Australia and Germany as well as China. The collaborations are based on agreements worked out earlier by CIRM with overseas groups, which fund their own countries' researchers. No CIRM cash is involved, according to the agency.

CIRM President Alan Trounson, a native of Australia and researcher there until joining the stem cell agency, said in a press release,

"The sun now never sets on the CIRM collaborative projects..."

The news release also said,

 "The Chinese Ministry of Science and Technology has committed roughly $850,000 in collaboration with a team at UCSF to study liver failure. This is the stem cell agency’s first joint effort with scientists in China, which is home to a fast-growing stem cell research community."

The UCSF liver team is led by Holger Willenbring, whose goal is "to develop a source of autologous therapeutic cells for patients with liver disease who otherwise would require a liver transplant," according to the CIRM review summary. The agency did not spell out the details of how the collaboration would work.

All of the winning applicants, with the exception of a Salk researcher, work for institutions linked to at least one of the 29-members of the CIRM governing board. CIRM directors, however, are barred from voting or even discussing applications in which CIRM attorneys have determined there is a conflict of interest.

You can find the names of all the successful applicants in the CIRM news release.    

Andy Grove on Medical Research's Great Pyramid of Egypt

Andy Grove and the $3 billion California stem cell agency need to talk.

Both have the same matter at the top of their minds – turning research into cures.

Grove, as many readers know, is the almost legendary former CEO of Intel whose interests have long spanned a wider arena than microchips.

Andy Grove

Currently, Grove is keenly focused on an area of science that he sometimes discusses in the context of a question: "key to progress or bridge to nowhere?"

It is an apt question for the California Institute for Regenerative Medicine, which will run out of funds by around 2017 unless it can come up with convincing evidence to persuade state voters that it deserves another multibillion dollar injection of cash. And that is not to mention the hopes and expectations of the millions of voters who approved creation of CIRM seven years ago.

What this is all about is translational medicine, an ill-defined term that generally means taking basic research, refining it, testing it further and developing a means to actually use it on people in clinics. Someplace in all that is the economic necessity to develop a plan that will generate profits for the enterprise that ultimately produces the therapy.

What nags at Grove is the egregiously slow pace of turning out new cures and treatments. He told a UCSF audience last month that 800,000 scientific papers related to new drugs are published annually, but only 20 new drugs come to market each year, according to a blog posting by Adam Mann of the California Institute of Quantitative Bioscience.

Grove said that the time and investment currently needed to create a new drug is about what it took, adjusted for time and inflation, to build the Great Pyramid of Egypt -- 20 years and $1.5 billion.

Grove's message is not new. In a Forbes magazine article in 2008, Kerry Dolan reported that in a speech at a neuroscience conference,

"Grove roundly criticized research funding at the National Institutes of Health, the unwillingness of researchers to share data and the lack of urgency in translating basic science into treatments that can help people. 'What is needed is a cultural revolution that values curiosity, follow-through and a problem-solving orientation and also puts the data being generated in full view, scrutinizable by all.'"

Heretical is what some might call his views, particularly regarding intellectual property. He says "trivial and obvious 'inventions'" are overwhelming the patent system. Overzealous pursuit of IP rights, which are ostensibly given out by the federal government for society's benefit, are keeping products off the market. The result is crippling innovation.

Grove's efforts go beyond rhetoric. He has pumped tens of millions of dollars into medical research in recent years, including stem cells. In 2010, he funded a $1.5 million program at UCSF and UC Berkeley to create a master's degree in translational medicine.

Currently, the California stem cell agency is acutely aware of the need to at least partially fulfill the promises of the 2004 ballot campaign that led to its creation. It has a new chairman, Jonathan Thomas, who is focusing on closer ties to industry in hopes that faster progress can be made. It is altering its grant review review process on its big-ticket rounds in hopes of generating better results. That includes its disease team rounds, which are designed to bring together a broad array of expertise in hopes of moving into clinical trials more quickly.

Grove's proposals are wide-ranging, including changes at the federal level, and not all possible to implement in a short timeframe. But fresh and innovative thinking is what any organization should be seeking. Grove's suggestions could well be of major benefit to California's unique experiment in stem cell research.

Some in the medical research establishment do not take kindly to Grove's suggestions. One writer a few years ago titled his commentary on the former CEO's proposals "Rich, Famous, Smart and Wrong." But clearly not all is well with the progress of drug development.

We do know that Grove, who had prostate cancer and has Parkinson's, is not going to drop his effort any time soon. Today, the latest edition of Science magazine published an article by Grove in which he makes specific recommendations for changes in the Byzantine clinical trial system. Fifty billion dollars a year for biomedical research to produce only 20 new drugs is not good enough. Grove is also to be a keynote speaker at next month's World Stem Cell Summit in Pasadena. The title of his speech? 
"Translational Medicine: Key to Progress or Bridge to Nowhere?"

(An earlier version of this item said that Science would publish the Grove piece tomorrow. The piece is behind a pay wall. If you would like a copy of it, please email a request to me at djensen@californiastemcellreport.com.)

Here is a copy of the slides that Grove used in his presentation at UCSF.

Andy Grove's Slides on Translational Medicine