Leukemia Treatment: California Stem Cell Agency Awards $3.8 Million to San Diego's Angiocrine Bioscience

CIRM graphic

The California stem cell agency today approved a $3.8 million award to a San Diego firm to help develop a better way to treat such afflictions as leukemia with cord  blood transplants despite concerns that the effort was too complex.

Shahin Rafii, Cornell photo

The funds will go to Angiocrine Bioscience, Inc., whose key technology is licensed from Weill Cornell Medical College and was invented and developed by Shahin Rafii, a professor of medicine at the New York school. He remains on the company's scientific advisory board.

Directors voted 13-0 to approve the award, but not before two directors raised questions. Joe Panetta, president of the San Diego-based industry group, Biocom, wondered about difficulties with the manufacturing process raised by the agency’s blue-ribbon reviewers, who earlier approved the application behind closed doors.

Steve Juelsgaard, former executive vice president of Genentech, also raised questions. If the effort flounders, he said, 

“We need to be able to put the brakes on.”

CIRM officials said that the research would be closely monitored with clear milestones that needed to be achieved before cash continued to flow to the company.

The agency’s press release said Angiocrine

“plans to develop a product called AB-110, which blends an expanded mix of stem cells from cord blood with genetically modified endothelial cells, the kind of cell that forms the lining of blood vessels, to improve the success rate of cord blood transplantation.

“The hope is that AB-110 will reduce the complications that can occur with a cord blood transplant – such as viral infections or pneumonia – and increase the likelihood the transplanted cells will successfully engraft, meaning they start growing and creating new, healthy, blood cells.”

No members of the public spoke at the teleconference meeting which had 12 public locations around the state. The next meeting of the agency’s directors will be March 16 near San Francisco International Airport and will be a face-to-face session with likely a handful of remote public locations.

Speak Up! A Chance to Sound Off to California Stem Cell Agency

If you would like to speak directly to the governing board of the $3 billion California stem cell agency, here’s your chance on Thursday.

The  directors are holding a teleconference meeting at 11 a.m. PST with public locations at 12 different sites around the state. The purpose of the meeting is to approve a $3.8 million application for work on process to manufacture a cord blood treatment for such afflictions as leukemia and lymphoma.

Approval is expected to be routine since the agency’s blue-ribbon reviewers, meeting behind closed doors, have already decided the application should be funded. The identity of recipient, as usual, is being withheld until after the board ratifies the decision by reviewers.

Every board meeting has a point at which any person can address the board on any issue. The board sets a three-minute time limit but has been very flexible in the past.

The teleconference locations are in Oakland, Redwood City, Napa, South San Francisco, Beverly Hills, Fresno, San Diego, Elk Grove, Los Gatos, San Francisco (two different locations there) and Irvine. Specific addresses can be found on the meeting agenda,

You may want to double-check in advance with the agency on the addresses. Only one lists a room number. Others may need to include that detail as well.

$25 Million for Stem Cell Research Plus Sharp Criticism of California Stem Cell Board

The California stem cell agency today approved $25.2 million for preclinical research aimed at speeding development of therapies for afflictions that include arthritis, Alzheimer's and “bubble boy” syndrome.

The action came during an agency governing board session that was marked by sharp criticism from an executive with a La Jolla firm associated with one of the rejected grant applicants, Jill Helms of Stanford. The executive, Sanford Madigan of Ankasa Regenerative Therapeutics, told the board he was "disturbed by board members not willing to do their jobs."

Sanford Madigan, LinkedIn photo

Several board members said they were offended by Madigan's remarks, although he later apologized. He appeared to be irritated by the reluctance of the board to override its reviewers. Five board members subsequently abstained from voting to overturn staff and reviewer rejection of Helms' application. The motion that would have funded her proposal failed on a vote of 5-1-5.

The public flare-up involving the board and a member of the public was unusual, although comments such as Madigan's are sometimes heard in private.

His remarks came at the end of a discussion about the weaknesses of the agency's closed-door review process. The discussion involved other applications in addition to Helms' proposal. Randy Mills, president of the agency, acknowledged the review process was "sub-optimal" and was being replaced by new procedures he has dubbed CIRM 2.0.

Ankasa was created by Avalon Ventures, which is raising $16 million to help commercialize Helm's work to develop a stem cell therapy to improve skeletal healing of elderly people.

The governing board of the agency handed out awards to seven scientists with the goal of moving their research closer to federal approval for a start of a clinical trial. The board approved applications from two researchers who made special appeals to the board after reviewers and staff nixed their proposals.

Prior to the vote on her application, Helms was told that she could revise her $7 million application and submit it for later consideration. She said the soonest that would occur would be in about 10 months, given the agency's timetable. By that time, she said the research team would be disbanded through lack of funding and the effort would "disintegrate." 

CIRM has already put $7 million into Helms' research. She has been something of a bright star for the agency, which has featured her on its Web site and asked her to appear on its panels.

The rejection of the Helms proposal highlighted some of the vagaries of the agency's longstanding review process.  She received an average scientific score  of 72 which knocked her out of the funding category(tier one). However, her median score was 75, a figure that two reviewer-approved grants received. What skewed the average figure was a low score of 45. No other grant in the top 10 received that a ranking that low. Eight reviewers recommended funding the proposal, Four did not with three recommending it be placed in "tier two," a grey area for applications.

No reviewers were listed as having conflicts of interest on the Helms proposal. However, their finanicial and professional interests are not disclosed to the public. Nor are they identified to the public.

On another proposal, John Cashman, CEO of Human BioMolecular Research Institute of San Diego, asked for a re-review of his firm's application for a treatment involving spinal fusion. He said that his firm has worked with CIRM for several years to make changes that the agency had requested. Nonetheless, he said reviewers do not seem to agree.  Cashman said,

"Certainly the system is broken."

The board did not act on Cashman's request for a re-review.

Here is the roll call vote on the Helms' application: Yes -- David Higgins, Steve Juelsgaard, Kathy LaPorte, Lauren Miller, Art Torres. No -- Jonathan Thomas. Abstain -- Francisco Prieto, Robert Quint, Al Rowlett, Jeff Sheehy, Diane Winokur.

Summaries of the reviews of the winning applications can be found on this 90-page document.

(Editor's note: An earlier version of this item did not contain the two paragraphs that deal with the vagaries of the grant review process and conflicts of interest.) 

$32 Million or $16 Million for California Preclinical Stem Cell Research?

The California stem cell agency board has begun discussion of the preclinical awards to be approved today. Reviewers approved five grants totaling $15.8 million. Three rejected researchers are asking the board to approve another $16 million. The board budgeted $40 million for the effort. At least one rejected researcher, Jill Helms of Stanford, is expected to address the full board.

California to Spend Nearly $16 Million More for Preclinical Stem Cell Research

The California stem cell agency next Thursday is expected to award $15.8 million to five scientists to help push their research into clinical use for afflictions ranging from arthritis to the “bubble boy” syndrome.

Another five researchers have been told that they need to improve their proposals and can bring them back to the agency in July. They will then be considered under the agency’s new, aggressive CIRM 2.0 program to speed action on development of stem cell therapies.

CIRM is the abbreviation for the California Institute for Regenerative Medicine, the official name of the $3 billion agency. Its president, Randy Mills, who has been in place since last May, is overhauling the agency’s grant process with sharp eye on faster development and calls the effort CIRM 2.0.

The applications scheduled to be acted by the CIRM board on March 26 in Berkeley are for early preclinical research that is ready for transition to the next preclinical stage. CIRM originally budgeted $40 million for this round.

The top five applications received scores ranging from 90 to 75 and covered possible therapies involving spina bifida, arthritis, Huntington’s Disease, diabetic wounds and SCID-X1(bubble boy syndrome).

The five in tier two total $27.3 million. A memo to the CIRM board from Mills said,

“While CIRM recognizes that some applications not in Tier 1 do have the potential to positively impact the field, none was without flaw and all could be improved with further refinement. Unfortunately, the application and review system for this RFA does not accommodate iterative refinement and resubmission, a key feature of CIRM 2.0. As a result, CIRM recommends that interested applicants consider improving their submission and reapplying under the CIRM 2.0 Translational program that will be brought to the ICOC (the CIRM board) in July.”

Mills also said the researchers may be able to resubmit their proposals under the current CIRM 2.0 process which is accepting applications at the end of each month.

The scores on each application in the two top tiers can be found on this 90-page document, which also includes summaries of the comments made during the closed-door grant review process. 

The names of the applicants have been withheld by the agency, although they can often be deduced by discerning readers. The names of the scientific reviewers are also not released. Scores on the rejected applications were not posted by the agency.