Alex Philippidis Senior News Editor Genetic Engineering & Biotechnology News

Focus of California’s stem cell agency has been on setting up a foundation for leadership.

Days before his death in October 2004, Christopher Reeve went before cameras one last time. Instead of playing Superman or another role, Reeve appeared as himself in TV commercials urging California voters to approve Proposition 71. The ballot measure authorized the state to borrow $3 billion over 10 years to use toward stem cell research at universities and institutions statewide.

“Stem cells have already cured paralysis in animals. Stem cells are the future of medicine,” Reeve declared. “Please support Prop 71. And, stand up for those that can’t.”

Those ads worked. California voters approved Prop 71, 59% to 41%, thrusting the Golden State into the business of fostering stem cell research. It funded everything from research, to facilities, to professors through a state agency called California Institute for Regenerative Medicine (CIRM).

At its meeting this year, held January 17, CIRM’s governing board, the Independent Citizens’ Oversight Committee (ICOC), began detailed review of a proposed strategic plan for 2012–2016. The proposed plan commits CIRM to focusing on driving more of the science it funds to clinical trials while also maintaining basic science work.

CIRM has been embracing the clinical focus in recent years. “We have been moving more aggressively to the clinic since Alan arrived,” CIRM spokesman Don Gibbons told GEN, referring to the 2009 appointment of Alan Trounson, Ph.D., as the agency’s president. Since then, Gibbons said, ICOC approved doubling to $210 million the money allotted to disease teams envisioned in CIRM’s initial 2006 Strategic Plan. CIRM also expanded the membership of its Grants Working Group to include more reviewers capable of looking at applications for translational and clinical research.

What’s Been Happening at CIRM

For its first roughly two years, CIRM was stymied by a lawsuit pursued by opponents of research using human embryonic stem cells. In May 2007, the state’s highest court declined to hear a challenge to a prior decision by the state Court of Appeals that upheld the program’s legality, effectively green-lighting the funds.

“CIRM’s first five years set priorities based on establishing a strong foundation for leadership in stem cell research, seeding the entire field with discoveries using a variety of stem cell-based platforms,” according to the plan.

That work, according to CIRM, has resulted in the agency awarding more than $1.327 billion in 483 grants to 61 institutions. The funded research reportedly resulted in more than 1,000 journal articles, 28% with impact factors greater than 10, as well as the construction of 12 stem cell facilities across the state, and the migration of more than 100 faculty stem cell researchers to California.

This year, CIRM said it will have up to $370 million in awards up for review by ICOC. Most of it ($240 million) will be set aside for disease teams comprising people with research, clinical, and regulatory expertise and a focus on bringing drug candidates into clinical trials.

Since 2006, CIRM awards have included disease-team assembly and planning; three “basic biology” award rounds for research into basic stem cell mechanisms; three “research leadership” awards to recruit out-of-state professors to California; two rounds of tools and technologies grants; two rounds of early translational research; three student training rounds; and awards for clinical development, conference development, labs and facilities, new ideas and investigators, stem cell transplantation immunology, derivation of pluripotent human stem cells, and research opportunities for faculty-level scientists from California academic institutions without major research and infrastructure funding from CIRM.

Where the Money’s Gone

According to a spot-check of CIRM’s funding database, Stanford University has received the most funding, at $192.5 million in 50 awards. The three next highest institutions were all schools from the University of California: UC Los Angeles won $148.8 million in 50 awards; UC San Francisco, $114.8 million through 38 awards; and UC San Diego racked up nearly $104.6 million in 44 awards. Rounding out the top-five winners was University of Southern California, with just over $72 million in 20 awards.

Research institutes, by comparison, haven’t fared as well. Scripps Research Institute won $40.9 million in 16 awards, followed by Buck Institute for Research on Aging with $33 million in six awards. More than half of Buck Institute’s money ($20 million) went toward building a CIRM Center of Excellence, set to be fully operational this year. Sanford-Burnham Medical Research Institute captured nearly $31.2 million in 19 awards, followed by Salk Institute for Biological Studies ($28.3 million; 14 awards) and J. William Gladstone ($24.3 million; 14 awards).

Salk, Sanford-Burnham, and Scripps joined with UC San Diego in 2006 to form a stem cell research group; a fifth institute, La Jolla Institute for Allergy & Immunology, joined last year. Sanford Consortium for Regenerative Medicine won a single $43 million grant toward its $127 million “Collaboratory,” which opened November 29.

The consortium and Buck were two of 12 institutions that in 2008 benefited from a key funding initiative, in which CIRM awarded $271 million toward construction of stem cell research facilities totaling 546,000 square feet. All are either completed or nearing completion. According to the agency, the 12 institutions in turn committed more than $800 million from charitable donations and their internal reserves.

Businesses have won only a small share of CIRM’s funding to date; a total $48.3 million was won by 12 companies, according to the database. A 13th company, Geron, repaid with interest the $6.42 million it received from a $25 million loan awarded last May, after the company announced in November that it was terminating its stem cell development programs and reducing its workforce by 38%. Geron, which had the most advanced stem cell program, won the loan toward a Phase III trial of a cellular therapy derived from hESCs and later won a $106,239 planning grant for preclinical development and first-in-human testing in advanced heart failure.

Addressing Criticisms for the Future

The wide gap between awards to academic and nonprofit institutions and businesses has been one area where CIRM has been criticized in recent years. The disparity reflects in large measure the commercial risk of stem cell research, much of which is carried out by universities and other nonprofits.

ICOC chair, Jonathan Thomas, Ph.D., restated CIRM’s commitment to funding more companies, which was included in its 2009/2010 Strategic Plan Update. “Industry needs to play an increased role during Stage II of CIRM’s programs. At the same time, the precise role of industry needs to be explored and defined,” CIRM’s external advisory panel concluded.

CIRM sought to address that issue in October, when it approved a $30 million Strategic Partnership Funding Program designed to attract companies through an approach aligned with industry timelines and processes. The program provides co-funding for earlier stages of clinical development as well as access to big biopharma partners capable of providing expertise in regulatory activities, clinical trial design, and manufacturing.

The strategic partnership fund is a component of a three-prong Opportunity Fund that also allows funding of California researchers who partner with out-of-state scientists, and supplemental support to projects previously funded by the agency.

Another criticism of CIRM has been the presence of ex-politicians in leadership roles and the six-figure salaries it pays top executives. The agency had defended Dr. Thomas’ $400,000 salary by noting it falls below the $529,000 maximum set for the job and that $250,000 of that is paid out of charitable contributions received by CIRM.

Governance issues are hardly on CIRM’s radar these days. The new strategic plan includes boosting clinical stem cell research as well as calls for advancing understanding of stem cell science, promoting economic development for California based on the research, and positioning the Golden State as a world leader in stem cell science. How the plan proposes to achieve all four goals, and challenges CIRM faces in doing so, will be covered in a follow-up article.

Alex Philippidis is senior news editor at Genetic Engineering & Biotechnology News.

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