Enabling Stem Cell Research in California Gil Sambrano, Ph.D. California Institute for Regenerative Medicine

What is a stem cell? 1. Mature/specialize 2. Self-renew

Stem Cell Capacity

Stem Cell Capacity Human embryonic stem cell lines were first derived in 1998 by Dr. James Thompson.

Embryonic Stem Cells via In Vitro Fertilization

Potential of Stem Cell Research An enabling technology for: Tissue/cell replacement Gene therapy/drug delivery Models of disease in vitro Drug screening and drug development Basic knowledge of human development A path to new therapies and cures for many diseases

Somatic Cell Nuclear Transfer

Scale of a Human Egg

2001 Presidential Executive Order for Embryonic Human Stem Cell Research Prohibits use of Federal funds on embryonic stem cell lines derived prior to August 9, 2001 Lines must have been derived from unused embryos that were made for IVF

States Respond California: California Institute of Regenerative Medicine Connecticut: Connecticut Stem Cell Research Grant Project Illinois: Illinois Regenerative Medicine Institute Maryland: Maryland Stem Cell Commission Massachusetts: Governor's Life Science Initiative Minnesota: Stem Cell Institute New Jersey: Stem Cell Institute of New Jersey New York: Empire State Stem Cell Trust Fund Ohio: Center for Stem Cell and Regenerative Medicine

Proposition 71 Approved by 59% of CA voters Authorized $3 billion to fund stem cell research in CA Affirmed the right to conduct research not supported by federal funding Banned reproductive cloning Required development of medical and ethical standards

Independent Citizens Oversight Committee (ICOC): 29 members Chair: Robert Klein Vice-Chair: Ed Penhoet, Ph.D California Institute for Regenerative Medicine (CIRM): 50 member staff (currently 26) President: Alan Trounson, Ph.D.

Mission Statement To support and advance stem cell research and regenerative medicine under the highest ethical and medical standards for the discovery and development of cures, therapies, diagnostics and research technologies to relieve human suffering from chronic disease and injury. “Turning stem cells into cures.” Roman Reed

Working Groups of the CIRM Standards and Ethics Working Group (19) (prominent ethicists, scientists, patient advocates) Grants Review Working Group (23) (distinguished scientists from outside California, patient advocates) Facilities Working Group (11) (real estate experts; patient advocates)

Building a State Agency Procedures Regulations Grants management Compliance Tracking and a Funding Agency

Legal Challenges For over two years legal challenges prevented the institute from issuing bonds Two consolidated lawsuits challenged our constitutional authority to spend state money Very strong decision in Superior Court in May 2006 upholding CIRM position; appealed In May 2007, the California Supreme Court declined to hear appeal and ended the legal challenge A third lawsuit (dismissed) asserted that we are depriving frozen embryos of their constitutional rights Two lawsuits have challenged our constitutional authority to spend state money A third lawsuit (dismissed) asserted that we are depriving frozen embryos of their constitutional rights

Funds for a Funding Agency Bond Anticipation Notes (BANs) -Authorized $14 M in BANs in April, 2006 for first year of training grants; -Additional $36 M in BANs for research grants. Governor’s Loan $150M loan provided to CIRM by Governor Schwarzenegger in July, following Presidential veto on Castle-DeGette bill

Making a plan

Scientific Strategic Plan Define long-term objectives that CIRM will pursue over ten years Involved interviews with scientists, clinicians, ethicists, patient advocates, public interest groups Focus group discussions and public meetings Heard from ~200 individuals A “living plan” with mechanisms for review and modification Published December 2006

Strategic Planning Framework Laying the Foundation Preparing for the Clinic Clinical Research Scientific Training & Development Innovation Science Mission-Oriented Science Tools, Technologies & Infrastructure Facilities Communities of Science Responsibility to the Public Funding Initiatives Resources

Strategic Plan Goals Aspirational Goals: Commitment Goals: What we hope to achieve Use stem cells to cure disease California as world-wide leader in stem cell research Commitment Goals: Our covenant with the people of California for what we will achieve over the next ten years

Commitment Goals: Context Scientifically young field Therapeutic drug development: takes time and fails more often than it succeeds New treatment modality: cellular therapy

Commitment Goals Focused on human embryonic stem cells, with emphasis on cell replacement therapy Ten year goals Goal 1: Clinical proof of principle that transplanted cells derived from pluripotent cells can be used to restore function for at least one disease. Goal 2: Therapies based on stem cell research in Phase I or Phase II clinical trials for 2-4 additional diseases On average, 7-9 years from the start of clinical development to approval for the market Thus, we are unlikely to bring a therapy all the way to market within ten year plan Attrition at every stage of development: only 1 in 8-10 therapeutics that enter clinical development are approved for the market Thus, need a strong pipeline that will continue to bring products into the clinic past the ten year period of plan.

Laying the Foundation New Faculty :59 letters of intent from researchers at 29 institutions 25 grants totaling $85 million fund the research of promising M.D. and Ph.D. scientists in their early years as independent lead investigators and faculty members. They are intended to develop a new generation of clinical and scientific leaders in stem cell research. Major facilities: to both accommodate the increase in researchers engaged in stem cell research in California as a result of CIRM’s research grant and training programs, and to provide research space that can be used for stem cell research that would otherwise not be available due to restrictions imposed by the federal government Up to 227 MM

CIRM Training Program 16 non-profit institutions in California 169 Trainees (pre-doc, post-doc, clinical) Course in stem cell biology Course in ethical, legal, and social issues Annual meeting of trainees Grants awarded in April, 2006 Total ~$38M for 3 years

“Jumpstart” Initiative to Enable Stem Cell Research CIRM SEED Grants $200K/yr, 2 yrs Innovative projects Comprehensive Research Grants $400K/yr, 4 yrs Established investigators in SCB/related field Shared Laboratory Space Fund renovation of lab space for hESC work Fund instructional course

Latest Initiatives New Faculty Awards New Cell Lines Awards Enable young faculty scientists and physicians to New Cell Lines Awards Enable the development of new pluripotent stem cell lines for research and therapies Disease Teams Create teams of researchers

What’s Next New President New Initiatives Develop for-profit funding Community outreach Growing the Institute Disease Teams New Pluripotent Stem Cell Lines

Acknowledgements Bob Klein Zach Hall Arlene Chiu Alan Trounson Rich Murphy CIRM Team All those who have generously contributed their time and expertise to making CIRM and the vision embodied in Proposition 71 a reality

Scientific Challenges Capabilities of different types of stem cells Control division in vitro and in vivo Control paths of differentiation Safe production of large numbers of cells Immunological tolerance Production of SC lines with disease phenotypes