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

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

5. Stem Cell Capacity

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

7. Embryonic Stem Cells via In Vitro Fertilization

9. 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

10. Somatic Cell Nuclear Transfer

11. Scale of a Human Egg

12. 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

13. 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

14. 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

15. 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.

16. 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

17. 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)

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

19. 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

20. 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

21. Making a plan

22. 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

23. 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

24. 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

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

26. 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.

27. 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

28. 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

29. “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

30. 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

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

32. 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

34. 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