presentation from dr. alan lewis

Research Update

Alan J. Lewis, PhDPresident & CEO

April 6, 2009

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JDRF Mission

To find a cure for diabetes and its complications through the support of research.

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JDRF: Constituents and Roadmap

JDRF Acts as: Catalyst / Driver Funder Advocate

T1D “Cure”

Product A

Academic Community

Biotech Companies

Pharma and Device

CompaniesProduct B

Product C

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We are Building a Bridge to the Cure!

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Type 1 Diabetes Landscape

Epidemic of T1D Incidence increasing worldwide (3%/year)

– 20-22 cases per 100,000 (US)– 50-60 cases per 100,000 (Finland)– Predominantly in children under 10 years

Unclear how many people diagnosed with T1D/year – 15,000-20,000?

Need for patient registry to identify, monitor patients plus allow registration for clinical trials

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Current Treatment For Type 1 Diabetes Relies On Insulin Replacement

Insulin is the only current therapeutic option Can cause increase in severe hypoglycemia and weight gain Glucose control NOT being met even with new insulin formulations

1st Line50% of patients

1 year

Basal-Bolus

2nd Line 3rd Line

Addition of insulin pumps and use of Symlin as co-therapy

4th LineLast Line

10% of patients

N/A

Organ Transplantation

• Kidney• Kidney+Pancreas• Islet Cell

40% of patients receiving pumps

Source: L.E.K. Interviews and Analysis

Increasing Severity

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Pancreas Derived Endocrine Cells

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Restore, Preserve Pancreatic Beta Cell Function

– Beta Cell Replacement– Beta Cell Regeneration

Reverse, Prevent Autoimmunity and Restore Immunoregulation

Restore Metabolic Control

Arrest and Reverse Diabetic Complications

Therapeutic Integration Requires Close Collaboration across JDRF Therapeutic Areas

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JDRF’s Research: Type 1 Diabetes Person/Patient Centric Orientation

Established Diabetes

Recent Onset

DiabetesPre-diabetes

Prevent Beta Cell

Destruction

Preserve Residual

Beta Cells

Restore Beta Cells, Beta Cell Function

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Regeneration– Novel beta cell regeneration targets and lead small

compounds identified – Gastrin-based regenerative therapeutics in clinic– Reprogramming of non-endocrine pancreatic cells to beta

cells

Replacement– Human embryonic stem cell differentiation to precursors that

mature to become fully functional in animals – Improved results of cadaveric islet transplantation

Autoimmunity– Repositioning antigen non-specific immunotherapeutics– Phase II and III clinical trials of antigen-specific and antigen

non-specific immunotherapeutics

Therapeutic Area Programs: FY09 Key Developments

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We Did It!

March 9, 2009 – President Barack Obama rescinds the directive limiting federal funding of hESC research

NIH still needs to develop guidelines and Congress to codify Executive Order

Opposition expected to limit guidelines

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Replacement and Regeneration

Small Molecules Biologics

hESCß-cell

ProgenitorsInsulin

Producing ß-cell

iPS

T1D Patient

1

2

3 4

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Functional Islets from hESCsToward a renewable source of

pancreatic -cells

Kroon et al. v.26; April 2008

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Adult Human Islet vs. hESC “Islet” Cell Grafts

Human Islet Graft Implant days : 360

hESC-Islet Graft Implant days : 377

Glucagon Somatostatin Insulin

15Immune Cells

Complement

02

Nutrients

GLUCOSE INSULINC-Peptide

HumanIslet

PEG

25-50

Delivery of Human Islets Without Immunosuppression

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Future of…Insulin Producing Cell Transplantation:

Islet cell transplantation still in its infancy (600 vs. 400,000 solid organ transplants)

Select cell population for further development– Safe and effective

Immunoprotection necessary– Immunomodulators with less side effects– Immune tolerance– Encapsulation

Transformation of treatment of T1D and T2D possible.

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Metabolic Control– JDRF’s CGM clinical trial results > change in

reimbursement

Complications– Diabetic eye disease Phase III clinical trials

Therapeutic Area Programs:FY09 Key Developments

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JDRF’s Artificial Pancreas Project

Accelerate the availability and adoption of a first generation artificial pancreas

Ensure devices from multiple companies are approved and reimbursed, encouraging investment in next generation technologies

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JDRF Artificial Pancreas Outreach

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JDRF’s Role in Catalyzing Reimbursement and Adoption of CGM

Continuous glucose monitors (CGM): new tools for control (Continuous readings, Trends, Alarms)

Three models approved by FDA, but health plan coverage limited

JDRF funded independent, multicenter clinical trial to provide data to support reimbursement and clinician adoption – accelerate path to next generation of devices

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JDRF Continuous Glucose Monitor Trial

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CGM group age 25yrs and above demonstrated significant improvements across all measures of glycemic control, without increasing hypoglycemia

Limited benefits were observed in patients ages 15-24yrs – likely due to limited CGM use in some patients

CGM group age 8-14 yrs had significant improvements across many measures of glycemic control

Twice as many reduced A1c by 10%, which reduces risk of long-term microvascular complications by about 40%

Increased time wearing CGM was associated with better outcomes in all three age groups

JDRF CGM Trial: Key Findings

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JDRF – Pharma Strategy

Partnering with Pharma is critical Importance of a push-pull strategy to advance and bundle IP

and of Pharma commitment Fostering a Pharma commitment to cell-based therapy, closed

loop, diabetes vaccine development, combination therapies, repositioning drugs for T1D

Educating/informing Pharma (Overlap of T1D/T2D, IP, market opportunities, etc.)

JDRF-Pharma Partnerships– GNF– J&J, Pfizer, Merck, GSK, BMS, Lilly, NovoNordisk, Sanofi,

Vaccine Industry, Genzyme, etc.– Various structures, experiments, non-exclusivity

Multi-Pharma alliance in precompetitive space– Biomarkers, imaging, animal models, regulatory

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JDRF commitment to keeping individuals with diabetes healthy to benefit from a cure when developed

Keeping our stakeholders engaged Short-term clinically impactful deliverables Created Department of Medical Affairs

JDRF as the Patient Advocate for a Cure

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No DKA: Community outreach program to educate public on symptoms and signs of DKA to prevent mortality and prolonged hospitalization at diagnosis of T1D

Prevention of Diabetic Eye Disease: Improved implementation of standard of care

Development of uniform standard of care for islet cell transplantation

Pregnancy and Diabetes: Increased public awareness of need for early first trimester medical care

Proposed Short-term Deliverables Related to Potential Immediate T1D Clinical Impact

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Progress Towards the Cure…One Step at a Time Tremendous research progress over past 20 years Good at predicting disease Several agents under clinical evaluation (anti-CD3,

anti-CD20 and GAD65 vaccine) Combinations of therapies likely to be next step (more

efficacious and synergistic) Need to determine efficacy then take them to

prevention studies Excellent progress to control blood sugar

– Artificial pancreas driving this ahead.

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Total Research Commitments

New Research Commitments

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Historical Context for Current FY09- FY11 Projections

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JDRF Family