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JDRF Research and Partnerships to Improve the Lives of People with Type 1

Diabetes and Keep our Promise of a Cure

Boston, April 6, 2010

Karin Hehenberger, MD, PhD

Senior Vice President, Strategic Alliances

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Mission and Research Strategy To find a cure for type 1 diabetes and its complications

Proactively accelerate the discovery, development, and delivery of drugs and devices to Cure, Better Treat or Prevent type 1 diabetes and its complications at any stage of the disease at the point-of-care

- Arrest the immune attack on insulin-producing cells- Restore or replace beta cell function- Better control blood sugars- Protect people from (or reverse) complications.

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Commitment to a Cure Placing the individual at the center with the end product in mind

- Providing solutions for the different stages of type 1 diabetes

Core principles

- People with T1DM, Pipeline, Priorities, Partners

Proactively managed pipeline through joint committees that govern projects

JDRF drives partnerships with academia, patients organizations, FDA, payers, providers, industry, venture capital and funders

At-Risk Sub-Clinical Recent Onset Established(without

Complications)

Established (with Complications)

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JDRF Research Strategy

PREVENT TREAT CURE

1° Prevention • Vaccines

2° Prevention• Diagnosis and staging

followed by antigen-specific immune therapy and beta cell therapies

Complications

Glucose Control

Beta Cell Survival & Glucose Control

Complications

Antigen-specific immune therapy and Beta Cell Regeneration

Encapsulated Alternative Beta Cell Source

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Primary Prevention: Vaccines

• Infectious

• Microbiota-based

• Immunoregulatory

Secondary Prevention: Diagnosis and Staging

PREVENT TREAT CURE

Time (Years)

% B

eta

Ce

lls

100

10

Followed by• Antigen-specific Immunotherapy, Anti-inflammatories + Beta Cell Therapy

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Preventing through Earlier Diagnostics

At-Risk Sub-Clinical Recent Onset Established(without Complications)

Established (with Complications)

Interventions based on earlier diagnostics

% B

eta

Ce

lls

Time (Years)

Current diagnosis based on glucose

Early diagnosis based on auto-antibodies

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PREVENT TREAT CURE

Complications

• Glucose-independent

•Genetics

•Modifiable risk factors

• Therapeutics

•Biomarkers

•Target validation

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Preventing and Treating Complications

Discover, develop, deliver therapies to prevent, arrest, and reverse diabetic complications

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PREVENT TREAT CURE

Glucose Control

• Drugs

• Insulins, Amylin, Leptin

• Devices

• Pumps and Sensors

Beta Cell Survival “Keep the beta cell happy”

• Glucose control

• Reduce apoptosis

• Limit inflammation

• Immunotherapy

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Treating by Improving Glucose Control

Drugs

– Glucose control

– Prevent hypoglycemia

Devices

– Closed loop “artificial pancreas”

– Improved delivery of insulin

Induce improved glucose control in people with established diabetes and the newly diagnosed with:

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JDRF Forms Partnership with Animas to Develop First-Generation Automated System for Managing Type 1 Diabetes and with Becton Dickinson to improve insulin delivery January 2010

Develop 1st generation semi-automated system to manage glucose control in people with diabetes

• Insulin pump connected to CGM to prevent hypoglycemia and extreme hyperglycemia

• Slow/stop insulin if blood sugar too low; delivery automatically resumes

• Increase insulin if blood sugar too high; automatically returns to pre-set basal rate

• Improve insulin delivery through better cannulae for insulin pumps

• Faster insulin delivery which will improve control

• Microneedles

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PREVENT TREAT CURE

Encapsulated Alternative Cell Source

• Encapsulation

• Alternative Beta Cell Source

Antigen-specific Immune Therapy + Beta Cell Regeneration

• Survival

• Neogenesis

• Proliferation

• Reprogramming

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Immune Cells

Complement

02

Nutrients

GLUCOSE INSULINC-Peptide

HumanIslet

PEG

25-50

Curing by Implanting Encapsulated Beta cells

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Curing by Arresting the Autoimmune Attack and…

Discover, develop, and deliver therapies that arrest the autoimmune attack and induce immunoregulation to:

Preserve function of restored beta cells in established diabetes Preserve residual beta cell function in recent onset diabetes or at-risk of developing diabetes Prevent the onset of autoimmunity in the at-risk population

BETA

CELL

MA

SS

TIME

NEWLY DIAGNOSED T1D

DIABETES

PRE-DIABETES

GENETIC PREDISPOSITION

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…Regenerating Native Beta Cells

Discover, develop, and deliver therapies that restore glucose-responsive, insulin-producing cells

Proliferation Reprogramming Survival Neogenesis

cells cells

cells

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Exploratoryresearch

Target ID/Validation

Lead identification

Lead optimization

Clinicaldevelopment

Generate new beta cells

Beta Cell Survival

Beta Cell Growth

Reprogram

JDRF has Formed Partnerships with NVS, JNJ and PFE in Regeneration and Pursuing Further Partners…..

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Multiple Immune Therapy Clinical Trials

Phase 3 new onset trials using anti-CD3 (TolerX, Macrogenics)

Phase 3 new onset trials using GAD-Alum (Diamyd)

Phase 2 secondary prevention trials using GAD-Alum and oral and intranasal insulin

Phase 2 trials using Insulin (Bayhill/DNA) and anti-CD20 (DNA/Roche)

Over a dozen different immune therapies in clinical testing in new onset T1D in 2010, ongoing planning for multiple prevention trials

Early-stage vaccines

18Diabetologia (2010) 53:614–623

TolerX Anti-CD3 Immunotherapy in Recent Onset DiabetesIncreased Preservation of Functional Beta Cell Mass for 4 Years

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Summary JDRF’s mission is to find a cure for type 1 diabetes and

keeping individuals healthy while pursuing this mission

Focus on the individual at all stages of the disease with the end product in mind

Advances in early stage research driven by JDRF have lead to multiple partnerships with industry

Accelerated effort with focus on curing, treating and preventing the disease by partnering with biotech, pharma and other funders

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Appendix

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Bet

a C

ell

The

rapi

es

Current Industry Partners

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Imm

une

The

rapi

es

Current Industry Partners (Continued)

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Glu

cose

Con

trol

C

ompl

icat

ions

The

rapi

es

Current Industry Partners (Continued)

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JDRF

VentureCapital

Industry

People with Type 1 Diabetes

Providers

Academia

Funders

FDA

Payers

JDRF

JDRF’s Partners