Juvenile Diabetes Research Juvenile Diabetes Research Foundation InternationalFoundation International

Research Update

Dayton Coles

JDRF Central Pennsylvania ChapterJDRF Central Pennsylvania Chapter

May 16, 2007May 16, 2007

What we’ll talk aboutWhat we’ll talk about

JDRF Research FundingJDRF Research Funding Cure GoalsCure Goals RegenerationRegeneration Artificial PancreasArtificial Pancreas JDRF’s Research Focus: JDRF’s Research Focus:

TherapeuticsTherapeutics

My Connection to Type 1My Connection to Type 1

How Research Has Made a How Research Has Made a DifferenceDifference

People with type 1 are living longer People with type 1 are living longer than ever beforethan ever before

The risk of complications is The risk of complications is declining for type 1declining for type 1

Tight control of blood glucose is Tight control of blood glucose is more achievable than evermore achievable than ever

JDRF Research FundingJDRF Research Funding

FY2005FY2005 $98 Million$98 Million

FY2006FY2006 $122 Million $122 Million

FY2007FY2007 $140 Million (estimate)$140 Million (estimate)

JDRF Funded ResearchJDRF Funded Research(FY06)(FY06)

JDRF Funded ResearchJDRF Funded Research(FY06)(FY06)

AutoimmunityAutoimmunity $41 million$41 million ComplicationsComplications $26 million$26 million Islet ReplacementIslet Replacement

TransplantTransplant $21 million$21 million Cell SourcesCell Sources $20 million$20 million

RegenerationRegeneration $8 million$8 million Metabolic Metabolic

ControlControl $6 million$6 million

TOTAL:TOTAL: $122 million$122 million

AutoimmunityAutoimmunity $41 million$41 million ComplicationsComplications $26 million$26 million Islet ReplacementIslet Replacement

TransplantTransplant $21 million$21 million Cell SourcesCell Sources $20 million$20 million

RegenerationRegeneration $8 million$8 million Metabolic Metabolic

ControlControl $6 million$6 million

TOTAL:TOTAL: $122 million$122 million

JDRF’s Cure Goal PathwaysJDRF’s Cure Goal Pathways

Islet Cell ReplacementIslet Cell Replacement (Transplantation & Source)(Transplantation & Source)

Regeneration of Native Beta CellsRegeneration of Native Beta Cells Restoring Immune ToleranceRestoring Immune Tolerance ComplicationsComplications (Preventing & Treating)(Preventing & Treating) Metabolic ControlMetabolic Control (Continuous Glucose (Continuous Glucose

Monitoring, Artificial Pancreas)Monitoring, Artificial Pancreas)

Therapeutic StrategiesTherapeutic StrategiesDefeat

Autoimmunity

Regenerate

Beta cells

Replace

Restore Metabolic Control

Restore Beta Cell Function

Replacing Beta CellsReplacing Beta Cells

Precursors

Beta cells

Beta cells

Neogenesis Replication

Islets• Cadaver (ex-vivo expanded) • Stem cell-derived• Reprogrammed (liver, K cell)• Xeno (pig, fish)• Encapsulation

• Pancreas-derived• Reprogrammed

Defeat Autoimmunity

Restore Metabolic Control

Restore Beta Cell Function

Regeneration of Regeneration of Native Beta CellsNative Beta Cells

Can beta cell regeneration occur in Can beta cell regeneration occur in patients with long standing patients with long standing

diabetes?diabetes? Many long-standing diabetes patients

have detectable C-peptide Research shows islets can expand under

different circumstances, like pregnancy and significant weight gain

Animal experiments indicate life-long cell generation

Post-mortem exams have shown insulin-positive cells in islets in long-standing diabetes patients

Can beta cell regeneration occur Can beta cell regeneration occur in patients with long standing in patients with long standing

diabetes? diabetes? Beta cell regenerative capacity may remain

clinically masked by Poor glycemia control and/or other metabolic

factors Residual anti-beta cell specific autoimmunity

Increase by directing careful attention to: Glycemia and lipid control Efforts to control anti-beta cell autoimmunity Delivering factors thought to promote beta

cell proliferation or survival in vivo

NeogenesisNeogenesis

ReplicationReplication

Cell DeathCell Death

Beta Cell MassBeta Cell Mass

(New Beta Cell Generation from Precursors)

(Cell Division)

Exocrine Exocrine DuctDuct

Therapeutics: Metabolic Control Immune Tolerance

Regeneration

Artificial Pancreas ProgramArtificial Pancreas Program

A1Cs Are High Even for Children A1Cs Are High Even for Children with Highly Involved Parentswith Highly Involved Parents

A1C results for 563 respondents in CWD A1C results for 563 respondents in CWD surveysurvey

<6.5

6.6-7.0

7.1-8.0

8.1-9.0

>9.0

13%13%

15%15%

40%40%

24%24%

8%8%73% are above the ADA recommended goal and 90% are above the recommended AACE goal - and these are among the most committed patients and families in the world.

Tremendous PotentialTremendous PotentialArtificial pancreas technologies have the potential to revolutionize diabetes care

Prevent highs that lead to heart attacks, amputations, blindness

Prevent life threatening lows Improve quality of life Facilitate other cure goals (e.g.,

regeneration)

1717

Continuous Glucose MonitorContinuous Glucose MonitorLook at the Difference in 9 DaysLook at the Difference in 9 Days

With CGM Use, 26% More Time in Normal Glucose With CGM Use, 26% More Time in Normal Glucose RangeRange

Diabetes Care 29:44-50.

Continuous Glucose Sensor

Insulin Pump

Control - Algorithm

What is an Artificial What is an Artificial Pancreas?Pancreas?

APP Project Goals

Accelerate the availability of a first generation artificial pancreas

Ensure the artificial pancreas and its components are available to the majority of people with type 1

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

APP/CGM Trials StatusAPP/CGM Trials StatusTwo tracks currently funded: Two tracks currently funded: Track One: continuous glucose sensors Track Two: artificial pancreas

Will Examine:Will Examine: Patient outcomes, e.g. HbA1c,

hypoglycemia Economic benefits, e.g. fewer

hospitalizations Quality of Life Various subpopulations Possible health plan partners

JDRF ApproachJDRF Approach Patient focused, independent from industry Commission independent, empirical research

Assess patient outcomes from use of artificial pancreas technologies

Answer regulator and payer questions Engage with key decision makers

FDA – Critical Path Opportunity List Center for Medicare and Medicaid Services Congress Private insurers Physicians

Product Developmen

t

Studies and

Trials

Coverageand

Reimbursement

Health Care System

Acceptance

Patient Acceptance and Use

Steps to Widespread AvailabilitySteps to Widespread Availability

JDRF’s Research FocusJDRF’s Research Focus

“Proactively accelerate the discovery, development, and delivery of disease-modifying

therapeutics to better treat and cure type 1 diabetes and its

complications.”

JDRF StrategyJDRF Strategy

From Discovery to TherapiesFrom Discovery to Therapies

Exploratory Research

Discovery Research

Preclinical Research

Clinical Research Clinical Trials Regulatory

Launch/AccessClinical DevelopmentTranslational ResearchBasic Research

Outcome Studies

3rd Party Coverage

• Screening/ rational Screening/ rational drug designdrug design

• Lead optimizationLead optimization• Proof-of-concept Proof-of-concept

in animal modelsin animal models• Safety studiesSafety studies

• Target Target identification/videntification/validationalidation

• Pathway Pathway evaluationevaluation

• Insights to Insights to disease disease processprocess

• Human Human proof-of-proof-of-concept concept testingtesting

• Safety and efficacy studiesSafety and efficacy studies• Phases I, II, IIIPhases I, II, III

• AcademiaAcademia • AcademiaAcademia

• Industry Industry (limited)(limited)

• Academia Academia (evolving)(evolving)

• IndustryIndustry • IndustryIndustry

• Academia Academia (evolving)(evolving)

• IndustryIndustry

Recent DevelopmentsRecent Developments Islet Cell ReplacementIslet Cell Replacement

Industry partner differentiates Embryonic Stem Cells into insulin-producing cells

Harvard scientists find that Natural Killer (NK) cells, knocked-out under current immunosuppressive protocols, may actually reduce the chance that transplanted tissue will be rejected

JDRF-funded researchers in San Diego have discovered that non-secreting tissue in the pancreas can be transformed into insulin-producing cells.

Xenotransplantation: Trials launched and FDA discussions have been initiated

Cadaver Islet Transplantation: Grant activated

Recent DevelopmentsRecent Developments

Regeneration of Native Beta CellsRegeneration of Native Beta Cells

JDRF-funded researchers at the University of Massachusetts have identified a protein in beta cells that regulates the production of insulin.

New RFA launched on physiologic beta cell regeneration

Academic R&D grants under development with Broad, Harvard, Stanford, etc

GLP-1/Gastrin preclinical studies completed and trial has launched

Insulin-Making Protein identified in Beta Cells

Recent DevelopmentsRecent Developments Restoring Immune ToleranceRestoring Immune Tolerance

Discovery that single protein can switch a key component of the immune system on or off depending on which molecule it teams with, sheds light on what is involved in keeping the immune system in check, paving the way for researchers to develop therapies for type 1 diabetes and other autoimmune afflictions such as arthritis and allergies

Using natural compounds derived from a shrub and the venom of a sea anemone, JDRF-funded researchers at the University of California-Irvine thwarted the autoimmune attack causing type 1 diabetes in experiments with human cells and animals.

Rituxan trial launched, ATG trial to launch, IL1RA and AAT trials in development

Innate Immunity Program launched Resource creation: Network for Pancreatic Organ donors with Diabetes to

launch

Recent DevelopmentsRecent Developments ComplicationsComplications

JDRF-funded researchers have identified a potential mechanism that may shed light on why some people with diabetes lose the ability to recognize and correct hypoglycemia

A JDRF-funded research project at Columbia University Medical Center that goes back 16 years has taken a major step toward translation into therapies to treat diabetic complications.

Dr. Lloyd Aiello of the Joslin Diabetes Center has shown that the compound ruboxistaurin slowed the progress of retinopathy by inhibiting an enzyme in the body called protein kinase C beta (PKC beta), which is believed to contribute to the blood vessel damage that leads to the disease.  This is the first time a drug has been shown to protect against the complication in a human clinical trial.

Recent DevelopmentsRecent Developments Metabolic ControlMetabolic Control

JDRF CGM Clinical Trial launched with enrollment initiated January

Funded six site Artificial Pancreas Project Consortium JDRF-FDA dialogue:

Resulted in removal of Investigational Device Exemption – saving considerable time and resources

“Critical Path” Initiative February meeting began to define pathway and approval metrics

What You Can DoWhat You Can Do

Pay attentionPay attention Time and TreasureTime and Treasure Advocate – NIH funding and APPAdvocate – NIH funding and APP Clinical TrialsClinical Trials OtherOther

QuestionsQuestions