Juvenile Diabetes Research Foundation International Research Update Dayton Coles

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Juvenile Diabetes Research Foundation
International Research Update Dayton Coles

• JDRF Central Pennsylvania Chapter
• May 16, 2007

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What well talk about

• JDRF Research Funding
• Cure Goals
• Regeneration
• Artificial Pancreas
• JDRFs Research Focus Therapeutics

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My Connection to Type 1
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How Research Has Made a Difference

• People with type 1 are living longer than ever
  before
• The risk of complications is declining for type 1
• Tight control of blood glucose is more achievable
  than ever

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JDRF Research Funding

• FY2005 98 Million
• FY2006 122 Million
• FY2007 140 Million (estimate)

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JDRF Funded Research(FY06)

• Autoimmunity 41 million
• Complications 26 million
• Islet Replacement
• Transplant 21 million
• Cell Sources 20 million
• Regeneration 8 million
• Metabolic Control 6 million
• TOTAL 122 million

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JDRFs Cure Goal Pathways

• Islet Cell Replacement (Transplantation
  Source)
• Regeneration of Native Beta Cells
• Restoring Immune Tolerance
• Complications (Preventing Treating)
• Metabolic Control (Continuous Glucose Monitoring,
  Artificial Pancreas)

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Therapeutic Strategies
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Replacing Beta Cells
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Regeneration of Native Beta Cells
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Can beta cell regeneration occur in patients with
long standing 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

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Can beta cell regeneration occur in patients with
long standing 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

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Artificial Pancreas Program
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A1Cs Are High Even for Children with Highly
Involved Parents
A1C results for 563 respondents in CWD survey
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.
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Tremendous Potential

• Artificial 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)

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Continuous Glucose MonitorLook at the Difference
in 9 DaysWith CGM Use, 26 More Time in Normal
Glucose Range
Diabetes Care 2944-50.
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What is an Artificial Pancreas?
Control - Algorithm
Continuous Glucose Sensor
Insulin Pump
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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

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APP/CGM Trials Status

• Two tracks currently funded
• Track One continuous glucose sensors
• Track Two artificial pancreas
• Will Examine
• Patient outcomes, e.g. HbA1c, hypoglycemia
• Economic benefits, e.g. fewer hospitalizations
• Quality of Life
• Various subpopulations
• Possible health plan partners

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JDRF 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

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Steps to Widespread Availability
Patient Acceptance and Use





Health Care System Acceptance






Coverage and Reimbursement






Studies and Trials




Product Development
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JDRFs Research Focus
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JDRF Strategy
Proactively accelerate the discovery,
development, and delivery of disease-modifying
therapeutics to better treat and cure type 1
diabetes and its complications.
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From Discovery to Therapies
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Recent Developments

• Islet 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

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Recent Developments

• Regeneration 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 RD 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

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Recent Developments

• Restoring 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

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Recent Developments

• Complications
• 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.

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Recent Developments

• Metabolic 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

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What You Can Do

• Pay attention
• Time and Treasure
• Advocate NIH funding and APP
• Clinical Trials
• Other

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Questions