Selective SST5 Agonists for the Treatment of Hyperinsulinism - - PowerPoint PPT Presentation

Selective SST5 Agonists for the Treatment of Hyperinsulinism

Congenital Hyperinsulinism Family Conference Philadelphia, Pennsylvania September 2019

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Crinetics: Who We Are and What We Do

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OUR VISION


To build the leading endocrine company that consistently pioneers new therapeutics to help patients better control their disease and improve their daily lives

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Our CHI hypothesis: an oral, selective-sst5 drug is the optimal strategy for treating all HI patients

Pancreatic Islet Cells

GLUCAGON

GLUCOSE

sst2 sst5

β−cell

INSULIN INSULIN

α−cell

GLUCAGON

GLUCOSE

Diazoxide Octreotide (inhibits insulin, glucagon, & pituitary GH secretion) sst2

KATP channel

SST5 Agonist (inhibits insulin secretion) sst5

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sst5 Agonists: Positive results from preclinical studies

• 120 -60

60 120 180 240 300 360 100 200 300 400

Time (minutes) Blood glucose (mg/dL)

PO glyburide PO CRN02481

Rescue of hypoglycemia in rats induced by treatment with sulfonylurea glyburide …while maintaining glucagon levels

Vehicle 5 mg/Kg CRNX agonist sc

Glyb + 10 mg/Kg CRN02481 Glyb + 3 mg/Kg CRN02481 30 mg/Kg glyburide Vehicle

In an OGTT, CRNX agonist suppressed

insulin…

• 60
• 30

30 60 90 120 1 2 3 4 5

Time (min) Insulin (ng/mL)

• 60
• 30

30 60 90 120 5 10 15 20 25

Time (min) Glucagon (ng/mL)

Vehicle 5 mg/Kg CRNX agonist sc

CRNX agonist dosed Glucose bolus CRNX agonist dosed Glucose bolus

• Rescue insulin induced hypoglycemia
• Suppress insulin secretion
• Maintain glucagon levels

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sbetz@crinetics.com

Our CHI Goals

• Deliver a new medicinal option for CHI

clinicians and families

• Oral pill (solution for infants)
• No Injections!
• Effective for most (all?) CHI mutations
• Lower insulin levels
• Prevent hypoglycemia
• Start human clinical trials asap!