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

Crinetics: Who We Are and What We Do � 2

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 � 3

Our CHI hypothesis: an oral, selective-sst5 drug is the optimal strategy for treating all HI patients Pancreatic Islet Cells SST5 Agonist Octreotide (inhibits insulin secretion) (inhibits insulin, glucagon, sst5 sst5 & pituitary GH secretion) sst2 sst2 β− cell α− cell GLUCAGON INSULIN K ATP INSULIN GLUCAGON channel Diazoxide GLUCOSE GLUCOSE � 4

sst5 Agonists: Positive results from preclinical studies Rescue of hypoglycemia in rats induced by In an OGTT, CRNX agonist suppressed treatment with sulfonylurea glyburide insulin … 5 400 CRNX agonist Vehicle dosed Blood glucose (mg/dL) 5 mg/Kg CRNX agonist sc 4 Insulin (ng/mL) 300 PO 3 Glucose glyburide bolus 200 2 1 100 0 PO -60 -30 0 30 60 90 120 CRN02481 0 Time (min) -120 -60 0 60 120 180 240 300 360 …while maintaining glucagon levels Time (minutes) Glyb + 10 mg/Kg CRN02481 CRNX agonist 25 Vehicle dosed Glyb + 3 mg/Kg CRN02481 5 mg/Kg CRNX agonist sc Glucagon (ng/mL) 20 Vehicle 30 mg/Kg glyburide 15 Rescue insulin induced hypoglycemia 10 • Glucose bolus Suppress insulin secretion • 5 Maintain glucagon levels • 0 -60 -30 0 30 60 90 120 Time (min) � 5

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! sbetz@crinetics.com � 6