Normal Metabolism: In Response to Insulin, the Liver Continuously Micromanages Glucose Pancreas Liver Clears 50% - 80% of insulin Stores 30%-50% of glucose Liver Clears 50% - 80% of insulin Stores 30%-50% of glucose 80% - 600% Insulin Oscillations 30% Insulin Oscillations 24/7/365 1 Portal Vein Peripheral Vein Tightly Controlled Peripheral Glucose Rare Occurrences of Hypoglycemia ©Copyright 2014, All Rights Reserved, Diasome Pharmaceuticals, Inc.

Current Insulin Therapies: Insufficient Hepatic Delivery Pancreas Liver (Insufficient glucose storage) Liver (Insufficient glucose storage) Pre-meal Injections Provide Non-Physiologic Post Meal Insulin Peaks 2 Portal Vein Peripheral Vein Long-acting Injections Provide Peripheral Basal Insulin Poor Peripheral Glucose Control Frequent Hypoglycemia Chronic Hyperglycemia ©Copyright 2014, All Rights Reserved, Diasome Pharmaceuticals, Inc.

Preferred Form of Insulin Therapies: Hepatic and Peripheral Insulin in a Single Dose Pancreas Liver (Normal Hepatic Glucose Storage) Liver (Normal Hepatic Glucose Storage) 3 Portal Vein Peripheral Vein HDV Pre-meal Injections Provide Both Hepatic and Peripheral Insulin HDV Basal Injections Provide Both Hepatic and Peripheral Insulin ©Copyright 2014, All Rights Reserved, Diasome Pharmaceuticals, Inc.