The landmark Diabetes Control and Complications Trial (DCCT) and the UK Prospective Diabetes Study (UKPDS), have clinically proven that tighter glycemic control, as measured by lower glycosylated hemoglobin A1c (HbAlc) levels, significantly reduces the incidence of long term diabetic complications. True glycemic control requires treatments that provide plasma glucose-regulated insulin replacement. SmartCells is addressing this need by offering Smartlnsulin, the only product to both sense and respond to altered serum glucose levels in a clinically relevant way. In order to file a Smartlnsulin IND with the FDA and initiate human clinical trials, safety and efficacy studies in Years 1 and 2 will address the following critical issues using streptozotocin-induced diabetic Sprague-Dawley (SD) rat models: - Scale-up Smartlnsulin from 4L to 40L batches while preserving performance as determined by in vitro glucose set point and in vivo glucose tolerance tests - Engineer Smartlnsulin subcutaneous injection compatibility and verify absence of fibrotic and necrotic tissue and macrophage and lymphocyte infiltration using standard histology scoring - Tailor Smartlnsulin for rapid absorption, action, and elimination as measured by key post-injection pharmacokinetic and pharmacodynamic parameters - Optimize Smartlnsulin formulation to control fasting and mealtime glucose levels using a single dose - Reduce 60-day HbA1c levels with daily injections of optimized Smartlnsulin
