Assessment of the glucagon receptor blocker REMD-477 on insulin requirements in type 1 diabetes

DESCRIPTION provided by applicant Fast Track Insulin remains the primary and often the only treatment for type diabetes mellitus T D However it is associated with chronic iatrogenic hyperinsulinemia secondary hyperlipidemia higher incidence and severity of cardiovascular complications and life threatening hypoglycemia events A higher mortality vs due to cardiovascular complications were reported in insulin treated T D patients versus the general public An effective add on therapy is needed to reduce daily insulin doses and to minimize its complications REMD is a fully human high affinity glucagon receptor GCGR antibody that blocks the hepatic GCGR and reduces hepatic glucose ketone production REMD restores euglycemia in animal models of type diabetes mellitus T D and shows preliminary but promising glucose lowering effect in a few T D mouse models REMD demonstrated a benign safety profile in animals and in healthy volunteers in a first in human study Since the overactive glucagon action is a common finding in both T D and T D a robust GCGR blocker such as REMD represents a promising novel strategy In Phase I of this project the glucose lowering effects of REMD will be thoroughly evaluated in animal models of T D including a chemical streptozotocin induced model in rats and an autoimmune non obese diabetic NOD model in mice both without insulin treatment The animal studies will be directed by Dr Roger Unger at the Touchstone Diabetes Center University of Texas Southwestern Medical Center Dallas TX In Phase II a randomized double blind vehicle controlled day in patient clinical study will be conducted i patients with T D to quantitatively assess the reduction in insulin requirements while maintaining standardized postprandial and postabsorptive glycemic control The study will be directed by Dr Sam Klein Chief Div of Geriatrics andamp Nutritional Sciences at the Washing University School of Medicine St Louis MO The small business REMD Inc provides research materials performs the hormone and metabolite assays and coordinates the overall project management and supportive duties for both Phase I and II of this project REMD is projected to be an add on therapy for T DM to substantially andgt reduce insulin daily doses leading to better glucose control fewer and milder complications and an improved quality of life

PUBLIC HEALTH RELEVANCE Fast Track Assessment of the glucagon receptor blocker REMD on insulin requirements in type diabetes The heavy reliance of type diabetic T D patients on multiple daily insulin injections often leads to secondary hyperinsulinemia and increased incidence and severity of cardiovascular events and life threatening hypoglycemia REMD is a fully human glucagon receptor antibody which has demonstrated a benign safety profile in animals and in humans and a robust glucose lowering effect by suppressing hepatic glucose output in various animal models of type diabetes This project plans to evaluate the effects of REMD in correcting hyperglycemia in two animal models of T D streptozotocin induced diabetic rats and Non obese diabetic mice without insulin treatment and to quantitatively assess the clinical efficacy of REMD versus vehicle control in minimizing insulin requirement for standardized glucose control in patients with T D