Background & Purpose

Webinar RFA Information

JDRF, the world’s leading non-profit organization with the mission to cure, treat and prevent type 1 diabetes (T1D) and Eli Lilly and Company, a global healthcare company working to make life better for people around the world, invite full proposal applications for the discovery of novel glucose responsive glucose modulating drugs for better treatment of insulin-dependent diabetes mellitus (IDDM) and reducing the burden of daily management of the disease, particularly T1D.

Since its discovery in 1921, insulin has been the lifeline for people with insulin-dependent diabetes mellitus, as well as playing a key role in the treatment of patients with insulin-independent diabetes mellitus. Yet almost 100 years later, truly adequate control of blood glucose concentration via therapeutic treatment has not been achieved. Despite the advent of better insulins, automated devices and diligent self-care, the disease remains challenging to manage, and is a huge burden on both the affected individual and the caregiver. Current treatment options do not provide adequate glycemic control, as evidenced by results from numerous clinical and epidemiological studies demonstrating prevailing high HbA1c levels, frequency of hypoglycemia and ketoacidosis, more than 70% time spent outside of target glucose values, as well as long term complications of the disease mostly arising from years of dysglycemia.

The efficacy of insulin-centered treatment in preventing hyperglycemia is limited by the risk of insulininduced hypoglycemia due to the glucose concentration-independent nature of insulin action. Additionally, maintaining glycemic control requires diligence and orchestration of several lifestyle factors throughout the day and lifetime of individuals with type 1 diabetes (T1D). In an effort to achieve tighter glucose control and reduce the burden of living with insulin dependent diabetes mellitus, JDRF has prioritized the development of insulin-based therapies whose actions are glucose-dependent. Such therapies may modulate the activity and/or the concentration of insulin as a function of glucose concentration, and consist of novel insulin analogs or other insulin receptor agonists. One may also consider glucagon analogs, glucagon receptor agonists, or insulin receptor antagonists engineered to reverse the effects of non-glucose-dependent insulins in a glucose concentration-dependent manner. Used in combination with insulins, such agents would also be expected to decrease the risk of insulin-induced hypoglycemia and afford greater glycemic control than currently available insulins alone. Mechanisms that modulate the systemic concentrations of agents such as insulin and glucagon in a glucose-dependent manner are also of interest provided they do not require an infusion pump or entail the large hysteresis associated with the current generation of controlled release approaches.