Zucara is developing the first therapeutic to prevent hypoglycemia in insulin treated diabetes, delivered as a once daily subcutaneous injection, which will benefit patients by addressing the significant morbidity and mortality associated with hypoglycemia. Preventing hypoglycemia will dramatically change Type 1 diabetes (T1D) disease management, improving both patient health and quality of life. Zucara’s initial focus is on the prevention of nocturnal hypoglycemia, which is of significant concern to both patients with T1D and their caregivers.
Unlocking the role of somatostatin
Our technology is aimed at creating the first treatment to prevent dangerous low blood sugar by restoring the body’s ability to counter-regulate hypoglycemia. This approach will reduce the likelihood of insulin therapy to cause hypoglycemia without affecting its efficacy. The immediate patient benefits would include the reduced occurrence of hypoglycemia and its associated acute symptoms and effects. This in turn would allow diabetic patients to more aggressively treat themselves with insulin, resulting in better overall health outcomes in the long term.
The approach is to block somatostatin type 2 (SSTR2) receptors on α-cells in the pancreas, which are stimulated at a higher than normal level by over-production of somatostatin in insulin-dependent diabetic patients. The effect of this dysregulated somatostatin on α-cells is to suppress glucagon secretion, which results in the insulin-dependent diabetic patient being unable to avoid or recover from hypoglycemia.
Advantages of the Technology
- First in class novel antagonist with the demonstrated potential to prevent hypoglycemia without affecting normal blood glucose levels
- Independently validated proof of concept efficacy data package supports the hypothesis. Demonstrated activity in multiple in vivo models and ex vivo in human pancreatic tissues.
Validated pre-clinical efficacy
The current focus of the project is on establishing safety and optimization of our selected lead molecule PRL-2903 for candidate selection. Studies include chronic dosing studies to assess safety and durability of efficacy with chronic receptor antagonism. In parallel, through chemical optimization we are selecting a candidate for formal non-clinical and clinical development.
Efficacy in the diabetic rat
Pre-treatment with our lead candidate results in little or no hypoglycemia after a simulated insulin overdose in an animal model of diabetes.