Type 1 Diabetes Mellitus (T1DM)

Type 1 diabetes mellitus (T1D) is a serious, chronic disease caused by a T-cell mediated autoimmune process which targets the insulin-producing β-cells in the pancreas leading to their complete or near complete destruction. The results are insulin deficiency and impaired glucose metabolism, mainly characterized by hyperglycemia, necessitating lifelong administration of exogenous insulin.

The diagnosis of T1D peaks during childhood between the ages of 5 and 15 years. Preceding the clinical diagnosis are many years of silent development of autoimmunity (Stage 1) with detectable circulating autoantibodies directed against insulin or other β-cell related proteins, like glutamic acid decarboxylase (GAD65), insulinoma-associated protein (IA2) or zinc transporter 8 (ZNT8) (Insel, 2015). The next phase is still asymptomatic but characterized by additional dysglycemia (Stage 2). At the time when the majority of β-cells are dysfunctional or lost, the insulin-secretory capacity becomes insufficient and hyperglycemia develops with typical symptoms (Stage 3). In this stage T1D is diagnosed requiring daily insulin injections and bearing the risks of acute metabolic derangements (DKA and severe hypoglycemia) as well as longer-term micro- and macrovascular complications of diabetes.

Over the past 2 to 3 decades numerous therapeutic strategies have been tried to prevent and/or reverse T1D, mostly without lasting success. The most encouraging results have been seen with anti-CD3 antibodies. Recently, a Biological License Application (BLA) has been submitted for humanized teplizumab and is currently being reviewed under Priority Review by the FDA for the indication of the delay of clinical T1D in at-risk individuals. Tiziana intends to initiate a Phase 1a single ascending dose study in healthy subjects in Q3 2022 using parenterally administered foralumab. The company anticipates that fully human foralumab will have a better safety profile that teplizumab and show clinical benefit in slowing onset of T1DM.