TTP399

Overview

TTP399 is an oral, small molecule, liver selective glucokinase activator being developed as an adjunct therapy to insulin in patients with type 1 diabetes.

Clinical Trials

TTP399 recently completed the SimpliciT-1 Study, a phase 2 trial in patients with type 1 diabetes as an add-on to insulin therapy. The study met its primary objective by demonstrating a statistically significant and clinically meaningful improvement in HbA1C (a measure of long-term glucose control) for TTP399 compared with placebo. TTP399 also improved patients’ daily time in glycemic range, without increasing hypoglycemia or ketoacidosis, relative to placebo. Additionally, treatment with TTP399 reduced total daily mealtime bolus insulin dose. NCT03335371 at Clinicaltrials.gov.

TTP399 also completed a 6 month phase 2 trial in patients with type 2 diabetes where it achieved statistically significant reductions in HbA1c with negligible incidences of hypoglycemia and hyperlipidemia.

Mechanism of Action

Glucokinase (GK) is a key regulator of glucose homeostasis and acts as the physiological glucose sensor, changing its conformation, activity, and/or intracellular location in parallel with changes in glucose concentrations. GK has two main distinctive characteristics that make it a good choice for blood glucose control. First, its expression is mostly limited to tissues that require glucose-sensing (mainly liver and pancreatic β-cells). Second, GK is able to sense changes in serum glucose levels and modulate changes in liver glucose metabolism that in turn regulate the balance between hepatic glucose production (HGP) and glucose consumption, and to modulate changes in insulin secretion by the beta-cells. The concept of GK activation for the treatment of diabetes is attractive because it has proven to be effective and safe in normalizing glycemia in animal models of type 1 and type 2 diabetes by a mechanism entirely distinct from the action of antidiabetic therapies currently on the market.

Publications

Links to the following publications and presentations, which are located on outside websites, are provided for informational purposes only and do not constitute the opinions or views of vTv Therapeutics

Presentations and Posters

Links to the following publications and presentations, which are located on outside websites, are provided for informational purposes only and do not constitute the opinions or views of vTv Therapeutics