TTP399

TTP399 is an oral, small molecule, liver selective glucokinase activator being evaluated for the treatment of type 1 diabetes mellitus. TTP399 is currently being studied in the SimpliciT-1 Study, a phase 2 trial in patients with type 1 diabetes as an add-on to insulin therapy. For additional information on the study, refer to NCT03335371 at Clinicaltrials.gov.

Part 1 of the two-part Simplici-T1 Study achieved positive topline results. In this double-blind, placebo-controlled 12-week trial, the baseline mean HbA1c for the groups treated with TTP399 and placebo was 7.3% and 7.4%, respectively. Patients treated with TTP399 (n=8) showed a statistically significant mean reduction in HbA1c of 0.6% at 12 weeks, while the group treated with placebo (n=11) showed a mean increase in HbA1c of 0.1%, resulting in a mean improvement of 0.7% in the TTP399 group relative to the placebo group (p=0.03). TTP399 treatment increased Time in Range from baseline to end of treatment by 11% (2.7 hours) (p=0.055) per day (24 hours), and by 12% (1.7 hours) (p=0.04) during the critical waking hours (7am-9pm) relative to placebo, without increasing time in hypoglycemia. TTP399 treatment also reduced the total daily mealtime bolus insulin dose by 23% compared to 4% for placebo while significantly improving glycemic control. TTP399 was well tolerated in the study, with no serious adverse event reported, and no report of diabetic ketoacidosis or severe hypoglycemia. Patients in the treatment group experienced fewer Level 1 (≥54-70 mg/dl) and Level 2 (<54 mg/dl) hypoglycemic events than patients in the placebo group

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.

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