TTP399

Type 1 Diabetes and Hypoglycemia

Type 1 Diabetes (T1D) is an autoimmune disease with no cure affecting over 1.6 million people in the United States. Adult-onset T1D has become more common than childhood-onset with more than half of all new cases diagnosed in adult patients. The patient population is expected to grow worldwide, with an estimated projection of 5 million patients in the U.S. by 2050.

Hypoglycemia is the most common acute complication in T1D, and hypoglycemic control continues to be an unmet need in the patient population. 

Graph displaying T1D US Population Estimated Growth from 2020 - 2050 showing an over 200% increase

Our Compound

TTP399 is a novel, oral, small molecule, liver selective glucokinase activator being developed as an adjunct therapy to insulin in patients with T1D. In a recent phase 2 study, TTP399 showed a 40% reduction in hypoglycemic episodes compared to placebo. In April 2021, the FDA granted Breakthrough Therapy designation to TTP399 for the treatment of T1D. This past October, vTv announced results of our mechanistic study of TTP399 in patients with T1D demonstrating no increased risk of ketoacidosis. TTP399 has now been tested in almost 600 subjects and demonstrated a good safety and tolerability profile. 

Mechanism of Action

TTP399 is a Glucokinase (GK) Activator, a mechanism entirely distinct from the action of antidiabetic therapies currently on the market. TTP399 restores the normal function of the liver in the presence of high glucose: it traps glucose inside liver cells, promotes further glucose uptake for energy and storage, and keeps the liver in a “fed” state, thereby preventing ketone production. You can read more about the mechanism of action here.

chart displaying the difference between non diabetic individuals, people with Type 1 Diabetes, and people with Type 1 Diabetes using TTP399

Clinical Trials

SimpliciT1 Phase 2 Study

TTP399 completed a phase 2 study in patients with T1D as an adjunctive treatment to insulin therapy. The study met its primary objective by demonstrating a statistically significant and clinically meaningful improvement to HbA1C, and treatment with TTP399 also showed a decrease in hypoglycemic episodes by 40%. TTP399 improved patients’ daily time in normal glycemic range with no reports of ketoacidosis during the study duration. Additionally, patients treated with TTP399 showed a reduction in their total daily mealtime bolus insulin dose. 

Graph displaying Simplicit1 Phase 2 Study results

You can read more about this study at ClinicalTrials.gov or read our article in Diabetes Care.

Mechanistic Study

In October 2021, vTv announced positive results for our mechanistic study of TTP399 in patients with T1D. The study demonstrated that patients taking TTP399 showed no increase in ketone levels relative to placebo during a period of acute insulin withdrawal, indicating no increased risk of ketoacidosis. TTP399 patients also showed improved fasting plasma glucose levels and fewer hypoglycemic events during the week of treatment prior to the insulin withdrawal test.

Graphs displaying Mechanistic Study results
Graph displaying Hypoglycemic Episodes of placebo patients versus TTP399 patients.

Type 2 Trial

TTP399 previously completed a 6-month phase 2 trial in 189 patients with type 2 diabetes where it achieved statistically significant reductions in HbA1c with negligible incidences of hypoglycemia and hyperlipidemia.   

You can read more about our AGATA study at ClinicalTrials.gov (1, 2)

 

 

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