Glucagon-like peptide-1 (GLP-1) is a member of the incretin family of neuroendocrine peptide hormones secreted from L-cells of the intestine in response to food ingestion. GLP-1 has multiple metabolic effects that are attractive for an anti-diabetic agent. A key function of GLP-1 is to activate its receptor, GLP-1R, on the pancreatic β-cell to enhance glucose-dependent insulin secretion. Additional positive metabolic benefits of GLP-1 include suppression of excessive glucagon production, decreased food intake, delayed gastric emptying and improvement of β-cell mass and function. Unfortunately, the rapid proteolysis of GLP-1 in blood limits its use as a therapeutic agent.
There are currently several marketed GLP-1 mimetics (biologic agents). These agents have demonstrated notable glucose lowering in addition to weight loss. However, their widespread use is hindered by the route of administration (injection), and by the high incidence of gastrointestinal side effects (nausea and vomiting).
TTP273 has been identified using TTP Translational Technology®, as an orally bioavailable, potent, non-peptide agonist of GLP-1R for the treatment of type 2 diabetes. This molecule is the second generation from our path-finder molecule TTP054, and it is anticipated to provide excellent glycemic control and an attractive safety profile for the treatment of type 2 diabetes.
The first generation compound has shown robust effects on glycemic control in multiple studies in patients with T2DM not well controlled on metformin. This includes a recently-completed 12-week study in 187 patients with T2DM, where notable HbA1c lowering, in addition to a trend for weight loss, was observed. The incidence of gastrointestinal adverse events noted with treatment is very low, and similar to placebo, in every study to date.
The program candidate, TTP273, has shown robust glucose lowering in a 2-week multiple dose study in patients with T2DM. Same as TTP054, the incidence of gastrointestinal adverse events noted with TTP273 is also no different than placebo. TTP273 is in phase 2 clinical development.
About the LOGRA Study
The LOGRA Phase 2 study will evaluate TTP273, which would be an orally bioavailable, potent, non-peptide agonist of GLP-1R for the treatment of type 2 diabetes. This molecule is the second generation from a path-finder molecule TTP054, and it is anticipated to provide enhanced glycemic control, weight loss and an attractive safety profile for the treatment of Type 2 diabetes. The completed Phase 1b trial in TTP273 demonstrated robust effects on postprandial fasting glucose.
The LOGRA study is expected to read out in late-2016.