(Licensed China/Pacific Rim rights to Huadong Pharmaceuticals)
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 program candidate, TTP273, has completed a 3 month phase 2 study in patients with T2DM where it demonstrated a statistically significant reduction in HbA1c. TTP273 was well-tolerated, with negligible incidences of nausea and vomiting across all arms of the study. Trends towards weight loss were also observed.
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
- Freeman J., Dunn I., Valcarce C. Beyond Topline Results for the Oral (Non-Peptide) GLP-1R Agonist TTP273 in Type 2 Diabetes: How much and When?; 53rd Annual Meeting of the European Association for the Study of Diabetes (EASD) held in Lisbon, Portugal, September 11–15, 2017
- Freeman J., Soeder T., Dunn I., Valcarce C. Is Less More? Learning to Dose the Oral, Nonpeptide GLP-1R Agonist, TTP273 in Type 2 Diabetics; Presented at the American Diabetes Association 77th Scientific Sessions in San Diego, CA, June 9-13, 2017
- Freeman J., Dvergsten C., Dunn I., Valcarce C. TTP273, Oral (Nonpeptide) GLP-1R Agonist: Improved Glycemic Control without Nausea and Vomiting in Phase 2; Presented at the American Diabetes Association 77th Scientific Sessions in San Diego, CA, June 9-13, 2017
- Freeman J, Agolory J, and Valcarce C. Preclinical Findings with Oral GLP-1 Receptor Agonist TTP273 Reinforce Importance of Neuro-Enteroendocrine Signaling; Presented at the American Diabetes Association 76th Scientific Sessions, June 12, 2016, New Orleans, Louisiana
- Freeman J, Gustafson S, Dunn I, Burstein A, and Valcarce C. Oral Small Molecule GLP-1 Receptor (GLP-1R) Agonists for Type 2 Diabetes (T2DM) with Negligible Nausea and Vomiting; Presented at the Keystone Symposia on New Therapeutics for Diabetes and Obesity, April 18, 2016, La Jolla, California – View Presentation Slides
- Freeman J, Weaver S, Davis S, Rao M, Quada J, Santhosh K, Yokum S, Polisetti D, Andrews R, Tabrizifard S, Sturchler E, McDonald P, Agolory J, Gustafson S and Valcarce C. TTP273: Oral, G protein Pathway Selective Clinical-Stage GLP-1 Receptor (GLP-1R) Agonist; poster presented at the Keystone Symposia on G-Protein Coupled Receptors: Structure, Signaling and Drug Discovery, held in Keystone, Colorado. February 22, 2016
- Gustavson, S.TTP273, an Orally-Available Glucagon-like Peptide-1 (GLP-1) Agonist, Notably Reduces Glycemia in Subjects with Type 2 Diabetes Mellitus (T2DM); (Abstract # 155-OR) Presented at the 74th Annual Scientific Session of the American Diabetes Association, June 13, 2014, San Francisco, California
- Gustavson, S.TTP054, a Novel, Orally-Available Glucagon-like Peptide-1 (GLP-1) Agonist, Lowers HbA1c in Subjects with Type 2 Diabetes Mellitus (T2DM); (Abstract # 156-OR) Presented at the 74th Annual Scientific Session of the American Diabetes Association, June 13, 2014, San Francisco, California
- Gustavson, S. TTP054, a Novel, Orally-Available Glucagon-Like Peptide-1 (GLP-1) Agonist: Results from a 28 Day Study in Subjects with Type 2 Diabetes Mellitus (T2DM); (Presentation) Presented at the 73rd Annual Scientific Session of the American Diabetes Association, June 21, 2013, Chicago, Illinois.