Data presented at Keystone Symposia on Molecular and Cellular Biology
KEYSTONE, CA, USA I February 22, 2016 I vTv Therapeutics Inc. (Nasdaq:VTVT), a clinical-stage biopharmaceutical company engaged in the discovery and development of new orally administered treatments for Alzheimer’s disease and diabetes, today announced that data from studies of its oral, small molecule GLP-1R agonist were reported at the Keystone Symposia on G-Protein Coupled Receptors: Structure, Signaling and Drug Discovery, held in Keystone, CO February 21-25, 2016.
Data presented showed that TTP273, vTv’s orally bioavailable GLP-1R agonist currently being evaluated in a Phase 2 trial, shows “functional selectivity” for a particular subset of the full GPCR signaling repertoire. “Functional selectivity” or “ligand bias” is an approach used by researchers to design drugs with improved efficacy or safety profiles. TTP273 is an allosteric standalone agonist that has demonstrated efficacy at lowering blood glucose in humans with better tolerability (very low incidence of nausea and vomiting), possibly making it an improved candidate for Type 2 diabetics over current GLP-1R analogues.
Patricia McDonald, Assistant Professor Department of Molecular Therapeutics at The Scripps Research Institute and coauthor of this work, stated: “GLP-1R G-protein biased ligands may offer new and unappreciated advantages in the context of chronic treatments. Further preclinical translational studies are ongoing to link the G-protein biased signaling with the absence of side effects such as nausea or cell proliferation.”
Study Details
In a poster presentation entitled, “TTP273: Oral, G-protein Pathway Selective, Clinical-Stage GLP-1 Receptor (GLP-1R) Agonist” researchers reported on TTP273, an orally bioavailable, small molecule GLP-1R agonist, along with data from studies using an earlier compound, TTP054. Current GLP-1R peptide-based agonists are available only as an injection, and while effective in lowering blood glucose and reducing weight, can cause serious gastrointestinal side effects in some patients, including nausea and vomiting.
Researchers evaluated receptor signaling through G-protein and ERK pathways, showing a relative selectivity of TTP273 for cAMP, with no significant activation of ERK at clinically relevant concentrations, unlike current injectable formulations. In mouse studies, TTP273 enhanced glucose-stimulated insulin secretion, decreased glucose levels following an Oral Glucose Tolerance Test, and decreased food intake.
In a Phase 1b study in Type 2 diabetics, TTP273 was found to be safe and well tolerated, with a low incidence of GI side effects. These results also showed that TTP273 was effective based on glucose measurements following a meal challenge.
vTv recently initiated the LOGRA Phase 2b study, a randomized, double-blind, placebo-controlled, parallel group trial evaluating the safety and efficacy of TTP273 in 156 Type 2 diabetics on stable doses of metformin. Data from this trial are expected to be reported by the end of 2016.
A copy of the poster will be made available in the Publications section of the vTv website.
About Type 2 Diabetes
Type 2 diabetes is the body’s inability to properly use insulin to control sugar in the bloodstream. It is the most common type of diabetes (representing 90 to 95% of diabetes patients), imposing a growing burden on healthcare systems globally. The goal of maintaining A1c levels below 7.0% is elusive for patients with this life-long disease. In addition to unregulated glucose, diabetics commonly have a variety of co-morbidities, including heart disease, stroke, high blood pressure, blindness, kidney disease, amputations, dental disease, and central and peripheral nervous system impairment.
About vTv Therapeutics Inc.
vTv Therapeutics Inc. is a clinical-stage biopharmaceutical company engaged in the discovery and development of orally administered small molecule drug candidates to fill significant unmet medical needs. vTv has a pipeline of clinical drug candidates led by programs for the treatment of Alzheimer’s disease and Type 2 diabetes as well as treatment of inflammatory disorders and the prevention of muscle weakness.
SOURCE: vTv Therapeutics
Post Views: 156
Data presented at Keystone Symposia on Molecular and Cellular Biology
KEYSTONE, CA, USA I February 22, 2016 I vTv Therapeutics Inc. (Nasdaq:VTVT), a clinical-stage biopharmaceutical company engaged in the discovery and development of new orally administered treatments for Alzheimer’s disease and diabetes, today announced that data from studies of its oral, small molecule GLP-1R agonist were reported at the Keystone Symposia on G-Protein Coupled Receptors: Structure, Signaling and Drug Discovery, held in Keystone, CO February 21-25, 2016.
Data presented showed that TTP273, vTv’s orally bioavailable GLP-1R agonist currently being evaluated in a Phase 2 trial, shows “functional selectivity” for a particular subset of the full GPCR signaling repertoire. “Functional selectivity” or “ligand bias” is an approach used by researchers to design drugs with improved efficacy or safety profiles. TTP273 is an allosteric standalone agonist that has demonstrated efficacy at lowering blood glucose in humans with better tolerability (very low incidence of nausea and vomiting), possibly making it an improved candidate for Type 2 diabetics over current GLP-1R analogues.
Patricia McDonald, Assistant Professor Department of Molecular Therapeutics at The Scripps Research Institute and coauthor of this work, stated: “GLP-1R G-protein biased ligands may offer new and unappreciated advantages in the context of chronic treatments. Further preclinical translational studies are ongoing to link the G-protein biased signaling with the absence of side effects such as nausea or cell proliferation.”
Study Details
In a poster presentation entitled, “TTP273: Oral, G-protein Pathway Selective, Clinical-Stage GLP-1 Receptor (GLP-1R) Agonist” researchers reported on TTP273, an orally bioavailable, small molecule GLP-1R agonist, along with data from studies using an earlier compound, TTP054. Current GLP-1R peptide-based agonists are available only as an injection, and while effective in lowering blood glucose and reducing weight, can cause serious gastrointestinal side effects in some patients, including nausea and vomiting.
Researchers evaluated receptor signaling through G-protein and ERK pathways, showing a relative selectivity of TTP273 for cAMP, with no significant activation of ERK at clinically relevant concentrations, unlike current injectable formulations. In mouse studies, TTP273 enhanced glucose-stimulated insulin secretion, decreased glucose levels following an Oral Glucose Tolerance Test, and decreased food intake.
In a Phase 1b study in Type 2 diabetics, TTP273 was found to be safe and well tolerated, with a low incidence of GI side effects. These results also showed that TTP273 was effective based on glucose measurements following a meal challenge.
vTv recently initiated the LOGRA Phase 2b study, a randomized, double-blind, placebo-controlled, parallel group trial evaluating the safety and efficacy of TTP273 in 156 Type 2 diabetics on stable doses of metformin. Data from this trial are expected to be reported by the end of 2016.
A copy of the poster will be made available in the Publications section of the vTv website.
About Type 2 Diabetes
Type 2 diabetes is the body’s inability to properly use insulin to control sugar in the bloodstream. It is the most common type of diabetes (representing 90 to 95% of diabetes patients), imposing a growing burden on healthcare systems globally. The goal of maintaining A1c levels below 7.0% is elusive for patients with this life-long disease. In addition to unregulated glucose, diabetics commonly have a variety of co-morbidities, including heart disease, stroke, high blood pressure, blindness, kidney disease, amputations, dental disease, and central and peripheral nervous system impairment.
About vTv Therapeutics Inc.
vTv Therapeutics Inc. is a clinical-stage biopharmaceutical company engaged in the discovery and development of orally administered small molecule drug candidates to fill significant unmet medical needs. vTv has a pipeline of clinical drug candidates led by programs for the treatment of Alzheimer’s disease and Type 2 diabetes as well as treatment of inflammatory disorders and the prevention of muscle weakness.
SOURCE: vTv Therapeutics
Post Views: 156
