Metabolic Drug Candidates

Liver-directed THR Beta Agonist

In December 2008, VIA exclusively licensed from Roche a liver-directed Thyroid Hormone Receptor (THR) beta agonist that is a clinically ready candidate for dyslipidemia to lower LDL cholesterol, triglyceride levels and Lp(a). The THR beta agonist is an orally administered, small-molecule beta-selective Thyroid Hormone Receptor agonist designed to specifically target receptors in the liver involved in metabolism and cholesterol regulation, and avoid side effects associated with Thyroid Hormone receptor activation outside the liver. The mechanism by which THR beta lowers cholesterol is distinct from statins and is believed to primarily be mediated by increased cholesterol excretion out of the body through the bile. The compound also reduces triglycerides in the liver by increasing fat metabolism. Preclinical studies demonstrated a rapid reduction of non-HDL cholesterol and the drug was shown to be synergistic with statins in animal studies. VIA will investigate the possibility of using the THR beta agonist alone or in combination with statins for the treatment of hypercholesterolemia in high risk patients whose LDL cholesterol is not controlled by statins alone. In addition, in animal studies, insulin sensitization and glucose lowering were observed making this compound a possible treatment of patients with type 2 diabetes in combination with other diabetes medications.

DGAT1

In December 2008, VIA exclusively licensed from Roche multiple compounds from Roche’s preclinical DGAT1 metabolic disorders program that targets the treatment of type 2 diabetes and has potential benefit in dyslipidemia and body weight loss. DGAT1 is an enzyme that catalyzes triglyceride synthesis and fat storage. Triglycerides are the principal component of fat, which is the major repository for storage of metabolic energy in the body. Overweight and obese individuals have significantly greater triglyceride levels, making them more prone to diabetes and its associated metabolic complications. DGAT1 inhibitors are an innovative class of compounds that may modify the way that lipids are absorbed in the intestine leading to elevation of peptides. In studies of obese animals, DGAT1 inhibitors have been shown to induce weight loss and improve insulin sensitization, glucose tolerance and lipid levels. These observations suggest DGAT1 inhibitors may have the potential to treat obesity, diabetes and dyslipidemia. VIA intends to identify potential clinical candidates from the compounds in this program and determine which compounds may be moved into further preclinical development.

Additional Compounds

VIA’s business development team remains focused on identifying additional clinical and pre-clinical compounds to add to the VIA development pipeline.