Trevena Inc., the leader in the discovery and development of G-protein coupled receptor (GPCR) biased ligands, today announced that its scientists are presenting two posters featuring compelling preclinical pharmacology data on TRV120027 at the 14th Annual Heart Failure Society of America Meeting being held September 12-15, 2010 in San Diego. Both posters will be presented on Monday, Sept. 13, 2010. TRV120027 is the most advanced drug in Trevena's pipeline, and the first biased ligand to be tested in humans. Phase 1 clinical studies of the drug were successfully completed earlier this year. Trevena is working to develop TRV120027 for the treatment of acute decompensated heart failure.
Dr. David Soergel, Head of Clinical Development at Trevena, will present a poster highlighting the unique in vivo pharmacokinetic and pharmacodynamic profile of TRV120027, demonstrated in a rat model, including a reduction of systemic blood pressure and improved cardiac performance, coupled with a short half-life which will lead to rapid reversibility.
Dr. Guido Boerrigter of the Cardiorenal Research Laboratory at the Mayo Clinic will present a poster outlining joint preclinical work with Trevena that demonstrates for the first time the cardiorenal actions of a β-arrestin biased AT1R ligand. In a canine preclinical model of paced heart failure, TRV120027 showed a beneficial profile, causing cardiac unloading actions while preserving renal function.
While blocking angiotensin-mediated G-protein signaling at the AT1R receptor, TRV120027 simultaneously stimulates AT1R-specific β-arrestin signaling. In preclinical studies, this biased ligand has demonstrated a unique range of biological effects that will be beneficial for patients with acute heart failure. The Phase 1 study of TRV120027 was a single-dose, dose escalation, crossover study in two cohorts of healthy subjects. The aims of the study were to assess the safety, tolerability and pharmacokinetics of TRV120027 and the results will inform dose selection and dosing regimens for an upcoming study of TRV120027 in patients with heart failure.