Trevena Inc., a leader in the discovery of G-protein coupled receptor (GPCR) biased ligands, today announced the initiation of a Phase I clinical trial of TRV120027, a titratable i.v. agent designed for the treatment of acute decompensated heart failure. TRV120027 is a biased ligand that targets the angiotensin II type 1 receptor (AT1R) and induces a unique mode of signaling. It simultaneously blocks angiotensin-mediated G-protein signaling while stimulating AT1R-specific β-arrestin signaling. In preclinical studies, this biased signaling has demonstrated a unique range of biological effects that are highly advantageous to patients with acute heart failure.
“TRV120027 is the first biased ligand to be discovered and tested in humans,” stated Maxine Gowen, Ph.D., president and CEO of Trevena. “It is not only an exciting new approach to the treatment of acute heart failure, but represents the first of an entirely new class of agent targeting the most successful drug target family, the G-protein-coupled receptors (GPCRs). This next generation of safer and more efficacious GPCR drugs is the sole focus of Trevena’s drug discovery engine, and we are excited to bring forward the first biased ligand agent into human trials.”
The Phase 1 study of TRV120027 is a single-dose, dose escalation, crossover study in 2 cohorts of healthy subjects. The aims of the study are to assess the safety, tolerability and pharmacokinetics of TRV120027 when delivered as a 4-hour continuous infusion. In addition, exploratory measures of TRV120027’s pharmacology are being performed. The results of this study will inform dose selection and dosing regimens for subsequent studies of TRV120027 in patients with heart failure.
“Acute heart failure is a major health problem worldwide, and despite advances in the treatment of chronic heart failure, no safe and effective new treatments have been introduced for many years,” said David Soergel, M.D., vice president of clinical development at Trevena. “I am excited to be involved with such a promising new therapy that could provide great benefit to patients who currently have few effective options.”.