Trevena, Inc., the leader in discovery and development of G-protein coupled receptor (GPCR) biased ligands, today announced that an article has been published describing the discovery and characterization of TRV130, a novel mu-opioid receptor biased ligand in development for the treatment of severe acute pain. The article illustrates how Trevena is able to translate the biased ligand hypothesis for the mu-opioid receptor, based on mouse knock-out data, into a differentiated molecule with a unique and beneficial profile. As a biased ligand, TRV130 stimulates the mu-opioid G-protein coupling to produce analgesia, without stimulating the β-arrestin pathway, thereby minimizing many opioid side effects. In preclinical studies, TRV130 was powerfully analgesic with an improved safety and tolerability profile when compared directly to morphine.
The article, entitled “A G protein-biased ligand at the μ-opioid receptor is potently analgesic with reduced gastrointestinal and respiratory dysfunction compared to morphine” was published online on January 8th, 2013 in the Journal of Pharmacology and Experimental Therapeutics (Link to JPET).
Michael Lark, Ph.D., Chief Scientific Officer of Trevena commented, “It is very exciting to have successfully validated the theory of biased GPCR ligands by designing molecules with the desired pharmacology that translate so well into preclinical studies. If we can demonstrate a similar therapeutic index advantage over morphine in humans, TRV130 has the potential to redefine the use of intravenous opioids for the management of severe post-operative pain.”
TRV130 is a first-in-class biased ligand that targets the mu-opioid receptor and optimizes analgesia while minimizing receptor-mediated adverse effects on gastrointestinal motility and respiratory effort. The drug recently completed a phase 1 first-in-human study, in which it was safe and generally well-tolerated. The next clinical study of TRV130 will investigate analgesic efficacy and tolerability in a direct comparison with intravenous morphine, a gold-standard post-operative analgesic.
About Post-Operative Pain
Intravenous opioids are used to manage the severe acute pain which results from an estimated 30 million surgical procedures in the US per year. Currently available opioid drugs such as i.v. versions of morphine, fentanyl and hydromorphone present physicians and patients with significant safety and tolerability problems, which often limit dose levels, and consequently leave up to 80% of patients enduring some degree of post-operative pain. Side effects include potentially dangerous respiratory depression, nausea, vomiting, exacerbation of post-operative ileus, and excessive sedation. There is a long-standing need for better post-operative pain drugs that have opioid-like analgesia, but which are safer to use and easier for patients to tolerate.
About Trevena and Biased Ligands
Trevena, Inc. is a clinical stage pharmaceutical company focused on discovering and developing the next generation of G-protein coupled receptor (GPCR) targeted medicines. GPCRs are the targets for at least one-third of modern medicinal products, and remain the predominant class of targets under clinical evaluation. Trevena’s expertise lies in engineering “biased ligands” that activate only the beneficial signaling pathways downstream of a GPCR to unlock new biology and avoid drug adverse effects. In addition to TRV130, Trevena’s pipeline currently includes a Phase 2 clinical stage angiotensin receptor biased ligand for acute heart failure, and discovery-stage programs for chronic pain and Parkinson’s disease. Trevena is based in King of Prussia, Pennsylvania and is backed by leading investors including Alta Partners, Healthcare Ventures, NEA, Polaris and Yasuda Enterprise Development Company.
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