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Going after GPCRs
July 2010
by David Hutton  |  Email the author
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KING OF PRUSSIA, Pa.—With a new collaboration announced recently, Trevena Inc. is working with a familiar partner in its ongoing research activities aimed at the development of biased G protein-coupled receptor (GPCR) ligand drugs—Scynexis.

Scynexis, located in Research Triangle Park, N.C., will provide medicinal chemistry services to support Trevena's ongoing research activities directed at the discovery of biased GPCR ligands. The collaboration's primary objective is to provide biased ligand tool compounds to the research community under the National Institutes of Health's (NIH) public access policy. Financial terms of the agreement were not disclosed, but the project will be funded by the NIH Grand Opportunities as part of economic stimulus efforts in the United States.

Trevena's biased ligands selectively turn on and off individual pathways at the GPCR, and in so doing provide an enhanced level of drug specificity. According to the company, specificity allows enhanced efficacy or decreased side effects to be designed into the drug candidate.

Trevena's emerging pipeline of highly differentiated biased ligand drugs is focused on therapy areas that have significant unmet medical needs such as cardiovascular disease, central nervous system pain, inflammation and oncology supportive care. Trevena recently announced the initiation of a Phase I clinical trial with TRV120027, a first-in-class agent that could provide a major advance in the treatment of acute heart failure, due to its unique spectrum of biological effects. TRV120027 is the first biased ligand to be discovered and tested in humans.

Trevena's second program is a small-molecule G-protein biased ligand in pain, currently in lead optimization. Trevena also has a number of early-stage discovery projects.
"Our early discovery efforts have been so productive that we require additional chemistry resources to fully optimize the portfolio of biased leads we have discovered," says Dr. Maxine Gowen, CEO of Trevena. "Scynexis is ideally suited to provide that capability."

Founded in 2000, Scynexis is a global contract research organization (CRO) that has built a pipeline of novel drug candidates based on the new area of cyclophilin inhibition. According to Scynexis, cyclophilin inhibitors represent a class of drugs that hold significant potential for the treatment of a broad range of diseases. Scynexis' drug discovery and development services are available on a fee-for-service basis or may be conducted in a shared risk arrangement.

Trevena worked previously with Scynexis in 2008, notes Dr. Yves Ribeill, president and CEO of Scynexis.

"Scynexis has a history of successful collaboration with Trevena, and we are pleased to undertake this new project with them and their innovative approach to GPCR technology," Ribeill adds.

Dennis Yamashita, Trevena's head of chemistry, says the company was impressed by the quality of Scynexis' management and its medicinal chemistry research abilities, "so the decision to initiate a formal collaboration between Trevena and Scynexis in 2010-2011 was an easy decision."

"Trevena had a positive previous experience working with Scynexis," Yamashita says. "Trevena needs to work with U.S.-based CROs on lead progression."

Yamashita points out the collaboration with Scynexis also will help Trevena optimize the portfolio of biased leads it has discovered.

"Scynexis will work alongside Trevena chemists to help optimize our biased lead hits identified from high-throughput screens," he notes. "They will provide medicinal chemistry support to enable us to explore a greater number of chemotypes."
 
 
Code: E071019

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