Merck licenses Arvinas' protein-clearing technology

Merck & Co has signed a broad-ranging deal to develop drugs based on Arvinas' PROTAC technology, which causes proteins to be broken down and removed from cells.

In contrast to traditional drug development approaches which rely on the creation of molecules that inhibit protein functions, Arvinas has developed tagging system that binds to a target protein and causes it to be degraded and cleared via the cell's normal housekeeping processes.

Specifically, the PROTAC (proteolysis-targeting chimaera) involves the use of bifunctional small molecules that recruit an E3 ubiquitin ligase to a specific targeted protein, labelling it for elimination by the cell's ubiquitin/proteasome system (UPS).

Only around a quarter of the body's 20,000 proteins can be targeted using traditional methods - generally those that function as enzymes such as tyrosine kinases - and Arvinas says platform promises to greatly increase the proportion that is "druggable".

Merck has taken a multi-year license to explore the use of PROTAC (proteolysis-targeting chimaera) for multiple disease targets across various therapeutic areas, including oncology, and the deal could be worth up to $434m to Arvinas in upfront and milestone payments, plus tiered royalties.

Merck also has the option to extend the collaboration to include additional targets, which would trigger another upfront payment plus milestones and royalties.

The PROTAC platform derived from the work of Craig Crews, a Yale University scientist and founder and chief scientific advisor to Arvinas.

Crews was also involved with the launch of Proteolix, the company behind multiple myeloma therapy Kyprolis (carfilzomib) that was subsequently acquired by Onyx and then Amgen. His lab has also collaborated on the PROTAC technology with GlaxoSmithKline (GSK), which retains rights to develop drugs against specific targets under the terms of an agreement signed in 2012.

Arvinas was formed in July 2013 and has concentrated in the first instance in getting the PROTAC platform and a companion technology that relies on tagging proteins with hydrophobic tags - which also results in their degradation.

The company has retained rights to some core platforms - including a cancer candidate that it hopes to bring to the clinical testing stage next year.

The deal is another example of big pharma's returning appetite for licensing technology platforms along with individual product candidates, which was a takeaway message from this year's JPMorgan healthcare conference in San Francisco.