Merck & Co. has formed a strategic collaboration with Arvinas LLC, a private biotechnology company creating a new class of drugs based on protein degradation, in which Arvinas' PROTAC technology will be used to degrade target proteins with the goal of creating novel therapeutics. The multi-year collaboration will encompass multiple disease targets across several therapeutic areas.

While the specifics of the financial arrangements were not disclosed, Arvinas will receive an up-front payment and funding to support Merck-related research. Additionally, Arvinas could earn up to $434 million if all research, development, regulatory and commercial milestone payments are successfully paid for products against all the targets initially selected by Merck, as well as tiered royalties. Merck may, at its discretion, elect to expand the collaboration to include additional disease targets. This decision would trigger an additional one-time payment, as well as payment of milestones and royalties on a product-by-product basis.

PROTACs, or proteolysis-targeting chimeras, are bifunctional small molecules that target proteins for degradation and removal from a cell. These molecules induce a cell's own “quality control machinery” to bind to a particular protein and “label” it for degradation, thus removing a protein from the system. This contrasts to a more traditional drug-development approach that inhibits proteins. Arvinas is focused on developing new small-molecule strategies aimed at degrading disease-causing cellular proteins. Its protein degradation technology uses small-molecule drugs to “tag” specific proteins to be degraded by the ubiquitin/proteasome system (UPS), which is responsible for the normal turnover of most proteins within the cell. The Arvinas platform technology (PROTAC) is used to induce the loss of intracellular proteins. The ability of PROTAC-based drugs to induce protein degradation (instead of protein inhibition) offers the advantage of potentially targeting “undruggable” as well as “druggable” elements of the proteome.

Source: Arvinas