A duo for protein degradation

NEW HAVEN, Conn.—Merck & Co., known as MSD outside of the United States and Canada, and Arvinas LLC, a biotechnology company specializing in the creation of a new class of drugs based on protein degradation, have launched a multi-year strategic collaboration. The two companies will apply Arvinas' novel PROTAC technology to degrade target proteins in hopes of creating novel therapeutics. This partnership will cover a number of disease targets across several therapeutic areas.

Arvinas' PROTACs, or proteolysis-targeting chimeras, are bifunctional small molecules that can target proteins for degradation and removal from a cell. The molecules use a cell's own quality-control infrastructure—the Ubiquitin/Proteasome System, which manages the normal turnover of most proteins within cells—to bind to particular proteins and label them for degradation. While the existing approach is to inhibit proteins, only 25 percent of the proteins in the body can be drugged using traditional approaches. It is thought that Arvinas' approach of protein degradation could act on “undruggable” targets to increase the array of disease-causing proteins that could be the targets of new drugs.

Per the terms of the agreement, Merck will pay Arvinas an upfront payment as well as funding to support Merck-related research, though no specific financial details were released. Arvinas also stands to receive up to $434 million in research, development, regulatory and commercial milestone payments if all milestones are met for products against all targets initially chosen by Merck. Arvinas is also eligible to receive tiered royalties. Merck has the right to elect to expand the collaboration to include additional disease targets, and should it choose to do so, the expansion would trigger an additional one-time payment, as well as further milestones and royalties on a product-by-product basis.

"We look forward to working with Merck to create novel drugs to address difficult targets, and we believe this alliance will maximize the value of Arvinas’ very exciting and innovative protein degradation technology," Dr. Manuel Litchman, president and CEO of Arvinas, said in a press release.

For Merck, this is the second agreement announced in a week. On March 31, the company announced that it had begun a clinical trial collaboration with Syndax Pharmaceuticals Inc., a late-stage biopharmaceutical company focused on developing and commercializing entinostat, its lead candidate. The companies will collaborate to evaluate the safety and efficacy of combining Syndax' entinostat, an investigational epigenetic therapy for treatment-resistant cancers, with Merck's KEYTRUDA (pembrolizumab), the first anti-PD-1 therapy approved in the United States. This Phase 1b/2 study will investigate the combination regimen in patients with either advanced non-small cell lung cancer or melanoma, and will be conducted in two parts: the Phase 1b portion will seek to evaluate the safety and tolerability of entinostat combined with KEYTRUDA, and the Phase 2 portion will evaluate the efficacy of entinostat and KEYTRUDA in patients with advanced non-small cell lung cancer or melanoma. Enrollment is expected to begin in the second half of this year

Financial terms were not disclosed, but the collaboration includes a provision whereby Merck and Syndax can extend the agreement to include a potential Phase 3 clinical trial.