Bayer buys into Arvinas protein degrader discovery platform

Bayer is paying $17.5 million upfront to US biotech Arvinas, tapping into a protein-targeting platform to seek new drugs for cardiovascular and gynaecological diseases and cancer, as well as agricultural products.

The pharmaceutical end of the alliance includes $60 million in payments over five years – including an equity investment in Arvinas – with another $685 million on the cards if programmes move through the clinic and onto the market.

Arvinas’ drug discovery platform is based on the creation of proteolysis-targeting chimeras or PROTACs, which harness the body’s natural protein-denaturing machinery to remove rogue proteins associated with disease.

According to Arvinas its PROTAC compounds sidestep the need to develop drugs that bind to and inhibit protein active sites, and means that proteins which until now have been considered undruggable can now be targeted.

PROTACs are bifunctional molecules that use one arm to bind to a target protein, and the other to an enzyme involved in the main ubiquitin proteasome pathway involved in breaking down proteins.

Bayer’s head of pharma R&D Joerg Moeller said that because PROTACs don’t inhibit proteins directly but bind tightly “it may be possible to retool previously ineffective inhibitor molecules as PROTACs.”

The German company will select the targets to be researched and will have rights to any drug candidates that emerge from the collaboration.

The Bayer deal comes shortly after Arvinas moved its first in-house candidate ARV-110 into clinical testing in men with metastatic castration-resistant prostate cancer (mCRPC) whose disease has progressed despite two or more prior lines of treatment.

ARV-110 targets the androgen receptor (AR) protein, and is intended to improve on current AR-targeted drugs that tend to be less effective in cases when the cancer has increased levels of androgen production or has mutations in the AR gene. It has been awarded fast-track status by the FDA.

The biotech is also working on other candidates for cancer as well as Alzheimer’s and Parkinson’s diseases. Arvinas’ chief executive John Houston said: “this collaboration enables us not only to expand our platform into new therapeutic areas, but also begins a new journey in applying our approach to agriculture.”

Arvinas has previously signed PROTAC research collaborations with Roche’s Genentech unit and Pfizer, as well as with Merck & Co/MSD although the latter deal expired last year.

It is one of a clutch of biopharma companies that are developing protein degrader-based drugs for human applications.

It is up against some heavyweight competition, including Novartis which is reported to be preparing to take its first degrader into the clinic this year, as well as smaller players such as Cedilla, C4, Mission, Forma and Kymera Therapeutics.