Ubiquitin activating enzyme protein E1
Credit: PASIEKA/Getty Images

With the goal of “drugging the undruggable,” developer of molecular glue degraders Proxygen has announced a multi-year research collaboration and license agreement with Merck & Co (known as MSD  outside North America). In a deal potentially worth up to $2.55 billion. The companies will identify and develop drugs against multiple undisclosed therapeutic targets.

Glue degrader companies are making plenty of deals and netting financing. Last year, for example, BMS made a deal worth $550M with SyntheX and extended its agreement with Evotec in this arena, which could be worth up to $5B.

Proxygen already has partnerships with Merck KGaA and Boehringer Ingelheim.

Under the terms of this agreement Merck (MSD), Proxygen will receive an undisclosed upfront payment and be eligible for future payments of up to $2.55 billion on the achievement of specified research, development, and commercial. Additionally, Proxygen is eligible to receive royalties on net sales of any such products.

Molecular glue degraders are small, drug-like compounds that induce interactions between an E3 ubiquitin ligase and a molecular target. This induced interaction results in ubiquitination and subsequent degradation of the target protein. The protein is not inhibited. Rather it is eliminated.

Revlimid and Pomalyst are two successful glue degraders that were discovered fortuitously.  The goal now it to be able to find more such drugs on scale.

“We are very excited to announce this collaboration with MSD and look forward to combining our innovative platform technology and unique expertise in identifying novel molecular glue degraders with MSD’s world class research and development capabilities. This partnership provides us with the framework and resources to further leverage our platform for the discovery of new drugs against challenging targets,” says Bernd Boidol, PhD, chief executive officer of Proxygen.

Proxygen is a spinout of the Center for Molecular Medicine of the Austrian Academy of Sciences. It was founded in 2020 by Giulio Superti-Furga, who is now on the board; Matthias Brand, Chief Scientific Officer; and Stefan Kubice, special adviser. Proxygen is part of a ripe field that is trying to make new therapeutics that modulate protein classes previously untapped by drug developers.

“Advances in our understanding of molecular glue degraders are opening exciting new avenues in the pursuit of novel therapeutic mechanisms,” said Robert M. Garbaccio PhD, vice president and head of Discovery Chemistry at MSD. “We look forward to working with the Proxygen team to advance this promising area of research and evaluate new opportunities to treat disease.”

Because molecular glue degraders can modulate protein classes that cannot be reached by  traditional drug discovery approaches, they could unlock a large proportion of the undruggable target space. Proxygen reports it has developed a highly versatile, proprietary discovery engine supporting the specific and unbiased identification of molecular glue degraders against difficult-to-drug or completely undruggable targets at large scale.

The company says it has also generated knowledge and data in the discovery and chemical optimization of degrader molecules, positioning it as a pioneer in this novel modality.

Other players in this currently vibrant field include Arvinis, Avilar Therapeutics, Biotheryx, C4 Therapeutics, Degron Therapeutics, and Plexium.

Also of Interest