The Austrian biotech company Proxygen GmbH has executed a new collaboration with a large pharma company to identify and develop compounds that can promote the degradation of disease-causing proteins. Known as molecular glue degrader therapies, these small molecule drugs accomplish their task by stabilising protein to protein interactions in the cell, enabling ubiquitin ligases to mark faulty or misfolded proteins for degradation.
Proxygen’s newest collaborator is Merck & Co Inc, which has agreed to make an upfront payment to the Austrian company of an undisclosed size and commit to milestone payments of up to $2.55 billion pending the successful development and commercialisation of new products. The target diseases were not identified.
The collaboration was announced on 5 April, less than three years after Proxygen entered a similar agreement with Boehringer Ingelheim GmbH focused on cancer, and 10 months after it secured a deal with Merck KGaA.
According to Robert Garbaccio, head of discovery chemistry at Merck’s European subsidiary MSD, advances in scientists’ understanding of molecular glue degraders are creating new opportunities. Specifically, proponents say the approach enables scientists to design drugs that modulate protein classes which are currently inaccessible.
Bristol Myers Squibb Co is active in the field, and in May 2022 renewed a long-term agreement with Evotec SE to develop molecular glue degraders for oncology and possibly for diseases of the central nervous system. BMS is the acquirer of Celgene Corp which itself was heavily invested in molecular glue degradation technology. Celgene’s portfolio included the cancer drugs lenalidomide (Revlimid) and pomalidomide (Pomalyst), analogues of thalidomide. Thalidomide is considered one of the first molecular glue degrader compounds, according to the UK company Cell Guidance Systems.
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