Proxygen added Merck to its partner roster on Wednesday, garnering an undisclosed upfront payment plus a potential $2.55 billion in milestones.
Pictured: Two business people shaking hands / iStock, Rawpixel
Proxygen has snagged its third collaboration with big pharma. The Viennese biotech added Merck to its partner roster on Wednesday, garnering an undisclosed upfront payment plus a potential $2.55 billion in milestones.
The molecular glue degrader space has caught fire since the 2013 discovery that thalidomide and its compounds could be used in this fashion. Where traditional therapeutics inhibit the activities of disease-causing enzymes, molecular glue degraders work to completely get rid of the troublesome proteins, Stephen Hinshaw, senior scientist at Stanford Cancer Center who is not associated with either company, told BioSpace.
“Unlike traditional inhibition, getting rid of something is irreversible. So that’s key.”
While other inhibitors such as kinase inhibitors are excreted or modified by the body, diminishing efficacy and allowing disease resurgence, molecular glue degraders hijack the body’s natural garbage disposal system, Hinshaw said.
Details of the partnership’s goal are scarce, but the duo will work together on therapeutic targets leveraging Proxygen’s discovery platform for molecular glue degraders, Proxygen CEO Bernd Boidol told BioSpace.
Proteolysis targeting chimeras (PROTACs) are molecules composed of two active domains and a linker that, like glue degraders, destroy disease-causing proteins.
Boidol pointed to two advantages of molecular glue degraders over PROTACs. Glue degraders are much smaller than PROTACs, with highly effective blood brain barrier penetration. PROTACs also require a ligandable site in the protein of interest, while glue degraders do not. Theoretically, the entire human proteome can be targeted with molecular glue degraders, he said.
While the currently approved glue degraders are for blood cancers, Hinshaw extoled the possibilities.
“There’s a lot of optimism right now that basically any disease indication will have a targetable factor that we just didn’t have access to before with conventional drugs,” he said.
The initial discovery of molecular glue degraders was serendipitous, with discoveries happening by chance. This is where Boidol believes Proxygen has a competitive edge.
Its platform can identify glue degraders in a systematic way. That allows for a “very broad net to go fishing” for potential targets, with a scalable approach that can potentially reveal undiscovered ligases while also screening for chemical diversity, he said.
Three’s the Charm
Big pharma appears to be on board with Proxygen. The biotech previously inked a collaboration with its German neighbor Merck KGaA in June 2022 valued at $554 million. While financial details of Proxygen’s 2020 deal with Boehringer Ingelheim were not disclosed, Boidol confirmed that Wednesday’s deal with Merck & Co. is the company’s largest.
In addition to its partnered programs, Proxygen’s internal pipeline is pushing toward the clinic. With the recent influx of funds, Boidol said the company will strategically expand its current headcount of 30–40 with an emphasis on maintaining the company culture.
Merck did not return BioSpace’s request for comment.
Kate Goodwin is a freelance life sciences writer based in Des Moines, Iowa. She can be reached at kate.goodwin@biospace.com and on LinkedIn.
