Big Pharma eyes a slew of molecular glues

At the end of October, Novartis and Monte Rosa Therapeutics signed a deal to license the start-up’s VAV1 degrader MRT-6160 for possible use in immune conditions. The deal is just one in a series of molecular glue deals as Big Pharma eyes the growing field and the biotechs building it. Biogen and the start-up Neomorph, along with Pfizer and Triana Biomedicines, agreed to partnerships last month, and Takeda Pharmaceutical and the start-up Degron Therapeutics entered into a deal in June.

Molecular glues are usually small molecules that join two proteins, typically a target and another agent that prompts the cell machinery to degrade said target. PROTACs, or proteolysis-targeting chimeras, are another type of degrader; they have similar but distinct functionalities compared with molecular glues. If molecular glues are like double-sided tape that binds a degrader and target, PROTACs are like a bungee cord, with hooks connected to both targets and a string acting as a linker to join the two.

Shyra Gardai, chief scientific officer at the extracellular protein degradation start-up EpiBiologics, says Big Pharma’s recent interest in glue degraders is likely in anticipation of an upcoming readout of upcoming data for ARV-471, a PROTAC that degrades the estrogen receptor to treat breast cancer. It was jointly developed by Arvinas and Pfizer.

“The clinical data is proving out some of the key hypotheses or theories around degradation,” Gardai says.

Degraders like PROTACs and glues have historically seen more use in oncology, but Gardai says the pharmaceutical industry has shown growing interest in them for autoimmune disorders. Monte Rosa’s MRT-6160 is one of the first molecular glue degraders to make the leap to autoimmunity.

An analyst note from investment bank J.P. Morgan on Oct. 28 says the Novartis–Monte Rosa deal is a testament to MRT-6160’s viability in the immunology and inflammation arena ahead of likely Phase 1 trial results in the first quarter of 2025. It estimates that the cash influx from the deal is likely to extend the start-up’s runway by about 12 months and that share prices will continue their momentum until the readout.

Drugs for autoimmune disorders have to clear “a higher bar” for side effect profiles, Gardai says, so proof-of-concept studies are often done faster in oncology than immunology.

“Now that these modalities are better understood and people know how to mitigate the side effects, thinking about how that can be applied to autoimmunity is the next frontier,” she says.