The technological renaissance in covalent inhibitor technology over the past decade is impressive. Relatively recent advances in structure-based drug design have unlocked the tantalizing opportunity to engineer covalency into small molecules. Now, RA Capital has incubated and seeded Hyku Biosciences to unlock histidines, tyrosines, and lysines for covalent modification to greatly expand the druggable proteome.

Created through the fusion of parallel efforts at RA Capital and Atlas Venture, TRIANA is a newly launched biotech that is building its pipeline using a target-first, rational approach to molecular glue discovery.

As more established targeted protein degradation companies produce promising data in the clinic, newcomers have been greeted with sustained enthusiasm from the investment community. Here we revisit a few key intellectual and scientific breakthroughs & focus on molecular glues as an exciting new frontier.