Principia Biopharma Inc. is developing a pipeline of small molecule reversible covalent inhibitors it is betting will have fewer off-target effects and lower immunogenicity than irreversible inhibitors.

The company is using its chemistry technology to add a reactive cyanoacrylamide group to small molecules. The group forms a reversible covalent bond with an exposed cysteine residue in the active site of a target protein. When the protein denatures, the inhibitor falls off.