“compound 23” is an oral, selective Factor XIa inhibitor intended as an anticoagulation agent. Since the clinical translatability of FXIa inhibition in preclinical models hasn’t been established, this program was driven by activity in in vitro human plasma coagulation assays. The team was able to turn a 0.6 uM hit originally from a complement factor D program into a subnanomolar FXIa inhibitor with excellent selectivity. I was surprised to see that the carboxylate plays an important role in binding to the target and is essentially desolvated in the co-crystal structure, given its normally high desolvation penalty. It was also impressive to see high oral exposure for a zwitterion containing a primary amine as well as often rapidly-metabolized benzofuran and indole groups.