Milvexian (BMS-986177/JNJ-70033093) is a small molecule, active-site inhibitor 
of factor XIa (FXIa) being developed to prevent and treat thrombotic events. The 
safety, tolerability, pharmacokinetics (PKs), and pharmacodynamics (PDs) of 
milvexian were assessed in a two-part, double-blind, placebo-controlled, 
sequential single ascending dose (SAD) and multiple ascending dose (MAD) study 
in healthy adults. Participants in SAD panels (6 panels of 8 participants; 
n = 48) were randomized (3:1) to receive milvexian (4, 20, 60, 200, 300, or 
500 mg) or placebo. The 200- and 500-mg panels investigated the pharmacokinetic 
impact of a high-fat meal. Participants in MAD panels (7 panels of 8 
participants; n = 56) were randomized (3:1) to receive milvexian (once- or 
twice-daily) or placebo for 14 days. All milvexian dosing regimens were safe and 
well-tolerated, with only mild treatment-emergent adverse events and no 
clinically significant bleeding events. In SAD panels, maximum milvexian plasma 
concentration occurred 3 h postdose in all fasted panels. The terminal half-life 
(T1/2 ) ranged from 8.3 to 13.8 h. In fasted panels from 20 to 200 mg, 
absorption was dose-proportional; results at higher doses (300 and 500 mg) were 
consistent with saturable absorption. Food increased milvexian bioavailability 
in a dose-dependent fashion. In MAD panels, steady-state milvexian plasma 
concentration was reached within 3 and 6 dosing days with once- and twice-daily 
dosing, respectively. Renal excretion was less than 20% in all panels. 
Prolongation of activated partial thromboplastin time was observed and was 
directly related to drug exposure. These results suggest that the safety, 
tolerability, PK, and PD properties of milvexian are suitable for further 
clinical development.