Asciminib is a potent, specific BCR-ABL1 inhibitor being developed for the 
treatment of patients with chronic myelogenous leukemia (CML) and Philadelphia 
chromosome positive acute lymphoblastic leukemia (Ph + ALL).Here, we present the 
results of human oral absorption, distribution, metabolism, excretion (ADME) and 
in vitro studies that together provide an overall understanding of the 
metabolism, distribution and clearance of asciminib in humans.Asciminib was 
rapidly absorbed with a maximum plasma concentration at two hours post-dose. 
Total radioactivity and asciminib showed similar terminal half-lives in 
plasma.Oral asciminib absorption ranged between a minimum of 33%, and a maximum 
of 57% based on the metabolite profiles of late time-point feces 
collections.Asciminib was eliminated mainly through feces via unchanged 
asciminib excretion and metabolism.Direct glucuronidation and oxidation were 
major metabolic pathways in human that were catalyzed predominantly by 
UDP-glucuronosyltransferase (UGT)2B7 and cytochrome P450 (CYP)3A4, 
respectively.The relative contribution of the glucuronidation pathway to the 
total clearance of asciminib via metabolism is estimated to range ∼28-58%, 
whereas the relative contribution of the oxidative pathway is estimated to range 
∼37-64%, based upon the maximum oral absorption in humans.