Exploring the Potency and Pharmacokinetics of TP-2846: A Promising Anti-Leukemia Agent

The study analyzed the pharmacokinetics of TP-2846 in mice, rats, and monkeys using intraperitoneal, oral, and intravenous administration. In mice, TP-2846 showed high maximum concentration, half-life, and area under the curve when dosed intraperitoneally. Intravenous dosing in mice revealed different pharmacokinetic parameters at varying doses. Rats dosed intravenously and orally exhibited low oral bioavailability. Monkeys dosed intravenously at different levels showed increasing maximum concentration, half-life, and area under the curve. TP-2846's plasma exposure was dose-linear in mice and monkeys.

TP-2846's in vivo efficacy was tested in several leukemia mouse models, showing significant tumor growth inhibition, particularly in MV4-11 and HL-60 models. Comparatively, it outperformed cytarabine and tigecycline. Intravenous dosing in HL-60 models indicated a dose-response relationship with tumor growth inhibition. PK/PD modeling suggested that the area under the curve is the main driver of TP-2846's efficacy.

Overall, TP-2846 demonstrated promising pharmacokinetic properties and potent efficacy in mouse leukemia models, driven by the area under the curve. These findings, along with other favorable characteristics, support the ongoing pre-clinical development of TP-2846 as a potential new anti-leukemia drug. The study was presented at the American Association for Cancer Research Annual Meeting in 2019.