M-054 Model Based Development Strategies for Covalent Molecules

Objectives: Covalent binding mechanisms offer unique opportunities in drug development, and have been utilized to overcome various development challenges, such as dosing frequency, poor pharmacokinetic (PK) properties and toxicity. However, the interconnection between various factors, such as target turnover, binding kinetics, covalent kinetics (CK), and PK makes identifying the best approach challenging. This report is intended to provide guidance on strategies for developing covalent molecules under various scenarios to improve compound profile, using PKPD modeling.