Abstract

Challenges and Opportunities in the Synthesis of Antibody Drug Conjugate Payloads

Jeremy Parker, Project Leader, AstraZeneca

Payloads for Antibody Drug Conjugates are typically highly complex molecules based on natural products, the preparation of which involves long and complex multi-step synthesies.  Process Chemistry is focussed on introducing new, more efficient routes (Route Design) and better, higher yielding steps (Process Design).  These activities can be applied to the preparation of Antibody Drug Conjugate Payloads, significantly reducing delivery times and campaign costs, as well as reducing the number steps that need to be performed in expensive high containment facilities. The high synthetic complexity of Antibody Drug Conjugate Payloads also drives the desire to identify alternative, simpler molecules.  The use of principal component analysis to analyse known lists of available cytotoxic molecules has the opportunity to promote the use of payloads that target alternative chemotherapeutic mechanisms as well as identifying those which are structurally simple and/or commercially available.