This online talk will be given by Elena de Orbe from AstraZeneca.

Registration is free. Click here to register.

Title: Design of antibody-drug conjugates with the aid of computational chemistry

Abstract: Antibody-drug conjugates (ADCs) have emerged as a powerful modality of oncology therapeutics for targeted
delivery since the first FDA-approval in 2000. ADCs comprise a small-molecule drug tethered to a monoclonal
antibody via a synthetic linker, and thus enable the selective delivery of a highly cytotoxic payload to specific
tumour cells expressing the target antigen. However, the design of ADCs with appropriate developability
properties is still challenging.
Here we have developed computational workflows to help to optimise key properties of these novel biologics.
On one hand, we can now identify reactive amino acids on the antibody surface for site-specific conjugation of
linker-payloads, leading to more homogenous and stable ADCs with improved physicochemical properties. On
the other hand, we have investigated how to predict and minimise the ADC aggregation propensity, a well-
known issue for the development of these macromolecules. Through modelling, we aim to accelerate the design
of the next generation of ADCs with optimal properties for cancer patients.