PETRA DIETERICH
Franchise Leader and Head of Scientific Leaders, Abzena

Abstract

Antibody drug conjugates (ADC’s) are nascent modalities that open the therapeutic window to allow high potent molecules to target specific tumour cell receptors. ADC’s are already established as the standard of care in breast cancer with Enhertu, Kadcyla and Trodelvy accounting for $4.1 Bn of the total $4.7 Bn ADC revenues in 2022. A further 460 novel ADC’s are in development for lung, gastric, ovarian and colorectal cancer alone with potential to superceed existing small molecule chemotherapies and capture a market of more than $140 bn.
Over the last 20 years, drug developers have invented a phlefora of technologies to supercharge antibodies via the conjugation with small molecules and this has created a toolbox of techniques to allow us to conjugate proteins and peptides with a variety of different molecules. Coupling of proteins with oligonucleotides allows us to create oligo drug conjugates which offer treatment solutions outside of the oncology space with potential in personalised medicines as well as high frequency conditions such as neurodenerative and respiratory diseases.
In this article we explore how we can use our toolbox of techniques to open more windows to hitherto untreated diseases.

Introduction
Bioconjugation is expanding the repertoire of drug modalities available to address previously intractable targets with precision and positively impact both rare and common life-limiting diseases. The most widely known examples are antibody drug conjugates (ADCs) and while the field is still relatively nascent, this modality has become increasingly prevalent in cancer treatments in the last 2 decades.

ADCs are designed to deliver highly potent small molecules through covalent binding to monoclonal antibodies that can target tumours through specific binding to receptors that are highly expressed on the surface of cancer cells. The superiority of ADCs in cancer treatment is substantiated by the high survival rates observed in clinical trials such as the DESTINY-Breast03 and DESTINY-Breast04 trials where Trastuzumab Deruxtecan (TDxd, marketed as Enhertu) extended progression free survival in 75.6% of patients with HER2-positive metastatic breast cancer (1). Whilst no direct head-to-head trials have been performed, response rates in trials with other small molecule Camptothecin analogs, utilising the same topoisomerase 1 in ...