ADCS on the rise: A Trojan Horse Race for Patients

Antibody-Drug Conjugates (ADCs) have emerged as a major therapeutic approach creating new opportunities for a range of cancer treatments. The recent scientific and clinical progress in the ADC field underscores its importance for ongoing research.

- Léo Marx, Medicinal Chemistry & Bioconjugation Manager, Debiopharm

The first Antibody-Drug Conjugate (ADC) prototypes were developed more than 55 years ago by researchers of the Institut de Chimie des Substances Naturelles (Institute of Chemistry of Natural Substances, ICSN) who showed that chemotherapies such as Methotrexate covalently linked to polyclonal antibodies could deliver immunoglobin conjugates with improved cytotoxicity in vitro. It wasn't until the year 2000 that the modality achieved clinical validity with the approval of Mylotarg, an ADC based on a DNA alkylating payload. This milestone triggered an ever-growing diversity of clinical programmes, which first led to the emergence of antitubulin ADCs from 2010.

Despite the early successes of auristatin and maytansinoid-based ADCs (Kadcyla and Adcetris), the technology also suffered several setbacks leading to project discontinuations. Later on between 2019 and 2020, the approval of Padcev, Enhertu, and Trodelvy sparked renewed optimism for the therapeutic potential of ADCs. These precisely-designed ADCs have shown promising clinical outcomes, significantly reducing the risk of disease progression or death in breast cancer patients. Despite these advances and successful treatments such as Kadcyla and Enhertu, challenges persist due to high discontinuation rates across multiple payload mechanisms.