When conducting drug developability, it is important to bear in mind whether it is possible to scale up manufacturing while keeping the molecule stable. Erika Kovacs, Senior Bioassay Director at Abzena, discussed Abzena’s bioassay strategy and cytotoxicity assays that can be used throughout their clients’ programs. The company's key focus areas are ADCs and biologics.
Kovacs described ADCs as simple concepts but complex products, meaning that there are lots of demands on ADCs, such as binding selectively to receptors, trafficking to the lysosomes, releasing the payload, and then killing the cells via their mode of action.
When Kovacs and her team select a mab (monoclonal antibody) to progress into becoming an ADC, the next stage is to choose a bioassay to measure cytotoxicity, which can be daunting. Kovacs suggested that the early and late stages of drug development benefit from simple, robust luminescence endpoint assays like CellTiter Glo for screening and potency testing.
She advocated for CellTiter Glo because it is sensitive, simple, and user friendly. During the early stages, it is key to have reliable and reproducible data. Abzena helps facilitate this via data trending and using clinical benchmarks, both of which assist with early de-risking. Furthermore, they leverage historical data for optimal cell line selection and reproducibility.
In the middle stages of a program, things are more complicated according to Kovacs. It is vital to probe the system so that one can understand how a molecule behaves in various environments, such as co-cultures. Complex assays, including real-time imaging, 3D spheroid models, and co-culture bystander effect assays, are particularly valuable during lead optimisation to characterise molecule behaviour in a range of settings.
The bystander assay evaluates the bystander effect, where antigen-negative cells are killed due to proximity to antigen-positive cells. Unlike traditional assays, which often use supernatant transfer or endpoint flow cytometry, focusing only on negative cells, the bystander setup allows real-time monitoring of different cell populations simultaneously. In terms of clinical relevance, Kovacs said these assays explain why some ADCs like Enhertu are more effective in heterogeneous tumour environments, where others like Kadcyla may fail.
In a nutshell, Abzena offers integrated bioassay solutions for ADCs and other complex biologics. The company supports its clients from early R&D through manufacturing and regulatory requirements.
