Modeling ADC payload biology using Simulated Cells – Update

ADCs represent a new era of targeted cancer therapy with 15 approved drugs. However, over 100 discontinued ADC programs and a similar number of active clinical trials highlight the difficulties of identifying the optimal combination of antibody, target, payload, linker, drug-antibody ratio and indication. Understanding mechanisms and factors contributing to different levels of payload sensitivity remains unsolved, while clinical ADC toxicity profiles resemble the conjugated payloads’ alone. As part of our broader objective to support ADC development, we first focused on understanding payload biology to resolve toxicity and resistance related issues.In our study, computational cell models were built and evaluated to predict novel perturbation responses in mono- and combination therapy and rationalize biomarker effects.