ATZ-IEP

ATZ-IEP is a novel targeted protein degradation (TPD) therapeutic candidate consisting of the anti-PD-L1 monoclonal antibody atezolizumab (ATZ) non-covalently complexed with an internalization-enhancing peptide (IEP). While atezolizumab typically acts as a checkpoint inhibitor by blocking the PD-1/PD-L1 interaction without significant receptor internalization, the addition of the IEP platform facilitates the rapid internalization and subsequent lysosomal degradation of cell-surface PD-L1. This approach aims to overcome resistance in tumors with low PD-L1 expression by actively reducing protein levels rather than just blocking signaling. Preclinical studies in triple-negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC) models have demonstrated significant PD-L1 reduction via the lysosomal pathway, suggesting that the IEP platform can broadly convert non-internalizing antibodies into effective targeted protein degraders.

Other names

Atezolizumab-IEP complexATZ/IEP