XB404

XB404 is a masked antibody-drug conjugate (ADC) designed to target both Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR1) and Receptor Tyrosine Kinase-Like Orphan Receptor 2 (ROR2). Developed by Exelixis in collaboration with Catalent and utilizing Adagene's masking platform, XB404 is engineered to deliver a cytotoxic topoisomerase 1 inhibitor payload specifically to ROR1/2-expressing tumor cells while minimizing on-target, off-tumor side effects in healthy tissues. The "masked" monoclonal antibody component remains relatively inactive in systemic circulation and is activated (unmasked) within the tumor microenvironment, typically by tumor-associated proteases. Preclinical characterization has demonstrated potent in vitro cytotoxicity and internalization, as well as significant in vivo anti-tumor activity and tumor regression in various models, including non-small cell lung cancer (NSCLC) and triple-negative breast cancer (TNBC).