YL242

YL242 is a novel, non-internalizing antibody-drug conjugate (ADC) designed to target soluble vascular endothelial growth factor (VEGF). Developed by MediLink Therapeutics using its proprietary Tumor Microenvironment Activable LINker-payload (TMALIN) technology, YL242 consists of an anti-VEGF monoclonal antibody conjugated to a novel DNA topoisomerase I inhibitor payload, designated as C24, via a protease-cleavable tripeptide linker. Unlike traditional ADCs that require cellular internalization and lysosomal degradation to release their payload, YL242 is engineered to be stable in systemic circulation and release its cytotoxic agent extracellularly within the tumor microenvironment (TME) upon cleavage by local proteases. This mechanism allows the drug to provide a dual therapeutic effect: the antibody component inhibits tumor angiogenesis by neutralizing VEGF, while the released payload exerts potent cytotoxic effects on nearby cancer cells through the bystander effect. YL242 is currently being investigated in clinical trials for the treatment of advanced solid tumors, both as a monotherapy and in combination with other agents such as pembrolizumab and chemotherapy.