LZU-WZLYCS01

LZU-WZLYCS01 is a novel, preclinical-stage antibody-drug conjugate (ADC) targeting fibroblast growth factor receptor 3 (FGFR3) for the treatment of bladder cancer. Developed by Lanzhou University, the ADC consists of a humanized anti-FGFR3 IgG1 monoclonal antibody conjugated to 7-ethyl-9-fluorocamptothecin (A2), a potent camptothecin derivative, via thiol-based chemistry. Upon binding to FGFR3 on bladder cancer cells, LZU-WZLYCS01 undergoes receptor-mediated endocytosis and lysosomal trafficking, where it is cleaved by lysosomal cathepsins to release the A2 payload. The released A2 payload directly binds to mitotic arrest deficient 2 like 1 (MAD2L1) at the Lys73 site, activating the cGAS-STING pathway and inducing apoptosis. LZU-WZLYCS01 has demonstrated robust antitumor efficacy, selectivity, and bystander effects in preclinical models, including patient-derived organoids (PDOs) and gemcitabine-cisplatin-resistant patient-derived xenografts (PDX).