ADC-2419

ADC-2419 is a first-in-class CD38-directed degrader antibody conjugate (DAC) designed for the treatment of multiple myeloma. It consists of a human CD38-targeting monoclonal antibody conjugated via a cathepsin-cleavable linker to P5, a high-affinity IKZF1/3 degrader. The P5 payload acts as a molecular glue that allosterically reprograms the E3 ubiquitin ligase cereblon (CRBN) to induce the degradation of Ikaros (IKZF1) and Aiolos (IKZF3). By targeting CD38, ADC-2419 achieves specific delivery to myeloma cells, where the catalytic degradation of IKZF1/3 bypasses common resistance mechanisms associated with immunomodulatory imide drugs (IMiDs). Preclinical studies demonstrate potent cytotoxicity and complete tumor regression in xenograft models, outperforming parental CD38 antibodies.