HDZ-C123A

HDZ-C123A is a first-in-class CD123-targeting degrader-antibody conjugate (DAC) developed by HealZen Therapeutics for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). It consists of a humanized IgG1 monoclonal antibody targeting CD123 (IL-3Rα) conjugated to CDG0501, a potent GSPT1 (G1 to S phase transition 1) molecular glue degrader, via a tumor-enriched protease-cleavable linker. Upon binding to CD123 and internalization into target cells, the payload CDG0501 is released. CDG0501 recruits the E3 ubiquitin ligase cereblon (CRBN) to induce the ubiquitination and subsequent proteasomal degradation of GSPT1, leading to potent anti-tumor activity. This conjugation strategy is designed to improve the therapeutic index of GSPT1 degraders by restricting their activity to CD123-expressing hematologic malignancies.