Sgn-Cd33a In Combination With Cytarabine Or Hypomethylating Agents Demonstrates Enhanced Anti-Leukemic Activity In Preclinical Models Of Aml

Long-term survival rates for acute myeloid leukemia (AML) patients remain poor, highlighting the need for further treatment options. AML cells express the myeloid marker CD33, making them amenable to CD33-targeted therapy. SGN-CD33A is a novel anti-CD33 antibody-drug conjugate (ADC) composed of a humanized antibody conjugated to a highly potent DNA-binding pyrrolobenzodiazepine (PBD) dimer drug via a protease-cleavable dipeptide linker. An engineered cysteine on each heavy chain attaching the PBD dimer to the antibody allows uniform drug loading of approximately two PBD dimers per antibody. Upon binding to CD33 on the cell surface, SGN-CD33A is internalized, the linker is cleaved by proteases in the lysosomes, and the released drug forms DNA crosslinks, resulting in cell death.