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IMGN632 + venetoclax is an investigational combination therapy under clinical investigation primarily for the treatment of **acute myeloid leukemia (AML)**, especially in patients with CD123-positive disease. IMGN632 (also known as pivekimab sunirine or PVEK) is an **antibody-drug conjugate (ADC)** targeting CD123 (interleukin-3 receptor alpha chain) and contains a high-affinity CD123 antibody conjugated via a cleavable linker to an indolinobenzodiazepine (IGN) DNA alkylating payload that induces single-strand DNA breaks. IMGN632 is designed for higher potency against AML blasts and leukemic stem cells, while minimizing toxicity to normal cells. Venetoclax is a **BCL-2 inhibitor** that induces apoptosis in malignant cells dependent on BCL-2 for survival. Preclinical and early clinical evidence indicates that the combination of IMGN632 and venetoclax is synergistic, as venetoclax impairs DNA damage response (DDR) pathways, thereby enhancing the cytotoxicity exerted by IMGN632 on AML cells. This combination is being evaluated with or without azacitidine in various ongoing clinical trials. Developed and manufactured by ImmunoGen (IMGN632) and AbbVie (venetoclax).
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