IO-202 + azacitidine

IO-202 + azacitidine is a combination therapy being investigated for the treatment of chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML). IO-202 is a first-in-class humanized IgG1 monoclonal antibody that targets leukocyte immunoglobulin-like receptor B4 (LILRB4, also known as ILT3), a cell surface receptor overexpressed in CMML cells. IO-202 binds with high specificity and affinity to LILRB4, leading to antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. This mechanism effectively converts a "don't kill me" signal to a "kill me" signal by activating T cell cytotoxicity and converts a "don't find me" signal to a "find me" signal by inhibiting infiltration of hematologic cancer cells. Azacitidine (Vidaza) is a standard hypomethylating agent administered at 75 mg/m² intravenously or subcutaneously on days 1-7 of each 28-day cycle. The combination has shown promising clinical benefits with acceptable tolerability in hypomethylating agent-naive CMML patients, with particularly strong efficacy in patients with high LILRB4 expression. Developed by Immune-Onc Therapeutics.