IK-364

IK-364 is a small molecule antagonist of the Aryl Hydrocarbon Receptor (AHR) developed by Ikena Oncology. It is currently in preclinical investigation for the treatment of Acute Myeloid Leukemia (AML), particularly in patients with FLT3-ITD mutations. AHR activation in AML is associated with immune resistance through the upregulation of HLA-E, a non-classical HLA molecule that inhibits natural killer (NK) cell activation. IK-364 has been shown to downregulate HLA-E expression on AML blasts and enhance susceptibility to NK-cell-mediated killing in vitro. High AHR expression in AML is also correlated with monocytic subtypes and poor immune response signatures, making AHR inhibition a potential strategy to augment immunotherapy in hematologic malignancies.