LILRB4, also known as ILT3, is an immune-modulatory transmembrane protein found on antigen presenting cells (APCs). LILRB4 is expressed on certain hematologic cancer cells and on certain pathogenic cells involved in autoimmunity and inflammatory processes.

IO-202 has completed the dose escalation part of the first-in-human, multicenter, open-label Phase 1 study in the US and the data was presented at European Hematology Association (EHA) Congress in 2023. This Phase 1 trial is currently enrolling patients with newly diagnosed chronic myelomonocytic leukemia (CMML) patients who have not received any hypomethylating agents (HMA), studying IO-202 in combination with azacitidine (NCT04372433).

The U.S. Food and Drug Administration granted IO-202 Orphan Drug designation for treatment of AML in 2020, Fast Track designation for relapsed or refractory AML in 2022, Fast Track designation for relapsed or refractory CMML in 2023, and Orphan Drug designation for treatment of CMML in 2024.

Engineered and optimized using a proprietary bispecific antibody platform, IO-312 is a first-in-class LILRB4-directed bispecific monoclonal antibody with potential against AML and other hematologic malignancies. Preclinical data presented at the 2023 American Association for Cancer Research Annual Meeting demonstrate that IO-312 led to potent and specific killing of monocytic AML cells in vitro and in vivo. Additional design features include high affinity and specific binding to LILRB4 as well as low affinity binding to CD3 to maximize anti-tumor effect without cytokine release-related toxicities, excellent biophysical properties for efficient manufacturing, and cross-reactivity to non-human primate LILRB4 and CD3 to enable preclinical toxicology assessment for rapid advancement to the clinic.