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Immune-Onc - Model IO-202 - (Anti-LILRB4) Mechanisms of Action in Hematologic Malignancies Program
Immune-Onc’s lead program is IO-202, an antagonist antibody targeting the myeloid checkpoint LILRB4 (also known as ILT3). Immune-Onc has a Phase I trial underway to evaluate IO-202 as a potential treatment for acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML).
LILRB4, also known as ILT3, is an immune-modulatory transmembrane protein found on antigen presenting cells (APCs). LILRB4 inhibits APC activation and induces immune tolerance via T-suppressor cells. It is expressed on certain hematologic cancer cells and on immune suppressive myeloid cells in the solid tumor microenvironment. Immune-Onc and The University of Texas published pioneering research in Nature illuminating the role of LILRB4 in immune suppression and tumor infiltration in AML.
IO-202 is a first-in-class monoclonal antibody that antagonizes LILRB4 with high binding affinity and specificity. It has broad potential in blood cancers and solid tumors and presents an opportunity to become a pipeline in a product.
As the first T-cell activator for AML, IO-202 is being evaluated in a Phase I trial in two forms of blood cancers, AML and CMML. The company plans to evaluate IO-202 in solid tumors and other blood cancers in the near future. The U.S. Food and Drug Administration has granted IO-202 Orphan Drug Designation for treatment of AML in October 2020.
In hematologic malignancies, preclinical studies show that IO-202 converts a “don’t kill me” to a “kill me” signal by activating T cell cytotoxicity and converts a “don’t find me” to a “find me” signal by inhibiting infiltration of hematologic cancer cells.
In solid tumors, IO-202 has potential to be combined with anti-PD-(L)1, other immunotherapies, and/or immunogenic chemotherapy.
