IO-202
Immune-Onc is evaluating IO-202, a first-in-class humanized IgG1 monoclonal antibody with high affinity and specificity towards LILRB4 (also known as ILT3). IO-202 has two ongoing clinical studies in the U.S.:
IO-202 AML/CMML Phase 1
Phase 1 dose escalation has completed, which enrolled patients with acute myeloid leukemia (AML) or chronic myelomonocytic leukemia (CMML) as a monotherapy and in combination with azacitidine. Three expansion cohorts are now open to study IO-202 with a combination of azacitidine +/- venetoclax (NCT04372433). To date, IO-202 has been well tolerated with demonstrated clinical activity, both as a monotherapy and in combination with azacitidine. The U.S. Food and Drug Administration granted IO-202 Orphan Drug designation for treatment of AML in 2020 and Fast Track designation for relapsed or refractory AML in 2022.
IO-202 AML/CMML Phase 1b Expansion Cohorts
R/R LILRB4high monocytic AML
IO-202 + azacitidine
Newly diagnosed CMML
IO-202 + azacitidine
Newly diagnosed unfit LILRB4high monocytic AML
IO-202 + azacitidine + venetoclax
IO-202 Solid Tumor Phase 1
The second Phase 1 trial of IO-202 is currently enrolling patients with advanced solid tumors to evaluate IO-202 as a monotherapy and in combination with an anti-PD-1 in dose escalation phase (NCT05309187).
About LILRB4 (ILT3)
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 have published pioneering research in Nature illuminating the role of LILRB4 in immune suppression and tumor infiltration in AML.
About IO-202
IO-202 is a first-in-class antagonist antibody targeting LILRB4 in Phase 1 clinical development for the treatment of AML, CMML and solid tumors. It blocks the interaction of LILRB4 with multiple ligands, including ApoE and fibronectin, and has broad potential as an immunotherapy in both blood cancers and solid tumors. In hematologic malignancies, IO-202 has 3 mechanisms of action including activation of T cell cytotoxicity, reduction of leukemia tissue infiltration and ADCC or ADCP.
Preclinical studies showed that IO-202 converts a “don’t kill me” to a “kill me” signal by activating T cell killing and converts a “don’t find me” to a “find me” signal by inhibiting infiltration of blood cancer cells. In the context of solid tumors, preclinical data presented at the 2021 American Association for Cancer Research annual meeting demonstrate that IO-202 enhances dendritic cell function and T cell activation in vitro and inhibits tumor growth in an immune competent model in vivo.
IO-202 has two ongoing clinical studies in the U.S.: Its first Phase 1 trial is currently enrolling patients with acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML) to evaluate IO-202 in combination with azacitidine +/- venetoclax (NCT04372433). The U.S. Food and Drug Administration granted IO-202 Orphan Drug designation for treatment of AML in 2020 and Fast Track designation for relapsed or refractory AML in 2022.
The second Phase 1 trial of IO-202 is currently enrolling patients with advanced solid tumors to evaluate IO-202 as a monotherapy and in combination with an anti-PD-1 (NCT05309187).
“Typically, T cells are deployed by the body to eradicate cancer but when T cells are controlled by the environment and rendered inactive, they must be reactivated to fight cancer. As described in Nature, we believe LILRB4 is an important pathway that controls T-cell suppression in AML and with this discovery, we feel we have a compelling target.”
— DR. CHARLENE LIAO, CHIEF EXECUTIVE OFFICER, IMMUNE-ONC THERAPEUTICS
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 is evaluating IO-202 in solid tumors and plans to evaluate IO-202 in 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.