INCB090244 / Incyte - LARVOL DELTA

Small molecule PD-L1 inhibitor modulates expression of PD-L1 on the cell surface – a potential mechanism of blocking interaction with PD-1 (AACR-NCI-EORTC 2022) - "INCB090244 transiently increased PD-L1 homodimer levels on the membrane, followed by internalisation and downregulation of PD-L1, making it unavailable for interaction with PD-1. In contrast, the anti-PD-L1 antibody atezolizumab had no effect on PD-L1 homo-dimerization and did not reduce cell surface levels of the protein."

IO biomarker • Oncology

INCB090244, a potent small molecule that inhibits the PD-L1/PD-1 axis and functions similarly to PD-L1 antibodies (SITC 2021) - "INCB090244 is a small molecule that blocks the PD-L1/PD-1 interaction and restores T cell function similar to the clinical stage PD-L1 inhibitor INCB086550...In vivo, INCB090244 reduced tumor growth in CD34+ humanized mice bearing MDA-MB-231 tumors, to similar levels as atezolizumab...Biodistribution studies demonstrated higher subcutaneous and brain tumor penetration by INCB090244 compared to PD-L1 antibodies, suggesting a potential advantage of small molecule PD-L1 inhibitors in accessing intratumoral regions. These data further support the clinical evaluation of small molecule PD-L1 inhibitors as an alternative approach to immune therapy."

IO biomarker • Brain Cancer • Glioma • Oncology • Solid Tumor • CD34 • IFNG • IL2