iTeos Therapeutics presents preclinical data on EOS-984

iTeos Therapeutics announced a poster presentation of preclinical data on EOS-984, a potential first-in-class small molecule inhibitor targeting the equilibrative nucleoside transporter 1 in oncology, at the American Association for Cancer Research Annual Meeting, being held April 5-10, 2024 in San Diego, California. Based on the company’s discovery and characterization of ENT1 in adenosine-mediated immunosuppression, this novel mechanism allows for the intracellular accumulation of adenosine, which then suppresses proliferation and effector function of T cells in the high adenosine tumor microenvironment. In mouse models, deletion of ENT1 led to potent control of tumor proliferation and increased CD8+ T cell frequency, proliferation, and cytokine production within tumors, further supporting ENT1’s role in tumor growth. In preclinical studies, blockade of intracellular adenosine accumulation by EOS-984 enabled proliferation of memory T cells and TILs despite high adenosine concentrations, resulting in the restoration of T cell function and enhanced tumor cell killing. Furthermore, combination of EOS-984 with anti-PD-1 therapy synergistically led to the control of tumor growth in a humanized mouse model of triple negative breast cancer resistant to anti-PD-1 blockade. Due to its mechanism of action, EOS-984 holds potential as a combination partner beyond anti-PD-1 therapy, including other immuno-oncology agents, cell therapies, and bispecific T cell engagers. EOS-984 is currently in the dose escalation portion of a Phase 1 trial in advanced malignancies. Topline data from the Phase 1 trial is anticipated in the second half of 2024.