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Adenosine A₂ₐ antagonist

Extracellular adenosine is a signaling molecule known to inhibit immune function. High levels of adenosine and adenosine-producing enzymes are found within the tumor microenvironment. The adenosine A2a receptor is the main adenosine receptor expressed on immune cell subsets including T cells, NK cells and dendritic cells. Binding of adenosine to the A2a receptor on immune cells suppresses the activation and effector functions of these anti-tumor immune cells and promotes an immune-suppressive phenotype. This allows the tumor to grow.

Scientific data have demonstrated that disruption of the adenosine-cancer-immune cell axis by inhibiting the A2a receptor promotes anti-tumor immune responses and leads to tumor regression. Several clinical development programs in oncology are currently ongoing with compounds that were initially developed for Parkinson Disease. However, these compounds were designed as competitive antagonists to be active in the central nervous system of patients to offset the neurotransmitter imbalance in that neurodegenerative disease. These compounds have been repurposed for oncology indications but have limited efficacy to reduce the immunosuppressive effects of high levels adenosine that are found in the tumor microenvironment. To date, these compounds have been only modestly effective and have potential side effects related to their brain penetration.

iTeos has created and patented selective proprietary A2a receptor antagonists, which inhibit suppression of T-cell activation even at high adenosine levels found in tumors. Our drugs were confirmed to work in preclinical models and increase cytotoxic activity and promote anti-tumor efficacy in mouse tumor models. iTeos A2a receptor antagonists are not brain-penetrant and the preclinical candidate from this research entered the clinical phase 1 in January 2019.

A2A Small Molecule Antagonist