A2A Receptor Antagonist

The ATP-adenosine pathway is recognized as a key pathway that modulates immune responses in pathological conditions. We designed Inupadenant to inhibit the ATP-adenosine pathway by specifically targeting A2AR, which is the primary adenosine receptor on immune cells with a high affinity for adenosine. We also chose to target A2AR because we believe it is a key mediator of immunosuppression in this pathway as opposed to targeting upstream enzymes that are involved in production of adenosine in tumors. A2AR is expressed across a number of solid tumors and hematological malignancies with high unmet medical need making it a target with broad clinical potential. As elevated levels of adenosine in the tumor microenvironment are known to be immunosuppressive, we also designed Inupadenant to remain potent at high adenosine concentrations and maintain continuous target coverage. With this profile, we believe that Inupadenant has the potential for enhanced antitumor activity as compared to other A2AR antagonists currently in clinical development. We are planning to assess Inupadenant in combination with pembrolizumab and with chemotherapy, initially evaluating safety and tolerability of the combination regimens before enrolling expansion cohorts in select indications.

Adenosine pathway