EXS-21546

EXS-21546 is a highly selective small molecule antagonist of the adenosine A2A receptor (A2AR; ADORA2A), developed through a collaboration between Exscientia and Evotec. It was designed using artificial intelligence-driven drug discovery platforms. The drug is intended to inhibit A2A receptor signaling in immune cells, thereby counteracting the immunosuppressive effects of high adenosine levels in the tumor microenvironment—a mechanism that can limit the efficacy of checkpoint inhibitors in cancer therapy. Preclinical and early clinical data demonstrate potent and selective inhibition of A2A receptor signaling with low central nervous system exposure, supporting its use as an immuno-oncology agent. Clinical development has focused on advanced solid tumors, particularly relapsed or refractory renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC), often in combination with anti-PD-1 therapy[1][4][5][6][7][8][10].