Adenosine receptor antagonists and inhibitors of adenosine production are expected to be highly synergistic with other immuno-oncology mechanisms, as well as with chemotherapy. Because of the promise of the adenosine pathway, several adenosine receptor antagonists that were discovered years ago and initially developed for other indications have been repurposed for oncology. Using our expertise in medicinal chemistry and drug discovery, we have generated novel, small molecule dual antagonists of key adenosine receptors A2aR and A2bR. We believe that our lead molecule, AB928, is the first clinical compound that was designed specifically for its immune-stimulating properties. AB928 is currently in a Phase 1/1b program where it is being combined with our anti-PD-1 antibody and with immunogenic cell death (ICD) inducing chemotherapy in select tumor types. We have other product candidates in earlier stages of development that target the adenosine pathway, including a CD73 inhibitor (which blocks the generation of extracellular adenosine in tumors) that could be the first small-molecule inhibitor of CD73 to enter clinical trials.
Arcus is utilizing its small molecule discovery and development capabilities to create innovative cancer immunotherapies.
Arcus’s lead program targets the adenosine pathway, which has been shown to play a significant role in driving immuno-suppression in the tumor micro-environment.
We also have several small-molecule programs in earlier stages of discovery targeting other key pathways in immuno-oncology.
In addition to our small- molecule programs, we are advancing several antibody programs against other targets. Our lead antibody product candidate, AB122 an anti-PD-1 antibody, is currently being evaluated in a Phase 1 trial. We expect to initiate clinical trials in 2018 for AB154, our lead antibody product candidate which targets TIGIT. An important element of our strategy is the development of intra-portfolio combinations of our small- molecule and antibody product candidates, and we believe that many of these combinations will be the first to advance into clinical trials.