ART0380 (ATR inhibitor)

Our orally dosed ataxia telangiectasia and Rad3-related protein (ATR) inhibitor, ART0380, has the potential to induce DNA damage in sensitive cancer tissue while preserving DNA integrity in healthy tissue. ART0380 is being developed as an oral anticancer agent as both a monotherapy and in combination with established as well as novel agents that cause DNA damage or suppress a cancer cell’s ability to repair DNA damage.

ART0380 is an orally available ATR inhibitor that has a distinct PK profile giving it the potential to exploit the difference in DNA repair capacity between tumor and normal cells. We believe ART0380 has the potential therapeutic advantage over some current oral clinical stage ATR inhibitors by reducing dose limited toxicities associated with continuous inhibition of ATR in bone marrow. Specifically, preclinical and preliminary clinical data suggest that ART0380 is rapidly absorbed, leading to a high concentration that we believe will induce DNA damage in sensitive DDR defective cancer tissue, and then is quickly eliminated, potentially preserving DNA integrity in DDR competent, normal tissue.

This PK profile has the potential to be better suited to drugs that inhibit ubiquitously expressed targets, like ATR. We have preclinical data that shows ART0380 has single agent activity in sensitive tumors including those with ATM deficiencies, works well in combination with DNA damaging agents such as gemcitabine and has a synergistic anti-tumor effect when dosed with a PD1 inhibitor in in vivo models. We achieved IND approval for ART0380 in December 2020. ART0380 is currently being evaluated in a Phase 1/2 clinical trial as a monotherapy in patients who have ATM null tumors and in combination with gemcitabine in patients with ovarian cancers.