ERK5 Inhibitor

KRAS mutations in the RAS signaling pathway occur in approximately 26% of all cancers. Although there has been recent progress with development-stage compounds that are designed to directly inhibit certain KRAS mutations, approximately 85% of KRAS mutations are not being addressed by current product candidates or approved therapies. We believe that inhibiting ERK5 provides an opportunity to address a high unmet medical need by modulating a key target downstream in the RAS signaling pathway.

In preclinical studies, we observed fewer tumors in genetically engineered KRAS mutant lung and pancreatic cancer mouse models where ERK5 was knocked out, as compared to wildtype control. We also observed that inhibition of the target using an ERK5 inhibitor tool compound blocked tumor growth in patient-derived KRAS mutated xenograft models. Additionally, in preclinical studies in KRAS primary human tumor models of lung and pancreatic cancer, we observed synergistic effects on tumor inhibition by combining an ERK5 inhibitor and trametinib, a mitogen- activated protein kinase, or MEK inhibitor.

We plan to pursue clinical development of oral ERK5 inhibitors both as single agent in KRAS mutated pancreatic and lung cancer and in combination with other targeted therapies to address resistance to MEK inhibitors. We anticipate nominating a development candidate and initiating IND-enabling studies in this program in the second half of 2021 and submitting an IND in the second half of 2022.