Olema Oncology KAT6 inhibitor compounds demonstrate anti-tumor activity

Olema Pharmaceuticals announced new preclinical data regarding the discovery of novel compounds targeting KAT6, an epigenetic target that is dysregulated in breast and other cancers. These data will be presented today at a poster session at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, ANE 2023, in Boston, Massachusetts. The poster, titled “The discovery of potent KAT6 inhibitors that demonstrate anti-tumor activity in preclinical models of ER+ breast cancer”, describes the discovery and preclinical characterization of orally bioavailable, potent KAT6A and KAT6B-selective inhibitors developed by Olema in collaboration with Aurigene Oncology. The poster highlights that: Olema KAT6 compounds were selective and potent against KAT6A and KAT6B with greater than250-fold selectivity over other KAT family members, including the essential genes KAT5 and KAT8; In KAT6-amplified and overexpressing breast cancer cell lines, Olema KAT6 compounds strongly inhibited cell proliferation whereas KAT6-low cell lines were insensitive to the compounds; Olema KAT6 inhibitor compounds caused dose-dependent tumor growth inhibition and tumor regression comparable to or better than a positive-control patented KAT6 inhibitor; Olema KAT6 inhibitor compounds are orally bioavailable with desirable pharmacokinetics; Olema KAT6 inhibitor compounds demonstrate histone target engagement and efficacy, as well as synergism with palbociclib or palazestrant.