Zentalis Pharmaceuticals to Highlight Preclinical Data Demonstrating that WEE1 Inhibitor Azenosertib Exerts Synergistic Anti-tumor Activity with KRAS(G12C) Inhibitors at AACR Annual Meeting 2024

Research supports azenosertib’s potential to be highly synergistic in combination with KRAS targeted cancer therapeutics, creating an additional large opportunity to combine with other standard of care agents

NEW YORK and SAN DIEGO, April 02, 2024 (GLOBE NEWSWIRE) -- Zentalis Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical-stage biopharmaceutical company discovering and developing clinically differentiated small molecule therapeutics targeting fundamental biological pathways of cancers, will present a poster with new preclinical data at the 2024 Annual Meeting of the American Association for Cancer Research (AACR) taking place in San Diego April 5-10, 2024. Research demonstrated that the Company’s WEE1 inhibitor, azenosertib, exerts synergistic anti-tumor activity when combined with KRAS^G12C inhibitors.

"As we advance azenosertib in multiple ongoing clinical studies, our understanding of its potential utility as a monotherapy and in combination across diverse tumor types and treatment settings continues to deepen,” said Mark Lackner, Ph.D., Chief Scientific Officer of Zentalis. “By exploiting azenosertib’s mechanism, which targets common vulnerabilities related to cancer cell cycle dysregulation and high levels of replication stress and DNA damage, we sought to evaluate the anti-tumor activity of azenosertib in KRAS-driven cancers when combined with KRAS^G12C inhibitors. Our preclinical data demonstrate that combining azenosertib with KRAS^G12C inhibitors dramatically enhances anti-tumor activity. This compelling approach warrants further investigation as a potential treatment option for patients with KRAS^G12C tumors.”

Azenosertib is a potent and selective inhibitor of WEE1, a master cell cycle regulator that acts to slow cell cycle progression and enable DNA repair. Inhibition of WEE1 by azenosertib suppresses key cell cycle checkpoints, preventing DNA repair and increasing DNA damage, resulting in mitotic catastrophe and cell death. Previous research has determined that cancer cells, which are often characterized by cell cycle dysregulation and high levels of DNA damage, are highly sensitive to azenosertib. KRAS is a potent oncogenic driver that results in unchecked cell cycle progression while increasing replication stress and accumulation of DNA damage.