NEW YORK, SAN DIEGO - 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 KRASG12C 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 KRASG12C inhibitors. Our preclinical data demonstrate that combining azenosertib with KRASG12C inhibitors dramatically enhances anti-tumor activity. This compelling approach warrants further investigation as a potential treatment option for patients with KRASG12C 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.

The research that will be presented at AACR Annual Meeting 2024 evaluated the anti-tumor activity of azenosertib when administered in combination with KRASG12C inhibitors sotorasib or adagrasib. The data demonstrated synergistic cell growth inhibition across a panel of KRASG12C cell lines in both 2D and 3D assays. Furthermore, administration of azenosertib in KRASG12C inhibitor-sensitive and resistant xenograft models, including using non-small cell lung cancer, colorectal cancer, and pancreatic cancer cell lines, demonstrated monotherapy activity as well as synergistic tumor growth inhibition when combined with KRASG12C inhibitors. In addition, extended administration of azenosertib combined with KRASG12C inhibitors increased the duration of response versus single agent use. Together, these results support continued study of the potential for azenosertib to provide clinical benefit as a combination therapy.

About Azenosertib

Azenosertib is a novel, selective, and orally bioavailable inhibitor of WEE1 currently being evaluated as a monotherapy and combination clinical studies in ovarian cancer and additional tumor types. WEE1 acts as a master regulator of the G1-S and G2-M cell cycle checkpoints, through negative regulation of both CDK1 and CDK2, to prevent replication of cells with damaged DNA. By inhibiting WEE1, azenosertib enables cell cycle progression, despite high levels of DNA damage, thereby resulting in the accumulation of DNA damage and leading to mitotic catastrophe and cancer cell death.

About Zentalis Pharmaceuticals

Zentalis Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company discovering and developing clinically differentiated small molecule therapeutics targeting fundamental biological pathways of cancers. The Company s lead product candidate, azenosertib (ZN-c3), is a potentially first-in-class and best-in-class WEE1 inhibitor for advanced solid tumors and hematologic malignancies. Azenosertib is being evaluated as a monotherapy and in combination across multiple clinical trials and has broad franchise potential. In clinical trials, azenosertib has been well tolerated and has demonstrated anti-tumor activity as a single agent across multiple tumor types and in combination with several chemotherapy backbones. As part of its azenosertib clinical development program, the Company is exploring enrichment strategies targeting tumors of high genomic instability, such as Cyclin E1 positive tumors, homologous recombination deficient tumors and tumors with oncogenic driver mutations. The Company is also leveraging its extensive experience and capabilities across cancer biology and medicinal chemistry to advance its research on protein degraders. Zentalis has operations in both New York and San Diego.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including statements regarding the potential benefits of combining azenosertib with KRAS targeted therapies; the potential benefits of azenosertib as a monotherapy and in combination; the potential for azenosertib to be best-in-class and first-in-class; the franchise potential of azenosertib. The terms potential, will and similar references are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.

ZENTALIS and its associated logo are trademarks of Zentalis and/or its affiliates. All website addresses and other links in this press release are for information only and are not intended to be an active link or to incorporate any website or other information into this press release.

Contact:

Carlo Tanzi

Email: ctanzi@kendallir.com

(C) 2024 Electronic News Publishing, source ENP Newswire