Research supports that azenosertib may be highly synergistic when combined with KRAS-targeted cancer therapies, creating further significant opportunities for combination with other standard treatments.
NEW YORK and SAN DIEGO, April 2, 2024 (Globe Newswire) — Zentalis® Pharmaceuticals, Inc. (NASDAQ: ZNTL) is a clinical-stage biopharmaceutical company discovering and developing clinically differentiated small molecule therapeutics that target fundamental biological pathways in cancer. We will present a poster containing new preclinical data at the 2024 American Cancer Society Annual Meeting. The study (AACR) was conducted April 5-10, 2024 in San Diego. The study demonstrated that our WEE1 inhibitor, azenosertib, exerts synergistic antitumor activity when combined with KRAS.G12C inhibitor.
“As we advance azenosertib in multiple ongoing clinical studies, we continue to see the potential of azenosertib as monotherapy and in combination across a variety of tumor types and treatment settings,” said Mark Lackner, Ph.D., chief scientific officer at Zentaris. “Our understanding of its usefulness continues to grow.” “Azenosertib in KRAS-driven cancers when combined with KRAS by exploiting azenosertib’s mechanism of targeting common vulnerabilities associated with cell cycle dysregulation and high levels of replication stress and DNA damage in cancer.” We sought to evaluate the antitumor activity of.G12C inhibitor.Our preclinical data show that the combination of azenosertib and KRASG12C Inhibitors dramatically increase antitumor activity. This convincing approach warrants further investigation as a potential treatment option for KRAS patients.G12C tumor. ”
Azenosertib is a potent and selective inhibitor of WEE1, a master cell cycle regulator that slows cell cycle progression and allows DNA repair. Inhibition of WEE1 by azenosertib suppresses critical cell cycle checkpoints, impedes DNA repair, and increases DNA damage, leading to mitotic catastrophe and cell death. Previous studies have found that cancer cells characterized by cell cycle dysregulation and high levels of DNA damage are highly sensitive to azenosertib. KRAS is a potent oncogenic driver that causes unrestrained cell cycle progression while increasing replication stress and DNA damage accumulation.
A study to be presented at the 2024 AACR Annual Meeting evaluated the antitumor activity of azenosertib when administered in combination with KRASG12C Inhibitors sotorasib or adaglasib. Data demonstrated synergistic cell growth inhibition across the KRAS panel.G12C Use cell lines for both 2D and 3D assays.Additionally, administration of azenosertib in KRASG12C Inhibitor-sensitive and inhibitor-resistant xenograft models using non-small cell lung cancer, colorectal cancer, and pancreatic cancer cell lines showed not only monotherapy activity but also synergistic effects when used in combination with KRAS. Tumor growth inhibition was also demonstrated.G12C inhibitor.Additionally, long-term coadministration of azenosertib and KRASG12C Inhibitors extended the duration of response compared to single agent use. Together, these results support continued investigation into the potential clinical benefit of azenosertib as combination therapy.
Poster presentation details
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title:Selective WEE1 inhibitor azenosertib exhibits synergistic antitumor activity with KRASG12C Multiple KRAS inhibitorsG12C model
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author: Jameson, New Mexico et al.
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Date Time: Tuesday, April 9, 2023, 1:30pm – 5:00pm PT
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abstract numbers: 6487
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session: Targets kinase and ERK pathway
About azenosertib
Azenosertib is a novel selective and orally bioavailable WEE1 inhibitor currently being evaluated as monotherapy and combination clinical studies in ovarian cancer and other 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, preventing replication of cells with damaged DNA. By inhibiting WEE1, azenosertib allows cell cycle progression despite high levels of DNA damage, resulting in accumulation of DNA damage leading to mitotic catastrophe and cancer cell death.
About Zentaris Pharmaceuticals
Zentaris® Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company discovering and developing clinically differentiated small molecule therapeutics that target fundamental biological pathways in cancer. The company's lead product candidate, azenosertib (ZN-c3), has the potential to be his first-in-class and best-in-class WEE1 inhibitor for advanced solid tumors and hematologic malignancies. Azenosertib has been evaluated as a monotherapy and as a combination therapy across multiple clinical trials and has broad franchise potential. In clinical trials, azenosertib is well tolerated and has demonstrated antitumor activity as a single agent across multiple tumor types and in combination with several chemotherapy backbones. As part of the azenosertib clinical development program, the company is exploring enrichment strategies targeting tumors with high genomic instability, including cyclin E1-positive tumors, homologous recombination-deficient tumors, and tumors with oncogenic driver mutations. The company also leverages its extensive experience and capabilities across cancer biology and medicinal chemistry to advance research into proteolytic substances. Zentalis has operations in both New York and San Diego.
For more information, please visit www.zentalis.com. X/ Follow Zentalis on Twitter (@ZentalisP) and LinkedIn (www.linkedin.com/company/zentalis-pharmaceuticals).
Forward-looking statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to historical facts should be deemed forward-looking statements. Potential benefits of combining azenosertib with KRAS-targeted therapy. Potential benefits of azenosertib as monotherapy and combination therapy. Potential for azenosertib to be best-in-class and first-in-class. Franchise potential for azenosertib. Although the words “potential,” “intended” and similar terms are intended to identify forward-looking statements, not all forward-looking statements contain these specific words. Not. These statements are neither promises nor guarantees, but are subject to known and unknown risks and uncertainties and that our actual results, performance or achievements may be different from any future results, performance or achievements expressed or implied by such forward-looking statements. There are other important factors that can cause significant differences. Statements including, but not limited to: Our limited operating history may make it difficult to evaluate our current operations and predict our future success and viability. We have incurred, and expect to continue to incur, significant losses. Additional funds are required and may not be available. our plans, including the cost of developing diagnostic tools; our reliance on the success of our lead product candidates; The results of preclinical and initial studies may not predict the success of subsequent clinical trials. failure to identify additional product candidates and failure to develop or commercialize marketable products; Potential unforeseen events during clinical trials may result in delays or other adverse effects. risks related to regulatory approval processes or ongoing regulatory obligations; failure to obtain U.S. or international marketing approval; Our product candidates may cause serious side effects. Unable to maintain collaborations or if these collaborations fail. Reliance on Third Parties. Significant competitive effects. potential system failure or security breach; Risks Related to Intellectual Property. our ability to attract, retain and motivate talented personnel and risks associated with management transitions; the significant costs of operating as a public company; and other important factors, the Company's most recent periodic reports on Form 10-K or 10-Q and subsequent filings with the Securities and Exchange Commission (SEC) and the Company's other filings with the SEC. This is explained in the document under the caption “Risk Factors”. Such forward-looking statements represent management's expectations as of the date of this press release. Although we may elect to update such forward-looking statements at some point in the future, we undertake no obligation to do so, even if subsequent events cause our views to change. .
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contact:
Dr. Carlo Tanzi
Kendal Investor Information
ctanzi@kendallir.com