Zentalis Pharmaceuticals to Present Preclinical Azenosertib Data at ESMO 2024

About this update from Zentalis Pharmaceuticals, Inc.

Azenosertib shows synergistic anti-tumor effects in combination with topoisomerase I (TOP1) inhibitor-based antibody drug conjugates SAN DIEGO, Sept. 09, 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, today announced that the company will present preclinical data from its selective WEE1 inhibitor azenosertib at the European Society of Medical Oncology (ESMO) 2024 Congress, occurring September 13-17 in Barcelona, Spain. “The confluence of DNA damage induced by TOP1 inhibitors and cell cycle deregulation and genomic instability induced by azenosertib provides a mechanistic rationale for this combination, as well as more broadly with antibody drug conjugates (ADCs) utilizing these inhibitors as payloads,” said Mark Lackner, PhD, Chief Scientific Officer. “The preclinical data demonstrated this synergistic effect and suggest that azenosertib in combination with ADCs could be an important therapeutic approach in treating patients with advanced solid tumors.” Presentation Details:Poster #35P: The Selective WEE1 Inhibitor Azenosertib Shows Synergistic Antitumor Effects in Combination with Topoisomerase I Inhibitor-Based Antibody-Drug ConjugatesPresenter: Jianhui Ma, Zentalis Pharmaceuticals Poster Display Date: Sunday, September 15, 2024 Data in the abstract showed that the combination of azenosertib with TOP1 inhibitors demonstrated significant synergistic effects in all cell lines tested. In HER2+ breast cancer animal models, those treated with the combination of azenosertib plus trastuzumab deruxtecan (T-Dxd) resulted in 50% of animals showing complete tumor regression (CR), compared with no CRs in monotherapy arms. Significant combination effects were also observed in a HER2+ ovarian model and a HER2-low breast cancer model. These data suggest that azenosertib significantly improves the anti-tumor effect of TOP1 inhibitors as well as ADCs with TOP1 inhibitor payload and that the combination could be a generalizable therapeutic approach for improving responses to ADCs in patients with advanced solid tumors. About AzenosertibAzenosertib is a novel, selective, and orally bioavailable inhibitor of WEE1 currently being evaluated as a monotherapy and combination c...

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