Bevacizumab

Median overall survival of 15.9 months in Cyclin E1-positive PROC, with 1–5 prior lines of therapy; safety profile in DENALI Part 1b was consistent with prior reportingMedian relative dose intensity was 84.6%, confirming high overall exposure to azenosertibDENALI Part 1b interim analysis adds to the body of evidence supporting Cyclin E1 protein expression as a predictive biomarker for azenosertib in platinum-resistant ovarian cancer SAN DIEGO, Oct. 23, 2026 (GLOBE NEWSWIRE) -- Zentalis® Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical oncology innovator advancing late-stage development of investigational first-in-class WEE1 inhibitor azenosertib as a biomarker-driven treatment approach for ovarian cancer, today presented results from an interim analysis of the DENALI Part 1b study (GOG-3066) as of a May 22, 2026 data cutoff, including the first overall survival analysis for azenosertib, at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid, Spain. "These data continue to build the body of evidence supporting azenosertib as a potential treatment in Cyclin E1-positive platinum-resistant ovarian cancer, underpinning our development approach through the ongoing registration-intended DENALI Part 2 and ASPENOVA Phase 3 confirmatory trials. For patients with Cyclin E1-positive PROC who have limited effective treatment options, we are working to deliver something that has not existed — a targeted, oral treatment that offers more convenience and choice," said Julie Eastland, Chief Executive Officer of Zentalis Pharmaceuticals. "The overall survival results from DENALI Part 1b are particularly meaningful given the poor prognosis associated with Cyclin E1-positive tumors and the heavily pretreated nature of this trial patient population," said Fiona Simpkins, M.D., Professor at the University of Pennsylvania Perelman School of Medicine and Lead Investigator for the DENALI study and The GOG Foundation, Inc. (GOG-F). "The separation in median overall survival between Cyclin E1-positive and Cyclin E1-negative patients — 15.9 months versus 7.5 months — strongly supports Cyclin E1 protein expression as a clinically relevant and predictive patient selection biomarker for azenosertib. Taken together with the response data and manageable adverse events, these findings provide important evidence supporting continued development of azenosertib in this biomarker-selected population with high unmet need." Updated DENALI Part 1b Efficacy ResultsAs of the May 22, 2026 data cutoff, DENALI Part 1b enrolled 102 patients with PROC regardless of Cyclin E1 protein expression who had received between one and five prior lines of therapy, with prior bevacizumab required. This was a heavily pretreated population: 97% had received a taxane, 91% bevacizumab, 55% a PARP inhibitor, and 15% mirvetuximab soravtansine, with a median of three prior lines of therapy. Cyclin E1 status was retrospectively determined by immunohistochemistry using a proprietary cutoff, with 94 patients evaluable (Cyclin E1 IHC-positive: n=48, 51%; Cyclin E1 IHC-negative: n=46). Overall Survival (OS): Cyclin E1 IHC-positive (n=48): median OS of 15.9 months (95% CI, 8.7–21.2); 31 events had occurred (65%)Cyclin E1 IHC-negative (n=46): median OS of 7.5 months (95% CI, 5.8–12.3); 34 events had occurred (74%) Objective Response Rate (ORR) and Duration of Response (DOR): ORR in response-evaluable Cyclin E1 IHC-positive patients (n=43): 37.2% (95% CI, 23.0–53.3)ORR in all Cyclin E1 IHC-positive patients (n=48): 33.3% (95% CI, 20.4–48.4)Median DOR: 5.5 months (95% CI, 4.5–15.9) The updated ORR includes a patient with a confirmed response after the prior cutoff. The current median DOR of 5.5 months reflects a more mature dataset with less censoring than the prior cutoff, including two patients with particularly durable responses exceeding 15 and 20 months. SafetyThe safety profile was consistent with prior reporting. The most common treatment-related adverse events (TRAEs) were nausea, fatigue, diarrhea, thrombocytopenia, decreased appetite, anemia, and neutropenia. The most common non-hematologic Grade ≥3 TRAE was fatigue (16%). Grade ≥3 hematologic TRAEs included thrombocytopenia (12%), anemia (11%), and neutropenia (11%). The median relative dose intensity was 84.6%, confirming that overall exposure to azenosertib remained high despite dose modifications. TRAEs led to dose interruption in 56.9% of patients, dose reduction in 43.1%, and discontinuation in 19.6%. Serious TRAEs occurred in 21.6% of patients. The ESMO slides inclusive of the full interim analysis dataset presented at the medical meeting are available on the Zentalis website under scientific publications at the following link: https://zentalis.com/science/scientific-publications/ About the DENALI Clinical TrialDENALI is a multi-part Phase 2 registration-intended clinical trial (NCT05128825, GOG-3066) studying azenosertib in patients with PROC, conducted in collaboration with The GOG Foundation, Inc. (GOG-F). Part 1b enrolled 102 patients with PROC regardless of Cyclin E1 protein expression, all treated at 400 mg QD 5:2 (five days of once-daily administration of azenosertib, followed by two days without azenosertib). The primary endpoint was objective response rate per RECIST v1.1; secondary endpoints included duration of response, progression-free survival, overall survival, and safety. Part 2 is prospectively enrolling PROC patients with Cyclin E1 protein overexpression based on Zentalis' proprietary immunohistochemistry cutoff. Part 2, in total, is designed to support accelerated approval, pending positive study outcomes and further discussions with the FDA. The study design consists of the following parts: Part 2a: Dose confirmation evaluated two doses, 300 mg QD 5:2 and 400 mg QD 5:2, with approximately 30 patients enrolled per dose group. 400 mg QD 5:2 was selected as the optimal monotherapy dose. Recruitment at the 300 mg QD 5:2 dose level has been discontinued. All patients enrolled in Part 2a will contribute to the overall safety database submitted to the FDA.Part 2b: Enrollment expansion at the selected 400 mg QD 5:2 dose up to approximately 100 patients, including patients at this dose in Part 2a. Enrollment in this cohort is complete.Part 2c: Expansion of the study population, expected to enroll approximately 40 patients previously treated with a taxane-containing regimen for PROC. This cohort is currently enrolling. For physician and patient information about the DENALI trial, please visit www.denalitrial.com. About ASPENOVA Clinical TrialASPENOVA is a Phase 3 randomized, confirmatory clinical trial designed to support full approval of azenosertib in patients with Cyclin E1-positive PROC. The trial is expected to enroll approximately 420 patients and compare azenosertib monotherapy at 400mg QD 5:2 to investigator's choice of standard-of-care single-agent chemotherapy (paclitaxel, pegylated liposomal doxorubicin [PLD], gemcitabine, or topotecan) in this biomarker-selected population. The primary endpoint is progression-free survival (PFS); key secondary endpoints include overall survival (OS) and overall response rate (ORR). The trial design was based on feedback from the U.S. FDA regarding requirements for seeking approval under the accelerated approval pathway and requirements to support potential conversion to full approval. About AzenosertibAzenosertib is an investigational, potentially first-in-class, selective, and orally bioavailable inhibitor of WEE1 currently being evaluated in 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. Azenosertib is in late-stage development as a potential treatment for Cyclin E1-positive platinum-resistant ovarian cancer (PROC). There is currently no approved treatment option specifically for this biomarker-selected population which comprises approximately 50% of PROC patients. Cyclin E1 protein overexpression has been established as a sensitive and specific predictive biomarker for identifying patients who could potentially derive benefit from azenosertib treatment. About Zentalis PharmaceuticalsZentalis is a clinical oncology innovator developing a treatment approach for ovarian cancer and multiple tumor types. Leveraging therapeutics development and biomarker expertise, Zentalis is advancing monotherapy and combination studies of its investigational first-in-class WEE1 inhibitor, azenosertib. Focused on translating WEE1 science into clinical practice, we aim to equip physicians with a targeted, non-chemo, orally available medicine that enhances treatment experience, choice, and outcomes. Our mission: to unburden cancer patients with more convenience and care.​ For more information, please visit www.zentalis.com. Follow Zentalis on LinkedIn at www.linkedin.com/company/zentalis-pharmaceuticals Forward-Looking Statements This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, as amended. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including, but not limited to, statements regarding the continued development of azenosertib; the clinical and therapeutic potential of azenosertib; the potential for azenosertib to be first-in-class; the broad franchise potential of azenosertib; the Company’s biomarker-driven strategy for azenosertib, including the ability of Cyclin E1 to be a highly selective and predictive biomarker for response to azenosertib; and our participation in conference presentations. The terms “anticipate,” “advance,” “believe,” “design,” “develop,” “expect,” “intent,” “look forward,” “on track,” “plan,” “position,” “potential,” “runway,” “strategy,” “support,” “target,” “upcoming,” and “will” and similar references are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: our limited operating history, which may make it difficult to evaluate our current business and predict our future success and viability; we have and expect to continue to incur significant losses; our need for additional funding, which may not be available; our substantial dependence on the success of azenosertib; our plans, including the costs thereof, of development of companion diagnostics; the outcome of preclinical testing and early trials may not be predictive of the success of later clinical trials; potential unforeseen events during clinical trials could cause delays or other adverse consequences; risks relating to the regulatory approval process or ongoing regulatory obligations; our product candidates may cause serious adverse side effects; inability to maintain our collaborations, or the failure of these collaborations; our reliance on third parties; effects of significant competition; the possibility of system failures or security breaches; risks relating to intellectual property; our ability to attract, retain and motivate qualified personnel, and risks relating to management transitions; significant costs as a result of operating as a public company; and the other important factors discussed under the caption “Risk Factors” in our most recently filed periodic report on Form 10-K or 10-Q and subsequent filings with the U.S. Securities and Exchange Commission (SEC) and our other filings with the SEC. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change.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: Aron FeingoldVP, Investor Relations & Corporate Communicationsir@zentalis.com