<div id="readability-page-1"><p>Zentalis Pharmaceuticals <span>NASDAQ: ZNTL<span></span></span> executives outlined a strategy centered on advancing its WEE1 inhibitor azenosertib toward potential approval in platinum-resistant ovarian cancer (PROC), emphasizing a targeted approach in patients with high cyclin E1 protein expression. Speaking at a Guggenheim fireside chat, President and CEO Julie Eastland and Chief Medical Officer Ingmar Bruns said the company’s near-term priorities are to complete enrollment activities across key trials, select a registration dose, and deliver expected clinical updates over the next 12–18 months.</p><h2>Strategy focused on azenosertib in cyclin E1-high PROC</h2> <p>Eastland said the leadership team brought a “very focused strategy” to the company: “to bring azenosertib to patients as quickly as possible.” The current focus is PROC patients whose tumors have high expression of cyclin E1, a biomarker the company believes identifies a subgroup likely to benefit. </p><p>The company is running a multi-part registration study called <strong>DENALI</strong>. Eastland said Zentalis is currently in the second part of that trial, which it views as a potential accelerated approval pathway in cyclin E1-high PROC. She added the company plans to enroll the first patient in a confirmatory Phase 3 randomized trial, <strong>ASPENOVA</strong>, in the first half of the year and expects a top-line readout from DENALI Part 2 at year-end 2026.  </p><h2>Positioning versus ADCs: oral, non-chemotherapy option</h2> <p>Asked about increasing competition in PROC—particularly antibody-drug conjugates (ADCs)—Eastland argued the field will likely support multiple therapies. She said azenosertib is differentiated as an <strong>oral</strong> agent (versus infused ADCs) and a <strong>non-chemotherapy</strong> option that may provide patients a “chemo break.” She also emphasized the drug’s use in a biomarker-defined population (high cyclin E1 expression), which she said has shown benefit with azenosertib in prior work.  </p><h2>Tolerability discussion and dose selection in DENALI</h2> <p>The executives addressed historical concerns around tolerability for WEE1 inhibitors as a class. Eastland cited data presented in January 2025 from historical monotherapy studies using 300 mg and 400 mg once-daily dosing on a 5-days-on/2-days-off schedule, describing the tolerability profile as “very manageable.” </p><p>Bruns added that, compared with standard-of-care therapies and even ADCs, the company believes azenosertib has a favorable profile, citing “10% high-grade neutropenia” and mostly low-grade gastrointestinal and fatigue adverse events that he said are manageable with supportive care. He also described a “data-driven approach” in which the clinical organization reviews data daily and proactively contacts investigators to help manage emerging adverse events during the trial. </p><p>On trial progress, Eastland said <strong>DENALI Part 2A</strong>—up to 60 patients split between the two dose cohorts (30 each)—has been enrolled. The study has a seamless design: the company will continue enrolling both doses until it has enough follow-up to select the dose, then complete enrollment to approximately 100 patients at the selected dose in Part 2B. Eastland said Zentalis expects to announce the dose selection in the first half of the year. </p><p>Bruns said dose selection will be based on an overall risk-benefit profile, with an emphasis on overall response rate; he also noted a PK/PD model being built primarily for regulators. He said tolerability differences between 300 mg and 400 mg have not appeared “materially different,” although 400 mg has looked “a little bit more pronounced” historically.  </p><h2>Biomarker assay development and patient selection</h2> <p>Zentalis said it developed an immunohistochemistry (IHC) assay for cyclin E1 protein expression. Eastland said the cutoff used for prospective screening in DENALI Part 2 and ASPENOVA was derived from retrospective analyses across prior azenosertib studies, including archived tumor tissue from early trials and subsequent monotherapy cohorts. She said the cutoff was determined using data “across several hundred patients” and has been discussed with regulators. The company expects the ongoing trials to validate the assay for commercial companion diagnostic purposes. </p><p>Eastland said prior trials have shown roughly <strong>50%</strong> of PROC patients meet the assay cutoff, and the company expects that rate to remain consistent, subject to what is observed in ongoing studies.  </p><h2>ASPENOVA confirmatory trial design and accelerated approval considerations</h2> <p>Bruns said ASPENOVA will use the same eligibility criteria as DENALI Part 2. He cited two reasons: leveraging the prior data set and aligning with the FDA’s preference that confirmatory trials enroll the same population as the accelerated approval study. </p><p>Executives also described an adaptive feature in ASPENOVA that can include a dose-confirmation component, resulting in a three-arm depiction. Bruns said this design was intended to allow an “immediate start” operationally without waiting for final dose confirmation from DENALI, and that the FDA confirmed the company could enroll only a small number of patients (or potentially none) in the adaptive portion, with DENALI providing most of the evidence for dose selection. </p><p>Eastland added the approach is intended to accelerate timelines, build a randomized control arm dataset specifically in cyclin E1-high PROC, and support requirements around accelerated approval, including enrolling the majority of the Phase 3 trial by the PDUFA date.  </p><p>On efficacy expectations for accelerated approval, Bruns said the regulatory threshold has not changed in the company’s view, describing a target around “30% ORR” and “something between 5 and 6 months” duration of response. He noted the company has previously observed up to 35% overall response rate and a median duration of response of 6.3 months.  </p><p>Looking beyond ovarian cancer, Eastland said the company is interested in combination approaches, including with cytotoxic agents and potentially ADCs, citing preclinical work suggesting combinations may be compelling in ovarian cancer and other tumor types.  </p><p>The executives also briefly discussed the company’s <strong>TETON</strong> study in uterine serous carcinoma (USC). Eastland said the trial was fully enrolled as of the company’s Q3 update and data are planned this year, but she described USC as a smaller indication with a meaningfully changed landscape and not a top commercial priority. Bruns characterized the dataset as roughly 40 patients and said azenosertib appears active in the indication, while reiterating it is not a primary focus.  </p><p>Finally, Eastland said the company’s longer-term strategy beyond azenosertib will be considered after key upcoming milestones, noting there is “nothing on the horizon” currently and that any additional program would need to fit company capabilities and investor interest, particularly given the capital requirements.</p><h2>About Zentalis Pharmaceuticals <span>NASDAQ: ZNTL<span></span></span></h2><p>Zentalis Pharmaceuticals, Inc is a clinical-stage biopharmaceutical company focused on discovering and developing small molecule therapeutics for oncology. Leveraging a proprietary structure-based drug discovery platform, the company designs selective inhibitors aimed at critical cancer targets. Zentalis' research and development efforts center on delivering differentiated therapies that address unmet medical needs in solid tumors and hematologic malignancies.  </p><p>The company's lead product candidate, ZN-c3, is an orally administered inhibitor of the p53-MDM2 interaction, currently being evaluated in Phase I clinical trials for advanced solid tumors and hematologic cancers.</p><h2>Read More</h2><ul><li>Five stocks we like better than Zentalis Pharmaceuticals</li><li>This $15 Stock Could Go Down as the #1 Stock of 2026</li><li>I'm 70 With $1.5M: Would Converting $120K a Year to a Roth Be Smart or a Costly Mistake? (Ask An Advisor)</li><li>URGENT: Sell this stock immediately</li><li>They just tried to kill gold</li><li>Your Bank Account Is No Longer Safe</li></ul><p><em>This instant news alert was generated by narrative science technology and financial data from MarketBeat in order to provide readers with the fastest reporting and unbiased coverage. Please send any questions or comments about this story to contact@marketbeat.com.</em></p><h2>Should You Invest $1,000 in Zentalis Pharmaceuticals Right Now?</h2><p>Before you consider Zentalis Pharmaceuticals, you'll want to hear this.</p><p>MarketBeat keeps track of Wall Street's top-rated and best performing research analysts and the stocks they recommend to their clients on a daily basis. MarketBeat has identified the five stocks that top analysts are quietly whispering to their clients to buy now before the broader market catches on... and Zentalis Pharmaceuticals wasn't on the list.</p><p>While Zentalis Pharmaceuticals currently has a Hold rating among analysts, top-rated analysts believe these five stocks are better buys.</p><p>View The Five Stocks Here</p>                  </div>

<p>Zentalis Pharmaceuticals (NASDAQ:ZNTL) is advancing its WEE1 inhibitor azenosertib towards potential approval for platinum-resistant ovarian cancer (PROC), focusing on patients with high cyclin E1 expression. Executives outlined plans to complete key trial enrollments and select a registration dose, with updates expected in the next 12-18 months. The company is currently in the second part of the DENALI trial and plans to start a confirmatory Phase 3 trial, ASPENOVA, soon. Azenosertib is positioned as an oral, non-chemotherapy option, with a favorable tolerability profile compared to standard therapies.</p>

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Zentalis Pharmaceuticals Details Azenosertib Path to PROC Approval, DENALI Dose Pick Coming Soon