Zentalis Q3 2026 net loss widens to $28.8M
ASPENOVA is designed as a randomized confirmatory study comparing azenosertib with investigator’s choice of chemotherapy in approximately 420 patients.
Sentiment and the balance of points
Rhea-AI Sentiment reads the wording of the document, how positive or negative its language is on a 1 to 5 scale. The balance of points shown with the takes weighs what the document actually discloses, so the two can disagree, for example when a trial that missed its main goal is described in upbeat language.
Form Type
8-K
Rhea-AI Filing Summary
Zentalis Pharmaceuticals, Inc. reported a third-quarter 2026 net loss of $28.8 million, compared with $26.7 million a year earlier, while total operating expenses were $31.2 million versus $33.7 million. Cash, cash equivalents and marketable securities were $228.9 million as of September 30, 2026, compared with $174.6 million as of June 30, 2026; the company expects the balance to fund operating expenses and capital expenditures into the first half of 2028.
DENALI Part 1b data showed median overall survival of 15.9 months among Cyclin E1-positive patients (n=48) and 7.5 months among Cyclin E1-negative patients (n=46). The updated overall response rate was 37.2% among response-evaluable Cyclin E1-positive patients, and median duration of response was 5.5 months.
Enrollment in DENALI Parts 2a and 2b is complete; Part 2c enrollment is scheduled to complete in November 2026, with an integrated topline readout expected in the first half of 2027. ASPENOVA, a Phase 3 confirmatory study, is enrolling. Zentalis plans to discuss DENALI data with the FDA in 2027 to assess the accelerated-approval opportunity.
Positive
- None.
Negative
- Minor pointNet loss widened to $28.8 million from $26.7 million year over year.
Filing Explained
The company reports the
8-K Event Classification
3 items: 2.02, 7.01, 9.01
3 items
Item 2.02
Results of Operations and Financial Condition
Financial
Disclosure of earnings results, typically an earnings press release or preliminary financials.
Item 7.01
Regulation FD Disclosure
Disclosure
Material non-public information disclosed under Regulation Fair Disclosure, often investor presentations or guidance.
Item 9.01
Financial Statements and Exhibits
Exhibits
Financial statements, pro forma financial information, or exhibit attachments filed with this report.
Key Figures
Cash, cash equivalents and marketable securities: $228.9 million
Net loss: $28.8 million
Total operating expenses: $31.2 million
+4 more
7 metrics
Cash, cash equivalents and marketable securities
$228.9 million
As of September 30, 2026; compared with $174.6 million as of June 30, 2026
Net loss
$28.8 million
Three months ended September 30, 2026; compared with $26.7 million in 2025
Total operating expenses
$31.2 million
Three months ended September 30, 2026; compared with $33.7 million in 2025
Research and development expenses
$22.3 million
Three months ended September 30, 2026; compared with $23.0 million in 2025
General and administrative expenses
$8.8 million
Three months ended September 30, 2026; compared with $10.8 million in 2025
Net loss per common share, basic and diluted
$(0.34)
Three months ended September 30, 2026; compared with $(0.37) in 2025
Median overall survival
15.9 months
DENALI Part 1b Cyclin E1-positive patients (n=48); 7.5 months among Cyclin E1-negative patients (n=46)
Key Terms
WEE1 inhibitor, Cyclin E1-positive, overall survival, duration of response, +1 more
5 terms
WEE1 inhibitor medical
"investigational, potentially first-in-class WEE1 inhibitor"
A Wee1 inhibitor is a drug that blocks the Wee1 protein, which normally acts like a safety brake that pauses damaged cells before they divide. By removing that brake, cancer cells with DNA damage are forced into division and often die, making the approach useful for targeting tumors. Investors track Wee1 inhibitors because their clinical trial success, safety profile and use with other therapies can greatly affect a biotechnology company's value.
Cyclin E1-positive medical
"Cyclin E1-positive PROC patients"
Cyclin E1-positive describes cells or tumors that show measurable levels of the Cyclin E1 protein, a regulator that helps drive cells to divide. For investors, this matters because Cyclin E1 positivity can signal a more aggressive disease course, influence which drugs are likely to work, and determine whether a therapy needs a companion test to identify the right patients—similar to a speedometer indicating which cars need engine-specific repairs or upgrades.
overall survival medical
"median OS was 15.9 months"
Overall survival is the average or median length of time patients remain alive after starting a treatment or entering a clinical study, measured regardless of cause of death. Investors care because it is a clear, hard measure of a therapy’s real-world benefit — like timing how long a new battery actually runs — and strong improvements in overall survival can drive regulatory approval, market adoption and revenue potential.
duration of response medical
"a median DOR of 5.5 months"
Duration of response is the length of time a patient’s condition stays improved after a treatment until it starts to worsen again; think of it as how long a freshly charged battery continues to power a device. For investors, longer duration of response implies a treatment provides sustained benefit, which can boost a drug’s commercial value, support stronger regulatory labeling and payer coverage, and reduce the need for additional therapies.
accelerated approval regulatory
"support an accelerated approval pathway"
Accelerated approval is a process that allows new medical treatments to be approved more quickly than usual if they address serious or life-threatening conditions and show promising early results. For investors, it signals that a treatment may reach the market sooner, potentially boosting a company's prospects, but it also involves some uncertainty since full evidence of effectiveness is still being gathered.
Earnings Snapshot
Net loss: $28.8 million · Guidance included
Third quarter 2026
Net loss
$28.8 million
Compared with $26.7 million in the third quarter of 2025
Total operating expenses
$31.2 million
Compared with $33.7 million in the third quarter of 2025
Research and development expenses
$22.3 million
Compared with $23.0 million in the third quarter of 2025
General and administrative expenses
$8.8 million
Compared with $10.8 million in the third quarter of 2025
Guidance
Zentalis expects existing cash, cash equivalents and marketable securities to fund operating expenses and capital expenditure requirements into the first half of 2028.
FAQ
AI-generated questions and answers. How Rhea-AI works. Not financial advice.
What is ZNTL's ASPENOVA trial designed to test?
ASPENOVA is a randomized Phase 3 study expected to enroll approximately 420 Cyclin E1-positive PROC patients, comparing azenosertib 400mg QD 5:2 with investigator’s choice of paclitaxel, pegylated liposomal doxorubicin, gemcitabine or topotecan. Progression-free survival is the primary endpoint; overall survival and overall response rate are key secondary endpoints.
AI-generated analysis. How Rhea-AI works. Not financial advice.
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
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FORM 8-K
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CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of report (Date of earliest event reported): November 9, 2026
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(Exact name of registrant as specified in its charter)
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(State or other jurisdiction of incorporation or organization) | (Commission File Number) | (I.R.S. Employer Identification No.) | ||||||||||||
(Address of principal executive offices) (Zip Code)
(858 ) 263-4333
(Registrant’s telephone number, include area code)
N/A
(Former name or former address, if changed since last report)
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Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
| Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) | |||||
| Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) | |||||
| Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) | |||||
| Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) | |||||
Securities registered pursuant to Section 12(b) of the Act:
| Title of each class | Trading Symbol(s) | Name of each exchange on which registered | ||||||
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company ☐
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Item 2.02 Results of Operations and Financial Condition.
On November 9, 2026, Zentalis Pharmaceuticals, Inc. (the “Company”) issued a press release announcing its financial results for the quarter ended September 30, 2026 and providing business updates. A copy of the press release is furnished as Exhibit 99.1 to this Current Report on Form 8-K (this "Current Report") and is incorporated herein by reference.
Item 7.01 Regulation FD Disclosure.
Beginning November 9, 2026, spokespersons of the Company plan to present the information in the Corporate Presentation furnished as Exhibit 99.2 to this Current Report and incorporated herein by reference at conferences and in meetings with investors and analysts.
The information in Items 2.02 and 7.01 of this Current Report (including Exhibits 99.1 and 99.2 attached hereto) shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Exchange Act or the Securities Act of 1933, as amended, whether made before or after the date hereof, except as expressly set forth by specific reference in such a filing.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
The following exhibit relating to Items 2.02 and 7.01 shall be deemed to be furnished, and not filed:
Exhibit No. | Description | |||||||
| 99.1 | Press Release issued on November 9, 2026 | |||||||
| 99.2 | Corporate Presentation dated November 2026 | |||||||
| 104 | Cover Page Interactive Data File (embedded within the inline XBRL document) | |||||||
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| ZENTALIS PHARMACEUTICALS, INC. | ||||||||||||||
| Date: November 9, 2026 | By: | /s/ Julie Eastland | ||||||||||||
| Julie Eastland | ||||||||||||||
| President and Chief Executive Officer | ||||||||||||||
Exhibit 99.1
Zentalis Pharmaceuticals Reports Third Quarter 2026 Financial Results and Business Updates
•DENALI Part 1b survival data strengthen azenosertib's position as the potential first-in-class oral, non-chemotherapy, non-ADC therapy in pivotal development for Cyclin E1-positive PROC
•DENALI Part 2c enrollment scheduled to complete in November 2026, with an integrated topline readout expected in 1H 2027
•$228.9 million in cash, cash equivalents and marketable securities as of September 30, 2026 provides runway into 1H 2028 to support execution of key milestones
SAN DIEGO, November 9, 2026 — Zentalis® Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical oncology innovator advancing late-stage development of an investigational, potentially first-in-class WEE1 inhibitor, azenosertib, as a biomarker-driven treatment approach for ovarian cancer, today announced financial results for the third quarter ended September 30, 2026, and highlighted recent business updates.
"Overall survival data from DENALI Part 1b presented at ESMO reinforce our confidence in azenosertib to offer a differentiated oral treatment for patients with Cyclin E1-positive platinum-resistant ovarian cancer (PROC), if approved," said Julie Eastland, Chief Executive Officer of Zentalis Pharmaceuticals. "We designed complementary paths through DENALI and ASPENOVA to support our goal of bringing azenosertib to patients as quickly as possible. In light of an evolving landscape in PROC, we plan to discuss the DENALI data with the FDA in 2027 to assess the accelerated approval opportunity. Meanwhile, we continue to advance ASPENOVA at full speed, ensuring we are well positioned to support our regulatory strategy under either an accelerated or full approval pathway. With DENALI Part 2c enrollment completing this month, we expect a topline readout from DENALI in the first half of 2027 — a key potential value-creating catalyst ahead of ASPENOVA.
Ms. Eastland continued: "Alongside our PROC program, our strategy includes advancing azenosertib as a combination therapy where we see meaningful therapeutic and scientific rationale. MUIR, evaluating azenosertib in combination with bevacizumab in platinum-sensitive ovarian cancer, is enrolling. Additionally, we are actively planning a combination clinical study in triple-negative breast cancer. Collectively, this strategy positions azenosertib to realize its full potential, both as the first targeted option for patients with Cyclin E1-positive PROC and through combinations across tumor types where WEE1 inhibition may enhance the benefit of standard-of-care therapies, including ADCs and other agents.
“With $228.9 million on the balance sheet providing an anticipated runway into the first half of 2028, we believe we are well resourced to support key DENALI milestones, full enrollment in ASPENOVA and combination trials in ovarian cancer and triple-negative breast cancer,” Ms. Eastland concluded.
Business Updates
Clinical Development
•DENALI Part 2 Enrollment Completing: Enrollment in DENALI Parts 2a and 2b is complete and enrollment in Part 2c is scheduled to complete in November 2026.
•DENALI Part 2 Topline Readout: Zentalis expects to provide a topline readout in the first half of 2027 which will reflect an integrated dataset across Parts 2a, 2b, and 2c.
•ASPENOVA Phase 3 Enrolling: We continue to execute on the global Phase 3 ASPENOVA study, with trial site initiations and enrollment advancing across multiple geographies.
•MUIR Phase 1b Enrolling: Enrollment in Part 2 is ongoing for azenosertib in combination with bevacizumab as the maintenance treatment for second-line platinum-sensitive ovarian cancer.
•Triple-Negative Breast Cancer Combination Study Planning: Zentalis is actively planning a combination clinical study of azenosertib in triple-negative breast cancer.
Congresses and Publications
•European Society for Medical Oncology (ESMO) 2026: In October 2026, the following were presented:
◦DENALI Part 1b Overall Survival Analysis: Meaningful overall survival data from DENALI Part 1b were presented at the ESMO Annual Meeting, further supporting the biomarker-driven development strategy. In Cyclin E1-positive PROC patients (n=48), median OS was 15.9 months (95% CI, 8.7–21.2), versus 7.5 months (95% CI, 5.8-12.3) in Cyclin E1-negative patients (n=46). Updated ORR in response-evaluable Cyclin E1-positive patients was 37.2%, with a median DOR of 5.5 months, including two patients with responses exceeding 15 and 20 months. The safety profile was consistent with prior reporting; median relative dose intensity was 84.6%.
◦ASPENOVA Trial-in-Progress: An overview of the ongoing Phase 3 ASPENOVA trial evaluating azenosertib in patients with Cyclin E1-positive PROC.
•College of American Pathologists Annual Meeting — Cyclin E1 IHC Assay Validation: In October 2026, Zentalis scientists presented analytical validation data for a laboratory-developed IHC test for Cyclin E1 detection in high-grade serous ovarian cancer, demonstrating high concordance across laboratories and readers and supporting prospective biomarker screening in ongoing clinical trials.
Corporate
•Follow-on Equity Offering: In August 2026, completed a follow-on offering of 26,450,000 shares of common stock, raising approximately $86.9 in net proceeds.
Third Quarter 2026 Financial Results
•Cash Position: Cash, cash equivalents and marketable securities were $228.9 million as of September 30, 2026, compared to $174.6 million as of June 30, 2026, including net proceeds from the August 2026 follow-on offering. Zentalis believes that existing cash, cash
equivalents and marketable securities will be sufficient to fund operating expenses and capital expenditure requirements into the first half of 2028.
•Research and Development Expenses: Research and development expenses for the three months ended September 30, 2026 were $22.3 million, compared to $23.0 million for the three months ended September 30, 2025. The $0.7 million decrease was primarily attributable to a $6.2 million decrease in clinical trial expenses for certain studies that reached or are near completion, partially offset by a $3.8 million increase in expenses for ongoing clinical trials open for enrollment, a $0.8 million increase in companion diagnostic development expenses and a $0.9 million increase in personnel-related expenses and allocated overhead.
•General and Administrative Expenses: General and administrative expenses for the three months ended September 30, 2026 were $8.8 million, compared to $10.8 million for the three months ended September 30, 2025. The $2.0 million decrease was primarily attributable to a $2.7 million decrease in personnel-related expenses partially offset by a $0.7 million increase primarily related to consulting and outside services.
•Total Operating Expenses: Total operating expenses were $31.2 million for the three months ended September 30, 2026, compared to $33.7 million for the three months ended September 30, 2025.
About Azenosertib
Azenosertib 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 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 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.
Azenosertib has not been approved by the U.S. Food and Drug Administration or any other regulatory authority.
About DENALI Clinical Trial
DENALI is a multi-part Phase 2 clinical trial (NCT05128825) studying azenosertib in PROC patients.
DENALI is a multi-part Phase 2 clinical trial (NCT05128825) studying azenosertib in PROC patients.
Part 1b enrolled patients with PROC regardless of Cyclin E1 protein expression, all treated at 400mg QD 5:2. Part 2 is prospectively enrolling PROC patients with Cyclin E1 protein overexpression based on Zentalis' proprietary immunohistochemistry cutoff.
Part 2, in total, was designed to support an accelerated approval pathway in the Cyclin E1-positive patient population, subject to the strength of the data, FDA feedback and the treatment landscape at the time of regulatory action.
•Part 2a: Dose confirmation evaluated two doses, 300mg QD 5:2 and 400mg QD 5:2, with approximately 30 patients enrolled per dose group. 400mg QD 5:2 was selected as the optimal monotherapy dose. Recruitment at the 300mg 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 400mg QD 5:2 dose up to approximately 100 patients, including patients at this dose in Part 2a. This cohort has completed enrollment.
•Part 2c: Broadening study population to include patients previously treated with a taxane-containing regimen for PROC. The enrollment in this cohort is scheduled to complete in November 2026.
For physician and patient information about the DENALI trial, please visit www.denalitrial.com.
About ASPENOVA Clinical Trial
ASPENOVA 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). ASPENOVA is intended to support approvals in the U.S. and major ex-U.S. markets, based on alignment with U.S. and EU regulators.
ASPENOVA 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). ASPENOVA is intended to support approvals in the U.S. and major ex-U.S. markets, based on alignment with U.S. and EU regulators.
About Zentalis Pharmaceuticals
Zentalis 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.
Zentalis 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 potential for azenosertib to be first-in-class; the continued development of azenosertib; the clinical and therapeutic potential of azenosertib, including the potential for azenosertib to be a differentiated oral treatment option for patients with Cyclin E1-positive platinum resistant ovarian cancer or other indications; the Company’s biomarker-driven strategy for azenosertib; the Company’s anticipated milestones and the timing thereof, including the anticipated enrollment completion of DENALI Part 2, the topline readout from DENALI Part 2, and the design, conduct and timing of our confirmatory ASPENOVA Phase 3 trial, MUIR Phase 1b trial and our potential clinical study of azenosertib in triple-negative breast cancer; the potential to advance research on additional areas of opportunity for azenosertib as maintenance therapy in ovarian cancer, triple-negative breast cancer and additional tumor types; the Company’s anticipated cash runway; and the Company’s planned regulatory strategy for azenosertib and the timing thereof, including the potential for an accelerated approval in light of the evolving treatment landscape. The terms “anticipate,” “advance,” “believe,” “complete,” “continue,” “design,” “develop,” “ensuring,” “expect,” “focus,” “future,” “goal,” “intend,” “may,” “plan,” “position,” “potential,” “provides,” “runway,” “scheduled,” “strategy,” “support,” “target,” 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 a companion diagnostic; risks relating to the regulatory approval process or ongoing regulatory obligations; 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; our product candidates may cause serious adverse side effects; the interim, initial, “topline,” and preliminary data from our clinical trials may change as more patient data becomes available, and are subject to audit and verification procedures that could result in material changes in the final data; 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.
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 potential for azenosertib to be first-in-class; the continued development of azenosertib; the clinical and therapeutic potential of azenosertib, including the potential for azenosertib to be a differentiated oral treatment option for patients with Cyclin E1-positive platinum resistant ovarian cancer or other indications; the Company’s biomarker-driven strategy for azenosertib; the Company’s anticipated milestones and the timing thereof, including the anticipated enrollment completion of DENALI Part 2, the topline readout from DENALI Part 2, and the design, conduct and timing of our confirmatory ASPENOVA Phase 3 trial, MUIR Phase 1b trial and our potential clinical study of azenosertib in triple-negative breast cancer; the potential to advance research on additional areas of opportunity for azenosertib as maintenance therapy in ovarian cancer, triple-negative breast cancer and additional tumor types; the Company’s anticipated cash runway; and the Company’s planned regulatory strategy for azenosertib and the timing thereof, including the potential for an accelerated approval in light of the evolving treatment landscape. The terms “anticipate,” “advance,” “believe,” “complete,” “continue,” “design,” “develop,” “ensuring,” “expect,” “focus,” “future,” “goal,” “intend,” “may,” “plan,” “position,” “potential,” “provides,” “runway,” “scheduled,” “strategy,” “support,” “target,” 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 a companion diagnostic; risks relating to the regulatory approval process or ongoing regulatory obligations; 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; our product candidates may cause serious adverse side effects; the interim, initial, “topline,” and preliminary data from our clinical trials may change as more patient data becomes available, and are subject to audit and verification procedures that could result in material changes in the final data; 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 Feingold
VP, Investor Relations & Corporate Communications
Aron Feingold
VP, Investor Relations & Corporate Communications
ir@zentalis.com
| Zentalis Pharmaceuticals, Inc. | |||||||||||||||||||||||
| Condensed Consolidated Statements of Operations | |||||||||||||||||||||||
| (Unaudited) | |||||||||||||||||||||||
| (In thousands, except per share amounts) | |||||||||||||||||||||||
| Three Months Ended September 30, | Nine Months Ended September 30, | ||||||||||||||||||||||
| 2026 | 2025 | 2026 | 2025 | ||||||||||||||||||||
| Operating Expenses | |||||||||||||||||||||||
| Research and development | $ | 22,334 | $ | 22,950 | $ | 86,213 | $ | 77,807 | |||||||||||||||
| General and administrative | 8,820 | 10,784 | 27,187 | 29,812 | |||||||||||||||||||
| Restructuring | — | — | — | 7,796 | |||||||||||||||||||
| Total operating expenses | 31,154 | 33,734 | 113,400 | 115,415 | |||||||||||||||||||
| Loss from operations | (31,154) | (33,734) | (113,400) | (115,415) | |||||||||||||||||||
| Investment and other income, net | 2,457 | 7,043 | 7,323 | 13,571 | |||||||||||||||||||
| Net loss before income taxes | (28,697) | (26,691) | (106,077) | (101,844) | |||||||||||||||||||
| Income tax expense | 118 | — | 376 | — | |||||||||||||||||||
| Net loss | $ | (28,815) | $ | (26,691) | $ | (106,453) | $ | (101,844) | |||||||||||||||
| Net loss per common share, basic and diluted | $ | (0.34) | $ | (0.37) | $ | (1.41) | $ | (1.42) | |||||||||||||||
| Common shares used in computing net loss per share, basic and diluted | 84,612 | 72,139 | 75,453 | 71,938 | |||||||||||||||||||
Zentalis Pharmaceuticals, Inc.
Selected Condensed Consolidated Balance Sheet Data
(Unaudited)
(In thousands)
| As of September 30, 2026 | As of December 31, 2025 | |||||||||||||
Cash, cash equivalents and marketable securities | $ | 228,893 | $ | 245,893 | ||||||||||
Working capital (1) | 204,909 | 216,632 | ||||||||||||
Total assets | 270,193 | 288,967 | ||||||||||||
Total liabilities | 65,306 | 72,763 | ||||||||||||
Total Zentalis equity | $ | 204,887 | $ | 216,204 | ||||||||||
(1) Zentalis defines working capital as current assets less current liabilities. | ||||||||||||||
Pioneering WEE1 Inhibition to Deliver More Convenient, Targeted Cancer Care Corporate Presentation | November 2026 Nasdaq: ZNTL
Zentalis Pharmaceuticals, Inc. (“we,” “us,” “our,” “Zentalis” or the “Company”) cautions that this presentation (including oral commentary that accompanies this presentation) contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. All statements contained in this presentation that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding the continued development of azenosertib, including the Company’s strategy to focus on bringing azenosertib to patients with PROC who are Cyclin E1-positive and the potential opportunities for azenosertib as a monotherapy and in combination in other indications and in other tumor types, including in earlier lines of ovarian cancer, triple-negative breast cancer and other tumor types; the clinical and therapeutic potential of azenosertib; the potential for azenosertib (ZN-c3) to be the first, oral, non- chemotherapy for ~50% of PROC patients; the market opportunity for azenosertib, including the opportunity in biomarker selected (Cyclin E1-positive) PROC patients and the potential size of the patient population; the potential for the opportunity for azenosertib to be broad/expansive; the potential for Cyclin E1 to serve as a predictive biomarker for response to azenosertib; the Company’s projected cash runway; planned clinical trials for our product candidates; the potential benefits of azenosertib, including compared to available therapies and therapies in development (not head-to-head comparisons); the potential unmet need in a particular indication and/or patient population; the timing and content of the Company’s anticipated milestones, including the completion of enrollment in all cohorts of DENALI Part 2 and the topline readout; and the Company’s planned regulatory strategy for azenosertib and the timing thereof, including the potential for DENALI Part 2 to support an accelerated approval and the potential for ASPENOVA to support a full approval; as well as statements that include the words such as “anticipate,” “beyond,” “design,” “estimate,” “expect,” “forward,” “intent,” “milestone,” “ongoing,” “opportunity,” “path,” “plan,” “potential,” “predictive,” “projected,” “strategy,” "support," “will” and similar statements of a future or forward-looking nature. 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 plans, including the costs thereof, of development of a companion diagnostic; the outcome of early clinical trials may not be predictive of the success of later clinical trials; failure to identify additional product candidates and develop or commercialize marketable products; potential unforeseen events during clinical trials could cause delays or other adverse consequences; risks relating to the regulatory approval process or ongoing regulatory obligations; failure to obtain U.S. or international marketing approval; azenosertib and any future product candidates may cause serious adverse side effects; the interim and preliminary data from our clinical trials may change as more patient data becomes available, and are subject to audit and verification procedures that could result in material changes in the final data; if our confirmatory trials do not verify clinical benefit, the FDA may seek to withdraw accelerated approval; our ability to establish effective sales or marketing capabilities; our reliance on third parties; the interim, initial, “line,” and preliminary data from our clinical trials may change as more patient data becomes available, and are subject to audit and verification procedures that could result in material changes in the final data; our reliance on third parties; effects of significant competition; 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; and significant costs as a result of operating as a public company. Other risks and uncertainties include those identified under the caption “Risk Factors” in our most recently filed periodic reports on Forms 10-K and 10-Q and subsequent filings with the U.S. Securities and Exchange Commission in the future could cause such forward-looking statements represent management’s estimates as of the date of this presentation. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. While we may elect to update these forward-looking statements at some point in the future, we assume no obligation to update or revise any forward-looking statements except to the extent required by applicable actual results to differ materially from those indicated by the forward-looking statements made in this presentation. Any law. Although we believe the expectations reflected in such forward-looking statements are reasonable, we can give no assurance that such expectations will prove to be correct. Accordingly, readers are cautioned not to place undue reliance on these forward-looking statements. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and other data about our industry. These data involve a number of assumptions and limitations, and you are cautioned not to give undue weight to such data and estimates. In addition, projections, assumptions and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk. Neither we nor our affiliates, advisors or representatives makes any representation as to the accuracy or completeness of that data or undertake to update such data after the date of this presentation. Statements such as “not head-to-head,” “direct cross-study comparison not intended” and similar references indicate that no head-to-head clinical trial has been conducted evaluating azenosertib against the indicated therapies. Notable differences exist between the Company’s trial designs, conditions under study and subject characteristics as compared to the evaluated third party results and caution should be exercised when comparing data across these studies. ZENTALIS® and its associated logos are trademarks of Zentalis and/or its affiliates. All other trademarks, trade names and service marks appearing in this presentation are the property of their respective owners. All website addresses given in this presentation are for information only and are not intended to be an active link or to incorporate any website information into this document. Azenosertib is an investigational drug and has not yet been approved by the U.S. Food and Drug Administration or any other regulatory authority. Forward Looking Statements and Disclaimer
A Focused Strategy to Address Critical Unmet Need in Ovarian Cancer and Beyond Initial focus to address ~20,000 Cyclin E1-positive PROC patients^, a poor prognostic biomarker population, with no specifically targeted treatment options Abbreviations: PROC = platinum-resistant ovarian cancer; ADC = anti-body drug conjugate; TNBC = triple-negative breast cancer ^ Based on 2025 Decision Resource estimates in US, EU4 (France, Germany, Italy, Spain), UK, and Japan † Cash, cash equivalents and marketable securities as of 9/30/26; Shares outstanding as of September 30, 2026 = 98.3M 3 As the potential first-in-class oral, non-chemotherapy, non-ADC oral investigational therapy in pivotal development specifically for Cyclin E1-positive PROC patients, azenosertib represents a clinically meaningful option in an evolving treatment landscape Meaningful survival, duration and response rates from DENALI Part 1b presented at ESMO 2026 strengthen the profile of azenosertib and support complementary DENALI and ASPENOVA development strategy to seek approval and bring azenosertib to Cyclin E1-positive PROC patients as soon as possible Establishing azenosertib's potential as a targeted therapy across tumor types where WEE1 inhibition may enhance the benefit of standard-of-care therapies: MUIR is ongoing, evaluating azenosertib in combination with bevacizumab in platinum-sensitive ovarian cancer. Actively planning a combination clinical study in triple-negative breast cancer Resourced to execute with ~$229M cash† providing runway into 1H 2028 and industry-leading WEE1 expertise and proven leadership
A Focused Pipeline Prioritizing Cyclin E1-Positive PROC With Potential for Franchise Expansion Abbreviations: PROC = platinum-resistant ovarian cancer; SOC = standard-of-care; 1L = first line; 2L = second line; PSOC = platinum-sensitive ovarian cancer; TNBC = triple-negative breast cancer * Also known as ZN-c3-002 4 DENALI Part 2 topline readout expected 1H2027; combinations in PSOC maintenance and expanding into TNBC TRIAL DEVELOPMENT APPROACH PHASE 1 PHASE 2 PHASE 3 STATUS Cyclin E1-Positive PROC Monotherapy (lead indication) DENALI DENALI Part 1b Demonstrated Cyclin E1 overexpression as biomarker predicting response to azenosertib Completed Data presented at ESMO 2026 DENALI Part 2a + 2b + 2c Registration-intended Cyclin E1-Positive FDA Fast Track Designation Topline Readout Expected 1H2027 Parts 2a&b enrollment complete; Part 2c enrollment scheduled to complete in Nov 2026 ASPENOVA Azenosertib vs. SOC chemo Randomized, confirmatory trial Cyclin E1-Positive First Patient Dosed Q2 2026 Enrolling Ovarian Cancer Combination Therapy MUIR* Part 2: Azenosertib + bevacizumab (1L/2L PSOC maintenance therapy) Part 1: Azenosertib + multiple chemo backbones (in PROC, completed) Ongoing Part 2 Enrolling TNBC Combination Therapy TNBC Study Azenosertib combination clinical study Actively planning Ongoing / completed Planned
~50% of PROC Patients Are Cyclin E1-Positive With No Approved, Specifically Targeted Therapy 1. Cyclin E1-positive determined by an IHC assay and Zentalis proprietary cutoff; 3. 4. Abbvie Q4 2025 Earnings Cyclin E1 IHC+% based on literature and the unbiased CCNE1 amp & Cyclin E1 overlapping data generated from Zentalis clinical trial samples 2. Based on 2025 Decision Resource estimates in US, EU4 (France, Germany, Italy, Spain), UK, and Japan Eskander, R., et al. Front Oncol. 2023 Note: Overlap between FRa high and Cyclin E1+ accounts for ~20% of all PROC, based on internal data Abbreviations: PROC = platinum-resistant ovarian cancer; ORR = overall response rate; PFS = progression free survival 5 The Unmet Need: • ~20,000 patients with Cyclin E1-positive PROC2 • Standard-of-care single-agent chemotherapy delivers only 4-13% ORR and 3-4 months PFS3 with high patient burden: • Due to safety and tolerability profiles, travel hours, and infusion time • Cyclin E1-positivity is a biomarker of poor prognosis and low benefit from available treatments Proven Market Demand for Biomarker-Directed PROC Therapy: • Elahere achieved $607M US sales in 20254 in FRα+ PROC patients • Strong commercial potential for targeted therapies in biomarker- selected PROC populations PROC FRα+ ~35% Cyclin E1-Positive ~50%1
Robust Clinical Foundation Supports Azenosertib as Potential First-in-Class WEE1 Inhibitor for Cyclin E1-Positive PROC Abbreviations: PROC = platinum-resistant ovarian cancer; TRAEs = treatment-related adverse events; 5:2 schedule = 5 days once-daily administration of azenosertib, followed by 2 days without azenosertib; ORR = overall response rate; DoR = duration of response # As reported in Zentalis April 9, 2026 press release; ^ Integrated dataset and DENALI Part 1b data @ ESMO 2026; † Most common TRAE represents all grade TRAEs ≥ 50% 6 Class-leading Clinical Experience • 1,000+ patients treated across multiple tumor types and dose levels in monotherapy and in combination with other agents • Integrated learnings from ZN-c3-001, MAMMOTH and DENALI Part 1b inform registration strategy Optimized Dose & Schedule • 400mg QD 5:2 selected based on DENALI Part 2a interim analysis • Clear response differentiation at 400mg vs. 300mg QD 5:2 • Key improvements in Part 2a vs. Part 1b: reported fewer discontinuations and improved select safety measures# Compelling Clinical Profile • ~35% ORR, ~5.5 month DOR, ~16 month OS^ in Cyclin E1- positive PROC at 400mg QD 5:2 • Most common TRAEs include nausea, diarrhea, and fatigue and are clinically manageable†, supporting oral at-home dosing with appropriate monitoring
DENALI Phase 2: Integrated Topline Readout Expected in 1H 2027 Abbreviations: 5:2 schedule = 5 days once-daily administration of azenosertib, followed by 2 days without azenosertib; IHC= immunohistochemistry; MIRV=mirvetuximab soravtansine; PROC=platinum resistant ovarian cancer; DOR=duration of response; ORR=overall response rate; PFS=progression free survival. 7 Part 2a and 2b Enrollment Complete; Part 2c Enrollment Scheduled to Complete in November 2026 Platinum-resistant ovarian cancer Cyclin E1+ by proprietary IHC cutoff criteria Part 2a & b: 1-3 prior lines of therapy; prior MIRV if high FRα, up to 4 prior lines allowed Part 2c: 1-4 prior lines of therapy, including prior taxane containing regimen for PROC; prior MIRV if high FRα Key Eligibility DENALI PART 2 DESIGNED FOR POTENTIAL ACCELERATED APPROVAL (N=up to ~140 at selected dose) Part 2a Dose Confirmation Part 2b Dose Expansion PROC Pts Cyclin E1+ 400mg QD 5:2 (N=30) 300mg QD 5:2 (N=30) Recruitment at this dose level has been discontinued following dose selection 1:1 Randomization 400mg QD 5:2 (N=up to ~70) Enrollment complete Endpoints DOR, PFS Safety and Tolerability ORR Pr es cr ee ni ng / Ti ss ue C on se nt Se am le ss E nr ol lm en t Dose Selected 400mg QD 5:2 (N=up to ~40) Enrollment scheduled to complete Nov 2026 Part 2c PROC Taxane- experienced Population Only
ASPENOVA PHASE 3: Confirmatory Study in Cyclin E1-Positive PROC To Support Approvals in the U.S. and Major Ex-U.S. Markets Abbreviations: 5:2 schedule = 5 days once-daily administration of azenosertib, followed by 2 days without azenosertib; IHC= immunohistochemistry; MIRV=mirvetuximab soravtansine; PROC=platinum resistant ovarian cancer; PLD=pegylated liposomal doxorubicin; OS=overall survival; ORR=overall response rate; PFS=progression free survival 8 Platinum-resistant ovarian cancer Cyclin E1+ by proprietary IHC cutoff criteria 1-3 prior lines of therapy Prior MIRV if high FRα, up to 4 prior lines allowed Key Eligibility PROC Pts Cyclin E1+ Azenosertib 400mg QD 5:2 (N = ~210) Primary Endpoint Key Secondary Endpoints PFS OS, ORR Pr es cr ee ni ng / Ti ss ue C on se nt Investigator’s Choice of Chemotherapy Paclitaxel, PLD, Gemcitabine, otecan (N = ~210) 1:1 Randomization ASPENOVA RANDOMIZED TRIAL INTENDED FOR FULL APPROVAL (FDA Aligned, N= ~420)
Cyclin E1-Positive PROC Patients Face Poor Prognosis with No Specifically Targeted Treatment Options Abbreviations: PROC = platinum-resistant ovarian cancer9
Cyclin E1 Protein Overexpression is the Key Biomarker Identifying PROC Patients Who May Benefit from Azenosertib Monotherapy Multiple mechanisms drive Cyclin E1 protein overexpression1, including: • CCNE1 gene amplification • Increased gene transcription • Reduced protein degradation *Cyclin E1 IHC+ based on Zentalis proprietary IHC cutoff and Cyclin E1 IHC assay developed from multiple early clinical trials; Cyclin E1 IHC+% based on literature and the unbiased CCNE1 amp & Cyclin E1 overlapping data generated from Zentalis clinical trial samples Cyclin E1/CDK2 activation defines a key vulnerability to WEE1 kinase inhibition in gynecological cancers Abbreviations: IHC = immunohistochemistry; CDx = companion diagnostic 1. Kim, D., et al. , npj Precis. Onc. 9, 3 (2025). 10 All PROC Patients Should Be Screened by IHC Regardless of CCNE1 Gene Amplification Status ~15% IHC- ~85% IHC+ CCNE1 Non-Amplified (~80% of PROC) CCNE1 Amplified (~20% of PROC) ~40% IHC+~60% IHC- IHC testing on archival tissues to identify Cyclin E1- positive patients • Zentalis’ proprietary IHC cutoff determined through results from multiple early clinical trials • Same cutoff being validated in registration-intended trials • CDx registration and market development under way ~50% of PROC patients estimated to be Cyclin E1 IHC+*, more than doubling the CCNE1 amplification population
Cyclin E1-Positive Patients Experience Significantly Worse Outcomes with Current Approved Treatments Abbreviations: mPFS = median progression-free survival; DCR = disease control rate; mTTNT = median time to next treatment; OC = ovarian cancer; PROC = platinum-resistant ovarian cancer; Tx = treatment; 1L = first line Cyclin E1 expression status was derived from CCNE1 RNA expression level^Jeong et al., AACR 2026, Poster #1708; † 11 • Cyclin E1-positive ovarian cancer patients show consistently poor outcomes with 1L treatments across two independent cohorts and worse prognosis independent of CCNE1 gene amplification status • Trend toward reduced clinical benefit from available PROC therapies in Cyclin E1-positive patients^ Tempus Lens Real World Data^† (N=193) Prior Tx Data from Patients Enrolled in Azenosertib Clinical Trials^ (N=79) Cyclin E1 Status 1L OC mPFS 1L OC mTTNT Cyclin E1-positive with CCNE1 amplification 13.6 months 13.2 months Cyclin E1-positive without CCNE1 amplification 13.5 months 14.9 months Cyclin E1-negative 18.9 months 19.5 months P-value 0.18 0.002 RWD, AACR 2026
Standard-of-Care* Single-Agent Chemotherapy Delivers Limited Benefits to PROC Patients Direct cross-study comparison of results from independently conducted clinical trials is not intended on this slide. * Excludes recently approved taxane combo regimens Abbreviations: bev, bevacizumab; FR , folate receptor alpha; IV: intravenous administration; mo, months; ORR, objective response rate; PFS, progression-free survival; PLD, pegylated liposomal doxorubicin; PROC, platinum-resistant ovarian cancer; mPFS = median progression-free survival; mOS = median overall survival 1. Pujade Lauraine E et al. Lancet Oncol. 2021;22(7):1034-1046, 2. Moore KN et al. ESMO 2019, 3. Gaillard SL et al. ESMO 2018, 4. Omatsu K ESMO 2020, 5. Pujade-Lauraine E et al. J Clin Oncol. 2014;32(13):1302–1308. α 12 Study Study Population Chemotherapy Arm ORR, % mPFS, mo mOS, mo JAVELIN Ovarian 2001 (n=190) ≤3 priors, 75% PROC and 25% Platinum refractory (28% prior bev) PLD 4 3.5 15.7 FORWARD I re-read2 (n=61) PROC 1–3 priors high FRα (33% prior bev) Paclitaxel or PLD or otecan 6 3.2 12 CORAIL3 (n=199) PROC ≤3 priors (46% prior bev) PLD or otecan 12 3.6 11 NINJA4 (n=159) PROC 77% >2 prior Gemcitabine or PLD 13 3.8 12.1 AURELIA5 (n=182) PROC ≤2 priors; 25% platinum refractory (8% prior bev) Paclitaxel or PLD or otecan 13 3.4 13.3 SOC with limited benefits and high patient burden (time toxicity from IV, hair loss, and neuropathy) highlights the urgent unmet needs in PROC
Azenosertib May Address Critical Gap in Cyclin E1-Positive PROC Treatment Landscape* *If successful in clinical testing and approved by regulators Abbreviations: PROC = platinum-resistant ovarian cancer; FRα = Folate Receptor alpha 1 Excludes recently approved taxane combo regimens in the U.S. and select ex-U.S. markets; 3 Eskander, R., et al. Overcoming the Challenges in Drug Development, Front Oncol. 2023 Oct 17; 13:1258228; 4 Clinical Trial SORAYA ORR 32%, MIRASOL ORR 42%; Jeong et al., AACR 2026, Poster #1708; 2 13 No approved therapies specifically for Cyclin E1+ PROC presents opportunity for azenosertib as potentially first, oral, non-chemotherapy for ~50% of PROC patients PARP Inhibitor or Bevacizumab + Olaparib Bevacizumab Combination Chemotherapy Platinum Doublet HRP PFI>6m PFI<6m PFI<6m Carboplatin + Paclitaxel High Unmet Need Cyclin E1+ Patients (2L+) Population with worse outcomes1 No approved therapies Global SOC 2L+ Therapy2 Chemo Mono ORR 4 – 13%3 Elahere (mirvetuximab) (FRα+ ~35% of PROC) ORR 32% - 42%4 First Line Maintenance Second Line Therapy First Line Therapy BRCAm/HRD Untreated Stage III/IV Ovarian Cancer PROC
Compelling Clinical Profile Across Multiple Studies Supports Cyclin E1-Positive PROC Registration Strategy Abbreviations: PROC = platinum-resistant ovarian cancer 14
Azenosertib: A Differentiated, Potentially First-in-Class WEE1 Inhibitor 15 • Cyclin E1 overexpression increases CDK2 activity and accelerates G1-S transition, rendering cells more dependent on the DNA repair at the G2-M checkpoint • Inhibition of WEE1 activates CDKs, accelerates G1-S and G2-M transitions, and increases DNA damage to intolerable levels, resulting in mitotic catastrophe and cell death • CDKs and their cyclin binding partners promote progression through the cell cycle • Following DNA damage, WEE1 kinase inactivates Cyclin/CDK complexes at both G1-S and G2-M checkpoints to halt the cell cycle and allow for repair • Upon DNA repair, cells progress through the cell cycle and proliferate Phosphorylation, causing inactivation of CDK1/2 DNA damageP G1 S G2 MDNA Damage Repaired CDK2 Inactive CDK2Cyclin E1 WEE1 P CDK1 Inactive WEE1 Cell Proliferation P Normal Cell Cycle Regulation Cancer Cell and Azenosertib Mitotic Catastrophe and Death G2-M Checkpoint DNA Damage Accumulates Cyclin E1 Overexpression accelerates G1-S transition Cyclin CDK Azenosertib Azenosertib CDK1 Active G1-S Checkpoint Cyclin E1 CDK2 G1 S G2 MCyclin CDK G2-M Checkpoint G1-S Checkpoint WEE1 WEE1
DENALI Part 1b Patient Characteristics: Heavily Pre-Treated PROC Population Data cutoff: May 22, 2026. aFull Analysis Set: all treated patients. Biomarker dataset: all treated patients with evaluable tissue and Cyclin E1 IHC status. bHispanic. cOne patient had ECOG PS 2. dCCNE1 amplification defined as copy number ratio ≥3 with genomic ploidy correction as per Foundation Medicine. eIHC positive based on Sponsor’s proprietary cutoff. ECOG PS, Eastern Cooperative Oncology Group performance status; IHC, immunohistochemistry; PARPi, poly(ADP-ribose) polymerase inhibitor. 16 ~50% of Patients Identified with Cyclin E1 Overexpression per IHC Retrospectively DENALI Part 1b, ESMO 2026 Characteristicsa (All treated patients, N=102) Median age (range), years 66 (34-82) Race, n (%) White 70 (69) Black/African American 6 (6) Asian 3 (3) Otherb 1 (1) Not reported 22 (22) ECOG PSc, n (%) 0 49 (48) 1 52 (51) Prior lines of treatment Median (range) 3 (1-5) 1-2, n (%) 35 (34) 3-4, n (%) 57 (56) 5, n (%) 10 (10) Characteristicsa (All treated patients, N=102) Prior therapy, n (%) Taxane 99 (97) Bevacizumab 93 (91) PARPi 56 (55) Mirvetuximab 15 (15) CCNE1 amplification,d Evaluable, n 88 Amplified, n (%) 27 (31) Cyclin E1 status Evaluable, n 94 IHC positivee, n (%) 48 (51) DENALI Part 1b enrolled patients with 1-5 prior lines of therapy (>65% had 3+ prior lines)
DENALI Part 1b Demonstrated Cyclin E1 as Predictive Biomarker for Response to Azenosertib Data cutoff: May 22, 2026. aBiomarker dataset: all treated patients with evaluable tissue and Cyclin E1 IHC status. bIncludes patients who received at least one post-baseline scan. Horizontal lines at -30% and +20% are marked as 'PR' and 'PD', respectively, for illustrative purposes based on target lesion change. Overall response was assessed by the Investigator according to RECIST v1.1. cMedian PFS in DENALI Part 1b confounded by early withdrawal, which is now addressed by mitigation strategies in DENALI Part 2 and ASPENOVA. CR, complete response; DOR, duration of response; IHC, immunohistochemistry; ORR, objective response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease. 17 15.9 months median OS in Cyclin E1-Positive vs 7.5 months in Cyclin E1-Negative Patients DENALI Part 1b, ESMO 2026 Cyclin E1 IHC+ (n=48) ORR, % (n/N; 95% CI) 33.3 (16/48; 20.4-48.4) ORR in response-evaluableb patients, % (n/N; 95% CI) 37.2 (16/43; 23.0-53.3) Median DOR, months (95% CI) 5.5 (4.5-15.9) Median PFS, months (95% CI) 4.1 (2.8-6.8)c Cyclin E1 IHC+ (n=48) Cyclin E1 IHC– (n=46) Median OS, months (95% CI) 15.9 (8.7-21.2) 7.5 (5.8-12.3) Events, n (%) 31 (65) 34 (74) Cyclin E1 IHC positive (n=48)a Cyclin E1 IHC+ (n=48) vs IHC– (n=46)a ORR in response-evaluable patientsb 37.2% B es t % C ha ng e fr om B as el in e Cyclin E1 positivity predicted longer OS with azenosertib
Subsequent Anti-Cancer Therapies Were Similar in Cyclin E1-Positive and All Treated Patients Data cutoff: May 22, 2026. Descriptive analysis; subsequent treatment was not randomized. Percentages are of patients in each analysis group. IHC, immunohistochemistry; PLD, pegylated liposomal doxorubicin.18 ~40% of Cyclin E1-Positive Patients Did Not Receive Subsequent Therapies; ~60% Primarily Received Single Agent Chemotherapy ± bevacizumab DENALI Part 1b, ESMO 2026 All Subsequent Therapies All treated (n=102) Cyclin E1 IHC+ (n=48) Patients receiving subsequent therapies, n (%) 55 (53.9) 29 (60.4) Including but not limited to: Bevacizumab 20 (19.6) 11 (22.9) Paclitaxel 21 (20.6) 10 (20.8) Investigational therapies 15 (14.7) 9 (18.8) PLD or doxorubicin 14 (13.7) 8 (16.7) Gemcitabine 18 (17.6) 7 (14.6) Pembrolizumab 13 (12.7) 7 (14.6) Cyclophosphamide 11 (10.8) 7 (14.6) Carboplatin 8 (7.8) 5 (10.4) Mirvetuximab soravtansine 6 (5.9) 4 (8.3) First Subsequent Therapies, % of patients 25 27 8 6 8 8 6 83 22 4 2 4 46 40 0% 20% 40% 60% 80% 100% All treated patients (n=102) Cyclin E1 positive (n=48) Pe rc en ta ge s of p at ie nt s Chemotherapy Chemotherapy + Bevacizumab Investigational therapies Mirvetuximab soravtansine Immunotherapy Hormonal therapy Trastuzumab deruxtecan Did not receive subsequent therapy
DENALI Part 1b Safety and Tolerability Summary Data cutoff: May 22, 2026; safety profile was consistent with prior reporting. bOne patient had sepsis and one patient had pancyenia. ALT, alanine aminotransferase; AST, aspartate aminotransferase; TRAE, treatment-related adverse event. aIf a patient had multiple grades of the same adverse event, the worse grade was reported. 19 DENALI Part 1b, ESMO 2026 12 11 11 4 7 3 2 3 16 7 3 5 1 23 18 5 62 44 20 13 15 11 44 8 14 10 11 11 6 10 0 25 50 75 Grade ≥3 Grades 1-2 % Patients Hematological Thrombocyenia Anemia Neutropenia Gastrointestinal Nausea Diarrhea Decreased appetite Constipation Dysgeusia Abdominal pain Other Fatigue ALT increased Asthenia Dizziness Headache Hypomagnesemia AST increased Dehydration TRAEs, n (%) Leading to dose reduction 44 (43.1) Leading to dose interruption 58 (56.9) Leading to discontinuation 20 (19.6) Leading to death 2 (2.0)b Serious TRAEs 22 (21.6) Exposure to Azenosertib Median relative dose intensity, % (range) 84.6 (20.0‒101.6) TRAEs occurring in ≥10% of patientsa • Part 1b informed enhanced trial management and supportive care protocols for registration-intended DENALI Part 2 • Part 2a showed ~50% reduction in discontinuation rate and no treatment-related deaths The Majority of Treatment-Related AEs Were Low Grade
Building Azenosertib Franchise in Ovarian Cancer and Beyond 20
MUIR: Ongoing Phase 1b, Part 2 Study of Azenosertib in Combination with Bevacizumab Focused on Platinum Sensitive Ovarian Cancer Abbreviations: PROC = platinum-resistant ovarian cancer; 1L = first line; 2L = second line; PARPi = poly(ADP-ribose) polymerase inhibitor; ORR = overall response rate; DOR = duration of response; PFS = progression-free survival; PSOC = platinum-sensitive ovarian cancer; PLD = pegylated liposomal doxorubicin; NCT0451644721 Key Eligibility Advanced ovarian, peritoneal, or fallopian tube cancer Part 1: 1-2 prior lines of therapy; platinum- resistant Part 2 Dose Escalation: 1L maintenance or platinum-sensitive 2L maintenance Part 2 Dose Expansion: Platinum-sensitive 2L maintenance; progressed while on a PARPi for 1L maintenance Part 1 Azenosertib + Chemo Combo in PROC Azenosertib + Paclitaxel Data Presented ASCO 2026 Primary Endpoints Key Secondary Endpoints Safety and Tolerability ORR, DOR, PFS Part 2 Azenosertib + Bevacizumab as 1L/2L PSOC Maintenance Therapy Dose Escalation Dose Expansion Assess safety and recommended dose of azenosertib + bevacizumab Evaluate azenosertib 300mg QD 5:2 in combination with bevacizumab Primary Endpoints Safety and Tolerability Key Secondary Endpoint PFS Completed EnrollingCompleted
Azenosertib Combinations Demonstrate Compelling Activity in Preclinical Triple-Negative Breast Cancer Models Preclinical data presented at AACR 2026 (Lee et al., Poster #3902, April 20, 2026) Abbreviations: TNBC = triple-negative breast cancer; ADC = antibody-drug conjugate; EV = enfortumab vedotin; SG = sacituzumab govitecan; Dato-DXd = daotamab deruxtecan; T-DXd = trastuzumab deruxtecan; O1i = oisomerase 1 inhibitor; CR = complete response; PR = partial response; PFS = progression-free survival; DoR = duration of response; TGI = tumor growth inhibition; 1L = first line 22 TNBC Exhibits High Cyclin E1 Expression and Sensitivity to WEE1 Inhibition Azenosertib + EV Induces Complete Responses in TOPO1i ADC-Resistant TNBC Model Preclinical TNBC, AACR 2026 Percent change in tumor volume for individual mice on last day of treatment. Orange dashed line = partial response threshold (-30%); Blue dashed line = complete response threshold (-100%) Azenosertib + T-Dxd Deepens and Extends Responses in ADC naïve TNBC Model
23 Pioneering WEE1 Inhibition to Deliver More Convenient, Targeted Cancer Care for Patients with Cyclin E1-Positive Ovarian Cancer and Beyond
Our Mission: Delivering a More Convenient, Targeted Approach to Cancer Care * ** Cash, cash equivalents and marketable securities as of 9/30/26; Shares outstanding as of September 30, 2026 = 98.3M Abbreviations: PROC = platinum-resistant ovarian cancer; ADC = anti-body drug conjugate; OS = overall survival; TNBC = triple-negative breast cancer Based on 2025 Decision Resource estimates in US, EU4 (France, Germany, Italy, Spain), UK, and Japan 24 • Focused on unmet need: ~20,000 Cyclin E1-positive PROC patients* with poor prognosis and no specifically targeted treatment options • Differentiated in an evolving landscape: the only non- chemo, non-ADC oral investigational therapy in pivotal development specifically for Cyclin E1-positive PROC • Compelling clinical data supports PROC program: ~35% ORR, ~5.5 month DOR, ~16 month OS (DENALI Part 1b, ESMO 2026) supports complementary regulatory paths with DENALI and ASPENOVA • Franchise expansion opportunities: MUIR combination with bevacizumab in platinum-sensitive ovarian cancer; TNBC combination study planned • Resourced to execute: ~$229M cash** with runway into 1H 2028, to support full enrollment in ASPENOVA Phase 3 and combination trials in ovarian cancer and TNBC
Julie Eastland Haibo Wang Chief Executive Officer jeastland@zentalis.com Chief Business Officer hwang@zentalis.com Aron Feingold VP, IR and Corporate Communications afeingold@zentalis.com