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Zentalis Pharmaceuticals (Nasdaq: ZNTL) outlines Q2 loss and WEE1 plans

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Form Type
8-K

Rhea-AI Filing Summary

Zentalis Pharmaceuticals reported a Q2 2026 net loss of $42.3 million, or $0.59 per share, as operating expenses rose to $44.4 million, driven mainly by $35.2 million of research and development spending that included a $7.0 million milestone payment tied to commencing the ASPENOVA Phase 3 trial.

Cash, cash equivalents and marketable securities were $174.6 million as of June 30, 2026, compared with $245.9 million at December 31, 2025, and the company states this provides runway into late 2027. Working capital totaled $143.7 million.

Clinically, Zentalis is advancing azenosertib, an investigational WEE1 inhibitor, in ovarian cancer. Following a Type D meeting, the FDA raised no objections to the selected 400 mg once-daily 5:2 dosing in the registration-intended DENALI Phase 2 trial and acknowledged the DENALI Part 2 population could support an accelerated approval pathway, subject to data and the treatment landscape. Enrollment in DENALI Parts 2a and 2b is complete, Part 2c is enrolling, and topline Part 2 results are expected in the first half of 2027. The confirmatory ASPENOVA Phase 3 trial has begun dosing and is enrolling approximately 420 Cyclin E1-positive platinum-resistant ovarian cancer patients.

Positive

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Negative

  • None.
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, and exhibit attachments filed with this report.
Cash, cash equivalents and marketable securities $174.6 million Balance as of June 30, 2026, supporting runway into late 2027
Cash, cash equivalents and marketable securities $245.9 million Balance as of December 31, 2025, prior to Q2 2026 cash usage
Research and development expenses Q2 2026 $35.2 million Three months ended June 30, 2026, versus $27.6 million in Q2 2025
Net loss Q2 2026 $42,286 (in thousands) Net loss for the three months ended June 30, 2026; $26,874 (in thousands) in Q2 2025
Net loss per share Q2 2026 $0.59 Basic and diluted net loss per common share for the quarter ended June 30, 2026
Total operating expenses Q2 2026 $44.4 million Three months ended June 30, 2026, compared with $36.1 million in Q2 2025
Working capital $143,653 (in thousands) Defined as current assets less current liabilities as of June 30, 2026
Cyclin E1-positive PROC patients 20,000 Estimated Cyclin E1-positive platinum-resistant ovarian cancer patients across US, EU4, UK and Japan
accelerated approval regulatory
"has the potential to support an accelerated approval pathway, subject to the strength of the data"
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.
platinum-resistant ovarian cancer (PROC) medical
"as a biomarker-driven treatment approach for ovarian cancer, including Cyclin E1-positive platinum-resistant ovarian cancer (PROC)"
WEE1 inhibitor medical
"an investigational, potentially first-in-class, selective, and orally bioavailable inhibitor of WEE1"
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.
progression-free survival (PFS) medical
"The primary endpoint is progression-free survival (PFS); key secondary endpoints include overall survival (OS)"
Progression-free survival (PFS) measures the length of time in a clinical trial or treatment period during which a patient’s disease does not get worse. Investors watch PFS because longer PFS in trials can signal a drug’s effectiveness, influence regulatory approval and reimbursement decisions, and affect commercial value—think of it as how long a product keeps a problem from returning, which helps estimate future sales and competitive advantage.
Type D meeting regulatory
"aligning with the U.S. Food and Drug Administration (FDA) following a Type D meeting on our selected dose"
companion diagnostic medical
"our plans, including the costs thereof, of development of a companion diagnostic"
A companion diagnostic is a medical test designed to identify which patients are likely to benefit from a specific drug or medical treatment, much like a key that shows whether a particular lock will open. For investors, these tests matter because they can increase a drug’s chances of approval and market uptake, create a separate revenue stream, and reduce commercial risk by matching treatments to the patients most likely to respond.
Net loss Q2 2026 $42,286 (in thousands) Compared with $26,874 (in thousands) for Q2 2025
Net loss per share Q2 2026 $0.59 Compared with $0.37 for Q2 2025
R&D expenses Q2 2026 $35.2 million Up from $27.6 million for Q2 2025, including a $7.0 million milestone payment to Recurium IP Holdings, LLC
G&A expenses Q2 2026 $9.2 million Compared with $8.4 million for the three months ended June 30, 2025
Cash, cash equivalents and marketable securities $174.6 million Down from $245.9 million at December 31, 2025
Guidance

The company states that existing cash, cash equivalents and marketable securities as of June 30, 2026 will be sufficient to fund operating expenses and capital expenditure requirements into late 2027.

AI-generated analysis. How Rhea-AI works. Not financial advice.

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FAQ

What were ZNTL’s key financial results for the second quarter of 2026?
Zentalis reported a Q2 2026 net loss of $42.3 million, or $0.59 per share, on $44.4 million of total operating expenses. Research and development expense was $35.2 million, including a $7.0 million milestone payment linked to the ASPENOVA Phase 3 trial.

How much cash and runway does ZNTL have as of June 30, 2026?
As of June 30, 2026, Zentalis held $174.6 million in cash, cash equivalents and marketable securities. The company states this balance is expected to fund operating and capital expenditure requirements into late 2027, supporting execution of key clinical and regulatory milestones.

What is the DENALI Part 2 trial for ZNTL and when is topline data expected?
DENALI Part 2 is a registration-intended Phase 2 study of azenosertib in Cyclin E1-positive platinum-resistant ovarian cancer. Enrollment in Parts 2a and 2b is complete and Part 2c is enrolling. Zentalis expects an integrated DENALI Part 2 topline readout in 1H 2027.

What is the ASPENOVA Phase 3 trial ZNTL is conducting?
ASPENOVA is a randomized Phase 3 confirmatory trial in approximately 420 patients with Cyclin E1-positive platinum-resistant ovarian cancer. It compares azenosertib 400 mg QD 5:2 against investigator’s choice of single-agent chemotherapy, with progression-free survival as the primary endpoint.

What patient population is ZNTL targeting with azenosertib?
Azenosertib is being developed as an oral, non-chemotherapy WEE1 inhibitor for Cyclin E1-positive platinum-resistant ovarian cancer. Zentalis estimates about 50% of platinum-resistant ovarian cancer patients are Cyclin E1-positive, representing roughly 20,000 patients across major markets.

How did ZNTL’s research and development expenses change in Q2 2026?
Research and development expenses were $35.2 million in Q2 2026, up from $27.6 million in Q2 2025. The $7.6 million increase was driven mainly by a $7.0 million milestone payment and higher clinical and manufacturing costs for the DENALI and ASPENOVA trials.
0001725160FALSE00017251602026-08-062026-08-06


UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
——————————————

FORM 8-K
——————————————

CURRENT REPORT

Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of report (Date of earliest event reported): August 6, 2026

——————————————  
ZENTALIS PHARMACEUTICALS, INC.
(Exact name of registrant as specified in its charter)   
——————————————
Delaware001-3926382-3607803
(State or other jurisdiction
of incorporation or organization)
(Commission
File Number)
(I.R.S. Employer
Identification No.)
10275 Science Center Drive, Suite 200
San Diego, California 92121
(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)  
——————————————
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 classTrading Symbol(s)Name of each exchange on which registered
Common Stock, $0.001 par value per shareZNTLThe Nasdaq Global Market

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 August 6, 2026, Zentalis Pharmaceuticals, Inc. (the “Company”) announced its financial results for the quarter ended June 30, 2026, and commented on certain business updates. The full text of the press release issued in connection with the announcement 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 August 6, 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 August 6, 2026
99.2
Corporate Presentation dated August 2026
104Cover 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: August 6, 2026By:/s/ Julie Eastland
Julie Eastland
President and Chief Executive Officer

image_0aa.jpg
Exhibit 99.1
Zentalis Pharmaceuticals Reports Second Quarter 2026 Financial Results and Business Updates

•Following U.S. regulatory discussions, accelerated approval strategy remains intact, supported by DENALI Part 2
•Enrollment completed in Part 2a and 2b of the DENALI trial; Part 2c is enrolling
•DENALI Part 2 topline readout expected in 1H 2027 to allow for data maturation post full enrollment
•$174.6 million in cash, cash equivalents and marketable securities as of June 30, 2026, providing runway into late 2027 to support execution of key milestones

SAN DIEGO — August 6, 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 second quarter ended June 30, 2026, and highlighted recent corporate, regulatory and clinical progress and upcoming expected milestones.

"We have achieved important milestones on the continued advancement of azenosertib in our registration-intended DENALI Phase 2 and ASPENOVA Phase 3 trials for patients with Cyclin E1-positive platinum-resistant ovarian cancer (PROC), including completing the enrollment of DENALI Part 2b and aligning with the U.S. Food and Drug Administration (FDA) following a Type D meeting on our selected dose and DENALI study population to support potential accelerated approval,” said Julie Eastland, Chief Executive Officer of Zentalis. "We remain as confident as ever that azenosertib has the potential to be an important oral, non-chemotherapy treatment option for the approximately 50% of PROC patients with Cyclin E1-positive tumors, who have limited options. We expect to provide the topline readout of DENALI Part 2 in 1H 2027. We continue to advance the confirmatory ASPENOVA Phase 3 trial with the goal of bringing a potential first-in-class WEE1 therapy to market for this underserved patient population globally. In addition to the lead indication, we see opportunity for expansion of azenosertib into platinum-sensitive settings of ovarian cancer and additional tumor types through combinations."

"We are well capitalized as of June 30, 2026 with cash, cash equivalents and marketable securities of $174.6 million to support the execution of key milestones and to continue advancing our regulatory strategy for both accelerated and full approval in PROC,” Ms. Eastland continued.

Business Updates

•Regulatory Update: Met with the FDA in a Type D meeting regarding the Company’s accelerated approval strategy, including dose. The FDA had no objection to the continued study of the selected monotherapy dose of azenosertib at the 400mg once daily on a 5-days-on, 2-days-off schedule (400mg QD 5:2) in patients with Cyclin E1-positive PROC, selected based on a pre-specified interim analysis from DENALI Part 2a. The FDA acknowledged the DENALI Part 2 study population, including the 2c cohort, has the potential to support an accelerated approval pathway, subject to the strength of the data and the landscape of approved agents at the time of regulatory action.
•DENALI Part 2 Enrollment and Integrated Topline Readout: Enrollment in DENALI Parts 2a and 2b is complete. Earlier this year, the Company expanded DENALI Part 2 to broaden the overall study population and enrich patients previously treated with a taxane-containing regimen for PROC, aligning the study population with the evolving treatment landscape of approved agents. DENALI Part 2c is currently enrolling. The integrated dataset of DENALI Parts 2a, 2b, and 2c is designed to support accelerated approval in the Cyclin E1 biomarker-selected patient



population, subject to regulatory review. The Company expects to provide a topline readout in 1H 2027 to allow for data maturation post full enrollment.
•ASPENOVA Phase 3 First Patient Dosed: In May 2026, announced the first patient was dosed in the Phase 3 ASPENOVA confirmatory trial designed to satisfy FDA requirements for U.S. full approval and to support approval in major ex-U.S. markets. The trial is currently enrolling.
•ESMO 2026 Abstract Acceptances: Announced that the European Society for Medical Oncology (ESMO) has accepted an abstract for rapid oral presentation at the 2026 ESMO Annual Meeting featuring overall survival analysis from Part 1b of the DENALI study of azenosertib in PROC patients. A second abstract featuring the ASPENOVA Phase 3 trial design has been accepted for a trial-in-progress poster presentation.
•MUIR Clinical Trial Data Presented at ASCO 2026: Presented results from Part 1 of the Phase 1b MUIR trial at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, focusing on an evaluation of azenosertib in combination with paclitaxel in PROC. The data showed combinability and activity of azenosertib in an all-comer PROC setting, demonstrating the potential for azenosertib in multiple lines of ovarian cancer and more broadly in combination with cytotoxic agents in other tumor types. Part 2 enrollment is ongoing for azenosertib in combination with bevacizumab for 2L platinum sensitive ovarian cancer.
•Expanded Commercial Capabilities: In May 2026, announced the appointments of Shannon Campbell to the Company’s Board of Directors and Sarah Kelly as SVP of Commercial Strategy to support commercialization readiness.

Second Quarter 2026 Financial Results
•Cash Position: Cash, cash equivalents and marketable securities were $174.6 million as of June 30, 2026, compared to $245.9 million as of December 31, 2025. The Company believes that its existing cash, cash equivalents and marketable securities as of June 30, 2026 will be sufficient to fund its operating expenses and capital expenditure requirements into late 2027.
•Research and Development Expenses: Research and development expenses for the three months ended June 30, 2026 were $35.2 million, compared to $27.6 million for the three months ended June 30, 2025. The increase of $7.6 million was primarily due to a $7.0 million milestone payment to Recurium IP Holdings, LLC required as a result of the commencement of the Phase 3 ASPENOVA clinical trial and an increase of $5.2 million related to clinical expenses and drug manufacturing, including costs associated with advancing the DENALI and ASPENOVA trials. This increase was partially offset by a decrease of $4.5 million for personnel expense, of which $2.1 million was non-cash stock-based compensation, and a decrease of $0.1 million related to allocated overhead.
•General and Administrative Expenses: General and administrative expenses for the three months ended June 30, 2026 were $9.2 million, compared to $8.4 million during the three months ended June 30, 2025. This increase of $0.8 million was primarily attributable to an increase of $1.7 million for consulting and outside services. This increase was partially offset by a decrease of $0.9 million for non-cash stock-based compensation.
•Total Operating Expenses: Total operating expenses were $44.4 million for the three months ended June 30, 2026, compared to $36.1 million for the three months ended June 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 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.

About DENALI Clinical Trial 
DENALI is a multi-part Phase 2 registration-intended 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, 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, 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, which is expected to include approximately 40 patients previously treated with a taxane-containing regimen for PROC. This cohort is currently enrolling. Zentalis expects to complete enrollment in all cohorts of DENALI Part 2 (2a, 2b, 2c) and provide a topline readout by 1H 2027.

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). 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 MUIR Clinical Trial
MUIR (NCT04516447) is a multi-part, open-label Phase 1b clinical trial evaluating the safety, efficacy, and preliminary clinical activity of azenosertib combinations in patients with ovarian cancer. Part 1 enrolled patients with platinum-resistant ovarian cancer (PROC) treated with azenosertib in combination with one of four chemotherapy regimens: carboplatin, gemcitabine, pegylated liposomal doxorubicin, or paclitaxel. Primary objectives are safety and tolerability, with key secondary objectives including clinical activity assessed by objective response rate, duration of response, and progression-free survival per RECIST v1.1.




Part 2 is evaluating azenosertib plus bevacizumab as maintenance regimen (first [1L] or second line [2L]) in patients with advanced ovarian, peritoneal, or fallopian tube cancer following platinum-based chemotherapy. The dose expansion portion will evaluate azenosertib at the recommended dose in combination with bevacizumab in patients with platinum-sensitive ovarian cancer in 2L who progressed while on a PARP inhibitor for 1L maintenance. The primary objective is safety and tolerability; secondary objectives include preliminary clinical activity of the combination as assessed by progression-free survival for the dose expansion portion. The dose expansion portion is currently open for enrollment.

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.

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 an important treatment option for patients with ovarian cancer or other indications; the Company’s biomarker-driven strategy for azenosertib; the potential to advance research on additional areas of opportunity for azenosertib as maintenance therapy in ovarian cancer and to explore additional tumor types; 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 and MUIR Phase 1b trials; the Company's commercialization planning and readiness activities; the potential for expansion of azenosertib into platinum-sensitive settings 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 DENALI Part 2 to support an accelerated approval and for ASPENOVA to support conversion to a full approval and ex-US approval. The terms “anticipate,” “advance,” “believe,” “continue,” “design,” “develop,” “expect,” “focus,” “intend,” “plan,” “potential,” “runway,” “strategy,” “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
ir@zentalis.com  



Zentalis Pharmaceuticals, Inc.
Condensed Consolidated Statements of Operations
(Unaudited)
(In thousands, except per share amounts)
Three Months Ended June 30,Six Months Ended June 30,
2026202520262025
Operating Expenses
Research and development$35,163 $27,610 $63,879 $54,857 
General and administrative9,228 8,448 18,367 19,028 
Restructuring— — — 7,796 
Total operating expenses44,391 36,058 82,246 81,681 
Loss from Operations(44,391)(36,058)(82,246)(81,681)
Other Income (Expense)
Investment and other income, net2,243 9,184 4,866 6,528 
Net loss before income taxes(42,148)(26,874)(77,380)(75,153)
Income tax expense138 — 258 — 
Net loss$(42,286)$(26,874)$(77,638)$(75,153)
Net loss per common share outstanding, basic and diluted$(0.59)$(0.37)$(1.10)$(1.05)
Common shares used in computing net loss per share, basic and diluted71,326 71,992 70,798 71,836 



Zentalis Pharmaceuticals, Inc.
Selected Condensed Consolidated Balance Sheet Data
(Unaudited)
(In thousands)


As of June 30,As of December 31,
20262025
Cash, cash equivalents and marketable securities
$174,608 $245,893 
Working capital (1)
143,653 216,632 
Total assets
215,330 288,967 
Total liabilities
71,684 72,763 
Total Zentalis equity
$143,646 $216,204 
(1) The Company defines working capital as current assets less current liabilities.
 



Pioneering WEE1 Inhibition to Deliver More Convenient, Targeted Cancer Care Corporate Presentation | August 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; 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 and best-in-class; the Company’s development strategy and approach for azenosertib, including the Company’s strategy to focus on bringing azenosertib to patients with PROC who are Cyclin E1-positive and the potential for azenosertib to be a new treatment option for ovarian cancer patients 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 and other tumor types; the Company’s planned strategy, vision and path forward; 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 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,” “continue,” “design,” “estimate,” “expect,” “forward,” “intent,” “milestone,” “ongoing,” “opportunity,” “path,” “plan,” “potential,” “predictive,” “projected,” “strategy,” "support," “vision,” “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, “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; 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 Addressing ~20,000 Cyclin E1-positive PROC patients^ with no specifically targeted treatment options Abbreviations: PROC = platinum-resistant ovarian 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 6/30/26; Shares outstanding as of Aug 3, 2026 = 71.7M 3 Investigational first-in-class WEE1 inhibitor, azenosertib demonstrates compelling clinical profile as a potential oral, non-chemo treatment in Cyclin E1-positive PROC Clear development and regulatory strategy: DENALI Part 2 topline readout expected 1H 2027 to support potential accelerated approval; ASPENOVA Phase 3 trial enrolling, designed to support full approval Building azenosertib franchise beyond PROC into earlier lines of ovarian cancer and other tumor types Resourced to execute with ~$175M cash† providing runway into late 2027 and industry-leading WEE1 expertise and proven leadership

 

Strong Execution Drives Momentum Towards Key Value Inflection Points Abbreviations: PROC = platinum-resistant ovarian cancer; 5:2 schedule = 5 days once-daily administration of azenosertib, followed by 2 days without azenosertib4 Completed enrollment in DENALI Part 2a, designed to confirm dose for the registration-intended studies 2H 2025 Selected 400mg QD 5:2 as the monotherapy dose for pivotal studies in Cyclin E1-positive PROC 1H 2026 ASPENOVA Phase 3 first patient dosed, designed to support full approval pathway Completed DENALI Part 2a & b enrollment 2H 2026 Enrolling DENALI Part 2c, ASPENOVA, and MUIR Part 2 Anticipated DENALI Part 2 topline readout (all cohorts); Part 2 designed as a registration intended, accelerated approval study 1H 2027 Aligned with the FDA on randomized, confirmatory ASPENOVA Phase 3 clinical trial design Launch preparedness activities advancing

 

~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 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 survival5 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-Positive1 ~50%

 

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 analysis across 001, MAMMOTH and DENALI Part 1b at 400mg QD 5:2; † 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 • Meaningful 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 • >30% ORR and ~6 month DOR^ 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 Registration-Intended Study in Cyclin E1-Positive PROC for Accelerated Approval 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  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 FOR POTENTIAL ACCELERATED APPROVAL (N= ~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 Part 2c Broadened Study Population 400mg QD 5:2 (N=~40) Enrolling

 

ASPENOVA: Phase 3 Confirmatory Study in Cyclin E1-Positive PROC for Full Approval 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, Topotecan (N = ~210) 1:1 Randomization ASPENOVA RANDOMIZED TRIAL INTENDED FOR FULL APPROVAL (FDA Aligned, N= ~420)

 

Focused Pipeline with Registration-Intended Cyclin E1-Positive PROC Trials Abbreviations: PROC = platinum-resistant ovarian cancer; SOC = standard-of-care; 1L = first line; 2L = second line; PSOC = platinum-sensitive ovarian cancer * Also known as ZN-c3-002 9 Potential for Franchise Expansion in Earlier Lines of Ovarian Cancer and Other Tumor Types 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 In Long-term Follow-up Only 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 enrolling 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

 

Cyclin E1-Positive PROC Patients Face Poor Prognosis with No Specifically Targeted Treatment Options Abbreviations: PROC = platinum-resistant ovarian cancer10

 

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). 11 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 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; † 12 • Cyclin E1-positive ovarian cancer patients show consistently poor outcomes 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 Worse outcome of Cyclin E1-positive ovarian cancer patients highlights critical unmet need for targeted therapies in this population

 

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 13 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 topotecan 6 3.2 12 CORAIL3 (n=199) PROC ≤3 priors (46% prior bev) PLD or topotecan 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 topotecan 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; 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 14 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 outcomes on SOC therapies1 No approved therapies 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 15

 

Azenosertib: A Differentiated, Potentially First-in-Class WEE1 Inhibitor 16 • 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

 

Integrated Data Across Multiple Early Clinical Studies Demonstrate Compelling Benefit-Risk Profile for Azenosertib Monotherapy in PROC 800+ patients have been treated with azenosertib across all studies, including additional tumor types, monotherapy and combination therapies. This slide focuses on PROC monotherapy data directly informing registration trials. Abbreviations: PROC = platinum-resistant ovarian cancer; PARPi = PARP inhibitor; 5:2 = 5 days once-daily administration followed by 2 days without azenosertib; QD = once daily 17 Learnings from ZN-c3-001, MAMMOTH, and DENALI Part 1b Inform Registration Strategy in Cyclin E1+ PROC ZN-c3-001 First-in-human, solid tumors N=40 (PROC, intermittent dosing) 300mg & 400mg QD 5:2  Therapeutic window established in PROC with intermittent dosing MAMMOTH PARPi-resistant PROC N=61 300mg & 400mg QD 5:2  Activity confirmed in heavily pre- treated, PARPi-resistant population DENALI Part 1b PROC, All-comers N=102 400mg QD 5:2  Retrospective analysis demonstrated Cyclin E1 as predictive biomarker Integrated Efficacy Analysis of Cyclin E1-positive PROC Patients Integrated Analysis 400mg QD 5:2 (N=73) 300mg QD 5:2 (N=20) Integrated Safety Analysis of PROC Patients 400mg QD 5:2 (N=165) 300mg QD 5:2 (N=38)

 

400mg QD 5:2 Shows >30% ORR and ~6 Month Duration in Cyclin E1-Positive PROC *Includes patients who received at least one post-treatment scan Abbreviations: CI = confidence interval; cPR = confirmed partial response; mDOR = median duration of response; PD = progressive disease; SD = stable disease; NE = not estimable due to small number of subjects and events. 18 Integrated Analysis PROC, Cyclin E1+ (001, MAMMOTH, DENALI Part 1b) 300 mg 5:2 400 mg 5:2 ORR in response evaluable* (95% CI) 22.2% (4/18) (6.4 - 47.6) 33.8% (23/68) (22.8 - 46.3) ORR in intent-to-treat (95% CI) 20.0% (4/20) (5.7 – 43.7) 31.5% (23/73) (21.1 – 43.4) mDOR (mos) (95% CI) 3.9 (2.8, NE) 5.5 (3.5, 6.3) mPFS (mos) (95% CI) 4.1 (1.3, 6.6) 4.4 (2.8, 6.8) + + + + + + + + +-100 — -80 — -60 — -40 — -20 — 0 — 20 — 40 — 60 — 80 — 100 — Be st P er ce nt C ha ng e fro m B as el in e in S um o f D ia m et er (% ) PR PD 300mg 5:2 (N=18) 400mg 5:2 (N=68) PDSDcPRBest Overall Response # # # # # # # # # ‡ ‡ ‡ + = treatment ongoing # = best % change ~0% ‡ = received a post-baseline scan as SD but did not qualify as SD due to the post-baseline scan occurring outside of a protocol defined window Data Cutoff Dec 2 2024 Active database; subject to further change

 

Safety and Tolerability at 300mg and 400mg QD 5:2 Broadly Comparable Data cutoff Dec 2, 2024. Active database; subject to further change. Neutropenia: Neutropenia, neutrophil count decreased, neutrophil percentage decreased; Thrombocytopenia: platelet count decreased and thrombocytopenia; Anemia: hematocrit decreased, hemoglobin decreased, RBC count decreased Abbreviations: AE, adverse event; TRAE, treatment related adverse event. SAE, serious adverse event. 19 Monotherapy Safety Profiles in PROC Patients from Integrated Analysis (001, MAMMOTH, DENALI Part 1b) Integrated Analysis 300mg (N=38) 400mg (N=165) Treatment-related AEs*, N (%) All Grade Grade 3+ All Grade Grade 3+ Gastrointestinal Decreased appetite 8 (21.1%) 1 (2.6%) 40 (24.2%) 2 (1.2%) Diarrhea 18 (47.4%) 1 (2.6%) 86 (52.1%) 12 (7.3%) Nausea 23 (60.5%) 0 101 (61.2%) 6 (3.6%) Vomiting 3 (7.9%) 0 17 (10.3%) 3 (1.8%) Dehydration 1 (2.6%) 0 14 (8.5%) 1 (0.6%) Fatigue 14 (36.8%) 2 (5.3%) 90 (54.5%) 20 (12.1%) Sepsis 0 0 4 (2.4%) 4 (2.4%) Hematologic Anemia 13 (34.2%) 3 (7.9%) 53 (32.1%) 20 (12.1%) Thrombocytopenia 13 (34.2%) 2 (5.3%) 36 (21.8%) 8 (4.8%) Neutropenia 4 (10.5%) 3 (7.9%) 30 (18.2%) 21 (12.7%) Febrile Neutropenia 0 0 4 (2.4%) 4 (2.4%) Treatment-related AEs, N (%) 300mg (N=38) 400mg (N=165) Treatment-Related SAE 6 (15.8%) 31 (18.8%) TRAE leading to dose reduction 13 (34.2%) 69 (41.8%) TRAE leading to dose interruption 16 (42.1%) 89 (53.9%) TRAE leading to discontinuation 5 (13.2%) 26 (15.8%) TRAE leading to death 0 3 (1.8%) * TRAEs listed here represent adverse events of special interest and adverse events of clinical significance for azenosertib and this class of molecules • While numerically different, broadly comparable safety profiles at 300mg and 400mg 5:2 • Low frequency of G3+ febrile neutropenia, sepsis, and previously reported G5 TRAEs observed at 400mg 5:2

 

DENALI Part 1b Patient Characteristics: Heavily Pre-Treated PROC Population Data cutoff date: January 13, 2025. aFull analysis set: all treated patients. Biomarker dataset: all treated patients with evaluable tissue and Cyclin E1 IHC status. bHispanic. c85% (23/27) of patients with CCNE1-amplified tumors were also Cyclin E1+ by IHC. Amp, amplified; CCNE1 amplification defined as Copy Number ratio ≥3 with genomic ploidy correction as per Foundation Medicine. ECOG PS, Eastern Cooperative Oncology Group performance status; IHC, immunohistochemistry; PARPi, poly(ADP-ribose) polymerase inhibitor.20 ~50% of Patients Identified with Cyclin E1 Overexpression per IHC Retrospectively DENALI Part 1b, SGO 2025 Characteristicsa (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 (21) ECOG PS, n (%) 0 53 (52) 1 49 (48) Prior lines of treatment Median (range) 3 (1-5) 1-2, n (%) 35 (34) 3-4, n (%) 57 (56) 5, n (%) 10 (10) Characteristicsa (N=102) Prior therapy, n (%) Bevacizumab 93 (91) PARPi 57 (56) Mirvetuximab 15 (15) CCNE1 amplification,c Evaluable, n 88 Amplified, n (%) 27 (31) Cyclin E1 status by IHC Evaluable, n 94 IHC+, 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 date: Jan 13, 2025. IHC, immunohistochemistry; ITT, Intent to treat population; ORR, objective response rate; PD, progressive disease; PR, partial response. aIntent to treat/Full analysis set: all treated patients. bBiomarker dataset: all treated patients with evaluable tissue and Cyclin E1 IHC status. cIncludes patients who received at least one post-treatment scan. Amp, amplified; 21 34.9% ORR in Cyclin E1-Positive Patients vs 20.4% in All-Comers DENALI Part 1b, SGO 2025 All treated patients (N=102) ORR in response-evaluablec patients, % (n/N; 95% CI) 20.4 (19/93; 12.8-30.1) ORR, ITTa % (n/N; 95% CI) 18.6 (19/102; 11.6-27.6) Cyclin E1 IHC+ (n=48) ORR in response-evaluablec patients, % (n/N; 95% CI) 34.9 (15/43; 21.0-50.9) ORR, ITTa % (n/N; 95% CI) 31.3 (15/48; 18.7-46.3) All treated patientsa (N=102) Cy cl in E 1 IH C+ Biomarker positive: Cyclin E1 IHCb (n=48) ORR in response-evaluable patients 20.4% ORR in response-evaluable patients 34.9% + Treatment ongoing CCNE1 Status: Amplified Non-amplified Not evaluable B es t % C ha ng e fr om B as el in e

 

Durable Responses Observed in Cyclin E1-Positive PROC Patients amDOR is subject to change, there are 4 ongoing responders as of the January 13, 2025 data cutoff. IHC, immunohistochemistry; cPR, confirmed partial response; SD, stable disease; PD, progressive disease; mDOR, median duration of response; mPFS, median progression free survival; NE, not evaluable 22 DENALI Part 1b, SGO 2025 17 180 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Pa tie nt s Treatment Duration (Months) mDOR 6.3 monthsa (95% CI, 2.7 - NE) mPFS 4.1 months (95% CI, 2.8 - 6.8) 4 ongoing responders Cyclin E1+ (N=48) PDSDcPRBest Overall Response First Partial Response CCNE1 Amplified NE • Durable responses observed regardless of CCNE1 amplification status, reinforcing Cyclin E1 IHC as the predictive biomarker • Supports potential for sustained clinical benefit in biomarker- selected PROC population with limited treatment options

 

DENALI Part 1b Safety and Tolerability Summary Data cutoff date: January 13, 2025 bOne patient had sepsis, and one patient had pancytopenia. 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 reported23 DENALI Part 1b, SGO 2025 12 11 11 4 7 3 2 3 16 7 3 5 1 23 18 5 62 44 20 13 15 11 44 8 10 13 12 12 6 10 0 25 50 75 100 Grade ≥3 Grades 1-2 % Patients Hematological Thrombocytopenia 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 59 (57.8) Leading to discontinuation 22 (21.6) Leading to death 2 (2.0)b Serious TRAEs 22 (21.6) 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, validating trial management & supportive care optimizations

 

Building Azenosertib Franchise in Ovarian Cancer and Beyond 24

 

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; NCT0451644725 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 + Carboplatin, Gemcitabine, Pegylated liposomal doxorubicin, or Paclitaxel Primary Endpoints Key Secondary Endpoints Safety and Tolerability ORR, DOR, PFS Completed Part 2 Azenosertib + Bevacizumab as 1L/2L PSOC Maintenance Therapy Dose Escalation Dose Expansion Assess safety and recommended dose of azenosertib + bevacizumab Evaluate azenosertib at recommended dose in combination with bevacizumab Primary Endpoints Safety and Tolerability Key Secondary Endpoint PFS Enrolling Open for enrollment

 

Azenosertib Combinations Demonstrate Compelling Activity in Preclinical ADC-Resistant 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 = datopotamab deruxtecan; T-DXd = trastuzumab deruxtecan; TOPO1i = topoisomerase 1 inhibitor; CR = complete response; PR = partial response; PFS = progression-free survival; DoR = duration of response; TGI = tumor growth inhibition; 1L = first line 26 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%) • As ADCs advance toward first-line use in TNBC, post-ADC resistance represents a growing unmet need that azenosertib combinations may be uniquely positioned to address • Azenosertib may address ADC resistance through multiple mechanisms: resensitizing tumors to chemotherapy, enhancing ADC responses, and extending duration of response 87.5% CR rate (7/8 mice) with Azenosertib + EV vs. 0% CR with EV alone

 

27 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 6/30/26 Abbreviations: PROC = platinum-resistant ovarian cancer; ORR = overall response rate; mDOR = median duration of response; 5:2 schedule = 5 days once- daily administration of azenosertib, followed by 2 days without azenosertib Integrated analysis across 001, MAMMOTH and DENALI Part 1b at 400mg QD 5:2 28 • First investigational oral, non-chemo targeted therapy for Cyclin E1-positive PROC patients with no specifically targeted treatment options • Compelling azenosertib clinical profile: >30% ORR and ~6 month mDOR* in biomarker-selected population at 400mg QD 5:2 • Clear development and regulatory strategy: DENALI Part 2 topline readout expected 1H 2027 to support potential accelerated approval; ASPENOVA confirmatory Phase 3 trial enrolling • Franchise expansion opportunities: in earlier lines of ovarian cancer and other tumor types • Resourced to execute: ~$175M cash** with runway into late 2027

 

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

 

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