Zentalis Pharmaceuticals Provides Corporate Update and Highlights Key Milestones and Expected Momentum in the Azenosertib Development Program for 2026

Rhea-AI Summary

Zentalis (Nasdaq: ZNTL) provided a corporate update on January 6, 2026 outlining 2026 milestones for azenosertib, its investigational WEE1 inhibitor for Cyclin E1-positive platinum-resistant ovarian cancer (PROC). Key points: DENALI Part 2a enrollment completed with dose confirmation expected in 1H 2026, DENALI Part 2 topline readout expected by year-end 2026 (could support accelerated approval, subject to FDA feedback), and initiation of the randomized Phase 3 ASPENOVA trial planned in 1H 2026. The company reported $280.7M cash and equivalents as of Sept 30, 2025, providing an estimated runway into late 2027.

Positive

• Completed enrollment in DENALI Part 2a, dose confirmation planned 1H 2026
• Planned initiation of randomized Phase 3 ASPENOVA in 1H 2026
• Reported $280.7M cash, runway estimated into late 2027

Negative

• DENALI Part 2 topline readout required by year-end 2026 to support approval
• Regulatory approval contingent on FDA feedback after topline results

Key Figures

DENALI Part 2a target enrollment up to approximately 30 patients per dose level Phase 2 DENALI Part 2a, two dose levels

Azenosertib dose level 400mg QD 5:2 DENALI Part 2a dosing schedule

Azenosertib dose level 300mg QD 5:2 DENALI Part 2a dosing schedule

Cyclin E1-positive PROC share approximately 50% of PROC patients Estimated Cyclin E1 protein overexpression rate

DENALI Part 2a timing dose confirmation expected 1H 2026 Phase 2 DENALI Part 2a milestone

DENALI Part 2 topline readout expected by year end 2026 Potential accelerated approval-supporting data

ASPENOVA Phase 3 start planned 1H 2026 Randomized confirmatory trial initiation

Cash and securities $280.7 million As of September 30, 2025; runway into late 2027

Market Reality Check

$3.74 Last Close

Volume Volume 368,314 is below 20-day average 775,671 (relative volume 0.47x). low

Technical Shares traded below the 200-day MA, at $1.37 vs 200-day MA of $1.44.

Peers on Argus

Peers in Biotechnology showed mixed moves, with names like PYXS up 5.22% and BMEA down 5.19%, indicating stock-specific rather than broad sector momentum for ZNTL.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Nov 10	Earnings and pipeline	Positive	+3.1%	Q3 cash runway into late 2027 and DENALI timelines reiterated.
Nov 03	Inducement grants	Neutral	-4.0%	Stock option grants to a new hire under inducement plan.
Nov 03	Conference participation	Neutral	-4.0%	Management participation in two November investor conferences.
Oct 13	Scientific posters	Neutral	-3.6%	Four azenosertib posters at AACR‑NCI‑EORTC conference on targets.
Oct 01	Inducement grants	Neutral	+7.8%	Equity inducement grants including 400,000 options to new CLO.

Pattern Detected

News tied directly to pipeline progress and finances has previously seen modestly positive or mixed price reactions, while routine items like inducement grants and conference participation have produced small, directionally varied moves.

Recent Company History

Over the last few months, Zentalis highlighted its cash runway of $280.7M and an expected operating runway into late 2027, while advancing the DENALI trial toward a Part 2 topline readout by year-end 2026. Routine governance and compensation updates, including inducement option grants and RSU awards, have been frequent. Scientific visibility increased via four azenosertib posters at a major molecular targets conference. Today’s corporate update reiterates and extends this focus on azenosertib in Cyclin E1‑positive PROC with clearer 2026 milestones.

Market Pulse Summary

The stock surged +29.9% in the session following this news. A strong positive reaction aligns with the company’s clear 2026 roadmap, including DENALI Part 2a dose confirmation in 1H 2026 and a topline readout by year end 2026 that may support accelerated approval, subject to FDA feedback. Prior news around azenosertib and cash runway, such as the Q3 update highlighting $280.7M in cash and runway into late 2027, also drew constructive responses, suggesting investors have previously rewarded pipeline-advancing milestones while remaining attentive to execution risk.

Key Terms

accelerated approval regulatory

"DENALI Part 2 trial topline readout expected by year end 2026; potential to support accelerated approval"

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.

phase 3 medical

"Initiation of the ASPENOVA Phase 3, randomized, confirmatory trial planned in 1H 2026"

Phase 3 is the late-stage clinical testing step for a new drug or medical treatment, where the product is given to large groups of patients to confirm effectiveness, monitor side effects, and compare it to standard care. Successful Phase 3 results are often the final scientific hurdle before regulators decide on approval and market launch—like passing a final exam before graduation—and can sharply change a company's valuation and future revenue prospects.

platinum-resistant ovarian cancer medical

"toward potential approval in Cyclin E1-positive platinum-resistant ovarian cancer (PROC)"

A form of ovarian cancer that stops responding to standard platinum-based chemotherapy, typically when the disease returns within about six months after treatment; think of it like a pest becoming resistant to a once-effective pesticide. It matters to investors because this resistance creates a large unmet medical need, shaping demand for new drugs, clinical trial strategies, regulatory priority and potential pricing — all of which can materially affect company value and market opportunity.

biomarker medical

"as a biomarker-driven treatment approach for ovarian cancer"

A biomarker is a measurable indicator found in the body, such as in blood or tissues, that provides information about health, disease, or how the body responds to treatment. For investors, biomarkers can signal the potential success or risk of medical products or therapies, influencing the value of related companies and industry trends. They act like signals or clues that help assess the progress of medical advancements and their market impact.

immunohistochemistry medical

"based on its proprietary immunohistochemistry cutoff"

Immunohistochemistry is a laboratory method that uses labelled antibodies to highlight specific proteins inside thin slices of tissue, producing visible color where those proteins are present—like using colored highlighters to mark words on a page. Investors care because it provides concrete evidence about whether a drug hits its intended target, whether a diagnostic test works, and how a treatment affects tissues, all of which can affect clinical success, regulatory approval, and market value.

standard-of-care chemotherapy medical

"evaluating azenosertib vs. standard-of-care chemotherapy in this biomarker-selected population"

The standard-of-care chemotherapy is the treatment or drug regimen that doctors currently use as the accepted, routine approach for a particular cancer because it has shown reliable benefits in clinical practice and trials. For investors, it acts like the market’s default product: new drugs are measured against it for regulatory approval, pricing, and adoption, so whether a competitor outperforms, complements, or fails against this benchmark can strongly influence a company’s prospects.

randomized medical

"ASPENOVA, our randomized Phase 3 confirmatory trial in the first half of 2026"

Randomized means participants or units in a study are assigned to different groups by chance rather than by choice, like flipping a coin to decide who gets a new treatment and who gets a comparison. For investors, randomized designs matter because they reduce bias and make results more trustworthy, so outcomes from randomized studies carry more weight when assessing regulatory approval, commercial prospects, and the risk that trial results will change a company’s valuation.

wee1 inhibition medical

"other indications where WEE1 inhibition may play a meaningful role"

Wee1 inhibition is the deliberate blocking of the Wee1 enzyme, a protein that acts like a safety brake to pause damaged cells so they can repair before dividing. In cancer therapy, removing that brake can push tumor cells with DNA damage into a fatal division, improving the effect of chemotherapy or radiation but raising the risk of harms to healthy cells; results influence drug trial outcomes, regulatory decisions and commercial potential.

AI-generated analysis. Not financial advice.

• Completed enrollment in DENALI Part 2a; dose confirmation expected in 1H 2026
• DENALI Part 2 trial topline readout expected by year end 2026; potential to support accelerated approval
• Initiation of the ASPENOVA Phase 3, randomized, confirmatory trial planned in 1H 2026
  

SAN DIEGO, Jan. 06, 2026 (GLOBE NEWSWIRE) -- Zentalis^® Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical oncology innovator advancing late-stage development of investigational first-in-class WEE1 inhibitor azenosertib as a biomarker-driven treatment approach for ovarian cancer, today provided a corporate update and highlighted key milestones and expected momentum in the azenosertib development program for 2026.

"2026 represents a pivotal year for Zentalis as we advance azenosertib toward potential approval in Cyclin E1-positive platinum-resistant ovarian cancer (PROC) and continue to assess its role in additional indications," said Julie Eastland, Chief Executive Officer of Zentalis. "The completion of DENALI Part 2a enrollment marks significant progress, positioning us for dose confirmation in the first half of 2026, followed by an expected topline readout by year end that could support accelerated approval, subject to FDA feedback. Equally important, we expect to initiate ASPENOVA, our randomized Phase 3 confirmatory trial in the first half of 2026, evaluating azenosertib vs. standard-of-care chemotherapy in this biomarker-selected population. Beyond the Cyclin E1-positive PROC setting, this year we plan to continue evaluating the potential of azenosertib in earlier lines of ovarian cancer and other indications where WEE1 inhibition may play a meaningful role.

"With our strong financial foundation providing an estimated runway into late 2027, we remain focused on executing our strategy to bring this potentially first-in-class, non-chemo, oral therapy to the approximately 50% of PROC patients who are Cyclin E1-positive—a population with significant unmet needs," Ms. Eastland added.

2025 Accomplishments

• Completed enrollment in DENALI Part 2a, supporting registration-intended development of azenosertib. The Company completed enrollment in Part 2a of the Phase 2 DENALI clinical trial (NCT05128825). Part 2a is designed to confirm the primary dose-of-interest with a target enrollment of up to approximately 30 patients at each of two dose levels: 400mg QD 5:2 and 300mg QD 5:2 (intermittent daily dosing with five days on, two days off dosing schedule).
• Aligned with the FDA on confirmatory ASPENOVA Phase 3 trial design. The Company aligned with the FDA on the design for ASPENOVA, a Phase 3 randomized, confirmatory trial of azenosertib vs. standard-of-care chemotherapy in patients with Cyclin E1-positive PROC.
• Strong data across three trials in PROC established a solid foundation for the lead indication in Cyclin E1-positive platinum-resistant ovarian cancer. For example, in Part 1b of DENALI at the 400mg 5:2 dosing schedule, azenosertib demonstrated clinically meaningful results with a manageable safety profile. In addition, Cyclin E1 overexpression, regardless of CCNE1 gene amplification status, was observed as a predictive biomarker to identify patients who could potentially benefit from azenosertib. Zentalis estimates that approximately 50% of PROC patients overexpress Cyclin E1 protein based on its proprietary immunohistochemistry cutoff.
• Maintained a strong cash position supporting an estimated runway into late 2027 following strategic restructuring to focus pipeline and resources. As of September 30, 2025, the Company had cash, cash equivalents and marketable securities of $280.7 million. The Company believes that its existing cash, cash equivalents and marketable securities is expected to provide runway into late 2027, beyond the anticipated DENALI Part 2 topline readout.

Anticipated 2026 Milestones

• DENALI Part 2a dose confirmation expected in first half of 2026.
• Confirmatory ASPENOVA Phase 3 trial initiation expected in first half of 2026. The planned Phase 3 trial is expected to be conducted concurrently with DENALI Part 2.
• DENALI Part 2 topline readout on track and expected by year end 2026. DENALI Part 2, if successful, has the potential to support an accelerated approval, subject to FDA feedback.
  

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 platinum-resistant ovarian cancer (PROC). There is currently no approved treatment option specifically for this biomarker-selected population which comprises approximately 50% of PROC patients. Cyclin E1 protein overexpression has been established as a sensitive and specific predictive biomarker for identifying patients who could potentially derive benefit from azenosertib treatment.

About DENALI Clinical Trial 
DENALI is a multi-part Phase 2 registration-intent clinical trial (NCT05128825) studying azenosertib in platinum-resistant ovarian cancer (PROC) patients. Part 1b enrolled patients with PROC regardless of Cyclin E1 protein expression, all treated at 400mg QD 5:2 (intermittent daily dosing with five days on, two days off dosing schedule). Interim results from Part 1b were presented at the Society of Gynecologic Oncology (SGO) 2025 Annual Meeting. Part 2 is enrolling PROC patients with Cyclin E1 protein overexpression based on Zentalis' proprietary immunohistochemistry cutoff. Part 2 includes Part 2a, a dose confirmation portion evaluating two doses, 300mg QD 5:2 and 400mg QD 5:2, and Part 2b, a portion designed to complete enrollment at the selected dose informed by Part 2a results. The trial design was aligned with the U.S. Food and Drug Administration (FDA). Part 2, in total, is designed for accelerated approval, pending study outcome and discussions with the FDA.

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 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 significance of the referenced data on the late-stage development of azenosertib; the potential benefits of azenosertib, including the potential for azenosertib to be an important treatment option for patients with ovarian cancer or other indications; the broad franchise potential of azenosertib; the Company’s biomarker-driven strategy for azenosertib; the potential to advance research on additional areas of opportunity for azenosertib outside PROC; our anticipated milestones and the timing thereof, including the anticipated timing of DENALI Part 2a dose confirmation and the topline readout from DENALI Part 2, and the initiation, design, conduct and timing of our confirmatory APSENOVA Phase 3 trial; our anticipated cash runway; and our planned regulatory strategy for azenosertib and the timing thereof, including the potential for DENALI Part 2 to support an accelerated approval. The terms “anticipate,” “advance,” “believe,” “design,” “develop,” “expect,” “intent,” “look forward,” “on track,” “plan,” “position,” “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 companion diagnostics; the outcome of preclinical testing and early trials may not be predictive of the success of later clinical trials; potential unforeseen events during clinical trials could cause delays or other adverse consequences; risks relating to the regulatory approval process or ongoing regulatory obligations; our product candidates may cause serious adverse side effects; inability to maintain our collaborations, or the failure of these collaborations; our reliance on third parties; effects of significant competition; the possibility of system failures or security breaches; risks relating to intellectual property; our ability to attract, retain and motivate qualified personnel, and risks relating to management transitions; significant costs as a result of operating as a public company; and the other important factors discussed under the caption “Risk Factors” in our most recently filed periodic report on Form 10-K or 10-Q and subsequent filings with the U.S. Securities and Exchange Commission (SEC) and our other filings with the SEC. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change.

ZENTALIS^® and its associated logo are trademarks of Zentalis and/or its affiliates. All website addresses and other links in this press release are for information only and are not intended to be an active link or to incorporate any website or other information into this press release. 

Contact:
Aron Feingold
VP, Investor Relations & Corporate Communications
ir@zentalis.com

FAQ

What did Zentalis (ZNTL) announce on January 6, 2026 about azenosertib?

Zentalis announced completion of DENALI Part 2a enrollment, dose confirmation expected in 1H 2026, DENALI Part 2 topline readout expected by year-end 2026, and ASPENOVA Phase 3 initiation planned in 1H 2026.

When is DENALI Part 2a dose confirmation for ZNTL expected?

Dose confirmation from DENALI Part 2a is expected in the first half of 2026.

Could Zentalis (ZNTL) seek accelerated approval for azenosertib in 2026?

The company said DENALI Part 2 topline, expected by year-end 2026, could support accelerated approval, subject to FDA feedback.

What is the planned timeline for Zentalis to start the ASPENOVA Phase 3 trial?

ASPENOVA, a randomized Phase 3 confirmatory trial vs standard chemotherapy, is planned to initiate in 1H 2026.

How long is Zentalis's cash runway based on the January 6, 2026 update?

As of Sept 30, 2025, Zentalis reported $280.7 million in cash and equivalents, which the company estimates provides runway into late 2027.

What patient population is Zentalis targeting with azenosertib (ZNTL)?

Zentalis is developing azenosertib for Cyclin E1-positive platinum-resistant ovarian cancer, estimated to include about 50% of PROC patients based on the company's immunohistochemistry cutoff.