Zentalis Pharmaceuticals Reports First Quarter 2025 Financial Results and Operational Progress

Rhea-AI Summary

Zentalis Pharmaceuticals (NASDAQ: ZNTL) reported Q1 2025 financial results and operational progress for its WEE1 inhibitor development program. The company announced the first patient dosing in DENALI Part 2a clinical trial of azenosertib for Cyclin E1+ platinum-resistant ovarian cancer (PROC). Previous data from Part 1b showed a 34.9% objective response rate and 6.3-month median duration of response. Financially, Zentalis reported $332.5 million in cash and equivalents, providing runway into late 2027. Q1 2025 saw reduced operating expenses at $45.6 million (vs $65.3 million in Q1 2024), including $7.8 million in restructuring costs. The company expects topline data from DENALI Part 2 by year-end 2026, which could potentially support accelerated FDA approval.

Positive

• Strong cash position of $332.5M providing runway into late 2027
• Promising clinical data with 34.9% objective response rate in PROC patients
• Significant reduction in operating expenses from $65.3M to $45.6M year-over-year
• Potential for accelerated FDA approval based on DENALI Part 2 results

Negative

• Restructuring expenses of $7.8M in Q1 2025
• Topline data from DENALI Part 2 not expected until end of 2026
• Ongoing clinical trial success and FDA approval still uncertain

Insights

Biotechnology/Clinical Trial Expert

Zentalis advances WEE1 inhibitor azenosertib in late-stage trials for ovarian cancer with promising 34.9% response rate and solid financial position.

The initiation of Part 2 of Zentalis' Phase 2 DENALI trial for azenosertib marks a significant milestone in the company's evolution into a late-stage development organization. This WEE1 inhibitor is being positioned as a potentially first-in-class and best-in-class treatment specifically for Cyclin E1+ platinum-resistant ovarian cancer (PROC), an area with limited therapeutic options.

The preliminary efficacy signals from Part 1b are particularly noteworthy, with an objective response rate of 34.9% in 43 evaluable patients and a median duration of response of 6.3 months (which could improve as some patients had ongoing responses at data cutoff). These response rates exceed the typical 10-15% seen with standard chemotherapy in PROC, suggesting azenosertib could represent a meaningful advancement for these patients.

The company's strategic approach to targeting WEE1, a key cell cycle checkpoint regulator, in Cyclin E1+ tumors shows rational pathway-directed drug development. By focusing on patients with Cyclin E1 overexpression, Zentalis is employing a biomarker-driven strategy that could enhance response rates in a pre-selected population most likely to benefit.

The two-part design of DENALI Part 2 is methodologically sound, with Part 2a confirming optimal dosing (400mg QD 5:2 vs 300mg QD 5:2) before proceeding to further expansion. With topline data expected by year-end 2026 and potential for accelerated approval pathway, Zentalis has a clear regulatory strategy and timeline.

The company's $332.5 million cash position provides runway into late 2027, well beyond the expected DENALI Part 2 readout, removing near-term financing concerns. The significant reduction in R&D expenses (down $22.4 million year-over-year) reflects their more focused approach following the January 2025 restructuring.

Oncology Financial Analyst

Zentalis presents promising PROC asset with 34.9% response rate while extending cash runway to 2027 through strategic operational restructuring.

Zentalis' financial position shows disciplined capital allocation with $332.5 million in cash, providing operational runway into late 2027. This timeline strategically extends beyond their critical DENALI Part 2 data readout expected by end of 2026, giving them negotiating leverage for potential partnerships or commercialization activities if the data supports accelerated approval.

The company has successfully executed a strategic restructuring announced in January 2025, resulting in a substantial 45% reduction in quarterly R&D expenses (from $49.6 million to $27.2 million) and 32% lower G&A expenses (from $15.7 million to $10.6 million). While the quarter included $7.8 million in one-time restructuring costs, the operational changes position Zentalis with a significantly lower burn rate going forward.

The focus on azenosertib as their lead program following divestiture of their ROR1 antibody-drug conjugate platform to Immunome represents a strategic narrowing of their pipeline to prioritize their most promising asset. Their $12.2 million stake in Immunome common stock provides additional potential upside beyond their core program.

Azenosertib's development in Cyclin E1+ PROC represents a targeted approach to a significant market opportunity. The platinum-resistant ovarian cancer space has seen limited innovation, with current therapies showing modest efficacy. The preliminary 34.9% response rate positions azenosertib competitively if confirmed in the larger DENALI Part 2 study.

The biomarker-driven approach focusing on Cyclin E1 expression could create a precision medicine paradigm in ovarian cancer treatment. This strategy aligns with industry trends toward targeted therapies with companion diagnostics, potentially commanding premium pricing and favorable reimbursement if approved. The clear regulatory strategy with potential accelerated approval pathway could significantly shorten time to market and improve return on R&D investment.

First patient dosed in DENALI Part 2a clinical trial of azenosertib in patients with Cyclin E1+ PROC

Topline data from DENALI Part 2 anticipated by year end 2026 with the potential to support an accelerated approval, subject to FDA feedback

$332.5 million cash, cash equivalents and marketable securities supports operational runway into late 2027

SAN DIEGO, May 14, 2025 (GLOBE NEWSWIRE) -- Zentalis® Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical-stage biopharmaceutical company developing a potentially first-in-class and best-in-class WEE1 inhibitor for patients with ovarian cancer and other tumor types, announced financial results for the first quarter 2025 and highlighted recent operational progress.

"We continued advancement of azenosertib and made solid progress against our strategic goals in the first quarter. The initiation of DENALI Part 2 moves us into a new chapter as a late-stage development company focusing on a significant patient population in platinum-resistant ovarian cancer with limited choices," said Julie Eastland, Chief Executive Officer of Zentalis. “Our team remains focused on the enrollment and execution of DENALI. Zentalis is financially and organizationally well-positioned to continue advancing azenosertib as a potential treatment option for PROC patients.”

Program Highlights

• First patient dosed in Part 2 of the Phase 2 DENALI clinical trial.   
  • In April 2025, the Company announced that the first patient had been dosed in Part 2a of the Phase 2 DENALI clinical trial (NCT05128825) of azenosertib in patients with Cyclin E1+ platinum-resistant ovarian cancer (PROC).
  • Part 2a is designed to confirm the primary dose-of-interest with a target enrollment of approximately 30 patients at each of two dose levels: 400mg QD 5:2 and 300mg QD 5:2 (intermittent daily dosing with a five days on, two days off dosing schedule).
  • The Company expects to disclose topline data from DENALI Part 2 (Part 2a and Part 2b) by year end 2026. DENALI Part 2, if successful, has the potential to support an accelerated approval, subject to FDA review.

• Azenosertib clinical data demonstrated clinically meaningful response rates and a consistent therapeutic profile.
  • Previously disclosed clinical data from Part 1b of the DENALI study showed clinically meaningful results in patients with Cyclin E1+ PROC. As of the January 13, 2025 data cutoff, patients who were response-evaluable (n=43) had an objective response rate (ORR) of 34.9% and a median duration of response (mDOR) of 6.3 months. The mDOR is subject to change as there were patients with ongoing responses as of the cutoff date.
  • Across multiple monotherapy studies of azenosertib with significant sample sizes, as of the December 2, 2024 data cutoff, azenosertib demonstrated meaningful antitumor activity (ORR >30% at 400mg QD 5:2) and a manageable safety profile in Cyclin E1+ PROC patients.
    

Upcoming Events

• Zentalis plans to participate in the following scientific and medical conference:
  • American Society of Clinical Oncology (ASCO) Annual Meeting – May 30 to June 3 in Chicago, IL
  • NRG Oncology Summer Meeting – July 24 to 26 in Washington, D.C.
    
    
• Zentalis plans to participate and present in the following investor events:
  
  • H.C. Wainwright 3rd Annual BioConnect Investor Conference – May 20 in New York, NY
  • TD Cowen’s 6th Annual Oncology Innovation Summit – May 27 Virtual
  • Jefferies Healthcare Conference – June 4 in New York, NY

First Quarter 2025 Financial Results

• Cash, Cash Equivalents and Marketable Securities Position: As of March 31, 2025, the Company had cash, cash equivalents and marketable securities of $332.5 million, which includes $12.2 million representing the March 31, 2025 fair value of Immunome common stock received by the Company from the sale of its ROR1 antibody-drug conjugate (ADC) product candidate and ADC platform to Immunome in October 2024. The Company believes that its existing cash, cash equivalents and marketable securities as of March 31, 2025 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 March 31, 2025 were $27.2 million, compared to $49.6 million for the three months ended March 31, 2024. The decrease of $22.4 million was primarily due to decreases of $10.7 million for clinical expenses, $4.8 million for drug manufacturing, $3.5 million for lab services and $5.1 million related to consulting and personnel expenses, including non-cash stock-based compensation. These decreases were partially offset by a one-time impairment charge of $1.2 million related to the disposal of research and development equipment and an increase of $0.5 million of allocated overhead.
  
  
• General and Administrative Expenses: General and administrative expenses for the three months ended March 31, 2025 were $10.6 million, compared to $15.7 million during the three months ended March 31, 2024. This decrease of $5.1 million was primarily attributable to non-cash stock-based compensation.
  
  
• Operating Expenses: Total operating expenses were $45.6 million for the three months ended March 31, 2025, compared to $65.3 million for the three months ended March 31, 2024. Total operating expenses for the first quarter of 2025 include the non-recurring restructuring expenses of $7.8 million associated with the strategic restructuring announced in January 2025.
  

About Azenosertib
Azenosertib is a novel, selective, and orally bioavailable inhibitor of WEE1 currently being evaluated as a monotherapy and combination 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.

About DENALI Clinical Trial
DENALI is a multi-part Phase 2 clinical trial 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 5:2 (intermittent daily dosing with a 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 ongoing and 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 5:2 and 400mg 5:2, and Part 2b, a portion designed to complete enrollment at the selected dose. Part 2, in total, is designed for accelerated approval, pending study outcome and discussions with the U.S. Food and Drug Administration.

About Zentalis Pharmaceuticals
Zentalis^® Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company developing azenosertib (ZN-c3), a potentially first-in-class and best-in-class WEE1 inhibitor for patients with Cyclin E1+ platinum-resistant ovarian cancer (PROC). Azenosertib is being evaluated as a monotherapy and in combination across multiple tumor types in clinical trials and has broad franchise potential. In clinical trials, azenosertib has been well tolerated and has demonstrated anti-tumor activity as a single agent across multiple tumor types. The Company is also leveraging its extensive experience and capabilities to translate its science to advance research on additional areas of opportunity for azenosertib outside PROC. Zentalis has operations in San Diego.

For more information, please visit www.zentalis.com. Follow Zentalis on X/Twitter at @ZentalisP and 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 of azenosertib; our anticipated milestones and the timing thereof, including the anticipated timing of clinical data disclosures; the potential to advance research on additional areas of opportunity for azenosertib outside PROC; our anticipated cash runway; the potential for azenosertib to be first-in-class and best-in-class; the broad franchise potential of azenosertib; the planned design of our clinical trials, including DENALI Part 2; our positioning to execute; our planned clinical development strategy and regulatory strategy for azenosertib and the timing thereof, including the potential for DENALI Part 2 to support an accelerated approval; and our plans to participate in conferences and events. The terms “advance,” “anticipated,” “believe,” “continue,” “design,” “expect,” “goal,” “opportunity,” “plan,” “potential,” “progress,” “projected,” “runway,” “target,” “well-positioned,” 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 plans, including the costs thereof, of development of companion diagnostics; our substantial dependence on the success of azenosertib; the outcome of preclinical testing and early 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; 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. 

Zentalis Pharmaceuticals, Inc. Condensed Consolidated Statements of Operations (Unaudited) (In thousands, except per share amounts)
	Three Months Ended March 31,
		2025				2024
License Revenue		$—			$40,560
Operating Expenses
Research and development		27,247				49,585
General and administrative		10,580				15,740
Restructuring		7,796				—
Total operating expenses		45,623				65,325
Loss from operations		(45,623)				(24,765)
Other Income (Expense)
Investment and other (expense) income, net		(2,656)				34,948
Net (loss) income before income taxes		(48,279)				10,183
Income tax expense		—				143
Net loss		(48,279)				10,040
Net loss attributable to noncontrolling interests		—				(28)
Net (loss) income attributable to Zentalis	$(48,279)				$10,068
Earnings per share
Basic	$(0.67)				$0.14
Diluted	$(0.67)				$0.14
Weighted average common shares outstanding
Basic		71,678				70,898
Diluted		71,678				71,192

Zentalis Pharmaceuticals, Inc. Selected Condensed Consolidated Balance Sheet Data (Unaudited) (In thousands)
		As of March 31,			As of December 31,
			2025			2024
Cash, cash equivalents and marketable securities		$332,453			$371,084
Working capital(1)			293,452			333,341
Total assets			384,021			430,337
Total liabilities			88,639			93,151
Total Zentalis equity		$295,382			$337,186
(1)The Company defines working capital as current assets less current liabilities.

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

FAQ

What were Zentalis Pharmaceuticals (ZNTL) key financial results for Q1 2025?

Zentalis reported $332.5M in cash and equivalents, reduced operating expenses to $45.6M (from $65.3M in Q1 2024), and maintains a cash runway into late 2027.

What is the status of ZNTL's DENALI clinical trial for azenosertib?

The first patient has been dosed in DENALI Part 2a, with topline data expected by year-end 2026. Previous Part 1b results showed a 34.9% objective response rate and 6.3-month median duration of response.

What is the potential market opportunity for Zentalis's azenosertib?

Azenosertib is being developed as a potentially first-in-class and best-in-class WEE1 inhibitor for patients with platinum-resistant ovarian cancer (PROC) and other tumor types, with potential for accelerated FDA approval.

How much did Zentalis reduce their research and development expenses in Q1 2025?

R&D expenses decreased by $22.4M to $27.2M in Q1 2025, compared to $49.6M in Q1 2024, primarily due to reduced clinical, manufacturing, and personnel expenses.