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What changed in Zentalis Pharmaceuticals, Inc.'s 10-K — 2024 vs 2025

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Paragraph-level year-over-year comparison of Zentalis Pharmaceuticals, Inc.'s 2024 and 2025 10-K annual filings, covering the Business, Risk Factors, Legal Proceedings, Cybersecurity, MD&A and Market Risk sections. Every new, removed and edited paragraph is highlighted side-by-side so you can see exactly what management changed in the 2025 report.

+484 added−493 removedSource: 10-K (2026-03-26) vs 10-K (2025-03-26)

Top changes in Zentalis Pharmaceuticals, Inc.'s 2025 10-K

484 paragraphs added · 493 removed · 398 edited across 6 sections

Item 1. Business

Business — how the company describes what it does

106 edited+32 added−27 removed171 unchanged
Biggest changeViolation of any of such laws or any other governmental regulations that apply may result in penalties, including, without limitation, significant administrative, civil and criminal penalties, damages, fines, additional reporting obligations and oversight if we become subject to a corporate integrity agreement or other agreement to resolve allegations of non-compliance with these laws, the curtailment or restructuring of operations, exclusion from participation in governmental healthcare programs and imprisonment.
Biggest changeViolation of any of such laws or any other governmental regulations that apply may result in penalties, including, without limitation, significant administrative, civil and criminal penalties, damages, fines, additional reporting obligations and oversight if we become subject to a corporate integrity agreement or other agreement to resolve allegations of non-compliance with these laws, the curtailment or restructuring of operations, exclusion from participation in governmental healthcare programs and imprisonment. 14 Coverage and Reimbursement Sales of any pharmaceutical product depend, in part, on the extent to which such product will be covered by third-party payors, such as federal, state and foreign government healthcare programs, commercial insurance and managed healthcare organizations, and the level of reimbursement for such product by third-party payors.
FDA Approval and Regulation of Companion Diagnostics If safe and effective use of a therapeutic depends on an in vitro diagnostic, then the FDA generally will require approval or clearance of that diagnostic, known as a companion diagnostic, at the same time that the FDA approves the therapeutic 16 product.
FDA Approval and Regulation of Companion Diagnostics 16 If safe and effective use of a therapeutic depends on an in vitro diagnostic, then the FDA generally will require approval or clearance of that diagnostic, known as a companion diagnostic, at the same time that the FDA approves the therapeutic product.
Other potential consequences include, among other things: 12 • restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls; • fines, warning letters, or untitled letters; • clinical holds on clinical studies; • refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of product license approvals; • product seizure or detention, or refusal to permit the import or export of products; • consent decrees, corporate integrity agreements, debarment or exclusion from federal healthcare programs; • mandated modification of promotional materials and labeling and the issuance of corrective information; • the issuance of safety alerts, Dear Healthcare Provider letters, press releases and other communications containing warnings or other safety information about the product; or • injunctions or the imposition of civil or criminal penalties.
Other potential consequences include, among other things: • restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls; • fines, warning letters, or untitled letters; • clinical holds on clinical studies; • refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of product license approvals; • product seizure or detention, or refusal to permit the import or export of products; • consent decrees, corporate integrity agreements, debarment or exclusion from federal healthcare programs; • mandated modification of promotional materials and labeling and the issuance of corrective information; • the issuance of safety alerts, Dear Healthcare Provider letters, press releases and other communications containing warnings or other safety information about the product; or • injunctions or the imposition of civil or criminal penalties.
We are currently focused on advancing the clinical development of azenosertib in Cyclin E1+ platinum-resistant ovarian cancer, or PROC. We believe that our DENALI (ZN-c3-005) Part 2 clinical trial of azenosertib in patients with Cyclin E1+ PROC, if successful, has the potential to support an accelerated approval, subject to U.S. Food and Drug Administration, or FDA, review.
We are currently focused on advancing the clinical development of azenosertib in Cyclin E1-positive platinum-resistant ovarian cancer, or PROC. We believe that our DENALI (ZN-c3-005) Part 2 clinical trial of azenosertib in patients with Cyclin E1-positive PROC, if successful, has the potential to support an accelerated approval, subject to U.S. Food and Drug Administration, or FDA, review.
In the intent-to-treat patients with Cyclin E1+ PROC (patients who received at least one dose of azenosertib), the ORR was 31.3% (15/48; 95% CI: 18.7 - 46.3). As of the December 2, 2024 data cutoff, the median duration of response, or mDOR, for the intent-to-treat population was still maturing and was approximately 5.5 months (95% CI: 2.7 - not estimable).
In the intent-to-treat patients with Cyclin E1-positive PROC (patients who received at least one dose of azenosertib), the ORR was 31.3% (15/48; 95% CI: 18.7 - 46.3). As of the December 2, 2024 data cutoff, the median duration of response, or mDOR, for the intent-to-treat population was still maturing and was approximately 5.5 months (95% CI: 2.7 - not estimable).
In addition to offering benefits such as medical, dental, vision, 401(k) with company matching, flexible spending for healthcare and dependent care, life insurance and both short and long-term disability, we offer work / life balance benefits and employee development opportunities. These include flexible time off, voluntary life-illness-accident insurance, wellness challenges and healthy food options onsite.
In addition to offering benefits such as medical, dental, vision, 401(k) with company matching, flexible spending for healthcare and dependent care, life insurance and both short and long-term disability, we offer work / life balance benefits and 18 employee development opportunities. These include flexible time off, voluntary life-illness-accident insurance, wellness challenges and healthy food options onsite.
As of the December 2, 2024 data cutoff, among Cyclin E1+ patients treated at the primary dose-of-interest, 400 mg QD 5:2 (n=16), an ORR of 31.3% (5/16; 95% CI: 11.0 - 58.7) and an mDOR of 4.2 months (95% CI: 3.0, not estimable) were observed, and among Cyclin E1+ patients treated at the 300 mg QD 5:2 dose level (n=14), an ORR of 21.4% (3/14; 95% CI: 4.7 - 50.8) and an mDOR of 4.9 months (95% CI: 3.0 - not estimable) were observed.
As of the December 2, 2024 data cutoff, among Cyclin E1-positive patients treated at the primary dose-of-interest, 400 mg QD 5:2 (n=16), an ORR of 31.3% (5/16; 95% CI: 11.0 - 58.7) and an mDOR of 4.2 months (95% CI: 3.0, not estimable) were observed, and among Cyclin E1-positive patients treated at the 300 mg QD 5:2 dose level (n=14), an ORR of 21.4% (3/14; 95% CI: 4.7 - 50.8) and an mDOR of 4.9 months (95% CI: 3.0 - not estimable) were observed.
The U.S. government and state legislatures have continued implementing cost-containment programs, including price controls, restrictions on coverage and reimbursement and requirements for substitution of generic products. Third-party payors are more and more challenging the prices charged, examining the medical necessity and reviewing the cost effectiveness of pharmaceutical products, in addition to questioning their safety and efficacy.
The U.S. government and state legislatures have continued implementing cost-containment programs, including price controls, restrictions on coverage and reimbursement and requirements for substitution of generic products. Third-party payors are more and more frequently challenging the prices charged, examining the medical necessity and reviewing the cost effectiveness of pharmaceutical products, in addition to questioning their safety and efficacy.
There are also requirements governing the reporting of ongoing clinical studies and clinical study results to public registries. Human clinical trials are typically conducted in three sequential phases that may overlap or be combined: 8 • Phase 1: The product candidate is initially introduced into healthy human subjects or patients with the target disease or condition.
There are also requirements governing the reporting of ongoing clinical studies and clinical study results to public registries. Human clinical trials are typically conducted in three sequential phases that may overlap or be combined: • Phase 1: The product candidate is initially introduced into healthy human subjects or patients with the target disease or condition.
A REMS is a safety strategy to manage a known or potential serious risk associated with a medicine and to enable patients to have continued access to such medicines by managing their safe use, and could include medication guides, physician communication plans, or elements to assure safe use, such as restricted distribution methods, patient registries, and other risk minimization tools.
A REMS is a safety strategy to manage a known or potential serious risk associated with a medicine and to enable patients to have continued access to such medicines by managing their safe use, and could include medication 9 guides, physician communication plans, or elements to assure safe use, such as restricted distribution methods, patient registries, and other risk minimization tools.
There were 23 patients with Cyclin E1+ PROC who were dosed at intermittent schedules at total daily doses of ≥300 mg. In these patients as of the December 2, 2024 data cutoff, an ORR of 34.8% (8/23; 95% CI: 16.4 - 57.3) and an mDOR of 5.2 months (95% CI: 2.8, 6.9) were observed.
There were 23 patients with Cyclin E1-positive PROC who were dosed at intermittent schedules at total daily doses of ≥300 mg. In these patients as of the December 2, 2024 data cutoff, an ORR of 34.8% (8/23; 95% CI: 16.4 - 57.3) and an mDOR of 5.2 months (95% CI: 2.8, 6.9) were observed.
Orphan drug designation entitles a party to financial incentives such as opportunities for limited grant funding towards clinical trial costs, research tax advantages, and user fee waivers. If a product that has orphan designation subsequently receives the first FDA approval for the disease or condition for which it has such designation, the product is entitled to orphan drug exclusivity.
Orphan drug designation entitles a party to financial incentives such as opportunities for limited grant funding towards clinical trial costs, research tax advantages, and user fee waivers. If a product that has orphan designation subsequently receives the first FDA approval within the disease or condition for which it has such designation, the product is entitled to orphan drug exclusivity.
While the EU Clinical Trials Directive required a separate clinical 14 trial application, or CTA, to be submitted in each member state in which the clinical trial takes place, to both the competent national health authority and an independent ethics committee, the CTR introduces a centralized process and only requires the submission of a single application for multi-center trials.
While the EU Clinical Trials Directive required a separate clinical trial application, or CTA, to be submitted in each member state in which the clinical trial takes place, to both the competent national health authority and an independent ethics committee, the CTR introduces a centralized process and only requires the submission of a single application for multi-center trials.
There were 11 patients with Cyclin E1+ USC who were dosed at intermittent schedules at total daily doses of ≥300 mg. In these patients as of the December 2, 2024 data cutoff, an ORR of 36.4% (4/11; 95% CI: 10.9 - 69.2) and an mDOR of 5.5 months (95% CI: 5.4, not estimable) were observed.
There were 11 patients with Cyclin E1-positive USC who were dosed at intermittent schedules at total daily doses of ≥300 mg. In these patients as of the December 2, 2024 data cutoff, an ORR of 36.4% (4/11; 95% CI: 10.9 - 69.2) and an mDOR of 5.5 months (95% CI: 5.4, not estimable) were observed.
With regard to a fast track product, the FDA may consider for 10 review sections of the NDA/BLA on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission of the sections of the NDA/BLA, the FDA agrees to accept sections of the NDA/BLA and determines that the schedule is acceptable, and the sponsor pays any required user fees upon submission of the first section of the NDA/BLA.
With regard to a fast track product, the FDA may consider for review sections of the NDA/BLA on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission of the sections of the NDA/BLA, the FDA agrees to accept sections of the NDA/BLA and determines that the schedule is acceptable, and the sponsor pays any required user fees upon submission of the first section of the NDA/BLA.
In addition, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life. During the development of a new drug, sponsors are given opportunities to meet with the FDA at certain points.
In addition, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life. 8 During the development of a new drug, sponsors are given opportunities to meet with the FDA at certain points.
The FDCA alternatively provides three years of non-patent exclusivity for an NDA, or supplement to an existing NDA if new clinical investigations, other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by the FDA to be essential to the approval of the application, for example new indications, dosages or strengths of an existing drug.
The FDCA alternatively provides three years of non-patent exclusivity for an NDA, or supplement to an existing NDA if new clinical investigations, other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by the FDA to be essential to the approval of the application, for example new indications, dosages or strengths of an existing 12 drug.
We believe that the key competitive factors affecting the success of any of our product candidates, if approved, will include efficacy, combinability, safety profile, convenience, cost, level of promotional activity devoted to them and intellectual property protection. Azenosertib WEE1 Inhibitors Currently, there are no WEE1 inhibitors approved by the FDA.
We believe that the key competitive factors affecting the success of any of our product candidates, if approved, will include efficacy, combinability, safety profile, convenience, cost, level of promotional activity devoted to them and intellectual property protection. WEE1 Inhibitors Currently, there are no WEE1 inhibitors approved by the FDA.
Azenosertib also has broad franchise potential beyond Cyclin E1+ PROC. We exclusively in-license or solely own worldwide development and commercialization rights to azenosertib. Strategy Our strategy includes the following key components: • Rapidly advance the clinical development of azenosertib as a monotherapy toward first regulatory approval in Cyclin E1+ PROC .
Azenosertib also has broad franchise potential beyond Cyclin E1-positive PROC. We exclusively in-license or solely own worldwide development and commercialization rights to azenosertib. Strategy Our strategy includes the following key components: • Rapidly advance the clinical development of azenosertib as a monotherapy toward first regulatory approval in Cyclin E1-positive PROC .
An applicant must request orphan drug designation before submitting an NDA/BLA. After the FDA grants orphan product designation, the identity of the therapeutic agent and its potential orphan use are disclosed 11 publicly by the FDA. Orphan drug designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process.
An applicant must request orphan drug designation before submitting an NDA/BLA. After the FDA grants orphan product designation, the identity of the therapeutic agent and its potential orphan use are disclosed publicly by the FDA. Orphan drug designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process.
Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintain compliance with cGMP and other aspects of regulatory compliance. The FDA may withdraw approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market.
Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintain compliance with cGMP and other aspects of regulatory compliance. 11 The FDA may withdraw approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market.
For products administered under the supervision of a physician, obtaining coverage and adequate reimbursement may be particularly difficult because of the higher prices often associated with such drugs. Additionally, separate reimbursement for the product itself or the treatment or procedure in which the product is used may not be available, 15 which may impact physician utilization.
For products administered under the supervision of a physician, obtaining coverage and adequate reimbursement may be particularly difficult because of the higher prices often associated with such drugs. Additionally, separate reimbursement for the product itself or the treatment or procedure in which the product is used may not be available, which may impact physician utilization.
We require that our CMOs produce active drug substance and finished drug product in accordance with current Good Manufacturing Practices, or cGMPs, and all other applicable laws and regulations. We maintain agreements 4 with our CMOs that include confidentiality and intellectual property provisions to protect our proprietary rights related to our product candidates.
We require that our CMOs produce active drug substance and finished drug product in accordance with current Good Manufacturing Practices, or cGMPs, and all other applicable laws and regulations. We maintain agreements with our CMOs that include confidentiality and intellectual property provisions to protect our proprietary rights related to our product candidates.
As a result, we believe there is a large market opportunity for azenosertib in Cyclin E1+ PROC patients. Moreover, the successful launch of mirvetuximab in PROC patients with high folate receptor alpha, or FRα-high, expression underscores the demand for biomarker-directed therapies for PROC patients.
As a result, we believe there is a large market opportunity for azenosertib in Cyclin E1-positive PROC patients. Moreover, the successful launch of mirvetuximab in PROC patients with high folate receptor alpha, or FRα-high, expression underscores the demand for biomarker-directed therapies for PROC patients.
However, the actual protection afforded by a patent varies on a product-by-product basis, from country-to-country, and depends upon many factors, including the type of patent, the scope of its coverage, the availability of regulatory-related extensions, the availability of legal remedies in a particular country, and the validity and enforceability of the patent.
However, the actual protection afforded by a patent varies on a product-by-product basis, from country-to-country, and depends upon many factors, including the type of patent, the scope of its coverage, the availability of regulatory-related extensions, the availability of legal 5 remedies in a particular country, and the validity and enforceability of the patent.
There were two previously reported treatment- 3 related Grade 5 events in the study (2.0%). The DENALI Part 2 protocol contains measures for enhanced patient monitoring, guidance and supportive care, which could potentially improve discontinuation rates.
There were two previously reported treatment-related Grade 5 events in the study (2.0%). The DENALI Part 2 protocol contains measures for enhanced patient monitoring, guidance and supportive care, which could potentially improve discontinuation rates.
Our competitors also may obtain FDA or other regulatory approval for their product candidates more rapidly than we may obtain approval for ours, which could result in competitors establishing a strong market position before we are able to enter the market.
Our competitors also may obtain FDA or other regulatory approval for their product candidates more rapidly 4 than we may obtain approval for ours, which could result in competitors establishing a strong market position before we are able to enter the market.
In addition, companion diagnostic tests require coverage and reimbursement separate and apart from the coverage and reimbursement for their companion pharmaceutical or biological products. Similar challenges to obtaining coverage and reimbursement, applicable to pharmaceutical or biological products, will apply to companion diagnostics. Third-party payors are increasingly reducing reimbursements for pharmaceutical products and services.
In addition, companion diagnostic tests require coverage and reimbursement separate and apart from the coverage and reimbursement for their companion pharmaceutical or biological products. Similar challenges to obtaining coverage and reimbursement, applicable to pharmaceutical or biological products, apply to companion diagnostics. Third-party payors are increasingly reducing reimbursements for pharmaceutical products and services.
If the FDA’s evaluation of the PMA or manufacturing facilities is not favorable, the FDA will deny approval of the PMA or issue a not approvable letter. A not approvable letter will outline the deficiencies in the application and, where practical, will identify what is necessary to make the PMA approvable.
If the FDA’s evaluation of the PMA or manufacturing facilities is not favorable, the FDA will deny approval of the 17 PMA or issue a not approvable letter. A not approvable letter will outline the deficiencies in the application and, where practical, will identify what is necessary to make the PMA approvable.
As of the January 13, 2025 data cutoff, the ORR in patients with Cyclin E1+ PROC tumors who were response-evaluable remained at 34.9% (15/43; 95% CI: 21.0 - 50.9).
As of the January 13, 2025 data cutoff, the ORR in patients with Cyclin E1-positive PROC tumors who were response-evaluable remained at 34.9% (15/43; 95% CI: 21.0 - 50.9).
We have aligned with the FDA on the design of our DENALI Part 2 study in patients with Cyclin E1+ PROC, which allows for seamless enrollment across Parts 2a and 2b.
We have aligned with the FDA on the design of our DENALI Part 2 study in patients with Cyclin E1-positive PROC, which allows for seamless enrollment across Parts 2a and 2b.
We believe azenosertib has the potential to set a new standard of care in patients with Cyclin E1+ PROC. Many patients with PROC receive single-agent chemotherapy, which has modest clinical benefits.
We believe azenosertib has the potential to set a new standard of care in patients with Cyclin E1-positive PROC. Many patients with PROC receive single-agent chemotherapy, which has modest clinical benefits.
If the FDA concludes that the applicable criteria have been met, the 17 FDA will issue a PMA for the approved indications, which can be more limited than those originally sought by the applicant.
If the FDA concludes that the applicable criteria have been met, the FDA will issue a PMA for the approved indications, which can be more limited than those originally sought by the applicant.
Tissue collection for biomarker assessment was mandated in the study and upon a retrospective analysis, approximately 50% of the patients were Cyclin E1+ per our IHC cutoff.
Tissue collection for biomarker assessment was mandated in the study and upon a retrospective analysis, approximately 50% of the patients were Cyclin E1-positive per our IHC cutoff.
In addition, based on published retrospective analyses, Cyclin E1 alteration is a biomarker of poor prognosis and low benefit from standard-of-care single-agent chemotherapy in PROC patients. 1 We are working with a diagnostic partner to develop a companion diagnostic test that will identify patients with PROC that overexpress the Cyclin E1 protein using our proprietary immunohistochemistry, or IHC, cutoff.
In addition, based on published retrospective analyses, Cyclin E1 alteration is a biomarker of poor prognosis and low benefit from standard-of-care single-agent chemotherapy in PROC patients. 1 We are working with a diagnostic partner to validate a companion diagnostic test that will identify patients with PROC that overexpress the Cyclin E1 protein using our proprietary immunohistochemistry, or IHC, cutoff.
The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA, within the 30-day time period, raises safety concerns or questions about the proposed clinical trial.
The IND 7 automatically becomes effective 30 days after receipt by the FDA, unless the FDA, within the 30-day time period, raises safety concerns or questions about the proposed clinical trial.
There was one previously reported treatment-related Grade 5 event in the study. ZN-c3-001 ZN-c3-001 is a Phase 1, dose-escalation study that evaluated azenosertib monotherapy in solid tumors across continuous and intermittent dosing schedules. ZN-c3-001 is fully enrolled (n=274). Greater anti-tumor activity was seen with intermittent dose schedules and in Cyclin E1+ patients.
There was one previously reported treatment-related Grade 5 event in the study. ZN-c3-001 3 ZN-c3-001 is a Phase 1, dose-escalation study that evaluated azenosertib monotherapy in solid tumors across continuous and intermittent dosing schedules. ZN-c3-001 is fully enrolled (n=274). Greater anti-tumor activity was seen with intermittent dose schedules and in Cyclin E1-positive patients.
Item 1. Business. Overview We are a clinical-stage biopharmaceutical company developing azenosertib (ZN-c3), a potentially first-in-class and best-in-class WEE1 inhibitor, for patients with ovarian cancer and other tumor types. In clinical trials, azenosertib has been well tolerated and has demonstrated anti-tumor activity as a single agent across multiple tumor types.
Item 1. Business. Overview We are a clinical-stage biopharmaceutical company developing azenosertib (ZN-c3), an investigational, potentially first-in-class and best-in-class WEE1 inhibitor, for patients with ovarian cancer and other tumor types. In clinical trials, azenosertib has been well tolerated and has demonstrated anti-tumor activity as a single agent across multiple tumor types.
The expected expiration dates for issued patents, or patents that may issue from any patent applications, directed to our WEE1 inhibitor program, including azenosertib, are between 2038 and 2046 plus any extensions or adjustments of term available under national law. However, there can be no assurance that any of the pending patent applications will issue.
The expected expiration dates for issued patents, or patents that may issue from any patent applications, directed to our WEE1 inhibitor program, including azenosertib, are between 2038 and 2047 plus any extensions or adjustments of term available under national law. However, there can be no assurance that any of the pending patent applications will issue.
A medical device manufacturer’s manufacturing processes and those of its suppliers are required to comply with the applicable portions of the QSR, which cover the methods and documentation of the design, testing, production, processes, controls, quality assurance, labeling, packaging and shipping of medical devices. Domestic facility records and manufacturing processes are subject to periodic unscheduled inspections by the FDA.
A medical device manufacturer’s manufacturing processes and those of its suppliers are required to comply with the applicable portions of the QMSR, which cover the methods and documentation of the design, testing, production, processes, controls, quality assurance, labeling, packaging and shipping of medical devices. Domestic facility records and manufacturing processes are subject to periodic unscheduled inspections by the FDA.
Based on our analysis utilizing our IHC cutoff, we estimate that approximately 50% of PROC patients overexpress Cyclin E1 protein, which account for approximately 21,500 patients on an annual basis in the United States, EU4 (France, Germany, Italy, Spain) and the United Kingdom, based on 2024 estimates.
Based on our analysis utilizing our IHC cutoff, we estimate that approximately 50% of PROC patients overexpress Cyclin E1 protein, which accounts for approximately 21,500 patients on an annual basis in the United States, EU4 (France, Germany, Italy, Spain) and the United Kingdom, based on 2024 estimates.
As a result, the coverage determination process can require manufactures to provide scientific and clinical support for the use of a product to each payor separately and can be a time-consuming process, with no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the first instance.
As a result, the coverage determination process can require manufacturers to provide scientific and clinical support for the use of a product to each payor separately and can be a time-consuming process, with no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the first instance.
Accelerated Approval In addition, depending on the design of the applicable clinical studies, a product candidate may be eligible for accelerated approval.
Accelerated Approval 10 In addition, depending on the design of the applicable clinical studies, a product candidate may be eligible for accelerated approval.
In January 2025, we disclosed a significant amount of clinical data showing an objective response rate, or ORR, of over 30% and a manageable safety profile in patients with Cyclin E1+ PROC who received azenosertib at our primary dose-of-interest, 400 mg QD 5:2 (intermittent daily dosing on a five days on, two days off dosing schedule).
In January 2025, we disclosed a significant amount of clinical data showing an objective response rate, or ORR, of over 30% and a manageable safety profile in patients with Cyclin E1-positive PROC who received azenosertib at our primary dose-of-interest, 400 mg QD 5:2 (single daily dose on an intermittent schedule of five days on and two days off).
DENALI Part 2, if successful, has the potential to support an accelerated approval, subject to FDA review. The FDA has granted Fast Track Designation to azenosertib for the treatment of patients with PROC who are positive via Cyclin E1 IHC for protein levels. • Monotherapy – Phase 3 Clinical Trial in Cyclin E1+ PROC.
We believe that DENALI Part 2, if successful, has the potential to support an accelerated approval, subject to FDA review. The FDA has granted Fast Track Designation to azenosertib for the treatment of patients with PROC who are positive via IHC for Cyclin E1 protein levels. • Monotherapy – Phase 3 Clinical Trial in Cyclin E1-positive PROC (ASPENOVA).
As of the December 2, 2024 data cutoff, in patients with Cyclin E1+ PROC tumors who were response-evaluable (patients who had at least one scan after receiving azenosertib), an ORR of 34.9% (15/43; 95% CI: 21.0 - 50.9) was observed.
As of the December 2, 2024 data cutoff, in patients with Cyclin E1-positive PROC tumors who were response-evaluable (patients who had at least one scan after receiving azenosertib), an ORR of 34.9% (15/43; 95% confidence interval, or CI: 21.0 - 50.9) was observed.
In addition, exclusive marketing rights in the United States may be lost if the FDA later determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition.
In addition, exclusive marketing rights in the United States may be lost if the FDA later determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantities of the product to meet the needs relating to the approved indication or use of patients with the rare disease or condition.
As part of the PMA review, the FDA will typically inspect the manufacturer’s facilities for compliance with the Quality System Regulation, or QSR, which imposes elaborate testing, control, documentation and other quality assurance requirements.
As part of the PMA review, the FDA will typically inspect the manufacturer’s facilities for compliance with the Quality Management System Regulation, or QMSR, which imposes elaborate testing, control, documentation and other quality assurance requirements.
The limited overlap between FRα-high PROC patients and those that have Cyclin E1 overexpression is estimated to be less than 20%, which highlights the significant unmet need in patients with Cyclin E1+ PROC. We believe there is additional market opportunity for azenosertib outside of ovarian cancer across other solid tumor types.
The limited overlap between FRα-high PROC patients and those that have Cyclin E1 overexpression is estimated to be less than 20%, which highlights the significant unmet need in patients with Cyclin E1-positive PROC. We believe there is additional market opportunity for azenosertib in earlier lines of treatment for ovarian cancer, and across other solid tumor types.
The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state, local and foreign statutes and regulations require the expenditure of substantial time and financial resources. 7 The process required by the FDA before a drug may be marketed in the United States generally involves the following: • completion of preclinical laboratory tests, animal studies and formulation studies in accordance with FDA’s Good Laboratory Practice, or GLP, requirements and other applicable regulations; • submission to the FDA of an IND, which must become effective before human clinical trials may begin; • approval by an independent institutional review board, or IRB, or ethics committee at each clinical site before each trial may be initiated; • performance of adequate and well-controlled human clinical trials in accordance with Good Clinical Practice, or GCP, requirements to establish the safety and efficacy of the proposed drug for its intended use; • submission to the FDA of an NDA/BLA after completion of all pivotal trials; • satisfactory completion of an FDA advisory committee review, if applicable; • satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the drug is produced to assess compliance with cGMP requirements to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity, and potential inspection of selected clinical investigation sites and the sponsor to assess compliance with GCPs; and • FDA review and approval of the NDA/BLA to permit commercial marketing of the product for particular indications for use in the United States.
The process required by the FDA before a drug may be marketed in the United States generally involves the following: • completion of preclinical laboratory tests, animal studies and formulation studies in accordance with FDA’s Good Laboratory Practice, or GLP, requirements and other applicable regulations; • submission to the FDA of an IND, which must become effective before human clinical trials may begin; • approval by an independent institutional review board, or IRB, or ethics committee at each clinical site before each trial may be initiated; • performance of adequate and well-controlled human clinical trials in accordance with Good Clinical Practice, or GCP, requirements to establish the safety and efficacy of the proposed drug for its intended use; • submission to the FDA of an NDA/BLA after completion of all pivotal trials; • satisfactory completion of an FDA advisory committee review, if applicable; • satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the drug is produced to assess compliance with cGMP requirements to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity, and potential inspection of selected clinical investigation sites and the sponsor to assess compliance with GCPs; and • FDA review and approval of the NDA/BLA to permit commercial marketing of the product for particular indications for use in the United States.
This means the FDA may not approve any other applications, including full NDAs/BLAs, to market the same drug, as defined by the FDA, for the same disease or condition for seven years from the date of such approval, except in limited circumstances, such as a showing of clinical superiority to the product with orphan exclusivity.
This means the FDA may not approve any other applications, including full NDAs/BLAs, to market the same drug, as defined by the FDA, for the same approved use or indication with the applicable rare disease or condition for seven years from the date of such approval, except in limited circumstances, such as a showing of clinical superiority to the product with orphan exclusivity within the relevant indication or use.
In January and March of 2025, we announced clinical data from this study, which is described below. ◦ DENALI Part 2 is designed to enroll approximately 100 patients with Cyclin E1+ PROC at the selected dose who have received one to three prior lines of therapy, or mirvetuximab soravtansine in the case of patients whose tumors are also FRα-high.
In January and March of 2025, we announced clinical data from this study, which is described in the next section below titled “Clinical Data – DENALI Part 1b”. ◦ DENALI Part 2 is designed to enroll approximately 100 patients with Cyclin E1-positive PROC at the selected dose who have received one to three prior lines of therapy, or for patients whose tumors are also FRα-high and who have received mirvetuximab soravtansine, one to four prior lines of therapy.
DENALI Part 2a is designed to confirm 400 mg QD 5:2 as the primary dose-of-interest by enrolling approximately 30 patients at each of two dose levels, 400 mg QD 5:2 and 300 mg QD 5:2.
DENALI Part 2a is designed to confirm 400 mg QD 5:2 as the recommended pivotal study dose by enrolling approximately 30 patients at each of two dose levels, 400 mg QD 5:2 and 300 mg QD 5:2.
Following certain corporate restructuring disclosed elsewhere in this Annual Report on 10-K, our wholly owned subsidiary, ZMI, became the Zentalis contracting party to the Recurium Agreement. The intellectual property rights exclusively licensed by ZMI under the Recurium Agreement include certain intellectual property covering azenosertib. See Part II, Item 7.
Following a corporate restructuring disclosed elsewhere in this Annual Report on Form 10-K, our wholly owned subsidiary, ZMI, became the Zentalis contracting party to the Recurium Agreement. The intellectual property rights exclusively licensed by ZMI under the Recurium Agreement include certain intellectual property covering azenosertib.
In addition, we are leveraging our extensive experience and capabilities to translate our science to advance research on additional areas of opportunity for azenosertib. • Evaluate additional strategic opportunities to maximize the value of our pipeline . We previously entered into development collaborations for azenosertib with Pfizer Inc., GSK plc, and Dana-Farber Cancer Institute.
In addition, we are leveraging our extensive experience and capabilities to translate our science to advance research on additional areas of opportunity for azenosertib in other tumor types beyond ovarian cancer. • Evaluate additional strategic opportunities to maximize the value of our pipeline . We previously had development collaborations for azenosertib with Pfizer Inc., GSK plc, and Dana-Farber Cancer Institute.
Privacy and security laws, regulations, and other obligations are constantly evolving, may conflict with each other to complicate compliance efforts, and can result in investigations, proceedings, or actions that lead to significant civil and/or criminal penalties and restrictions on data processing Environmental, Social and Governance (ESG) Human Capital Management As of December 31, 2024, Zentalis had a total of 166 employees all of whom were full-time employees.
Privacy and security laws, regulations, and other obligations are constantly evolving, may conflict with each other to complicate compliance efforts, and can result in investigations, proceedings, or actions that lead to significant civil and/or criminal penalties and restrictions on data processing Human Capital Resources As of December 31, 2025, Zentalis had a total of 106 employees all of whom were full-time employees.
A prototype of this test is ready for use in DENALI Part 2. Market Opportunity In 2022, the global ovarian cancer market was approximately $3 billion, with significant growth expected over the next several years. PROC is a subset of the ovarian cancer market.
A prototype of this test is being used in DENALI Part 2 and is ready for use in our Phase 3 trial, ASPENOVA. Market Opportunity In 2022, the global ovarian cancer market was approximately $3 billion, with significant growth expected over the next several years. PROC is a subset of the ovarian cancer market.
While we believe that our product candidate, development capabilities, experience and scientific knowledge provide us with competitive advantages, we face potential competition from many different sources, including major and specialty pharmaceutical and biotechnology companies, academic research institutions, governmental agencies and public and private research institutions.
While we believe that our product candidate azenosertib as a potential biomarker-directed, oral, non-chemotherapy treatment, development capabilities, experience and scientific knowledge provide us with competitive advantages, we face potential competition from many different sources, including major and specialty pharmaceutical and biotechnology companies, academic research institutions, governmental agencies and public and private research institutions.
Clinical trials of medicinal products in the EU must be conducted in accordance with EU and national regulations and the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use, or ICH, guidelines on GCPs, as well as the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki.
These GLP standards reflect the Organization for Economic Co-operation and Development requirements. 13 Clinical trials of medicinal products in the EU must be conducted in accordance with EU and national regulations and the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use, or ICH, guidelines on GCPs, as well as the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki.
We will continue to selectively evaluate additional collaborations for azenosertib with partners whose assets and capabilities complement our own. Azenosertib (WEE1 Inhibitor) Mechanism of Action Azenosertib is a potentially best-in-class and first-in-class oral, small molecule WEE1 inhibitor.
While these collaborations have completed, we will continue to selectively evaluate new collaborations for azenosertib with partners whose assets and capabilities complement our own. Azenosertib (WEE1 Inhibitor) Mechanism of Action Azenosertib is an investigational, potentially first-in-class and best-in-class oral, small molecule WEE1 inhibitor.
Competitors, however, may receive approval of either a different product for the same disease or condition or the same product for a different disease or condition.
Competitors, however, may receive approval of either a different product for the same indication or use of the same product for a different indication or use.
The Centers for Medicare & Medicaid Services has published the negotiated prices for the initial ten drugs, which will first be effective in 2026, and has published the list of the subsequent 15 drugs that will be subject to negotiation.
The Centers for Medicare & Medicaid Services, or CMS, has published the negotiated prices 15 for the initial ten drugs, which became effective in 2026, and the subsequent fifteen drugs, which will first be effective in 2027. CMS has also published the next set of fifteen drugs that will be subject to negotiation.
We will be required to follow a “Centralized MA” process. Centralized MAs are issued by the European Commission through the centralized procedure based on the opinion of the Committee for Medicinal Products for Human Use, or CHMP, of the European Medicines Agency, or EMA, and are valid throughout the EU.
Centralized MAs are issued by the European Commission through the centralized procedure based on the opinion of the Committee for Medicinal Products for Human Use, or CHMP, of the European Medicines Agency, or EMA, and are valid throughout the EU.
Pediatric exclusivity provides for an additional six months of exclusivity attached to another existing patent term or period of regulatory exclusivity if a sponsor conducts clinical trials in children in response to a written request from the FDA. The issuance of a written request does not require the sponsor to undertake the described clinical trials.
Pediatric exclusivity is another type of marketing exclusivity available in the United States. Pediatric exclusivity provides for an additional six months of exclusivity attached to another existing patent term or period of regulatory exclusivity if a sponsor conducts clinical trials in children in response to a written request from the FDA.
License Agreements and Strategic Collaborations Recurium IP Holdings, LLC License Agreement In December 2014, our wholly owned subsidiary, Zeno Pharmaceuticals, Inc., entered into a license agreement, or the Recurium Agreement, with Recurium IP, which was subsequently amended, under which Zeno Pharmaceuticals, Inc. was granted an exclusive worldwide license to certain intellectual property rights owned or controlled by Recurium IP to develop and commercialize pharmaceutical products for the treatment or prevention of disease, other than for providing pain relief.
To the extent that our commercial partners, collaborators, employees and consultants use intellectual property owned by others in their work for us, disputes may arise as to the rights in related or resulting know-how and inventions. 6 License Agreements and Strategic Collaborations Recurium IP Holdings, LLC License Agreement In December 2014, our wholly owned subsidiary, Zeno Pharmaceuticals, Inc., entered into a license agreement, or the Recurium Agreement, with Recurium IP, which was subsequently amended, under which Zeno Pharmaceuticals, Inc. was granted an exclusive worldwide license to certain intellectual property rights owned or controlled by Recurium IP to develop and commercialize pharmaceutical products for the treatment or prevention of disease, other than for providing pain relief.
We are dedicated to supporting a talented team and strive to offer competitive compensation, including salaries, bonuses and equity awards, and benefits in order to support our business objectives, assist in the achievement of our strategic goals and create value for our stockholders.
Our Code of Business Conduct and Ethics prohibits discrimination of any protected group, and our employees participate in regular anti-harassment training. • We are dedicated to supporting a talented team and strive to offer competitive compensation, including salaries, bonuses and equity awards, and benefits in order to support our business objectives, assist in the achievement of our strategic goals and create value for our stockholders.
Among other things, the IRA requires manufacturers of certain drugs to engage in price negotiations with Medicare, with prices that can be negotiated subject to a cap; imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation (which first became due by certain manufacturers in 2023, as applicable); and replaces the Part D coverage gap discount program with a new discounting program (which began on January 1, 2025).
Among other things, the IRA requires manufacturers of certain drugs to engage in price negotiations with Medicare, with prices that can be negotiated subject to a cap, imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation; redesigns the Medicare Part D benefit; and replaces the Part D coverage gap discount program with a new manufacturer discount program.
DENALI Part 2, if successful, has the potential to support an accelerated approval, subject to FDA review. • Advance the development of azenosertib outside of Cyclin E1+ PROC, as resources allow.
DENALI Part 2, if successful, has the potential to support an accelerated approval, subject to FDA review. • Advance the development of azenosertib outside of Cyclin E1-positive PROC, as resources allow. We believe that the opportunity for azenosertib is broad, and we plan to advance the clinical development of azenosertib outside of Cyclin E1-positive PROC, as our resources allow.
Any product candidate that we successfully develop and commercialize will compete with current therapies and new therapies that may become available in the future. Many of the companies against which we may compete have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do.
Many of the companies against which we may compete have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do.
Schrödinger, Inc., or Schrödinger, has disclosed that it is evaluating multiple WEE1 inhibitors, including SGR-3515, a Wee1/Myt1 inhibitor, as potential monotherapy or combination therapy approaches for the treatment of gynecological cancers and other solid tumors. Schrödinger has disclosed that it initiated a Phase 1 study for SGR-3515 in June 2024.
Aprea Therapeutics, Inc., or Aprea, has disclosed that it is clinically evaluating a WEE1 inhibitor, APR-1051 (formerly ATRN-W1051) for advanced solid tumors. Schrödinger, Inc., or Schrödinger, has disclosed that it is evaluating multiple WEE1 inhibitors, including SGR-3515, a WEE1/Myt1 inhibitor, as potential monotherapy or combination therapy approaches for the treatment of gynecological cancers and other solid tumors.
Orphan exclusivity also could block the approval of a product for seven years if a competitor obtains approval of the same drug or if such drug is determined to be contained within the competitor’s product for the same disease or condition.
Orphan exclusivity also could block the approval of a product for seven years in the relevant indication or use if a competitor obtains approval of the “same drug,” as defined by the FDA, or if such drug is determined to be contained within the competitor’s product.
In 2021, we completed the first offering period under the Zentalis Pharmaceuticals, Inc. 2020 Employee Stock Purchase Plan for all full-time employees who elected to participate—a benefit we are proud to offer and that we believe helps to foster our corporate culture and encourage collaboration towards our shared business success.
We also have a variety of company-wide events designed to support camaraderie and encourage teamwork and collaboration. We maintain the Zentalis Pharmaceuticals, Inc. 2020 Employee Stock Purchase Plan for all full-time employees who elected to participate—a benefit we are proud to offer and that we believe helps to foster our corporate culture and encourage collaboration towards our shared business success.
Acrivon Therapeutics, Inc. has disclosed that it is developing and evaluating a dual WEE1/PKMYT1 inhibitor, ACR-2316, as monotherapy for the treatment of solid tumors and initiated a Phase 1 study in October 2024. WuXi AppTec has disclosed that SC0191, a WEE1 inhibitor, is currently in Phase 1 development as a monotherapy or combination in advanced colorectal cancer.
Acrivon Therapeutics, Inc. has disclosed that it is developing and evaluating a dual WEE1/PKMYT1 inhibitor, ACR-2316, currently in a Phase 1 trial as monotherapy for the treatment of solid tumors. Impact Therapeutics has disclosed that it is investigating IMP7068, a WEE1 inhibitor, currently in a Phase 1 trial for advanced solid tumors.
We plan to disclose data from this trial in the first half of 2026. • Combination – Phase 1b Clinical Trial of Azenosertib and Chemotherapy or Bevacizumab in Ovarian Cancer (ZN-c3-002).
We plan to initiate ASPENOVA in the first half of 2026 and enroll concurrently with DENALI Part 2b. • Combination – Phase 1b Clinical Trial of Azenosertib and Chemotherapy or Bevacizumab in Ovarian Cancer (MUIR - ZN-c3-002).
We plan to initiate enrollment of our DENALI Part 2 clinical trial of azenosertib in patients with Cyclin E1+ PROC in the first half of 2025 and to disclose topline data from the trial by year end 2026.
We completed enrollment in Part 2a of our Phase 2 DENALI clinical trial of azenosertib in patients with Cyclin E1-positive PROC in 2025 and anticipate a topline readout from the trial by year end 2026.
However, an applicant submitting a full NDA would be required to conduct or obtain a right of reference to any preclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and effectiveness. 13 Pediatric exclusivity is another type of marketing exclusivity available in the United States.
Five-year and three-year exclusivity will not delay the submission or approval of a full NDA. However, an applicant submitting a full NDA would be required to conduct or obtain a right of reference to any preclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and effectiveness.
The information found on our website is not part of this Annual Report on Form 10-K or any other report we file with, or furnish to, the SEC. The SEC also maintains a website that contains reports, proxy statements and other information about issuers, like us, that file electronically with the SEC. The address of that website is https://www.sec.gov. 19
The SEC also maintains a website that contains reports, proxy statements and other information about issuers, like us, that file electronically with the SEC. The address of that website is https://www.sec.gov. 19
The sponsor of the trial must have an EU representative, an insurance policy, and a compensation plan for any injuries. The regulatory landscape related to clinical trials in the EU has been subject to recent changes. The EU Clinical Trials Regulation, or CTR, repealed the EU Clinical Trials Directive and became applicable on January 31, 2022.
The regulatory landscape related to clinical trials in the EU has been subject to recent changes. The EU Clinical Trials Regulation, or CTR, repealed the EU Clinical Trials Directive and became applicable on January 31, 2022.
Healthcare Reform In the United States and certain foreign jurisdictions, there have been, and we expect there will continue to be, a number of legislative and regulatory changes to the healthcare system.
Healthcare Reform In the United States and certain foreign jurisdictions, there have been, and we expect there will continue to be, a number of legislative and regulatory changes to the healthcare system. The ACA, was enacted in 2010, which substantially changed the way healthcare is financed by both governmental and private insurers in the United States.
Impact Therapeutics has disclosed that it is investigating IMP7068, a WEE1 inhibitor, currently in a Phase 1 trial for advanced solid tumors. Shouyao Holdings has disclosed that it is investigating SY-4835, a WEE1 inhibitor, in a Phase 1 trial for patients with advanced solid tumors.
Shouyao Holdings has disclosed that it is investigating SY-4835, a WEE1 inhibitor, in a Phase 1 trial for patients with advanced solid tumors. WuXi AppTec has disclosed that SC0191, a WEE1 inhibitor, is currently in Phase 2 development as a monotherapy or combination in advanced colorectal cancer.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeFuture growth would impose significant added responsibilities on members of management, including: • identifying, recruiting, integrating, maintaining and motivating additional employees; • managing our internal development efforts effectively, including the clinical, FDA and ex-U.S. regulatory agencies’ review process for our product candidates, while complying with any contractual obligations to contractors and other third parties we may have; and • improving our operational, financial and management controls, reporting systems and procedures.
Biggest changeFuture growth would impose significant added responsibilities on members of management, including: • identifying, recruiting, integrating, maintaining and motivating additional employees; • managing our internal development efforts effectively, including the clinical, FDA and ex-U.S. regulatory agencies’ review process for our product candidates, while complying with any contractual obligations to contractors and other third parties we may have; and • improving our operational, financial and management controls, reporting systems and procedures. 45 Our future financial performance and our ability to successfully develop and, if approved, commercialize, our product candidates will depend, in part, on our ability to effectively manage any future growth, and our management may also have to divert a disproportionate amount of its attention away from day-to-day activities in order to devote a substantial amount of time to managing these growth activities.
If these third parties do not make data available to us, or, if applicable, make regulatory submissions in a timely manner, in each case pursuant to our agreements with them, our development programs may be significantly delayed, and we may need to conduct additional studies or collect additional data independently. In either case, our development costs would increase.
If these third parties do not make data available to us, or, if applicable, do not make regulatory submissions in a timely manner, in each case pursuant to our agreements with them, our development programs may be significantly delayed, and we may need to conduct additional studies or collect additional data independently. In either case, our development costs would increase.
If the scope of any patent protection our licensors obtain is not sufficiently broad, or if our licensors lose any of the patent protection we license, our ability to prevent our competitors from commercializing similar or identical product candidates would be adversely affected.
If the scope of our patent protection or any patent protection our licensors obtain is not sufficiently broad, or if our licensors lose any of the patent protection we license, our ability to prevent our competitors from commercializing similar or identical product candidates would be adversely affected.
These risks and uncertainties include the following: • the USPTO and various foreign governmental patent agencies require compliance with a number of procedural, documentary, fee payment and other provisions during the patent process, the noncompliance with which can result in abandonment or lapse of a patent or patent application, and partial or complete loss of patent rights in the relevant jurisdictions; • patent applications may not result in any patents being issued; • patents may be challenged, invalidated, modified, revoked, circumvented, found to be unenforceable or otherwise may not provide any competitive advantage; • our competitors, many of whom have substantially greater resources than we or our licensors do and many of whom have made significant investments in competing technologies, may seek, may have filed patent applications, or may have already obtained patents that will limit, interfere with or block our ability to make, use and sell our product candidates; • there may be significant pressure on the U.S. and ex-U.S. governments and international governmental bodies to limit the scope of patent protection both inside and outside the United States for disease treatments that prove successful, as a matter of public policy regarding worldwide health concerns; and • countries other than the United States may have patent laws less favorable to patentees than those upheld by U.S. courts, allowing ex-U.S. competitors a better opportunity to create, develop and market competing products.
These risks and uncertainties include the following: • the USPTO and various foreign governmental patent agencies require compliance with a number of procedural, documentary, fee payment and other provisions during the patent process, the noncompliance with which can result in abandonment or lapse of a patent or patent application, and partial or complete loss of patent rights in the relevant jurisdictions; • patent applications may not result in any patents being issued; • patents may be challenged, invalidated, modified, revoked, circumvented, found to be unenforceable or otherwise may not provide any competitive advantage; • our competitors, many of whom have substantially greater resources than we or our licensors do and many of whom have made significant investments in competing technologies, may seek, may have filed patent applications, or may have already obtained patents that will limit, interfere with or block our ability to make, use and sell our product candidates; • there may be significant pressure on the U.S. and ex-U.S. governments and international governmental bodies to limit the scope of patent protection both inside and outside the United States for disease treatments that prove successful, as a matter of public policy regarding worldwide health concerns; and 51 • countries other than the United States may have patent laws less favorable to patentees than those upheld by U.S. courts, allowing ex-U.S. competitors a better opportunity to create, develop and market competing products.
In addition to the factors discussed in this “Risk Factors” section these factors include: 62 • the timing and results of preclinical studies and clinical trials of our product candidates or those of our competitors; • the success of competitive products or announcements by potential competitors of their product development efforts; • regulatory actions with respect to our products or product candidates or our competitors’ products or product candidates; • actual or anticipated changes in our growth rate relative to our competitors; • regulatory or legal developments in the United States and other countries; • developments or disputes concerning patent applications, issued patents or other proprietary rights; • the recruitment or departure of key personnel; • announcements by us or our competitors of significant acquisitions, strategic collaborations, joint ventures, collaborations or capital commitments; • actual or anticipated changes in estimates as to financial results, development timelines or recommendations by securities analysts; • fluctuations in the valuation of companies perceived by investors to be comparable to us; • market conditions in the pharmaceutical and biotechnology sector; • changes in the structure of healthcare payment systems; • speculative trading in and short sales of our common stock, as well as trading phenomena such as the "short squeeze"; • share price and volume fluctuations attributable to inconsistent trading volume levels of our shares; • announcement or expectation of additional financing efforts; • sales of our common stock by us, our insiders or our other stockholders; • expiration of market stand-off or lock-up agreements; and • general economic, industry and market conditions.
In addition to the factors discussed in this “Risk Factors” section these factors include: • the timing and results of preclinical studies and clinical trials of our product candidates or those of our competitors; • the success of competitive products or announcements by potential competitors of their product development efforts; • regulatory actions with respect to our products or product candidates or our competitors’ products or product candidates; • actual or anticipated changes in our growth rate relative to our competitors; • regulatory or legal developments in the United States and other countries; • developments or disputes concerning patent applications, issued patents or other proprietary rights; • the recruitment or departure of key personnel; • announcements by us or our competitors of significant acquisitions, strategic collaborations, joint ventures, collaborations or capital commitments; • actual or anticipated changes in estimates as to financial results, development timelines or recommendations by securities analysts; • fluctuations in the valuation of companies perceived by investors to be comparable to us; • market conditions in the pharmaceutical and biotechnology sector; • changes in the structure of healthcare payment systems; • speculative trading in and short sales of our common stock, as well as trading phenomena such as the "short squeeze"; • share price and volume fluctuations attributable to inconsistent trading volume levels of our shares; • announcement or expectation of additional financing efforts; • sales of our common stock by us, our insiders or our other stockholders; • expiration of market stand-off or lock-up agreements; and • general economic, industry and market conditions.
The degree of market acceptance of any of our approved product candidates will depend on a number of factors, including: • the efficacy and safety profile as demonstrated in clinical trials compared to alternative treatments; • the timing of market introduction of the product candidate as well as competitive products; • the clinical indications for which the product candidate is approved; • if applicable (which we expect to be the case for monotherapy azenosertib in Cyclin E1+ PROC), the availability and/or reimbursement of diagnostic tools such as companion diagnostics for biomarkers associated with our product candidates or any other future product candidates; • restrictions on the use of our product candidates, such as boxed warnings or contraindications in labeling, or a REMS, or similar risk management measures, if any, which may not be required of alternative treatments and competitor products; • the potential and perceived advantages of the product candidate over alternative treatments; • the cost of treatment in relation to alternative treatments; • the availability of coverage and adequate reimbursement, as well as pricing, by third-party payors, including government authorities; • for combination therapies, the availability of the combination product ; • relative convenience and ease of administration; • the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies; • the effectiveness of sales and marketing efforts; • unfavorable publicity relating to our products or product candidates or similar approved products or product candidates in development by third parties; and • the approval of other new therapies for the same indications.
The degree of market acceptance of any of our approved product candidates will depend on a number of factors, including: • the efficacy and safety profile as demonstrated in clinical trials compared to alternative treatments; • the timing of market introduction of the product candidate as well as competitive products; • the clinical indications for which the product candidate is approved; • if applicable (which we expect to be the case for monotherapy azenosertib in Cyclin E1-positive PROC), the availability and/or reimbursement of diagnostic tools such as companion diagnostics for biomarkers associated with our product candidates or any other future product candidates; • restrictions on the use of our product candidates, such as boxed warnings or contraindications in labeling, or a REMS, or similar risk management measures, if any, which may not be required of alternative treatments and competitor products; • the potential and perceived advantages of the product candidate over alternative treatments; • the cost of treatment in relation to alternative treatments; • the availability of coverage and adequate reimbursement, as well as pricing, by third-party payors, including government authorities; • for combination therapies, the availability of the combination product ; • relative convenience and ease of administration; • the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies; • the effectiveness of sales and marketing efforts; • unfavorable publicity relating to our products or product candidates or similar approved products or product candidates in development by third parties; and • the approval of other new therapies for the same indications.
For example: • others may be able to develop products that are similar to our product candidates but that are not covered by the claims of the patents that we own or license; • we or our licensors might not have been the first to make the inventions covered by the issued patents or patent application that we own or in-license; • we or our licensors might not have been the first to file patent applications covering certain of our inventions; • others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our intellectual property rights; • it is possible that our licensors’ pending patent applications will not lead to issued patents; • issued patents that we own or in-license may be held invalid or unenforceable, as a result of legal challenges by our competitors; 54 • our competitors might conduct research and development activities in countries where we do not have patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets; • we may not develop additional proprietary technologies that are patentable; and • the patents of others may have an adverse effect on our business. • Should any of these events occur, it could significantly harm our business, results of operations and prospects.
For example: • others may be able to develop products that are similar to our product candidates but that are not covered by the claims of the patents that we own or license; • we or our licensors might not have been the first to make the inventions covered by the issued patents or patent application that we own or in-license; • we or our licensors might not have been the first to file patent applications covering certain of our inventions; • others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our intellectual property rights; • it is possible that our licensors’ pending patent applications will not lead to issued patents; • issued patents that we own or in-license may be held invalid or unenforceable, as a result of legal challenges by our competitors; • our competitors might conduct research and development activities in countries where we do not have patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets; • we may not develop additional proprietary technologies that are patentable; and • the patents of others may have an adverse effect on our business. • Should any of these events occur, it could significantly harm our business, results of operations and prospects.
Patient enrollment for any of our clinical trials may be affected by other factors, including: • size and nature of the patient population; • severity of the disease under investigation; • availability and efficacy of approved drugs for the disease under investigation; • patient eligibility criteria for the trial in question as defined in the protocol; • perceived risks and benefits of the product candidate under study; • clinicians’ and patients’ perceptions as to the potential advantages of the product candidate being studied in relation to other available therapies, including any new products that may be approved for the indications we are investigating; • efforts to facilitate timely enrollment in clinical trials; • patient referral practices of physicians; • the ability to monitor patients adequately during and after treatment; • proximity and availability of clinical trial sites for prospective patients; • continued enrollment of prospective patients by clinical trial sites; • the risk that patients enrolled in clinical trials will drop out of the trials before completion or, because they may be late-stage cancer patients, will not survive the full terms of the clinical trials; and • Geopolitical changes may impact the ability to enroll in countries selected for clinical trials.
Patient enrollment for any of our clinical trials may be affected by other factors, including: • size and nature of the patient population; 30 • severity of the disease under investigation; • availability and efficacy of approved drugs for the disease under investigation; • patient eligibility criteria for the trial in question as defined in the protocol; • perceived risks and benefits of the product candidate under study; • clinicians’ and patients’ perceptions as to the potential advantages of the product candidate being studied in relation to other available therapies, including any new products that may be approved for the indications we are investigating; • efforts to facilitate timely enrollment in clinical trials; • patient referral practices of physicians; • the ability to monitor patients adequately during and after treatment; • proximity and availability of clinical trial sites for prospective patients; • continued enrollment of prospective patients by clinical trial sites; • the risk that patients enrolled in clinical trials will drop out of the trials before completion or, because they may be late-stage cancer patients, will not survive the full terms of the clinical trials; and • geopolitical changes may impact the ability to enroll in countries selected for clinical trials.
These provisions, among other things: 64 • establish a classified Board of Directors so that not all members of our Board of Directors are elected at one time; • permit only the Board of Directors to establish the number of directors and fill vacancies on the Board of Directors; • provide that directors may only be removed “for cause” and only with the approval of two-thirds of our stockholders; • authorize the issuance of “blank check” preferred stock that our Board of Directors could use to implement a stockholder rights plan (also known as a “poison pill”); • eliminate the ability of our stockholders to call special meetings of stockholders; • prohibit stockholder action by written consent, which requires all stockholder actions to be taken at a meeting of our stockholders; • prohibit cumulative voting; • authorize our Board of Directors to amend the bylaws; • establish advance notice requirements for nominations for election to our Board of Directors or for proposing matters that can be acted upon by stockholders at annual stockholder meetings; and • require a super-majority vote of stockholders to amend some provisions described above.
These provisions, among other things: • establish a classified Board of Directors so that not all members of our Board of Directors are elected at one time; • permit only the Board of Directors to establish the number of directors and fill vacancies on the Board of Directors; • provide that directors may only be removed “for cause” and only with the approval of two-thirds of our stockholders; • authorize the issuance of “blank check” preferred stock that our Board of Directors could use to implement a stockholder rights plan (also known as a “poison pill”); • eliminate the ability of our stockholders to call special meetings of stockholders; • prohibit stockholder action by written consent, which requires all stockholder actions to be taken at a meeting of our stockholders; • prohibit cumulative voting; • authorize our Board of Directors to amend the bylaws; • establish advance notice requirements for nominations for election to our Board of Directors or for proposing matters that can be acted upon by stockholders at annual stockholder meetings; and • require a super-majority vote of stockholders to amend some provisions described above.
Clinical trials can be delayed for a variety of reasons, including delays related to: • the FDA or ex-U.S. regulatory authorities disagreeing as to the design or implementation of our clinical studies; • obtaining regulatory authorizations to commence a trial or reaching a consensus with regulatory authorities on trial design; • any failure or delay in reaching an agreement with CROs and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites; • obtaining approval from one or more IRBs or ethics committees; • IRBs or ethics committees refusing to approve, suspending or terminating the trial at an investigational site, precluding enrollment of additional subjects, or withdrawing their approval of the trial; • changes to the clinical trial protocol; • clinical sites deviating from the trial protocol or dropping out of a trial; • manufacturing sufficient quantities of product candidate or obtaining sufficient quantities of combination therapies for use in clinical trials; • subjects failing to enroll or remain in our trial at the rate we expect, or failing to return for post-treatment follow-up; • subjects choosing an alternative treatment for the indication for which a product candidate is being developed, or participating in competing clinical trials; • lack of adequate funding to continue the clinical trial; • subjects experiencing severe or unexpected drug-related AEs; • occurrence of serious AEs in trials of the same class of agents conducted by other companies; • selection of clinical end points that require prolonged periods of clinical observation or analysis of the resulting data; • a facility manufacturing our product candidates or any of their components being ordered by the FDA or ex-U.S. regulatory authorities to temporarily or permanently shut down due to violations of cGMP regulations or similar ex-U.S. requirements or other applicable requirements, or infections or cross-contaminations of product candidates in the manufacturing process; • any changes to our manufacturing process that may be necessary or desired; • the imposition of a clinical hold by the FDA, such as the azenosertib partial clinical hold we announced in June 2024 that was lifted in September 2024 without any changes required by FDA to the azenosertib clinical development plan; • third-party clinical investigators losing the licenses or permits necessary to perform our clinical trials, not performing our clinical trials on our anticipated schedule or consistent with the clinical trial protocol, GCP, or other regulatory requirements; • third-party contractors not performing data collection or analysis in a timely or accurate manner; • third-party contractors becoming debarred or suspended or otherwise penalized by the FDA or other government or regulatory authorities for violations of regulatory requirements, in which case we may need to find a substitute contractor, and we may not be able to use some or all of the data produced by such contractors in support of our marketing applications; and/or • if we are collaborating with a third party on a clinical trial, our collaborator may not devote sufficient resources to or prioritize our clinical trial.
Clinical trials can be delayed for a variety of reasons, including delays related to: • the FDA or ex-U.S. regulatory authorities disagreeing as to the design or implementation of our clinical studies; • obtaining regulatory authorizations to commence a trial or reaching a consensus with regulatory authorities on trial design; • any failure or delay in reaching an agreement with CROs and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites; • obtaining approval from one or more institutional review boards, or IRBs, or ethics committees; • IRBs or ethics committees refusing to approve, suspending or terminating the trial at an investigational site, precluding enrollment of additional subjects, or withdrawing their approval of the trial; • changes to the clinical trial protocol; • clinical sites deviating from the trial protocol or dropping out of a trial; • manufacturing sufficient quantities of product candidate or obtaining sufficient quantities of combination therapies for use in clinical trials; • subjects failing to enroll or remain in our trial at the rate we expect, or failing to return for post-treatment follow-up; • subjects choosing an alternative treatment for the indication for which a product candidate is being developed, or participating in competing clinical trials; • lack of adequate funding to continue the clinical trial; • subjects experiencing severe or unexpected drug-related AEs; • occurrence of serious AEs in trials of the same class of agents conducted by other companies; • selection of clinical end points that require prolonged periods of clinical observation or analysis of the resulting data; • a facility manufacturing our product candidates or any of their components being ordered by the FDA or ex-U.S. regulatory authorities to temporarily or permanently shut down due to violations of cGMP regulations or similar ex-U.S. requirements or other applicable requirements, or infections or cross-contaminations of product candidates in the manufacturing process; • any changes to our manufacturing process that may be necessary or desired; • the imposition of a clinical hold by the FDA, such as the azenosertib partial clinical hold we announced in June 2024 that was lifted in September 2024 without any changes required by FDA to the azenosertib clinical development plan; • third-party clinical investigators losing the licenses or permits necessary to perform our clinical trials, not performing our clinical trials on our anticipated schedule or consistent with the clinical trial protocol, GCP, or other regulatory requirements; • third-party contractors not performing data collection or analysis in a timely or accurate manner; • third-party contractors becoming debarred or suspended or otherwise penalized by the FDA or other government or regulatory authorities for violations of regulatory requirements, in which case we may need to find a substitute contractor, and we may not be able to use some or all of the data produced by such contractors in support of our marketing applications; and/or • if we are collaborating with a third party on a clinical trial, our collaborator may not devote sufficient resources to or prioritize our clinical trial.
Our ability to generate product revenue and achieve profitability depends significantly on our ability, or any future collaborator’s ability, to achieve a number of objectives, including: • successful and timely completion of the clinical development of azenosertib as a monotherapy for the treatment of Cyclin E1+ PROC, successful and timely completion of the development of a companion diagnostic with a diagnostic partner to identify patients with Cyclin E1+ PROC, and meeting the associated costs thereof, including any unforeseen costs we have incurred and may continue to incur as a result of delays including due to public health emergencies, U.S. and global economic issues, such as rising inflation and interest rates, or ongoing military conflicts, among other causes; • successful and timely completion of the clinical development of azenosertib for additional oncology indications and of any future product candidates, resources allowing; • if applicable, the availability or successful development of diagnostic tools for biomarkers for any future product candidates or for additional biomarkers for azenosertib; • establishing and maintaining relationships with CROs and clinical sites for the clinical development, both in the United States and internationally, of azenosertib and any future product candidates, resources allowing; • timely receipt of marketing approvals from applicable regulatory authorities for azenosertib for the treatment of Cyclin E1+ PROC and, resources allowing, additional oncology indications for azenosertib and any future product candidates, in each case for which we successfully complete clinical development; • timely receipt by our diagnostic partner of a marketing approval for a companion diagnostic to identify patients with Cyclin E1+ PROC and, if applicable, marketing approval of diagnostic tools for biomarkers for any future product candidates and any additional biomarkers for azenosertib; • maintaining marketing approvals, including our diagnostic partner's maintaining its marketing approval of a companion diagnostic to identify patients with Cyclin E1+PROC, and making any required post-marketing approval commitments to applicable regulatory authorities; • developing an efficient and scalable manufacturing process for our product candidates, including obtaining finished products that are appropriately packaged for sale; • establishing and maintaining commercially viable supply and manufacturing relationships with third parties that can provide adequate, in both amount and quality, products and services to support clinical development and meet the market demand for product candidates that we develop, if approved; • successful commercial launch following any marketing approval, including the development of a commercial infrastructure, whether in-house or with one or more collaborators; • a continued acceptable safety profile following any marketing approval of our product candidates; • commercial acceptance of our product candidates by patients, the medical community and third-party payors; • identifying, assessing and developing new product candidates; • obtaining, maintaining and expanding our intellectual property rights, including patents, trade secrets and know how, and regulatory exclusivity, both in the United States and internationally; • protecting our rights in our intellectual property portfolio; • defending against third-party interference or infringement claims, if any; • negotiating favorable terms in any collaboration, licensing or other arrangements that may be necessary or desirable to develop, manufacture or commercialize our product candidates; • obtaining adequate pricing, coverage and reimbursement by hospitals, government and third-party payors for product candidates that we develop; • addressing any competing therapies and technological and market developments; and • attracting, hiring and retaining qualified personnel, especially in the current labor market.
Our ability to generate product revenue and achieve profitability depends significantly on our ability, or any future collaborator’s ability, to achieve a number of objectives, including: • successful and timely completion of the clinical development of azenosertib as a monotherapy for the treatment of Cyclin E1-positive PROC, successful and timely completion of the development of a companion diagnostic with a diagnostic partner to identify patients with Cyclin E1-positive PROC, and meeting the associated costs thereof, including any unforeseen costs we have incurred and may continue to incur as a result of delays including due to public health emergencies, U.S. and global economic issues, such as rising inflation, or ongoing military conflicts, among other causes; • successful and timely completion of the clinical development of azenosertib for additional oncology indications and of any future product candidates, resources allowing; • if applicable, the availability or successful development of diagnostic tools for biomarkers for any future product candidates or for additional biomarkers for azenosertib; • establishing and maintaining relationships with CROs and clinical sites for the clinical development, both in the United States and internationally, of azenosertib and any future product candidates, resources allowing; • timely receipt of marketing approvals from applicable regulatory authorities for azenosertib for the treatment of Cyclin E1-positive PROC and, resources allowing, additional oncology indications for azenosertib and any future product candidates, in each case for which we successfully complete clinical development; • timely receipt by our diagnostic partner of a marketing approval for a companion diagnostic to identify patients with Cyclin E1-positive PROC and, if applicable, marketing approval of diagnostic tools for biomarkers for any future product candidates and any additional biomarkers for azenosertib; • maintaining marketing approvals, including our diagnostic partner's maintaining its marketing approval of a companion diagnostic to identify patients with Cyclin E1-positive PROC, and making any required post-marketing approval commitments to applicable regulatory authorities; • developing an efficient and scalable manufacturing process for our product candidates, including obtaining finished products that are appropriately packaged for sale; • establishing and maintaining commercially viable supply and manufacturing relationships with third parties that can provide adequate, in both amount and quality, products and services to support clinical development and meet the market demand for product candidates that we develop, if approved; • successful commercial launch following any marketing approval, including the development of a commercial infrastructure, whether in-house or with one or more collaborators; • a continued acceptable safety profile following any marketing approval of our product candidates; • commercial acceptance of our product candidates by patients, the medical community and third-party payors; • identifying, assessing and developing new product candidates; • obtaining, maintaining and expanding our intellectual property rights, including patents, trade secrets and know how, and regulatory exclusivity, both in the United States and internationally; • protecting our rights in our intellectual property portfolio; • defending against third-party interference or infringement claims, if any; • negotiating favorable terms in any collaboration, licensing or other arrangements that may be necessary or desirable to develop, manufacture or commercialize our product candidates; • obtaining adequate pricing, coverage and reimbursement by hospitals, government and third-party payors for product candidates that we develop; • addressing any competing therapies and technological and market developments; and • attracting, hiring and retaining qualified personnel, especially in the current labor market.
We or our collaborators may also experience delays in developing a sustainable, reproducible and scalable manufacturing process for a companion diagnostic, such as the one our diagnostic partner is developing for identifying patients with Cyclin E1+ PROC, or in transferring that process to commercial partners, if applicable, or negotiating insurance reimbursement plans, all of which may prevent us from completing our clinical trials or commercializing azenosertib and any future product candidates, if approved, on a timely or profitable basis, if at all.
We or our collaborators may also experience delays in developing a sustainable, reproducible and scalable manufacturing process for a companion diagnostic, such as the one our diagnostic partner is developing for identifying patients with Cyclin E1-positive PROC, or in transferring that process to commercial partners, if applicable, or negotiating insurance reimbursement plans, all of which may prevent us from completing our clinical trials or commercializing azenosertib and any future product candidates, if approved, on a timely or profitable basis, if at all.
In cases where data from ex-U.S. clinical trials are intended to serve as the sole basis for marketing approval in the United States, the FDA will generally not approve the application on the basis of ex-U.S. data alone unless i) the data are applicable to the U.S. population and U.S. medical practice; ii) the trials were performed by clinical investigators of recognized competence and pursuant to current GCP requirements; and iii) the FDA is able to validate the data through an on-site inspection or other appropriate means.
In cases where data from ex-U.S. clinical trials are intended to serve as the sole basis for marketing approval in the United States, the FDA will generally not approve the application on the basis of ex-U.S. data alone unless (i) the data are applicable to the U.S. population and U.S. medical practice; (ii) the trials were performed by clinical investigators of recognized competence and pursuant to GCP requirements; and (iii) the FDA is able to validate the data through an on-site inspection or other appropriate means.
If independent investigators or CROs fail to devote sufficient resources to the development of our product candidates, or if CROs do not successfully carry out their contractual duties or obligations or meet expected deadlines, if they need to be replaced or if the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical protocols, regulatory requirements or for other reasons, our clinical trials may be extended, delayed or terminated and we may not be able to obtain regulatory approval for or successfully commercialize our product candidates.
If independent investigators or CROs fail to devote sufficient resources to the development of our product candidates, or if CROs do not successfully carry out their contractual duties or obligations or meet expected deadlines, if they need to be replaced or if 60 the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical protocols, regulatory requirements or for other reasons, our clinical trials may be extended, delayed or terminated and we may not be able to obtain regulatory approval for or successfully commercialize our product candidates.
Such a suspension or termination may be due to a number of factors, including failure to conduct the clinical trial in 27 accordance with regulatory requirements or our clinical protocols, inspection of the clinical trial operations or trial site by the FDA or ex-U.S. regulatory authorities resulting in the imposition of a clinical hold, unforeseen safety issues or adverse side effects resulting in the imposition of a clinical hold, failure to demonstrate a benefit from using a drug, changes in governmental regulations or administrative actions or lack of adequate funding to continue the clinical trial.
Such a suspension or termination may be due to a number of factors, including failure to conduct the clinical trial in accordance with regulatory requirements or our clinical protocols, inspection of the clinical trial operations or trial site by the FDA or ex-U.S. regulatory authorities resulting in the imposition of a clinical hold, unforeseen safety issues or adverse side effects resulting in the imposition of a clinical hold, failure to demonstrate a benefit from using a drug, changes in governmental regulations or administrative actions or lack of adequate funding to continue the clinical trial.
Although we have taken steps to protect our trade secrets and unpatented know-how, including entering into confidentiality agreements with third parties, and confidential information and inventions agreements with employees, consultants, licensors and advisors, we cannot provide any assurances that all such agreements have been duly executed, and any of these parties may breach the agreements and disclose our proprietary information, including our trade secrets, and we may not be able to obtain adequate remedies for such breaches.
Although we have taken steps to protect our trade secrets and unpatented know-how, including entering into confidentiality agreements with third parties, and confidential information 59 and inventions agreements with employees, consultants, licensors and advisors, we cannot provide any assurances that all such agreements have been duly executed, and any of these parties may breach the agreements and disclose our proprietary information, including our trade secrets, and we may not be able to obtain adequate remedies for such breaches.
If we have not identified the optimal immunohistochemistry cutoff, or if our Cyclin E1 biomarker assay does not function as it functioned previously, or if the historical correlation between retrospective tissue analysis and response rates is not replicated with prospective tissue analysis, then the clinical data we announced in January 2025 may be materially different in future studies, such as DENALI Part 2.
If we have not identified the optimal immunohistochemistry cutoff, or if our Cyclin E1 biomarker assay does not function as it functioned previously, or if the historical correlation between retrospective tissue analysis and response rates is not replicated with prospective tissue analysis, then the clinical data we announced in January 2025 may be materially different in DENALI Part 2 and in future studies.
These requirements or restrictions might include limiting prescribing to certain physicians or medical centers that have undergone specialized training, limiting treatment to 35 patients who meet certain safe-use criteria and requiring treated patients to enroll in a registry. These limitations and restrictions may significantly limit the size of the market for the drug and affect reimbursement by third-party payors.
These requirements or restrictions might include limiting prescribing to certain physicians or medical centers that have undergone specialized training, limiting treatment to patients who meet certain safe-use criteria and requiring treated patients to enroll in a registry. These limitations and restrictions may significantly limit the size of the market for the drug and affect reimbursement by third-party payors.
Consequently, even if we attain profitability in the future, we may not be able to utilize a material portion of our NOLs and certain other tax attributes, which could have a material adverse effect on our cash flows and results of operations. A variety of risks associated with marketing our product candidates internationally could materially adversely affect our business.
Consequently, even if we attain profitability in the future, we may not be able 48 to utilize a material portion of our NOLs and certain other tax attributes, which could have a material adverse effect on our cash flows and results of operations. A variety of risks associated with marketing our product candidates internationally could materially adversely affect our business.
We cannot predict whether our product candidates will cause toxicities in humans that would preclude or lead to the revocation of regulatory approval based on preclinical studies or early-stage clinical trials. 36 The FDA and ex-U.S. regulatory authorities may not accept data from trials conducted in locations outside of their jurisdiction.
We cannot predict whether our product candidates will cause toxicities in humans that would preclude or lead to the revocation of regulatory approval based on preclinical studies or early-stage clinical trials. The FDA and ex-U.S. regulatory authorities may not accept data from trials conducted in locations outside of their jurisdiction.
Our relationships with healthcare professionals, clinical investigators, CROs and third party payors in connection with our current and future business activities may be subject to fraud and abuse laws and other healthcare laws and regulations. 40 Healthcare providers and third-party payors will play a primary role in the recommendation and prescription of any product candidates for which we obtain marketing approval.
Our relationships with healthcare professionals, clinical investigators, CROs and third party payors in connection with our current and future business activities may be subject to fraud and abuse laws and other healthcare laws and regulations. Healthcare providers and third-party payors will play a primary role in the recommendation and prescription of any product candidates for which we obtain marketing approval.
In order to commercialize any product candidates, if approved, for which we retain commercialization rights, we must build marketing, sales, distribution, market access, managerial and other 44 non-technical capabilities or make arrangements with third parties to perform these services for each of the territories in which we may have approval to sell or market our product candidates.
In order to commercialize any product candidates, if approved, for which we retain commercialization rights, we must build marketing, sales, distribution, market access, managerial and other non-technical capabilities or make arrangements with third parties to perform these services for each of the territories in which we may have approval to sell or market our product candidates.
A worsening or prolonged economic downturn or recession could result in a variety of risks to our business, including our ability to raise additional capital when needed on acceptable terms, if at all. There can be no assurance that further deterioration in credit and financial markets and confidence in economic conditions will not occur.
A worsening or prolonged economic downturn or recession 47 could result in a variety of risks to our business, including our ability to raise additional capital when needed on acceptable terms, if at all. There can be no assurance that further deterioration in credit and financial markets and confidence in economic conditions will not occur.
Intellectual property generated under a government funded program is also subject to certain reporting requirements, compliance with which may require us to expend substantial resources. In addition, the U.S. government requires that any products embodying any of these inventions or produced through the use of any of these inventions be manufactured substantially in the United States.
Intellectual property generated under a government funded program is also subject to certain reporting requirements, compliance with which may require us to expend substantial resources. In addition, the U.S. government requires that any products embodying any of these inventions or produced through the use of any of these inventions be manufactured 54 substantially in the United States.
If we, in collaboration with our diagnostic partner, are unable to successfully develop a Cyclin E1+ PROC companion diagnostic for azenosertib, or experience delays in doing so, including delays in obtaining regulatory approvals, the development of monotherapy azenosertib for patients with Cyclin E1+ PROC will be adversely affected, which will have a material adverse effect on our business.
If we, in collaboration with our diagnostic partner, are unable to successfully develop a Cyclin E1-positive PROC companion diagnostic for azenosertib, or experience delays in doing so, including delays in obtaining regulatory approvals, the development of monotherapy azenosertib for patients with Cyclin E1-positive PROC will be adversely affected, which will have a material adverse effect on our business.
It is possible that defects as to form in the preparation or filing of our patents or patent applications or those of our licensors may exist, or may arise in the future, for example with respect to proper priority claims, inventorship, written descriptions, claim scope, or requests for patent term adjustments, patent term extensions or any foreign equivalents thereof.
It is possible that defects as to form in the preparation or filing of our patents or patent applications or those of our licensors may exist, or may arise in the future, for example with respect to proper priority claims, inventorship, written descriptions, claim scope, or requests for patent term adjustments, patent term extensions or any 53 foreign equivalents thereof.
Proceedings to enforce our or our licensors’ patent rights in ex-U.S. 58 jurisdictions could result in substantial costs and divert our efforts and attention from other aspects of our business, could put our or our licensors’ patents at risk of being invalidated or interpreted narrowly and our or our licensors’ patent applications at risk of not issuing and could provoke third parties to assert claims against us.
Proceedings to enforce our or our licensors’ patent rights in ex-U.S. jurisdictions could result in substantial costs and divert our efforts and attention from other aspects of our business, could put our or our licensors’ patents at risk of being invalidated or interpreted narrowly and our or our licensors’ patent applications at risk of not issuing and could provoke third parties to assert claims against us.
If the FDA or any ex-U.S. regulatory authority does not accept such data, it would result in the need for additional trials, which would be costly and time-consuming and delay aspects of our business plan, and which may result in our product candidates not receiving approval for commercialization in the applicable jurisdiction.
If the FDA or any ex-U.S. regulatory authority does not accept such data, it 36 would result in the need for additional trials, which would be costly and time-consuming and delay aspects of our business plan, and which may result in our product candidates not receiving approval for commercialization in the applicable jurisdiction.
The FCPA also requires public companies to make and keep 43 books and records that accurately and fairly reflect the transactions of the corporation and to devise and maintain an adequate system of internal accounting controls. Our business is heavily regulated and therefore involves significant interaction with public officials, including officials of non-U.S. governments.
The FCPA also requires public companies to make and keep books and records that accurately and fairly reflect the transactions of the corporation and to devise and maintain an adequate system of internal accounting controls. Our business is heavily regulated and therefore involves significant interaction with public officials, including officials of non-U.S. governments.
Many ex-U.S. regulatory authorities have similar requirements as the FDA for companion diagnostics. If there is not a satisfactory companion diagnostic commercially available for a particular biomarker, which is the case for Cyclin E1+ PROC, we would be required to develop or obtain such diagnostic, which would be subject to regulatory approval requirements.
Many ex-U.S. regulatory authorities have similar requirements as the FDA for companion diagnostics. If there is not a satisfactory companion diagnostic commercially available for a particular biomarker, which is the case for Cyclin E1-positive PROC, we would be required to develop or obtain such diagnostic, which would be subject to regulatory approval requirements.
In addition, there have been a significant number of recent business combinations among large pharmaceutical companies that have resulted in a reduced number of potential future collaborators. Even if we are successful in entering into a collaboration, the terms and conditions of that collaboration may restrict us from entering into future agreements on certain terms with potential collaborators.
In addition, there have been a significant number of recent business combinations among large pharmaceutical companies that have resulted in a reduced number of potential future collaborators. Even if we are successful in entering into a 62 collaboration, the terms and conditions of that collaboration may restrict us from entering into future agreements on certain terms with potential collaborators.
Any of these matters could materially and adversely affect our business and results of operations. In addition, manufacturing interruptions or failure to comply with regulatory requirements by any of these manufacturers could significantly delay clinical development of potential products and reduce third-party or clinical researcher interest and support of proposed trials.
Any of these matters could materially and adversely affect our business and 50 results of operations. In addition, manufacturing interruptions or failure to comply with regulatory requirements by any of these manufacturers could significantly delay clinical development of potential products and reduce third-party or clinical researcher interest and support of proposed trials.
If we decide to establish collaborations in the future, but are not able to establish those collaborations on commercially reasonable terms, we may have to alter our development and commercialization plans. Our drug development programs and the potential commercialization of azenosertib and any future product candidates will require substantial additional cash to fund expenses.
If we decide to establish collaborations in the future, but are not able to establish those collaborations on commercially reasonable terms, we may have to alter our development and commercialization plans. Our development programs and the potential commercialization of azenosertib and any future product candidates will require substantial additional cash to fund expenses.
We believe that quarterly comparisons of our financial results are not necessarily meaningful and should not be relied upon as an indication of our future performance. 63 Our principal stockholders and management own a significant percentage of our stock and are able to exert significant influence over matters subject to stockholder approval.
We believe that quarterly comparisons of our financial results are not necessarily meaningful and should not be relied upon as an indication of our future performance. Our principal stockholders and management own a significant percentage of our stock and are able to exert significant influence over matters subject to stockholder approval.
In many countries, particularly the member states of the EU, medical product prices are subject to varying price control mechanisms as part of national health systems. In these countries, pricing negotiations with 34 governmental authorities can take considerable time after a product receives marketing authorization.
In many countries, particularly the member states of the EU, medical product prices are subject to varying price control mechanisms as part of national health systems. In these countries, pricing negotiations with governmental authorities can take considerable time after a product receives marketing authorization.
If we or a regulatory agency discover previously unknown problems with a product, such as AEs of unanticipated severity or frequency, or problems with 37 the facilities where the product is manufactured, a regulatory agency may impose restrictions on that product, the manufacturing facility or us, including requiring recall or withdrawal of the product from the market or suspension of manufacturing.
If we or a regulatory agency discover previously unknown problems with a product, such as AEs of unanticipated severity or frequency, or problems with the facilities where the product is manufactured, a regulatory agency may impose restrictions on that product, the manufacturing facility or us, including requiring recall or withdrawal of the product from the market or suspension of manufacturing.
These current or future laws and regulations may impair our research, development or commercialization efforts. Failure to comply with these laws and regulations also may result in substantial fines, penalties or other sanctions. Our research and development activities could be affected or delayed as a result of possible restrictions on animal testing.
These current or future laws and regulations may impair our research, development or commercialization efforts. Failure to comply with these laws and regulations also may result in substantial fines, penalties or other sanctions. 43 Our research and development activities could be affected or delayed as a result of possible restrictions on animal testing.
We do not have complete control over all aspects of the manufacturing process of, and are dependent on, our third-party contract manufacturing partners for compliance with cGMP regulations or similar ex-U.S. requirements for manufacturing both active drug substances and finished drug products.
We do not have complete control over all aspects of the manufacturing process of, and are dependent on, our third-party contract manufacturing partners for compliance with cGMP regulations or similar ex-U.S. requirements for manufacturing both 61 active drug substances and finished drug products.
We are working with a diagnostic partner to develop a companion diagnostic to identify patients with Cyclin E1+ PROC in connection with our clinical development of monotherapy azenosertib for the treatment of patients with Cyclin E1+ PROC, and we expect the FDA and ex-U.S. regulatory authorities to require approval of this companion diagnostic in connection with approval of monotherapy azenosertib for this indication.
We are working with a diagnostic partner to develop a companion diagnostic to identify patients with Cyclin E1-positive PROC in connection with our clinical development of monotherapy azenosertib for the treatment of patients with Cyclin E1-positive PROC, and we expect the FDA and ex-U.S. regulatory authorities to require approval of this companion diagnostic in connection with approval of monotherapy azenosertib for this indication.
Further, others, including regulatory agencies, may not accept or agree with our assumptions, estimates, calculations, conclusions or analyses or may interpret or weigh the importance of data differently, which could impact the value of the particular program, the approvability or commercialization of the particular product candidate or product and our company in general.
Further, others, including regulatory agencies, may not accept or agree with our assumptions, estimates, calculations, conclusions or analyses or may interpret or weigh the importance of data differently, which could impact the value of the 29 particular program, the approvability or commercialization of the particular product candidate or product and our company in general.
If our efforts to comply with new laws, regulations and standards differ from the activities intended by regulatory or governing bodies 49 due to ambiguities related to their application and practice, regulatory authorities may initiate legal proceedings against us and our business may be adversely affected.
If our efforts to comply with new laws, regulations and standards differ from the activities intended by regulatory or governing bodies due to ambiguities related to their application and practice, regulatory authorities may initiate legal proceedings against us and our business may be adversely affected.
We also face competition in establishing clinical trial sites, enrolling subjects for clinical trials and in identifying and in-licensing new product candidates. 32 We have chosen to initially address well-validated biochemical targets, and therefore expect to face competition from existing products and products in development for each of our product candidates.
We also face competition in establishing clinical trial sites, enrolling subjects for clinical trials and in identifying and in-licensing new product candidates. We have chosen to initially address well-validated biochemical targets, and therefore expect to face competition from existing products and products in development for each of our product candidates.
Regardless of the 33 merits or eventual outcome, liability claims may also result in decreased demand for our products, injury to our reputation, costs to defend the related litigation, a diversion of management’s time and our resources and substantial monetary awards to trial participants or patients.
Regardless of the merits or eventual outcome, liability claims may also result in decreased demand for our products, injury to our reputation, costs to defend the related litigation, a diversion of management’s time and our resources and substantial monetary awards to trial participants or patients.
Similar challenges to obtaining coverage and reimbursement, applicable to pharmaceutical or biological products, may apply to diagnostic tools, such as companion diagnostics, that we or our collaborators develop. Any product candidates we develop may become subject to unfavorable third-party coverage and reimbursement practices, as well as pricing regulations.
Similar challenges to obtaining coverage and reimbursement, applicable to pharmaceutical or biological products, may apply to diagnostic tools, such as companion diagnostics, that we or our collaborators develop. 33 Any product candidates we develop may become subject to unfavorable third-party coverage and reimbursement practices, as well as pricing regulations.
Additionally, we or our collaborators may develop diagnostic tests, including companion diagnostic tests, for use with azenosertib or any of our future product candidates, such as the companion diagnostic test being developed by our diagnostic collaborator to identify patients with Cyclin E1+ PROC relating to our development of monotherapy azenosertib for patients with Cyclin E1+ PROC.
Additionally, we or our collaborators may develop diagnostic tests, including companion diagnostic tests, for use with azenosertib or any of our future product candidates, such as the companion diagnostic test being developed by our diagnostic collaborator to identify patients with Cyclin E1-positive PROC relating to our development of monotherapy azenosertib for patients with Cyclin E1-positive PROC.
Our competitors or other third parties may be able to circumvent our or our licensors' patents by developing similar or 52 alternative technologies or products in a non-infringing manner, which could materially adversely affect our business, financial condition, results of operations and prospects.
Our competitors or other third parties may be able to circumvent our or our licensors' patents by developing similar or alternative technologies or products in a non-infringing manner, which could materially adversely affect our business, financial condition, results of operations and prospects.
Collaborations involving our research programs, our product candidates and any future research programs or product candidates we may develop pose risks to us, including the following: • Collaborators have significant discretion in determining the efforts and resources that they will apply to these collaborations. 23 • Collaborators may not pursue development and commercialization of any product candidates we may develop or may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in the collaborator's strategic focus or market considerations, including as a result of a sale or disposition of a business unit or development function, or available funding or external factors such as an acquisition or business combination that diverts resources or creates competing priorities.
Collaborations involving azenosertib and any future research programs or product candidates we may develop pose risks to us, including the following: • Collaborators have significant discretion in determining the efforts and resources that they will apply to these collaborations. • Collaborators may not pursue development and commercialization of any product candidates we may develop or may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in 23 the collaborator's strategic focus or market considerations, including as a result of a sale or disposition of a business unit or development function, or available funding or external factors such as an acquisition or business combination that diverts resources or creates competing priorities.
A failure of one or more clinical trials can occur at any stage of the process. The outcome of preclinical studies and early-stage clinical trials may not be predictive of the success of later clinical trials, including that potential biomarkers, even if validated preclinically or in early-stage clinical trials, may not be functionally validated in later 26 clinical trials.
A failure of one or more clinical trials can occur at any stage of the process. The outcome of preclinical studies and early-stage clinical trials may not be predictive of the success of later clinical trials, including that potential biomarkers, even if validated preclinically or in early-stage clinical trials, may not be functionally validated in later clinical trials.
If the therapies we use in combination with our product candidates are replaced as the standard of care for the indications we choose for any of our product candidates, the FDA or ex-U.S. regulatory authorities may require us to conduct additional clinical trials.
If the therapies we use in combination with our product candidates are replaced as the 31 standard of care for the indications we choose for any of our product candidates, the FDA or ex-U.S. regulatory authorities may require us to conduct additional clinical trials.
As a result of the continued hybrid working environment, we may also face increased cybersecurity risks due to our reliance on internet technology and the number of our employees who are working remotely, which may create additional opportunities for cybercriminals to exploit vulnerabilities.
As a result of the hybrid working environment, we may also face increased cybersecurity risks due to our reliance on internet technology and the number of our employees who are working remotely, which may create additional opportunities for cybercriminals to exploit vulnerabilities.
There can be no assurance that our or our licensors’ patent applications will 50 result in patents being issued or that issued patents will afford sufficient protection against competitors with similar technology, nor can there be any assurance that the patents, if issued, will be infringed or will not be designed around by third parties.
There can be no assurance that our or our licensors’ patent applications will result in patents being issued or that issued patents will afford sufficient protection against competitors with similar technology, nor can there be any assurance that the patents, if issued, will be infringed or will not be designed around by third parties.
Specifically, drugs and biologic are eligible for fast track designation if they are intended, alone or in combination with one or more drugs or biologics, to treat a serious or life-threatening disease or condition and demonstrate the potential to address unmet medical needs for the disease or condition.
Specifically, drugs and biologics are eligible for fast track designation if they are intended, alone or in combination with one or more drugs or biologics, to treat a serious or life-threatening disease or condition and demonstrate the potential to address unmet medical needs for the disease or condition.
Undesirable side effects caused by our product candidates could cause us or regulatory authorities to interrupt, delay or halt clinical trials and could result in a more restrictive label or the delay or denial of regulatory approval by the FDA or ex-U.S. regulatory authorities.
Undesirable side effects caused by our product candidates could cause us or regulatory authorities to interrupt, delay or halt clinical trials and could result in a more restrictive label or the delay or denial of regulatory 35 approval by the FDA or ex-U.S. regulatory authorities.
A failure to obtain accelerated approval or any other form of expedited development, review or approval for our product candidate would result in a longer time period to commercialization of such product candidate, could increase the cost of development of such product candidate and could harm our competitive position in the marketplace.
A failure to obtain accelerated approval or any other form of expedited development, review or approval for azenosertib would result in a longer time period to commercialization of such product candidate, could increase the cost of development of such product candidate and could harm our competitive position in the marketplace.
Our employees, independent contractors, consultants, commercial collaborators, principal investigators, CROs, CMOs, suppliers and vendors may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements. 42 We are exposed to the risk that our employees, independent contractors, consultants, commercial collaborators, principal investigators, CROs, CMOs, suppliers and vendors may engage in misconduct or other improper activities.
Our employees, independent contractors, consultants, commercial collaborators, principal investigators, CROs, CMOs, suppliers and vendors may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements. We are exposed to the risk that our employees, independent contractors, consultants, commercial collaborators, principal investigators, CROs, CMOs, suppliers and vendors may engage in misconduct or other improper activities.
To the extent that we raise additional capital through the sale of equity or convertible debt or equity securities, your ownership interest will be diluted, and the terms may include liquidation or other preferences that adversely affect your rights as a stockholder.
To the extent that we raise additional capital through the sale of equity or convertible debt or equity securities, your ownership interest will be diluted, and 64 the terms may include liquidation or other preferences that adversely affect your rights as a stockholder.
Most product candidates that begin clinical trials are never approved by regulatory authorities for commercialization. In addition, we may rely in part on preclinical, clinical and quality data generated by CROs, our collaborators and other third parties for regulatory submissions for our product candidates.
Most product candidates that begin clinical trials are never approved by regulatory authorities for commercialization. 26 In addition, we may rely in part on preclinical, clinical and quality data generated by CROs, our collaborators and other third parties for regulatory submissions for our product candidates.
Such litigation or proceedings could substantially increase our operating losses and reduce the resources available for development activities or any future sales, marketing or distribution activities. We may not have sufficient financial or other resources to conduct such litigation or proceedings adequately.
Such litigation or proceedings could substantially increase our operating losses and reduce the resources available for development activities or any future sales, marketing or distribution activities. We may not have sufficient financial or other 56 resources to conduct such litigation or proceedings adequately.
An unfavorable outcome could require us to cease using the related 56 technology or to attempt to license rights to it from the prevailing party. Our business could be harmed if the prevailing party does not offer us a license on commercially reasonable terms.
An unfavorable outcome could require us to cease using the related technology or to attempt to license rights to it from the prevailing party. Our business could be harmed if the prevailing party does not offer us a license on commercially reasonable terms.
We face similar risks with our relationships with diagnostic partners as we face with other collaborations - see "We have and in the future may enter into collaborations with third parties for the research, development and commercialization of certain of the product candidates we may develop.
We face similar risks 28 with our relationships with diagnostic partners as we face with other collaborations - see "We have and in the future may enter into collaborations with third parties for the research, development and commercialization of certain of the product candidates we may develop.
For example, in January 2025, we announced monotherapy azenosertib clinical data in patients with Cyclin E1+ PROC, who were identified using a proprietary immunohistochemistry cutoff defined by retrospective tissue analysis utilizing a Cyclin E1 biomarker assay.
For example, in January 2025, we announced monotherapy azenosertib clinical data in patients with Cyclin E1-positive PROC, who were identified using a proprietary immunohistochemistry cutoff defined by retrospective tissue analysis utilizing a Cyclin E1 biomarker assay.
If we are unable to protect our trade secrets, our business and competitive position would be harmed. In addition, we rely on the protection of our trade secrets, including unpatented know-how, technology and other proprietary information to maintain our competitive position.
If we are unable to protect our trade secrets, our business and competitive position would be harmed. In addition to patents, we rely on the protection of our trade secrets, including unpatented know-how, technology and other proprietary information to maintain our competitive position.
In addition, increased scrutiny by Congress of the FDA’s approval process may significantly delay or prevent marketing approval, as well as subject us to more stringent product labeling and post-marketing testing and other requirements.
In addition, increased scrutiny by Congress of the FDA’s 40 approval process may significantly delay or prevent marketing approval, as well as subject us to more stringent product labeling and post-marketing testing and other requirements.
Accordingly, a third party may attempt to use the USPTO procedures to invalidate our patent claims that would not have been invalidated if first challenged by the third party as a defendant in a district court action.
Accordingly, a third party may attempt to use the USPTO procedures to invalidate our 57 patent claims that would not have been invalidated if first challenged by the third party as a defendant in a district court action.
We are developing azenosertib in combination with other therapies, which exposes us to additional risks. 31 We are developing azenosertib in combination with one or more other approved therapies to treat cancer and may in the future develop azenosertib or additional product candidates in combination with other approved or unapproved therapies.
We are developing azenosertib in combination with other therapies, which exposes us to additional risks. We are developing azenosertib in combination with one or more other approved therapies to treat cancer and may in the future develop azenosertib or additional product candidates in combination with other approved or unapproved therapies.
Established pharmaceutical and biotechnology companies may also invest heavily to accelerate discovery and development of novel compounds or to in-license novel compounds that could make the product candidates that we develop obsolete.
Established pharmaceutical and biotechnology companies may 32 also invest heavily to accelerate discovery and development of novel compounds or to in-license novel compounds that could make the product candidates that we develop obsolete.
The competition for qualified personnel in the biotechnology field is intense and as a result, we may be unable to continue to attract and retain qualified personnel necessary for the future success of our business.
The competition for qualified personnel in the biotechnology field is intense and as a result, we may be unable to continue to attract and retain qualified personnel necessary for the future 44 success of our business.
Any claims of patent infringement asserted by third parties would be time consuming and could: • result in costly litigation that may cause negative publicity; • divert the time and attention of our technical personnel and management; • cause development delays; • prevent us from commercializing any of our product candidates until the asserted patent expires or is held finally invalid or unenforceable or not infringed in a court of law; • require us to develop non-infringing technology, which may not be possible on a cost-effective basis; • subject us to significant liability to third parties; or • require us to enter into royalty or licensing agreements, which may not be available on commercially reasonable terms, or at all, or which might be non-exclusive, which could result in our competitors gaining access to the same technology.
Any claims of patent infringement asserted by third parties would be time consuming and could: 55 • result in costly litigation that may cause negative publicity; • divert the time and attention of our technical personnel and management; • cause development delays; • prevent us from commercializing azenosertib and any future product candidates until the asserted patent expires or is held finally invalid or unenforceable or not infringed in a court of law; • require us to develop non-infringing technology, which may not be possible on a cost-effective basis; • subject us to significant liability to third parties; or • require us to enter into royalty or licensing agreements, which may not be available on commercially reasonable terms, or at all, or which might be non-exclusive, which could result in our competitors gaining access to the same technology.
Adverse differences between interim data and final data could significantly harm our business 29 prospects. Further, disclosure of interim data by us or by our competitors could result in volatility in the price of our common stock.
Adverse differences between interim data and final data could significantly harm our business prospects. Further, disclosure of interim data by us or by our competitors could result in volatility in the price of our common stock.
Securities litigation against us could result in substantial costs and divert our management’s attention from other business concerns, which could seriously harm our business. Item 1B. Unresolved Staff Comments. None.
Securities litigation against us could result in substantial costs and divert our management’s attention from other business concerns, which could seriously harm our business. Item 1B. Unresolved Staff Comments. None. 66
The ability of the FDA and other regulatory authorities to review and approve new products can be affected by a variety of factors, including government budget and funding levels, ability to hire and retain key personnel and accept the payment of user fees, and statutory, regulatory, and policy changes, changes in presidential administrations, and other events that may otherwise affect the FDA’s and ex-U.S. regulatory authorities’ ability to perform routine functions.
The ability of the FDA and other regulatory authorities to review and approve new products can be affected by a variety of factors, including government budget and funding levels, ability to hire and retain key personnel and accept the payment of user fees, and statutory, regulatory, and policy changes, changes in presidential administrations, political fluctuations, and other events that may otherwise affect the FDA’s and ex-U.S. regulatory authorities’ ability to perform routine functions.
Companion diagnostic tests require coverage and reimbursement separate and apart from the coverage and reimbursement for their companion pharmaceutical or biological products. Similar challenges to obtaining coverage and reimbursement, applicable to pharmaceutical products, will apply to companion diagnostics.
Companion diagnostic tests require coverage and reimbursement separate and apart from the coverage and reimbursement for their companion pharmaceutical or biological products. Similar challenges to 34 obtaining coverage and reimbursement, applicable to pharmaceutical products, will apply to companion diagnostics.
Slight deviations anywhere in the manufacturing process, including filling, labeling, packaging, storage and shipping and quality control and testing, may result in lot failures, stock recovery or 61 spoilage.
Slight deviations anywhere in the manufacturing process, including filling, labeling, packaging, storage and shipping and quality control and testing, may result in lot failures, stock recovery or spoilage.
We contract with third parties for the manufacture of azenosertib for preclinical studies and our ongoing clinical trials, and expect to continue to do so for additional clinical trials and ultimately for commercialization.
We contract with third parties for the manufacture of azenosertib for preclinical studies and ongoing clinical trials, and expect to continue to do so for additional clinical trials and ultimately for commercialization.
Based on current business plans, we believe that our existing cash, cash equivalents and marketable securities as of December 31, 2024 will be sufficient to fund our operating expenses and capital expenditure requirements into late 2027, but will not be sufficient to fund all of the activities that are necessary to complete the development of azenosertib and any future product candidates.
Based on current business plans, we believe that our existing cash, cash equivalents and marketable securities as of December 31, 2025 will be sufficient to fund our operating expenses and capital expenditure requirements into late 2027, but will not be sufficient to fund all of the activities that are necessary to complete the development of azenosertib and any future product candidates.
Depending on the data from our clinical trials, we may decide to collaborate with diagnostic companies during our clinical trial enrollment process to help identify patients with characteristics that we believe will be most likely to respond to our product candidates, which we 28 have done for our development of monotherapy azenosertib for the treatment of Cyclin E1+ PROC.
Depending on the data from our clinical trials, we may decide to collaborate with diagnostic companies during our clinical trial enrollment process to help identify patients with characteristics that we believe will be most likely to respond to our product candidates, which we have done for our development of monotherapy azenosertib for the treatment of Cyclin E1-positive PROC.
We are conducting international clinical trials for azenosertib and may in the future conduct international clinical trials for other product candidates. The acceptance of study data from clinical trials conducted outside the U.S. or another jurisdiction by the FDA or ex-U.S. regulatory authority may be subject to certain conditions or may not be accepted at all.
We are conducting international clinical trials for azenosertib and may in the future conduct international clinical trials for other product candidates. The acceptance of study data from clinical trials conducted outside the United States or another jurisdiction by the FDA or ex-U.S. regulatory authority may be subject to certain conditions or may not be accepted at all.
We do not believe that we are currently acting as a covered 41 entity or business associate under HIPAA and thus are not directly subject to its requirements or penalties, but we may obtain health information from third parties (including research institutions from which we obtain clinical trial data) that are subject to privacy and security requirements under HIPAA.
We do not believe that we are currently acting as a covered entity or business associate under HIPAA and thus are not directly subject to its requirements or penalties, but we may, however, obtain health information from third parties (including research institutions from which we obtain clinical trial data) that are subject to privacy and security requirements under HIPAA.
Companies that must comply with the GDPR face increased compliance obligations and risk, including more robust regulatory enforcement of data protection requirements, administrative penalties and potential fines for noncompliance of up to €20 million or 4% of the annual global revenues of the noncompliant company, whichever is greater.
Companies that must comply with the GDPR face increased compliance obligations and risk, including more robust regulatory enforcement of data protection requirements, administrative penalties and potential fines for noncompliance of up to €20 million / £17.5 million or 4% of the annual global revenues of the noncompliant company, whichever is greater.
Although we in-license issued patents in the United States and ex-U.S. countries, we cannot be certain that the claims in our other U.S. pending patent applications, corresponding international patent applications and patent applications in certain ex-U.S. countries will be considered patentable by the USPTO, courts in the United States or by the patent offices and courts in ex-U.S. countries, nor can we be certain that the claims in our issued patents will not be found invalid or unenforceable if challenged.
Although we in-license issued patents in the United States and ex-U.S. countries, we cannot be certain that the claims in our other U.S. pending patent applications, corresponding international patent applications and patent applications in certain ex-U.S. countries will be considered patentable by the United States Patent and Trademark Office, or USPTO, courts in the United States or by the patent offices and courts in ex-U.S. countries, nor can we be certain that the claims in our issued patents will not be found invalid or unenforceable if challenged.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Biggest changeWe reference various security industry frameworks and other guidance to help us assess, identify and manage cybersecurity risks. We also actively engage with industry participants as part of our continuing efforts to evaluate and enhance the effectiveness of our information security policies and procedures.
Biggest changeWe also actively engage with industry participants as part of our continuing efforts to evaluate and enhance the effectiveness of our information security policies and procedures. From time to time, we engage consultants and other third parties to assist us with assessing and improving our cybersecurity program.
Our management team takes steps to stay informed about and monitor efforts to prevent, detect, mitigate and remediate cybersecurity risks and incidents through various means, which may include briefings from internal security personnel; threat intelligence and other information obtained from governmental, public or private sources, including external consultants engaged by us; and alerts and reports produced by security tools deployed in our IT environment.
Our management team takes steps to stay informed about and monitor efforts to prevent, detect, mitigate and remediate cybersecurity risks and incidents through various means, which may include briefings from internal security personnel; threat intelligence and other information obtained from governmental, public or private sources, including external consultants engaged by us; and alerts and reports produced by security tools deployed in our IT environment. 67
See “Risk Factors—Risks Related to Employee Matters, Managing Our Growth and Other Risks Related to Our Business—Our business and operations may suffer in the event of information technology system failures, cyberattacks or deficiencies in our cybersecurity.” The Board considers cybersecurity risk as part of its overall risk oversight function and has delegated to the Audit Committee oversight of cybersecurity and information security risks, including oversight of management’s implementation of our cybersecurity risk management program.
For more information, see “Risk Factors—Risks Related to Employee Matters, Managing Our Growth and Other Risks Related to Our Business—Our business and operations may suffer in the event of information technology system failures, cyberattacks or deficiencies in our cybersecurity.” Cybersecurity Governance The Board considers cybersecurity risk as part of its overall risk oversight function and has delegated to the Audit Committee oversight of cybersecurity and information security risks, including oversight of management’s implementation of our cybersecurity risk management program.
Our Chief Executive Officer has thirty years of experience overseeing information technology, or IT, functions and has eight years of experience serving on the audit committees of companies that had oversight responsibility of the company’s cybersecurity risk management program. Our Chief Legal Officer has overseen our IT team since 2023.
Our Chief Executive Officer has thirty years of experience overseeing information technology, or IT, functions and has eight years of experience serving on the audit committees of companies that had oversight responsibility of the company’s cybersecurity risk management program.
Certain members of our management team are part of our Cyber Incident Response Team and are responsible for executing the processes set forth therein, including with respect to our key third party service providers. Cybersecurity events are escalated to the Audit Committee or to our Board as appropriate.
Certain members of our management team are part of our Cyber Incident Response Team and are responsible for executing the processes set forth therein, including with respect to our key third party service providers.
We may engage consultants or other third parties from time to time to assist us with assessing and improving our cybersecurity program. We have not identified risks from known cybersecurity threats, including as a result of any prior cybersecurity incidents, that have materially affected us, including our operations, business strategy, results of operations or financial condition.
We have not identified risks from known cybersecurity threats, including as a result of any prior cybersecurity incidents, that have materially affected us, including our operations, business strategy, results of operations or financial condition.
The Audit Committee receives periodic reports from management regarding our cybersecurity program. These reports include updates on our cybersecurity program and the status of projects to strengthen our information security systems. The Audit Committee reports to the full Board regarding its activities, including those related to cybersecurity.
The Audit Committee receives periodic reports from management regarding our cybersecurity program. These reports include updates on our cybersecurity program and the status of projects to strengthen our information security systems. In addition, management updates the Audit Committee, where it deems appropriate, regarding cybersecurity incidents it considers to be significant.
We face risks from cybersecurity threats that, if realized, are reasonably likely to materially affect us, including our operations, business strategy, results of operations, or financial condition. There can be no assurance that our cybersecurity risk management program and processes, including our policies, controls or procedures, will be fully implemented, complied with or effective in protecting our systems and information.
We face risks from cybersecurity threats that, if realized, are reasonably likely to materially affect us, including our operations, business strategy, results of operations, or financial condition.
Our management team, including our Chief Executive Officer, our Chief Legal Officer and our Executive Director, IT Infrastructure & Information Security, is responsible for assessing and managing our risks from cybersecurity threats.
The Audit Committee periodically reports to the full Board regarding its activities, including those related to cybersecurity. Our management team, including our Chief Executive Officer, our Chief Legal Officer and our Vice President, Information Technology, is responsible for assessing and managing our risks from cybersecurity threats.
Removed
Our Executive Director, IT Infrastructure & Information Security, has close to thirty years of experience in information security, including twenty years of experience building and leading information security teams, and has held Certified Information Systems Security Professional certification from the 66 International Information System Security Certification Consortium since 2002, as well as Qualified Technical Expert certification from the Digital Directors Network.
Added
We reference various security industry frameworks and controls, such as National Institute of Standards and Technology, or NIST, Cybersecurity Framework 2.0, ISO/IEC 27001:2022, the Sarbanes-Oxley Act, Title 21 Code of Federal Regulations Part 11, Network and Information Security Directive 2, and other guidance to help us assess, identify and manage cybersecurity risks.
Added
This does not imply that we meet any particular technical standards, specifications, or requirements, only that we use the frameworks and controls as a guide to help us identify, assess, and manage cybersecurity risks relevant to our business.
Added
Key elements of our cybersecurity risk management program include but are not limited to the following: • risk assessments designed to help identify material risks from cybersecurity threats to our critical systems and information; • the use of external service providers, where appropriate, to assess, test or otherwise assist with aspects of our security processes; • cybersecurity awareness training of our employees, including incident response personnel and senior management; • a cyber incident response team and cyber incident response plan that includes procedures for responding to cybersecurity incidents; and • a third-party risk management process for key service providers based on our assessment of their criticality to our operations and respective risk profile.
Added
Our Vice President, Information Technology has over thirty years of experience in information security, and previously held a Certified Information Systems Auditor certification from the Information Systems Audit and Control Association from 2006 to 2022.

Item 2. Properties

Properties — owned and leased real estate

1 edited+0 added−0 removed1 unchanged
Biggest changeLegal Proceedings. We are not subject to any material legal proceedings. Item 4. Mine Safety Disclosures. Not applicable. 67 PART II
Biggest changeLegal Proceedings. We are not subject to any material legal proceedings. Item 4. Mine Safety Disclosures. Not applicable. 68 PART II

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

8 edited+2 added−2 removed1 unchanged
Biggest changeThe actual number of holders of our common stock is greater than this number of record holders, and includes stockholders who are beneficial owners, but whose shares are held in street name by brokers or held by other nominees.
Biggest changeThe actual number of holders of our common stock is greater than this number of record holders, and includes stockholders who are beneficial owners, but whose shares are held in street name by brokers or held by other nominees. This number of holders of record also does not include stockholders whose shares may be held in trust by other entities.
Any future determination related to our dividend policy will be made at the discretion of our Board of Directors after considering our financial condition, results of operations, capital requirements, business prospects and other factors the Board of Directors deems relevant, and subject to the restrictions contained in any future financing instruments.
Any future determination related to our dividend policy will be made at the discretion of our Board of Directors after 69 considering our financial condition, results of operations, capital requirements, business prospects and other factors the Board of Directors deems relevant, and subject to the restrictions contained in any future financing instruments.
Recent Sales of Unregistered Securities The Company did not sell any equity securities during the year ended December 31, 2024 that were not registered under the Securities Act. Securities Authorized for Issuance Under Equity Compensation Plans Information about our equity compensation plans is incorporated herein by reference to Item 12.
Recent Sales of Unregistered Securities The Company did not sell any equity securities during the quarter ended December 31, 2025 that were not registered under the Securities Act. Securities Authorized for Issuance Under Equity Compensation Plans Information about our equity compensation plans is incorporated herein by reference to Item 12.
The comparisons reflected in the graph and table represent past performance and are not intended to forecast the future performance of our stock and may not be indicative of our future performance. Holders As of March 21, 2025, there were approximately 9 holders of record of our common stock.
The comparisons reflected in the graph and table represent past performance and are not intended to forecast the future performance of our stock and may not be indicative of our future performance. Holders As of March 21, 2026 , there were approximately 8 holders of record of our common stock.
"Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters—Securities Authorized for Issuance Under Equity Compensation Plans" of this Annual Report on Form 10-K. Item 6. [Reserved] 69
"Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters—Securities Authorized for Issuance Under Equity Compensation Plans" of this Annual Report on Form 10-K.
The graph and the table assume that $100 was invested on April 3, 2020 in each of our common stock, the Nasdaq Composite Index, and the Nasdaq Biotechnology Index, and that any dividends were reinvested.
The graph and the table assume that $100 was invested on December 31, 2020 in each of our common stock, the Nasdaq Composite Index, and the Nasdaq Biotechnology Index, and that any dividends were reinvested.
Stock Performance Graph The following graph and table illustrate the total return from April 3, 2020 (the date of our IPO) through December 31, 2024, for (i) our common stock, (ii) the Nasdaq Composite Index, and (iii) the Nasdaq Biotechnology Index.
Stock Performance Graph The following graph and table illustrate the total return from December 31, 2020 through December 31, 2025, for (i) our common stock, (ii) the Nasdaq Composite Index, and (iii) the Nasdaq Biotechnology Index.
We intend to retain future earnings, if any, to finance the operation and expansion of our business and do not anticipate paying any cash dividends in the foreseeable future.
Dividend Policy We have never declared or paid any cash dividends on our capital stock. We intend to retain future earnings, if any, to finance the operation and expansion of our business and do not anticipate paying any cash dividends in the foreseeable future.
Removed
The graph assumes our closing sales price on April 3, 2020 of $23.20 per share as the initial value of our common stock and not the initial offering price to the public of $18.00 per share.
Added
Issuer Repurchases of Equity Securities During the fiscal quarter ended December 31, 2025, the Company made the following repurchases of shares of our common stock: Total Number of Shares Purchased Average Price Paid Per Share Total Number of Shares Purchased as Part of Publicly Announced Plans or Programs Maximum Number (or Approximate Dollar Value) of Shares That May Yet Be Purchased Under The Plans or Programs October 1, 2025 - October 31, 2025 — — — — November 1, 2025 - November 30, 2025 — — — — December 1, 2025 - December 31, 2025 7,500,000 (1) $1.33 — — Total 7,500,000 $1.33 — — (1) On December 15, 2025, the Company repurchased 7,500,000 shares of common stock from Matrix Capital Master Fund, LP pursuant to a privately negotiated Stock Purchase Agreement at $1.33 per share.
Removed
This number of holders of record also does not include stockholders whose shares may be held in trust by other entities. 68 Dividend Policy We have never declared or paid any cash dividends on our capital stock.
Added
This repurchase was not made pursuant to a publicly announced repurchase plan or program. Item 6. [Reserved]. 70

Item 7. Management's Discussion & Analysis

Management's Discussion & Analysis (MD&A) — revenue / margin commentary

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Biggest changeResults of Operations Comparison of Years Ended December 31, 2024 and 2023 The following table summarizes our results of operations for the years ended December 31, 2024 and 2023, together with the changes in those items in dollars: Year Ended December 31, 2024 2023 Increase (Decrease) (in thousands) Revenues from Licensing and Sales of Intellectual Property $ 67,425 $ — $ 67,425 Operating Expenses Research and development 167,768 189,590 (21,822) Zentera in-process research and development — 45,568 (45,568) General and administrative 87,115 64,351 22,764 Goodwill impairment 3,736 — Total operating expenses 258,619 299,509 (40,890) Loss from operations (191,194) (299,509) 108,315 Investment and other income, net 25,504 22,617 2,887 Net loss before income taxes (165,690) (276,892) 111,202 Income tax expense (benefit) 177 (601) 778 Loss on equity method investment — 16,014 (16,014) Net loss (165,867) (292,305) 126,438 Net loss attributable to noncontrolling interests (28) (114) 86 Net loss attributable to Zentalis $ (165,839) $ (292,191) $ 126,352 Revenues from Licensing and Sales of Intellectual Property Revenues from licensing and sales of intellectual property for the year ended December 31, 2024 were $67.4 million compared to zero for the year ended December 31, 2023.
Biggest changeResults of Operations Comparison of Years Ended December 31, 2025 and 2024 The following table summarizes our results of operations for the years ended December 31, 2025 and 2024, together with the changes in those items in dollars: 76 Year Ended December 31, 2025 2024 Increase (Decrease) (in thousands) Revenues from Licensing and Sales of Intellectual Property $ — $ 67,425 $ (67,425) Operating Expenses Research and development 107,295 167,768 (60,473) General and administrative 37,717 87,115 (49,398) Restructuring 7,796 — 7,796 Goodwill impairment — 3,736 (3,736) Total operating expenses 152,808 258,619 (105,811) Loss from operations (152,808) (191,194) 38,386 Investment and other income, net 16,190 25,504 (9,314) Net loss before income taxes (136,618) (165,690) 29,072 Income tax expense (benefit) 442 177 265 Net loss (137,060) (165,867) 28,807 Net loss attributable to noncontrolling interests — (28) 28 Net loss attributable to Zentalis $ (137,060) $ (165,839) $ 28,779 Revenues from Licensing and Sales of Intellectual Property Revenues from licensing and sales of intellectual property for the year ended December 31, 2025 were zero compared to $67.4 million for the year ended December 31, 2024.
License Agreements and Strategic Collaborations Recurium IP Holdings, LLC License Agreement In December 2014, our wholly owned subsidiary, Zeno Pharmaceuticals, Inc., entered into the Recurium Agreement with Recurium IP, which was subsequently amended, under which Zeno Pharmaceuticals, Inc. was granted an exclusive worldwide license to certain intellectual property rights owned or controlled by Recurium IP to develop and commercialize pharmaceutical products for the treatment or prevention of disease, other than for providing pain relief.
License Agreements and Strategic Collaborations Recurium IP Holdings, LLC License Agreement In December 2014, our wholly owned subsidiary, Zeno Pharmaceuticals, Inc., entered into the Recurium Agreement with Recurium IP Holdings, LLC, or Recurium IP, which was subsequently amended, under which Zeno Pharmaceuticals, Inc. was granted an exclusive worldwide license to certain intellectual property rights owned or controlled by Recurium IP to develop and commercialize pharmaceutical products for the treatment or prevention of disease, other than for providing pain relief.
Investing Activities Net cash provided by investing activities for the year ended December 31, 2024 of $176.6 million was attributable to proceeds from maturities of $271.2 million of marketable debt securities, the sale of marketable equity securities of $33.5 million and proceeds from the sale of property and equipment of $65 thousand offset by net investment of excess cash of $128.0 million and the purchases of property and equipment of $221 thousand.
Net cash provided by investing activities for the year ended December 31, 2024 of $176.6 million was attributable to proceeds from maturities of $271.2 million of marketable debt securities, the sale of marketable equity securities of $33.5 million and proceeds from the sale of property and equipment of $65 thousand offset by net investment of excess cash of $128.0 million and the purchases of property and equipment of $221 thousand.
As a result of many important factors, including those set forth under “Risk Factors” and elsewhere in this Annual Report on 10-K, our actual results may differ materially from those anticipated in these forward-looking statem e nts. For convenience of presentation some of the numbers have been rounded in the text below.
As a result of many important factors, including those set forth under “Risk Factors” and elsewhere in this Annual Report on Form 10-K, our actual results may differ materially from those anticipated in these forward-looking statem e nts. For convenience of presentation some of the numbers have been rounded in the text below.
We believe that our DENALI (ZN-c3-005) Part 2 clinical trial of azenosertib in patients with Cyclin E1+ PROC, if successful, has the potential to support an accelerated approval, subject to U.S. Food and Drug Administration, or FDA, review. Azenosertib also has broad franchise potential beyond Cyclin E1+ PROC.
We believe that our DENALI (ZN-c3-005) Part 2 clinical trial of azenosertib in patients with Cyclin E1-positive PROC, if successful, has the potential to support an accelerated approval, subject to U.S. Food and Drug Administration, or FDA, review. Azenosertib also has broad franchise potential beyond Cyclin E1-positive PROC.
Under the terms of the deal, we received an up-front payment of $35 million in cash and Immunome common stock (with the stock valued at the trailing 30-day volume-weighted average price). In October 2024, we entered into an asset purchase agreement with Immunome, pursuant to which Immunome purchased the ADC Assets, or the Immunome Purchase Agreement.
Under the terms of the deal, we received an up-front payment of $35.0 million in cash and Immunome common stock (with the stock valued at the trailing 30-day volume-weighted average price). In October 2024, we entered into an asset purchase agreement with Immunome, pursuant to which Immunome purchased the ADC Assets, or the Immunome Purchase Agreement.
Immunome Agreements 74 In January 2024, we entered into an exclusive, worldwide license agreement with Immunome, or the Immunome License Agreement, under which Immunome licensed from us ZPC-21 (now known as IM-1021), a preclinical ROR1 ADC with best-in-class potential, and our proprietary ADC platform technology, or the ADC Assets.
Immunome Agreements In January 2024, we entered into an exclusive, worldwide license agreement with Immunome, or the Immunome License Agreement, under which Immunome licensed from us ZPC-21 (now known as IM-1021), a preclinical ROR1 ADC with best-in-class potential, and our proprietary ADC platform technology, or the ADC Assets.
If we fail to become profitable or are unable to sustain profitability on a continuing basis, then we may be unable to continue our operations at planned levels and be forced to reduce or terminate our operations. 78 We do not currently have any approved products and have never generated any revenue from product sales.
If we fail to become profitable or are unable to sustain profitability on a continuing basis, then we may be unable to continue our operations at planned levels and be forced to reduce or terminate our operations. We do not currently have any approved products and have never generated any revenue from product sales.
In clinical trials, azenosertib has been well tolerated and has demonstrated anti-tumor activity as a single agent across multiple tumor types. We are currently focused on advancing the clinical development of azenosertib in Cyclin E1+ platinum-resistant ovarian cancer, or PROC.
In clinical trials, azenosertib has been well tolerated and has demonstrated anti-tumor activity as a single agent across multiple tumor types. We are currently focused on advancing the clinical development of azenosertib in Cyclin E1-positive platinum-resistant ovarian cancer, or PROC.
Following certain corporate restructuring disclosed elsewhere in this Annual Report on Form 10-K, our wholly owned subsidiary, ZMI, became the Zentalis contracting party to the Recurium Agreement. The intellectual property rights exclusively licensed by ZMI under the Recurium Agreement include certain intellectual property covering azenosertib.
Following a corporate restructuring disclosed elsewhere in this Annual Report on Form 10-K, our wholly owned subsidiary, ZMI, became the Zentalis contracting party to the Recurium Agreement. The intellectual property rights exclusively licensed by ZMI under the Recurium Agreement include certain intellectual property covering azenosertib.
As a result, we believe there is a large market opportunity for azenosertib in Cyclin E1+ PROC patients. Moreover, the successful launch of mirvetuximab in PROC patients with high folate receptor alpha, or FRα-high, expression underscores the demand for biomarker-directed therapies for PROC patients.
As a result, we believe there is a large market opportunity for azenosertib in Cyclin E1-positive PROC patients. Moreover, the successful launch of mirvetuximab in PROC patients with high folate receptor alpha, or FRα-high, expression underscores the demand for biomarker-directed therapies for PROC patients.
GSK Clinical Trial Collaboration and Supply Agreement In April 2021, we entered into a clinical trial collaboration and supply agreement with GSK under which we have evaluated the combination of azenosertib and niraparib, GSK’s poly (ADP-ribose) polymerase (PARP) inhibitor, in patients with PROC.
GSK Clinical Trial Collaboration and Supply Agreement In April 2021, we entered into a clinical trial collaboration and supply agreement with GSK under which we have evaluated the combination of azenosertib and niraparib, GSK’s poly (ADP-ribose) polymerase (PARP) inhibitor, in patients 73 with PROC.
We received $25 million worth of Immunome common stock, with the shares valued at the trailing 30-day volume-weighted average price of Immunome's common stock. On the date of execution of the transaction, the Immunome stock was valued at $21.9 million based on the closing price of Immunome's common stock on that date.
We received $25.0 million worth of Immunome common stock, with the shares valued at the trailing 30-day volume-weighted average price of Immunome's common stock. On the date of execution of the transaction, the Immunome stock was valued at $21.9 million based on the closing price of Immunome's common stock on that date.
We have aligned with the FDA on the design of our DENALI Part 2 study in patients with Cyclin E1+ PROC, which allows for seamless enrollment across Parts 2a and 2b.
We have aligned with the FDA on the design of our DENALI Part 2 study in patients with Cyclin E1-positive PROC, which allows for seamless enrollment across Parts 2a and 2b.
Our future capital requirements will depend on many factors, including: • the clinical development of azenosertib for the treatment of oncology indications; • the preclinical and clinical development of other programs, resources allowing; • the development of a companion diagnostic with a partner in conjunction with our clinical development of azenosertib as a monotherapy for the treatment of Cyclin E1+ PROC, if applicable, diagnostics tools for additional biomarkers for azenosertib and any future product candidates; • the costs of in-licensing or acquiring the rights to other products, product candidates or technologies; • the legal costs related to maintaining, expanding and protecting our intellectual property portfolio; • hiring additional personnel, if needed; • to costs to seek regulatory approval for azenosertib for the treatment of Cyclin E1+ PROC and support our diagnostic partner's seeking regulatory approval of a companion diagnostic to identify patients with Cyclin E1+ PROC, and resources allowing, seek regulatory approval of azenosertib for additional oncology indications, assuming supportive clinical data; and • to costs to seek regulatory approval for any future product candidates and, if needed, diagnostics tools for biomarkers associated with such product candidates, that successfully complete clinical development, resources allowing.
Funding Requirements Our future capital requirements will depend on many factors, including: • the clinical development of azenosertib for the treatment of oncology indications; • the preclinical and clinical development of other programs, resources allowing; 79 • the development of a companion diagnostic with a partner in conjunction with our clinical development of azenosertib as a monotherapy for the treatment of Cyclin E1-positive PROC, if applicable, diagnostics tools for additional biomarkers for azenosertib and any future product candidates; • the costs of in-licensing or acquiring the rights to other products, product candidates or technologies; • the legal costs related to maintaining, expanding and protecting our intellectual property portfolio; • hiring additional personnel, if needed; • the costs to seek regulatory approval for azenosertib for the treatment of Cyclin E1-positive PROC and support our diagnostic partner's seeking regulatory approval of a companion diagnostic to identify patients with Cyclin E1-positive PROC, and resources allowing, seek regulatory approval of azenosertib for additional oncology indications, assuming supportive clinical data; and • the costs to seek regulatory approval for any future product candidates and, if needed, diagnostics tools for biomarkers associated with such product candidates, that successfully complete clinical development, resources allowing.
Tissue collection for biomarker assessment was mandated in the study and upon a retrospective analysis, approximately 50% of the patients were Cyclin E1+ per our IHC cutoff.
Tissue collection for biomarker assessment was mandated in the study and upon a retrospective analysis, approximately 50% of the patients were Cyclin E1-positive per our IHC cutoff.
At this time, we cannot determine with certainty the duration and costs of our existing and future clinical trials of our product candidates or any other product candidate we may develop or if, when, or to what extent we will generate revenue from the commercialization and sale of any product candidate for which we obtain marketing approval.
At this time, we cannot determine with certainty the duration and costs of our existing and future clinical trials of azenosertib or any other product candidate we may develop or if, when, or to what extent we will generate revenue from the commercialization and sale of any product candidate for which we obtain marketing approval.
Based on our analysis utilizing our IHC cutoff, we estimate that approximately 50% of PROC patients overexpress Cyclin E1 protein, which account for approximately 21,500 patients on an annual basis in the United States, EU4 (France, Germany, Italy, Spain) and the United Kingdom, based on 2024 estimates.
Based on our analysis utilizing our IHC cutoff, we estimate that approximately 50% of PROC patients overexpress Cyclin E1 protein, which accounts for approximately 21,500 patients on an annual basis in the United States, EU4 (France, Germany, Italy, Spain) and the United Kingdom, based on 2024 estimates.
To date, we have financed our operations primarily through the sale of equity securities. From inception through December 31, 2024, we raised a total of $1.2 billion in gross proceeds from the sale of shares of our common stock and convertible preferred units.
To date, we have financed our operations primarily through the sale of equity securities. From inception through December 31, 2025, we raised a total of $1.2 billion in gross proceeds from the sale of shares of our common stock and convertible preferred units.
We believe that our existing cash, cash equivalents and marketable securities as of December 31, 2024 will be sufficient to fund our operating expenses and capital expenditure requirements into late 2027. We 73 have based these estimates on assumptions that may prove to be imprecise, and we could utilize our available capital resources sooner than we expect.
We believe that our existing cash, cash equivalents and marketable securities as of December 31, 2025 will be sufficient to fund our operating expenses and capital expenditure requirements into late 2027. We have based these estimates on assumptions that may prove to be imprecise, and we could utilize our available capital resources sooner than we expect.
For a discussion regarding our financial condition and results of operations for the year ended December 31, 2022, including a year-to-year comparison between 2023 and 2022, refer to Part II, Item 7.
For a discussion regarding our financial condition and results of operations for the year ended December 31, 2023, including a year-to-year comparison between 2024 and 2023, refer to Part II, Item 7.
Any inability to access or delay in accessing these funds could adversely affect our business and financial position. We had no indebtedness as of December 31, 2024.
Any inability to access or delay in accessing these funds could adversely affect our business and financial position. We had no indebtedness as of December 31, 2025.
A discussion regarding our financial condition and results of operations for the years ended December 31, 2024 and 2023, including a year-to-year comparison between 2024 and 2023, is presented below.
A discussion regarding our financial condition and results of operations for the years ended December 31, 2025 and 2024, including a year-to-year comparison between 2025 and 2024, is presented below.
Sales of common stock, if any, pursuant to the Sales Agreement, may be made in sales deemed to be an “at the market offering” as defined in Rule 415(a) of the Securities Act, including sales made directly through The Nasdaq Global Market or any other existing trading market for our common stock.
Sales of common stock pursuant to the Sales Agreement, may be made in sales deemed to be an “at the market offering” as defined in Rule 415(a) of the Securities Act, including sales made directly through the Nasdaq Global Market or any other existing trading market for the Company's common stock.
Recent Accounting Pronouncements See Note 2 to our audited consolidated financial statements included elsewhere in this Annual Report on Form 10-K for further information on certain accounting standards that have been adopted during 2024 or that have not yet been required to be implemented and may be applicable to our future operations.
Recent Accounting Pronouncements See Note 2 to our audited consolidated financial statements included elsewhere in this Annual Report on Form 10-K for further information on certain accounting standards that have been adopted during 2025 or that have not yet been required to be implemented and may be applicable to our future operations. Item 7A.
DENALI Part 2, if successful, has the potential to support an accelerated approval, subject to FDA review. The FDA has granted Fast Track Designation to azenosertib for the treatment of patients with PROC who are positive via Cyclin E1 IHC for protein levels. • Monotherapy – Phase 3 Clinical Trial in Cyclin E1+ PROC.
We believe that DENALI Part 2, if successful, has the potential to support an accelerated approval, subject to FDA review. The FDA has granted Fast Track Designation to azenosertib for the treatment of patients with PROC who are positive via IHC for Cyclin E1 protein levels. • Monotherapy – Phase 3 Clinical Trial in Cyclin E1-positive PROC (ASPENOVA).
We exclusively in-license or solely own worldwide development and commercialization rights to azenosertib. Azenosertib (WEE1 Inhibitor) Mechanism of Action Azenosertib is a potentially best-in-class and first-in-class oral, small molecule WEE1 inhibitor.
We exclusively in-license or solely own worldwide development and commercialization rights to azenosertib. Azenosertib (WEE1 Inhibitor) Mechanism of Action Azenosertib is an investigational, potentially first-in-class and best-in-class oral, small molecule WEE1 inhibitor.
Our future funding requirements will depend on many factors, including: • the progress, costs and results of our clinical trials for azenosertib for patients with Cyclin E1+ PROC and, resources allowing, any additional indications, and any future product candidates; • the progress, costs and results to develop a companion diagnostic to identify patients with Cyclin E1+ PROC; • the progress, costs and results of additional research and preclinical studies in other research programs we initiate in the future and, if needed, of diagnostics tools for additional biomarkers for azenosertib and any future product candidates; • the costs and timing of process development and manufacturing scale-up activities associated with azenosertib and, resources allowing, our product candidates and other programs as we advance them through preclinical and clinical development; • our ability to establish and maintain strategic collaborations, licensing or other agreements and the financial terms of such agreements; • the extent to which we in-license or acquire rights to other products, product candidates or technologies; • the costs and timing of preparing, filing and prosecuting patent applications, maintaining and protecting our intellectual property rights and defending against any intellectual property-related claims; and • our ability to attract and retain skilled personnel. 80 Further, our operating results may change in the future, and we may need additional funds to meet operational needs and capital requirements associated with such operating plans.
Our future funding requirements will depend on many factors, including: • the progress, costs and results of our clinical trials for azenosertib for patients with Cyclin E1-positive PROC and, resources allowing, any additional indications, and any future product candidates; • the progress, costs and results to develop a companion diagnostic to identify patients with Cyclin E1-positive PROC; • the progress, costs and results of additional research and preclinical studies in other research programs we initiate in the future and, if needed, of diagnostics tools for additional biomarkers for azenosertib and any future product candidates; • the costs and timing of process development and manufacturing scale-up activities associated with azenosertib and, resources allowing, our product candidates and other programs as we advance them through preclinical and clinical development; • our ability to establish and maintain strategic collaborations, licensing or other agreements and the financial terms of such agreements; • the extent to which we in-license or acquire rights to other products, product candidates or technologies; • the costs and timing of preparing, filing and prosecuting patent applications, maintaining and protecting our intellectual property rights and defending against any intellectual property-related claims; and • our ability to attract and retain skilled personnel.
If actual results are not consistent with the assumptions used, the share-based compensation expense reported in our financial statements may not be representative of the actual economic cost of the share-based compensation. A 10% change in our share-based compensation expense for the year ended December 31, 2024, would have affected pre-tax earnings by approximately $6.7 million.
If actual results are not consistent with the assumptions used, the share-based compensation expense reported in our financial statements may not be representative of the actual economic cost of the share-based compensation. A 10% change in our share-based compensation expense for the year ended December 31, 2025, would have affected pre-tax earnings by approximately $2.1 million.
The limited overlap between FRα-high PROC patients and those that have 70 Cyclin E1 overexpression is estimated to be less than 20%, which highlights the significant unmet need in patients with Cyclin E1+ PROC. We believe there is additional market opportunity for azenosertib outside of ovarian cancer across other solid tumor types.
The limited overlap between FRα-high PROC patients and those 71 that have Cyclin E1 overexpression is estimated to be less than 20%, which highlights the significant unmet need in patients with Cyclin E1-positive PROC. We believe there is additional market opportunity for azenosertib in earlier lines of treatment for ovarian cancer, and across other solid tumor types.
If we are unable to secure adequate additional funding as and when needed, we may have to significantly delay, scale back or discontinue the development and commercialization of one or more product candidates or delay our pursuit of potential in-licenses or acquisitions.
If we are unable to secure adequate additional funding as and when needed, we may have to significantly delay, scale back or discontinue the development and commercialization of azenosertib or delay our pursuit of potential in-licenses or acquisitions.
“Management’s Discussion and Analysis of Financial Condition and Results of Operations” in our Annual Report on 10-K for the year ended December 31, 2023 filed on February 27, 2024. Overview We are a clinical-stage biopharmaceutical company developing azenosertib (ZN-c3), a potentially first-in-class and best-in-class WEE1 inhibitor, for patients with ovarian cancer and other tumor types.
“Management’s Discussion and Analysis of Financial Condition and Results of Operations” in our Annual Report on Form 10-K for the year ended December 31, 2024 filed on March 26, 2025. Overview We are a clinical-stage biopharmaceutical company developing azenosertib (ZN-c3), an investigational, potentially first-in-class and best-in-class WEE1 inhibitor, for patients with ovarian cancer and other tumor types.
DENALI Part 2a is designed to confirm 400 mg QD 5:2 as the primary dose-of-interest by enrolling approximately 30 patients at each of two dose levels, 400 mg QD 5:2 and 300 mg QD 5:2.
DENALI Part 2a is designed to confirm 400 mg QD 5:2 as the recommended pivotal study dose by enrolling approximately 30 patients at each of two dose levels, 400 mg QD 5:2 and 300 mg QD 5:2.
The increase relates to the Immunome License Agreement and related stock issue agreement with Immunome entered during the three months ended March 31, 2024 and the Asset Purchase Agreement and the related stock issuance agreement with Immunome entered during the three months ended December 31, 2024.
The decrease relates to the Immunome License Agreement and related stock issuance agreement with Immunome entered during the three months ended March 31, 2024 and the Immunome Purchase Agreement and the related stock issuance agreement with Immunome entered during the three months ended December 31, 2024.
As of December 31, 2024, we had $33.9 million in cash and cash equivalents, $318.0 million in marketable debt securities, $19.2 million in marketable equity securities, and an accumulated deficit of $1.1 billion. We maintain the majority of our cash and cash equivalents in accounts with major financial institutions, and our deposits at these institutions exceed insured limits.
As of December 31, 2025, we had $36.0 million in cash and cash equivalents, $209.9 million in marketable debt securities, and an accumulated deficit of $1.2 billion. We maintain the majority of our cash and cash equivalents in accounts with major financial institutions, and our deposits at these institutions exceed insured limits.
As of December 31, 2024, we have $3.1 million and $39.6 million in current and long-term lease liabilities, respectively. We believe that our existing cash, cash equivalents and marketable securities as of December 31, 2024 will be sufficient to fund our operating expenses and capital expenditure requirements into late 2027.
As of December 31, 2025, we have $3.9 million and $35.7 million in current and long-term lease liabilities, respectively. We believe that our existing cash, cash equivalents and marketable securities as of December 31, 2025 will be sufficient to fund our operating expenses and capital expenditure requirements into late 2027.
We are working with a diagnostic partner to develop a companion diagnostic test that will identify patients with PROC that overexpress the Cyclin E1 protein using our proprietary immunohistochemistry, or IHC, cutoff. A prototype of this test is ready for use in DENALI Part 2.
We are working with a diagnostic partner to validate a companion diagnostic test that will identify patients with PROC that overexpress the Cyclin E1 protein using our proprietary immunohistochemistry, or IHC, cutoff. A prototype of this test is being used in DENALI Part 2 and is ready for use in our Phase 3 trial, ASPENOVA.
We may never succeed in obtaining marketing approval for any product candidate.
We may never succeed in obtaining marketing approval for azenosertib, or any future product candidate.
Interest Income Interest income consists of interest earned on cash, cash equivalents and available-for-sale marketable securities. 76 Income Taxes Since our inception, we and our corporate subsidiaries have generated cumulative federal, state and foreign net operating loss in certain jurisdictions for which we have not recorded any net tax benefit due to uncertainty around utilizing these tax attributes within their respective carryforward periods.
Income Taxes Since our inception, we and our corporate subsidiaries have generated cumulative federal, state and foreign net operating loss in certain jurisdictions for which we have not recorded any net tax benefit due to uncertainty around utilizing these tax attributes within their respective carryforward periods.
In January and March of 2025, we announced clinical data from this study, which is described below. ◦ DENALI Part 2 is designed to enroll approximately 100 patients with Cyclin E1+ PROC at the selected dose who have received one to three prior lines of therapy, or mirvetuximab soravtansine in the case of patients whose tumors are also FRα-high.
In January and March of 2025, we announced clinical data from this study, which is described in Part I Item 1, “Business – Clinical Data – DENALI Part 1b” in this Annual Report on Form 10-K. ◦ DENALI Part 2 is designed to enroll approximately 100 patients with Cyclin E1-positive PROC at the selected dose who have received one to three prior lines of therapy, or for patients whose tumors are also FRα-high and who have received mirvetuximab soravtansine, one to four prior lines of therapy.
We also expect to continue to incur expenses associated with being a public company, including costs of accounting, audit, legal, regulatory and tax-related services associated with maintaining compliance with Nasdaq and SEC requirements; director and officer insurance costs; and investor and public relations costs.
We also expect to continue to incur expenses associated with being a public company, including costs of accounting, audit, legal, regulatory and tax-related services associated with maintaining compliance with Nasdaq and SEC requirements; director and officer insurance costs; and investor and public relations costs. Restructuring Expenses Restructuring expenses consist of involuntary employee termination benefits pursuant to a one-time benefit arrangement.
Following the strategic restructuring announced in January 2025 for which we expect to incur the associated non-recurring expenses in the first quarter of 2025, we expect an initial decrease in general and administrative expenses; however, if our azenosertib development program continues to advance successfully, we expect our general and administrative expenses to increase as we initiate and execute our Phase 3 confirmatory study and prepare for commercialization.
Following the strategic restructuring announced in January 2025 for which we incurred certain associated non-recurring expenses in the first quarter of 2025, we have realized a decrease in general and administrative expenses during the year ended December 31, 2025; however, if our azenosertib development program continues to advance successfully, we expect our general and administrative expenses to increase as we initiate and execute our planned Phase 3 ASPENOVA confirmatory study and prepare for potential commercialization.
The successful development of our product candidates is highly uncertain.
The successful development of azenosertib, and any of our future product candidates is highly uncertain.
We track external development costs by product candidate or development program, but we do not allocate personnel costs, general license payments made under our licensing arrangements or other internal costs to specific development programs or product candidates. These costs are included in unallocated research and development expenses and discontinued programs in the table below.
We track external development costs by product candidate or development program, but we do not allocate personnel costs, general license payments made under our licensing arrangements or other internal costs to specific development programs or product candidates.
For example, if the FDA or another regulatory authority were to require us to conduct clinical trials beyond those that we anticipate will be required for the completion of clinical development of a product candidate, or if we experience significant delays in our clinical trials due to patient enrollment or other reasons, we would be required to expend significant additional financial resources and time on the completion of clinical development.
For example, if the FDA or another regulatory authority were to require us to conduct clinical trials beyond those that we anticipate will be required for the completion of clinical development of a product candidate, or if we experience significant delays in our clinical trials due to patient enrollment or other reasons, we would be required to expend significant additional financial resources and time on the completion of clinical development. 75 General and Administrative Expenses General and administrative expenses consist primarily of salaries and other related costs, including non-cash stock-based compensation, for personnel in our executive, finance, business development and administrative functions.
Share-Based Payments Methodology Judgment and Uncertainties Effect if Actual Results Differ From Assumptions We maintain equity incentive plans, which provide for share-based awards, including stock options, restricted stock units, or RSUs, restricted stock and performance awards. We also maintain an employee stock purchase plan.
There were no such significant changes during the years ended December 31, 2025 or 2024. 81 Share-Based Payments Methodology Judgment and Uncertainties Effect if Actual Results Differ From Assumptions We maintain equity incentive plans, which provide for share-based awards, including stock options, restricted stock units, or RSUs, restricted stock and performance awards. We also maintain an employee stock purchase plan.
Cash Flows The following table summarizes our sources and uses of cash for the period presented: Year Ended December 31, 2024 2023 (in thousands) Net cash used in operating activities $ (170,860) $ (207,822) Net cash provided by (used in) investing activities 176,561 (44,458) Net cash provided by financing activities 108 237,303 Net increase (decrease) in cash, cash equivalents and restricted cash $ 5,809 $ (14,977) Operating Activities We have incurred losses since inception.
Cash Flows The following table summarizes our sources and uses of cash for the period presented: Year Ended December 31, 2025 2024 (in thousands) Net cash used in operating activities $ (125,247) $ (170,860) Net cash provided by investing activities 131,623 176,561 Net cash (used in) provided by financing activities (4,282) 108 Net increase in cash, cash equivalents and restricted cash $ 2,094 $ 5,809 Operating Activities We have incurred losses since inception.
Revenue is recognized when we determine it is probable a milestone will be achieved. This assessment is based on market insight and customer communications. An adjustment of our estimate of the overall transaction price and reversal of revenue will be required in the event it is determined that achievement of a milestone, previously deemed probable, will not occur.
An adjustment of our estimate of the overall transaction price and reversal of revenue will be required in the event it is determined that achievement of a milestone, previously deemed probable, will not occur. This adjustment and reversal may be material.
Net cash used in operating activities for the year ended December 31, 2023 was $207.8 million, consisting primarily of our net loss of $292.3 million as we incurred expenses associated with research activities for our lead product candidates and incurred general and administrative expenses, as well as changes in operating assets and liabilities of $5.9 million, partially offset by non-cash adjustments of $78.6 million.
Net cash used in operating activities for the year ended December 31, 2025 was $125.2 million, consisting primarily of our net loss of $137.1 million as we incurred expenses associated with the restructuring event, research activities for our product candidate and incurred general and administrative expenses, as well as changes in operating assets and liabilities of $9.1 million, partially offset by non-cash adjustments of $20.9 million.
If we do not identify costs that we have begun to incur or if we underestimate or overestimate the level of services performed or the costs of these services, our actual expenses could differ from our estimates. There were no such significant changes during the years ended December 31, 2024 or 2023.
If we do not identify costs that we have begun to incur or if we underestimate or overestimate the level of services performed or the costs of these services, our actual expenses could differ from our estimates.
The following table summarizes our research and development expenses by product candidate or development program: Year Ended December 31, 2024 2023 (in thousands) Azenosertib $ 75,837 $ 67,019 Unallocated research and development expenses and discontinued programs 91,931 122,571 Total research and development expenses $ 167,768 $ 189,590 Research and development activities are central to our business model.
These costs are included in unallocated research and development expenses and discontinued programs in the table below. 74 The following table summarizes our research and development expenses by product candidate or development program: Year Ended December 31, 2025 2024 (in thousands) Azenosertib $ 48,102 $ 75,837 Unallocated research and development expenses and discontinued programs 59,193 91,931 Total research and development expenses $ 107,295 $ 167,768 Research and development activities are central to our business model.
Liquidity Overview Since our inception, our operations have been limited to organizing and staffing our company, business planning, raising capital, establishing our intellectual property portfolio and performing research and development of our product pipeline. We do not have any products approved for commercial sale and have not generated any revenues from product sales.
We do not plan further development of azenosertib in USC. 72 Liquidity Overview Since our inception, our operations have been limited to organizing and staffing our company, business planning, raising capital, establishing our intellectual property portfolio and performing research and development of our product pipeline.
General and Administrative Expenses General and administrative expenses for the year ended December 31, 2024 were $87.1 million, compared to $64.4 million during the year ended December 31, 2023. The increase of $22.8 million was primarily attributable to a $27.1 million increase related to personnel expense, of which $22.2 million is related to non-cash stock-based compensation.
General and Administrative Expenses General and administrative expenses for the year ended December 31, 2025 were $37.7 million, compared to $87.1 million during the year ended December 31, 2024. The decrease of $49.4 million was primarily due to a decrease of $47.1 million of personnel expense, of which $40.8 million was non-cash stock-based compensation.
We plan to disclose data from this trial in the first half of 2026. • Combination – Phase 1b Clinical Trial of Azenosertib and Chemotherapy or Bevacizumab in Ovarian Cancer (ZN-c3-002).
We plan to initiate ASPENOVA in the first half of 2026 and enroll concurrently with DENALI Part 2b. • Combination – Phase 1b Clinical Trial of Azenosertib and Chemotherapy or Bevacizumab in Ovarian Cancer (MUIR - ZN-c3-002).
Our net losses were $165.9 million for the year ended December 31, 2024. We had an accumulated deficit of $1.1 million as of December 31, 2024. We expect to continue to incur significant expenses and operating losses for the foreseeable future. We had cash, cash equivalents and marketable securities of $371.1 million as of December 31, 2024.
We expect to continue to incur significant expenses and operating losses for the foreseeable future. We had cash, cash equivalents and marketable securities of $245.9 million as of December 31, 2025.
Product candidates in later stages of clinical development generally have higher development costs than those in earlier stages of clinical development, primarily due to the 75 increased size and duration of later-stage clinical trials.
Product candidates in later stages of clinical development generally have higher development costs than those in earlier stages of clinical development, primarily due to the increased size and duration of later-stage clinical trials. Following the strategic restructuring announced in January 2025, we incurred certain associated non-recurring expenses in the first quarter of 2025.
We recognize revenue when it is deemed probable that these milestones will be achieved, which could be in a period preceding its actual occurrence. At the end of each reporting period, we re-evaluate the probability of achievement of such milestones, and if necessary, adjust our estimate of the overall transaction price.
At the end of each reporting period, we re-evaluate the probability of achievement of such milestones, and if necessary, adjust our estimate of the overall transaction price. Revenue is recognized when we determine it is probable a milestone will be achieved. This assessment is based on market insight and customer communications.
While our significant accounting policies are described in more detail in the notes to our audited consolidated financial statements included elsewhere in this Annual Report on Form 10-K, we believe that the following accounting policies are those most critical to the judgments and estimates used in the preparation of our financial statements. 81 Revenue Recognition Methodology Judgment and Uncertainties Effect if Actual Results Differ From Assumptions For revenue with customers, we are entitled to receive event-based payment subject to the customer's achievement of specific regulatory milestones.
While our significant accounting policies are described in more detail in the notes to our audited consolidated financial statements included elsewhere in this Annual Report on Form 10-K, we believe that the following accounting policies are those most critical to the judgments and estimates used in the preparation of our financial statements.
DENALI Part 2b is designed to enroll approximately 70 patients at a single dose, the selection of which will be informed by the Part 2a results subject to FDA feedback. We plan to initiate enrollment of DENALI Part 2 in the first half of 2025 and to disclose topline data from DENALI Part 2 by year end 2026.
DENALI Part 2b is designed to enroll approximately 70 patients at a single dose, the selection of which will be informed by the Part 2a results and FDA interaction. In April 2025, we announced that the first patient was dosed in DENALI Part 2a.
If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market products or product candidates that we would otherwise prefer to develop and market ourselves.
If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market products or product candidates that we would otherwise prefer to develop and market ourselves. 80 Critical Accounting Estimates Our management’s discussion and analysis of financial condition and results of operations is based on our financial statements, which have been prepared in accordance with generally accepted accounting principles in the United States.
Following the strategic restructuring announced in January 2025 for which we expect to incur the associated non-recurring expenses in the first quarter of 2025, we expect an initial decrease in research and development expenses; however, if our azenosertib development program continues to advance successfully, we expect our research and development expenses to increase as we initiate and execute our Phase 3 confirmatory study and prepare for commercialization.
As a result of the strategic restructuring, we realized a decrease in research and development expenses during the year ended December 31, 2025. If our azenosertib development program continues to advance successfully, we expect our research and development expenses to increase as we initiate and execute our planned Phase 3 ASPENOVA confirmatory study and prepare for potential commercialization.
This adjustment and reversal may be material. Research and Development Expenses - Clinical Trial Accruals Methodology Judgment and Uncertainties Effect if Actual Results Differ From Assumptions All of our clinical trials have been executed with support from CROs and other vendors.
Research and Development Expenses - Clinical Trial Accruals Methodology Judgment and Uncertainties Effect if Actual Results Differ From Assumptions All of our clinical trials have been executed with support from CROs and other vendors. We accrue costs for clinical trial activities performed by CROs and other vendors based upon the estimated amount of work completed on each trial.
ATM Program In May 2021, we entered into a sales agreement, or the Sales Agreement, with Leerink Partners LLC, as sales agent, pursuant to which we may, from time to time, issue and sell common stock in “at-the-market” offerings, or the ATM, under a registration statement.
ATM Program In May 2021, the Company entered into a sales agreement, or the Sales Agreement, with SVB Leerink LLC, or SVB Leerink, as sales agent (the "Sales Agreement"), pursuant to which the Company may, from time to time, issue and sell common stock with an aggregate value of up to $75.0 million in “at-the-market” offerings, or the ATM, under the Company's Registration Statement on Form S-3 (File No. 333-286122) filed with the SEC on March 26, 2025.
Net cash used in investing activities for the year ended December 31, 2023 of $44.5 million was attributable to the investment of excess cash of $549.2 million and the purchases of property and equipment of $0.6 million, partially offset by proceeds from marketable securities of $505.3 million. 79 Financing Activities Net cash provided by financing activities for the year ended December 31, 2024 of $108.0 thousand consisted of $349 thousand provided from the issuance of common stock under equity incentive plans, offset by cash used in the net-settlement of restricted stock unit vesting of $241 thousand.
Net cash provided by financing activities in the year ended December 31, 2024 of $108 thousand consisted of $349 thousand provided from the issuance of common stock under equity incentive plans, offset by cash used in the net-settlement of restricted stock unit vesting of $241 thousand.
We plan to conduct a randomized Phase 3 clinical trial of azenosertib versus standard-of-care chemotherapy for the treatment of patients with Cyclin E1+ PROC designed to support a full approval of azenosertib in this setting, which we plan to enroll concurrently with DENALI Part 2b, subject to FDA feedback. • Monotherapy – Phase 2 Clinical Trial in USC (TETON - ZN-c3-004).
We have aligned with the FDA on the trial design for ASPENOVA, a randomized Phase 3 confirmatory clinical trial of azenosertib versus standard-of-care chemotherapy for the treatment of patients with Cyclin E1-positive PROC designed to support a full approval of azenosertib in this setting.
We do not have any products approved for commercial sale and have not generated any revenues from product sales, and we have incurred significant operating losses.
We do not have any products approved for commercial sale and have not generated any revenues from product sales, and we have incurred significant operating losses. As a result, we will need to raise substantial additional capital to support our continuing operations and pursue our strategy.
We will not generate revenue from product sales unless and until we successfully complete clinical development, obtain regulatory approval for, and commercialize one or more of our product candidates. We will need to raise substantial additional capital to support our continuing operations and pursue our growth strategy. Since inception, we have incurred significant operating losses.
We do not have any products approved for commercial sale and have not generated any revenues from product sales. We will not generate revenue from product sales unless and until we successfully complete clinical development, obtain regulatory approval for, and commercialize one or more of our product candidates.
Net cash provided by financing activities in the year ended December 31, 2023 of $237.3 million primarily relates to the June 2023 follow-on offering, which provided net cash of $235.7 million. An additional $1.6 million was provided from the issuance of common stock under equity incentive plans.
Financing Activities Net cash used in financing activities for the year ended December 31, 2025 of $4.3 million was attributable to the Repurchase of $10.0 million offset by the $5.4 million net cash provided by shares sold through the SVB Leerink ATM agreement, and an additional $304 thousand provided from the issuance of common stock under equity incentive plans.
We are currently enrolling patients in an arm of our ZN-c3-002 Phase 1b clinical trial that is evaluating azenosertib in combination with bevacizumab in platinum sensitive ovarian cancer. • Combination - Phase 1/2 Clinical Trial of Azenosertib with Encorafenib and Cetuximab (BEACON Regimen) in BRAF V600E Mutant Metastatic Colorectal Cancer (mCRC) (ZN-c3-016).
We are currently enrolling patients in an arm of our ZN-c3-002 Phase 1b clinical trial that is evaluating azenosertib in combination with bevacizumab as maintenance therapy in ovarian cancer. The dose expansion portion will enroll second-line platinum-sensitive ovarian cancer (PSOC) patients for maintenance treatment, whose disease progressed while on a PARP inhibitor.
Investment and Other Income, Net Investment and other income was $25.5 million for the year ended December 31, 2024, compared to $22.6 million for the year ended December 31, 2023. The increase of $2.9 million was primarily the result of higher rates of return from our invested marketable securities.
Goodwill Impairment 77 Goodwill impairment for 2024 of $3.7 million was the result of an impairment test performed in the fourth quarter of 2024. Investment and Other Income, Net Investment and other income, net was $16.2 million for the year ended December 31, 2025, compared to $25.5 million for the year ended December 31, 2024.
Research and Development Expenses Research and development, or R&D, expenses for the year ended December 31, 2024 were $167.8 million, compared to $189.6 million for the year ended December 31, 2023. The decrease of $21.8 million was primarily due to a decrease of $10.7 million for personnel expense, of which $9.7 million is related to non-cash stock-based compensation.
Research and Development Expenses Research and development, or R&D, expenses for the year ended December 31, 2025 were $107.3 million, compared to $167.8 million for the year ended December 31, 2024.
During the year ended December 31, 2024, we did not sell any shares of common stock under the Sales Agreement. As of December 31, 2024 there was $200.0 million of our common stock remaining available for sale under our ATM.
In December 2025, the Company sold 3,928,571 shares of common stock under the Sales Agreement at a price of $1.40 per share, raising aggregate gross proceeds of $5.5 million before fees and expenses of $0.1 million. As of December 31, 2025 there was $69.5 million of our common stock remaining available for sale under our ATM.
We also saw an increase of $3.1 million for facilities and allocable expenses. These increases were partially offset by decreases of $4.9 million for the operating lease impairment charge during the twelve months ended December 31, 2023, and $2.5 million for outside services and other expense.
Decreases of $3.3 million related to consulting and outside services also contributed to the overall reduction in general and administrative expenses. These decreases were partially offset by an increase of $1.0 million related to allocated and other costs.
As a result, we will need to raise substantial additional capital to support our continuing operations and pursue our strategy.
We will need to raise substantial additional capital to support our continuing operations and pursue our growth strategy. Since inception, we have incurred significant operating losses. Our net losses were $137.1 million for the year ended December 31, 2025. We had an accumulated deficit of $1.2 billion as of December 31, 2025.
Removed
We are generating data from our Phase 2 TETON (ZN-c3-004) clinical trial of azenosertib in USC, which we expect to announce in the first half of 2026.
Added
In January 2026, we announced that the enrollment for Part 2a was completed in 2025 and we plan to announce dose selection from Part 2a in the first half of 2026. We anticipate a topline readout for DENALI Part 2 by year end 2026.
Removed
We previously disclosed data from our Phase 1 ZN-c3-003 clinical trial of azenosertib in combination with gemcitabine in osteosarcoma that supported further investigation of the combination in this setting in an upcoming investigator-initiated Phase 2 trial.
Added
We also completed enrollment in a Phase 2 clinical trial evaluating azenosertib as a monotherapy in patients with uterine serous carcinoma, or USC (TETON - ZN-c3-004). We plan to publish results from this trial in the future.
Removed
Azenosertib is currently being evaluated as a monotherapy in a Phase 2 clinical trial in patients with USC. The FDA granted Fast Track Designation to azenosertib in patients with advanced or metastatic USC who have received at least one prior platinum-based chemotherapy regimen for management of advanced or metastatic disease.
Added
Investment and Other Income, Net Investment and other income, net consists of interest earned on cash, cash equivalents and available-for-sale marketable securities, sublease income and the change in value of equity securities during the period.

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