ZNTL 10-K & 10-Q changes, risk factors and insider trading

You should carefully consider the risks and uncertainties described below and the other information in this Annual Report on Form 10-K, including our consolidated financial statements and related notes appearing elsewhere in this Annual Report on Form 10-K and in the section titled “Management’s Discussion and Analysis of Financial Condition and Results of Operations,” before deciding whether to invest in our common stock. Our business, financial condition, results of operations or prospects could be materially and adversely affected if any of these risks occurs, and as a result, the market price of our common stock could decline and you could lose all or part of your investment. This Annual Report on Form 10-K also contains forward-looking statements that involve risks and uncertainties. See “Cautionary Note Regarding Forward-Looking Statements.” Additional risks and uncertainties not presently known to us or that we currently deem immaterial also may impair our business operations. Our actual results could differ materially and adversely from those anticipated in these forward-looking statements as a result of certain important factors, including those set forth below.

We are a clinical-stage biopharmaceutical company with a limited operating history upon which you can evaluate our business and prospects. We have no products approved for commercial sale and have not generated any revenue from product sales. To date, we have devoted substantially all of our resources and efforts to organizing and staffing our company, business planning, executing partnerships, raising capital, discovering, identifying and developing potential product candidates, securing related intellectual property rightsrights, and conducting preclinical studies and clinical trials of our product candidates, including the ongoing clinical trials of azenosertib. We have not yet demonstrated our ability to obtain marketing approvals, manufacturesupply a product at commercial scale or arrange for a third party to do so on our behalf, or conduct sales and marketing activities necessary for successful product commercialization. As a result, it may be more difficult for you to accurately predict our future success or viability than it could be if we had a longer operating history.

We expect to continue to incur significant expenses and increasing operating losses for the foreseeable future as we continue our research and development efforts and seek to obtain regulatory approval and commercialization of ourazenosertib and any future product candidates. The net losses we incur may fluctuate significantly from quarter to quarter such that a period-to-period comparison of our results of operations may not be a good indication of our future performance. The size of our future net losses will depend, in part, on the rate of future growth of our expenses and our ability to generate revenue. Our prior losses and expected future losses have had and will continue to have an adverse effect on our working capital and our ability to achieve and maintain profitability.

•successful and timely completion of the clinical development of azenosertib as a monotherapy for the treatment of Cyclin E1+E1-positive PROC, successful and timely completion of the development of a companion diagnostic with a diagnostic partner to identify patients with Cyclin E1+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 and interest rates,inflation, or ongoing military conflicts, among other causes;

•timely receipt of marketing approvals from applicable regulatory authorities for azenosertib for the treatment of Cyclin E1+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+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+E1-positive PROC, and making any required post-marketing approval commitments to applicable regulatory authorities;

Developing pharmaceutical products, including conducting preclinical studies and clinical trials, is a very time-consuming, expensive and uncertain process that takes years to complete. Our operations have consumed substantial amounts of cash since inception. Following our 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 expenses; however, ifIf our azenosertib development program continues to advance successfully, we expect our expensesexpenditures to increase as we initiate and execute our planned Phase 3 confirmatory studyclinical trial and prepare for potential commercialization. Even if azenosertib or any future product candidate that we develop is approved for commercial sale, we anticipate incurring significant costs associated with commercializing any approved product candidate. Our expenses could increase beyond our expectations if we are required by the FDA, the European Medicines Agency, or the EMA, or other regulatory agencies to perform clinical trials or preclinical studies in addition to those that we currently anticipate. We willare incurincurring costs related to collaborating with a diagnostic company for the development, manufacturing and supply of a companion diagnostic to identify patients with Cyclin E1+E1-positive PROC, and we may in the future incur costs relating to additional diagnostic tools for biomarkers associated with azenosertib and any future product candidates. Other unanticipated costs may also arise. In addition, if we obtain marketing approval for any of our product candidates, including azenosertib, we expect to incur significant commercialization expenses related to drug sales, marketing, manufacturing and distribution. Because the design and outcome of our planned and anticipated clinical trials are highly uncertain, we cannot reasonably estimate the actual amounts necessary to successfully complete the development and commercialization of any product candidate we develop. We have also incurred, and expect to continue to incur, costs associated with operating as a public company. Accordingly, we will need to obtain substantial additional funding in order to maintain our continuing operations.

We will be required to obtain further funding through public or private equity offerings, debt financings, collaborations and licensing arrangements or other sources, which may dilute our stockholders or restrict our operating activities. We do not have any committed external source of funds. Adequate additional financing may not be available to us on acceptable terms, or at all. Market volatility resulting from public health emergencies, U.S. and global economic issues, global supply chain disruptions, international political instability, rising inflation and interest rates or other factors could also adversely impact our ability to access capital as and when needed. Our failure to raise capital as and when needed or on acceptable terms would have a negative impact on our financial condition and our ability to pursue our business strategy, and we may have to delay, reduce the scope of, suspend or eliminate one or more of our research-stage programs, clinical trials or future commercialization efforts.

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. If any of these collaborations isare not successful, we may not be able to capitalize on the market potential of those product candidates.

We have in the past and in the future may seek third-party collaborators for the research, development and commercialization of one or more of our product candidates. For example, we arehave collaboratingcollaborated with Pfizer, GSK and Dana Farber on the development of azenosertib. Our likely collaborators in any future collaboration arrangements we may enter into include large and mid-size pharmaceutical companies and biotechnology companies. If we were to enter into any collaboration arrangements with third parties, those agreements may limit our control over the amount and timing of resources that our collaborators dedicate to the development and commercialization of any product candidates we may seek to develop with them. We cannot predict the success of any collaboration in which we have entered or may enter. Our ability to generate revenues from these arrangements will depend on our collaborators’ abilities and efforts to successfully perform the functions assigned to them in these arrangements.

Collaborations involving our research programs, our product candidatesazenosertib and any future research programs or product candidates we may develop pose risks to us, including the following:

Following our January 2025 strategic restructuring, we are primarily focused on the late-stage clinical development of azenosertib. However, our long-term success may also depend on our ability to successfully discover, develop, obtain regulatory approval for and commercialize additional product candidates beyond azenosertib. Our future operating results are dependent on our ability to successfully discover, develop, obtain regulatory approval for and commercialize product candidates beyond azenosertib. A product candidate can unexpectedly fail at any stage of preclinical and clinical development. The historical failure rate for product candidates is high due to risks relating to safety, efficacy, clinical execution, changing standards of medical care and other unpredictable variables. The results from preclinical testing or early clinical trials of a product candidate may not be predictive of the results that will be obtained in later stage clinical trials of the product candidate.

•the data collected from clinical trials of our product candidates may not be sufficient to support the submission of ana NDANew Drug Application, or BLANDA, or Biologics License Application, or BLA, or other submission or to obtain regulatory approval in the United States or elsewhere;

•if the FDA or ex-U.S. regulatory authority requires approval or clearance of a companion diagnostic for a particular product candidate, which we expect to be the case for monotherapy azenosertib for the treatment of patients with Cyclin E1+E1-positive PROC, and the FDA or comparable regulatory authority does not provide such approval or clearance, then the product candidate may not be approved for marketing; and/or

In addition, the policies and practices of the FDA and ex-U.S. regulatory authorities with respect to clinical trials may change and additional government regulations may be enacted. For example, in recent years the FDA has issued guidance and launched programs aiming to reform and modernize the dose optimization procedures used by clinical trial sponsors during the development of oncology drugs. Since these guidelines are new and can potentially evolve during the conduct of our clinical trials, changes in the FDA’s thinking with respect to dose selection and optimization could require us to change the design of our planned or ongoing clinical trials or otherwise conduct additional preclinical, clinical or manufacturing studies beyond those we currently anticipate, which could increase our costs and/or delay the development of our product candidates. In June 2024, the FDA issued a revised draft guidance regarding the creation of diversity action plans for certain clinical trials. The purpose of this draft guidance is to provide recommendations to sponsors developing medical products on the approach for developing a Diversity Action Plan designed to improve enrollment of representative numbers of participants from underrepresented racial and ethnic populations in the United States. This guidance, if finalized, could require us to change the way we decide to enroll our planned clinical trials, which could increase our costs and/or delay the development of our product candidates.

In addition, the regulatory landscape related to clinical trials in the EU has evolved in the last few years. The EU Clinical Trials Regulation, or CTR, which was adopted in April 2014 and repeals the EU Clinical Trials Directive, became applicable on January 31, 2022. 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. The CTR allows sponsors to make a single submission to both the competent authority and an ethics committee in each member state, leading to a single decision per member state. The assessment procedure of the CTA has been harmonized as well, including a joint assessment by all member states concerned, and a separate assessment by each member state with respect to specific requirements related to its own territory, including ethics rules. Each member state’s decision is communicated to the sponsor via the centralized EU portal. Once the CTA is approved, clinical study development may proceed. The CTR instituted a three-year transition period.period Theended extenton toJanuary which31, ongoing2025, and newall clinical trials will be governed by the CTR varies. Clinical trials for which an application was submitted (i) prior to January 31, 2022 under the EU Clinical Trials Directive, or (ii) between January 31, 2022 and January 31, 2023 and for which the sponsor has opted for the application of the EU Clinical Trials Directive remain governed by said Directive until January 31, 2025. After this date, all clinical trials, including thoserelated thatapplications) are ongoing,now becamefully subject to the provisions of the CTR. Compliance with the CTR requirements by us, our collaborators and third-party service providers, such as CROs, may impact our development plans.

In addition, even if we obtain approval of our product candidates, regulatory authorities may approve any of our product candidates for fewer or more limited indications than we request, may impose significant limitations in the form of narrow indications, warnings and precautions, or a Risk Evaluation and Mitigation Strategy, or REMS, or similar risk management measures. Regulatory authorities may not approve the price we intend to charge for products we may develop, may grant approval contingent on the performance of costly post-marketing clinical trials, or may approve a product candidate with a label that does not include the labeling claims necessary or desirable for the successful commercialization of that product candidate. Any of the foregoing scenarios could seriously harm our business.

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. While we have or will have agreements governing our relationships with these third parties, we have limited influence over their actual performance. 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.

•obtaining approval from one or more IRBsinstitutional review boards, or IRBs, or ethics committees;

We are working with a diagnostic partner to develop a companion diagnostic to identify patients with Cyclin E1+E1-positive PROC in connection with our clinical development of monotherapy azenosertib for the treatment of patients with Cyclin E1+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. In addition, in the future, we may develop diagnostic tools for additional biomarkers for azenosertib and future product candidates for which the FDA and ex-U.S. regulatory authorities may require us or a third party collaborator to obtain marketing approval.

According to FDA guidance, if the FDA determines that a companion diagnostic device is essential to the safe and effective use of a novel therapeutic product or indication, the FDA generally will not approve the therapeutic product or new therapeutic product indication if the companion diagnostic is not also approved or cleared for that indication. 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+E1-positive PROC, we would be required to develop or obtain such diagnostic, which would be subject to regulatory approval requirements. The approval or clearance of a companion diagnostic as part of the therapeutic product’s further labeling limits the use of the therapeutic product to only those patients who express the specific characteristic that the companion diagnostic was developed to detect. 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+E1-positive PROC. The process of obtaining or creating a companion diagnostic is time consuming and costly and may not result in any future income. This could require us to raise additional funds, which could dilute our current investors or impact our ability to continue our operations in the future.

If we, in collaboration with our diagnostic partner, are unable to successfully develop a Cyclin E1+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+E1-positive PROC will be adversely affected, which will have a material adverse effect on our business. In addition, if additional indications of azenosertib or any future product candidates require a companion diagnostic or other diagnostic tool and we, in collaboration with diagnostic partners, are unable to successfully develop such tools, or such tools are not available commercially, or we experience delays in doing so, then the development of such product candidates will be adversely affected, which could have a material adverse effect on our business.

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+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.

We may publicly disclose initial, preliminary or topline data from our preclinical studies and clinical trials, which are based on a preliminary analysis of then-available data, and the results and related findings and conclusions are subject to change following a more comprehensive review of the data related to the particular study or trial. We also make assumptions, estimations, calculations and conclusions as part of our analyses of data, and we may not have received or had the opportunity to fully and carefully evaluate all data. As a result, the initial, topline or preliminary results that we report may differ from future results of the same studies, or different conclusions or considerations may qualify such results, once additional data have been received and fully evaluated. Certain of these data also remain subject to audit and verification procedures that may result in the final data being materially different from the preliminary data we previously published. As a result, initial, topline and preliminary data should be viewed with caution until the final data are available. For example, in January 2025, we announced monotherapy azenosertib clinical data in patients with Cyclin E1+E1-positive PROC, who were identified using a proprietary immunohistochemistry cutoff defined by retrospective tissue analysis utilizing a Cyclin E1 biomarker assay. In our DENALI Part 2 clinical trial, we planare to identifyidentifying patients using our proprietary immunohistochemistry cutoff with a prospective tissue analysis utilizing the Cyclin E1 biomarker assay. 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 2.2 and in future studies.

•if applicable (which we expect to be the case for monotherapy azenosertib in Cyclin E1+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;

The FDA has granted fast track designation for azenosertib in (i) patients with advanced or metastatic USC who have received at least one prior platinum-based chemotherapy regimen for management of advanced or metastatic disease, and (ii) for the treatment of patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who are positive via Cyclin E1 immunohistochemistry for protein levels,levels. and weWe intend to seek such fast track designation for some or all of our otherfuture product candidates when applicable. The fast track program is intended to expedite or facilitate the process for reviewing new product candidates that meet certain criteria. Specifically, drugs and biologicbiologics 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. Fast track designation applies to the combination of the product candidate and the specific indication for which it is being studied. The sponsor of a fast track product candidate has opportunities for more frequent interactions with the applicable FDA review team during product development and, once an NDA or BLA is submitted, the application may be eligible for priority review. An NDA or BLA submitted for a fast track product candidate may also be eligible for rolling review, where the FDA may consider for review sections of the NDA or 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 or BLA, the FDA agrees to accept sections of the NDA or BLA and determines that the schedule is acceptable, and the sponsor pays any required user fees upon submission of the first section of the application.

The biotechnology and pharmaceutical industries are characterized by rapidly advancing technologies, intense competition and a strong emphasis on proprietary and novel products and product candidates. Our competitors have developed, are developing or may develop products, product candidates and processes competitive with ourazenosertib and any future product candidates. Any product candidates that we successfully develop and commercialize will compete with existing therapies and new therapies that may become available in the future. We believe that a significant number of products are currently under development, and may become commercially available in the future, for the indications for which we are currently developing azenosertib and for the indications for which we may attempt to develop azenosertib and any future product candidates. In addition, our products may need to compete with off-label drugs used by physicians to treat the indications for which we seek approval. This may make it difficult for us to replace existing therapies with our products.

There is significant uncertainty related to third-party payor coverage and reimbursement of newly approved products. In the United States, for example, principal decisions about reimbursement for new products are typically made by the Centers for Medicare & Medicaid Services, or CMS, an agency within the U.S. Department of Health and Human Services, or HHS. CMS decides whether and to what extent a new product will be covered and reimbursed under Medicare, and private third-party payors often follow CMS’s decisions regarding coverage and reimbursement to a substantial degree. However, one third-party payor’s determination to provide coverage for a product candidate does not assure that other payors will also provide coverage for the product candidate. As a result, the coverage determination process is often time-consuming and costly. This process will require us to provide scientific and clinical support for the use of our products to each third-party payor separately, with no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the first instance.

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+E1-positive PROC relating to our development of monotherapy azenosertib for patients with Cyclin E1+E1-positive PROC. 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. If coverage and adequate reimbursement are not available, or are available only to limited levels, we may not be able to successfully commercialize any product candidates that we develop.

We have not conducted, managed or completed large-scale or pivotal clinical trials nor managed the regulatory approval process with the FDA or any other regulatory authority. The time required to obtain approvals from the FDA and other regulatory authorities is unpredictable, and requires successful completion of extensive clinical trials which typically takes many years, depending upon the type, complexity and novelty of the product candidate. The standards that the FDA and its ex-U.S. counterparts use when evaluating clinical trial data can change during drug development, which makes it difficult to predict with any certainty how they will be applied. In addition, the FDA and its ex-U.S. counterparts may require approval or clearance of a companion diagnostic for a particular product candidate and may not approve the product candidate for marketing if such regulatory authority does not approve or clear the companion diagnostic. For example, we expect the FDA and its ex-U.S. counterparts to require regulatory approval of the companion diagnostic test being developed by our diagnostic collaborator to identify patients with Cyclin E1+E1-positive PROC relating to our development of monotherapy azenosertib for patients with Cyclin E1+E1-positive PROC.PROC, and any delays in obtaining approval or clearance for such companion diagnostic could similarly delay potential regulatory approval of azenosertib. We may also encounter unexpected delays or increased costs due to new government regulations, including future legislation or administrative action, or changes in FDA or ex-U.S. regulatory authorities policy during the period of drug development, clinical trials and FDA or ex-U.S. regulatory authorities regulatory review.

If ourazenosertib or any future product candidates are associated with undesirable side effects or have unexpected characteristics in preclinical studies or clinical trials when used alone or in combination with other approved products or investigational new drugs, we may need to interrupt, delay or abandon their development or limit development to more narrow uses or subpopulations in which the undesirable side effects or other characteristics are less prevalent, less severe or more acceptable from a risk-benefit perspective. Treatment-related side effects could also affect patient recruitment or the ability of enrolled subjects to complete the trial, or result in potential product liability claims. Any of these occurrences may prevent us from achieving or maintaining market acceptance of the affected product candidate and may harm our business, financial condition and prospects significantly.

If significant AEs or other side effects are observed in any of our current or future clinical trials, we may have difficulty recruiting patients to the clinical trials, patients may drop out of our trials, or we may be required to abandon the trials or our development efforts of that product candidate altogether. We, the FDA or ex-U.S. regulatory authorities, or an IRB (or similar body) may suspend clinical trials of a product candidate at any time for various reasons, including a belief that subjects in such trials are being exposed to unacceptable health risks or adverse side effects.

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.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. 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. Additionally, the FDA's clinical trial requirements, including the adequacy of the patient population studied and statistical powering, must be met. Furthermore, even where the ex-U.S. study data are not intended to serve as the sole basis for approval, if the trial was not otherwise subject to an IND, the FDA will not accept the data as support for an application for marketing approval unless the study is well-designed and well-conducted in accordance with GCP requirements and the FDA is able to validate the data from the study through an onsite inspection if deemed necessary. Many ex-U.S. regulatory authorities have similar approval requirements. In addition, such ex-U.S. trials would be subject to the applicable local laws of the ex-U.S. jurisdictions where the trials are conducted. There can be no assurance that the FDA or any ex-U.S. regulatory authority will accept data from trials conducted outside of its applicable jurisdiction. 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.

The FDA’s and ex-U.S. regulatory authorities’ policiespolicies, or implementation of existing policies, may change,change and additional government regulations may be enactedenacted, including as a result of the new U.S. presidential administration, that could prevent, limit or delay regulatory approval of our product candidates. We also cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative action, either in the United States or abroad.

If any of our product candidates areis approved and we are found to have improperly promoted off-label uses of those products, we may become subject to significant liability. The FDA and other regulatory agencies strictly regulate the promotional claims that may be made about prescription products, such as our product candidates, if approved. In particular, a product may not be promoted for uses that are not approved by the FDA or such other regulatory agencies as reflected in the product’s approved labeling. If we receive marketing approval for a product candidate, physicians may nevertheless prescribe it to their patients in a manner that is inconsistent with the approved label. If we are found to have promoted such off-label uses, we may become subject to significant liability. The U.S. federal government has levied large civil and criminal fines against companies for alleged improper promotion of off-label use and has enjoined several companies from engaging in off-label promotion. The FDA has also requested that companies enter into consent decrees or permanent injunctions under which specified promotional conduct is changed or curtailed. If we cannot successfully manage the promotion of our product candidates, if approved, we could become subject to significant liability, which would materially adversely affect our business and financial condition.

Changes and/or disruptions at the FDA, the SEC and other government agencies, including as a result of thegovernment new presidential administration,shutdowns, funding shortagesshortages, staffing changes or limitations, or global health concerns could prevent those agencies from performing normal business functions onas whichthey thewere operationpreviously of our business may rely,performed, which could negatively impact our business.

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. Average review times at the FDA and ex-U.S. regulatory authorities have fluctuated in recent years as a result. In addition, government funding of the SEC and other government agencies on which our operations may rely, including those that fund research and development activities is subject to the political process, which is inherently fluid and unpredictable.

DisruptionsChanges and/or disruptions at the FDA and other agencies, such as the EMA, following its relocation to Amsterdam and resulting staff changes,agencies may also slow the time necessary for new drugs to be reviewed and/or approved by necessary government agencies, which would adversely affect our business. For example, in 2025 and in recent years, including in 2018 and 2019, the U.S. government has shut down several times and certain regulatory agencies, such as the FDA and the SEC, had to furlough critical employees and stop critical activities. Further, in our operations as a public company, future or prolonged government shutdowns or delays could impact our ability to access the public markets and obtain necessary capital in order to properly capitalize and continue our operations. Further, the current U.S. presidential administration has issued certain policies and executive orders directed towards reducing the employee headcount and costs associated with U.S. administrative agencies, including the FDA, and it remains unclear the degree to which these efforts may limit or otherwise adversely affect the FDA’s ability to conduct routine activities.

Separately, in response to COVID-19, the FDA postponed most inspections of domestic and ex-U.S. manufacturing facilities at various points. If a prolonged government shutdown occurs, if renewed global health concerns prevent the FDA or other regulatory authorities from conducting their regular reviews or other regulatory activities,occurs or if there are delays and slowdowns caused by reductionsstaffing inlimitations, forcefunding of government employeesshortages, or for other reasons, itthese actions and events could significantly impact the ability of the FDA or ex-U.S. regulatory authorities to timely review and process our regulatory submissions, which could have a material adverse effect on our business. It could also impact our ability to access the public markets and obtain necessary capital in order to properly fund our operations.

We plan to seek accelerated approval from the FDA for monotherapy azenosertib for the treatment of Cyclin E1+E1-positive PROC, subject to supportive clinical data and FDA review. In addition, we may in the future seek accelerated approval or another form of expedited development or review for azenosertib in another indication or future product candidates. Under the accelerated approval program, the FDA may grant accelerated approval to a product candidate designed to treat a serious or life-threatening condition that provides meaningful therapeutic benefit over available therapies upon a determination that the product candidate has an effect on a surrogate endpoint or intermediate clinical endpoint that is reasonably likely to predict clinical benefit. The FDA considers a clinical benefit to be a positive therapeutic effect that is clinically meaningful in the context of a given disease, such as irreversible morbidity or mortality. For the purposes of accelerated approval, a surrogate endpoint is a marker, such as a laboratory measurement, radiographic image, physical sign, or other measure that is thought to predict clinical benefit, but is not itself a measure of clinical benefit. An intermediate clinical endpoint is a clinical endpoint that can be measured earlier than an effect on irreversible morbidity or mortality that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit. The accelerated approval pathway may be used in cases in which the advantage of a new drug over available therapy may not be a direct therapeutic advantage, but is a clinically important improvement from a patient and public health perspective. If granted, accelerated approval is usually contingent on the sponsor’s agreement to conduct, in a diligent manner, additional confirmatory studies to verify and describe the drug’s clinical benefit. If such confirmatory studies fail to confirm the drug’s clinical benefit, the FDA may withdraw its approval of the drug on an expedited basis. In addition, in December 2022, the former President signedaddition the Food and Drug Omnibus Reform Act of 2022, which, among other things,2022 provided the FDA statutory authority to mitigate potential risks to patients from continued marketing of ineffective drugs previously granted accelerated approval,approval and additional oversight over confirmatory trials. Under these provisions, the FDA may, among other things, require a sponsor of a product seeking accelerated approval to have a confirmatory trial underway prior to such approval being granted.

Prior to seeking accelerated approval or another form of expedited development or review for any of our product candidates, we intend to seek feedback from the FDA or ex-U.S. regulatory authorities and will otherwise evaluate our ability to seek and receive accelerated approval or another form of expedited development or review. There can be no assurance that after our evaluation of the feedback and other factors we will decide to pursue or submit an NDA or BLA, whichever is applicable, for accelerated approval or another form of expedited development, review or approval. Furthermore, if we decide to submit an application for accelerated approval or another form of expedited development, review or approval for ourazenosertib or any future product candidates,candidate, there can be no assurance that such submission or application will be accepted or that any such expedited development, review or approval will be granted on a timely basis, or at all. The FDA or ex-U.S. regulatory authorities could also require us to conduct further studies prior to considering our application or granting approval of any type. A failure to obtain accelerated approval or any other form of expedited development, review or approval for our product candidateazenosertib 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.

Existing regulatory policies may change and additional government regulations may be enacted that could prevent, limit or delay regulatory approval of ourazenosertib and any future product candidates and affect our ability to profitably sell our products for which we receive approval. We cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative action, including by executive order, either in the United States or abroad. If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we are not able to maintain regulatory compliance, we may lose any marketing approval that we may have obtained and we may not achieve or sustain profitability.

New and changing laws and regulations, including by executive order, may also create uncertainty about how suchexisting laws and regulations will be interpreted and applied.applied, including pricing. If the Company is found to have violated laws and regulations, it could materially adversely affect the Company’s business, results of operations and financial condition.

For example, in March 2010, the ACA was passed,enacted in 2010, which substantially changeschanged the way healthcare is financed by both the government and private insurers, and significantly impacts the U.S. pharmaceutical industry. Other legislative changes have been proposed and adopted in the United States since the ACA was enacted. These changes include the American Rescue Plan Act of 2021, which eliminated the statutory Medicaid drug rebate cap, beginning January 1, 2024. The rebate was previously capped at 100% of a drug’s average manufacturer price. It is unclear how other healthcare reform measures will impact our business.

Moreover, there has been heightened governmental scrutiny recently over the manner in which drug manufacturers set prices for their marketed products, which has resulted in executive orders, several U.S. Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drug products. Most significantly, on August 16, 2022, theThe IRA was signedenacted intoin law.2022. This statute marks the most significant action by Congress with respect to the pharmaceutical industry since adoption of the ACA in 2010. 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;cap, imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation; (firstredesigns duethe inMedicare 2023,Part asD applicable)benefit; and replaces the Part D coverage gap discount program with a new discountingmanufacturer programdiscount (which began in 2025).program. CMS has published the negotiated prices for the initial ten drugs, which became effective in 2026, and the subsequent fifteen drugs, which will first be effective in 2026,2027. andCMS has also published the listnext set of the subsequent fifteen drugs that will be subject to negotiation. Additional drugs will become subject to the Medicare price negotiation program in each following year. The IRA permits the Secretary of HHS to implement many of these provisions through guidance, as opposed to regulation, for the initial years. EachHHS year thereafter, more Part Bhas and Part D products will become subjectcontinue to issue and update guidance as these programs are implemented, although the HHSMedicare price negotiation program, although the program is currently subject to legal challenges. While the impact of the IRA on the pharmaceutical industry cannot yet be fully determined, it is likely to be significant.

At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing. Some states have also enacted legislation creating so-called prescription drug affordability boards, which ultimately may attempt to impose price limits on certain drugs in these states.states, and at least one state board is imposing an upper payment limit. States are also seeking to implement general, across the board price caps for pharmaceuticals, or are seeking to regulate drug distribution.

In addition, new and changing laws, regulations, executive orders and other governmental actions, particularlyas fromwell theas newchanging presidentialinterpretations administration,by government of laws and regulations, may also create uncertainty about how to comply with laws and regulationsregulations. willChanges bein interpretedbinding andlegal applied. Regulatory changes and other actionsstandards that materially affect our business may be announced with little or no advance notice,announced, and we may be unable to effectively mitigate all adverse impacts from such measures. Differing interpretations of such legal obligations can expose us to significant fines, government investigations, litigation and reputational harm. If we are found to have violated laws,binding regulations,legal orstandards, executivewe orders,could itface significant fines, government investigations, litigation, and reputational harm, which could materially adversely affect our business, reputation, results of operationsoperations, and financial condition.

In the United States, HIPAA imposes, among other things, certain standards relating to the privacy, security, transmission and breach reporting of individually identifiable health information. 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 maymay, 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. Depending on the facts and circumstances, we could be subject to significant penalties if we violate HIPAA. For example,Additionally, the California Consumer Privacy Act, as amended by the California Privacy Rights Act, or collectively, the CCPA, requires covered businesses that process the personal information of California residents to, among other things: provide certain disclosures to California residents regarding the business’s collection, use, and disclosure of their personal information; receive and respond to requests from California residents to access, delete, and correct their personal information, or to opt out of certain disclosures of their personal information, and enter into specific contractual provisions with service providers that process California resident personal information on the business’s behalf. Similar laws have passed in other states, and are continuing to be proposed at the state and federal level, reflecting a trend toward more stringent privacy legislation in the United States. The enactment of such laws could have potentially conflicting requirements that would make compliance challenging. InTo the eventextent that we are subject to or affected by HIPAA, the CCPA or other domestic privacy and data protection laws, any liability from failure to comply with the requirements of these laws could adversely affect our financial condition.

Our operations abroad may also be subject to increased scrutiny or attention from data protection authorities. For instance, the EUEuropean Union General Data Protection Regulation, or EU GDPR, wentand intoto effectthe inUnited MayKingdom 2018General Data Protection Regulation and Data Protection Act 2018, collectively the UK GDPR, and together with the EU GDPR, the GDPR, imposes strict requirements for processing the personal data of individuals within the European Economic Area, or the EEA, and the UK or in the context of our activities in the EEA.EEA, and the UK. In addition, some of the personal data we process in respect of clinical trial participants is special category or sensitive personal data under the GDPR, and subject to additional compliance obligations and to local law derogations. 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. In addition to fines, a breach of the GDPR may result in regulatory investigations, reputational damage, orders to cease/change our data processing activities, enforcement notices, assessment notices (for a compulsory audit) and/or civil claims (including class actions). Among other requirements, the GDPR regulates transfers of personal data subject to the GDPR to third countries that have not been found to provide adequate protection to such personal data, including the United States, and the efficacy and longevity of current transfer mechanisms between the EEA and the United States remains uncertain. On July 10, 2023, the European Commission adopted its Adequacy Decision in relation to the new EU-US Data Privacy Framework, or the DPF, rendering the DPF effective as a GDPR transfer mechanism to U.S. entities self-certified under the DPF. We currently rely on the EU standard contractual clauses, the UK Addendum to the EU standard contractual clauses and the UK International Data Transfer Agreement, as relevant, to transfer personal data outside the EEA and the UK, including to the United States, with respect to both intragroup and third party transfers. We may also rely on individual consent to transfer personal data in certain circumstances. We expect the existing legal complexity and uncertainty regarding international personal data transfers to continue. In particular, we expect the DPF Adequacy Decision to be challengedcontinue and international transfers to the United States and to other jurisdictions more generally to continue to be subject to enhanced scrutiny by regulators. As athe result,regulatory we may have to make certain operational changesguidance and weenforcement willlandscape havein relation to implement revised standard contractual clauses and other relevant documentation for existing data transfers withincontinue requiredto timedevelop, frames.we could incur additional costs, complaints and/or regulatory investigations or fines, and/or if we are otherwise unable to transfer personal data between and among countries and regions in which we operate, it could affect the manner in which we operate our business, the geographical location or segregation of our relevant systems and operations, and could adversely affect our financial results.

We arehave been and may in the future be subject to numerous environmental, health and safety laws and regulations, including those governing laboratory procedures and the handling, use, storage, treatment and disposal of hazardous materials and wastes. Our operations have and may in the future involve the use of hazardous and flammable materials, including chemicals and biological materials. Our operations also have and may in the future produce hazardous waste products. We generallyhave contractpreviously contracted with third parties for the disposal of these materials and wastes.wastes Weand cannotwere not able to eliminate the risk of contamination or injury from these materials. In the event of contamination or injury resulting from our use of hazardous materials, we could be held liable for any resulting damages, and any liability could exceed our resources. We also could incur significant costs associated with civil or criminal fines and penalties.

If we further expand our operations outside of the United States, we must dedicate additional resources to comply with numerous laws and regulations in each jurisdiction in which we plan to operate. Our business activities may be subject to the FCPA and similar anti-bribery or anti-corruption laws, regulations or rules of other countries in which we operate. The FCPA generally prohibits companies and their employees and third party intermediaries from offering, promising, giving or authorizing the provision of anything of value, either directly or indirectly, to a non-U.S. government official in order to influence official action or otherwise obtain or retain business. 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. Additionally, in many other countries, hospitals owned and operated by the government, and doctors and other hospital employees would be considered ex-U.S. officials under the FCPA. RecentlyDuring the prior U.S. presidential administration, the SEC and the U.S. Department of Justice have increased their FCPA enforcement activities with respect to biotechnology and pharmaceutical companies. There is no certainty that all of our employees, agents or contractors, or those of our affiliates, will comply with all applicable laws and regulations, particularly given the high level of complexity of these laws. Violations of these laws and regulations could result in fines, criminal sanctions against us, our officers or our employees, disgorgement, and other sanctions and remedial measures, and prohibitions on the conduct of our business. Any such violations could include prohibitions on our ability to offer our products in one or more countries and could materially damage our reputation, our brand, our international activities, our ability to attract and retain employees and our business, prospects, operating results and financial condition.

In addition, losing employees, including as a result of a workforce reduction such as the one announced in January 2025, which was operationally completed during the year ended December 31, 2025, subjects us to a number of risks, including the failure to transition responsibilities and tasks, the need to adapt or create systems and processes, the impact on corporate culture, and the loss of historical knowledge.

You should read the following discussion and analysis of financial condition and operating results together with our consolidated financial statements and the related notes and other financial information included elsewhere in this Annual Report on Form 10-K. Some of the information contained in this discussion and analysis or set forth elsewhere in this Annual Report on Form 10-K contains forward-looking statements based upon current plans, expectations and beliefs involving significant risks and uncertainties. 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 statements. For convenience of presentation some of the numbers have been rounded in the text below.

A discussion regarding our financial condition and results of operations for the years ended December 31, 20242025 and 2023,2024, including a year-to-year comparison between 20242025 and 2023,2024, is presented below. For a discussion regarding our financial condition and results of operations for the year ended December 31, 2022,2023, including a year-to-year comparison between 20232024 and 2022,2023, refer to Part II, Item 7. “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, 20232024 filed on FebruaryMarch 27,26, 2024.2025.

We are a clinical-stage biopharmaceutical company developing azenosertib (ZN-c3), aan 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. We are currently focused on advancing the clinical development of azenosertib in Cyclin E1+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+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+E1-positive PROC. We exclusively in-license or solely own worldwide development and commercialization rights to azenosertib.

Azenosertib is aan investigational, potentially best-in-classfirst-in-class and first-in-classbest-in-class oral, small molecule WEE1 inhibitor. The inhibition of WEE1, a DNA damage response kinase, drives cancer cells into mitosis without being able to repair damaged DNA, resulting in cell death and thereby preventing tumor growth and potentially causing tumor regression. We have designed azenosertib to have advantages over other investigational therapies targeting WEE1, including superior selectivity and pharmacokinetic, or PK, properties.

We are working with a diagnostic partner to developvalidate 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 DENALIour PartPhase 2.3 trial, ASPENOVA.

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. Based on our analysis utilizing our IHC cutoff, we estimate that approximately 50% of PROC patients overexpress Cyclin E1 protein, which accountaccounts 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, we believe there is a large market opportunity for azenosertib in Cyclin E1+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. 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+E1-positive PROC.

◦DENALI Part 1b is a single-arm study that evaluated azenosertib monotherapy at our primary dose-of-interest, 400 mg QD 5:2, in 102 patients with PROC. Tissue collection for biomarker assessment was mandated in the study and upon a retrospective analysis, approximately 50% of the patients were Cyclin E1+E1-positive per our IHC cutoff. In January and March of 2025, we announced clinical data from this study, which is described below.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+E1-positive PROC at the selected dose who have received one to three prior lines of therapy, or mirvetuximab soravtansine in the case offor patients whose tumors are also FRα-high.-high and who have received mirvetuximab soravtansine, one to four prior lines of therapy. We have aligned with the FDA on the design of our DENALI Part 2 study in patients with Cyclin E1+E1-positive PROC, which allows for seamless enrollment across Parts 2a and 2b. DENALI Part 2a is designed to confirm 400 mg QD 5:2 as the primaryrecommended dose-of-interestpivotal study dose by enrolling approximately 30 patients at each of two dose levels, 400 mg QD 5:2 and 300 mg QD 5:2. 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 toand FDA feedback.interaction. WeIn April 2025, we announced that the first patient was dosed in DENALI Part 2a. In January 2026, we announced that the enrollment for Part 2a was completed in 2025 and we plan to initiateannounce enrollmentdose ofselection DENALIfrom Part 22a in the first half of 20252026. andWe toanticipate disclosea topline datareadout fromfor DENALI Part 2 by year end 2026. 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 IHC for protein levels.

•Monotherapy – Phase 3 Clinical Trial in Cyclin E1+E1-positive PROC.PROC (ASPENOVA). We planhave toaligned conductwith 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+E1-positive PROC designed to support a full approval of azenosertib in this setting,setting. which weWe plan to initiate ASPENOVA in the first half of 2026 and enroll concurrently with DENALI Part 2b, subject to FDA feedback.2b.

•Combination – Phase 1b Clinical Trial of Azenosertib and Chemotherapy or Bevacizumab in Ovarian Cancer (MUIR - ZN-c3-002). 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 platinum sensitive 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.

Since inception, we have incurred significant operating losses. Our net losses were $165.9$137.1 million for the year ended December 31, 2024.2025. We had an accumulated deficit of $1.1$1.2 millionbillion as of December 31, 2024.2025. 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$245.9 million as of December 31, 2024.2025. We believe that our existing cash, cash equivalents and marketable securities as of December 31, 20242025 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.

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. Following certaina 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. ZMI has the right to sublicense its rights under the Recurium Agreement, subject to certain conditions. ZMI is required to use commercially reasonable efforts to develop and commercialize at least one product that comprises or contains a compound modulating one of ten specific biological targets and to execute certain development activities.

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. In January 2025, we announced that the trial was fully enrolled and that we were not proceeding further with the development of the combination of azenosertib with niraparib as efficacious exposures of azenosertib were not reached. Pursuant to this agreement, we were responsible for the conduct and cost of the study, under the supervision of a joint development committee made up of our representatives and representatives of GSK. GSK supplied niraparib for use in the collaboration, at no cost to us. We are required to provide to GSK clinical data and other reports upon completion of the study.

Research and development activities are central to our business model. 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 for which2025, we expectincurred to incur thecertain associated non-recurring expenses in the first quarter of 2025,2025. As a result of the strategic restructuring, we expectrealized an initiala decrease in research and development expenses; however,during ifthe 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.

The successful development of azenosertib, and any of our future product candidates is highly uncertain. At this time, we cannot determine with certainty the duration and costs of our existing and future clinical trials of our product candidatesazenosertib 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. We may never succeed in obtaining marketing approval for azenosertib, or any future product candidate. The duration, costs and timing of clinical trials and development of our product candidates and any other product candidate we may develop in the future will depend on a variety of factors, including:

Following the strategic restructuring announced in January 2025 for which we expectincurred to incur thecertain associated non-recurring expenses in the first quarter of 2025, we expecthave anrealized initiala 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. 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.

InterestInvestment Incomeand Other Income, Net

InterestInvestment incomeand other income, net consists of interest earned on cash, cash equivalents and available-for-sale marketable securities.securities, sublease income and the change in value of equity securities during the period.

Revenues from licensing and sales of intellectual property for the year ended December 31, 20242025 were $67.4 millionzero compared to zero$67.4 million for the year ended December 31, 2023.2024. The increasedecrease relates to the Immunome License Agreement and related stock issueissuance agreement with Immunome entered during the three months ended March 31, 2024 and the AssetImmunome Purchase Agreement and the related stock issuance agreement with Immunome entered during the three months ended December 31, 2024.

Research and development, or R&D, expenses for the year ended December 31, 20242025 were $167.8$107.3 million, compared to $189.6$167.8 million for the year ended December 31, 2023.2024. The decrease of $21.8$60.5 million was primarily due to adecreases of $22.3 million for clinical expenses, $12.9 million for lab services, $8.8 million for drug manufacturing, and $1.3 million for supplies and other expense. A decrease of $10.7$16.4 million forfrom personnel expense, of which $9.7$6.5 million is related towas non-cash stock-based compensation. Wecompensation, also sawcontributed decreasesto ofthe $5.8overall millionreduction forin clinical, $4.5 million for allocable expensesresearch and $4.3 million for consulting, outside services and otherdevelopment expenses. These decreases were partially offset by increasesan increase of $3.5$1.2 million asfrom a resultone-time ofimpairment changescharge inrecorded coston sharingresearch withand Zentera.development equipment during the first quarter ended March 31, 2025.

General and administrative expenses for the year ended December 31, 20242025 were $87.1$37.7 million, compared to $64.4$87.1 million during the year ended December 31, 2023.2024. The increasedecrease of $22.8$49.4 million was primarily attributabledue to a $27.1decrease of $47.1 million increase related toof personnel expense, of which $22.2$40.8 million is related towas non-cash stock-based compensation. WeDecreases of $3.3 million related to consulting and outside services also sawcontributed anto increasethe ofoverall $3.1reduction millionin for facilitiesgeneral and allocableadministrative expenses. These increasesdecreases were partially offset by decreasesan increase of $4.9$1.0 million forrelated theto operating lease impairment charge during the twelve months ended December 31, 2023, and $2.5 million for outside servicesallocated and other expense.costs.

Goodwill impairment for 2024 of $3.7 million was the result of an impairment test performed in the fourth quarter of 2024. Impairment tests performed in 2023 did not identify any impairment expense.

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, and we have incurred significant operating losses. 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 expenses; however, if our azenosertib development program continues to advance successfully, we expect our expenses to increase as we initiate and execute our Phase 3 confirmatory study and prepare for commercialization.

As a result, we will need to raise substantial additional capital to support our continuing operations and pursue our strategy. Until such time as we can generate significant revenue from product sales, if ever, we plan to finance our operations through the sale of equity, debt financings or other capital sources, which may include collaborations with other companies or other strategic transactions. There are no assurances that we will be successful in obtaining an adequate level of financing as and when needed to finance our operations on terms acceptable to us or at all, particularly in light of the global macroeconomic environment and fluctuating inflation and interest rates. 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 candidatesazenosertib or delay our pursuit of potential in-licenses or acquisitions.

We do not currently have any approved products and have never generated any revenue from product sales. To date, we have financed our operations primarily through the sale of equity securities. From inception through December 31, 2024,2025, we raised a total of $1.2 billion in gross proceeds from the sale of shares of our common stock and convertible preferred units. As of December 31, 2024,2025, we had $33.9$36.0 million in cash and cash equivalents, $318.0$209.9 million in marketable debt securities, $19.2 million in marketable equity securities, and an accumulated deficit of $1.1$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. Market conditions can impact the viability of these institutions. In the event of failure of any of the financial institutions where we maintain our cash and cash equivalents, there can be no assurance that we would be able to access uninsured funds in a timely manner or at all. 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, 2024.2025.

In May 2021, wethe Company entered into a sales agreement, or the Sales Agreement, with SVB Leerink PartnersLLC, LLC,or SVB Leerink, as sales agent,agent (the "Sales Agreement"), pursuant to which wethe 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 athe registrationCompany's statement.Registration Statement on Form S-3 (File No. 333-286122) filed with the SEC on March 26, 2025. Sales of common stock, if any,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 Thethe Nasdaq Global Market or any other existing trading market for ourthe Company's common stock. DuringIn December 2025, the yearCompany endedsold December 31, 2024, we did not sell any3,928,571 shares of common stock under the Sales Agreement.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, 20242025 there was $200.0$69.5 million of our common stock remaining available for sale under our ATM.

We have incurred losses since inception. Net cash used in operating activities for the year ended December 31, 20242025 was $170.9$125.2 million, consisting primarily of our net loss of $165.9$137.1 million as we incurred expenses associated with the restructuring event, research activities for our lead product candidatescandidate and incurred general and administrative expenses, as well as changes in operating assets and liabilities of $16.5$9.1 million, partially offset by non-cash adjustments of $11.5$20.9 million.

We have incurred net losses in almost every reporting period since our inception, we have not generated any revenue from product sales to date, and we have financed our operations principally through private financings, our initial public offering, or IPO, and follow-on public offerings of our common stock. We incurred a net loss of $137.1 million for the year ended December 31, 2025. We had a net loss of $35.4$77.6 million and $48.3$75.2 million for the threesix months ended MarchJune 31,30, 2026 and MarchJune 31,30, 2025, respectively. As of MarchJune 31,30, 2026, we had an accumulated deficit of $1.2$1.3 billion. Our losses have resulted principally from expenses incurred in research and development of our product candidates and from management and administrative costs and other expenses that we have incurred while building our business infrastructure. We expect that it will be several years, if ever, before we have a commercialized product and generate revenue from product sales. Even if we succeed in receiving marketing approval for and commercializing one or more of our product candidates, we expect that we will continue to incur substantial research and development and other expenses as we discover, develop and market additional potential products.

•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 competing clinical trials leading to lower enrollment in our clinical trials, public health emergencies, U.S. and global economic issues, such as rising inflation, or ongoing military conflicts, among other causes;

As of MarchJune 31,30, 2026, we had cash and cash equivalents and marketable securities of $211.8$174.6 million. Based on current business plans, we believe that our existing cash, cash equivalents and marketable securities as of MarchJune 31,30, 2026 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. This estimate is based on assumptions that may prove to be wrong, such as those relating to the timing and anticipated results of our clinical trials, and we could use our available capital resources sooner than we currently expect. Changing circumstances, some of which may be beyond our control, could cause us to consume capital significantly faster than we currently anticipate, and we may need to seek additional funds sooner than planned.

•the data collected from clinical trials of our product candidates may not be sufficient to support the submission of a New Drug Application, or an NDA, or Biologics License Application, or BLA, or other submission or to obtain regulatory approval in the United States or elsewhere;

•subjects choosing an alternative treatment for the indication for which a product candidate is being developed, or participating in competing clinical trials, which could lead to enrollment in our clinical trials being lower than required or taking longer than we have planned;

If we experience delays or difficulties in activating clinical trial sites or the enrollment and/or continuing participation of patients in clinical trials, our clinical development activities could be delayed or otherwise adversely affected.

Patient enrollment is a significant factor in the timing of clinical trials, and the timing of our clinical trials depends, in part, on the speed at which we can activate clinical trial sties and recruit patients to participate in our trials, as well as completion of required follow-up periods. We may not be able to initiate or continue clinical trials for azenosertib and any future product candidates if we or our CROs are unable to identify, contract with or timely activate a sufficient number of clinical trial sites at which to conduct these trials, or are unable to locate and enroll a sufficient number of eligible patients to participate in these trials to each such trial’s conclusion as required by the FDA or ex-U.S. regulatory authorities. Additionally, certain clinical trials for future product candidates may be focused on indications with relatively small patient populations, which may further limit enrollment of eligible patients or may result in slower enrollment than we anticipate. The eligibility criteria of our clinical trials, once established, may further limit the pool of available trial participants.

As is common in the biopharmaceutical industry, in addition to our employees, we engage the services of consultants to assist us in the development of our product candidates. Many of these consultants, and many of our employees, were previously employed at, or may have previously provided or may be currently providing consulting services to, other biopharmaceutical companies including our competitors or potential competitors. We may become subject to claims that we, our employees or a consultant inadvertently or otherwise used or disclosed trade secrets or other information proprietary to their former employers or their former or current clients. Litigation may be necessary to defend against these claims. If we fail in defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel, which could adversely affect our business. Even if we are successful in defending against these claims, litigation could result in substantial costs and be a distraction to our management team and other employees.

As of MarchJune 31,30, 2026, our executive officers and directors, combined with our stockholders who owned more than 5% of our common stock, together with their respective affiliates, owned a significant percentage of our outstanding common stock. As a result, if these stockholders were to choose to act together, they would be able to significantly influence all matters submitted to our stockholders for approval, as well as matters related to our management and affairs. For example, these stockholders may be able to control elections of directors, amendments of our organizational documents or approval of any merger, sale of assets or other major corporate transaction. This may prevent or discourage unsolicited acquisition proposals or offers for our common stock that you may feel are in your best interest as one of our stockholders. The interests of this group of stockholders may not always coincide with your interests or the interests of other stockholders and they may act in a manner that advances their best interests and not necessarily those of other stockholders, including seeking a premium value for their common stock, and might affect the prevailing market price for our common stock.

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. 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. Our Phase 3 ASPENOVA (ZN-c3-020) clinical trial is designed as a confirmatory trial to support conversion to potential full approval, subject to data outcomes. We also believe that azenosertib has broad franchise potential beyond Cyclin E1-positive PROC. We exclusively in-license or solely own worldwide development and commercialization rights to azenosertib.

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. Based on our retrospective, historical analysis utilizing our IHC cutoff, we estimate that approximately 50% of PROC patients overexpress Cyclin E1 protein, which accounts for approximately 21,50020,000 patients on an annual basis in the United States, EU4 (France, Germany, Italy, Spain) and, the United Kingdom,Kingdom and Japan, based on 20242025 estimates. As a result, we believe there is a significant 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. The limited overlap between FRα-high PROC patients and those that have Cyclin E1 overexpression is estimated to be less than 20% of all PROC patients, which highlights the significant unmet need in patients with Cyclin E1-positive PROC.

◦DENALI Part 1b is a fully enrolled single-arm study that evaluated azenosertib monotherapy at 400 mg QD 5:2 (single daily dose on an intermittent schedule of five days on and two days off), in 102 patients with PROC. 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 2025, we announced clinical data from this study.

◦▪DENALI Part 2 is prospectively enrolling PROC patients with Cyclin E1 protein overexpression based on our proprietary IHC cutoff. Part 2 consists of three cohorts across a seamless design that may support accelerated approval in patients with Cyclin E1-positive PROC, pending positive study outcomes and further discussions with the FDA. The study design consists of the following parts:

▪◦Part 2a: Dose confirmation in patients with 1-3 prior lines of therapy, or up to 4 prior lines allowed in prior mirvetuximab treatment in patients with high FRα. Two doses were evaluated, 300mg QD 5:2 and 400mg QD 5:2, with approximately 30 patients enrolled per dose group. In April 2026, we announced that 400mg QD 5:2 was selected as the pivotal monotherapy dose and that recruitment at the 300mg QD 5:2 dose level has been discontinued. All patients enrolled in Part 2a will contribute to the overall safety database submitted to the FDA.

▪◦Part 2b: Enrollment expansion in the same patient population as Part 2a at the selected 400mg QD 5:2 dose up to approximately 100 patients, including patients at that dose in Part 2a. ThisEnrollment in this cohort is currently enrolling.complete.

▪◦Part 2c: Broadening study population, which is expected to include approximately 40 patients previously treated with a taxane-containing regimen for PROC, with 1-4 prior lines of therapy allowed, including prior mirvetuximab in patients with high FRα. This cohort is currently enrolling.

◦▪Part 1: Enrolled patients with PROC treated with azenosertib in combination with one of four chemotherapy regimens: carboplatin, gemcitabine, pegylated liposomal doxorubicin, or paclitaxel. Primary objectives were safety and tolerability, with key secondary objectives including clinical activity assessed by objective response rate, duration of response, and progression-free survival per RECIST v1.1. In AprilMay 2026, we announced that data from MUIR Part 1 focusing on azenosertib in combination with paclitaxel in PROC haveas beenpaclitaxel acceptedis forcommonly presentationused across multiple tumor types, including ovarian cancer. These data are described in the next section below titled “Recent Data and Presentations.” Data from the other combination arms will be presented at thea 2026later American Society for Clinical Oncology (ASCO) Annual Meeting in June 2026.date.

◦▪Part 2: Evaluating azenosertib in combination with bevacizumab as a maintenance regimen (in the first line, or 1L, or second line, or 2L, of treatment) in patients with advanced ovarian, peritoneal, or fallopian tube cancer following platinum-based chemotherapy. The dose escalation portion will determine the recommended dose for azenosertib orally once daily 5 days on, 2 days off in 21-day cycles in combination with bevacizumab 15mg/kg intravenously on Day 1 of each 21-day cycle. The dose expansion portion will evaluate azenosertib at the recommended dose determined from the dose escalation portion in combination with bevacizumab. The dose expansion portion is expected to enroll approximately 40 patients with platinum-sensitive ovarian cancer in 2L who progressed while on a PARP inhibitor for 1L maintenance. The primary objective is safety and tolerability; secondary objectives include preliminary clinical activity of the combination as assessed by progression-free survival for the dose expansion portion. The dose expansion portion is currently open for enrollment.enrolling.

In April 2026 at the AACR Annual Meeting, we presented a poster with preclinical data showing encouraging activity and tolerability of azenosertib combinations in treatment-naïve and ADC-resistant triple-negativetriple negative breast cancer, or TNBC, supporting the potential for pipeline expansion beyond ovarian cancer. At this meeting, we also presented a poster with real-world data demonstrating that Cyclin E1-positive ovarian cancer patients have significantly worse outcomes, independent of CCNE1 gene amplification status, reinforcing the potential for azenosertib to address the unmet need for these patients.

Since inception, we have incurred significant operating losses. Our net losses were $137.1 million for the year ended December 31, 2025. We had net losses of $35.4$77.6 million and $48.3$75.2 million for the threesix months ended MarchJune 31,30, 2026 and MarchJune 31,30, 2025, respectively. We had an accumulated deficit of $1.2$1.3 billion as of MarchJune 31,30, 2026. We expect to continue to incur significant expenses and operating losses for the foreseeable future. We had cash, cash equivalents and marketable securities of $211.8$174.6 million as of MarchJune 31,30, 2026. We believe that our existing cash, cash equivalents and marketable securities as of MarchJune 31,30, 2026 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.

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. Following a corporate restructuring, our wholly owned subsidiary, Zeno Management, Inc., or 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. ZMI has the right to sublicense its rights under the Recurium Agreement, subject to certain conditions. ZMI is required to use commercially reasonable efforts to develop and commercialize at least one product that comprises or contains a compound modulating one of ten specific biological targets and to execute certain development activities.

Under the terms of the Recurium Agreement, ZMI is obligated to make development and regulatory milestone payments, pay royalties on net sales, and make certain sublicensing payments with respect to products that comprise or contain a compound modulating one of ten specific biological targets, including azenosertib. ZMI is obligated to make development and regulatory milestone payments for each such licensed product of up to $44.5 million, which covers the first two indications for which such licensed product receives regulatory approval and includes a $7.0 million milestone payment payableincurred as a result of the commencement of our Phase 3 ASPENOVA clinical trial.trial and paid during the three months ended June 30, 2026. In the event that a licensed product receives regulatory approval in any additional indications beyond the first two, ZMI would be obligated to pay an additional one-time milestone payment for each such approval. In addition, ZMI is obligated to make milestone payments of up to $150,000 for certain licensed products used in animals. ZMI is also obligated to pay royalties on sales of such licensed products at a mid- to high-single digit percentage. In addition, if ZMI chooses to sublicense or assign to any third parties its rights under certain patents exclusively in-licensed under the Recurium Agreement, ZMI must pay to Recurium IP 20% of certain sublicensing income received in connection with such transaction.

Comparison of Three Months Ended MarchJune 31,30, 2026 to Three Months Ended MarchJune 31,30, 2025

Research and development expenses for the three months ended MarchJune 31,30, 2026 were $28.7$35.2 million, compared to $27.2$27.6 million for the three months ended MarchJune 31,30, 2025. The increase of $1.5$7.6 million was primarily due to a $7.0 million milestone payment to Recurium IP Holdings, LLC required as a result of the commencement of our Phase 3 ASPENOVA clinical trial and an increase of $6.8$5.2 million related to clinical expenses and drug manufacturing, including costs associated with advancing the DENALI and ASPENOVA trials. This increase was partially offset by decreasesa decrease of $3.9$4.5 million for personnel expense, of which $1.2$2.1 million was non-cash stock-based compensation, a decrease of $1.2 million related to a one time impairment charge recorded during the quarter ended March 31, 2025, and a decrease of $0.2$0.1 million forrelated to allocated overhead.

General and administrative expenses for the three months ended MarchJune 31,30, 2026 were $9.1$9.2 million, compared to $10.6$8.4 million during the three months ended MarchJune 31,30, 2025. This decreaseincrease of $1.5$0.8 million was primarily attributable to aan decreaseincrease of $2.0$1.7 million infor personnelconsulting expense,and ofoutside whichservices. $1.2This million was non-cash stock-based compensation. The decreaseincrease was partially offset by ana increasedecrease of $0.5$0.9 million relatedfor tonon-cash consulting,stock-based outside services and other allocated costs.compensation.

On January 22, 2025, our Board of Directors approved a strategic restructuring of the Company to support execution of late-stage development for azenosertib, and extend its cash runway beyond a potentially registration-enabling azenosertib data readout from the Company’s DENALI Part 2 study, anticipated byin the endfirst half of 2026.2027. In connection with this strategic restructuring, the Company reduced its workforce by approximately 40%.

Restructuring expenses for the threesix months ended MarchJune 31,30, 2026 were zero, compared to $7.8 million during the threesix months ended MarchJune 31,30, 2025.

Investment and Other Income (Expense),Income, Net

Investment and other income (expense), net was $2.6$4.9 million for the threesix months ended MarchJune 31,30, 2026, compared to $(2.7)$6.5 million for the threesix months ended MarchJune 31,30, 2025. The increasedecrease of $5.3$1.6 million was primarily driven by a decrease of $3.5 million in returns on invested cash and marketable debt securities partially offset by a non-cash recognized loss of $7.0$2.4 million on the mark to market adjustment for equity securities during the threesix months ended MarchJune 31,30, 2025. A gain of $0.5 million on fixed assets sold during the six months ended June 30, 2025 partiallyalso offsetcontributed byto athe decreaseoverall of $1.7 million in returns on invested cash and marketable debt securities.decrease.

We do not currently have any approved products and have never generated any revenue from product sales. To date, we have financed our operations primarily through the sale of equity securities. From inception through MarchJune 31,30, 2026, we raised a total of $1.2 billion in gross proceeds from the sale of shares of our common stock and convertible preferred units. As of MarchJune 31,30, 2026, we had $31.9$24.8 million in cash and cash equivalents, $179.8$149.8 million in marketable debt securities, and an accumulated deficit of $1.2$1.3 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. Market conditions can impact the viability of these institutions. In the event of failure of any of the financial institutions where we maintain our cash and cash equivalents, there can be no assurance that we would be able to access uninsured funds in a timely manner or at all. Any inability to access or delay in accessing these funds could adversely affect our business and financial position. We had no indebtedness as of MarchJune 31,30, 2026.

In May 2021, the Company entered into a sales agreement, or the Sales Agreement, with SVB Leerink Partners 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. 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. 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 MarchJune 31,30, 2026, there was $69.5 million of our common stock remaining available for sale under our ATM.

Net cash used in operating activities for the threesix months ended MarchJune 31,30, 2026 was $33.0$70.2 million, consisting primarily of our net loss of $35.4$77.6 million as we incurred expenses associated with research and development activities for our product candidate and general and administrative activities, andpartially offset by changes in operating assets and liabilities of $0.7$1.0 million,million partially offset byand non-cash adjustments of $3.1$6.4 million.

Net cash used in operating activities for the threesix months ended MarchJune 31,30, 2025 was $32.6$67.3 million, consisting primarily of our net loss of $48.3$75.2 million as we incurred expenses associated with the restructuring event, research and development activities for our product candidates and incurred general and administrative expenses, as well as changes in operating assets and liabilities of $1.8$6.6 million and non-cash adjustments of $13.9$14.4 million.

Net cash provided by investing activities for the threesix months ended MarchJune 31,30, 2026 of $30.0$60.0 million was primarily attributable to proceeds from maturities of marketable securities of $60.0$120.0 million, offset by net investment of excess cash of $30.0$59.9 million.

Net cash provided by investing activities for the threesix months ended MarchJune 31,30, 2025 of $40.5$70.9 million was attributable to proceeds from maturities of marketable securities of $60.0$130.0 million and proceeds from sale of property and equipment of $0.6 million, offset by net investment of excess cash of $19.5$59.7 million.

Net cash used in financing activities for the threesix months ended MarchJune 31,30, 2026 of $1.1 million resulted from cash used for the net-settlement of restricted stock unit vesting of $1.4$1.5 million partially offset by proceeds of $0.3$0.4 million from the issuance of common stock under equity incentive plans .

Net cash provided by financing activities for the threesix months ended MarchJune 31,30, 2025 of $189 thousand was provided from the issuance of common stock under equity incentive plans.

As of MarchJune 31,30, 2026, we have $4.0$4.1 million and $34.7$33.6 million in current and long-term lease liabilities, respectively. We believe that our existing cash, cash equivalents and marketable securities as of MarchJune 31,30, 2026 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.

•the progress, costs and results of our clinical trials and seeking regulatory and marketing authorizations for azenosertib as a treatment 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 and commercialize a companion diagnostic to identify patients with Cyclin E1-positive PROC;