ARVINAS, INC.

Current report

New Risk Factor

Current report

We currently have only one approved product, VEPPANU™ (vepdegestrant), and the success of VEPPANU will depend on our and Pfizer’s ability to identify and successfully execute a commercialization arrangement with a third party and on the terms of any such deal.

Current report

In the second quarter of 2026, we announced that the FDA approved our new drug application for VEPPANU™ (vepdegestrant) for the treatment of adults with ER+/ HER2-, ESR1-mutated advanced or metastatic breast cancer, as detected by an FDA-authorized test, with disease progression following at least one line of endrocrine-based therapy. VEPPANU is the first and only FDA-approved PROteolysis TArgeting Chimera (PROTAC) protein degrader, a type of heterobifunctional protein degrader therapy.

Current report

In the third quarter of 2025, we announced that we and our collaborator, Pfizer, have agreed to jointly select a third party for the commercialization and potential future development of vepdegestrant. In the second quarter of 2026, we announced that, we and Pfizer remain on track to announce selection of a third party to commercialize VEPPANU. We expect that all decisions related to pricing, access, reimbursement, and ex-U.S. regulatory plans for VEPPANU will be determined by the selected partner. We will have no control over these decisions.

Current report

While we believe we are on track to announce selection of a third party, there is no assurance that we actually will be able to identify a suitable partner for VEPPANU or that, if we are able to identify such a partner, we will be able to enter into a definitive agreement with that partner on acceptable terms, or at all, or enter into such an agreement in a timely manner. The failure to enter into a definitive agreement for VEPPANU would significantly delay or prevent the further development and commercialization of VEPPANU. Further, a new partner may not adequately fund or perform its obligations to commercialize or further develop VEPPANU or may not achieve desired results in a timely manner. If we and Pfizer are successful in entering into a strategic relationship with a third party, we would be substantially dependent on the resources and expertise of such third party for the commercialization and further development of VEPPANU.

Current report

The commercial success of VEPPANU will be dependent upon our ability to enter into an agreement, and close any transaction, with a third party. Failure to enter into an agreement or close a transaction or entering into an agreement where the third party does not perform its obligations, may mean that VEPPANU does not enter the market on a timely basis, or at all.

Current report

We have an ongoing collaboration with Pfizer related to vepdegestrant, but have announced that we and Pfizer have agreed to jointly select a third party for the commercialization and potential future development of vepdegestrant. If our collaboration with Pfizer or another party is not successful, we may not be able to capitalize on the market potential of vepdegestrant.

Current report

In July 2021, we entered into a collaboration agreement with Pfizer, or the Vepdegestrant (ARV-471) Collaboration Agreement, pursuant to which we granted Pfizer worldwide co-exclusive rights to develop and commercialize products containing our proprietary compound vepdegestrant, or the Licensed Products. Although pursuant to the terms of the Vepdegestrant (ARV-471) Collaboration Agreement, we and Pfizer share equally (50/50) all development costs, including costs for conducting clinical trials, for the Licensed Products, subject to certain exceptions, our control over the amount and timing of resources that Pfizer dedicates to the development or commercialization of the Licensed Products is limited, including with respect to oversight and management of CMOs, CDMOs and CROs. Our ability to generate revenues from the Vepdegestrant (ARV-471) Collaboration Agreement will depend, in part, on Pfizer’s ability to successfully perform the functions assigned to it in such agreement.

Current report

While our agreement with Pfizer is ongoing, in the third quarter of 2025, we announced that we and Pfizer have agreed to jointly select a third party for the commercialization and potential future development of vepdegestrant, now approved as VEPPANU. We cannot predict the success of our collaboration with Pfizer, or any efforts by Pfizer and us to engage a third party for commercialization of vepdegestrant. We cannot guarantee that our collaboration with Pfizer or the engagement of a third party commercialization partner, if we and Pfizer are successful in doing so, will lead to development or commercialization of the Licensed Products in the most efficient manner or at all. In the second quarter of 2026, we announced that the FDA approved our new drug application for VEPPANU for the treatment of adults with ER+/ HER2-, ESR1-mutated advanced or metastatic breast cancer, as detected by an FDA-authorized test, with disease progression following at least one line of endocrine-based therapy. In the second quarter of 2026, we announced that, we and our collaborator, Pfizer, remain on track to announce selection of a third party to commercialize VEPPANU.

Current report

There is no assurance that we will be able to identify a suitable partner for VEPPANU, or that, if we are able to identify such a partner, we will be able to enter into a definitive agreement with that partner on acceptable terms, or at all, or in a timely manner. The failure to enter into a definitive agreement for VEPPANU would significantly delay or prevent the further development and commercialization of VEPPANU. Further, a new partner may not adequately fund or perform its obligations to commercialize VEPPANU or may not achieve desired results in a timely manner. If we and Pfizer are successful in entering into a strategic relationship with a third party, we would be substantially dependent on the resources and expertise of such third party for the commercialization of VEPPANU.

Current report

We have yet to determine how any potential transaction with a third party commercialization partner will impact us under the existing terms of the Vepdegestrant (ARV-471) Collaboration Agreement. Further, we cannot predict the potential terms of any third party arrangement with respect to the commercialization of vepdegestrant. In addition, Pfizer has a right to terminate the Vepdegestrant (ARV-471) Collaboration Agreement for convenience, subject to certain notice periods. As a result of any of the above, we may not receive any of the $1.4 billion in contingent payments based on specified regulatory and sales-based milestones for the Licensed Products under the Vepdegestrant (ARV-471) Collaboration Agreement.

Previous report

New Risk Factors

Previous report

Our cost savings plan and the associated workforce reductions implemented in April 2025 and September 2025 may not result in anticipated savings, could result in total costs and expenses that are greater than expected and could disrupt our business.

Previous report

In April 2025, we committed to and approved a reduction in our workforce by approximately 33% across all areas of our company, as part of our decision to streamline operations across the organization and enable the efficient progression of our portfolio. In addition, in September 2025, we announced further reductions to our workforce by an additional 15% to streamline operations, with the most significant reductions being roles related to vepdegestrant commercialization. We may not realize, in full or in part, the anticipated benefits, savings and improvements in our cost structure from our cost savings plan and associated workforce reductions due to unforeseen difficulties, delays or unexpected costs. If we are unable to realize the expected operational efficiencies and cost savings from our cost savings plan and associated workforce reductions, our operating results and financial condition would be adversely affected. We also cannot guarantee that we will not have to undertake additional workforce reductions or restructuring activities in the future. Furthermore, our cost savings plan may be disruptive to our operations, including conducting clinical trials and potentially commercializing our product candidates, including vepdegestrant, which could affect our ability to generate product revenue. In addition, our reductions in workforce could yield unanticipated consequences, such as attrition beyond planned staff reductions, or disruptions in our day-to-day operations. Our workforce reductions could also harm our ability to attract and retain qualified management, scientific, clinical, manufacturing and sales and marketing personnel who are critical to our business. Any failure to attract or retain qualified personnel could prevent us from successfully developing and commercializing, if approved, our product candidates, including ARV-102, ARV-393, ARV-806 and vepdegestrant, in the future.

Previous report

Disruptions at the U.S. Food and Drug Administration, or FDA, and other government agencies from funding cuts, personnel losses, regulatory reform, government shutdowns and other developments could hinder our ability to obtain guidance from the FDA regarding our clinical development program and develop and secure approval of our product candidates in a timely manner, which would negatively impact our business.

Previous report

The FDA and comparable regulatory agencies in foreign jurisdictions, such as the European Medicines Agency, or EMA, play an important role in the development of our product candidates by providing guidance on our clinical development programs and reviewing our regulatory submissions, including investigational new drug applications, or INDs, requests for special designations and marketing applications. If these oversight and review activities are disrupted, then correspondingly our ability to develop and secure timely approval of our product candidates could be impacted in a negative manner.

Previous report

For example, the loss and retirement of FDA leadership and personnel could lead to disruptions and delays in FDA guidance, review and approval of our product candidates. Pursuant to President Trump's Executive Order, or E.O., 14210, “Implementing the President’s ‘Department of Government Efficiency’ Workforce Optimization Initiative,” the Secretary of Health and Human Services, or HHS, announced on March 27, 2025, a reorganization and reduction in force, or RIF, across the Department of HHS of approximately 20,000 employees (82,000 to 62,000), with FDA’s workforce of approximately 20,000 to decrease by 3,500 full-time employees. Shortly thereafter, thousands of employees at the FDA were fired on April 1, 2025. Subsequently, the FDA indicated that roughly a quarter of those employees who received RIF notices had been reinstated. On July 14, 2025, following litigation reaching the U.S. Supreme Court, the administration began to carry out these layoffs across HHS, including the FDA. There are also ongoing deliberations within the administration and Congress over potentially substantial proposed cuts to the overall budget for HHS and funding of the FDA for the 2026 federal fiscal year.

Previous report

While the FDA’s review of marketing applications and other activities for new drugs and biologics is largely funded through the user fee program established under the Prescription Drug User Fee Act, or PDUFA, it remains unclear how the administration’s RIF and budget cuts will impact this program and the ability of the FDA to provide guidance and review our product candidates in a timely manner. For example, while the FDA RIF did not reportedly specifically target FDA reviewers, many operations, administrative and policy staff that help support such reviews were affected and those losses could lead to delays in PDUFA reviews and related activities. There has been at least one report in which the FDA failed to meet a PDUFA goal date for approval of an NDA due to heavy workload and limited resources. In addition, while currently unclear, there is a risk that the RIF and budget cutbacks could threaten the integrity of the PDUFA program itself. That is because, for the FDA to obligate user fees collected under PDUFA in the first place, a certain amount of non-user fee appropriations must be spent on the process for the review of applications plus certain other costs during the same fiscal year.

Previous report

Similarly, actions by the U.S. government have significantly disrupted the operations of U.S. government agencies such as the National Institutes of Health, National Science Foundation, Centers for Disease Control and Prevention, and FDA, which have traditionally provided funding for basic research, research and development, and clinical testing. These U.S. government actions have included, among other things, suspending, terminating and withholding of disbursements of funds owed under ongoing contracts, grants, and other financial assistance agreements; declining to continue multi-year research projects for additional annual budget periods; canceling or delaying solicitations for new contract, grant and other financial assistance awards; canceling or delaying proposal evaluation processes and issuance of such new awards; substantially reducing federal agency staff responsible for managing contract and financial assistance programs; eliminating agency information and resources for facilitating research activity; delaying or terminating federal agency procedures for authorizing international transactions; initiating aggressive enforcement actions that may disrupt the operations of major research universities that are significant contributors to life sciences research in the U.S., and threatening access to federal agency contracts and other funding awards based on companies’ otherwise lawful corporate policies and choice of counsel. These U.S. government actions could, directly or indirectly, significantly disrupt, delay, prevent, or increase the costs of our research and product commercialization programs, including our ability to develop new product candidates, conduct clinical trials, implement research collaborations with other companies or institutions, and obtain approvals to market and sell new products.

Previous report

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. Over the last several years, the U.S. government has shut down several times and certain regulatory agencies, such as the FDA and the SEC, have had to furlough critical FDA, SEC and other government employees and stop critical activities. If a prolonged government shutdown occurs, it could significantly impact the ability of the FDA to timely review and process our regulatory submissions and could impact our ability to access the public markets and obtain necessary capital in order to properly capitalize and continue ouroperations.

Previous report

For example, the federal government shut down on October 1, 2025, and as of November 5, 2025, it has not reopened. On October 1, 2025, the FDA issued a public notice stating that agency operations would continue to the extent permitted by law, such as activities necessary to address imminent threats to the safety of human life and activities funded by carryover user fee funds. At the same time, the FDA declared that, during the shutdown period, it does not have legal authority to accept user fees assessed for fiscal year 2026 until a fiscal year 2026 appropriation or continuing resolution for the FDA is enacted. As a result, the FDA will not be able to accept any regulatory submissions for fiscal year 2026 that require a fee payment and that are submitted during the lapse period.

Previous report

Accordingly, if any of the foregoing developments and others impact the ability of the FDA to provide us with guidance regarding our clinical development programs or delay the agency’s review and processing of our regulatory submissions, including INDs and new drug applications or biologic license applications, our business would be negatively impacted. Further, any future government shutdown could impact our ability to access the public markets and obtain necessary capital in order to properly capitalize and continue our operations.

Previous report

Though we may repurchase shares of our common stock pursuant to our share repurchase program, we are not obligated to do so and if we do, we may purchase only a limited number of shares of our common stock.

Previous report

In September 2025, we announced a share repurchase program under which we are authorized to repurchase, in the aggregate, up to$100.0 million of our outstanding common stock. Though in September 2025 we repurchased 2,560,030 shares of our common stock, we are not obligated to acquire any shares of our common stock, and holders of our common stock should not rely on the share repurchase program to increase their liquidity. Our utilization of the share repurchase program depends upon a variety of factors, including the trading price of our common stock, liquidity, securities laws restrictions, tax and other regulatory restrictions, alternative uses of capital, and market and economic conditions. Any share repurchase would be through open market transactions or in privately negotiated transactions, in accordance with applicable securities laws and regulatory limitations. We may reduce or eliminate our share repurchase program in the future. The reduction or elimination of our share repurchase program, particularly if we do not repurchase the full number of shares authorized under the program, could adversely affect the market price of our common stock.

Previous report

We have incurred significant losses since our inception. We expect to incur losses over at least the next several years and may never achieve or maintain profitability.

Previous report

Our net losses totaled $198.9 million, $367.3 million and $282.5 million for the years ended December 31, 2024, 2023, and 2022, respectively. As of December 31, 2024, we had an accumulated deficit of $1,531.6 million. We have historically incurred losses, and expect to continue to incur losses in the future. To date, we have not generated any revenue from product sales and have financed our operations primarily through sales of our assets and equity interests, proceeds from our collaborations, grant funding and debt financing. We are still in the early stages of development of our product candidates, and we have not completed development of any product candidates.

Previous report

Our ability to achieve profitability also depends on our ability to manage our expenses. For example, in April 2025, we committed to and approved a reduction in our workforce by approximately 33% across all areas of our company, as part of our decision to streamline operations across the organization and enable the efficient progression of our portfolio, which workforce reduction was substantially completed by the end of the second quarter of 2025. In addition, in September 2025, we committed to and approved an additional reduction in our workforce of approximately 15% to streamline operations, with the most significant reductions being roles related to vepdegestrant commercialization, which workforce reduction is expected to be substantially completed by the first quarter of 2026. Additionally, the workforce reductions could impact our operations, which could affect our ability to generate future revenue.

Previous report

We expect to continue to incur significant expenses and increasing operating losses for at least the next several years. In addition to any additional costs not currently contemplated due to events associated with or resulting from the workforce reduction noted above, our ability to achieve profitability and our financial position will depend, in part, on the rate of our future expenditures, on product revenue, if any, collaboration revenue, if any, and our ability to obtain additional funding. We expect to continue to incur significant expenses and anticipate that our expenses will increase substantially if and as we:

Previous report

•continue our ongoing and planned clinical trials of our product candidates, including ARV-102, our PROTAC protein degrader designed to target the LRRK2 protein, ARV-393, our PROTAC protein degrader designed to target the BCL6 protein, ARV-806, our PROTAC protein degrader designed to target KRAS G12D for mutated cancers, and vepdegestrant, for the treatment of patients with locally advanced or metastatic ER+/HER2- breast cancer;

Previous report

•progress our preclinical programs, including ARV-027 and ARV-6723;

Previous report

•progress additional PROTAC protein degrader programs into IND- or CTA-enabling studies;

Previous report

•apply our PROTAC Discovery Engine to advance additional product candidates into preclinical and clinical development;

Previous report

•expand the capabilities of our PROTAC Discovery Engine;

Previous report

•utilize our share repurchase program;

Previous report

•make decisions with respect to our personnel, including retention or future hiring of key employees, and establishment of a sales, marketing, market access, and distribution infrastructure to launch commercial sales of our products, if and when approved, whether alone or in collaboration with others;

Previous report

•make decisions with respect to our infrastructure and capabilities, including to support our operations as a public company and our research, product development and future commercialization efforts;

Previous report

•make or maintain arrangements with third-party manufacturers, or establish manufacturing capabilities, for both clinical and commercial supplies of our product candidates; and

Previous report

•expand, maintain and protect our intellectual property portfolio.

Previous report

Our expenses could increase beyond our expectations if we are required by the FDA, EMA, or other regulatory authorities to perform trials in addition to those that we currently expect or anticipate, or if there are any delays in establishing appropriate manufacturing arrangements for or in completing our clinical trials or the development of any of our current or future product candidates.

Previous report

Because of the numerous risks and uncertainties associated with pharmaceutical product development, we are unable to accurately predict the timing or amount of increased expenses we will incur or when, if ever, we will be able to achieve profitability. Even if we do achieve profitability, we may not be able to sustain or increase profitability on a quarterly or annual basis. Our failure to become and remain profitable would depress the value of our company and could impair our ability to raise capital, expand our business, maintain our research and development efforts, diversify our product offerings or even continue our operations. A decline in the value of our company could also cause our stockholders to lose all or part of their investment.

Previous report

We will need substantial additional funding to continue our operations. If we are unable to raise capital when needed, we may be required to delay, limit, reduce or terminate our research or product development programs or future commercialization efforts.

Previous report

We expect our expenses to continue to increase substantially in connection with our ongoing activities, particularly as we continue our ongoing and initiate our planned clinical trials of our product candidates, including ARV-102, ARV-393, ARV-102, ARV-806 and vepdegestrant, advance our other oncology programs and neurodegenerative programs and other preclinical programs, including ARV-027 and ARV-6723, continue research and development and initiate additional clinical trials of and potentially seek marketing approval for our lead programs and our other product candidates. In addition, if we obtain marketing approval for any of our product candidates, we expect to incur significant commercialization expenses related to product manufacturing, marketing, sales and distribution. We continue to incur significant costs associated with operating as a public company. In addition, we will incur certain costs in connection with our reductions in workforce, and may incur additional costs not currently contemplated due to events associated with or resulting from the reductions in workforce and the charge that we expect to incur in connection with the workforce reductions is an estimate and subject to a number of assumptions, and actual results may differ materially. Accordingly, we will need to obtain substantial additional funding in connection with our continuing operations. If we are unable to raise capital when needed or on acceptable terms or not at all, we may be required to delay, limit, reduce or terminate our research, product development programs or any future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.

Previous report

We had cash, cash equivalents and marketable securities totaling approximately $787.6 million as of September 30, 2025. Based on our current operating plan, we believe that our cash, cash equivalents and marketable securities as of September 30, 2025 will enable us to fund our planned operating expenses and capital expenditure requirements into the second half of 2028. We have based this estimate on assumptions that may prove to be wrong, and we could use our capital resources sooner than we currently expect. Our future capital requirements will depend on many factors, including:

Previous report

•the progress, scope, costs and results of our ongoing and planned clinical trials of ARV-102, ARV-393, ARV-806 and vepdegestrant;

Previous report

•the progress, scope, costs and results of preclinical and clinical development for our other product candidates and development programs, including ARV-027 and ARV-6723;

Previous report

•the number of, and development requirements for, other product candidates that we pursue, including our other oncology and neurodegenerative research programs;

Previous report

•the success of our collaborations, including with Pfizer and Genentech;

Previous report

•our utilization of our share repurchase program;

Previous report

•our ability to establish additional collaboration arrangements with other biotechnology or pharmaceutical companies on favorable terms, if at all, or enter into license, marketing and royalty arrangements, and similar transactions for the development or commercialization of our product candidates.

Previous report

Identifying potential product candidates and conducting preclinical testing and clinical trials is a time-consuming, expensive and uncertain process that takes years to complete, and we may never generate the necessary data or results required to obtain marketing approval and achieve product sales. In addition, our product candidates, if approved, may not achieve commercial success. Our commercial revenues, if any, will be derived from sales of products that we do not expect to be commercially available for many years, if at all. Accordingly, we will need to obtain substantial additional funds to achieve our business objectives. Adequate additional funds may not be available to us on acceptable terms, or at all. In addition, we may seek additional capital due to favorable market conditions or strategic considerations, even if we believe we have sufficient funds for our current or future operating plans.

Previous report

Because we have limited financial and managerial resources, we focus on research programs and product candidates that we identify for specific indications. As a result, we may forego or delay pursuit of opportunities with other product candidates or for other indications that later prove to have greater commercial potential. For example, though we have since out-licensed JSC462 (previously luxdegalutamide (ARV-766) to Novartis and completed our clinical trials for bavdegalutamide, in 2023, we announced that we planned to prioritize the initiation of a Phase 3 clinical trial with luxdegalutamide (ARV-766)inmetastatic castration resistant prostate cancer instead of the previously planned Phase 3 clinical trial for bavdegalutamide. In addition, in September 2025, we announced that, with Pfizer, wehave agreed to jointly select a third party for the commercialization and potential further development of vepdegestrant. Our resource allocation decisions may cause us to fail to capitalize on viable commercial products or profitable market opportunities. In addition, our April 2025 and September 2025 workforce reductions may cause us to reprioritize our portfolio and evaluate future strategic decisions.