Investing in our common stock involves a high degree of risk. You should carefully consider the risks and uncertainties discussed in “Part I, Item 1A, Risk Factors,” in our Annual Report on Form 10-K for the year ended December 31, 2025 filed with the U.S. Securities and Exchange Commission, or SEC, on February 24, 2026, together with all of the other information contained in this Quarterly Report on Form 10-Q, including our unaudited condensed consolidated financial statements and the related notes appearing elsewhere in this Quarterly Report on Form 10-Q. New or revised risk factors can emerge from time to time, and it is not possible to predict the impact that any factor or combination of factors may have on our business, prospects, financial condition and results of operations. The risk factor disclosures in our Annual Report on Form 10-K for the year ended December 31, 2025 are qualified by the information that is described in this Quarterly Report on Form 10-Q. If any of the risks in our Annual Report on Form 10-K for the year ended December 31, 2025 actually occur, our business, prospects, operating results and financial condition could suffer materially. In such an event, the trading price of our common stock could decline and you might lose all or part of your investment. The new and revised risks described below and the risks described in our Annual Report on Form 10-K for the year ended December 31, 2025 are not our only risks. Additional risks and uncertainties not currently known to us or that we currently deem to be immaterial also may materially adversely affect our business, financial condition or future results. Amended Risk Factors The risks listed below, versions of which were included in our Annual Report on Form 10-K for the year ended December 31, 2025 and Quarterly Report on Form 10-Q for the quarter ended March 31, 2026, are replaced in their entirety by the following. We and Pfizer entered into the Rigel License Agreement for the commercialization and future development of VEPPANU™ (vepdegestrant), which is currently our only approved product. The success of VEPPANU will be entirely dependent on Rigel's performance of its obligations under the Rigel License Agreement. In July 2021, we entered into a collaboration agreement with Pfizer, or the Original 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. Pursuant to the terms of the Original Vepdegestrant (ARV-471) Collaboration Agreement, we and Pfizer shared 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 dedicated to the development or commercialization of the Licensed Products was limited, including with respect to oversight and management of CMOs, CDMOs and CROs. In the second quarter of 2026, we announced that the FDA granted approval 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. VEPPANU is the first and only FDA-approved PROTAC protein degrader, a type of heterobifunctional protein degrader therapy. Also in the second quarter of 2026, we, Pfizer and Rigel entered into the Rigel License Agreement for the exclusive global development, manufacturing, and commercialization rights for VEPPANU. Under the terms of the Rigel License Agreement, Rigel is responsible for the launch and commercialization of VEPPANU in the U.S. and will own global rights with the ability to sublicense to potential partners to further develop and commercialize VEPPANU outside of the U.S. We and Pfizer will be entitled to a percentage of sublicensing 47 Table of Contents revenue generated outside the U.S. All decisions related to pricing, access, reimbursement, sublicense and ex-U.S. regulatory plans for VEPPANU will be determined by Rigel. We will have no control over these decisions. We are entirely dependent on the resources and expertise of Rigel for the commercialization and further development of VEPPANU. Rigel may not adequately fund or perform its obligations to commercialize VEPPANU or may not achieve desired results in a timely manner. Rigel not performing its obligations under the Rigel License Agreement may mean that VEPPANU does not enter the market on a timely basis, or at all, and could mean that we and Pfizer do not receive any milestone or royalty payments under the Rigel License Agreement, which may adversely impact our business operations. We currently depend, and expect to continue to depend, on collaborations, license arrangements, and other strategic alliances with third parties for the research, development, and the potential future commercialization of certain of the product candidates we may develop. If any such collaborations are not successful, we may not be able to capitalize on the market potential of those product candidates. We have in the past entered into, and anticipate in the future seeking additional, third-party collaborators for the research, development, and potential future commercialization of some of our PROTAC programs. For example, in September 2015 we entered into a research collaboration with Genentech, which we amended and restated in November 2017, and which will terminate in August 2026; in December 2017 we entered into a research collaboration with Pfizer, for which the research program term has concluded; in July 2021 we entered into a development and commercialization collaboration with Pfizer, and in May 2026 we, Pfizer and Rigel entered into the Rigel License Agreement pursuant to which Rigel will be responsible for the commercialization and development of VEPPANU; and in April 2024 we entered into an out-license agreement with Novartis for luxdegalutamide (ARV-766). Rigel may not adequately fund or perform its obligations to commercialize VEPPANU or may not achieve desired results in a timely manner. We are entirely dependent on the resources and expertise of Rigel for the commercialization of VEPPANU. Failure of Rigel to perform its obligations under the Rigel License Agreement may mean that VEPPANU does not enter the market on a timely basis, or at all. In addition, Novartis may not adequately fund or perform its obligations under the Novartis License Agreement and we are entirely dependent on the resources and expertise of Novartis for the development and potential commercialization of luxdegalutamide (ARV-766). Failure of Novartis to perform its obligations under the Novartis License Agreement may mean that luxdegalutamide (ARV-766) does not continue in its development or reach commercialization on a timely basis, or at all. Our likely collaborators for any other collaboration arrangements include large and mid-size pharmaceutical companies and biotechnology companies. Any such arrangements with third parties will likely limit our control over the amount and timing of resources that our collaborators dedicate to the development or commercialization of any product candidates we may seek to develop with them. Our ability to generate revenues from these arrangements will depend on our collaborators’ abilities to successfully perform the functions assigned to them in these arrangements. We are unable to predict when, if ever, we will enter into any additional strategic collaborations because of the numerous risks and uncertainties associated with establishing them, and we cannot predict the success of any collaboration that we enter into. We may enter into strategic collaborations that we subsequently no longer wish to pursue, and we may not be able to negotiate strategic collaborations on acceptable terms, or at all. At the current time, we cannot predict what form any future strategic collaboration might take, and we are likely to face significant competition in seeking appropriate strategic collaborators, and strategic collaborations can be complicated and time consuming to negotiate and document. Any collaborations or license agreements involving our research programs or any product candidates we may develop, including our out-licenses to Novartis and Rigel, pose the following risks to us: •Collaborators and licensees have significant discretion in determining the efforts and resources that they will apply to these collaborations or licenses. For example, our research collaboration with Pfizer is managed by a joint research committee composed of an equal number of representatives from us and our respective collaborative partners, with the collaborative partner having final decision-making authority. In addition, following our out-license of luxdegalutamide (ARV-766) to Novartis, Novartis is responsible for worldwide clinical development and commercialization of ARV-766 and therefore has full decision-making authority with respect to the luxdegalutamide (ARV-766) program. Following our out-license of VEPPANU to Rigel pursuant to the Rigel License 48 Table of Contents Agreement, Rigel is solely responsible for commercialization and development of VEPPANU and has full decision-making authority with respect to the program. •Collaborators or licensees may not pursue development and commercialization of any product candidates we may develop or may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in the collaborator’s or licensee's strategic focus or available funding or external factors such as an acquisition or business combination that diverts resources or creates competing priorities. •Collaborators have broad rights to select any target for protein degradation development on an exclusive basis, even as to us, so long as not excluded by us under the terms of each collaboration and may select targets we are considering but have not taken sufficient action to exclude under the collaboration. •Collaborators and licensees may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a product candidate, repeat or conduct new clinical trials, or require a new formulation of a product candidate for clinical testing. •Collaborators and licensees could independently develop, or develop with third parties, products that compete directly or indirectly with our products or product candidates if the collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours. •Collaborators with marketing and distribution rights to one or more products may not commit sufficient resources to the marketing and distribution of such product or products. •Collaborators and licensees may not properly obtain, maintain, enforce, or defend our intellectual property or proprietary rights or may use our proprietary information in such a way that could jeopardize or invalidate our proprietary information or expose us to potential litigation. For example, Pfizer, Genentech, Novartis and Rigel have had, or have, the first right to enforce or defend certain intellectual property rights under the applicable collaboration arrangement or license agreement with respect to particular licensed programs, and although we may have the right to assume the enforcement and defense of such intellectual property rights if the collaborator does not, our ability to do so may be compromised by their actions. •Disputes may arise between the collaborators or licensees and us that result in the delay or termination of the research, development, or commercialization of our products or product candidates or that result in costly litigation or arbitration that diverts management attention and resources. •We may lose certain valuable rights under circumstances identified in our collaborations and licenses, including if we undergo a change of control. •Collaborations and licenses may be terminated and, if terminated, may result in a need for additional capital to pursue further development or commercialization of the applicable product candidates. For example, Genentech provided notice of termination in June 2026 and the Restated Genentech Agreement will therefore terminate in August 2026. Additionally, the research term under the Pfizer Collaboration Agreement has ended. Novartis may terminate its agreement with us upon our material breach or for convenience or upon a safety or regulatory issue, subject to specified notice periods. Rigel may terminate its agreement with us and Pfizer upon material breach of us and/or Pfizer or upon a certain prior written notice period, following a pre-defined period of time. •Collaboration or license agreements may not lead to development or commercialization of product candidates in the most efficient manner or at all. If a present or future collaborator or licensee of ours were to be involved in a business combination, the continued pursuit and emphasis on our product development or commercialization program under such collaboration or license could be delayed, diminished, or terminated. If our collaborations and licenses do not result in the successful development and commercialization of products, or if one of our collaborators or licensees terminates its agreement with us, we may not receive any future research funding or milestone or royalty payments under the collaboration or license, as appropriate. If we do not receive the funding we expect under these agreements, our development of product candidates could be delayed, and we may need additional resources to develop product candidates. In addition, if one of our 49 Table of Contents collaborators or licensees terminates its agreement with us, we may find it more difficult to find a suitable replacement collaborator or licensee or attract new collaborators or licensees, and our development programs may be delayed or the perception of us in the business and financial communities could be adversely affected. All of the risks relating to product development, marketing approval, and commercialization described in our Annual Report on Form 10-K for the year ended December 31, 2025, apply to the activities of our collaborators. We may seek to establish additional collaborations or out-license the development of our product candidates. If we are not able to establish collaborations or enter into these out-licenses on commercially reasonable terms, we may have to alter our business development plans or product development and commercialization plans. To realize the full potential of our PROTAC Discovery Engine and accelerate the development of our PROTAC programs, we plan to continue to selectively pursue collaborations with companies with particular experience, including development and commercial expertise and capabilities. For example, in the third quarter of 2025, we announced that we and Pfizer were seeking a third party collaborator for the commercialization and potential future development of vepdegestrant, and we entered into the Rigel License Agreement in May 2026. In addition, in the second quarter of 2026, we announced that we are planning to seek an out-licensing agreement for any additional clinical trials, including dose expansion or combination clinical trials, for ARV-806. We face significant competition in attracting appropriate collaborators to advance the development of any product candidates for which we may seek a collaboration. We also may choose to out-license product candidates at any time. Whether we reach a definitive agreement for a collaboration or out-license will depend, among other things, upon our assessment of the potential collaborator’s or licensee's resources and expertise, the terms and conditions of the proposed collaboration or license, and the proposed collaborator’s or licensee's evaluation of a number of factors. Those factors may include the design or results of clinical trials, the likelihood of approval by the FDA or other regulatory authorities, the potential market for the subject product candidate, the costs and complexities of manufacturing and delivering such product candidate to patients, the potential of competing products, the existence of uncertainty with respect to our ownership of technology, which can exist if there is a challenge to such ownership without regard to the merits of the challenge, the terms of any existing collaboration or license agreements, and industry and market conditions generally. The collaborator or licensee may also have the opportunity to collaborate on other product candidates or technologies for similar indications and will have to evaluate whether such a collaboration could be more attractive than one with us. Collaborations and licenses are complex and time-consuming to negotiate, document and execute. In addition, consolidation among large pharmaceutical companies has reduced the number of potential future collaborators. Our existing collaboration and license agreements limit our ability to enter into future agreements on certain terms with potential collaborators. For example, we previously granted exclusive rights to Genentech and Pfizer for the discovery, development and commercialization of PROTAC targeted protein degraders directed to certain protein targets, and during the terms of those agreements, we are restricted from granting rights to other parties to use our PROTAC technology for those targets. The agreement with Genentech will terminate in August 2026, and the research program term under the research collaboration agreement with Pfizer has concluded. In addition, we granted an exclusive worldwide license for the development, manufacture and commercialization of luxdegalutamide (ARV-766) to Novartis and during the term of the Novartis License Agreement, are restricted from granting rights to other parties related to luxdegalutamide (ARV-766). We also granted an exclusive license for the global development, manufacturing, and commercialization rights for VEPPANU to Rigel, and during the term of the Rigel Agreement, we are restricted from granting rights to other parties related to VEPPANU. Any collaboration or license we enter into may limit our ability to enter into future agreements on particular terms or covering similar target indications with other potential collaborators or licensees We may not be able to negotiate collaborations or licenses on a timely basis, on acceptable terms or at all. If we are unable to do so, we may have to curtail the development of the product candidate for which we are seeking to collaborate or license, reduce or delay its development program or one or more of our other development programs, delay its potential commercialization or reduce the scope of any sales or marketing activities, or increase our expenditures and undertake development or commercialization activities at our own expense. If we elect to fund development or commercialization activities on our own, we may need to obtain additional capital, which may not be available to us on acceptable terms or at all. If we do not have sufficient funds, we may not be able to further develop our product candidates or bring them to market and generate 50 Table of Contents revenue from product sales, which could have an adverse effect on our business, prospects, financial condition and results of operations. Raising additional capital may cause dilution to our stockholders, restrict our operations or require us to relinquish rights to our technologies or product candidates. Until such time, if ever, as we can generate substantial revenue from product sales, we expect to finance our cash needs through a combination of equity offerings, debt financings, collaborations, strategic alliances and marketing, distribution or licensing arrangements. Although we may receive potential future payments under any collaboration and our out-licenses of luxdegalutamide to Novartis and VEPPANU to Rigel, we do not currently have any committed external source of funds. To the extent that we raise additional capital through the sale of equity or convertible debt securities, our stockholders’ ownership interests will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect our stockholders’ rights as common stockholders. Debt financing and equity financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making acquisitions or capital expenditures or declaring dividends. If we raise additional funds through collaborations, strategic alliances or marketing, distribution or licensing arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs or product candidates or grant licenses on terms that may not be acceptable or favorable to us. New Risk Factor In addition to the risks included in our Annual Report on Form 10-K for the year ended December 31, 2025 and Quarterly Report on Form 10-Q for the quarter ended March 31, 2026, the following risk may also affect our business: Issues relating to the use of artificial intelligence and machine learning could adversely affect our business and operating results. As part of our continuous effort to be innovative and increase efficiency throughout our business, we have incorporated artificial intelligence (“AI”) and machine learning solutions in applications that are important to our operations and our drug discovery processes, including our PROTAC Discovery Engine, which is an interlocking suite of tools and expertise that assists with our goal of creating and advancing our programs. Specifically, we have deployed AI and machine learning tools in the prediction of preclinical pharmacokinetic properties to find drug-like PROTACs early in the discovery process, structural biology modeling, and ligand identification. While AI and machine learning present opportunities for enhanced productivity and innovation, they also introduce cybersecurity, data privacy, information technology (“IT”), intellectual property, regulatory, legal, operational, competitive, reputational and other risks that could adversely impact our business. Specifically, risks related to AI hallucinations, rogue AI agent behaviors, targeted attacks (including model poisoning or data poisoning), misinformation, data leakage, bias, discrimination, harmful content, fraud, scams, surveillance, inequality, environmental harms, and other harms may flow from our development, use, or deployment of AI or machine learning technologies. If the data used to train AI or the content, analyses, or recommendations that AI applications assist in producing are or are alleged to be deficient, inaccurate, incomplete, overbroad or biased, our business, financial condition, and results of operations may be adversely affected. The rapid evolution of AI will require the application of significant resources to help ensure that AI is implemented in accordance with applicable laws and regulations and in a socially responsible manner and to minimize any real or perceived unintended harmful impacts. The use of certain AI technology can give rise to intellectual property risks, including compromises to proprietary intellectual property and intellectual property infringement. There can be no assurance that any governance and control mechanisms that we implement will adequately prevent or mitigate the adverse effects that the integration and use of AI may have on our business, financial condition, and results of operations. The evolving regulatory landscape surrounding AI also poses a risk, as new laws and regulations could impose additional compliance burdens, resulting in increased operational costs to comply with U.S. and non- 51 Table of Contents U.S. laws concerning the use of AI. We expect to see increasing regulation related to AI use and ethics, which may also significantly increase the burden and cost of research, development and compliance in this area. For example, the EU’s Artificial Intelligence Act (“AI Act”) entered into force on August 1, 2024, and, with some exceptions, will become fully effective in August 2026. As enacted, the AI Act imposes significant obligations on providers and deployers of high-risk AI systems and general purpose AI models and encourages providers and deployers to account for EU ethical principles when developing and using AI technology. In the United States, the regulatory environment is complex and uncertain. Over the past year, states have advanced, and in some cases passed, dozens of laws focusing on AI governance and regulation, including on deployment of AI in healthcare settings. At the federal level, although there is no comprehensive federal AI status, the current administration has endorsed a federal moratorium on the enforcement of state AI laws, including through a December 11, 2025, executive order on “Ensuring a National Policy Framework for Artificial Intelligence” and related National Policy Framework for Artificial Intelligence released on March 20, 2026. So far, these efforts have not been successful at curtailing state action on AI regulation, contributing to a complicated legislative patchwork, which may be litigated in state and federal courts. Various federal and state regulators have also issued guidance and focused enforcement efforts on the use of AI in regulated sectors, such as healthcare. The FDA, for example, issued guidance on the use of AI in regulatory decision-making for drug and biological products that centers on the context of use while establishing a credibility assessment framework for establishing and evaluating AI model outputs intended to support regulatory decision-making. If we develop or use AI systems that are governed by these laws or regulations, including as informed by regulatory guidance, we will need to meet higher standards of data quality, transparency, and human oversight, as well as adhering to specific and potentially burdensome and costly ethical, accountability, and administrative requirements. We may also be subject to significant enforcement or litigation in the event of any perceived non-compliance. In addition, our vendors may in turn incorporate AI tools into their offerings, and the providers of these AI tools may not meet existing or rapidly evolving regulatory or industry standards, including with respect to privacy and data security. Further, bad actors around the world use increasingly sophisticated methods, including the use of AI, to engage in illegal activities involving the theft and misuse of personal information, confidential information and intellectual property. In addition, the use of generative AI models in our internal or third-party systems may create new attack surfaces or methods for adversaries, which could impact us and our vendors. The integration of AI systems, by us or by our vendors, may increase cybersecurity risk. Any of these effects could damage our reputation, result in the loss of valuable property and information, cause us to breach applicable laws and regulations, and adversely impact our business.