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

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

Our net losses totaled $198.9$80.8 million, $367.3$198.9 million and $282.5$367.3 million for the years ended December 31, 2025, 2024, 2023, and 2022,2023, respectively. As of December 31, 2024,2025, we had an accumulated deficit of $1,531.6$1,612.4 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 equity interests,equity, proceeds from our collaborations, grant funding and debt financing. We are still in the early stages of development ofdeveloping our product candidates, and we have not completed development of any product candidates. We expect to continue to incur significant expenses and increasing operating losses for at least the next several years. We anticipate that our expenses will increase substantiallyyears if and as we:

•progress additionalour PROTACpreclinical proteinprograms, degraderincluding programs into IND- or CTA-enabling studiesARV-6723 and through preclinical development, including our PROTAC KRAS G12Dpan-KRAS degrader program;

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

•addmake operational,decisions financialwith respect to our infrastructure and managementcapabilities, information systems and personnelincluding to support our operations as a public company and our research, product development and future commercialization efforts and support our operations as a public company.;

Our expenses could increase beyond our expectations if we are required by the U.S. Food and Drug Administration, or FDA, the European Medicines Agency, or 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.

We have never generated revenue from product sales. Our ability to generate revenue from product sales and achieve profitability depends on our ability, alone or with collaboration partners, to successfully complete the development of, and obtain the regulatory approvals necessary to commercialize, product candidates we may identify for development. We do not anticipate generating revenues from product sales for the next several years, if ever. We may never succeed in these activities and, even if we do, may never generate revenues that are significant enough to achieve profitability. To become and remain profitable, we must succeed in developing, obtaining marketing approval for and commercializingcommercializing, either alone or with collaboration partners, products that generate significant revenue. This will require us to be successful in a range of challenging activities, including completing preclinical testing and clinical trials of our product candidates, discovering additional product candidates, establishing arrangements with third parties for the manufacture of clinical supplies of our product candidates, obtaining marketing approval for our product candidates and manufacturing, marketing and selling any products for which we may obtain marketing approval.approval, either alone or with collaboration partners.

If one or more of the product candidates that we develop is approved for commercial sale,sale and we decide to commercialize such products ourselves, we anticipate incurring significant costs associated with commercializing any approved product candidate. Even if we are able to generate revenues from the sale of any approved products, we may not become profitable and may need to obtain additional funding to continue operations.

We expect ourto expensescontinue to increaseincur substantiallysignificant expenses in connection with our ongoing activities, particularly as we continue our ongoing and initiate our planned clinical trials of vepdegestrant,ARV-102, ARV-393ARV-806, ARV-393, ARV-027 and ARV-102, in addition to our ongoing bavdegalutamide (ARV-110) clinical trials,vepdegestrant, advance our other oncology programs, including our KRAS G12D program,programs and neurodegenerative programs and other preclinical programs, including ARV-6723 and our pan-KRAS degrader program, continue research and development and initiate additional clinical trials of and potentially seek marketing approval for our lead programs and our other product candidates.candidates and decide to commercialize such products ourselves. In addition,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. However, if we decide to commercialize any other product candidates ourselves, and obtain marketing approval for any of ourthese 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. 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.

We had cash, cash equivalents and marketable securities of approximately $1.0$685.4 billionmillion as of December 31, 2024.2025. WeBased on our current operating plan, we believe that our cash, cash equivalents and marketable securities as of December 31, 20242025 will enable us to fund our planned operating expenses and capital expenditure requirements into 2027.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:

•the progress, scope, costs and results of our ongoing and planned clinical trials forof vepdegestrant,ARV-102, ARV-806, ARV-393, ARV-102,ARV-027 and our ongoing clinical trials for bavdegalutamidevepdegestrant;

•the progress, scope, progress, costs and results of preclinical and clinical development for our other product candidates and development programs, including ARV-6723 and our KRASpan-KRAS G12Ddegrader program;

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

•the costs and timing of future commercialization activities, including product manufacturing, marketing, sales and distribution, for any of our product candidates for which we receive marketing approval and which we choose to commercialize ourselves;

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 our collaborations with Pfizer and Genentech and our out-license of ARV-766luxdegalutamide to Novartis, we do not currently have any committed external source of funds.

Our operations to date have been limited to organizing and staffing our company, business planning, raising capital, conducting discovery and research activities, filing patent applications, identifying potential product candidates, undertaking preclinical studies, establishing arrangements with third parties for the manufacture of initial quantities of our product candidates, conducting Phase 1, Phase 2 and Phase 3 clinical trials for our product candidates, and preparing for commercialization, including by building a commercial infrastructure.commercialization. However, we have not yet demonstrated our ability to successfully complete any clinical trials, obtain marketing approvals, manufacture a commercial scale product, or arrange for a third party to do so on our behalf, or conduct sales, marketing and distribution activities necessary for successful product commercialization.commercialization, or arrange for a third party to do so on our behalf. Consequently, any predictions stockholders make about our future success or viability may not be as accurate as they could be if we had a longer operating history.

In addition, as a business with limited operating experience and no history of revenue-generating commercial activity, we may encounter unforeseen expenses, difficulties, complications, delays and other known and unknown factors. WeIf we choose to commercialize any of our approved products ourselves, we will need to transition at some point from a company with a research and development focus to a company capable of supporting commercial activities. While we have begun to build such a commercial infrastructure, we may not be successful in such a transition.

InIncome, additionsales, use or other tax laws, statutes, rules, or regulations could be enacted or amended at any time, which could affect our business or financial condition, including causing potentially adverse impacts to theour CARESeffective Act,tax asrate, parttax of Congress’s response to the COVID-19 pandemic, economic relief legislation was enacted in 2020liabilities, and 2021 containingcash tax provisions.obligations. TheFor example, the Inflation Reduction Act, or IRA, was also signed into law in August 2022.2022, and the One Big Beautiful Bill Act, or OBBB Act, was signed into law in July 2025. The IRA introduced new tax provisions, including a 1% excise tax imposed on certain stock repurchases by publicly traded corporations. The 1% excise tax generally applies to any acquisition by the publicly traded corporation (or certain of its affiliates) of stock of the publicly traded corporation in exchange for money or other property (other than stock of the corporation itself), subject to acertain de minimis exception.exceptions. Thus, the excise tax could apply to certain transactions that are not traditional stock repurchases. The OBBB Act is not expected to have a material impact on our business or financial condition, however, this could change in the future and we will continue to assess the impact of the OBBB Act on subsequent periods. The recent changes under the OBBB Act include tax rate extensions and changes to the business interest deduction limitation, the expensing of domestic research and development expenditures (in contrast to the continued capitalization and amortization of foreign research and development expenditures), the bonus depreciation deduction rules, and the international tax framework. Regulatory guidance under the TCJA,IRA, the IRA,OBBB Act, and suchother additionaltax-related legislation is and continues to be forthcoming, and such guidance could ultimately increase or lessen the impact of these laws on our business and financial condition. In addition, it is uncertain if and to what extent various states will conform to the TCJA,IRA, the IRA,OBBB Act and additional tax legislation.

As of December 31, 2024,2025, we had $111.0$533.6 million of federal net operating loss carryforwards, $129.0$563.2 million of state and local net operating loss carryforwards, $37.7$44.7 million federal tax credit carryforwards and $22.4$22.3 million of state tax credit carryforwards. To the extent they expire unused, these net operating loss and tax credit carryforwards arising after 2017 will not be available to offset our future income tax liabilities. Federal net operating loss carryforwards may be carried forward indefinitely, but the deductibility of such carryforwards is limited to 80% of our taxable income in the year in which carryforwards are used.

There is also a risk that due to regulatory changes, such as suspensions on the use of net operating losses, or other unforeseen reasons, our existing and any future net operating losses could expire or otherwise become unavailable to offset future income tax liabilities. As described above in “Changes in tax laws or in their implementation or interpretation may adversely affect our business and financial condition,” the TCJA, as amended by the CARES Act, includes changes to U.S. federal tax rates and the rules governing net operating loss carryforwards that may significantly impact our ability to utilize our net operating losses to offset taxable income in the future. In addition, state net operating losses generated in one state cannot be used to offset income generated in another state. For these reasons, even if we attain profitability, we may be unable to use a material portion of our net operating losses and other tax attributes.

Our PROTAC technology platform is still a relatively new technology. Our future success depends on the successful development of this novel therapeutic approach. Prior to the initiation of our Phase 1 clinical trial for bavdegalutamide in 2019, no product candidates that use a chimeric small molecule approach to protein degradation, such as our PROTAC targeted protein degraders, had been tested in humans. No product candidates of this type have been approved in the United States or Europe, and the data underlying the feasibility of developing chimeric small molecule-based therapeutic products is both preliminary and limited. We have not yet succeeded and may not succeed in demonstratingobtaining themarketing efficacy and safety of anyapprovals of our product candidatescandidates. in clinical trials or in obtaining marketing approval thereafter. We have not yet completed a clinical trial of any product candidate and we have not yet completed assessment of the safety of any product candidate in humans. As such, thereThere may be adverse effects from treatment with any of our current or future product candidates that we cannot predict at this time.

We aredo earlynot inhave ourany developmentproduct efforts.candidates that have been approved for commercialization. If we are unable to commercialize our product candidates or experience significant delays in doing so, our business will be materially harmed.

All of our product candidates are in clinical or preclinical development. We are developing vepdegestrant for the treatment of patients with locally advanced or metastatic ER+/HER2- breast cancer, ARV-393, an investigational PROTAC designed to degrade BCL6, ARV-102, an investigational PROTAC designed to degrade the LRRK2 protein, and we plan to file an IND for our KRAS G12D program in 2025. Additional product candidates are still in preclinical development. Our ability to generate revenue from product sales, which we do not expect will occur for several years, if ever, will depend heavily on the successful development and eventual commercialization of one or more of our product candidates. The success of our product candidates will depend on several factors, including the following:

•for products we choose to commercialize ourselves, establishing sales, marketing, market access and distribution capabilities and launching commercial sales of our products, if and when approved, whether alone or in collaboration with others;

•regulators or institutional review boardsIRBs may not authorize us or our investigators to commence a clinical trial or conduct a clinical trial at a prospective trial site;

•our product candidates may have undesirable side effects or other unexpected characteristics, causing us or our investigators, regulators or institutional review boardsIRBs to suspend or terminate the trials;

Further, cancer therapies are sometimes characterized as first-line, second-line, or third-line, and the FDA often approves new therapies initially only for third-line use. When cancer is detected early enough, first-line therapy, usually hormone therapy, surgery, radiation therapy or a combination of these, is sometimes adequate to cure the cancer or prolong life without a cure. Second- and third-line therapies are administered to patients when prior therapy is not effective. Our current clinical trials for vepdegestrant, ARV-393, ARV-102,ARV-393 and bavdegalutamideARV-806 are in both first- and second-line settings. Subsequently, for those products that prove to be sufficiently beneficial, if any, we would expect to seek approval potentially as a first-line therapy, but any product candidates we develop, even if approved, may not be approved for first-line therapy, and, prior to any such approvals, we may have to conduct additional clinical trials.

Further, we do not know whether clinical trials will begin as planned, will need to be restructured or will be completed on schedule, or at all. In addition, if we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies governing clinical trials, our development plans may be impacted. For example, in December 2022, with the passage of FDORA, Congress required sponsors to develop and submit a DAP for each Phase 3 clinical trial or any other “pivotal study” of a new drug or biological product. These plans are meant to encourage the enrollment of more diverse patient populations in late-stage clinical trials of FDA-regulated products. In June 2024, as mandated by FDORA, the FDA issued draft guidance outlining the general requirements for DAPs. Unlike most guidance documents issued by the FDA, the DAP guidance when finalized will have the force of law because FDORA specifically dictates that the form and manner for submission of DAPs are specified in FDA guidance. On January 27, 2025, in response to an Executive Order issued by the President Trump on January 21, 2025, on Diversity, Equity and Inclusion programs, the FDA removed this draft guidance from its website.website; however, they have since been restored with a note that they could in the future be modified or removed. In light of these ongoing actions, there is considerable uncertainty. This action raises questions about the applicability of statutory obligations to submit DAPs and the agency’s current thinking on best practices for clinical development.

Similarly, the regulatory landscape related to clinical trials in the EU recently evolved. The CTR, which was adopted in April 2014 and repeals the EU Clinical Trials Directive, became applicable on January 31, 2022. While the Clinical Trials Directive required a separate clinical trial application to be submitted in each member state, 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 to all member states concerned. If we are not able to fulfill these new requirements, our ability to conduct clinical trials may be delayed or halted.

If serious adverse events,SAEs, undesirable side effects, or unexpected characteristics are identified during the development of any product candidates we may develop, we may need to abandon or limit our further clinical development of those product candidates.

If any product candidates we develop are associated with serious adverse events,SAEs, or undesirable side effects, or have characteristics that are unexpected, we may need to abandon their development or limit development to certain uses or subpopulations in which the adverse events,AEs, undesirable side effects or other characteristics are less prevalent, less severe, or more acceptable from a risk-benefit perspective, any of which would have a material adverse effect on our business, financial condition, results of operations, and prospects. Many product candidates that initially showed promise in early-stage testing for treating cancer or other diseases have later been found to cause side effects that prevented further clinical development of the product candidates or limited their competitiveness in the market. It is impossible to predict when or if any product candidates we may develop will prove safe in humans. There can be no assurance that our PROTAC technology will not cause undesirable side effects.

A potential risk in any protein degradation product is that healthy proteins or proteins not targeted for degradation will be degraded or that the degradation of the targeted protein in itself could cause adverse events, undesirable side effects, or unexpected characteristics. It is possible that healthy proteins or proteins not targeted for degradation could be degraded using our PROTAC technology in any of our ongoing, planned or future clinical studies. There is also the potential risk of delayed adverse eventsAEs following treatment using our PROTAC technology.

The results of preclinical studies may not be predictive of the results of clinical trials, and the results of early-stage clinical trials may not be predictive of the results of the later-stage clinical trials. In addition, initial success in clinical trials may not be indicative of results obtained when such trials are completed. In particular, the small number of patients in our ongoing early clinical trials may make the results of these trials less predictive of the outcome of later clinical trials. For example, even if successful, the results of the ongoing and planned clinical trials of vepdegestrant,ARV-102, ARV-393ARV-806, ARV-393, ARV-027 and ARV-102, and the ongoing clinical trials of bavdegalutamide,vepdegestrant, may not be predictive of the results of any future clinical trials of these product candidates or any of our other product candidates. Moreover, preclinical and clinical data are often susceptible to varying interpretations and analyses, and many companies that have believed their product candidates performed satisfactorily in preclinical studies and clinical trials have nonetheless failed to obtain marketing approval of their products. Our current or future preclinical studies and clinical trials may not ultimately be successful or support further clinical development of any of our product candidates. There is a high failure rate for product candidates proceeding through clinical trials. A number of companies in the pharmaceutical and biotechnology industries have suffered significant setbacks in clinical development even after achieving encouraging results in earlier studies. Any such setbacks in our clinical development could materially harm our business and results of operations.

From time to time, we have published and may in the future publish interim top-line or preliminary data from our clinical trials. Interim data from clinical trials are subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more patient data become available. For example, the initial safety, tolerability, pharmacokineticPK and efficacy data that we have disclosed in connection with our ongoing clinical trials of vepdegestrantARV-102, ARV-806, ARV-393, and bavdegalutamide (ARV-110)vepdegestrant may not be indicative of the full results of those trials obtained upon completion. Preliminary or top-line 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, interim and preliminary data should be viewed with caution until the final data are available. Adverse differences between preliminary or interim data and final data could significantly harm our reputation and business prospects.

We may not be able to initiate or continue clinical trials for our product candidates if we are unable to locate and enroll a sufficient number of eligible patients to participate in these trials as required by the FDA or similar regulatory authorities outside of the United States. In particular, we are conducting and planning several clinical trials of vepdegestrant,ARV-102, ARV-393ARV-806, ARV-393, ARV-027 and ARV-102.vepdegestrant. We cannot predict how difficult it will be to enroll patients for trials in these indications. Therefore, our ability to identify and enroll eligible patients for our clinical trials may be limited or may result in slower enrollment than we anticipate. In addition, some of our competitors have ongoing clinical trials for product candidates that treat the same indications as our product candidates, and patients who would otherwise be eligible for our clinical trials may instead enroll in clinical trials of our competitors’ product candidates. Patient enrollment is affected by other factors including:

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. ForIn example,addition, though we have since out-licensed luxdegalutamide (ARV-766) to Novartis, in 2023, we announced that we planned to prioritize the initiation of a Phase 3 clinical trial with luxdegalutamide (ARV-766) in mCRPC instead of the previously planned Phase 3 clinical trial for bavdegalutamide. Ourour resource allocation decisions may cause us to fail to capitalize on viable commercial products or profitable market opportunities. OurFor spendingexample, onin currentSeptember 2025, we announced that, with Pfizer, we have agreed to jointly select a third party for the commercialization and futurepotential researchfurther development of vepdegestrant instead of commercializing ourselves. Furthermore, our April 2025 and developmentSeptember programs2025 andworkforce product candidates for specific indicationsreductions may not yield any commercially viable products. If we do not accurately evaluate the commercial potential or target market for a particular product candidate, we may relinquish valuable rights to that product candidate through collaboration, licensing, marketing or other royalty arrangements or similar transactions in cases in which it would have been more advantageous forcause us to retainreprioritize soleour developmentportfolio and commercializationevaluate rightsfuture tostrategic such product candidate.decisions.

We are currently conducting clinical trials of vepdegestrant,ARV-102, ARV-393, ARV-102ARV-806, ARV-027 and bavdegalutamide (ARV-110)vepdegestrant and intend to conduct other clinical trials for each of vepdegestrant, ARV-393, ARV-102these and potentially other product candidates,candidates. We may conduct clinical trials in combination with other therapies.therapies, and have conducted combination clinical trials of vepdegestrant and preclinical combination studies of ARV-393. We are planning to initiate enrollment of a combination cohort of ARV-393 with glofitamab in patients with DLBCL in the ongoing Phase 1 clinical trial in the first half of 2026. We did not develop or obtain marketing approval for, nor do we manufacture or sell, any of the currently approved drugs or therapies that we are or may study in combination with vepdegestrant,our ARV-393product or ARV-102.candidates. If the FDA or similar regulatory authorities outside of the United States revoke their approval of the drug or drugs in combination with which we determine to develop vepdegestrant,with ARV-393our product candidates, including ARV-102, ARV-806, ARV-393, ARV-027 or ARV-102,vepdegestrant, we will not be able to market vepdegestrant,our ARV-393product candidates, including ARV-102, ARV-806, ARV-393, ARV-027 or ARV-102vepdegestrant, in combination with such revoked drugs.

If safety or efficacy issues arise with any of these drugs, we could experience significant regulatory delays, and the FDA or similar regulatory authorities outside of the United States may require us to redesign or terminate the applicable clinical trials. If the drugs we use are replaced as the standard of careSOC for the indications we choose for vepdegestrant,ARV-393, ARV-393ARV-102, ARV-806 or ARV-102,vepdegestrant, the FDA or similar regulatory authorities outside of the United States may require us to conduct additional clinical trials. In addition, if manufacturing or other issues result in a shortage of supply of the drugs with which we determine to combine with vepdegestrant,ARV-102, ARV-806, ARV-393, ARV-102,ARV-027 or vepdegestrant, we may not be able to complete clinical development of vepdegestrant,ARV-102, ARV-393ARV-806, ARV-393, ARV-027 or ARV-102vepdegestrant on our current timeline or at all.

Even if vepdegestrant,any ARV-393of our product candidates, including ARV-102, ARV-806, ARV-393, ARV-027 or ARV-102vepdegestrant, were to receive marketing approval or be commercialized for use in combination with other existing drugs, we would continue to be subject to the risks that the FDA or similar regulatory authorities outside of the United States could revoke approval of the drug used in combination with vepdegestrant,our ARV-393product candidates, including ARV-102, ARV-806, ARV-393, ARV-027 or ARV-102vepdegestrant, or that safety, efficacy, manufacturing or supply issues could arise with these existing drugs. Combination therapies are commonly used for the treatment of cancer, and we would be subject to similar risks if we develop any of our other product candidates for use in combination with other drugs or for indications other than cancer. This could result in our own products being removed from the market or being less successful commercially.

We planhave toconducted, conductand may in the future conduct, clinical trials for our product candidates at sites outside the United States, and the FDA may not accept data from trials conducted in such locations.

WeIn planaddition, even where the foreign trial data are not intended to conductserve clinical trials of our product candidates outsideas the Unitedsole States, including our Phase 1 trialsbasis for ARV-102 and ARV-393. Althoughapproval, the FDA maywill not accept the data fromas clinicalsupport trialsfor conductedan outsideapplication for marketing approval unless the Unitedtrial States,satisfies acceptancecertain of these data is subject to conditions imposed by the FDA.conditions. For example, the clinical trial must be well designed and conducted and be performed by qualified investigators in accordance with ethical principles. The trial population must also adequately represent the U.S. population, and the data must be applicable to the U.S. population and U.S. medical practice in ways that the FDA deems clinically meaningful. In addition, while these clinical trials are subject to the applicable local laws, FDA acceptance of the data will depend on its determination that the trials also complied with all applicable U.S. laws and regulations. If the FDA does not accept the data from any trial that we conduct outside the United States, it would likely result in the need for additional trials, which would be costly and time-consuming and couldwould delay or permanently halt our development of the applicable product candidates. Even if the FDA accepted such data, it could require us to modify our planned clinical trials to receive clearance to initiate such trials in the United States or to continue such trials once initiated.

In addition, there areOther risks inherent in conducting international clinical trials inor multipleusing jurisdictions,international insidetrial andsites outside of the United States, such asinclude:

•foreign regulatory requirements, differences in healthcare services, and administrativedifferences requirementsin ofcultural the jurisdiction where the trial is conductedcustoms that could burdenrestrict or limit our ability to conduct our clinical trials;

Our PreclinicalClinical Stage Programs

In addition to the risks included in our Annual Report on Form 10-K for the year ended December 31, 2025,2025 and Quarterly Report on Form 10-Q for the quarter ended March 31, 2026, the following risk may also affect our business:

In the second quarter of 2026, the U.S. Food and Drug Administration, or FDA, approved VEPPANU™ (vepdegestrant) for the treatment of adults with estrogen receptor-positive, or ER+,/human epidermal growth factor receptor 2-negative, or HER2-, estrogen receptor 1, or 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. FDA approval was received in advance of the FDA-assigned Prescription Drug User Fee Act, or PDUFA, date of June 5, 2026.

Our pipeline, which includes an overview of our clinical and preclinical programs, as well as out-licensed programs, is summarized below.

*The agentsagents, other than VEPPANU which has been approved by the FDA, in the pipeline graphic above are currently under investigation; their safety and effectiveness for these investigational uses have not been established.

**Upon submissionhealth of final chronic toxicology data in non-human primates and FDAauthority clearance to proceed with the Phase 1b clinical trial.trials.

•Defined terms used in pipeline graphic: AR, androgen receptor; BCL6, B-cell lymphoma 6; ER+, estrogen receptor positive; ESR1, estrogen receptor 1,1; DLBCL, diffuse large b-cell lymphoma; HER2-, human epidermal growth factor receptor 2-negative,2-negative; HPK1, hematopoietic progenitor kinase 1; HV: healthy volunteers; I-O, immuno-oncology; KRAS, Kirsten rat sarcoma viral oncogene homolog; LRRK2, leucine-rich repeat kinase 2; mCRPC, metastatic castration resistant prostate cancer; mHSPC, metastatic hormone sensitive prostate cancer; NSCLC, non smallnon-small cell lung cancer; NDA, new drug application; NHL, non-Hodgkin lymphoma; polyQ, expanded polyglutamine; PSP, progressive supranuclear palsy; SBMA, spinal bulbarspinal-bulbar muscular atrophy.

•Footnotes included in pipeline graphic: a.1. Includes relapsed/refractory angioimmunoblastic T-cell lymphoma (AITL) and relapsed/refractory mature B cell NHL; b.2. Phase 1/2 combination trials with palbociclib, atirmociclib, abemaciclib, ribociclib, samuraciclib, everolimus.

In addition to the programs above and ourany early-stage collaborations, including with Pfizer and Genentech, Inc. and F. Hoffman-La Roche Ltd., or Genentech,Pfizer, we are conducting exploratory research and development work on multiple other undisclosed targets.

•PSP, where genetic variations in LRRK2 are associated with PSP progression and accelerated time to death. PSP is a primary tau-driven disease, and tau uptake by human neurons requires LRRK2 activity. Additionally, we have published data associating the tau pathology of PSP with LRRK2-mediated endolysosomal dysfunction.dysfunction; and

Based on the data, we plan to continue investigation of ARV-102 in neurodegenerative diseases associated with LRRK2 and endolysosomal dysfunction. We plan to share additional biomarker data from the Phase 1 clinical trial in patients with PD at the International Congress on Parkinson’s Disease and Movement Disorders in the secondfourth halfquarter of 2026.

We submitted an investigational new drug application, or IND, earlier this year for ARV-102 with the intention of initiating a Phase 1b clinical trial in patients with PSP in the U.S. during first half of 2026. Following the 30-day review period, the FDA requested final data from our chronic toxicology studies in non-human primates prior to authorizing the initiation of the Phase 1b clinical trial in the U.S. in patients with PSP.PSP, the FDA requested additional information as well as final data from our chronic toxicology studies in non-human primates, which we recently completed. As a result,result of the FDA’s request, the planned Phase 1b clinical trial, in which we have not yet dosed any patients, is on clinical hold and will not begin until wethe provideFDA thesecompletes dataits toreview and authorizes initiation of the FDA, which we expect will be available in mid-2026. We anticipate the Phase 1b clinical trialtrial. inIn theaddition, U.S. to begin induring the second halfquarter of 2026.2026, we engaged with European and Japanese health authorities on our ARV-102 program in patients with PSP. Our discussions with global health authorities are ongoing. We do not expect thisplan to impactcontinue ourthese plansdiscussions forand, subject to regulatory clearance, we plan to initiate clinical trials in PSPpatients in the EU, and therefore also believe we have the potential to initiate a registrational trial inwith PSP in late 2026, pending regulatory feedback, which we are planning as a global clinical trial.2027. We continue to evaluate development options for ARV-102 in Parkinson's disease.PD.

In the second quarter of 2026, we announced that we had completed dose escalation enrollment of the Phase 1 clinical trial evaluating ARV-806 in patients with solid tumors harboring KRAS G12D mutations. We planare planning to initiatecomplete enrollment in the dose expansion cohort of thethis Phase 1 monotherapy dose escalation clinical trial ofand ARV-806 in patients with solid tumors harboring KRAS G12D mutations. We anticipate sharing initialshare clinical data in patientsthe withsecond solidhalf tumors harboring KRAS G12D mutations inof 2026. In the second quarter of 2026 we also announced that we plan to seek an out-licensing agreement for any additional clinical trials of ARV-806, including dose expansion or combination clinical trials.

Approved Product: VEPPANU™ (vepdegestrant)

VEPPANU™ (vepdegestrant) is an orally bioavailable PROTAC, estrogen receptor degrader approved in the U.S. for use as a monotherapy in 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 therapy. VEPPANU is the first and only FDA-approved PROTAC protein degrader, a type of heterobifunctional protein degrader therapy.

We have been co-developing vepdegestrant with Pfizer, pursuant to a collaboration agreement that we and Pfizer entered into in July 2021. Pursuant to this agreement, we granted Pfizer worldwide co-exclusive rights to develop and commercialize vepdegestrant, which at that time, was an investigational, oral PROTAC estrogen receptor degrader. We and Pfizer remain on track to announce selection of a third party to commercialize VEPPANU.

VERITAC-2 Clinical Trial, VEPPANU™ (vepdegestrant) FDA Approval and Rigel License Agreement

In the first quarter of 2025, we, along with Pfizer, announced positive topline results from the Phase 3 VERITAC-2 clinical trial in the estrogen receptor 1-mutant, or ESR1m, population, and in the second quarter of 2025, we, along with PfizerPfizer, announced detailed results from this clinical trial.

In the clinical trial, vepdegestrant, now approved as VEPPANU™,VEPPANU, demonstrated a statistically significant and clinically meaningful improvement in progression-free survival, or PFS, among ER+/HER2- advanced and metastatic breast cancer patients with an ESR1 mutation, reducing the risk of disease progression or death by 43% compared to fulvestrant, which is administered via an intramuscular injection. The median PFS, as assessed by blinded independent central review, was 5.0 months with VEPPANU versus 2.1 months with fulvestrant. In the clinical trial, VEPPANU was generally well tolerated in the trial,tolerated, with a safety profile consistent with what has been observed in previous studies, and mostly low-grade treatment-emergent adverse events, or TEAEs. The three most common TEAEs observed with VEPPANU were fatigue, increased alanine transaminase, and increased aspartate aminotransferase. Detailed results were presented in a late-breaking oral presentation at the American Society of Clinical Oncology, or ASCO, 2025 Annual Meeting and were highlighted in the ASCO press briefing and selected for Best of ASCO, and were also simultaneously published in the New England Journal of Medicine.

Based on the results from VERITAC-2, in the second quarter of 2025, we and Pfizer submitted an NDA to the FDA for vepdegestrant for the treatment of patients with ER+/HER2- ESR1-mutated advanced or metastatic breast cancer previously treated with endocrine-based therapy. This represented the first NDA submitted for a PROTAC. In the third quarter of 2025, we announced that the FDA accepted the NDA for vepdegestrant and assigned a PDUFA action date of June 5, 2026. In the second quarter of 2026, we announced that the FDA has approved the Company’s 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 and Pfizer entered into the Rigel License Agreement with Rigel for the exclusive global development, manufacturing, and commercialization rights for VEPPANU, which is discussed in greater detail below and in Note 3, Research Collaboration and License Agreements.

ARV-6723 is an investigational,oral preclinical oralinvestigational PROTAC designed to degrade HPK1 in solid malignancies. Preclinically, ARV-6723 has shown potent, selective HPK1 degradation and strong anti-tumor immune responses with superior tumor control in low- and high- immunogenic murine syngeneic tumor models. In solid tumor malignancies, such as NSCLC, melanoma, and renal cell carcinoma, or RCC, HPK1 acts as a negative regulator in T-cell receptor signaling, contributing to T-cell exhaustion and suppressing antitumor immunity. In addition, HPK1 has a regulatory role in other immune cell types that can be co-opted by tumors, thus enabling these cancers to resist immuno-oncology therapy. Degrading HPK1 and thus eliminating both its kinase and scaffolding functions has the potential to unleash an immune response with potent anti-tumor effects and minimum off-target toxicity.

At the AACR Annual Meeting in the second quarter of 20262026, we presented preclinical data that demonstrated greater antitumor activity than SOC ICIs or an investigational HPK1 inhibitor. These preclinical data presented showed that ARV-6723, unlike an inhibitor and the ICIs, reverses T-cell exhaustion, reverses the immunosuppressive microenvironment and boosts innate cell immunity in ICI ICI-(aPD1 and aCTLA4) resistant models. We believe these preclinical results support future investigation of ARV-6723 alone or in combination with other agents in patients with high- or low-immunogenic tumors.

We plan to initiate a Phase 1 clinical trial of ARV-6723 in patients with advanced solid tumors in mid-2026.the third quarter of 2026. Upon initiation of the clinical trial, ARV-6723 will be our first clinical candidate in immuno-oncology. The trial design includes a plan for dose escalation and an expansion combination cohort with pembrolizumab once sufficient monotherapy data are available.

In the second quarter of 2024, we completed a transaction with Novartis Pharma AG, or Novartis, which comprised a license agreement, or the Novartis License Agreement, and an asset agreement, or the Novartis Asset Agreement. Pursuant to the Novartis License Agreement, we granted Novartis an exclusive worldwide license for the development, manufacture and commercialization of luxdegalutamide, and we completed the transition of our ongoing and planned clinical trials of luxdegalutamide to Novartis in the fourth quarter of 2024. Pursuant to the Novartis Asset Agreement, we sold Novartis all of our rights, title and interest in our PROTAC protein degrader targeting AR-V7, a splice variant of the AR.

We commenced operations in 2013. Our operations to date have been limited to organizing and staffing our company, business planning, raising capital, conducting discovery and research activities, filing patent applications, identifying potential product candidates, undertaking preclinical studies and clinical trials, establishing arrangements with third parties for collaborations or licensing arrangements and for the manufacture of initial quantities of our product candidates and preparing for potential commercialization. To date, we have not generated any revenue from product sales and have financed our operations primarily through sales of assets and equity interests, proceeds from our collaborations and a licensing arrangement,arrangements, an asset sale, grant funding and debt financing. Since inception through MarchJune 31,30, 2026, we raised approximately $1.7 billion in gross proceeds from the sale of assets and equity interests and the exercise of stock options and had received an aggregate of $933.1$1.0 millionbillion in payments primarily from collaboration partners and a licensing arrangement.

In the second quarter of 2026, we announced that the FDA has approved 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 endocrine-based therapy. InAlso Septemberin 2025,the second quarter of 2026, we and Pfizer announcedentered ourinto planthe toRigel jointlyLicense selectAgreement awith third partyRigel for the commercializationexclusive global development, manufacturing, and potentialcommercialization furtherrights development of vepdegestrant. We, along with Pfizer, remain on track to announce selection of a third party to commercializefor VEPPANU. We expect that allAll decisions related to pricing, access, reimbursement, sublicense and ex-U.S. regulatory plans for VEPPANU will be determined by Rigel. Our ability to generate revenue from the selectedsale partner.of VEPPANU will be entirely dependent on Rigel, and we may never generate product revenue from the Rigel License Agreement to realize any profits from the out-license of VEPPANU.

We regularly review our operations and make decisions we believe best support our business strategy. In April 2025, as part of our decision to streamline operations across our organization and enable the efficient progression of our portfolio, we committed to and approved a reduction of our workforce by approximately 33% across all areas of our company. The workforce reduction was aimed at reducing internal costs while minimally impacting our targeted clinical stage programs to drive value over the next several years by aligning our operations with long-term program development objectives. The April 2025 workforce reduction was substantially completed by the end of the second quarter of 2025.

In September 2025, we announced an update on our collaboration with Pfizer and further actions to support value creation by optimizing organizational and cost structures and streamlining operations in advance of multiple anticipated upcoming value inflection points, including: further limiting additional expenditures on the vepdegestrant program to support activities required for commercialization readiness and identification, with Pfizer, of a third party for the commercialization and potential further development of vepdegestrant; reducing our workforce by an additional 15% to streamline operations, with the most significant reductions being roles related to vepdegestrant commercialization; and proactively managing pipeline cost by seeking strategic business development opportunities and by identifying further efficiencies across the business. The September 2025 workforce reduction is expected to bewas completed by the second quarter of 2026. Refer to Note 14, Restructuring Activity, in this Quarterly Report on Form 10-Q for further details.

In the first quarter of 2026, we announced the appointment of Randy Teel, Ph.D., as our President, Chief Executive Officer and as a member of our board of directors. Dr. Teel, who previously served as our Chief Business Officer, succeeds John Houston, Ph.D., who is retired from his role as President, Chief Executive Officer, and Chair of Arvinas’our board of directors. Dr. Houston will continue to serve as a member of the Board and has entered into a consulting agreement with us whereby he will provide consulting and advisory services. Briggs Morrison, M.D., our lead independent director, has been elected to serve as Chair of our board of directors. In the second quarter of 2026, we announced that Noah Berkowitz, M.D., Ph.D. would depart from his employment with us as chief medical officer effective July 3, 2026. We have begun a search to find a new chief medical officer to replace Dr. Berkowitz.

As of MarchJune 31,30, 2026, we had cash, cash equivalents and marketable securities of $614.9$567.9 million. We believe the existing cash, cash equivalents and marketable securities on hand will be sufficient to fund our operations into the second half of 2028, which will enable us to execute on multiple data readouts across our programs. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect. See “Liquidity and Capital Resources” below.

To date, we have not generated any revenue from product sales and do not expect to generate any revenue from the sale of products in the near future.future, other than potentially pursuant to the Rigel License Agreement. Our revenues to date have been generated through research collaborations, licensing arrangements and an asset sale. Revenue is recognized ratably over our expected performance period under each agreement.

While we do have one approved product, VEPPANU, asand we announcedhave inentered September 2025, we are planning, with Pfizer, to jointly select a third party forinto the commercializationRigel andLicense potentialAgreement, furtherour development of VEPPANU. Given this, we do not expect to beginability to generate revenue,revenue iffrom any,the until after selectionsale of aVEPPANU thirdwill partybe forentirely dependent on Rigel's performance of its obligations under the commercializationRigel ofLicense VEPPANU.Agreement, Further,and we may never generate product revenue from athe thirdRigel partyLicense agreementAgreement to realize any profits from the out-license of VEPPANU. We and Pfizer remain on track to select a third party, and will not know financial terms until the deal is announced. We expect that allAll decisions related to pricing, access, reimbursement, sublicense and ex-U.S. regulatory plans for VEPPANU will be determined by the selected partner.Rigel.

We expect that any revenue recognized in the near term will be derived primarily from our current collaboration agreements and licensing arrangementarrangements and any additional arrangements that we may enter into in the future. DuringWe received a $20.0 million development milestone during the year ended December 31, 2025, we received a development milestone totaling $20.0 million,2025 pursuant to the terms of the Novartis License Agreement.Agreement and a $50.0 million development milestone during the three months ended June 30, 2026 pursuant to the Original Vepdegestrant (ARV-471) Collaboration Agreement in connection with the FDA’s approval of VEPPANU. To date, no other development, regulatory and commercial milestone payments or royalties have been received under any of our other collaboration agreements or licensing arrangement. However, pursuant to the Vepdegestrant (ARV-471) Collaboration Agreement, the Company will receive $50.0 million as a development milestone payment in connection with the FDA’s approval of VEPPANU, or the Milestone Payment. The Milestone Payment will be offset by certain amounts that the Company will owe to Yale University, or Yale, pursuant to the amended and restated license agreement, dated June 18, 2024, by and between the Company, one of its subsidiaries, and Yale, or the Amended License Agreement.arrangements.