Reimbursement

Sales of our ~~principal~~ products are dependent on the availability and extent of coverage and reimbursement from third-party payers. In many markets around the world, these payers, including government health systems, private health insurers and other organizations, remain focused on reducing the cost of healthcare; and their efforts have intensified, in part, as a result of uncertain macroeconomic conditions, rising healthcare costs ~~economic~~and pressures ~~and broader challenges generated by the COVID-19 pandemic.~~on healthcare budgets. Drugs remain heavily scrutinized for cost containment. As a result, payers are becoming more restrictive regarding the use of biopharmaceutical products and are scrutinizing the prices of these products while requiring a higher level of clinical evidence to support the benefits such products bring to patients and the broader healthcare system.These pressures become intensified when our products become subject to competition, including from biosimilars.

In the United States, healthcare providers and other entities such as pharmacies and PBMs are reimbursed for covered services and products they deliver through both private-payer and government healthcare programs such as Medicare and Medicaid. We provide negotiated rebates to healthcare providers, private payers, government payers and PBMs. In addition, we are required to (i) provide rebates or discounts on our products that are reimbursed through certain government programs, including Medicare and Medicaid, and (ii) provide discounts to qualifying healthcare providers under the federal 340B Drug Pricing Program.

Both private and some government payers use formularies to manage access to and utilization of drugs. A drug’s inclusion and favorable positioning on a formulary are essential to ensure patients have access to a particular drug. Even when access is available, some patients abandon their prescriptions for economic reasons. Payers continue to institute cost reduction and containment measures that lower drug utilization and/or spending altogether and/or shift a greater portion of the costs to patients. Such measures include, but are not limited to, more-limited benefit plan designs, higher patient co-pays or coinsurance obligations, limitations on patients’ use of commercial manufacturer co-pay payment assistance programs (including through co-pay accumulator adjustment or maximization programs), stricter utilization management criteria (such as prior authorization and step therapy) before a patient may get access to a drug, higher-tier formulary placement that increases the level of patient out-of-pocket costs and formulary exclusion, which effectively encourages patients and providers to seek alternative treatments or pay 100% of the cost of a drug. The use of such measures by PBMs and insurers has continued to intensify and has thereby limited Amgen product usage and sales. Furthermore, during the past few years, many PBMs and insurers have consolidated, resulting in a smaller number of PBMs and insurers overseeing a large portion of total covered lives in the United States. As a result, PBMs and insurers have greater market power and negotiating leverage to mandate stricter utilization criteria and/or exclude drugs from their formularies in favor of competitor drugs or alternative treatments. In highly competitive treatment markets such as the markets for ENBREL, Otezla, Repatha and Aimovig, PBMs are also able to exert negotiating leverage by requiring incremental rebates from manufacturers in order for them to gain and/or maintain their formulary position.

In addition to market actions taken by private and government payers in the United States, policy makers in both of the major U.S. political parties ~~are pursuing~~have supported policies to lower drug costs. Potential policies cover a wide range of areas, including allowing the importation of drugs from other countries; instituting IRP schemes, which would set the prices of certain drugs based on those available in other countries; implementing policies that in effect would require manufacturers to accept government-set prices for certain drugs, with price ceilings based on a domestic reference-pricing scheme; redesigning the Medicare Part D benefit so as to establish a cap on patient out-of-pocket costs, paired with new requirements that manufacturers cover a share of the costs of Part D drugs; stipulating penalties if drug price benchmarks rise faster than inflation; increasing transparency in drug pricing; and using third-party value assessments to determine drug prices. Examples of such policies include, but are not limited to, the previous Administration’s November 2020 interim final rule, which attempts to institute an MFN IRP model in Medicare Part B and a final rule instituting rebate reform in Medicare Part D. Both of the resulting rules are being challenged in court and have not yet been implemented. Further, although CMS withdrew the MFN IRP, policy makers continue to express strong interest in policies to address drug pricing. See Item 1A. Risk Factors—Our sales depend on coverage and reimbursement from government and commercial third-party payers, and pricing and reimbursement pressures have affected, and are likely to continue to affect, our profitability. Although the IRA was enacted in August 2022, the environment remains dynamic, and the Administration and Congress continues to consider drug pricing legislation. The IRA includes provisions requiring that beginning on January 1, 2026, mandatory price setting be introduced in Medicare for certain drugs paid for under Parts B and D, whereby manufacturers must accept a price established by the government or face penalties on all U.S. sales (starting with 10 drugs in 2026, adding 15 in 2027 and 2028, and adding 20 in 2029 and subsequent years such that by 2031 approximately 100 drugs could be subject to such set prices). In August 2023, ENBREL, a product in which the rights to the BLA are held by our wholly owned subsidiary Immunex Corporation, was selected for the first round of 10 drugs subject to price setting that will be applicable beginning January 1, 2026. As of January 1, 2024, Medicare Part D has been redesigned to cap beneficiary out-of-pocket costs and, beginning January 1, 2025, Federal reinsurance will be reduced in the catastrophic phase (resulting in a shift and increase of such costs to Part D plans and manufacturers, including by requiring manufacturer discounts on certain drugs). Further, beginning October 1, 2022, manufacturers owe rebates on drugs reimbursed under Medicare Part D if price increases outpace inflation, and beginning January 1, 2023, owe rebates on drugs reimbursed under Medicare Part B if price increases outpace inflation.

Other potential policies cover a wide range of areas, including allowing the importation of drugs from other countries; increasing transparency in drug pricing; using third-party value assessments to determine drug prices; and changes to government rebate programs. For example, on January 5, 2024, the FDA authorized Florida to move forward with its importation program proposal, which excludes biologics. The Infrastructure Investment and Jobs Act, signed into law on November 15, 2021, ~~delays implementation of the rebate reform rule until 2026 and~~ requires manufacturers of certain Part B–covered drugs packaged in single-use containers to give refunds to the government starting in 2023 for discarded amounts. ~~Although~~CMS also issued a proposed Medicaid Drug Rebate Program rule that, if finalized, would require manufacturers to aggregate or “stack” all rebates, discounts or other price concessions made to separate, unrelated entities across the ~~direction~~pharmaceutical supply chain on a given unit of ~~drug-pricing-policy reforms remains unclear~~product to determine the “Best Price,” a

metric that is used to determine Medicaid rebates and 340B statutory rates. Further, at ~~this time, Congress is continuing~~the state level, seven states (Colorado, Maine, New Hampshire, Maryland, Minnesota, Oregon and Washington) have enacted laws that establish PDABs to ~~consider prescription-drug-pricing reforms, including legislative proposals~~identify drugs that pose affordability challenges, and in four states (Colorado, Maryland, Minnesota and Washington) include authority for ~~a number of~~ the ~~concepts discussed above (including a full repeal of the prior Administration’s Part D rebate reform rule).~~state PDAB to set upper payment limits on certain drugs for in-state patients, payers, and providers.

In many countries other than the United States, government-sponsored healthcare systems are the primary payers for drugs and biologics. With increasing budgetary constraints and/or difficulty in understanding the value of medicines, governments and payers in many countries are applying a variety of measures to exert downward price pressure. These measures can include mandatory price controls, price referencing, therapeutic-reference pricing, increases in mandates, incentives for generic substitution and biosimilar usage and government-mandated price cuts. In this regard, many countries have health technology assessment organizations that use formal economic metrics such as cost-effectiveness to determine prices, coverage and reimbursement of new therapies; and these organizations are expanding in both established and emerging markets. Many countries also limit coverage to populations narrower than those specified on our product labels or impose volume caps to limit utilization. We expect that countries will continue taking aggressive actions to seek to reduce expenditures on drugs and biologics. Similarly, fiscal constraints may also affect the extent to which countries are willing to approve new and innovative therapies and/or allow access to new technologies. The EU is currently undergoing a review and possible revision of its pharmaceutical legislation. Various proposals are now being considered with a possible first reading in the EU Parliament in the first quarter of 2024, with full implementation not expected until 2027 or possibly later. The new legislation, ~~scheduled~~if implemented, will likely have a significant impact on the landscape for access and pricing decisions within Member States. There are both positive and negative aspects to ~~conclude at~~ the ~~end 2022. There is a risk that this review will lead to~~current proposals ~~that may reduce~~being debated within the EU Commission and Parliament, including various proposals which could alter the intellectual property protection regime in Europe. Nevertheless, the legislation, if implemented, is unlikely to significantly impact the difficult financial situation facing many Member States and is, therefore, not likely to improve the overall business climate for ~~new products, as well as change~~biopharmaceutical firms operating in the ~~reimbursement and regulatory landscape in ways that are difficult to predict at this point.~~

EU.

The dynamics and developments discussed above create pressures on the pricing and potential usage of our products and on the industry. Given the diverse interests in play between payers, biopharmaceutical manufacturers, policy makers, healthcare providers and independent organizations, if and whether the parties involved can achieve alignment on the matters discussed above remain unclear, and the outcome of any such alignment is difficult to predict. We remain focused on pricing our products responsibly and delivering breakthrough treatments for unmet medical needs. Amgen is committed to working with the entire healthcare community to ensure continued innovation and to facilitate patient access to needed medicines. We do this by:

•investing billions of dollars annually in R&D;

•pricing our medicines to reflect the value they provide;

•developing more affordable therapeutic choices in the form of high-quality and reliably supplied biosimilars;

•partnering with payers to share risk and accountability for health outcomes;

•providing patient support and education programs;

•helping patients in financial need access our medicines; and

•working with policy makers, patients and other stakeholders to establish a sustainable healthcare system with access to affordable care and in which patients and their healthcare professionals are the primary decision makers.

See Item 1A. Risk Factors—Our sales depend on coverage and reimbursement from government and commercial third-party payers, and pricing and reimbursement pressures have affected, and are likely to continue to affect, our profitability and Item 1A. Risk Factors—Guidelines and recommendations published by various organizations can reduce the use of our products.

Manufacturing, Distribution and Raw Materials

Manufacturing

We believe we are a leader in the manufacture of biologics and that our manufacturing capabilities represent a competitive advantage. The products we manufacture consist of both biologics and small molecule drugs. The majority of our products are biologics that are produced in living cells and that are inherently complex due to naturally occurring molecular variations. Highly specialized knowledge and extensive process and product characterization are required to transform laboratory-scale processes into reproducible commercial manufacturing processes. Further, our expertise in the manufacture of biologics positions us well for leadership in the global biosimilars market. For additional information regarding manufacturing facilities, see Item 2. Properties.

We have been innovating our manufacturing facilities designed to extend our manufacturing advantage by optimizing our manufacturing network and/or by mitigating risks while continuing to ensure adequate supply of our products. For example, our licensed next-generation biomanufacturing ~~plant~~plants operating in Singapore and ~~our recently FDA approved facility in~~ West Greenwich, Rhode Island, incorporate multiple innovative technologies into a single facility. Next-generation biomanufacturing plants require smaller manufacturing footprints and offer greater environmental benefits, including reduced consumption of water and energy and lower levels of carbon emissions. Within such plants, the equipment is portable and smaller, which provides greater flexibility and speed in the manufacture of different medicines simultaneously. This enables Amgen to respond to changing demands for its medicines with increased agility. The Singapore site also has a plant that has been approved by several agencies, including the FDA and EMA, to produce small molecule drugs for commercial manufacturing.

Our internal manufacturing network has commercial production capabilities for bulk manufacturing, formulation, fill, finish, tableting and device assembly. These activities are performed within the United States and its ~~territories~~territory in our Puerto Rico, Rhode Island and California facilities as well as internationally in our Ireland, Netherlands and Singapore facilities. In addition, we use third-party contract manufacturers to supplement the capacity or capability of our commercial manufacturing network.

To support our clinical trials, we manufacture product candidates primarily at our California facilities. We also use third-party contract manufacturers to supplement the capacity or capability of our overall clinical manufacturing network.

See Item 1A. Risk Factors for a discussion of the factors that could adversely impact our manufacturing operations and the global supply of our products.

Distribution

We operate distribution centers in Puerto Rico, Kentucky, California and the Netherlands for worldwide distribution of the majority of our commercial and clinical products. We also use third-party distributors to supplement distribution of our products worldwide.

Other

In addition to the manufacturing and distribution activities noted above, each of our manufacturing locations includes key manufacturing support functions such as quality control, process development, engineering, procurement, production scheduling and warehousing. Certain of those manufacturing and distribution activities are highly regulated by the FDA as well as international regulatory agencies. See Government Regulation—Regulation in the United States—Regulation of Manufacturing Standards.

Manufacturing Initiatives

As discussed above, we have been expanding capacity and advancing new innovations with multiple ongoing projects.

Our next-generation biomanufacturing plant at our West Greenwich, Rhode Island, campus, the first of its kind in the United States, ~~received~~has been approved by the FDA ~~approval in January 2022.~~and EMA. This plant expands our capacity to manufacture certain products for U.S. and global markets, as we receive regulatory approval in those markets.

~~We initiated projects~~In November 2021, we broke ground for our newest biomanufacturing plant located in ~~2019 to expand our clinical~~New Albany, Ohio, which received FDA licensure for commercial production in January 2024. This final product assembly and ~~commercial manufacturing capabilities in Thousand Oaks, California, which we have completed.~~packaging plant will support the growing demand for Amgen’s medicines and will use state-of-the-art technologies.

In ~~August 2021,~~March 2022, we ~~initiated a project to build a~~broke ground for our new multi-product drug substance manufacturing facility in Holly Springs, North Carolina. The new plant will support both traditional stainless steel-fed batch manufacturing and next-generation single-use technologies, allowing flexibility in the production of multiple products in one plant.

~~In November 2021,~~Subsequent to the Horizon acquisition, we ~~broke ground for our newest biomanufacturing plant located in New Albany, Ohio. This final product assembly~~are evaluating Horizon’s supply chains and ~~packaging plant will~~pursuing activities to further improve resiliency and efficiency. See Item 1A. Risk factors—Our efforts to collaborate with or acquire other companies, products, or technology, and to integrate the operations of companies or to support the ~~growing demand for Amgen’s medicines~~products or technology we have acquired, may not be successful, and may result in unanticipated costs, delays or failures to realize the ~~United States~~benefits of the transactions.

Amgen continues to embed environmental sustainability into the upfront design, development and ~~will use state-of-the-art technologies.~~execution of our new facilities. The new facility under construction in North Carolina and our recently FDA approved facility in Ohio contain many examples of environmental advances, including on-site photovoltaic renewable energy generation at both sites. We expect our North Carolina facility’s carbon, waste and water footprints to be substantially lower than those at a traditional drug substance

manufacturing plant, and we expect lower footprints per unit produced as well at our Ohio facility compared with existing similar facilities.

See Item 1A. Risk Factors—Manufacturing difficulties, disruptions or delays could limit supply of our products and limit our product sales.

Raw Materials and Medical Devices

Certain raw materials, medical devices (including companion diagnostics) and components necessary for the commercial and/or clinical manufacturing of our products are provided by and are the proprietary products of unaffiliated third-party suppliers, certain of which may be our only sources for such materials. We currently attempt to manage the risk associated with such suppliers by means of inventory management, relationship management and evaluation of alternative sources when feasible. We also monitor the financial condition of certain suppliers and their ability to supply our needs. See Item 1A. Risk Factors—We rely on third-party suppliers for certain of our raw materials, medical devices and components.

We perform various procedures to help authenticate the sources of raw materials, including intermediary materials used in the manufacture of our products; the procedures include verification of country of origin and are incorporated into the manufacturing processes we and our third-party contract manufacturers perform.

To better ensure supply, Amgen has a risk mitigation strategy that uses a combination of methods, including multiple sources or backup inventory of critical raw materials. ~~In response to the COVID-19 pandemic and as~~As part of our ongoing business continuity efforts, we continue to closely monitor our inventory levels and have taken additional measures to mitigate against raw material supply interruption. See Item 1A. Risk Factors for a discussion of the factors that could adversely impact our manufacturing operations and the global supply of our products.

Government Regulation

Regulation by government authorities in the United States and other countries is a significant factor in the production and marketing of our products and our ongoing R&D activities. To clinically test, manufacture and market products for therapeutic use, we must satisfy mandatory procedures and safety and effectiveness standards established by various regulatory bodies. Compliance with these standards is complex, and failure to comply with any of these standards can result in significant implications. See Item 1A. Risk Factors for a discussion of factors, including global regulatory implications, that can adversely impact our development and marketing of commercial products.

Regulation in the United States

In the United States, the Public Health Service Act; the FDCA; and the regulations promulgated thereunder as well as other federal and state statutes and regulations govern, among other things, the production, research, development, testing, manufacture, quality control, labeling, storage, record keeping, approval, advertising, promotion and distribution of our products in addition to the reporting of certain payments and other transfers of value to healthcare professionals and teaching hospitals.

Clinical Development and Product Approval. Drug development in our industry is complex, challenging and risky, and failure rates are high. Product development cycles are typically very long—approximately 10 to 15 years from discovery to market. A potential new medicine must undergo many years of preclinical and clinical testing to establish its safety and efficacy for use in humans at appropriate dosing levels and with an acceptable risk–benefit profile. We continue to work toward reducing cycle times by applying our expertise in human genetics and innovation in technology, clinical trials and real-world evidence.

After laboratory analysis and preclinical testing in animals, we file an IND with the FDA to begin human testing. Typically, we undertake an FDA-designated three-phase human clinical testing program.

•In phase 1, we conduct small clinical trials to investigate the safety and proper dose ranges of our product candidates in a small number of human subjects.

•In phase 2, we conduct clinical trials to investigate side-effect profiles and the efficacy of our product candidates in a patient population larger than phase 1 but still relatively small, who have the disease or condition under study.

•In phase 3, we conduct clinical trials to investigate the short- and long-term safety and efficacy of our product candidates, compared to commonly used treatments, in a large number of patients who have the disease or condition under study.

The FDA monitors the progress of each trial conducted under an IND and may, at its discretion, reevaluate, alter, suspend or terminate the testing based on data accumulated to that point and the FDA’s risk–benefit assessment with regard to the

patients enrolled in the trial. The results of preclinical and clinical trials are submitted to the FDA in the form of either a BLA for biologic products or a New Drug Application for small molecule products. We are not permitted to market or promote a new product until the FDA has approved our marketing application.

Approval of Biosimilars. The ~~ACA~~Affordable Care Act authorized the FDA to approve biosimilars via a separate, abbreviated pathway. The pathway allows sponsors of a biosimilar to seek and obtain regulatory approval based in part on the nonclinical-trial and clinical-trial data of an originator product to which the biosimilar has been demonstrated to be “highly similar” and to have no clinically meaningful differences with regard to safety, purity and potency. The relevance of demonstrating “similarity” is that in many cases, biosimilars can be brought to market without conducting the full suite of clinical trials typically required of originators, because risk–benefit has previously been established. To preserve incentives for future innovation, the law establishes a period of exclusivity for originators’ products, which in general prohibits biosimilars from gaining FDA approval based in part on reliance on or reference to the originator’s data in their application to the FDA for 12 years after initial FDA approval of the originator product. The law does not change the duration of patents granted on biologic products. As part of the implementation of the abbreviated approval pathway for biosimilars, the FDA released a number of guidance documents, some of which remain in draft form. See Item 1A. Risk Factors—We currently face competition from biosimilars and generics and expect to face increasing competition from biosimilars and generics in the future.

Regulation of Product Marketing and Promotion. The FDA regulates the marketing and promotion of drug products. Our product promotions for approved product indications must comply with the statutory standards of the FDCA and the FDA’s implemented regulations and guidance. The FDA’s review of marketing and promotional activities encompasses but is not limited to direct-to-consumer advertising, healthcare-provider-directed advertising and promotion, sales representative communications to healthcare professionals, promotional programming and promotional activities involving electronic media. The FDA may also review industry-sponsored scientific and educational activities that make representations regarding product safety or efficacy in a promotional context. The FDA may take enforcement action against a company for ~~promoting unapproved uses of a product or for other~~ violations of the FDA’s advertising and labeling laws and regulations. Enforcement action may include product seizures, injunctions, civil or criminal penalties or regulatory letters, which may require corrective advertising or other corrective communications to healthcare professionals. Failure to comply with the FDA’s regulations also can result in adverse publicity or increased scrutiny of company activities by the U.S. Congress or other legislators. Additionally, as described below, such failure may lead to additional liability under U.S. healthcare fraud and abuse laws.

Regulation of Manufacturing Standards. The FDA regulates and inspects the equipment, facilities, laboratories and processes used in the manufacturing and testing of products prior to granting approval to market products. If after receiving approval from the FDA we make a material change in manufacturing equipment, location or process, additional regulatory review may be required. We also must adhere to current Good Manufacturing Practice regulations and product-specific regulations enforced by the FDA through its facilities inspection program. The FDA conducts regular, periodic visits to reinspect our equipment, facilities, laboratories and processes following an initial approval.

Regulation of Combination Products. Combination products are defined by the FDA as products composed of two or more regulated components (e.g., a biologic and/or drug and a device). Biologics/drugs and devices each have their own regulatory requirements, and combination products may have additional requirements. A number of our marketed products meet this definition and are regulated under this framework, and we expect that a number of our pipeline product candidates will be evaluated for regulatory approval under this framework as well.

Regulation of Orphan Medicines. Orphan drugs are defined by the FDA as products intended to treat a rare disease or condition that affects less than 200,000 persons in the United States. A company must request orphan drug designation prior to filing and, if granted for being the first medicine to treat such a rare disease, means the FDA will not approve another sponsor’s marketing application for the same drug for the same indication for seven years. Orphan drug exclusivity will not bar approval of another medicine for the same indication if it is shown to be clinically superior. In the United States, a number of our products, including products such as TEPEZZA and UPLIZNA acquired in connection with the Horizon acquisition, have orphan drug exclusivity under this framework.

Regulation outside the United States

In EU countries as well as in the United Kingdom, Switzerland, Canada, Australia and Japan, regulatory requirements and approval processes are similar in principle to those in the United States.

In the EU, there are currently two potential tracks for seeking marketing approval for a product not authorized in any EU member state: a decentralized procedure and a centralized procedure. In the decentralized procedure, identical applications for marketing authorization are submitted simultaneously to the national regulatory agencies. Regulatory review is led by one member state (the reference-member state), and its assessment—based on safety, quality and efficacy—is reviewed and approved (assuming there are no concerns that the product poses a serious risk to public health) by the other member states

from which the applicant is seeking approval (the concerned-member states). The decentralized procedure leads to a series of single national approvals in all relevant countries. In the centralized procedure, which is required of all products derived from biotechnology, a company submits a single ~~Marketing Authorisation Application~~MAA to the EMA, which conducts an evaluation of the dossier, drawing upon its scientific resources across Europe. If the drug product is proven to fulfill requirements for quality, safety and efficacy, the EMA’s CHMP adopts a positive opinion, which is transmitted to the EC for final decision on granting of the marketing authorization. Even though the EC generally follows the CHMP’s opinion, it is not bound to do so. Subsequent commercialization is enabled by country-by-country reimbursement approval.

In the EU, biosimilars are approved under a specialized pathway of the centralized procedure. As with the U.S. pathway, an applicant seeks and obtains regulatory approval for a biosimilar once the data exclusivity period for the original reference product has expired, relying in part on the data submitted for the originator product together with data evidencing that the biosimilar is “highly similar” with regard to quality, safety and efficacy to the original reference product authorized in the European Economic Area. See Item 1A. Risk Factors—We currently face competition from biosimilars and generics and expect to face increasing competition from biosimilars and generics in the future.

In the EU, Regulation (EC) No 141/2000, as implemented by Regulation (EC) No. 847/2000, provides that a medicine can be designated as an orphan medicinal product by the EC if its sponsor can establish that: (i) the product is intended for the diagnosis, prevention or treatment of life-threatening or chronically debilitating conditions; (ii) either (a) such conditions affect not more than 5 in 10,000 persons in the EU when the application is made, or (b) the product without the benefits derived from orphan status, would not generate sufficient return in the EU to justify the necessary investment in developing the medicinal product; and (iii) there exists no satisfactory authorized method of diagnosis, prevention, or treatment of the condition that has been authorized in the EU, or even if such method exists, the product will be of significant benefit to those affected by that condition. An application for the designation of a medicinal product as an orphan medicinal product may be submitted at any stage of development of the medicinal product but before the filing of an MAA. A marketing authorization for an orphan medicinal product may only include indications designated as orphan. For non-orphan indications treated with the same active pharmaceutical ingredient, a separate marketing authorization has to be sought. Approved orphan drugs in the EU receive 10 years of market exclusivity for the approved indication in all EU member states. We currently have orphan medicinal product designation for BLINCYTO in the EU and intend to seek medicinal product designation for a number of our products in the future.

Other countries such as ~~Russia, Turkey and~~ those in Latin America and the Middle East have review processes and data requirements similar to those of the EU and in some cases can rely on prior marketing approval from U.S. or EU regulatory authorities. The regulatory process in these countries may include manufacturing/testing facility inspections, testing of drug product upon importation and other domestic requirements.

In Asia Pacific, a number of countries such as China, Japan, South Korea and Taiwan may require local clinical-trial data for bridging purposes as part of the drug registration process in addition to global clinical trials, which can add to overall drug development and registration timelines. In most of the Asian markets, registration timelines depend on marketing approval in the United States or the EU. In some markets in Asia, such as China, Indonesia and Thailand, regulatory timelines can be less predictable. The regulatory process may also include manufacturing/testing facility inspections, testing of drug product upon importation and other domestic requirements. Countries such as Australia and Japan have more-mature systems that would allow for submissions under more-competitive time frames. With regard to biosimilars, several of these countries have pathways to register biosimilars (e.g., Australia, India, Singapore, South Korea and Taiwan), and biosimilar products are already present on the markets (e.g., Australia and South Korea).

In some countries, such as Japan and those in the EU, medical devices may be subject to regulatory regimes whereby manufacturers must establish that their medical devices conform to essential requirements set out in the law for the particular device category. For example, in the EU, with limited exceptions, medical devices placed on the market must bear the Conformité Européenne marking to indicate their conformity with legal requirements.

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Postapproval Phase

After approval, we continue to monitor adverse events and product complaints reported following the use of our products through routine postmarketing surveillance and studies when applicable. We report such events to the appropriate regulatory agencies as required by local regulations for individual cases and aggregate reports. We proactively monitor (according to good pharmacovigilance practices) and ensure the implementation of signal detection, assessment and the communication of adverse events that may be associated with the use of our products. We also proactively monitor product complaints through our quality systems, which includes assessing our drug delivery devices for device complaints, adverse events and malfunctions. We may also be required by regulatory agencies to conduct further clinical trials on our marketed products as a condition of their approval or to provide additional information on safety and efficacy. Health regulators, including the FDA, have authority to mandate labeling changes to products at any point ~~in a product’s life cycle~~ based on new safety information or as part of an evolving label change to a particular class of products.

Health regulators, including the FDA, also have authority both before and after approval to require that a company implement a risk management program for a product to ensure that the benefits of the drug outweigh the risks. Each risk management program is unique and varies depending on the specific factors required. In the United States, such a risk management program is known as a ~~REMS;~~REMS, and we currently have REMSs for Prolia, Nplate and BLINCYTO.

Other Regulation

We are also subject to various laws pertaining to healthcare fraud and abuse, including antikickback laws and false-claims laws. Antikickback laws make it illegal to solicit, offer, receive or pay any remuneration in exchange for or to induce the referral of business, including the purchase or prescribing of a particular drug that is reimbursed by a state or federal program. False-claims laws prohibit knowingly and willingly presenting or causing to be presented for payment to third-party payers (including Medicare and Medicaid) any claims for reimbursed drugs or services that are false or fraudulent, claims for items or services not provided as claimed or claims for medically unnecessary items or services. Violations of fraud and abuse laws may be punishable by criminal and/or civil sanctions, including fines and civil monetary penalties, as well as by the possibility of exclusion from federal healthcare programs (including Medicare and Medicaid). Liability under false-claims laws may also arise when violation of certain laws or regulations related to the underlying product (e.g., a violation regarding improper promotional activity or unlawful payments) contributes to the submission of a false claim.

On April 25, 2019, we entered into a settlement agreement with the DOJ and the OIG of the HHS to settle certain allegations related to our support of independent charitable organizations that provide patients with financial assistance to access medicines. Additionally, we entered into a corporate integrity agreement that requires us to both maintain a corporate compliance program and undertake a set of defined corporate integrity obligations for a period of five years. Due to the breadth of the statutory provisions and the absence of guidance in the form of regulations or court decisions addressing some of our practices, it is possible that in the future, our practices might be further challenged under antikickback or similar laws.

The FCPA prohibits U.S. corporations and their representatives from offering, promising, authorizing or making payments to any foreign government official, government staff member, political party or political candidate in an attempt to obtain or retain business abroad. The scope of the FCPA arguably includes interactions with certain healthcare professionals in many countries. Other countries have enacted similar anticorruption laws and/or regulations. Failure by our employees, agents, contractors, vendors, licensees, partners or collaborators to comply with the FCPA and other anticorruption laws and/or regulations could result in significant civil or criminal penalties.

We are subject to various laws and regulations globally with regard to privacy and data protection. These laws and regulations involve the collection, storage, handling, use, disclosure, transfer and security of personal data. The legislative and regulatory environments regarding privacy and data protection are continually evolving and developing because these issues are subjects of increasing amounts of attention in countries globally. For example, we are subject to the EU’s GDPR, which became effective on May 25, ~~2018,~~2018; the ~~California Consumer Privacy Act of 2018,~~CCPA, which became effective on January 1, 2020; the California Privacy Rights Act of 2020, which amended the CCPA and became effective on January 1, 2023; and China’s Personal Information Protection Law, which became effective on November 1, 2021. Other jurisdictions where we operate have enacted or proposed similar legislation and/or ~~regulations. For example,~~regulations, such as consumer privacy laws that went into effect in Virginia, Colorado, Utah, Connecticut and Florida in 2023. Consumer privacy laws were also passed in 11 other states, with the ~~Virginia Consumer~~earliest effective dates later this year, and proposed in three additional states. In April 2023, a new type of state privacy law focused on protection of consumer health data emerged in Washington with the enactment of the My Health My Data ~~Protection~~ Act, ~~and the Colorado Privacy Act are set to~~with similar legislation passed subsequently in Nevada. Both these new consumer health privacy laws become effective ~~on January 1, 2023, and July 1, 2023, respectively.~~March 31, 2024. Failure to comply with these current and future laws could result in significant penalties.

Our business has been and will continue to be subject to various other U.S. and foreign laws, rules and ~~regulations.~~regulations, including provisions of the IRA. See Reimbursement section above.

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Research and Development and Selected Product Candidates

We focus our R&D on novel human therapeutics for the treatment of serious illness. We capitalize on our strengths in human genetics, novel biology and protein engineering. We leverage our biologic expertise and seek to choose the optimal modality for a drug target and disease. And we use cutting-edge science and technology to study subtle biological mechanisms in search of therapies that will improve the lives of those who suffer from diseases.

Our discovery research programs may therefore yield targets that lead to the development of human therapeutics delivered as large molecules, small molecules, other combination modalities or new modalities. We have reshaped our portfolio and have increasingly focused our efforts on human genetics when possible to enhance the likelihood of success.

Since early 2021, COVID-19 global vaccination efforts have been under way to control the pandemic. However, uncertainty remains as to the length of time required for vaccination of a meaningful portion of the population and as to the efficacy of such vaccinations on the trajectory of the pandemic. Challenges to vaccination efforts, new variants and other causes of virus spread may require governments to issue additional restrictions and/or order shutdowns in various geographies. As a result, we expect to see continued volatility for at least the duration of the pandemic as governments respond to current local conditions. With regard to our ~~drug development~~clinical trial activities, we are continuously monitoring ~~COVID-19 infection rates,~~the possible impacts from health-related events, including changes from new COVID-19 variants; we are working to mitigate effects on future study enrollment in our clinical trials; and we are evaluating the impact in all ~~countries where clinical trials occur.~~relevant countries. We remain focused on supporting our active clinical sites in their providing care for patients and in our providing investigational drug supply.

For the years ended December 31, ~~2021, 2020~~2023, 2022 and ~~2019,~~2021, our R&D expenses were $4.8 billion, ~~$4.2~~$4.4 billion and ~~$4.1~~$4.8 billion, respectively.

We have major R&D centers in Thousand Oaks and San Francisco, ~~California;~~California, and Deerfield, Illinois; Iceland; and the United Kingdom, as well as smaller research centers and development facilities globally. See Item 2. Properties.

Our clinical trial activities are conducted by both our internal staff and third-party contract clinical trial service providers. To increase the number and diversity of patients available for enrollment in our clinical trials, we have opened clinical sites and will continue opening clinical sites and enrolling patients in a number of geographic locations. See Government Regulation—Regulation in the United States—Clinical Development and Product Approval for a discussion of government regulation over clinical development. Also see Item 1A. Risk Factors—We must conduct clinical trials in humans before we commercialize and sell any of our product candidates or existing products for new indications.

Some of our competitors are actively engaged in R&D in areas in which we have products or in which we are developing product candidates or new indications for existing products. For example, we compete with other clinical trials for eligible patients, which may limit the number of available patients who meet the criteria for certain clinical trials. The competitive marketplace for our product candidates is greatly dependent on the timing of entry into the market. Early entry may have important advantages in gaining product acceptance, thereby contributing to a product’s eventual success and profitability. Accordingly, we expect that in some cases, the relative speed with which we can develop products, complete clinical testing, receive regulatory approval and supply commercial quantities of a product to the market will be important to our competitive position.

In addition to product candidates and marketed products generated from our internal R&D efforts, we acquire companies, acquire and license certain product and R&D technology rights and establish R&D arrangements with third parties to enhance our strategic position within our industry by strengthening and diversifying our R&D capabilities, product pipeline and marketed product base. In pursuing these R&D arrangements and licensing or acquisition activities, we face competition from other pharmaceutical and biotechnology companies that also seek to license or acquire technologies, product candidates or marketed products from those entities performing the R&D.

The following table shows a selection of certain of our product candidates by phase of development in our therapeutic areas of focus as of ~~February 8, 2022,~~January 31, 2024, unless otherwise indicated. Additional product candidate information can be found on our website at www.amgen.com. (The website address is not intended to function as a hyperlink, and the information contained on our website is not intended to be a part of this filing.) The information in this section does not include other, nonregistrational clinical trials that we may conduct for purposes other than for submission to regulatory agencies for their approval of a new product indication.

We may conduct nonregistrational clinical trials for various reasons, including to evaluate real-world outcomes or to collect additional safety information with regard to the use of products.

1617


Molecule						Investigational indication
Phase 3 programs
AMJEVITA						Interchangeability
Bemarituzumab						GEJ adenocarcinoma
BLINCYTO						Ph-negative B-cell precursor ~~Acute~~acute lymphoblastic leukemia
Dazodalibep						Sjögren’s Syndrome
EVENITY						Male osteoporosis
~~KYPROLIS~~LUMAKRAS/LUMYKRAS						~~Weekly dosing for relapsed multiple myeloma~~Advanced colorectal cancer; NSCLC
Nplate						Chemotherapy-induced thrombocytopenia
~~Otezla~~Olpasiran						~~Genital psoriasis~~
~~Repatha~~						Cardiovascular disease
Otezla						Palmoplantar pustulosis
Repatha						Cardiovascular disease
Rocatinlimab						Atopic dermatitis
Tarlatamab						Small cell lung cancer
TEPEZZA						Active TED in Japan; Chronic/Low CAS TED in Japan
TEZSPIRE						Chronic rhinosinusitis with nasal ~~polyps~~ polyps; Eosinophilic esophagitis; Severe asthma
~~ABP 654~~UPLIZNA						IgG4-related disease; Myasthenia gravis
Wezlana						Investigational biosimilar to STELARA (ustekinumab)
ABP 206						Investigational biosimilar to OPDIVO (nivolumab)
ABP 938						Investigational biosimilar to EYLEA (aflibercept)
ABP 959						Investigational biosimilar to SOLIRIS (eculizumab)
Phase 2 programs
Bemarituzumab						Other tumors
Daxdilimab						Dermatomyositis or anti-synthetase inflammatory myositis; discoid lupus erythematosus
Efavaleukin alfa						~~Systemic lupus erythematosus~~ Ulcerative colitis
Fipaxalparant						Diffuse cutaneous systemic sclerosis; idiopathic pulmonary fibrosis
LUMAKRAS/LUMYKRAS						~~Advanced colorectal cancer~~ ~~NSCLC monotherapy~~ Other solid tumors with KRASG12C mutations
~~Olpasiran~~Maridebart cafraglutide						~~Cardiovascular disease~~Obesity
Ordesekimab						Celiac disease
~~Otezla~~						~~Palmoplantar pustulosis~~
~~Rozibafusp alfa~~						~~Systemic lupus erythematosus~~
~~Tarlatamab~~						~~Small cell lung cancer~~
TEZSPIRE						Chronic obstructive pulmonary ~~disease~~ disease; Chronic spontaneous urticaria
~~AMG 451/KHK 4083~~						~~Atopic dermatitis~~
Phase 1 programs
~~Acapatamab~~Bemarituzumab						~~Prostate cancer~~
~~Pavurutamab~~						~~Multiple myeloma~~NSCLC
Tarlatamab						Neuroendocrine prostate cancer
TEPEZZA						Subcutaneous administration for TED
Xaluritamig						~~Small-cell lung~~Prostate cancer
AMG 104						Asthma
~~AMG 119~~						~~Small-cell lung cancer~~
~~AMG 133~~						~~Obesity~~
~~AMG 176~~						~~Hematologic malignancies~~
AMG 193						Solid tumors
AMG 305						Solid tumors
AMG 329						Autoimmune disease
AMG 355						Solid tumors
AMG ~~199~~651						~~Metastatic GEJ cancer~~
~~AMG 256~~						Solid tumors
AMG ~~330~~786						~~Acute myeloid leukemia~~Obesity
AMG ~~340~~794						~~Prostate cancer~~
~~AMG 404~~						Solid tumors
~~AMG 427~~						~~Acute myeloid leukemia~~
~~AMG 506~~						~~Solid tumors~~
~~AMG 509~~						~~Prostate cancer~~
~~AMG 609~~						~~Nonalcoholic steatohepatitis~~
~~AMG 650~~						~~Solid tumors~~
~~AMG 994~~						~~Solid tumors~~

1718


Phase 3			Clinical trials investigate the short- and long-term safety and efficacy of our product candidates, compared to commonly used treatments, in a large number of patients who have the disease or condition under study.
Phase 2			Clinical trials investigate side-effect profiles and efficacy of product candidates in a larger patient population than phase 1, but still relatively small, who have the disease or condition under study.
Phase 1			Clinical trials investigate the safety and proper dose ranges of product candidates in a small number of human subjects.

Phase 3 Product Candidate Program Changes

As of ~~February 2, 2021,~~January 31, 2023, we had 1318 phase 3 programs. As of ~~February 8, 2022,~~January 31, 2024, we ~~continued to~~ have 1324 phase 3 programs, as ~~regulatory approvals~~five phase 3 programs were ~~received for~~acquired from Horizon, three ~~programs, four~~ programs initiated phase 3 studies, one program was approved by the FDA and one program ~~was terminated.~~concluded. These changes are set forth in the following table.

Molecule

Investigational indication

Program change

Dazodalibep

Sjögren’s Syndrome

Horizon acquired program

KYPROLIS

Weekly dosing for relapsed multiple myeloma

Concluded—program did not meet its primary endpoint

LUMAKRAS/LUMYKRAS

NSCLC in combination with chemotherapy

~~NSCLC with KRAS G12C mutations~~

~~Approved by the FDA and conditional marketing approval by the EC~~

~~Otezla~~

~~Mild-to-moderate psoriasis~~

~~Approved by the FDA~~

~~RIABNI~~

~~Non-Hodgkin’s lymphoma~~

~~Approved by the FDA~~

~~AMJEVITA~~

~~Interchangeability~~

Initiated phase 3 study

~~Bemarituzumab~~Otezla

Genital psoriasis

~~GEJ adenocarcinoma~~

Approved by the FDA

Tarlatamab

Small cell lung cancer

Initiated phase 3 study

TEPEZZA

Active TED (OPTIC-J); Chronic/Low CAS TED in Japan

Horizon acquired programs

UPLIZNA

IgG4-related disease; Myasthenia gravis

~~BLINCYTO~~Horizon acquired programs

ABP 206

~~Ph-negative B-cell precursor Acute lymphoblastic leukemia~~

Biosimilar to OPDIVO

Initiated phase 3 study

~~TEZSPIRE~~

~~Chronic rhinosinusitis with nasal polyps~~

~~Initiated phase 3 study~~

~~Otezla~~

~~COVID-19~~

~~Terminated~~

Phase 3 Product Candidate Patent Information

The following table describes our composition-of-matter patents that have been issued thus far for our product candidates in phase 3 development that have yet to be approved for any indication in the United States or the EU. Patents for products already approved for one or more indications in the United States or the EU but that are currently undergoing phase 3 clinical trials for additional indications have been previously described. See Marketing, Distribution and Selected Marketed Products—Patents.

Molecule

Territory

General subject matter

Estimated expiration*

Bemarituzumab

U.S.

Polypeptides

2029

Europe

Polypeptides

2029

Dazodalibep

U.S.

Polypeptides

2034

Europe

Polypeptides

2032

Olpasiran

U.S.

Compounds

2036

Europe

Compounds

2036

Rocatinlimab

U.S.

Polypeptides

2027

Europe

Polypeptides

2026

Tarlatamab

U.S.

Polypeptides

2036

Europe

Polypeptides

2036

* Patent expiration estimates are based on issued patents, which may be challenged, invalidated or circumvented by competitors. The estimates do not include any term adjustments, extensions or supplemental protection certificates that may be obtained in the future and thereby extend these dates. Corresponding patent applications are pending in other jurisdictions. Additional patents may be filed or issued and may provide additional exclusivity for the product candidate or its use. In addition to patent exclusivity, the product candidates may be protected by regulatory exclusivities upon approval in some countries. For example, new chemical entities would receive a five year exclusivity period and new molecular entities would receive a 12 year exclusivity period in the United States, whereas new chemical and molecular entities would receive a 10 year exclusivity period in Europe.

Phases 3 and 2 Program Descriptions

The following provides additional information about selected products and product candidates that have advanced into human clinical trials.

AMJEVITA

AMJEVITA is a biosimilar to HUMIRA, which is a monoclonal antibody that inhibits binding of ~~TNF-alpha~~tumor necrosis factor (TNF) alpha to cell surface TNF receptor / TNF-alpha.

Bemarituzumab

Bemarituzumab is a monoclonal antibody that inhibits ~~FGFR2b.~~fibroblast growth factor receptor 2b (FGFR2b). It is being investigated for the treatment of advanced ~~GEJ adenocarcinoma.~~

~~In April 2021, Amgen announced that the FDA had granted Breakthrough Therapy designation for bemarituzumab.~~

gastroesophageal junction (GEJ) adenocarcinoma and advanced solid tumors other than advanced squamous NSCLC.

BLINCYTO

BLINCYTO is an anti-CD19 x anti-CD3 BiTE® molecule. It is being investigated in newly diagnosed adults ~~age~~aged 40 and older with Ph negative ~~B-Cell~~B-cell precursor ALL.

Daxdilimab

Daxdilimab is a fully human monoclonal antibody against ILT7 that depletes certain dendritic cells. It is being investigated for the treatment of both dermatomyositis and anti-synthetase inflammatory myositis and discoid lupus erythematosus.

Dazodalibep

Dazodalibep is a fusion protein binding CD40L on T cells, blocking their interaction with CD40-expressing B cells. It is being investigated for the treatment of Sjögren’s syndrome.

Efavaleukin alfa

Efavaleukin alfa is an ~~IL-2~~interleukin (IL)-2 mutein Fc fusion protein. It is being investigated for the treatment of ~~systemic lupus erythematosus and~~ ulcerative colitis.

EVENITY

EVENITY is a monoclonal antibody that inhibits the action of sclerostin. It is being evaluated as a treatment for male ~~osteoporosis.~~osteoporosis. EVENITY is being developed in collaboration with UCB.

~~KYPROLIS~~Fipaxalparant

~~KYPROLIS~~Fipaxalparant is a ~~small~~ molecule ~~proteasome inhibitor.~~that blocks lysophosphatidic acid receptor 1 (LPAR1). It is being investigated for ~~weekly dosing in combinations with lenalidomide and dexamethasone for relapsed multiple myeloma.~~

In December 2021, we announced that the FDA had approved the expansion of the KYPROLIS prescribing information to include its use in combination with DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) and dexamethasone for the treatment of ~~adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy.~~diffuse cutaneous systemic sclerosis and idiopathic pulmonary fibrosis.

LUMAKRAS/LUMYKRAS

~~LUMAKRAS~~LUMAKRAS/LUMYKRAS is a KRASG12C small molecule inhibitor. It is being investigated as treatment for a variety of solid tumors, including NSCLC, colorectal cancerand other solid tumor cancers.

In ~~May 2021,~~October 2023, we announced ~~that~~positive data from the global Phase 3 CodeBreaK 300 trial. This global Phase 3 study evaluated two doses of LUMAKRAS/LUMYKRAS (960 mg or 240 mg) in combination with Vectibix versus investigator’s choice of therapy (trifluridine and tipiracil, or regorafenib) in patients with chemorefractory G12C-mutated mCRC.

In June 2023, based on data from the previous CodeBreaK 101 study, the FDA ~~had approved~~granted Breakthrough Therapy Designation to LUMAKRAS in combination with Vectibix for the treatment of ~~adult~~ patients with metastatic KRAS ~~G12C–mutated locally advanced or metastatic NSCLC,~~G12C-mutated CRC, as determined by an ~~FDA-approved~~FDA approved test, who have received ~~at least one~~ prior ~~systemic therapy.~~chemotherapy.

In November 2021, we announced that the EMA’s CHMP had adopted a positive opinion and recommended conditional marketing authorization of LUMYKRAS, known as LUMAKRAS in the United States, for the treatment of adults with advanced NSCLC with KRAS ~~G12C~~ ~~mutation and who have progressed after at least one prior line of systemic therapy.~~

In January 2022, we announced that the EC had granted conditional marketing authorization for LUMYKRAS for the treatment of adults with advanced NSCLC with KRAS G12C mutation and who have progressed after at least one prior line of systemic therapy. We also announced that LUMAKRAS had been approved in Japan for the treatment of KRAS G12C-mutated positive, unresectable, advanced and/or recurrent NSCLC that has progressed after systemic anticancer therapy.Maridebart cafraglutide

~~Nplate~~

~~Nplate~~Maridebart cafraglutide is a ~~TPO-RA.~~gastric inhibitory polypeptide receptor (GIPR) antagonist and glucagon-like peptide 1 (GLP-1) receptor agonist. It is being investigated for the treatment of ~~CIT.~~obesity.

Nplate

Nplate is a thrombopoietin receptor agonist (TPO-RA). It is being investigated for the treatment of chemotherapy-induced thrombocytopenia (CIT).

Olpasiran

Olpasiran is an siRNA that lowers ~~lipoprotein(a), also known as~~ Lp(a). It is being investigated in phase 23 for the treatment of ~~atherosclerotic CV disease.~~ASCVD.

Ordesekimab

Ordesekimab is a monoclonal antibody that inhibits the action of IL-15. It is being investigated for the treatment of celiac disease and is being developed in collaboration with Provention Bio, Inc.

Otezla

Otezla is a small molecule that inhibits PDE4. It is being investigated in phase 3 studies for the treatment of ~~patients with moderate-to-severe genital psoriasis. It is being investigated in a phase 2 study for treatment of~~ palmoplantar pustulosis.

~~In February 2021, we announced the submission of an sNDA to the FDA for the treatment of adults with mild-to-moderate plaque psoriasis who are candidates for phototherapy or systemic therapy.~~

In May 2021, we announced that the FDA had accepted for review our sNDA for the treatment of adults with mild-to-moderate plaque psoriasis who are candidates for phototherapy or systemic therapy. The FDA had set a PDUFA action date of December 19, 2021.

In December 2021, we announced that the FDA had approved the expanded indication for Otezla for the treatment of adult patients with plaque psoriasis, who are candidates for phototherapy or systemic therapy, across all severities.

Repatha

Repatha is a human monoclonal antibody that inhibits PCSK9. It is being investigated as a treatment for ~~atherosclerotic CV disease~~ASCVD in high-risk patients with high LDL-C without prior heart attack or stroke.

~~Rozibafusp alfa~~Rocatinlimab

~~Rozibafusp alfa~~Rocatinlimab is a ~~novel antibody-peptide conjugate~~monoclonal antibody that ~~simultaneously blocks the BAFF and ICOSLactivity.~~inhibits OX-40. It is being investigated ~~as a~~for the treatment ~~for systemic lupus erythematosus.~~of moderate-to-severe atopic dermatitis. Rocatinlimab is being developed in collaboration with Kyowa Kirin.

Tarlatamab

Tarlatamab is ~~an HLE anti- DLL3~~a half-life extended (HLE) anti-DLL3 x anti-CD3 BiTE® molecule. It is being investigated for the treatment of small cell lung cancer.

In October 2023, we announced results from the global Phase 2 DeLLphi-301 study, evaluating tarlatamab, an investigational DLL3 targeting BiTE® molecule, in patients with advanced stage SCLC who had failed two or more prior lines of treatment. With a median follow-up of 10.6 months, an intention-to-treat analysis that included 100 patients at the selected 10 mg dose, tarlatamab demonstrated an ORR (primary endpoint) of 40%. For key secondary endpoints, mPFS was 4.9 months, and mOS was 14.3 months. There were no new safety signals observed compared to the Phase 1 study. Additionally in October 2023, the FDA granted tarlatamab Breakthrough Therapy Designation for the treatment of adult patients with extensive-stage SCLC with disease progression on or after platinum-based chemotherapy.

In December 2023, we announced the FDA accepted and granted Priority Review for the Company’s BLA for tarlatamab, with a PDUFA date of June 12, 2024.

TEPEZZA

TEPEZZA is a monoclonal antibody against IGF-1R. It is being investigated in phase 3 studies for patients with moderate-to-severe active TED and chronic/low clinical activity score (CAS) TED. It is also being investigated for subcutaneous administration.

TEZSPIRE

TEZSPIRE is a human monoclonal antibody that inhibits the action of thymic stromal lymphopoietin. It is being evaluated in phase 3 studies as a treatment for severe asthma, ~~and~~ chronic rhinosinusitis with nasal ~~polyps.~~polyps and eosinophilic esophagitis. It is also being investigated in phase 2 studies as a treatment for chronic obstructive pulmonary disease and chronic spontaneous urticaria. TEZSPIRE is being developed jointly in collaboration with AstraZeneca.

~~In May 2021, we announced that our partner AstraZeneca had submitted~~

UPLIZNA

UPLIZNA is a ~~BLA to the FDA for tezepelumab, a potential first-in-class medicine in severe asthma.~~

~~In July 2021, we announced that the FDA had accepted a BLA and granted Priority Review of TEZSPIRE for the treatment of asthma.~~

In December 2021, we announced that the FDA had approved Amgen and AstraZeneca's TEZSPIRE for the add-on maintenance treatment of adult and pediatric patients aged 12 years and older with severe asthma.

~~In January 2022, we announced that TEZSPIRE is available for shipment to wholesalers in the United States.~~

~~AMG 451/KHK4083~~

~~AMG 451/KHK4083 is a~~humanized, affinity-optimized, afucosylated IgG1 kappa (IgG1κ) monoclonal antibody that ~~inhibits OX-40.~~binds to the B cell-specific surface antigen CD19. It is being investigated for the treatment of ~~moderate-to-severe atopic dermatitis. AMG 451/KHK4083 is being developed~~flare in ~~collaboration~~patients with ~~KKC.~~IgG4-related disease and myasthenia gravis.

~~ABP 654~~Wezlana

~~ABP 654,~~Wezlana, a biosimilar candidate to STELARA,~~(ustekinumab),~~ is a monoclonal antibody that inhibits IL-12 and IL-23. It is being investigated in a phase 3 study for biosimilarity to STELARA. The reference-product primary conditions are psoriasis, psoriatic arthritis and Crohn’s disease.

ABP 206

ABP 206, a biosimilar candidate to OPDIVO, is a monoclonal antibody that binds to the receptor protein called programmed death protein 1 (PD-1).

ABP 938

ABP 938, a biosimilar candidate to EYLEA, is a ~~VEGFR~~vascular endothelial growth factor receptor (VEGFR) Fc fusion protein. It is being investigated in a phase 3 study for biosimilarity to EYLEA. The reference-product primary conditions are wet ~~AMD,~~age-related macular degeneration (AMD), macular edema following retinal vein occlusion, diabetic macular edema and diabetic retinopathy.

ABP 959

ABP 959, a biosimilar candidate to SOLIRIS, is a monoclonal antibody that specifically binds to the complement protein C5. It is being investigated in a phase 3 study for biosimilarity to SOLIRIS. The reference-product primary conditions are ~~PNH~~paroxysmal nocturnal hemoglobinuria (PNH) and ~~aHUS.~~atypical hemolytic uremic syndrome (aHUS).

Business Relationships

From time to time, we enter into business relationships, including joint ventures and collaborative arrangements, for the R&D, manufacture and/or commercialization of products and/or product candidates. In addition, we acquire product and R&D technology rights and establish R&D collaborations with third parties to enhance our strategic position within our industry by strengthening and diversifying our R&D capabilities, product pipeline and marketed-product base. These arrangements generally provide for nonrefundable upfront license fees, development and commercial-performance milestone payments, cost sharing, ~~royalty payments~~royalties and/or profit sharing. The activities under these collaboration agreements are performed with no guarantee of either technological or commercial success, and each is unique in nature.

Trade secret protection for our unpatented confidential and proprietary information is important to us. To protect our trade secrets, we generally require counterparties to execute confidentiality agreements upon commencement of a business relationship with us. However, others could either develop independently the same or similar information or unlawfully obtain access to our information.

BeiGene, Ltd.

OnIn January 2, 2020, we acquired ~~a 20.5%~~an equity stake in BeiGene for approximately $2.8 billion in cash as part of a collaboration to expand our oncology presence in China. For additional information regarding our equity investment in BeiGene, see Part IV—Note 10, Investments, to the Consolidated Financial Statements. Under the collaboration, BeiGene began selling XGEVA in 2020, BLINCYTO in 2021 and KYPROLIS in ~~early~~ 2022 in China, and Amgen shares profits and losses equally during the initial product-specific commercialization periods; thereafter, product rights may revert to Amgen, and Amgen will pay royalties to BeiGene on sales in China of such products for a specified period. Amgen manufactures and supplies the collaboration products to BeiGene.

In addition, we jointly develop a portion of our oncology portfolio with BeiGene, which shares in global R&D costs by providing cash and development services of up to $1.25 billion. Upon regulatory approval, BeiGene will assume commercialization rights in China for a specified period, and Amgen and BeiGene will share profits equally until certain of these product rights revert to Amgen. Upon return of the product rights, Amgen will pay royalties to BeiGene on sales in China for a specified period. For product sales outside China, Amgen will also pay royalties to BeiGene.

~~Novartis~~

AstraZeneca plc

We are in a collaboration with ~~Novartis~~AstraZeneca for the development and commercialization of TEZSPIRE. Under our collaboration, both companies share global costs, profits and losses equally after payment by AstraZeneca of a mid-single-digit royalty to ~~jointly develop~~Amgen. AstraZeneca leads global development, and ~~commercialize Aimovig. On January 31, 2022, concurrent with the settlement of the previously disclosed litigation between~~both Amgen and ~~Novartis we modified the terms of the collaboration. See Part IV—Note 19, Contingencies and commitments, to the Consolidated Financial Statements.~~

~~Arrangement through December 31, 2021~~

AstraZeneca jointly commercialize TEZSPIRE in North America. In ~~the United States, Amgen and Novartis jointly developed and collaborated on the commercialization of Aimovig.~~North America, Amgen, as the principal, ~~recognized~~recognizes product sales of Aimovig in the United States, shared U.S. commercialization costs with Novartis and paid Novartis a significant royalty on net sales in the United States. Novartis held global co-development rights and exclusive commercial rights outside the United States and Japan for Aimovig (the ex-U.S. Novartis Rights). Novartis paid Amgen double-digit royalties on net sales of the product in the ex-U.S. Novartis Rights territories and funded a portion of global R&D expenses. In addition, Novartis was required to make a payment to Amgen of up to $100 million if certain commercial and expenditure thresholds were achieved with respect to Aimovig in the United States.

~~Arrangement after January 1, 2022~~

Pursuant to the amendment effective January 1, 2022, Novartis retains the ex-U.S. Novartis Rights and will continue to pay double-digit royalties on net sales in the ex-U.S. Novartis Rights territories. In the United States, Novartis will no longer collaborate with Amgen, share Aimovig commercialization costs or pay milestones and Amgen will no longer pay royalties to Novartis on sales of Aimovig. Amgen and Novartis will continue to share development expenses worldwide.

~~Amgen manufactures and supplies Aimovig worldwide.~~

~~DaVita Inc.~~

In January 2017, we entered into a six-year supply agreement with DaVita, which superseded the previously existing, seven-year supply agreement that commenced in 2012. Pursuant to the 2017 agreement, we supply EPOGEN and Aranesp in amounts necessary to meet specified annual percentages of DaVita’s and its affiliates’ requirements for ESAs used in providing dialysis servicesTEZSPIRE in the United States, and ~~Puerto Rico. Such percentages vary during~~AstraZeneca, as the ~~term~~principal, recognizes product sales of TEZSPIRE in Canada. AstraZeneca leads commercialization for TEZSPIRE outside North America. Amgen manufactures and supplies TEZSPIRE worldwide.

UCB

We are in a collaboration with UCB for the ~~agreement, but~~development and commercialization of EVENITY. Under our collaboration, UCB has rights to lead commercialization for EVENITY in ~~each year~~most countries in Europe. Amgen, as the principal, leads commercialization for EVENITY and recognizes product sales in all other territories, including the United States. Global development costs and commercialization profits and losses related to the collaboration are at least 90%. The agreement expires in December 2022. The agreement may be terminated by either party before expiration of its term in the event of certain breaches of the agreement by the other party.shared equally. Amgen manufactures and supplies EVENITY worldwide.

For financial information about our significant collaborative arrangements, see Part IV—Note 8,9, Collaborations, to the Consolidated Financial Statements.

Human Capital Resources

Overview

Amgen’s approach to human capital resource management starts with our mission to serve patients. We strive to serve patients by transforming the promise of science and biotechnology into therapies that have the power to restore health or save lives. The way we approach our business is guided by ~~our~~the Amgen Values:


Amgen Values
Be Science-Based	Compete Intensely and Win	Create Value for Patients, Staff and Stockholders	Be Ethical
Trust and Respect Each Other	Ensure Quality	Work in Teams	Collaborate, Communicate and Be Accountable

Our staff are also guided by, and receive annual training on, the Company’s Code of Conduct, which is designed to help every person who does business on our behalf worldwide (including all staff, management, consultants, contract workers and temporary workers) to understand what is expected of them.

Our industry ~~exists in~~ is subject to a ~~complex~~complex regulatory and reimbursement environment. The unique demands of our industry, together with the challenges of running an enterprise focused on the discovery, development, manufacture and commercialization of innovative medicines, requires a highly engaged and committed workforce.

As of December 31, ~~2021,~~2023, Amgen had approximately ~~24,200~~26,700 staff members in over50 countries, and we have had relatively low global turnover ~~rates.~~rates compared to available industry information. We also supplement our workforce with independent contractors, contingent workers and temporary workers, as needed. Outside of the United States, some of our employees are represented by unions or works councils. We consider our staff relations to be good, supported by regular assessments of staff engagement surveys on a wide range of topics (including ~~engagement in the COVID-19 environment, diversity, inclusion and belonging,~~flexible work environments, career development, and maintaining a culture of compliance). We discuss the results of these surveys with our workforce and our Board of Directors. Reflecting our staff members’ desire to retain a flexible approach to work, we offer a flexible workspace initiative that enables many employees to work together with their manager to determine the location that best enables their work at hand, supporting virtual work as well as working in person.

Compensation, Benefits and Development

Our approach to employee compensation and benefits is designed to deliver cash, equity and benefit programs that are competitive with those offered by leading companies in the biotechnology and pharmaceutical industries, and to attract, motivate and retain talent with a focus on encouraging performance, promoting accountability and adherence to ~~Company values~~the Amgen Values and alignment with the interests of the Company’s ~~shareholders.~~stockholders.

Our base pay program aims to compensate staff members relative to the value of the contributions of their role, which takes into account the skills, knowledge and abilities required to perform each position, as well as the experience brought to the job. We also provide annual incentive programs to reward our staff in alignment with achievement of Company-wide goals that are established annually and designed to drive aspects of our strategic priorities that support and advance our strategy across our ~~Company.~~Company and are intended to positively position us for both near- and long-term success. The majority of our staff members are also eligible for ~~the grant of~~ equity ~~awards~~award grants under our long-term incentive program that are designed to align the ~~experience of these staff with that~~interests of our ~~shareholders.~~staff members with those of our stockholders. For senior level staff, a significant proportion of equity award value is dependent on Company performance.

All staff ~~also~~ participate in a regular performance measurement process through which staff receive performance and development feedback, and pay is aligned to performance. The Amgen Values and Leadership Attributes (Inspire, Accelerate, Integrate and Adapt) are an integral part of the performance assessments of our staff members, and these evaluations serve as an important information tool and basis for compensation decisions.

To support the development of our staff, we provide a variety of programs, including leadership development programs, classroom-based and virtual instructor-led courses, and self-paced learning ~~options.~~options as well as mentoring, networking and coaching opportunities.

2224

Our benefit programs are ~~also~~ generally broad-based, promote health and overall well-being and emphasize saving for retirement. All regular U.S. staff members are eligible to participate in the same core health and welfare and retirement savings plans. Other U.S. employee benefits include ~~medical plans, dental plans,~~ adoption assistance, paid parental leave programs, access to childcare, employee assistance programs, employee stock purchase plan, flexible spending accounts, life, long-term care and business travel accident insurance, short and long-term disability benefits, wellness benefits and work-life resources and referrals. Comparable programs and benefits are available globally, with the same health and well-being intent, and consistent with local statutory requirements.

Our Compensation and Management Development Committee provides oversight of our compensation plans, policies and programs.

Safety and Wellness ~~and Our Response to COVID-19~~

Creating a safe and healthy workplace for our staff is aan important priority at Amgen. Our goal is to have a world class safety record through safety leadership, risk management practices and integrating safety throughout our business processes. To foster our safety culture, we implement a comprehensive safety program and reinforce desired safety behaviors, driving to understand and mitigate the root cause of safety incidents and manage and control variability. We use leading indicators to assess the effectiveness of our safety programs and make course corrections as needed. Additionally, we perform formal executive management review of functional safety performance for Operations, Global Commercial Operations and R&D on a quarterly basis with a focus on identifying early signals and taking action to drive continuous improvement.

In response to the COVID-19 pandemic and as part of our commitment to work to ensure the safety and well-being of our employees, for 2020 and much of 2021, we have activated our applicable business continuity plans, including having those of our employees who were able to work from home to do so, and for employees returning to the workplace and the field, we took additional safety measures, including implementing occupancy limits, restricting business travel, providing and requiring the use of personal protective equipment, temperature screening and COVID-19 testing to access our workplaces. Staff member access to our facilities has been in accordance with applicable government health and safety protocols and guidance issued in response to the COVID-19 pandemic, and in 2021 we required staff members in the United States and Puerto Rico to be fully vaccinated against COVID-19.1 In the fourth quarter of 2021, we enabled our U.S. based workforce to return to the workplace for work that benefits from face-to-face interactions, while maintaining appropriate safety measures to ensure staff well-being. This approach intentionally combines the benefits of remote and in-person working at Amgen for the future as COVID-19 restrictions ease around the globe. We will continue to learn and adapt this approach as needed for the future.

Our ~~Corporate Responsibility and Compliance Committee~~CRCC provides general oversight of our safety programs and ~~initiatives, while our Board of Directors, as a whole, has overseen our specific responses to the COVID-19 pandemic.~~initiatives.

~~Diversity, Inclusion and Belonging~~Culture

We believe that a diverse and inclusive culture fosters innovation, which supports our ability to serve patients. Further, we also believe our global presence is strengthened by having a workforce that reflects the diversity of the patients we ~~serve. It is with these beliefs in mind that we have continued to strengthen and grow our culture of diversity, inclusion and belonging.~~serve(1). Our ~~internal efforts include, in 2019, establishing a~~ Diversity, Inclusion and Belonging Council ~~chaired~~is led by our ~~Chief Executive Officer. In 2020, we implemented~~executive leadership and is responsible for overseeing our strategy to further a ~~global unconscious-bias training program,~~diverse and ~~we launched an ongoing learning journey with tools~~inclusive workplace. We offer a variety of diversity, inclusion and belonging programs and have continued to launch enhanced resources that ~~guides~~guide staff on the role they play in creating an inclusive culture. Further, we continue to incorporate diversity, inclusion and belonging ~~throughout~~considerations into our business operations, including clinical trial design and procurement, to broaden access to patients and suppliers to the ~~organization.~~ benefit of our business.

Each of Amgen’s ~~ERGs~~Employee Resource Groups is sponsored by ansenior executive ~~leader who reports to the CEO. We are leveraging our ERGs to represent~~leadership. Our Employee Resource Groups promote leadership, development and ~~support the diversity of Amgen staff,~~belonging for members while also working to positively impact our business by leading business initiatives and providing ~~opportunities to Amgen’s business~~diverse perspectives and ~~the community.~~experience.

1(1) ~~The vaccination requirement did~~Amgen is an equal opportunity employer and does not ~~apply to staff who were unable to receive a COVID-19 vaccine because of qualifying religious~~make employment decisions based on race, gender, ethnicity, or ~~medical reasons.~~any other protected characteristic.

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Global Employee Resource Groups
Amgen Asian Association (AAA)			Amgen Black Employee Network (ABEN)
Ability Bettered through Leadership and Education (ABLE), a resource group for those with disabilities, visible and invisible, including those conditions also experienced by the patients that Amgen ~~serves.~~serves
Amgen Early Career Professionals (AECP)			Amgen ~~Indian Subcontinent~~International Network ~~(AISN)~~(AIN)
Amgen Latin Employee Network (ALEN)			Amgen PRIDE – LGBTQ and Allies Network (PRIDE)
Amgen South Asian Network (ASAN)			Amgen Veterans Employees Network (AVEN)
Recognition of Indigenous Peoples, Values and Environmental Resources (RIVER)
Women Empowered to be Exceptional (WE2)
Women in ~~Information Systems~~STEM Enrichment (WISE)			~~Amgen International Network (AIN)~~

~~For 2021, to tangibly deepen and drive~~Building on the successful execution of our ~~diversity, inclusion and belonging activities enterprise-wide and actively communicate~~2022 ESG goal under our ~~culture of belonging to all staff, we established an~~ annual ~~diversity, inclusion and belonging~~incentive plan, our enhanced ESG goal for 2023 was designed to advance our progress on key ESG initiatives, including by driving measurable achievement of our Representation in Clinical Research (RISE) objectives that seek to improve the diversity and representation of racial and ethnic minority populations in our clinical trial research to help us develop medicines that are studied in participants who better reflect the populations affected by serious illness, and further expanding the number of leaders ~~at executive director~~accountable for establishing, documenting and ~~above levels to establish, document and execute~~executing on diversity, inclusion and belonging action ~~plans, with a target goal~~plans.

As of ~~75% participation, which we achieved~~December 31, 2023, women comprised approximately 53% of our global workforce, and ~~exceeded in 2021.~~

ethnic minorities accounted for approximately 50% of our U.S. and Puerto Rico-based workforce. In ~~areas of underrepresentation, we develop plans with a goal of bringing~~ our ~~representation in line with availability. We engage in outreach efforts~~effort to attract and retain the best talent, we seek out and ~~advance more women~~support talent across the globe, including in underrepresented populations, consistent with our commitment to equal opportunity. In 2023, we launched our Apprenticeship Program as part of our multidimensional inclusive hiring and ~~minorities~~talent development strategy, with the first phase of the program beginning with our Manufacturing and DTI functions. Our Apprenticeship Program is a skills-based approach that proactively seeks to hire candidates from nontraditional sources and backgrounds, and is designed to invest in our ~~workforce. For example,~~future workforce through attracting, hiring and upskilling non-four-year degreed talent in the United States. Through the Apprenticeship Program, we ~~have worked to enhance our diverse candidate recruiting pool by developing relationships~~will provide individuals with ~~organizations that can serve as a source of diverse candidates, such as the National Black MBA Association~~classroom-based and ~~National Sales Network,~~on-the-job training as well as ~~historically black colleges~~mentorship opportunities needed to develop proficiency in targeted business areas and ~~universities. In 2021,~~roles. We believe that our Apprenticeship Program and other skills-based approaches to hiring will provide us with access to a ~~fellowship program between Amgen~~larger pool of highly motivated and ~~Howard University was established~~productive talent while also providing underrepresented groups greater access to ~~expand the talent pool and diversify ranks in research and development.~~

Additionally, at the end of 2020, we became a founding member of OneTen, a coalition of the world’s largest, best-known companies, that aims to hire one million Black Americans (with a specific focus on those without four-year college degrees) into good-paying, family-sustaining jobs over the next ten years. As a member of OneTen, Amgen is taking a leadership role in the greater Los Angeles region, where the company is headquartered, to help expand the coalition organizations that share our desire to offer opportunities to diverse talent. Other examples of actions that we are taking in this area include investment and participation in the Healthcare Businesswomen’s Association (a global organization focused on development and business networking for women in healthcare) and the UCLA Anderson School of Management leadership programs for women and underrepresented talent.innovation economy careers.

Our ~~2020~~2022 Consolidated EEO-1 Report can be viewed on our website at www.amgen.com (the website address is not intended to function as a hyperlink, and the information contained in our website is not intended to be a part of this filing).

In 2021, our Corporate Responsibility and Compliance Committee provided oversight of our policies, programs and initiatives focusing on workforce diversity and inclusion. In 2022, oversight of diversity, inclusion and belonging shifted to theOur Compensation and Management Development Committee ~~which also provides oversight of~~oversees our ~~human capital management.~~labor and employment policies, programs and initiatives, including those relating to diversity, inclusion and belonging.

Information about Our Executive Officers

The executive officers of the Company as of February ~~16, 2022,~~14, 2024, are set forth below.

Mr. Robert A. Bradway, age ~~59,~~61, has served as a director of the Company since 2011 and Chairman of the Board of Directors since 2013. Mr. Bradway has been the Company’s President since 2010 and Chief Executive Officer since 2012. From 2010 to 2012, Mr. Bradway served as the Company’s President and Chief Operating Officer. Mr. Bradway joined the Company in 2006 as Vice President, Operations Strategy, and served as Executive Vice President and Chief Financial Officer from 2007 to 2010. Prior to joining the Company, Mr. Bradway was a Managing Director at Morgan Stanley in London, where, beginning in 2001, he had responsibility for the firm’s banking department and corporate finance activities in Europe. Mr. Bradway has been a director of The Boeing Company, an aerospace company and manufacturer of commercial airplanes, defense, space and securities systems, since 2016. He has served on the board of trustees of the University of Southern California since 2014. From 2011 to 2017, Mr. Bradway was a director of Norfolk Southern Corporation, a transportation company.

Dr. James E. Bradner, age 51, became Executive Vice President, Research and Development, and Chief Scientific Officer, in December 2023. Prior to joining the Company, from 2022 to 2023, Dr. Bradner was a clinician at the Dana-Farber Cancer Institute. From 2016 to 2022, Dr. Bradner served as President of the Novartis Institutes for BioMedical Research, where he was a member of the Executive Committee of Novartis AG. Dr. Bradner previously served on the faculty at Harvard Medical School.

Mr. Murdo Gordon, age ~~55,~~57, became Executive Vice President, Global Commercial Operations, in 2018. Prior to joining the Company, Mr. Gordon was Chief Commercial Officer at BMS, a pharmaceutical company, from 2016 to 2018. Mr. Gordon served as Head of Worldwide Markets at BMS from 2015 to 2016. Prior to this, Mr. Gordon served in a variety of leadership roles at BMS for more than 25 years.

Mr. Jonathan P. Graham, age ~~61,~~63, became Executive Vice President, General Counsel and Secretary in 2019. Mr. Graham joined the Company in 2015. From 2015 to 2019, Mr. Graham was Senior Vice President, General Counsel and Secretary. Prior to joining Amgen, from 2006 to 2015, Mr. Graham was Senior Vice President and General Counsel at Danaher Corporation. From 2004 to 2006, Mr. Graham was Vice President, Litigation and Legal Policy, at General Electric Company (GE). Prior to GE, Mr. Graham was a partner at Williams & Connolly LLP.

Mr. Peter H. Griffith, age ~~63,~~65, became Executive Vice President and Chief Financial Officer in 2020. Mr. Griffith joined the Company in 2019 as Executive Vice President, Finance. Prior to joining Amgen, Mr. Griffith was President of Sherwood Canyon Group, LLC, a private equity firm. From 1997 to 2019, Mr. Griffith was a partner at EY, an accounting and professional services firm, and served in a variety of senior leadership roles, with his last position being Global Vice Chair, Corporate Development. Prior to EY, Mr. Griffith was a Managing Director and head of the investment banking division of Wedbush Securities Inc.

Ms. Nancy A. Grygiel, age ~~54,~~56, became Senior Vice President and Chief Compliance Officer in 2020. Ms. Grygiel joined the Company in 2015. From 2016 to 2020, Ms. Grygiel was Vice President, Compliance. Prior to joining Amgen, from 2011 to 2015, Ms. Grygiel served as Vice President, Compliance, Corporate & International, at Allergan, Inc. (Allergan). Prior to Allergan, Ms. Grygiel held several management positions at Mylan Pharmaceuticals, Inc.

Ms. Lori A. Johnston, age 57, became Executive Vice President, Human Resources, in 2019. From 2016 to 2019, Ms. Johnston served as the Company’s Senior Vice President, Human Resources. From 2012 to 2016, Ms. Johnston was Executive Vice President and Chief Administrative Officer of Celanese Corporation (Celanese). Prior to Celanese, Ms. Johnston served in a series of progressive leadership roles at Amgen from 2001 to 2012, with her last position being Vice President, Human Resources. Prior to joining the Company, Ms. Johnston held human resources and other positions at Dell Inc.

~~Ms.~~ Rachna Khosla, age ~~49,~~51, became Senior Vice President, Business Development, in 2021. Ms. Khosla joined the Company in 2013 as Corporate Development Director. From ~~2016~~2018 to ~~2018,~~2021, Ms. Khosla was ~~Executive Director,~~Vice President, Business Development, and from 2016 to 2018, ~~to 2021,~~ was ~~Vice President,~~Executive Director, Business Development. Prior to joining the Company, Ms. Khosla was a Director at Lazard Ltd. (Lazard) responsible for healthcare mergers and acquisitions. Prior to Lazard, Ms. Khosla ~~had~~held various roles in investment banking (mergers and acquisitions) and corporate venture capital at Credit Suisse Group AG, Sanofi Aventis, Aventis Capital, J.P. Morgan Chase & Co., and Salomon Brothers, Inc.

Mr. Derek Miller, age 51, became Senior Vice President, Human Resources, in 2022. Mr. Miller joined the Company in 2003 and has held human resources leadership roles supporting each of the Company’s major business functions. From 2020 to 2022, Mr. Miller was Vice President, Global Total Rewards, and from 2018 to 2020, was Vice President, Human Resources. From 2015 to 2018, Mr. Miller was an Executive Director, Human Resources. Prior to 2015, Mr. Miller served as a Senior Manager in the Human Resources organization, before his promotion to Director, Human Resources, and then to Strategy Director.

Dr. David M. Reese, age ~~59,~~61, became the Company’s inaugural Executive Vice President ~~R&D,~~and Chief Technology Officer, in ~~2018.~~December 2023, responsible for accelerating the use of technology and artificial intelligence across the organization. From 2018 to December 2023, Dr. Reese served as Executive Vice President, Research and Development. Dr. Reese joined the Company in 2005 and has held leadership roles in development, translational and medical sciences, and discovery ~~research. Dr. Reese was~~research, including as Senior Vice President, Translational Sciences and Oncology, from 2017 to ~~2018 and Senior Vice President, Translational Sciences, from 2015 to 2017.~~2018. Prior to joining Amgen, Dr. Reese was ~~director of Clinical Research at the Breast Cancer International Research Group from 2001 to 2003 and~~ a cofounder, president, and chief medical officer of Translational Oncology Research International, a not-for-profit academic clinical research organization, ~~from 2003 to 2005.~~and director of Clinical Research at the Breast Cancer International Research Group. Dr. Reese previously served on the faculty at UCLA and the University of California, San Francisco.

Mr. Esteban Santos, age ~~54,~~56, became Executive Vice President, Operations, in 2016. Mr. Santos joined the Company in 2007 as Executive Director, Manufacturing Technologies. From 2013 to 2016, Mr. Santos was Senior Vice President, Manufacturing. From 2008 to 2013, Mr. Santos held a number of Vice President roles at the Company in engineering, manufacturing, site operations and drug product. ~~From 2013 to 2016, Mr. Santos was Senior Vice President, Manufacturing.~~ Prior to joining the Company, Mr. Santos served as Site General Manager of J&J’s Cordis operation in Puerto Rico. Prior to J&J, Mr. Santos held several management positions in GE’s industrial and transportation businesses.

Geographic Area Financial Information

For financial information concerning the geographic areas in which we operate, see Part IV—Note 3,4, Revenues, and Note ~~11,~~12, Property, plant and equipment, to the Consolidated Financial Statements.

Investor Information

Financial and other information about us is available on our website at www.amgen.com. We make available on our website, free of charge, copies of our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, current reports on Form 8-K and amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the Exchange Act as soon as reasonably practicable after we electronically file such material with or furnish it to the U.S. Securities and Exchange Commission (SEC). In addition, we have previously filed registration statements and other documents with the SEC. Any document we file may be inspected without charge at the SEC’s website at www.sec.gov. (These website addresses are not intended to function as hyperlinks, and the information contained in our website and in the SEC’s website is not intended to be a part of this filing.)


Item 1A.			RISK FACTORS

SUMMARY

Risks Related to ~~Economic Conditions and Operating a Global Business, Including During the COVID-19 Pandemic~~

•The COVID-19 pandemic, and the public and governmental effort to mitigate against the spread of the disease, have had, and are expected to continue to have, an adverse effect, and may have a material adverse effect, on our clinical trials, operations, manufacturing, supply chains, distribution systems, product development, product sales, business and results of operations.

•A breakdown, cyberattack or information security breach could compromise the confidentiality, integrity and availability of our information technology systems, network-connected control systems and/or our data, interrupt the operation of our business and/or affect our reputation.

•~~Our sales and operations are subject to the risks of doing business internationally, including in emerging markets.~~

~~Risks Related to~~ Government Regulations and Third-Party Policies

•Our sales depend on coverage and reimbursement from government and commercial third-party payers, and pricing and reimbursement pressures have affected, and are likely to continue to affect, our profitability.

•Guidelines and recommendations published by various organizations can reduce the use of our products.

•~~The~~We could be subject to additional tax liabilities, including from an adverse outcome in our ongoing tax dispute with the IRS and other tax examinations, enactment of the OECD minimum corporate tax rate agreement and the adoption and interpretation of new tax legislation, ~~or exposure to~~and we anticipate additional tax liabilities from certain provisions of the 2017 Tax Act that will go into effect in 2026; such tax liabilities could adversely affect our ~~profitability.~~profitability and results of operations.

•Our business may be affected by litigation and government investigations.

Risks Related to Economic Conditions and Operating a Global Business

•Our efforts to collaborate with or acquire other companies, products, or technology, and to integrate the operations of companies or to support the products or technology we have acquired, may not be successful, and may result in unanticipated costs, delays or failures to realize the benefits of the transactions.

•We may not be able to access the capital and credit markets on terms that are favorable to us, or at all.

•A breakdown of our information technology systems, cyberattack or information security breach could significantly compromise the confidentiality, integrity and availability of our information technology systems, network-connected control systems and/or our data, interrupt the operation of our business and/or affect our reputation.

•Our sales and operations are subject to the risks of doing business internationally, including in emerging markets.

Risks Related to Competition

•Our products face substantial competition and our product candidates are also likely to face substantial competition.

•Our intellectual property positions may be challenged, invalidated or circumvented, or we may fail to prevail in current and future intellectual property litigation.

•We currently face competition from biosimilars and generics and expect to face increasing competition from biosimilars and generics in the future.

•Concentration of sales at certain of our wholesaler distributors, and ~~at one free-standing dialysis clinic business and~~ consolidation of private payers, such as insurers, and PBMs has negatively affected, and may continue to negatively affect, our business.

Risks Related to Research and Development

•We may not be able to develop commercial products despite significant investments in R&D.

•We must conduct clinical trials in humans before we commercialize and sell any of our product candidates or existing products for new indications.

•Our current products and products in development cannot be sold without regulatory approval.

•Some of our products are used with drug delivery or companion diagnostic devices that have their own regulatory, manufacturing and other risks.

•Some of our pharmaceutical pipeline and our commercial product sales rely on collaborations with third parties, which may adversely affect the development and ~~sale~~sales of our products.

Risks Related to Operations

•We perform a substantial majority of our commercial manufacturing activities at our facility in the U.S. territory of Puerto Rico and a substantial majority of our clinical manufacturing activities at our facility in Thousand Oaks, California; significant disruptions or production failures at these facilities could significantly impair our ability to supply our products or continue our clinical trials.

•We rely on third-party suppliers for certain of our raw materials, medical devices and components.

•Manufacturing difficulties, disruptions or delays could limit supply of our products and limit our product sales.

•Our business and operations may be negatively affected by the failure, or perceived failure, of achieving our environmental, social and governance objectives.

•The effects of global climate change and related natural disasters could negatively affect our business and operations.

General Risk Factors

•Global economic conditions may negatively affect us and may magnify certain risks that affect our business.

•Our stock price is volatile.

•~~We may not be able to access the capital and credit markets on terms that are favorable to us, or at all.~~

~~RISKS RELATED TO ECONOMIC CONDITIONS AND OPERATING A GLOBAL BUSINESS, INCLUDING DURING THE COVID-19 PANDEMIC~~

The COVID-19 pandemic, and the public and governmental effort to mitigate against the spread of the disease, have had, and are expected to continue to have, an adverse effect, and may have a material adverse effect, on our clinical trials, operations, manufacturing, supply chains, distribution systems, product development, product sales, business and results of operations.

The novel coronavirus identified in late 2019, SARS-CoV-2, which causes the disease known as COVID-19, is an ongoing global pandemic that has resulted in public and governmental efforts to contain or slow the spread of the disease, including widespread shelter-in-place orders, social distancing interventions, quarantines, travel restrictions and various forms of operational shutdowns. The COVID-19 pandemic and the resulting measures implemented in response to the pandemic are adversely affecting, and are expected to continue to adversely affect, our business (including our R&D, clinical trials, operations, manufacturing, supply chains, distribution systems, product development and sales activities), the business activities of our suppliers, customers, third-party payers and our patients. See ~~Our current products and products in development cannot be sold without regulatory approval~~;~~see also~~ ~~We must conduct clinical trials in humans before we commercialize and sell any of our product candidates or existing products for new indications~~. Due to the pandemic and these measures and their effects, we have experienced, and expect to continue to experience, unpredictable reductions in demand for certain of our products, exacerbated by COVID-19 surges resulting in repeated shutdowns and/or disruptions in certain geographies.

Federal, state and local, and international governmental policies and initiatives designed to reduce the transmission of COVID-19 also have resulted in the cancellation or delay of diagnostic, elective, specialty and other procedures and

appointments to avoid non-essential patient exposure to medical environments and potential infection with COVID-19 and to focus limited resources and personnel capacity toward the treatment of COVID-19. For example, an NPR/Harvard poll in 2021 found that, with hospitals crowded from COVID-19, one in five U.S. households has had to delay care for serious illnesses. These measures and challenges will likely continue to varying degrees for the duration of the pandemic and have significantly reduced patient access to, and administration of, certain of our drugs. For example, Prolia requires administration by a healthcare provider in doctors’ offices or other healthcare settings that are affected by COVID-19. The U.S. label for Prolia instructs healthcare professionals who discontinue Prolia to transition the patient to an alternative antiresorptive, including oral treatments that do not require administration by a healthcare provider. Further, as a result of COVID-19, oncology patients, in consultation with their doctors, may be selecting therapies that are less immunosuppressive or therapies that do not require administration in a hospital setting, potentially adversely affecting sales of certain of our products. Also, new patients have been, and are expected to continue to be, less likely to be diagnosed and/or to start therapeutics during the pandemic, and these effects, together with the lower treatment rates during the pandemic, have had, and are expected to continue to have, a cumulative negative effect on the commercial performance of our business. The decrease in diagnoses over the course of the pandemic has suppressed the volume of new patients starting treatment, which we expect to continue to impact our business. Once the pandemic subsides, we anticipate there could be a backlog of patients seeking appointments with physicians relating to a variety of medical conditions, and as a result, patients seeking treatment with certain of our products may have to navigate lower provider capacity, and this lower provider capacity could have a continued adverse effect on our sales following the opening up of various geographies and/or the end of the pandemic. Further, the effects of the COVID-19 pandemic may result in long-term shifts in preferences among healthcare professionals and patients toward treatments that do not require administration by healthcare professionals or visits to medical facilities.

As the pandemic continues, and if conditions worsen or if the duration of the pandemic extends significantly, we expect to experience additional adverse effects on our development, operational and commercial activities, customer purchases and our collections of accounts receivable. It remains uncertain the degree to which these adverse effects would impact our future operational and commercial activities, customer purchases and our collections as conditions begin to improve. There was a resurgence in COVID-19 infections in numerous jurisdictions in 2021, resulting in the reinstatement of stricter restrictions and shutdowns in a number of jurisdictions, including in the United States, Europe and Asia Pacific regions. It is expected that the pandemic will continue to ebb and flow, with different jurisdictions having higher levels of infections than others over the course of the pandemic. New variants of the SARS-CoV-2 virus have emerged, including the delta and omicron variants, and have been shown to be present in many geographies and appear to spread more easily and quickly than other variants. Further, although some studies suggest that antibodies generated with currently authorized vaccines may be effective against these variants, it remains uncertain whether currently available vaccines will retain their efficacy against future variants of the virus. Further, even while vaccine booster shots are available for certain patients, persistent vaccine hesitancy may result in under-vaccinated populations which may prolong the duration of the COVID-19 pandemic and continue to disrupt the availability of healthcare services to the patients we serve. Jurisdictions may implement, continue or reinstate border closures, impose or reimpose prolonged quarantines and further restrict travel and business activity. These measures could significantly affect our ability to support our operations and customers and the ability of our employees to get to their workplaces to discover, study, develop and produce our product candidates and products, disrupt the movement of our products through the supply chain, and further prevent or discourage patients from participating in our clinical trials, seeking healthcare services and the administration of certain of our products. The increased availability of remote working arrangements in response to the COVID-19 pandemic has expanded the pool of companies that can compete for our employees and employment candidates. Further, in connection with the global outbreak and spread of COVID-19 and in an effort to increase the wider availability of needed medical products, we or our suppliers may elect to, or governments may require us or our suppliers to, allocate manufacturing capacity (for example pursuant to the U.S. Defense Production Act) in a way that adversely affects our regular operations, customer relationships and financial results. In the United States, on January 21, 2021, President Biden issued an Executive Order instructing federal agencies to use all available legal authorities, including the Defense Production Act, to improve current and future pandemic response and biological threat preparedness. The rapid reallocation of resources for the treatment and prevention of COVID-19 (including the production of COVID-19 vaccinations or related therapies, such as our agreement to contribute to the production of COVID-19 antibody therapies for Lilly) and/or disruptions and shortages in the global supply chain caused by the pandemic, could also result in increased competition for, or reduced availability of, materials or components used in the development, manufacturing, distribution, or administration of our products. For example, during the second quarter of 2021, an industry-wide shortage of certain lab kit supplies necessary for some activities that support our clinical trials has developed that we are actively monitoring and managing. We have also experienced challenges in obtaining certain COVID-19-related supplies, including COVID-19 antigen rapid test kits for our staff, as a result of high demand and limited supplies during the omicron variant surge. In addition, unpredictable increases in demand for certain of our products could exceed our capacity to meet such demand, which could adversely affect our financial results and customer relationships.

The COVID-19 pandemic and the volatile global economic conditions stemming from it may precipitate or amplify the other risks described in this “Risk Factors” section, which could materially adversely affect our business, operations and

financial condition and results. For example, if a natural disaster or other potentially disruptive event occurs concurrently with the COVID-19 pandemic, such disaster or event could deplete our inventory levels and we could experience a disruption to our manufacturing or ability to supply our products.

The rapid development and fluidity of the pandemic precludes any prediction as to the ultimate effect of COVID-19 on us. The duration of the measures being taken by the authorities to mitigate against the spread of COVID-19 (including the distribution and/or availability of vaccines and boosters), and the extent to which such measures are effective, if at all, remain highly uncertain. The magnitude and degree of COVID-19’s adverse effect on our business (including our product development, product sales, operating results and resulting cash flows) and financial condition will be driven by the severity and duration of the pandemic, the pandemic’s effect on the United States and global economies and the timing, scope and effectiveness of federal, state, local and international governmental responses to the pandemic. If mitigation of the pandemic continues to require further shelter-in-place and shutdown orders and/or restrictions on individual and/or group conduct, any adverse effects of the COVID-19 pandemic will likely grow and could be enduring, and our business and financial position could be materially adversely affected.

A breakdown, cyberattack or information security breach could compromise the confidentiality, integrity and availability of our information technology systems, network-connected control systems and/or our data, interrupt the operation of our business and/or affect our reputation.

To achieve our business objectives, we rely on sophisticated information technology systems, including software, mobile applications, cloud services and network-connected control systems, some of which are managed, hosted, provided or serviced by third parties. Internal or external events that compromise the confidentiality, integrity and availability of our systems and data may significantly interrupt the operation of our business, result in significant costs and/or adversely affect our reputation.

Our information technology systems are highly integrated into our business, including our R&D efforts, our clinical and commercial manufacturing processes and our product sales and distribution processes. Further, as the majority of our employees are working remotely, our reliance on our and third-party information technology systems has increased substantially and is expected to continue to increase. The complexity and interconnected nature of our systems makes them potentially vulnerable to breakdown or other service interruptions. Upgrades or changes to our systems or the software that we use may result in the introduction of new cybersecurity vulnerabilities and risks. Our systems are also subject to frequent cyberattacks. As the cyber-threat landscape evolves, these attacks are growing in frequency, sophistication and intensity, and are becoming increasingly difficult to detect. Such attacks could include the use of harmful and virulent malware, including ransomware or other denials of service, that can be deployed through various means, including the software supply chain, e-mail, malicious websites and/or the use of social engineering. We have also experienced denial of service attacks against our network, and although such attacks did not succeed, there can be no assurance that our efforts to guard against the wide and growing variety of potential attack techniques will be successful in the future. Attacks such as those experienced by governmental entities (including those that approve and/or regulate our products, such as the EMA) and other multi-national companies, including some of our peers, could leave us unable to utilize key business systems or access or protect important data, and could have a material adverse effect on our ability to operate our business, including developing, gaining regulatory approval for, manufacturing, selling and/or distributing our products. For example, in 2017, a pharmaceutical company experienced a cyberattack involving virulent malware that significantly disrupted its operations, including its research and sales operations and the production of some of its medicines and vaccines. As a result of the cyberattack, its orders and sales for certain products in certain markets were negatively affected. In December 2020, SolarWinds Corporation, a leading provider of software for monitoring and managing information technology infrastructure, disclosed that it had suffered a cybersecurity incident whereby attackers had inserted malicious code into legitimate software updates for its products that were installed by myriad private and government customers, enabling the attackers to access a backdoor to such systems.

Our systems also contain and utilize a high volume of sensitive data, including intellectual property, trade secrets, financial information, regulatory information, strategic plans, sales trends and forecasts, litigation materials and/or personal information belonging to us, our staff, our patients, customers and/or other parties. In some cases, we utilize third-party service providers to process, store, manage or transmit such data, which may increase our risk. Intentional or inadvertent data privacy or security breaches (including cyberattacks) resulting from attacks or lapses by employees, service providers (including providers of information technology-specific services), nation states (including groups associated with or supported by foreign intelligence agencies), organized crime organizations, “hacktivists” or others, create risks that our sensitive data may be exposed to unauthorized persons, our competitors, or the public. For example, a supplier recently experienced a data breach in which an unauthorized third party acquired access to certain information provided to the supplier in the course of its provision of services to us, including business documents and certain personally identifiable patient information (not including social security or other financial or health insurance information). As required, we promptly notified the applicable state attorneys general and the individuals whose personally identifiable information was affected of this data breach at the supplier. Although the supplier data breach did not result in a material adverse effect on our business, there can be no assurance that a similar

future cybersecurity incident would not result in a material adverse effect on our business or results of operations. Another vendor experienced a cyberattack and, while initially reporting that our information was not involved, the vendor subsequently informed us that the attacker had accessed limited, non-significant information. Although this breach did not have a significant adverse effect on us, we may not receive timely reporting of future breaches. Cyberattackers are increasingly exploiting vulnerabilities in commercially available software from shared or open-source code. We rely on third party commercial software that may have such vulnerabilities, but as use of open-source code is frequently not disclosed, our ability to fully assess this risk to our systems is limited. For example, in December 2021, a remote code execution vulnerability was discovered in a widely used software library that is used in a variety of commercially available software and services. Although this vulnerability has not resulted in any significant adverse effects on us, there can be no assurances that a similar future vulnerability in the software and services that we use would not result in a material adverse effect on our business or results of operations.

Domestic and global government regulators, our business partners, suppliers with whom we do business, companies that provide us or our partners with business services, and companies we have or may acquire face similar risks, and security breaches of their systems or service outages could adversely affect our security, leave us without access to important systems, products, raw materials, components, services or information or expose our confidential data or sensitive personal information. For example, in 2019, two vendors that perform testing and analytical services that we use in developing and manufacturing our products experienced cyberattacks, and in April and September of 2020, vendors that provide us with information technology services and clinical data services, respectively, each experienced ransomware attacks. Although there was no breach of our systems, each of these incidents required us to disconnect our systems from those vendors’ systems. While we were able to reconnect our systems following restoration of these vendors’ capabilities without significantly affecting product availability, a more extended service outage affecting these or other vendors, particularly where such vendor is the single source from which we obtain the services, could have a material adverse effect on our business or results of operations. In addition, we distribute our products in the United States primarily through three pharmaceutical wholesalers, and a security breach that impairs the distribution operations of our wholesalers could significantly impair our ability to deliver our products to healthcare providers and patients.

Although we have experienced system breakdowns, attacks and information security breaches, we do not believe such breakdowns, attacks and breaches have had a material adverse effect on our business or results of operations. We continue to invest in the monitoring, protection and resilience of our critical and/or sensitive data and systems. However, there can be no assurances that our efforts will detect, prevent or fully recover systems or data from all breakdowns, service interruptions, attacks and/or breaches of our systems that could adversely affect our business and operations and/or result in the loss or exposure of critical, proprietary, private, confidential or otherwise sensitive data, which could result in material financial, legal, business or reputational harm to us or negatively affect our stock price. While we maintain cyber-liability insurance, our insurance is not sufficient to cover us against all losses that could potentially result from a service interruption, breach of our systems or loss of our critical or sensitive data.

We are also subject to various laws and regulations globally regarding privacy and data protection, including laws and regulations relating to the collection, storage, handling, use, disclosure, transfer and security of personal data. The legislative and regulatory environment regarding privacy and data protection is continuously evolving and developing and the subject of significant attention globally. For example, we are subject to the European Union’s General Data Protection Regulation, which became effective in May 2018, and the California Consumer Privacy Act of 2018 (CCPA), which became effective in January 2020, both of which provide for substantial penalties for non-compliance. The CCPA was amended in late 2020, to create the California Privacy Rights Act to create opt-in requirements for the use of sensitive personal data and the formation of a new dedicated agency for the enforcement of the law, the California Privacy Protection Agency. Since then, Virginia and Colorado both passed similar consumer privacy laws that will go into effect in 2023. Other jurisdictions where we operate have passed, or continue to propose, similar legislation and/or regulations. Failure to comply with these current and future laws could result in significant penalties and reputational harm and could have a material adverse effect on our business and results of operations.

~~Our sales and operations are subject to the risks of doing business internationally, including in emerging markets.~~

~~in emerging markets. See~~ ~~We must conduct clinical trials in humans before we commercialize and sell any of our product candidates or existing products for new indications~~. Our expansion efforts in China and emerging markets around the world is dependent upon the establishment of an environment that is predictable, navigable and supportive of biopharmaceutical innovation, sustained access for our products and predictable pricing controls. For example, China continues to strengthen regulations on the collection, use and transmission of Chinese human genetic resources, and has expanded regulations on the conduct of biotechnology R&D activities in China. Our applications to the HGRAC seeking approval to conduct clinical trials in China are delayed pending further guidance from HGRAC. Our international operations and business may also be subject to less protective intellectual property or other applicable laws, diverse data privacy and protection requirements, changing tax laws and tariffs, trade restrictions or other barriers designed to protect industry in the home country against foreign competition, far-reaching antibribery and anticorruption laws and regulations and/or evolving legal and regulatory environments.

As we expand internationally, we are subject to fluctuations in foreign currency exchange rates relative to the U.S. dollar. While we have a program in place that is designed to reduce our exposure to foreign currency exchange rate fluctuations through foreign currency hedging arrangements, our hedging efforts do not completely offset the effect of these fluctuations on our revenues and earnings. In addition, we have a number of financial instruments referencing the LIBOR. On July 27, 2017, the U.K. Financial Conduct Authority, which regulates LIBOR, announced that it will no longer require banks to submit rates for the calculation of LIBOR to the LIBOR administrator after 2021, and it is anticipated that LIBOR will be completely phased out and replaced by 2023. In March 2020 and in January 2021, the FASB issued a new accounting standard to ease the financial burdens of the expected market transition from LIBOR and other interbank offered rates to alternative reference rates. While it appears likely that SOFR will be the replacement reference rate adopted in the market, the specific mechanisms to replace LIBOR in our existing LIBOR-linked financial instruments have not been finalized. As such, the replacement of LIBOR could have an adverse effect on the market for, or value of, our LIBOR-linked financial instruments. See Part IV—Note 1, Summary of significant accounting policies—Recent accounting pronouncements. We are also subject to the economic and political uncertainties stemming from the United Kingdom’s exit from the EU, commonly referred to as “Brexit,” which occurred on January 31, 2020. While our manufacturing and packaging activities take place largely outside the United Kingdom, minimizing the need to make costly and significant changes to those operations, we have nevertheless been working to put in place contingency plans to attempt to mitigate the effects of Brexit on us. Overall, the legal and operational challenges of our international business operations, along with government controls, the challenges of attracting and retaining qualified personnel and obtaining and/or maintaining necessary regulatory or pricing approvals of our products, may result in material adverse effects on our international product sales, business and results of operations.

RISKS RELATED TO GOVERNMENT REGULATIONS AND THIRD-PARTY POLICIES

Our sales depend on coverage and reimbursement from government and commercial third-party payers, and pricing and reimbursement pressures have affected, and are likely to continue to affect, our profitability.

Sales of our products depend on the availability and extent of coverage and reimbursement from third-party payers, including government healthcare programs and private insurance plans. Governments and private payers continue to pursue initiatives to manage drug utilization and contain costs. ~~These payers~~Further, pressures on healthcare budgets from the economic downturn and inflation continue and are likely to increase across the markets we serve. Payers are increasingly focused on costs, which have resulted, and are expected to continue to result, in lower reimbursement rates for our products or narrower populations for ~~whom~~which payers will reimburse. Continued intense public scrutiny of the price of drugs and other healthcare costs, together with payer dynamics, have limited, and are likely to continue to limit, our ability to set or adjust the price of our products based on their value, which can have a material adverse effect on our business. In the United States, particularly over the past few years, a number of legislative and regulatory proposals have been introduced ~~in an~~and/or signed into law that attempt to lower drug prices. These include ~~proposals~~the IRA legislation that ~~would allow~~enables the U.S. government to ~~negotiate drug~~set prices ~~directly, limit drug reimbursement~~for certain drugs in Medicare, and/or the commercial market based on reference prices or permit importation of drugs from Canada. Additional proposals would require a rebate to the government for any price increase in excess of the Consumer Price Index for All Urban Consumers and/orredesigns Medicare Part D benefits to shift ~~some~~a greater portion of the costs ~~of these Medicare Part D reforms~~ to manufacturers and enables the U.S. government to ~~offset the cost. Certain~~impose penalties if drug prices are increased at a rate faster than inflation. Additional proposals focused on drug pricing ~~have been adopted~~continue to be debated, and additional ~~proposals~~executive orders focused on drug pricing and competition are likely to be adopted and implemented in some form. Government actions or ballot initiatives at the state level also represent a highly active area of policymaking and experimentation, including pursuit of proposals that limit drug reimbursement under state run Medicaid programs based on reference prices or permitting importation of drugs from Canada. Such state policies may also eventually be adopted at the federal level.

We are unable to predict which or how many policy, regulatory, administrative or legislative changes may ultimately be, or effectively estimate the consequences to our business if, enacted and implemented. However, to the extent that payer actions further decrease or modify the coverage or reimbursement available for our products, require that we pay increased rebates or shift other costs to us, limit or affect our decisions regarding the pricing of or otherwise reduce the use of our products, such actions could have a material adverse effect on our business and results of operations.

—Changing U.S. federal coverage and reimbursement policies and practices have affected and ~~may~~are likely to continue to affect access to, pricing of and sales of our products

A substantial portion of our U.S. business relies on reimbursement from federal government healthcare programs and commercial insurance plans regulated by federal and state governments. See Part I, Item 1. Business—Reimbursement. Our business has been and will continue to be affected by legislative actions changing U.S. federal reimbursement policy. ~~Congress has been focused on drug pricing reforms~~For example, in 2022, the IRA was enacted and ~~oversight since 2018, and this activity is still ongoing and has intensified.In 2019, 2020 and 2021, a number of Congressional committees debated drug pricing reform proposals and,~~includes provisions requiring that beginning in ~~2020, Amgen participated~~2026, mandatory price setting be introduced in House Oversight and Reform Committee hearings on drug pricing practices. In 2019, the Senate Finance Committee advanced a bill that would, among other things, penalize pharmaceutical manufacturers for raising prices on drugs

~~covered by~~ Medicare Parts B and/or D faster than the rate of inflation, cap out-of-pocket expenses for Medicare Part D beneficiaries and require higher/additional manufacturer discounts in Medicare Part D. Additionally, in late 2019, a drug-pricing bill, H.R. 3, passed the House of Representatives, which would, among other things, enable direct price negotiations by the federal government on certain drugs (with the maximum price paid by Medicare capped by prices derived from an international index), include a penalty for failing to reach agreement with the government and require that manufacturers offer these negotiated prices to other payers. In 2021, proposals from H.R. 3 were incorporated and adapted into other proposed legislation. These proposals, which included penalties if drug price benchmarks rise faster than inflation, Medicare price setting for certain drugs paid for under Parts B and D, ~~(whereby~~whereby manufacturers must accept a price established by the government or face ~~a penalty~~penalties on all U.S. ~~sales),~~sales (starting with ten drugs in 2026, adding 15 in 2027 and 2028, and adding 20 in 2029 and subsequent years such that by 2031 approximately 100 drugs could be subject to such set prices). The Medicare

price setting process began on August 29, 2023 when CMS announced the first ten drugs for Medicare price setting, which includes ENBREL. Our wholly owned subsidiary, Immunex Corporation, which holds the rights to the ENBREL BLA, entered into an agreement with the U.S. government to participate in the price setting process and submitted the required data to CMS for ENBREL, including certain price, cost and patent data. The Medicare price setting process will conclude by August 1, 2024, and by September 1, 2024, CMS will publish prices that will be applicable to these ten drugs in the Medicare program beginning January 1, 2026. Also under the IRA, starting on January 1, 2024, Medicare Part D ~~redesign including a~~was redesigned to cap on beneficiary ~~spending~~out-of-pocket costs and, ~~a new manufacturer discount program, are also likely to~~beginning January 1, 2025, Federal reinsurance will be ~~considered~~reduced in the catastrophic phase (resulting in a ~~reconciliation~~shift and increase of such costs to Part D plans and manufacturers, including by requiring manufacturer discounts on certain drugs). Further, the IRA created a mechanism for CMS to collect rebates from manufacturers if price increases outpace inflation. Rebate obligations began to accrue October 1, 2022 for Medicare Part D and January 1, 2023 for Medicare Part B, but CMS has not yet issued invoices and has some discretion as to when it must bill manufacturers. We expect that remains to be further debated between the Senate, House and White House. This framework remains in discussion with policymakers in Congress and the Administration. There are other outstanding proposals that, if enacted and implemented in whole or in part, could also affect access to and salesseveral of our products will be subject to these inflation rebates, and several of our products have been on lists that are issued and updated on a quarterly basis by CMS under a related program under which Medicare beneficiaries are charged reduced coinsurance if price increases exceed inflation. The IRA’s drug pricing controls and Medicare redesign are likely to have a material adverse effect on our sales, our business and our results of operations, and such impact is expected to increase through the end of the decade and will depend on factors including ~~but not limited~~the extent of our portfolio’s exposure to ~~proposals~~Medicare reimbursement, the rate of inflation over time, the number of our products selected for mandatory price setting and the timing of market entry of generic or biosimilar competition. Further, following the passage of the IRA, the environment remains dynamic and U.S. policymakers continue to ~~allow importation of prescription medications from Canada~~demonstrate interest in health care and drug pricing changes. For example, CMS issued a proposed Medicaid Drug Rebate Program rule that, if finalized, would require manufacturers to aggregate or “stack” all rebates, discounts, or other ~~countries.~~price concessions made to separate, unrelated entities across the pharmaceutical supply chain on a given unit of product to determine the “Best Price,” a metric that is used to determine Medicaid rebates and 340B statutory rates. In ~~July~~early 2023, the HHS selected new healthcare payment and delivery models for testing, in response to an October 2022 Executive Order on Lowering Prescription Drug Costs for Americans, including the Accelerating Clinical Evidence Model, which could introduce new payment methods that reduce reimbursement for drugs approved under accelerated approval. That Executive Order followed a 2021 ~~the Administration issued an~~ Executive Order designed to ~~address anticompetitive behavior across multiple sectors, and for~~increase competition in the healthcare sector, ~~called~~including by calling for ~~among other things,~~ the FDA ~~to work with states and Indian Tribes~~ to develop prescription drug importation programs ~~more~~and the FTC to apply greater scrutiny of anticompetitive activity byand responses to which include actions from the FTC, emphasized the need for actions to allow for greater competition from generics and biosimilars, and included a process and timeline for federal agencies to deliver ideas to address drug pricing to the Administration. Subsequently, in September 2021, HHS (which released a report ~~that presented guiding principles for the Administration’s~~with drug pricing proposals ~~including changes~~that seek to promote ~~competition throughout~~competition) and from the ~~prescription drug industry, highlighting potential legislative policies that Congress could pursue (including drug price negotiation in Medicare Parts B and D, making those negotiated prices available~~USPTO (which has taken steps to ~~commercial plans and legislation to speed~~strengthen coordination with the ~~entry of biosimilar and generic drugs) and examples of potential administrative tools available to the HHS (including testing various models and enhanced focus of the FTC and the USPTO~~FDA to address impediments to generic drug and biosimilar competition). Also, in response to the July 2021 Executive Order, the FDA sent a letter to the USPTO describing ways to strengthen coordination between the two agencies, offering training to help identify prior art, and seeking USPTO’s views on practices that extend market exclusivities, whether pharmaceutical patent examiners need additional resources, and the effect of post-grant challenges at the PTAB on drug patents.

Legislation enacted in 2021 has also contained drug pricing reforms, including the Infrastructure Investment and Jobs Act and the American Rescue Plan Act of 2021 that include provisions requiring, starting in 2023, manufacturers to provide refunds to the government for discarded amounts of drugs from single use containers under Medicare Part B, and starting in 2024, increases the Medicaid rebate liability for certain medicines that raise prices in excess of inflation, respectively. The Infrastructure Investment and Jobs Act also delays implementation until January 1, 2026 of a final rule issued by HHS, that revises regulations under the federal antikickback statute to encourage PBMs to use rebates received from biopharmaceutical manufacturers to reduce patient cost-sharing at the point of sale under Medicare Part D. This rule is also subject to litigation, has numerous logistical hurdles to overcome before it can be effectively implemented, and it is unclear how PBMs will respond to the implementation of such rule. Further, a permanent repeal of this rule is also being considered in other legislation.

Our business has been, and is expected to continue to be, affected by changes in U.S. federal reimbursement policy resulting from federal regulations and federal demonstration projects. Over the past several years, federal agencies, including the CMS, announced a number of recommendations, policies, proposals and demonstration projects addressing drug pricing. The Administration has also developed and sought to advance a range of policy proposals that could impact U.S. federal reimbursement policy for drugs and biologics, including changes to Medicare Parts B and D. For example, in 2020, in response to an Executive Order, HHS released a rule to allow states to potentially enable the importation of certain drugs from Canada. While this rule is in litigation, should such litigation be unsuccessful, it could allow for the importation of Canadian versions of certain of Amgen’s products (including Otezla), that could have a material adverse effect on Amgen’s business. Also in response to an Executive Order, CMS released an interim final rule to implement the MFN pricing approach aimed at setting the reimbursement rate for 50 Medicare Part B drugs (including our products, such as Prolia, XGEVA, KYPROLIS, Neulasta, Nplate, EPOGEN and Aranesp) equal to the lowest adjusted price in 22 OECD nations for these drugs. In December 2021, subsequent to challenges, including procedural defects, CMS announced it was withdrawing the MFN rule. Notwithstanding the withdrawal of the rule, the MFN rule’s approach to drug pricing and other similar approaches remain of interest to policymakers. In connection with its withdrawal of the MFN rule, CMS noted that it will “… explore all options to incorporate value into payments for Medicare Part B drugs, improve beneficiaries’ access to evidence-based care, and reduce drug spending for consumers and throughout the health care system.” Further, we expect continued significant focus on healthcare and similar drug pricing proposals for the foreseeable future, including proposals under which the government would set drug prices or limit drug reimbursement.

Other CMS policy changes and demonstration projects to test new care, delivery and payment models can also significantly affect how drugs, including our products, are covered and reimbursed. ~~For example, we believe that CMS’ Oncology Care Model demonstration (which has since 2016 provided participating physician practices with performance-based financial~~

~~incentives that aim to manage or reduce Medicare costs without negatively affecting~~In the ~~efficacy~~fourth quarter of ~~care) has reduced utilization of certain of our oncology products by participating physician practices and expect that it will continue to do so in the future. Further, HHS’s September~~ 2021, ~~comprehensive~~HHS released a plan to address drug pricing that included potential future mandatory models that link payment for prescription drugs and biologics to certain factors, ~~such as: improved patient outcomes, reductions in health disparities, patient affordability and lower~~including the overall ~~costs; bundled payment models; total~~ cost of ~~care models; models in which~~care. In March 2023, the Administration released its budget plan for fiscal year 2024 that included proposals to expand the number of drugs subject to mandatory Medicare ~~Part B savings from utilization of biosimilars, generics, or other high-value products are shared between prescribing providers~~price setting under the IRA, imposing such price setting activity earlier, and extending to commercial health insurance the ~~government; additional Medicare Part D cost-sharing support for biosimilars and generics; and potential expansion~~requirement that drug manufacturers pay rebates if price increases outpace inflation. While those proposed expansions of the ~~Part D Senior Savings Model~~IRA’s drug pricing controls have not been enacted, the proposals demonstrate that this area continues to ~~additional classes of drugs. CMS also recently proposed~~be a national coverage determination for Medicare which limits coverage of certain Alzheimer’s disease medications approved by the FDA only to patients in qualifying clinical trials, suggesting that regulatory approval does not necessarily result in full Medicare coverage. In this dynamic environment, particularly in lightfocus of the pressures on healthcare budgets as a result of the pandemic, we are unable to predict which or how many federal policy, legislative, regulatory, executive or administrative changes may ultimately be, or effectively estimate the consequences to our business if, enacted and implemented. However, to the extent that these or other federal government initiatives further decrease or modify the coverage or reimbursement available for our products, require that we pay increased rebates or shift other costs to us, limit or affect our decisions regarding the pricing of or otherwise reduce the use of our U.S. products, or limit our ability to offer co-pay payment assistance to commercial patients, such actions could have a material adverse effect on our business and results of operations.Administration.

We also face risks ~~relating~~related to the reporting of pricing data that affects ~~the~~ reimbursement of and discounts provided for our products. U.S. government price reporting regulations are complex and may require a biopharmaceutical ~~manufacturer~~manufacturers to update certain previously submitted data. If our submitted pricing data are incorrect, we may become subject to substantial fines and penalties or other government enforcement actions, which could have a material adverse effect on our business and results of operations. In addition, as a result of restating previously reported price data, we ~~also~~ may be required to pay additional rebates and provide additional discounts. CMS finalized a rule in December 2020 providing that, starting January 1, 2023, unless a manufacturer can ensure that the full amount of manufacturer patient assistance programs is passed on to the patient, such amount will be treated as a price reduction that will be taken into account when reporting our Best Price and/or Average Manufacturer Price. Given the use by PBMs and insurers of copay accumulator adjustment programs to apply such patient assistance for the benefit of such companies and not to defray costs to patients, it could be difficult to impossible for manufacturers to ensure that the full value of such amounts is being passed on to the patient. This new policy, if implemented, would have significant implications for our ability to offer copay assistance programs. Although implementation has been delayed by the current Administration, the prior Administration finalized a rule (which was to be effective January 1, 2022) mandating price and cost-sharing transparency for almost all health plans and insurers in the individual and group commercial markets. Additionally, the Administration recently finalized transparency provisions required under the Consolidated Appropriations Act of 2021 for health plans and insurer reporting of certain drug pricing information by December 27, 2022, and each June thereafter, resulting in a biennial public report highlighting drug pricing trends and the impact of prescription drug costs on premiums and out-of-pocket costs. It is unclear how group health plans and health insurers may respond.

—Changing reimbursement and pricing actions in various states have negatively affected and may continue to negatively affect access to and have affected and may continue to affect sales of our products

At the state level, government actions or ballot initiatives can also affect how our products are covered and reimbursed and/or create additional pressure on our pricing decisions. A number of states have adopted, and many other states are considering, drug importation programs or other new pricing actions, including proposals designed to require biopharmaceutical manufacturers publicly to report proprietary pricing information, limit price increases or place a maximum price ceiling or cap on biopharmaceutical products. Existing and proposed state pricing laws have added complexity to the pricing of drugs and may already be affecting industry pricing decisions. ~~For example, a California law, the constitutionality~~A number of ~~which is currently being challenged, purports~~states have adopted, and many other states are considering, drug importation programs and other pricing actions, including proposals designed to require biopharmaceutical manufacturers to ~~notify health insurers and government health plans at least 60 days before scheduled prescription drug~~report to the state proprietary pricing information or provide advance notice of certain price ~~increases that exceed certain thresholds. Similar laws exist in Oregon and Washington.~~ increases.

States are also enacting laws referencing the IRA and seeking to ~~change~~regulate the ~~way they pay~~340B Drug Pricing Program. For example, following the passage of the IRA, bills have been proposed in multiple states that would apply the drug price caps set by HHS for ~~drugs for~~Medicare to drug prices in an individual state. For Medicaid patients, covered by state programs. California adopted a 2020-21 budget that incorporates international pricing into Medicaid supplemental rebate negotiations and allows its Medicaid program to seek federal approval to extend supplemental rebates to non-Medicaid populations. New York, Massachusetts and Ohiostates have established a Medicaid drug spending ~~caps,~~cap (New York) and ~~additional~~implemented a new review and supplemental rebate negotiation process (Massachusetts). Seven states ~~may consider doing so~~(Colorado, Maine, New Hampshire, Maryland, Minnesota, Oregon and Washington) have enacted laws that establish PDABs to

identify drugs that pose affordability challenges, and four such states include authority for the state PDAB to set upper payment limits on certain drugs for in-state patients, payers and providers. So far in 2024, no fewer than 11 states have pending PDAB legislation. States with enacted PDAB laws are in various phases of implementation, with Colorado’s PDAB being the furthest along. In August 2023, the Colorado PDAB announced the first five drugs to undergo an affordability review, one of which is ENBREL. If the PDAB process determines that ENBREL is unaffordable, ENBREL could be subject to an upper payment limit as ~~they face budget deficits~~early as Q4 2024. Louisiana and Arkansas have enacted laws with mandates on manufacturers participating in 340B, and thus far in 2024, no fewer than 15states have similar legislation pending. These bills vary, but include provisions on restricting a manufacturer’s ability to direct drugs in 340B channels, recognizing 340B contract pharmacies and a prohibition on requiring the inclusion of 340B claims modifiers. Further, in Genesis Health Care, Inc. v. Becerra, the U.S. District Court for the District of South Carolina issued an order in November 2023 that enjoins the Health Resources and Services Administration from enforcing its more restrictive interpretation of what is considered a patient under the ~~effects~~340B program, to the potential benefit of ~~COVID-19.~~ healthcare systems seeking to expand the application of 340B discounts.

Additionally, on January 5, 2024, the FDA authorized Florida to move forward with its importation program proposal. Colorado, ~~Florida,~~ Maine, New Hampshire, New Mexico, Texas and Vermont have also enacted state importation laws, and ~~several other states~~some have ~~proposed laws,~~submitted plans for approval to ~~facilitate~~ the ~~importation of drugs from Canada.~~FDA. Other states could adopt similar approaches or could pursue different policy changes in a continuing effort to reduce their costs.

Ultimately, as with U.S. federal government actions, existing or future state government actions or ballot initiatives may also have a material adverse effect on our product sales, business and results of operations.

—U.S. commercial payer actions have affected and may continue to affect access to and sales of our products

Payers, including healthcare insurers, PBMs, integrated healthcare delivery systems (vertically-integrated organizations built from ~~the consolidation~~consolidations of healthcare insurers and PBMs) and group purchasing organizations, increasingly seek ways to reduce their costs. With increasing frequency, payers are adopting benefit plan changes that shift a greater proportion of drug costs to patients. Such measures include more limited benefit plan designs, high deductible plans, higher patient ~~copay~~co-pay or coinsurance obligations and more significant limitations on patients’ use of manufacturer commercial ~~copay~~co-pay assistance programs. Further, government regulation of payers may affect these trends. For example, CMS finalized a policy ~~in May 2020 (for~~for plan years starting on or after January 1, 2021 ~~and remains standing policy for 2022)~~ that has caused commercial payers to more widely adopt ~~copay~~co-pay accumulator adjustment programs. While the U.S. District Court for the District of Columbia struck down this policy in September 2023 and further clarified in December 2023 that its ruling had the effect of reinstating the co-pay accumulator adjustment policy from 2020, CMS and HHS have signaled that they do not intend to enforce certain restrictions from the 2020 policy that would reduce the adoption of co-pay accumulator adjustment programs. Payers, including PBMs, have sought, and continue to seek, price discounts or rebates in connection with the placement of our products on their formularies or those they manage, ~~particularly in treatment areas where the payer has taken the position that multiple branded products are therapeutically comparable. Payers~~and to also ~~control costs by imposing~~impose restrictions on access to or usage of our products ~~such~~(such as Step ~~Therapy, or requiring~~Therapy), require that patients receive the payer’s prior authorization before covering the product, and/or ~~that patients use a mail-order pharmacy or a limited network of payer fully-owned mail-order or specialty pharmacies. Payers have also~~ chosen to exclude certain indications for which our products are ~~approved or chosen to exclude coverage entirely.~~approved. For example, some payers require physicians to demonstrate or document that the patients for whom Repatha has been prescribed meet ~~payer~~their utilization ~~management~~ criteria, and these requirements have ~~limited,~~served to limit and may continue to limit patient access to Repatha treatment. In an effort to reduce barriers to access, we reduced the net price of Repatha by providing greater discounts and rebates to payers ~~including~~(including PBMs that administer Medicare Part D prescription drug ~~plans. However, affordability of patient out-of-pocket co-pay cost has limited~~plans), and ~~may continue to limit patient use. For example, in late 2018 and early 2019,~~ in response to a very high percentage of Medicare patients abandoning their Repathaprescriptions rather than ~~pay~~paying their co-pay, ~~payment,~~ we introduced a set of new National Drug Codes to make Repatha available at a lower list ~~price~~price. However, affordability of patient out-of-pocket co-pay cost has limited and may continue to ~~attempt to address affordability for patients, particularly those on Medicare, and on December 31, 2019, we discontinued the higher list price option for Repatha. Despite~~limit patient use. Further, despite these net and list price reductions, some payers have restricted, and may continue to restrict, patient access and ~~have and~~ may ~~continue to change formulary coverage for Repatha,~~ seek further discounts or rebates or take other actions, such as changing formulary coverage for Repatha, that could reduce our sales of Repatha. These factors have limited, and may continue to limit, patient affordability and use, ~~and~~ negatively ~~affect~~affecting Repatha sales.

Further, significant consolidation in the health insurance industry has resulted in a few large insurers and PBMs, which places greater pressure on pricing and usage negotiations with biopharmaceutical manufacturers, significantly increasing discount and rebate requirements and limiting patient access and usage. For example, in the United States, as of the beginning of ~~2021,~~2024, the top five integrated health plans and PBMs controlled about ~~85%~~92% of all pharmacy prescriptions. ~~The~~This high degree of consolidation among insurers, PBMs and other payers, including ~~through~~ integrated healthcare delivery systems and/or with specialty or mail-order pharmacies and pharmacy retailers, has increased the negotiating leverage such entities have over us and other biopharmaceutical manufacturers and has resulted in greater price discounts, rebates and service fees realized by those ~~payers. In 2019, 2020 and 2021,~~payers from our business. Each of CVS, Express Scripts and United Health Group ~~respectively, each created~~(among the top five integrated health plans and PBMs), have Rebate Management Organizations that further increase their ~~respective~~ leverage to negotiate deeper discounts. Ultimately, additional discounts, rebates, fees, coverage orchanges, plan changes, restrictions or exclusions imposed by these commercial payers could have a material adverse effect on our product sales, business and results of operations. Policy reforms advanced by Congress or the Administration that refine the role of PBMs in the U.S. marketplace could have downstream implications or

consequences for our business and how we interact with these entities. For example, in June 2022, the FTC launched an inquiry into the business practices of PBMs and subsequently expanded the investigation to the three rebate management organizations owned by the three largest PBMs. In addition, multiple Congressional Committees are investigating PBM practices and have also proposed legislation that could increase transparency and reporting of these practices and/or impact rebates and service fees. The results of such inquiry could have an effect on manufacturer interactions with PBMs, resulting in changes to access for certain medicines. See Concentration of sales at certain of our wholesaler distributors, and ~~at one free-standing dialysis clinic business and~~ consolidation of private payers, such as insurers, and PBMs has negatively affected, and may continue to negatively affect, our business.

Our business is also affected by policies implemented by private healthcare entities that process Medicare claims, including Medicare Administrative Contractors. For example, in the second quarter of 2022, several Medicare Administrative Contractors issued notice that TEZSPIRE would be added to their “self-administered drug” exclusion lists. Although the Medicare Administrative Contractors subsequently removed TEZSPIRE from their exclusion lists, these exclusions, if reintroduced and/or implemented, would result in Medicare beneficiaries with severe asthma losing access to TEZSPIRE coverage under Medicare Part B and potentially also under Medicare Advantage.

—Government and commercial payer actions outside the United States have affected and will continue to affect access to and sales of our products

Outside the United States, we expect countries will also continue to take actions to reduce their drug ~~expenditures.~~expenditures and to reduce intellectual property protections. See Part I, Item 1. Business—Reimbursement. ~~IRP~~Pressures to decrease drug expenditures may intensify as governments take actions to address budgets strained by high inflation, expenditures to respond to the COVID-19 pandemic and weak economic conditions, including in Europe where the effects of the Russia–Ukraine conflict have challenged the economies in that region. Further, the EU is currently undergoing a review and possible revision of its pharmaceutical legislation that, while full implementation is not expected before 2027, could lead to proposals that will reduce intellectual property protection for new products (including potentially shortening the duration of regulatory data exclusivity and orphan drug exclusivity protections), as well as change the reimbursement and regulatory landscape. International reference pricing has been widely used by many countries outside the United States to control costs based on an external benchmark of a product’s price in other countries. ~~IRP~~International reference pricing policies can change quickly and frequently and may not reflect differences in the burden of disease, indications, market structures or affordability differences across countries or regions. Other expenditure control practices, including but not limited to the use of revenue clawbacks, rebates and ~~percentage~~ caps on ~~price increases,~~product sales, are used in various foreign jurisdictions as well. In addition, countries may refuse to reimburse or may restrict the reimbursed population for a product when their national health technology assessments do not consider a medicine to demonstrate sufficient clinical benefit beyond existing therapies or to meet certain cost effectiveness thresholds. For example, despite the EMA’s approval of Repatha for the treatment of patients with established atherosclerotic disease, prior to 2020, the reimbursement ~~for~~of Repatha in France ~~prior to 2020~~ was limited to a narrower patient population (such as those with ~~HoFH)~~homozygous familial hypercholesterolemia (HoFH)) following a national health technology ~~assessment, which had limited our efforts in France to expand Repatha access to the broader patient population covered by the approved label. Some~~assessment. Many countries decide on reimbursement between potentially competing products through national or regional tenders that often result in one product receiving most or all of the sales in that country or region. Failure to obtain coverage and reimbursement for our products, a deterioration in their existing coverage and

reimbursement or a decline in the timeliness or certainty of payment by payers to ~~physicians~~hospitals and other providers has negatively affected, and may further negatively affect, the ability or willingness of healthcare providers to prescribe our products for their patients and otherwise negatively affect the use of our products or the prices we realize for them. Such changes have had, and could in the future have, a material adverse effect on our product sales, business and results of operations.

Guidelines and recommendations published by various organizations can reduce the use of our products.

Government agencies promulgate regulations and guidelines directly applicable to us and to our products. Professional societies, practice management groups, insurance carriers, physicians’ groups, private health and science foundations and organizations involved in various diseases also publish guidelines and recommendations to healthcare providers, administrators and payers, as well as patient communities. Recommendations by government agencies or other groups and organizations may relate to such matters as usage, dosage, route of administration and use of related therapies. In addition, a growing number of organizations are providing assessments of the value and pricing of biopharmaceutical products, and even organizations whose guidelines have historically been focused on clinical matters have begun to incorporate analyses of the cost effectiveness of various treatments into their treatment guidelines and recommendations. Value assessments may come from private organizations that publish their findings and offer recommendations relating to the products’ reimbursement by government and private payers. Some companies and payers have announced pricing and payment decisions based in part on the assessments of private organizations. In addition, government health technology assessment organizations in many countries make reimbursement recommendations to payers in their jurisdictions based on the clinical effectiveness, cost-effectiveness and service effects of new, emerging and existing medicines and treatments. Such health technology assessment organizations have recommended, and may in the future recommend, reimbursement for certain of our products for a narrower indication than was

approved by applicable regulatory agencies or may recommend against reimbursement entirely. See Our sales depend on coverage and reimbursement from government and commercial third-party payers, and pricing and reimbursement pressures have affected, and are likely to continue to affect, our profitability. ~~Such~~The EU has adopted regulations, effective beginning in January 2025, that are intended to increase cooperation among EU member states and harmonize various procedures and standards at the EU level in assessing health technologies and in support of joint clinical assessments of health technologies and medicines. These and other such recommendations or guidelines may affect our reputation, and any recommendations or guidelines that result in decreased use, dosage or reimbursement of our products could have a material adverse effect on our product sales, business and results of operations. In addition, the perception by the investment community or stockholders that such recommendations or guidelines will result in decreased use and dosage of our products could adversely affect the market price of our common stock.

~~The~~We could be subject to additional tax liabilities, including from an adverse outcome in our ongoing tax dispute with the IRS and other tax examinations, enactment of the OECD minimum corporate tax rate agreement and the adoption and interpretation of new tax legislation, ~~or exposure to~~and we anticipate additional tax liabilities from certain provisions of the 2017 Tax Act that will go into effect in 2026; such tax liabilities could adversely affect our ~~profitability.~~profitability and results of operations.

We are subject to income and other taxes in the United States and other jurisdictions in which we do business. As a result, our provision for income taxes is derived from a combination of applicable tax rates in the various places we operate. Significant judgment is required for determining our provision for income tax.

One or more of our legal entities file income tax returns in the U.S. federal jurisdiction, various U.S. state jurisdictions and ~~certain~~ foreign jurisdictions. Our income tax returns are routinely examined by tax authorities in those jurisdictions. Significant disputes can ~~arise~~and have arisen with tax authorities involving issues regarding the timing and amount of deductions, the use of tax credits and allocations of income and expenses among various tax jurisdictions because of differing interpretations of tax laws, regulations and relevant facts, and such tax authorities (including the IRS) are becoming more aggressive in their audits and are particularly focused on such matters. In 2017, we received an RAR and a modified RAR from the IRS for the years ~~2010, 2011 and~~ 2010–2012, proposing significant adjustments that primarily relate to the allocation of profits between certain of our entities in the United States and the U.S. territory of Puerto Rico. We disagreed with the proposed adjustments and calculations and pursued resolution with the IRS administrative appeals office but were unable to reach resolution. In July 2021, we filed a petition in the U.S. Tax Court to contest two duplicate Statutory Notices of Deficiency (Notices) for ~~2010, 2011 and~~ the years 2010–2012 that we received in May and July 2021 which seek to increase our U.S. taxable ~~income. We firmly believe that~~income for the IRS’s positions set forth in the Notices are without merit, and are contesting the Notices through the judicial process. See Part II, Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations—Results of Operations, Income Taxes, and Part IV—Note 6, Income taxes, to the Consolidated Financial Statements.years 2010–2012.

In 2020, we received an RAR and a modified RAR from the IRS for the years ~~2013, 2014 and~~ 2013–2015, also proposing significant adjustments that primarily relate to the allocation of profits between certain of our entities in the United States and the U.S. territory of Puerto Rico similar to those proposed for the years ~~2010, 2011 and~~ 2010–2012. We disagreed with the proposed adjustments and calculations and pursued resolution with the IRS appeals ~~office. We~~office but were unable to reach ~~resolution at~~resolution. In July 2022, we filed a petition in the ~~administrative appeals level, and we anticipate~~U.S. Tax Court to contest a Notice for the years 2013–2015 that we ~~will receive a statutory notice of deficiency~~previously reported receiving in April 2022 that seeks to increase our U.S. taxable income for ~~these~~the years ~~as well.~~ 2013–2015 and asserts penalties.

We ~~expect to contest any such notice related to~~firmly believe that the IRS positions set forth in the 2010–2012 and 2013–152015 Notices are without merit. We are contesting the 2010–2012 and 2013–2015 Notices through the judicial process. The cases were consolidated on December 19, 2022.

We are currently also ~~currently~~ under examination by the IRS for the years ~~2016, 2017 and~~ 2016–2018 ~~and~~with respect to issues similar to those for the 2010 through 2015 period. In addition, we are under examination by a number of state and foreign tax jurisdictions.

Final resolution of these complex tax matters is not likely within the next 12 months. We continue to believe our accrual for income tax liabilities is appropriate based on past experience, interpretations of tax law, application of the tax law to our facts

and judgments about potential actions by tax authorities; however, due to the complexity of the provision for income taxes and uncertain resolution of these matters, the ultimate outcome of any tax matters may result in payments substantially greater than amounts accrued and could have a material adverse effect on the results of our operations.

See Part II, Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations—Results of Operations, Income Taxes, and Part IV—Note 7, Income taxes, to the Consolidated Financial Statements.

Our provision for income taxes and results of operations in the future could be adversely affected by changes to our operating structure, changes in the mix of income and expenses in countries with differing tax rates, changes in the valuation of deferred tax assets and liabilities and changes in applicable tax laws, regulations or administrative interpretations thereof. The 2017 Tax Act is complex and a large volume of regulations and guidance has been issued and could be subject to different interpretations. We could face audit challenges to our application of the 2017 Tax Act. ~~The Administration proposed and Congress is considering significant changes to existing tax law. These changes, if enacted, could substantially increase taxes we pay to the U.S. government. Further,~~

As previously reported, the OECD ~~recently~~ reached an agreement to align countries on a minimum corporate tax rate and an expansion of the taxing rights of market countries. IfEffective January 1, 2024, select individual countries, including the United Kingdom and EU member countries, have enacted ~~this~~the global minimum tax agreement. Our legal entities in the countries that have enacted the agreement, along with their direct and indirect subsidiaries, are now subject to a 15% minimum tax rate on adjusted financial statement income. Additional provisions of the OECD agreement may come into effect in future years, and the OECD is expected to continue to release additional guidance that may impact the application and interpretation of the agreement that could further increase our tax liabilities. Other countries, including the United States and the U.S. territory of Puerto Rico, have not yet enacted the OECD agreement and implementation remains highly uncertain. The continued enactment of the agreement, either by all OECD participants or unilaterally by individual countries, could result in tax increases or double taxation in ~~both~~ the United States ~~and~~or foreign jurisdictions.

The ~~U.S. Treasury recently released final foreign~~ tax ~~credit regulations that eliminate U.S. creditability~~rates associated with certain international provisions of the ~~Puerto Rico Excise~~2017 Tax Act are set to increase beginning ~~2023, which will increase our~~in 2026. If those changes take effect as scheduled, we anticipate that the overall U.S. tax ~~liability.~~rate on our foreign income would increase. The Administration and U.S. ~~territory~~Congress continue to discuss various proposals that would change the international provisions of ~~Puerto Rico is considering changes to its~~the 2017 Tax Act and other corporate provisions of U.S. tax ~~system that may minimize or eliminate this impact, but the outcome of such potential changes are uncertain.~~law. Changes to existing tax law in the United States, the U.S. territory of Puerto Rico or other jurisdictions, including the changes and potential changes discussed above, could result in tax increases where we do business and could have a material adverse effect on the results of our operations.

Our business may be affected by litigation and government investigations.

We and certain of our subsidiaries are involved in legal proceedings. See Part IV—Note ~~19,~~20, Contingencies and commitments, to the Consolidated Financial Statements. Civil and criminal litigation is inherently unpredictable, and the outcome can result in costly verdicts, fines and penalties, exclusion from federal healthcare programs and/or injunctive relief that affect how we operate our business. Defense of litigation claims can be expensive, time consuming and distracting, and it is possible that we could incur judgments or enter into settlements of claims for monetary damages or change the way we operate our business, which could have a material adverse effect on our product sales, business and results of operations. In addition, product liability is a major risk in testing and marketing biotechnology and pharmaceutical products. We may face substantial product liability exposure in human clinical trials and for products we sell after regulatory approval. Product liability claims, regardless of their merits, could be costly and divert management’s attention and could adversely affect our reputation and the demand for our products. We and certain of our subsidiaries have previously been named as defendants in product liability actions for certain of our products.

We are also involved in government investigations that arise in the ordinary course of our business. In recent years, there has been a trend of increasing government investigations and litigations against companies operating in our industry, both in the United States and around the world. See Our sales depend on coverage and reimbursement from government and commercial third-party payers, and pricing and reimbursement pressures have affected, and are likely to continue to affect, our profitability. Our business activities outside of the United States are subject to the FCPA and similar antibribery or anticorruption laws, regulations or rules of other countries in which we operate, including the U.K. Bribery Act. We cannot ensure that all our employees, agents, contractors, vendors, licensees, partners or collaborators will comply with all applicable laws and regulations. On April 25, 2019, we entered into a settlement agreement with the DOJ and the OIG of the HHS to settle certain allegations relating to our support of independent charitable organizations that provide patients with financial assistance to access their medicines. As a result, we entered into a corporate integrity agreement with the OIG that requires us to maintain a corporate compliance program and to undertake a set of defined corporate integrity obligations ~~for a period of five years.~~through April 2024. While we expect to fully comply with all of our obligations under the corporate integrity agreement, failure to do so could result in substantial penalties and potential exclusion from government healthcare programs. We may also see new government investigations of or actions against us citing novel theories of recovery. For example, prosecutors are placing greater scrutiny on patient support programs, including commercial copay assistance programs, and further enforcement actions and investigations regarding such programs could limit our ability to provide co-pay assistance to commercial patients. Greater scrutiny has also been placed on sponsorships, speaker programs and other arrangements where healthcare professionals receive remuneration, travel or other value to participate in certain events, and further enforcement actions could limit our ability to participate in such arrangements. Any of these results could have a material adverse effect on our business and results of operations.

RISKS RELATED TO ECONOMIC CONDITIONS AND OPERATING A GLOBAL BUSINESS

Our efforts to collaborate with or acquire other companies, products, or technology, and to integrate the operations of companies or to support the products or technology we have acquired, may not be successful, and may result in unanticipated costs, delays or failures to realize the benefits of the transactions.

We seek innovation through significant investment in both internal R&D and external transactions, including collaborations, partnerships, alliances, licenses, joint ventures, mergers and acquisitions (collectively, acquisition activity).

Acquisition activities may be subject to regulatory approvals or other requirements that are not within our control. Antitrust scrutiny by regulatory agencies and changes to regulatory approval process in the U.S. and foreign jurisdictions may cause approvals to take longer than anticipated to obtain, not be obtained at all, or contain burdensome conditions, which may jeopardize, delay or reduce the anticipated benefits of acquisitions to us and could impede the execution of our business strategy. There can be no assurance that such regulatory or other approvals will be obtained or that all closing conditions required in connection with our acquisition activities will be satisfied or waived, which could result in us being unable to complete the planned acquisition activities.

Acquisition activities are complex, time consuming and expensive and may result in unanticipated costs, delays or other operational or financial problems related to integrating the acquired company and business with our company, which may divert our management’s attention from other business issues and opportunities and restrict the full realization of the anticipated benefits of such transactions within the expected timeframe or at all. We may pay substantial amounts of cash, incur debt or issue equity securities to pay for acquisition activities, which could adversely affect our liquidity or result in dilution to our stockholders, respectively. For example, the primary sources of funds for our acquisition of Horizon were those received from our $24 billion of senior notes issued on March 2, 2023, together with the $4 billion drawn down from our term loan facility, and while the Company currently has investment grade credit ratings, this substantial additional indebtedness has resulted in downgrades to our credit ratings. Further, failures or difficulties in integrating or retaining new personnel or in integrating the operations of the businesses, products or assets we acquire (including related technology, research, development and commercial operations, compliance programs, manufacturing, distribution and general business operations and procedures and ESG activities) may affect our ability to realize the benefits of the transaction and grow our business and may result in us incurring asset impairment or restructuring charges. These and other challenges may arise in connection with our acquisitions of Otezla, Five Prime, Teneobio, ChemoCentryx, Horizon and/or our collaborations with BeiGene and Kyowa Kirin, or with other acquisition activities, which could have a material adverse effect on our business, results of operations and stock price.

We may not realize the anticipated strategic benefits of our acquisition of Horizon, including our efforts to leverage Amgen’s global presence and commercial and medical capabilities in inflammation and nephrology to accelerate revenue growth of Horizon’s products. Our assumptions and estimates about the future revenue growth of Horizon’s products may prove to be incorrect. Sales of our rare disease products acquired through our acquisition of Horizon will depend on our ability to increase awareness and educate physicians on the rare conditions that such medicines are designed to treat, as well as successfully identifying target patients and educating them about our treatments. We may also face greater than expected challenges associated with rare disease drug development (such as challenges obtaining patients for clinical trials and/or regulatory approvals) and reimbursement (such as obtaining reimbursement of orphan drugs by public health systems). We are in the process of integrating the Horizon business into ours, including a large number of complex operational and administrative systems, to form a unified combined company, including with respect to human resources, intellectual property management, research and development activities, finance, accounting and internal control processes and systems, sales operations, product distribution, commercialization efforts, information and information security systems, compliance programs and policies and supply chain systems and third party relationships (including vendors and third party manufacturers). For example, Horizon adds more than 30 contract manufacturing organizations (CMOs) to our operations, many of which are single source suppliers (including the CMO that produces TEPEZZA drug substance and the CMO that produces all of our KRYSTEXXA drug substance in Israel that is affected by the current conflict in Israel and Gaza). Business integrations generally, and our integration of Horizon specifically, are complex, time consuming and expensive, and we may experience unanticipated costs, delays or other operational or financial challenges. These integration efforts may also divert our management’s attention and resources away from other business operations, which may disrupt to some degree our ongoing business. Failure to successfully integrate the Horizon business into ours and/or achieve its anticipated strategic benefits may result in our incurring significant asset impairment or restructuring charges, and could have a material adverse effect on our business, results of operations and stock price.

We may not be able to access the capital and credit markets on terms that are favorable to us, or at all.

While we have historically accessed capital markets to supplement our existing funds and cash generated from operations to satisfy our needs for capital expenditures, debt service requirements, to pay dividends and repurchase stock, and engage in other business initiatives, including acquisitions and licensing activities, in 2023, we substantially increased our outstanding indebtedness in connection with our acquisition of Horizon, which may limit our ability to timely obtain additional financing on desired terms. See Our efforts to collaborate with or acquire other companies, products, or technology, and to integrate the

operations of companies or to support the products or technology we have acquired, may not be successful, and may result in unanticipated costs, delays or failures to realize the benefits of the transactions. While our plans include reducing our debt leverage levels before returning to the capital or credit markets for new funds, if we are required to access the capital and credit markets at an inopportune time, including when adverse capital and credit market conditions prevail, we may be unable to obtain financing on favorable terms, or at all, which could have a material adverse effect on our business and results of operations or our ability to complete business acquisitions. Changes in credit ratings issued by nationally recognized credit-rating agencies could also adversely affect our ability to obtain capital and credit market financing and the cost of such financing and have an adverse effect on the market price of our securities.

A breakdown of our information technology systems, cyberattack or information security breach could significantly compromise the confidentiality, integrity and availability of our information technology systems, network-connected control systems and/or our data, interrupt the operation of our business and/or affect our reputation.

To achieve our business objectives, we rely on sophisticated information technology systems, including hardware, software, technology infrastructure, online sites and networks for both internal and external operations, mobile applications, cloud services and network-connected control systems, some of which are managed, hosted, provided or serviced by third parties. Internal or external events that compromise the confidentiality, integrity and availability of our systems and data may significantly interrupt the operation of our business, result in significant costs and/or adversely affect our reputation.

Our information technology systems are highly integrated into our business, including our R&D efforts, our clinical and commercial manufacturing processes and our product sales and distribution processes. Further, as the majority of our employees work remotely for some portion of their jobs in our hybrid work environment, our reliance on our and third-party information technology systems has increased substantially and is expected to continue to increase. Remote and hybrid working arrangements, including those of at many third-party providers, can increase cybersecurity risks due to the challenges associated with managing remote computing assets and security vulnerabilities that are present in many non-corporate and home networks. The complexity and interconnected nature of software, hardware and our systems make them vulnerable to breakdown or other service interruptions, and to software errors or defects, misconfiguration and other security vulnerabilities. Upgrades or changes to our systems or the software that we use have resulted and we expect, in the future, will result in the introduction of new cybersecurity vulnerabilities and risks. In 2022, we identified a number of security vulnerabilities introduced into our information systems as a result of flaws that we subsequently identified in software that we had purchased and installed, and these flaws required that we apply emergency patches to certain of our systems. While we did not experience any significant adverse effects as a result of these vulnerabilities, there can be no assurance that we will timely identify and address future vulnerabilities. Our systems are also subject to frequent perimeter network reconnaissance and scanning, phishing and other cyberattacks. For example, as a result of our cybersecurity monitoring of the Horizon legacy information systems, we detected phishing activity in the accounts of two Horizon executives. These accounts were de-activated, the incidents were investigated and the determination was made separately by both our internal cybersecurity team and our external digital forensics and incident response supplier that no confidential information had been exfiltrated. As the cyber-threat landscape evolves, these attacks are growing in frequency, sophistication, and intensity, and are becoming increasingly difficult to detect and increasingly sophisticated in using techniques and tools—including artificial intelligence—that circumvent security controls, evade detection and remove forensic evidence. Such attacks could include the use of harmful and virulent malware, including ransomware or other denials of service, which can be deployed through various means, including the software supply chain, e-mail, malicious websites and/or the use of social engineering/phishing.

We have also experienced denial of service attacks against our network, and, although such attacks did not succeed, there can be no assurance that our efforts to guard against the wide and growing variety of potential attack techniques will be successful in the future. Attacks such as those experienced by government entities (including those that approve and/or regulate our products, such as the EMA) and other multi-national companies, including some of our peers, could leave us unable to utilize key business systems or access or protect important data, and could have a material adverse effect on our ability to operate our business, including developing, gaining regulatory approval for, manufacturing, selling and/or distributing our products. For example, in 2017, a pharmaceutical company experienced a cyberattack involving virulent malware that significantly disrupted its operations, including its research and sales operations and the production of some of its medicines and vaccines. As a result of the cyberattack, its orders and sales for certain products were negatively affected. In late 2020, SolarWinds Corporation, a leading provider of software for monitoring and managing information technology infrastructure, disclosed that it had suffered a cybersecurity incident whereby attackers had inserted malicious code into legitimate software updates for its products that were installed by myriad private and government customers, enabling the attackers to access a backdoor to such systems. In 2022, Okta, Inc., a provider of software that helps companies manage user authentication, disclosed that several hundred of its corporate customers were vulnerable to a security breach that allowed attackers to access Okta’s internal network. Although this breach did not have a significant effect on our business, there can be no assurance that a similar future breach would not result in a material adverse effect on our business or results of operations.

Our systems also contain and use a high volume of sensitive data, including intellectual property, trade secrets and other proprietary business information, financial information, regulatory information, strategic plans, sales trends and forecasts, litigation materials and/or personal identifiable information belonging to us, our staff, our patients, customers and/or other parties. In some cases, we utilize third-party service providers to collect, process, store, manage or transmit such data, which have increased our risk. Intentional or inadvertent data privacy or security breaches (including cyberattacks) resulting from attacks or lapses by employees, service providers (including providers of information technology-specific services), business partners, nation states (including groups associated with or supported by foreign intelligence agencies), organized crime organizations, “hacktivists” or others, create risks that our sensitive data may be exposed to unauthorized persons, our competitors or the public. System vulnerabilities and/or cybersecurity breaches experienced by our third-party service providers have constituted a substantial share of the information security risks that have affected us. For example, in the first half of 2021, a supplier experienced a data breach in which an unauthorized third party acquired access to certain information provided to the supplier in the course of its provision of services to us, including business documents and certain personally identifiable patient information (not including social security or other financial or health insurance information). As required, we promptly notified the applicable state attorneys general and the individuals whose personally identifiable information was affected of this data breach at the supplier. In the third quarter of 2022, another service provider experienced a similar cybersecurity breach in which an attacker exfiltrated certain data (including non-significant Amgen data) from the service provider’s systems. Although these supplier data breaches have not resulted in material adverse effects on our business, there can be no assurance that a similar future cybersecurity incident would not result in a material adverse effect on our business or results of operations. Further, the timeliness of our awareness of a cybersecurity incident affects our ability to respond to and work to mitigate the severity of such events. For example, in 2020 and 2022, two of our vendors experienced cyberattacks and each initially reported to us that neither event involved our data. However, upon further investigation, they each subsequently informed us that the attackers had accessed limited, non-significant Amgen information. Although neither of these breaches had a significant adverse effect on our business, in the future we may again not receive timely reporting of cybersecurity events and such events could have a material adverse effect on our business.

Cyberattackers are also increasingly exploiting vulnerabilities in commercially available software from shared or open-source code. We rely on third party commercial software that have had and may have such vulnerabilities, but as use of open-source code is frequently not disclosed, our ability to fully assess this risk to our systems is limited. For example, in December 2021, a remote code execution vulnerability was discovered in a software library that is widely used in a variety of commercially available software and services. Although this vulnerability has not resulted in any significant adverse effects on us, there can be no assurances that a similar future vulnerability in the software and services that we use would not result in a material adverse effect on our business or results of operations.

Domestic and global government regulators, our business partners, suppliers with whom we do business, companies that provide us or our partners with business services and companies we have acquired or may acquire face similar risks. Security breaches of their systems or service outages have adversely affected systems and could, in the future, affect our systems and security, leave us without access to important systems, products, raw materials, components, services or information, or expose our confidential data or sensitive personal information. For example, in 2019, two vendors that perform testing and analytical services that we use in developing and manufacturing our products experienced cyberattacks, and in April and September of 2020, vendors that provide us with information technology services and clinical data services, respectively, each experienced ransomware attacks. Although there was no breach of our systems, each of these incidents required us to disconnect our systems from those vendors’ systems. While we were able to reconnect our systems following restoration of these vendors’ capabilities without significantly affecting product availability, a more extended service outage affecting these or other vendors, particularly where such vendor is the single source from which we obtain the services, could have a material adverse effect on our business or results of operations. In addition, we distribute our products in the United States primarily through three pharmaceutical wholesalers, and a security breach that impairs the distribution operations of our wholesalers could significantly impair our ability to deliver our products to healthcare providers and patients. There can be no assurance that our cybersecurity risk management program and processes, including our policies, controls, or procedures, will be fully implemented, complied with or effective in protecting our information technology systems and sensitive data.

Although we have experienced system breakdowns, attacks and information security breaches, we do not believe such breakdowns, attacks and breaches have had a material adverse effect on our business or results of operations. We will continue to experience varying degrees of cyberattacks and other incidents in the future. Even though we continue to invest in the monitoring, protection and resilience of our critical and/or sensitive data and systems, there can be no assurances that our efforts will detect, prevent or fully recover systems or data from all breakdowns, service interruptions, attacks and/or breaches of our systems that could adversely affect our business and operations and/or result in the loss or exposure of critical, proprietary, private, confidential or otherwise sensitive data, which could result in material financial, legal business or reputational harm to us or negatively affect our stock price. While we maintain cyber-liability insurance, our insurance is not sufficient to cover us against all losses that could potentially result from a service interruption, breach of our systems or loss of our critical or sensitive data.

We are also subject to various laws and regulations globally regarding privacy and data protection, including laws and regulations relating to the collection, storage, handling, use, disclosure, transfer and security of personal data. The legislative and regulatory environment regarding privacy and data protection is continuously evolving and developing and the subject of significant attention globally. For example, we are subject to the EU’s GDPR, which became effective in May 2018, and the CCPA, which became effective in January 2020, both of which provide for substantial penalties for noncompliance. The CCPA was amended in late 2020, to create the California Privacy Rights Act to create opt in requirements for the use of sensitive personal data and the formation of a new dedicated agency for the enforcement of the law, the California Privacy Protection Agency. Similar consumer privacy laws went into effect in Virginia, Colorado, Utah, Connecticut and Florida in 2023. Consumer privacy laws were also passed in eleven other states, with the earliest effective dates later this year, and proposed in three additional states. Outside the United States, other jurisdictions where we operate have passed, or continue to propose, similar legislation and/or regulations. For example, in China, the Personal Information Protection Law and the Data Security Law, which regulate data processing activities associated with personal and nonpersonal data, are in effect and build upon the existing Cybersecurity Law. Failure to comply with these current and future laws could result in significant penalties and reputational harm and could have a material adverse effect on our business and results of operations.

Our sales and operations are subject to the risks of doing business internationally, including in emerging markets.

As we continue our expansion efforts in emerging markets around the world, through acquisitions and licensing transactions as well as through the development and introduction, both independently and through collaborations such as our collaboration with BeiGene, of our products in new markets, we face numerous risks to our business. There is no guarantee that our efforts and strategies to expand sales in emerging markets will succeed. Our international business, including in China and emerging market countries, may be especially vulnerable to periods of global and local political, legal, regulatory and financial instability, including issues of geopolitical relations, the imposition of international sanctions in response to certain state actions and/or sovereign debt issues, and management of health policy in response to pressures such as global pandemics. If relations between the United States and other governments deteriorate, our business and investments in such markets may also be adversely affected. We may also be required to increase our reliance on third-party agents and unfamiliar operations and arrangements including those previously utilized by companies we partner with or acquire in emerging markets. See We must conduct clinical trials in humans before we commercialize and sell any of our product candidates or existing products for new indications. Our expansion efforts in China and emerging markets around the world are dependent upon the establishment of an environment that is predictable, navigable and supportive of biopharmaceutical innovation, sustained access for our products and predictable pricing controls. For example, China continues to strengthen regulations on the collection, use and transmission of Chinese human genetic resources, and has expanded regulations on the conduct of biotechnology R&D activities in China. Between 2020 and 2022, we experienced delays in our applications to the Human Genetic Resources Administration of China that sought approval to conduct clinical trials in China. Our international operations and business may also be subject to less protective intellectual property or other applicable laws, diverse data privacy and protection requirements, changing tax laws and tariffs, trade restrictions or other barriers designed to protect industry in the home country against foreign competition, far-reaching antibribery and anticorruption laws and regulations and/or evolving legal and regulatory environments. For example, recent cross-border data transfer compliance requirements in China may also impose additional costs of doing business, including costs associated with localizing operations.

In response to the ongoing armed conflict in Ukraine, the U.S. government, numerous state governments, the EU and other countries in which we conduct business have imposed a wide range of economic sanctions that restrict commerce and business dealings with Russia, certain regions of Ukraine and certain entities and individuals. Additionally, the armed conflict in the Middle East that has been ongoing since October 2023 has caused regional disruptions to economic activity. For a description of the conflict’s impact on our third-party contract manufacturing of KRYSTEXXA, see Our efforts to collaborate with or acquire other companies, products, or technology, and to integrate the operations of companies or to support the products or technology we have acquired, may not be successful, and may result in unanticipated costs, delays or failures to realize the benefits of the transactions. These conflicts may also precipitate or amplify the other risks described herein, including risks relating to cybersecurity, global economic conditions, clinical trials and supply chains, which could adversely affect our business, operations and financial condition and results.

RISKS RELATED TO COMPETITION

Our products face substantial competition and our product candidates are also likely to face substantial competition.

We operate in a highly competitive environment. See Item 1. Business—Marketing, Distribution and Selected Marketed Products—Competition. We expect that our products and product candidates will compete with existing drugs, new drugs

currently in development, drugs currently approved for other indications that may later be approved for the same indications as those of our products and drugs approved for other indications that are used off-label. Large pharmaceutical companies and generics manufacturers of pharmaceutical products have expanded into, and are expected to continue expanding into, the biotechnology field, and some pharmaceutical companies and generics manufacturers have formed partnerships to pursue biosimilars. With the proliferation of companies pursuing biopharmaceuticals, several of our biosimilar products have entered, and a number of our product candidates may enter, markets with one or more competitors or with competitors soon to arrive. ~~For example, several of our biosimilar products have entered into markets with one or more existing competitors.~~ In addition, some of our competitors may have technical, competitive or other advantages over us for the development of technologies and processes or greater experience in particular therapeutic areas, and consolidation among pharmaceutical and biotechnology companies can enhance such advantages. These advantages may make it difficult for us to compete with them successfully to discover, develop and market new products and for our current products to compete with new products or new product indications they may bring to market. As a result, our products have been competing and may continue to compete, and our product candidates may compete, against products or product candidates that offer higher rebates or discounts, lower prices, equivalent or superior efficacy, better safety profiles, easier administration, earlier market availability or other competitive features. If we are unable to compete effectively, this could reduce our sales, which could have a material adverse effect on our business and results of operations.

Our intellectual property positions may be challenged, invalidated or circumvented, or we may fail to prevail in current and future intellectual property litigation.

Our success depends in part on our ability to obtain and defend patent rights and other intellectual property rights that are important to the commercialization of our products and product candidates. The patent positions of pharmaceutical and biotechnology companies can be highly uncertain and often involve complex legal, scientific and factual questions. Driven by cost pressures, efforts to limit or weaken patent protection for our industry are increasing. For example, the COVID-19 pandemic has resulted in increased interest in compulsory licenses, march-in rights or other governmental interventions, both in the United States and internationally, related to the procurement of ~~drugs. See~~ ~~The COVID-19 pandemic,~~drugs, and the ~~public and governmental effort~~World Trade Organization has agreed to ~~mitigate against~~a waiver of COVID-19 vaccine intellectual property protections through the ~~spread~~Trade-Related Aspects of Intellectual Property Rights waiver process. Also, in December 2023, the ~~disease, have had, and are expected~~Administration released a proposed framework that would consider price as a factor when determining whether to ~~continue~~exercise march-in rights pursuant to have, an adverse effect, and may have a material adverse effect, on our clinical trials, operations, manufacturing, supply chains, distribution systems, product development, product sales, business and results of operations. the Bayh-Dole Act with respect to drugs or other taxpayer-funded inventions. Third parties have challenged and may continue to challenge, invalidate or circumvent our patents ~~and~~(including any patent applications, term extensions, term adjustments and supplemental protection certificates) relating to our products, product candidates and technologies. See Part IV—Note 20, Contingencies and commitments, to the Consolidated Financial Statements. Challenges to patents may come from potential competitors or from parties other than those who seek to market a potentially-infringing product. In addition, our patent positions might not protect us against competitors with similar products or technologies because competing products or technologies may not infringe our patents. For certain of our product candidates, there are third parties who have patents or pending patent applications that they may claim necessitate payment of a royalty or prevent us from commercializing these product candidates in certain territories. Further, disputes may arise with third parties from whom we have licensed rights to intellectual property necessary for the development and commercialization of some of our products. For example, we are in a dispute with Roche regarding a license agreement that we acquired through our acquisition of Horizon for patents and know-how for TEPEZZA. Patent disputes are frequent, costly and can preclude, delay or increase the cost of commercialization of products. We have been in the past, are currently and expect to be in the future, involved in patent litigation. These matters have included, and may in the future include, litigation with manufacturers of products that purport to be biosimilars of certain of our products for patent infringement, invalidity, unenforceability and ~~for~~ failure to comply with certain provisions of the BPCIA. A determination made by a court, agency or tribunal concerning infringement, validity, enforceability, injunctive or economic remedy, or the right to patent protection, for example, are typically subject to appellate or administrative review. Upon review, such initial determinations may be afforded little or no deference by the reviewing tribunal and may be affirmed, reversed or made the subject of reconsideration through further proceedings. A patent dispute or litigation has not discouraged, and may not in the future discourage, a potential violator from bringing the allegedly infringing product to market prior to a final resolution of the dispute or litigation. The period from inception until resolution of a patent dispute or litigation is subject to the availability and schedule of the court, agency or tribunal before which the dispute or litigation is pending. We have been, and may in the future be, subject to competition during this period and may not be able to recover fully from the losses, damages and harms we incur from infringement by the competitor product even if we prevail. Moreover, if we lose or settle current or future litigations at certain stages or entirely, we could be subject to competition and/or significant liabilities, be required to enter into third-party licenses for the infringed product or technology or be required to

cease using the technology or product in dispute. In addition, we cannot guarantee that such licenses will be available on terms acceptable to us, or at all.

Further, under the Hatch–Waxman Act, our products approved by the FDA under the FDCA have been, and may in the future be, the subject of patent litigation with generics competitors before expiry of the five-year period of data exclusivity provided for under the Hatch-Waxman Act and prior to the expiration of the patents listed for the product. Likewise, our innovative biologic products have been, and may in the future be, the subject of patent litigation prior to the expiration of our patents and, with respect to competitors seeking approval as a biosimilar or interchangeable version of our products, prior to the 12-year exclusivity period provided under the BPCIA. In addition, we have faced, and may in the future face, patent litigation involving claims that ~~the~~our biosimilar product candidates ~~we are working to develop~~ infringe the patents of other companies, including those that manufacture, market or sell the applicable reference products or who are developing or have developed other biosimilar versions of such products. Alternatively, patents held by other entities have contributed, and may in the future

contribute, to a decision by us to not pursue all of the same labeled indications as are held by these companies. ~~Due to the COVID-19 pandemic, there have been delays in ongoing or new patent office and court proceedings in the United States and abroad that have delayed the outcome of such proceedings.~~ While we have attempted, and expect to continue to attempt, to challenge the patents held by other companies, our efforts may be unsuccessful. For examples of and information related to our patent litigation, see Part IV—Note ~~19,~~20, Contingencies and commitments, to the Consolidated Financial Statements.

Certain of the existing patents on our products have expired or will soon expire. See Item 1. Business—Marketing, Distribution and Selected Marketed Products—Patents. As our patents expire, competitors are able to legally produce and market similar products or technologies, including biosimilars, which has had, and may continue to have, a material adverse effect on our product sales, business and results of operations. In addition, competitors have been, and may continue to be, able to invalidate, design around or otherwise circumvent our patents and sell competing products.

We currently face competition from biosimilars and generics and expect to face increasing competition from biosimilars and generics in the future.

We currently face competition from biosimilars and generics in most of the territories in which we operate, including the United States and Europe, and we expect to face increasing biosimilar and/or generics competition this year and beyond. Expiration or successful challenge of applicable patent rights or expiration of an applicable exclusivity period has accelerated such competition, and we expect to face more litigation regarding the validity and/or scope of our patents. Our products have also experienced greater competition from lower cost biosimilars or generics that come to market when branded products that compete with our products lose their own patent protection. To the extent that governments adopt more permissive regulatory approval standards and competitors are able to obtain broader or expedited marketing approval for biosimilars and generics, the rate of increased competition for our products ~~could~~would likely accelerate.

In the EU, biosimilars are evaluated for marketing authorization pursuant to a set of general and product class-specific guidelines. In addition, in an effort to spur biosimilar utilization and/or increase potential healthcare savings, some EU countries and some Canadian provinces have adopted, or are considering the adoption of, biosimilar uptake measures such as physician prescribing quotas or automatic pharmacy substitution of biosimilars for the corresponding reference products. Some EU countries impose automatic price reductions upon market entry of one or more biosimilar competitors. In September 2022, the EMA and the EU Heads of Medicines’ Agencies (HMA) issued a joint statement providing that biosimilar medicines approved in the EU are “interchangeable” with their reference products and other biosimilars of the same reference product. This EMA-HMA statement could further contribute to the prescribing of biosimilars and to greater competition in Europe. While the degree of competitive effects of biosimilar competition differs between EU countries and between products, in the EU the overall use of biosimilars and the rate at which product sales of innovative products are being affected by biosimilar competition is increasing.

In the United States, the BPCIA authorizes the FDA to approve biosimilars via a separate, abbreviated pathway. See Item 1. Business—Government Regulation—Regulation in the United States—Approval of Biosimilars. In the United States, the FDA has approved numerous biosimilars, including biosimilar versions of Neulasta, EPOGEN and ENBREL, and a growing number of companies have announced that they are also developing biosimilar versions of our products. ~~Four~~For example, six biosimilar versions of Neulasta are now ~~marketed~~approved in the United States, including an on-body injector presentation that was approved in December 2023 for a Neulasta biosimilar, and we expect that other biosimilar versions of Neulasta tomay be marketed or receive approval in ~~2022 and beyond.~~the future. Impact to our Neulasta sales has accelerated as additional competitors have launched. See Item 1. Business—Marketing, Distribution and Selected Marketed Products—Competition. ~~An approved biosimilar version of EPOGEN has also launched in the United States.~~ Manufacturers of biosimilars have attempted, and may in the future attempt, to compete with our products by offering lower list prices, greater discounts or rebates, or contracts that offer longer-term pricing or a broader portfolio of other products. Companies pursuing development of biosimilar versions of our products have challenged and may continue to challenge our patents well in advance of the expiration of our material patents. For examples of and information related to our biosimilars and generics patent litigation, see Part IV—Note ~~19,~~20, Contingencies and commitments, to the Consolidated Financial Statements. See Our

intellectual property positions may be challenged, invalidated or circumvented, or we may fail to prevail in current and future intellectual property litigation.

The U.S. biosimilar pathway includes the option for biosimilar products that meet certain criteria to be approved as interchangeable with their reference products. Some companies currently developing or already marketing biosimilars may seek to obtain interchangeable status from the FDA, which could potentially allow pharmacists to substitute those biosimilars for our reference products without prior approval from the prescriber in most ~~states.~~states under state law. The FDA approved the first interchangeable biosimilar in ~~July~~ 2021 and has subsequently granted an interchangeability ~~designation~~designations to additional biosimilars, including without always requiring a ~~second biosimilar~~switching study. For example, in ~~October 2021. In November 2019,~~August 2022, the FDA ~~issued draft guidance that provides that comparative immunogenicity studies will not generally be expected for~~designated a monoclonal antibody biosimilar as interchangeable without requiring a switching study to support the interchangeability determination, and ~~interchangeable insulin products. This may open the door for~~has continued to make other ~~product-specific guidance development and the removal~~such designations of the expectation for certain studies, which may contribute to increased biosimilar competition for our innovative products. For example, the FDA 2021 guidance agenda lists four guidances related to biosimilars, including documents that address exclusivity for the first interchangeable biological product, and product class-specific recommendations for developing biosimilars and interchangeables.interchangeability on a case-by-case basis.

In addition, critics of the 12-year exclusivity period in the biosimilar pathway law will likely continue to seek to shorten the data exclusivity period and/or to encourage the FDA to interpret narrowly the law’s provisions regarding which new

products receive data exclusivity. In ~~late~~ 2019, the ~~previous~~ Administration agreed to remove from the United States-Mexico-Canada Agreement a requirement for at least 10 years of data exclusivity for biologic products. Also, the FDA is considering whether subsequent changes to a licensed biologic would be protected by the remainder of the reference product’s original 12-year exclusivity period (a concept known in the generic drug context as “umbrella exclusivity”). If the FDA were to decide that umbrella exclusivity does not apply to biological reference products or were to make other changes to the exclusivity period, this could expose us to biosimilar competition at an earlier time. There also have been, and may continue to be, legislative and regulatory efforts to promote competition through policies enabling easier generic and biosimilar approval and commercialization, including efforts to lower standards for demonstrating biosimilarity or interchangeability, eliminate the standard for interchangeability and declare by law that all biosimilars are de facto interchangeable with their reference products, limit patents that may be litigated and/or patent settlements, implement preferential reimbursement policies for biosimilars and pass new laws requiring more disclosure in the FDA’s Orange Book and Purple ~~Books.~~Book. For example, in 2021 the FDA sent a letter to the USPTO describing ways to strengthen coordination between the two agencies, offered training to help identify prior art, and seeking USPTO’s views on practices that extend market exclusivities, whether pharmaceutical patent examiners need additional resources, and the effect of post-grant challenges at the ~~PTAB~~Patent Trial and Appeal Board on drug patents. The USPTO responded in July 2022 with a letter to the FDA stating that it is prepared to create formal mechanisms to collaborate with the FDA on patent issues that may affect the timing of generic and biosimilar entry. In January 2023, the USPTO held a joint listening session with the FDA on USPTO-FDA collaboration efforts.

Upon the expiration or loss of patent protection and/or applicable exclusivity for one of our ~~small molecule~~ products, we can lose the majority of revenues for that product in a very short period of time. See Item 1. Business—Marketing, Distribution and Selected Marketed Products—Competition. Additionally, if one of our ~~small molecule~~ products is the subject of an FDA Written Request for pediatric studies and we are unable to adequately complete these studies, we may not obtain the pediatric exclusivity award that extends ~~existing patents and~~ unexpired regulatory exclusivity for the product (and existing patents for a small molecule product) by an additional six months. Further, in 2023, FDA draft guidance contemplates that the agency may no longer grant pediatric exclusivity for studies conducted solely to fulfill Pediatric Research Equity Act (PREA) requirements.

While we are unable to predict the precise effects of biosimilars and generics on our products, we are currently facing and expect to face greater competition in the United States, Europe and elsewhere as a result of biosimilar and generic competition and, in turn, downward pressure on our product prices and sales. This competition has had, and could increasingly have, a material adverse effect on our product sales, business and results of operations. State laws may also have an impact on our business. For example, California is the first state to have passed legislation, effective on January 1, 2020, against “pay for delay” settlements of patent infringement claims filed by manufacturers of generics or biosimilars where anything of value is given in exchange for settlement. Under this law, such settlement agreements are presumptively anticompetitive. The law may result in prolonged litigation and fewer settlements. ~~Other~~Similar legislation based on California’s law continues to be introduced in other states, including Connecticut and New ~~York, Illinois and Minnesota, may adopt similar laws or a similar law could be adopted~~York. Efforts to target such settlements are also active at the federal ~~level.~~level, including legislation introduced such as the Preserving Access to Affordable Generics and Biosimilars Act that adopts California’s anticompetitive presumption approach.

Concentration of sales at certain of our wholesaler distributors, and ~~at one free-standing dialysis clinic business and~~ consolidation of private payers, such as insurers, and PBMs has negatively affected, and may continue to negatively affect, our business.

Certain of our distributors, customers and payers have substantial purchasing leverage, due to the volume of our products they purchase or the number of patient lives for which they provide coverage. The substantial majority of our U.S. product sales is made to three pharmaceutical product wholesaler distributors: McKesson Corporation, Cencora, Inc. (formerly AmerisourceBergen ~~Corporation~~Corporation) and Cardinal Health, Inc. These distributors, in turn, sell our products to their customers, which include physicians or their clinics, dialysis centers, hospitals and pharmacies. One of our products, EPOGEN, is sold primarily to free-standing dialysis clinics. DaVita owns or manages a large number of the outpatient dialysis facilities located in the United States and accounts for approximately 90% of all EPOGEN~~sales.~~ Similarly, as discussed above, there has been significant consolidation in the health insurance industry, including that a small number of PBMs now oversee a

substantial percentage of total covered lives in the United States. See Our sales depend on coverage and reimbursement from government and commercial third-party payers, and pricing and reimbursement pressures have affected, and are likely to continue to affect, our profitability. ~~The three~~For example, the five largest PBMs in the United States are now part of major health insurance ~~providers.~~providers, and nationally account for 92% of prescription drug claims. The growing concentration of purchasing and negotiating power by these entities has, and may continue to, put pressure on our pricing due to their ability to extract price discounts on our products, fees for other services or rebates, negatively affecting our bargaining position, sales and/or profit margins. In addition, decisions by these entities to purchase or cover less or none of our products in favor of competing products could have a material adverse effect on our product sales, business and results of operations due to their purchasing volume. Further, if one of our significant wholesale distributors encounters financial or other difficulties and becomes unable or unwilling to pay us all amounts that such distributor owes us on a timely basis, or at all, it could negatively affect our business and results of operations. In addition, if one of our significant wholesale distributors becomes insolvent or otherwise unable to continue its commercial relationship with us in its present form, it could significantly disrupt our business and adversely affect our product sales, our business and results of operations unless suitable alternatives are timely found or lost sales are absorbed by another distributor.

RISKS RELATED TO RESEARCH AND DEVELOPMENT

We may not be able to develop commercial products despite significant investments in R&D.

Amgen invests heavily in R&D. Successful product development in the biotechnology industry is highly uncertain, and very few R&D projects yield approved and commercially viable products. Product candidates, including biosimilar product

candidates, or new indications for existing products (collectively, product candidates) that appear promising in the early phases of development have failed to reach the market for a number of reasons, such as:

•the product candidate did not demonstrate acceptable clinical trial results even though it achieved its primary endpoints and/or demonstrated positive preclinical or early clinical trial results, for reasons that could include changes in the standard of care of medicine or expectations of health authorities;

•the product candidate was not effective or not more effective than currently available or potentially competitive therapies in treating a specified condition or illness;

•the product candidate was not cost effective in light of existing or potentially competitive therapeutics;

•the product candidate had harmful side effects in animals or humans;

•the necessary regulatory bodies, such as the FDA or EMA, did not approve the product candidate for an intended use;

•reimbursement for the product candidate is limited despite regulatory approval;

•the product candidate was not economical for us to manufacture and commercialize;

•the patient population size is smaller than anticipated;

•other parties had or may have had proprietary rights relating to our product candidate, such as patent rights, and did not let us sell it on reasonable terms, or at all;

•we and certain of our licensees, partners, contracted organizations or independent investigators failed to effectively conduct clinical development or clinical manufacturing activities;

•the pathway to regulatory approval or reimbursement for product candidates was uncertain or not well-defined;

•the biosimilar product candidate failed to demonstrate the requisite biosimilarity to the applicable reference product, or was otherwise determined by a regulatory authority to not meet applicable standards for approval; and

•a companion diagnostic device that is required with the use of a product candidate is not approved by the necessary regulatory authority.

We ~~have spent considerable time, energy and resources developing our expertise in human~~believe that genetics, ~~and acquiring access to libraries of genetic information~~together with the ~~belief that genetics~~benefit of artificial intelligence and computational evidence, could meaningfully aid our search for new medicines and help guide our R&D decisions and ~~investments. We~~investments, and have focused our R&D strategy on drug targets validated by genetic or other compelling human evidence. We have invested considerable time, energy and resources into developing our expertise in human genetics, acquiring access to libraries of genetic information, and are applying artificial intelligence to our R&D activities, including applying such technologies to advance our human data efforts and our generative biology platform that seek to discover and design new drugs. However, product candidates based on

genetically validated targets or developed with the assistance of such technologies remain subject to the uncertainties of the drug development process and may not reach the market for a number of reasons, including the factors listed above.

We must conduct clinical trials in humans before we commercialize and sell any of our product candidates or existing products for new indications.

Before a product may be sold, we must conduct clinical trials to demonstrate that our product candidates are safe and effective for use in humans. The results of those clinical trials are used as the basis to obtain approval from regulatory authorities such as the FDA and EMA. See Our current products and products in development cannot be sold without regulatory approval. We are required to conduct clinical trials using an appropriate number of trial sites and patients to support the product label claims. The length of time, number of trial sites and number of patients required for clinical trials vary substantially, and we may spend several years and incur substantial expense in completing certain clinical trials. In addition, we may have difficulty finding a sufficient number of clinical trial sites ~~and~~and/or patients to participate in our clinical trials, particularly if competitors are conducting clinical trials in similar patient ~~populations. See~~ ~~The COVID-19 pandemic, and the public and governmental effort to mitigate against the spread of the~~populations and/or in rare disease ~~have had, and are expected to continue to have, an adverse effect, and may have a material adverse effect, on our~~therapy clinical trials ~~operations, supply chains, distribution systems, product development, product sales, business and results of operations.~~ due to the inherently small patient population potentially served by such therapies. Patients may withdraw from clinical trials at any time (including trials in which patients believe that they may not be receiving a clinical benefit), and privacy laws and/or other restrictions in certain countries may restrict the ability of clinical trial investigators to conduct further follow-up on such patients, which may adversely affect the interpretation of study results. Delays and complications in planned clinical trials can result in increased development costs, associated delays in regulatory approvals and in product candidates reaching the market and revisions to existing product labels.

Further, to increase the number of patients available for enrollment in our clinical trials, we have opened, and will continue to open, clinical sites and enroll patients in a number of locations where our experience conducting clinical trials is more limited, including ~~Russia,~~ India, China, South Korea, the Philippines, Singapore and some Central and South American countries, either through utilization of third-party contract clinical trial providers entirely or in combination with local staff.

Conducting clinical trials in locations where we have limited experience requires substantial time and resources to understand the unique regulatory environments of individual countries. For other examples of the risks of conducting clinical trials in China, see also Our sales and operations are subject to the risks of doing business internationally, including in emerging markets. Further, we must ensure the timely production, distribution and delivery of the clinical supply of our product candidates to numerous and varied clinical trial sites. Additionally, regional disruptions, including natural and man-made disasters, or health emergencies (such as novel viruses or pandemics, ~~such~~including the COVID-19 pandemic), or geopolitical conflicts (such as the ~~one we are currently experiencing with COVID-19),~~ongoing armed conflicts in Ukraine and the Middle East) have significantly disrupted the timing of clinical trials, and in the future could disrupt the timing, execution and outcome of clinical trials. If we fail to adequately manage the design, execution and diverse regulatory aspects of our ~~large and/or complex~~ clinical trials or to manage the production or distribution of our clinical supply, or such sites experience disruptions as a result of a natural/man-made disaster, or health emergency or geopolitical conflict, corresponding regulatory approvals may be delayed or we may fail to gain approval for our product candidates or could lose our ability to market existing products in certain therapeutic areas or altogether. For example, our clinical trials ~~have been~~were adversely affected by the COVID-19 pandemic. ~~See~~ The COVID-19 pandemic, and the public and governmental effort to mitigate against the spread of the disease, have had, and are expected to continue to have, an adverse effect, and may have a material adverse effect, on our clinical trials, operations, supply chains, distribution systems, product development, product sales, business and results of operations. If we are unable to market and sell our products or product candidates or to obtain approvals in the timeframe needed to execute our product strategies, our business and results of operations could be materially and adversely affected.

We rely on independent third-party clinical investigators to recruit patients and conduct clinical trials on our behalf in accordance with applicable study protocols, laws and regulations. Further, we rely on unaffiliated third-party vendors to perform certain aspects of our clinical trial operations. In some circumstances, we enter into co-development arrangements with other pharmaceutical and medical devices companies that provide for the other company to conduct certain clinical trials for the product we are co-developing or to develop a diagnostic test used in screening or monitoring patients in our clinical trials. See Some of our pharmaceutical pipeline and our commercial product sales rely on collaborations with third parties, which may adversely affect the development and ~~sale~~sales of our products. We also may acquire companies that have past or ongoing clinical trials or rights to products or product candidates for which clinical trials have been or are being conducted. These trials may not have been conducted to the same standards as ours; however, once an acquisition has been completed we assume responsibility for the conduct of these trials, including any potential risks and liabilities associated with the past and prospective conduct of those trials. If regulatory authorities determine that we or others, including our licensees or co-development partners, or the independent investigators or vendors selected by us, our co-development partners or by a company we have acquired or from which we have acquired rights to a product or product candidate, have not complied with regulations applicable to the clinical trials, those authorities may refuse or reject some or all of the clinical trial data or take other actions that could delay or otherwise negatively affect our ability to obtain or maintain marketing approval of the product or indication. In addition, delays or failures to develop diagnostic tests for our clinical trials can affect the timely enrollment of such trials and lead to delays or inability to obtain marketing approval. If we were unable to market and sell our products or product candidates, our business and results of operations could be materially and adversely affected.

In addition, some of our clinical trials utilize drugs and combination products manufactured and marketed by other pharmaceutical ~~companies.~~companies or vendors. These drugs, devices and/or products may be administered or used in clinical trials in combination with one of our products or product candidates or in a head-to-head study comparing the products’ or product candidates’ relative efficacy and safety. In the event that any of these vendors or pharmaceutical companies have unforeseen issues that negatively affect the quality of their work product or create a shortage of supply, or if we are otherwise unable to obtain an adequate supply of these other drugs, our ability to complete our applicable clinical trials and/or evaluate clinical results may also be negatively affected. As a result, such quality or supply problems could adversely affect our ability to timely file for, gain or maintain regulatory approvals worldwide.

Clinical trials must generally be designed based on the current standard of medical care. However, in certain diseases, such as cancer, the standard of care is evolving rapidly. In some cases, we may design a clinical trial based on the standard of care we anticipate will exist at the time our study is completed. The duration of time needed to complete certain clinical trials may result in the design of such clinical trials being based on standards of medical care that are no longer or that have not become the current standards by the time such trials are completed, limiting the utility and application of such trials. Additionally, the views of regulatory agencies relating to the requirements for accelerated approval may change over time, and trial designs that were sufficient to support accelerated approvals for some oncology products may not be considered sufficient for later candidates. We may not obtain favorable clinical trial results and therefore may not be able to obtain regulatory approval for new product candidates or new indications for existing products and/or maintain our current product labels. Participants in clinical trials of our products and product candidates may also suffer adverse medical events or side effects that could, among other factors, delay or terminate clinical trial programs and/or require additional or longer trials to gain approval.

Even after a product is on the market, safety concerns may require additional or more extensive clinical trials as part of a risk management plan for our product or for approval of a new indication. Additional clinical trials we initiate, including those required by the FDA, could result in substantial additional expense, and the outcomes could result in further label restrictions or

the loss of regulatory approval for an approved indication, each of which could have a material adverse effect on our product sales, business and results of operations. Additionally, any negative results from such trials could materially affect the extent of approvals, the use, reimbursement and sales of our products, our business and results of operations.

Our current products and products in development cannot be sold without regulatory approval.

Our business is subject to extensive regulation by numerous state and federal government authorities in the United States, including the FDA, and by foreign regulatory authorities, including the EMA. We are required in the United States and in the other regions and countries in which we, or our partners and affiliates, sell to obtain approval from regulatory authorities before we manufacture, market and sell our products. Once our products are approved, the FDA and other U.S. and ex-U.S. regulatory agencies have substantial authority to require additional testing and reporting, perform inspections, change product labeling or mandate withdrawals of our products. Failure to comply with applicable regulatory requirements may subject us to administrative and/or judicially imposed sanctions or monetary penalties as well as reputational and other harms. The sanctions could include the FDA’s or ex-U.S. regulatory authorities’ refusals to approve pending applications, delays in obtaining or withdrawals of approvals, delays or suspensions of clinical trials, warning letters, product recalls or seizures, total or partial suspensions of our operations, injunctions, fines, civil penalties and/or criminal prosecutions.

Obtaining and maintaining regulatory approvals have been, and will continue to be, increasingly difficult, time-consuming and costly. Legislative bodies or regulatory agencies could enact new laws or regulations, change existing laws or regulations or change their interpretations of laws or regulations at any time, which could affect our ability to obtain or maintain approval of our products or product candidates. The rate and degree of change in existing laws and regulations and regulatory expectations have accelerated in established markets, and regulatory expectations continue to evolve in emerging markets. We are unable to predict whether and when any further changes to laws or regulatory policies affecting our business could occur, such as changes to laws or regulations governing manufacturer communications concerning drug products and drug product candidates and whether such changes could have a material adverse effect on our product sales, business and results of operations. Further, we are reliant on regulators having the resources necessary to evaluate and approve our products. In the United States, a partial federal government shutdown halted the work of many federal agencies and their employees from late December 2018 through late January 2019. A subsequent extended shutdown could result in reductions or delays of FDA’s activities, including with respect to our ongoing clinical programs, our manufacturing of our products and product candidates and our product approvals.

Regulatory authorities have questioned, and may in the future question, the sufficiency for approval of the endpoints we select for our clinical trials. A number of our products and product candidates have been evaluated in clinical trials using surrogate endpoints that measure an effect that is known to correlate with an ultimate clinical benefit. For example, a therapeutic oncology product candidate may be evaluated for its ability to reduce or eliminate ~~MRD,~~minimal residual disease (MRD), or to extend the length of time during and after the treatment that a patient lives without the disease worsening, measured by ~~PFS.~~progression-free survival (PFS). Demonstrating that the product candidate induces MRD-negative responses or produces a statistically significant improvement in PFS does not necessarily mean that the product candidate will show a statistically significant improvement in overall survival or the time that the patients remain alive. In the CVcardiovascular (CV) setting, a heart disease therapeutic candidate may be evaluated for its ability to reduce LDL-C levels, as an elevated LDL-C level has been a surrogate endpoint for CV events such as death, heart attack and stroke. The use of surrogate endpoints such as PFS and LDL-C reduction, in the absence of other measures of clinical benefit, may not be sufficient for broad usage or approval even when such results are statistically significant. Regulatory authorities could also add new requirements, such as the completion of enrollment in a confirmatory study or the completion of an outcomes study or a meaningful portion of an outcomes study, as conditions for obtaining approval or obtaining an indication. For example, despite demonstrating that Repatha reduced LDL-C levels in a broad patient population, only after our large phase 3 outcomes study evaluating the ability of Repatha to prevent CV events met certain of its primary composite endpoint and key secondary composite endpoint did the FDA grant a broader approval of Repatha to reduce the risk of certain CV events. There may also be situations in which demonstrating the efficacy and safety of a product candidate may not be sufficient to gain regulatory approval unless superiority to other existing treatment options can be shown. The imposition of additional requirements or our inability to meet them in a timely fashion, or at all, has delayed, and may in the future delay, our clinical development and regulatory filing efforts, delay or prevent us from obtaining regulatory approval for new product candidates or new indications for existing products, or prevent us from maintaining our current product labels.

Some of our products have been approved by U.S. and ex-U.S. regulatory authorities on an accelerated or conditional basis with full approval conditioned upon fulfilling the requirements of regulators. For example, ~~in March 2018, we announced that~~ the FDA has approved ~~BLINCYTO~~LUMAKRAS under accelerated approval for the treatment of ~~certain~~adult patients with ~~B-cell precursor ALL. Continued approval~~KRAS G12C-mutated local advanced or metastatic NSCLC. Following our submission of the LUMAKRAS/LUMYKRAS CodeBreaK 200 Phase 3 confirmatory data submission in March 2023 to the FDA and EMA, we received a Complete Response Letter from the FDA and a new post-marketing requirement for ~~this indication may be contingent upon verification and description of clinical benefit in~~an additional confirmatory ~~trials.~~study to support full approval. Regulatory authorities are placing greater focus on ~~monitoring~~whether the sponsors of products originally approved on an accelerated or conditional basis ~~and on whether the sponsors of such products~~ have met the conditions of the accelerated or conditional approvals. If we are unable to fulfill the regulators’ requirements that were conditions of a product’s accelerated or conditional approval and/or if regulators reevaluate the data or risk-benefit profile of our product, the conditional approval may not result in

full approval or may be revoked or not renewed. Alternatively, we may be required to change the product’s labeled indications, conduct an additional confirmatory clinical trial, or even withdraw the product from the market.

Regulatory authorities can also impose post-marketing pediatric study requirements. Failure to fulfill such requirements may result in regulatory or enforcement action, including financial penalties or the invalidation of a product’s marketing authorization.

Safety problems or signals can arise as our products and product candidates are evaluated in clinical trials, including investigator sponsored studies, or as our marketed products are used in clinical practice. We are required continuously to collect and assess adverse events reported to us and to communicate to regulatory agencies these adverse events and safety signals regarding our products. Regulatory agencies periodically perform inspections of our pharmacovigilance processes, including our adverse event reporting. In the United States, for our products with approved ~~REMS (see~~Risk Evaluation and Mitigation Strategies (REMS, see Part I, Item 1. Business—Government Regulation—Postapproval Phase), we are required to submit periodic assessment reports to the FDA to demonstrate that the goals of the REMS are being met. REMS and other risk management programs are designed to help ensure that a drug’s benefits outweigh the risks and vary in the elements they contain. If the FDA is not satisfied with the results of the periodic assessment reports we submit for any of our REMS, the FDA may also modify our REMS or take other regulatory actions, such as implementing revised or restrictive labeling. The drug delivery devices approved for use in combination with our products are also subject to regulatory oversight and review for safety and malfunctions. See Some of our products are used with drug delivery or companion diagnostic devices that have their own regulatory, manufacturing and other risks. If regulatory agencies determine that we or other parties (including our clinical trial investigators, those operating our patient support programs or licensees of our products) have not complied with the applicable reporting, other pharmacovigilance or other safety or quality assessment requirements, we may become subject to additional inspections, warning letters or other enforcement actions, including fines, marketing authorization withdrawal and other penalties. Our product candidates and marketed products can also be affected by safety problems or signals occurring with respect to products that are similar to ours or that implicate an entire class of products. Further, as a result of clinical trials, including sub-analyses or meta-analyses of earlier clinical trials (a meta-analysis involves the use of various statistical methods to combine results from previous separate but related studies) performed by us or others, concerns may arise about the

sufficiency of the data or studies underlying a product’s approved label. Such actual or perceived safety problems or concerns can lead to:

•revised or restrictive labeling for our products, or the potential for restrictive labeling that has resulted, and may in the future result, in our decision not to commercialize a product candidate;

•requirement of risk management or minimization activities or other regulatory agency compliance actions related to the promotion and sale of our products;

•post-marketing commitments, mandated post-marketing requirements or pharmacovigilance programs for our approved products;

•product recalls of our approved products;

•required changes to the processes used in the manufacture of our products, which could increase our manufacturing costs and affect the availability of contract manufacturers we may utilize to assist in such manufacturing;

•revocation of approval for our products from the market completely, or within particular therapeutic areas or patient types;

•increased timelines or delays in being approved by the FDA or other regulatory bodies; and/or

•treatments or product candidates not being approved by regulatory bodies.

For example, after an imbalance in positively adjudicated CV serious adverse events was observed in one of the phase 3 clinical trials for EVENITY but not in another, larger phase 3 study, in April 2019 the FDA approved EVENITY for the treatment of osteoporosis in postmenopausal women at high risk for fracture, along with a post-marketing requirement. The requirement includes a five-year observational feasibility study that could be followed by a comparative safety study or trial.

In addition to our innovative products, we are working to develop and commercialize biosimilar versions of a number of products currently manufactured, marketed and sold by other pharmaceutical companies. In some markets outside the United States and EU, there is not yet a legislative or regulatory pathway for the approval of biosimilars. In the United States, the BPCIA provided for such a ~~pathway; while~~pathway. Discussions within the FDA ~~continues to develop~~and other regulatory authorities, and ~~scientific policies for biosimilars, discussions~~between regulatory authorities and sponsors, continue as to the evidence needed to demonstrate biosimilarity or interchangeability for specific products. See We currently face competition from biosimilars and generics and expect to face increasing competition from biosimilars and generics in the future. Delays or uncertainties in the development or implementation of such pathways, or changes in existing regulatory pathways, including degradation of regulatory standards, could result in delays or difficulties in getting our biosimilar products approved by regulatory authorities, subject us to unanticipated development costs or otherwise reduce the value of the investments we have

made in the biosimilars area. Further, we cannot predict ~~whether~~the extent to which any ~~repeal or reform of the ACA or other legislation~~potential legislative or policy initiatives would affect the biosimilar pathway or have a material adverse effect on our development of biosimilars, on our marketed biosimilars or on our ~~marketed biosimilars.~~pursuit of interchangeability designations for any biosimilar. In addition, if we are unable to bring our biosimilar products to market on a timely basis and secure “first-to-market” or other advantageous positions, our future biosimilar sales, business and results of operations could be materially and adversely affected.

Some of our products are used with drug delivery or companion diagnostic devices that have their own regulatory, manufacturing and other risks.

Many of our products and product candidates may be used in combination with a drug delivery device, such as an injector or other delivery system. For example, Neulasta is available as part of the Neulasta Onpro kit, ~~and~~ our AutoTouch reusable autoinjector is used with ENBREL Mini single-dose prefilled ~~cartridges.~~cartridges, and Repatha can be administered with the Repatha SureClick autoinjector or Pushtronex automated mini doser. In addition, some of our products or product candidates, including many of our oncology product candidates and products, including ~~LUMAKRAS,~~LUMAKRAS/LUMYKRAS and bemarituzumab, may also require the use of a companion or other diagnostic device such as a device that determines whether the patient is eligible to use our drug or that helps ensure its safe and effective use. In some regions, including the United States, regulatory authorities may require contemporaneous approval of the companion diagnostic device and the therapeutic product; in others the regulatory authorities may require a separate study of the companion diagnostic device. Our product candidates or expanded indications of our products used with such devices may not be approved or may be substantially delayed in receiving regulatory approval if development or approval of such devices is delayed, such devices do not also gain or maintain regulatory approval or clearance, or if such devices do not remain commercially available. When approval of the product and device is sought under a single marketing drug application, the increased complexity of the review process may delay receipt of regulatory approval. In addition, some of these devices may be provided by single-source unaffiliated third-party companies. We are dependent on the sustained cooperation and effort of those third-party companies to supply and/or market the devices and, in some cases, to conduct the studies required for approval or clearance by the applicable regulatory agencies. We are also dependent on those

third-party companies continuing to meet applicable regulatory or other requirements. Failure to successfully develop, modify, or supply the devices, delays in or failures of the Amgen or third-party studies, or failure of us or the third-party companies to obtain or maintain regulatory approval or clearance of the devices could result in increased development costs; delays in, or failure to obtain or maintain, regulatory approval; and/or associated delays in a product candidate reaching the market or in the addition of new indications for existing products. We are also required to collect and assess user complaints, adverse events and malfunctions regarding our devices, and actual or perceived safety problems or concerns with a device used with our product can lead to regulatory actions and adverse effects on our products. See Our current products and products in development cannot be sold without regulatory approval. Additionally, regulatory agencies conduct routine monitoring and inspections to identify and evaluate potential issues with our devices. For example, in 2017, the FDA reported on its adverse event reporting system that it was evaluating our Neulasta Onpro kit. Subsequently, we implemented device and labeling enhancements to address product complaints received on this device. We continuously monitor complaints and adverse events and implement additional enhancements as needed. Loss of regulatory approval or clearance of a device that is used with our product may also result in the removal of our product from the market. Further, failure to successfully develop, supply, or gain or maintain approval for these devices could adversely affect sales of the related approved products.

Some of our pharmaceutical pipeline and our commercial product sales rely on collaborations with third parties, which may adversely affect the development and ~~sale~~sales of our products.

We depend on alliances with other companies, including pharmaceutical and biotechnology companies, vendors and service providers, for the development of a portion of the products in our pharmaceutical pipeline and for the commercialization and sales of certain of our commercial products. For example, we have collaborations with third parties under which we share development rights, obligations and costs and/or commercial rights and obligations. See Item 1. Business—Business Relationships.

Failures by these parties to meet their contractual, regulatory, or other obligations to us or any disruption in the relationships between us and these third parties, could have a material adverse effect on our pharmaceutical pipeline and business. In addition, our collaborative relationships for R&D and/or commercialization and sales often extend for many years and have given, and may in the future give, rise to disputes regarding the relative rights, obligations and revenues of us and our collaboration partners, including the ownership or prosecution of intellectual property and associated rights and obligations. This could result in the loss of intellectual property rights or protection, delay the development and sale of potential pharmaceutical products, affect the ~~effective~~ sale and delivery of our commercialized products and lead to lengthy and expensive litigation, administrative proceedings or arbitration.

We seek innovation through significant investment in both internal R&D and external transactions, including collaborations, partnering, alliances, licenses, joint ventures, mergers and acquisitions (collectively, acquisition activity). Acquisition activities may be subject to regulatory approvals or other requirements that are not within our control. There can be no assurance that such regulatory or other approvals will be obtained or that all closing conditions required in connection with our acquisition activities will be satisfied or waived, which could result in us being unable to complete the planned acquisition activities.

Acquisition activities are complex, time consuming and expensive and may result in unanticipated costs, delays or other operational or financial problems related to integrating the acquired company and business with our company, which may divert our management’s attention from other business issues and opportunities and restrict the full realization of the anticipated benefits of such transactions within the expected timeframe or at all. We may pay substantial amounts of cash, incur debt or issue equity securities to pay for acquisition activities, which could adversely affect our liquidity or result in dilution to our stockholders, respectively. Further, failures or difficulties in integrating or retaining new personnel or in integrating the operations of the businesses, products or assets we acquire (including related technology, commercial operations, compliance programs, manufacturing, distribution and general business operations and procedures) may affect our ability to realize the benefits of the transaction and grow our business and may result in us incurring asset impairment or restructuring charges. These and other challenges may arise in connection with our acquisition of Otezla, Five Prime, Teneobio and/or our collaborations with BeiGene and KKC, or with other acquisition activities, which could have a material adverse effect on our business, results of operations and stock price.

RISKS RELATED TO OPERATIONS

We perform a substantial majority of our commercial manufacturing activities at our facility in the U.S. territory of Puerto Rico and a substantial majority of our clinical manufacturing activities at our facility in Thousand Oaks, California; significant disruptions or production failures at these facilities could significantly impair our ability to supply our products or continue our clinical trials.

The global supply of our products and product candidates for commercial sales and for use in our clinical trials is significantly dependent on the uninterrupted and efficient operation of our manufacturing facilities, in particular those in the U.S. territory of Puerto Rico and Thousand Oaks, California. See Manufacturing difficulties, disruptions or delays could limit supply of our products and limit our product sales.

We currently perform a substantial majority of our clinical manufacturing that supports our product candidates at our facility in Thousand Oaks, California. A substantial disruption in our ability to operate our Thousand Oaks manufacturing facility could materially and adversely affect our ability to supply our product candidates for use in our clinical trials, leading to delays in development of our product candidates.

In addition, we currently perform a substantial majority of our commercial manufacturing activities at our facility in the U.S. territory of Puerto Rico. In recent years, Puerto Rico has been affected by a number of natural disasters, including ~~droughts in mid-2020,~~Hurricanes Maria (2017) and Fiona (2022), as well as earthquakes ~~in early 2020 and Hurricane Maria in 2017.~~(2020). These natural disasters have affected, and may continue to affect, public and private properties and Puerto Rico’s electric grid and communications ~~networks in the future.~~networks. While the critical manufacturing areas of our commercial manufacturing facility were not significantly affected by these natural disasters, the restoration of electrical service on the island after Hurricane Maria was a slow process, and our facility ~~operated with electrical power from~~relied on backup diesel powered generators for some time. We also operated on backup generators for a few weeks after the early 2020 earthquakes in Puerto Rico. In 2021, the baseload power generation units of the Puerto Rico Electric Power Authority malfunctioned due to the lack of adequate maintenance for over a ~~decade. The problems experienced by these units, which are among the oldest in North America, have led~~decade, leading to selective outages across the island. In September 2022, Hurricane Fiona caused further damage to the island’s utility infrastructure which again resulted in widespread power outages and water supply issues. Although these events did not directly have a material effect on our

business, they have resulted in disruptions to our third-party suppliers on the island. Further instability of the electric grid ~~and unreliability on the generation units~~ could require us to increase ~~the~~our use of our generators or to ~~continue using~~use them exclusively. In addition, future storms, earthquakes or other natural or man-made disasters or events (including political unrest or labor shortages) could ~~cause~~have a more significant effect on our manufacturing operations. ~~Puerto Rico and the rest of the world are facing the effects of the~~The COVID-19 pandemic ~~and~~also resulted in disruptions to activities on the ~~associated health and economic implications.~~island. In March 2020, the Governor of Puerto Rico issued Executive Orders requiring the lockdown of businesses and government facilities, imposing restrictions on business operations and a curfew on residents. Our operations and employees were exempted from the lockdown and curfew, but we cannot predict whether the Governor will issue future Executive Orders imposing stricter lockdown and curfew measures should COVID-19 cases riseresidents in ~~Puerto Rico.~~response to COVID-19. Additionally, during the summer of 2021, a labor dispute arose between the maritime terminal operation company and its employees, represented by the International Longshoremen’s Association (ILA), which resulted in a strike that delayed cargo movement from the San Juan Port Zone for several days. Hurricanes Maria and Fiona, the 2020 earthquakes, the COVID-19 pandemic and the ILA strike have placed greater stress on the island’s already challenged economy. Beginning in 2016, the government of Puerto Rico defaulted on its roughly $72 billion of debt. In response, the U.S. Congress passed the Puerto Rico Oversight, Management, and Economic Stability Act, which established a financial oversight board for Puerto Rico. After years of negotiations with bondholders and other creditors, this financial oversight board reached an agreement with the same, which was confirmed by the U.S. District Court for the District of Puerto Rico effective March 2022. Although our ability to manufacture and supply our products has not,

to date, been significantly affected by ~~these~~ natural disasters, ~~the unreliability of the~~unreliable electric ~~service, the ILA strike~~utility services, strikes, pandemic lockdowns or the ~~COVID-19 pandemic,~~island’s economic challenges, these, or a combination of these challenges, or other issues that ~~could give rise to any~~create a substantial disruption to our ability to operate our Puerto Rico manufacturing facility or get supplies and manufactured products transported to and from that location, could make it more expensive or difficult for us to operate in Puerto Rico, and could materially and adversely affect our ability to supply our products and affect our product sales. See Manufacturing difficulties, disruptions or delays could limit supply of our products and limit our product ~~sales.~~sales

Hurricane Maria, the earthquakes of early 2020 and the COVID-19 pandemic have placed greater stress on the island’s already challenged economy. Beginning in 2016, the government of Puerto Rico defaulted on its roughly $72 billion in debt. In response, the U.S. Congress passed the PROMESA, which established the FOMBPR to provide fiscal oversight. Title III of PROMESA provides Puerto Rico with a judicial process for restructuring its debt similar to, but not identical to, Chapter 9 of the U.S. Bankruptcy Code, including a stay of debtholder litigation. In 2017, the FOMBPR approved and certified the filing in the U.S. District Court for the District of Puerto Rico of a voluntary petition under Title III of PROMESA for the government of Puerto Rico and certain of its governmental entities, including the Puerto Rico Electric Power Authority, which recently privatized its transmission and distribution infrastructure. After years of negotiations with bondholders and other creditors, the FOMBPR reached an agreement with the same and presented a Plan of Adjustment to the Title III Court. The Plan of Adjustment requires the Puerto Rico government to enact legislation authorizing the issuance of new bonds in exchange for older bonds and a reduction of the U.S. territory’s debt. On October 26, 2021, Act 53-2021, known as the “Law to End the Bankruptcy of Puerto Rico,” was enacted. From November to December 2021, the Court held several hearings regarding the approval of the Plan of Adjustment, and the Modified Eighth Plan of Adjustment was confirmed by the Court on January 18, 2022, to be effective on March 15, 2022.

Each year since 2017, the FOMBPR has updated Puerto Rico’s fiscal plans implementing various measures intended to achieve fiscal responsibility and to restore Puerto Rico’s access to the capital markets, including significant expense reductions and suggested measures for economic growth. Each plan has stressed the need for fiscal and structural reforms to address Puerto Rico’s challenging economic and demographic trends. However, the government has not made significant progress during 2021 on the implementation of the fiscal and structural reforms required in the fiscal plan, in part due to the COVID-19 pandemic.

While the government and the FOMBPR have authorized emergency relief packages due to the COVID-19 pandemic, it is uncertain how, or the degree to which, the pandemic will impact Puerto Rico’s fiscal and structural reforms and its economy. In addition, the 2017 Tax Act no longer permits deferral of U.S. taxation on Puerto Rico earnings, although these earnings generally will be taxed in the United States at a reduced rate. Given Puerto Rico’s challenged economy, disaster recovery needs and impact from the COVID-19 pandemic, it may be difficult for Puerto Rico to sustain or grow its manufacturing base, which contributes significantly to Puerto Rico’s economy, due to competition from other locations subject to similar levels of taxation.

While PROMESA and the actions above continue to be important factors in moving Puerto Rico toward economic stability, Puerto Rico’s ongoing economic and demographic trend challenges and political situation, the effects of natural disasters, the unreliability of its electric system, the COVID-19 pandemic and the effects of the 2017 Tax Act or other potential tax law changes have negatively affected, and may in the future negatively affect, the territorial government’s provision of utilities or other services in Puerto Rico that we use in the operation of our business and could create the potential for increased taxes or fees to operate in Puerto Rico, result in a migration of workers from Puerto Rico to the mainland United States, or make it more expensive or difficult for us to operate in Puerto Rico. These factors could have a material adverse effect on our ability to supply our products, on our business and on our product sales..

We rely on third-party suppliers for certain of our raw materials, medical devices and components.

We rely on unaffiliated third-party suppliers for certain raw materials, medical devices and components necessary for the manufacturing of our commercial and clinical products. Certain of those raw materials, medical devices and components are proprietary products of those unaffiliated third-party suppliers and are specifically cited in our drug applications with regulatory agencies so that they must be obtained from that specific sole source or sources and could not be obtained from another supplier unless and until the regulatory agency approved such supplier. For example, we rely on a single source for the SureClick autoinjectors used in the drug delivery of Repatha, ENBREL, Aimovig, AMJEVITA/AMGEVITA and ~~Aranesp.~~Aranesp, and we also rely on a single source for the Pushtronex automated mini doser used in the drug delivery of Repatha. Also, certain of the raw materials required in the commercial and clinical manufacturing of our products are sourced from other countries and/or derived from biological sources, including mammalian tissues, bovine serum and human serum albumin.

Among the reasons we may be unable to obtain these raw materials, medical devices and components include:

•regulatory requirements or action by regulatory agencies or others;

•adverse financial or other strategic developments at or affecting the supplier, including bankruptcy;

•unexpected demand for or shortage of raw materials, medical devices or components;

•failure to comply with our quality standards which results in quality and product failures, complaints, product contamination and/or recall;

•a material shortage, contamination, recall and/or restrictions on the use of certain biologically derived substances or other raw materials;

•discovery of previously unknown or undetected imperfections in raw materials, medical devices or components;

•cyberattacks on supplier systems; ~~and~~

•natural or other disasters, including hurricanes, earthquakes, volcanoes or fires;

•labor disputes (such as strikes) or shortages, including from the effects of health emergencies (such as novel viruses or ~~pandemics such~~pandemics) or natural disasters; and

•geopolitical conflicts (such as the ~~one we are currently experiencing with COVID-19)~~ongoing conflicts in Ukraine and ~~natural disasters.~~the Middle East).

For example, in prior years we have experienced shortages in certain components necessary for the formulation, fill and finish of certain of our products in our Puerto Rico ~~facility.~~facility, and we have also experienced shortages related to single use systems and packaging which has caused disruptions to our manufacturing plans. Further quality issues that result in unexpected additional demand for certain components have resulted in shortages and in the future may lead to shortages of required raw materials or components (such as we have experienced with EPOGEN glass vials). We may experience similar or

other shortages in the future resulting in delayed shipments, supply constraints, clinical trial delays, contract disputes and/or stock-outs of our products. These or other similar events could negatively affect our ability to satisfy demand for our products or conduct clinical trials, which could have a material adverse effect on our product sales, business and results of operations.

Manufacturing difficulties, disruptions or delays could limit supply of our products and limit our product sales.

Manufacturing biologic and small molecule human therapeutic products is difficult, complex and highly regulated. We manufacture many of our commercial products and product candidates internally. In addition, we ~~currently~~ use third-party contract manufacturers to produce, or assist in the production of, a number of our products, and we currently use contract manufacturers to produce, or assist in the production of, a number of our late-stage product candidates and drug delivery devices. The number of third-party contract manufacturers that we use has increased with our recent acquisition of Horizon, as Horizon required such contract manufacturers for all of its products. See Item 1. Business—Manufacturing, Distribution and Raw Materials—~~Manufacturing.~~Manufacturing; see also Our efforts to collaborate with or acquire other companies, products, or technology, and to integrate the operations of companies or to support the products or technology we have acquired, may not be successful, and may result in unanticipated costs, delays or failures to realize the benefits of the transactions. Our ability to adequately and timely manufacture and supply our products (and product candidates to support our clinical trials) is dependent on the uninterrupted and efficient operation of our facilities and those of our third-party contract manufacturers, which may be affected by:

•capacity of manufacturing facilities;

•contamination by microorganisms or viruses, or foreign particles from the manufacturing process;

•natural or other disasters, including hurricanes, earthquakes, volcanoes or fires;

•labor disputes or shortages, including the effects of health emergencies (such as novel viruses or ~~pandemics such as the one we are currently experiencing with COVID-19)~~pandemics) or natural disasters;

•compliance with regulatory requirements;

•changes in forecasts of future demand;

•timing and actual number of production runs and production success rates and yields;

•updates of manufacturing specifications;

•contractual disputes with our suppliers and contract manufacturers;

•timing and outcome of product quality testing;

•power failures and/or other utility failures;

•cyberattacks on supplier systems;

•breakdown, failure, substandard performance or improper installation or operation of equipment (including our information technology systems and network-connected control systems or those of our contract manufacturers or third-party service providers); ~~and/or~~

•delays in the ability of the FDA or foreign regulatory agencies to provide us necessary reviews, inspections and approvals, including as a result of a subsequent extended U.S. federal or other government ~~shutdowns.~~shutdowns; and/or

•geopolitical conflicts (such as the ongoing conflicts in Ukraine and the Middle East).

If any of these or other problems affect production in one or more of our facilities or those of our third-party contract manufacturers, or if we do not accurately forecast demand for our products or the amount of our product candidates required in

clinical trials, we may be unable to start or increase production in our unaffected facilities to meet demand. If the efficient manufacture and supply of our products or product candidates is interrupted, we may experience delayed shipments, delays in our clinical trials, supply constraints, stock-outs, adverse event trends, contract disputes and/or recalls of our products. From time to time, we have initiated recalls of certain lots of our products. For example, in July 2014 we initiated a voluntary recall of an Aranesp lot distributed in the EU after particles were detected in a quality control sample following distribution of that lot, and in April 2018 we initiated a precautionary recall of two batches of Vectibix distributed in Switzerland after potential crimping defects were discovered in the metal seals on some product vials. If we are at any time unable to provide an uninterrupted supply of our products to patients, we may lose patients and physicians may elect to prescribe competing therapeutics instead of our products, which could have a material adverse effect on our product sales, business and results of operations.

Our manufacturing processes, those of our third-party contract manufacturers and those of certain of our third-party service providers must undergo regulatory approval processes and are subject to continued review by the FDA and other regulatory authorities. It can take longer than five years to build, validate and license another manufacturing plant, and it can take longer than three years to qualify and license a new contract manufacturer or service provider. If we elect or are required to make changes to our manufacturing processes because of new regulatory requirements, new interpretations of existing requirements or other reasons, this could increase our manufacturing costs and result in delayed shipments, delays in our clinical trials, supply constraints, stock-outs, adverse event trends or contract negotiations or disputes. Such manufacturing challenges may also occur if our existing contract manufacturers are unable or unwilling to timely implement such changes, or at all.

In addition, regulatory agencies conduct routine monitoring and inspections of our manufacturing facilities and processes as well as those of our third-party contract manufacturers and service providers. If regulatory authorities determine that we or our third-party contract manufacturers or certain of our third-party service providers have violated regulations, they may mandate corrective actions and/or issue warning letters, or even restrict, suspend or revoke our prior approvals, prohibiting us from manufacturing our products or conducting clinical trials or selling our marketed products until we or the affected third-party contract manufacturers or third-party service providers comply, or indefinitely. See also Our current products and products in development cannot be sold without regulatory approval. Such issues may also delay the approval of product candidates we have submitted for regulatory review, even if such product candidates are not directly related to the products, devices or processes at issue with regulators. Because our third-party contract manufacturers and certain of our third-party service providers are subject to the FDA and foreign regulatory authorities, alternative qualified third-party contract manufacturers and third-party service providers may not be available on a timely basis, or at all. If we or our third-party contract manufacturers or third-party service providers cease or interrupt production or if our third-party contract manufacturers and third-party service providers fail to supply materials, products or services to us, we may experience delayed shipments, delays in our clinical trials, supply constraints, contract disputes, stock-outs and/or recalls of our products. Additionally, we distribute a substantial volume of our commercial products through our primary distribution centers in Louisville, Kentucky for the United States and in Breda, Netherlands for Europe and much of the rest of the world. We also conduct most of the labeling and packaging of our products distributed in Europe and much of the rest of the world in Breda. Our ability to timely supply products is dependent on the uninterrupted and efficient operations of our distribution and logistics centers, our third-party logistics providers and our labeling and packaging facility in Breda. Further, we rely on commercial transportation, including air and sea freight, for the distribution of our products to our customers, which ~~may be~~has been negatively affected by the COVID-19 pandemic, labor unrest, natural disasters and geopolitical security ~~threats and/or the ongoing COVID-19 pandemic.~~threats.

There have also been legislative and administrative proposals seeking to incentivize greater drug manufacturing in the United States with the stated goal of improving supply reliability in the United States. For example, on August 6, 2020, the previous Administration issued an Executive Order aimed at boosting domestic production of essential medicines, medical countermeasures, and critical inputs titled “Executive Order on Ensuring Essential Medicines, Medical Countermeasures, and Critical Inputs are Made in the United States.” Additionally, one legislative proposal would ~~prohibit~~have prohibited the U.S. Department of Veterans Affairs from purchasing certain drugs that have active pharmaceutical ingredients manufactured outside the United States. While we perform a substantial majority of our commercial manufacturing activities in the United States, including in the U.S. territory of Puerto Rico, and a substantial majority of our clinical manufacturing activities at our facility in Thousand Oaks, California, the passage of such legislation could result in foreign governments enacting retaliatory legislation or regulatory actions, which may have an adverse effect on our product sales, business and results of operations.

Our business and operations may be negatively affected by the failure, or perceived failure, of achieving our environmental, social and governance objectives.

We continue to work towards operating our business in an environmentally responsible and socially inclusive manner. Stakeholders, including our investors and our employees, have increasingly focused on, and are expected to continue to focus

on, our ESG practices. Policymakers, regulators and investors globally have increased their focus on ESG matters, resulting in rapidly evolving and diverging expectations and standards. For example, California recently enacted the Climate Corporate Data Accountability Act that requires, among other things, disclosure of greenhouse gas emissions. In contrast, in other states, there are a growing number of anti-ESG initiatives that may conflict with certain of our stakeholders’ expectations. For example, 11 states have enacted laws prohibiting the consideration of ESG factors in connection with state pension asset investment decisions. If our ESG practices fail to meet ~~these~~our stakeholders’ expectations and standards, or if we fail to comply with ESG-related regulations across our global business, there could be a material adverse effect on our reputation, business and, ultimately, our stock price.

Our ESG report is made available on our website and describes our current ESG goals and the progress we have made on the ESG issues ~~deemed most important to~~that we believe our external and internal stakeholders consider to be important, based on surveys, interviews and certain frameworks for corporate responsibility. Achieving our ESG goals requires long-term investments and broad,

coordinated activity, and we may be required to incur additional costs or allocate additional resources towards monitoring, reporting and implementing our ESG ~~practices.~~programs. Further, we may fail to accurately assess our stakeholders’ ESG priorities and concerns, as such priorities and concerns have ~~evolved and will continue to evolve.~~been rapidly changing. While we have achieved most of our goals set in prior years, whether we can achieve our current and future ESG goals continues to be uncertain and remains subject to numerous risks, including evolving regulatory requirements and social expectations affecting ESG practices, our ability to recruit, develop and retain a diverse workforce, the availability of suppliers and collaboration partners that can meet our ~~ESG~~environmental goals, the effects of the organic growth of our business and potential acquisitions of other businesses on our ESG performance, and the availability and cost of technologies or resources, such as carbon credits, that support our goals. Any failure or perceived failure to meet our ESG program priorities could result in a material adverse effect on our reputation, business and stock price.

The effects of global climate change and related natural disasters could negatively affect our business and operations.

Many of our operations and facilities, including those essential to our manufacturing, R&D and distribution activities, are in locations that are subject to natural disasters, including droughts, fires, extreme temperatures, hurricanes, tropical storms and/or floods. For example, in 2017 Hurricane Maria caused catastrophic damage, compounded in 2022 by Hurricane Fiona, to the U.S. territory of Puerto Rico, where we perform a substantial majority of our commercial manufacturing activities. Although our site was well-protected and suffered minimal damage, there can be no assurances that we would have similar results in the face of future natural disasters. The severity and frequency of weather-related natural disasters has been amplified, and is expected to continue to be amplified by, global climate change. Such natural disasters have caused, and in the future may cause, damage to and/or disrupt our operations, which may result in a material adverse effect on our product sales, business and results of operations. Our suppliers, vendors and business partners also face similar risks, and any disruption to their operations could have an adverse effect on our supply and manufacturing chain. Further, many of our key facilities are located on islands, including Puerto Rico, Singapore and Ireland, which rely on essential port facilities that may be vulnerable to climate change-related or other natural disasters. Although we have detailed business continuity plans in place and periodic assessments of our natural disaster risk, any natural disaster may also result in prolonged interruption to our critical operational and business activities, and we may be required to incur significant costs to remedy the effects of such natural disasters and fully resume operations, which may result in a material adverse effect on our product sales, business and results of operations. See We perform a substantial majority of our commercial manufacturing activities at our facility in the U.S. territory of Puerto Rico and a substantial majority of our clinical manufacturing activities at our facility in Thousand Oaks, California; significant disruptions or production failures at these facilities could significantly impair our ability to supply our products or continue our clinical trials and Manufacturing difficulties, disruptions or delays could limit supply of our products and limit our product sales.

GENERAL RISK FACTORS

Global economic conditions may negatively affect us and may magnify certain risks that affect our business.

Our operations and performance have been, and may continue to be, affected by global economic conditions. The economic downturn resulting from the COVID-19 pandemic ~~has~~ precipitated a global recession, which was followed by high rates of inflation and actions taken by financial regulators to raise interest rates. Instability in the financial system, tighter lending standards and higher interest rates have added stress that may create additional vulnerabilities in the global economy, the effects of which may be of an extended duration. Additionally, with higher interest rates, deficits, and other fiscal pressures, governments may be unable to sustain their previously high levels of fiscal spending. Further, in the United States, although Congress has approved stopgap measures to fund the government through early March, the federal government continues to be at risk of a shutdown if legislation providing funding for the fiscal year is not passed as a result of political divisions in Congress and an impasse on budgetary and spending matters. Consequently, these and other financial pressures have caused, and may continue to cause, government or other third-party payers to more aggressively seek cost containment ~~measures.~~measures in healthcare and other settings. See Our sales depend on coverage and reimbursement from government and commercial third-party payers, and pricing and reimbursement pressures have affected, and are likely to continue to affect, our profitability. As a result of global economic conditions, some third-party payers may delay or be unable to satisfy their reimbursement obligations. Job losses or other economic hardships (including inflation) may also affect patients’ ability to afford ~~health care~~healthcare as a result of increased co-pay or deductible obligations, greater cost sensitivity to existing co-pay or deductible obligations, lost healthcare insurance coverage or for other reasons. We believe such conditions have led and could continue to lead to reduced demand for our products, which could have a material adverse effect on our product sales, business and results of operations. The current inflationary environment related to increased aggregate demand, ~~and~~ supply chain constraints and the effects from the armed conflict in Ukraine (including the effects of the sanctions that were implemented in response to the conflict and the resulting impacts on the commodity market and supply chains) and the Middle East have also increased our operating expenses and may continue to affect our operating expenses. Our operational costs, including the cost of energy, materials, labor, distribution and our other operational and facilities costs are subject to market conditions and are being adversely affected by inflationary pressures. Economic conditions may also adversely affect the ability of our distributors, customers and suppliers to

obtain the liquidity required to buy inventory or raw materials and to perform their obligations under agreements with us, which could disrupt our operations. Although we monitor our distributors’, customers’ and suppliers’ financial condition and their liquidity to mitigate our business risks, some of our distributors, customers and suppliers may become insolvent, which could have a material adverse effect on our product sales, business and results of operations. A significant worsening of global economic conditions could precipitate or materially ~~increase these~~amplify the other risks ~~we face.~~described herein

We maintain a significant portfolio of investments disclosed as cash equivalents and marketable securities on our consolidated balance sheets. ~~The~~In recent years, the global ~~spread of~~ COVID-19 ~~has also~~pandemic and interest rate increases have led to disruption and volatility in the global capital markets. We have certain assets, including equity investments, that are exposed to market fluctuations that could, in a sustained or recurrent series of market disruptions, result in impairments. The value of our investments may also be adversely affected by interest rate fluctuations, inflation, downgrades in credit ratings, illiquidity in the capital markets, geopolitical events and other factors that may result in other-than-temporary declines in the value of our investments. Any of those events could cause us to record impairment charges with respect to our investment portfolio or to realize losses on sales of investments. We also maintain a majority of our cash and cash equivalents in accounts with major multi-national financial institutions, and our deposits at these institutions exceed insured limits. Market conditions can adversely affect the viability of these institutions. In the event of failure of any of the financial institutions where we maintain our cash and cash equivalents, there can be no assurance that we would be able to access uninsured funds in a timely manner or at all. Inability to access, or a delay in accessing these funds, could adversely affect our business and financial position.

Our stock price is volatile.

Our stock price, like that of our peers in the biotechnology and pharmaceutical industries, is volatile. Our revenues and operating results may fluctuate from period to period for a number of reasons. Events such as a delay in product development, changes to our expectations or strategy or even a relatively small revenue shortfall may cause financial results for a period to be below our expectations or projections. As a result, our revenues and operating results and, in turn, our stock price may be subject to significant fluctuations. Announcements or discussions, including via social media channels, of possible restrictive actions by government or private payers that would negatively affect our business or industry if ultimately enacted or adopted may also cause our stock price to fluctuate, whether or not such restrictive actions ever actually occur. Similarly, actual or perceived safety issues with our products or similar products or unexpected clinical trial results can have an immediate and rapid effect on our stock price, whether or not our operating results are materially affected.

~~We may not be able to access the capital and credit markets on terms that are favorable to us, or at all.~~

The capital and credit markets may experience extreme volatility and disruption, which may lead to uncertainty and liquidity issues for both borrowers and investors. For example, early in 2020, there were significant disruptions in the commercial paper market and several borrowers were unable to obtain funding at normal rates or maturities, which resulted in a significant increase in draws of corporate credit lines with banks. Similarly, the bond markets experienced extreme volatility in terms of interest rates and credit spreads, with several days without new issuances of corporate bonds. We expect to access the capital markets, from time to time, to supplement our existing funds and cash generated from operations in satisfying our needs for working capital; capital expenditure and debt service requirements; our plans to pay dividends and repurchase stock; and other business initiatives we strategically plan to pursue, including acquisitions and licensing activities. In the event of adverse capital and credit market conditions, we may be unable to obtain capital market financing on similar favorable terms, or at all, which could have a material adverse effect on our business and results of operations. Changes in credit ratings issued by nationally recognized credit-rating agencies could adversely affect our ability to obtain capital market financing and the cost of such financing and have an adverse effect on the market price of our securities.


Item 1B.			UNRESOLVED STAFF COMMENTS

None.


Item 1C.			CYBERSECURITY

Risk Management and Strategy

Amgen has a multi-layered and iterative approach towards assessing, identifying, managing and mitigating risks from cybersecurity threats. The Company’s Digital, Technology & Innovation (DTI) function is designed to support our productivity, innovation and outreach globally through the quality delivery of information systems, solutions and services for our business and operations. The DTI function has a Cybersecurity & Digital Trust (CDT) team that assesses and reduces cybersecurity exposure, including by providing employees with training and resources to identify potential cybersecurity threats and implementing information technology security practices. The CDT team also monitors for cybersecurity threat activity and seeks to mitigate the impact from cybersecurity incidents by deploying information security engineers, system architects, analysts and cybersecurity specialists to provide monitoring, reporting and management of cybersecurity incidents.

To evaluate the progress of its activities, our DTI function uses various industry and regulatory frameworks as guides to assess the state of the Company’s cybersecurity program maturity and controls, including our organizational, people, physical and technological controls. The CDT team also conducts reviews and evaluations of our cybersecurity resilience program with Amgen’s Cybersecurity & Digital Trust Governance Council (which includes leaders from information security, compliance, regulatory affairs, manufacturing, audit, law and business development functions).

Our cybersecurity risk management program is considered by and integrated into our Company-wide Enterprise Risk Management program, and shares common methodologies, reporting channels and governance processes that apply across the Enterprise Risk Management program to that of other enterprise level risks (such as product development, safety and surveillance, financial and intellectual property risks). Regular evaluations are conducted of the greatest risks to our business and their underlying risk drivers as well as the associated mitigation activities, maturity and controls. This program is overseen by our Executive Vice President and Chief Financial Officer and guided by the Enterprise Risk Council, a cross-functional group of the Company’s business leaders representing key business functions that is chaired by our Chief Audit Executive. The results of the enterprise risk evaluations and the status and operation of the Enterprise Risk Management program are presented to our Board of Directors, which oversees the Company’s enterprise-level risks.

Further, our corporate audit function is responsible for assessing risk and testing whether, and the extent to which, our information security policies and practices are being implemented effectively within our business and by third party providers. Findings from such reports and related corrective action plans are shared with our CDT team, Company leadership, and the Audit Committee and Corporate Responsibility and Compliance Committee (CRCC) of our Board of Directors.

In addition to leveraging the Company’s own information technology resources, our Incident Response and Cyber Threat Intelligence teams engage, as needed, third-party cybersecurity risk assessors and consultants to assist in recognizing threats, identifying security vulnerabilities, and evaluating the impact of cybersecurity attacks and incidents when they occur. On a biennial basis, our DTI organization also engages external third-party experts to assess the Company’s cybersecurity control maturity across the organization and develops plans to address such experts’ recommendations.

Our CDT function has processes to oversee and identify the risks of cybersecurity threats associated with third-party service providers and monitors and works to mitigate the impact of cybersecurity incidents encountered by our third-party service providers. Upon becoming aware of cybersecurity incidents encountered by our third-party service providers, the CDT function’s Incident Response and Cyber Threat Intelligence teams are deployed to evaluate and mitigate the impact of such incidents on our business.

Despite our layered controls and cybersecurity efforts, the Company and its third-party vendors have experienced cyberattacks and information security vulnerabilities, and while such incidents have not had a material adverse effect on the Company, there can be no assurance that future cybersecurity attacks or incidents would not result in a material adverse effect on our business strategy, results of operations or financial condition. For examples of such matters and a discussion of the risks that we face, see Item 1A. Risk Factors—A breakdown of our information technology systems, cyberattack or information security breach could significantly compromise the confidentiality, integrity and availability of our information technology systems, network-connected control systems and/or our data, interrupt the operation of our business and/or affect our reputation. However, we have not identified risk from known cybersecurity threats, including as a result of any prior cybersecurity incidents, that have materially affected or are reasonably likely to materially affect us, including our operations, business strategy, results of operations or financial condition.

Governance

Our Board of Directors oversees an enterprise-wide approach to risk management, including risks related to information systems and cybersecurity, and each Board committee has primary risk oversight responsibilities aligned with its areas of focus. At each regular meeting of the Board, the Board receives and considers reports from each of its committees, and such reports provide additional detail on significant risk management issues as appropriate, including cybersecurity. The CRCC is the committee that has primary oversight responsibility for the Company’s information systems and management of cybersecurity and receives reports from our Senior Vice President and Chief Information Officer (CIO) and Chief Information Security Officer (CISO) that includes reviews of our information systems strategy, technology investments, cybersecurity risks and incidents, and third-party risk management, as well as an annual evaluation of the Company’s cybersecurity status. The Board’s Audit Committee has oversight responsibility of our internal controls, assurances and financial risks. The Audit Committee is provided with copies of materials presented to our CRCC by our CIO and CISO and receives reports from our CIO regarding topics including integration or implementation of new financial systems and key controls and governance designed to address cybersecurity risks associated with the use of such new financial systems.

Our management team, including our CIO and CISO, supervises efforts to prevent, detect, mitigate, and remediate cybersecurity risks and incidents through various means, which may include briefings from internal information security personnel; threat intelligence and other information obtained from governmental, public or private sources, including external consultants engaged by us; and alerts and reports produced by security tools deployed in the information systems environment.

Our CISO, who heads our CDT team and is accountable for the Company’s cybersecurity risk management program, joined the Company’s information systems organization in 2016, is a Certified Information Systems Security Professional and is certified in risk and information systems control. Previously, our CISO served in both leadership and operational positions as a cybersecurity professional in the U.S. government and was a cybersecurity consultant, providing a wide range of cybersecurity services to various U.S. government agencies and departments. Our DTI organization is led by, and our CISO is overseen by, our CIO, who has held roles of increasing responsibility within our information systems organization since 2001 and has developed his knowledge and skills in the cybersecurity area over the course of his career in information systems. Our inaugural Executive Vice President and Chief Technology Officer (CTO), effective as of the end of 2023, oversees our CIO. Prior to the establishment of the CTO role, our CIO was overseen by our Executive Vice President and Chief Financial Officer.

As leaders of the DTI organization and CDT function, respectively, the Company’s CIO and CISO are informed about and monitor significant cybersecurity threats and incidents through the Company’s internal cybersecurity reporting structure. Our CDT team is responsible for monitoring and detecting cybersecurity threats and incidents. Our CDT team, overseen by our CISO, is also responsible for the mitigation and remediation of cybersecurity incidents. When members of the CDT team detect a cybersecurity threat or incident or are made aware of a cybersecurity incident encountered by a third-party service provider, the discovery is communicated to the Incident Response team, which includes our CISO and other senior members of the CDT function. The Incident Response team evaluates the severity of the cybersecurity threat or incident and shares its findings with our CISO.

Our CISO and/or his senior team leaders, in addition to our CIO and CTO, also provide regular reports to executives leading our finance, compliance, law and human resources functions on potentially significant cybersecurity incidents and the progress made towards mitigation and remediation of those incidents. These leaders oversee reporting to our CRCC and Audit Committee, and reporting of such cybersecurity incidents are included in the course of regular meetings of such committees. Additionally, in appropriate circumstances, reporting of potentially significant cybersecurity incidents are made directly to the leaders of our CRCC and Audit Committee or directly to the Board of Directors outside of their regular meeting schedule. Further, in support of our internal controls, our CISO also reviews cybersecurity matters and trends with our accounting and law functions on a quarterly basis.

Information Systems Acquired from Horizon Therapeutics plc

On October 6, 2023, we completed our acquisition of Horizon. Horizon’s legacy information systems are currently maintained separately from Amgen’s preexisting information system infrastructure. After we are able to fully evaluate Horizon’s legacy information systems, protocols and practices, we plan to operationally integrate the legacy Horizon systems into our own, and these integrated systems will then be subject to Amgen’s cybersecurity risk management structure and strategy. While we integrate these systems, our CISO and CDT function are engaging in cybersecurity risk management activities, and any cybersecurity incidents detected on the legacy Horizon information systems are assessed, mitigated and remediated by our CDT function’s Incident Response and Cyber Threat Intelligence teams and reported in accordance with the governance processes detailed above. See Item 1A. Risk Factors—Our efforts to collaborate with or acquire other companies, products, or technology, and to integrate the operations of companies or to support the products or technology we have acquired, may not be successful, and may result in unanticipated costs, delays or failures to realize the benefits of the transactions and Item 1A. Risk Factors—A breakdown of our information technology systems, cyberattack or information

security breach could significantly compromise the confidentiality, integrity and availability of our information technology systems, network-connected control systems and/or our data, interrupt the operation of our business and/or affect our reputation.


Item 2.			PROPERTIES

As of December 31, ~~2021,~~2023, we owned or leased approximately 160 ~~properties.~~properties, including properties acquired from Horizon in Deerfield, Illinois and Ireland. The locations and primary functions of significant properties are summarized in the following tables:

U.S. Location:

Manufacturing

Administrative

R&D

Sales & marketing

Warehouse

Distribution center

Thousand Oaks, CA*

San Francisco, CA

Deerfield, IL

Louisville, KY

Cambridge, MA

Juncos, Puerto Rico

West Greenwich, RI

Tampa, FL

Other U.S. cities

____________

* Corporate headquarters

ROW Location:

Manufacturing

Administrative

R&D

Sales & marketing

Warehouse

Distribution center

Brazil

Canada

China

Denmark

France

Germany

Iceland

Ireland

~~Canada~~Japan

~~China~~

~~Denmark~~

~~Germany~~

~~Iceland~~

~~Ireland~~

~~Japan~~

Netherlands

Singapore

Switzerland

~~Turkey~~

United Kingdom

Other countries

Excluded from the information above are (i) undeveloped land and leased properties that have been abandoned and (ii) certain buildings we still own but that are no longer used in our business. Additionally, in January 2024 our U.S. manufacturing facility in New Albany, Ohio received licensure from the FDA for commercial production, and our facility in Holly Springs, North Carolina is currently under construction. There are no material encumbrances on our owned properties.

We believe our facilities are suitable for their intended uses and, in conjunction with our third-party contract manufacturing agreements, provide adequate capacity and are sufficient to meet our expected needs. See Item 1A. Risk Factors for a discussion of the factors that could adversely impact our manufacturing operations and the global supply of our products.

See Item 1. Business—Manufacturing, Distribution and Raw Materials.


Item 3.			LEGAL PROCEEDINGS

Certain of the legal proceedings in which we are involved are discussed in Part IV—Note ~~19,~~20, Contingencies and commitments, to the Consolidated Financial Statements and are hereby incorporated by reference.


Item 4.			MINE SAFETY DISCLOSURES

Not applicable.

5157

PART II


Item 5.			MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES

Common stock

Our common stock trades on the NASDAQ Global Select Market under the symbol AMGN. As of February ~~11, 2022,~~9, 2024, there were approximately ~~5,069~~ 4,614holders of record of our common stock.

Performance graph

The following graph shows the value of an investment of $100 on December 31, ~~2016,~~2018, in each of Amgen common stock, the Amex Biotech Index, the Amex Pharmaceutical Index and Standard & Poor’s 500 Index. All values assume reinvestment of the pretax value of dividends and are calculated as of December 31 of each year. The historical stock price performance of the Company’s common stock shown in the performance graph is not necessarily indicative of future stock price performance.


		12/31/2016	12/31/2017	12/31/2018	12/31/2019	12/31/2020	12/31/2021
	12/31/2018									12/31/2018		12/31/2019		12/31/2020		12/31/2021		12/31/2022		12/31/2023
Amgen (AMGN)	Amgen (AMGN)	$100.00	$122.32	$140.76	$179.65	$176.05	$177.59	Amgen (AMGN)	$100.00		$127.62		$125.07		$126.16		$152.01		$172.55
Amex Biotech (BTK)	Amex Biotech (BTK)	$100.00	$137.81	$138.18	$166.41	$189.00	$182.34	Amex Biotech (BTK)	$100.00		$120.43		$136.78		$131.96		$126.68		$130.31
Amex Pharmaceutical (DRG)	Amex Pharmaceutical (DRG)	$100.00	$116.63	$125.31	$148.36	$161.31	$199.02	Amex Pharmaceutical (DRG)	$100.00		$118.39		$128.73		$158.82		$171.14		$184.35
Standard & Poor’s 500 (SPX)	Standard & Poor’s 500 (SPX)	$100.00	$121.89	$116.56	$153.26	$181.44	$233.47	Standard & Poor’s 500 (SPX)	$100.00		$131.48		$155.65		$200.29		$163.90		$207.07

5258

The material in the above performance graph is not soliciting material, is not deemed filed with the SEC and is not incorporated by reference in any filing of the Company under the Securities Act or the Exchange Act, whether made on, before or after the date of this filing and irrespective of any general incorporation language in such filing.

Stock repurchase program

During the ~~three months and~~ year ended December 31, ~~2021,~~2023, we had one outstanding stock repurchase program, under which ~~the repurchasing activity was as follows:~~we had no repurchase activity.

Total
number of
shares
purchased
Average
price paid
per share(1)
Total number
of shares
purchased as
part of
publicly
announced
program
Maximum dollar
value that may
yet be purchased
under the
program(2)
October 1 - October 31 1,874,976 $ 208.06 1,874,976 $ 6,960,277,756
November 1 - November 30 2,484,905 $ 208.35 2,484,905 $ 6,442,554,907
December 1 - December 31 2,559,300 $ 216.14 2,559,300 $ 10,889,377,513
6,919,181 $ 211.15 6,919,181
January 1 - December 31 21,730,283 $ 229.50 21,730,283

~~(1)Average price paid per share includes related expenses.~~

~~(2)In October 2021 and December 2021, our Board of Directors increased the amount authorized under the stock repurchase program by an additional $4.5 billion and an additional $5.0 billion, respectively.~~


	Total number of shares purchased	Average price paid per share	Total number of shares purchased as part of publicly announced program	Maximum dollar value that may yet be purchased under the program
October 1 - October 31	—		—	$	6,979,263,848
November 1 - November 30	—		—	$	6,979,263,848
December 1 - December 31	—		—	$	6,979,263,848
	—		—
January 1 - December 31	—		—

Dividends

For the years ended December 31, ~~2021~~2023 and ~~2020,~~2022, we paid quarterly dividends. We expect to continue to pay quarterly dividends, although the amount and timing of any future dividends are subject to approval by our Board of Directors. Additional information required by this item is incorporated herein by reference to Part IV—Note ~~16,~~17, Stockholders’ equity, to the Consolidated Financial Statements.

Securities Authorized for Issuance Under Existing Equity Compensation Plans

Information about securities authorized for issuance under existing equity compensation plans is incorporated by reference from Part III, Item 12—Securities Authorized for Issuance Under Existing Equity Compensation Plans.


Item 6.			RESERVED

5359


Item 7.			MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS

The following MD&A is intended to assist the reader in understanding Amgen’s business. MD&A is provided as a supplement to, and should be read in conjunction with, our consolidated financial statements and accompanying notes. Our results of operations discussed in MD&A are presented in conformity with GAAP. Amgen operates in one business segment: human therapeutics. Therefore, our results of operations are discussed on a consolidated basis.

Forward-looking statements

This report and other documents we file with the SEC contain forward-looking statements that are based on current expectations, estimates, forecasts and projections about us, our future performance, our business, our beliefs and our management’s assumptions. In addition, we, or others on our behalf, may make forward-looking statements in press releases, written statements or our communications and discussions with investors and analysts in the normal course of business through meetings, webcasts, phone calls and conference calls. Such words as “expect,” “anticipate,” “outlook,” “could,” “target,” “project,” “intend,” “plan,” “believe,” “seek,” “estimate,” “should,” “may,” “assume” and “continue” as well as variations of such words and similar expressions are intended to identify such forward-looking statements. These statements are not guarantees of future performance and they involve certain risks, uncertainties and assumptions that are difficult to predict. We describe our respective risks, uncertainties and assumptions that could affect the outcome or results of operations in Part I, Item 1A. Risk Factors. We have based our forward-looking statements on our management’s beliefs and assumptions based on information available to our management at the time the statements are made. We caution you that actual outcomes and results may differ materially from what is expressed, implied or forecasted by our forward-looking statements. Reference is made in particular to forward-looking statements regarding product sales, regulatory activities, clinical trial results, reimbursement, expenses, EPS, liquidity and capital resources, trends, planned dividends, stock repurchases, collaborations and effects of pandemics. Except as required under the federal securities laws and the rules and regulations of the SEC, we do not have any intention or obligation to update publicly any forward-looking statements after the distribution of this report, whether as a result of new information, future events, changes in assumptions or otherwise.

5460

Overview

Amgen ~~is a~~Inc. (including its subsidiaries, referred to as “Amgen,” “the Company,” “we,” “our” or “us”) discovers, develops, manufactures and delivers innovative medicines to fight some of the world’s toughest diseases. Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that dramatically improve people’s lives, while also reducing the social and economic burden of disease. We helped launch the biotechnology ~~company committed to unlocking the potential of biology for patients suffering from serious illnesses. A biotechnology pioneer since 1980, Amgen has~~industry more than 40 years ago and have grown to be one of the world’s leading independent biotechnology ~~companies, has reached millions~~companies. Our robust pipeline includes potential first-in-class medicines at all stages of ~~patients around the world and is developing a pipeline of medicines with breakaway potential.~~development.

Our principal products are Prolia, ENBREL, ~~Prolia,~~ Otezla, XGEVA, ~~Neulasta,~~Repatha, Nplate, KYPROLIS, Aranesp, ~~Repatha, KYPROLIS~~EVENITY, Vectibix, BLINCYTO, TEPEZZA and ~~Nplate.~~KRYSTEXXA. We also market a number of other products, including but not limited to Neulasta, MVASI, ~~Vectibix, KANJINTI, EVENITY, EPOGEN, BLINCYTO,~~ AMJEVITA/AMGEVITA, ~~Aimovig,~~TEZSPIRE, Parsabiv, ~~NEUPOGEN,~~Aimovig, LUMAKRAS/LUMYKRAS, ~~Sensipar/Mimpara~~EPOGEN, KANJINTI, TAVNEOS, RAVICTI, UPLIZNA and ~~TEZSPIRE.~~PROCYSBI. For additional information about our products, see Part I, Item 1. Business—Marketing, Distribution and Selected Marketed Products.

Our strategy includes integrated activities intended to ~~maintain and~~ strengthen our competitive position in the industry. ~~We focus on six commercial areas: inflammation, oncology/hematology, bone health, CV disease, nephrology and neuroscience. And~~In 2023, we ~~conduct discovery research primarily in three therapeutic areas: inflammation, oncology/hematology and general medicine. In 2021, we~~completed our acquisition of Horizon, advanced our innovative pipeline ~~launched new products, completed several strategic transactions to augment~~and generated strong volume growth across our ~~pipeline~~product portfolio and ~~research capabilities, and continued providing uninterrupted supplies of our medicines globally through the second year of the COVID-19 pandemic.~~regions. We accomplished these objectives while maintaining a strategic and disciplined approach to capital ~~allocation~~allocation.

Our newly established rare disease therapeutic area is designed to maximize the potential of medicines acquired in connection with our Horizon acquisition, including TEPEZZA for thyroid eye disease, KRYSTEXXA for chronic refractory gout and ~~while~~UPLIZNA for neuromyelitis optica spectrum disorder, as well as TAVNEOS, acquired from the ChemoCentryx acquisition in 2022, for severe active ANCA-associated vasculitis.

We are advancing our ~~ESG efforts.~~

~~In 2021, we continued to advance~~pipeline of innovative medicines, including initiating and completing enrollment of our Phase 2 study of maridebart cafraglutide for the treatment of obesity; announcing results from our Phase 2 study of tarlatamab in patients with SCLC; and rapidly enrolling patients in Phase 2 and Phase 3 studies for several of our later-stage clinical programs across our therapeutic areas. For more information on our pipeline, including ~~achieving key regulatory approvals for LUMAKRAS~~programs acquired from our Horizon acquisition, see Part I, Item 1. Business—Research and TEZSPIRE. Our external business development activities for 2021 included: (i) acquiring Five Prime, including a later-stage gastric cancer bemarituzumab program; (ii) entering into a license agreement with KKC to develop a later-stage molecule for atopic dermatitisDevelopment and other diseases; and (iii) acquiring Teneobio for its proprietary technologies and oncology programs in development. We also continued to advance our biosimilar program with the launch of RIABNI in the United States and introduced our other biosimilars into new markets. Our biosimilars are expected to continue launching in new markets throughout 2022.Selected Product Candidates.

~~During 2021, while meeting the challenges of a global pandemic and facing increased competition from biosimilars and generics, total~~Total product sales ~~were relatively flat as volume growth was offset by lower net selling prices. Product sales decreased 4%~~increased in ~~the United States, driven by lower net selling prices, partially offset by volume growth, and increased 12% ROW,~~2023, primarily driven by volume growth for certain brands, including Repatha, TEZSPIRE, EVENITY, Prolia and BLINCYTO, and the contribution of $954 million in product sales from the Horizon acquisition during the period from the acquisition date of October 6, 2023 through December 31, 2023, partially offset by ~~lower~~declines in net selling ~~prices. Total operating expenses increased 13%, driven by IPR&D expense from the Five Prime acquisition~~prices of certain products, including Neulasta, MVASI and ~~the upfront payment associated with the KKC licensing agreement.~~ENBREL.

Cash flows from operating activities totaled ~~$9.3~~$8.5 billion, which supported investment in our business, including our Horizon acquisition, while returning capital to shareholders through the payment of cash ~~dividends and stock repurchases.~~dividends. For ~~2021,~~2023, we increased our quarterly cash dividend by 10% to ~~$1.76~~$2.13 per share of common stock. In December ~~2021,~~2023, we declared a cash dividend of ~~$1.94~~$2.25 per share of common stock for the first quarter of ~~2022,~~2024, an increase of ~~10%~~6% for this period, to be paid in March 2022. We also repurchased 21.7 million shares of our common stock during 2021 at an aggregate cost of $5.0 billion. In 2021, we issued $4.9 billion and repaid $4.2 billion of debt that was coming due in 2022.2024.

Amgen’s approach to and investment in human capital resource management is directed at attracting, motivating, developing and retaining talent to tackle the challenges of running an enterprise focused on the discovery, development and commercialization of innovative medicines. Our compensation, benefits and development programs are designed to encourage performance, promote accountability and adherence to Company values, and align with the interests of the Company’s shareholders. Further, we believe that a diverse and inclusive culture fosters innovation, which supports our ability to serve patients. ~~We are engaging~~In our effort to attract and retain the best talent, we seek out and support talent across the globe, including in ~~activities and setting goals~~underrepresented populations, consistent with our commitment to ~~improve our focus on diversity, inclusion and belonging.~~equal opportunity. For further information on these and other efforts, see Part I, Item 1. Business—Human Capital Resources.

We have a long-standing ambition to be environmentally responsible, and we regularly set targets to challenge ourselves to deliver further improvements. In 2020, we met or exceeded our environmental sustainability targets set out in 2013 that called for reducing fleet carbon output by up to 20%, facility carbon output by 10%, water consumption by 10% and waste disposal by 35%.2We achieved our targets for the 2013–2020 ~~targets~~period while growing revenues, increasing production capacity and expanding to approximately 100 countries over the same ~~2013–20~~ period. To continue on our path to greater environmental sustainability, in January 2021 we announced a new set of long-term environmental targets to achieve by 2027, including achieving carbon neutrality, reducing water consumption by 40% and reducing waste disposed by 75%.~~2, 3~~(2)(3) Additionally, in 2022 we issued our first green bonds, which were used to finance eligible projects that met specified criteria to reduce our impact on the environment.

2(2) Represents reductions against established baselines, taking into account only verified reduction projects and does not take into account changes associated with contraction or expansion of the Company.

3(3) Carbon neutrality goal refers to Scope 1 and 2.

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Our long-term success depends, to a great extent, on our ability to continue to discover, develop and commercialize innovative products and acquire or collaborate on therapies currently in development by other companies. We must ~~develop~~grow sales from existing and new products to achieve revenue growth and to offset revenue losses from when products lose their exclusivity or when competing products are launched. Certain of our products face increasing pressure from competition, including biosimilars and generics. For additional information, including information on the expirations of patents for various products, see Part I, Item 1. Business—Marketing, Distribution and Selected Marketed Products—Patents, and Part I, Item 1. Business—Marketing, Distribution and Selected Marketed Products—Competition. We devote considerable resources to R&D activities, but successful product development in the biotechnology industry is highly uncertain. We also face increasing regulatory scrutiny of safety and efficacy both before and after products launch.

~~Rising~~Macroeconomic and other challenges

Uncertain macroeconomic conditions, including higher inflation, rising interest rates and instability in the financial system, as well as rising healthcare costs ~~and uncertain economic conditions~~ continue to pose challenges to our ~~business, including increasing pressure by third-party payers, such as governments and private payers,~~business. Further, ongoing geopolitical conflicts continue to ~~reduce healthcare expenditures. As a result of~~create additional uncertainty in global macroeconomic conditions. Additionally, with public and private healthcare-provider focus, the industry continues to be subject to cost containment measures and significant pricing pressures, including net price declines. Moreover, legislation enacted to reduce healthcare expenditures, including provisions of the IRA, have affected, and are likely to continue to affect, our business. Finally, wholesale and end-user buying patterns can affect our product sales. These buying patterns can cause fluctuations in quarterly product sales but have generally not been significant to date when comparing full-year product performance to the prior year. See Part I, Item 1. Business—Marketing, Distribution and Selected Marketed Products, and Part I, Item 1A. Risk Factors for further discussion of certain factors that could impact our future product sales.

~~COVID-19 pandemic~~

~~Since the onset of the pandemic in 2020, we have been closely monitoring the pandemic’s effects on our global operations. We continue to take appropriate steps to minimize risks to our employees,~~Our product sales were affected by reduced demand as a significant number of whom have continued to work virtually. Employee access to company facilities has been in accordance with applicable government health and safety protocols and guidance issued in response to the COVID-19 pandemic. To date, our remote working arrangements have not significantly affected our ability to maintain critical business operations, and we have not experienced disruptions to or shortages of our supply of medicines.

~~Since the beginning~~result of the COVID-19 pandemic, ~~we have seen changes in demand for some of our products driven by changes in~~and the frequency of patient visits to doctors’ offices that has impacted the provision of treatments to existing patients and reduced diagnoses in new patients. During 2021, there was gradual recovery in both patient visits and diagnoses that approached pre-COVID-19 levels early in the fourth quarter. However late in 2021, the Omicron variant began to impact the healthcare sector and as a result we expect ongoing variability in demand patterns in the first half of 2022. The cumulative decrease in diagnoses over the course of the pandemic ~~has~~ suppressed the volume of new patients starting treatment, which ~~we expect to continue~~continues to impact ~~our~~the business. ~~We will continue to closely monitor~~Given the ~~effects~~unpredictable nature of ~~emerging COVID-19 variants on~~ future virus surges, there could be similar intermittent disruptions in the future in physician–patient ~~behavior and access to care.~~interactions.

Since early 2021, global vaccination efforts have been under way to control the pandemic. However, uncertainty remains as to the length of time required for vaccination of a meaningful portion of the population and as to the efficacy of such vaccinations withWith regard to the trajectory of the pandemic. Challenges to vaccination efforts, new variants and other causes of virus spread may require governments to issue additional restrictions and/or order shutdowns in various geographies. As a result, we expect to see continued volatility for at least the duration of the pandemic as governments respond to current local conditions.

~~With respect to~~ our ~~drug development~~clinical trial activities, we are continuously monitoring ~~COVID-19 infection rates,~~the possible impacts from health-related events, including changes from new ~~variants, and~~COVID-19 variants; we are working to mitigate effects on future study enrollment in our clinical ~~trials~~trials; and we are evaluating the ~~impacts~~impact in all ~~countries where our clinical trials occur.~~relevant countries. We remain focused on supporting our active clinical sites in their ~~provision of~~providing care tofor patients and in our ~~provision of~~providing investigational drug supply.

Despite the ongoing pandemic and business impacts noted above, we believe that existing funds, cash generated from operations and existing sources of and access to financing are adequate to satisfy our needs for working capital, capital expenditures and debt service requirements as well as to engage in capital-return and other business initiatives that we plan to pursue. For a discussion of the risks the COVID-19 pandemic presents to our results, see Risk Factors in Part I, Item 1A. Risk Factors of this Form 10-K.

Selected Financial Information

The following is an overview of our results of operations (in millions, except percentages and per-share data):


		Year ended December 31, 2021		Change		Year ended December 31, 2020
	Year ended December 31, 2023							Year ended December 31, 2023	Change	Year ended December 31, 2022
Product sales:	Product sales:
U.S.
U.S.
U.S.	U.S.	$	17,286	(4)	%	$	17,985
ROW	ROW	7,011		12	%	6,255
Total product sales	Total product sales	24,297		—	%	24,240
Other revenues	Other revenues	1,682		42	%	1,184
Total revenues	Total revenues	$	25,979	2	%	$	25,424
Operating expenses	Operating expenses	$	18,340	13	%	$	16,285
Operating income	Operating income	$	7,639	(16)	%	$	9,139
Net income	Net income	$	5,893	(19)	%	$	7,264
Diluted EPS	Diluted EPS	$	10.28	(16)	%	$	12.31
Diluted shares	Diluted shares	573		(3)	%	590

In the following discussion of changes in product sales, any reference to ~~unit demand~~volume growth or decline refers to changes in the purchases of our products by healthcare providers (such as physicians or their clinics), dialysis centers, hospitals and pharmacies. In addition, any reference to increases or decreases in inventory refers to changes in inventory held by wholesaler customers and end users (such as pharmacies).

Total product sales ~~were relatively flat for 2021, as~~increased in 2023, primarily driven by volume growth ~~was~~for certain brands, including Repatha, TEZSPIRE, EVENITY, Prolia and BLINCYTO, and the contribution of $954 million in product sales from the Horizon

acquisition during the period from the acquisition date of October 6, 2023 through December 31, 2023, partially offset by declines in net selling ~~prices.~~prices of certain products, including Neulasta, MVASI and ENBREL. For ~~2022,~~2024, we expect that net selling prices will continue to decline at a portfolio level driven by increased competition. Further, the first quarter of a year historically represents the lowest product sales quarter for the year, in part due to plan changes, insurance reverifications and higher co-pay expenses as U.S. patients work through deductibles, particularly for products acquired through pharmacy benefit programs.

~~Throughout the pandemic, we experienced changes in demand for some~~The impact of our products. The pandemic has interrupted many physician–patient interactions, which has led to delays in diagnoses and treatments, with varying degrees of impact across our portfolio. In general, declines in the sales of our products that were impacted by the dynamics of the pandemic were most significant in the early months of the pandemic with product demand beginning to show some recovery in late 2020. During 2021, we observed gradual recovery from the COVID-19 pandemic, with patient visits and diagnosis rates that approached pre-pandemic levels early in the fourth quarter. However, late in the year, the Omicron variant began to impact the healthcare sector and as a result, we have seen some shift back to virtual engagement by our field staff and variability in demand patterns. The cumulative decrease in diagnoses over the course of the pandemic has suppressed the volume of new patients starting treatment, which we expect to continue to impact our business. Given the unpredictable nature of the pandemic, we expect there could be ongoing intermittent disruptions in physician–patient interactions, and as a result, we continue to expect quarter-to-quarter variability. In addition, other changes in the healthcare ecosystem have the potential to introduce variability into product sales trends. For example, changes in U.S. employment have led to changes to the insured population. Growth in numbers of Medicaid enrollees and uninsured individuals may have a negative impact on product demand and sales. Overall, uncertainty remains around the timing and magnitude of our sales during the COVID-19 pandemic. See Risk Factors in Part I, Item 1A. of this Form 10-K.

~~Other revenues increased for 2021, primarily driven by the sale of COVID-19 antibody material resulting from our manufacturing collaboration.~~

Operating expenses increased for 2021, driven by IPR&D expense related to the bemarituzumab program acquired as part of the Five Prime acquisition and by the upfront payment associated with the KKC licensing agreement.

~~Although changes in~~ foreign currency exchange rates ~~result in increases or decreases in our reported international product sales, the benefit or detriment that such movements have on our international product sales is~~will be partially offset by corresponding ~~increases or decreases~~changes in our international operating ~~expenses and our related~~expenses. While not designed to completely address foreign currency ~~hedging activities. Our~~changes, our hedging activities also seek to offset, ~~the impacts, both positive and negative, that foreign currency exchange rate changes may have~~in part, such effects on our net income by hedging our net foreign currency exposure, primarily with respect to product sales denominated in euros. ~~The net impact from~~

Uncertain macroeconomic conditions, changes in ~~foreign currency exchange rates was not material~~the healthcare ecosystem and geopolitical conflicts have the potential to introduce variability into product sales. For example, actions by governments and other entities to curb high inflation, provisions of the IRA and growth in ~~2021, 2020 or 2019.~~numbers of Medicaid enrollees and uninsured individuals may have a negative impact on product sales. Furthermore, our product sales were affected by reduced demand as a result of the COVID-19 pandemic, and the cumulative decrease in diagnoses over the course of the pandemic suppressed the volume of new patients starting treatment, which continues to impact the business. Given the unpredictable nature of future virus surges, there could be future intermittent disruptions in physician–patient interactions. See Risk Factors in Part I, Item 1A. of this Form 10-K.

Other revenues decreased for 2023, primarily due to lower revenue from our COVID-19 manufacturing collaboration.

Operating expenses increased for 2023, due to higher amortization and acquisition-related expenses incurred as a result of the Horizon acquisition, a net impairment charge resulting from the termination of AMG 340, higher profit share and royalty expense, changes in our product mix and higher spend in later-stage clinical programs and marketed products support, partially offset by a loss on the divestiture of Gensenta in 2022. See Part IV—Note 3, Acquisitions and divestitures; Note 13, Goodwill and other intangible assets; and Note 18, Fair value measurement, to the Consolidated Financial Statements.

5763

Results of Operations

Product sales

Worldwide product sales were as follows (dollar amounts in millions):


		Year ended December 31, 2021		Change		Year ended December 31, 2020		Change		Year ended December 31, 2019
	Year ended December 31, 2023											Year ended December 31, 2023	Change	Year ended December 31, 2022	Change	Year ended December 31, 2021
Prolia
ENBREL	ENBREL	$	4,465	(11)	%	$	4,996	(4)	%	$	5,226
Prolia		3,248		18	%	2,763		3	%	2,672
Otezla	Otezla	2,249		2	%	2,195		*		178
XGEVA	XGEVA	2,018		6	%	1,899		(2)	%	1,935
Neulasta		1,734		(24)	%	2,293		(29)	%	3,221
Repatha
Nplate
KYPROLIS
Aranesp	Aranesp	1,480		(6)	%	1,568		(9)	%	1,729
Repatha		1,117		26	%	887		34	%	661
KYPROLIS		1,108		4	%	1,065		2	%	1,044
Nplate		1,027		21	%	850		7	%	795
Other products		5,851		2	%	5,724		21	%	4,743
EVENITY
Vectibix
BLINCYTO
TEPEZZA(1)
KRYSTEXXA(1)
Other products(2)
Total product sales	Total product sales	$	24,297	—	%	$	24,240	9	%	$	22,204
Total U.S.	Total U.S.	$	17,286	(4)	%	$	17,985	9	%	$	16,531
Total ROW	Total ROW	7,011		12	%	6,255		10	%	5,673
Total product sales	Total product sales	$	24,297	—	%	$	24,240	9	%	$	22,204

* ChangeNM = not meaningful

____________

(1) TEPEZZA and KRYSTEXXA were acquired from our Horizon acquisition on October 6, 2023, and include product sales from the acquisition date through December 31, 2023.

(2) Consists of product sales of our non-principal products, as well as sales prior to the divestiture of our Bergamo and Gensenta subsidiaries in ~~excess~~the second quarter of ~~100%.~~2023 and fourth quarter of 2022, respectively.

Future sales of our products will depend in part on the factors discussed in the Overview, Part I, Item 1. Business—Marketing, Distribution and Selected Marketed Products—Competition, in Part I, Item 1A. Risk Factors, and any additional factors discussed in the individual product sections below. In addition, for a list of our products’ significant competitors, see Part I, Item 1. Business—Marketing, Distribution and Selected Marketed Products—Competition.

Prolia

Total Prolia sales by geographic region were as follows (dollar amounts in millions):


	Year ended December 31, 2023		Change		Year ended December 31, 2022		Change		Year ended December 31, 2021
Prolia — U.S.	$	2,733	11	%	$	2,465	15	%	$	2,150
Prolia — ROW	1,315		13	%	1,163		6	%	1,098
Total Prolia	$	4,048	12	%	$	3,628	12	%	$	3,248

The increase in global Proliasales for 2023 was primarily driven by volume growth and higher net selling price.

The increase in global Prolia sales for 2022 was driven by volume growth and higher net selling price, partially offset by unfavorable changes to foreign currency exchange rates.

For a discussion of ongoing litigation related to Prolia, see Part IV—Note 20, Contingencies and commitments, to the Consolidated Financial Statements.

ENBREL

Total ENBREL sales by geographic region were as follows (dollar amounts in millions):


		Year ended December 31, 2021		Change		Year ended December 31, 2020		Change		Year ended December 31, 2019
	Year ended December 31, 2023											Year ended December 31, 2023	Change	Year ended December 31, 2022	Change	Year ended December 31, 2021
ENBREL — U.S.	ENBREL — U.S.	$	4,352	(10)	%	$	4,855	(4)	%	$	5,050
ENBREL — Canada	ENBREL — Canada	113		(20)	%	141		(20)	%	176
Total ENBREL	Total ENBREL	$	4,465	(11)	%	$	4,996	(4)	%	$	5,226

The decrease in ENBREL sales for ~~2021~~2023 was driven by lower net selling price, ~~unit demand~~lower inventory and unfavorable changes ~~in inventory.~~to estimated sales deductions. For ~~2022,~~2024, we expect ENBREL to follow the historical pattern of lower sales in the first quarter relative to subsequent quarters due to the impact of benefit plan changes, insurance reverification and increased co-pay expenses as U.S. patients work through deductibles. In addition, for ~~2022,~~2024, we expect further declines in net selling ~~price to decline.~~price.

The decrease in ENBREL sales for ~~2020~~2022 was primarily driven by ~~lower unit demand and net selling price, partially offset by favorable~~unfavorable changes to estimated sales deductions, lower volume and ~~inventory.~~

~~Prolia~~

~~Total Prolia sales by geographic region were as follows (dollar amounts in millions):~~

Year ended December 31, 2021 Change Year ended December 31, 2020 Change Year ended December 31, 2019
Prolia — U.S. $ 2,150 17 % $ 1,830 3 % $ 1,772
Prolia — ROW 1,098 18 % 933 4 % 900
Total Prolia $ 3,248 18 % $ 2,763 3 % $ 2,672

~~The increase in global Proliasales for 2021 was primarily driven by higher unit demand.~~

~~The increase in global Prolia sales for 2020 was driven by higher unit demand and~~lower net selling price.

Otezla

Total Otezla sales by geographic region were as follows (dollar amounts in millions):

Year ended December 31, 2021 Change Year ended December 31, 2020 Change Year ended December 31, 2019
Otezla — U.S. $ 1,804 1 % $ 1,790 * $ 139
Otezla — ROW 445 10 % 405 * 39
Total Otezla $ 2,249 2 % $ 2,195 * $ 178

* Change in excess of 100%.


	Year ended December 31, 2023		Change		Year ended December 31, 2022		Change		Year ended December 31, 2021
Otezla — U.S.	$	1,777	(6)	%	$	1,886	5	%	$	1,804
Otezla — ROW	411		2	%	402		(10)	%	445
Total Otezla	$	2,188	(4)	%	$	2,288	2	%	$	2,249

The ~~increase~~decrease in global Otezla sales for ~~2021~~2023 was driven ~~by higher unit demand, partially offset~~ by lower net selling price and ~~unfavorable changes to inventory.~~inventory, partially offset by volume growth. For ~~2022,~~2024, we expect Otezla to follow the historical pattern of lower sales in the first quarter relative to subsequent quarters due to the impact of benefit plan changes, insurance reverification and increased co-pay expenses as U.S. patients work through deductibles.

The increase in global Otezla ~~was acquired on November 21, 2019, and generated $2.2 billion and $178 million in global~~ sales for ~~the years ended December 31, 2020 and 2019, respectively.~~

~~For a discussion of ongoing litigation related~~2022 was primarily driven by volume growth, partially offset by lower net selling price. ROW Otezla sales for 2022 were impacted by unfavorable changes to ~~Otezla, see Part IV—Note 19, Contingencies and commitments, to the Consolidated Financial Statements.~~foreign currency exchange rates.

XGEVA

Total XGEVA sales by geographic region were as follows (dollar amounts in millions):


		Year ended December 31, 2021		Change		Year ended December 31, 2020		Change		Year ended December 31, 2019
	Year ended December 31, 2023											Year ended December 31, 2023	Change	Year ended December 31, 2022	Change	Year ended December 31, 2021
XGEVA — U.S.	XGEVA — U.S.	$	1,434	2	%	$	1,405	(4)	%	$	1,457
XGEVA — ROW	XGEVA — ROW	584		18	%	494		3	%	478
Total XGEVA	Total XGEVA	$	2,018	6	%	$	1,899	(2)	%	$	1,935

The increase in global XGEVA sales for ~~2021~~2023 was primarily driven by higher ~~unit demand, partially~~net selling price.

Global XGEVA sales were relatively unchanged for 2022 as higher net selling price was offset by lower ~~net selling price.~~

~~The decrease in global XGEVA sales for 2020 was driven by lower unit demand~~volume as a result of increased competition and unfavorable changes to foreign currency exchange rates.

For a discussion of ongoing litigation related to XGEVA, see Part IV—Note 20, Contingencies and commitments, to the ~~COVID-19 pandemic.~~Consolidated Financial Statements.

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~~Neulasta~~Repatha

Total ~~Neulasta~~Repatha sales by geographic region were as follows (dollar amounts in millions):

Year ended December 31, 2021 Change Year ended December 31, 2020 Change Year ended December 31, 2019
Neulasta — U.S. $ 1,514 (24) % $ 2,001 (29) % $ 2,814
Neulasta — ROW 220 (25) % 292 (28) % 407
Total Neulasta $ 1,734 (24) % $ 2,293 (29) % $ 3,221


	Year ended December 31, 2023		Change		Year ended December 31, 2022		Change		Year ended December 31, 2021
Repatha — U.S.	$	793	30	%	$	608	9	%	$	557
Repatha — ROW	842		22	%	688		23	%	560
Total Repatha	$	1,635	26	%	$	1,296	16	%	$	1,117

The ~~decreases~~increase in global ~~Neulasta~~ Repathasales for ~~2021 and 2020~~2023 was ~~primarily~~ driven by volume growth, partially offset by lower net selling price.

The increase in global Repathasales for 2022 was driven by volume growth, partially offset by lower net selling price and ~~unit demand. Increased competition~~unfavorable changes to foreign currency exchange rates. Volume benefited from contracting changes to support and improve Medicare Part D and commercial patient access and the inclusion of Repatha on China’s National Reimbursement Drug List as ~~a result~~ of ~~biosimilar versions~~January 1, 2022, both of ~~Neulasta has had and will continue~~which resulted in decreases to ~~have a significant adverse impact on brand sales, including accelerating~~the net selling price ~~erosion and lower unit demand. We also expect other biosimilar versions, including biosimilars that will use an on-body injector that would compete with our Onpro injector, to be approved~~ in ~~the future.~~2022.

For a discussion of ongoing ~~patent litigations~~litigation related to ~~biosimilars,~~Repatha, see Part IV—Note ~~19,~~20, Contingencies and commitments, to the Consolidated Financial Statements.

Nplate

Total Nplate sales by geographic region were as follows (dollar amounts in millions):


	Year ended December 31, 2023		Change		Year ended December 31, 2022		Change		Year ended December 31, 2021
Nplate — U.S.	$	996	17	%	$	848	50	%	$	566
Nplate — ROW	481		5	%	459		—	%	461
Total Nplate	$	1,477	13	%	$	1,307	27	%	$	1,027

The increase in global Nplate sales for 2023 was primarily driven by volume growth, including U.S. government orders totaling $286 million.

The increase in global Nplate sales for 2022 was driven by volume growth, including a U.S. government order of $207 million.

KYPROLIS

Total KYPROLIS sales by geographic region were as follows (dollar amounts in millions):


	Year ended December 31, 2023		Change		Year ended December 31, 2022		Change		Year ended December 31, 2021
KYPROLIS — U.S.	$	921	8	%	$	850	15	%	$	736
KYPROLIS — ROW	482		21	%	397		7	%	372
Total KYPROLIS	$	1,403	13	%	$	1,247	13	%	$	1,108

The increases in global KYPROLIS sales for 2023 and 2022 were driven by volume growth.

Aranesp

Total Aranesp sales by geographic region were as follows (dollar amounts in millions):


		Year ended December 31, 2021		Change		Year ended December 31, 2020		Change		Year ended December 31, 2019
	Year ended December 31, 2023											Year ended December 31, 2023	Change	Year ended December 31, 2022	Change	Year ended December 31, 2021
Aranesp — U.S.	Aranesp — U.S.	$	537	(15)	%	$	629	(17)	%	$	758
Aranesp — ROW	Aranesp — ROW	943		—	%	939		(3)	%	971
Total Aranesp	Total Aranesp	$	1,480	(6)	%	$	1,568	(9)	%	$	1,729

~~19.~~20. Contingencies and commitments

Contingencies

In the ordinary course of business, we are involved in various legal proceedings, government investigations and other matters that are complex in nature and have outcomes that are difficult to predict. See Part I, Item 1A. Risk Factors—Our business may be affected by litigation and government investigations. We describe our legal proceedings and other matters that are significant or that we believe could become significant in this footnote.

We record accruals for loss contingencies to the extent that we conclude it is probable that a liability has been incurred and the amount of the related loss can be reasonably estimated. We evaluate, on a quarterly basis, developments in legal proceedings and other matters that could cause an increase or decrease in the amount of the liability that has been accrued previously.

Our legal proceedings involve various aspects of our business and a variety of claims, some of which present novel factual allegations and/or unique legal theories. In each of the matters described in this filing, in which we could incur a liability, our opponents seek an award of a not-yet-quantified amount of damages or an amount that is not material. In addition, a number of the matters pending against us are at very early stages of the legal process, which in complex proceedings of the sort we face often extend for several years. As a result, none of the matters described in this filing, in which we could incur a liability, have progressed sufficiently through discovery and/or the development of important factual information and legal issues to enable us to estimate a range of possible loss, if any, or such amounts are not material. While it is not possible to accurately predict or determine the eventual outcomes of these matters, an adverse determination in one or more of these matters currently pending could have a material adverse effect on our consolidated results of operations, financial position or cash flows.

Certain recent developments concerning our legal proceedings and other matters are discussed ~~below:~~below.

~~ANDA Patent Litigation~~

~~Otezla ANDA Patent Litigation~~

~~Amgen Inc. v. Sandoz Inc., et al.~~

Beginning in June 2018, Celgene filed 19 separate lawsuits in the U.S. District Court for the District of New Jersey (the New Jersey District Court) against Alkem Laboratories Ltd. (Alkem); Amneal Pharmaceuticals LLC (Amneal); Annora Pharma Private Ltd. and Hetero USA Inc. (collectively, Hetero); Aurobindo Pharma Ltd. and Aurobindo Pharma USA Inc. (collectively, Aurobindo); Cipla Limited (Cipla Ltd); DRL; Emcure Pharmaceuticals Ltd. and Heritage Pharmaceuticals Inc. (collectively, Emcure); Glenmark Pharmaceuticals Ltd. (Glenmark); Macleods Pharmaceuticals Ltd. (Macleods); Mankind Pharma Ltd. (Mankind); MSN Laboratories Private Limited (MSN); Pharmascience Inc. (Pharmascience); Prinston Pharmaceutical Inc. (Prinston); Sandoz Inc. (Sandoz); Shilpa Medicare Ltd. (Shilpa); Teva Pharmaceuticals USA, Inc. and Actavis LLC (collectively, Actavis); Torrent Pharmaceuticals Ltd. (Torrent); Unichem Laboratories, Ltd. (Unichem); and Zydus Pharmaceuticals (USA) Inc. (Zydus), each for infringement of one or more of the following patents: U.S. Patent Nos. 6,962,940 (the ’940 Patent), 7,208,516 (the ’516 Patent), 7,427,638 (the ’638 Patent), 7,659,302 (the ’302 Patent), 7,893,101 (the ’101 Patent), 8,455,536 (the ’536 Patent), 8,802,717 (the ’717 Patent), 9,018,243 (the ’243 Patent) and 9,872,854 (the ’854 Patent), which are listed in the Orange Book for Otezla. Each of these lawsuits was based on each defendant’s submission of an ANDA seeking FDA approval to market a generic version of Otezla. The New Jersey District Court consolidated these 19 lawsuits for discovery and case management purposes into a single case, ~~Celgene Corp. v. Sandoz Inc., et al.~~ ~~Each lawsuit seeks an order of the New Jersey District Court making any FDA approval of the respective defendant’s ANDA effective no earlier than the expiration of the applicable patents.~~

In August 2018, Celgene filed amended complaints against Alkem, Amneal, Aurobindo, Cipla Ltd, DRL, Glenmark, Pharmascience, Sandoz, Actavis, Unichem and Zydus additionally asserting U.S. Patent No. 9,724,330 (the ’330 Patent), which is listed in the Orange Book for Otezla. Between October 15 and November 27, 2018, Celgene filed amended complaints against Alkem, Amneal, Hetero, Aurobindo, Cipla Ltd, DRL, Emcure, Glenmark, Macleods, Mankind, MSN, Pharmascience, Prinston, Sandoz, Actavis, Torrent, Unichem and Zydus additionally asserting U.S. Patent No. 10,092,541 (the ’541 Patent), which is listed in the Orange Book for Otezla. Between March 1 and April 4, 2019, Celgene filed amended complaints against Hetero, MSN and Emcure for infringement of one or more of the above-listed patents. On October 1, 2019, Celgene filed an amended complaint against Mankind for infringement of the ’940, ’302, ’536, ’243 and ’330 Patents. On October 8, 2019, Celgene filed a separate lawsuit against Zydus in the New Jersey District Court for infringement of U.S. Patent Nos. 8,093,283 (the ’283 Patent) and 8,629,173, which are not listed in the Orange Book for Otezla. On December 19, 2019, the New Jersey District Court consolidated this lawsuit for discovery and case management purposes into the existing consolidated case, ~~Celgene Corp. v. Sandoz Inc., et al~~. Each defendant has filed an answer to the above-listed complaints and amended complaints disputing infringement and/or validity of the patents asserted against it. Along with their answers, each of Alkem, Hetero, Cipla

~~F-46~~

Ltd, DRL, Emcure, Glenmark, Macleods, Mankind, Pharmascience, Sandoz, Shilpa, Actavis, Torrent, Unichem and Zydus filed declaratory judgment counterclaims asserting that some or all of the patents are not infringed and/or are invalid. In August 2019, based on a joint request by Celgene and Glenmark, the New Jersey District Court entered a consent judgment and injunction prohibiting the making, having made, using, selling, offering to sell, importing, or distributing of Glenmark’s apremilast product during the term of the ’940, ’638, ’302, ’101, ’536, ’243, ’330 and ’541 Patents, unless authorized pursuant to a confidential settlement agreement.

Following Amgen’s acquisition of the patents-in-suit and the new drug application for Otezla, on February 14, 2020, the New Jersey District Court issued an order substituting Amgen for Celgene as plaintiff in the consolidated action and all related actions, terminating Celgene as plaintiff in the consolidated action and all related actions, and amending the case caption in the consolidated action and all related actions to reflect Amgen as the sole plaintiff.

On March 25, 2020, based on a joint request by Amgen and Unichem, the New Jersey District Court entered a consent judgment and injunction prohibiting the making, using, selling, offering to sell, or importing of Unichem’s apremilast product during the term of the ’940, ’638, ’302, ’101, ’536, ’243, ’330 and ’541 Patents, unless authorized pursuant to a confidential settlement agreement. On April 3, 2020, based on a joint request by Amgen and Hetero, the New Jersey District Court entered a consent judgment and injunction prohibiting the making, using, selling, offering to sell, or importing of Hetero’s apremilast product during the term of the ’940, ’516, ’638, ’302, ’101, ’536, ’717, ’243, ’330, ’854 and ’541 Patents, unless authorized pursuant to a confidential settlement agreement. On May 28, 2020, based on a joint request by Amgen and Emcure, the New Jersey District Court entered a consent judgment and injunction prohibiting the making, using, selling, offering to sell, or importing of Emcure’s apremilast product during the term of the ’638, ’101, ’854 and ’541 Patents unless authorized pursuant to a confidential settlement agreement. On July 7, 2020, the New Jersey District Court ordered a stipulated dismissal without prejudice of all claims, counterclaims, and affirmative defenses between Amgen and Sandoz with respect to the ’717, ’516 and ’854 Patents, leaving the ’940, ’302, ’536, ’243, ’330, ’638, ’101 and ’541 Patents asserted by Amgen against Sandoz in the litigation. On August 6, 2020, based on a joint request by Amgen and Mankind, the New Jersey District Court entered a consent judgment and injunction prohibiting the making, using, selling, offering to sell, or importing of Mankind’s apremilast product during the term of the ’940, ’302, ’536, ’243, ’330, ’638, ’101 and ’541 Patents, unless authorized pursuant to a confidential settlement agreement. On August 14, 2020, based on a joint request by Amgen and Macleods, the New Jersey District Court entered a consent judgment and injunction prohibiting the making, using, selling, offering to sell, or importing of Macleods’ apremilast product during the term of the ’638 and ’541 Patents, unless authorized pursuant to a confidential settlement agreement. On October 7, 2020, based on a joint request by Amgen and Amneal, the New Jersey District Court entered a consent judgment and injunction prohibiting the making, using, selling, offering to sell, or importing of Amneal’s apremilast product during the term of the ’101, ’940, ’638, ’302, ’536, ’243, ’330 and ’541 Patents, unless authorized pursuant to a confidential settlement agreement. On December 30, 2020, based on a joint request by Amgen and Shilpa, the New Jersey District Court entered a consent judgment and injunction prohibiting the making, using, selling, offering to sell, or importing of Shilpa’s apremilast product during the term of the ’638, ’101 and ’854 Patents, unless authorized pursuant to a confidential settlement agreement. On January 26, 2021, based on a joint request by Amgen and Actavis, the New Jersey District Court entered a consent judgment and injunction prohibiting the making, using, selling, offering to sell, or importing of Actavis’ apremilast product during the term of the ’940, ’516, ’638, ’302, ’536, ’717, ’330, ’854 and ’541 Patents, unless authorized pursuant to a confidential settlement agreement. On March 24, 2021, based on a joint request by Amgen and Prinston, the New Jersey District Court entered a consent judgment and injunction prohibiting the making, using, selling, offering to sell, or importing of Prinston’s apremilast product during the term of the ’638 and ’541 Patents, unless authorized pursuant to a confidential settlement agreement. On April 6, 2021, based on a joint request by Amgen and Aurobindo, the New Jersey District Court entered a consent judgment and injunction prohibiting the making, using, selling, offering to sell, or importing of Aurobindo’s apremilast product during the term of the ’940, ’516, ’638, ’302, ’101, ’536, ’717, ’243, ’330, ’854 and ’541 Patents, unless authorized pursuant to a confidential settlement agreement.

On May 5, 2021, based on a joint request by Amgen and Cipla, the New Jersey District Court entered a consent judgment and injunction prohibiting the making, using, selling, offering to sell, or importing of Cipla’s apremilast product during the term of the ’940, ’638, ’302, ’536, ’330 and ’541 Patents, unless authorized pursuant to a confidential settlement agreement. On May 14, 2021, based on a joint request by Amgen and Torrent, the New Jersey District Court entered a consent judgment and injunction prohibiting the making, using, selling, offering to sell, or importing of Torrent’s apremilast product during the term of the ’101, ’638, ’854 and ’541 Patents, unless authorized pursuant to a confidential settlement agreement. On May 19, 2021, based on a joint request by Amgen and Alkem, the New Jersey District Court entered a consent judgment and injunction prohibiting the making, using, selling, offering to sell, or importing of Alkem’s apremilast product during the term of the ’940, ’638, ’302, ’536, ’330 and ’541 Patents, unless authorized pursuant to a confidential settlement agreement. On May 25, 2021, based on a joint request by Amgen and MSN, the New Jersey District Court entered a consent judgment and injunction prohibiting the making, using, selling, offering to sell, or importing of MSN’s apremilast product during the term of the ’940, ’638, ’302, ’536, ’330 and ’541 Patents, unless authorized pursuant to a confidential settlement agreement. On June 11, 2021, based on a joint request by Amgen and Pharmascience, the New Jersey District Court entered a consent judgment and

~~F-47~~

injunction prohibiting the making, using, selling, offering to sell, or importing of Pharmascience’s apremilast product during the term of the ’243, ’940, ’638, ’302, ’101, ’536, ’330 and ’541 Patents, unless authorized pursuant to a confidential settlement agreement. On June 17, 2021, based on a joint request by Amgen and DRL, the New Jersey District Court entered a consent judgment and injunction prohibiting the making, using, selling, offering to sell, or importing of DRL’s apremilast product during the term of the ’638, ’101, ’536 and ’541 Patents, unless authorized pursuant to a confidential settlement agreement.

~~Trial on the consolidated patent infringement action against Sandoz and Zydus was held at the New Jersey District Court from June 14 to 25, 2021, with closing arguments on July 28, 2021.~~

On September 28, 2021, consistent with its September 20, 2021 opinion and order, the New Jersey District Court entered final judgment in favor of Amgen and against Zydus with respect to claims 3 and 6 of the ’638 Patent, claim 6 of the ’536 Patent and claims 2 and 27 of the ’283 Patent; and final judgment in favor of Zydus and against Amgen with respect to claims 1 and 15 of the ’101 Patent and claims 2, 19 and 21 of the ’541 Patent. The final judgment ordered that the effective date of any final approval by the FDA of Zydus’s ANDA must be after expiration of the three infringed patents (the ’638, ’536 and ’283 Patents) and any regulatory exclusivity to which Amgen may become entitled. The final judgment also includes an injunction prohibiting Zydus from making, using, offering to sell, or selling in the United States, or importing into the United States, Zydus’s generic apremilast products during the term of the three infringed patents. On October 27, 2021, Zydus filed a notice of appeal to the Federal Circuit Court with respect to the ’638 Patent. On October 28, 2021, Amgen filed a notice of appeal to the Federal Circuit Court.

On October 12, 2021, the New Jersey District Court also entered final judgment in favor of Amgen and against Sandoz with respect to claims 3 and 6 of the ’638 Patent, claim 6 of the ’536 Patent and claims 1 and 15 of the ’101 Patent; and final judgment in favor of Sandoz and against Amgen with respect to claims 2, 19 and 21 of the ’541 Patent. The final judgment ordered that the effective date of any final approval by the FDA of Sandoz’s ANDA must be after expiration of the three infringed patents (the ’638, ’536 and ’101 Patents) and any regulatory exclusivity to which Amgen may become entitled. The final judgment also includes an injunction prohibiting Sandoz from making, using, offering to sell, or selling in the United States, or importing into the United States, Sandoz’s generic apremilast products during the term of the three infringed patents. On November 9, 2021, Sandoz filed a notice of appeal to the Federal Circuit Court with respect to the ‘638 and ‘101 Patents. On November 10, 2021, Amgen filed a notice of appeal to the Federal Circuit Court.

~~ENBREL Patent Litigation~~

~~Immunex Corporation, et al. v. Samsung Bioepis Co., Ltd.~~

On April 30, 2019, 2 affiliates of Amgen Inc., Immunex Corporation and Amgen Manufacturing, Limited (collectively, Amgen), along with Hoffmann-La Roche Inc. (Roche), filed a lawsuit in the New Jersey District Court against Samsung Bioepis Co., Ltd. (Bioepis). This lawsuit stems from Bioepis’ submission of an application for FDA licensure of an etanercept product as biosimilar to Amgen’s ENBREL. Amgen and Roche have asserted infringement of five patents: U.S. Patent Nos. 8,063,182, 8,163,522 (the ’522 Patent), 7,915,225, 8,119,605 and 8,722,631. By their complaint, Amgen and Roche seek an injunction to prohibit Bioepis from commercializing its biosimilar etanercept product in the United States prior to the expiry of such patents. On August 5, 2019, Bioepis responded to the complaint, denying infringement and seeking judgment that the patents-in-suit are invalid, unenforceable and/or not infringed. On January 9, 2020 and subject to the terms of a confidential stipulation and court order of January 6, 2020, the New Jersey District Court entered a consent injunction that prohibits Bioepis from making, using, offering to sell, selling or importing into the United States Bioepis’ etanercept product. Amgen and Bioepis entered into an agreement with respect to an injunction regarding etanercept as set out in the New Jersey District Court’s order of January 6, 2020. On January 15, 2020, the New Jersey District Court entered an order administratively staying the case pursuant to a joint request of Amgen and Bioepis.

On November 2, 2021, Amgen and Bioepis, with the consent of Roche, jointly submitted to the New Jersey District Court a confidential stipulation and a form of final judgment and order of permanent injunction resolving the dispute between the parties and enjoining Bioepis from making, using, offering to sell, or selling within the United States, or importing into the United States, any product containing etanercept until the April 24, 2029 expiry of Roche’s ’522 Patent. On November 3, 2021, the New Jersey District Court entered final judgment and ordered a permanent injunction against Bioepis in conformity with the parties’ submission.

~~F-48~~

Repatha Patent Litigation

~~Amgen Inc., et al. v. Sanofi, et al.~~

In October 2014, Amgen initiated a series of lawsuits that were consolidated by the U.S. District Court for the District of Delaware (Delaware District Court) in December 2014 into a single case against Sanofi, Sanofi-Aventis U.S. LLC and Aventisub LLC, formerly doing business as Aventis Pharmaceuticals Inc. (collectively, Sanofi) and Regeneron Pharmaceuticals, Inc. (Regeneron), addressing 7 of our patents: U.S. Patent Nos. 8,563,698; 8,829,165 (the ’165 Patent); 8,859,741 (the ’741 Patent); 8,871,913; 8,871,914; 8,883,983; and 8,889,834. These patents describe and claim monoclonal antibodies to PCSK9. By its complaints, Amgen seeks an injunction to prevent the infringing manufacture, use and sale of Sanofi and Regeneron’s alirocumab, a monoclonal antibody targeting PCSK9. In January 2016, the Delaware District Court granted Amgen’s motion to amend the complaint to add its affiliates, Amgen Manufacturing, Limited and Amgen USA Inc., as plaintiffs and to add the allegation that Sanofi and Regeneron’s infringement of Amgen’s patents is willful.

In February 2016, the Delaware District Court entered a stipulated order finding alirocumab and the drug product containing it, PRALUENT infringe certain of Amgen’s patents, including claims 2, 7, 9, 15, 19 and 29 of the ’165 Patent and claim 7 of the ’741 Patent. In March 2016, the Delaware District Court entered judgment in favor of Amgen following a five-day jury trial and a unanimous jury verdict that these patent claims are all valid. In January 2017, the Delaware District Court denied Sanofi and Regeneron’s post-trial motions seeking a new trial and for judgment as a matter of law, and granted Amgen’s motion for a permanent injunction prohibiting the infringing manufacture, use, sale, offer for sale or import of alirocumab in the United States. Sanofi and Regeneron filed an appeal of the judgment and the permanent injunction to the Federal Circuit Court. In February 2017, following a motion by Sanofi and Regeneron, the Federal Circuit Court entered a stay of the permanent injunction during the pendency of the appeal. In October 2017, the Federal Circuit Court reversed in part the judgment of the Delaware District Court and remanded for a new trial two of the patent validity defenses (lack of written description and enablement of the claimed inventions), and affirmed the Delaware District Court’s judgment of infringement of claims 2, 7, 9, 15, 19 and 29 of the ’165 Patent and claim 7 of the ’741 Patent and the third patent validity defense (finding that the claimed inventions were not obvious to a person of ordinary skill in the field of the patents).

In March 2018, the Federal Circuit Court issued a mandate returning the case to the Delaware District Court for a new trial on 2 of Sanofi and Regeneron’s challenges to the validity of our patents (lack of written description and enablement of the claimed inventions) and for further consideration of a permanent injunction. In July 2018, Amgen filed a petition for certiorari with the U.S. Supreme Court seeking review of the Federal Circuit Court’s conclusion that the judgment affirming the validity of Amgen’s patents was based, in part, on an erroneous application of the law of written description. On January 7, 2019, the U.S. Supreme Court denied Amgen’s petition for certiorari. On remand, the Delaware District Court scheduled a new trial on Sanofi and Regeneron’s challenges to the validity of our patents based on lack of written description and enablement of the claimed inventions. The Delaware District Court also entered judgment on the pleadings for Sanofi and Regeneron on Amgen’s claim of willful infringement.

On February 25, 2019, a jury of the Delaware District Court again unanimously upheld the validity of claims 19 and 29 of the ’165 Patent and claim 7 of the ’741 Patent. The jury also found that claims 7 and 15 of the ’165 Patent meet the enablement requirement, but are invalid for failure to meet the written description requirement. On March 18, 2019, Sanofi and Regeneron filed post-trial motions seeking to reverse the jury verdict against them or for a new trial, and Amgen filed a motion for a permanent injunction. On August 28, 2019, the Delaware District Court ruled on the post-trial motions, denying Sanofi and Regeneron’s request for a new trial and their request to reverse the jury verdict that the ’165 Patent and the ’741 Patent provide written description support for the claimed inventions. The Delaware District Court also ruled as a matter of law that claims 19 and 29 of the ’165 Patent and claim 7 of the ’741 Patent are invalid for failing to meet the enablement requirement, overturning the jury verdict.

On October 23, 2019, Amgen filed a notice of appeal to the Federal Circuit Court and based on the subsequent hearing, on February 11, 2021 the Federal Circuit Court issued a decision affirming the Delaware District Court’s ruling. Amgen filed a petition for rehearing en banc which was denied on June 21, 2021. On November 18, 2021, Amgen filed a petition for writ of certiorari with the U.S. Supreme Court seeking review of the invalidation of claims 19 and 29 of the ’165 Patent and claim 7 of the ’741 Patent as lacking an enabling disclosure of the invention. On January 11, 2022, the U.S. Supreme Court requested that Sanofi and Regeneron file a response to Amgen’s petition, which is due March 14, 2022.

Patent Disputes in the International Region

We are involved in and expect future involvement in additional disputes regarding our PCSK9 patents in other jurisdictions and regions. This includes matters filed against us and that we have filed in Germany ~~Spain~~ and Japan.

~~F-49~~

Germany

In February 2016, the European Patent Office (EPO) granted European Patent No. 2,215,124 ~~(EP 2,215,124)~~(the EP’124 Patent) to Amgen. This patent describes and claims monoclonal antibodies to PCSK9 and methods of treatment and Sanofi filed an opposition to the patent in the EPO seeking to invalidate it. In November 2016, Sanofi-Aventis Deutschland GmbH, Sanofi-Aventis Groupe S.A. and Sanofi Winthrop Industrie S.A. filed a joint opposition against Amgen’s patent, and each of Lilly, Regeneron Pharmaceuticals, Inc. (Regeneron) and Strawman Ltd. also filed oppositions to Amgen’s patent. In November 2018, the EPO confirmed the validity of Amgen’s ~~EP 2,215,124,~~EP’124 Patent, which was appealed to the Technical Board of Appeal (TBA). On October 29, 2020, the TBA upheld the validity of certain claims, including claims that protect Repatha, but ruled that broader claims encompassing PRALUENT were invalid. As a result of the TBA’s decision, national litigations regarding PRALUENT in ~~Europe~~Germany are in the process of being resolved.

In Germany, Sanofi-Aventis Deutschland GmbH and Regeneron ~~have~~ filed actions seeking damages arising from the provisional enforcement of an injunction against PRALUENT that was lifted after the TBA’s October ~~29,~~ 2020 ruling. Amgen filed counterclaims alleging that PRALUENT infringes Amgen’s European Patent No. 2,641,917 (the EP’917 Patent). On November 29, 2023, the Regional Court of Munich ruled that PRALUENT does not infringe the EP’917 Patent. A hearing has been

F-51

scheduled for February 28, 2024 in the Munich Regional Court on Sanofi-Aventis Deutschland GmbH’s and Regeneron’s action for damages.

On July 21, 2022, Sanofi Biotechnology SAS filed an action against Amgen GmbH and Amgen (Europe) B.V. before the Regional Court of Dusseldorf alleging that the marketing and sale of Repatha infringes European Patent No. 2,756,004 (the EP’004 Patent), which Sanofi Biotechnology SAS licensed from Regeneron. Sanofi Biotechnology SAS is seeking infringement damages and injunctive relief. The court scheduled a hearing on this infringement action for May 28, 2024.

On August 3, 2023, Amgen GmbH filed a Nullity Action before the German Federal Patent Court seeking invalidation of Regeneron’s EP’004 Patent. Regeneron filed a Statement of Defense on November 20, 2023. On January 22, 2024, Amgen filed its brief in reply.

Amgen and an anonymous third party opposed the EP’004 Patent in the EPO, but on December 6, 2023 the patent was finally upheld by the TBA as granted.

Unified Patent Court of the European Union

On June 1, 2023, Amgen filed an action before the Local Division of the Unified Patent Court in Munich against Sanofi-Aventis Deutschland GmbH, Sanofi-Aventis Groupe S.A., Sanofi Winthrop Industrie S.A. (collectively, Sanofi-Aventis), and Regeneron alleging that the importation, marketing, sale and use of PRALUENT infringes European Patent 3,666,797 (the EP’797 Patent) seeking an injunction and damages for past infringement. Regeneron filed counterclaims for revocation, but on February 5, 2024, the court transferred the counterclaims to the Central Division of the Unified Patent Court that is presiding over Sanofi’s revocation action. The Local Division scheduled the hearing on our EP’797 Patent infringement action to begin on October 16, 2024.

On June 29, 2023, the Central Division of the Unified Patent Court in Munich served Amgen with an action that was filed by Sanofi-Aventis that seeks revocation of the EP’797 Patent. The Central Division scheduled a hearing on the revocation action to begin on June 4, 2024.

On January 10, 2024, Sanofi Biotechnologies SAS and Regeneron filed an action against Amgen Inc., Amgen Europe B.V., Amgen N.V., Amgen GmbH, Amgen B.V., Amgen SAS, and Amgen S.R.L before the Unified Patent Court, alleging infringement of EP 3,536,712, which Sanofi Biotechnology SAS licensed from Regeneron. Sanofi and Regeneron are seeking an injunction against the sale, marketing, use, importation, or storage of Repatha for certain specified uses in Belgium, France, Germany, Italy and the Netherlands.

Japan

On April 24, 2020, the Supreme Court of Japan declined to hear Sanofi K.K.’s appeals making final the Japanese High Court’s decisions that PRALUENT infringes Amgen’s valid patent rights in Japan. On June 24, 2020, Amgen filed written answers to the invalidity trials initiated by Regeneron on February 12, 2020 before the Japan Patent Office seeking to invalidate Amgen’s Japanese patents that were previously held infringed by PRALUENT and valid over challenges filed by Sanofi K.K. ~~The~~On April 15, 2021, the Japanese Patent Office dismissed Regeneron’s invalidity trials, and in August 2021 Regeneron ~~has~~ appealed the decisions to the Japanese High Court. On January 26, 2023, the Japanese High Court found Amgen’s patent claims invalid for lacking adequate support. On March 13, 2023, Amgen appealed to the Japanese Supreme Court the High Court’s decision that Amgen’s Japanese patent claims relating to PCSK9 were invalid for lacking adequate support. On September 15, 2023, the Japanese Supreme Court declined to hear Amgen’s appeal. The case will be remanded to the Japan Patent Office for further proceedings.

Damages proceedings against Sanofi K.K. are ongoing before the Tokyo District Court, where Sanofi K.K. has initiated new validity challenges to Amgen patents in Japan. On September 27, 2023, the Tokyo District Court found Amgen’s patent claims invalid and dismissed Amgen’s lawsuit for damages. Amgen appealed the District Court’s decision to the IP High Court on December 28, 2023.

~~NEUPOGEN (filgrastim)/Neulasta Patent~~Prolia/XGEVA Biologics Price Competition and Innovation Act (BPCIA) Litigation

Amgen Inc., et al. v. ~~Hospira~~Sandoz Inc., et al.

On ~~February 11, 2020,~~May 1, 2023, Amgen Inc. and ~~its wholly owned subsidiary,~~ Amgen Manufacturing Limited (collectively, Amgen), filed a lawsuit in the Delaware District Court against Hospira Inc. and Pfizer Inc. (collectively, Pfizer). This lawsuit stems from Pfizer’s submission of an application for FDA licensure of a pegfilgrastim product as biosimilar to Amgen’s Neulasta. Amgen has asserted infringement of U.S. Patent No. 8,273,707 (the ’707 Patent) and seeks, among other remedies, injunctive relief to prohibit Pfizer from infringing the ’707 Patent. On March 4, 2020, Pfizer filed a motion requesting the Delaware District Court to dismiss the complaint by Amgen alleging noninfringement of the ’707 Patent. In June 2020, the FDA approved Pfizer’s NYVEPRIA, a biosimilar to Amgen’s Neulasta.

On April 6, 2021, the Delaware District Court stayed further proceedings in the matter pending claim construction of the patent claims and, based on a subsequent hearing, determined on June 11, 2021 that the term at issue required no construction.~~Currently pending before the Delaware District Court is Pfizer’s motion for summary judgment of noninfringement, which has been fully briefed.No date has been set for argument on the motion.~~

~~Patent Trial and Appeal Board (PTAB) Challenge~~

~~Apotex PTAB Challenge~~

In February 2017, the PTAB of the USPTO granted Apotex’s petition to institute inter partes review (IPR) proceeding of U.S. Patent No. 8,952,138 (the ’138 Patent), challenging claims of the ’138 Patent as unpatentable. In May 2017, Amgen filed its response. In February 2018, the PTAB issued a final decision holding all but 1 claim of the ’138 Patent as unpatentable and Apotex filed a request for rehearing in March 2018.

On May 20, 2019, the PTAB issued a decision denying Apotex’s request for rehearing on the PTAB’s finding and sua sponte amending the final decision with a finding that the 1 remaining claim in Amgen’s ’138 Patent is unpatentable. On July 22, 2019, Amgen filed a notice of appeal to the Federal Circuit Court with respect to all claims held to be unpatentable. On August 5, 2019, Apotex provided notice that it would not participate in the appeal. On September 16, 2019, the USPTO filed a notice of intervention on the appeal. On March 24, 2020, the Federal Circuit Court vacated the decision by the PTAB and remanded the case to the PTAB for proceeding consistent with the Federal Circuit Court’s decision in ~~ArthrexInc. v. Smith & Nephew, Inc., 941 F.3d 1320 (Fed. Cir. 2019).~~

On July 14, 2020, Amgen and Apotex filed a joint motion to terminate the IPR proceedings stating that there is no current dispute between the parties with respect to the ’138 Patent. On July 29, 2020, the U.S. government filed a petition for writ of certiorari with respect to the cases that the Federal Circuit Court remanded to the PTAB, including the case regarding the ’138 Patent, for proceedings consistent with its decision in ~~Arthrex Inc. v. Smith & Nephew, Inc., requesting that such remanded cases be held pending the U.S. Supreme Court’s disposition of the petition for writ of certiorari in~~ ~~United States v. Arthrex, Inc.~~, No. 19-1434. On August 25, 2020, Amgen filed its response to the U.S. government’s petition for writ of certiorari indicating that Amgen did not intend to respond unless requested by the U.S. Supreme Court.

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~~On June 21, 2021, the U.S. Supreme Court decided~~ ~~United States v. Arthrex, Inc.~~ ~~On June 28, 2021, the U.S. Supreme Court granted the government’s pending certiorari petition and vacated and remanded the Federal Circuit Court’s judgment for further consideration under~~ ~~Arthrex.~~

On September 2, 2021, the Federal Circuit Court issued a remand to permit Amgen to request rehearing of the PTAB’s final written decision holding that all claims of the ’138 Patent as unpatentable.

~~On October 4, 2021, Amgen filed a request for the USPTO Director for a rehearing and review of the Final Written Decision pursuant to~~ ~~Arthrex. On November 22, 2021, the Director denied this request. On December 6, 2021, Amgen filed the Notice of Director review with the patent office.~~

~~Pfizer PTAB Challenge~~

On February 10, 2021, Pfizer filed a petition to institute IPR proceeding at the USPTO of U.S. Patent No. 8,273,707 (the ’707 Patent), challenging claims of the ’707 Patent as unpatentable. Amgen’s preliminary response was filed on May 18, 2021.

On August 17, 2021, the PTAB of the USPTO granted Pfizer’s petition to institute IPR of the ’707 Patent. On August 23, 2021, the PTAB issued the schedule for the proceeding, including oral argument (if requested) on May 18, 2022. On November 17, 2021, Amgen filed its Patent Owner’s Response.

~~Breach of Contract Action~~

~~Novartis Pharma AG v. Amgen Inc.~~

~~On April 4, 2019, Amgen~~ filed a lawsuit in the U.S. District Court for the ~~Southern~~ District of New ~~York (the New York Southern~~Jersey (New Jersey District Court) against Sandoz Inc., Sandoz GmbH, Lek Pharmaceuticals d.d., Novartis ~~seeking a declaratory judgment that Novartis materially breached 2 collaboration agreements Amgen~~Pharmaceutical Productions d.o.o., and Novartis ~~entered into in 2015 and 2017 (the 2015 Agreement and~~AG (collectively, Defendants) based on the ~~2017 Agreement, respectively) related~~submission to the ~~development~~FDA of a BLA seeking approval to market and ~~commercialization~~sell a biosimilar version of Aimovig due to Novartis’ affiliate Sandoz GmbH entering into a contract manufacturing agreement with Alder BioPharmaceuticals, Inc. (Alder) related to eptinezumab, an expected direct competitor to AimovigAmgen’s Prolia and ~~entrant~~XGEVA products. The complaint asserts infringement of the following 21 patents, which are listed in the ~~CGRP-related migraine therapy market.~~FDA’s Purple Book for Amgen’s Prolia and XGEVA products: U.S. Patent Nos. 7,364,736; 7,928,205; 8,058,418; 9,012,178; 9,133,493; 9,228,168; 9,320,816; 9,328,134; 9,359,435;

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9,481,901; 10,167,492; 10,513,723; 10,583,397; 10,822,630; 10,894,972; 11,077,404; 11,098,079; 11,130,980; 11,254,963; 11,299,760; and 11,434,514 (collectively, the Asserted Patents). Amgen seeks a judgment from the New Jersey District Court that Defendants have infringed or will infringe one or more claims of each of the Asserted Patents and based on that judgment, a permanent injunction prohibiting the commercial manufacture, use, offer to ~~terminate its collaboration agreements with Novartis and~~sell, or sale within the United States or importation into the United States of Defendants’ proposed denosumab biosimilar before expiration of each of the Asserted Patents found to infringe. Amgen also seeks ~~damages from Novartis~~monetary remedies for ~~breach~~any past acts of ~~contract~~infringement.

On June 16, 2023, Amgen filed an amended and ~~negligent misrepresentation. Also~~supplemental complaint to include additional information regarding the completion of the BPCIA information exchange after the filing of the original complaint. Sandoz Inc. (Sandoz) responded to the amended and supplemental complaint on April 4, 2019, Novartis initiated a separate lawsuit against Amgen in the same court seeking declaratory judgment that Novartis, alternatively, did not materially breach the collaboration agreements or, even if it did breach the collaboration agreements, such breach was not materialJuly 7, 2023, denying infringement and ~~has been cured, and that Amgen may not terminate the collaboration agreements. On April 8, 2019, Amgen answered Novartis’ complaint and filed~~asserting counterclaims seeking a declaratory judgment that Novartis materially breached the collaboration agreements due to its affiliate Sandoz GmbH entering into the contract manufacturing agreement with Alder. In its counterclaim, Amgen seeks to terminate its collaboration agreements with Novartis and also seeks damages from Novartis for breach of contract and negligent misrepresentation.asserted patents are invalid and/or unenforceable. On July ~~16, 2019, Novartis filed an amended complaint adding a claim for breach of contract alleging Novartis is owed amounts associated with 2018 budget overruns, and~~28, 2023, Amgen responded, ~~with~~seeking a ~~counterclaim alleging additional breaches by Novartis~~denial and dismissal of the collaboration agreements. On September 17, 2019 and October 8, 2019, Novartis and Amgen, respectively, each filed its motion for judgment on the pleadings. On February 3, 2020, Amgen was granted leave to file its amended counterclaims. On February 4, 2020, Amgen filed its amended answer to Novartis’ first amended complaint and second amended counterclaims for affirmative relief to add a fraudulent inducement claim. On February 18, 2020, Novartis filed its answer and affirmative defenses to Amgen’s second amendedSandoz’s counterclaims.

On ~~June 9, 2020,~~August 23, 2023, the New ~~York Southern~~Jersey District Court entered ana stipulation and order ~~granting Novartis’~~dismissing without prejudice Sandoz GmbH, Lek Pharmaceuticals d.d., Novartis Pharmaceutical Productions d.o.o., and Novartis AG (collectively, Foreign Defendants) from the action. Pursuant to the stipulation entered by the New Jersey District Court, the Foreign Defendants agreed to be bound by any judgment order or decision in the matter (including appeals) as if the Foreign Defendants were named as defendants and parties to the judgment order or decision. Sandoz is now the sole named Defendant in the action.

On October 30, 2023, the New Jersey District Court commenced a hearing on Amgen’s motion for a preliminary injunction to prohibit Sandoz from engaging in the commercial manufacture, use, offer for sell or sale within the United States, or importation into the United States of its proposed denosumab biosimilar until judgment is entered after trial on the ~~pleadings that Novartis did not breach~~merits. Closing arguments on Amgen’s motion for the ~~2017 Agreement, and denying~~preliminary injunction were held on December 21, 2023.

ABP 938 (aflibercept) Patent Litigation

On January 10, 2024, Regeneron filed a lawsuit in the U.S. District Court for the Central District of California (the California Central District Court) against Amgen alleging infringement of 32 patents listed by Regeneron in the BPCIA exchange. The lawsuit stems from Amgen’s ~~motions~~submission of an application under the BPCIA for ~~judgment on~~FDA licensure of ABP 938 as biosimilar to Regeneron’s EYLEA. By its complaint, Regeneron seeks, among other remedies, an injunction prohibiting the ~~pleadings seeking dismissal~~commercial manufacture, use, offer for sale or sale in the United States or import into the United States of ~~Novartis’ amended complaint that Novartis did not breach~~ABP 938 before the ~~2015 Agreement or~~expiration of each of the ~~2017 Agreement, and Novartis timely cured any breach.~~patents found to be infringed. On ~~June 23, 2020, Amgen~~January 11, 2024, Regeneron filed a motion with the Judicial Panel on Multidistrict Litigation to transfer this case from the California Central District Court to the U.S. District Court for ~~clarification~~the Northern District of West Virginia for coordinated pretrial proceedings with the five other cases involving EYLEA biosimilars pending in that district. A hearing on Regeneron’s motion to transfer has been scheduled for March 28, 2024. Amgen responded to Regeneron’s complaint on February 2, 2024, denying infringement and asserting counterclaims seeking a declaratory judgment that the asserted patents are not infringed, invalid, and/or ~~reconsideration of the June 9, 2020 order, which was denied on September 14, 2020.~~unenforceable.

On June 2, 2021, the parties executed agreements to settle 2 claims in the litigation, relating to the 2018 budget overrun dispute and certain counterclaims alleging breaches by Novartis of the 2015 and 2017 Agreements related to the development and commercialization of Aimovig, and to amend and restate the 2017 collaboration agreement. As part of the agreement, Amgen paid $48 million to Novartis to resolve the 2018 budget dispute.

On October 26, 2021, the New York Southern District Court held a status conference with the parties and set the dates for Novartis’ opening brief for its motion for partial summary judgment on 2 claims, fraudulent inducement and negligent misrepresentation.

~~On January 31, 2022, the parties resolved all claims in the litigation.~~

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Antitrust Class Action

Sensipar Antitrust Class Actions

From February to April 2019, 4four plaintiffs filed putative class action lawsuits against Amgen and various entities affiliated with Teva Pharmaceuticals USA, Inc. (Teva) alleging anticompetitive conduct in connection with settlements between Amgen and manufacturers of generic cinacalcet product. ~~NaN~~Two of those actions were brought in the U.S. District Court for the District of Delaware (the Delaware District ~~Court,~~Court), captioned UFCW Local 1500 Welfare Fund v. Amgen Inc., et al. (February 21, 2019) (Local 1500) and Cesar Castillo, Inc. v. Amgen Inc., et al. (February 26, 2019) (Castillo). The third action was brought in the New Jersey District Court, captioned Teamsters Local 237 Welfare Fund, et al. v. Amgen Inc., et al. (March 14, 2019) (Local 237) and the ~~4th~~fourth action was brought in the U.S. District Court for the Eastern District of Pennsylvania (the Eastern Pennsylvania District Court), captioned KPH Healthcare Services, Inc. a/k/a Kinney Drugs, Inc. v. Amgen Inc., et al (April 10, 2019) (KPH). Each of the lawsuits is brought on behalf of a putative class of direct or indirect purchasers of Sensipar and alleges that the plaintiffs have overpaid for Sensipar as a result of Amgen’s conduct that allegedly improperly delayed market entry by manufacturers of generic cinacalcet products. The lawsuits focus predominantly on the settlement among Amgen, Watson Laboratories, Inc. (Watson) and Teva of the parties’ patent infringement litigation. Each of the lawsuits seeks, among other things, treble damages, equitable relief and attorneys’ fees and costs. On April 10, 2019, the plaintiff in the KPH lawsuit filed a motion seeking to have the 4four lawsuits consolidated and designated as a multidistrict litigation (MDL) in the Eastern Pennsylvania District Court, and the plaintiff in the Local 1500 lawsuit filed a motion seeking to have the 4four lawsuits, along with Cipla Ltd. v. Amgen Inc., consolidated and designated as an MDL in the Delaware District Court.

On July 31, 2019, the MDL panel entered an order consolidating in the Delaware District Court the 4four class action lawsuits. On September 13, 2019, the plaintiffs filed amended complaints, and on October 15, 2019, Amgen filed its motion to dismiss both the direct purchaser plaintiffs’ consolidated class action complaint and the indirect purchaser end ~~payor~~payer plaintiffs’

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complaint. On December 6, 2019, the plaintiffs responded to Amgen’s motion to dismiss and, on January 10, 2020, Amgen filed its response. On February 6, 2020, the motions in the class action lawsuits were transferred to the U.S. Magistrate Judge for the District of Delaware (Magistrate Judge) for a recommendation. The MDL panel certified its conditional transfer order on February 6, 2020 transferring the additional class action lawsuit brought in the U.S. District Court for the Southern District of Florida, captioned MSP Recovery Claims v. Amgen Inc., et al., to the Delaware District Court.

On July 22, 2020, the Magistrate Judge issued a recommendation to the Delaware District Court that the claims against Amgen be dismissed but leave be given to plaintiffs to amend their complaints. On August 5, 2020, the plaintiffs filed objections to the Magistrate Judge’s report and recommendation. On August 19, 2020, Amgen filed a response to the plaintiffs’ objections. On November 30, 2020, the Delaware District Court adopted the Magistrate Judge’s recommendation in part and denied it in part, denying Amgen’s motion to dismiss on the grounds that plaintiffs adequately alleged reverse payment claims but granted Amgen’s motion to dismiss with respect to the other Federal antitrust claims. On December 23, 2020, Teva, Watson and Actavis filed a motion for interlocutory appeal and for a stay pending appeal and Amgen filed its joinder (the 1292 Motion). On January 5, 2021, a joint status report was filed advising the Delaware District Court that the defendants are still considering whether to withdraw the 1292 Motion and plaintiffs’ offer to stay discovery, pending further rulings on motions to dismiss the amended complaints. On January 19, 2021, a joint status report was filed pursuant to the Delaware District Court’s January 6, 2021 order along with a stipulation to defer the 1292 Motion until after rulings on the amended complaints.

On February 16, 2021, the plaintiffs in the antitrust class action lawsuit brought on behalf of putative classes of direct or indirect purchasers of Sensipar filed their amended complaints. On March 4, 2021, a stipulation and order regarding the filing of a second amended complaint were filed to add another plaintiff: Teamsters Western Region & Local 177 Health Care Fund. On March 17, 2021, a defendant, MSP Recovery Claims, Series LLC, filed its notice of voluntary dismissal. On March 30, 2021, the remaining defendants, including Amgen, filed their motions to dismiss the second amended complaint.

On April 27, 2021, plaintiffs filed their oppositions to defendants’ (including Amgen’s) motion to dismiss, and defendants’ reply was filed on May 25, 2021. A hearing on defendants’ motion to dismiss was held in the Delaware District Court on July 13, 2021.

~~Humira Biosimilar Antitrust Class Actions~~

~~From~~On March ~~to May 2019, 12 purported class actions against Amgen, along with AbbVie Inc. and AbbVie Biotechnology Ltd. (collectively, AbbVie), were filed in~~11, 2022, the ~~U.S.~~Delaware District Court ~~for~~granted defendants’ (including Amgen’s) motion to dismiss except as to the ~~Northern District of Illinois (the Illinois Northern District Court). The cases are captioned:~~ ~~UFCW Local 1500 Welfare Fund v. AbbVie Inc., et al.~~ ~~(March 18, 2019) (Local 1500);~~ ~~Fraternal Order of Police, Miami Lodge 20, Insurance Trust Fund v. AbbVie Inc., et al.~~ ~~(March 20, 2019);~~ ~~Mayor~~reverse payment claim and ~~City Council of Baltimore v. AbbVie Inc., et al.~~ ~~(March 22, 2019);~~ ~~PipeTrades Services MN Welfare Fund v. AbbVie Inc., et al.~~ ~~(March 29, 2019);~~ ~~St. Paul Electrical Workers’ Health Plan v. AbbVie Inc., et al.~~ ~~(March 29, 2019);~~ ~~Welfare Plan of the International Union of Operating Engineers Locals 137, 137A, 137B, 137C and 137R v. AbbVie Inc., et al.~~ ~~(April 1,~~

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~~2019);~~ ~~Law Enforcement Health Benefits, Inc. v. AbbVie, Inc., et al.~~ ~~(April 9, 2019) (Law Enforcement);~~ ~~Kentucky Laborers District Council Health and Welfare Fund v. AbbVie, Inc., et al.~~ ~~(April 16, 2019);~~ ~~Sheet Metal Workers’ Local Union No. 28 Welfare Fund v. AbbVie, Inc., et al.~~ ~~(April 19, 2019) (Sheet Metal Workers’);~~ ~~Locals 302 & 612 of The International Union of Operating Engineers-Employers Construction Industry Health And Security Trust Fund v. AbbVie Inc., et al.~~ ~~(April 25, 2019) (Construction Industry);~~ ~~Louisiana Health Service & Indemnity Co., d/b/a Blue Cross and Blue Shield of Louisiana and HMO Louisiana, Inc. v. AbbVie Inc.~~, ~~et al.~~ ~~(April 30, 2019) (Louisiana Health); and~~ ~~Cleveland Bakers and Teamsters Health and Welfare Fund v. AbbVie Inc., et al.~~ ~~(May 10, 2019) (Cleveland Bakers) (collectively, Humira Antitrust Class Actions).~~

~~In each of the Humira Antitrust Class Actions, the plaintiffs bring federal antitrust claims along with~~ various state law claims under common law and antitrust, consumer protection and unfair competition statutes. In each case, the plaintiffs specifically allege that AbbVie has unlawfully monopolized the alleged market for Humira and biosimilars of Humira, including by creating an allegedly unlawful so-called patent thicket around Humira. In the Local 1500, Sheet Metal Workers’ and Construction Industry cases, the plaintiffs further allege that AbbVie entered into allegedly unlawful market division agreements with Amgen and other companies that had developed Humira biosimilars, including Bioepis, Mylan, Sandoz, Fresenius Kabi USA, LLC (Fresenius), Pfizer Inc. and Momenta Pharmaceuticals, Inc., in connection with the settlement of patent litigation relating to Humira, whereby Amgen and the other defendants that have developed Humira biosimilars were permitted to market those products in Europe as early as October 2018, while remaining off the market in the United States until 2023. In eachfrom ten of the ~~Humira Antitrust Class Actions other than~~states in which plaintiffs reside. On May 11, 2022, the ~~Local 1500~~parties filed motions asking permission to seek interlocutory appeal. The plaintiffs did not oppose Amgen’s motion and ~~Construction Industry cases,~~instead argued all issues should be appealed at this time. Amgen filed its opposition to plaintiffs’ motion on June 10, 2022, and reply briefs were filed on June 24, 2022.

On February 16, 2023, the plaintiffs allege that AbbVie and Amgen entered into an allegedly unlawful settlement agreement under which Amgen allegedly agreed to delay its entry into the U.S. market with AMGEVITA, its Humira biosimilar, in exchange for an alleged promise of exclusivity as the sole Humira biosimilar in that market for five months, beginning in January 2023. In each of the Humira Antitrust Class Actions, plaintiffs seek injunctive relief, treble damages and attorney’s fees on behalf of a putative class of third-party payers and/or consumers that have indirectly purchased, paid for or provided reimbursement for Humira in the United States. Defendants’ responses to the first 6 complaints were stayed by the court. On June 4, 2019, the Illinois NorthernDelaware District Court ~~entered an order consolidating the 12 purported class action cases~~denied Amgen’s motion for ~~pre-trial purposes.~~

interlocutory appeal. On ~~August 9, 2019, the plaintiffs filed their consolidated complaint, naming as defendants~~March 2, 2023, Amgen ~~along with AbbVie, Bioepis, Sandoz and Fresenius. On October 11, 2019, the defendants~~ filed a ~~joint~~ motion ~~to dismiss~~for reargument, which the consolidated complaint (as well as brief individual motions), challenging the legal sufficiency of the plaintiffs’ allegations to state any claim for relief under the law. On November 19, 2019, plaintiffs filed their opposition to the motion to dismiss. On December 20, 2019, defendants filed their reply in support of the motion to dismiss. On June 8, 2020, the Illinois NorthernDelaware District Court ~~issued an order granting~~denied while also certifying a question regarding whether the ~~motion~~current judge has the authority to certify a question decided by ~~the defendants to dismiss the consolidated class action complaint.~~a predecessor judge. On ~~June 29, 2020, the plaintiffs~~April 17, 2023, Amgen filed a ~~status report asking the Illinois Northern District Court to convert the dismissal to one~~petition with prejudice. On June 30, 2020, the Illinois Northern District Court granted the motion. On July 28, 2020, the plaintiffs filed a notice of appeal. On October 5, 2020, the plaintiffs-appellants filed their opening brief to the U.S. Court of Appeals for the ~~Seventh Circuit. Plaintiffs-appellants amicus briefs were~~Third Circuit (the Third Circuit Court), seeking a grant of our request for interlocutory appeal of the certified question as well as the Delaware District Court’s denial of our motion to dismiss the reverse payment claim. Amgen’s response to the class action complaints is due 30 days after resolution or denial of the interlocutory appeal.

On June 26, 2023, the Third Circuit Court entered an order granting defendants’ (including Amgen’s) petition for interlocutory appeal and denying plaintiffs’ cross-petition. The questions certified are whether (1) the statute for interlocutory decisions authorizes a district court judge to certify for interlocutory appeal an order issued in the same case by a predecessor district court judge; and (2) the settlement of a patent infringement claim that involves the forgiveness of damages associated with that patent’s alleged infringement, on its own or combined with an acceleration clause, constitutes a reverse payment. On July 3, 2023, Amgen and Teva Pharmaceuticals USA, Inc. filed a notice of appeal, and on October 17, 2023, Amgen submitted its initial brief in ~~October 2020, including one by~~its appeal before the ~~FTC~~Third Circuit Court.

On January 12, 2024, Amgen reached an agreement in principle to settle with the putative class of indirect purchasers of Sensipar. The action with respect to the putative class of direct purchasers of Sensipar will proceed with the pending appeal before the Third Circuit Court.

Regeneron Pharmaceuticals, Inc. Antitrust Action

On May 27, 2022, Regeneron filed suit against Amgen in the Delaware District Court for federal and ~~one~~state antitrust and unfair competition violations and tortious interference with prospective business relations. Regeneron alleges that Amgen’s sales contracting practices for Repatha, ENBREL and Otezla with key insurers, third-party payers and PBMs have harmed the sales of its product PRALUENT and focuses on ~~behalf~~two primary arguments: that Amgen improperly bundled sales of ~~20 states, each~~Repatha with ENBREL, Otezla and potentially other products and sought exclusive or de facto exclusive formulary positioning for Repatha. Amgen’s initial responsive pleading, a motion to dismiss, was filed on ~~October 13, 2020.~~ August 1, 2022.

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On ~~December 21, 2020,~~August 11, 2022, Amgen moved to stay the ~~defendants-appellees filed their opposition brief. Defendants-appellees amicus briefs, including one by~~case pending the ~~DoJ, were filed~~ultimate decision on ~~December 28, 2020.~~the merits of the ongoing patent litigation between Amgen and Regeneron in Amgen Inc., et al. v. Sanofi, et al. On January 6, 2023, the Delaware District Court heard oral argument on the motion to stay and the motion to dismiss. On February ~~25, 2021, oral argument was held by~~10, 2023, the ~~U.S.~~Delaware District Court ~~of Appeals~~denied Amgen’s motion to stay this action, and on March 21, 2023, the Delaware District Court denied Amgen’s motion to dismiss the complaint.

On August 28, 2023, Regeneron filed its amended complaint, and on September 20, 2023, Amgen filed a counterclaim, alleging Regeneron’s own anticompetitive conduct with respect to formulary position for ~~the Seventh Circuit~~Regeneron’s drug, PRALUENT, at CVS.

Trial is scheduled to begin on ~~the appeal by plaintiffs-appellants of the lower court’s dismissal of the consolidated complaint with prejudice.~~November 12, 2024.

U.S. Tax Litigation and Related Matters

Amgen Inc. & Subsidiaries v. Commissioner of Internal Revenue

See Note 6,7, Income taxes, for discussion of the IRS tax dispute and the Company’s ~~petition~~petitions in the U.S. Tax Court.

Securities Class Action Litigation

On March 13, 2023, Roofers Local No. 149 Pension Fund filed a purported class action against Amgen, Robert Bradway and Peter Griffith. The action was brought on behalf of an alleged class of Amgen shareholders who owned stock between July 29, 2020 and April 27, 2022 (the alleged class period). Plaintiffs allege that the defendants made a series of materially false and misleading statements and omissions during the alleged class period regarding the failure to timely disclose the potential tax liability claimed by the IRS. Plaintiffs further allege that they and other purported class members suffered losses and damages resulting from declines in the market value of Amgen’s common stock after the potential tax liability claimed by the IRS was disclosed.

On August 31, 2023, plaintiff filed an amended complaint and Amgen filed its motion to dismiss on November 6, 2023. Plaintiff’s response was filed on January 12, 2024and Amgen’s reply is due February 26, 2024.

Shareholder Derivative Litigation (Martin)

On August 2, 2023, Leon Martin filed a derivative action (the Martin Derivative Action) captioned Leon Martin v. Robert A. Bradway, et al., No. 1:23-cv-06754 (S.D.N.Y. Aug. 2, 2023), purportedly on behalf of Amgen, against Amgen, Robert Bradway, Peter Griffith and Amgen’s independent Board members. The action was filed in the U.S. District Court for the Southern District of New York (Southern District Court of New York) as related to the pending federal securities class action filed by Roofers Local No. 149 Pension Fund on March 13, 2023 (the Roofers securities class action). The complaint in this matter alleges claims for violations of the Securities Exchange Act of 1934, breach of fiduciary duty, aiding and abetting breach of fiduciary duty, unjust enrichment and waste of corporate assets. The factual allegations that form the basis for these claims are essentially the same as the allegations asserted in the Roofers securities class action regarding purportedly false and misleading statements and omissions made from July 29, 2020 through April 27, 2022 relating to Amgen’s tax liabilities, business and finances, and the adequacy and maintenance of its internal controls.

On October 2, 2023, the Southern District Court of New York granted a stay of the matter pending an outcome on the motion to dismiss in the federal securities class action filed by plaintiff. On December 7, 2023, Plaintiff filed a Notice of Voluntary Dismissal as to Board member Michael Drake.

Shareholder Derivative Litigation (Clearwater)

On December 1, 2023, a second derivative action (the Clearwater Derivative Action) was filed, captioned Cheri Clearwater v. Robert A. Bradway, et al., No. 1:23-cv-10538 (S.D.N.Y. Dec. 1, 2023), in the same court as the earlier-filed Martin Derivative Action. The second action is largely duplicative of the Martin Derivative Action, asserting the same claims purportedly on behalf of the Company against the individual directors that sat on Amgen’s Board during the relevant time period (July 29, 2020 through April 27, 2022). The complaint asserts claims for breach of fiduciary duty, unjust enrichment, waste of corporate assets, abuse of control, gross mismanagement, and violations of Section 10(b) of the Exchange Act arising out of Amgen’s disclosures with respect to its transfer pricing dispute with the IRS. However, the Clearwater Derivative Action complaint adds (1) two additional claims for violations of Sections 14(a) and 20(a) of the Exchange Act; (2) allegations that Amgen repurchased its own stock at artificially inflated prices during the relevant period; and (3) more detailed allegations as to why first making a demand on the Board would have been futile.

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On January 16, 2024, the Southern District Court of New York consolidated the Martin Derivative Action and Clearwater Derivative Action (the Consolidated Action). The stay entered in the Martin Derivative Action also applies to the Consolidated Action.

ChemoCentryx, Inc. Securities Matters

On May 5 and June 8 of 2021, ChemoCentryx and its Chief Executive Officer were named as defendants in two putative shareholder class actions filed in the U.S. District Court for the Northern District of California (Northern District Court of California). These cases were consolidated into Homyk v. ChemoCentryx, Inc. in which the plaintiffs allege violations of Sections 10(b) and 20(a) of the Securities Exchange Act in connection with statements regarding the New Drug Application for TAVNEOS and the underlying Phase 3 clinical trial, seeking an award of damages, interest and attorneys’ fees. On March 28, 2022, the plaintiffs filed their consolidated amended complaint, and on May 19, 2022, ChemoCentryx moved to dismiss these claims.

On February 23, 2023, the Northern District Court of California substantially denied ChemoCentryx’s motion to dismiss the matter in its entirety, while granting the motion to dismiss with respect to certain allegations of the plaintiffs. On April 4, 2023, the parties submitted a case management statement to the Northern District Court of California, and on April 10, 2023, the Northern District Court of California entered an order setting dates for amendment of pleadings and briefing on class certification. On April 27, 2023, ChemoCentryx submitted its answer to the complaint.

On August 25, 2023, the lead plaintiff moved to certify a class composed of all purchasers of ChemoCentryx stock between November 25, 2019 and May 6, 2021. ChemoCentryx filed its opposition on November 22, 2023.

Lead plaintiff filed its reply brief in support of class certification on January 23, 2024. A hearing on class certification is set for February 15, 2024.

Commitments – U.S. repatriation tax

Under the 2017 Tax Act, we elected to pay in 8eight annual installments the repatriation tax related primarily to prior indefinitely invested earnings of our foreign operations. The following table summarizes the remaining scheduled repatriation tax payments as of December 31, ~~2021~~2023 (in millions):


		Amounts
2022		$	587
2023		1,100
	Amounts			Amounts
2024	2024	1,467
2025	2025	1,834
Total remaining U.S. repatriation tax commitments	Total remaining U.S. repatriation tax commitments	$	4,988


Delaware						95-3540776
(State or other jurisdiction of incorporation or organization)						(I.R.S. Employer Identification No.)
One Amgen Center Drive						91320-1799
Thousand Oaks
California
(Address of principal executive offices)						(Zip Code)


Title of each class	Trading Symbol (s)	Name of each exchange on which registered
Common stock, $0.0001 par value	AMGN	The Nasdaq Stock Market LLC
2.00% Senior Notes due 2026	AMGN26	The Nasdaq Stock Market LLC


		Page No.
	~~Defined Terms and Products~~DEFINED TERMS AND PRODUCTS	ii
PART I		1
Item 1.	BUSINESS	1
	Significant Developments	1
	Marketing, Distribution and Selected Marketed Products	32
	Reimbursement	910
	Manufacturing, Distribution and Raw Materials	11
	Government Regulation	1213
	Research and Development and Selected Product Candidates	1617
	Business Relationships	2122
	Human Capital Resources	2224
	Information about our Executive Officers	2427
	Geographic Area Financial Information	2528
	Investor Information	2628
Item 1A.	RISK FACTORS	2629
Item 1B.	UNRESOLVED STAFF COMMENTS	5054
Item 1C.	CYBERSECURITY	54
Item 2.	PROPERTIES	5156
Item 3.	LEGAL PROCEEDINGS	5157
Item 4.	MINE SAFETY DISCLOSURES	5157
PART II		5258
Item 5.	MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES	5258
Item 6.	RESERVED	5359
Item 7.	MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS	5460
Item 7A.	QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK	7380
Item 8.	FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA	7582
Item 9.	CHANGES IN AND DISAGREEMENTS WITH ACCOUNTANTS ON ACCOUNTING AND FINANCIAL DISCLOSURE	7582
Item 9A.	CONTROLS AND PROCEDURES	7683
Item 9B.	OTHER INFORMATION	7885
Item 9C.	DISCLOSURE REGARDING FOREIGN JURISDICTIONS THAT PREVENT INSPECTIONS	85
PART III		7885
Item 10.	DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE	7885
Item 11.	EXECUTIVE COMPENSATION	7885
Item 12.	SECURITY OWNERSHIP OF CERTAIN BENEFICIAL OWNERS AND MANAGEMENT AND RELATED STOCKHOLDER MATTERS	7986
Item 13.	CERTAIN RELATIONSHIPS AND RELATED TRANSACTIONS AND DIRECTOR INDEPENDENCE	8086
Item 14.	PRINCIPAL ~~ACCOUNTANT~~ACCOUNTANT FEES AND SERVICES	8086
PART IV		8187
Item 15.	EXHIBITS AND FINANCIAL STATEMENT SCHEDULES	8187
Item 16.	FORM 10-K SUMMARY	8793
SIGNATURES		8894


Term		Description

~~Acapatamab~~ACTIMMUNE		~~Acapatamab (formerly AMG 160)~~ACTIMMUNE® (interferon gamma-1b)(1)
Aimovig		Aimovig® (erenumab-aooe)
AMJEVITA/AMGEVITA		~~AMGEVITA~~™ ~~(adalimumab)~~
~~AMJEVITA~~		AMJEVITA® (adalimumab-atto)/AMGEVITA™ ~~(adalimumab-atto)~~(adalimumab)
Aranesp		Aranesp® (darbepoetin alfa)
AutoTouch		AutoTouch®
AVSOLA		AVSOLA® (infliximab-axxq)
~~BLINCYTO~~BEKEMV	BEKEMV™ (eculizumab)
BLINCYTO	BLINCYTO® (blinatumomab)

BUPHENYL		BUPHENYL® (sodium phenylbutyrate)(1)
~~Efavaleukin alfa~~Corlanor	Corlanor® (ivabradine)


DUEXIS	~~Efavaleukin alfa (formerly AMG 592)~~DUEXIS® (ibuprofen and famotidine)(1)
ENBREL		Enbrel® (etanercept)
ENBREL Mini		ENBREL Mini®
EPOGEN		EPOGEN® (epoetin alfa)
EVENITY		EVENITY® (romosozumab-aqqg)
IMLYGIC		IMLYGIC® (talimogene laherparepvec)
KANJINTI		KANJINTI® (trastuzumab-anns)
~~KYPROLIS~~KRYSTEXXA	KRYSTEXXA® (pegloticase)(1)
KYPROLIS	KYPROLIS® (carfilzomib)
LUMAKRAS/LUMYKRAS		LUMAKRAS®/LUMYKRAS™ (sotorasib)
~~MVASI~~Maridebart cafraglutide	Maridebart cafraglutide (formerly AMG 133)
MVASI	MVASI® (bevacizumab-awwb)
Neulasta		Neulasta® (pegfilgrastim)
NEUPOGEN		NEUPOGEN® (filgrastim)
Nplate		Nplate® (romiplostim)
~~Olpasiran~~		~~Olpasiran (formerly AMG 890)~~
Onpro		Onpro®
~~Ordesekimab~~		~~Ordesekimab (formerly AMG 714)~~
Otezla		Otezla® (apremilast)
Parsabiv		Parsabiv® (etelcalcetide)
~~Pavurutamab~~PENNSAID	PENNSAID® 2% (diclofenac sodium topical solution)(1)
PROCYSBI	~~Pavurutamab (formerly AMG 701)~~PROCYSBI® (cysteamine bitartrate)(1)
Prolia		Prolia® (denosumab)
~~Repatha~~Pushtronex	Pushtronex®
QUINSAIR	QUINSAIR® (levofloxacin)(1)
RAVICTI	RAVICTI® (glycerol phenylbutyrate)(1)
RAYOS	RAYOS® (prednisone)(1)
Repatha	Repatha® (evolocumab)
RIABNI		RIABNI™® (rituximab-arrx)
~~Rozibafusp alfa~~
~~Rozibafusp alfa (formerly AMG 570)~~
Sensipar/Mimpara		Sensipar®/Mimpara™ (cinacalcet)
SureClick		SureClick®

~~Tarlatamab~~TAVNEOS	TAVNEOS® (avacopan)
TEPEZZA	TEPEZZA® (teprotumumab-trbw)(1)


Term	~~Tarlatamab (formerly AMG 757)~~Description
TEZSPIRE		TEZSPIRE™® (tezepelumab-ekko)
~~Vectibix~~UPLIZNA	UPLIZNA® (inebilizumab-cdon)(1)
Vectibix	Vectibix® (panitumumab)
~~XGEVA~~Wezlana	WEZLANA™ (ustekinumab-auub)
Xaluritamig	Xaluritamig (formerly AMG 509)
XGEVA	XGEVA® (denosumab)


☒			ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934


☐			TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934


		2021				2020				2019
	2023																					2023									2022									2021
Product Sales by Geography:	Product Sales by Geography:
U.S.
U.S.
U.S.	U.S.	$	17,286	71	%	$	17,985	74	%	$	16,531	74	%	$	19,272		72	72	%				$	17,743		72	72	%				$	17,286		71	71	%
ROW	ROW	7,011		29	%	6,255		26	%	5,673		26	%	ROW		7,638			28	28	%				7,058			28	28	%				7,011			29	29	%
Total	Total	$	24,297	100	%	$	24,240	100	%	$	22,204	100	%	Total		$	26,910		100	100	%				$	24,801		100	100	%				$	24,297		100	100	%


	Total number of shares purchased	Average price paid per share(1)		Total number of shares purchased as part of publicly announced program	Maximum dollar value that may yet be purchased under the program(2)
October 1 - October 31	1,874,976	$	208.06	1,874,976	$	6,960,277,756
November 1 - November 30	2,484,905	$	208.35	2,484,905	$	6,442,554,907
December 1 - December 31	2,559,300	$	216.14	2,559,300	$	10,889,377,513
	6,919,181	$	211.15	6,919,181
January 1 - December 31	21,730,283	$	229.50	21,730,283


Category						Description
Research and early pipeline						R&D expenses incurred in activities substantially in support of early research through the completion of phase 1 clinical trials, including drug discovery, toxicology, pharmacokinetics and drug metabolism and process development
Later-stage clinical programs						R&D expenses incurred in or related to phase 2 and phase 3 clinical programs intended to result in registration of a new product or a new indication for an existing product primarily in the United States or the EU
Marketed products						R&D expenses incurred in support of the Company’s marketed products that are authorized to be sold primarily in the United States or the EU. Includes clinical trials designed to gather information on product safety (certain of which may be required by regulatory authorities) and their product characteristics after regulatory approval has been obtained, as well as the costs of obtaining regulatory approval of a product in a new market after approval in either the United States or the EU has been obtained


		Years ended December 31,
		2021		2020		2019
	Years ended December 31,									Years ended December 31,
	2023							2023	2022		2021
Research and early pipeline	Research and early pipeline	$	1,670	$	1,405	$	1,649
Later-stage clinical programs	Later-stage clinical programs	1,726		1,365		1,062
Marketed products	Marketed products	1,423		1,437		1,405
Total R&D expense	Total R&D expense	$	4,819	$	4,207	$	4,116


		December 31,
		2021		2020
	December 31,						December 31,
	2023					2023		2022
Cash, cash equivalents and marketable securities	Cash, cash equivalents and marketable securities	$	8,037	$	10,647
Total assets	Total assets	$	61,165	$	62,948
Current portion of long-term debt	Current portion of long-term debt	$	87	$	91
Long-term debt	Long-term debt	$	33,222	$	32,895
Stockholders’ equity	Stockholders’ equity	$	6,700	$	9,409


		Rebates		Chargebacks		Other deductions		Total
Balance as of December 31, 2018		$	2,589	$	454	$	127	$	3,170
Amounts charged against product sales		6,825		7,090		1,292		15,207
Payments		(6,249)		(6,985)		(1,263)		(14,497)
Balance as of December 31, 2019		3,165		559		156		3,880
Amounts charged against product sales		9,167		8,223		1,818		19,208
Payments		(8,353)		(8,191)		(1,735)		(18,279)
	Rebates									Rebates	Chargebacks	Other deductions	Total
Balance as of December 31, 2020	Balance as of December 31, 2020	3,979		591		239		4,809
Amounts charged against product sales	Amounts charged against product sales	10,195		9,619		2,065		21,879
Payments	Payments	(10,027)		(9,413)		(2,074)		(21,514)
Balance as of December 31, 2021	Balance as of December 31, 2021	$	4,147	$	797	$	230	$	5,174
Amounts charged against product sales
Payments
Balance as of December 31, 2022
Additions (1)
Amounts charged against product sales
Payments
Balance as of December 31, 2023


	(a)	(b)		(c)
Plan category	Number of securities to be issued upon exercise of outstanding options and rights	Weighted-average exercise price of outstanding options and rights		Number of securities remaining available for future issuance under equity compensation plans (excluding securities reflected in column (a))
Equity compensation plans approved by Amgen security holders:
Amended and Restated 2009 Equity Incentive Plan(1)	10,217,143	$	197.27	18,987,053
Amended and Restated 1991 Equity Incentive Plan(2)	3,550	—		—
Amended and Restated Employee Stock Purchase Plan	—	—		4,280,585
Total approved plans	10,220,693	197.27		23,267,638
Equity compensation plan not approved by Amgen security holders:
Amgen Profit Sharing Plan for Employees in Ireland(3)	—	—		242,172
Total unapproved plans	—	—		242,172
Total all plans	10,220,693	$	197.27	23,509,810


			Page number
Report of Independent Registered Public Accounting Firm (PCAOB ID: 42)			F-1

Consolidated Statements of Income for each of the three years in the period ended December 31, ~~2021~~2023			F-4F-5

Consolidated Statements of Comprehensive Income for each of the three years in the period ended December 31, ~~2021~~2023			F-5F-6

Consolidated Balance Sheets as of December 31, ~~2021~~2023 and ~~2020~~2022			F-6F-7

Consolidated Statements of Stockholders’ Equity for each of the three years in the period ended December 31, ~~2021~~2023			F-7F-8

Consolidated Statements of Cash Flows for each of the three years in the period ended December 31, ~~2021~~2023			F-8F-9

Notes to Consolidated Financial Statements			F-9F-10


			Page number
Schedule II. Valuation and Qualifying Accounts			F-55F-57


Exhibit No.						Description
2.1						Asset Purchase Agreement, dated August 25, 2019, by and between Amgen Inc. and Celgene Corporation. (Filed as an exhibit to Form 8-K on August 26, 2019 and incorporated herein by reference.)

~~2.2~~2.1.1						Amendment No. 1 to the Asset Purchase Agreement, dated October 17, 2019, by and between Amgen Inc. and Celgene Corporation. (Filed as an exhibit to Form 8-K on October 17, 2019 and incorporated herein by reference.)

~~2.3~~2.1.2						Amendment No. 2 to the Asset Purchase Agreement, dated October 17, 2019, by and between Amgen Inc. and Celgene Corporation. (Filed as an exhibit to Form 10-K for the year ended December 31, 2019 on February 12, 2020 and incorporated herein by reference.)

~~2.4~~2.2						Letter Agreement, dated November 21, 2019, by and between Amgen Inc. and the parties named therein re: Treatment of Certain Product Inventory in connection with Amgen’s acquisition of ~~Otezla~~Otezla. (Filed as an exhibit to Form 10-K for the year ended December 31, 2019 on February 12, 2020 and incorporated herein by reference.)

~~2.5~~2.3						Irrevocable Guarantee, dated August 25, 2019, by and between Amgen Inc. and Bristol-Myers Squibb Company. (Filed as an exhibit to Form 8-K on August 26, 2019 and incorporated herein by reference.)

~~2.6~~2.4						Agreement and Plan of Merger, dated July 27, 2021, by and among Amgen Inc., Teneobio, Inc., Tuxedo Merger Sub, Inc., and Fortis Advisors LLC. (portions of the exhibit have been omitted because they are both (i) not material and (ii) is the type of information that the Company treats as private or confidential)(Filed as an exhibit to Form 10-Q for the quarter ended September 30, 2021 on November 3, 2021 and incorporated herein by reference.)


Exhibit No.						Description
2.5						Agreement and Plan of Merger, dated as of August 3, 2022, among ChemoCentryx, Inc., Amgen Inc. and Carnation Merger Sub, Inc. (Filed as an exhibit to Form 8-K on August 4, 2022 and incorporated herein by reference.)

2.6						Transaction Agreement, dated as of December 11, 2022, by and among Amgen Inc., Pillartree Limited and Horizon Therapeutics plc. (Filed as an exhibit to Form 8-K on December 12, 2022 and incorporated herein by reference.)

2.7						Appendix 3 to the Rule 2.7 Announcement, dated as of December 12, 2022 (Conditions Appendix). (Filed as an exhibit to Form 8-K on December 12, 2022 and incorporated herein by reference.)

3.1						Restated Certificate of Incorporation of Amgen Inc. (As Restated March 6, 2013.) (Filed as an exhibit to Form 10-Q for the quarter ended March 31, 2013 on May 3, 2013 and incorporated herein by reference.)

3.2						Amended and Restated Bylaws of Amgen Inc. (As Amended and Restated February 15, 2016.) (Filed as an exhibit to Form 8-K on February 17, 2016 and incorporated herein by reference.)

4.1						Form of stock certificate for the common stock, par value $.0001 of the Company. (Filed as an exhibit to Form 10-Q for the quarter ended March 31, 1997 on May 14, 1997 and incorporated herein by reference.)

4.2						Form of Indenture, dated January 1, 1992. (Filed as an exhibit to Form S-3 Registration Statement filed on December 19, 1991 and incorporated herein by reference.)

4.3						Agreement of Resignation, Appointment and Acceptance dated February 15, 2008. (Filed as an exhibit to Form 10-K for the year ended December 31, 2007 on February 28, 2008 and incorporated herein by reference.)

4.4						First Supplemental Indenture, dated February 26, 1997. (Filed as an exhibit to Form 8-K on March 14, 1997 and incorporated herein by reference.)

4.5						8-1/8% Debentures due April 1, 2097. (Filed as an exhibit to Form 8-K on April 8, 1997 and incorporated herein by reference.)

4.6						Officer’s Certificate of Amgen Inc., dated April 8, 1997, establishing a series of securities entitled “8 1/8% Debentures due April 1, 2097.” (Filed as an exhibit to Form 8-K on April 8, 1997 and incorporated herein by reference.)

4.7						Indenture, dated August 4, 2003. (Filed as an exhibit to Form S-3 Registration Statement on August 4, 2003 and incorporated herein by reference.)

4.8						Corporate Commercial Paper - Master Note between and among Amgen Inc., as Issuer, Cede & Co., as Nominee of The Depository Trust Company, and Citibank, N.A., as Paying Agent. (Filed as an exhibit to Form 10-Q for the quarter ended March 31, 1998 on May 13, 1998 and incorporated herein by reference.)

4.9						Officers’ Certificate of Amgen Inc., dated May 30, 2007, including form of the Company’s 6.375% Senior Notes due 2037. (Filed as an exhibit to Form 8-K on May 30, 2007 and incorporated herein by reference.)

4.10						Officers’ Certificate of Amgen Inc., dated May 23, 2008, including form of the Company’s 6.90% Senior Notes due 2038. (Filed as exhibit to Form 8-K on May 23, 2008 and incorporated herein by reference.)

4.11						Officers’ Certificate of Amgen Inc., dated January 16, 2009, including form of the Company’s 6.40% Senior Notes due 2039. (Filed as exhibit to Form 8-K on January 16, 2009 and incorporated herein by reference.)

4.12						Officers’ Certificate of Amgen Inc., dated March 12, 2010, including form of the Company’s 5.75% Senior Notes due 2040. (Filed as exhibit to Form 8-K on March 12, 2010 and incorporated herein by reference.)

4.13						Officers’ Certificate of Amgen Inc., dated September 16, 2010, including form of the Company’s 4.95% Senior Notes due 2041. (Filed as an exhibit to Form 8-K on September 17, 2010 and incorporated herein by reference.)

4.14						Officers’ Certificate of Amgen Inc., dated June 30, 2011, including form of the Company’s 5.65% Senior Notes due 2042. (Filed as an exhibit to Form 8-K on June 30, 2011 and incorporated herein by reference.)

4.15						Officers’ Certificate of Amgen Inc., dated November 10, 2011, including form of the Company’s 5.15% Senior Notes due 2041. (Filed as an exhibit to Form 8-K on November 10, 2011 and incorporated herein by reference.)


Exhibit No.						Description
4.16						Officers’ Certificate of Amgen Inc., dated December 5, 2011, including form of the Company’s 5.50% Senior Notes due 2026. (Filed as an exhibit to Form 8-K on December 5, 2011 and incorporated herein by reference.)

4.17						Officers’ Certificate of Amgen Inc., dated May 15, 2012, including form of the Company’s 5.375% Senior Notes due 2043. (Filed as an exhibit to Form 8-K on May 15, 2012 and incorporated herein by reference.)

4.18						Officers’ Certificate of Amgen Inc., dated September 13, 2012, including form of the Company’s 4.000% Senior Notes due 2029. (Filed as an exhibit to Form 8-K on September 13, 2012 and incorporated herein by reference.)


~~Exhibit No.~~						~~Description~~
4.19						Indenture, dated May 22, 2014, between Amgen Inc. and The Bank of New York Mellon Trust Company, N.A., as Trustee. (Filed as an exhibit to Form 8-K on May 22, 2014 and incorporated herein by reference.)

4.20						Officers’ Certificate of Amgen Inc., dated May 22, 2014, including form of the Company’s 3.625% Senior Notes due 2024. (Filed as an exhibit to Form 8-K on May 22, 2014 and incorporated herein by reference.)

4.21						Officer’s Certificate of Amgen Inc., dated May 1, 2015, including forms of the Company’s 3.125% Senior Notes due 2025 and 4.400% Senior Notes due 2045.~~(Filed~~ (Filed as an exhibit on Form 8-K on May 1, 2015 and incorporated herein by reference.)

4.22						Officer’s Certificate of Amgen Inc., dated as of February 25, 2016, including form of the Company’s 2.000% Senior Notes due 2026. (Filed as an exhibit on Form 8-K on February 26, 2016 and incorporated herein by reference.)

4.23						~~Form of Permanent Global Certificate for the Company’s 0.410% bonds due 2023.~~ ~~(Filed as an exhibit on Form 8-K on March 8, 2016 and incorporated herein by reference.)~~

~~4.24~~						~~Terms of the Bonds for the Company’s 0.410% bonds due 2023.~~ ~~(Filed as an exhibit on Form 8-K on March 8, 2016 and incorporated herein by reference.)~~

~~4.25~~						Officer’s Certificate of Amgen Inc., dated as of June 14, 2016, including forms of the Company’s 4.563% Senior Notes due 2048 and 4.663% Senior Notes due 2051. (Filed as an exhibit to Form 8-K on June 14, 2016 and incorporated herein by reference.)

~~4.26~~4.24						Officer’s Certificate of Amgen Inc., dated as of August 19, 2016, including forms of the Company’s ~~2.250% Senior Notes due 2023 and~~ 2.600% Senior Notes due 2026. (Filed as an exhibit to Form 8-K on August 19, 2016 and incorporated herein by reference.)

~~4.27~~4.25						Officer’s Certificate of Amgen Inc., dated as of November 2, 2017, including in the form of the Company’s 3.200% Senior Notes due 2027. (Filed as an exhibit to Form 8-K on November 2, 2017 and incorporated herein by reference.)

~~4.28~~4.26						Officer’s Certificate of Amgen Inc., dated as of February 21, 2020, including forms of the Company’s 1.900% Senior Notes due 2025, 2.200% Senior Notes due 2027, 2.450% Senior Notes due 2030, 3.150% Senior Notes due 2040 and 3.375% Senior Notes due 2050. (Filed as an exhibit to Form 8-K on February 21, 2020 and incorporated herein by reference.)

~~4.29~~4.27						Officer’s Certificate of Amgen Inc., dated as of May 6, 2020, including form of the Company’s 2.300% Senior Notes due 2031. (Filed as an exhibit to Form 8-K on May 6, 2020 and incorporated herein by reference.)

~~4.30~~4.28						Officer’s Certificate of Amgen Inc., dated as of August 17, 2020, including forms of the Company’s 2.770% Senior Notes due 2053. (Filed as an exhibit to Form 8-K on August 18, 2020 and incorporated herein by reference.)

4.29						Officer’s Certificate of Amgen Inc., dated as of August 9, 2021, including forms of the Company’s 1.650% Senior Notes due 2028, 2.000% Senior Notes due 2032, 2.800% Senior Notes due 2041 and 3.000% Senior Notes due 2052. (Filed as an exhibit to Form 8-K on August 9, 2021 and incorporated herein by reference.)

4.30						Officer’s Certificate of Amgen Inc., dated as of February 22, 2022, including forms of the Company’s 3.000% Senior Notes due 2029, 3.350% Senior Notes due 2032, 4.200% Senior Notes due 2052 and 4.400% Senior Notes due 2062. (Filed as an exhibit to Form 8-K on February 22, 2022 and incorporated herein by reference.)

4.31						~~Registration Rights Agreement,~~Officer’s Certificate of Amgen Inc., dated as of August ~~17, 2020, by~~18, 2022, including forms of the Company’s 4.050% Senior Notes due 2029, 4.200% Senior Notes due 2033 and among Amgen Inc., BofA Securities, Inc. and J.P. Morgan Securities LLC, as lead dealer managers, and BNP Paribas Securities Corp., Deutsche Bank Securities Inc., RBC Capital Markets, LLC, Blaylock Van, LLC and Siebert Williams Shank & Co., LLC, as co-dealer managers. 4.875% Senior Notes due 2053.~~(Filed~~ (Filed as an exhibit to Form 8-K on August 18, ~~2020~~2022 and incorporated herein by reference.)

4.32						Officer’s Certificate of the Company, dated as of March 2, 2023, including forms of the Company’s 5.250% Senior Notes due 2025, 5.507% Senior Notes due 2026, 5.150% Senior Notes due 2028, 5.250% Senior Notes due 2030, 5.250% Senior Notes due 2033, 5.600% Senior Notes due 2043, 5.650% Senior Notes due 2053 and 5.750% Senior Notes due 2063. (Filed as an exhibit to Form 8-K on March 2, 2023 and incorporated herein by reference.)


Exhibit No.						Description
4.32*
4.33*						Description of Amgen Inc.’s Securities Registered Pursuant to Section 12 of the Securities Exchange Act of 1934.

10.1+						Amgen Inc. Amended and Restated 2009 Equity Incentive Plan. (Filed as Appendix C to the Definitive Proxy Statement on Schedule 14A on April 8, 2013 and incorporated herein by reference.)

~~10.2+~~10.1.1+						First Amendment to Amgen Inc. Amended and Restated 2009 Equity Incentive Plan, effective March 4, 2015. (Filed as an exhibit to Form 10-Q for the quarter ended March 31, 2015 on April 27, 2015 and incorporated herein by reference.)

~~10.3+~~10.1.2+						Second Amendment to Amgen Inc. Amended and Restated 2009 Equity Incentive Plan, effective March 2, ~~2016~~2016.. (Filed as an exhibit to Form 10-Q for the quarter ended March 31, 2016 on May 2, 2016 and incorporated herein by reference.)

~~10.4+~~10.2+*						Form of Grant of Stock Option Agreement for the Amgen Inc. Amended and Restated 2009 Equity Incentive Plan. (As Amended and Restated on December 11, 2023.)

10.3+*						Form of Restricted Stock Unit Agreement for the Amgen Inc. Amended and Restated 2009 Equity Incentive Plan. (As Amended and Restated on December ~~2, 2021.~~11, 2023.)


~~Exhibit No.~~10.4+						~~Description~~
10.5+*						~~Form of Restricted Stock Unit Agreement for the Amgen Inc. Amended and Restated 2009 Equity Incentive Plan. (As Amended~~ ~~and Restated~~ ~~on December~~ ~~2, 2021.)~~

~~10.6+~~						Amgen Inc. 2009 Performance Award Program. (As Amended on December 12, 2017.) (Filed as an exhibit to Form 10-K for the year ended December 31, 2017 on February 13, 2018 and incorporated herein by reference.)

~~10.7+~~10.5+*						Form of Performance Unit Agreement for the Amgen Inc. 2009 Performance Award Program. (As Amended and Reinstated on December ~~2, 2021.~~11, 2023.)

~~10.8+~~10.6+*						Amgen Inc. 2009 Director Equity Incentive Program. (As Amended and Restated on October ~~21, 2020.~~24, 2023.) ~~(Filed as an exhibit to Form 10-K for the year ended December 31, 2020 on February 9, 2021 and incorporated herein by reference.)~~

~~10.9+~~10.7+						~~Form of Grant of Non-Qualified Stock Option Agreement for the Amgen Inc. 2009 Director Equity Incentive Program.~~ ~~(Filed as an exhibit to Form 8-K on May 8, 2009 and incorporated herein by reference.)~~

~~10.10+~~						Form of Restricted Stock Unit Agreement for the Amgen Inc. 2009 Director Equity Incentive Program. (As Amended on December 11, 2019.)~~(Filed~~ (Filed as an exhibit to Form 10-K for the year ended December 31, 2019 on February 12, 2020 and incorporated herein by reference.)

~~10.11+~~10.8+						Form of Cash-Settled Restricted Stock Unit Agreement for the Amgen 2009 Director Equity Incentive Program. (As Amended on December 11, 2019.) ~~(Filed~~(Filed as an exhibit to Form 10-K for the year ended December 31, 2019 on February 12, 2020 and incorporated herein by reference.)

~~10.12+~~10.9+						Amgen Inc. Supplemental Retirement Plan. (As Amended and Restated effective October 16, 2013.) (Filed as an exhibit to Form 10-K for the year ended December 31, 2013 on February 24, 2014 and incorporated herein by reference.)

~~10.13+~~10.9.1+						First Amendment to the Amgen Inc. Supplemental Retirement Plan, effective October 14, 2016. (Filed as an exhibit to Form 10-Q for the quarter ended September 30, 2016 on October 28, 2016 and incorporated herein by reference.)

~~10.14+~~10.9.2+						Second Amendment to the Amgen Inc. Supplemental Retirement Plan, effective October 23, 2019. (Filed as an exhibit to Form 10-K for the year ended December 31, 2019 on February 12, 2020 and incorporated herein by reference.)

10.15+*10.9.3+						Third Amendment to the Amgen Inc. Supplemental Retirement Plan, effective October 20, 2021. (Filed as an exhibit to Form 10-K for the year ended December 31, 2021 on February 16, 2022 and incorporated herein by reference.)

10.9.4+						Fourth Amendment to the Amgen Inc. Supplemental Retirement Plan, effective October 20, 2022. (Filed as an exhibit to Form 10-K for the year ended December 31, 2022 on February 9, 2023 and incorporated herein by reference.)

~~10.16+~~10.9.5+*						Fifth Amendment to the Amgen Inc. Supplemental Retirement Plan, effective January 1, 2024.

10.10+						Amended and Restated Amgen Change of Control Severance Plan. (As Amended and Restated effective December 9, 2010 and subsequently amended effective March 2, 2011.) (Filed as an exhibit to Form 10-Q for the quarter ended March 31, 2011 on May 10, 2011 and incorporated herein by reference.)

~~10.17+~~10.11+						Amgen Inc. Executive Incentive Plan. (As Amended and Restated effective January 1, ~~2009.~~2022.) ~~(Filed as an exhibit to Form 10-Q for the quarter ended September 30, 2008 on November 7, 2008 and incorporated herein by reference.)~~

~~10.18+~~						~~First Amendment to the Amgen Inc. Executive Incentive Plan, effective December 13, 2012.~~ ~~(Filed as an exhibit to Form 10-K for the year ended December 31, 2012 on February 27, 2013 and incorporated herein by reference.)~~

~~10.19+~~						~~Second Amendment to the Amgen Inc. Executive Incentive Plan, effective January 1, 2017.~~ (Filed as an exhibit to Form 10-Q for the quarter ended March 31, ~~2017~~2022 on April ~~27, 2017~~28, 2022 and incorporated herein by reference.)


Exhibit No.						Description
~~10.20+~~10.12+						Amgen Nonqualified Deferred Compensation Plan. (As Amended and Restated effective October 16, 2013.) (Filed as an exhibit to Form 10-K for the year ended December 31, 2013 on February 24, 2014 and incorporated herein by reference.)

~~10.21+~~10.12.1+						First Amendment to the Amgen Nonqualified Deferred Compensation Plan, effective October 14, 2016. (Filed as an exhibit to Form 10-Q for the quarter ended September 30, 2016 on October 28, 2016 and incorporated herein by reference.)

~~10.22+~~10.12.2+						Second Amendment to the Amgen Nonqualified Deferred Compensation Plan, effective January 1, 2020. (Filed as an exhibit to Form 10-K for the year ended December 31, 2019 on February 12, 2020 and incorporated herein by reference.)


~~Exhibit No.~~						~~Description~~
~~10.39~~						~~Amendment No. 1 to the Exclusive License and Collaboration Agreement, dated April 21, 2017, by and between Amgen Inc. and Novartis Pharma AG~~ (portions of the exhibit have been omitted pursuant to a request for confidential treatment). (Filed as an exhibit to Form 10-Q for the quarter ended June 30, 2017 on July 26, 2017 and incorporated herein by reference.)

~~10.40~~						~~Amendment No. 2 to the Exclusive License and Collaboration Agreement, dated April 21, 2017, by and between Amgen Inc. and Novartis Pharma AG~~ (portions of the exhibit have been omitted pursuant to a request for confidential treatment). (Filed as an exhibit to Form 10-Q for the quarter ended June 30, 2017 on July 26, 2017 and incorporated herein by reference.)

~~10.41~~						~~Amendment No. 3 to the Exclusive License and Collaboration Agreement, dated January 31, 2022, by and between Amgen Inc. and Novartis Pharma AG~~ (portions of the exhibit have been omitted because they are both (i) not material and (ii) is the type of information that the Company treats as private or confidential). (Filed as an exhibit to the Company’s Current Report on Form 8-K on January 31, 2022 and incorporated herein by reference.)

~~10.42~~						Collaboration Agreement, dated October 31, 2019, by and between Amgen Inc. and BeiGene Switzerland GmbH, a wholly-owned subsidiary of BeiGene, Ltd. (portions of the exhibit have been omitted because they are both (i) not material and (ii) would be competitively harmful if publicly disclosed). (Filed as an exhibit to Form 10-K for the year ended December 31, 2019 on February 12, 2020 and incorporated herein by reference.)

10.19.1						First Amendment to Collaboration Agreement, dated April 20, 2022, by and between Amgen Inc. and BeiGene Switzerland GmbH, and BeiGene, Ltd. (portions of the exhibit have been omitted because they are both (i) not material and (ii) is the type of information that the Company treats as private or confidential.) (Filed as an exhibit to Form 10-Q for the quarter ended June 30, 2022 on August 5, 2022 and incorporated herein by reference.)


Exhibit No.						Description
~~10.43~~10.19.2						Second Amendment to Collaboration Agreement, entered into as of February 26, 2023, by and between Amgen Inc. and BeiGene Switzerland GmbH, and BeiGene, Ltd. (portions of the exhibit have been omitted because they are both (i) not material and (ii) is the type of information that the Company treats as private or confidential.) (Filed as an exhibit to Form 10-Q for the quarter ended March 31, 2023 on April 28, 2023 and incorporated herein by reference.)

10.20						Guarantee, dated as of October 31, 2019, made by and among BeiGene, Ltd. and Amgen Inc. (Filed as an exhibit to Form 10-K for the year ended December 31, 2019 on February 12, 2020 and incorporated herein by reference.)

~~10.44~~10.21						Share Purchase Agreement, dated October 31, 2019, by and between Amgen Inc. and BeiGene, Ltd. (portions of the exhibit have been omitted because they are both (i) not material and (ii) would be competitively harmful if publicly disclosed). (Filed as an exhibit to Schedule 13D on January 8, 2020 and incorporated herein by reference.)

~~10.45~~10.21.1						Amendment No. 1 to Share Purchase Agreement, dated December 6, 2019, by and among BeiGene, Ltd. and Amgen Inc. (Filed as an exhibit to Schedule 13D on January 8, 2020 and incorporated herein by reference.)

~~10.46~~10.21.2						Restated Amendment No. 2 to Share Purchase Agreement, dated September 24, 2020, by and among BeiGene, Ltd. and Amgen Inc. (Filed as an exhibit to Form 10-Q for the quarter ended September 30, 2020 on October 29, 2020 and incorporated herein by reference.)

10.21.3						Amendment No. 3 to Share Purchase Agreement, dated January 30, 2023, by and among BeiGene, Ltd. and Amgen Inc. (Filed as an exhibit to Form 8-K on January 31, 2023 and incorporated herein by reference.)

~~10.47~~10.22						Collaboration Agreement dated March 30, 2012 by and between Amgen Inc. and AstraZeneca Collaboration Ventures, LLC, a wholly owned subsidiary of AstraZeneca Pharmaceuticals LP~~(portions~~ (portions of the exhibit have been omitted ~~pursuant to a request for confidential treatment).~~because they are both (i) not material and (ii) is the type of information that the Company treats as private or confidential.) (Filed as an exhibit to Form 10-Q for the quarter ended ~~March 31, 2012~~June 30, 2022 on ~~May 8, 2012~~August 5, 2022 and incorporated herein by reference.)

~~10.48~~10.22.1						Amendment No. 1 to the Collaboration Agreement, dated October 1, 2014, by and among Amgen Inc., AstraZeneca Collaboration Ventures, LLC and AstraZeneca Pharmaceuticals LP~~(portions~~ (portions of the exhibit have been omitted ~~pursuant to a request for confidential treatment).~~because they are both (i) not material and (ii) is the type of information that the Company treats as private or confidential.) (Filed as an exhibit to Form ~~10-K~~10-Q for the ~~year~~quarter ended ~~December 31, 2014~~June 30, 2022 on ~~February 19, 2015~~August 5, 2022 and incorporated herein by reference.)

~~10.49~~10.22.2						Amendment Nos. 2 through 6 to the March 30, 2012 Collaboration Agreement between Amgen Inc. and AstraZeneca Collaboration Ventures, LLC, dated May 2 and 27 and October 2, 2016, January 31, 2018, and May 15, 2020, respectively (portions of the exhibit have been omitted because they are both (i) not material and (ii) would be competitively harmful if publicly disclosed.) (Filed as an exhibit to Form 10-Q for the quarter ended June 30, 2020 on July 29, 2020 and incorporated herein by reference.)

~~10.50~~10.22.3						Amendment No. 7 to the Collaboration Agreement, dated December 17, 2020, by and between Amgen Inc. and AstraZeneca Collaboration Ventures, LLC (portions of the exhibit have been omitted because they are both (i) not material and (ii) would be competitively harmful if publicly disclosed.) (Filed as an exhibit to Form 10-K for the year ended December 31, 2020 on February 9, 2021 and incorporated herein by reference.)

10.51*10.22.4						Amendment No. 8 to the Collaboration Agreement, dated November 19, 2021, by and between Amgen Inc. and AstraZeneca Collaboration Ventures, LLC (portions of the exhibit have been omitted because they are both (i) not material and (ii) is the type of information that the Company treats as private or confidential.) (Filed as an exhibit to Form 10-K for the year ended December 31, 2021 on February 16, 2022 and incorporated herein by reference.)

10.22.5*


~~Exhibit No.~~						~~Description~~
~~10.52~~10.23						License and Collaboration Agreement, dated June 1, 2021, by and between Amgen Inc. and Kyowa Kirin Co., Ltd. (portions of the exhibit have been omitted because they are both (i) not material and (ii) ~~would be competitively harmful if publicly disclosed)~~is the type of information that the Company treats as private or confidential). (Filed as an exhibit to Form 10-Q for the quarter ended June 30, 2021 on August 4, 2021 and incorporated herein by reference.)

21*						Subsidiaries of the Company.


Exhibit No.						Description
23						Consent of the Independent Registered Public Accounting Firm. The consent is set forth on page 8995 of this Annual Report on the 10-K.

24						Power of Attorney. The Power of Attorney is set forth on page 9096 of this Annual Report on Form 10-K.

31*						Rule 13a-14(a) Certifications.

32**						Section 1350 Certifications.

97*						Policy Relating to Recovery of Erroneously Awarded Compensation.

101.INS						Inline XBRL Instance Document - The instance document does not appear in the interactive data file because its XBRL tags are embedded within the Inline XBRL document.

101.SCH*						Inline XBRL Taxonomy Extension Schema Document.

101.CAL*						Inline XBRL Taxonomy Extension Calculation Linkbase Document.

101.DEF*						Inline XBRL Taxonomy Extension Definition Linkbase Document.

101.LAB*						Inline XBRL Taxonomy Extension Label Linkbase Document.

101.PRE*						Inline XBRL Taxonomy Extension Presentation Linkbase Document.

104						Cover Page Interactive Data File (formatted as Inline XBRL and contained in Exhibit 101).


						Sales deductions
Description of the Matter						As of December 31, ~~2021,~~2023, the Company recorded accrued sales deductions of ~~$5.2~~$7.3 billion. As described in Note 1 to the financial statements under the caption “Product sales and sales deductions,” revenues from product sales are recognized net of accruals for estimated rebates, wholesaler chargebacks, discounts and other deductions (collectively sales deductions), which are established at the time of sale. Auditing the estimation of sales deductions, specifically estimated chargebacks, commercial rebates, and Medicaid rebates related to U.S. product sales, which are netted against product sales, is complex, requires significant judgment, and the amounts involved are material to the financial statements taken as a whole. Revenue from product sales is recognized upon transfer of control of a product to a customer, generally upon delivery, and is based on an amount that reflects the consideration to which the Company expects to be entitled, which represents an amount that is net of accruals for estimated sales deductions. The estimated sales deductions are based on current contractual and statutory requirements, market events and trends, internal and external historical data, and forecasted customer buying patterns.

How We Addressed the Matter in Our Audit						We obtained an understanding, evaluated the design and tested the operating effectiveness of internal controls over the sales deduction processes. This included testing controls over management’s review of significant assumptions and inputs used in the estimate of sales deductions, including actual sales, contractual terms, historical experience, wholesaler inventory levels, demand data and estimated patient population. We also tested management’s controls over the accuracy of forecasting demand activity as well as the completeness and accuracy of the significant components included in the final sales deduction estimates. To test management’s estimated sales deductions, we obtained management’s calculations for the respective estimates and performed the following procedures, among others. We tested management’s estimation process over the determination of sales discount accruals by developing an independent expectation of the estimated accrual balances, including comparing accrual balances recorded by management to those implied by historical payment trends, performing a lookback analysis using actual historical data to evaluate the forecasted amounts, assessing subsequent events to determine whether there was any new information that would require adjustment to the initial accruals, evaluating trends in actual sales and discount accrual balances, ~~comparing cash receipts to product sales,~~ confirming terms and conditions for a sample of contracts, ~~with the Company’s customers,~~ testing a sample of credits issued and payments made throughout the year, and agreeing rates to underlying contract terms.


						Unrecognized tax benefits
Description of the Matter						As discussed in Notes 1 and 67 to the consolidated financial statements, the Company operates in various jurisdictions in which differing interpretations of complex tax laws and regulations create uncertainty and necessitate the use of significant judgment in the determination of the Company’s unrecognized tax benefits, ~~related to allocation of profits among various jurisdictions (“transfer pricing”),~~ particularly in the U.S. federal tax jurisdiction where the Company has significant assets and operations. In this regard, the Company uses significant judgment in (1) determining whether a tax position’s technical merits are more-likely-than-not to be sustained and (2) measuring the amount of tax benefit that qualifies for recognition. As of December 31, ~~2021,~~2023, the Company accrued ~~$3.5~~$4.0 billion of gross unrecognized tax ~~benefits including those related to transfer pricing.~~benefits. Auditing the assessment of the technical merits and measurement of the Company’s unrecognized tax benefits is challenging ~~and can be complex, highly judgmental, and based on interpretations of tax laws and regulations and application of those interpretations~~due to the ~~Company’s facts~~high degree of estimation and ~~circumstances.~~management judgement, given the ultimate resolution is dependent on uncontrollable factors such as the resolution of audit disputes with the IRS.

How We Addressed the Matter in Our Audit						We obtained an understanding, evaluated the design and tested the operating effectiveness of internal controls over the Company’s process to assess the technical merits of its tax positions, as well as management’s process to measure the unrecognized tax benefits of those tax positions, particularly in regard to ~~transfer pricing.~~matters in dispute with the IRS. This included testing controls over management’s review of the inputs, calculations, assumptions and methods selected to measure the amount of tax benefits that qualify for recognition. We involved tax controversy and transfer pricing specialists to assist in assessing the technical merits and measurement of certain of the Company’s unrecognized tax benefits. Depending on the nature of the specific tax position and, as applicable, developments with the relevant tax authorities, our procedures included obtaining and reviewing the Company’s correspondence with such tax authorities and evaluating certain third-party advice to support the Company’s evaluations and recorded positions. We used our knowledge of and experience with how the income tax laws and regulations related to transfer pricing are applied by the relevant tax authorities to evaluate the Company’s accounting for its unrecognized tax benefits. We evaluated developments in the applicable regulatory environments to assess potential effects on the Company’s recorded positions. We assessed management’s consideration of current tax controversy, litigation and tax litigation trends. We analyzed the assumptions and data used by the Company when it determined the amount of tax benefits to recognize, including applicable interest and penalties, and we tested the accuracy of those underlying calculations. We have also evaluated the Company’s income tax disclosures included in Note 67 in relation to these matters.


						Valuation of intangible assets acquired in a business combination
Description of the Matter						As described in Note 3 to the financial statements, on October 6, 2023, the Company completed its acquisition of Horizon Therapeutics plc (“Horizon”) (“Horizon acquisition”). The transaction was accounted for as a business combination using the acquisition method of accounting. The acquisition date fair values of acquired intangible assets, primarily consisted of finite-lived developed-product-technology rights, inclusive of the TEPEZZA intangible asset. The finite-lived intangible assets were valued using a multi-period excess earnings income approach that discounts expected future cash flows to present value. Auditing the acquisition date fair values of the TEPEZZA finite-lived developed-product-technology rights intangible asset acquired from Horizon was complex due to the significant judgment required in estimating the fair value. In particular, the fair value estimate required the use of a valuation methodology that was sensitive to changes in significant assumptions (e.g., revenue projections and discount rate), which were affected by expected future market or economic conditions.

How We Addressed the Matter in Our Audit						We evaluated and tested the design and operating effectiveness of the Company’s internal controls over the determination of the estimated fair value of the intangible assets. For example, we tested controls over management's review of the valuation methodologies and the significant assumptions used to develop the fair value estimate of the TEPEZZA intangible asset. We also tested management's controls to validate that the data used in the fair value estimate was complete and accurate. To test the Company’s estimated fair value of the TEPEZZA intangible asset, our audit procedures included, among others, evaluating the Company’s selection of the valuation methodology and the significant assumptions, with the assistance of a valuation specialist. We also tested the completeness and accuracy of the underlying data utilized in the valuation. For example, we compared the TEPEZZA revenue projections to analyst reports, current industry and market trends, historical results of the acquired business and to other relevant factors. We also performed sensitivity analyses over significant assumptions to evaluate the impact that changes in significant assumptions would have on the fair value of the TEPEZZA acquired intangible asset. In addition, we tested the estimated discount rate applied to the TEPEZZA intangible asset value.
						/s/ Ernst & Young LLP


		Number of shares of common stock	Common stock and additional paid-in capital		Accumulated deficit		Accumulated other comprehensive (loss) income		Total
Balance as of December 31, 2018		629.6	$	31,246	$	(17,977)	$	(769)	$	12,500
	Number of shares of common stock										Number of shares of common stock	Common stock and additional paid-in capital	Accumulated deficit	Accumulated other comprehensive (loss) income	Total
Balance as of December 31, 2020

Net income	Net income	—	—		7,842		—		7,842
Other comprehensive income, net of taxes		—	—		—		241		241
Dividends declared on common stock ($5.95 per share)		—	—		(3,555)		—		(3,555)
Issuance of common stock in connection with the Company’s equity award programs		2.0	97		—		—		97
Stock-based compensation expense		—	323		—		—		323
Tax impact related to employee stock-based compensation expense		—	(135)		—		—		(135)
Repurchases of common stock		(40.2)	—		(7,640)		—		(7,640)
Balance as of December 31, 2019		591.4	31,531		(21,330)		(528)		9,673
Cumulative effect of changes in accounting principles, net of taxes		—	—		(2)		—		(2)
Net income	Net income	—	—		7,264		—		7,264
Other comprehensive loss, net of taxes		—	—		—		(457)		(457)
Dividends declared on common stock ($6.56 per share)		—	—		(3,843)		—		(3,843)
Issuance of common stock in connection with the Company’s equity award programs		2.1	91		—		—		91
Stock-based compensation expense		—	349		—		—		349
Tax impact related to employee stock-based compensation expense		—	(169)		—		—		(169)
Repurchases of common stock		(15.2)	—		(3,497)		—		(3,497)
Balance as of December 31, 2020		578.3	31,802		(21,408)		(985)		9,409

Net income	Net income	—	—		5,893		—		5,893
Other comprehensive income, net of taxes	Other comprehensive income, net of taxes	—	—		—		189		189
Dividends declared on common stock ($7.22 per share)	Dividends declared on common stock ($7.22 per share)	—	—		(4,098)		—		(4,098)
Issuance of common stock in connection with the Company’s equity award programs	Issuance of common stock in connection with the Company’s equity award programs	1.7	82		—		—		82
Stock-based compensation expense	Stock-based compensation expense	—	361		—		—		361
Tax impact related to employee stock-based compensation expense	Tax impact related to employee stock-based compensation expense	—	(149)		—		—		(149)
Repurchases of common stock	Repurchases of common stock	(21.7)	—		(4,987)		—		(4,987)
Balance as of December 31, 2021

Balance as of December 31, 2021		558.3	$	32,096	$	(24,600)	$	(796)	$	6,700
Net income
Net income
Net income
Other comprehensive income, net of taxes
Dividends declared on common stock ($7.95 per share)
Issuance of common stock in connection with the Company’s equity award programs
Stock-based compensation expense
Tax impact related to employee stock-based compensation expense
Repurchases of common stock
Balance as of December 31, 2022

Net income
Net income
Net income
Other comprehensive loss, net of taxes
Dividends declared on common stock ($8.64 per share)
Issuance of common stock in connection with the Company’s equity award programs
Stock-based compensation expense
Equity awards issued for Horizon acquisition, net
Tax impact related to employee stock-based compensation expense
Repurchases of common stock

Balance as of December 31, 2023
Balance as of December 31, 2023
Balance as of December 31, 2023


	Year ended December 31, 2023
	Separation costs		Asset impairments and other charges		Total
Cost of sales	$	—	$	36	$	36
Research and development	—		29		29
Selling, general and administrative	—		13		13
Other	186		3		189
Total	$	186	$	81	$	267


	Amounts
Cash and cash equivalents	$	681
Inventories	5,025
Property, plant and equipment, net	318
Finite-lived intangible assets – developed-product-technology rights	19,590
IPR&D	1,060
Goodwill	3,111
Deferred tax asset	834
Deferred tax liability	(2,492)
Other assets and liabilities, net	(294)
Total assets acquired, net	$	27,833


	Amounts
Cash and cash equivalents	$	86
Marketable securities	235
Inventories	41
Finite-lived intangible assets – developed-product-technology rights	3,499
Goodwill	649
Other liabilities, net	(83)
Deferred tax liability, net	(502)
Total assets acquired, net	$	3,925


	Amounts
Cash purchase price	$	~~994~~993
Contingent consideration	~~309~~299
Total consideration	$	~~1,303~~1,292

Cash and cash equivalents	$	100
IPR&D	~~1,054~~991
Finite-lived intangible asset – R&D technology rights	94115
Finite-lived intangible assets – licensing rights	41
Goodwill	~~251~~273
Other assets, net	16
Deferred tax liability	~~(253)~~(244)
Total assets acquired, net	$	~~1,303~~1,292