What changed in this filing

/stocks — the workspaceLOADING

Item 1A. Risk Factors

2025-02-12 compared with 2024-02-21 · 241 added, 267 removed, 404 unchanged (56% of the section changed)

You should consider carefully the risks described below in addition to the financial and other information contained in this Annual Report, including our financial statements and related notes hereto and the matters addressed under the caption “Cautionary Note Concerning Forward-Looking Statements,” and in our other public filings with the SEC.

If any events described by the following risks actually occur, they could materially adversely affect our business, financial condition, cash flows or results of operations.

This could cause the market price of our ordinary shares to decline.

You should consider carefully the risks described below in addition to the financial and other information contained in this Annual Report, including our financial statements and related notes thereto and the matters addressed under the caption “Cautionary Note Concerning Forward-Looking Statements,” and in our other public filings with the SEC.

If any events described by the following risks actually occur, such events could materially adversely affect our business, financial condition, cash flows or results of operations.

This could cause the market price of our ordinary shares to materially decline.

The risks described below are not intended to be exhaustive and are not the only risks that we face.

New risk factors can emerge from time to time, and it is not possible to predict the impact that any factor or combination of factors may have on our business, prospects, financial condition and results of operations.

Risks Related to Our Business and Our Industry

We receive substantial revenue from our key proprietary products and our success depends on our ability to successfully manufacture and commercialize such products.

Sales of our proprietary products comprise an increasingly significant portion of our revenues.

Sales of our proprietary products comprise a significant portion of our revenues.

We developed and exclusively manufacture VIVITROL for the treatment of adults with alcohol dependence and opioid dependence, ARISTADA for the treatment of adults with schizophrenia, ARISTADA INITIO for initiation onto ARISTADA for the treatment of adults with schizophrenia, and LYBALVI for the treatment of adults with schizophrenia and for the treatment of adults with bipolar I disorder, and we exclusively commercialize these products in the U.S.

1 unchanged sentence

Any significant negative developments relating to these products could have a material adverse effect on our revenues from these products and, in turn, on our business, financial condition, cash flows and results of operations and the market price of our ordinary shares.

We rely heavily on our licensees in the commercialization and continued development of products from which we receive revenue and, if our licensees are not effective, or if disputes arise in respect of our contractual arrangements, our revenues could be materially adversely affected.

Our arrangements with licensees are critical to bringing to market and/or successfully commercializing products using our proprietary technologies and from which we receive manufacturing and/or royalty revenue.

We rely on these licensees in various respects, including commercializing such products, conducting development activities with respect to new formulations or new indications for such products, and/or managing the regulatory approval process for such products.

We earn significant royalty revenue from sales by our licensees of our licensed products and third-party products incorporating our proprietary technologies.

We also earn manufacturing revenues for products that we currently manufacture on behalf of other parties.

The revenues we receive from such products depend primarily upon the success of our licensees in commercializing such products.

For example, we receive substantial revenue from Janssen’s sales of the long-acting INVEGA products and RISPERDAL CONSTA and from Biogen’s sales of VUMERITY.

We have no involvement in the commercialization efforts for these and other products sold by third parties from which we receive revenue and cannot control the extent or effectiveness of such commercialization efforts.

Disputes may also arise between us and a licensee involving the ownership of technology developed under a license, the use of our technology, including know-how, in third-party products, the terms and amounts of royalty payments to be paid under a license, or other issues arising out of any licenses or other collaborative agreements.

Such disputes may delay related development programs, impact commercialization or manufacturing activities for the related products, impact the timing or amount of revenue that we receive in respect of such products, or result in expensive arbitration, litigation or other dispute resolution, which may not be resolved in our favor and may adversely impact our financial condition.

Further, certain of our license agreements may be terminated, with or without cause, or assigned in connection with a change in control or other event, and we cannot guarantee that any of these relationships will continue or that our licensees will be able or willing to continue to perform their obligations, including development, commercialization or payment obligations, under such agreements.

Any significant negative developments relating to our relationships with our licensees or our collaborative arrangements could have a material adverse effect on our business, financial condition, cash flows and results of operations and on the market price of our ordinary shares.

For example, in November 2021 we received notice of partial termination of an exclusive license agreement with Janssen.

Under this license agreement, we provided Janssen with rights to, and know-how, training and technical assistance in respect of, our small particle pharmaceutical compound technology, known as NanoCrystal technology, which was used to develop INVEGA SUSTENNA/XEPLION, INVEGA TRINZA/TREVICTA, INVEGA HAFYERA/BYANNLI, and CABENUVA.

While we ultimately prevailed in arbitration proceedings related to, among other things, this partial termination and Janssen’s royalty and other obligations under the license agreement, the announcement of the partial termination, expectations regarding the loss of royalty revenues, actual delays in receipt of royalty revenues that resulted from such termination, and the ultimate announcement of the resumption of payment of such royalty revenues, caused the market price of our ordinary shares to fluctuate significantly.

For these and other reasons that may be outside of our control, our revenues from products sold by our licensees, and related commercial milestone payments, may fall below our expectations, the expectations of our licensees or those of our shareholders, which could have a material adverse effect on our results of operations and the market price of our ordinary shares.

We face competition in the biopharmaceutical industry.

4 unchanged sentences

In many cases, there are already products on the market that may be in direct competition with our commercial products or products in development.

In addition, there are many companies developing generic versions of our products, or products with similar technologies to ours or for use in similar indications with whom we and our licensees compete, many of whom are larger and have significantly greater financial and other resources than we do.

Other smaller or earlier stage companies may also prove to be significant competitors, particularly through focused development programs and collaborative arrangements with large, established companies.

Some of the products being developed by our competitors are being designed to work differently than our products and may turn out to be safer or more effective than our products, which may render our products or technologies obsolete or noncompetitive.

In addition, there are many companies with which we and our licensees compete that are developing generic versions of our products, or products with similar technologies to ours or for use in similar indications, and many of these competitors are larger and have significantly greater financial, operational and other resources than we do.

Smaller or earlier stage companies may also prove to be significant competitors, whether through focused or more abbreviated development programs or collaborative arrangements with large, established companies.

Some of the products being developed by our competitors are being designed to work differently than our products and may prove to be safer or more effective than our products or achieve regulatory approval and be commercialized earlier than our products, which may render our products or technologies obsolete or noncompetitive or make it more challenging for us to successfully commercialize our products.

For a detailed discussion of the competition that we face with respect to our current marketed products, technologies and product indications, please see the section entitled “ Competition ” in “Item 1—Business” in this Annual Report.

If we are unable to compete successfully in this highly competitive biopharmaceutical industry, our business, financial condition, cash flows and results of operations could be materially adversely affected.

If we are unable to compete successfully in the highly competitive biopharmaceutical industry, our business, financial condition, cash flows and results of operations could be materially adversely affected.

Our revenues from sales of our products may decrease or grow at a slower than expected rate due to many factors.

3 unchanged sentences

Factors that may cause revenues from our products to grow at a slower than expected rate, decrease or cease all together, include, among others:

• the perception of physicians and other members of the healthcare community as to our products’ safety and efficacy relative to that of competing products and the willingness or ability of physicians and other members of the healthcare community to prescribe, dispense and/or administer, and patients to use, our products;

• unfavorable publicity concerning us, our licensees, our products, similar classes of drugs or the industry generally;

• the perception of physicians and other members of the healthcare community as to our products’ safety and efficacy relative to that of current or future competing products and the willingness or ability of physicians and other members of the healthcare community to prescribe, dispense and/or administer, and patients to use, our products;

• unfavorable publicity concerning us, our licensees, our products, similar classes of drugs or our industry generally;

• the cost-effectiveness of our products and reimbursement policies of government and third-party payers that may impact use of our products;

5 unchanged sentences

• changes to the product labels of our products, or of products within the same drug classes, to add new significant warnings or restrictions on use;

• our continued ability to engage third parties to manufacture, package and/or distribute our products on acceptable terms;

• the unfavorable outcome of investigations, arbitrations, litigation or other legal proceedings, including government requests for information regarding VIVITROL, securities litigation, IP litigation, including so-called “Paragraph IV” litigation relating to products from which we receive revenue, litigation or other proceedings before the U.S.

Patent and Trademark Office’s (the “USPTO”) Patent Trial and Appeal Board (the “PTAB”) or its equivalent in other jurisdictions outside of the U.S., including opposition proceedings in the EU and any other litigation or arbitration related to any of our products;

• our ability to engage third parties to manufacture, package and/or distribute our products on acceptable terms, or at all;

• the unfavorable outcome of investigations, arbitrations, litigation or other legal proceedings, including government requests for information related to one or more of our products, securities litigation, IP litigation, including so-called “Paragraph IV” litigation relating to products from which we receive revenue, litigation or other proceedings before the USPTO Patent Trial and Appeal Board (the “PTAB”) or its equivalent in other jurisdictions outside of the U.S., and any other litigation or arbitration related to any of our products;

• regulatory developments and actions related to the manufacture, commercialization or continued use of our products, including FDA actions such as the issuance of a REMS or warning letter, or conduct of an audit by the FDA or another regulatory authority in which a manufacturing or quality deficiency is identified;

• the extent and effectiveness of the sales, marketing and distribution support for our products, including our and our licensees’ decisions as to the timing and volume of product orders and shipments, the timing of product launches, and product pricing and discounting;

• disputes with our licensees relating to the use of our technology in, and marketing and sale of, products from which we received, or currently receive, manufacturing and/or royalty revenue and the amounts to be paid with respect to such products;

• the extent and effectiveness of the sales, marketing and distribution support for our products, including the size of our and our licensees’ sales forces and investments in marketing strategies, and our and our licensees’ decisions as to the timing and volume of product orders and shipments, the timing of product launches, and product pricing and discounting;

• exchange rate valuations and fluctuations;

and global political changes, conflicts and/or instability, public health matters, economic conditions and/or any related changes in applicable laws and regulations, that may impact resources and markets for our products;

and global political and administrative changes, conflicts and/or instability, public health matters, economic conditions and/or any related changes in applicable laws and regulations or federal and state policy efforts, that may impact resources and markets for our products or the systems and environments in which we operate;

• any other material adverse developments with respect to the commercialization of our products.

7 unchanged sentences

pressure by employers on private health insurance plans to reduce costs;

and consolidation and increasing assertiveness of payors seeking price discounts or rebates in connection with the placement of our products on their formularies and, in some cases, the imposition of restrictions on access or coverage of particular drugs or pricing determined based on perceived value.

and consolidation and increasing assertiveness of payors and pharmacy benefit managers (“PBMs”) seeking price discounts or

rebates in connection with the placement of our products on their formularies and, in some cases, the imposition of restrictions on access or coverage of particular drugs or pricing determined based on perceived value.

We cannot predict the availability, amount, or consistency of reimbursement for, or the prevalence and extent of other access barriers to, our products.

In the U.S., federal and state legislatures, health agencies and third-party payers continue to focus on containing the cost of healthcare.

In August 2022, the Inflation Reduction Act was signed into law.

The Inflation Reduction Act includes several provisions that will impact our business to varying degrees, including the Drug Price Negotiation Program applicable to Medicare Parts D and B and those provisions that impose new manufacturer financial liability on all drugs in Medicare Part D beginning in 2025, and require companies to pay rebates to Medicare for drug prices that increase faster than inflation.

5 unchanged sentences

This may result in managed care organizations influencing prescription decisions for a larger segment of the population and a corresponding constraint on prices and reimbursement for our products.

Furthermore, we may face uncertainties as a result of efforts to repeal, substantially modify or invalidate some or all of the provisions of the PPACA, whether by legislative means or through litigation, and further potential reforms to government negotiation or regulation of drug pricing.

Furthermore, we may face uncertainties as a result of efforts to repeal, substantially modify or invalidate some or all of the provisions of the PPACA, the Inflation Reduction Act and other legislation that impacts us, whether by legislative means or through litigation, and further potential reforms to government negotiation or regulation of drug pricing.

The PPACA significantly expanded coverage of mental health and substance use disorders and provided federal parity protections to such coverage benefits.

If successful, such efforts and proposed legislation or other future federal or state legislative or administrative changes relating to healthcare reform and drug pricing could adversely affect our business and financial

If efforts to reform or repeal PPACA, or to implement differently certain of its provisions, are successful, such efforts and proposed legislation or other future federal or state legislative or administrative changes relating to healthcare reform and drug pricing could adversely affect our business and financial results.

Additional discounts, rebates, coverage or plan changes, restrictions or exclusions as described above could have a material adverse effect on sales of our affected products.

Our failure to obtain or maintain adequate coverage, pricing or reimbursement for our products could have an adverse effect on our business, reputation, revenue and results of operations.

Our failure to obtain or maintain adequate coverage, pricing or reimbursement for our products could have an adverse effect on our business, reputation, revenue, results of operations, financial condition and cash flows.

Many payors continue to adopt benefit plan changes that shift a greater portion of prescription costs to patients, including more limited benefit plan designs, higher patient co-pay or co-insurance obligations and limitations on patients' use of commercial manufacturer co-pay payment assistance programs (including through co-pay accumulator adjustment or maximization programs).

Significant consolidation in the health insurance industry has resulted in a few large insurers and pharmacy benefit managers exerting greater pressure in pricing and usage negotiations with drug manufacturers, significantly increasing discounts and rebates required of manufacturers and limiting patient access and usage.

In addition, pharmacy benefit managers have combined with specialty and mail order pharmacies and provider groups.

Further consolidation among insurers, pharmacy benefit managers, other entities in the pharmaceutical supply chain and other payors would increase the negotiating leverage such entities have over us and other drug manufacturers.

In addition, pharmacy benefit managers have merged with or acquired specialty and mail order pharmacies and provider groups.

This consolidation, and any further consolidation, among insurers, pharmacy benefit managers, other entities in the pharmaceutical supply chain and other payors has increased and will increase, respectively, the negotiating leverage such entities have over us and other drug manufacturers.

In the U.S., to help patients afford our approved products, we may utilize programs to assist them, including patient assistance programs and co-pay programs for eligible patients.

6 unchanged sentences

It is possible that changes in insurer policies regarding co-pay programs and/or the introduction and enactment of new legislation or regulatory action could restrict or otherwise negatively affect these patient support programs, which could result in fewer patients using affected products, and therefore could have a material adverse effect on our sales, business, and financial condition.

If there are changes in, or we fail to comply with, the extensive legal and regulatory requirements affecting the healthcare industry, we could be subject to investigations, litigation, costs, penalties and business losses.

Our activities, and the activities of our licensees and third-party providers, are subject to extensive government regulation.

Government regulation by various national, state and local agencies includes detailed inspections of, and controls over, research and laboratory procedures, clinical investigations, product approvals and manufacturing, marketing and promotion, adverse event reporting, sampling, distribution, recordkeeping, storage, and disposal practices, among others.

Achieving and maintaining compliance with these regulations substantially increases the time, difficulty and costs incurred in obtaining and maintaining approvals to market newly developed and existing products.

Government regulatory actions, including audits, records requests and inspections of manufacturing facilities, can result in delay in the release of products, seizure or recall of products, suspension or revocation of the authority necessary for the manufacture and sale of products, and other regulatory enforcement actions, including the levying of civil fines or criminal penalties, the issuance of a warning letter, or the imposition of an injunction.

Biopharmaceutical companies have also been the target of government lawsuits and investigations alleging violations of government regulation, including claims asserting submission of incorrect pricing information, impermissible promotion of pharmaceutical products, improper payments intended to influence the referral of healthcare business, submission of false claims for government reimbursement, antitrust violations, violations related to anti-corruption and anti-bribery laws, and violations related to environmental matters.

We have been, and may continue to be, the subject of certain government inquiries or requests for documentation.

For example, we have received a subpoena and civil investigative demands from U.S.

state and federal authorities for documents related to VIVITROL, and have cooperated with the government in each instance.

If, as a result of government requests, proceedings are initiated, including under the U.S.

federal Anti-Kickback Statute or False Claims Act, or under state False Claims Acts or other laws, and we are found to have violated one or more applicable laws, we may be subject to significant liability, including without limitation, civil fines, criminal fines and penalties, civil damages and exclusion from U.S.

federal funded healthcare programs such as Medicare and Medicaid, any of which could materially affect our reputation, business, financial condition, cash flows and results of operations.

Conduct giving rise to such liability could also form the basis for private civil litigation by third-party payers or other persons allegedly harmed by such conduct.

Additionally, regardless of whether or not there is merit to claims underlying any investigation or legal proceedings to which we are subject, or whether or not we are found as a result of such investigations or lawsuits to have violated any applicable laws, such lawsuits and inquiries can be expensive to defend or respond to, may divert the attention of our management and other resources that would otherwise be engaged in managing our business, and may further cause significant and potentially irreparable harm to our public reputation.

If we or our agents fail to comply with any of those laws or regulations, a range of actions could result, including the suspension or termination of clinical trials, the failure to approve a product, restrictions on sales of our products or our manufacturing processes, withdrawal of our products from the market, significant fines, exclusion from government healthcare programs or other sanctions or litigation.

Changes affecting the healthcare industry, including new laws, regulations or judicial decisions, or new interpretations of existing laws, regulations or decisions, related to patent protection and enforcement, access to healthcare, environmental issues or product pricing and marketing, could also adversely affect our revenues, our public reputation or our potential to be profitable.

For example, and as discussed above, the Inflation Reduction Act includes several provisions that will impact our business to varying degrees, including those that impose new manufacturer financial liability on all drugs in Medicare Part D beginning in 2025, allow the U.S.

government to negotiate prices for some drugs covered under Medicare Part B and Part D with effect beginning in 2026, and require companies to pay rebates to Medicare for drug prices that increase faster than inflation.

Additionally, in its 2024 decision in Loper Bright Enterprises v.

Raimondo , the U.S.

Supreme Court overruled the “Chevron doctrine,” which gave deference to regulatory agencies’ statutory interpretations in litigation against federal government agencies, such as the FDA, where the law was ambiguous.

Supreme Court decision may lead to challenges of longstanding decisions and policies of the FDA, and other federal agencies, which could lead to uncertainties in the industry and disrupt or alter such federal agencies’ operations.

Any further changes in laws, regulations or decisions or in the interpretation of existing laws, regulations and decisions, could have a material adverse effect on our business, financial condition, cash flows and results of operations.

We earn significant royalty revenue from sales by our licensees of our licensed products and third-party products incorporating our proprietary technologies.

We also earn manufacturing revenues for products that we currently manufacture on behalf of other parties.

The revenues we receive from such products depend primarily upon the success of our licensees in commercializing such products.

For example, we receive substantial revenue from Janssen’s sales of XEPLION, INVEGA TRINZA/TREVICTA, INVEGA HAFYERA/BYANNLI and RISPERDAL CONSTA, and from Biogen’s sales of VUMERITY.

In addition, certain of these products are currently subject to ANDA litigation proceedings to which we are not a party and, if such proceedings are not resolved favorably or are settled by our licensees, generic versions of these products could be launched and there may be an adverse impact on the commercialization of these products and therefore on the revenue that we receive from sales of these products.

Further, certain of our license agreements may be terminated, with or without cause, or assigned in connection with a change in control or other event, and we cannot guarantee that any of these licensing relationships will continue or that our licensees will be able or willing to continue to perform their obligations, including development, commercialization or payment obligations, under such agreements.

Any significant negative developments relating to our relationships with our licensees could have a material adverse effect on our business, financial condition, cash flows and results of operations and on the market price of our ordinary shares.

For example, in November 2021 we received notice of partial termination of an exclusive license agreement with Janssen.

For these and other reasons that may be outside of our control, our revenues from products sold by our licensees, and any related commercial milestone payments, may fall below our expectations, the expectations of our licensees or those of our shareholders, which could have a material adverse effect on our results of operations and the market price of our ordinary shares.

Clinical trials for our products are expensive, may take several years to complete, and their outcomes are uncertain.

In order to obtain regulatory approvals for the commercial sale of any product, we or our licensees must demonstrate, through preclinical testing and clinical trials, that such product is safe and effective for use in humans.

Designing, conducting and completing a clinical development program is often a lengthy, time-consuming and expensive process.

Designing, conducting and completing a clinical development program is often a lengthy, time-consuming and expensive process and the risk of a product not successfully completing full clinical development and receiving marketing approval is high.

We have incurred, and we will continue to incur, substantial expenses for preclinical testing, clinical trials and other activities related to our clinical development programs.

1 unchanged sentence

Timelines for the initiation, conduct and completion of clinical trials may be delayed by many factors, including:

• issues with the opening, operation or inspection of a new or ongoing clinical trial site, including those located in or near areas of conflict or areas impacted by political, environmental, public health or economic events;

• issues with the opening, operation or inspection of a new or ongoing clinical trial site, including those located in or near geographic areas of conflict or areas impacted by political, environmental, public health or economic events;

• delays or failures of third-party CROs and other third-party service providers and clinical investigators to manage and conduct the trials, perform oversight of the trials, including data audit and verification procedures, or to meet expected timelines;

• an inability to recruit and enroll clinical trial participants at the expected rate or at all, or to adequately follow participants following treatment;

• safety or tolerability issues;

• an inability to recruit, enroll and retain clinical trial participants at the expected rate or at all, or to adequately follow participants after treatment;

• safety or tolerability issues that may arise during clinical trials;

• an inability to manufacture or obtain sufficient quantities of materials used for clinical trials;

• unforeseen governmental or regulatory issues or concerns, including those of the FDA and other regulatory agencies, that may impact the strategies for, and design, timelines or feasibility of, our clinical development programs.

In addition, we are currently conducting and enrolling patients in clinical studies in a number of countries where our experience is more limited.

In addition, we are currently conducting and enrolling patients in clinical studies in a number of countries where our experience is more limited and in disease areas in which we have not previously conducted clinical trials.

In these instances, we must depend on third parties, including independent clinical investigators, CROs and other third-party service providers, to successfully conduct our clinical trials and to audit, verify and accurately report results from such trials.

Though we do not have much control over many aspects of such third-party activities, we are responsible for ensuring that each

of our clinical trials is conducted in accordance with the general investigational plan and protocols for the trial.

Though we do not have much control over many aspects of such third-party activities, we are responsible for ensuring that each of our clinical trials is conducted in accordance with the general investigational plan and protocols for the trial.

Third parties may not complete planned activities on schedule or conduct our trials in accordance with regulatory requirements or our stated protocols.

1 unchanged sentence

The results from preclinical testing and early clinical trials often have not predicted results of later clinical trials.

A number of products have shown promising results in early clinical trials but subsequently failed to establish sufficient safety and efficacy data in later clinical trials to obtain necessary regulatory approvals.

If a product fails to demonstrate safety and efficacy in clinical trials, or if we and/or third parties fail to manage or conduct clinical trials in a timely manner or in accordance with study protocols or obligations, the development, approval and commercialization of our products may be delayed or prevented, and such events could materially adversely affect our business, financial condition, cash flows and results of operations.

A number of products have shown promising results in early clinical trials but subsequently failed to establish sufficient safety and/or efficacy data in later clinical trials to obtain necessary regulatory approvals.

If we and/or third parties fail to manage or conduct clinical trials in a timely manner or in accordance with study protocols or obligations or if a product fails to demonstrate clinical safety and efficacy or to possess features that may give such product a competitive commercial advantage over other products for the same indication, the development, approval and/or commercialization of our products may be delayed or prevented or less successful than anticipated, and such events could materially adversely affect our business, financial condition, cash flows and results of operations.

Preliminary, topline or interim data from our clinical trials that we may announce, publish or report from time to time may change as more patient data become available or based on subsequent audit and verification procedures, and may not be indicative of final data from such trials, data from future trials or real-world results.

2 unchanged sentences

In addition, such data may remain subject to audit confirmation and verification procedures that may result in the final data being materially different from the preliminary, topline or interim data disclosed.

As a result, all preliminary, topline and interim data should be viewed with caution until the final data are available.

Material adverse differences between preliminary, topline or interim data and final data could significantly harm our business, financial condition, cash flows and results of operations.

The FDA or other regulatory agencies may not agree with our regulatory approval strategies or components of our filings for our products and may not approve, or may delay approval of, our products.

As a result, all preliminary, topline and interim data, and data from early clinical trials with a small number of participants, should be viewed with caution until the final data or more extensive datasets are available, as applicable.

Material adverse differences between preliminary, topline or interim data and final data, or initial proof-of-concept data and data from later or larger trials, could significantly harm our business, financial condition, cash flows and results of operations.

Our success depends, in part, on our ability to successfully obtain and maintain regulatory approval for our products.

We must obtain government approvals before marketing or selling our products.

The FDA in the U.S., and comparable regulatory agencies in other jurisdictions, impose substantial and rigorous requirements for the development, manufacture and commercialization of medicines, the satisfaction of which can take a significant number of years and can vary substantially based upon the type, complexity and novelty of the product.

In addition, regulation is not static, and regulatory agencies, including the FDA, evolve in their staff, interpretations and practices and may impose more stringent requirements than currently in effect, which may adversely affect our plans for product development, manufacture and/or commercialization.

The approval procedure and the time required to obtain approval also varies among countries.

In addition, regulation is not static, and regulatory agencies, including the FDA, evolve in their staff, interpretations and practices, including as a result of changes in government, and may impose different or more stringent requirements than currently in effect, which may adversely affect our plans for product development, manufacture and/or commercialization.

The approval procedures and the time and requirements necessary to obtain and maintain approvals may also vary among countries.

Regulatory agencies may have varying interpretations of the same data, and approval by one regulatory agency does not ensure approval by regulatory agencies in other jurisdictions.

In addition, the FDA or other regulatory agencies may choose not to communicate with or update us during clinical testing and regulatory review periods and the ultimate decision by the FDA or other regulatory agencies regarding drug approval may not be consistent with prior communications.

The product approval process can last many years, be very costly and still be unsuccessful.

11 unchanged sentences

In addition, any failure to obtain, or delay in obtaining, approval for our products could have a material impact on our shareholders’ confidence in the strength of our development capabilities and/or our ability to generate significant revenue from our development programs and could result in a significant decline in our share price.

Disruptions at the FDA, the SEC and other government agencies caused by funding shortages or other events could hinder their ability to hire and retain key leadership and other personnel, prevent new products and services from being developed or commercialized in a timely manner, or otherwise prevent those agencies from performing normal business functions, which could negatively impact our business.

The ability of the FDA to review and approve new products can be affected by a variety of factors, including government budget and funding levels, ability to hire and retain key personnel and accept the payment of user fees, and statutory, regulatory, and policy changes.

Average review times at the agency have fluctuated in recent years as a result.

In addition, government funding of the SEC and other government agencies on which our operations may rely is subject to the impacts of political events, which are inherently fluid and unpredictable.

Disruptions at the FDA and other agencies may increase the time necessary for new drugs to be reviewed and/or approved by necessary government agencies, which could adversely affect our business.

For example, over the last several years, the U.S.

government has shut down several times and certain regulatory agencies, such as the FDA and the SEC, have had to furlough critical FDA, SEC and other government employees and stop critical activities.

If a prolonged government shutdown occurs, it could significantly impact the ability of the FDA and the SEC to timely review and process our submissions, which could have a material adverse effect on our business.

The FDA or other regulatory agencies may impose limitations or post-approval requirements on approvals for our products.

Even if regulatory approval to market a product is granted by the FDA or other regulatory agencies, the approved label for the product may not be consistent with our initial expectations or commercial plans.

2 unchanged sentences

In addition, legislation and regulatory policies relating to post-approval requirements and restrictions on promotional activities for pharmaceutical products, or FDA or other regulatory agency regulations, guidance or interpretations with respect to such legislation or regulatory policy may change, which may impact the development and commercialization of our products.

Disruptions at the FDA, the SEC and other government agencies could negatively impact our business.

Disruptions at the FDA and other regulatory agencies that are unrelated to our company or our products, including due to changes in government, could increase the time required for new drugs to be reviewed and approved, or otherwise cause delays to the regulatory approval or post-approval processes for our products, which could adversely affect our business.

The ability of the FDA or other regulatory agencies to review and approve new products or manage post-approval requirements for marketed products can be affected by a variety of factors, including government budget and funding levels, ability to hire and retain key personnel and accept the payment of user fees, and statutory, regulatory, and policy changes.

Average review times for product submissions have fluctuated in recent years as a result.

In addition, government funding of the SEC and other government agencies on which our operations may rely is subject to the impacts of political events, which are inherently fluid and unpredictable.

For example, over the last several years, the U.S.

If a prolonged government shutdown occurs, or if other global, political or economic conditions impact the regulatory agencies with which we interact, it could significantly impact the ability of the FDA and the SEC or other agencies to timely review and process our submissions, which could have a material adverse effect on our business.

We may not be able to successfully expand our R&D pipeline or our commercial product portfolio, which could limit our growth potential.

Our business is focused on the development and commercialization of medicines in the field of neuroscience, and we invest substantial resources toward the research and development of new potential product candidates to advance into clinical trials.

Notwithstanding this investment, our development programs may not yield viable product candidates in a timely manner or at all, and our product candidates may not obtain regulatory approval, which could limit our growth potential.

In addition to our internal development programs, our strategy for pipeline and commercial portfolio expansion includes identifying and evaluating potential transactional opportunities, including mergers and acquisitions, licenses and collaborations, and development and supply, commercialization or co-promotion arrangements, among others, to acquire or license additional products, product candidates, or technologies that could be additive to our business and to our strategy to create value for our shareholders.

However, such transactions are highly competitive, and many other companies may pursue the same or similar assets to those that we may consider attractive.

In particular, larger companies with greater financial resources or development or commercialization capabilities may have a competitive advantage over us.

Furthermore, companies that perceive us to be a competitor may be unwilling to assign or license rights to us.

We may also be unable to enter into transactions on acceptable terms that would allow us to realize an appropriate return on our investment.

Even if we succeed in our efforts to obtain rights to suitable products, product candidates, or technologies, the competitive business environment may result in high transaction costs, and our investment in these potential assets would remain subject to the inherent risks associated with the development and commercialization of new medicines and may not yield the growth or success that we anticipate, which could have a material adverse effect on our business and financial results and the market price of our ordinary shares.

We are subject to risks related to the manufacture of our products.

9 unchanged sentences

We may not be able to resolve any such issues in a timely manner, or at all, which could result in declines in sales and reputational damage as well as significant remediation costs to address any issues that arise.

We rely solely on our manufacturing facility in Wilmington, Ohio for the manufacture of RISPERDAL CONSTA, VIVITROL, ARISTADA, ARISTADA INITIO and LYBALVI and currently rely on the Athlone Facility for the manufacture of FAMPYRA, VUMERITY, other products using our NanoCrystal or OCR technologies and certain of our other products in development.

Due to regulatory and technical requirements, we have limited ability to shift production among our facilities or to outsource any portions of our manufacturing to third parties in the event of an interruption in manufacturing or demand for manufacturing that exceeds our capacity at the applicable facility.

Any need to shift production among our facilities or transition our manufacturing processes, or portions thereof, to a third party, whether due to an interruption in our manufacturing or to demand for a product that exceeds our manufacturing capacity or otherwise, could take a significant amount of time and money, may not be successful, and could cause significant interruption or delay in our ability to supply product.

In addition, in December 2023 we announced entry into a definitive agreement to sell the Athlone Facility to Novo and plans to enter into subcontracting arrangements to continue certain development and manufacturing activities currently performed at the Athlone Facility for a period of time after the closing of the transaction, which may continue through the end of 2025.

Such transaction is subject to various uncertainties and risk, including, without limitation, satisfaction of the conditions to closing of the transaction on the anticipated timeline, potential negative impacts on our relationships with current suppliers or licensees or diversion of management and employee attention from daily business operations, and risks inherent in the transition to subcontracting arrangements.

Any interruption or delay in supply, whether resulting from issues with equipment, materials, personnel, manufacturing processes, or internal or external quality audits or reviews, or issues related to the sale of the Athlone Facility and related subcontracting arrangements, could result in delays in meeting our contractual obligations and could damage our reputation and relationships with our licensees, and result in potential loss of revenues.

Our manufacturing facilities also require specialized personnel and are expensive to operate and maintain.

Any interruption in manufacturing, delay in a regulatory approval or commercial launch, or recall or suspension of sales of products manufactured in our facilities, may cause operating losses as we continue to operate these facilities and retain the required specialized personnel.

In addition, any significant personnel shortages at our manufacturing facilities, whether temporary or prolonged, including shortages related to the labor market, may cause significant interruptions to our manufacturing facilities and to our supply of products.

We rely solely on our manufacturing facility in Wilmington, Ohio for the manufacture of VIVITROL, ARISTADA, ARISTADA INITIO, LYBALVI and RISPERDAL CONSTA.

Due to regulatory and technical requirements, we have limited ability to shift production within our facility or to outsource any portions of our manufacturing to third parties in the event of an interruption in manufacturing or demand for manufacturing that exceeds our capacity.

Any need to transition our manufacturing processes, or portions thereof, to a third party, whether due to an interruption in our manufacturing or due to demand for a product that exceeds our manufacturing capacity or otherwise, could take a significant amount of time and resources, may not be successful, and could cause significant interruption or delay in our ability to supply products.

VUMERITY and other products using our NanoCrystal or OCR technologies are currently manufactured through subcontracting arrangements at the Athlone Facility, which we previously owned and sold to Novo in May 2024.

Any interruption or delay in supply from the Athlone Facility, whether resulting from issues with equipment, materials, personnel, manufacturing processes, or internal or external quality audits or reviews, or issues related to the subcontracting arrangements under which these products are manufactured, could result in delays in meeting our contractual obligations and could damage our reputation and relationships with our licensees, and result in potential loss of revenues.

Manufacturing facilities also require specialized personnel and are expensive to operate and maintain.

Any interruption in manufacturing, delay in a regulatory approval or commercial launch, or recall or suspension of sales of products manufactured in our facilities, may cause operating losses as we continue to operate our facilities and retain the required specialized personnel.

In addition, any significant personnel shortages at our manufacturing facilities or the Athlone Facility, whether temporary or prolonged, including shortages related to the labor market, may cause significant interruptions to our supply of products.

We are also dependent in certain cases on third parties who manufacture or distribute certain products from which we receive revenue.

9 unchanged sentences

In addition, we rely heavily on the three largest pharmaceutical wholesalers in the U.S.

market—Cardinal Health Inc., AmerisourceBergen Corp.

and McKesson Corp—in the distribution of the products that we market and sell in the U.S.

market—Cardinal Health Inc., Cencora, and McKesson Corp—in the distribution of the products that we market and sell in the U.S.

If we are unable to maintain our business relationships with these wholesalers on commercially acceptable terms, if these wholesalers experience prolonged business disruptions, if the buying patterns of these wholesalers fluctuate due to seasonality or any other reason or if wholesaler buying decisions or other factors outside of our control change, our business, financial condition, cash flows and results of operations could be materially adversely affected.

If we or our third-party providers fail to meet the stringent requirements of governmental regulation in the manufacture of our products, we could incur substantial remedial costs and a reduction in sales and/or revenues.

We and the third-party providers that play a role in our manufacturing activities are generally required to comply with cGMP regulations and other applicable non-U.S.

We and the third-party providers involved in our manufacturing activities are generally required to comply with cGMP regulations and other applicable non-U.S.

standards in the manufacture of our products or components of our products.

If any of our products or components of our products in the U.S.

Additionally, if any of our products or components of our products in the U.S.

are scheduled by the DEA as controlled substances, we would also be subject to DEA regulations.

We and our third-party providers are subject to unannounced inspections by the FDA and other agencies to confirm compliance with all applicable laws.

We and our third-party providers are subject to unannounced inspections by the FDA and other governmental agencies to confirm compliance with all applicable laws.

Any changes to our suppliers or modifications of methods of manufacturing require submission of amendments to our marketing applications to the FDA or other applicable regulatory agencies, and ultimate acceptance by such agencies of such amendments, prior to release of product to the applicable marketplace.

1 unchanged sentence

Any delay, interruption or other issues that may arise in the manufacture, formulation, packaging or storage of our products as a result of a failure of our facilities or operations or the facilities or operations of third-party providers to pass any regulatory agency inspection could significantly impair our ability to develop, obtain and maintain regulatory approval of, and commercialize or supply, products.

This could increase our costs, cause us to lose revenue or market share and damage our reputation with our collaboration partners or in the market generally.

This interruption could increase our costs, cause us to lose revenue or market share and damage our reputation with our collaboration partners or in the market generally.

In March 2020, in response to the COVID-19 pandemic, the Coronavirus Aid, Relief, and Economic Security Act (the “CARES Act”) was signed into law in the U.S., and served to increase the FDA’s existing authority with respect to drug shortage measures.

1 unchanged sentence

Each of our facilities operates in accordance with a comprehensive quality management system, which includes risk assessment, preventive actions and regular review of inventory levels for each of the marketed products that we manufacture;

however, there is no guarantee that the FDA will consider our risk management program to be sufficient upon inspection or that we will not experience shortages in the supply of marketed products that we manufacture, which could materially adversely affect the patients who rely on such marketed products and our business, financial condition, cash flows and results of operations.

however, the FDA may not consider our risk management program to be sufficient upon inspection and we may still experience

shortages in the supply of marketed products that we manufacture, which could materially adversely affect the patients who rely on such marketed products and our business, financial condition, cash flows and results of operations.

The FDA and various regulatory agencies outside the U.S.

have inspected and approved our commercial manufacturing facilities.

However, we cannot guarantee that the FDA or any other regulatory agencies will approve any other facility that we or our third-party providers may operate or, once approved, that any of these facilities will remain in compliance with cGMP and other regulations.

However, the FDA and any other regulatory agencies may not approve any other facility that we or our third-party providers may operate and, once approved, any of these facilities may not remain in compliance with cGMP and other regulations.

Any third party we use to manufacture bulk drug product for use in the U.S.

1 unchanged sentence

Failure by us or our third-party providers to gain or maintain regulatory compliance with and approvals from the FDA or other regulatory agencies could materially adversely affect our business, financial condition, cash flows and results of operations.

Adverse market conditions may exacerbate certain risks inherent to our business, including risk of non-payment from licensees and customers and reimbursement for our products.

Adverse market conditions or other business developments may cause disruptions, delays or significant financial impact to our business or to the businesses of third parties from which we receive revenues, or reductions in the availability or extent of reimbursement available to us.

For example, we depend on our licensees and customers for substantial portions of our revenue, and the contracts with our licensees and customers pursuant to which we supply product, or under which we are eligible for certain development or sales milestones or royalties related to licensed products or products that incorporate our proprietary technologies, may not be secured by collateral or other security.

Accordingly, we bear the risk that our licensees may not be able to pay amounts due to us under such contracts.

In addition, as a result of adverse market conditions, organizations that provide reimbursement for use of our products, such as government health administration authorities and private health insurers, may be unable to satisfy such reimbursement obligations or may delay payment.

In addition, U.S.

federal and state health authorities may reduce the extent of their reimbursements (including Medicare and Medicaid reimbursements in the U.S.) or payments, and private insurers may increase their scrutiny of claims.

If our licensees or other third parties are unable or unwilling to pay amounts owed to us or satisfy their commitments to us, or if there are reductions to such payments or commitments, our business, financial condition, cash flows and results of operations may be materially adversely affected.

Our success largely depends upon our ability to attract, recognize and retain key personnel.

Our ability to compete and succeed in the highly competitive biopharmaceutical industry and in the disease states in which we market and sell products depends largely upon our ability to attract, recognize and retain highly skilled technical, scientific, manufacturing, management, regulatory, compliance and selling and marketing personnel.

Each of our executive officers and all of our employees are employed “at will,” meaning we or each officer or employee may terminate the employment relationship at any time.

We face intense competition for employees, due, among many factors, to the geographic locations in which we operate and the competitive benefits and compensation practices in our industry, and in recent years, new competition as employees are increasingly able to work remotely.

The loss of key personnel due to any of these factors or our inability to hire and retain personnel who have technical, scientific, manufacturing, management, regulatory, compliance or commercial backgrounds could materially adversely impact our business, including the achievement of our manufacturing, research and development, commercial, financial and other operational and strategic business objectives.

We face intense competition for employees due to, among many factors, the geographic locations in which we operate and the competitive benefits and compensation practices in our industry, and in recent years, new competition as employees are increasingly able to work remotely.

The loss of key personnel due to any of these factors or our inability to hire and retain personnel who have technical, scientific, manufacturing, management, regulatory, legal, compliance or commercial backgrounds could materially adversely impact our business, including the achievement of our manufacturing, research and development, commercial, financial and other operational and strategic business objectives.

Risks Related to Intellectual Property

11 unchanged sentences

The development of new technologies or products may take a number of years, and there can be no assurance that any patents which may be granted in respect of such technologies or products will not have expired or be due to expire by the time such products are commercialized, or that such patents will successfully withstand any challenges during their respective terms.

Although we make reasonable efforts to protect our IP rights and to ensure that our proprietary technology does not infringe the rights of third parties, we cannot ascertain the existence of all potentially conflicting IP claims.

Although we make reasonable efforts to protect our IP rights and to ensure that our proprietary products and technologies do not infringe the IP rights of third parties, we cannot ascertain the existence of all potentially conflicting IP claims.

Therefore, there is a risk that third parties may make claims of infringement against our products or technologies.

4 unchanged sentences

Even if we have an agreement that may serve to indemnify us against such costs, the indemnifying party may be unable to uphold its contractual obligations.

If we cannot, or do not, license the infringed technology on reasonable terms or at all, or substitute similar technology from another source, our business, financial condition, cash flows and results of operations could be materially adversely affected.

Patents, if issued, may be challenged, invalidated or circumvented.

As our products achieve greater commercial sales, potential competitors are more likely to seek to challenge our patents.

If we cannot, or do not, license the infringed IP on reasonable terms or at all, or substitute similar IP from another source, our business, financial condition, cash flows and results of operations could be materially adversely affected.

The laws of certain countries may not protect our IP rights to the same extent as the laws of the U.S., and any patents that we own or license from others may not provide any protection against competitors.

6 unchanged sentences

If any trade secret, know-how or other invention not protected by a patent were to be disclosed to, or independently developed by, a competitor, such event could materially and adversely affect our business, financial condition, cash flows and results of operations.

Uncertainty over IP in the biopharmaceutical industry has been the source of litigation and other legal proceedings, which are inherently costly and unpredictable, could significantly delay or prevent approval or negatively impact commercialization of our products, and could adversely affect our business.

Uncertainty over IP in the biopharmaceutical industry has been the source of litigation and other legal proceedings, and we or our licensees may face claims against IP rights covering our products and competition from generic drug manufacturers.

There is considerable uncertainty within the biopharmaceutical industry about the validity, scope and enforceability of many issued patents in the U.S.

1 unchanged sentence

We cannot currently determine the ultimate scope, validity and enforceability of patents which may be granted to third parties in the future or which patents third parties may assert are infringed by the manufacture, use or sale of our products.

Stemming in part from this uncertainty, there has been, and we expect that there may continue to be, significant litigation and an increasing number of inter partes reviews (“IPRs”) and administrative proceedings in the pharmaceutical industry regarding patents and other IP rights.

A patent holder might file an IPR, interference and/or infringement action against us, including in response to patent certifications required under the Hatch-Waxman Act, claiming that certain claims of one or more of our issued patents are invalid or that the manufacture, use, offer for sale, sale or import of our products infringed one or more of such party’s patents.

We may have to expend considerable time, effort and resources to defend such actions, and litigation may be necessary in some instances to determine the validity and scope of certain of our proprietary rights.

Patents, if issued, may be challenged, invalidated or circumvented.

As our products achieve greater commercial sales, potential competitors are more likely to seek to challenge our patents.

In the biopharmaceutical industry, there has been, and we expect that there may continue to be, significant litigation, inter partes reviews (“IPRs”), post-grant reviews (“PGRs”) and administrative proceedings regarding patents and other IP rights.

A third party may file an IPR, PGR, interference and/or infringement action against us, including in response to patent certifications required under the Hatch-Waxman Act, claiming that certain claims of one or more of our issued patents are invalid or that the manufacture, use, offer for sale, sale or import of our products infringed one or more of such party’s patents.

For example, in December 2024, Argentum Pharmaceuticals LLC filed a request with the USPTO for ex parte reexamination of the validity of certain claims of our U.S.

7,919,499 that covers VIVITROL, which request was granted in January 2025 and is pending.

And in January 2025, Apotex Inc.

filed with the USPTO a petition for IPR of certain claims of U.S.

7,919,499 that cover VIVITROL, which petition has not yet been instituted.

In addition, we may need to enforce our IP rights against third parties who infringe on our patents and other IP or challenge our patents, patent applications or trademark applications.

Litigation and trial proceedings, such as so-called Paragraph IV litigation and IPRs, concerning patents and other IP rights may be expensive, protracted and distracting to management, with no certainty of success.

As a result, we may at times give up certain rights with respect to our IP in order to avoid or resolve timely and costly IP litigation or IPR proceedings.

For example, in July 2019, in order to resolve an IPR instituted by Amneal with the PTAB, we granted Amneal a non-exclusive license under certain patents covering VIVITROL, including the latest to expire patent covering VIVITROL in the U.S., to market and sell a generic formulation of VIVITROL in the U.S.

beginning sometime in 2028 or earlier under certain circumstances.

In addition, in August 2023, we settled Paragraph IV litigation proceedings with Teva (described in more detail below) by granting Teva a license to market and sell a generic version of VIVITROL in the U.S.

beginning on January 15, 2027, or earlier under certain circumstances.

Ultimately, the outcome of such litigation and other proceedings, or any settlement arrangements with respect thereto, could adversely affect our business and the validity and scope of our patents or other proprietary rights or delay or prevent us from manufacturing and marketing our products.

We or our licensees may face claims against IP rights covering our products and competition from generic drug manufacturers.

In the U.S., generic manufacturers of innovator drug products may file ANDAs and, in connection with such filings, certify that their products do not infringe the innovator’s patents or that the innovator’s patents are invalid.

This often results in litigation between the innovator and the ANDA applicant.

This type of litigation is commonly known in the U.S.

as “Paragraph IV” litigation.

For example, Teva entities filed an ANDA seeking approval to engage in the commercial manufacture, use or sale of a generic version of VIVITROL and alleging that one of our Orange-Book patents related to VIVITROL is invalid, unenforceable and/or will not be infringed by Teva’s proposed product.

In September 2020, we initiated a Paragraph IV lawsuit against Teva to dispute such claims.

A trial was held in February 2023.

In August 2023, we entered into a confidential settlement and license agreement (the “Settlement Agreement”) with Teva to resolve the proceedings between the parties.

This often results in litigation between the innovator and the ANDA applicant, commonly known in the U.S.

as “Paragraph IV” litigation, which can be expensive, protracted and distracting to management, with no certainty of success.

For example, Teva entities filed an ANDA seeking approval to engage in the commercial manufacture, use or sale of a generic version of VIVITROL and alleged that one of our Orange-Book patents related to VIVITROL is invalid, unenforceable and/or will not be infringed by Teva’s proposed product.

In response, we initiated a Paragraph IV lawsuit against Teva in September 2020 to dispute such claims.

In order to avoid or resolve timely and costly IP litigation or IPR, PGR or other administrative proceedings, we may enter into settlement agreements in which we grant an adverse party certain rights with respect to our IP.

For example, in August 2023, following a trial in the Teva patent infringement lawsuit discussed above, we entered into a confidential settlement and license agreement (the “Settlement Agreement”) with Teva in August 2023 to resolve the proceedings between the parties.

Pursuant to the terms of the Settlement Agreement, we granted Teva a non-exclusive, royalty-free, non-transferable, non-sublicensable limited license to market and sell a generic version of VIVITROL in the U.S.

beginning on January 15, 2027, or earlier under certain circumstances.

Although we intend to vigorously defend our IP rights, and we expect our licensees to do the same, there can be no assurance that we or our licensees will prevail or settle any such legal proceedings or disputes on favorable terms.

And in July 2019, in order to resolve an IPR instituted by Amneal with the PTAB, we granted Amneal a non-exclusive license under certain patents covering VIVITROL, including the latest to expire patent covering VIVITROL in the U.S., to market and sell a generic formulation of VIVITROL in the U.S.

beginning sometime in 2027 or earlier under certain circumstances.

There can be no assurance that we or our licensees will prevail or settle any IP legal proceedings or disputes on favorable terms.

Our and our licensees’ existing patents could be invalidated, found unenforceable or found not to cover generic forms of our or our licensees’ products.

If any ANDA filers were to receive FDA approval to sell generic versions of our products or the products from which we receive revenue and/or prevail in any patent litigation with respect to such products, such products would become subject to increased competition, and our business, financial condition, cash flows and results of operations could be materially adversely affected.

If any ANDA filers were to receive FDA approval to sell generic versions of our products or the products from which we receive revenue and/or prevail in any patent litigation with respect to such products, our business, financial condition, cash flows and results of operations could be materially adversely affected.

Risks Related to Regulatory or Legal Matters

8 unchanged sentences

If successful, such petitions can significantly delay, or even prevent, the approval of the marketing application in question or cause such marketing application approval to be withdrawn.

Even if the FDA ultimately denies such a petition, the FDA may substantially delay approval while it considers and responds to the petition, or may impose additional approval requirements as a result of such petition.

Even if the FDA ultimately denies such a petition, the FDA may substantially delay approval while it considers and responds to the petition, or may impose additional approval or post-approval requirements as a result of such petition.

These outcomes and others could adversely affect our share price as well as our ability to generate revenues from the commercialization and sale of our products and products using our proprietary technologies.

2 unchanged sentences

The administration of drugs in humans carries the inherent risk of product liability claims whether or not the drugs are actually the cause of an injury.

Our products may cause, or may appear to have caused, injury or dangerous drug interactions, and we may not learn about or understand those effects until the products have been administered to study participants or patients for a prolonged period of time.

Our products may cause, may appear to have caused or may be claimed to have caused, injury or dangerous drug interactions, and we may not learn about or understand those claims or effects until the products have been administered to patients for a prolonged period of time.

Additionally, incidents of product misuse may occur.

4 unchanged sentences

These types of events could have a material adverse effect on our business, financial condition, cash flows and results of operations.

If there are changes in, or we fail to comply with, the extensive legal and regulatory requirements affecting the healthcare industry, we could face litigation, costs, penalties and business losses.

Our activities, and the activities of our licensees and third-party providers, are subject to extensive government regulation.

Achieving compliance with these regulations substantially increases the time, difficulty and costs incurred in obtaining and maintaining approvals to market newly developed and existing products.

Biopharmaceutical companies also have been the target of government lawsuits and investigations alleging violations of government regulation, including claims asserting submission of incorrect pricing information, impermissible promotion of pharmaceutical products, payments intended to influence the referral of healthcare business, submission of false claims for government reimbursement, antitrust violations, violations related to anti-corruption and anti-bribery laws, and violations related to environmental matters.

We have been, and may continue to be, the subject of certain government inquiries or requests for documentation.

For example, we have received a subpoena and civil investigative demands from U.S.

state and federal authorities for documents related to VIVITROL.

We are cooperating with the government in each instance.

If, as a result of government requests, proceedings are initiated, including under the U.S.

federal anti-kickback statute and False Claims Act and state False Claims Acts or other laws, and we are found to have violated one or more applicable laws, we may be subject to significant liability, including without limitation, civil fines, criminal fines and penalties, civil damages and exclusion from U.S.

federal funded healthcare programs such as Medicare and Medicaid, any of which could materially affect our reputation, business, financial condition, cash flows and results of operations.

Conduct giving rise to such liability could also form the basis for private civil litigation by third-party payers or other persons allegedly harmed by such conduct.

While we have implemented numerous risk mitigation measures, we cannot guarantee that we, our employees, our licensees, our consultants or our contractors are, or will be, in compliance with all applicable laws, regulations or interpretations of the applicability of these laws to our products, operations and marketing practices.

If we or our agents fail to comply with any of those laws, regulations or interpretations, a range of actions could result, including the suspension or termination of clinical trials, the failure to approve a product, restrictions on sales of our products or our manufacturing processes, withdrawal of our products from the market, significant fines, exclusion from government healthcare programs or other sanctions or litigation.

For example, and as discussed above, the Inflation Reduction Act, signed into law in August 2022, includes several provisions that will impact our business to varying degrees, including those that impose new manufacturer financial liability on all drugs in Medicare Part D beginning in 2025, allow the U.S.

government to negotiate prices for some drugs covered under Medicare Part B and Part D beginning in 2026, and require companies to pay rebates to Medicare beginning in 2023 for drug prices that increase faster than inflation.

This law and any further changes in laws, regulations or decisions or in the interpretation of existing laws, regulations and decisions could have a material adverse effect on our business, financial condition, cash flows and results of operations.

If we fail to comply with our reporting and payment obligations under the Medicaid Drug Rebate Program or other governmental pricing programs, we could be subject to additional reimbursement requirements, penalties, sanctions and fines, which could have a material adverse effect on our business, financial condition, results of operations and growth prospects.

10 unchanged sentences

CMS issued a final regulation, which became effective in April 2016, to implement the changes to the Medicaid Drug Rebate Program under the Affordable Care Act.

In December 2020, CMS issued a final regulation that modified prior Medicaid Drug Rebate Program regulations to permit reporting multiple best price figures with regard to value-based purchasing arrangements (beginning in 2022);

and provided definitions for “line extension,” “new formulation,” and related terms, with the practical effect of expanding the scope of drugs considered to be line extensions that are subject to an alternative rebate formula (beginning in 2022).

Regulatory and legislative changes, and judicial rulings relating to the Medicaid Drug Rebate Program and related policies (including coverage expansion), have increased and will continue to increase our costs and the complexity of compliance, have been and will continue to be time-consuming to implement, and could have a material adverse effect on our results of operations, particularly if CMS or another agency challenges the approach we take in our implementation.

Since that time, CMS has issued multiple proposed and final rules that change the Medicaid Drug Rebate Program.

Regulatory and legislative changes, and judicial rulings relating to the Medicaid Drug Rebate Program and related policies, have increased and will continue to increase our costs and the complexity of compliance, have been and will continue to be time-consuming to implement, and could have a material adverse effect on our results of operations, particularly if CMS or another agency challenges the approach we take in our implementation.

HRSA issued a final regulation regarding the calculation of the 340B ceiling price and the imposition of civil monetary penalties on manufacturers that knowingly and intentionally overcharge covered entities, which became effective in January 2019.

2 unchanged sentences

Any charge by HRSA that we have violated this regulation or other requirements of the program could negatively impact our financial results.

Moreover, HRSA newly established an administrative dispute resolution (“ADR”) process under a final regulation effective January 2021 for claims by covered entities that a manufacturer engaged in overcharging, including claims that a manufacturer limited the ability of a covered entity to purchase the manufacturer’s drugs at the 340B ceiling price, and by manufacturers that a covered entity violated the prohibitions against diversion or duplicate discounts.

Moreover, HRSA has established an administrative dispute resolution (“ADR”) process, which is governed by a final regulation effective June 2024, for claims by covered entities that a manufacturer engaged in overcharging, including claims that a manufacturer limited the ability of a covered entity to purchase the manufacturer’s drugs at the 340B ceiling price, and by manufacturers that a covered entity violated the prohibitions against diversion or duplicate discounts.

Such claims are to be resolved through an ADR panel of government officials rendering a decision that could be appealed only in federal court.

This ADR regulation has been challenged in separate litigation instituted by PhRMA and by pharmaceutical manufacturers in multiple federal courts.

Under the ADR final rule which became effective in January 2021, an ADR proceeding could potentially subject us to discovery by covered entities and other onerous procedural requirements and could result in additional liability.

An ADR proceeding could potentially subject us to discovery by covered entities and other onerous procedural requirements and could result in additional liability.

HRSA could also decide to terminate a manufacturer’s agreement to participate in the 340B program for a violation of that agreement or other good cause shown, in which case the manufacturer’s covered outpatient drugs may no longer be eligible for federal payment under the Medicaid or Medicare Part B program.

In November 2022, HRSA issued a proposed rule to revise the ADR procedures contained in its January 2021 final regulation for disputes arising under the 340B drug pricing program between covered entities and manufacturers.

Further, legislation may be introduced that, if passed, would, among other things, further expand the 340B program to additional covered entities or would require participating manufacturers to agree to provide 340B discounted pricing on drugs used in an inpatient setting, and any additional future changes to the definition of average manufacturer price or the Medicaid rebate amount could affect our 340B ceiling price calculations and negatively impact our results of operations.

Additionally, certain pharmaceutical manufacturers are involved in ongoing litigation regarding their initiatives that restrict covered entities’ ability to purchase products at the 340B program price for shipment through an unlimited number of contract pharmacies.

Based on the outcome of litigation related to this topic or for other reasons, we may implement, and other pharmaceutical manufacturers have implemented, similar restrictions.

The outcome of pending judicial proceedings and the potential impact on the way in which manufacturers extend discounts to covered entities through contract pharmacies remain uncertain and one or more negative legal rulings, or the passage of legislation in respect of this topic, may materially adversely impact our results of operations if we were to impose limitations on contract pharmacy arrangements.

Additionally, we have implemented a policy governing the eligibility of covered entities to purchase our products at the 340B price for shipment to a contract pharmacy.

We implemented this policy out of concern that contract pharmacy arrangements are diverting the benefits of the 340B program from patients to contract pharmacies and contributing to the pervasive lack of transparency within the 340B program, rendering it difficult to identify inappropriate duplicate discounts and product diversion.

Certain pharmaceutical manufacturers and the industry group, Pharmaceutical Research and Manufacturers of America (“PhRMA”) are involved in ongoing litigation with the HRSA regarding manufacturer initiatives that restrict covered entities’ ability to purchase products at the 340B program price for shipment through an unlimited number of contract pharmacies.

Additionally, several states have enacted, and many other states are considering, laws that prohibit manufacturer restrictions on contract pharmacies.

Certain pharmaceutical manufacturers and PhRMA have initiated litigation challenging these state laws.

The outcome of pending judicial proceedings and the potential impact on the way in which manufacturers extend discounts to covered entities through contract pharmacies remain uncertain and negative legal rulings, or the passage of legislation in respect of this topic, may materially adversely impact our results of operations.

We have obligations to report the average sales price for certain of our drugs to the Medicare program.

18 unchanged sentences

We may not be able to maintain profitability on a sustained basis.

At December 31, 2023, our accumulated deficit was $1.3 billion, which was primarily the result of net losses incurred from continuing operations from 1987, the year Alkermes, Inc., was founded, through December 31, 2022, partially offset by net income from continuing operations over certain fiscal periods, including net income earned during the year ended December 31, 2023.

At December 31, 2024, our accumulated deficit was $1.0 billion, which was primarily the result of net losses incurred from continuing operations from 1987, the year Alkermes, Inc.

was founded, through December 31, 2022, partially offset by net income from continuing operations over certain fiscal periods, including net income earned during the years ended December 31, 2024 and December 31, 2023.

Our ability to maintain profitability on a sustained basis will depend on our ability to continue to grow and diversify our revenue and to effectively and efficiently manage our costs.

Factors that may impact our future revenue, and in turn our future profitability, include our or our licensees’ (as applicable) ability to:

• successfully commercialize VIVITROL, the ARISTADA product family, LYBALVI, VUMERITY, the long-acting INVEGA products and any other marketed products for which we earn revenue in the countries in which such products are approved;

Factors that may impact our future revenue, and in turn our future profitability, include, among others, our or our licensees’ (as applicable) ability to:

• successfully commercialize VIVITROL, the ARISTADA product family, LYBALVI, VUMERITY, XEPLION, INVEGA TRINZA/TREVICTA and INVEGA HAFYERA/BYANNLI and any other marketed products from which we earn revenue in the countries in which such products are approved;

• successfully develop, and obtain and maintain regulatory approval for, products in the U.S.

and in other countries;

and/or in other countries;

• successfully manufacture our products and third-party products efficiently and in a cost-effective manner;

• obtain adequate reimbursement coverage for our products and third-party products from insurance companies, government programs and other third-party payers;

• achieve certain product development and sales milestones under our collaborative arrangements;

• successfully protect and defend our confidential information and IP rights related to our technologies and our products;

• achieve product development or sales milestones under our collaborative arrangements;

• resolve favorably any commercial disputes that may arise in respect of collaborative arrangements from which we receive revenues.

Factors that may impact our future spend, and in turn our future profitability, include:

Factors that may impact our future spend, and in turn our future profitability, include, among others:

• the scope of our research and development activities, including the number of programs, products, indications or new technologies that we may pursue, and our ability, if sought, to share development costs through potential collaborations;

2 unchanged sentences

• the costs of operating and maintaining our manufacturing and research facilities, including the costs and availability of raw materials or components of our products;

• the costs of doing business with third-party vendors, including suppliers, manufacturers, packagers and distributors;

• the scope and costs of our commercial activities, including our investment in direct-to-consumer campaigns and other initiatives;

• the cost of possible business development activities, including licenses or acquisitions of technologies, compounds or product rights or the potential acquisition of other assets, including equipment, facilities, businesses or entire companies;

• the costs of doing business with third-party vendors, including suppliers, manufacturers, packagers and distributors and CROs;

• the scope and costs of our commercial activities, including expansion of our sales force and our investment in direct-to-consumer campaigns and other initiatives;

• the costs related to potential litigation, arbitration or other legal proceedings or government requests for information;

• the costs of defending against potential or actual proxy contests or other activist shareholder actions;

• the costs of compliance with new regulations applicable to us, including those related to the measurement, reporting and assurance of environmental performance data;

• the costs of compliance with new regulations applicable to us, including those related to the measurement, reporting and assurance of environmental performance data and other sustainability matters;

• the costs associated with recruiting, compensating and retaining a highly-skilled workforce in an environment where competition for highly-skilled employees is intense.

18 unchanged sentences

federal income tax consequences of investments in us.

If goodwill becomes impaired, we could have to take significant charges against earnings.

If goodwill becomes impaired, we may have to take significant charges against earnings.

At December 31, 2024, we had $83.0 million of goodwill.

11 unchanged sentences

Changes in tax rules and regulations, or interpretations thereof, may adversely affect our financial condition.

Effective January 2022, the Tax Cuts and Jobs Act of 2017 eliminated the option to deduct R&D expenses in the year incurred and instead requires taxpayers to capitalize, and subsequently amortize such expenses over five years for research activities conducted in the U.S., and over fifteen years for research activities conducted outside of the U.S.

As such, we expect a material decrease in cash flows provided from operations and a material increase in our net deferred tax assets over the next number of years, which could have a material adverse effect on our business, financial condition, cash flows and results of operations.

In December 2023, the IRS issued Notice 2024-12 that provided clarity on the application of Section 174 of the Code (“Section 174”).

On this basis, we adjusted our estimate of expenses that should be capitalized and amortized which resulted in lower taxable income for the year ended December 31, 2023.

In December 2022, the EU agreed to implement a corporate minimum tax rate of 15% on companies with combined annual revenue of at least €750.0 million.

The Irish government has transposed the corporate minimum tax rules into Irish legislation with effect as of January 1, 2024.

As such, we expect a material increase in our tax expense and a material decrease in cash flows provided from operations, which could have a material adverse effect on our business, financial condition, cash flows and results of operations.

Congress, the EU, the Organization for Economic Co-operation and Development (“OECD”), and other government agencies in jurisdictions where we and our affiliates do business are focused on the taxation of multinational corporations.

As a result of this focus, the tax laws in Ireland and the U.S.

could change on a prospective or retroactive basis, and any such changes could adversely affect us.

The Tax Cuts and Jobs Act amended Section 174 of the Code (“Section 174”) and, with effect from January 2022, eliminated the option to deduct R&D expenses in the year incurred and instead requires taxpayers to capitalize, and subsequently amortize such expenses over five years for research activities conducted in the U.S., and over fifteen years for research activities conducted outside of the U.S.

As such, we expect a material decrease in cash flows provided from operations and a material increase in our net U.S.

deferred tax assets over the next number of years, which could have a material adverse effect on our business, financial condition, cash flows and results of operations.

In December 2022, the EU implemented a new corporate minimum tax rate of 15% on companies with combined annual revenue of at least €750.0 million, which was transposed into Irish law effective as of January 1, 2024.

We do not expect such rules to have a material effect on our business in 2025;

however, such minimum tax rate rules or other similar rules could have a material adverse effect on our business, financial condition, cash flows and results of operations in future years.

Our deferred tax assets may not be realized.

2 unchanged sentences

in the future.

Losses may arise from operating events (including clinical program progression), or the occurrence of significant excess tax benefits arising from the exercise of stock options and/or the vesting of restricted stock units.

Unless we are able to generate sufficient taxable income in the future, a substantial valuation allowance to reduce the carrying value of our U.S.

2 unchanged sentences

net deferred tax assets of $121.6 million an amount of $30.0 million relating to employee share-based compensation expense.

It is possible that a material portion of this deferred tax asset will not be realized, especially if the price of our ordinary shares remains at its current level (refer to “Item 5—Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities” in this Annual Report for details of the price of our ordinary shares).

It is possible that a significant portion of this deferred tax asset will not be realized, especially if the price of our ordinary shares remains at its current level (see “Item 5—Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities” in this Annual Report for details of the price of our ordinary shares).

Unless the price of our ordinary shares increases, we will incur a deferred tax expense as our U.S.-based employees exercise or forfeit their stock options and their restricted stock unit awards vest.

This could materially increase our tax expense and may materially adversely affect our financial condition and results of operations.

As of December 31, 2023, we had $94.7 million of net deferred tax assets in Ireland including $87.5 million relating to net operating losses (“NOL”).

The NOLs can be carried forward, without time limit, against trading income of the same trade in future accounting periods.

The disposition of the Athlone Facility may result in (i) a significant change to the existing trade such that the same trade is no longer continued, and (ii) a complete discontinuance of the existing trade and the commencement of a new trade.

We do not believe that the disposition would amount to a significant change or a discontinuance of our existing trade;

This could significantly increase our tax expense and may adversely affect our financial condition and results of operations.

The disposition of the Athlone Facility may limit our ability to use our net operating losses and result in unanticipated tax liabilities.

As of December 31, 2023, we had $94.7 million of net deferred tax assets in Ireland, including $87.5 million relating to net operating losses (“NOLs”).

These NOLs can be carried forward, without time limit, against trading income of the same trade in future accounting periods.

In May 2024, we completed the sale of the Athlone Facility to Novo.

The disposition of the Athlone Facility may be deemed to result in (i) a significant change to the existing trade such that the same trade is no longer continued, and (ii) a complete discontinuance of the existing trade and the commencement of a new trade.

We do not believe that the disposition of the Athlone Facility would amount to a significant change or a discontinuance of our existing trade;

however, the Irish Tax Authority could assert a contrary position, in which case we could become involved in tax controversy with the Irish Tax Authority regarding possible additional tax liabilities.

If we were to be unsuccessful in resolving any such tax controversy in our favor, we could be liable for significant tax liabilities which would materially adversely affect our financial condition, cash flows and results of operations.

The business combination in 2011 of Alkermes, Inc.

and the drug technology business (“EDT”) of Elan Corporation, plc may limit our ability to use our tax attributes to offset taxable income, if any, generated from such business combination.

On September 16, 2011, the businesses of Alkermes, Inc.

and EDT were combined under Alkermes plc (this combination is referred to as the “Business Combination”).

If we were to be unsuccessful in resolving any such tax controversy in our favor, we could be liable for significant additional tax liabilities than that which we anticipate, which would materially adversely affect our financial condition, cash flows and results of operations.

The IRS may not agree with our conclusion that we should be treated as a foreign corporation for U.S.

federal income tax purposes.

In September 2011, the business of Alkermes, Inc., a U.S.

corporation, and the drug technology business of Elan Corporation, plc, an Irish-incorporated public limited company, were combined under Alkermes plc, an Irish-incorporated public limited company (the “Business Combination”).

federal income tax purposes, a corporation is generally considered tax resident in the place of its incorporation.

Because we are incorporated in Ireland, we should be deemed an Irish corporation under these general rules.

Because we are incorporated in Ireland, we should be classified as an Irish corporation under these general rules.

However, Section 7874 of the Code generally provides that a corporation organized outside the U.S.

5 unchanged sentences

corporation own at least 80% (of either the voting power or the value) of the stock of the acquiring foreign corporation after the acquisition by reason of holding stock in the domestic corporation, and the “expanded affiliated group” (as defined in Section 7874) that includes the acquiring corporation does not have substantial business activities in the country in which it is organized.

In addition, Section 7874 provides that if a corporation organized outside the U.S.

acquires substantially all of the assets of a corporation organized in the U.S., the taxable income of the U.S.

corporation during the period beginning on the date the first assets are acquired as part of the acquisition, through the date which is ten years after the last date assets are acquired as part of the acquisition, shall be no less than the income or gain recognized by reason of the transfer during such period or by reason of a license of property by the expatriated entity after such acquisition to a foreign affiliate during such period, which is referred to as the “inversion gain,” if shareholders of the acquired U.S.

corporation own at least 60% (of either the voting power or the value) of the stock of the acquiring foreign corporation after the acquisition by reason of holding stock in the domestic corporation, and the “expanded affiliated group” of the acquiring corporation does not have substantial business activities in the country in which it is organized.

If this rule was to apply to the Business Combination, among other things, Alkermes, Inc.

would have been restricted in its ability to use the approximately $274.0 million of U.S.

federal NOL carryforwards and $38.0 million of U.S.

state NOL carryforwards that it had as of March 31, 2011.

We do not believe that either of these limitations should apply as a result of the Business Combination.

We believe that Alkermes plc should be classified as an Irish tax resident corporation and should not be treated as a U.S.

corporation for U.S.

federal income tax purposes.

However, the IRS could assert a contrary position, in which case we could become involved in tax controversy with the IRS regarding possible additional U.S.

tax liability.

If we were to be unsuccessful in resolving any such tax controversy in our favor, we could be liable for significantly greater U.S.

federal and state income tax than we anticipate being liable for as a result of the Business Combination, which would place further demands on our cash needs.

If we were to be unsuccessful in resolving any such tax controversy in our favor, we could be liable for significant additional U.S.

federal and state income tax than those we anticipate, which would materially adversely affect our financial condition, cash flows and results of operations.

If the separation of our oncology business completed in November 2023 does not ultimately qualify as a transaction that is generally tax-free for U.S.

10 unchanged sentences

Notwithstanding the U.S.

Tax Opinion or IRS Ruling, the U.S.

Internal Revenue Service, or the IRS, could determine that a distribution or any related transaction is taxable for U.S.

Tax Opinion or IRS Ruling, the IRS could determine that a distribution or any related transaction is taxable for U.S.

federal income tax purposes if it determines that any of these facts, assumptions, representations or undertakings are not correct or have been violated, or that the distribution should be taxable for other reasons, including if the IRS were to disagree with the conclusions in the U.S.

10 unchanged sentences

In such an event, we and/or our shareholders could incur significant tax liabilities.

Our level of indebtedness, and the interest-rate transition to SOFR, could adversely affect our business and limit our ability to plan for or respond to changes in our business.

In March 2021, we amended and refinanced our then-existing term loan (the “2023 Term Loans”), in order to, among other things, provide for a new class of replacement term loans equal to $300.0 million;

extend the due date of the loan from March 26, 2023 to March 12, 2026;

amend the interest payable from London Interbank Offered Rate (“LIBOR”) plus 2.25% with no LIBOR floor to LIBOR plus 2.50% with a LIBOR floor of 0.5%;

and increase covenant flexibility (such refinancing, the “Term Loan Refinancing” and the 2023 Term Loans as so amended and refinanced, the “2026 Term Loans”).

In June 2023, we amended the 2026 Term Loans to transition the interest rate available for borrowings thereunder from a LIBOR-based interest rate to an interest rate based on SOFR and to make other confirming and mechanical changes.

SOFR is a relatively new reference rate and its composition and characteristics are not the same as LIBOR.

Given SOFR’s very limited history and potential volatility as compared to other benchmark or market rates, the future performance of SOFR cannot be predicted based on historical performance.

The consequences of using SOFR could include an increase in the cost of our variable rate indebtedness.

As of December 31, 2023, our borrowings consisted of $291.8 million outstanding under the 2026 Term Loans.

The 2026 Term Loans are secured by a first priority lien on substantially all of the combined company assets and properties of Alkermes plc and most of its subsidiaries, which serve as guarantors.

The agreements governing the 2026 Term Loans include a number of restrictive covenants that, among other things, and subject to certain exceptions and baskets, impose operating and financial restrictions on us.

Our failure to comply with these restrictions could lead to an event of default that could result in an acceleration of the indebtedness.

Our future operating results may not be sufficient to ensure our ability to make our debt payments or to remedy any such default.

In the event of an acceleration of this indebtedness, we may not have, or be able to obtain, sufficient funds to make any accelerated payments.

Our business strategy may involve future transactions which may harm the market price of our ordinary shares or require us to seek additional funds, and such funding may not be available on commercially favorable terms or at all and may cause dilution to our existing shareholders.

In order to achieve our business strategy, we regularly review potential transactions related to technologies, products or product rights, and businesses that are complementary to our business, including mergers and acquisitions, licenses and collaborations, and development and supply, commercialization or co-promotion arrangements, among others.

In order to achieve our business strategy, we regularly review potential transactions related to technologies, products or product rights or other assets, and businesses that are complementary to our business, including mergers and acquisitions, licenses and collaborations, and development and supply, commercialization or co-promotion arrangements, among others.

We may choose to enter into one or more of these or other transactions at any time, which may cause substantial fluctuations in the market price of our ordinary shares.

4 unchanged sentences

In addition, under Irish law, the directors of an Irish public limited company must have specific authority, as approved by the company’s shareholders, to allot and issue any ordinary shares (other than pursuant to employee equity plans) and, if such directors desire to allot and issue ordinary shares for cash, such shares must first be offered on the same or more favorable terms to the Company’s existing shareholders on a pro-rata basis, unless this statutory pre-emption right is disapplied by approval of the company’s shareholders.

In June 2023, our shareholders authorized our board of directors to allot and issue ordinary shares in an amount equal to approximately 20% of our issued ordinary share capital (as of May 15, 2023), and to issue ordinary shares for cash on a non-pre-emptive basis in an amount equal to approximately 20% of our issued share capital (as of May 15, 2023) under certain specified circumstances;

In May 2024, our shareholders renewed our board of directors’ general authority to allot and issue ordinary shares in an amount equal to approximately 20% of our issued ordinary share capital (as of April 10, 2024), and to issue ordinary shares for cash on a non-pre-emptive basis in an amount equal to approximately 20% of our issued share capital (as of April 10, 2024);

however, these share issuance authorities were granted for eighteen months only, at which point they will lapse unless renewed by our shareholders.

If we are unable to obtain renewal of share issuance authorities from our shareholders, or are otherwise limited by the terms of new share issuance authorities approved by our shareholders, our ability to use our authorized but unissued share capital to effect or to fund acquisition or other transaction opportunities, or to otherwise raise capital, could be adversely affected.

If we are unable to obtain renewal of share issuance authorities from our shareholders, or are otherwise

limited by the terms of new share issuance authorities approved by our shareholders, our ability to use our authorized but unissued share capital to effect or to fund acquisition or other transaction opportunities, or to otherwise raise capital, could be adversely affected.

In addition, future investors or lenders may demand, and may be granted, rights superior to those of existing shareholders.

If we issue additional debt securities, our existing debt service obligations will increase further.

If we are unable to generate sufficient cash to meet these obligations and need to use existing cash or liquidate investments in order to fund our debt service obligations or to repay our debt, we may be forced to curtail our operations.

If we issue debt securities, we would likely be subject to restrictive covenants and debt service obligations that may impact our operations and financial condition.

We cannot be certain that additional financing will be available from any of these sources when needed or, if available, will be on acceptable terms.

If we fail to obtain additional capital if needed, we may not be able to execute our business strategy successfully and may have to give up rights to our product platforms, and/or products, or grant licenses on terms that may not be favorable to us.

If we fail to obtain additional capital if needed, we may not be able to execute our business strategy successfully.

Even if we are able to finance potential transactions without seeking any external financing, expenditure of a significant amount of cash on such transactions may require difficult capital allocation decisions and may limit our ability to pursue other important business and strategic objectives, may significantly impact our financial condition and profitability and limit our potential to return capital to shareholders.

12 unchanged sentences

During the year ended December 31, 2024, the closing price of our ordinary shares on the Nasdaq Global Select Market ranged from $23.01 to $32.56 per share.

The market price of our ordinary shares is likely to continue to be volatile and subject to significant price and volume fluctuations in response to market and industry factors, our results of operations, our ability to maintain and increase sales of our products, the success of our key development programs, our ability to achieve and sustain profitability, the outcomes of business development transactions in which we may participate, our capital allocation decisions, and other factors, including the risk factors described in this Annual Report.

The market price of our ordinary shares is likely to continue to be volatile and subject to significant price and volume fluctuations in response to market and industry factors, our results of operations, our ability to maintain and increase sales of our products, the success of our key development programs and expansion of our development pipeline and commercial portfolio, our ability to achieve and sustain profitability, the outcomes of business development transactions in which we may participate, our capital allocation decisions, and other factors, including the risk factors described in this Annual Report.

We have also experienced significant volatility in the market price of our ordinary shares based on our business performance, including in relation to our commercial sales and the financial guidance that we issue for such sales, results from our clinical development programs, and events relating to regulatory actions and interactions related to our product candidates and commercial products.

For example, a series of adverse actions by the FDA in 2018 relating to our NDA for ALKS 5461, our investigational product for the treatment of major depressive disorder, caused the market price of our ordinary shares to decline significantly.

In addition, the stock market in general, including the market for biopharmaceutical companies, has experienced extreme price and trading volume fluctuations that have often been unrelated or disproportionate to the operating performance of those companies.

12 unchanged sentences

Information security breaches and other disruptions could compromise our information and expose us to liability, which would cause our business and reputation to suffer.

In the ordinary course of our business, we collect and store sensitive data, including IP, proprietary business information of ours and that of our suppliers and partners, as well as personally identifiable information of persons who use our medicines, clinical trial participants and employees.

Our partners and third-party providers also possess certain of our sensitive data.

In the ordinary course of our business, we and our third-party service providers collect, store, maintain and transmit sensitive data, including IP, proprietary business information of ours and that of our suppliers and partners, as well as personally identifiable information of persons who use our medicines, clinical trial participants and employees.

In addition, we outsource some of our operations to a number of third-party vendors who may have, or could gain, access to our confidential information.

The secure maintenance of all such information and the secure performance of our information technology (“IT”) systems are critical to our operations and business strategy.

1 unchanged sentence

While we take prudent measures to secure our IT systems, the risk still exists that such systems may become compromised by successful breaches, malfeasance, human error or technological fault.

Moreover, the prevalent use of mobile devices to access confidential information, the expansion of remote work, and the increased use of artificial intelligence presents new and increased risk of security breaches.

Cyber-attacks have increased in frequency, persistence, sophistication and intensity, often conducted by sophisticated and organized groups and individuals with a wide range of motives (including, but not limited to, industrial espionage, hactivists and organized crime).

Moreover, the prevalent use of mobile devices to access confidential information, remote working practices, and the increased use of artificial intelligence present new and increased risk of security breaches.

In addition to the extraction of important information, such attacks could include the deployment of harmful malware, ransomware, denial-of-service attacks, social engineering and other means to affect service reliability and threaten the confidentiality, integrity and availability of our information.

Certain types of attacks or breaches on our IT systems or infrastructure, or those of our partners and third-party providers, may go undetected for a prolonged period.

Although to our knowledge we have not experienced any material incident or interruption to date, any breakdown, invasion, corruption, destruction or breach of our, our partners’ or our third-party providers’ technology systems could compromise such IT systems and the information stored there could be accessed, modified, publicly disclosed, lost or stolen, which could result in legal claims or proceedings and liability under laws that protect the privacy of personal information, demands for ransom or other forms of blackmail, disruptions to our development programs or commercial operations, damage to our reputation and adverse effects on our business.

Certain types of attacks or breaches on our IT systems or infrastructure, or those of our licensees and third-party providers, may go undetected for a prolonged period.

This could result in legal claims or proceedings and liability under laws that protect the privacy of personal information, demands for ransom or other forms of blackmail, disruptions to our development programs or commercial operations, damage to our reputation and adverse effects on our business.

We retain cybersecurity insurance to cover costs and expenses related to a breach or similar event;

8 unchanged sentences

In addition, each of these current and potential future laws may be subject to varying interpretations by courts and government agencies, creating complex compliance issues for us and the third parties upon whom we rely.

If we fail to comply with applicable laws and regulations, we could be subject to penalties or sanctions, including criminal penalties if we knowingly obtain or disclose individually identifiable health information from a covered entity in a manner that is not authorized or permitted by the Health Insurance Portability and Accountability Act of 1996, as amended by the Health Information Technology for Economic and Clinical Health Act, or HIPAA.

Numerous other countries have, or are developing, laws governing the collection, use and transmission of personal information as well.

9 unchanged sentences

Outbreaks of contagious diseases and other adverse public health developments affecting us and/or the third parties on which we rely could have a material and adverse effect on our business, financial condition and results of operations.

For example, the COVID-19 pandemic, which impacted the operation of healthcare systems, global travel, supply and labor markets and other business and economic activity worldwide, had an adverse impact on our financial condition and results of operations.

For example, commercial sales of the medicines from which we derive revenue—including injectable medications administered by healthcare professionals—were adversely impacted as a result of COVID-19-related restrictions, labor shortages and other developments that transpired, many of which contributed to limited access to, or reduced willingness to access, healthcare providers and locations where injectable medications may be administered.

In addition, the COVID-19 pandemic disrupted, to varying degrees, the business operations of the third parties on which we rely, including our suppliers, packagers, distributors, contract research organizations, customers, clinical site investigators, community advocacy partners, and others.

Any prolonged material disruption to the third parties on which we rely could negatively impact our ability to conduct our clinical development, manufacturing or other business activities in the manner and on the timelines presently planned, which could have a material adverse impact on our business, results of operations and financial condition.

The COVID-19 pandemic also impacted, at various stages of the pandemic, the regulatory agencies with which we interact in the development, manufacture, regulatory review and commercialization of our medicines, including the FDA, the HPRA and other regulatory agencies.

Any disruptions to these agencies can negatively impact expected timelines for regulatory interactions related to, and/or review and approval of, our product candidates, which could have an adverse effect on our business and the market price of our ordinary shares.

For example, the COVID-19 pandemic, which impacted the operation of healthcare systems, global travel, supply and labor markets and other business and economic activity worldwide, had a disruptive and adverse impact on our financial condition and results of operations and on those of many of the third parties on which we rely.

Although the acute COVID-19 public health emergency has lapsed, we will continue to monitor its long-term impacts, including impacts on market practices and on the labor market, and adjust our policies and practices as needed to mitigate any adverse impacts to our business operations and financial condition.

9 unchanged sentences

Failure to comply with reporting requirements could also subject us to sanctions and/or investigations by Nasdaq or the SEC or other regulatory authorities.

The increasing use of social media platforms presents new risks and challenges.

The increasing use of social media platforms and artificial intelligence tools present new risks and challenges.

Social media is increasingly being used as a means of corporate communications and for purposes of social networking and commentary.

We are increasingly using social media tools to communicate certain information about our business, our employees, our company values and corporate responsibility initiatives, to support disease state education in our areas of focus, and to provide information about our products or development programs.

Despite our efforts to monitor evolving social media guidance and to comply with applicable rules, regulations and regulatory guidance relating to social media, such practices are evolving and not always clear.

There is a risk that the use of social media by us or our employees to communicate about our products or business may cause us to be found in violation of applicable requirements and could result in regulatory actions or legal claims against us related to off-label marketing or other prohibited activities.

In addition, our employees may knowingly or inadvertently engage on social media in ways

that may not comply with our social media policy or other legal, contractual or regulatory requirements, which may give rise to liability, lead to the loss of trade secrets and other intellectual property, or result in public disclosure of personal information of our employees, clinical trial patients, customers, and others.

In addition, negative or inaccurate posts or comments about us or our products on any social media platforms could damage our reputation, brand image and goodwill.

If such disclosures were to occur, there is a risk that we fail to monitor and comply with applicable adverse event reporting obligations or that we may not be able to defend the Company or the public’s legitimate interests due to restrictions on what we may say about our products or our business.

We use social media tools to communicate certain information about our business, our employees, our company values and initiatives, to support disease state education in our areas of focus, and to provide information about our products or development programs.

Additionally, the use of artificial intelligence tools (“AI”) is increasing in the biopharmaceutical industry and, as with many developing technologies, presents risks and challenges that could affect its further development, adoption and use.

Despite our efforts to monitor evolving guidance regarding use of social media and AI and to comply with applicable rules, regulations and regulatory guidance, such practices are evolving and can be unclear.

There is a risk that the use of social media and AI by us or our employees to communicate about our products or business or for other business purposes may cause us to be found in violation of applicable requirements and could result in regulatory actions or legal claims against us related to off-label marketing or other prohibited activities.

In addition, our employees may knowingly or inadvertently engage on social media and with AI in ways that may not comply with our social media policy or guidelines with respect to AI or other legal, contractual or regulatory requirements.

Any misuse of social media or AI may give rise to liability, lead to the loss of trade secrets and other IP, result in public disclosure of personal information of our employees, clinical trial participants, customers, patients using our products, or others, result in reputational harm or lead to other consequences.

Negative or inaccurate posts or comments about us or our products on any social media or other public platforms could also damage our reputation, brand image and goodwill.

Any of these events, if they were to occur, could cause us to incur liability, face overly restrictive regulatory actions or suffer reputational or other harm to our business.

2 unchanged sentences

Risk Management and Strategy

In the ordinary course of our business, we collect and store sensitive data, including intellectual property, proprietary business information of ours and that of our suppliers and partners, and personally identifiable information of persons who use our medicines, clinical trial participants and employees.

Our partners and third-party providers also possess certain of our sensitive data.

The secure maintenance of all such information and the secure performance of our information technology (“IT”) systems are critical to our operations and business strategy.

In the ordinary course of our business, we collect and store sensitive data, including IP, proprietary business information of ours and that of our suppliers and licensees, and personally identifiable information of persons who use our medicines, clinical trial participants and employees.

Our licensees and third-party providers also possess certain of our sensitive data.

The secure maintenance of such information and the secure performance of our information technology (“IT”) systems are critical to our operations and business strategy.

As our dependency on, and the complexity of, our IT systems increases, the confidentiality, integrity and availability of our IT systems and the data that they store is critical to managing our business.

Our Information Security Management System (“ISMS”) is a key element of our information security program, and it is designed to identify, assess, help mitigate, and monitor information technology risks across the organization, including information security risks.

Our Information Security Management System (“ISMS”) is a key element of our information security program, designed to identify, assess, help mitigate, and monitor IT risks across our organization, including information security risks.

The ISMS is informed by the structured principles of International Standard- ISO/IEC27001:2022 (Information security, cybersecurity, and privacy protection), which outlines guidance for the establishment, implementation, maintenance, and improvement of information security management systems.

Our ISMS is comprised of processes designed to identify cybersecurity risks, safeguard information assets and preserve the confidentiality, integrity , and availability of information owned, managed and maintained by us.

Our ISMS includes formal written policies and procedures, technical security controls, such as automated tools designed to detect and prevent cybersecurity incidents, and programs designed to promote internal and third-party risk management, audit management, incident response and security awareness, including employee security awareness trainings and other initiatives.

Our ISMS also includes periodic security audits, vulnerability assessments and penetration testing to proactively identify potential system vulnerabilities.

Our ISMS is periodically assessed by third-party assessors and the results of such assessments, including any cybersecurity risks identified and managed thereby, are reported to the audit and risk committee of our board of directors, as described below, and are used by us to improve our ISMS specifically and our information security program generally.

As part of our information security program, we also have a program in place for management of cybersecurity risks associated with third-party handling of our confidential information, including their provision of critical services on our behalf.

We conduct due diligence of our third-party vendors through an assessment of their security practices and overall risk profile, including through their completion of vendor assessment questionnaires and our application of established mechanisms for ongoing monitoring of such third parties, including tools such as security ratings services and periodic reassessment questionnaires.

Our ISMS includes formal written policies and procedures, technical security controls, such as automated tools designed to detect and prevent cybersecurity incidents, and programs designed to promote internal and third-party IT risk management, audit management, incident response and security awareness, including employee awareness trainings and other initiatives.

Our ISMS includes periodic security audits, vulnerability assessments and penetration testing to proactively identify potential system vulnerabilities.

Our ISMS is periodically assessed by third-party assessors and the results of such assessments, including any cybersecurity risks and related mitigations identified, are reported to the audit and risk committee of our board of directors, as described below, and are used by us to improve our ISMS and our broader information security program.

As part of our information security program, we also have processes in place for management of cybersecurity risks associated with third-party handling of our confidential information, including in such third parties’ provision of critical services on our behalf.

We conduct due diligence of our third-party vendors through an assessment of their security practices and overall risk profile, including through their completion of vendor assessment questionnaires and ongoing monitoring of such third parties, utilizing tools such as security ratings services and periodic reassessment questionnaires.

As of the date of this Annual Report, we have not experienced any information security incidents that have materially affected, or are reasonably likely to materially affect, our business strategy, results of operations, or financial condition, and we have not identified any current cybersecurity threats that we believe are reasonably likely to materially affect our business strategy, results of operations, or financial condition.

2 unchanged sentences

This governance framework includes procedures for escalation of identified information security risks, threats or incidents through various management levels, including up to our Information Security Governing Body, which is comprised of our Chief Executive Officer, Chief Information Officer, Chief Operating Officer, Chief Financial Officer, Chief Legal Officer and other members of management, and as appropriate, up to our board of directors.

Our information security team, led by our Chief Information Officer, is responsible for developing, implementing and overseeing our Company-wide information security strategy and related policies and practices.

The information security team is managed on a day-to-day basis by our Director and Executive Director of Information Security and works cross-functionally throughout the organization to assess and prepare the Company for identification and mitigation of, and if necessary response to, information security risks.

Our information security team members collectively have extensive IT, IT security and cloud industry experience, as well as certifications pertaining to information security and privacy (such as such as Certified Information Systems Security Professional, Certified Information Security Manager, Certified Information Privacy Technologist, GIAC Security Essentials and GIAC Information Security Professional certifications).

Our information security team is responsible for developing, implementing and overseeing our Company-wide information security strategy and related policies and practices.

This team works cross-functionally throughout our organization to assess and prepare the Company for identification and mitigation of, and if necessary respond to, information security risks.

The information security team is led by our Chief Information Officer , who has over 35 years of experience in various information technology roles, including 18 years at the Company serving in roles with increasing levels of responsibility.

Our Vice President of Information Security and Technology, a Certified Information Systems Security Professional, with over 20 years of global experience in various information security roles, including 14 years of experience at the Company, is responsible for day-to-day management of information security team initiatives.

The other members of the information security team have extensive IT, IT security and cloud industry experience, as well as certifications pertaining to information security and privacy (such as Certified Information Security Manager, Certified Information Privacy Technologist, GIAC Security Essentials and GIAC Information Security Professional certifications).

Our board of directors, as a whole and through its committees, has responsibility for the oversight of risk management.

The audit and risk committee of our board of directors specifically oversees critical risks and opportunities facing the Company and, in this context, reviews and provides feedback on our company-wide enterprise risk management program, which encompasses risks related to information technology and cybersecurity and mitigations put in place, or to be put in place, in response to such risks.

The audit and risk committee periodically reports to the full board of directors regarding the audit and risk committee’s oversight of the Company’s enterprise risk management program and periodic risk assessment results.

In addition, our board of directors receives periodic updates from our Chief Information Officer and our Executive Director of Information Security on the ISMS and other information security initiatives, and on our information security governance framework.

We lease approximately 14,600 square feet of corporate office space in Dublin, Ireland, which houses our corporate headquarters.

In 2023, we exercised our option to extend the lease term for a four-year period.

This extended lease expires in 2027 and does not include an additional tenant option to further extend the term.

We lease approximately 231,000 square feet of office and laboratory space in Waltham, Massachusetts.

The audit and risk committee of our board of directors specifically oversees critical risks and opportunities facing the Company and, in this context, reviews and provides feedback on our company-wide enterprise risk management program, which encompasses risks related to IT and cybersecurity and mitigations put in place, or to be put in place, in response to such risks and opportunities.

The audit and risk committee periodically reports to the full board of directors regarding its oversight of the Company’s enterprise risk management program and periodic risk assessment results.

In addition, our board of directors receives periodic updates from our CIO and Vice President of Information Security on our ISMS and other information security initiatives, and on our information security governance framework.

We lease an approximately 14,600 square foot corporate office space in Dublin, Ireland, which is our corporate headquarters.

This lease expires in 2027 and does not include an additional tenant option to further extend the term.

We lease an approximately 231,000 square foot corporate office and R&D center in Waltham, Massachusetts.

This lease, which commenced in January 2020, expires in 2035 and includes a tenant option to extend the term for an additional ten-year period.

We serve as the guarantor of a lease assigned to Mural Oncology, Inc.

for a facility in Waltham, Massachusetts with approximately 180,000 square feet of corporate offices, administrative areas and laboratories.

We serve as the guarantor of a lease assigned to Mural Oncology, Inc., a subsidiary of Mural Oncology plc, for a facility in Waltham, Massachusetts with approximately 180,000 square feet of corporate offices, administrative areas and laboratories.

This lease expires in 2026 and includes a tenant option to extend the term for an additional five-year period.

We lease approximately 7,000 square feet of corporate office and administrative space in Washington, DC.

We lease an approximately 7,000 square foot corporate office and administrative space in Washington, DC.

This lease expires in 2029 and includes a tenant option to extend the term for an additional five-year period.

We own the Athlone Facility (approximately 400,000 square feet).

In December 2023, we announced our entry into an agreement to sell this facility, which is expected to occur in mid-2024.

We own a manufacturing facility in Wilmington, Ohio (approximately 375,000 square feet).

We own an approximately 375,000 square foot manufacturing facility in Wilmington, Ohio.

We believe that our current facilities are suitable and adequate for our current and near-term preclinical, clinical and commercial requirements.

Legal Proceedings

For information regarding legal proceedings, refer to the discussion under the heading “Litigation” in Note 19, Commitments and Contingent Liabilities in the “Notes to Consolidated Financial Statements” in this Annual Report, which discussion is incorporated into this Item 3 by reference.

Mine Saf ety Disclosures

Not Applicable.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1A. Risk Factors