Vertex Pharmaceuticals (VRTX) Risk Factor Changes

•the effectiveness of our governance, plans and strategy with respect to managing cybersecurity risks and other

•our ability to use our research programs to identify and develop new product candidates to address serious diseases

•our expectations regarding the amount of cash to generated by operations, our cash balance and expected generation

•the establishment, development and maintenance of collaborative relationships, including potential milestone

•potential business development activities, including the identification of potential collaborative partners or

•our plans to expand, strengthen, and invest in our global supply chains and manufacturing infrastructure and

Alpine and its lead asset, povetacicept, its potential to become a pipeline-in-a-product, and our expectations

•our plans to continue investing in our research and development programs, including anticipated timelines for our

•our beliefs regarding the support provided by clinical trials and preclinical and nonclinical studies of our therapies

•our expectations regarding our ability to continue to grow our CF business by increasing the number of people with

launch, commercialize and market our products or any of our other therapies for which we obtain regulatory

•our beliefs, expectations, and plans with respect to the commercial launches of CASGEVY for the treatment of SCD

expected timing of data from our ongoing and planned clinical trials, and regulatory authority filings and other

•our expectations regarding the amount of, timing of, and trends with respect to our financial performance, including

We have adopted provisions in our articles of organization and by-laws and are subject to Massachusetts corporate laws

The use of social media platforms presents risks and challenges.

Future indebtedness could materially and adversely affect our financial condition, and the terms of our credit agreements

positions we have taken, and exposure to additional income tax liabilities could have a material impact on our future

A breakdown or breach of our information technology systems, or unauthorized access to confidential information could

•global or regional public health emergencies.

which appear to have increased in the current political environment;

•import and export licensing requirements, tariffs, trade barriers, and other trade and travel restrictions, the risks of

•economic weakness, including recession and inflation, or political instability globally or with respect to particular

property, manufacturing capabilities and supply chain, foreign exchange risks, and reliance on third parties, risks associated

•expand our compliance and legal resources.

•effectively grow, train and manage our global employee base; and

•improve our administrative, financial and management processes, including decision-making processes and budget

•enhance our operational and financial infrastructure, including data and information controls;

•implement and clearly communicate corporate-wide strategies and effectively prioritize resources;

We may face manufacturing, supply, and distribution delays, difficulties, and disruptions, among other challenges,

We are subject to various and evolving laws and regulations governing the privacy and security of personal data.

acceptance continues to be dependent in part on the prevalence and severity of side effects associated with the procedure by

If we are unable to successfully develop and commercialize medicines for acute and neuropathic pain, our business could

If we are not able to successfully develop and commercialize additional medicines, our business would be materially

•the failure to obtain adequate pricing or reimbursement levels from third-party payors or foreign governments; and

•the inability to manufacture on economically feasible terms;

•the failure to obtain marketing approval;

Risks Related to Our Business and Products

Any such forward-looking statements are made on the basis of our views and assumptions as of the date of the filing and are not estimates of future performance.

Forward-looking statements are subject to certain risks, uncertainties, or other factors that are difficult to predict and could cause actual events or results to differ materially from those indicated in any such sta…

•our beliefs that ALYFTREK will provide additional clinical benefits to eligible people with CF, regarding the durable efficacy and effectiveness of CASGEVY as one-time functional cure for people with SCD and TDT, and…

•the data that will be generated by ongoing and planned clinical trials and the ability to use that data to advance compounds, continue development, support regulatory filings, or accelerate regulatory approval, inclu…

This Annual Report on Form 10-K, including the descriptions of our Business set forth in Part I, Item 1, our Risk Factors set forth in Part I, Item 1A, and our Management’s Discussion and Analysis of Financial Conditi…

Provisions of our articles of organization, by-laws and Massachusetts state laws may frustrate any attempt to remove or replace members of our current Board of Directors and may discourage certain types of business co…

In February 2023, our Board of Directors approved a share repurchase program pursuant to which we are authorized to repurchase up to $3.0 billion of our common stock from time to time through open market or privately…

In addition, we may issue additional common stock or restricted securities in the future as part of financing activities or business development activities and any such issuances may have a dilutive effect on our then…

The majority of our unvested RSUs are likely to vest based on our employees’ continued employment.

As of December 31, 2024, we had 256.9 million shares of common stock issued and outstanding.

Issuances of additional shares of our common stock could cause the price of our common stock to decline.

as well as other factors that are beyond our control.

In July 2022, we entered into a credit agreement providing for a $500.0 million revolving credit facility.

Any new information regarding our products and product candidates, or competitive products or potentially competitive product candidates, can substantially affect investors’ perceptions regarding our future prospects.

We expect that results from our clinical development activities and the clinical development activities of our competitors will continue to be released periodically, and may result in significant volatility in the pri…

Our operating results have fluctuated from quarter to quarter in the past, and we expect that they will continue to do so in the future.

Our quarterly operating results are subject to significant fluctuation.

We are subject to ongoing tax audits in various jurisdictions, and local tax authorities may disagree with certain positions we have taken and assess additional taxes.

implemented that affect accounting periods withing our group starting on or after December 31, 2023, the full impact of this initiative on our effective tax rate will depend on the timing of implementation within each…

Various jurisdictions in which the group operates, including the U.K.

Our effective tax rate is derived from a combination of applicable tax rates in the various places that we operate globally.

Our effective tax rate fluctuates, and changes in tax laws, regulations and treaties, unfavorable resolution to the tax positions we have taken or exposure to additional income tax liabilities could have a material im…

Following periods of volatility in the market price of a company’s securities, stockholder derivative lawsuits and securities class action litigation are common.

•general worldwide or national economic, political and capital market conditions, including as a result of inflation and rapid fluctuations in interest rates.

•business development, capital structuring or financing activities; and

•developments relating specifically to other companies and market conditions for pharmaceutical and biotechnology stocks or stocks in general;

•information disclosed by third parties regarding our business or products;

•developments in patent or other intellectual property rights or announcements relating to these matters;

•public concern as to the safety of drugs developed by us or our competitors;

•technological innovations or the introduction of new drugs by our competitors;

•developments in domestic and international governmental policy or regulation, for example, relating to drug pricing and tax law changes;

•announcements we make or commentary by public equity analysts with respect to clinical development of the product candidates in our pain program;

•announcements of FDA actions with respect to our therapies or those of our competitors, or regulatory filings for our therapies or those of our competitors, or announcements of interim or final results of clinical tr…

•the information contained in our quarterly earnings releases, including updates regarding our commercialized products or our product candidates, our net product revenues and operating expenses for completed periods a…

Market prices for securities of companies such as ours are highly volatile.

Social media is being used by third parties to communicate about our products and product candidates and the diseases our therapies are designed to treat.

Most of our operations, including our research and development activities, are conducted in a limited number of facilities.

If our facilities were to experience a catastrophic loss, our operations would be seriously harmed.

Due to the highly technical nature of our drug discovery and development activities, we require the services of highly qualified and trained scientists who have the skills necessary to conduct these activities.

If we fail to attract and retain skilled employees, our business could be materially harmed.

Our business depends on relationships with third parties for a variety of functions, including activities critical to supply and manufacturing, commercialization, research and development, and technology.

We rely on third parties to carry out our operations.

Cyber-attacks are increasing in their frequency, sophistication, and intensity, and are becoming increasingly difficult to detect.

We maintain and rely extensively on information technology systems and network infrastructures for the effective operation of our business.

A breakdown or breach of our information technology systems could subject us to liability or interrupt the operation of our business.

We have product liability insurance and clinical trial insurance in amounts that we believe are adequate to cover this risk.

•Substantial monetary awards to patients or other claimants; and

•Distraction of management’s attention from our primary business;

•Costs as a result of related litigation;

•Withdrawal of clinical trial participants;

•New or increased warnings on our product labels;

•Impairment of our business reputation and exposure to adverse publicity;

•Inability to successfully commercialize approved products;

•Decreased demand for our approved products, such as TRIKAFTA and ALYFTREK, or any product candidate for which we obtain marketing approval;

The use of our approved products and our product candidates exposes us to the risk of product liability claims.

For example, we pay royalties on certain sales of TRIKAFTA/KAFTRIO, SYMDEKO/SYMKEVI, KALYDECO, ORKAMBI and ALYFTREK pursuant to our agreement with the Cystic Fibrosis Foundation.

We are or may be involved in various legal proceedings, including securities/shareholder matters and claims related to product liability, intellectual property, employment law, competition law, data privacy, and breac…

In addition, our international operations are subject to regulation under U.S.

Our revenues are subject to foreign exchange rate fluctuations due to the global nature of our operations.

trade.

These risks are increased with respect to countries such as China that have substantially different local laws and business practices and weaker protections for intellectual property.

•production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; and