Investing in VERTEX PHARMACEUTICALS INC / MA's common stock involves a high degree of risk.

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The trading price of Vertex PHarmaceuticalS Inc /MA'scommon stock could decline.

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VERTEX PHarmaceuticalS Inc /MA rely on third parties to conduct pre-clinical work, clinical trials and other activities.

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Third parties may not perform satisfactorily.

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Risks associated with the global CO-19 pandemic could adversely affect the Company's business, financial condition and growth prospects.

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The company is investing significant resources in the research and development of medicines for serious diseases.

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Product development is highly uncertain and expensive.

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There can be no guarantee that the number of patients that are eligible for enrollment in clinical trials or treatment with the company's drug candidates will turn out to be able to turn them into successful treatments.

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If one or more competing therapies prove to be superior to Vertex PHarmaceuticalS Inc /MA's then existing products and/or drug candidate, the company's business could be materially adversely affected.

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Drugs are more widely used by patients once approval has been obtained.

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Discovery of previously unknown or underestimated problems with a product could negatively affect commercial sales.

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In most ex-U.S. markets, the pricing and reimbursement of therapeutic and other pharmaceutical products is subject to governmental control.

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Complying with these laws is expensive and requires significant personnel and operational resources and deters focus on the business.

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Third-party payors throughout the world also have been attempting to control drug spending through various other actions.

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VERTEX PHARMACEUTICALS INC. cannot predict the ultimate content, timing or effect of any healthcare reform legislation or action.

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There is no assurance that coverage and reimbursability will be available outside of the U.S. for Vertex PHarmaceuticalS Inc /MA's four approved medicines or any future medicine.

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For programs addressing rare genetic diseases with small patient populations, there may not be able to identify, recruit and enroll a sufficient number of patients.

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There are many risks that could result in delays and additional costs, including the need to hire and train qualified employees and obtain access to necessary equipment and third-party technology.

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There also is significant uncertainty related to the insurance coverage and reimbursement of cell or genetic therapy products.

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VERTEX PHarmaceuticalS Inc /MA's business depends upon the successful development and commercialization of drug candidates.

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Drug candidates must satisfy rigorous standards of safety and efficacy before they can be approved for sale by the FDA.

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Discovery and development efforts for new pharmaceutical products are resource-intensive and may take 10 to 15 years or longer for each drug candidate.

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VERTEX PHARMACEUTICALS INC / MA may seek a Fast Track, Priority Review, Breakthrough Therapy, and/or RMAT designation for some of its drug candidates.

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Drug candidates that receive one or more of these designations may be eligible for, among other things, a priority regulatory review.

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The ability to enroll patients in VERTEX PHARMACEUTICALS INC / MA's clinical trials is subject to a number of factors.

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Clinical trials are expensive and require significant operational resources.

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Delays in patient enrollment or unforeseen drop-out rates may result in increased costs and longer development times.

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Manufacturers are prohibited from promoting their products for such off-label uses.

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Failure to comply with the reporting requirements could result in significant civil monetary penalties.

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VERTEX PHARMACEUTICALS INC / MA participate in the Medicaid Drug Rebate Program, the 340B Drug Pricing Program and a number of other federal and state government pricing programs.

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Changes to the price reporting or rebate requirements of these programs would affect VERT EX PHarmaceuticals' obligations.

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The E.U.

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General Data Protection Regulation, or GDPR, went into effect in 2018.

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Failure to comply could lead to fines of up to 4% of the total worldwide annual revenue for the preceding financial year, whichever is higher.

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California has passed the California Consumer Privacy Act, which went to effect on January 1, 2020.

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The ability of third parties to review and/or analyze data from the company's clinical trials may increase the risk of commercial confidentiality breaches.

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Additional federal, state and local laws and regulations affecting the business may be adopted in the future.

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The firm could be held liable for resulting damages, which can be substantial.

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The cost of acquiring, in-licensing or otherwise obtaining rights to such drugs and technologies has grown dramatically in recent years.

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It is challenging to effectively integrate businesses or technologies.

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Collaborators may have limited experience in developing, manufacturing and commercializing therapies.

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Disagreements with collaborators, including disagreements over proprietary rights, contract interpretation or the preferred course of development, might cause delays or termination of the research, development orCommercialization of drug candidate.

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VERTex PHarmaceuticalS Inc /MA's drug candidates could be subject to significant supply disruptions outside of its control.

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Third party manufacturers may supply raw materials and manufacturing product ready for distribution.

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Establishing, managing and expanding this global supply chain requires a significant financial commitment and the creation and maintenance of numerous third-party contractual relationships.

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Supply disruptions may result from a number of factors, including shortages in product raw materials, labor or technical difficulties, regulatory inspections or restrictions.

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VertEX PHarmaceuticalS Inc /MA engage third party contractors to support numerous other research, commercial and administrative activities.

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Failure of any thirdparty contractor to conduct activities in accordance with VEREX.

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PHARMA UTILITY S.C.E.’s expectations could adversely affect the relevant research,.

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development,.

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commercial or administrative activity.

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The company's ability to obtain and defend U.S. and foreign patents.

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The Leahy-Smith America Invents Act includes a number of significant changes to U.S. patent law.

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VERTEX PHARMACEUTICALS INC / MA cannot be certain that it was the first to invent or file a patent application on a drug or drug candidate.

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Many foreign jurisdictions do not protect intellectual property rights in the same way as the United States.

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Because of the extensive time required for the discovery, development, testing and regulatory review of drug candidates, it is possible that a patent may expire before a drug candidate can be commercialized.

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Uncertainty over intellectual property in the pharmaceutical and biotechnology industry has been the source of litigation and other disputes.

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There is considerable uncertainty within VERTEX PHARMACEUTICALS INC / MA's industry about the validity, scope and enforceability of many issued patents.

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CRisPR has licensed certain rights to a worldwide patent portfolio.

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Patents and patent applications in this portfolio have been the subject of numerous contentious proceedings in the U.S., Europe and other jurisdictions.

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Risks associated with operating a global biotechnology company include: - workforce uncertainty in countries where labor unrest is more common than in the U.S. - business interruptions resulting from geo-political actions, including war and terrorism.

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The effects on VERTEX PHARMACEUTICALS INC / MA's research, development, manufacturing and commercialization activities, including the virtual launch of KAFTRIO in the E.U., will be dependent on the severity and duration of the Pandemic.

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Any negative impacts that materialize could materially adversely affect the company's operations, financial performance, stock price and other risk factors.

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The U.K. formally withdrew from the E.U.

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on January 31, 2020.

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The high cost of living can make it difficult to attract employees from other parts of the country.

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With respect to product liability and clinical trial risks, in the ordinary course of business VERTEX PHARMACEUTICALS INC / MA are subject to liability claims and lawsuits, including potential class actions.

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A breakdown or breach of the company's information technology systems could subject the firm to liabilities.

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Most of VERTEX PHarmaceUTICALS INC / MA's operations are conducted in a limited number of facilities.

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If any of the company's major facilities were to experience a catastrophic loss, due to an earthquake, severe storms, fire or similar event, the operations could be seriously harmed.

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Social media practices in the pharmaceutical and biotechnology industries are evolving.

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Foreign exchange rate fluctuations due to the global nature of VERT EX PHarmaceuticalS Inc /MA's operations may affect the company's operating results.

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The timing of the release of information by the Company regarding its drug development programs can substantially affect investors’ perceptions about the firm's future prospects.

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VERT EX PHarmaceuticalS Inc /MA may need to raise additional capital that may not be available.

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The company may have to curtail significantly or discontinue one or more of its research, drug discovery or development programs.

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In 2019, VERTEX PHARMACEUTICALS INC / MA entered into a credit agreement providing for a $500 million revolving facility.

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In September 2020, the company entered in to a second credit deal for $2.0 billion.

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The credit agreements include negative covenants, subject to exceptions, restricting or limiting the Company's ability to incur additional indebtedness.

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VertEXPHARMaceUTicals INC. /MA's ability to obtain reimbursement for its medicines in ex-U.S. markets and its expectations regarding the possibility of raising additional capital are among the factors that could cause actual events or results to differ.

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The trading price of Vertex PHarmaceuticalS Inc /MA'scommon stock could decline.

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Current health care laws and regulations in the U.S. and future legislative or regulatory reforms may affect the Company's ability to commercialize its marketed products profitably.

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- If regulatory authorities interpret any of VERTEX PHARMACEUTICALS INC. / MA's conduct as being in violation of applicable health care laws, the company may be subject to civil or criminal penalties.

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The Company may not realize the anticipated benefits of acquisitions of businesses or technologies.

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VERTEX PHarmaceuticalS Inc / Ma invest significant resources in the research and development of medicines for serious diseases.

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Product development is highly uncertain and expensive, and product candidates that may appear promising may fail to reach commercial success.

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If one or more competing therapies prove to be superior to the existing products and/or product candidates, Vertex PHarmaceuticals Inc /MA's revenues could decline.

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Mergers and acquisitions in the pharmaceutical and biotechnology industries may result in even more resources being concentrated among a smaller number of competitors.

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Products are more widely used by patients once approval has been obtained.

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Discovery of previously unknown or underestimated problems with a product could negatively affect commercial sales of the product.

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In most ex-U.S. markets, the pricing and reimbursement of therapeutic and other pharmaceutical products is subject to governmental control.

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Government authorities are making greater efforts to limit or regulate the price of drug products.

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Third-party payors throughout the world also have been attempting to control drug spending.

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VERTEX PHarmaceUTICALS INC / MA face increased enforcement activity by the U.S. federal government, state governments, and private payors against pharmaceutical and biotechnology companies.

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The company cannot predict the ultimate content, timing, or effect of any health care reform legislation or action.

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There is no assurance that coverage and reimbursement will be available outside of the U.S. for any future medicines.

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For programs addressing rare genetic diseases with small patient populations, the Company may not be able to identify, recruit and enroll a sufficient number of patients in adequate and timely manner.

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The FDA established the Office of Tissues and Advanced Therapies within its Center for Biologics Evaluation and Research, or CBER, to consolidate the review of cell therapies.

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The commercial success of cell and gene therapy treatments will depend, in part, on the acceptance of physicians, patients, and third-party payers.

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Negative public opinion or more restrictive government regulations may delay or impair the successful commercialization.

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It is impossible to predict when or if any of the Company's product candidates will prove effective and safe in humans.

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Failure to advance product candidate through clinical development could impair the Corporation's ability to ultimately commercialize products.

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Results of nonclinical studies conducted concurrently with clinical trials could lead to abrupt changes in the development activities associated with a particular product.

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Many companies in the pharmaceutical and biotechnology industries have suffered significant setbacks in later-stage clinical trials.

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Third party review and scrutiny could result in public misconceptions regarding the company's drugs and product candidates.

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VERTEX PHARMACEUTICALS INC / MA may seek a Fast Track, Priority Review, Breakthrough Therapy, and/or RMAT designation for some of its product candidates.

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Non-U.S. jurisdictions have different approval procedures than those required by the FDA.

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For planning purposes, VERTEX PHarmACEUTICALS INC / MA estimate the timing of the accomplishment of various scientific, clinical, regulatory, and other product development goals.

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Delays in patient enrollment or unforeseen drop-out rates may result in increased costs and longer development times.

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The FDA and other regulatory agencies closely regulate the post-approval marketing and promotion of products.

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VERTEX PHARMACEUTICALS INC. market its products to eligible people with CF for whom the applicable product has been approved.

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Vertex participates in the Medicaid Drug Rebate Program, the 340B Drug Pricing Program and a number of other federal and state government pricing programs.

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Changes to the price reporting or rebate requirements of these programs would affect VERTex's obligations to paid rebate or offer discounts.

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VERT EX PHarmaceuticals Inc / Ma may experience delays in filing for regulatory approval for VertEXPHARMaceUTicalSInc /MA's product candidate.

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There is a risk that there may be a change to V ERTC's business practices.

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Commercialization of cell and gene therapies requires the collection and processing of a greater amount of personal data than traditional therapies.

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Failure to comply with data protection laws may expose VERTEX PHARMACEUTICALS INC / MA to risk of enforcement actions.

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Research and development efforts involve the regulated use of hazardous materials, chemicals, and various controlled and radioactive compounds.

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If an accident occurs, the company could be held liable for resulting damages, which may be substantial.

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Acquisitions, licensing arrangements and other strategic transactions are inherently risky.

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VERTEX PHARMACEUTICALS INC / MA may later incur impairment charges related to assets acquired in any such transaction.

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If a collaborator were to be involved in a business combination with a third party, it might de-emphasize or terminate the development or commercialization of any product candidate licensed to it.

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VERTEX PHARMACEUTICALS INC / MA may not be able to attract collaborators or external funding.

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Third-party contract manufacturers perform different parts of VERTEX PHARMACEUTICALS INC / MA's manufacturing process.

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Supply disruptions may result from a number of factors, including shortages in product raw materials, labor or technical difficulties, regulatory inspections or restrictions, shipping or customs delays.

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If VERTEX PHARMACEUTICALS INC / MA's third-party manufacturers become unable or unwilling to continue manufacturing product, a disruption in the commercial supply of medicines could have a significant effect on patients and business.

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To ensure the stability of the company's supply chains, it continues to develop alternatives.

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Failure of any third-party contractor to conduct activities could adversely affect the relevant research, development, commercial or administrative activity.

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Leahy-Smith America Invents Act made a number of significant changes to U.S. patent law in 2011.

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The issuance of a patent is not conclusive as to its inventorship, scope, validity, or enforceability.

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Any litigation, including litigation related to Abbreviated New Drug Applications, may delay the introduction of Vertex's products into the market.

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Litigation may be necessary in some instances to determine the validity and scope of certain of VERTEX PHARMACEUTICALS INC / MA's proprietary rights.

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The outcome of such litigation could adversely affect the legality of the company's patent.

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CRISPR has licensed certain rights to a worldwide patent portfolio.

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In addition to the Broad Institute, other third parties have filed patent applications claiming CRISPR/Cas9-related inventions.

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Defense of these claims, regardless of their merit, could involve substantial litigation expense.

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Payments under any licenses that the company are able to obtain would reduce the profits derived from the covered products.

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The company is subject to risks related to operating in foreign countries.

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Risks associated with operating a global biotechnology company include: - workforce uncertainty in countries where labor unrest is more common than in U.S.

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High cost of living can make it difficult to attract employees from other parts of the country to Vertex PHarmaceuticalS Inc /MA's Massachusetts headquarters.

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If immigration laws change in a manner that increases restrictions on immigration, there could be a material adverse effect on the firm's business.

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There can be no assurance that VERTEX PHARMACEUTICALS INC. / MA's sites will remain open.

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Any site closure, pause, or delay of a clinical trial could harm the company's operations.

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Health regulatory agencies globally may experience disruptions in their operations as a result of the COVID-19 pandemic.

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On January 31, 2020, the U.K. formally withdrew from the E.U.

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VERTEX PHARMACEUTICALS INC / MA's European headquarters and European research facility are located in the UK.

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The company may be involved in various legal proceedings.

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A disruption, infiltration, or failure of VERTEX PHARMACEUTICALS INC. / MA's information technology systems could adversely affect the company's business.

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Cyber-attacks are increasing in their frequency, sophistication, and intensity.

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Most of VERTEX PHARMACEUTICALS INC / MA's operations are conducted in a limited number of facilities.

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Social media practices in the pharmaceutical and biotechnology industries are evolving, which creates uncertainty and risk of noncompliance with regulations applicable to the business.

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The Tax Cuts and Jobs Act of 2017 eliminates the currently available option to deduct research and development expenditures.

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Recommendations from the Organization for Econo mic Co-operation and Development that are part of the base erosion and profit shifting framework could result in changes in tax laws.

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Risk Factors include variable amounts of revenues, expenses related to business development activities, changes in the fair value of VERTEX PHARMACEUTICALS INC / MA's strategic investments.

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Foreign exchange rate fluctuations due to the global nature of the company's operations may affect its operating results, often in unpredictable ways.

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VERT EX PHarmaceuticalS Inc /MA may have to curtail significantly or discontinue one or more of its research, drug discovery or development programs, including clinical trials.

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The terms of the Company's credit agreements impose restrictions on its business, reducing its operational flexibility and creating default risks.

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As of December 31, 2021, VERTEX PHarmaceUTICALS INC / MA had 254.5 million shares of common stock issued and outstanding.

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As of the same date, the company also had outstanding options to purchase 3.6 million Shares of Common Stock with a weighted-average exercise price of $141.76 per share.

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VERTEX PHARMACEUTICALS INC / MA's views and assumptions are not estimates of future performance.

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