▸ If we are not able to successfully develop and commercialize additional products our business could be materially harmed.· · · · ● 1 ▸ If we are not successful in commercializing CASGEVY, our business could be materially harmed.· · · · ● 1 ▸ If we are unable to successfully develop and commercialize additional products, our business could be materially harmed.· · · · ● 1 ▸ If we are unable to sustain and grow revenues from sales of our CF medicines, our business would be materially harmed and the market price of our common stock would likely decline.· · · · ● 1 ▸ We may face manufacturing, supply, and distribution difficulties, among other challenges, delays, or interruptions, including at our third-party providers.· · · · ● 1 ▸ Cell and genetic therapies face increased scrutiny from the public and medical communities and commercial success will depend, in part, upon the acceptance of those communities.· · · ● ● 2 ▸ If we are not successful in commercializing CASGEVY, our revenue growth could be limited and our business could be materially harmed.· · · ● ● 2 ▸ If we are unable to successfully develop, obtain approval and commercialize treatments for acute and neuropathic pain, our business could be materially harmed.· · · ● ● 2 ▸ If we fail to scale our operations to accommodate growth, our business may suffer.· · · ● ● 2 ▸ Insurance coverage and reimbursement of cell and genetic therapies is uncertain.· · · ● ● 2 ▸ The regulatory approval process for our cell or genetic therapies involves additional consultations with regulatory agencies, costs, and potentially longer timelines as compared to those for small molecules.· · · ● ● 2 ▸ group Risks Related to Pricing of Our Products· · ● ● ● 3 ▸ Current health care laws and regulations in the U.S. and future legislative or regulatory reforms to the U.S. health care system may affect our ability to commercialize our marketed products profitably.· ● ● ● ● 4 ▸ Difficulty in enrolling patients could delay or prevent clinical trials of our product candidates, and ultimately delay or prevent regulatory approval.· ● ● ● ● 4 ▸ If we are unable to obtain or are delayed in obtaining regulatory approval, we may incur additional costs, experience delays, or be unable to commercialize our product candidates.· ● ● ● ● 4 rw ▸ Our product candidates remain subject to clinical testing and regulatory approval, and our future success is dependent on our ability to successfully develop additional product candidates for both CF and non-CF indications.· ● ● ● ● 4 ▸ We are subject to health care fraud and abuse laws, such as the FCA and the AKS, and other similar laws and regulations both in the U.S. and in non-U.S. markets.· ● ● ● ● 4 ▸ We may experience pricing pressure on our products, which could reduce our revenues and future profitability.· ● ● ● ● 4 rw ▸ If these third parties do not successfully carry out their contractual duties or meet expected deadlines, we may be· · · ● · 1 ▸ Our business depends upon the successful development and commercialization of product candidates. These product candidates are in various stages of development and must satisfy rigorous standards of safety and efficacy before they can be· · · ● · 1 ▸ Our products and any products that we develop in the future may not be able to compete effectively with marketed· · · ● · 1 ▸ The regulatory approval process and clinical trial requirements for cell and genetic therapies can be more expensive and take longer than for other, better known or more extensively studied product candidates, and regulatory requirements· · · ● · 1 ▸ There is considerable uncertainty within our industry about the validity, scope, and enforceability of many issued patents in the U.S. and elsewhere in the world, and, to date, the law and practice remains in flux both in the agencies that grant· · · ● · 1 ▸ We may later incur impairment charges related to assets acquired in any such transaction. Even if we achieve the long-· · · ● · 1 ▸ Health regulatory agencies globally may continue to experience disruptions in their operations as a result of COVID-19· · ● · · 1 ▸ In the U.S., there have been, and we expect that there will continue to be, a number of federal and state proposals to implement governmental controls that are similar to those that currently exist in Europe. For example, the ACA required· · ● · · 1 ▸ In the course of providing its services, a contract manufacturer may develop process technology related to the· · ● · · 1 ▸ We are investing significant resources in the research, development, manufacturing, and commercialization of cell and· · ● · · 1 ▸ Our effective tax rate fluctuates, and changes in tax laws, regulations and treaties, unfavorable resolution of tax contingencies or exposure to additional income tax liabilities could have a material impact on our future taxable income.· ● · · · 1 ▸ Our medicines may not gain or maintain market acceptance among physicians and patients or other members of the· ● · · · 1 ▸ The COVID-19 pandemic has broadly affected the global economy, resulted in significant travel and work restrictions in· ● · · · 1 ▸ The U.S. government, individual states and some foreign jurisdictions also have been aggressively pursuing legislative· ● · · · 1 ▸ We must devote significant resources to understanding and complying with the changing landscape in this area. Failure to comply with data protection laws may expose us to risk of enforcement actions taken by data protection authorities, private· ● · · · 1 ▸ While we have developed internal capabilities to supply product candidates for use in our clinical trials as well as our· ● · · · 1 ▸ Changes in tax laws, regulations and treaties could affect our future taxable income.● · · · · 1 ▸ If our patents do not protect our products or our products infringe third-party patents, we could be subject to litigation which could result in injunctions preventing us from selling our products or substantial liabilities.● ● ● · · 3 rw ▸ If we are unable to obtain regulatory approval, we will be unable to commercialize our drug candidates.● · · · · 1 ▸ If we fail to manage our operations effectively, our business may suffer.● ● ● · · 3 ▸ If we or our collaborators, or third-parties acting on our behalf, fail to comply with applicable continuing regulatory requirements, we or our collaborators may be subject to fines, suspension or withdrawal of regulatory approvals for specific● · · · · 1 ▸ Our business faces potential risks relating to the U.K.’s withdrawal from the E.U.● ● · · · 2 rw ▸ We also are subject to numerous foreign regulatory requirements governing the conduct of clinical trials, manufacturing and marketing authorization, pricing and third-party reimbursement. Non-U.S. jurisdictions have different approval● · · · · 1 ▸ We are dependent upon a small number of customers for a significant portion of our revenue, and the loss of, or significant reduction in sales to, these customers would adversely affect our results of operations.● ● ● · · 3 ▸ We are subject to health care fraud and abuse laws, such as the federal False Claims Act and anti-kickback laws, which prohibit off-label product promotion and other similar laws and regulations both in the U.S. and in non-U.S. markets.● · · · · 1 ▸ We are subject to risks associated with COVID-19.● ● ● · · 3 rw ▸ We have adopted anti-takeover provisions and are subject to Massachusetts corporate laws that may frustrate any attempt to remove or replace our current management or effectuate a business combination involving Vertex.● ● · · · 2 ▸ We have limited experience developing cell and genetic therapies and could experience challenges with these programs, which could result in delays or prevent the development, manufacturing and commercialization of our cell and genetic therapies.● · · · · 1 ▸ We invest significant resources in the research, development, manufacturing and supply of therapies for serious diseases, and if we are unable to successfully develop and commercialize additional products, our business could be materially harmed.● ● · ● · 3 rw ▸ We may need to raise additional capital that may not be available.● ● ● · · 3 ▸ We may not be able to attract collaborators or external funding for the development and commercialization of certain of our product candidates.● ● ● · · 3 rw ▸ A breakdown or breach of our information technology systems could subject us to liability or interrupt the operation of our business.● ● ● ● ● 5 ▸ A variety of risks associated with operating in foreign countries could materially adversely affect our business.● ● ● ● ● 5 rw ▸ Future indebtedness could materially and adversely affect our financial condition, and the terms of our credit agreements impose restrictions on our business, reducing our operational flexibility and creating default risks.● ● ● ● ● 5 ▸ If our competitors bring products with superior product profiles to market, our products may not be competitive, and our revenues could decline.● ● ● ● ● 5 rw ▸ If our facilities were to experience a catastrophic loss, our operations would be seriously harmed.● ● ● ● ● 5 ▸ If our medicines fail to achieve or maintain market acceptance, we may not be able to generate significant revenues in future periods.● ● ● ● ● 5 ▸ If our processes and systems are not compliant with regulatory requirements, we could be subject to restrictions on marketing our products or could be delayed in submitting regulatory filings seeking approvals for our product candidates.● ● ● ● ● 5 rw ▸ If physicians and patients do not accept our products, or if patients do not remain on treatment or comply with their prescribed dosing regimen, our product revenues would decline in future periods.● ● ● ● ● 5 rw ▸ If we do not comply with laws regulating the protection of the environment and health and human safety, our business could be adversely affected.● ● ● ● ● 5 ▸ If we fail to attract and retain skilled employees, our business could be materially harmed.● ● ● ● ● 5 ▸ Issuances of additional shares of our common stock could cause the price of our common stock to decline.● ● ● ● ● 5 ▸ Our ability to execute on our long-term strategy depends in part on our ability to engage in transactions and collaborations with other entities that add to our pipeline or provide us with new commercial opportunities.● ● ● ● ● 5 ▸ Our business has a substantial risk of product liability claims and other litigation liability.● ● ● ● ● 5 ▸ Our quarterly operating results are subject to significant fluctuation.● ● ● ● ● 5 ▸ Our stock price may fluctuate.● ● ● ● ● 5 ▸ group Risks Related To Our Operations● ● ● ● ● 5 ▸ group Risks Related to Business Development Activities● ● ● ● ● 5 ▸ Risks Related to Development and Clinical Testing of Our Products and Product Candidates● ● ● ● ● 5 rw ▸ group Risks Related to Financial Results and Holding Our Common Stock● ● ● ● ● 5 ▸ group Risks Related to Government Regulation● ● ● ● ● 5 ▸ group Risks Related to Intellectual Property● ● ● ● ● 5 ▸ group Risks Related to Our Business● ● ● ● ● 5 ▸ group Risks Related to Supply, Manufacturing and Reliance on Third Parties● ● ● ● ● 5 rw ▸ group SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS● ● ● ● ● 5 ▸ The use of social media platforms and artificial intelligence tools presents risks and challenges.● ● ● ● ● 5 rw ▸ There can be no assurance that we will repurchase shares of common stock or that we will repurchase shares at favorable prices.● ● ● ● ● 5 ▸ Uncertainty over intellectual property in the pharmaceutical and biotechnology industry has been the source of litigation and other disputes that are inherently costly and unpredictable.● ● ● ● ● 5 rw ▸ We are subject to various and evolving laws and regulations governing the privacy and security of personal data, and our failure to comply could adversely affect our business, result in fines and/or criminal penalties, and damage our reputation.● ● ● ● ● 5 ▸ 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 price of our common stock.● ● ● ● ● 5 ▸ We face risks in connection with existing and future collaborations with respect to the development, manufacture and commercialization of our products and product candidates.● ● ● ● ● 5 rw ▸ We have experienced challenges commercializing products outside of the U.S., and our future revenues will be dependent on our ability to obtain adequate reimbursement for our products in ex-U.S. markets.● ● ● ● ● 5 rw ▸ We may be subject to claims by third parties asserting that our employees or we have misappropriated their intellectual property, or claiming ownership of what we regard as our own intellectual property.● ● ● ● ● 5 ▸ We may not realize the anticipated benefits of existing or future acquisitions of businesses or technologies, and the integration following any such acquisition may disrupt our business and management.● ● ● ● ● 5 rw 
