VERTEX PHARMACEUTICALS INC / MA (VRTX) Risk Factors

ITEM 1A. RISK FACTORS

Investing in our common stock involves a high degree of risk, and you should carefully consider the risks and

uncertainties described below in addition to the other information included or incorporated by reference in this Annual

Report on Form 10-K. If any of the following risks or uncertainties occur, our business, financial condition or results of

operations would likely suffer, possibly materially. In that case, the trading price of our common stock could decline.

Risks Related to Our Business and Products

Our success depends on our ability to develop and commercialize additional medicines.

We invest significant resources in research and development to discover and develop transformative medicines for

people with serious diseases. Product development is highly uncertain and expensive. Product candidates may appear

promising in research and development but may fail to reach commercial success for many reasons, including:

•the failure to establish safety and efficacy through clinical trials;

•the failure to obtain marketing approval;

•the inability to manufacture on economically feasible terms;

•the failure to gain and maintain market acceptance among physicians and patients or other members of the medical

community;

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

•competition based on, among other factors, safety, efficacy, patient convenience, pricing and reimbursement.

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

harmed.

Our business is substantially dependent on the success of our CF medicines.

Substantially all our net product revenues have been derived from the sale of our CF medicines. We may be unable to

sustain or increase revenues from sales of our CF medicines in the future for any number of reasons, including the potential

introduction of competitive products or the inability to successfully develop and commercialize next-generation medications

or medicines to treat people with CF who cannot benefit from our current CF medicines. Our concentrated source of revenue

increases the risks associated with potential manufacturing or supply disruptions, safety issues that may be identified with

respect to our CF medicines, and failure to gain and/or maintain market acceptance or adequate pricing or reimbursement for

our CF medicines. If we are unable to sustain or increase revenues from sales of our CF medicines, or if we do not meet the

expectations of investors, our business would be materially harmed and our ability to fund our operations could be adversely

affected.

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

be materially harmed.

A portion of the value attributed to our company by investors is based on the expected commercial success of

JOURNAVX for acute pain and on our development programs for both acute and peripheral neuropathic pain. JOURNAVX

may not gain or maintain market acceptance among physicians, patients, or payors due to various factors, including the

availability of lower-cost alternatives, and sales, marketing, pricing, and/or distribution challenges associated with

introducing a product into a highly competitive market. Furthermore, we may not succeed in developing JOURNAVX for

additional indications or in advancing other product candidates, including NaV1.8 or NaV1.7 inhibitors, for the treatment of

acute or peripheral neuropathic pain. Even if we obtain marketing approvals for these product candidates, they will face

significant competition and there can be no assurance of commercial success.

We may not be able to increase or maintain CASGEVY product revenues.

The future commercial success of CASGEVY depends on physicians, patients, or payors accepting it as medically

useful, cost-effective, ethical, safe, and preferred with respect to current and potential future competitive therapies, and on

26

payors providing adequate reimbursement. In addition to risks generally associated with the commercialization of medicines,

the cell collection processes, manufacturing and other procedures required to manufacture and administer CASGEVY are

more complex, resource-intensive, and operationally demanding than for small molecules. For example, the cost of

manufacturing CASGEVY as a percentage of revenue is significantly higher than for our CF medicines. Moreover, market

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

which CASGEVY is administered, including those resulting from the myeloablative preconditioning regime. There can be no

assurance that we will be able to increase or maintain our revenues from CASGEVY in future periods.

Risks Related to Commercialization

We are subject to pricing and reimbursement pressures that could have a material adverse effect on our business,

revenues, and results of operations.

Revenues from our products depend, to a large degree, on the extent to which the products are purchased by customers,

such as wholesalers, pharmacies, and hospitals, and reimbursed by third-party payors, such as government health programs,

commercial insurers, and managed health care organizations. Increasingly, these third-party payors are becoming more

critical in evaluating and reimbursing medicines. The containment of health care costs continues to be a priority for many

governments, and drug pricing has been a focus in this effort. The U.S. federal government and state legislatures and foreign

governments have shown significant and evolving interest in implementing cost-containment programs, including price

controls, restrictions on reimbursement, value-based and reference pricing, compulsory licensing, including the pursuit of so-

called “march in” rights, and mandatory substitution with generic products, all of which could limit the prices of, or access to,

our products. Decisions by third-party payors to not cover a product or restrict access to a product may shift over time and

could reduce market acceptance of the product and limit product revenues. We must also compete to be placed on formularies

of managed care providers, as exclusion of our products from a formulary would limit usage by managed care providers and

patients.

In the U.S., pricing and access is primarily governed by practices of private managed care providers and institutional and

governmental purchasers, federal laws and regulations related to Medicare and Medicaid, including the ACA and the IRA,

and state activities, including the establishment of PDABs and price transparency rules. For example, in August 2023, the

Colorado PDAB selected five drugs for an affordability review, including TRIKAFTA. Although the Colorado PDAB later

found TRIKAFTA to be ineligible for an upper payment limit we cannot predict whether future reviews by the Colorado

PDAB, or any other PDAB, will come to the same conclusion about TRIKAFTA or any of our other therapies, or the amount

of any potential upper payment limit. Furthermore, changes to the health care system enacted as part of health care reform in

the U.S., as well as increased purchasing power of entities that negotiate on behalf of Medicare, Medicaid, and private

payors, could result in further pricing pressures. For example, initiatives by the U.S. government to impose most-favored-

nation pricing on U.S. prescription drug prices in government programs, including the recently proposed GUARD Model by

the CMS. While there is significant uncertainty around the related executive orders and rulemaking, mandatory initiatives

could result in reduced pricing and reimbursement for our products.

In most markets outside of the U.S., the pricing and reimbursement medicines is subject to governmental control and

governments are making greater efforts to reduce drug prices and limit drug spending. The reimbursement process in ex-U.S.

markets vary widely and can take a significant time to complete, and reimbursement decisions are made on a country-by-

country and region-by-region basis. Reimbursement for our products by governments, including the timing of any

reimbursements, may also be affected by budgetary or political constraints, particularly in challenging economic

environments. We have experienced challenges in obtaining timely reimbursement for our products in various countries

outside the U.S., and our future revenues depend on maintaining such reimbursement. There is no assurance that coverage

and reimbursement will continue for our current products or be available for our future products. Even if reimbursement is

available, there is no assurance that the timing or level of reimbursement will be sufficient. Furthermore, many ex-U.S.

governments are introducing new legislation focused on cost containment measures applicable to the pharmaceutical

industry; such legislation, if finalized, could lead to lower prices, rebates or other forms of discounts or special taxes.

Our failure to obtain or maintain adequate prices, coverage, or reimbursement for our products would have an adverse

effect on our business, revenue and results of operations, could curtail or eliminate our ability to adequately fund our research

and development programs and/or could cause a decline or volatility in our stock price.

27

Competing products and technological advances from our competitors may negatively affect our business and market

position.

Our products and product candidates face or may face competition from existing and potential competing products. See

also Item 1., Business – Competition of this Annual Report on Form 10-K. Competing products may be more effective, safer,

more effectively marketed, have lower prices or better coverage or reimbursement levels, eliminate or minimize the need for

treatment with our products or product candidates, or have other differentiating factors that negatively affect the demand for

our products or product candidates. If a competitor obtains approval and reimbursement before we do, approval and/or

reimbursement of our products or product candidates could be delayed, denied, or otherwise adversely affected. We compete

with an array of companies and other organizations, including those that have substantially greater resources, more mature

development, manufacturing and commercial organizations, and/or other competitive advantages. Smaller companies with

innovative programs or technologies are frequently acquired by and enter into collaborations with larger competitors, which

may result in the acceleration or enhancement of competitive programs. We cannot predict the timing or impact of the

introduction of competitive products. If a competing product is successfully developed and commercialized for a patient

population we are currently treating or are seeking to treat, our revenues, business or market position could be materially

adversely affected. In addition, the release of new information, including clinical data and regulatory approval timelines, by

our competitors regarding competitive products or potentially competitive product candidates can affect investors’

perceptions regarding the prospects of our products and product candidates, and has caused and may in the future cause our

stock price to decline or experience periods of significant volatility.

If we discover safety or efficacy issues with any of our products, commercialization efforts for the product could be

negatively affected, the approved product could lose its approval, and our business could be materially harmed.

After regulatory approval and launch, our products are used over longer periods of time and by larger populations of

patients than during pre-approval clinical trials. Additional clinical and non-clinical studies, such as for label expansions, new

combinations or otherwise, may also be conducted after regulatory approval. For example, as part of FDA approval for

CASGEVY, we are required to conduct post-marketing safety studies to assess certain long-term risks associated with the

treatment. Additionally, when post-marketing studies involve our marketed products, or an active pharmaceutical ingredient

thereof, they can raise new safety issues for our existing products. The subsequent discovery or appearance of previously

unknown or underestimated safety or efficacy concerns with a product could negatively affect commercial sales of the

product, result in reduced coverage or reimbursement by payors, cause reputational harm, government investigations, and/or

lawsuits against us. Subsequent adverse safety events, as well as safety or efficacy issues affecting suppliers or competing

products, may also lead to recalls, denial or withdrawal of regulatory approvals, non-renewal of conditional regulatory

approvals, label changes, obligations to conduct additional or more extensive clinical trials or to implement a risk

management plan, and reductions in market acceptance. Each of our CF products shares at least one active pharmaceutical

ingredient with another of our products. If any of our CF products were to experience safety issues or labeling modifications,

our other CF products may be adversely affected. For example, in December 2024, the FDA required us to modify the

TRIKAFTA label by revising information regarding liver injury and liver failure and moving that information from the

“warnings and precautions” section to a “boxed warning” section; the FDA required similar language in the ALYFTREK

label. In addition, safety or efficacy issues affecting suppliers’ or competitors’ products also may reduce the market

acceptance of our products.

The discovery of safety events involving our products or public speculation about such events could limit or reduce

product revenues and cause our stock price to decline or experience periods of volatility.

Risks Related to Product Development

The data from our product development activities may not support advancement or regulatory approval of our product

candidates, or label expansions for our marketed products, or provide sufficient data to support the successful

commercialization of our approved products.

Extensive testing is required for our product candidates and for new indications of our marketed products. The outcomes

of such clinical and non-clinical testing are highly uncertain, may not generate sufficient safety, efficacy, or other data, and

may not support regulatory approval of our product candidates. Clinical and non-clinical testing, and in particular our later-

stage clinical trials, are expensive and resource intensive. The data from our preclinical studies and other research activities

have in the past and may in the future fail to predict results in clinical trials. For example, despite considerable non-clinical

testing, the clinical study of VX-264 in T1D did not meet its efficacy endpoint. Similarly, results from earlier-stage clinical

28

trials may not be predictive of the results from later-stage clinical trials, or of the likelihood of approval of a product

candidate for commercial sale. In addition, interim or preliminary data from a clinical trial may not be predictive of final

results from the clinical trial and are subject to the risk that one or more of the clinical outcomes may materially change as

patient enrollment and treatment continues, more patient data become available, or as patients continue other treatments for

their disease.

The data from our clinical programs may not support approval or successful commercialization of our product

candidates, and we may be unable to recoup the significant research and development, clinical trial, acquisition-related, and

other expenses incurred, which could have an adverse effect on our business, financial condition and results of operations,

and/or cause our stock price to decline or experience periods of volatility.

In addition, results of our clinical trials and findings from nonclinical studies could lead to abrupt changes in our

development activities, including the possible cessation of development activities associated with a particular product

candidate or program. For example, after VX-264 did not meet its efficacy endpoint, we announced that the program would

not advance into further clinical studies. Failure to advance product candidates through clinical development would impair

our ability to commercialize products, which could materially harm our business, financial condition and long-term prospects.

Our research and development activities are highly regulated, and it is possible that the FDA and other regulatory

authorities:

•pause or halt our clinical trials based on their assessment of the potential or actual risks of continuing;

•disagree with our conclusions about the results from our clinical trials;

•require additional clinical trials, including confirmatory trials, or disagree with our clinical trial design or endpoint;

•fail to approve the facilities or processes used to manufacture a product candidate, or our dosing or delivery

methods;

•grant marketing approval that is more restricted than anticipated, including limiting indications to narrow patient

populations and imposing safety monitoring requirements, or risk evaluation and mitigation strategies;

•withdraw approval of a product or indication, including when the product or indication was approved under an

accelerated approval pathway and confirmatory studies were unsuccessful.

Furthermore, we periodically release new information, including clinical data, regarding our products and product

candidates, which may affect investors’ perceptions regarding our products and product candidates, and cause our stock price

to decline or experience periods of significant volatility. For example, our stock price decreased in August 2025 after we

released Phase 2 data for VX-993 and informed investors that the FDA did not see a path toward a broad peripheral

neuropathic pain label for suzetrigine at that time. The timing of the release of information by us regarding our product

development programs is often beyond our control and is influenced by the timing of receipt of communications from

regulators and data from our clinical trials, among other things.

If we fail to successfully conduct our clinical activities, our clinical trials or future regulatory approvals may be delayed or

denied.

Conducting clinical trials is a complex, lengthy and expensive process. Our ability to complete clinical trials on our

anticipated timelines depends on numerous factors, including proper and efficient protocol design, regulatory and institutional

review board approval, adequate patient enrollment and retention rates, and compliance with current good clinical practices.

Delays or complications in clinical trials may arise from difficulties in enrolling or retaining patients, competition from other

clinical trials, the occurrence of significant and/or unexpected adverse safety events, changes in regulatory requirements,

supply chain issues or disruptions at clinical trial sites. Further, we may face additional challenges identifying and enrolling

sufficient patients for clinical trials for rare diseases and cell and gene therapies due to small patient populations. With respect

to cell and genetic therapies there may be additional concerns regarding the safety of these more novel therapeutic approaches

to the treatment of these diseases. If we or our third-party clinical trial providers, including contract research organizations

(“CROs”), do not successfully conduct and manage our clinical activities or adequately comply with regulatory requirements,

our clinical trials may experience delays or increased costs, and the potential regulatory approval of a product candidate or

29

expansion of a label for a marketed product may be delayed or denied. Any delay in obtaining required regulatory approvals

could adversely affect our ability to successfully commercialize a product candidate.

Regulatory, Intellectual Property and Other Legal Risks

The extensive regulatory framework governing the health care industry could adversely affect our ability to obtain

approval and market our medicines and failure to comply with these regulations could result in fines, penalties or other

non-monetary remedies.

The health care industry is highly regulated and subject to complex and increasing regulations. U.S. federal and state

regulators, including the FDA and comparable ex-U.S. regulators directly regulate our most critical business activities,

including those related to research, development, manufacturing, and commercialization, as described in Item 1, “Business –

Government Regulation.”

The process for obtaining regulatory approvals to market a product is costly and time consuming, and approvals may not

be granted for future products, or additional indications of existing products, on a timely basis or at all. In addition, we cannot

guarantee that we will remain compliant with applicable regulatory requirements once approval has been obtained. These

requirements govern, among other things, our manufacturing practices, communications regarding our products, and

reporting of safety events. Maintaining compliance with these extensive regulations is complex, expensive, and time

consuming, and failure to comply may result in additional regulatory actions, including recalls, withdrawal or suspension of

product approvals, civil and criminal charges, reputational harm, and fines, penalties, or other monetary or non-monetary

remedies, including exclusion from receipt of payment from U.S. federal and state healthcare programs like Medicare and

Medicaid. Compliance with the regulatory requirements for biologics and cell and gene therapies can be more burdensome,

expensive and time-consuming than for other, better known or more extensively studied types of medicines, such as small

molecules. Regulatory requirements governing cell and genetic therapy products have changed frequently and may continue

to change in the future. Furthermore, risks relating to compliance with laws and regulations may be heightened as we

continue to expand our global operations and enter new therapeutic areas with different patient populations, which may

require different commercialization activities from those we currently utilize.

We expect that regulation of the healthcare industry will continue to evolve through political and legal action, as future

proposals to reform healthcare systems are considered by U.S. and foreign governments and regulatory authorities. We

cannot predict when additional changes in the healthcare industry in general, or the pharmaceutical industry in particular, will

occur, or what the impact of such changes may be. For example, new proposals or requirements regarding local

manufacturing of pharmaceutical products, enhanced data security and privacy measures, sustainability, importation

restrictions, embargoes, or trade sanctions may negatively impact our business. In addition, our development and

commercialization activities could be harmed or delayed by a shutdown of the U.S. government or events that affect the

manner in which the FDA operates.

Commercialization of our products requires that we operate in compliance with applicable health care laws, including

laws regulating promotional activities, prohibiting fraud and abuse and requiring reporting of government pricing

information.

We market our products to health care providers and provide promotional materials and informational programs

regarding the use of each product in these patient populations. In jurisdictions where permitted, we also market our products

to patients for whom the applicable product has been approved, as well as to their caregivers. If a regulatory authority

interprets any of our conduct, including our marketing practices or patient support programs, as promotion of unapproved

uses or otherwise false and misleading, it could request that we modify or withdraw our promotional materials or issue

corrective advertising. It could also take enforcement action, such as issuing warning or untitled letters, prohibiting certain of

our activities, seizing products, and imposing civil fines and criminal penalties. It is also possible that other federal, state, or

foreign enforcement authorities might take action if they believe that the alleged conduct led to the submission and payment

of claims for unapproved uses of our product, which could result in significant fines or penalties. Even if it is later determined

we were not in violation of these laws, we may be faced with negative publicity, incur significant expenses defending our

actions, and have to divert significant management resources from other matters.

Our interactions with health care providers that prescribe or purchase our products are also subject to laws and

regulations designed to prevent fraud and abuse in the sale and use of medicines and that place significant restrictions on the

marketing practices of biopharmaceutical companies. The relationships between companies and health care providers are

30

scrutinized and have been the target of lawsuits and investigations alleging various problematic conduct, including

submission of incorrect pricing information, improper promotion of pharmaceutical products, payments intended to influence

the referral of health care business, submission of false claims for government reimbursement, and anticompetitive behavior.

We are required to track and disclose financial interactions with health care providers and health care organizations, which

may increase government and public scrutiny of these financial interactions. Failure to comply with these reporting

requirements could result in significant civil monetary penalties. As we commercialize products for new patient populations

and in new geographies, we will have more interactions with a broader set of healthcare providers and we must continue to

expend significant efforts to establish, maintain and enhance systems and processes to comply with laws and regulations

governing those interactions.

Government price reporting and payment regulations are also complex, requiring us to continually assess the methods by

which we calculate and report pricing in accordance with these obligations. Our methodologies for calculations are inherently

subject to assumptions and may be subject to review and challenge by various government agencies, which may disagree

with our interpretation. If the government disagrees with our reported calculations, we may need to restate previously

reported data and could be subject to additional financial and legal liability.

If we are unable to obtain, maintain and enforce our intellectual property rights, our business could be harmed.

Our success depends, in significant part, on our ability to obtain, maintain, and enforce patents and intellectual property

rights such as trademarks and copyrights that protect our products, product candidates, and technologies. In addition, we rely

upon trade secret protection and contractual arrangements to protect certain of our proprietary information. Due to the

complexity of the legal standards and factual questions relating to the patentability, validity, and enforceability of patents

covering pharmaceutical and biotechnological inventions and the scope of claims made under these patents, our ability to

obtain, maintain and enforce our patents is uncertain. The initial grant of patents or regulatory exclusivity in the U.S. and ex-

U.S. markets depends upon decisions of the patent offices, courts, and governments in those countries. We may fail to obtain,

defend or otherwise preserve patent and other intellectual property rights, including certain forms of regulatory exclusivity,

and our current intellectual property rights or protections and those we obtain in the future may not be broad enough or

sufficient to protect our commercial interests in all countries where we conduct business.

In the U.S. and ex-U.S. markets, third parties have challenged and may continue to challenge, invalidate, or circumvent

our patents and patent applications relating to our products, product candidates, and technologies. We have had and may

continue to have disputes with respect to the rights to products, product candidates, and technologies developed in

collaboration with other parties. If we cannot resolve disputes and obtain adequate intellectual property right protections, we

may not be able to develop or market our products. Settlements of such proceedings could also result in reducing the period

of exclusivity and other protections, resulting in a reduction in revenue from affected products. Any litigation, including

litigation related to Abbreviated New Drug Applications (“ANDA”), litigation related to 505(b)(2) applications, interference

proceedings to determine priority of inventions, derivations proceedings, inter partes review, oppositions to patents in foreign

countries, litigation against our collaborators, or similar actions, could harm our business.

Difficulties in, or preclusion from, protecting our intellectual property rights in foreign jurisdictions could substantially

harm our business. Third-party manufacturers may be able to sell generic versions of our products in countries that do not

provide effective mechanisms for enforcement of our patents or other intellectual property rights. For example, we have

experienced a violation of our intellectual property rights in Russia, where a copy product that infringes our patents has been

made available. In addition, many foreign countries have compulsory licensing laws under which a patent owner must grant

licenses to third parties in certain circumstances. Compulsory licenses have been used in certain countries for market access

purposes and, in some cases, as a cost-containment measure. Compulsory licenses issued for our patents may diminish or

reduce revenue from those jurisdictions and negatively affect our results of operations. Third parties may also illegally

distribute and sell counterfeit versions of our products. Copy or counterfeit products may not meet our rigorous

manufacturing and testing standards and a patient who receives such product may be at risk for a number of dangerous health

consequences. Our business and reputation could suffer harm as a result of illegally produced and distributed generic versions

of our products, as well as counterfeit products sold under our brand name. The diversion of products from their authorized

market into other channels may result in reduced revenues and negatively affect our profitability.

31

If we are not able to operate without infringing upon intellectual property rights of third parties, our business could be

harmed.

Our competitors seek to protect their products, product candidates and proprietary information through patents,

trademarks, trade secrets, and copyrights. Third parties have claimed and may claim in the future that our products or other

activities infringe their intellectual property rights or that our employees have misappropriated their intellectual property

rights. See also Item 1., Business – Intellectual Property of this Annual Report on Form 10-K. Resolving an intellectual

property infringement or other claim can be costly and time consuming and may require us to enter into license agreements,

which may not be available on commercially reasonable terms. A successful claim of patent infringement or other violation

or misappropriation of intellectual property rights by a third party could subject us to significant damages and/or an

injunction preventing the manufacture, sale, or use of the affected product or products, and/or require us to pay royalties or

redesign our infringing products, which may be impossible or require substantial time and monetary expenditure.

Our business has a substantial risk of product liability claims and other litigation liability.

The testing, manufacturing, marketing and use of our products and product candidates involve substantial risk of product

liability claims. These claims may be made directly by consumers, patients, healthcare providers, or others. Product liability

claims and lawsuits and safety alerts or product recalls, regardless of their ultimate outcome, may decrease demand for our

products or any product candidate for which we obtain marketing approval, and may have a material adverse effect on our

business, results of operations, reputation, and our ability to market our products. Our product liability and clinical trial

insurance may not provide adequate coverage against all potential liabilities.

There continues to be a significant volume of government and regulatory investigations and litigation against companies

operating in our industry, as well as robust regulatory enforcement and whistleblower claims. Investigations into aspects of

our business include inquiries, subpoenas, and other types of information demands from government and regulatory

authorities. We are also involved in and are subject to other various legal proceedings, including litigation, and other dispute-

related proceedings. These activities require significant financial and internal resources. This includes the arbitration initiated

by the third party to whom the CFF has assigned its ALYFTREK royalty rights. Please see Item 7. Management’s Discussion

and Analysis of Financial Condition and Results of Operations of this Annual Report on Form 10-K for more information.

The outcome of such legal proceedings, investigations or any other dispute-related proceedings are inherently uncertain and

adverse developments or outcomes can result in significant expenses, monetary damages, penalties, injunctions, or other

relief against us, and in the ALYFTREK arbitration, could result in higher future costs of goods if royalty fees are higher than

anticipated. For a description of our litigation, investigation and other dispute-related matters, see Note P., Commitments and

Contingencies — Legal Matters and Other Contingencies, included in this Annual Report on Form 10-K.

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

We are subject to a variety of evolving and developing data privacy and security laws and regulations in various

jurisdictions related to the collection, storage, use, sharing, and security of personal data, including health information.

Regulators globally are imposing data privacy and security requirements, such as the E.U.’s GDPR and other domestic data

privacy and security laws, such as the California Consumer Privacy Act and the California Privacy Rights Act. These and

other similar types of laws and regulations that have been or may be passed often include requirements with respect to

personal information. Compliance with privacy laws and regulations is a rigorous and time-intensive process that may

increase our cost of doing business or require us to change our business practices. Failure to comply may result in liability

through government enforcement, private actions, civil and criminal fines and penalties, litigation, and reputational harm.

Although we are not directly subject to HIPAA, we could face penalties, including criminal liability, for knowingly obtaining

or disclosing protected health information from non-compliant HIPAA-covered entities. The commercialization of cell and

genetic therapies involves processing more personal data than traditional therapies, increasing our risk exposure.

Furthermore, the number of government investigations, enforcement actions, and class action lawsuits related to data security

incidents and privacy violations, particularly focused on online data sharing, continue to increase. Government investigations

typically require significant resources and generate negative publicity, which could harm our business and reputation.

32

Risks Related to Our Operations

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

including at our third-party providers.

We could be subject to significant supply interruptions for our commercial products or product candidates as a result of

disruptions to our internal manufacturing capabilities or those of our suppliers or partners. Supply disruptions may result from

a variety of factors, including shortages in product raw materials or labor, technical difficulties, regulatory inspections or

restrictions, delays in construction, regulatory approval, and inspection of new facilities or the expansion of existing facilities,

shipping or customs delays, inability to maintain compliance with quality or other regulations, including cGMP requirements,

general global supply chain disruptions, and performance failures by us or any third-party manufacturer on which we rely.

Disruption in our supply chain or manufacturing capabilities can result in shipment delays, inventory shortages, lot failures,

product withdrawals, recalls and other interruptions in the commercial and clinical supply of our products and product

candidates. Any such disruption with respect to our commercial products could result in a failure to meet market demand,

could negatively affect our patients, could reduce our net product revenues and/or increase our costs. Any such disruption in

the supply of product candidates to our clinical trials could negatively affect the subjects enrolled in our clinical trials and/or

cause delays in our clinical trials and applications for regulatory approval.

Additionally, unfavorable geopolitical events could affect our ability to interact with or conduct business with specific

vendors within our global supply network or could prevent or delay the transportation of supplies or products to their planned

destination. For example, we depend on China-based suppliers for portions of our supply chain. Finding alternative suppliers

due to geopolitical developments or otherwise may not be feasible or could take a significant amount of time and involve

significant expense due to the nature of our products and the need to obtain regulatory approvals.

If we are unable to maintain and expand our supply chain and manufacturing capabilities, our ability to develop our

product candidates and manufacture our products would be harmed.

We continue to invest in and expand our manufacturing capabilities and supplier relationships to ensure the stability of

our supply chains and to support the anticipated demand for our products. Establishing, managing and expanding our global

manufacturing capabilities and supply chain, particularly as we enter new therapeutic modalities, requires significant

financial commitment. This includes the creation and maintenance of numerous third-party contractual relationships upon

which we rely. There can be no assurance that we will be able to identify, establish and maintain additional manufacturers or

capacity for our product candidates and products on a timely basis, on commercially reasonable terms, or at all. The

foregoing risks may be heightened where our products and the materials that we utilize in our operations are manufactured by

only one supplier or at only one facility. In addition, in the course of providing its services, a contract manufacturer may

develop process technology related to the manufacture of our products or product candidates that the manufacturer owns,

either independently or jointly with us. This would increase our reliance on that manufacturer or require us to obtain a license

from that manufacturer to have our products or product candidates manufactured by other suppliers utilizing the same

process.

In addition, we and our CMOs and corporate partners are subject to cGMP, as well as comparable regulations in other

jurisdictions. Manufacturing operations are also subject to routine inspections by regulatory agencies. Even after a supplier is

qualified by the regulatory authority, the supplier must continue to expend time, money and effort in the area of production

and quality control to maintain full compliance with applicable regulatory requirements, including cGMP. If, as a result of

these inspections, a regulatory authority determines that the equipment, facilities, laboratories or processes do not comply

with applicable regulations and conditions of product approval, the regulatory authority may suspend the manufacturing

operations. There can be no assurance that we or our CMOs and corporate partners will be able to remedy any deficiencies

cited by FDA or other regulatory agencies in their inspections.

Furthermore, the manufacturing and logistics for drug products are highly complex and can require significant

investment, including to scale-up manufacturing processes and to secure capacity at third parties with expertise to meet our

requirements. This capacity may be limited by the number of other clinical trials and commercial manufacturing ongoing for

other companies seeking similar support. 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. Additionally,

even with relevant experience and expertise, drug manufacturers often encounter difficulties in scale-up and production,

including difficulties with production costs and yields, quality control, and compliance with federal, state and foreign

33

regulations, which can prevent manufacturers from completing clinical trials or commercializing products on a timely or

profitable basis, if at all.

Reliance on third-party relationships could adversely affect our business.

Our business depends on relationships with third parties, including activities critical to research, development,

manufacturing, commercialization, and technology. For example, we rely on third parties such as CROs for the day-to-day

management and oversight of our clinical trials, on CMOs for active ingredient manufacturing and finishing operations, and

on logistics providers for the distribution of our products. We are expanding our relationships with CROs, CMOs, and other

third parties as we enter markets in which we have no or limited experience. Failure by any of our third parties to meet their

contractual, regulatory, or other obligations, any disruption in the relationship between Vertex and a third party upon whom

we rely, or the failure of a third party to conduct activities in accordance with our expectations, could adversely affect the

relevant research, development, manufacturing, commercial, or administrative activity and our business. The foregoing risks

may be heightened as a result of the limited number or specialized nature of certain third parties, as we may not be able to

replace such third party in a timely manner, on commercially reasonable terms, or at all.

The third parties upon which we rely are subject to their own operational and financial risks, as well as other difficulties,

which, if realized, could negatively affect our business. If any of our third parties violate, or are alleged to have violated, any

laws or regulations, including anti-corruption or anti-bribery regulations, the GDPR, or other laws and regulations, during the

performance of their obligations to us, we could suffer financial and reputational harm or other negative outcomes, including

possible legal consequences.

If we fail to scale our operations to accommodate growth, our business may suffer.

As we continue to expand our global operations and capabilities, we face increasing demands on our management and

infrastructure. To effectively manage our growing business, we need to:

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

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

•effectively leverage technology and automation where appropriate to enable efficient growth and remain

competitive;

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

prioritization;

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

•expand our compliance and legal resources.

A variety of risks associated with operating in foreign countries could materially adversely affect our business.

Our global operations subject us to risks that could adversely affect our business and revenue. In addition to the ex-U.S.

risks we face with respect to compliance with local laws and regulatory requirements, pricing and reimbursement, intellectual

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

with operating a global biotechnology company include the potential for:

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

foreign economies and markets;

•business interruptions resulting from geo-political actions, including war and terrorism;

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

which appear to have increased in the current political environment;

•credit risks related to our customers, which may be higher in less developed markets; and

•global or regional public health emergencies.

34

If any of the above risks were to occur, our revenues, results of operations, financial condition or business could be

materially harmed.

Current or future U.S. legislation, including executive orders, or other new changes in laws, regulations or policies in the

U.S. or other countries could negatively impact our business by increasing costs, decreasing demand for our products, and

increasing government cost controls, among other risks. For example, U.S. legislation has been introduced to limit certain

U.S. biotechnology companies from using equipment or services from select Chinese biotechnology companies, and others in

Congress have advocated for limitations on those Chinese service providers’ ability to engage in business in the U.S. We

cannot predict what actions may ultimately be taken with respect to trade relations between the United States and China or

other countries, what products and services may be subject to such actions, the effective date or duration of such actions, or

what actions may be taken by the other countries in response to actions by the United States. If we are unable to obtain or use

services from existing service providers or become unable to export or sell our products to any of our customers or service

providers, our business could be materially and adversely affected.

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

adversely affect our business.

We maintain and rely extensively on information technology systems and network infrastructures, internally and with

third parties for the effective operation of our business. We collect, store, and transmit confidential information, including

personal information, financial information and intellectual property. Disruption, infiltration, or failure of our information

technology systems because of software or hardware malfunctions, computer viruses, cyber-attacks, employee theft or

misuse, power disruptions, natural disasters or accidents could cause breaches of data security and/or loss of critical data,

which in turn could materially adversely affect our business.

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

Cyber-attacks are carried out by well-resourced groups and individuals with a wide range of motives and expertise. Due to

the nature of some cyber-attacks and incidents, there is a risk that they may remain undetected for a period of time. Recent

developments in the threat landscape include the use of adversarial artificial intelligence techniques and machine learning, as

well as an increased number of cyber extortion attacks with higher financial ransom demand amounts and increasing

sophistication and variety of ransomware techniques. Cyber-attacks and incidents also include manufacturing, hardware or

software supply chain attacks, which could cause disruption to or a delay in the manufacturing of our products or product

candidates, or lead to data privacy or security breach. We use cloud technologies and any failure by cloud or other technology

service providers to adequately safeguard their systems and prevent cyber-attacks or data privacy incidents could disrupt our

operations and result in misappropriation, corruption, or loss of confidential or proprietary information. The third parties

upon which we rely face similar risks and when they experience a security breach of their systems, our security can be

adversely affected.

Like many companies, we have experienced immaterial cybersecurity incidents, including temporary service

interruptions of third-party suppliers. There can be no assurance that our efforts to protect our data and information systems

will prevent breakdowns or breaches in our systems that could adversely affect our business. While we maintain cyber

liability insurance, this insurance may not be sufficient to cover the financial, legal, business or reputational losses that may

result from an interruption or breach of our systems and those of critical third parties. Cybersecurity incidents can cause the

loss of critical or sensitive information, including personal information, and could give rise to legal liability and regulatory

action under data protection and privacy laws.

In addition, we face certain risks as we seek to leverage artificial intelligence to optimize productivity and efficiency in

various aspects of the organization. Flaws, biases, or malfunctions in these systems could lead to operational disruptions, data

loss, or erroneous decision-making, impacting our operations, financial condition, and reputation. Ethical and legal

challenges may arise, including biases or discrimination in generated outcomes, non-compliance with data protection

regulations and laws specifically governing the use of artificial intelligence systems and tools, and lack of transparency.

Furthermore, the deployment of artificial intelligence systems could expose us to increased cybersecurity threats, such as data

breaches and unauthorized access. We also face competitive risks if we do not implement artificial intelligence or other

machine learning technologies in a timely fashion.

35

Our operations may be disrupted by the occurrence of a natural disaster, catastrophic event, or by other serious accidents

occurring at our facilities.

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

facilities. If any of our major facilities were to experience a catastrophic loss due to an earthquake, flood, severe storms, fire

or similar event, our operations would be seriously harmed. For example, our corporate headquarters, as well as additional

leased space that we use for certain logistical and laboratory operations and manufacturing, are located in a flood zone along

the Massachusetts coast. If we are unable to effectively implement our business continuity plans, we may experience delays

in recovery of data and/or an inability to perform vital corporate functions, which could result in a significant disruption in

our operations, large expenses to repair or replace the facility and/or the loss of critical data. Additionally, we use hazardous

materials in some of our facilities, and any accident, injury or other loss related thereto could result in substantial liability.

Our property or other relevant insurance may not be sufficient to cover all potential losses that may result from an

interruption to our operations or damage resulting from these risks.

Strategic and Financial Risks

Our business development strategy, including strategic transactions and collaborations, may not be successful, and there

may be delays or failures in realizing the anticipated benefits of these activities.

As part of our business strategy, we seek to enter into strategic transactions to acquire, license, or collaborate with other

entities, in each case that have potential to complement and advance our ongoing research, development, manufacturing, and

commercialization efforts. Over the last several years we have engaged in a number of strategic transactions and

collaborations, including our acquisition of Alpine and its lead asset, povetacicept, as well as several smaller transactions and

collaboration arrangements. See also Item 1., Business – Strategic Transactions of this Annual Report on Form 10-K. Our

future transactions and collaborations may be similar to prior transactions, may be structured differently from prior

transactions, or may involve larger transactions or later-stage assets. We face significant competition for potential strategic

transactions and collaborations from a variety of other companies, some of which have significantly more financial resources

and experience in business development activities. We may not complete future transactions in a timely manner, or at all,

including due to the possibility that a governmental entity or regulatory body may delay or refuse to grant approval for the

consummation of the transaction.

We may not realize the anticipated benefits of our completed or future strategic transactions. The product candidates or

products contemplated by those transactions may be delayed or terminated at any point during research or clinical

development. Even if a product is approved, we may not be able to successfully commercialize it. As a result, we may fail to

generate expected revenue growth or income contribution within the anticipated timeframe or at all. We also face risks that

we:

•may not effectively integrate acquired assets or businesses into our ongoing business;

•may incur additional expenses or fail to achieve anticipated cost savings related to the strategic transactions;

•may incur impairment charges related to assets acquired in any such transactions; or

•may acquire unanticipated liabilities.

In addition, future strategic transactions could result in potentially dilutive issuances of equity securities or the incurrence

of debt.

We continue to collaborate with outside partners on research, development, manufacturing, and/or commercialization

activities with respect to product candidates and products. We face the same research, development, manufacturing, and

commercialization risks with respect to product candidates and products that are subject to collaborations as with product

candidates and products that we have developed ourselves. We face additional risks in connection with our current and future

collaborative arrangements, including with respect to the performance of the collaborator and their compliance with

contractual obligations.

36

Our effective tax rate fluctuates, and changes in tax laws, regulations and treaties, unfavorable resolution to the tax

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

taxable income.

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 may be different than experienced in the past due to numerous factors, including:

•changes in the mix of our profitability from country to country;

•tax authority examinations/audits of our tax filings;

•adjustments to the value of our uncertain tax positions;

•changes in accounting for income taxes; and

•changes in tax laws or modifications of treaties in various jurisdictions.

Any of these factors could cause us to experience an effective tax rate that is significantly different from previous periods

or our current expectations. For example, actions taken with respect to tax-related matters by associations such as the

Organisation for Economic Co-operation and Development and the European Commission could influence tax laws in

jurisdictions in which we operate, such as the enactments by both E.U. and non-E.U. member countries of a global minimum

tax. 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. We regularly assess the probable outcomes of these audits to determine the

appropriateness of our tax provision, and we have established contingency reserves for material tax exposures. However,

there can be no assurance that we will accurately predict the outcomes of these disputes or other tax audits or that issues

raised by tax authorities will be resolved at a financial cost that does not exceed our related reserves and the actual outcomes

of these disputes and other tax audits could have a material impact on our results of operations or financial condition.

Changes in foreign currency rates, interest rate risks, the value of our investment portfolio, and inflation affect our results

of operations and financial condition.

Fluctuations in currency exchange rates and interest rates, changes in the value of our investment portfolio, and inflation

have affected and will continue to affect our cash flows, results of operations, and financial condition. The exchange rates

among our reporting currency, the U.S. dollar, and the currencies in which we do business are volatile and our efforts to

mitigate against these risks may not be successful. We invest our available cash in a range of investments, including

investments in cash equivalents and debt securities, and fluctuations in interest rates, among other factors, could materially

negatively affect the value of this investment portfolio. In addition, systemic economic downturns, as well as inflationary

pressures, such as those observed in recent periods, may adversely impact our business and financial results. See also Item

7A., Quantitative and Qualitative Disclosures About Market Risk of this Annual Report on Form 10-K.

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

impose restrictions on our business.

If we borrow under our current credit agreement or any future credit agreements, or otherwise issue or incur additional

debt, such indebtedness could have important consequences to our business. The credit agreement requires that we comply

with certain financial covenants, including a consolidated leverage ratio covenant and negative covenants, restricting or

limiting our ability and the ability of our subsidiaries to, among other things, incur additional indebtedness, grant liens,

engage in certain investment, acquisition and disposition transactions, and enter into transactions with affiliates. As a result,

we may be restricted from engaging in business activities that may otherwise improve our business. Failure to comply with

the covenants could result in an event of default that could trigger acceleration of our indebtedness. If we incur additional

indebtedness, the risks related to our business and our ability to service or repay our indebtedness would increase.

There can be no assurance that we will repurchase shares of common stock or that we will repurchase shares at favorable

prices.

In May 2025, our Board of Directors approved a share repurchase program pursuant to which we are authorized to

repurchase up to $4.0 billion of our common stock from time to time through open market or privately negotiated

transactions, of which $618.5 million has been repurchased as of December 31, 2025. Our stock repurchases will depend

37

upon, among other factors, market conditions, our cash balances and potential future capital requirements, results of

operations, financial condition, and other factors that we may deem relevant. We can provide no assurance that we will

repurchase stock at favorable prices, if at all.

General Risk Factors

Our stock price is volatile.

Our stock price is subject to significant fluctuations. From January 1, 2025 to December 31, 2025, our common stock

traded between $362.50 and $519.68 per share. Our future stock price could be significantly and adversely affected by:

•announcements or investor analyst commentary regarding the clinical development of our product candidates as new

information, including efficacy and safety information becomes available;

•our financial guidance and/or financial results, including quarterly and annual fluctuations resulting from factors

such as the timing and amount of our revenues and expenses; and

•other factors including the risks described in these “Risk Factors.”

Fluctuations in our stock price can result in substantial losses for shareholders. Following periods of volatility in the

market price of a company’s securities, shareholder derivative lawsuits and securities class action litigation are common.

Such litigation, if instituted against us or our officers and directors, could result in substantial costs and other harm to our

business.

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

We must attract and retain highly qualified and trained scientists, as well as employees with experience in the

development, manufacture, and commercialization of medicines, including biologic and cell and genetic therapies. We face

intense competition for such talent from our competitors, other companies, academic institutions, and other organizations

throughout our industry, especially with respect to employees with expertise in cell or genetic therapies. Our compensation

program, including equity awards, may not be sufficient to retain employees, especially if our stock price declines or other

employers offer more attractive opportunities. Our ability to commercialize our products and achieve our research and

development objectives depends on our ability to respond effectively to these demands. If we are unable to hire and retain

qualified personnel, our ability to advance our pipeline, commercialize our products, and achieve our business objectives

could be materially adversely affected.

The use of social media platforms presents risks and challenges.

Social media is increasingly used by patients, advocacy groups, and other third parties to discuss our products and

product candidates. Social media posts may include statements about efficacy or adverse events that could create reporting

obligations or regulatory scrutiny. Our employees’ use of social media also presents risks, including potential noncompliance

with legal or regulatory requirements, inappropriate disclosure of confidential information or personal information, and loss

of intellectual property. In addition, misinformation, negative sentiment, or impersonation of our business on social media

could cause reputational damage or otherwise harm our business. Failure to appropriately manage these risks could result in

regulatory actions, liability, or other adverse consequences.

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

that may frustrate any attempt to remove or replace members of our board or to effectuate certain types of business

combinations involving us.

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 combinations involving us.

Our by-laws allow the Board of Directors to adjourn any meetings of shareholders prior to the time the meeting has been

convened. We may issue shares of any class or series of preferred stock in the future without shareholder approval and upon

such terms as our Board of Directors may determine. The rights of the holders of common stock will be subject to, and may

be adversely affected by, the rights of the holders of any class or series of preferred stock that may be issued in the future.

Massachusetts state law also prohibits us from engaging in specified business combinations with an interested stockholder,

subject to certain exceptions, unless the combination is approved or consummated in a prescribed manner, and places

38

restrictions on voting by any shareholder who acquires 20% or more of the aggregate shareholder voting power without

approval by non-interested shareholders. As a result, shareholders or other parties may find it difficult to remove or replace

our directors or to effectuate certain types of business combinations involving us.

SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS

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 Condition and Results of Operations

set forth in Part II, Item 7, contains forward-looking statements. Forward-looking statements are not purely historical and

may be accompanied by words such as “anticipates,” “may,” “forecasts,” “expects,” “intends,” “plans,” “potentially,”

“believes,” “seeks,” “estimates,” and other words and terms of similar meaning. Such statements may relate to:

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

revenues, costs and expenses, and other gains and losses;

•our expectations regarding clinical trials, including expectations for patient enrollment, development timelines, the

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

submissions for our therapies;

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

and TDT, ALYFTREK for the treatment of CF, and JOURNAVX for the treatment of moderate-to-severe acute

pain, and the anticipated launch of povetacicept for the treatment of IgAN;

•our ability to maintain and obtain adequate reimbursement for our products and product candidates, our ability to

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

approval, and our ability to obtain label expansions for existing therapies;

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

CF eligible and able to receive our medicines and providing improved treatment options for people who are already

eligible for one of our medicines, and our beliefs that the majority of people with CF will transition to ALYFTREK

over time;

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

for further investigation, clinical trials or potential use as a treatment, including with respect to povetacicept as a

pipeline-in-a-product and as a potential best-in-class approach for the treatment of IgAN, pMN, and gMG;

•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, including our plans

to complete the full submission for potential accelerated approval of povetacicept in IgAN in the first half of 2026

and to share data from the interim analysis of the Phase 2/3 clinical trial of inaxaplin in AMKD in late 2026 or early

2027 and from the Phase 2 trial in people with AMKD in mid-2026;

•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

regarding the clinical benefits of JOURNAVX without the evidence of the several limitations of other available

therapies;

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

programs, and our strategy to develop our pipeline programs, alone or with third-party collaborators;

•our beliefs regarding the approximate patient populations for the disease areas on which we focus;

•the potential benefits and therapeutic scope of our acquisitions and collaborations, including our acquisition of

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

regarding our agreements with Zai, Ono and WuXi;

•our expectations regarding the lower royalty burden for ALYFTREK;

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

capabilities, including for biologic and cell and gene therapies;

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

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

acquisition targets;

39

•our ability to expand and protect our intellectual property portfolio and otherwise maintain exclusive rights to

products;

•our expectations or beliefs regarding any legal proceedings in which we are involved, including any litigation,

arbitration or other similar proceedings involving our products, product candidates or activities;

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

payments or other obligations;

•potential fluctuations in foreign currency exchange rates and the effectiveness of our foreign currency management

program;

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

and interest income;

•our expectations regarding our provision for or benefit from income taxes and the utilization of our deferred tax

assets;

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

and significant unmet medical needs;

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

threats to our information technology systems;

•our ability to effectively implement artificial intelligence systems and tools;

•our ability to attract and retain skilled personnel;

•our expectations involving governmental cost containment and other regulatory efforts;

•our expectations surrounding the competitive landscape facing our products and product candidates; and

•our liquidity and our expectations regarding the possibility of raising additional capital.

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 statements. These risks,

uncertainties, and other factors include, but are not limited to, those described in our Risk Factors, set forth in Part I, Item 1A,

and elsewhere in this report and those described from time to time in our future reports filed with the Securities and Exchange

Commission.

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. Except as required by law, we undertake no obligation to publicly update any

forward-looking statements. The reader is cautioned not to place undue reliance on any such statements.