Except as set forth below, there have been no material changes to the risk factors previously disclosed in Part I, "Item 1A. Risk Factors" of our Annual Report on Form 10-K for the year ended December 31, 2025, filed with the SEC on February 18, 2026. “Topline” and preliminary data or observed trends from our clinical trials that we announce or publish from time to time may change as more patient data become available and are subject to audit and verification procedures that could result in material changes in the final data. From time to time, we have disclosed and in the future may publicly disclose preliminary or “topline” data or observed trends from our clinical trials, which are based on a preliminary analysis of then-available data, and the results and related findings and conclusions are subject to change following a more comprehensive review of the data related to the particular study or clinical trial. We also make assumptions, estimations, calculations and conclusions as part of our analyses of data, and we may not have received or had the opportunity to fully and carefully evaluate all data. As a result, the “topline” or preliminary results that we report may differ from future results of the same studies, or different conclusions or considerations may qualify such results, once additional data have been received and fully evaluated. Additionally, trends that we observe at one point in a study or trial may not exist at the time of a later analysis or at the conclusion of a study or trial. “Topline” data also remain subject to audit and verification procedures that may result in the final data being materially different from the data we previously published. As a result, preliminary or “topline” data or trends should be viewed with caution until the final data and analyses are available. For instance, we have conducted a preliminary review of blinded two-year data from our PREVAIL CVOT trial and have observed certain trends, including a Year 1 MACE event rate that is consistent with the event rate observed in BROADWAY and a greater than expected Year 1-to-Year 2 decline in MACE events, that have led us to prepare to conduct an interim analysis in that trial. However, the blinded PREVAIL data available to us is preliminary and subject to change as additional MACE events continue to be identified and adjudicated (including with respect to the Year 1-to-Year 2 period). Additionally, the Year 1 and Year 1-to-Year 2 MACE event trends observed to date may not be indicative of future trends. Our review of additional blinded data from PREVAIL as it becomes available could negatively impact our assessment of the potential benefits of conducting the interim analysis. Additionally, while we are currently observing a Year 1 MACE event rate in PREVAIL that is consistent with the event rate observed in BROADWAY, and a greater than expected Year 1 to Year 2 decline in MACE events, these trends are based on blinded data and may not be driven by a treatment effect of the obicetrapib treatment arm. For example, the MACE event rates in the placebo arm may be less than we expect due to continued advances in the standard of care for this patient population, heightened medical care and better risk factor management in trial participants or other currently unanticipated or unknown factors. Further, others, including regulatory authorities and collaboration or regional partners, may not accept or agree with our assumptions, estimates, calculations, conclusions or analyses or may interpret or weigh the importance of data differently, which could impact the value of our particular program, the approvability or commercialization of obicetrapib or any future product candidate and our company in general. In addition, the information we choose to publicly disclose regarding a particular study or clinical trial is based on what is typically extensive information, and you or others may not agree with what we determine is material or otherwise appropriate information to include in our disclosure. If the “topline” or preliminary data or observed trends that we report differ from actual results, or if others, including regulatory authorities, disagree with the conclusions reached, our ability to obtain approval for, and commercialize, obicetrapib may be harmed, which could significantly harm our business, financial condition, results of operations and prospects. Interim data or results of interim analyses from our clinical trials that we announce or publish from time to time may not meet pre-specified criteria or endpoints to support continuation of our clinical trials and may change as additional patient data become available. We have disclosed and in the future may disclose interim data or results of interim analyses from our clinical trials. There is a risk that any interim data or the results of interim analyses we disclose in the future may not meet pre-specified criteria or endpoints to support continuation of the clinical trial. Interim data and analyses from clinical trials that we may complete are also subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more patient data become available or as patients from our clinical trials continue other treatments for their disease. Adverse differences between interim data and final data could significantly harm our 32 business prospects. Further, disclosure of interim data or results of interim analyses by us or by our competitors could result in volatility in the price of our Ordinary Shares. For example, we expect to conduct an interim analysis of our Phase 3 PREVAIL CVOT in the fourth quarter of 2026. The interim analysis will be conducted by the DSMB for the trial and will remain blinded to us. Based on certain pre-specified criteria that we have set, as well as other considerations for which the DSMB has discretion, the DSMB may recommend that the trial be stopped early for efficacy or for futility or that the trial continue until the full target number of MACE events has occurred. The interim analysis will be based on a lower number of total MACE events than the trial protocol for PREVAIL contemplates being available at the conclusion of the trial and may, as a result, fail to detect a statistically significant treatment benefit of obicetrapib, if one exists. If, as a result of the interim analysis, the DSMB recommends that PREVAIL is discontinued for futility, our business prospects may be substantially harmed. If the trial is not stopped early for efficacy or futility, we expect to complete the trial by the end of 2027. Any material difference between the final data and any interim data or results of analyses we disclose could materially negatively impact our likelihood of receiving regulatory approval or, along with any other delays in our ability to file for marketing approval, could require significant additional time and expenditure. If the interim data or results of interim analyses that we report do not support continuation of our clinical trials or differ from final results, our ability to obtain approval for, and commercialize, obicetrapib may be harmed, which could significantly harm our business, financial condition, results of operations and prospects. Current and future legislation and executive actions affecting the healthcare industry, including healthcare reform, may impact our business generally and may increase limitations on reimbursement, rebates and other payments, which could adversely affect third-party coverage of our products, our operations and/or how much or under what circumstances healthcare providers will prescribe or administer obicetrapib, if approved. The United States and some foreign jurisdictions are considering or have enacted a number of legislative and regulatory proposals to change the healthcare system in ways that could affect our ability to sell obicetrapib or any other commercialized product profitably. Among policy makers and payors in the United States and elsewhere, there is significant interest in containing healthcare costs, improving quality and expanding access. In the United States, the pharmaceutical industry has been a particular focus of these efforts and has been significantly affected by major federal and state legislative initiatives and executive actions. For example, the IRA sets forth meaningful changes to drug product reimbursement by Medicare. The IRA, among other things, (i) directs HHS to negotiate the price of certain high-expenditure, single-source drugs and biologics covered under Medicare, and subjects drug manufacturers to civil monetary penalties and a potential excise tax for offering a price that is not equal to or less than the negotiated “maximum fair price” under the law, and (ii) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation. Specifically, with respect to price negotiations, Congress authorized Medicare to negotiate lower prices for certain single-source drug and biologic products that do not have competing generics or biosimilars and are reimbursed under Medicare Part B and Part D (the "Negotiation Program"). Starting in 2029 and for all subsequent years, CMS may negotiate prices for 20 high-cost drugs paid for by Medicare Part B or Part D. The Negotiation Program applies to drug products that have been approved for at least 7 years at the time of selection and biologics that have been licensed for 11 years at the time of selection. Nonetheless, because CMS may establish a "maximum fair price" for certain products in price negotiations, we may be exposed to government action if our product candidates, if approved, become the subject of Medicare price negotiations. Moreover, these provisions of the IRA may further heighten the risk that, if our product candidates are approved, we would not be able to achieve the expected return on such product candidates or realize the full value of the patents protecting them, including if prices are set after such product candidates have been on the market for seven years. The IRA permits HHS to engage in price-capped negotiation to set the price of certain drugs and biologics reimbursed under Medicare Part B and Part D. The IRA contains statutory exclusions to the Negotiation Program, including for certain orphan-designated drugs for which the only approved indication (or indications) is for the orphan disease or condition. Should our product candidates be approved and covered by Medicare Part B or Part D and fail to fall within a statutory exclusion, such as that for orphan drugs, those products could, after a period of time, be selected for negotiation and become subject to prices representing a significant discount from average prices to wholesalers and direct purchasers. The IRA also establishes a rebate obligation for drug manufacturers that increase prices of Medicare Part B and Part D covered drugs at a rate greater than the rate of inflation. The IRA may require us to pay rebates if we increase the cost of a covered Medicare Part B or Part D approved product faster than the rate of inflation. In addition, the law eliminates the coverage gap or “donut hole” under Medicare Part D beginning in 2025, significantly lowers the beneficiary maximum out-of-pocket cost, and requires manufacturers to subsidize, through a newly established manufacturer discount program, 10% of Part D enrollees’ prescription costs for brand drugs below the out-of-pocket maximum and 20% once the out-of-pocket maximum has been reached. Our cost-sharing responsibility for any approved product covered by Medicare Part D could be significantly greater under the newly redesigned Part D benefit structure compared to the pre-IRA benefit design. Additionally, manufacturers that fail to comply with certain provisions of the IRA may be subject to penalties, including civil monetary 33 penalties. The IRA is anticipated to have significant effects on the pharmaceutical industry and may reduce the prices we can charge and reimbursement we can receive for our products, among other effects. The One Big Beautiful Bill Act of 2025 (“OBBBA”) also included significant reforms to Medicaid, including an estimated $1 trillion in reduced federal Medicaid spending from 2025 through 2034 and the imposition of work requirements for certain enrollees. These changes are expected to reduce overall Medicaid enrollment and to reduce the services covered by Medicaid, which could adversely affect the sales of any product candidates that we commercialize. In addition, as a result of the Budget Control Act of 2011, providers are subject to Medicare payment reductions of 2% per fiscal year, which went into effect on April 1, 2013. This 2% reduction was temporarily suspended during the COVID-19 pandemic, but has since been reinstated and, unless Congress and/or the Executive Branch take additional action, will begin to increase gradually starting in April 2030, reaching 4% in April 2031, until sequestration ends in October 2031. Additionally, there has been heightened governmental scrutiny in the United States of pharmaceutical pricing practices in light of the rising cost of prescription drugs and biologics. Such scrutiny has resulted in several recent Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs and reform government program reimbursement methodologies for products. At the federal level, the Trump Administration has issued executive orders relating to prescription drug pricing and sent letters to pharmaceutical manufacturers that direct drug manufacturers to, among other things, offer most favored nation (“MFN”) pricing in Medicaid, offer MFN pricing for all newly launched drugs, repatriate increased revenue from abroad to lower drug prices in the United States and implement direct-to-consumer and direct-to-business distribution of their products at MFN pricing. The Trump Administration has warned that manufacturers that fail to make “significant progress” toward MFN pricing will face enumerated regulatory and enforcement consequences. In September 2025, the Administration began announcing deals with specific manufacturers to address the Administration’s MFN goals. The Administration has also developed three payment models that would test MFN pricing in Medicaid, Medicare Part D, and Medicare Part B. Participation in the Medicaid model, announced in November 2025, is voluntary for pharmaceutical manufacturers. Under the proposed rules for the Medicare Part D and Medicare Part B models published in December 2025, participation would be mandatory, and pharmaceutical manufacturers would be required to pay MFN-based rebates on eligible products for 25% of eligible Medicare beneficiaries during the applicable testing period. If these Medicare models are finalized and we obtain regulatory approval and commence commercialization of obicetrapib or any of our future product candidates during the testing period, and these products qualify for inclusion under the models, we may be required to pay MFN-based rebates in these models. Moreover, pursuant to the Menarini License, Menarini is responsible for the commercialization and local development of obicetrapib in certain areas of Europe, if approved. In August 2025, the European Medicines Agency (the “EMA”) accepted for review the Marketing Authorization Applications (“MAAs”) submitted by Menarini for obicetrapib 10 mg monotherapy and the FDC of 10 mg obicetrapib plus 10 mg ezetimibe for the treatment of primary hypercholesterolemia, including heterozygous familial and non-familial or mixed dyslipidemia. Subsequently, MAAs were also submitted to regulators in the United Kingdom (“UK”) and Switzerland and accepted for review. We anticipate that Menarini will receive decisions on the MAAs from each of the regulators in the second half of 2026. Pursuant to the Menarini License, Menarini has sole discretion to set the price of the products in the European markets covered by its license. The price for prescription drug products in European and other non-U.S. markets is generally less, and in many cases significantly less, than the pricing for the same products sold in the United States. We expect the price of obicetrapib, if approved, in the European markets in which MAAs are currently under review by regulators, as well as the other European markets covered by the Menarini license, will be lower, and in most cases significantly lower, than the expected price for obicetrapib, if approved, in the United States. Since prices in the European markets in which Menarini has sole discretion to set the price of obicetrapib may serve as benchmarks for any mandatory MFN pricing models, if adopted, we may be unable to control the MFN price that must be made available under the announced payment models, if adopted, or in any future efforts to adopt MFN pricing. As a result, these payment models and other efforts to impose MFN pricing could have a material adverse effect on our business, financial condition or results of operations, including the net sales potential of obicetrapib, if approved. Further, on November 30, 2020, HHS, finalized a regulation removing safe harbor protection for price reductions from pharmaceutical manufacturers to plan sponsors under Part D, either directly or through pharmacy benefit managers, unless the price reduction is required by law. The IRA delayed the implementation of the rule to January 1, 2032. The rule also creates a new safe harbor for price reductions reflected at the point-of-sale, as well as a new safe harbor for certain fixed fee arrangements between pharmacy benefit managers and manufacturers; the implementation of these provisions has also been delayed by the IRA until January 1, 2032. 34 If we obtain regulatory approval and commence commercialization of obicetrapib or any of our future product candidates, these laws and regulatory requirements could have an adverse effect on the market opportunities for obicetrapib or any of our future product candidates and may result in additional reductions in healthcare funding, which could have an adverse effect on our customers and accordingly, our financial operations. Legislative and regulatory proposals have been made to expand post-approval requirements and restrict sales and promotional activities for pharmaceutical products. We cannot be sure whether additional legislative changes will be enacted, or whether additional executive actions will be taken, or whether the FDA regulations, guidance or interpretations will be changed, or what the impact of such changes on the marketing approvals of obicetrapib or our future product candidates may be. Although we cannot predict the full effect on our business of the implementation of existing legislation and regulations or the adoption of additional legislation or further regulatory requirements pursuant to healthcare and other legislative reform, we believe that legislation or regulations that would reduce reimbursement for, or restrict coverage of, obicetrapib, if approved, or any of our future products could adversely affect how much or under what circumstances healthcare providers will prescribe or administer our products. This could adversely affect our business by reducing our ability to generate revenues, raise capital, obtain licenses and market our products. In addition, we believe the increasing emphasis on managed care in the United States has and will continue to put pressure on the price and usage of pharmaceutical products, which may adversely impact product sales. In December 2025, the European Parliament and the Council of the European Union reached a provisional agreement on legislation to amend the current EU pharmaceutical regulatory framework. The text of the new legislation is due to be released in late 2026 following formal adoption by both the Parliament and Council. The potential reforms include altering the periods of regulatory and/or marketing protections available for innovative products and also making some of these protections conditional on fulfilling certain criteria. Depending on the final wording of these reforms, a reduction in the potential period of marketing protection available for obicetrapib or any of our future product candidates may adversely affect the commercial viability of such products in the EU. These changes could adversely affect our business by reducing our protection against generic competitors entering the EU market. Depending on the progress of the EU Parliament and Council to finalize the text of the legislation, changes to EU pharmaceutical legislation are not expected to come into force until early 2027 and additional transitional periods mean that most changes will most likely not take effect until early 2029. Changes in U.S. government policies, including increased tariffs, could adversely affect our business. Significant political, trade, or regulatory developments in the jurisdictions in which we may sell our product, if approved, such as those stemming from the change in U.S. federal administration, are difficult to predict and may have a material adverse effect on us. Similarly, changes in U.S. federal policy that affect the geopolitical landscape could give rise to circumstances outside our control that could have negative impacts on our business operations. For example, policy actions by the Administration, including the imposition of new tariffs on imported materials and goods from certain non-U.S. countries, may have an adverse impact on our business. Recently, trade and tariff policies among the United States and other countries have been unsettled and are subject to frequent changes. In April 2025, the Administration imposed a baseline ten percent tariff on imports from all nations importing goods to the United States, with that baseline supplemented in certain cases by additional tariffs that vary by nation, product or industry. In February 2026, the U.S. Supreme Court ruled against the Administration’s use of tariffs under the International Emergency Economic Powers Act, but the Administration imposed a new worldwide tariff under other legal authority, effective for 150 days from February 24, 2026. While the baseline tariff has been temporarily reduced, the underlying trade tensions and the potential reimposition of elevated tariffs may continue to pose risks to global supply chains and economic relations. The Bureau of Industry and Security, U.S. Department of Commerce, has initiated an investigation to determine whether pharmaceutical ingredients, including finished drug products, manufactured outside the United States pose a national security risk and should be subject to additional tariffs. The imposition of tariffs generally has historically led to increased trade and political tensions between the United States and other countries in the international community. Retaliatory tariffs on U.S. goods have been imposed by, among others, China and Canada. Political tensions as a result of trade policies could reduce trade volume, investment, technological exchange, and other economic activities between major international economies, resulting in a material adverse effect on global economic conditions and the stability of global financial markets. Any changes in political, trade, regulatory, and economic conditions could have a material adverse effect on our financial condition or results of operations. In addition, increased tariffs on critical raw materials, components, and finished goods could raise our production costs and disrupt our supply chain, which could adversely affect our clinical development activities. The actual impact of the new tariffs on our business is subject to a number of factors including, but not limited to, restrictions on trade, the effective date and duration of such tariffs, countries included in the scope of tariffs, changes to amounts of tariffs, 35 potential retaliatory tariffs imposed by other countries, and the extent to which tariffs are imposed on finished or unfinished pharmaceutical products. If these or similar policy changes continue or expand, we may face increased costs. Although we cannot predict the full extent of these impacts, any prolonged disruption could adversely affect our business, financial condition, and results of operations. Marketing and reimbursement regulations may materially affect our ability to market and receive coverage for our products in foreign jurisdictions. We intend to seek approval to market our current and future product candidates in the United States, the EU and selected other foreign jurisdictions. If we obtain approval in one or more foreign jurisdictions for our product candidates, we will be subject to rules and regulations in those jurisdictions. In some countries, particularly certain EU member states, the pricing of drugs is subject to governmental control and other market regulations which could put pressure on the pricing and usage of our product candidates. In these countries, pricing negotiations with governmental authorities can take considerable time after obtaining marketing approval of a product candidate. In addition, market acceptance and sales of our product candidates will depend significantly on the availability of adequate coverage and reimbursement from third-party payors for our product candidates and may be affected by existing and future healthcare reform measures. In the EU, the requirements governing drug pricing and reimbursement vary widely between EU member states. Some EU member states provide that products may be marketed only after a reimbursement price has been agreed. Some EU member states may require the completion of additional studies that compare the cost effectiveness of a particular product candidate to currently available therapies (so called health technology assessments) in order to obtain reimbursement or pricing approval. Moreover, at the national level, EU member states may restrict the range of products for which their national health insurance systems provide reimbursement and to control the prices of medicinal products for human use. EU member states may approve a specific price for a product or may instead adopt a system of direct or indirect controls on the profitability of the company placing the product on the market. Other EU member states allow companies to fix their own prices for products, but monitor and control prescription volumes and issue guidance to physicians to limit prescriptions. Recently, many EU member states have increased the amount of discounts required on pharmaceuticals and these efforts could continue as EU member states attempt to manage healthcare expenditures, especially in light of the severe fiscal and debt crises experienced by many countries in the EU. The downward pressure on health care costs in general, particularly prescription products, has become significant. This is likely to increase as a result of the EU Health Technology Assessment Regulation (EU) 2021/2282. This legislation will apply to all new active substances approved via the EU centralized procedure from 2030. It already applies for new active substance oncology products and advanced therapy medicinal products, i.e., gene and cell therapy products, as well as tissue engineered products. It will apply to all orphan medicinal products from January 2028. The EU will prepare joint clinical assessment (“JCA”) reports in parallel with the marketing authorization review processes. The JCA will report on the relative or “added value” effectiveness of the product in comparison with existing health technologies. While EU member states remain responsible for pricing and reimbursement decisions, they must take “due consideration” of JCA and it is likely that more and more member states will factor the added clinical value offered by new products into their market access decisions. Accordingly, increasingly high barriers are being erected to the entry of new products in the marketplace in the EU. Political, economic and regulatory developments in the EU may further complicate pricing negotiations, and pricing negotiations may continue after reimbursement has been obtained. Reference pricing used by various EU member states and parallel trade (arbitrage between low-priced and high-priced member states) can further reduce prices. Acceptance of any medicinal product for reimbursement may come with cost, use and often volume restrictions, which again can vary by country. In addition, results based rules of reimbursement may apply. There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement and pricing arrangements for any of our products, if approved in those countries. Historically, products launched in the EU do not follow price structures of the United States and generally prices tend to be significantly lower. Publication of discounts by third-party payors or authorities may lead to further pressure on the prices or reimbursement levels within the country of publication and other countries. If pricing is set at unsatisfactory levels or if reimbursement of our products is unavailable or limited in scope or amount, our revenues from sales and the potential profitability of any of our product candidates in those countries would be negatively affected. In December 2025, the EU Parliament and Council reached political agreement on the proposals to amend the current EU pharmaceutical regulatory framework. As discussed above, the final agreed text is likely to be released in late 2026, but it is generally expected that it will contain provisions that may cause additional pressure on pricing issues across the EU. For example, it is expected that the legislation will give EU member states the power, within one year of marketing authorization, to request that the marketing authorization holder places a product benefiting from regulatory data exclusivity protection or extended orphan market protection on its market in sufficient quantities and in the presentations necessary to cover patient needs. The request must be “proportionate” and may include: submission of a valid pricing and 36 reimbursement application; participating in public procurement procedures; and establishing a roll-out plan. Failure to comply with the request within three years of the member state request would mean that regulatory data protection no longer applies in that member state and that the member state or EMA are able to validate generic/biosimilar applications after six years. However, the regulator cannot grant the marketing authorization until regulatory exclusivity, and, where applicable, orphan exclusivity, has expired. The new legislation also provides for the loss of market protection or orphan market protection prolongation in the member state, meaning that generics/biosimilars may launch earlier. A separate parallel mechanism allows member states to request that marketing authorization holders for centrally authorized products launch and supply medicinal products benefiting from patent, supplementary patent term, regulatory data and extended orphan market protection. A failure by the marketing authorization holder to ensure adequate supplies may result in member state escalation to the European Commission. It is possible that these provisions could result in companies being forced to engage with member states that may otherwise be lower priority markets, which may result in downward pressure on price. Both these supply mechanisms mean that companies may find themselves under pressure to launch in jurisdictions earlier than they might otherwise do. Some of these may be associated with lower pharmaceutical pricing and may have the potential to serve as benchmarks for US MFN pricing models. Any changes to EU pharmaceutical legislation are not expected to come into force until 2027. Additional transitional periods mean that, while some of these changes, including the first mechanism for member states to request supplies, may take effect in early 2028, others will most likely not take effect until early 2029. Based on the available draft text of the legislation, however, we expect that the new legislation should not apply to products for which marketing authorization applications are filed and approved under the current rules.