What changed in this filing

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Item 5. Market for Registrant’s Common Equity

2023-03-01 compared with 2022-03-01 · 212 added, 311 removed, 594 unchanged (47% of the section changed)

12 unchanged sentences

Our depositary, Citibank, N.A., constitutes a single record holder of our ordinary shares.

We have never paid dividends on common shares and do not anticipate paying any cash dividends on the common shares in the foreseeable future.

We have never paid dividends on our ordinary shares and do not anticipate paying any cash dividends on our ordinary shares in the foreseeable future.

Under English law, any payment of dividends would be subject to relevant legislation and our Articles of Association, which requires that all dividends must be approved by our board of directors and, in some cases, our shareholders, and may only be paid from our distributable profits available for the purpose, determined on an unconsolidated basis.

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An investment of $100 (with reinvestment of all dividends) is assumed to have been made in our ADSs and in each of the indices on December 31, 2017, and its relative performance is tracked through December 31, 2022.

Included in this 5-year time period is the substantial positive impact on the price of Amarin’s ADSs in 2018 following presentation and publication of positive REDUCE-IT results and, in late 2019, following approval by the FDA of a new indication and label expansion for VASCEPA to reduce cardiovascular risk.

label expansion for VASCEPA to reduce cardiovascular risk.

Also included during this 5-year period is the substantial negative impact on the price of Amarin’s ADSs in 2020 following the loss of the Company’s patent litigation and subsequent appeal.

the majority of this 5-year time period, cumulative total return for Amarin’s ADSs approximated or exceeded both the NASDAQ Composite Index and NASDAQ Biotechnology Index.

Company/Market/Peer Company

22 unchanged sentences

Holder (as defined below).

This summary applies to you only if you hold ordinary shares or ADSs as a capital asset.

This summary applies to you only if you hold ordinary shares or ADSs

as a capital asset.

This summary is based upon the U.S.

Report on Form 10-K, all of which are subject to change and to differing interpretations, possibly with retroactive effect, which could result in U.S.

Internal Revenue Code of 1986, as amended, which is referred to herein as the Code, regulations promulgated under the Code and administrative rulings and judicial decisions as in effect on the date of this Annual Report on Form 10-K, all of which are subject to change and to differing interpretations, possibly with retroactive effect, which could result in U.S.

federal income tax considerations different from those summarized below.

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Subject to the discussion under “—Passive Foreign Investment Company,”

below, as long as our ordinary shares or ADSs (as applicable) are treated as publicly traded on an established securities market, or we are eligible for the benefits of the U.S.-Irish Tax

Treaty, any distributions treated as dividends will generally be qualified dividend income in the hands of non-corporate U.S.

below, as long as our ordinary shares or ADSs (as applicable) are treated as publicly traded on an established securities market, or we are eligible for the benefits of the U.S.-Irish Tax Treaty, any distributions treated as dividends will generally be qualified dividend income in the hands of non-corporate U.S.

Holders, provided that certain significant holding period and other requirements are met.

48 unchanged sentences

The application of these factors depends upon our financial results for the year, which are beyond our ability to predict or control, and the application of the relevant rules is subject to legal and factual uncertainties.

Based on certain estimates of our gross income and gross assets, the latter determined by reference to the expected value of our ADSs and ordinary shares, we believe that we will not be classified as a PFIC for the taxable year ended December 31, 2021 and we do not expect to be treated as a PFIC in any future taxable year for the foreseeable future.

PFIC for the taxable year ended December 31, 2022, and we do not expect to be treated as a PFIC in any future taxable year for the foreseeable future.

However, there can be no assurance that we will not be classified as a PFIC for any taxable year.

In general terms, we will be a PFIC for any taxable year in which either (i) 75% or more of its our gross income is passive income, or the income test, or (ii) the average percentage, by fair market value, of our assets that produce or are held for the

production of passive income is 50% or more, or the asset test.

“Passive income”

47 unchanged sentences

If a mark-to-market election is made after the first taxable year of a U.S.

Holder’s holding period, any gain recognized in the year of the election will be treated like an excess distribution (as described above).

Holder’s holding period, any gain recognized in the year of the election will be treated like an excess distribution (as

described above).

Whether or not the mark-to-market election is available will depend on whether the ordinary shares or ADSs are regularly traded on a qualifying exchange and we cannot provide assurance that the ordinary shares or ADSs will be considered regularly traded (which determination is based on the volume of trading of the ordinary shares or ADSs) for all years in which we may be a PFIC.

74 unchanged sentences

(iv) in the case of a corporate holder, is not a resident in Ireland for Irish tax purposes and is not ultimately controlled by persons resident in Ireland;

and (v) is not engaged in any trade or business and does not perform independent personal services through a permanent establishment or fixed base in Ireland;

and (v) is not engaged in any trade or business and does not

perform independent personal services through a permanent establishment or fixed base in Ireland;

and (vi) is a qualified person as defined in Article 23 of the Treaty.

75 unchanged sentences

We are a pharmaceutical company focused on the commercialization and development of therapeutics to improve cardiovascular, or CV, health and reduce CV risk.

Our lead product, VASCEPA ® (icosapent ethyl) was first approved by the U.S.

FDA for use as an adjunct to diet to reduce triglyceride, or TG, levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia, or the MARINE indication.

We launched VASCEPA in the United States in January 2013.

Our commercialized product, VASCEPA ® (icosapent ethyl) was first approved by the United States, or U.S., Food and Drug Administration, or U.S.

FDA, for use as an adjunct to diet to reduce triglyceride, or TG, levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia, or the MARINE indication and commercially launched in 2013.

On December 13, 2019, the U.S.

FDA approved another indication and label expansion for VASCEPA based on the landmark results of our cardiovascular outcomes trial, REDUCE-IT ® , or Reduction of Cardiovascular Events with EPA –

FDA approved an indication and label expansion for VASCEPA based on the landmark results of our cardiovascular outcomes trial, REDUCE-IT ® , or Reduction of Cardiovascular Events with EPA –

Intervention Trial.

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FDA as an adjunct to maximally tolerated statin therapy for reducing persistent cardiovascular risk in select high risk-patients, or the REDUCE-IT indication.

On March 26, 2021, the European Commission, or EC, granted approval of the marketing authorization application in the EU for VAZKEPA, hereinafter along with the U.S.

On March 26, 2021, the European Commission, or EC, granted approval of the marketing authorization application in the European Union, or EU, for VAZKEPA ® , hereinafter along with the U.S.

brand name VASCEPA, collectively referred to as VASCEPA, which is the first and only EC approved therapy to reduce cardiovascular risk in high-risk statin-treated patients with elevated TG levels.

On September 13, 2021, we launched VAZKEPA in Germany, representing our first European launch.

On April 22, 2021, we announced that we received marketing authorization from the Medicines and Healthcare Products Regulatory Agency, or MHRA, for VAZKEPA in England, Wales and Scotland to reduce cardiovascular risk through MHRA’s new ‘reliance’

route following the end of the Brexit transition period.

VASCEPA is currently available by prescription in the U.S., Germany, Canada, Lebanon and the United Arab Emirates.

We are responsible for supplying VASCEPA to all markets in which the branded product is sold, either to and through our collaborations with third-party companies or by us.

Subject to commercial launches in additional countries within Europe and approval in China and Hong Kong, we will be responsible for supplying products to those markets as well.

VASCEPA is currently available by prescription in the U.S.

and certain other countries throughout the world, as described below.

We are responsible for the supply of VASCEPA to all markets in which the branded product is sold, either to and through our collaborations with third-party companies or by us.

We are not responsible for providing any generic company with drug product.

Geographies outside the United States in which VASCEPA is sold and under regulatory review are not subject to the U.S.

patent litigation and judgment described below.

No similar litigation involving potential generic version of VASCEPA is pending outside the United States.

patent litigation and judgment described below and no similar litigation is pending outside of the United States.

United States

We commenced the commercial launch of VASCEPA in the United States in January 2013 based on the MARINE indication for VASCEPA.

In October 2016, in addition to the original 1-gram capsule size, we introduced a smaller 0.5-gram capsule size.

FDA-approved dosing for VASCEPA continues to be 4 grams per day, and as expected, the majority of new and existing patients continue to be prescribed the 1-gram size VASCEPA capsule.

VASCEPA is sold principally to a limited number of major wholesalers, as well as selected regional wholesalers and mail order pharmacy providers, or collectively, our distributors or our customers, most of whom in turn resell VASCEPA to retail pharmacies for subsequent resale to patients and healthcare providers.

We employ various medical affairs and marketing personnel to support our commercialization of VASCEPA.

On March 30, 2020, following conclusion of a trial in late January 2020, the U.S.

District Court for the District of Nevada, or the Nevada Court, issued a ruling in favor of two generic drug companies, Dr.

Since VASCEPA was made commercially available in 2013, more than twenty million estimated normalized total prescriptions of VASCEPA have been reported by Symphony Health.

In 2020, following our unsuccessful appeals of a court ruling in favor of two generic drug companies, Dr.

Reddy’s Laboratories, Inc., or Dr.

Reddy’s, and Hikma Pharmaceuticals USA Inc., or Hikma, (formerly known as West-Ward), and certain of their affiliates, or, collectively, the Defendants, that declared as invalid several of our patents covering the MARINE indication for use to reduce severely high triglyceride levels.

We sought appeals of the Nevada Court judgment up to the United States Supreme Court, but we were unsuccessful.

Most recently, on June 18, 2021, we were notified that our petition for writ of certiorari to the United States Supreme Court was denied.

On May 22, 2020, Hikma received U.S.

FDA approval to market its generic versions of VASCEPA for the MARINE indication of VASCEPA as an adjunct to diet to reduce TG levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia.

In November 2020, Hikma launched their generic version of VASCEPA on a limited scale.

On November 30, 2020 we filed a patent infringement lawsuit against Hikma for making, selling, offering to sell and importing generic icosapent ethyl capsules in and into the United States in a manner that we allege has induced the infringement of patents covering the use of VASCEPA to reduce specified cardiovascular risk.

The earlier ANDA litigation did not pertain to our patents covering cardiovascular risk reduction.

On January 25, 2021 we expanded the scope of the patent infringement lawsuit to include a health care insurance provider, Health Net, LLC.

On January 4, 2022, the district court hearing the case granted Hikma's motion to dismiss.

We intend to appeal the decision of the district court.

We also intend to continue to vigorously pursue our ongoing litigation with Health Net, LLC, but cannot predict the outcome or the impact on our business.

On August 10, 2020, Dr.

Reddy's received U.S.

FDA approval to market its generic version for the MARINE indication of VASCEPA.

In June 2021, Dr.

Reddy’s launched its generic version of VASCEPA with labeling that is substantially similar to labeling of the Hikma generic product.

On September 11, 2020, Teva Pharmaceuticals USA, Inc.'s, or Teva's, ANDA was approved by the U.S.

FDA and on June 30, 2021, Apotex, Inc.'s, or Apotex's, ANDA was approved by the U.S.

In January 2022, Apotex launched its generic version of VASCEPA with labeling that is substantially consistent with the labeling of the Hikma and Dr.

Reddy's generic product, not the cardiovascular risk reduction indication.

We have continued to monitor the effect of COVID-19 and its impact on patient visits to doctors.

Our level and type of promotion has varied during the pandemic based on the determination of whether the cost was justified in light of COVID-19's impact at a given time.

We anticipate that at-risk patients will increasingly resume visiting their doctors for non-urgent medical care after they are vaccinated for COVID-19, however, we cannot accurately predict when this resumption in visits to doctors will occur and, because many patients have multiple medical issues, we cannot predict the degree to which healthcare professionals will be proactive in seeking to reduce cardiovascular risk in at-risk patients when these patients resume visiting their doctors.

The timing is likely to vary by geography.

We resumed on a very limited basis, a direct-to-patient campaign in January 2021, including television-based promotion, digital and social media promotion to continue to grow consumer awareness of VASCEPA.

In June 2021, we launched an educational campaign, It's Clear to Me Now , to help physicians and patients learn more about the differentiation between VASCEPA and fenofibrates for CV risk reduction.

The differentiation is important for physicians and patients as the U.S.

FDA removed use with statins for CV risk reduction from the fenofibrates' label based on a failed CV risk outcomes trial.

In September 2021, we announced our Go-to-Market strategy to optimize provider engagement and drive demand for VASCEPA and contains three key strategic priorities:

Expanding healthcare provider engagement:

Our omnichannel approach which is designed to enhance our reach to healthcare professionals, and aims to target a far greater number of the almost 700,000 statin prescribers through high frequency, and tailored messaging regarding the significant benefits of VASCEPA for CV risk reduction.

We plan to optimize our U.S.

field force and focus on the most productive territories.

As a result, we reduced our U.S.

field force to approximately 300 sales representatives who will remain a critical part of the commercial strategy going forward.

Enhancing managed care access:

We plan to continue working with payers in an effort to enhance our managed care position and further remove barriers to VASCEPA prescriptions to ensure that patients in need of CV risk reduction receive proper therapy.

Importantly, several large Commercial and Medicare Part D payers currently cover VASCEPA as the exclusive icosapent ethyl product.

Optimizing VASCEPA prescriptions for CV risk reduction:

Branded VASCEPA remains the only available U.S.

FDA approved icosapent ethyl medication for CV risk reduction.

To prevent improper generic substitution for this indication, we continue to aggressively educate critical stakeholders in the prescribing continuum to ensure proper fulfillment at each step.

Additionally, we continue to evaluate various innovative solutions designed to better manage prescriptions for CV risk reduction.

As a result of our Go-to-Market strategy and our omnichannel approach, which we launched in the fourth quarter, we digitally approached a significant number of physicians across numerous digital channels.

In addition, on November 1, 2021, we partnered with BlinkRx to provide patients an enhanced digital prescription fulfillment channel.

As COVID-19 protocols ease and ordinary course activities continue to resume, we will continue to adjust our promotional initiatives accordingly, including pursuit of increased face-to-face interactions with healthcare professionals and expanding various forms of direct-to-patient promotion.

We obtain data from two third parties, Symphony Health and IQVIA, who collect and report estimates of weekly, monthly, quarterly and annual prescription information.

There is a limited amount of information available to determine the actual number of total prescriptions for prescription products like VASCEPA during such periods.

Each vendor’s estimates utilize a proprietary projection methodology and are based on a combination of data received from pharmacies and other distributors, and historical data

when actual data is unavailable.

Based on data from Symphony Health and IQVIA, the below chart represents the estimated number of normalized total VASCEPA prescriptions over the year ended December 31, 2021.

Reddy’s, and Hikma Pharmaceuticals USA Inc., or Hikma, and certain of their affiliates, several of our patents covering the MARINE indication were declared as invalid.

As a result, the following generic versions of VASCEPA have obtained U.S.

FDA approval with labeling consistent with the MARINE indication and have entered the U.S.

market with a 1-gram capsule:

FDA MARINE Indication Approval

Hikma Pharmaceuticals USA Inc.

November 2020

Reddy’s Laboratories, Inc.

Teva Pharmaceuticals USA, Inc.

September 2020

September 2022 (1)

(1) - Teva launched a 0.5-gram capsule in September 2022 and a 1-gram capsule in January 2023.

In June 2022, to address shifts within our U.S.

business due to these generic competitors, we announced a comprehensive cost and organizational restructuring plan which is expected to result in savings of $100.0 million over the subsequent twelve months compared to 2021 operating expenses.

cost reduction plan included:

workforce reduction:

The reduction of our U.S.

field force and corporate positions.

field force was reduced from approximately 300 sales representatives to approximately 75 sales representatives.

Streamlined operational expenditures:

Includes reductions and reallocations in overall selling, general and administrative expenses as well as savings related to refining our research and development strategy to a more focused, stepwise approach for our fixed-dose combination, or FDC, program.

In alignment with our U.S.

cost reduction plan, our focus is primarily on engaging with our top VASCEPA brand prescribers, maintaining our exclusive formulary coverage with specific payers, and implementing targeted promotional initiatives amid the continued pressure from generic competitors.

We obtain data from a third party, Symphony Health, who collects and reports estimates of weekly, monthly, quarterly and annual prescription information.

There is a limited amount of information available to determine the actual number of total prescriptions for products like VASCEPA during such periods.

The vendor's estimate utilizes a proprietary projection methodology and are based on a combination of data received from pharmacies and other distributors, as well as historical data when actual data is unavailable.

Based on data from Symphony Health, the below chart represents the estimated number of normalized total VASCEPA prescriptions over the year ended December 31, 2022.

Normalized total prescriptions represent the estimated total number of VASCEPA prescriptions dispensed to patients, calculated on a normalized basis (i.e., one month’s supply, or total capsules dispensed multiplied by the number of grams per capsule divided by 120 grams).

Inventory levels at wholesalers tend to fluctuate based on seasonal factors, prescription trends and other factors.

The resulting conclusions from Symphony Health and IQVIA are rarely identical and should be viewed with caution.

The previous calculations of prescription levels by these vendors can change between periods and can be significantly affected by lags in data reporting from various sources or by changes in pharmacies and other distributors providing data.

The previous calculations of prescription levels by this vendor can change between periods and can be significantly affected by lags in data reporting from various sources or by changes in pharmacies and other distributors providing data.

Such methods can from time to time result in significant inaccuracies in information when ultimately compared with actual results.

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Further, data for a single and limited period may not be representative of a trend or otherwise predictive of future results.

We are not responsible for the accuracy of these companies’

information and we do not receive prescription data directly from retail pharmacies.

In December 2019, we announced that the EMA validated the marketing authorization application seeking approval for VAZKEPA.

The validation confirmed the submission was sufficiently complete for the EMA to begin its review.

In August 2020, we announced our plans to launch VAZKEPA in major markets in Europe through our own European sales and marketing team.

Such an approach allows us to retain substantially all of the economic potential of VAZKEPA in Europe and helps ensure that VAZKEPA would get the highest level of priority and focus.

On January 28, 2021, the Committee for Medicinal Products for Human Use, or CHMP, of the EMA adopted a positive opinion, recommending that a marketing authorization be granted to icosapent ethyl in the EU for the reduction of risk of cardiovascular events in patients at high cardiovascular risk, under the brand name VAZKEPA.

On March 26, 2021, the EC granted approval of the marketing authorization application in the EU.

In Europe, launch of VAZKEPA in individual countries is gated by timing of achieving product reimbursement on a country-by-country basis as is typical for new drugs.

In seeking market access, we have filed ten dossiers in European countries, including in all of the largest countries in Europe, and expect to file additional dossiers in Europe and select other parts of the world in the first half of 2022.

We are not responsible for the accuracy of this vendor's information and we do not receive prescription data directly from retail pharmacies.

In 2021, we received marketing authorization and regulatory approval in the EU, England, Wales and Scotland.

Launch of VAZKEPA in individual countries depends on the timing of achieving product reimbursement on a country-by-country basis.

To date we have filed thirteen dossiers to gain market access in European countries, including in all of the largest countries in Europe.

In most European countries, securing product reimbursement is a requisite to launching.

In certain countries, such as Denmark, individual patient reimbursement is allowed prior to national, general organization reimbursement.

In countries where

individual price reimbursement is allowed prior to national reimbursement, product can be made available on a patient by patient basis, while the national reimbursements negotiations are ongoing.

In all countries, securing adequate reimbursement is a requisite for commercial success of any therapeutic.

The time required to secure reimbursement tends to vary from country to country and cannot be reliably predicted at this time.

While we believe that we have strong arguments regarding the cost effectiveness of VAZKEPA, the success of such reimbursement negotiations could have a significant impact on the assessment of the commercial opportunity of VAZKEPA in Europe.

Additionally, we are continuing to grow our European staff by hiring Market access and Medical affairs teams, among others, across Europe.

On September 1, 2021, VAZKEPA was made available in Germany and was included in the country's electronic prescribing system as of October 1, 2021.

The commercial launch in Germany was accompanied by a scientific conference in Berlin titled, “New therapeutic strategies for residual CV risk management,”

which highlighted the scientific underpinnings and clinical benefits of VASCEPA/VAZKEPA in reducing cardiovascular risk.

We are building a digitally native commercial model balancing optimally digital and face-to-face approach for more impact and cost efficiency, which will also be utilized as other countries throughout Europe are launched.

In order to launch impactfully in other countries throughout Europe we are building a core team of experienced professionals and a highly capable commercial team involved with pre-launch planning and other commercial preparation activities and are leveraging third-party relationships for various support activities.

In Europe, patients at high risk for cardiovascular disease tend, in contrast to the United States, to be treated more often by specialists, such as cardiologists rather than by physicians who are general practitioners.

The time required to secure reimbursement tends to vary from country to country and cannot be reliably predicted.

While we believe that we have strong arguments regarding the cost effectiveness of VAZKEPA, the success of such reimbursement negotiations have a significant impact on the assessment of the commercial opportunity of VAZKEPA in Europe.

Through the date of this Annual Report on Form 10-K, we have received and made VAZKEPA available under individual reimbursement or received national reimbursement and launched commercial operations in the following countries, respectively.

Individual Reimbursement

National Reimbursement

Product Availability

December 2022

United Kingdom

September 2022

In order to launch impactfully in targeted major markets in Europe we are building a core team of experienced professionals and highly capable local commercial teams involved with pre-launch planning and commercial launch activities and we are leveraging third-party relationships for various support activities.

We are implementing an impactful and cost-effective hybrid commercial model balancing optimally digital and face-to-face approach for more impact and cost efficiency, which is or will be utilized throughout Europe as launches are rolled out.

Patients at high risk for cardiovascular disease tend to be treated more often by specialists, such as cardiologists rather than by general practitioners.

Privacy laws and other factors impact the availability of data to inform European commercial operations at an individual physician level.

Generally, less data is available and at reduced frequencies as compared to the United States.

However, this greater concentration of at-risk patients being treated by specialists in Europe should allow for more efficient promotion in Europe than in the United States.

Generally, less data is available and at reduced frequencies than in the United States.

However, this greater concentration of at-risk patients being treated by specialists in Europe should allow for more efficient promotion than in the United States.

In Europe, VAZKEPA has the benefit of ten years of market protection, and we have been issued a patent that expires in 2033 with additional pending applications that could extend exclusivity into 2039.

In September 2021, as part of the German reimbursement process, VAZKEPA was made available in Germany with temporary reimbursement while negotiations for final reimbursement were ongoing and VAZKEPA was included in the country's electronic prescribing system as of October 1, 2021.

On August 19, 2022, reimbursement negotiations were concluded without agreement.

As a result, we discontinued our German business operations as of September 1, 2022.

Following the local reimbursement process and initiated by G-KV, we moved to the Arbitration Board.

In November 2022, the Arbitration Board process was concluded without reaching a deal.

German legislation allows re-submission of a pricing and reimbursement dossier with new data and we plan to resubmit once we have a new dossier ready.

Rest of World

In February 2015, we announced an exclusive agreement with Eddingpharm (Asia) Macao Commercial Offshore Limited, or Edding, to develop and commercialize VASCEPA capsules in what we refer to as the China Territory, consisting of the territories of Mainland China, Hong Kong, Macau and Taiwan, for uses that are currently commercialized and under development by us in the United States.

Edding, with our support, conducted a clinical trial of VASCEPA in China, which evaluated the effect of VASCEPA on patients with very high triglyceride levels (>500 mg/dL).

In February 2015, we entered into an exclusive agreement with Eddingpharm (Asia) Macao Commercial Offshore Limited, or Edding, to develop and commercialize VASCEPA capsules in what we refer to as the China Territory, consisting of the territories of Mainland China, Hong Kong, Macau and Taiwan.

Edding, with our support, conducted a clinical trial of VASCEPA in China, which evaluated the effect of VASCEPA on patients with very high triglyceride levels (≥500 mg/dL).

In November 2020, we announced statistically significant topline positive results from this Phase 3 clinical trial of VASCEPA conducted by Edding.

The study, which investigated VASCEPA as a treatment for patients with very high triglycerides (≥500 mg/dL), met its primary efficacy endpoint as defined in the clinical trial protocol and demonstrated a safety profile similar to placebo.

Importantly, the VASCEPA 4 gram per day dose in this study appeared to be well-tolerated with a safety profile similar to placebo.

There were no treatment-related serious adverse events in this study.

On February 9, 2021, we announced that the regulatory review processes in Mainland China and Hong Kong have commenced.

The National Medical Products Administration, or NMPA, has accepted for review the new drug application for VASCEPA, submitted by Edding, based on the results from the Phase 3 clinical trial and the results from our prior studies of VASCEPA.

We expect to receive a decision from the NMPA in Mainland China in the second half of 2022.

The Hong Kong Department of Health is evaluating VASCEPA based on current approvals in the United States and Canada.

The review process in Hong Kong is expected to conclude in the second half of 2022.

The National Medical Products Administration, or NMPA, accepted for review the new drug application for VASCEPA, submitted by Edding, based on the results from the Phase 3 clinical trial and the results from our prior studies of VASCEPA.

On February 23, 2022 the Hong Kong Department of Health completed their evaluation of the clinical trial conducted in China and approved the use of VASCEPA under the REDUCE-IT indication.

In China, on October 10, 2022, following the completion of product testing by the China National Institutes for Food and Drug Control, or NIFDC, the final NMPA review of the VASCEPA NDA was initiated with Edding expecting approval by the end of 2022.

Due to delays at CDE as a result of the resurgence of COVID-19 in the Beijing area at the end of 2022, Edding has communicated that an approval in Mainland China could be achieved by mid-year of 2023.

Middle East and North Africa (MENA)

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December 2021

VASCEPA is under registration in additional countries in the MENA region.

In September 2017, we entered into an agreement with HLS Therapeutics Inc., or HLS, to register, commercialize and distribute VASCEPA in Canada.

In March 2019, HLS received formal confirmation from Health Canada that the Canadian regulatory authority has granted priority review status for the upcoming New Drug Submission, which was filed in April 2019, for VASCEPA.

In December 2019, HLS received formal confirmation from Health Canada that the Canadian regulatory authority has granted approval for VASCEPA to reduce the risk of cardiovascular events (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularization or hospitalization for unstable angina) in statin-treated patients with elevated triglycerides, who are at high risk of cardiovascular events due to:

In March 2019, HLS received formal confirmation from Health Canada that Canadian regulatory authority has granted priority review status for the upcoming New Drug Submission, which was filed in April 2019.

In December 2019, HLS received formal confirmation from Health Canada that the Canadian regulatory authority granted approval for VASCEPA to reduce the risk of cardiovascular events (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularization or hospitalization for unstable angina) in statin-treated patients with elevated triglycerides, who are at high risk of cardiovascular events due to:

established cardiovascular disease, or diabetes, and at least one other cardiovascular risk factor.

In January 2020 HLS obtained a regulatory exclusivity designation and launched commercially in February 2020.

In July 2020, the Canadian Agency for Drugs and Technologies in Health recommended that VASCEPA be reimbursed by participating public drug

plans for statin-treated patients with established cardiovascular diseases and elevated triglycerides.

In January 2020, HLS obtained regulatory exclusivity designation and launched commercially in February 2020.

In July 2020, the Canadian Agency for Drugs and Technologies in Health recommended that VASCEPA be reimbursed by participating public drug plans for statin-treated patients with established cardiovascular diseases and elevated triglycerides.

In April 2022, HLS completed negotiations with Canada’s pan-Canadian Pharmaceutical Alliance for the terms and conditions under which VASCEPA would qualify for public market reimbursement in Canada.

Following these negotiations, HLS signed a Letter of Intent which allows HLS to work with all participating provincial jurisdictions to secure coverage from publicly funded drug plans across Canada, and for VASCEPA to potentially be added to their respective plans.

HLS also received notification by the Patented Medical Prices Review Board that, further to its review, VASCEPA’s price did not trigger the investigation criteria for excessive pricing.

As of December 31, 2022, reimbursement coverage is approximately 70% of publicly covered lives and 95% for private coverage.

Public reimbursement is now available in Ontario, Quebec, Saskatchewan, New Brunswick Northwest Territories and for the Non-Insured Health Benefits program for the First Nations and Inuit people.

Coverage of patients with established cardiovascular disease represents a substantial portion of VASCEPA’s approved label in Canada.

VASCEPA has the benefit of data protection afforded through Health Canada until the end of 2027, in addition to separate patent protection with expiration dates that could extend into 2039.

We plan to continue to assess other potential partnership opportunities for VASCEPA with partners outside of the United States and Europe with the intention of partnering in all other international markets.

Our plan is to file three waves of regulatory submissions for approval of VASCEPA in 20 additional countries in order to ensure that patients in the top 50 cardiometabolic markets worldwide can benefit from VASCEPA.

We have initiated the first wave of regulatory filings in 2022 and in February 2022 obtained acceptance of VASCEPA for regulatory review in Australia and Israel.

We continue to assess other potential partnership opportunities for VASCEPA with companies outside of the United States and Europe with the intention of partnering in all other international markets where VASCEPA receives local regulatory approval.

We have completed the first year of a three year plan to submit and obtain regulatory approval in 20 additional countries in order to ensure that patients in the top 50 cardiometabolic markets worldwide can benefit from VASCEPA.

Through the date of this Annual Report on Form 10-K, we have filed for regulatory review in 10 countries and have received approval in seven countries outside of the United States and European Medicines Agency, or EMA, regulatory approval authority, including in Switzerland, Australia and New Zealand, under the REDUCE-IT indication.

In February 2023, we entered into an agreement with CSL Seqirus to secure pricing and reimbursement, commercialize and distribute VAZKEPA in Australia and New Zealand.

Research and Development

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Most of our other research and development during this period also pertained to VASCEPA, including study of the mechanism of action of the single active ingredient in VASCEPA, icosapent ethyl.

The REDUCE-IT study was conducted based on a special protocol assessment, or SPA, agreement with the U.S.

Based on the final positive results of REDUCE-IT, we sought additional indicated uses for VASCEPA in the United States and continue to pursue approval for VASCEPA around the world.

We also anticipate continuing to publish additional details of the REDUCE-IT study to address scientific interest beyond the primary results of this study derived from the over 35,000 patient years of study experience which were accumulated in the REDUCE-IT study.

The REDUCE-IT study topline results were made public in September 2018, and the primary results of the REDUCE-IT study were presented at the 2018 Scientific Sessions of the AHA on November 10, 2018 with such results concurrently published in The New England Journal of Medicine .

The total (first and subsequent) cardiovascular events results of the REDUCE-IT study were presented at the American College of Cardiology’s 68 th Annual Scientific Session in March 2019 and concurrently published in the Journal of the American College of Cardiology.

FDA granted Priority Review designation to our March 2019 sNDA seeking an expanded indication for VASCEPA in the United States based on the positive results of the REDUCE-IT study.

FDA grants Priority Review designation to applications for drugs that, if approved, have the potential to offer significant improvements in the effectiveness and safety of the treatment of serious conditions when compared to standard applications.

In November 2019, the U.S.

FDA held an EMDAC meeting to review the REDUCE-IT sNDA.

The EMDAC voted unanimously (16-0) to recommend approval of an indication and label expansion for VASCEPA to reduce cardiovascular events in high-risk patients based on the REDUCE-IT results.

On December 13, 2019, the U.S.

FDA approved an indication and related label expansion based on REDUCE-IT.

VASCEPA is the first and only drug approved by the U.S.

FDA as an adjunct to maximally tolerated statin therapy to reduce the risk of myocardial infarction, stroke, coronary revascularization, and unstable angina requiring hospitalization in adult patients with elevated TG levels (≥150 mg/dL) and either established cardiovascular disease or diabetes mellitus and two or more additional risk factors for cardiovascular disease.

Reflecting the robust results of the clinical development program for VASCEPA, no additional post-approval clinical study or other special post-approval requirement (as often seen with other drug approvals) was requested by the U.S.

FDA in conjunction with its approval of VASCEPA.

Based on REDUCE-IT results, as of the date of the filing of this Annual Report on Form 10-K, 26 clinical treatment guidelines, consensus statements or scientific statements from medical societies or journals have been updated recommending the use of icosapent ethyl in appropriate at-risk patients, including those statements which we were informed of by our global partners in Canada, China and the Middle East as well as guidelines which were newly received during the fourth quarter of 2021 through the filing date of this Annual Report on Form 10-K as listed below:

The Polish Cardiac Society Working Group on Cardiovascular Pharmacotherapy, or SFSN PTK, published a consensus statement on the management of dyslipidemia.

The statement by SFSN PTK recommends 4g of EPA, icosapent ethyl, daily in combination with statins for patients with TG levels 135–499 mg/dL in the high- and very-high-risk categories.

The statement mentions that based on the REDUCE-IT study, 2g of icosapent ethyl twice daily in combination with statins significantly reduced the risk of CV events and lowered TG levels.

SFSN PTK acknowledges that icosapent ethyl is not approved for use in Poland and data from REDUCE-IT cannot be extrapolated to other doses and formulation of omega-3s.

The Diabetes CardioRenal Metabolic Diseases, or DCRM, Task Force published practice recommendations for the management of DCRM.

The practice recommendation recommends icosapent ethyl, VASCEPA, for the primary prevention of myocardial infarction, coronary artery disease, or stroke in patients with diabetes and for secondary prevention of these events in those with and without diabetes.

DCRM further states that based on evidence from

REDUCE-IT, adding IPE to statin therapies further reduces the risk of ASCVD events in patients with TG levels 135–500 mg/dL (1.5–5.7 mmol/L) who have ASCVD or diabetes plus 2 major ASCVD risk factors.

The AHA issued a scientific statement on the comprehensive management of CV risk factors for adults with type 2 diabetes.

The AHA statement recommends patients with diabetes and ASCVD or patients with diabetes at high risk for ASCVD with serum TG levels of 135–500 mg/dL despite maximally tolerated statin therapy, and addressing contributory factors including lifestyle modification, prescription IPE at a dose of 4 grams/day should be considered given the 30% additional CV risk reduction in the REDUCE-IT trial.

AHA further states that for primary prevention in type 2 diabetes, a moderate-intensity statin should be considered based on age, absolute ASCVD risk, or the presence of risk-enhancing factors.

Non-statin therapies including ezetimibe, PCSK9 inhibitors, IPE, bile acid resins, and fibrates should be considered after thorough evaluation of risk, LDL-C level after optimal statin therapy, and presence of hypertriglyceridemia.

Based on our current understanding of the biological effects of a COVID-19 infection, including that patients at high risk of cardiovascular disease are at higher risk of mortality and severe effects from a COVID-19 infection, and based on data related to the mechanism of action and effects of VASCEPA in lowering cardiovascular risk in certain high-risk patients, we believe that VASCEPA could play a beneficial clinical role in helping patients infected by the virus.

We have supported investigator initiated studies by providing study drug product and limited financial support to investigators in multiple pilot studies designed to better understand the potential of VASCEPA and its potentially beneficial role.

On December 12, 2020, we announced at the National Lipid Association Scientific Sessions 2020 positive clinical results from the first study of VASCEPA in COVID-19 infected outpatients, CardioLink-9.

On August 31, 2021 and November 16, 2021, we announced the results from the PREPARE-IT-1 and PREPARE-IT-2 studies on the effects of VASCEPA reducing COVID-19 infections and hospitalizations, respectively, neither of which met the primary and/or other endpoints studied.

If the results of the other pilot study is positive, we will evaluate whether additional studies will be appropriate.

The clinical effects of VASCEPA are multi-factorial.

Multiple mechanisms of action associated with VASCEPA from clinical and mechanistic studies support the rationale to study its effects in patients with the COVID-19 infection.

Additional postulated mechanisms that might play a role in the use of VASCEPA in the patients infected with COVID-19 include potential antiviral/antimicrobial effects, fibrosis and cardiac damage mitigation in animal models and anti-inflammatory effects (acute) in pulmonary/lung tissue.

In June 2018, we entered into a multi-faceted collaboration with Mochida Pharmaceutical Co.

Ltd., or Mochida, related to the development and commercialization of drug products and indications based on the active pharmaceutical ingredient in VASCEPA, the omega-3 acid, EPA.

Among other terms in the agreement, we obtained an exclusive license to certain Mochida intellectual property to advance our interests in the United States and certain other territories.

In addition, the parties will collaborate to research and develop new products and indications based on EPA for our commercialization in the United States and certain other territories.

The potential new product and indication opportunities contemplated under this agreement are currently in early stages of development.

Upon closing of the collaboration agreement, we made a non-refundable, non-creditable upfront payment of approximately $2.7 million.

In addition, the agreement provides for milestone payments from us upon the achievement of certain product development milestones and royalties on net sales of future products arising from the collaboration, if any.

During 2021, we added to our growing body of knowledge on VASCEPA as a result of our continued analysis of the REDUCE-IT trial results.

The REDUCE-IT STROKE analyses examined stroke rates across the enrolled patient population, noting a relative risk reduction in strokes and ischemic stroke of 28% and 36%, respectively.

The REDUCE-IT HEART FAILURE analyses examined the effects of icosapent ethyl on the incidence of the new heart failure by achieved on-treatment serum EPA levels, with further testing needed.

We also analyzed the effect of VASCEPA on patients with prior myocardial infarction to determine if treatment reduced further ischemic events in those subjects, noting VASCEPA reduced first and total primary endpoints by 26% and 35%, respectively.

Finally, we analyzed the effects of VASCEPA on patients with prior peripheral artery diseases to determine if it reduced further ischemic events, noting VASCEPA reduced first and total primary endpoints by 32%.

Based on REDUCE-IT results, as of the date of the filing of this Annual Report on Form 10-K, 30 clinical treatment guidelines, consensus statements or scientific statements from medical societies or journals have been updated recommending the use of icosapent

ethyl in appropriate at-risk patients, including those statements which we were informed of by our global partners in Canada, China and the Middle East as well as guidelines which were newly received during the fourth quarter of 2022 as listed below:

In November 2022, the American Society of Preventive Cardiology published a clinical practice statement delineating key attributes that define the field of preventive cardiology, including that REDUCE-IT established that IPE reduced CV events among patients fasting TG 135 to 499 mg/dL and that results from REDUCE-IT have not been replicated in trials using mixed omega-3 fatty acids suggesting that the CV benefit is attributed to EPA.

In November 2022, NICE released its guidelines on lipid management, which included that IPE is recommended for patients with established CVD and elevated fasting TG and who are taking statins with LDL-C levels between 1.04 and 2.60 mmol/L, as per the REDUCE-IT results.

In December 2022, the Finnish Medical Association and the Finnish Association of Internists published updated guidelines on dyslipidemia treatment, including that IPE is indicated for patients on statin therapy who have elevated TG levels and are at particularly high risk for arterial disease.

In December 2022, the National Society of Cardiometabolic Medicine in China released its consensus statement on the role of omega-3 fatty acids in the prevention and treatment of CVD in Chinese patients.

The consensus statement reviewed current knowledge about omega-3 fatty acids and their use in managing CVD in the Chinese population.

The following key recommendations were included on use of IPE:

o High-dose IPE can confer CV benefits in patients with high TG levels at high risk for ASCVD and who have additional CV risk factors.

o EPA levels may be the driving force behind CV benefit reported with IPE, a concept supported by JELIS and REDUCE-IT trials in which serum EPA levels were inversely associated with CV risk in a dose-response relationship as well as in a sub-analysis of REDUCE-IT, which showed that the CV reduction reported with IPE was attributed to changes in EPA levels rather than lipid biomarkers.

o IPE is the only omega-3 fatty acid approved by the FDA, Health Canada and the EMA for CV risk reduction in patients with CVD or diabetes with other ASCVD risk factors.

During 2022, we announced the following data which added to our growing body of knowledge on VASCEPA as a result of our continued analysis of the REDUCE-IT trial results:

In March 2022, a post hoc sub-analysis of REDUCE-IT, published in the Journal of the American Heart Association, or JAHA, found VASCEPA reduced the risk of cardiovascular death, strokes, heart attacks, coronary revascularization and unstable angina by 34% in patients with a history of percutaneous coronary intervention, or PCI, noting 8.5% and 5.4% absolute risk reductions, respectively, for the primary and secondary composite endpoints.

In May 2022, a post hoc sub-analysis of REDUCE-IT, published in the Journal of the American College of Cardiology found VASCEPA significantly reduced the total ischemic event risk of cardiovascular death, stroke, myocardial infarction, coronary revascularization, or hospitalization for unstable angina by 35% in patients who had a prior heart attack.

In May 2022, we presented data at the 2022 European Society of Cardiology Congress that VASCEPA significantly reduced ST-segment elevation myocardial infarction by 40% and non-ST segment elevated myocardial by 27%.

In August 2022, a post hoc exploratory analysis of REDUCE-IT found VASCEPA significantly reduced the risk of cardiovascular death, strokes, heart attacks, coronary revascularization and unstable angina in current/former smokers by 23% and former smokers by 29%.

In addition, in November 2022, we presented at the American Heart Association, or AHA, 2022 Scientific Sessions data related to RESPECT-EPA, A Randomized Trial for Evaluation in Secondary Prevention Efficacy of Combination Therapy - Statin and Eicosapentaenoic Acid and PROMINENT, Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes Study.

The RESPECT-EPA clinical trial is an independent study funded by the Japanese Heart Foundation and is the third study to show CV benefit consistent with REDUCE-IT and JELIS.

The study achieved a borderline statistical significance with a 21.5% reduction in the primary composite endpoint measuring cardiovascular risk and achieved a statistically significant 26.6% reduction in the secondary composite endpoint.

On January 10, 2022, we announced that we have initiated development of a fixed-dose combination product that has both icosapent ethyl and a statin.

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FDA-approved international API suppliers, encapsulators and packagers to support the VASCEPA commercial franchise.

We also have multiple international API suppliers, encapsulators and packagers to support the commercialization of VASCEPA in geographies where the drug is approved

outside the United States.

We also have multiple international API suppliers, encapsulators and packagers to support the commercialization of VASCEPA in geographies where the drug is approved outside the United States.

Not all of our suppliers approved by the U.S.

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The amount of supply we seek to purchase in future periods will depend on the level of growth of VASCEPA revenues and minimum purchase commitments with certain suppliers.

While our current supply chain is scalable, we continue efforts to expand, diversify and further enhance it.

Impact of COVID-19

As of December 31, 2021, according to CDC data, approximately 60% of the U.S.

population has been fully vaccinated, which does not include a booster shot, and approximately 75% of the U.S.

population has received at least one dose of a vaccine.

While according to CDC data, the population's vaccination rate has increased, the number of new cases increased at the end of 2021 and into early 2022, driven by the Omicron variant.

Our ability to directly promote VASCEPA to healthcare professionals has been limited due to appropriate social distancing practices associated with COVID-19 and by patients electing to forego visiting their doctors for non-urgent medical examinations and/or choosing to not get blood tests which the results of these tests provide useful information to the treatment of cardiovascular risk.

These limitations have had a significant impact on slowing VASCEPA prescription and revenue growth.

Although some of these restrictions were lifted throughout parts of 2021, in light of the increase in cases in the fourth quarter of 2021 due to the Omicron variant and despite the prevalence of the vaccines, many restrictions have been put back in place and access remains variable and challenging due to COVID-19.

While COVID-19 continues to impact our promotion of VASCEPA, we have seen signs of improvement in access to face-to-face interactions with healthcare providers.

In the United States, prior to the recent surge at the end of 2021, at-risk patients increasingly resumed visiting their doctors for non-urgent medical care after they are vaccinated for COVID-19 and we anticipate that to continue when the current surge in cases decreases.

We continued to adjust our promotional initiatives throughout 2021 and plan to adjust throughout 2022, including pursuing increased face-to-face interactions with health care professionals and expanding various forms of direct-to-patient promotion based on COVID-19 protocols that are in place.

In Europe, the rapid spread of the Omicron variant throughout Europe has led to a significant increase in COVID-19 related patients for healthcare professionals and hospitals.

This has limited our access to and ability to directly promote VAZKEPA to healthcare professionals.

We continue to explore other avenues, including digital, to reach and engage healthcare professionals despite the current restrictions and challenges.

Thus far, while COVID-19 has created some added logistical challenges regarding supply deliveries, these challenges have been manageable and COVID-19 has not materially impacted our ability to secure and deliver supply of VASCEPA.

And, thus far, COVID-19 is not known to have significantly impacted ongoing clinical trials of VASCEPA.

The extent to which COVID-19 impacts our business, results of operations and financial condition will depend on future developments, which, despite progress in vaccination efforts, are highly uncertain and cannot be predicted with confidence, including the duration of the outbreak, new information that may emerge concerning the severity of COVID-19, such as new strains of the virus, including the Delta and Omicron variants and any future variants that may emerge, which may impact rates of infection and vaccination efforts, developments or perceptions regarding the safety of vaccines and the extent and effectiveness of actions to contain COVID-19 or treat its impact, including vaccination campaigns and lockdown measures, among others.

We are actively monitoring the situation and evaluating the pandemic's effect on patients, distributors, customers and our employees, as well as on our operations and the operations of our business partners and communities.

We may take precautionary and preemptive or reactive actions that we determine are in the best interests of our business.

We cannot predict the effects that such actions may have on our business or on our financial results, in particular with respect to demand for or access to VASCEPA.

Management Succession Plans

As announced in April 2021, effective August 1, 2021, John Thero retired from his positions as President and Chief Executive Officer and member of our board of directors and is now providing phased transitional and consulting services to us.

Effective August 1, 2021, our board of directors appointed Karim Mikhail, previously our Senior Vice President, Commercial Head Europe, to succeed Mr.

Thero as our President and Chief Executive Officer, as well as, a member of our board of directors.

In addition, we have announced the appointment of Laurent Abuaf as our new Senior Vice President, and President of Europe to fill the opening left by Mr.

Mikhail's promotion.

Effective August 1, 2021, Joseph Kennedy retired from his position of Executive Vice President and General Counsel.

Our search to hire a new General Counsel was completed with Jason Marks joining the Company in August 2021, in the role of Senior Vice President and Chief Legal Officer with Mr.

Kennedy supporting this transition and providing consulting support on certain legal matters.

In addition, we announced that Per Wold-Olsen joined our board of directors on January 10, 2022.

In 2022, we reviewed our contractual supplier purchase obligations and have taken steps to amend supplier agreements to align supply arrangements with current and future market demand, while we decrease our current inventory levels primarily related to North America approved inventory.

As of December 31, 2022, we had inventory $392.4 million, of which 90% is inventory approved for use in North America.

We continue to negotiate with our contract suppliers to align our supply arrangements with current and future global market demand.

Financial Operations Overview

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All of our product revenue is derived from product sales of 1-gram and 0.5-gram size capsules of VASCEPA, net of allowances, discounts, incentives, rebates, chargebacks and returns.

In the United States, we sell product to a limited number of major wholesalers, as well as selected regional wholesalers and mail order pharmacy providers, or collectively, our distributors or our customers, most of whom resell the product to retail pharmacies for purposes of their reselling the product to fill patient prescriptions.

Revenues from product sales are recognized when the customer obtains control of our product, which occurs at a point in time, typically upon delivery to the customer.

Timing of shipments to wholesalers, as used for revenue recognition, and timing of prescriptions as estimated by third-party sources such as Symphony Health and IQVIA may differ from period to period.

During the years ended December 31, 2021 and 2020, our Product revenue, net included adjustment for co-pay mitigation rebates provided by us to commercially insured patients.

In the United States, VASCEPA is sold to three major wholesalers, as well as several regional wholesalers along with mail order pharmacy providers, or collectively, our distributors or our customers.

Most of these customers resell VASCEPA to retail pharmacies for purposes of dispensing VASCEPA to patients.

Revenues from VASCEPA sales are recognized upon delivery to the distributor or customer.

Timing of shipments to wholesalers, as used for revenue recognition, and timing of prescriptions as estimated by third-party sources such as Symphony Health may differ from period to period.

During the years ended December 31, 2022 and 2021, our Product revenue, net included adjustment for co-pay mitigation rebates provided by us to commercially insured patients in the United States.

Such support is intended to offset a portion of the out-of-pocket expense that patients are required to pay for VASCEPA based upon the benefit design of their prescription drug coverage.

Our cost for these co-payment support payments in both of the years ended December 31, 2021 and 2020 was up to $150 per 30-day prescription filled and up to $450 per 90-day prescription filled.

Our cost for these co-payment support payments in both years ended December 31, 2022 and 2021 was up to $150 per 30-day prescription filled and up to $450 per 90-day prescription filled.

Outside of the United States, currently the majority of our product revenue is derived from the sales of VASCEPA to our commercial partners based on the net price for VASCEPA established in our contracts with such partners.

These commercial partners then resell the product in their agreed commercial territory.

Revenues from product sales to our international commercial partners are recognized when the commercial partners obtain control of our product, which occurs at a point in time, typically upon delivery to the commercial partner.

Revenues from sales to our international commercial partners are recognized when the commercial partners obtain control of our product upon delivery to the commercial partner.

The net price of VASCEPA sold by us to our customers where we directly sell VASCEPA is generally significantly higher than the net price of VASCEPA that we sell to commercial partners who then incur the cost of promoting and reselling the product in their territories.

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We also derive product revenue from sales of our product to a limited number of wholesalers in Europe, most of whom in turn resell the product to pharmacies for purposes of their reselling the product to fill patient prescriptions.

Currently the majority of our product revenue is derived from direct sales of VASCEPA in the United States.

Licensing and royalty revenue.

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Our cost of goods sold is not materially impacted by whether we sell VASCEPA directly in a country or we sell VASCEPA to a commercial partner for resale in a country.

In the year ended December 31, 2022, we incurred costs of $18.1 million in Cost of goods sold - restructuring inventory related to steps taken to amend supplier agreements to align supply arrangements with current and future market demand.

Selling, general and administrative expense.

Selling, general and administrative expense consists primarily of salaries and other related costs, including stock-based compensation expense, for personnel in our sales, marketing, executive, business development, finance and information technology functions.

finance and information technology functions.

Other costs primarily include facility costs and professional fees for accounting, consulting and legal services.

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Restructuring expense.

Restructuring expense consists of restructuring costs incurred under our September 2021 Go-to-Market strategy implementation, which consists of severance pay, incentive compensation, insurance benefits and stock-based compensation expense.

Restructuring expense consists of restructuring costs incurred under our June 2022 cost reduction plan, the discontinuation of German operations and our September 2021 Go-to-Market strategy implementation, which consists of severance pay, incentive compensation, insurance benefits, stock-based compensation expense and other contract related costs.

Interest and other (expense) income, net.

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Other (expense) income, net, consists primarily of foreign exchange losses and gains.

Income tax (provision) benefit.

Income tax (provision) benefit, deferred tax assets and liabilities, and reserves for unrecognized tax benefits reflect management’s best assessment of estimated future taxes to be paid.

Income tax provision.

Income tax provision, deferred tax assets and liabilities, and reserves for unrecognized tax benefits reflect management’s best assessment of estimated future taxes to be paid.

We are subject to income taxes in both the United States and foreign jurisdictions.

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The preparation of these financial statements requires us to make estimates and judgments that affect the reported amounts of assets, liabilities, revenue and expenses.

On an ongoing basis, we evaluate our estimates and judgments.

We base our estimates on historical experience and on various market-specific and other relevant assumptions that we believe to be reasonable under the circumstances, the results of which form the basis for making judgments about the carrying values of assets and liabilities that are not readily apparent from other sources.

On an ongoing basis, estimates are assessed and adjusted based on historical experience and current market-specific indicators, environment and assumptions.

Actual results may differ from these estimates under different assumptions or conditions.

Estimates are assessed each period and updated to reflect current information.

A summary of our critical accounting policies, significant judgments and estimates is presented in Note 2—Significant Accounting Policies to our consolidated financial statements included elsewhere in this Annual Report on Form 10-K.

We believe the following critical accounting policies affect our more significant judgments and estimates used in the preparation of our consolidated financial statements.

Revenue Recognition —In accordance with GAAP, under Accounting Standards Codification, or ASC, Topic 606, Revenue from Contracts with Customers , which we adopted on a modified retrospective basis effective January 1, 2018, we recognize revenue when our distributors obtain control of promised goods or services, in an amount that reflects the consideration which we expect to receive in exchange for those goods or services.

Revenue Recognition —In accordance with GAAP, under Accounting Standards Codification, or ASC, Topic 606, Revenue from Contracts with Customers , which we adopted on a modified retrospective basis effective January 1, 2018, revenue is recognized when product has been delivered to the wholesaler, in an amount that reflects the consideration which we expect to receive in exchange for those goods or services.

To determine revenue recognition for arrangements that we determine are within the scope of Topic 606, we perform the following five steps:

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We then recognize as revenue the amount of the transaction price that is allocated to the respective performance obligation when (or as) the performance obligation is satisfied.

We recognized Total revenue, net of $583.2 million and $614.1 million during the years ended December 31, 2021 and 2020, respectively.

For a complete discussion of our accounting for net product revenue and licensing and royalty revenues, which make up Total revenue, net, see Note 2—Significant Accounting Policies.

We sell VASCEPA principally to a limited number of distributors that in turn resell VASCEPA to retail pharmacies that subsequently resell it to patients and healthcare providers.

We began recognizing revenue from the sale of VASCEPA following our commercial launch in the United States in January 2013.

Prior to 2013, we recognized no revenue from VASCEPA sales.

In accordance with GAAP, we recognize revenue when the Distributor obtains control of our product, which occurs at a point in time, typically upon delivery to the Distributor.

We recognized Product revenue, net of $580.3 million and $607.0 million based on sales to distributors during the years ended December 31, 2021 and 2020, respectively.

We recognized Total revenue, net of $369.2 million and $583.2 million during the years ended December 31, 2022 and 2021, respectively, of which $366.5 million and $580.3 million, respectively, was based on VASCEPA sales.

For a complete discussion of our accounting for net product revenue, licensing and royalty revenues, which make up Total revenue, net, see Note 2—Significant Accounting Policies.

We have written contracts with our distributors, and transfer of control typically occurs upon delivery of our product to the Distributor.

We evaluate the creditworthiness of each of our distributors to determine whether revenues can be recognized upon delivery, subject to satisfaction of the other requirements, or whether recognition is required to be delayed until receipt of payment.

We calculate gross product revenues based on the wholesale acquisition cost that we charge our distributors for VASCEPA.

We estimate our Product revenue, net by deducting from our gross product revenues (a) trade allowances, such as invoice discounts for prompt payment and distributor fees, (b) estimated government and private payor rebates, chargebacks and discounts, such as Medicaid reimbursements, (c) reserves for expected product returns and (d) estimated costs of incentives offered to certain indirect customers, including patients.

The gross to net deductions are estimated based on available actual information, historical data, known trends, and levels of inventory in the distribution channel.

We calculate gross product revenues based on the wholesale acquisition cost charged to our distributors for VASCEPA.

our Product revenue, net by deducting from our gross product revenues (a) trade allowances, such as invoice discounts for prompt payment and distributor fees, (b) estimated government and private payor rebates, chargebacks and healthcare discounts, such as Medicaid reimbursements, (c) expected product returns and (d) estimated costs of incentives offered to certain indirect customers, including patients.

The gross to net deductions are estimated based on available actual prescription data, historical industry trends, and levels of inventory in the distribution channel.

We rely on resale data provided by our distributors as well as prescription data provided by Symphony Health and IQVIA in estimating the level of inventory held in the distribution channel.

A hypothetical 5%

change in estimated aggregate bottles of channel inventory would result in a change of less than 1% in net product revenues reported during each of the three and twelve months ended December 31, 2021 and 2020.

A hypothetical 5% change in estimated aggregate bottles of channel inventory would result in a change of less than 1% in net product revenues reported during each of the three and twelve months ended December 31, 2022 and 2021.

When evaluating licensing arrangements, we perform the following steps:

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The evidence considered included the (i) historical taxable profitability of our U.S.

operations, (ii) historical pre-tax book loss position, (iii) sources of future taxable income, giving weight to sources according to the extent to which they can be objectively verified, (iv) the provisions of the Tax Cuts and Jobs Act enacted in 2017 and their impact on our future taxable income, and (v) the risks to our business related to the commercialization and development of VASCEPA.

operations, (ii) historical pre-tax book loss position, (iii) sources of future taxable income, giving weight to

sources according to the extent to which they can be objectively verified, (iv) the provisions of the Tax Cuts and Jobs Act enacted in 2017 and their impact on our future taxable income, and (v) the risks to our business related to the commercialization and development of VASCEPA.

Based on our assessment, we concluded that all of our net deferred tax assets are not more likely than not to be realizable as of both December 31, 2022 and 2021.

Changes in historical earnings performance, future earnings projections, and changes in tax laws and tax rates, among other factors, may cause us to adjust our valuation allowance on deferred tax assets in the future, which would impact our income tax expense in the period in which we determine that these factors have changed.

maintain the valuation allowance until sufficient positive evidence exists to conclude that it is more likely than not that our deferred tax benefits will be realized.

We intend to maintain the valuation allowance until sufficient positive evidence exists to conclude that it is more likely than not that our deferred tax benefits will be realized.

We will continue to monitor the need for valuation allowances in each jurisdiction and may adjust our positions in the future.

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For a comparison of our results of operations and financial condition for fiscal years 2021 and 2020, see “Item 7—Management’s Discussion and Analysis of Financial Condition and Results of Operations”

of our 2020 Annual Report on Form 10-K, filed with the SEC on February 25, 2021 .

of our 2021 Annual Report on Form 10-K, filed with the SEC on March 1, 2022 .

Comparison of Fiscal Years Ended December 31, 2022 and December 31, 2021

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Total revenue, net consists primarily of revenue from the sale of VASCEPA in the United States.

In addition to the United States, we also sell VASCEPA by prescription in Germany and is available by prescription in Canada, Lebanon and the United Arab Emirates through collaborations with third-party companies.

In addition to the United States, we also sell VASCEPA by prescription in certain countries in Europe and is available by prescription in Canada, Lebanon and the United Arab Emirates through collaborations with third-party companies.

As further discussed below, this decrease consists of a $218.0 million decrease in U.S.

product revenue, a decrease of $6.5 million in net product revenue from sales of VASCEPA outside of the United States and a $4.2 million decrease licensing and royalty revenue.

product revenue, $0.2 million decrease in licensing and royalty revenue, offset by an increase of $4.3 million in net product revenue from sales of VASCEPA outside of the United States.

Product revenue, net.

We recorded product revenue, net, of $366.5 million and $580.3 million during the years ended December 31, 2022 and 2021, respectively, a decrease of $213.8 million, or 37%.

This decrease was driven primarily by volume of VASCEPA sales to our customers in the United States, which was adversely impacted by generic availability in the U.S., as well as timing of sales outside the U.S., as further described below.

Generics in the U.S.

- Inclusive of generic icosapent ethyl, based on prescription levels reported by Symphony Health, the icosapent ethyl market increased for the year ended December 31, 2021 by 11% as compared to the year ended December 31, 2020.

Based on the available data from Symphony Health, generic prescriptions of icosapent ethyl for the year ended December 31, 2021 were approximately 15% of the total icosapent ethyl prescriptions, which includes the second generic entrant into the market, Dr.

Reddy's, late in the second quarter of 2021 providing additional generic supply, further impacting the volume of branded sales during the year ended December 31, 2021.

Product revenue, net in the fourth quarter of 2021 was flat as compared to the third quarter of 2021, following the launch of our Go-to-Market strategy which was announced on September 22, 2021.

We will continue to monitor the generic prescription market in the U.S.

and will vigorously protect our cardiovascular risk reduction patents, as deemed appropriate.

In addition, based on available information, we believe that a significant number of icosapent ethyl prescriptions in the U.S.

have gone unfilled during 2021, due to general market disruption of order fulfillment processes.

These processes at the pharmacy level have favored generic products in that in anticipation of receiving generic supply, in certain circumstances pharmacists have opted to wait to fill prescriptions with generic product by ordering product for later fulfillment.

In the case of icosapent ethyl, in many U.S.

markets, generic product has been delayed or unavailable.

In addition, we have heard multiple reports of patients finding that the generic product is more expensive than they have historically paid for the branded product resulting in their refusal to fill their prescriptions.

In addition, we recognized net product revenue of approximately $2.4 million and $8.9 million as of December 31, 2021 and 2020, respectively for VASCEPA sales outside of the United States, primarily as a result of an initial order to ensure availability of adequate product supply for the launch of VASCEPA in Canada in 2020.

We also recognized product revenue of $0.7 million related to VAZKEPA sales in Europe, where the launch of VAZKEPA occurred at the end of the third quarter of 2021.

Despite the generic competition in the U.S., including a third generic entrant in January 2022, we remain confident that the patient need for VASCEPA is high.

We believe that our U.S.

Go-to-Market strategy began showing early signs of positive results in the fourth quarter of 2021.

We will continue to work closely with payers to ensure that VASCEPA maintains a net cost advantage compared to generic icosapent ethyl products.

We have partnered with BlinkRx, a unique patient solution, to provide an enhanced, digital first prescription fulfillment channel.

As a result of the continued uncertainty of the global impact of COVID-19, the impact of generic competition in the U.S.

and challenges for most drugs seeking market access in Europe, we are not providing revenue guidance at this time.

We will consider resuming revenue guidance when there is greater clarity on the impact of these items.

This decrease was driven primarily by a 38% decrease in VASCEPA sales to our customers in the United States.

This decrease was driven by a decline in volume and net selling price as a result of the impact from generic competition in the market.

During the year ended December 31, 2022 there were three generics in the market for the majority of the year, with a fourth generic entering in the fourth quarter for the 0.5-gram capsule.

During the majority of the year ended December 31, 2021 there was only one generic in the market, with the second generic entering the market in the third quarter of 2021.

The overall icosapent ethyl market in the United States, based on prescription levels reported by Symphony Health, increased for the year ended December 31, 2022 by 7% as compared to the year ended December 31, 2021.

Our share of the icosapent ethyl market has decreased to approximately 60% in the year ended December 31, 2022 compared to approximately 85% in the year ended December 31, 2021.

Additionally, based on prescription levels reported by Symphony Health, VASCEPA branded prescriptions decreased by 19% in the year ended December 31, 2022 as compared to the year ended December 31, 2021.

In Europe, our commercial launch and growth of the market has been slower than expected due to government health care spending pressure, the resurgence of COVID-19 earlier this year, political unrest in eastern Europe and the Company's decision to cease commercial operations in Germany resulting in product revenue, net of $2.6 million and $0.7 million as of December 31, 2022 and 2021, respectively.

The initial launch of VAZKEPA in Europe occurred at the end of the third quarter of 2021.

For the year ended December 31, 2022 we recorded $4.1 million of product revenue, net, to our collaboration partners compared to $1.7 million during the year ended December 31, 2021.

Despite the generic competition in the U.S., we remain confident that the global patient need for VASCEPA is high.

During 2022 and through the date of this Annual Report on Form 10-K, we launched commercial operations in five countries throughout Europe, while also receiving regulatory approval in seven countries outside of EMA regulatory approval authority.

In 2023, we will continue to focus on obtaining pricing reimbursement and launching commercial operations in all remaining European markets as well as progressing international regulatory filings and supporting approval processes in up to nine countries.

Licensing and royalty revenue.

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Cost of goods sold.

Cost of goods sold during the years ended December 31, 2021 and 2020 was $121.3 million and $131.4 million, respectively, a decrease of $10.1 million, or 8%.

Cost of goods sold includes the cost of API for VASCEPA on which revenue was recognized during the period, as well as the associated costs for encapsulation, packaging, shipment, supply management, insurance and quality assurance.

Cost of goods sold during the years ended December 31, 2022 and 2021 was $126.7 million and $121.3 million, respectively, an increase of $5.4 million, or 4%.

Cost of goods sold includes the cost of API for VASCEPA as well as the associated costs for encapsulation, packaging, shipment, supply management, insurance and quality assurance, which revenue was recognized during the period.

The cost of the API included in cost of goods sold reflects the average cost of API included in inventory.

This average cost reflects the actual purchase price of VASCEPA API.

During 2022, as part of our cost reduction plan, we have taken steps to amend supplier agreements to align supply arrangements with current and future demand resulting in a $18.1 million charge, which was recorded as Cost of goods sold - restructuring inventory.

In addition, during 2022, we recorded an approximately $9.6 million inventory write-off due to unsellable inventory unrelated to product dating.

The API included in the calculation of the average cost of goods sold during the years ended December 31, 2022 and 2021 was sourced from multiple API suppliers.

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Our gross margin on product sales for the years ended December 31, 2022 and 2021 was 65% and 79%, respectively.

Excluding the restructuring inventory and inventory write-off, gross margin was 73% for the year ended December 31, 2022.

The remaining decrease in gross margin is primarily as a result of a decrease in net selling price.

Selling, General and Administrative Expense.

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(1) Selling expense for the years ended December 31, 2022 and 2021 was $185.6 million and $266.5 million, respectively, a decrease of $80.9 million, or 30%.

This decrease is primarily due to a decrease in marketing and direct-to-consumer promotions in 2021, as a result of the impact of COVID-19 and our focus on improving the profitability of our operations in the United States.

The decrease also includes a reduction in costs associated with our Go-to-Market strategy resulting in decreased promotional initiatives, reduced travel and a decrease in our sales force.

(2) General and administrative expense for the years ended December 31, 2021 and 2020 was $109.6 million and $73.4 million, respectively, an increase of $36.1 million, or 49%.

This increase is primarily due to increased personnel costs related to preparing for and commencing expansion into Europe.

This decrease is primarily related to the reduction in our U.S.

sales force from approximately 600 sales representatives at the beginning of 2021 to 300 sales representatives in September 2021, with a further reduction in

force to 75 sales representatives in June 2022.

In addition, there has been a related decrease in promotional initiatives in the United States during 2022.

(2) General and administrative expense for the years ended December 31, 2022 and 2021 was $96.5 million and $109.6 million, respectively, a decrease of $13.1 million, or 12%.

This decrease is primarily due to a decrease in employee related costs as a result of the reduction in force from the September 2021 and the June 2022 restructuring activities.

The decrease was further impacted by a decrease in branded pharma fees as a result of lower sales due to additional generic entrants in the market as well as higher legal fees related to the patent infringement litigation during the year ended December 31, 2021.

(3) Non-cash stock-based compensation expense for the years ended December 31, 2022 and 2021 was $22.3 million and $32.3 million, respectively, a decrease of $10.0 million, or 31%.

Non-cash stock-based compensation expense represents the estimated costs associated with equity awards issued to internal personnel supporting our selling, general and administrative functions.

The decrease is due to the reversal of certain performance-based awards as it was no longer deemed probable that the performance criteria for vesting would be achieved within the required timeframe and the reversal of expense associated with the reduction in U.S.

We are investing in building an appropriate foundation for the successful launch of VAZKEPA throughout Europe, advancing regulatory filings internationally and continuing our orchestrated omnichannel engagement for VASCEPA in the U.S.

As a result, we will continue to evaluate all of our spending commitments and priorities as well as adjust our level of education and promotional activities based on various factors, including the impact of COVID-19 and U.S.

generic competition.

The decrease is primarily due to the decrease in U.S.

field force as well as the reversal of expense associated with certain performance-based awards as it was no longer deemed probable that the performance criteria for vesting would be achieved within the required timeframe.

We are investing in building an appropriate foundation for the successful launch of VAZKEPA throughout Europe, advancing regulatory filings internationally and navigating the dynamic U.S.

generic competition as well as timing of pricing reimbursements throughout Europe.

Research and Development Expense.

Research and development expense for the years ended December 31, 2021 and 2020 was $29.3 million and $39.0 million, respectively, a decrease of $9.7 million, or 25%.

Research and development expense for the years ended December 31, 2022 and 2021 was $30.4 million and $29.3 million, respectively, an increase of $1.1 million, or 4%.

Research and development expenses for the years ended December 31, 2022 and 2021 are summarized in the table below:

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REDUCE-IT study (1)

Fixed-dose combination (2)

Regulatory filing fees and expenses (3)

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Total research and development expense

(1) In September 2018, we announced landmark positive topline results of the REDUCE-IT cardiovascular outcomes trial.

The decrease in expenses is primarily driven by the completion of certain analyses performed beyond the REDUCE-IT cardiovascular outcomes trial.

(1) The decrease in expenses for the REDUCE-IT study is primarily driven by the decrease in the number of analyses performed beyond the original REDUCE-IT cardiovascular outcomes trial.

(2) Fixed-dose combination expenses relate to the cost associated with the development of the fixed-dose combination of VASCEPA and a statin, which began in 2022.

(3) The regulatory filing fees in each of the years ended December 31, 2022 and 2021 included annual U.S.

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Such fees primarily represent fees for qualification of new suppliers, including increasing capacity capabilities, and fees to support international regulatory review of VASCEPA, particularly in Europe, sites used for the manufacture of product used in the REDUCE-IT clinical outcomes study.

(3) Internal staffing, overhead and other research and development expenses primarily relate to the costs of our personnel employed to manage research, development and regulatory affairs activities and related overhead costs including consulting and other professional fees that are not allocated to specific projects, including costs associated with securing regulatory approvals for VAZKEPA in Europe as achieved in 2021.

Also included are costs related to qualifying suppliers.

Also included are costs associated with various other investigations, including other costs in collaboration with Mochida and pilot studies regarding VASCEPA.

(4) Internal staffing, overhead and other research and development expenses primarily relate to the costs of our personnel employed to manage research, development and regulatory affairs activities and related overhead costs including consulting and other professional fees that are not allocated to specific projects, including costs associated with securing regulatory approvals for VAZKEPA in Europe as achieved in 2021 as well as further regulatory expansion in other countries throughout 2022.

Also included are costs related to qualifying suppliers and costs associated with various other investigations, including other costs in collaboration with Mochida and pilot studies regarding VASCEPA.

(5) Non-cash stock-based compensation expense represents the estimated costs associated with equity awards issued to personnel supporting our research and development and regulatory functions.

We anticipate our research and development expenses to significantly increase in 2022 primarily due to our initiative to reduce residual cardiovascular risk by developing a fixed dose combination of VASCEPA and a statin.

We continuously evaluate all of our spending commitments and priorities and we plan to adjust our level of research and development activities based on various factors, including the impact of U.S.

generic competition as well as timing of pricing reimbursements throughout Europe.

Restructuring expense .

Restructuring expense for the years ended December 31, 2021 and 2020 was $13.7 million and nil, respectively.

The charge is due to the launch of the Go-to-Market strategy announced on September 22, 2021, which primarily related to the reduction of our U.S.

field force to approximately 300 sales professionals.

Restructuring expense for the years ended December 31, 2022 and 2021 was $13.5 million and $13.7, respectively, a decrease of $0.2 million or 1%.

The charge in the current year is due to the implementation of the Comprehensive Cost Reduction Plan announced on June 6, 2022 as well as the discontinuation of the German operations announced on August 19, 2022.

These two plans were related to the reduction of our U.S.

field force from approximately 300 sales representatives to approximately 75 sales representatives and the closure of our German operations due to a viable agreement on the reimbursement price of VAZKEPA in Germany not being reached, respectively.

The prior year charge was the result of a September 2021 restructuring that reduced the U.S.

sales force from approximately 600 sales representatives to approximately 300 sales representatives at that time.

Refer to Note 2 Significant Accounting Policies for additional information.

Interest Income, net.

Net interest income for the years ended December 31, 2021 and 2020 was $1.1 million and $2.3 million, respectively, a decrease of $1.2 million, or 52%.

Net interest income for the years ended December 31, 2021 and 2020 is summarized in the table below:

Year ended December 31,

Debt from royalty-bearing instrument (1):

Cash interest

Non-cash interest

Total debt from royalty-bearing instrument interest expense

Other interest expense

Total interest expense

Interest income (2)

Total interest income, net

(1) Cash and non-cash interest expense related to the December 2012 royalty-bearing instrument for the years ended December 31, 2021 and 2020 was nil and $2.2 million, respectively.

In November 2020, we made the final payment on our royalty-bearing instrument and, as a result, no interest from this instrument was incurred in 2021.

(2) Interest income for the years ended December 31, 2021 and 2020 was $1.2 million and $4.9 million, respectively.

Interest income represents income earned on cash and investment balances.

The decrease is a result of COVID-19 and the related economic conditions, including a reduction in interest rates in 2021 as compared to the prior year, resulting in a decrease in interest income, as well as, an overall decrease in our short-term and long-term investment balance during 2021.

Net interest income for the years ended December 31, 2022 and 2021 was $2.8 million and $1.1 million, respectively, an increase of $1.7 million, or 157%.

The increase is primarily due to higher interest rates in the current year compared to the prior year.

Other (expense) income, net .

Other (expense) income, net, for the year ended December 31, 2021 and 2020 was expense of $0.3 million and income of $0.1 million, respectively.

Other (expense) income, net, for the year ended December 31, 2022 and 2021 was expense of $0.7 million and $0.3 million, respectively.

Other (expense) income, net, in the years ended December 31, 2022 and 2021 primarily consists of gains and losses on foreign exchange transactions.

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Provision for income taxes for the year ended December 31, 2022 and 2021 was $2.0 million and $3.6 million, respectively.

The increase in the provision for income taxes is due to a change in geographic mix of pre-tax income as well as an increase in our uncertain tax positions.

The decrease in the provision for income taxes is due to a change in geographic mix of pre-tax income.

Liquidity and Capital Resources

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Increase (decrease) in cash and cash equivalents and restricted cash

Net cash used in operating activities during 2021 compared to 2020 increased primarily as a result of a decrease in product sales as well as due to costs associated with our expansion into Europe.

Net cash provided by investing activities during the year ended December 31, 2021 is due to the proceeds from the maturity of our investment-grade interest bearing instruments of $394.3 million, partially offset by our purchase of approximately $290.2 million of securities during 2021.

Net cash used in investing activities during the year ended December 31, 2020 is as a result of our purchasing approximately $678.7 million investment-grade interest bearing instruments during 2020, partially offset by $302.0 million in proceeds from the maturity and sale of securities.

Net cash used in financing activities during the year ended December 31, 2021 is primarily as a result of costs associated with our stock compensation plan.

Net cash used in financing activities during the year ended December 31, 2020 primarily reflects the payments made on our royalty-bearing instrument with CPPIB, with the final payment made in the fourth quarter of 2020.

Net cash provided by financing activities during the year ended December 31, 2019 is primarily due to completing a public offering of 22,222,223 ADS with each ADS representing one ordinary share at a price of $18.00 per ADS, $17.235 per ADS after commission, on July 18, 2019.

In addition, we granted the underwriters a 30-day option to purchase up to an additional 3,333,333 ADS at the same price per ADS.

On July 29, 2019, the underwriters exercised the full option.

This public offering, including the exercised option, resulted in net proceeds of $440.1 million, after deducting customary commissions and offering expenses.

As of December 31, 2021, we had net accounts receivable of $163.7 million and inventory of $355.9 million.

We have incurred annual operating losses since our inception until this year and, as a result, we had an accumulated deficit of $1.4 billion as of December 31, 2021.

We anticipate that quarterly net cash outflows in future periods will continue to be variable as a result of the timing of certain items, including our purchases of API, promotional activities under our Go-to-Market strategy and the impact from COVID-19 on our operations and those of our customers, the generic competition in the United States as a result of our ANDA litigation and commercialization of VAZKEPA in Europe.

We believe that our cash and cash equivalents of $219.5 million as of December 31, 2021 together with our short-term investments of $234.7 million as of December 31, 2021, will be sufficient to fund our projected operations for at least twelve months and is adequate to achieve positive cash flow from VASCEPA based on our current plans.

Net cash used in operating activities during 2022 compared to 2021 increased primarily as a result of a decrease in U.S.

product revenue, costs associated with commercial and pre-launch operations in Europe as well as an increase in inventory purchases in the first half of 2022.

Net cash provided by investing activities during the year ended December 31, 2022 is primarily due to the proceeds from the maturity of $257.5 million in investment-grade interest bearing instruments, partially offset by $81.6 million in purchases of investment-grade interest bearing instruments as compared to the same period in 2021 where proceeds from the maturity of investment-grade interest bearing instruments was $394.3 million, partially offset by $290.2 million in purchases of investment-grade interest bearing instruments.

Net cash used in financing activities during the years ended December 31, 2022 and 2021 are primarily as a result of costs associated with our stock compensation plan.

As of December 31, 2022, we had net accounts receivable of $131.0 million, current inventory of $228.7 million and long-term inventory of $163.6 million.

We have incurred annual operating losses since our inception and, as a result, we had an accumulated deficit of $1.5 billion as of December 31, 2022.

We anticipate that quarterly net cash outflows in future periods will continue to be variable as a result of the timing of certain items, including our purchases of API, the generic competition in the United States and commercialization of VAZKEPA in Europe.

VAZKEPA is available in certain countries throughout Europe, including the UK, and we commenced pre-launch planning and other commercial preparation activities, and continue to grow our European staff by hiring Market access and Medical affairs teams, among others, across Europe as deemed appropriate on a country by country basis.

As of December 31, 2022, we had cash and cash equivalents of $217.7 million and short-term investments of $91.7 million.

In accordance with ASC 205-40, management is required to evaluate our ability to continue as a going concern for at least one year after the date of the financial statements are issued.

We believe that our cash and cash equivalents and our short-term investments will be sufficient to fund our projected operations for at least twelve months from the issuance date of our audited consolidated financial statements included elsewhere within this Annual Report and is adequate to support continued operations based on our current plans.

We have based this estimate on assumptions that may prove to be wrong, including as a result of the risks discussed under Part II, Item IA, “Risk Factors”, and we could use our capital resources sooner than we expect or fail to achieve positive cash flow.

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All of our investments are held in U.S.

From time to time, we maintain a small amount of our cash and cash equivalents in Euro and Pound Sterling.

We purchase a portion of our supply from Novasep based on a U.S.

We maintain a small amount of our cash and cash equivalents in Euro and from time to time, maintain a small amount of our cash and cash equivalents in other currencies.

We purchase a portion of our supply based on a U.S.

dollar to Euro exchange rate and, as such, remain subject to currency fluctuation risk for such purchases.

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 5. Market for Registrant’s Common Equity