What changed in this filing

/stocks — the workspaceLOADING

Item 1. Legal Proceedings

2022-08-03 compared with 2022-05-04 · 157 added, 161 removed, 1408 unchanged (18% of the section changed)

5 unchanged sentences

Refer to Note 5 –

Commitments and Contingencies to our unaudited condensed consolidated financial statements included elsewhere in this Quarterly Report for further details on our legal proceedings during the three months ended March 31, 2022.

Commitments and Contingencies in this Quarterly Report for further details on our legal proceedings during the six months ended June 30, 2022.

Ri sk Factors

1 unchanged sentence

Because our actual results may differ materially from any forward-looking statements that we make or that are made on our behalf, this section includes a discussion of important factors that could affect our actual future results, including, but not limited to, our ability to successfully commercialize VASCEPA and VAZKEPA, collectively referred to as VASCEPA, our capital resources, the progress and timing of our clinical programs, the safety and efficacy of our product candidates, risks associated with regulatory filings, the potential clinical benefits and market potential of our product candidates, commercial market estimates, future development efforts, patent protection, effects of healthcare reform, reliance on third parties effects of tax reform, and other risks set forth below.

These risk factors have not been materially updated from our Annual Report on 10-K for the year ended December 31, 2021 filed with the SEC on March 1, 2022, or our Annual Report.

Except where denoted with an “*”, these risk factors have not been materially updated from our Annual Report on 10-K for the year ended December 31, 2021 filed with the SEC on March 1, 2022, or our Annual Report.

Summary Risk Factors

1 unchanged sentence

These risks include, but are not limited to, the following:

We are substantially dependent upon VASCEPA ® (icosapent ethyl), its commercialization in the United States and its development and commercialization in Europe and other major markets.

We are substantially dependent upon VASCEPA ® (icosapent ethyl), its commercialization in the United States and its development, launch and commercialization in Europe and other major markets.

In the United States, VASCEPA is facing increasing competition from generic versions of the drug.

1 unchanged sentence

however, we may not be successful in obtaining such approvals in a timely manner, or at all and, even if successfully obtained, we may not be successful in commercializing VAZKEPA in Europe or elsewhere.

In the United States, we face increasing competition from generic drug companies in the near term and our revenues and results of operations could be materially and adversely affected.

Factors outside of our control may make it more difficult for VASCEPA to achieve a level of market acceptance by physicians, patients, healthcare payors and others in the medical community at levels sufficient to meet our expectations for commercial success.

Factors outside of our control make it more difficult for VASCEPA to achieve a level of market acceptance by physicians, patients, healthcare payors and others in the medical community at levels sufficient to meet our expectations for commercial success.

The continued scale, scope and duration of business interruptions caused by the ongoing COVID-19 pandemic and related recovery efforts are uncertain as the impact of the pandemic continues to cause negative effects on our business.

Our current and planned commercialization efforts, including our implemented Go-to-Market strategy, may not be successful in increasing sales of VASCEPA in the United States and developing sales internationally.

Our recently announced cost and organizational restructuring plan may not be successful in addressing current shifts within the Company's U.S.

business and developing sales internationally.

Our promotion and supply of VASCEPA is subject to regulatory scrutiny and associated risk.

3 unchanged sentences

Omega-3 fatty acids are also marketed by other companies as non-prescription dietary supplements.

As a result, VASCEPA is subject to non-prescription competition and consumer substitution.

As a result, in the U.S., VASCEPA is subject to non-prescription competition and consumer substitution.

The commercial value of VASCEPA outside the United States may be smaller than we anticipate, including adequacy of product reimbursement which can vary from country to country.

17 unchanged sentences

In recent years and currently, much of our financial results and revenue has been dependent on our ability to execute our development and commercial strategy for VASCEPA in the United States.

Generic version of VASCEPA launched in the United States in November 2020, June 2021 and January 2022.

Generic versions of VASCEPA launched in the United States in November 2020, June 2021 and January 2022.

We expect that VASCEPA could face more competition from generic companies in the United States in the near term in light of the patent litigation rulings against us, applicable only in this territory.

Increasing sales of generic versions of VASCEPA could continue to have a material and adverse impact on our revenues and results of operations in the United States.

We implemented a Go-to-Market strategy in an effort to optimize provider engagement and drive demand of VASCEPA in the United States by shifting reliance on sales force interactions with healthcare professionals to providing managed care and prescription access through an omnichannel platform, and, in connection with this initiative, we reduced our U.S.

field force to approximately 300 sales representatives.

Although we believe this initiative will provide greater access to VASCEPA and ultimately result in an improved expense structure, such efforts are costly to implement, could impact employee morale and make hiring and retaining talented personnel more challenging, and may not result in all or any of the benefits we anticipate.

In June 2022, we implemented a cost and organizational restructuring plan, which included a further reduction to our U.S.

commercial team from approximately 300 sales representatives to approximately 75 sales representatives.

Although we believe this will result in an improved expense structure, such efforts could impact employee morale and make hiring and retaining talented personnel more challenging, may not result in all or any of the cost-savings or other benefits we anticipate and are costly to implement.

We continue our development efforts to support commercialization of VASCEPA in major markets outside the United States.

In March 2021 we announced that the European Commission, or the EC, approved the marketing authorization application for icosapent ethyl, under the brand name VAZKEPA, hereafter along with VASCEPA, collectively referred to as VASCEPA, to reduce the risk of cardiovascular events in high-risk, statin-treated adult patients who have elevated triglycerides (≥150 mg/dL) and either established cardiovascular disease or diabetes and at least one additional cardiovascular risk factor.

In September 2021, we launched VAZKEPA in Germany, representing our first European launch, In March 2022, we received national reimbursement for VAZKEPA in Sweden, representing our first national reimbursement in a European country.

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

We are in the process of obtaining further pricing and reimbursement approvals for VAZKEPA in relevant jurisdictions in Europe.

This process is conducted on a country-by-country basis and is time-consuming and complex.

On March 25, 2022, Amarin received its first national reimbursement in a European country with official confirmation that the Swedish Dental and Pharmaceutical Benefits Agency (TLV) approved VAZKEPA for national reimbursement in Sweden.

W e may not be successful in obtaining such approvals in a timely manner with acceptable terms, or in additional countries.

On March 25, 2022, Amarin received its first national reimbursement in a European country with official confirmation that the Swedish Dental and Pharmaceutical Benefits Agency, or TLV, approved VAZKEPA for national reimbursement in Sweden.

On July 13, 2022 the UK’s National Institute for Health and Care Excellence, or NICE, announced final guidance for reimbursement for VAZKEPA ® and use across the National Health Service, or NHS, in England and Wales to reduce the risk of CV events in adult statin-treated patients at high cardiovascular risk who have elevated triglycerides (≥150 mg/dL [≥

1.7 mmol/L]), LDL-C levels >1.04 mmol/L (and ≤

2.60 mmol/L) and established cardiovascular disease.

In June 2022 HLS Therapeutics Inc., or HLS, entered into Product Listing Agreements with New Brunswick, Northwest Territories and the non-insurance health benefits, for the listing and public reimbursement of VASCEPA on their respective Public Prescription Drug Insurance Plans.

We may not be successful in obtaining additional approvals in a timely manner with acceptable terms, or in additional countries.

Our expansion and development of VASCEPA outside the United States is generally not subject to the adverse patent ruling in the United States.

2 unchanged sentences

We have been developing VAZKEPA on our own in Europe for the approved cardiovascular risk reduction indication and are exploring possible strategic collaborations in smaller markets within Europe and in other major markets.

We currently have multiple partners for the development and commercialization of VASCEPA in select geographies and intend to assess potential partners to

commercialize VASCEPA in other parts of the world.

For example, we have strategic collaborations for the development and commercialization of VASCEPA in Canada, the Middle East and Greater China.

We currently have multiple partners for the development and commercialization of VASCEPA in select geographies and intend to assess potential partners to commercialize VASCEPA in other parts of the world.

For example, we have strategic collaborations for the development and

commercialization of VASCEPA in Canada, the Middle East and Greater China.

However, we cannot make any guarantees as to the success of these efforts or that our beliefs about the value potential are accurate, and if commercialization plans for VASCEPA do not meet expectations in major markets such as the United States and Europe, our business and prospects could be materially and adversely affected.

6 unchanged sentences

As a result, the lack of alternative markets and products we develop could constrain our ability to generate revenues and achieve profitability.

In the United States, we face increasing competition from generic drug companies in the near term and our revenues and results of operations could be materially and adversely affected.

*In the United States, we face increasing competition from generic drug companies in the near term and our revenues and results of operations could continue to be materially and adversely affected.

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

8 unchanged sentences

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 when permitted and 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.

We intend to appeal the decision of the district court when permitted and also continue to vigorously pursue our ongoing litigation with Health Net, LLC, but cannot predict the outcome or the impact on our business.

In June 2021, Dr.

19 unchanged sentences

VASCEPA supply that are not known to us and that are more efficient or less expensive than our sources.

Furthermore, generic companies could potentially convince our suppliers to prioritize supply to the generic companies ahead of any applicable contractual commitments to supply us.

While we anticipate that our suppliers will honor their commitments to us, if generic competitors are successful in gaining an advantage in the supply chain, manufacturing and supply with respect to VASCEPA will suffer and consequentially VASCEPA prescriptions will likely decrease.

In addition, we may need to litigate with such suppliers to protect our rights, which can be costly and distracting to management.

Such circumstances could have a material and adverse impact on our revenues and results of operations directly in the United States and potentially outside of the United States as well if supply costs and availability are affected or promotion and education programs reduced.

Furthermore, generic companies could potentially convince suppliers to prioritize supply to the generic companies.

We have limited experience as a company in commercializing VASCEPA outside of the United States and may be unsuccessful in developing sales internationally.

While we have been working internally and with partners to support efforts toward approvals and commercialization outside the United States in light of the REDUCE-IT results and the recent EC approval of VAZKEPA, we may be unsuccessful in expanding our global footprint.

For example, we plan to launch VAZKEPA on our own in the most commercially significant markets in Europe and launched VAZKEPA in Germany, representing our first European launch.

While we have been working internally and with partners to support efforts toward approvals and commercialization outside the United States in light of the REDUCE-IT results and the EC approval of VAZKEPA, we may be unsuccessful in expanding our global footprint.

For example, we are launching VAZKEPA on our own in the most commercially significant markets in Europe and launched VAZKEPA in Germany, representing our first European launch.

The commercial launch of a new pharmaceutical product is a complex and resource heavy undertaking for a company to manage, and we have no prior experience as a company operating a commercial-stage pharmaceutical business in Europe.

2 unchanged sentences

the impact of the expiration of regulatory exclusivities and entry into the market of additional generic versions of VASCEPA;

our inability to attract and retain adequate numbers of effective sales and marketing personnel, particularly in light of our recent reduction in force;

our inability to attract and retain adequate numbers of effective sales and marketing personnel, particularly in light of our recent reductions in force;

our inability to adequately train our sales and marketing personnel and our inability to adequately monitor compliance with applicable regulatory and other legal requirements;

the inability of our new sales personnel, to obtain access to or persuade adequate numbers of physicians to prescribe VASCEPA;

if our Go-to-Market strategy and omnichannel approach does not provide improved managed care and prescription access, or if healthcare providers are reluctant or delayed in shifting to the omnichannel platform;

if we have overestimated the addressable market, the inability of our sales personnel, to obtain access to or persuade adequate numbers of physicians to prescribe or patients to use VASCEPA;

regulators may impose restrictions on VASCEPA’s conditions for use, distribution or marketing, and may impose ongoing requirements for post-market surveillance, post-approval studies or clinical trials, which may be costly or result in label or other use restrictions;

complexities and challenges in connection with pricing and reimbursement, including our ability to secure adequate reimbursement coverage, which in Europe is almost exclusively covered through public national funding, and not individual private insurance companies;

if we have overestimated the addressable market or are unable to convince healthcare providers to prescribe, or if patients are unwilling to use, VASCEPA;

the lack of complementary products to be offered by sales personnel, which may put us at a competitive disadvantage relative to companies with more extensive product lines;

10 unchanged sentences

In many countries outside the United States, government-sponsored healthcare systems are the primary payors for drugs.

With increasing budgetary constraints and differing views on or challenges in valuing medicines, governments and payors in many countries are applying a variety of measures to exert downward price pressure.

With increasing budgetary constraints and differing views on or challenges in valuing medicines, governments and payors in many

countries are applying a variety of measures to exert downward price pressure.

These measures can include mandatory price controls, price referencing, therapeutic-reference pricing, increases in mandates, incentives for generic substitution and biosimilar usage and government-mandated price cuts.

33 unchanged sentences

MACE events were defined as a composite of cardiovascular death, nonfatal myocardial infarction (MI), nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization.

This result was supported by robust demonstrations of efficacy across multiple secondary endpoints.

This result was supported by robust

demonstrations of efficacy across multiple secondary endpoints.

VASCEPA was well tolerated in REDUCE-IT with a safety profile generally consistent with clinical experience associated with omega-3 fatty acids and current U.S.

33 unchanged sentences

FDA-approved labeling that is more closely tied to the patient population studied in a clinical trial could limit use generally and could make reimbursement more difficult.

The continued scale, scope and duration of business interruptions caused by the ongoing COVID-19 pandemic are uncertain as the impact of the pandemic continues to cause negative effects on our business.

*The continued scale, scope and duration of business interruptions caused by the ongoing COVID-19 pandemic and related recovery efforts are uncertain as the impact of the pandemic continues to cause negative effects on our business.

The global spread of COVID-19 has created significant volatility, uncertainty and disruption in healthcare, social, supply and economic infrastructures.

6 unchanged sentences

ability to access supplies of VASCEPA and the willingness of patients to visit doctors for non-urgent medical examination or to visit labs for blood tests to assess biomarkers such as lipid levels;

our ability to commercialize VASCEPA, including as a result of ongoing travel restrictions, social distancing and other containment measures or the restoration of such measures;

the enrolment or monitoring of patients in clinical trials, particularly at clinical trial sites located in highly impacted jurisdictions and jurisdictions where vaccination rates are low;

our ability to commercialize VASCEPA, including as a result of ongoing travel restrictions, social distancing and other containment measures or the restoration of such measures in areas where such measures have been relaxed;

the enrollment or monitoring of patients in clinical trials, particularly at clinical trial sites located in highly impacted jurisdictions and jurisdictions where vaccination rates are low;

the ability to access, secure and otherwise obtain and deliver sufficient and timely commercial or clinical supplies of VASCEPA at reasonable prices and sufficient to meet demand if the production capabilities of suppliers is disrupted;

4 unchanged sentences

offices, operations and facilities impeding our ability to work together as a company and with our business and healthcare partners.

To comply with travel restrictions, social distancing, quarantines and other containment measures implemented in various geographies, in March 2020, we suspended field based face-to-face interactions.

Although by the end of summer of 2020, substantially all of our field force personnel had the ability to resume face-to-face customer interactions, in a manner consistent with state and local guidance, limitations on such interactions have been imposed.

As variants emerge and as vaccine protocols develop, face-to-face interactions are challenging for us to predict and the number of patient visits to doctors’

As variants emerge and as vaccine usage and protocols evolve, face-to-face interactions are challenging for us to predict and the number of patient visits to doctors’

offices and patients undergoing blood testing remains down considerably from pre-COVID-19 levels.

In September 2021, to optimize provider engagement and drive demand for VASCEPA in the United States and to counteract the changing engagement dynamics, including those introduced as a result of COVID-19, we announced our Go-to-Market strategy which incorporates omnichannel communications with healthcare providers.

The circumstances surrounding COVID-19 vary geographically and vary over time, with continued risk of resurgences in COVID-19 cases, and reinstitution of protocols, in various geographies and as the efficacy of the vaccine on various strains remains uncertain.

While we have supplemented our face-to-face interactions with virtual outreach and our omnichannel platform, these efforts may not

be as impactful as traditional, in-person interactions.

The circumstances surrounding COVID-19 vary geographically and vary over time, with continued risk of potential resurgences in COVID-19 cases, and the possibility of reinstitution of protocols, in various geographies as the efficacy of the vaccine on various strains remains uncertain.

While we have supplemented our face-to-face interactions with virtual outreach, these efforts may not be as impactful as traditional, in-person interactions.

Specifically, access to healthcare professionals through the internet or other channels, may not be as productive as in-person interactions.

Although we have a geographically diversified supply chain for VASCEPA and believe we have sufficient inventory on hand at pharmacies throughout the United States and other markets where it is approved for sale, and at various stages of manufacturing with our suppliers, the global spread of the pandemic and containment measures has been unprecedented and could have a negative impact on the availability of VASCEPA at various points in our supply chain, including limiting the ability of new suppliers to be inspected, which would have a material and adverse effect on our business.

Since the beginning of the COVID-19 pandemic, three vaccines for COVID-19 have received Emergency Use Authorization by the U.S.

FDA and two of those later received marketing approval.

Additional vaccines may be authorized or approved in the future.

which would have a material and adverse effect on our business.

The ongoing demand for vaccines, including boosters, and potential for manufacturing facilities and materials to be commandeered under the Defense Production Act of 1950, or equivalent foreign legislation, may make it more difficult to obtain materials or manufacturing slots for the products needed for our commercial product, which could lead to issues with our commercial supply.

The disruptions associated with the coronavirus pandemic could also delay the timing of a determination on our ability to seek legal remedies as travel, operational resources and personnel are disrupted or slow to resume pre-pandemic levels, with respect to our efforts and capabilities, as well as those of our advisors and the courts.

The disruptions associated with the coronavirus pandemic could delay the potential timing of subsequent steps for the launch of commercialization of VAZKEPA in Europe, including plans to hire additional employees in Europe.

The disruptions associated with the coronavirus pandemic could delay the potential timing of subsequent steps for the launch of commercialization of VAZKEPA in Europe.

Additionally, COVID-19 has already and could continue to limit our ability to have access with healthcare professionals to help educate them regarding VAZKEPA so that they are more likely to prescribe it to their at-risk patients.

And, similar to our experience in the United States, the effects of COVID-19 and social distancing considerations may reduce the frequency at which at-risk patients seek non-urgent preventative medical care.

And, similar to our experience in the United States, the effects of COVID-19 and related preventative measures may reduce the frequency at which at-risk patients seek non-urgent preventative medical care.

As with any cardiovascular outcomes trial, over time further data assessment related to REDUCE-IT by international regulatory authorities or otherwise could yield additional useful information to inform greater understanding of study outcome.

38 unchanged sentences

Results from the investigator sponsored study in Argentina called PREPARE-IT-2 were presented by the lead trial investigator at the American Heart Association Scientific Sessions in November 2021 and the results did not meet the primary and/or other endpoints studied.

Results from the other investigational study, called MITIGATE, is expected during 2022.

Results from the other investigational study, called MITIGATE, are expected during 2022.

If the outcomes of one or more of these studies do not meet expectations, the perception of existing clinical results of VASCEPA, such as MARINE or REDUCE-IT, or the perceived clinical profile and commercial value of VASCEPA and its regulatory status may suffer.

If this occurs our revenue and business could suffer and our stock price could significantly decline.

If we are not successful in maintaining a sales force that is rightsized for our efforts to market and sell VASCEPA in the United States, including in light of our Go-to-Market strategy, including our omnichannel approach and reduced sales force, our anticipated revenues or our expenses could be materially and negatively affected, and we may not obtain profitability, may need to cut back on research and development activities or implement other cost-containment measures, or we may need to raise additional funding that could result in substantial dilution or impose considerable restrictions on our business.

Given the dynamics related to COVID-19, we cannot predict when we will be able to substantially resume and sustain our business efforts, or how those efforts will be impacted in the long term.

While we have supplemented traditional face-to-face interactions with virtual outreach, including our omnichannel platform, these efforts may not be as successful as in-person interactions.

*Our recently announced cost and organizational restructuring plan may not be successful in addressing the current shift in the United States business and developing sales internationally.

If we are not successful in our efforts to market and sell VASCEPA in the United States, including from the implementation of our recent cost and organizational restructuring plan, reduced sales force, our anticipated revenues or our expenses could be materially and negatively affected, and we may not maintain profitability in the United States or obtain profitability internationally, may need to cut back on research and development activities or implement other cost-containment measures, or we may need to raise additional funding that could result in substantial dilution or impose considerable restrictions on our business.

Given the dynamics related to COVID-19, we cannot predict our ability to effectively sustain business efforts, or how those efforts will be impacted in the long term.

While we have supplemented traditional face-to-face interactions with virtual outreach, these efforts may not be as successful as in-person interactions.

Specifically, access to healthcare professionals through digital or other channels, may not be as productive as in-person interactions in promoting use of VASCEPA.

We continued to adjust our promotional initiatives, 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.

We continue to adjust our promotional initiatives, including pursuing increased face-to-face interactions with health care professionals based on COVID-19 protocols that are in place.

Such efforts are costly and there can be no assurance that they will result in an increase in VASCEPA prescriptions and sales in the near future, or at all.

11 unchanged sentences

This use of VASCEPA at issue reflected recognized medical practice at the time but was not approved by the U.S.

FDA and was thus not covered by then U.S.

and was thus not covered by then U.S.

FDA-approved labeling for the drug.

36 unchanged sentences

We cannot predict when these investigations will be resolved, the outcome of the investigations or their potential impact on our business.

Such investigations can be

lengthy, costly and could materially affect and disrupt our business.

Such investigations can be lengthy, costly and could materially affect and disrupt our business.

If the government determines that we have violated the U.S.

5 unchanged sentences

pharmaceutical products.

Further, results of trials for similar or competing products could have a negative impact on the perceived safety and efficacy of VASCEPA, which could have a materially adverse impact on sales of VASCEPA.

The biotechnology and pharmaceutical industries are highly competitive.

28 unchanged sentences

Results of these failed outcomes studies, as described below and analysis, while not done with VASCEPA, may negatively affect sales of VASCEPA if omega-3 mixtures are broadly viewed as ineffective.

For example, results of one of these two studies, the VITamin D and OmegA-3 TriaL, or VITAL, as announced immediately before the presentation of REDUCE-IT results at the 2018 Scientific Sessions of the AHA on November 10, 2018, failed to achieve its

primary endpoint of lowering cardiovascular events.

VITAL was an NIH funded randomized double-blind, placebo-controlled, 2x2 factorial trial of 2000 IU per day of vitamin D3 and 1 gram per day of omega-3 fatty acid mixture supplementation (Lovaza) for the primary prevention of cancer and cardiovascular disease in a nationwide USA cohort of 25,874 adults not selected for elevated cardiovascular or cancer risk.

2 unchanged sentences

In a meta-analysis, presented in 2018 by the Cochrane Foundation and separately as published in JAMA, additional omega-3 studies were evaluated.

Similar to the VITAL and ASCEND studies, most of the studies in these omega-3 meta-analyses were of omega-3 mixtures, including DHA, and most were studies of relatively low doses of omega-3 as is associated with dietary supplementation and/or they studied relatively low risk patient populations.

Similar to the VITAL and ASCEND studies, most of the studies in these omega-3 meta-analyses were of

omega-3 mixtures, including DHA, and most were studies of relatively low doses of omega-3 as is associated with dietary supplementation and/or they studied relatively low risk patient populations.

The exception was the JELIS study, conducted in Japan, of highly pure EPA which showed a positive outcome benefit but had significant limitations in its application to a wider population.

14 unchanged sentences

In ENHANCE-IT, plasma EPA concentrations were significantly higher with LYPDISO versus VASCEPA, with a 46% relative percentage increase in the change from baseline EPA level versus VASCEPA.

ENHANCE-IT study results were published in March 2022 in the Journal of the American Heart Association (JAHA).

Matinas has announced that the results from ENHANCE-IT suggest potential for LYPDISO as a drug for cardiovascular risk reduction and announced that it is pursuing external partnerships to further develop LYPDISO for cardiovascular outcomes indication.

9 unchanged sentences

Phase 3 studies for homozygous familial (hypercholesterolemia, or HoFH), heterozygous familial hypercholesterolemia, or HeFH, and non-familial hypercholesterolemia in ASCVD patients are planned.

NeuroBO is currently assessing Gemcabene as an acute treatment for COVID-19.

NeuroBO is currently assessing Gemcabene for additional indications, including, as an acute treatment for COVID-19.

Afimmune Ltd.

4 unchanged sentences

Although epeleuton failed to meet the primary endpoint to demonstrate effects on liver enzyme elevation, it demonstrated significant reduction of triglycerides, HbA1c and potential for CV risk reduction.

In September 2020, Afimmune announced the start of TRIglyceride And Glucose control with Epeleuton in Metabolic Syndrome Patients, or TRIAGE, a Phase IIb study of epeleuton in patients with high triglycerides and type 2 diabetes to assess the safety and efficacy of orally administered epeleuton capsules vs placebo in the treatment of hypertriglyceridemia and type 2 diabetes.

administered epeleuton capsules vs placebo in the treatment of hypertriglyceridemia and type 2 diabetes.

Results are expected in the third quarter of 2022.

32 unchanged sentences

FDA approval based on preclinical or clinical studies conducted by others.

In addition to

relying on U.S.

In addition to relying on U.S.

FDA prior findings of safety and effectiveness for a referenced drug product, the U.S.

52 unchanged sentences

A tentative approval does not allow the applicant to market the generic drug product and postpones the final ANDA approval until applicable exclusivity protections have expired.

Generic versions of VASCEPA made available in the market, even if based on a MARINE indication, only are often used to fill a prescription for any intended use of the drug.

If any approved ANDA filers are able to supply the product in significant commercial quantities, generic companies could introduce generic versions of VASCEPA in the market, as did Hikma in November 2020, Dr.

Reddy's in June 2021 and Apotex in January 2022, although each on a limited scale to date.

Generic versions of VASCEPA made available in the market, even if based on a MARINE indication, are often used to fill a prescription for any intended use of the drug.

If any approved ANDA filers are able to supply the product in significant commercial

quantities, generic companies could introduce generic versions of VASCEPA in the market, as did Hikma in November 2020, Dr.

Reddy's in June 2021 and Apotex in January 2022.

Although any such introduction of a generic version of VASCEPA would also be subject to any litigation settlement terms and patent infringement claims (including any new claims and those that may then be subject to an appeal), pursuing such litigation may be prohibitively costly or could put a substantial constraint on our resources.

10 unchanged sentences

While an authorized generic could be profitable the market opportunity for growth from an authorized generic is likely less than from promotion of a branded drug, and as such we have not launched an authorized generic version of VASCEPA to date, but may elect to do so in the future.

The active pharmaceutical ingredient in VASCEPA is difficult and time consuming to manufacture, often requires considerable advanced planning and long-term financial commitments to ensure sufficient capacity is available when needed and, perhaps not surprisingly, is reportedly in limited supply to our generic competitors, one of which has filed a lawsuit against us claiming we have engaged in anticompetitive practices related to our building of adequate supply for our needs and, in activities we believe were prompted by the generic competitor, government agencies are investigating our business as it relates to the supply of the active pharmaceutical ingredient in VASCEPA.

One of the generic competitors which has filed a lawsuit against us claiming we have engaged in anticompetitive practices related to our building of adequate supply for our needs and, in activities we believe were prompted by the generic competitor, government agencies are investigating our business as it relates to the supply of the active pharmaceutical ingredient in VASCEPA.

Consumer lawsuits with similar allegations have also been filed.

2 unchanged sentences

We have invested over a decade of resources and expenses to develop with our third-party, active pharmaceutical ingredient supply chain the technical knowhow, manufacturing processes and related regulatory approvals that have helped enable our suppliers to supply our clinical and commercial needs globally.

Based on statements made by Hikma and Dr.

Reddy’s, the active pharmaceutical ingredient of VASCEPA needed to manufacture their generic versions of VASCEPA is in limited supply to them.

We believe this may be due to their lack of adequate planning, knowhow and expertise regarding this fragile active ingredient.

As has been a practice in the generic pharmaceutical industry, on April 27, 2021, Dr.

20 unchanged sentences

VASCEPA is subject to non-prescription competition and consumer substitution.

This dynamic also exists in markets outside the United States.

Our only product, VASCEPA, is a prescription-only form of EPA, an omega-3 fatty acid in ethyl ester form.

2 unchanged sentences

We cannot be sure physicians and other providers will view the U.S.

FDA approval, pharmaceutical grade purity and proven efficacy and safety of VASCEPA as having a superior therapeutic profile to unproven and loosely regulated omega-3 fatty acid dietary supplements.

FDA approval, pharmaceutical grade purity and proven efficacy and safety of

VASCEPA as having a superior therapeutic profile to unproven and loosely regulated omega-3 fatty acid dietary supplements.

In addition, the U.S.

26 unchanged sentences

If healthcare providers or patients favor dietary supplements over prescribing VASCEPA, we may be constrained in how we price our product or VASCEPA’s market acceptance may be less than expected, which would have a negative impact on our revenues and results of operations.

The commercial value to us of sales of VASCEPA outside the United States may be smaller than we anticipate, including adequacy of product reimbursement such as in Europe, which can vary from country to country resulting in potential patient access restrictions.

The commercial value of VASCEPA outside the United States may be smaller than we anticipate, including adequacy of product reimbursement, which can vary from country to country.

If we are unable to realize product reimbursement rates at reasonable levels, or at all, patient access to VASCEPA may be limited.

There can be no assurance as to the market for VASCEPA outside the United States.

For example, despite having received EC approval to commercialize VAZKEPA in Europe and as we expect to obtain further, through our partner Edding, marketing approval for VASCEPA in Mainland China, Hong Kong, Macau and Taiwan, or the China Territory, applicable regulatory agencies may impose restrictions on the product’s conditions for use, distribution or marketing and in some cases may impose ongoing requirements for post-market surveillance, post-approval studies or clinical trials.

For example, despite having received EC approval to commercialize VAZKEPA in Europe and through our partner, Edding, marketing approval for VASCEPA in Hong Kong as well as we expect to obtain through Edding, marketing approval for VASCEPA in Mainland China, Macau and Taiwan, applicable regulatory agencies may impose restrictions on the product’s conditions for use, distribution or marketing and in some cases may impose ongoing requirements for post-market surveillance, post-approval studies or clinical trials.

Further, securing adequate reimbursement is critical for commercial success of any therapeutic and pricing and reimbursement levels of medications in markets outside the United States can be unpredictable and vary considerably on a country-by-country basis.

2 unchanged sentences

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

In certain European countries, securing product reimbursement is a requisite to commercial launch.

In certain European countries, securing product reimbursement is a requisite to

commercial launch.

To obtain reimbursement or pricing approval in some countries, we may be required to conduct a pharmacoeconomic study that compares the cost-effectiveness of VASCEPA to other available therapies.

36 unchanged sentences

As discussed above, in June 2020, we received a CID from the DOJ informing us that the DOJ is investigating whether aspects of our promotional speaker programs and copayment waiver programs during the period from January 1, 2015 to the present violated the U.S.

Anti-Kickback

Statute and the U.S.

Anti-Kickback Statute and the U.S.

FCA in relation to the sale and marketing of VASCEPA by us and our previous co-marketing partner, Kowa America.

13 unchanged sentences

In addition, all of the above factors may also apply to any regulatory approval for VASCEPA obtained in territories outside the United States.

In Europe, for example, restrictions regarding off-label promotion are in some ways more stringent than in the United States, including restrictions covering certain communications with shareholders.

In Europe, for example, restrictions regarding off-label promotion are in some ways more stringent than in the United

States, including restrictions covering certain communications with shareholders.

Given our inexperience with marketing and commercializing products outside the United States, in certain territories we may need to rely on third parties, such as our partners in Canada, China and the Middle East, to assist us in dealing with any such issues and we will have limited or no control over such partners.

7 unchanged sentences

In concert with subsequent legislation, this has resulted in aggregate reductions to Medicare payments to providers of, on average, 2% per fiscal year through 2030 with the exception of a temporary suspension from May 1, 2020 through March 31, 2022 due to the COVID-19 pandemic.

Following the suspension, a 1% payment reduction took place beginning April 1, 2022 and will continue through June 30, 2022, and the 2% payment reduction will resume on July 1, 2022.

Following the suspension, a 1% payment reduction occurred from April 1, 2022 through June 30, 2022, and the 2% payment reduction resumed on July 1, 2022.

These cuts reduce reimbursement payments related to our products, which could potentially negatively impact our revenue.

8 unchanged sentences

Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to drug pricing, reduce the cost of prescription drugs under Medicare, and review the relationship between pricing and manufacturer patient programs.

At a federal level, President Biden signed an Executive Order on July 9, 2021 affirming the administration's policy to (i) support legislative reforms that would lower the prices of prescription drug and biologics, including by allowing Medicare to negotiate drug prices, by imposing inflation caps, and, by supporting the development and market entry of lower-cost generic drugs and biosimliars;

and (ii) support the enactment of a public health insurance option.

Among other things, the Executive Order also directs HHS to provide a report on actions to combat excessive pricing of prescription drugs, enhance the domestic drug supply chain, reduce the price that the federal government pays for drugs,

and address price gouging in the industry;

and directs the FDA to work with states and Indian Tribes that propose to develop section 804 Importation Programs in accordance with the Medicare Prescription Drug, Improvement, and Modernization Act of 2003, and the FDA's implementing regulations.

7 unchanged sentences

The rule also creates a new safe harbor for price reductions reflected at the point-of-sale, as well as a safe harbor for certain fixed fee arrangements between pharmacy benefit managers and manufacturers.

Pursuant to court order, the removal and addition of the aforementioned safe harbors were delayed and recent legislation imposed a moratorium on implementation of the rule until January 1, 2026.

Pursuant to court order, the removal and addition of the aforementioned safe harbors were delayed and recent legislation imposed a moratorium on implementation of the rule

until January 1, 2026.

Although a number of these and other proposed measures may require authorization through additional legislation to become effective, and the Biden administration may reverse or otherwise change these measures, both the Biden administration and Congress have indicated that they will continue to seek new legislative measures to control drug costs.

20 unchanged sentences

These 340B covered entities include a variety of community health clinics and other entities that receive health services grants from the Public Health Service, as well as hospitals that serve a disproportionate share of low-income patients.

program, and in general, products subject to Medicaid price reporting and rebate liability are also subject to the 340B ceiling price calculation and discount requirement.

The 340B ceiling price is calculated using a statutory formula based on the average manufacturer price and Medicaid rebate amount for the covered outpatient drug as calculated under the Medicaid Drug Rebate program, and in general, products subject to Medicaid price reporting and rebate liability are also subject to the 340B ceiling price calculation and discount requirement.

Any additional future changes to the definition of average manufacturer price and the Medicaid rebate amount under the ACA, other legislation, or in regulation could affect our 340B ceiling price calculations and negatively impact our results of operations.

5 unchanged sentences

In the case of our Medicaid pricing data, if we become aware that our reporting for a prior quarter was incorrect, or has changed as a result of recalculation of the pricing data, we are obligated to resubmit the corrected data for up to three years after those data originally were due.

Such restatements and recalculations increase our costs for complying with the laws and regulations governing the Medicaid Drug Rebate program and could result in an overage or underage in our rebate liability for past quarters.

Such restatements and recalculations increase our costs for complying with the laws and regulations governing the Medicaid Drug Rebate program and could result in an overage or underage in

our rebate liability for past quarters.

Price recalculations also may affect the ceiling price at which we are required to offer our products under the 340B program or could require us to issue refunds to 340B covered entities.

26 unchanged sentences

We are unable to predict the reimbursement policies employed by third-party healthcare payors.

We expect to experience pricing and reimbursement pressures in connection with the sale of our products due to the trend toward managed healthcare, the increasing influence of health maintenance organizations and additional legislative and executive

proposals, as well as the availability of generic versions of VASCEPA.

In addition, we may confront limitations in, or exclusions from, insurance coverage for our products, particularly as generic competition intensifies.

8 unchanged sentences

Further, on June 14, 2018, U.S.

Court of Appeals for the Federal Circuit ruled that, due to Congressional appropriations riders that prohibited the HHS from paying out more in risk corridor payments than it collected, HHS was not required to pay more than $12.0 billion in ACA risk corridor payments owed to insurers under the risk corridor formula.

Court of Appeals for the Federal Circuit ruled that, due to Congressional appropriations riders that prohibited the HHS from paying out more in risk corridor

payments than it collected, HHS was not required to pay more than $12.0 billion in ACA risk corridor payments owed to insurers under the risk corridor formula.

On November 6, 2018, the Federal Circuit declined to rehear the case en banc.

40 unchanged sentences

We and any potential collaborators may be subject to federal, state, and foreign data protection laws and regulations (i.e., laws and regulations that address privacy and data security).

In the United States, numerous federal and state laws and regulations, including federal health information privacy laws, state data breach notification laws, state health information privacy laws, and federal and state consumer protection laws (e.g., Section 5 of the Federal Trade Commission Act), that govern the collection, use, disclosure and protection of health-related and other personal information could apply to our operations or the operations of our collaborators.

collaborators.

In addition, we may obtain health information from third parties (including research institutions from which we obtain clinical trial data) that are subject to privacy and security requirements under the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA.

38 unchanged sentences

FDA-approved VASCEPA label or our settlement.

If we are found to have promoted VASCEPA outside the terms of the litigation settlement or in violation of what federal or state government may determine to be acceptable, we may become subject to significant government fines and other related liability, such as under the FDCA, the FCA, or other theories of liability.

we are found to have promoted VASCEPA outside the terms of the litigation settlement or in violation of what federal or state government may determine to be acceptable, we may become subject to significant government fines and other related liability, such as under the FDCA, the FCA, or other theories of liability.

Government may also seek to hold us responsible for the non-compliance of our former co-promotion partner, Kowa America, or our commercialization partners outside the United States or other third-parties that we retain to help us implement our business plan.

37 unchanged sentences

Clinical trials that we or potential partners conduct may not provide sufficient safety and efficacy data to obtain the requisite regulatory approvals for product candidates.

The failure of clinical trials to demonstrate safety and efficacy for our desired indications could harm the development of that product candidate as well as other product candidates, and our business and results of operations would suffer.

The failure of clinical trials to

demonstrate safety and efficacy for our desired indications could harm the development of that product candidate as well as other product candidates, and our business and results of operations would suffer.

For example, during the public advisory committee meeting held by U.S.

20 unchanged sentences

The process of establishing, maintaining, expanding and streamlining a commercial infrastructure is difficult, expensive and time-consuming.

We implemented a Go-to-Market strategy in an effort to optimize provider engagement and drive demand for VASCEPA in the United States by shifting reliance on sales force interactions with healthcare professionals to providing managed care and prescription access through an omnichannel platform.

Accordingly, as announced on September 22, 2021 we reduced our U.S.

field force to approximately 300 sales representatives.

As we observe the results of the Go-to-Market strategy and as practices impacted by COVID-19 stabilize, we will continue to evaluate our needs, including the need to fill open positions, or expand or further streamline our sales force, as appropriate to meet our business needs.

Our sales team promotes VASCEPA to a limited group of physicians and other healthcare professionals in select geographies in the United States and is not large enough to call upon all physicians.

In addition to sales force reductions and the shift to omnichannel in the United States, we continue to work on our own and with our international partners to support regulatory efforts outside the United States based on REDUCE-IT results.

In June 2022, we implemented a cost and organizational restructuring plan, which included a further reduction to our U.S.

commercial team from approximately 300 sales representatives to approximately 75 sales representatives.

Our sales team promotes VASCEPA to a targeted group of physicians and other healthcare professionals in select geographies in the United States who recognize the potential benefit to patients and is not large enough to call upon all physicians.

In addition to sales force reductions in the United States, we continue to work on our own and with our international partners to support regulatory efforts outside the United States based on REDUCE-IT results.

As our operations expand with the anticipated growth of our product sales, we expect that we will need to manage additional relationships with various collaborative partners, suppliers and other third parties.

10 unchanged sentences

The potential success of any fixed-dose combination will depend on a number of factors, including the following:

Our ability to successfully manufacture a combination of VASCEPA and statin;

Our ability to successfully manufacture a combination of VASCEPA and a statin;

Our ability to maintain a supply of necessary statin for use in the fixed-dose combination;

8 unchanged sentences

If we are not able to continue to operate our business relationships in a manner that is sufficiently profitable for us and our suppliers, certain members of our supply chain could compete with us through supply to competitors, such as generic drug companies, through breach of our agreements or otherwise.

Any manufacturing problem, natural or manmade disaster affecting manufacturing facilities, government action, or the loss of a contract manufacturer could be disruptive to our operations and result in lost sales.

Any manufacturing problem, natural or manmade disaster affecting manufacturing facilities, government action, or the loss of a contract manufacturer could potentially be disruptive to our operations and result in lost sales.

Any reliance on suppliers may involve several risks, including a potential inability to obtain critical materials and reduced control over production costs, delivery schedules, reliability and quality.

3 unchanged sentences

We have entered into supply agreements with multiple suppliers who also rely on other third-party suppliers to manufacture the API and other elements necessary for the sale of VASCEPA.

Our strategy in sourcing API and other components in our supply chain from

multiple suppliers has been to expand manufacturing capacity, maintain competitive advantages, and mitigate the risk of reliance on any single supplier.

Our strategy in sourcing API and other components in our supply chain from multiple suppliers has been to expand manufacturing capacity, maintain competitive advantages, and mitigate the risk of reliance on any single supplier.

Expanding manufacturing capacity and qualifying such capacity is complex and subject to numerous regulations and other operational challenges.

We require supply capacity to support our direct commercialization of VASCEPA in the United States and VAZKEPA in Europe.

We require supply capacity to support our direct and indirect commercialization of VASCEPA.

We are also committed to providing supply to our commercial partners and distributors in Canada, China, the Middle East and North Africa, and we anticipate potential additional supply requirements as we pursue commercial opportunities in other countries.

1 unchanged sentence

costs associated with projected expansion and qualification can be significant, and lead-times for supply purchases and capacity expansion are long requiring certain supply related decisions and commitment to be made in advance, for example, prior to commercial launch in China and in various European countries.

There can be no assurance that the expansion plans of any of our suppliers will be successful.

Our aggregate capacity to produce API is dependent upon the continued qualification of our API suppliers and, depending on the ability of existing suppliers to meet our supply demands, potentially the qualifications of new suppliers.

Each of our API suppliers has outlined plans for potential further capacity expansion, with certain of these expansion plans delayed due to COVID-19 and other market uncertainties.

If no additional API supplier is approved by the U.S.

1 unchanged sentence

Similarly, the EMA has not initially approved use of each of our suppliers used for VASCEPA in the United States for VAZKEPA in the EU.

While we believe that we have sufficient supply of VAZKEPA to support our initial launch plans in Europe, our supply in Europe will be limited until additional suppliers are qualified which qualifications may be delayed by COVID-19 and our exposure to manufacturing issues with our approved suppliers for the EU is less mitigated than is our objective by having more suppliers qualified.

If our third-party manufacturing capacity is not expanded and/or compliant with applicable regulatory requirements, we may not be able to supply sufficient quantities of VASCEPA to meet anticipated demand.

While we believe that we have sufficient supply of VAZKEPA to support our initial launch plans in Europe, our supply in Europe will be limited until additional suppliers are qualified which qualifications could be delayed by COVID-19 and our exposure to manufacturing issues with our approved suppliers for the EU.

If our third-party manufacturing capacity is not appropriately qualified and/or compliant with applicable regulatory requirements, we may not be able to supply sufficient quantities of VASCEPA to meet anticipated demand.

We cannot guarantee that we can contract with any future manufacturer on acceptable terms or that any such alternative supplier will not require capital investment from us in order for them to meet our requirements.

38 unchanged sentences

FDA or another regulatory authority.

The delays associated with the verification of a new third-party manufacturer could negatively affect our ability to develop product candidates or commercialize our products in a timely manner or within budget.

delays associated with the verification of a new third-party manufacturer could negatively affect our ability to develop product candidates or commercialize our products in a timely manner or within budget.

Furthermore, a third-party manufacturer may possess technology related to the manufacture of our product candidate that such third-party manufacturer owns independently.

21 unchanged sentences

FDA or similar foreign regulatory bodies.

For example, since March 2020 when foreign and domestic inspections of facilities were largely placed on hold, the

For example, since March 2020 when foreign and domestic inspections of facilities were largely placed on hold, the U.S.

FDA has been working to resume routine surveillance, bioresearch monitoring and pre-approval inspections on a prioritized basis.

6 unchanged sentences

FDA does not determine a remote interactive evaluation to be adequate, the agency has stated that it generally intends to issue, depending on the circumstances, a complete response letter or defer action on the application until an inspection can be completed.

During the COVID-19 public health emergency, a number of companies announced receipt of complete response letters due to the U.S.

FDA’s inability to complete required inspections for their applications.

Regulatory authorities outside the U.S.

may adopt similar restrictions or other policy measures in response to the ongoing COVID-19 pandemic and may experience delays in their regulatory activities.

*Our commercialization of VASCEPA outside the United States is substantially dependent on third parties and other circumstances outside our control.

9 unchanged sentences

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

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

On February 23, 2022 the Hong Kong Department of Health completed their

evaluation and approved the use of VASCEPA under the REDUCE-IT indication.

Even though such results are similar to the MARINE study, additional clinical development efforts may be necessary in this market to demonstrate the effectiveness of VASCEPA in reducing major adverse cardiovascular events in Chinese patients with persistent cardiovascular risk.

Any development and regulatory efforts in the China Territory may be negatively impacted if the coronavirus pandemic continues or spreads, and if resources by regulators and industry professionals continue to be diverted to address the prolonged coronavirus pandemic.

Any development and regulatory efforts in the China Territory may be negatively impacted if the coronavirus pandemic worsens, continues or spreads, and if resources by regulators and industry professionals continue to be diverted to address the prolonged coronavirus pandemic.

Any development and regulatory efforts in the China Territory may be negatively impacted by heightened political tension between China and the United States, including in connection with COVID-19 and other issues expressed between the countries regarding trade practices, tariffs and honoring intellectual property rights.

5 unchanged sentences

VASCEPA was approved under the REDUCE-IT indication in the following countries:

Qatar in April 2021, Lebanon in August 2021 and United Arab Emirates in October 2021.

Qatar in April 2021, Lebanon in August 2021, United Arab Emirates in October 2021 and Bahrain in April 2022.

VASCEPA was launched in Lebanon and the United Arab Emirates in June 2018 and February 2019, respectively.

6 unchanged sentences

In January 2020, HLS obtained an extended regulatory exclusivity designation.

In February 2020, HLS

launched VASCEPA in Canada, with strong initial uptake before the impact of COVID-19 pandemic.

In February 2020, HLS launched VASCEPA in Canada, with strong initial uptake before the impact of COVID-19 pandemic.

In July 2020, Patented Medicine Prices Review Board confirmed VASCEPA price is compliant with current guidelines, and CADTH recommended reimbursement for VASCEPA in Canada in secondary prevention population.

In June 2022 HLS entered into Product Listing Agreements with New Brunswick, Northwest Territories and the non-insured health benefits, for the listing and public reimbursement of VASCEPA on their respective Public Prescription Drug Insurance Plans.

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

However, if HLS is not able to effectively commercialize VASCEPA in Canada through effective pricing (initially and over time), reimbursement or otherwise we may not be able to generate revenue from the sale of VASCEPA in Canada.

10 unchanged sentences

Arrangements with third-party payors and customers can expose pharmaceutical manufacturers to broadly applicable fraud and abuse and other healthcare laws and regulations, which may constrain the business or financial arrangements and relationships through which such companies sell, market and distribute pharmaceutical products.

In particular, the promotion, sales and marketing of healthcare items and services, as well as a wide range of pricing, discounting, marketing and promotion, structuring and commission(s), certain customer incentive programs and other business arrangements, are subject to extensive laws designed to prevent fraud, kickbacks, self-dealing and other abusive practices.

In particular, the promotion, sales and marketing of healthcare items and services, as well as a wide range of pricing,

discounting, marketing and promotion, structuring and commission(s), certain customer incentive programs and other business arrangements, are subject to extensive laws designed to prevent fraud, kickbacks, self-dealing and other abusive practices.

The applicable federal and state healthcare laws and regulations laws that may affect our ability to operate include, but are not limited to:

16 unchanged sentences

When an entity is determined to have violated the FCA, the government may impose civil fines and penalties for each false claim, plus treble damages, and exclude the entity from participation in Medicare, Medicaid and other federal healthcare programs.

Pharmaceutical and other healthcare

companies also are subject to other federal false claims laws, including, among others, federal criminal healthcare fraud and false statement statutes that extend to non-government health benefit programs;

Pharmaceutical and other healthcare companies also are subject to other federal false claims laws, including, among others, federal criminal healthcare fraud and false statement statutes that extend to non-government health benefit programs;

HIPAA, which, among other things, imposes criminal and civil liability for knowingly and willfully executing a scheme to defraud any healthcare benefit program, including private third-party payor and knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services;

3 unchanged sentences

the federal Physician Payment Sunshine Act, being implemented as the Open Payments Program, which requires manufacturers of drugs, devices, biologics, and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) to report annually to CMS information related to direct or indirect payments and other transfers of value to physicians (defined to include doctors, dentists, optometrists, podiatrists, and chiropractors) and teaching hospitals, as well as ownership and investment interests held in the company by physicians and their immediate family members.

Beginning in 2022, applicable manufacturers also will be required to report information regarding payments and transfers of value provided to physician assistants, nurse practitioners, clinical nurse specialists, certified nurse anesthetists, and certified nurse-midwives;

Effective January 2022, applicable manufacturers also are required to report information regarding payments and transfers of value provided to physician assistants, nurse practitioners, clinical nurse specialists, certified nurse anesthetists, and certified nurse-midwives;

federal governmental price reporting laws, which require the calculation and reporting of complex pricing metrics in an accurate and timely manner to government programs;

20 unchanged sentences

Such investigations can be lengthy, costly and could materially affect and disrupt our business.

If the government determines that we have

violated the U.S.

If the government determines that we have violated the U.S.

Anti-Kickback Statute, the FCA or antitrust regulations, we could be subject to significant civil and criminal fines and penalties.

10 unchanged sentences

Specifically, in recent years there have been multiple settlements resulting out of government claims challenging the legality of their patient assistance programs under a variety of federal and state laws.

It is possible that we may make grants to independent charitable foundations that help financially needy patients with their premium, co-pay, and co-insurance obligations.

It is possible that we may make grants to independent charitable foundations that help financially needy patients with their premium,

co-pay, and co-insurance obligations.

If we choose to do so, and if we or our vendors or donation recipients are deemed to fail to comply with relevant laws, regulations or evolving government guidance in the operation of these programs, we could be subject to damages, fines, penalties, or other criminal, civil, or administrative sanctions or enforcement actions.

19 unchanged sentences

Risks Related to Our Intellectual Property

We are dependent on patents, proprietary rights and confidentiality to protect the commercial potential of VASCEPA.

We are dependent on patents, proprietary rights and confidentiality to protect the commercial value and potential of VASCEPA.

Our success depends in part on our ability to obtain and maintain intellectual property protection for our drug candidates, technology and know-how, and to operate without infringing the proprietary rights of others.

22 unchanged sentences

four additional patents covering a pharmaceutical composition comprised of EPA and a hydroxyl compound with a term that expires in 2034;

five additional patents covering a new combination therapy comprised of EPA and another drug.

six additional patents covering a new combination therapy comprised of EPA and another drug.

A Notice of Allowance is issued after the USPTO makes a determination that a patent can be granted from an application.

24 unchanged sentences

We may in the future discover the existence of products that infringe patents that we own or that have been licensed to us.

If we were to initiate legal proceedings against a third party to stop such an infringement, such proceedings could be costly and time consuming, regardless of the outcome.

If we were to initiate legal proceedings against a third party to stop such an infringement, such proceedings could be costly and time

consuming, regardless of the outcome.

No assurances can be given that we would prevail, and it is possible that, during such a proceeding, our patent rights could be held to be invalid, unenforceable or both.

4 unchanged sentences

Such proceedings are generally highly technical, expensive, and time consuming, and there can be no assurance that such a challenge would not result in the narrowing or complete revocation of any patent of ours that was so challenged.

Our issued patents may not prevent competitors from competing with VASCEPA, even if we seek to enforce our patent rights.

Our issued patents may not prevent competitors from competing with VASCEPA, even if we are successful in enforcing our patent rights.

We plan to vigorously defend our rights under issued patents.

2 unchanged sentences

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

appeal the decision of the district court when permitted and 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.

Patent litigation is a time-consuming and costly process.

26 unchanged sentences

In addition to our patent portfolio and strategy, we will also rely upon trade secrets and know-how to help protect our competitive position.

We rely on trade secrets to protect technology in cases when we believe patent protection is not appropriate or obtainable.

We rely on trade secrets to protect technology in cases when we believe patent protection is not appropriate or

However, trade secrets are difficult to protect.

3 unchanged sentences

In January 2022, we disclosed our 2022 financial outlook.

Such outlook is based on estimates, assumptions and the judgment of management.

Because of the inherent nature of estimates, including during the uncertainty of COVID-19’s impact on our business, we have suspended providing net revenue guidance and there could be significant differences between our estimates and the actual amount of product demand.

If we fail to realize or if we change or update any element of our publicly disclosed financial guidance as we have done in the past or other expectations about our business change, our stock price could decline in value.

Subsequent to that, including in connection with the announcement of our cost and organizational restructuring plan, we have made statements about expected cost reductions and expenditures.

Such outlook and estimates are based on estimates, assumptions and the judgment of management.

Because of the inherent nature of estimates, including during the uncertainty of the European launch and COVID-19’s impact on our business, we have suspended providing net revenue guidance and there could be significant differences between our estimates and the actual amount of product demand.

If we fail to realize or if we change or update any element of our publicly disclosed financial guidance as we have done in the past or other expectations about our business and initiative change, our stock price could decline in value.

*The loss of key personnel could have an adverse effect on our business, particularly in light of our recent announcement of management succession plan.

1 unchanged sentence

The loss of the services of one or more members of senior management could have a material adverse effect on us.

Given our rapidly expanding enterprise coupled with a streamlined management structure and sales force, the departure of any key person could have a significant impact and would be potentially

disruptive to our business until such time as a suitable replacement is hired.

Given our rapidly expanding enterprise coupled with a streamlined management structure and sales force, the departure of any key person could have a significant impact and would be potentially disruptive to our business until such time as a suitable replacement is hired.

Furthermore, because of the specialized nature of our business, as our business plan progresses, we will be highly dependent upon our ability to attract and retain qualified scientific, technical and key management personnel.

As we continue to expand our commercialization efforts, particularly on a global scale, we may experience increased turnover among members of our senior management team.

As we continue to expand our commercialization efforts, particularly on a global scale, we may experience continued or increased turnover among members of our senior management team.

We may have difficulty identifying, attracting and integrating new executives to replace any such losses.

As we prepare for commercialization in Europe, we need to rapidly hire employees and ensure that they are well trained and working cohesively with core values which are consistent with our existing operations and which, we believe, help improve our position for success.

As we expand commercialization efforts in Europe, we need to rapidly hire employees and ensure that they are well trained and working cohesively with core values which are consistent with our existing operations and which, we believe, help improve our position for success.

In the United States, employees are increasingly being recruited by other companies.

While our business priorities emphasize continued promotion of VASCEPA in the United States, the current and potential threat of generic competition can create employee uncertainty which could lead to increased employee turnover.

While our business remains focused on continued promotion of VASCEPA in the United States, and expansion in Europe, the current and potential threat of generic competition and our recent reductions in force can create employee uncertainty which could lead to increased employee turnover.

There is intense competition for qualified personnel in the areas of our activities.

In this environment, we may not be able to attract and retain the personnel necessary for the development of our business, particularly if we do not achieve profitability.

In this environment, we may not be able to attract or retain the personnel necessary for the development of our business, particularly if we do not achieve profitability.

The failure to recruit key scientific, technical and management personnel would be detrimental to our ability to implement our business plan.

37 unchanged sentences

It is possible that in the future, whether as a result of a change in law or the practice of any relevant tax authority or as a result of any change in the conduct of our affairs, we could become, or be regarded as having become resident in a jurisdiction other than Ireland.

Should we cease to be an Irish tax resident, we may be subject to a charge to Irish capital gains tax on our assets and the basis on which our income is taxed may also change.

Should we cease to be an Irish tax resident, we may be subject to a charge to Irish capital gains tax on our assets and the basis on which our

income is taxed may also change.

Similarly, if the tax residency of our Irish or UK subsidiaries were to change from their current jurisdiction, they may be subject to a charge to local capital gains tax on their assets and the basis on which their income is taxed may also change.

8 unchanged sentences

gross product sales.

Customers A, B, and C accounted for 21%, 39%, and 31%, respectively, of gross product sales for the three months ended March 31, 2022, and represented 29%, 37%, and 28%, respectively, of the gross accounts receivable balance as of March 31, 2022.

Customers A, B, and C accounted for 27%, 35%, and 31%, respectively, of gross product sales for the three months ended March 31, 2021, and represented 35%, 36%, and 24%, respectively, of the gross accounts receivable balance as of March 31, 2021.

Customers A, B, and C accounted for 25%, 38%, and 31%, respectively, of gross product sales for the six months ended June 30, 2022, and represented 41%, 33%, and 21%, respectively, of the gross accounts receivable balance as of June 30, 2022.

Customers A, B, and C accounted for 27%, 36%, and 30%, respectively, of gross product sales for the six months ended June 30, 2021, and represented 40%, 34%, and 21%, respectively, of the gross accounts receivable balance as of June 30, 2021.

We expect that we may have customer concentration risk as we enter additional countries.

4 unchanged sentences

We have not yet reached sustained profitability.

For the fiscal years ended December 31, 2021, we reported net income of approximately $7.7 million.

For the fiscal year ended December 31, 2021, we reported net income of approximately $7.7 million.

For the fiscal years ended December 31, 2020 and 2019, we reported net losses of approximately $18.0 million and $22.6 million, and we had an accumulated deficit as of December 31, 2021 of $1.4 billion.

For the three months ended March 31, 2022 and 2021, we reported losses of approximately $31.6 million and $1.6 million, respectively, and we had an accumulated deficit as of March 31, 2022 of $1.5 billion.

For the three months ended June 30, 2022 and 2021, we reported losses of approximately $70.0 million and income of approximately $7.8 million, respectively, and we had an accumulated deficit as of June 30, 2022 of $1.5 billion.

Substantially all of our operating losses resulted from costs incurred in connection with our research and development programs, from general and administrative costs associated with our operations, and costs related to the commercialization of VASCEPA.

Additionally, as a result of our significant expenses relating to research and development and to commercialization, we expect to continue to incur significant operating losses for an indefinite period.

Because of the numerous risks and uncertainties associated with developing and commercializing pharmaceutical products, we are unable to

predict the magnitude of these future losses.

Because of the numerous risks and uncertainties associated with developing and commercializing pharmaceutical products, we are unable to predict the magnitude of these future losses.

Our historic losses, combined with expected future losses, have had and will continue to have an adverse effect on our cash resources, shareholders’

13 unchanged sentences

VASCEPA sales are difficult to predict from period to period and as a result, you should not rely on VASCEPA sales results in any period as being indicative of future performance, and sales of VASCEPA may be below the expectation of securities analysts or investors in the future.

We believe that our quarterly and annual results of operations may be affected by a variety of factors, including those risks and uncertainties described in this Part II, Item 1A and the following:

We believe that our quarterly and annual results of

operations may be affected by a variety of factors, including those risks and uncertainties described in this Part II, Item 1A and the following:

the recent and potential launches of additional generic versions of VASCEPA;

3 unchanged sentences

the extent to which coverage and reimbursement for VASCEPA is available from government and health administration authorities, private health insurers, managed care programs and other third-party payors and the timing and extent to which such coverage and reimbursement changes;

the timing, cost and level of investment in our sales and marketing efforts to support VASCEPA sales, including our implemented Go-to-Market strategy, and the resulting effectiveness of those efforts;

the timing, cost and level of investment in our sales and marketing efforts to support VASCEPA sales, and our cost and reorganization efforts, including our recent cost reduction plan, and the resulting effectiveness of those efforts;

disruptions or delays in our or our partners’

7 unchanged sentences

We currently operate with limited resources.

We believe that our cash and cash equivalents balance of $219.2 million and short-term investment balance of $143.4 million as of March 31, 2022 will be sufficient to fund our projected operations for at least 12 months.

We have based this estimate on assumptions that may prove to be wrong, and we could deplete our capital resources sooner

than we expect or fail to achieve positive cash flow.

We believe that our cash and cash equivalents balance of $228.0 million and short-term investment balance of $85.2 million as of June 30, 2022 will be sufficient to fund our projected operations for at least 12 months.

We have based this estimate on assumptions that may prove to be wrong, and we could deplete our capital resources sooner than we expect or fail to achieve positive cash flow.

Depending on the level of cash generated from operations, and depending in part on the rate of prescription growth for VASCEPA, additional capital may be required to support planned VASCEPA promotion and potential VASCEPA promotion beyond which we are currently executing and for commercialization of VAZKEPA in Europe.

4 unchanged sentences

the timing, amount and consistency of revenue generated from the commercial sale of VASCEPA;

the costs associated with commercializing VASCEPA in the United States, including expenditures such as potential direct-to-consumer advertising and increased sales force sizing, and for commercializing VAZKEPA in Europe, including hiring experienced professionals, and for additional regulatory approvals internationally, if any, the cost and timing of securing commercial supply of VASCEPA and the timing of entering into any new strategic collaboration with others relating to the commercialization of VASCEPA, if at all, and the terms of any such collaboration;

the costs associated with commercializing VASCEPA in the United States and increased sales force sizing, and for commercializing VAZKEPA in Europe, including hiring experienced professionals, and for additional regulatory approvals internationally, if any, the cost and timing of securing commercial supply of VASCEPA and the timing of entering into any new strategic collaboration with others relating to the commercialization of VASCEPA, if at all, and the terms of any such collaboration;

continued costs associated with litigation and other legal proceedings and governmental inquiries;

5 unchanged sentences

Tax law and policies in the United States and Ireland are unsettled and may be subject to significant change, including based on adjustments in political perspectives and administration shifts.

In the United States and internationally, how to tax entities with international operations, like Amarin, has been subject to significant re-evaluation.

In the United States and internationally, how to tax entities with international operations, like us, has been subject to significant re-evaluation.

We believe we developed VASCEPA in and from Ireland based on understanding of applicable requirements.

18 unchanged sentences

In addition, the market prices of the securities of many pharmaceutical and medical technology companies have been especially volatile in the past, and this trend is expected to continue in the future.

As of April 29, 2022, we had 397,008,153 common shares outstanding including 396,811,326 shares held as ADSs and 196,827 held as ordinary shares (which are not held in the form of ADSs).

As of July 29, 2022, we had 403,205,514 common shares outstanding including 403,021,687 shares held as ADSs and 183,827 held as ordinary shares (which are not held in the form of ADSs).

There is a risk that there may not be sufficient liquidity in the market to accommodate significant increases in selling activity or the sale of a large block of our securities.

26 unchanged sentences

corporation will be treated as owning its proportionate share of the assets and earning its proportionate share of the income of any other corporation in which it owns, directly or indirectly, no more than 25% (by value) of the stock.

Based on certain estimates of our gross income and gross assets, the latter determined by reference to the expected value of our ADSs and 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.

However, because PFIC status is based on our income, assets and activities for the entire taxable year, which we expect may vary substantially over time, it is not possible to determine whether we will be characterized as a PFIC for any taxable year until after the close of the taxable year.

79 unchanged sentences

We cannot assure you that research and discoveries by others will not render some or all of our programs or product candidates uncompetitive or obsolete.

Our business strategy is based in part upon new and unproven technologies to the development of therapeutics to improve cardiovascular health.

Our business strategy is based in part upon new and unproven technologies to the development of therapeutics to improve cardiovascular

We cannot assure you that unforeseen problems will not develop with these technologies or applications or that any commercially feasible products will ultimately be developed by us.

11 unchanged sentences

Since the regulatory framework in the UK covering quality, safety and efficacy of pharmaceutical products, clinical trials, marketing authorization, commercial sales and distribution of pharmaceutical products is derived from EU directives and regulations, Brexit could materially impact the future regulatory regime with respect to the commercialization of our products in the UK.

Any delay in commercializing our products in the UK and/or the EU

could restrict our ability to generate revenue and achieve and sustain profitability.

Any delay in commercializing our products in the UK and/or the EU could restrict our ability to generate revenue and achieve and sustain profitability.

The uncertainty around the UK’s future relationship with the EU continues to cause economic uncertainty which could adversely impact customer confidence resulting in customers reducing their spending budgets on our solutions, which could adversely affect our business, revenue, financial condition, results of operations and could adversely affect the market price of our ADSs.

19 unchanged sentences

If we are unsuccessful in consummating any such transaction or collaboration, we may be required to reevaluate our business only after we have incurred substantial expenses and devoted significant management time and resources.

*We are currently operating in a period of economic uncertainty and capital markets disruption, which has been significantly impacted by geopolitical instability, including in Europe, and record inflation.

Our business, financial condition and results of operations could be materially and adversely affected by any negative impact on the global economy and capital markets resulting from these global economic conditions, particularly if such conditions are prolonged or worsen.

Economic uncertainty in various global markets, including the U.S.

and Europe, caused by political instability and conflict, such as Russia's invasion of Ukraine, and economic challenges caused by the COVID-19 pandemic, have led to market disruptions, including significant volatility in commodity prices, credit and capital market instability and supply chain interruptions, which have caused record inflation globally.

Although, to date, our business has not been materially impacted by these global economic and geopolitical conditions, it is impossible to predict the extent to which our operations will be impacted in the short and long term, or the ways in which such instability could impact our business and results of operations.

The extent and duration of these market disruptions, whether as a result of the military conflict between Russia and Ukraine, geopolitical tensions, record inflation or otherwise, are impossible to predict, but could be substantial.

Any such disruptions may also magnify the impact of other risks described in this report.

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-Q

Item 1. Legal Proceedings