Leaders in Managing Lipids for Improved Cardiovascular Health - INVESTOR PRESENTATION June 2015 - Jefferies

Leaders in Managing Lipids for
Improved Cardiovascular Health

INVESTOR PRESENTATION
June 2015
Nasdaq: AMRN

Forward-Looking Statement and Disclaimer

This presentation contains forward-looking statements, such as those relating to the
commercial potential of Vascepa®, Amarin’s product development, clinical and
regulatory efforts and timelines, potential FDA approvals, intellectual property, cash
flow, and other statements that are predictive in nature and that depend upon or refer
to future events or conditions. These statements involve known and unknown risks,
uncertainties and other factors that can cause actual results to differ materially.
Investors should not place undue reliance on forward-looking statements, which
speak only as of the presentation date of this presentation. Please refer to the “Risk
Factors” section in Amarin’s most recent Quarterly Report on Form 10-Q filed with the
SEC for a more complete description of risks of an investment in Amarin.

Vascepa® (icosapent ethyl) capsules are FDA approved for use as an adjunct to diet
to reduce triglyceride (TG) levels in adult patients with severe (TG >500 mg/dL)
hypertriglyceridemia (commonly known as very high TGs).

This presentation is intended for communication with investors only. Nothing in this
presentation should be construed as marketing the use of Amarin’s product or
product candidates.

                                                                                         2

Amarin: Blockbuster Opportunity and Growing Revenues

Upcoming: Cardiovascular outcomes data on
Vascepa® (>96% ethyl-EPA1) as add-on to statins
  REDUCE-IT CV outcomes study >93% enrolled
  Events driven study incorporates learnings from positive
     JELIS (Japan CV outcomes study of EPA) and others
    Leverages strong lipid efficacy & safety profile: two Phase 3s
    Studying at-risk patients with persistent elevated triglycerides
    CV outcomes results expected 2018, potentially 2016

Today: Marketing Vascepa for very high TGs
  U.S. launch in 2013
  $54M in revenues in 2014 and growing
  Marketing concentrated on top physician targets
  Co-promotion partner Kowa Pharmaceuticals America added
     in mid-2014 adds to Amarin’s 130 sales reps
    Addressing chronic patient condition

  1EPA:   eicosapentaenoic acid, a unique polyunsaturated omega-3 fatty acid
                                                                               3

Cardiovascular Risk: Significant Unmet Need

Cardiovascular Disease: #1 cause of death in the United States
  >700,000 people die of heart disease in the United States every year
     ‒ Represents ~1 in every 3 deaths (AHA Heart and Stroke Statistics)
  Heart attacks, stroke and other CV disease are expensive to treat
     ‒ Estimated annual total cost of >$300 billion

Standard of care first therapy beyond diet and exercise: Statins
  $40.2 billion annual market at its height
  Statins target LDL-C and are reported to have other “pleiotropic” effects such as:
     ‒ Improving endothelial function
     ‒ Enhancing the stability of atherosclerotic plaques
     ‒ Decreasing oxidative stress and inflammation
  Statins lower coronary heart disease risk by up to 25 to 40%

                                                                                    4

Seeking Solution to Address Residual Cardiovascular Risk

Limited success in prior CV outcomes studies with statin add-on therapies
    Ezetimibe (IMPROVE-IT):
      ‒ ~6% additional risk decline
      ‒ Focus on additional LDL-C lowering, other lipid reductions

    Fenofibrate (ACCORD-Lipid)
      ‒ No benefit in general population of low HDL-C patients
      ‒ Benefit trend seen in high TG, low HDL-C subset population

    Niacin: HDL-C increase focus (AIM-HIGH and HPS2-THRIVE)
      ‒ No benefit in the AIM-HIGH general population of low HDL-C patients
      ‒ In AIM-HIGH, benefit seen in high TG, low HDL-C subset population
      ‒ No benefit in the HPS2-THRIVE population with half of the patients having low
        HDL-C

Exception: 19% to 53% risk reduction in Japan-based study
    Ethyl-EPA (JELIS):
     ‒ Benefit shown in general population of statin treated patients
     ‒ Greater benefit in patient subpopulation with high TG and low HDL-C

                                                                                   5

Ethyl-EPA Reduced Coronary Events 19% to 53% on
                                                    Top of Statin Therapy in Japan Outcomes Study (JELIS)
                                                    Patients Randomized to Statin Alone or Statin + Ethyl-EPA (Epadel) and Followed
                                                    for 5 Years with Comparison of Cumulative Incidence of Major Coronary Events

                                                    TOTAL COHORT                                                                                                                SUB GROUP
                                                    No pre-specified minimum TG level                                                                                       TG>150 mg/dL and HDL

Ethyl-EPA: Lowers Triglycerides (TGs)
  Plus Spectrum of Other Lipid and Pleiotropic Effects

Triglycerides (fat in blood) lowered
    Studied by Amarin in two Phase 3 studies
        ‒ MARINE trial: TGs >500mg/dL and ANCHOR trial: TGs 200-499mg/dL on statins
    Also significantly lowered other key lipid parameters including total cholesterol,
     Non-HDL-C, Apo-B, Apo-CIII, VLDL-C and remnant-like particle cholesterol
    Did not increase LDL-C (bad cholesterol)

Pleiotropic effects of EPA beyond lipid improvements1
    Improves endothelial function
        ‒ Alone and in combination with statin therapy
    Anti-inflammatory effects
        ‒ Lowers Lp-PLA2 and hsCRP (>14% and >22% declines, respectively, vs. placebo in
          Phase 3 Vascepa studies)
    Anti-oxidant effects
        ‒ More potent antioxidant than historically used TG-lowering therapies and vitamin E
    Inhibits formation of cholesterol crystalline domains; disrupts existing domains
        ‒ No other TG-lowering therapy has been shown to share all these effects

1Pleiotropic effects based on clinical and non-clinical scientific literature

                                                                                               7

Lowering TGs in Patients with Baseline TG>150 mg/dL and low HDL-C in
Outcomes Studies Suggests Double Digit Relative Risk Reduction (RRR)
on Top of Statin Therapy

                                      Statin
   Trial                    Subgroup                                                   Subgroup
                                       Use                   Subgroup
Publication    Therapy        Size                                          Endpoint     RRR
                                     Through-                Published
   Year                        (N)                                                     (p-value)
                                        out
   JELIS                                                   TG ≥150 mg/dL    Expanded    -53%
                 EPA          957         Yes
   2007                                                   HDL-C ≤40 mg/dL    MACE       (0.043)
 ACCORD-                              Delayed
                                                           TG ≥204 mg/dL                -31%
   Lipid      Fenofibrate     941      start                                 MACE
                                     (inflates starting   HDL-C ≤34 mg/dL              (0.0567)
   2010                                  baselines)

 AIM-HIGH                                                  TG ≥ 200 mg/dL   Expanded    -36%
              Niacin ER       523         Yes
   2011                                                   HDL-C

Genetic Studies: TG Levels Predict Heart Disease (CHD)

           CHD Risk
 Predictor Effect Size                            Perspective    P-value

                        0.40               TGs and LDL-C

Broad Data Supports Link Between TGs and CV Risk
•   Epidemiological, genetic, and clinical data suggest that TGs and the lipoproteins that carry them are within the
    causal pathway of CV disease, and that treating elevated TGs may result in reduced CV risk.

                                                                                                                       10

Amarin: Positioned with First Outcomes Study of Ethyl-
  EPA as Add-on to Statin Outside of Japan

Purpose of REDUCE-IT cardiovascular outcomes study:
  Evaluate effectiveness of Ethyl-EPA (Vascepa) in reducing cardiovascular events
   in at risk patients
  FDA has strongly urged Amarin to complete REDUCE-IT outcomes study

Addresses unanswered medical questions; 1st outcomes study designed to
prospectively evaluate each of:
  TG-lowering in patients with elevated TGs despite statin therapy
  Ethyl-EPA on top of statins in a broad-based patient population

CV outcomes benefit in REDUCE-IT to be measured by:
  Randomizing statin treated patients to placebo and to Ethyl-EPA (Vascepa)
  Measuring cumulative incidence of major CV events (death, myocardial infarction,
   stroke, coronary revascularization and hospitalization for unstable angina)
  Comparing cumulative first CV events in active vs. placebo trial arms

                                                                                     11

REDUCE-IT Approaching Key Milestones

DESIGN                                                   TIMING
SPA Agreement reached with FDA in 2011                   Complete at 1,612 composite MACE events
  –   ~8,000 Patients on optimized statin therapy          –   First patient randomized November 2011
  –   Population with CVD or “at Risk,” incl. TGs          –   Interim efficacy look ~2016
      >150 mg/dL                                                    By independent data monitoring committee, DMC,
  –   90% power to detect 15% relative risk                          pre-specified at 967 events (60% of target events)
      reduction (>95% power to detect >20% relative        –   Completion of 100% of target events ~2017
      risk reduction)
                                                           –   Publication ~2018
  –   Amarin blind to ongoing trial results
                                                         OPPORTUNITY
STATUS
                                                          Incremental risk reduction beyond statin
 >7,400 patients enrolled (>93% of target)                therapy
 Enrollment completion anticipated in 2015               Positioned to address patient populations of
  –   Enrolling in 11 countries at >450 clinical sites     >70 million in U.S. alone; billions of dollars
  –   Safety data reviewed throughout study by DMC        Unique product profile
  –   Mean and median baseline TG of >200 mg/dL
      (higher than levels enrolled for recent outcome
      studies of other lipid modifying therapies)

                                                                                                                   12

REDUCE-IT and JELIS Study Design Differences
“Enriched” Patient Population in REDUCE-IT
 REDUCE-IT: all patients have elevated TG’s and other CV risk factors despite statin therapy
    –   Mean and median baseline TG’s >200 mg/dL and ~1/2 of patients expected to also have low HDL
 JELIS: many patients had normal TG levels and a 19% risk reduction was achieved
    –   Published subgroup with 53% risk reduction population had TG >150 mg/dL and low HDL
Higher Treatment Dose in REDUCE-IT
 REDUCE-IT 4 grams/day of ethyl-EPA (Vascepa); JELIS 1.8 grams/day of ethyl-EPA
 In 12-week Phase 3 ANCHOR study, 4 grams/day of Vascepa increased EPA at the plasma
  level to the same level as achieved with 1.8 grams/days of ethyl-EPA in JELIS
    –   Difference likely due to high fish diet in Japan
    –   EPA levels in REDUCE-IT control likely lower than JELIS due to dietary differences outside Japan
 Statin therapy targeted to goal in REDUCE-IT and JELIS
    –   REDUCE-IT LDL-C target

Elevated TGs More Prevalent than Elevated LDL-C

Tens of millions of people have lipid disorders
   13.1% of U.S. adults have elevated LDL-C               LDL-C and TG
   25.1% of U.S. adults have above normal TGs          Prevalence in Adults
                                                               (U.S.)
                                                  30%
Lipid disorders contribute to atherosclerosis,
  heart disease, pancreatitis and other health    25%
  issues                                          20%
                                                  15%
REDUCE-IT: Focused on statin treated patients     10%
 with persistently elevated TG levels and other   5%
 CV risk factors
                                                  0%
                                                          LDL-C  TG
Seeking right to promote Vascepa as add-on to             >130 >150
 statin therapy, not replace statin therapy               mg/dL mg/dL

                                                           Source: NHANES 2009-2012

                                                                                      14

Large Underpenetrated Market Opportunities
                                   U.S. Adult Population Stratified Based on TG Levels

                                    150 Million
                                     People                            Includes Statin-treated
                                                                         Patients in Ongoing
                                                                             REDUCE-IT
           U.S. Adult Population

                                                                          Outcomes Study
                                                                                                             Current
                                                                                                           Indication*
                                       67%                                              ANCHOR              MARINE
                                                                                          Study               Study
                                                             34 Million                 36 Million         3.8 Million
                                                              People                     People             People

                                                                 15%                       16%
                                                                                                               2%

          TG levels: 0-149 mg/dL                          150-199 mg/dL               200-499 mg/dL       500-2000 mg/dL

*Current indication for Vascepa; same as Lovaza ®                                       Only 3.6% Treated with Rx Meds
Source: Datamonitor and Archives of Internal Medicine, 2009;169(6):572-578

  >100M People in Top 7 Global Markets for Initially-Targeted Indications
                                                                                                                           15

Vascepa: New Paradigm in Cardiovascular Health

             Traditional Cholesterol             Historically Limited TG                      New Generation
FOCUS                                                                                  TG Lowering w/o LDL-C Increase
              Management Priority                  Treatment Options
                                                                                       (LDL-C decrease in ANCHOR vs. placebo)

                LDL-C                                 TGs                                   TGs
                                                                                                         LDL-C
LIPID
PARAMETERS

                           HDL-C                                LDL-C

KEY                                                                                                  Amarin’s
TREATMENTS     Statins, Niacin, Fibrates      Fibrates, Other Prescription
                                                                                                                 ®
                                              Omega-3 which contain DHA

        Vascepa: Potential to Redefine Lipid Management Therapies

                                       Note: Arrows show direction only—not to scale                                       16

Vascepa: Lowers TGs and Other Lipid Markers
Very High TGs (≥500 mg/dL)

    Phase 3 Results: MARINE Trial (4g/day dose)
    Supported FDA Approved Indication (median placebo-adjusted data)

                                      TG >750
                      TG               mg/dL         Non-HDL-C            LDL-C                 Apo B

                                                                           -2%*

                                                                                                 -9%

                                                         -18%

                                                   Only reported adverse reaction across the clinical profile for
                                                   Vascepa with an incidence > 2% and greater than placebo in
                     -33%                          Vascepa treated patients was arthralgia (2.3% for Vascepa,
                                                   1.0% for placebo)

                                        -45%

                                                                              Ref: American Journal of Cardiology 2011; 108:682–690.

◼     All Primary Endpoints Achieved
◼     Favorable Safety and Tolerability Profile
◼     Favorable Effect on Other Endpoints (Total Cholesterol, VLDL-C)
 Note: median % change versus placebo at week 12      *=not significant                                                          17

Vascepa: Lowers TGs and Other Lipid Markers
High TGs (200 – 499 mg/dL) on Statin Therapy

    Phase 3 Results: ANCHOR Trial (4g/day dose)
    Indication not approved by FDA (median placebo-adjusted data)

                        TG                    Non-HDL-C               LDL-C                    Apo B

                                                                      -6%

                                                                                                -9%

                                                          Only reported adverse reaction across the clinical profile
                                               -14%
                                                          for Vascepa with an incidence > 2% and greater than
                                                          placebo in Vascepa treated patients was arthralgia
                                                          (2.3% for Vascepa, 1.0% for placebo)
                        -22%

                                                                                Ref: American Journal of Cardiology 2012;110:984-992

◼     All Primary and Secondary Endpoints Achieved
◼     Favorable Safety and Tolerability Profile
◼     Favorable Effect on Other Endpoints (Total Cholesterol, VLDL-C)
 Note: median % change versus placebo at week 12                                                                                  18

Vascepa: Not Fish Oil, Pure EPA

                              Earlier Generation Rx Therapy                                            VASCEPA
                              A Complex Mixture of Fatty Acids                                         Icosapent Ethyl (Pure EPA)
                                                               Ethyl EPA
                                                               (465 mg)                                                       Ethyl-EPA
                                                                                                                              (>960 mg)

                                                               Ethyl DHA
                                                               (375 mg)

                                                            Additional omega
                                                            6, 7 & 9 (100mg)

                                                                  Other
                                                                Omega-3
                                                                Acid Ethyl                                                       fatty
                                                                 Esters                                                          acids
                                                                 (60mg)                                                         ~30 mg

APPROVED INDICATION
   TG >500 mg/dL                             Marketed since 2004 (generic 2014)                     Marketed since 2013
   LDL-C effect*                             Elevated LDL-C over 49%                                No Elevation (LDL-C reduction in ANCHOR study)
   NON-HDL-C effect*                         Reduced 10.2%                                          Reduced 17.7%
   Total cholesterol effect*                 Reduced 8.0%                                           Reduced 16.3%
                                             Limited, Variable or Not Characterized
    Additional biomarkers*                                                                          Additional Beneficial Effects
                                             in Label for Approved Indication
    Taste/eructation*                        Fishy Taste / Smell / Burp                             None
    Atrial fibrillation warning*             Added to package insert                                None
OTHER INDICATION POTENTIAL
                                             Studied, LDL-C Endpoint Not Achieved                   Biomarker Endpoints Achieved
    TG >200 mg/dL and 150 mg/dL                            Not Studied                                            Being Studied in REDUCE-IT

*median placebo adjusted data and other info from FDA approved package inserts in TG >500 mg/dL patients                                             19

Vascepa: Marketed in U.S. for Treating
  Patients with Very High TGs (>500 mg/dL)

130 Amarin sales reps target high prescribing
physicians of earlier generation therapy                    Vascepa Net Revenues
   Augmented since mid-2014 with co-promotion by                 (millions)
    Kowa Pharmaceuticals America                      $60

Wholesale price $221 per month (120 capsules;         $50
daily dose 4 capsules per day)                        $40
   $9 co-pay card for patients
   Vascepa price at parity to generics of prior      $30
    generation omega-3 on net basis for most payors
   >125M lives on tier 2                             $20

Competes on a basis of broad efficacy and             $10
placebo-like safety and tolerability
   Works alone or as add-on to statin therapy        $-
   Doesn’t work against LDL-C lowering of statins            2012 2013 2014
   >29,000 prescribers

                                                                               20

Vascepa Future Growth Potential

Early stages of marketing Vascepa for current indication
   Prior generation therapy grew to $1B drug based on same indication, despite
    it increasing LDL-C
   Applying lessons learned from first two years of launch for Amarin (Kowa’s co-
    promotion is in early stages)

International expansion
   In February 2015, executed licensing partnership for Vascepa in China
      ‒ Received $15M up-front payment with the potential for $154M in additional
          milestones plus tiered double digit royalties on future revenues
      ‒   Partner funding China regulatory approval
   Reviewing other ex-US opportunities

Seeking broader opportunities to market Vascepa
   REDUCE-IT cardiovascular outcomes study
   Pursuing judicial authority to promote truthful and non-misleading data to
    physicians regarding ANCHOR study and EPA effects on CV risk while
    REDUCE-IT is ongoing (1st Amendment suit)

                                                                                     21

Amarin Priorities for 2015

Grow Revenues from Current Vascepa Label
       Leverage Vascepa clinical experience and expanded tier 2 coverage
       Ensure focus and high sales call volume on highest potential prescribers
       Increasing Vascepa experience and outreach from co-promotion partner (Kowa)
       Tier 2 coverage for branded Lovaza disappears in 2015; generic Lovaza is expensive
       Increase awareness of Vascepa efficacy, safety and tolerability profile

REDUCE-IT Outcomes Study
     Complete enrollment in 2015
     Prepare for interim look by independent DMC in 2016

Cost-Effectively Advance Other Opportunities
     Evaluate additional Ex-US opportunities for Vascepa and consider strategic options
        without losing focus on other priorities
       Feasibility established for fixed-dose combination of Vascepa with leading statin
        (AMR102); work to accelerate closer to completion of REDUCE-IT study
       Further document Vascepa patient successes showing positive clinical effect of
        switching patients to Vascepa from other TG lowering therapy

                                                                                             22

Capitalization Summary (in Millions)
As of March 31, 2015, except as noted

Cash                                                           $161.2M

Debt Obligations

  ROYALTY-LIKE DEBT1                                           $142.7M     Carrying value $90.1M for accounting purposes

  EXCHANGEABLE SENIOR NOTES2                                   $150.0M     Carrying value $123.2M for accounting purposes

Common Stock and Equivalent Shares (Millions, Except per Share Amounts)
  COMMON/PREFERRED SHARES3                                      212.2    Preferred shares mirror common but non-voting
  OPTIONS                                                        12.1    Average Exercise Price of $4.95

  RESTRICTED STOCK UNITS                                           4.1

      TOTAL IF ALL EXERCISED                                    228.4

                                                                         12.5% Tax Rate
TAX JURISDICTION (PRIMARY)                                     Ireland
                                                                         (Est. Global Blended Rate 15%)

  1 The total remaining cash payments due on this debt are $142.7 million which is a fixed amount and includes the
   contractual interest paid quarterly at 10% of Vascepa revenues subject to quarterly maximum amounts. Lower carrying
   value reported for accounting purposes per GAAP.
  2 Total principal of $150.0 million has put provisions for $31 million in Jan 2017 and $119 million in Jan 2019. Notes accrue

   3.5% interest, paid semi-annually. Lower carrying value reported for accounting purposes per GAAP.
  3 Includes 35.2 million common share equivalents issuable upon conversion of preferred shares issued in March 2015

                                                                                                                                  23

Investment Highlights

                          •   Multi-billion dollar potential with REDUCE-IT outcomes study
     Large Global
                          •   FDA approved for severe hypertriglyceridemia (TG >500 mg/dL)
    Sales Potential       •   Multiple underserved patient populations with elevated TG levels

                          • TG reduction -- no increase, or a decrease, in LDL-C
 Differentiated Product   • Reductions in apo B, non-HDL-C, VLDL-C and total cholesterol
                          • Safety comparable to placebo

                          •   Growing sales productivity; growing managed care coverage
                          •   Phase 3 trials completed–all primary endpoints achieved
  Positive Execution      •   Recently announced licensing partnership for Vascepa in China
                          •   Outcomes study >93% enrolled and positioned for success

  Commercialization       • Grow revenues through specialty sales focus
                          • Seek broader promotional opportunities for Vascepa
     Strategy
                          • Cost-effectively advance other opportunities

                          • Team with history of product development and commercial successes
     Experienced
                          • Direct sales team of 130 sales representatives, excluding sales managers
     Management           • Amarin team supplemented by 250 Kowa sales representatives

Leading a New Paradigm in Cardiovascular Health Management
                                              .                                                        24

Leaders in Managing Lipids for
Improved Cardiovascular Health

INVESTOR PRESENTATION
June 2015
Nasdaq: AMRN