Leaders in Managing Lipids for Improved Cardiovascular Health

Transcription

1 Leaders in Managing Lipids for Improved Cardiovascular Health INVESTOR PRESENTATION June 2015 Nasdaq: AMRN

2 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

3 Amarin: Blockbuster Opportunity and Growing Revenues Upcoming: Cardiovascular outcomes data on Vascepa (>96% ethyl-epa 1 ) 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 1 EPA: eicosapentaenoic acid, a unique polyunsaturated omega-3 fatty acid 3

4 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

5 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

6 Cumulative Incidence of Major Coronary Events (%) Ethyl-EPA Reduced Coronary Events 19% to 53% on Top of Statin Therapy in Japan Outcomes Study (JELIS) Cumulative Incidence of Major Coronary Events (%) 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 No pre-specified minimum TG level SUB GROUP TG>150 mg/dl and HDL<40 mg/dl 4 3 Control (statin) EPA (statin+epadel) - 19% 5 4 Control (statin) EPA (statin+epadel) 53% N=18,645 (p=0.011) 1 N=957 HR: %CI: (p=0.043) Years Source: Yokoyama M. et al, Lancet 2007; 369: Years P value adjusted for age, gender, smoking, diabetes, and hypertension. CI=confidence interval. Source: Saito et al, Atherosclerosis 2008; 200:

7 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 mg/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 improvements 1 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 1 Pleiotropic effects based on clinical and non-clinical scientific literature 7

8 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 Trial Publication Year Therapy Subgroup Size (N) Statin Use Throughout Subgroup Published Endpoint Subgroup RRR (p-value) JELIS 2007 EPA 957 Yes TG 150 mg/dl HDL-C 40 mg/dl Expanded MACE -53% (0.043) ACCORD- Lipid 2010 Fenofibrate 941 Delayed start (inflates starting baselines) TG 204 mg/dl HDL-C 34 mg/dl MACE -31% (0.0567) AIM-HIGH 2011 Niacin ER 523 Yes TG 200 mg/dl HDL-C <32 mg/dl Expanded MACE -36% (0.032) HPS2- THRIVE 2013 Niacin + Laropiprant 4,362 Yes TG 151 mg/dl HDL-C <35 mg/dl Major vascular events No significant difference CONFIDENTIAL 8

9 Genetic Studies: TG Levels Predict Heart Disease (CHD) Predictor CHD Risk Effect Size Perspective P-value TG 0.40 TGs and LDL-C levels are <<< comparably strong LDL-C 0.39 <<< predictors of CHD HDL-C 0.04 HDL-C is weak predictor 0.32 Modified from: Do R et al. Nat Genet. 2013;45(11): (N=86,995); 9

10 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

11 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

12 REDUCE-IT Approaching Key Milestones DESIGN SPA Agreement reached with FDA in 2011 ~8,000 Patients on optimized statin therapy Population with CVD or at Risk, incl. TGs >150 mg/dl 90% power to detect 15% relative risk reduction (>95% power to detect >20% relative risk reduction) Amarin blind to ongoing trial results STATUS >7,400 patients enrolled (>93% of target) Enrollment completion anticipated in 2015 Enrolling in 11 countries at >450 clinical sites Safety data reviewed throughout study by DMC Mean and median baseline TG of >200 mg/dl (higher than levels enrolled for recent outcome studies of other lipid modifying therapies) TIMING Complete at 1,612 composite MACE events First patient randomized November 2011 Interim efficacy look ~2016 By independent data monitoring committee, DMC, pre-specified at 967 events (60% of target events) Completion of 100% of target events ~2017 Publication ~2018 OPPORTUNITY Incremental risk reduction beyond statin therapy Positioned to address patient populations of >70 million in U.S. alone; billions of dollars Unique product profile 12

13 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 <100 mg/dl; JELIS LDL-C target <130 mg/dl; studies of statin therapy demonstrated similar outcome results in Japan at <130 mg/dl to Western populations at 100 mg/dl REDUCE-IT is a Global Study REDUCE-IT: enrollment in 11 countries including strong participation in the United States; randomized double blinded study JELIS: Japan only, mostly women; open label, randomized with blinded endpoint analysis 13

14 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 25.1% of U.S. adults have above normal TGs Lipid disorders contribute to atherosclerosis, heart disease, pancreatitis and other health issues REDUCE-IT: Focused on statin treated patients with persistently elevated TG levels and other CV risk factors Seeking right to promote Vascepa as add-on to statin therapy, not replace statin therapy 30% 25% 20% 15% 10% 5% 0% LDL-C and TG Prevalence in Adults (U.S.) LDL-C >130 mg/dl TG >150 mg/dl Source: NHANES

15 U.S. Adult Population Large Underpenetrated Market Opportunities U.S. Adult Population Stratified Based on TG Levels 150 Million People Includes Statin-treated Patients in Ongoing REDUCE-IT Outcomes Study Current Indication* 67% 34 Million People ANCHOR Study 36 Million People MARINE Study 3.8 Million People TG levels: 15% 16% mg/dl mg/dl mg/dl mg/dl 2% *Current indication for Vascepa; same as Lovaza Source: Datamonitor and Archives of Internal Medicine, 2009;169(6): Only 3.6% Treated with Rx Meds >100M People in Top 7 Global Markets for Initially-Targeted Indications 15

16 Vascepa: New Paradigm in Cardiovascular Health FOCUS Traditional Cholesterol Management Priority Historically Limited TG Treatment Options New Generation TG Lowering w/o LDL-C Increase (LDL-C decrease in ANCHOR vs. placebo) LIPID PARAMETERS LDL-C TGs TGs LDL-C HDL-C LDL-C KEY TREATMENTS Statins, Niacin, Fibrates Fibrates, Other Prescription Omega-3 which contain DHA Amarin s Vascepa: Potential to Redefine Lipid Management Therapies Note: Arrows show direction only not to scale 16

17 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% -33% Only reported adverse reaction across the clinical profile for Vascepa with an incidence > 2% and greater than placebo in Vascepa treated patients was arthralgia (2.3% for Vascepa, 1.0% for placebo) -45% Ref: American Journal of Cardiology 2011; 108: 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

18 Vascepa: Lowers TGs and Other Lipid Markers High TGs ( 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% -14% Only reported adverse reaction across the clinical profile 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: 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

19 Vascepa: Not Fish Oil, Pure EPA Earlier Generation Rx Therapy A Complex Mixture of Fatty Acids Ethyl EPA (465 mg) VASCEPA Icosapent Ethyl (Pure EPA) Ethyl-EPA (>960 mg) Ethyl DHA (375 mg) Additional omega 6, 7 & 9 (100mg) Other Omega-3 Acid Ethyl Esters (60mg) fatty acids ~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% Additional biomarkers* Limited, Variable or Not Characterized in Label for Approved Indication Additional Beneficial Effects Taste/eructation* Fishy Taste / Smell / Burp None Atrial fibrillation warning* Added to package insert None OTHER INDICATION POTENTIAL TG >200 mg/dl and <500 mg/dl Studied, LDL-C Endpoint Not Achieved (No Outcomes Study for Population) Biomarker Endpoints Achieved (Outcomes Benefit Being Studied in REDUCE-IT) TG >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

20 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 Augmented since mid-2014 with co-promotion by Kowa Pharmaceuticals America Wholesale price $221 per month (120 capsules; daily dose 4 capsules per day) $9 co-pay card for patients Vascepa price at parity to generics of prior generation omega-3 on net basis for most payors >125M lives on tier 2 Competes on a basis of broad efficacy and placebo-like safety and tolerability Works alone or as add-on to statin therapy Doesn t work against LDL-C lowering of statins >29,000 prescribers $60 $50 $40 $30 $20 $10 $- Vascepa Net Revenues (millions)

21 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 copromotion 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

22 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

23 Capitalization Summary (in Millions) As of March 31, 2015, except as noted Cash $161.2M Debt Obligations ROYALTY-LIKE DEBT 1 $142.7M Carrying value $90.1M for accounting purposes EXCHANGEABLE SENIOR NOTES 2 $150.0M Carrying value $123.2M for accounting purposes Common Stock and Equivalent Shares (Millions, Except per Share Amounts) COMMON/PREFERRED SHARES 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 TAX JURISDICTION (PRIMARY) Ireland 12.5% Tax Rate (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 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

24 Investment Highlights Large Global Sales Potential Differentiated Product Positive Execution Commercialization Strategy Experienced Management Multi-billion dollar potential with REDUCE-IT outcomes study FDA approved for severe hypertriglyceridemia (TG >500 mg/dl) Multiple underserved patient populations with elevated TG levels TG reduction -- no increase, or a decrease, in LDL-C 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 Recently announced licensing partnership for Vascepa in China Outcomes study >93% enrolled and positioned for success Grow revenues through specialty sales focus Seek broader promotional opportunities for Vascepa Cost-effectively advance other opportunities Team with history of product development and commercial successes Direct sales team of 130 sales representatives, excluding sales managers Amarin team supplemented by 250 Kowa sales representatives Leading a New Paradigm in Cardiovascular Health Management. 24

25 Leaders in Managing Lipids for Improved Cardiovascular Health INVESTOR PRESENTATION June 2015 Nasdaq: AMRN