34 th Annual JP Morgan Healthcare Conference. January 13, 2016

Transcription

1 34 th Annual JP Morgan Healthcare Conference January 13, 2016

2 SAFE HARBOR Forward Looking Statements These slides and the accompanying oral presentation contain forward-looking statements and information. The use of words such as may, might, will, should, expect, plan, anticipate, believe, estimate, project, intend, future, potential, or continue, and other similar expressions are intended to identify forward looking statements. For example, all statements we make regarding the initiation, timing, progress and results of our preclinical and clinical studies and our research and development programs, our ability to advance ETC-1002 into, and successfully complete, clinical studies, and the timing or likelihood of regulatory filings and approvals are forward looking. All forward-looking statements are based on estimates and assumptions by our management that, although we believe to be reasonable, are inherently uncertain. All forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those that we expected. These statements are also subject to a number of material risks and uncertainties that are described in the preliminary prospectus supplement and the accompanying prospectus. Any forward-looking statement speaks only as of the date on which it was made. Neither we, nor our affiliates, advisors, or representatives, including the underwriters of this offering, undertake any obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law. 2

3 BEMPEDOIC ACID: LOWERING LDL-C A DIFFERENTIATED ORAL THERAPY Pioneering a differentiated oral therapy for hypercholesterolemia Works like a statin ; but with reduced potential for muscle-related side effects Targeting statin intolerance in patients with elevated LDL-C, a high unmet medical need ETC-1002 (bempedoic acid) lowers elevated LDL-C Up to 30% as monotherapy and 50% in combination with ezetimibe Incremental 24% LDL-C lowering when added to stable statin therapy Lowers high-sensitivity C-reactive protein (hscrp) up to 44% Appears safe and well tolerated Continuing progress on Phase 3 global development plans Robust Phase 1 & 2 program completed in >1,000 patients Phase 3 global development plans to be formalized and communicated 1H

4 INVESTMENT HIGHLIGHTS Phase 3 program initiated with launch of 040 long-term safety study First-in-class ACL-inhibitor (ACLi), inhibiting cholesterol biosynthesis Designed to significantly lower elevated levels of LDL-C with reduced potential for muscle-related side effects Compelling, positive clinical results in Phase 1 and 2 studies Appears safe and well-tolerated Bempedoic acid addresses high unmet medical need Currently, no approved therapies for statin intolerance in the US Large and growing market opportunity 3.5M statin intolerant patients in US represents an estimated $7B opportunity Strong financial position Well-funded with ~$300M in cash Experienced management team Prior success in development and approval of lipid regulating drugs 4

5 BEMPEDOIC ACID MOA: ACL INHIBITION INHIBITS CHOLESTEROL BIOSYNTHESIS VIA INHIBITION OF ATP CITRATE LYASE (ACL) Bempedoic acid is an oral, once-daily, small molecule targeting the well-known cholesterol biosynthesis pathway; works like a statin to up-regulate LDL-receptors, lower plasma LDL-C levels and lower hscrp, but with reduced potential for muscle-related side effects. 5 5

6 Cardiovascular Disease Cancer Pulmonary Disease Accidents Alzheimer's Disease CARDIOVASCULAR DISEASE #1 CAUSE OF DEATH IN THE US Top 5 Causes of Death 80M people at risk of cardiovascular disease ~800,000 deaths annually Recent guidelines emphasize need to manage CV risk in even more patients 6 Source: NIH

7 LOWERING LDL-C DECREASES CV RISK ELEVATED LDL-C IS THE #1 MODIFIABLE LIPID RISK FACTOR IMPROVE-IT 7

8 UNMET (RESIDUAL) NEEDS IN LDL-C LOWERING 3.5M PATIENTS UNABLE TO TOLERATE ANY LEVEL OF STATIN THERAPY Statin Intolerance is an estimated $7B opportunity Statin Intolerant; Patients for whom maximally tolerated statin (MTS) is no statin therapy at all 8 Sources: NHANES, Source Health Analytics, NCEP ATP III guidelines, Esperion analysis

9 STATIN INTOLERANCE INCREASINGLY ATTRACTIVE High unmet medical need Estimated 3.5 million SI patients in the US No approved therapies for SI in the US: new therapies urgently needed Patients who can t/won t take statins have very high LDL-C levels Baseline LDL-C levels for SI patients in clinical trials mg/dl Liver-specific and differentiated MOA Bempedoic acid is a pro-drug that inhibits ACL Conversion to active drug only in liver cells results in reduced potential for muscle-related side effects Phase 2 clinical results strongly support Phase 3 success in SI patients Bempedoic acid well-tolerated in hundreds of SI patients LDL-C lowering of 30%/50% in SI patients as mono/combo therapy Details of the Phase 3 SI program to be formalized Q FDA has already requested that Esperion have a CVOT well underway to support initial approval of an LDL-C lowering label in SI 9 9

10 UNMET (RESIDUAL) NEEDS IN LDL-C LOWERING Esperion Focus Partnership Opportunities Statin Intolerant HeFH ASCVD High LDL-C levels comparable to pre-statin era Pragmatic diagnostic approach used by physicians Low satisfaction level with existing treatment options Patients and physicians actively searching for alternatives POPULATION: 3.5M US PATIENTS Well defined but underdiagnosed population Requires significant effort to raise awareness Population: ~600K US patients Large and diverse population All patients with previous CV event Significant overlap with diabetes population Population: ~10M US patients 10 Source: US NHANES, Decision Resources, Esperion analysis

11 UNMET (RESIDUAL) NEEDS IN LDL-C LOWERING BEMPEDOIC ACID TARGET PATIENT POPULATION Esperion Focus No Statin Some Statin Statin Tolerant DESCRIPTION Patients do not tolerate any dose of statin Patients tolerate low or moderate dose statins Patients are generally tolerant of statins, including high-intensity statins PATIENT POPULATION 10% or 3.5 million patients Estimated additional 10% of patients 80-95% UNMET NEED First-line, low-cost LDL-C lowering Most patients require additional LDL-C lowering ~1/3 of patients require additional LDL-C lowering BEMPEDOIC ACID OPPORTUNITY As oral, once daily monotherapy or addon to ezetimibe As add-on to low or moderate dose statins As add-on to statins No Statin Some Statin Statin Tolerant 11 Source: Maningat and Breslow. NEJM 2011; NLA 2014

12 LSMean (95%Cl) Percent Change From Baseline BEMPEDOIC ACID: SUMMARY OF LDL-C LOWERING 30% LDL-C LOWERING ACROSS ALL COMPLETED STUDIES; ALMOST 50% IN COMBINATION WITH EZETIMIBE Placebo, reference line Monotherapy Combo with ezetimibe ETC-1002 Daily Dose, mg Adapted from Integrated Summary of Efficacy, Table , dated 18May Integrated Phase 2 data includes , -005, -006, -007, -008 and -009

13 DELIVERING POSITIVE RESULTS IN CLINICAL TRIALS CONSISTENT DELIVERY OF SAFETY, TOLERABILITY AND EFFICACY POSITIVE RESULTS: PHASE 1 POSITIVE RESULTS: PHASE 2A 005 STUDY POSITIVE RESULTS: PHASE 2A 007 STUDY POSITIVE RESULTS: PHASE 2B 009 STUDY POSITIVE RESULTS: PHASE 2A 003 STUDY POSITIVE RESULTS: PHASE 2A 006 POSITIVE RESULTS: PHASE 2B 008 POSITIVE RESULTS: PHASE COMPLETION OF ALL NONCLINICAL STUDIES AHA MOA MUSCLE- SPARING DATA & -009 DATA PRESENTATIONS REMOVAL OF PPAR PARTIAL CLINICAL HOLD REMOVAL OF 240 MG PARTIAL CLINICAL HOLD -003 PUBLICATION BALANTYNE et. al., JACC PUBLICATION GUTIERREZ et. al., ATVB PUBLICATION THOMPSON et. al., JCL PUBLICATION THOMPSON et. al., JCL 2016 (in press) 13 References available upon request

14 US REGULATORY ENVIRONMENT FOR LDL-C CLARIFICATION OF APPROVAL REQUIREMENTS HISTORICAL FOCUS CURRENT FOCUS Statins approved for LDL-C lowering based on positive CVOT data from non-statins (cholestyramine, gemfibrozil, niacin) Each new LDL-C lowering drug class is evaluated independently Statin CVOTs consistently showed significant CV risk reduction benefit in all patient populations tested LDL-C lowering hypothesis is valid when reducing elevated LDL-C levels CVOTs as add-on to statin have NOT demonstrated incremental clinical benefit: Fenofibrate: ACCORD (2010) Niacin: AIM-HIGH (2011), HPS2-THRIVE (2012) CETP inhibitors: ILLUMINATE (2006), dal- OUTCOMES (2012), ACCELERATE (2015) All sponsors are expected to demonstrate favorable risk:benefit profile for each new LDL-C lowering drug Changes in regulatory environment evident in recent EMDAC meetings 14 14

15 2016 BEMPEDOIC ACID MILESTONE PREVIEW Q2 16 Mid 16 2H 16 Announce global Phase 3 CLEAR SI development plans Initiate Phase 3 CLEAR SI efficacy studies Initiate SI CVOT Announce top-line results from Phase 2 (035) high-dose statin (HDS) study File IND for the FDC of bempedoic acid and ezetimibe Announce top-line results from Phase 1 PK (037) HDS study 15

16 BEMPEDOIC ACID DEVELOPMENT OPPORTUNITIES Esperion Focus Partnership Opportunities Statin Intolerant Patients Add-on to Statins (in HeFH and ASCVD Patients) No Approved Therapeutic Options in the US Similar to Recently Approved Antibody Therapies 16 16

17 BEMPEDOIC ACID FOCUSED DEVELOPMENT PLAN Phase 3 Program CLEAR (Cholesterol Lowering via ETC-1002, an ACL-inhibiting Regimen) Focused on patients with statin intolerance Long-term safety study (040) initiated with 52 week dosing Additional studies (035, 037) initiated to address specific questions of bempedoic acid in combination with HDS Remainder of Phase 3 program studies to be formalized Q Proposed indications Pursue initial approval for LDL-C reduction in statin intolerant patients Expand label in SI patients with CVOT data for CV Risk Reduction 17 17

18 BEMPEDOIC ACID -040 PHASE 3 STUDY 52 WEEK LONG-TERM SAFETY STUDY: TOP-LINE RESULTS EXPECTED Q Patients at High CV Risk with Hyperlipidemia not Adequately Controlled by Lipid Modifying Therapy Bempedoic acid 180 mg (n=600) Placebo (n=300) 52 Week Treatment Primary Objective Long-term safety and tolerability of bempedoic acid 180 mg versus placebo in high CV risk patients with hyperlipidemia: High CV risk patients who are not at LDL-C goal Maximally tolerated lipid-modifying therapy Limited to include patients on stable low to moderate dose statin therapy Secondary Objective At 12, 24, and 52 weeks, assess: LDL-C, HDL-C, non-hdl-c, total cholesterol and triglycerides Apolipoprotein B (apob) and hscrp 18 18

19 BEMPEDOIC ACID -035 PHASE 2 STUDY HIGH-DOSE STATIN STUDY: TOP-LINE RESULTS EXPECTED MID-2016 Elevated LDL-C Patients While on Stable High-Dose Statin Therapy (Atorvastatin 80mg) 1 week Screening (patients on low, moderate, or high intensity statin therapy at least 4 weeks prior to screening) 4 Week Treatment with 80 mg Atorvastatin (n=60) 4 Week Treatment with 80 mg Atorvastatin + bempedoic acid 180 mg (n=40) or placebo (n=20) Primary Objectives LDL-C lowering efficacy of bempedoic acid 180 mg versus placebo Multiple-dose plasma pharmacokinetics (PK) of atorvastatin 80 mg Secondary Objectives Efficacy of bempedoic acid 180 mg versus placebo Safety and tolerability Steady state plasma PK of bempedoic acid 180 mg 19 19

20 BEMPEDOIC ACID -037 PHASE I STUDY PK STUDY: TOP-LINE RESULTS EXPECTED MID-2016 Phase 1 PK study to assess effects of bempedoic acid on single doses of HDS: 80 mg of atorvastatin 40 mg of simvastatin 80 mg of pravastatin 40 mg of rosuvastatin Statin PK, safety and tolerability will be evaluated Study to initiate in February 2016 with top-line results expected mid

21 PROVEN LEADERSHIP TEAM Tim Mayleben President and CEO Experience Products to Market Narendra Lalwani, PhD, MBA Executive VP, R&D and COO Mary McGowan, MD Chief Medical Officer Roger Newton, PhD, FAHA CSO and Executive Chairman Marianne Andreach Sr. VP, Strategic Marketing Ashley Hall VP, Global Regulatory Affairs Rick Bartram VP, Finance 21

22 INVESTMENT HIGHLIGHTS Phase 3 program initiated with launch of 040 long-term safety study First-in-class ACLi, inhibiting cholesterol biosynthesis Designed to significantly lower elevated levels of LDL-C with reduced potential for muscle-related side effects Compelling, positive clinical results in Phase 1 and 2 studies Appears safe and well-tolerated Bempedoic acid addresses high unmet medical need Currently, no approved therapies for statin intolerance in the US Large and growing market opportunity 3.5M statin intolerant patients in US represents an estimated $7B opportunity Strong financial position Well-funded with ~$300M in cash Experienced management team Prior success in development and approval of lipid regulating drugs 22

23 Q&A