JMP 2017 Life Sciences Conference. Tim Mayleben

Transcription

1 JMP 2017 Life Sciences Conference Tim Mayleben PRESIDENT AND CEO JUNE 21, 2017

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 COPYRIGHT 2017 ESPERION. ALL RIGHTS RESERVED DO NOT COPY OR DISTRIBUTE

3 Esperion Today Two Phase 3 convenient, complementary, cost-effective, non-statin, once-daily, oral LDL-C lowering therapies: Bempedoic Acid 30% LDL-C lowering, safe and well-tolerated Consistent incremental LDL-C lowering with with statins & ezetimibe Bempedoic Acid + Ezetimibe (BA+EZ) Fixed dose combination or doublet pill of bempedoic acid + ezetimibe ~50% LDL-C lowering, safe and well-tolerated Confirmed regulatory approval pathway for LDL-C lowering indication Completion of on-going global pivotal Phase 3 LDL-C lowering studies will support submissions by 1H 2019 Experienced Lipid Management Team Focused on unmet needs of patients with hypercholesterolemia at high CVD risk; ASCVD and/or HeFH and/or SI ~$208 in cash at March 31, COPYRIGHT 2017 ESPERION. ALL RIGHTS RESERVED DO NOT COPY OR DISTRIBUTE

4 A Global Problem: The Unmet Need Patients Not Adequately Treated With Statins TOTAL STATIN ADD-ON (ASCVD & HeFH) ASCVD, HeFH & High Risk for CVD (NO STATIN BACKGROUND) TOTAL Decision Resources, NHANES, Esperion analysis 4 COPYRIGHT 2017 ESPERION. ALL RIGHTS RESERVED DO NOT COPY OR DISTRIBUTE

5 The Lipid Management Team TIM MAYLEBEN President and Chief Executive Officer Products to Market EXPERIENCE Esperion, Aastrom, NightHawk NARENDRA LALWANI, PhD, MBA, FAHA Executive Vice President, R&D, and Chief Operating Officer EXPERIENCE Esperion, Pfizer, Parke-Davis, Cerenis MARY McGOWAN, MD Chief Medical Officer EXPERIENCE Sanofi Genzyme, Dartmouth-Hitchcock Med Ctr MARIANNE ANDREACH Senior Vice President, Product Planning EXPERIENCE Esperion, Bristol-Myers Squibb, Parke-Davis ASHLEY HALL Vice President, Global Regulatory Affairs EXPERIENCE AMGEN, Micromet, Revogenex RICK BARTRAM Vice President, Finance EXPERIENCE PwC 5 COPYRIGHT 2017 ESPERION. ALL RIGHTS RESERVED DO NOT COPY OR DISTRIBUTE

6 Bempedoic Acid Mechanism Of Action Converted to ETC-1002-CoA, the Active Form, in the Liver Liver Targeted, Muscle-sparing Drug Bempedoic acid (BA) acts in the same cholesterol biosynthesis pathway as statins BA targets ATP-Citrate Lyase, an enzyme upstream of HMG-CoA reductase Upregulates LDL receptors and lowers LDL-C BA is a prodrug; the specific isozyme (ACSVL1) which converts BA into an active CoA form is not present in skeletal muscle Source: Pinkosky, S. L., Newton, R. S. et al. (2016). Nature Communications, 7, doi: /ncomms COPYRIGHT 2017 ESPERION. ALL RIGHTS RESERVED DO NOT COPY OR DISTRIBUTE

7 Lowering LDL-C Through the LDL Receptor Confirmed by Genetic Validation Studies BEMPEDOIC ACID FDC (BEMPEDOIC ACID + EZETIMIBE) EZETIMIBE STATIN PCSK9s LDL-C LOWERING Up to 30% Up to 50% 15-18% 25-55% 45-55% EFFECT ON THE LDL RECEPTOR TARGET Inhibits ATP Citrate Lyase Inhibits ATP Citrate Lyase and NPC1L1 Inhibits NPC1L1 Inhibits HMG- CoA reductase Inhibits PCSK9 hscrp LOWERING ~40% ~26% No change Up to 40% No change DOSING Oral Oral Oral Oral Injectable MENDELIAN RANDOMIZATION DATA 7 COPYRIGHT 2017 ESPERION. ALL RIGHTS RESERVED DO NOT COPY OR DISTRIBUTE

8 Bempedoic Acid (ETC-1002) A Targeted LDL-C Lowering Therapy in Phase 3 Convenient, complementary, cost-effective, non-statin, once-daily, oral pill patient-friendly, physician-friendly, and payer-friendly Consistent and complementary LDL-C lowering 30% as monotherapy ~Incremental 20%+ on top of statins, including high-intensity statins Bempedoic Acid actual pill (1 pill/day) Consistent and complementary hscrp reduction of up to 40%; a key biomarker of inflammation Safe and well-tolerated Not a replacement for statins or ezetimibe; an oral drug to complement statins and ezetimibe, to provide even greater LDL-C lowering 8 COPYRIGHT 2017 ESPERION. ALL RIGHTS RESERVED DO NOT COPY OR DISTRIBUTE

9 Bempedoic Acid Phase 2 Program Overview Robust Phase 2 Program Completed; 8 Studies and 1,045 Patients Patient Population: Background Therapy: Study: none 003 (N=177) 12 weeks Elevated LDL-C atorva 10 low/mod statins 007 (N=58) 009 (N=134) 8 weeks 12 weeks atorva (N=68) 4 weeks Elevated LDL-C / Statin Intolerance none none or eze 006 (N=56) 008 (N=349) 8 weeks 12 weeks Elevated LDL-C / Hypertension none 014 (N=143) 6 weeks Elevated LDL-C / T2 Diabetes none 005 (N=60) 4 weeks 9 COPYRIGHT 2017 ESPERION. ALL RIGHTS RESERVED DO NOT COPY OR DISTRIBUTE

10 Bempedoic Acid Phase 3 Program for LDL-C Lowering Comparable in Design and Scale to PCSK9i Programs LDL-C Lowering Indication (Total N=~3200): Study 1; Long-Term, N=2233 (Fully Enrolled) 52 weeks safety ASCVD and/or HeFH Statin Add-On OLE N=~1400 (actively enrolling) 1.5 yrs safety Study 2; High Risk, N=~ weeks safety / 12 weeks LDL-C ASCVD and/or HeFH Study 3; SI, N=300 No Statin Background Therapy* Study 4; SI, +EZ, N= weeks LDL-C 24 weeks safety / 12 weeks LDL-C *Studies are being conducted to obtain an indication for use in patients on no background statin therapy in Europe 10 COPYRIGHT 2017 ESPERION. ALL RIGHTS RESERVED DO NOT COPY OR DISTRIBUTE

11 CLEAR Outcomes Global CVOT to Support CVD Risk Reduction Submission in 2022 ASCVD/High-Risk 1 Prevention CVOT: Top-Line Results by 2022 Event-driven, global, randomized, double-blind, placebo-controlled study to assess the effects of bempedoic acid in patients with ASCVD or at high risk for CVD and only able to tolerate less than the lowest approved daily starting dose of their statin Primary Endpoint: Effect of bempedoic acid vs placebo on four-component MACE CV death, non-fatal MI, non-fatal stroke, or coronary revascularization (minimum of 1437 events) Target Enrollment: Approximately 12,600 patients randomized 1:1 Target Sites/Geography: More than 600 sites in ~30 countries Patient Population: High CV risk patients (ASCVD or high-risk primary prevention) with hypercholesterolemia Patients can be on background LDL-C lowering therapies including ezetimibe and PCSK9i CVD Risk: History of ASCVD or be at high risk for CVD Baseline LDL-C levels: Between 100 mg/dl and 190 mg/dl in secondary prevention and > 100 mg/dl in primary prevention (no upper limit); expected mean baseline of 135 mg/dl Study Chairman: Steven Nissen M.D. Co-Principal Investigators: A. Michael Lincoff M.D. and Stephen Nicholls M.D. Academic Research Organization Collaborators: Cleveland Clinic (C5) Research Powering: >85% power to detect ~14% relative risk reduction in primary endpoint of bempedoic acid as compared with placebo (assumes 3.79% annual event rate in placebo group) 11 COPYRIGHT 2017 ESPERION. ALL RIGHTS RESERVED DO NOT COPY OR DISTRIBUTE

12 CVOT Comparison Table Study Name Drug (Company) CLEAR Outcomes Bempedoic Acid (Esperion) FOURIER SPIRE-1 SPIRE-2 PCSK9i (Amgen) PCSK9i (Pfizer) PCSK9i (Pfizer) ODYSSEY OUTCOMES PCSK9i (Sanofi/REGN) IMPROVE-IT Ezetimibe (Merck) MDCO PCSK9i (MDCO) Number of Patients ~12,600 27,564 16,817 10,621 18,000 18,141 ~14,000 Patient Population ASCVD/High Risk 1º Prev ASCVD ASCVD/ High Risk 1º Prev ASCVD/High Risk 1º Prev Post-ACS Post-ACS ASCVD Background Statin Less than Starting Dose Statins: HI: 69% MI: 30% LI: <1% Eze: 5% Statins: Any: 99% HI: 91% Eze: 8% Statins: Any: 83% HI: 73% No:17% Eze: 13% atorva 40/80 mg rosuva 20/40 mg or max tol dose of atorva or rosuva simva 40mg Not disclosed Mean Baseline LDL-C ~135 mg/dl 92 mg/dl 94 mg/dl 133 mg/dl 87 mg/dl (median) 94 mg/dl ~130 mg/dl Primary Endpoint CV Death, MI, Stroke, Cor Revasc CV Death, MI, Stroke, Hosp for UA, Cor Revasc CV Death, MI, Stroke, Hosp for UA req Revasc CV Death, MI, Stroke, Hosp for UA req Revasc CHD Death, MI, Stroke, Hosp for UA CV Death, MI, Stroke, Hosp for UA, Cor Revasc CHD Death, MI, Stroke Mean Duration of Therapy 3.75 years 26 months 10 months 10 months >3 years (est.) 6 years >2 years (est.) 12 COPYRIGHT 2017 ESPERION. ALL RIGHTS RESERVED DO NOT COPY OR DISTRIBUTE

13 Development and Regulatory Strategy Bempedoic Acid and Fixed Dose Combination Global Clinical Development Programs to Support Target Label(s) Bempedoic Acid LDL-C Lowering Submission (1H 2019) CV RR FDC LDL-C Lowering Submission (TBA) Submission (2022) LDL-C Lowering Program Initial LDL-C Lowering Label in U.S. and Europe (like PCSK9i labels) CLEAR Outcomes CVOT CV Risk Reduction Label in U.S. and Europe (Note: breadth of LDL-C lowering label will likely depend on PCSK9i CV label) 13 COPYRIGHT 2017 ESPERION. ALL RIGHTS RESERVED DO NOT COPY OR DISTRIBUTE

14 Bempedoic Acid Clinical Program s Translation into Market Opportunity P3 Clinical Studies Expected Labels Market Opportunity ASCVD and/or HeFH Statin and other LLT Background N=2983 ASCVD, HeFH or High Risk 1 0 Prev No statin Background* N=525 Study 1; N=2233 (52wks) Entry LDL -C= >70mg/dL OLE N=~1400 (1.5 yrs) only 040 patients Study 2; N=750 (52 wks) Entry LDL-C =>100mg/dL Study 3; N=300 (24 wks) Entry LDL-C =>100mg/dL Study 4 +EZE; N=225 (12 wks) Entry LDL-C =>100mg/dL U.S. - adjunct to diet and maximally tolerated statin therapy in adults w/ HeFH or ASCVD (same as PCSK9i) Europe - adjunct to diet: in combination with maximally tolerated statin therapy +/- other lipid lowering therapies in patients unable to reach LDL-C goals alone or +/- other lipid lowering therapies in statin intolerant patients (same as PCSK9i) Patients Not Adequately Treated With Statins STATIN ADD-ON (ASCVD & HeFH) No STATIN TOTAL 8.6M 8.4M 3.5M 3.3M 12.1M 11.7M CVOT ASCVD & High Risk 1 0 Prev No statin Background* N= 12,600 High risk 1 0 prevention patients and ASCVD patients U.S./Europe: Bempedoic acid is indicated to reduce the risk of CV death, myocardial infarction (MI), stroke, or coronary revascularization procedures in patients with ASCVD, or at high risk for CVD, including those who are considered statin intolerant *includes no, low and very low statin doses 14 COPYRIGHT 2017 ESPERION. ALL RIGHTS RESERVED DO NOT COPY OR DISTRIBUTE

15 FDC (Bempedoic Acid + Ezetimibe) Overview Convenient, complementary, cost-effective, non-statin, once-daily, oral LDL-C lowering therapy FDC efficacy comparable to injectable PCSK9i (~50% LDL-C lowering) plus differentiated hscrp reduction Profile: Once-daily, oral combination pill ~50% LDL-C lowering 26% hscrp reduction No effects on HDL-C, TGs, blood pressure, or blood glucose Safe and well-tolerated IND accepted by FDA in June 2016 Bioavailability clinical study successfully completed Q with formulation (tablet) selected for development and commercialization Patent filings in process Clinical development and regulatory plans to be announced next week *Thompson PD et al. J Clin Lipidol: 2016;10: ; ezetimibe US patent(s) expire April 2017 Bempedoic Acid (top), FDC (bottom) 15 COPYRIGHT 2017 ESPERION. ALL RIGHTS RESERVED DO NOT COPY OR DISTRIBUTE

16 FDC Potential in LDL-C Lowering The Zetia/Vytorin Non-Statin, Oral Precedent Zetia/Vytorin franchise differentiated, oral, partially non-statin LDL-C lowering therapies (e.g., statin-sparing ) Over $50 billion in cumulative revenue FDC key positioning factors: ~50% LDL-C lowering; plus significant hscrp reduction NON-STATIN LDL-C lowering MOA Complementary MOAs; potential for lower occurrence of muscle-related side effects Patient convenience: once-daily, oral dosing Physician convenience: complementary to SOC oral therapies, two distinct efficacy profiles, and limited step-edits/prior-authorizations Payer convenience: limited formulary management effort due to costeffective pricing 16 COPYRIGHT 2017 ESPERION. ALL RIGHTS RESERVED DO NOT COPY OR DISTRIBUTE

17 FDC Potential in LDL-C Lowering The Zetia(ezetimibe) and Vytorin Precedent $6,000.0 Zetia and Vytorin Annual Sales Sales in s $5,000.0 $4,000.0 $3,000.0 $2,000.0 $1,000.0 $ Vytorin Zetia Source: SEC Filings, EvaluatePharma 17 COPYRIGHT 2017 ESPERION. ALL RIGHTS RESERVED DO NOT COPY OR DISTRIBUTE

18 LDL-C Lowering Therapeutic Landscape Evolution Convenient, Oral, Complementary, Cost-Effective Therapies Will Drive Usage and Market Growth patient-friendly, physician-friendly, payer-friendly Statins Ezetimibe Bempedoic Acid and FDC PCSK9i Standard of Care: Oral Statins +/- ezetimibe Second Line: Oral Patients with elevated LDL-C on optimized background lipidmodifying therapy, including maximally tolerated statin therapy Third Line: Injectable - HeFH, HoFH - LDL-C > 190 mg/dl - Continued failure to achieve goal Medicine Use and Shifting costs of healthcare in the United States - IMS Institute for Healthcare Informatics, April 2014 Current company expectation for therapeutic applicability, subject to FDA approval 18 COPYRIGHT 2017 ESPERION. ALL RIGHTS RESERVED DO NOT COPY OR DISTRIBUTE

19 FDC + Statin ( ) Phase 2 Study Top-Line Results Q patients with elevated LDL-C between mg/dl following wash-out Bempedoic acid 180 mg + Ezetimibe 10 mg + Atorvastatin 20 mg (n = 40) Placebo (n=20) 6-week screening and washout 6-Week Treatment Study Initiated Q1 2017; Fully enrolled Q Patients Without a History of CVD or Diabetes (low risk) Primary Objective: % LDL-C lowering of FDC + atorvastatin versus placebo Secondary Objectives: Non-HDL-C, TC, ApoB, hscrp, TG, and HDL-C % of patients achieving LDL-C <70 mg/dl LDL-C reduction >50% Safety and tolerability 19 COPYRIGHT 2017 ESPERION. ALL RIGHTS RESERVED DO NOT COPY OR DISTRIBUTE

20 Esperion Financial Outlook Funded Through Global Pivotal Phase 3 Results and Into 2019 Global Pivotal Phase 3 LDL-C lowering program estimated cost is ~$125M Study 1: Global pivotal Phase 3 long-term safety study in 2233 ASCVD and/or HeFH patients, and open-label extension Study 2: Global pivotal Phase 3 LDL-C lowering efficacy study in 750 ASCVD and/or HeFH patients Studies 3 & 4: Global pivotal Phase 3 LDL-C lowering efficacy studies in 525 patients considered statin intolerant FDC or doublet pill development plan/regulatory pathway to be announced in June 2017 (costs included in the above total) CMC and other development activities supportive of NDA/MAA submissions by 1H 2019 Global CVOT in ASCVD/high-risk primary prevention patients estimated cost is ~$250M Study will be well-underway and may cost up to $125M prior to global NDA/MAA submissions for LDL-C lowering indication 2017 net cash used in operating activities expected to be approximately $125M to $135M Current cash resources expected to be sufficient to fund operations into COPYRIGHT 2017 ESPERION. ALL RIGHTS RESERVED DO NOT COPY OR DISTRIBUTE

21 Key Upcoming Milestones June 2017 Announce FDC Development & Regulatory Strategy Q Phase 2 FDC + Statin Study Top-Line Results Q Phase 3 Long-term Safety Study (Study 1) Top-Line Results Mid-2018 Phase 3 LDL-C Efficacy Studies (Studies 2 4) Top-Line Results Q Initiate Phase 2 PCSK9i Study 2H 2017 Complete Enrollment in Phase 3 LDL-C Efficacy Studies (Studies 2 4) 2H 2017 Publication of ACLi Mendelian Randomization Results 1H 2019 LDL-C Lowering Indication NDA/MAA Submissions 2022 Cardiovascular Disease Risk Reduction Indication NDA/MAA Submissions 21 COPYRIGHT 2017 ESPERION. ALL RIGHTS RESERVED DO NOT COPY OR DISTRIBUTE

22 Esperion Investment Thesis Significant Market Opportunity Confirmed Regulatory Pathway to Approval Well Funded with Lean, Efficient Operating Model Targeting patients at high CV risk who require additional LDL-C lowering, who prefer a convenient, complementary, oral therapies, and need cost-effective solutions; including those patients considered statin intolerant Total potential addressable market exceeds $20B Clear regulatory pathway to approval for an LDL-C lowering indication by 1H 2020 Global pivotal Phase 3 program supports LDL-C lowering indication submissions in U.S., Europe and most of ROW Cash resources to fund operations through: Completion of Phase 3 clinical development program; and NDA/MAA global regulatory submissions for an LDL-C lowering indication by 1H COPYRIGHT 2017 ESPERION. ALL RIGHTS RESERVED DO NOT COPY OR DISTRIBUTE

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