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Esperion is focused on developing LDL-C lowering therapies to address the unmet needs of patients with
atherosclerotic cardiovascular disease (ASCVD), or who are at a high risk for ASCVD, with
hypercholesterolemia who continue to have elevated levels of LDL-C despite the use of maximally-tolerated
statins and ezetimibe
Source: AHA Heart Disease, Stroke and Research Statistics At-A-Glance 2016
84% (8M) of these patients will get Patients achieving goals on either BA or BA+EZ
Additional LDL-C Lowering*
Statins and ezetimibe are the standard of care for the treatment of patients with hypercholesterolemia
Approximately 90% of patients on LDL-C lowering therapy are taking a low- (12%), moderate- (63%) or high-intensity (25%) statin*
12 – 13 million patients in the U.S. can’t/don’t achieve their LDL-C lowering goal with statins and/or ezetimibe alone.
Approximately four out of five patients require less than 50% additional LDL-C lowering to reach their treatment goal. Most
patients can’t/won’t access expensive, inconvenient, injectable PCSK9i therapies.
The goal of our Phase 3 Program is to evaluate the efficacy and long-term safety and tolerability of bempedoic acid
added-on to maximally tolerated LDL-C lowering therapies in high-risk patients with hypercholesterolemia
(LDL-C > 100 mg/dL) in two patient populations:
1 2
High-risk patients on maximally tolerated doses of
statins who require additional LDL-C lowering High-risk patients who are considered statin intolerant
Targeted
Payers drawn to cost-effective, convenient, once-daily, oral Mechanism of Action
LDL-C lowering therapies
Complementary and Convenient Once-
daily, Oral Treatment Option
March August
Study 4 1002FDC-053
(1002-048) BA / EZ Combo Pill
BA Ph 3 TLRs Ph 3 TLRs
Q1 2019
Q1 2018
2018 LDL-C Lowering
Indication NDA
Announce Submissions 1H 2020
March 2018
Phase 2
Combination +
Statin Future
May September Q2 2019
LDL-C Lowering
Anticipated
2022
CLEAR
BA PCSK9 Development Study 1 Study 2 LDL-C Lowering
Indication MAA
Commercial Outcomes
Add-on TLRs Plans Launch CVOT TLRs
(1002-040) (1002-047) Submissions
BA Ph 3 TLRs BA Ph 3 TLRs
ASCVD
and/or
HeFH OLE N=1,462| (Fully Enrolled) 1.5 yrs safety
Statin Add-On
12 weeks LDL-C /
Study 2; High Risk, N=779| (Fully Enrolled) TLRs Expected in September
52 weeks safety
Study 3; SI, N=345| TLRs Announced May 23 12 weeks LDL-C / 24 weeks safety
ASCVD and/or HeFH/10;
Low, Very Low or No Statin
Background Therapy* Study 4; SI, +EZ, N=269
TLRs Announced March 7
12 weeks LDL-C / 12 weeks safety
*Studies are being conducted to obtain an indication for use in patients on no background statin therapy in Europe
• Primary Objective:
• 12-week LDL-C lowering
• Secondary Objectives:
• 24-week LDL-C lowering
• 12-week hsCRP, non-HDL-C, total cholesterol and apoB
• Safety and tolerability
*Patients with no evidence of ASCVD must as a minimum have a history of requiring lipid-modifying therapy based on local guidelines (AHA/ACC or Canadian
Cardiovascular Society). ASCVD includes CAD, symptomatic PAD, and/or cerebrovascular atherosclerotic disease based on 2013 ACC/AHA and/or HeFH
Mean ± SD
Total Across
Bempedoic Acid Placebo Study
N=234 N=111 N=345
Primary Efficacy Endpoint
LDL-C: mg/dL 158 ± 40.4 156 ± 38.8 158 ± 39.9
Secondary Efficacy Endpoints
non-HDL-C: mg/dL 193 ± 45.1 191 ± 43.8 193 ± 44.6
Total Cholesterol: mg/dL 246 ± 47.3 241 ± 44.3 244 ± 46.3
apoB: mg/dL 141 ± 31.6 142 ± 30.4 141 ± 31.2
2.9 2.8 2.9
hsCRP: mg/L*
(1.34, 5.29) (1.21, 5.15) (1.29, 5.15)
Other Endpoints
HDL-C: mg/dL 52 ± 14.5 50 ± 14.4 51.6 ± 14.5
156.5 164.0 159.5
Triglycerides: mg/dL*
(114.5, 219) (120.0, 225.5) (117.0, 222.5)
N=101 N=204
-2% -24% 0
placebo- -1% -22%
-10 corrected
-23% placebo-
p<0.001 -10 corrected
-26%
p<0.001
-20 -20
Placebo
Placebo
Bempedoic Acid
-30 Bempedoic Acid -30
*On treatment population includes patients who were on treatment at the visit analyzed.
hsCRP
N=106 N=231
10
Median % Change from Baseline
3%
0
Placebo
-10 -25%
p<0.001
-30
% (Number) of Patients
Treatment Emergent Bempedoic acid Placebo
Adverse Events (AEs) N=234 N=111
Overview of AEs in All Patients (patient incidence)
Any AE(s) 64.1% (150) 56.8% (63)
Serious AE(s)* 6.0% (14) 3.6% (4)
Discontinuation due to AE(s) 18.4% (43) 11.7% (13)
Fatal Adverse Events – Unrelated to Study Treatment 0 0
Safety Population
*No SAE reported as related to study medication
% (Number) of Patients
Bempedoic acid Placebo
Potential Muscle AESI
N=234 N=111
Overview of Potential Muscle AESIs in All Patients (patient incidence)
Any Potential Muscle AESI(s)* 12.8% (30) 16.2% (18)
Discontinuation of Study Drug due to Potential Muscle
7.7% (18) 6.3% (7)
AESI(s)*
All Potential Muscle AESIs by MedDRA Preferred Term*
Myalgia 4.7% (11) 7.2% (8)
Muscular weakness 0.4% (1) 1.8% (2)
Muscle Spasms 4.3% (10) 4.5% (5)
Pain in extremity 5.6% (13) 3.6% (4)
*Includes all “muscular disorders” defined in the SAP as: muscle spasms, myalgia, muscular weakness, myoglobin blood increased, myoglobin blood present, myoglobin urine present, myoglobinaemia,
myoglobinuria, myopathy, myopathy toxic, necrotizing myositis, pain in extremity, rhabdomyolysis
In this Phase 3 study, bempedoic acid and provided clinically relevant and statistically significant
LDL-C lowering and reductions in hsCRP in high-risk statin intolerant patients, and was observed to
be safe and well-tolerated.
Bempedoic acid could be an important, new, convenient, once-daily, oral treatment option that
complements the LDL-C lowering efficacy of available LDL-C lowering therapies, including statins,
ezetimibe and PCSK9i.
In the coming months, results from our remaining pivotal Phase 3 studies are expected to further
validate the efficacy, safety and tolerability profile of bempedoic acid and the bempedoic acid /
ezetimibe combination pill as convenient, once-daily, oral therapies that are complementary to
existing standard of care LDL-C lowering therapies.
Mean ± SD
Study 4 Study 1 Study 3
N=269 N=2230 N=345
Primary Efficacy Endpoint
LDL-C: mg/dL 127.6 ± 29.8 103 ± 29.4 158 ± 39.9
Secondary Efficacy Endpoints
non-HDL-C: mg/dL 159 ± 34.9 130 ± 33.7 193 ± 44.6
Total Cholesterol: mg/dL 215 ± 36.0 179 ± 35.3 244 ± 46.3
apoB: mg/dL 121 ± 25.7 88 ± 21.6 141 ± 31.2
hsCRP: mg/L* 3.6 1.5 2.9
Other Endpoints
HDL-C: mg/dL 56 ± 18.1 49 ± 11.7 51.6 ± 14.5
Triglycerides: mg/dL* 159.2 125.0 159.5
*Median Values
• Among all of the phase 2 and 3 trials, the reductions in hsCRP have ranged from 22-40% across
all patient populations
*Reported topline results
23 COPYRIGHT © 2018 ESPERION. ALL RIGHTS RESERVED - CONFIDENTIAL - DO NOT COPY OR DISTRIBUTE
Phase 2/Phase 3 Program - Cumulative Safety & Tolerability (Completed Studies)
Overview of Adverse Events and Discontinuations
% (Number) of Patients
Atorva Placebo Rosuva Placebo Simva Placebo Eze Placebo Vytorin Placebo
10mg 0.2% - 1.1% 0.5% - - 0.5% 0.3% 1.7% -
20mg 0.2% - 1.1% 0.5% - - N/A N/A 1.7% -
40mg 0.6% - 1.1% 0.5% 0.9% - N/A N/A 1.7% -
80mg 2.3% - N/A N/A 2.1% - N/A N/A 2.6% -
4Data collected from FDA approved package inserts for each drug. Note that all reported Liver Function Test increases occurred within 12 weeks of initiating therapy.
% (Number) of Patients
27 COPYRIGHT © 2018 ESPERION. ALL RIGHTS RESERVED - CONFIDENTIAL - DO NOT COPY OR DISTRIBUTE
CLEAR Outcomes Powering Assumptions: Insights from Study 3
• Study 3 enrolled a very similar patient population to CLEAR Outcomes: statin intolerant, taking no or
very low doses of statins, ASCVD or at high risk for ASCVD, higher baseline LDL-C than other studies.
• In a CVOT with a baseline LDL-C of ~135 mg/dL, the LDL-C lowering in Study 3 in statin intolerant
patients would be expected to produce an absolute LDL-C reduction of ~35 mg/dL.
• Based on the Cholesterol Treatment Trialists’ meta-analysis of major statin CVOTs, this reduction in LDL-C
would be expected to translate to a ~20% reduction in major CV events.
• The CTT also referenced length of treatment as a factor in the magnitude of CV risk reduction;
therefore the expected ~4 year follow up in CLEAR Outcomes (similar to statin CVOTs; longer than
PCSK9 CVOTs) helps support the expected relative risk reduction.
• Based on the expected unit reduction in LDL-C in CLEAR Outcome based on our findings in Study 3, we
are confident that bempedoic acid will show a statistically significant and clinically relevant reduction
in CV risk.
Across the Phase 2 and Phase 3 programs, bempedoic acid provided clinically relevant and
statistically significant LDL-C lowering and reductions in hsCRP in high-risk patients, including those
on background statin therapy and those unable to tolerate statins and considered statin intolerant,
and was observed to be safe and well-tolerated.
Bempedoic acid can be an important, new, convenient, once-daily, oral treatment option that
complements the LDL-C lowering efficacy of available LDL-C lowering therapies, including statins,
ezetimibe and PCSK9i.
In the coming months, results from our two remaining pivotal Phase 3 studies are expected to
further validate the efficacy, safety and tolerability profile of bempedoic acid and the bempedoic acid
/ ezetimibe combination pill as convenient, once-daily, oral therapies that are complementary to
existing standard of care LDL-C lowering therapies.
Q&A