Bempedoic Acid CLEAR Serenity Study Results Published in the JAHA Demonstrated Significant LDL-Cholesterol Lowering and Reduced hsCRP in Statin Intolerant Patients

- Bempedoic acid is an oral, once-daily ATP citrate lyase (ACL)
inhibitor that reduces cholesterol and fatty acid synthesis in the
liver
- Bempedoic acid significantly reduced LDL-Cholesterol (LDL-C) vs
placebo at week 12 (primary endpoint, absolute reduction -36mg/dL,
-21,4%)
- Over 24-weeks, bempedoic acid was observed to be well-tolerated,
and the muscle-related adverse event rate did not differ from
placebo
- Treated patients showed lower rates of new-onset or worsening of
diabetes compared with those on placebo

Munich and Ann Arbor, Michigan (ots/PRNewswire) - Daiichi Sankyo
Europe GMbH (hereafter, 'Daiichi Sankyo') and Esperion Therapeutics
(NASDAQ: ESPR) announced today that results from the 345 patient,
24-week, Phase 3 double-blind, placebo-controlled study of bempedoic
acid (CLEAR Serenity, also known as Study 3) were published in the
Journal of the American Heart Association (JAHA). Bempedoic acid is
being developed as a complementary, convenient, once-daily, oral
therapy for the treatment of patients with elevated low-density
lipoprotein cholesterol (LDL-C). Bempedoic acid and the bempedoic
acid / ezetimibe combination tablet new drug applications are under
regulatory review for marketing authorisation by the European
Medicines Agency (EMA) and have been submitted to the United States
Food and Drug Administration (FDA).

The JAHA publication highlights that bempedoic acid met the
primary efficacy endpoint and significantly lowered LDL-C by 21%
(absolute reduction -36mg/dL) at 12-weeks.1

The publication also shows key secondary efficacy endpoints at 12
and 24 weeks and safety and tolerability outcomes, demonstrating that
bempedoic acid:1

- significantly reduced hsCRP, an important marker of the underlying
inflammation associated with cardiovascular disease, by 24%;
- showed numerically fewer muscle-related adverse events compared
with placebo (BA 12.8% vs placebo 16.2%);
- was observed to be well-tolerated;
- showed numerically fewer new-onset or worsening of diabetes
compared with the placebo group (BA 2.1% vs 4.5% placebo).

"In the challenging group of patients with statin intolerance,
CLEAR Serenity demonstrates that bempedoic acid reduced LDL-C
significantly more than placebo. Patients taking bempedoic acid
reported less frequent occurrences of myalgia and muscular weakness
compared with placebo. These results demonstrate bempedoic acid could
offer a well-tolerated and effective oral therapeutic option
especially for the millions of patients needing LDL-C lowering but
have difficulty tolerating statin treatment due to muscle-related
side effects," said Ulrich Laufs, MD, PhD.

"For patients who have experienced the side effects commonly
attributed to statin treatment and can't or won't take statins, there
is an urgent need to significantly lower their LDL-C and hsCRP
levels. The publication of the CLEAR Serenity Study in the Journal of
American Heart Association further demonstrates that bempedoic acid
could be a well-tolerated and efficacious treatment option for
hypercholesterolemia patients, including those patients considered
statin intolerant," said Wolfgang Zierhut, MD, Head of Antithrombotic
and Cardiovascular Medical Affairs Department at Daiichi Sankyo
Europe.

Design of Global Phase 3 Study 3 (1002-046, also known CLEAR
Serenity)

The 24-week, global pivotal Phase 3 randomised, double-blind,
placebo-controlled, multicenter study evaluated the LDL-C lowering
efficacy and safety of bempedoic acid 180 mg/day versus placebo added
to background lipid-modifying therapy in patients with
hypercholesterolemia who are considered statin intolerant. The study
was conducted at 67 sites in the U.S. and Canada. A total of 345
patients were randomised 2:1 to receive bempedoic acid or placebo.
The primary efficacy objective was to assess the 12-week LDL-C
lowering efficacy of bempedoic acid versus placebo. Secondary
objectives included evaluating the 24-week LDL-C lowering efficacy of
bempedoic acid versus placebo and its effects on other risk markers
after 12 weeks of treatment, including hsCRP. Safety and tolerability
were evaluated through continuous monitoring of patients.

Bempedoic Acid / Ezetimibe Fixed Dose Combination Tablet

Through the complementary mechanisms of action of inhibition of
cholesterol synthesis (bempedoic acid) and inhibition of cholesterol
absorption (ezetimibe), the bempedoic acid / ezetimibe fixed dose
combination tablet is a non-statin, orally available, once-daily,
LDL-C lowering therapy. Inhibition of ATP Citrate Lyase (ACL) by
bempedoic acid reduces cholesterol biosynthesis and lowers LDL-C by
up-regulating the LDL receptor. Inhibition of Niemann-Pick C1-Like 1
(NPC1L1) by ezetimibe results in reduced absorption of cholesterol
from the gastrointestinal tract, thereby reducing delivery of
cholesterol to the liver, which in turn upregulates the LDL
receptors. Phase 3 data demonstrated that this well tolerated
combination results in a 35% lowering of LDL-C when used with
maximally tolerated statins, a 43% lowering of LDL-C when used as a
monotherapy, and a 34% reduction in high sensitivity C-reactive
protein (hsCRP). Rates of treatment-emergent adverse events,
muscle-related adverse events and discontinuations were similar in
the bempedoic acid and placebo treatment groups.2

Bempedoic Acid

With a targeted mechanism of action, bempedoic acid is a
first-in-class, complementary, oral, once-daily ATP Citrate Lyase
(ACL) inhibitor that reduces cholesterol and fatty acid biosynthesis
and lowers LDL-C by up-regulating the LDL receptor. Similar to
statins, bempedoic acid also reduces high sensitivity C-reactive
protein (hs-CRP), a key marker of inflammation associated with
cardiovascular disease.3 Bempedoic acid is a prodrug that requires
activation by the very long-chain acyl-CoA synthetase-1 (ACSVL1).
Furthermore, it was demonstrated that the absence of ACSVL1 in
skeletal muscle provides a mechanistic basis for bempedoic acid to
potentially avoid the myotoxicity associated with statin therapy.4
Completed Phase 2 and Phase 3 studies conducted in almost 4,800
patients, and approximately 3,100 patients treated with bempedoic
acid, have produced an additional 20% LDL-C lowering when used with
maximally tolerated statins, up to 30% LDL-C lowering as monotherapy,
35% LDL-C lowering in combination with ezetimibe when used with
maximally tolerated statins and up to 48% LDL-C lowering in
combination with ezetimibe as monotherapy.5 Rates of
treatment-emergent adverse events, muscle-related adverse events and
discontinuations were similar in the bempedoic acid and placebo
treatment groups.3

The effect of bempedoic acid on cardiovascular morbidity and
mortality has not yet been determined. The company initiated a global
cardiovascular outcomes trial (CVOT) to assess the effects of
bempedoic acid on the occurrence of major cardiovascular events in
patients with, or at high risk for, cardiovascular disease (CVD) who
are only able to tolerate less than the lowest approved daily
starting dose of a statin and considered "statin intolerant." The
CVOT - known as CLEAR Outcomes - is an event-driven, randomised,
double-blind, placebo-controlled study expected to enroll
approximately 12,600 patients with hypercholesterolemia and high CVD
risk at over 1,000 sites in approximately 30 countries.6

About Daiichi Sankyo

Daiichi Sankyo Group is dedicated to the creation and supply of
innovative pharmaceutical products to address diversified, unmet
medical needs of patients in both mature and emerging markets. With
over 100 years of scientific expertise and a presence in more than 20
countries, Daiichi Sankyo and its 15,000 employees around the world
draw upon a rich legacy of innovation and a robust pipeline of
promising new medicines to help people. In addition to a strong
portfolio of medicines for hypertension and thrombotic disorders,
under the Group's 2025 Vision to become a "Global Pharma Innovator
with Competitive Advantage in Oncology", Daiichi Sankyo research and
development is primarily focused on bringing forth novel therapies in
oncology, including immuno-oncology, with additional focus on new
horizon areas, such as pain management, neurodegenerative diseases,
heart and kidney diseases, and other rare diseases. For more
information, please visit: www.daiichisankyo.com.

Esperion's Commitment to Patients with Hypercholesterolemia

High levels of LDL-C can lead to a build-up of fat and cholesterol
in and on artery walls (known as atherosclerosis), potentially
leading to cardiovascular events, including heart attack or stroke.
In the U.S., 96 million people, or more than 37% of the adult
population have elevated LDL-C. There are approximately 18 million
people in the U.S. with atherosclerotic cardiovascular disease
(ASCVD) who live with elevated levels of LDL-C despite taking
maximally tolerated lipid-modifying therapy - including individuals
considered statin intolerant - leaving them at high risk for
cardiovascular events. More than 50% of ASCVD patients who are not
able to reach their LDL-C goals with statins alone, need less than a
40% reduction to reach their LDL-C threshold.

Esperion's mission as the Lipid Management Company is to deliver
once-daily, oral therapies that complement existing oral drugs to
provide the additional LDL-C lowering that these patients need.

The Lipid Management Company

Esperion is the Lipid Management Company passionately committed to
developing and commercialising complementary, cost-effective,
convenient, once-daily, oral therapies for the treatment of patients
with elevated LDL-C. Through scientific and clinical excellence, and
a deep understanding of cholesterol biology, the experienced Lipid
Management Team at Esperion is committed to developing new LDL-C
lowering therapies that will make a substantial impact on reducing
global cardiovascular disease; the leading cause of death around the
world. Bempedoic acid and the company's lead product candidate, the
bempedoic acid / ezetimibe combination tablet, are targeted therapies
that have been shown to significantly lower elevated LDL-C levels in
patients with hypercholesterolemia, including patients inadequately
treated with current lipid-modifying therapies. For more information,
please visit www.esperion.com and follow us on Twitter at
https://twitter.com/EsperionInc.

Forward Looking Statement: Esperion

This press release contains forward-looking statements that are
made pursuant to the safe harbor provisions of the federal securities
laws, including statements regarding the regulatory approval pathway
for the bempedoic acid / ezetimibe combination tablet and bempedoic
acid and the therapeutic potential of, clinical development plan for,
the bempedoic acid / ezetimibe combination tablet and bempedoic acid,
including Esperion's timing, designs, plans and announcement of
results regarding its CLEAR Outcomes study and other ongoing clinical
studies for bempedoic acid and the bempedoic acid / ezetimibe
combination tablet, Esperion's expectations for the market for
therapies to lower LDL-C, including the market adoption of bempedoic
acid and the bempedoic acid / ezetimibe combination tablet, if
approved, the expected upcoming milestones described in this press
release, and Esperion's cash position and financial outlook. Any
express or implied statements contained in this press release that
are not statements of historical fact may be deemed to be
forward-looking statements. Forward-looking statements involve risks
and uncertainties that could cause Esperion's actual results to
differ significantly from those projected, including, without
limitation, delays or failures in Esperion's studies, that positive
results from a clinical study of bempedoic acid may not be sufficient
for FDA or EMA approval or necessarily be predictive of the results
of future or ongoing clinical studies, that notwithstanding the
completion of Esperion's Phase 3 clinical development programme for
LDL-C lowering, the FDA or EMA may require additional development in
connection with seeking regulatory approval, that DSE is able to
successfully commercialise the bempedoic acid / ezetimibe combination
tablet and bempedoic acid, if approved, that existing cash resources
may be used more quickly than anticipated, and the risks detailed in
Esperion's filings with the Securities and Exchange Commission.
Esperion disclaims any obligation or undertaking to update or revise
any forward-looking statements contained in this press release, other
than to the extent required by law.

References

1 Laufs U, et al. Efficacy and Safety of Bempedoic Acid in
Patients With Hypercholesterolemia and Statin Intolerance. JAHA 2019.

2 Top-Line Results from the Bempedoic Acid / Ezetimibe Combination
Pill Phase 3 Study. Esperion Investor. JAHA 2019 Presentation. Aug
27, 2018. Available at https://investor.esperion.com/static-files/163
9de53-9494-4299-98a5-0b6f1317678a. Last accessed March 8, 2019.

3 Phase 3 Top-Line Results from Study 2 & Cumulative Phase 3
Program Results. Esperion Investor Presentation. Oct 29, 2018.
Available at https://investor.esperion.com/static-files/32936da0-96f9
-40e5-a12b-bd00ece6698d. Last accessed March 8, 2019.

4 Pinkosky L et al. Liver-specific ATP-citrate lyase inhibition by
bempedoic acid decreases LDL-C and attenuates atherosclerosis.
Nature. 2016: 10.1038.

5 Thompson PD, et al. Treatment with ETC-1002 alone and in
combination with ezetimibe lowers LDL cholesterol in
hypercholesterolemic patients with or without statin intolerance. J
Clin Lipidol (2016) 10, 556-567.

6 Evaluation of Major Cardiovascular Events in Patients With, or
at High Risk for, Cardiovascular Disease Who Are Statin Intolerant
Treated with Bempedoic Acid (ETC-1002) or Placebo (CLEAR Outcomes).
Available at https://clinicaltrials.gov/ct2/show/NCT02993406?term=bem
pedoic+acid&rank=4. Last accessed December 12, 2018.

Contact
Lydia Worms (Europe)
Daiichi Sankyo Europe GmbH
Communications & Product PR Europe
+49 (89) 7808751

Investor Contact
Alex Schwartz
Esperion
+1-734-249-3386
aschwartz@esperion.com

April 2019 BEM/19/0001

ots Originaltext: Daiichi Sankyo
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