Esperion Therapeutics: A Biotech Success Story in - Purdue University

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Dec 6, 2012 (4 years and 10 months ago)

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Discovery Lecture Series

Purdue University Discovery Park

Thursday, November 8, 2007



“Esperion Therapeutics: A Biotech Success Story in the Midwest”


Roger S. Newton, Ph.D., FAHA

Former Senior VP and Director,

Pfizer Global R & D


2

Time Frame of 1998
-
Key Questions

What issues existed within the cardiovascular
therapeutic space within the pharmaceutical
industry which promoted change?


What critical business factors provided a template
for the establishment of Esperion?


What financial conditions fostered the rapid growth
and development of Esperion and its product
candidates?



3

Key Factors Affecting Innovation in CV Franchises


Increased merger and acquisition activity/ reorganizations
lead to consolidation


Outcomes:


a. Reduced number of CV R & D groups


b. Company/departmental integration leads to chaos and a
lack of focus


c. Loss of continuity and institutional memory


d. Monolith organizations lacking innovation with a
“Blockbuster” mentality


e. New innovative opportunities are created outside of Big
Pharma as small, high risk, but focused biotech companies

4

Key Factors Affecting Innovation in CV Franchises




Every cloud has a silver lining…

5

Esper
ion
-

From Big Pharma to Biotech


Big pharma mergers and reorganizations (people
and process) can leave researchers with an
inability to pursue their science.



Decision Point:


Stay in stable, low risk, comfortable but
compromised setting



Start anew with a high risk, uncertain future



Co
-
founders combined a common vision, a
willingness to embrace risk, access to appropriate
levels of financial support, and a proven record of
success.


.

Our Story

6

Esper
ion

Therapeutics

Our Name

Esp

refers to
esprit de corps
:


the common spirit existing in the members

of a group, inspiring enthusiasm, devotion,

comradeship


Esper

refers to “
esperance



hope


-
ion

a suffix meaning activity, process, resulting

from

Our Mission

Esperion Therapeutics is dedicated to
discovering new therapies through vibrant
teamwork in the hope of treating patients
with cardiovascular diseases



7

Esper
ion

Therapeutics

Our Values

Individual Dignity

Vibrant Teamwork

Excellence in Science

Our Purpose

To Explore

To Create

To Build

Our Vision

To treat cardiovascular disorders by
discovering new therapies using an
approach which integrates traditional and
cutting edge theories and technologies

8

9

Heart Disease and HDL




Heart Disease is # 1 Killer
-

65M Americans have it




20% of all individuals with lipid disorders have low


levels of HDL
-
cholesterol




50% of all CHD patients have low HDL
-

cholesterol




No drugs indicated only for low HDL
-
cholesterol





10

The Function of HDL and the Esper
ion

Solution

11

The Esper
ion

Solution

HDL Therapy for promoting Reverse Lipid Transport (RLT)

The Four
-
Step RLT Pathway

4


Elimination

Waste

3


Transport

Liver

2


Conversion

HDL

HDL

Cholesterol
-
loaded
Artery

1


Removal

12

13


HDL Therapy

The Acute Coronary Syndrome (ACS) Patient


Usual care: aspirin, clopidogrel,
heparin, nitrates, IIb/IIIa
inhibitors,

beta
-
blockers, fibrinolytic
therapy, statins, ACE inhibitors,
revascularization


Short
-
term risk for recurrent
events: 6.2%
-

25%


Can HDL Therapy target unstable
plaques?

14

Science

Business

Series

A & B

$16
million

2000

1998

Esper
ion

History

Patent
Small
Molecules

Phase 1
Clinical
Trials

SIDF

$6 million

Series

C & D

$27 million

IPO

$62 million

In
-
license HDL Product
Candidates


1999

PIPE

$24 million

2001

Phase 2
Clinical
Trials

2002

2003

Company

Downsizing

Secondary
Financing

$67 million

Phase
1/2
Clinical
Trials

Proof of
concept

Clinical
Trials

15

HDL Therapies from Esper
ion

ETC
-
642


RLT Peptide

ETC
-
216

AIM

ETC
-
588

LUV

ETC
-
1001

ETC
-
1002

Next

generation

Sub
-
acute

Chronic

Biopharmaceuticals

(Infused)

Small Molecules

(Oral)

16

Limone sul Garda

•Rare R173C mutation in apoA
-
I


•Circulates as dimers and monomers


•HDL/apoA
-
I deficiency


•Mild hypertriglyceridemia


•Paradoxical resistance to heart


disease

“Gain of Function”

Mutation

Characteristics of human

ApoA
-
I
Milano
Carriers

Discovered in 1979

17

Trial Design and Objectives


We sought to test the potential of recombinant

ApoA
-
I Milano to regress human coronary artery disease.


We employed intravascular ultrasound to assess effect of
short term infusions of an ApoA
-
I Milano/ phospholipid
complex (ETC
-
216, Esperion Therapeutics).


Primary hypothesis:


Five weekly infusions of ETC
-
216 would produce
significant regression of coronary atherosclerosis as
measured by intravascular ultrasound (IVUS)

Nissen et al. JAMA 2003;290:2292
-
2300

18

Side

Branch

Side

Branch

EEM area

14.37 mm
2

EEM area

11.58 mm
2

Lumen area

6.23 mm
2

Lumen area

6.27 mm
2

Atheroma

area
-

8.10 mm
2

Atheroma

area
-

5.35 mm
2

Nissen et al. JAMA 2003;290:2292
-
2300

19

Conclusions


Five weekly infusions of an ApoA
-
I Milano/
phospholipid complex produced significant
regression of coronary atheroma burden by
IVUS.


There was no detectable difference in efficacy
for two different doses of ETC
-
216 (15 mg/kg and
45 mg/kg).


Adverse events were similar to placebo.


Coronary disease is more dynamic than
previously realized and can be rapidly affected
by agents that augment reverse cholesterol
transport.

20


Rapidly eliminates cholesterol and other lipids

from the

arterial walls and related tissues


Disease modifying therapy

to treat unstable plaques


May prevent

future ischemic events, such as heart
attacks and strokes


Can be used

synergistically

with established
cardiovascular medications, including statins


Acute or sub
-
acute

treatment

Key Advantages of HDL Therapy

21


Pfizer Acquisition of Esper
ion



Cash tender offer to acquire shares
of common stock at $35 per share
(55% premium)


Announced December 21, 2003


Deal closed on Feb. 10, 2004


Operated in Ann Arbor, Michigan as
Esperion Therapeutics, A Pfizer Inc.
Company


Esperion closed its doors in May
2007



$1.3B



Pfizer
Offer

22


Do the best science you can do and be fiscally
conservative


Don’t eliminate your options, develop competing
alternatives, and constantly (re)assess your prospects


Surround yourself with people who complement your
strengths and counteract your weaknesses


Never burn your bridges no matter how chaotic the
situation


Your colleagues are your teammates, not your
adversaries


Never underestimate the resilience of you and your
team
-

be optimistic that new opportunities abound





Lessons Learned Along the Journey

23



Never lose your passion!!!



Live your mission



Keep your values alive



Focus on your purpose



Avoid unnecessary reorganization



Maintain and grow your vision



Make a difference



Communicate…Communicate…Communicate

Lessons Learned on the Entrepreneurial Road

Maximize investor return in a people
-
first, science
-
driven organization

24


Conclusion




The triumph of innovation

lies with the
focused franchise players

who have
numerous “
shots on goal
” in a specific
therapeutic category, in which they can be
the
best in the world
.

25


Special Recognition to Esperion Colleagues/Advisors


Co
-
Founders
: Charlie Bisgaier, Mike Pape and Tom Rea


Senior Leaders
: Tim Mayleben (CFO, COO), Frank Thomas
(Finance), Dawn Evans (Administration), Brian Krause
(Discovery), Jean
-
Louis Dasseaux (Chemistry), Marianne
Andreach (Medical Affairs), Bill Brinkerhoff (Business
Development), Narendra Lalwani (Toxicology) and others


Business/Bank Advisors
: David Scheer, Bob Quinn,
Robertson
-
Stephens, Lehman Brothers


Venture/Loan Capital
: Oak, TL, HealthCap, Alta, Canaan,
Domain, Investor, Swedish Industrial Development Fund


Board Members
: David Scheer, Annie Lamont, Ginger
More, Seth Rudnick, Anders Wiklund, Susan Bayh, Tony
Gotto, Henry Blair, Ronnie Cresswell

26

Acknowledgements

Institute of Pharmacological
Sciences, Milan, Italy

Giulia Chiesa

Elena Monteggia

Marta Marchesi

Guido Franceschini

Cesare R. Sirtori


Columbus Clinic, Milan,Italy


Evangelia Karvouni

Carlo Di Mario


Bracco S.p.A.,Milan, Italy

Paolo Lorenzon

Massimo Laucello

Vito Lorusso

Cleveland Clinic

Steve Nissen and the ETC
-
216

Investigators

Cedars Sinai Medical Center,CA

P.K.Shah and his Collaborators

University of British Columbia,
Canada

Inex Corporation, British
Columbia, Canada

Talaria, Boston, MA

Esperion Therapeutics, Inc.

Ann Arbor, MI, Kalamazoo, MI

and Stockholm, Sweden