LeAnne Bloedon (Aegerion) Rare Disease Day 2016 Conference

Proprietary & Confidential. © 2015 Aegerion Pharmaceuticals, Inc. All Rights Reserved.
LeAnne Bloedon, MS, RD
Senior Director, Clinical Science
Aegerion Pharmaceuticals, Inc.
CORD’s Rare Disease Day Conference
March 10, 2016
Development of Juxtapid®
for Homozygous FH: a
story of perseverance &
collaboration

Proprietary & Confidential. © 2015 Aegerion Pharmaceuticals, Inc. All Rights Reserved. 2
Aegerion’s Vision
DEVELOPING AND
COMMERCIALIZING
CLINICALLY IMPACTFUL
THERAPIES FOR PATIENTS
WITH RARE, DEBILITATING
DISEASES WITH UNMET
MEDICAL NEED

z
History of Juxtapid & Aegerion Pharmaceuticals
3
1990s 2002 2004 2006 2007 2010
BMS donates certain
rights to lomitapide
to the University of
Pennsylvania (Penn)
Aegerion obtains certain
license for exclusive
worldwide rights to
Juxtapid from Penn
2012
Completes
enrollment of
pivotal Phase III
clinical trial for
adult patients with
HoFH
Submits marketing applications
for lomitapide in US and EU for HoFH
Based on 56 weeks data
2013
FDA approves
JUXTAPID for
the treatment of
HoFH
FDA grants Juxtapid
orphan drug designation
for the treatment of HoFH
Penn completes
Proof of Concept trial
for patients with HoFH
EMA approves
LOJUXTA for the
treatment of
HoFH
2014
Health Canada
approves
JUXTAPID for
the treatment of
HoFH
BMS conducts early clinical
trials of Juxtaapid
as a broad, monotherapy
treatment before
discontinuing
Penn obtains funding
from FDA’s ODP for P3
study
First patient enrolled in P3
2008 2015
Aegerion
Acquires
Myalept™ from
AstraZeneca
Juxtapid
reduces LDL-C
significantly in
Watanabe rabbit
(HoFH model)

Homozygous Familial Hypercholesterolemia:
Disease Overview
●  HoFH is a serious, rare genetic form of hypercholesterolemia that is
inherited from both parents
●  Patients with HoFH inherit a genetic mutation from each parent in the low
density lipoprotein receptor (LDL-R) or other genes known to affect LDL-R
function
●  A loss of LDL-R function results in extreme elevation of LDL (“bad”)
cholesterol levels. HoFH patients often develop premature and
progressive atherosclerosis, a narrowing or blocking of the arteries.
●  Conventional lipid lowering medications (e.g. statins, ezetimibe) primarily
exert their effect by upregulating LDL-Rs and therefore have limited
response in patients with HoFH
●  Apheresis is the standard recommended therapy for patients with HoFH,
which is a mechanical procedure that temporary reduces LDL-C.

Proprietary. © 2015 Aegerion Pharmaceuticals, Inc. All Rights Reserved.
HoFH Prevalence
•  Historically, the prevalence of HoFH was reported as 1 in 1,000,0001
•  Recent data indicate that HoFH, while still rare, may be more
common2
•  Based on a 2013 estimate of FH prevalence of 1 in 200, reported in
the European Heart Journal, the calculated prevalence of HoFH would
be between 3.33-6.25 per 1,000,0002-4
•  Founder effects make the prevalence of HoFH more common in
certain populations that have descended from relatively small founding
populations5-7
–  1 in 270,000 in the French-Canadian population
1.  Goldstein JL, et al. J Clin Invest. 1973;52(7):1544-1568.
2.  Nordestgaard BG, et al. Eur Heart J. 2013;34(45):3478a-3490a.
3.  Benn M, et al. J Clin Endocrinol Metab. 2012;97(11):3956-3964.
4.  Goldberg AC, et al. J Clin Lipidol. 2011;5(3 suppl):S1-S8.
5.  Moorjani S, et al. Arteriosclerosis. 1989;9(2):211-216.
6.  Kusters DM, et al. Neth Heart J. 2011;19(4):175-182.
7.  Seftel HC, et al. Br Med J. 1980;281(6241):633-636.

Indication and Clinical Use
•  JUXTAPID (lomitapide) is indicated as an adjunct to a low-fat diet and other lipid-
lowering drugs, with or without LDL apheresis, to reduce low-density lipoprotein
cholesterol (LDL-C) in adult patients with homozygous familial hypercholesterolemia
(HoFH). Due to its benefit-risk profile, the prescribing of JUXTAPID should be limited to
physicians experienced in the diagnosis and treatment of familial hypercholesterolemia.
The effect of JUXTAPID on cardiovascular morbidity and mortality has not been
determined.
Geriatrics (≥ 65 years of age)
•  Clinical studies of JUXTAPID did not include sufficient numbers of patients with HoFH
aged 65 years and over to determine whether they respond differently than younger
patients. Other reported clinical experience has not identified differences in responses
between elderly and younger patients.
Pediatrics (< 18 years)
•  The safety and effectiveness in pediatric patients have not been established.
There is a risk of hepatotoxicity with Juxtapid, including hepatic steatosis and elevations in
aminotransferases (liver enzymes).
- Juxtapid Product Monograph and Data on File, Aegerion Pharmaceuticals (2014).

Juxtapid development: it all began with a rare
disease…
Microsomal Triglyceride Transfer Protein (MTP) as a therapeutic target for HoFH
originated from the discovery that MTP was the gene that causes abetalipoproteinemia, a
very rare disease characterized by extremely low levels of LDL cholesterol1
Abetalipoproteinemia is:
•  A rare autosomal recessive disease caused by mutations in the gene encoding MTP
affecting ~ 1:1,000,0002
•  Characterized by extremely low levels of VLDL and LDL cholesterol3
•  Clinical manifestations include: gastrointestinal (diarrhea, steatorrhea), neurologic,
hematologic, hepatic and ophthalmologic symptoms
Could inhibiting MTP, which is independent of the LDL-R, significantly
reduce LDL cholesterol?
1.  Wetterau JR, et al. Absence of microsomal triglyceride transfer protein in
individuals with abetalipoproteinemia. Science. 1992. 258: 999-1001.
2.  Wetterau JR, et al. Biochimica Biophysica Acta. 1997;1345(2):136-150.
3.  Benayoun L, et al. Mol Genet Metab. 2007;90(4):453-457.
4. Hussain MM, et al. Nutr Metab (Lond). 2012;9:14.
5. Linton MF, et al. J. Lipid Res. 1993;34(4):521-541.
6. Wetterau JR, et al. Science. 1998;282(5389):751-754.

Microsomal Triglyceride Transfer Protein (MTP)
•  MTP is an intracellular lipid-transfer protein found in the lumen of the
Endoplasmic Reticulum, responsible for binding and shuttling individual lipid
molecules between membranes1
•  Normal concentrations and function of MTP are necessary for the proper
assembly and secretion of ApoB-containing lipoproteins in the liver (VLDL)
and intestine (chylomicrons)2
1. Hussain MM, et al. J Lipid Res. 2003;44(1);22-32.
2. Liao W, et al. J Lipid Res. 2003;44(5):978-985.
Liver Cell
ER
Lumen
Cytoplasm
MTP
Intestinal
Epithelial Cell
ER
Lumen
Cytoplasm
MTP

Juxtapid, a MTP Inhibitor
•  Juxtapid binds and inhibits MTP, thereby preventing the assembly of ApoB-
containing lipoproteins in the liver (VLDL) and the intestine (chylomicrons)
•  Inhibition of VLDL results in reduced LDL-C in the blood
Hussain MM, et al. J Lipid Res. 2003;44(1):22-32.
Decreases Secretion
into Bloodstream
ApoB-48
MTP
Intestinal Cell
Chylomicron
Diet Source
TGs
Cholesterol
ApoB-100
MTP
Liver Cell
VLDL
Liver Source
TGs
Cholesterol

Legislation to Support Development to Treat Rare
Diseases
●  The Orphan Drug Act of 1983 was passed in the US to encourage
pharmaceutical companies to develop drugs to treat diseases which affect
fewer than 200,000 people in the US

z
History of Juxtapid & Aegerion Pharmaceuticals
1
1
1990s 2002 2004 2006 2007 2010
BMS donates certain
rights to lomitapide
to the University of
Pennsylvania (Penn)
Aegerion obtains certain
license for exclusive
worldwide rights to
Juxtapid from Penn
2012
Completes
enrollment of
pivotal Phase III
clinical trial for
adult patients with
HoFH
Submits marketing applications
for lomitapide in US and EU for HoFH
Based on 56 weeks data
2013
FDA approves
JUXTAPID for
the treatment of
HoFH
FDA grants Juxtapid
orphan drug designation
for the treatment of HoFH
Penn completes
Proof of Concept trial
for patients with HoFH
EMA approves
LOJUXTA for the
treatment of
HoFH
2014
Health Canada
approves
JUXTAPID for
the treatment of
HoFH
BMS conducts early clinical
trials of Juxtaapid
as a broad, monotherapy
treatment before
discontinuing
Penn obtains funding
from FDA’s ODP for P3
study
First patient enrolled in P3
2008 2015
Aegerion
Acquires
Myalept™ from
AstraZeneca
Juxtapid
reduces LDL-C
significantly in
Watanabe rabbit
(HoFH model)
P2 study in broad
hypercholesterolemia
showed significant ↓ LDL-
C but high incidence of
GI side effects & attrition
rate

Factors Contributing to the Development of Juxtapid for
HoFH
Development of Juxtapid for HoFH was made possible due to perseverance,
collaboration, and securing the right capabilities & resources.
●  The Orphan Drug Act provides a pathway to pursue an indication in orphan
disease
●  Big pharma (BMS) was open to other opportunities for a shelved product
●  Identification & Collaboration with global academic experts in HoFH
●  Government and foundation funding opportunities to support proof of
concept studies
●  FDA grants Juxtapid orphan drug designation for HoFH
●  Aegerion knowledge of rare disease development and commercialization
capabilities & infrastructure

Areas to consider targeting
● Identify researchers and clinicians working on rare disorders
in Canada & globally
● Connect stakeholders working in rare disease
● Identify and make stakeholders aware of funding
opportunities for proof of concept studies
● Support pathways for legislation in Canada that would
encourage stakeholders to develop new treatments for rare
disorders
● Create opportunities where pharmaceutical companies with
drugs no longer in development would have incentives for
treating rare disorders

LeAnne Bloedon (Aegerion) Rare Disease Day 2016 Conference

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LeAnne Bloedon (Aegerion) Rare Disease Day 2016 Conference