Proprietary & Confidential. © 2015 Aegerion Pharmaceuticals, Inc. All Rights Reserved.
LeAnne Bloedon, MS, RD
Senior Direc...
Proprietary & Confidential. © 2015 Aegerion Pharmaceuticals, Inc. All Rights Reserved. 2
Aegerion’s Vision
DEVELOPING AND
...
Proprietary & Confidential. © 2015 Aegerion Pharmaceuticals, Inc. All Rights Reserved. 3
z
History of Juxtapid & Aegerion ...
Proprietary & Confidential. © 2015 Aegerion Pharmaceuticals, Inc. All Rights Reserved. 4
Homozygous Familial Hypercholeste...
Proprietary. © 2015 Aegerion Pharmaceuticals, Inc. All Rights Reserved.
HoFH Prevalence
•  Historically, the prevalence of...
Proprietary. © 2015 Aegerion Pharmaceuticals, Inc. All Rights Reserved.
Indication and Clinical Use
•  JUXTAPID (lomitapid...
Proprietary. © 2015 Aegerion Pharmaceuticals, Inc. All Rights Reserved.
Juxtapid development: it all began with a rare
dis...
Proprietary. © 2015 Aegerion Pharmaceuticals, Inc. All Rights Reserved.
Microsomal Triglyceride Transfer Protein (MTP)
•  ...
Proprietary. © 2015 Aegerion Pharmaceuticals, Inc. All Rights Reserved.
Juxtapid, a MTP Inhibitor
•  Juxtapid binds and in...
Proprietary & Confidential. © 2015 Aegerion Pharmaceuticals, Inc. All Rights Reserved. 10
Legislation to Support Developme...
Proprietary & Confidential. © 2015 Aegerion Pharmaceuticals, Inc. All Rights Reserved. 11
z
History of Juxtapid & Aegerion...
Proprietary & Confidential. © 2013 Aegerion Pharmaceuticals, Inc. All Rights Reserved. 12
Factors Contributing to the Deve...
Proprietary & Confidential. © 2013 Aegerion Pharmaceuticals, Inc. All Rights Reserved. 13
Areas to consider targeting
● Id...
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LeAnne Bloedon (Aegerion) Rare Disease Day 2016 Conference

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Rare Disease Day 2016 Conference March 9 - 10: Day 2

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LeAnne Bloedon (Aegerion) Rare Disease Day 2016 Conference

  1. 1. 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
  2. 2. 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
  3. 3. Proprietary & Confidential. © 2015 Aegerion Pharmaceuticals, Inc. All Rights Reserved. 3 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)
  4. 4. Proprietary & Confidential. © 2015 Aegerion Pharmaceuticals, Inc. All Rights Reserved. 4 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.
  5. 5. 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.
  6. 6. Proprietary. © 2015 Aegerion Pharmaceuticals, Inc. All Rights Reserved. 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).
  7. 7. Proprietary. © 2015 Aegerion Pharmaceuticals, Inc. All Rights Reserved. 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.
  8. 8. Proprietary. © 2015 Aegerion Pharmaceuticals, Inc. All Rights Reserved. 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
  9. 9. Proprietary. © 2015 Aegerion Pharmaceuticals, Inc. All Rights Reserved. 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
  10. 10. Proprietary & Confidential. © 2015 Aegerion Pharmaceuticals, Inc. All Rights Reserved. 10 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
  11. 11. Proprietary & Confidential. © 2015 Aegerion Pharmaceuticals, Inc. All Rights Reserved. 11 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
  12. 12. Proprietary & Confidential. © 2013 Aegerion Pharmaceuticals, Inc. All Rights Reserved. 12 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
  13. 13. Proprietary & Confidential. © 2013 Aegerion Pharmaceuticals, Inc. All Rights Reserved. 13 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

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