2014 - IR - Alirocumab


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2014 - IR - Alirocumab

  1. 1. March 31st, 2014 IR Thematic Call on Alirocumab
  2. 2. 2 Sanofi Forward Looking Statements This presentation contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. These statements include projections and estimates and their underlying assumptions, statements regarding plans, objectives, intentions and expectations with respect to future financial results, events, operations, services, product development and potential, and statements regarding future performance. Forward-looking statements are generally identified by the words "expects", "anticipates", "believes", "intends", "estimates", "plans" and similar expressions. Although Sanofi's management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Sanofi, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include among other things, the uncertainties inherent in research and development, future clinical data and analysis, including post marketing, decisions by regulatory authorities, such as the FDA or the EMA, regarding whether and when to approve any drug, device or biological application that may be filed for any such product candidates as well as their decisions regarding labeling and other matters that could affect the availability or commercial potential of such product candidates, the absence of guarantee that the product candidates if approved will be commercially successful, the future approval and commercial success of therapeutic alternatives, the Group's ability to benefit from external growth opportunities, trends in exchange rates and prevailing interest rates, the impact of cost containment policies and subsequent changes thereto, the average number of shares outstanding as well as those discussed or identified in the public filings with the SEC and the AMF made by Sanofi, including those listed under "Risk Factors" and "Cautionary Statement Regarding Forward-Looking Statements" in Sanofi's annual report on Form 20-F for the year ended December 31, 2013. Other than as required by applicable law, Sanofi does not undertake any obligation to update or revise any forward-looking information or statements.
  3. 3. 3 Regeneron Forward Looking Statements This presentation includes forward-looking statements that involve risks and uncertainties relating to future events and the future performance of Regeneron Pharmaceuticals, Inc. (“Regeneron” or the “Company”), and actual events or results may differ materially from these forward-looking statements. Words such as “anticipate,” “expect,” “intend,” “plan,” “believe,” “seek,” “estimate,” variations of such words and similar expressions are intended to identify such forward-looking statements, although not all forward-looking statements contain these identifying words. These statements concern, and these risks and uncertainties include, among others, the nature, timing, and possible success and therapeutic applications of Regeneron's products, product candidates, and research and clinical programs now underway or planned; unforeseen safety issues resulting from the administration of products and product candidates in patients, including serious complications or side effects in connection with the use of Regeneron’s product candidates in clinical trials, including without limitation the Phase 3 ODYSSEY MONO study and the ODYSSEY global Phase 3 trial program for alirocumab; the likelihood and timing of possible regulatory approval and commercial launch of Regeneron's late-stage product candidates and new indications for marketed products, including without limitation alirocumab; ongoing regulatory obligations and oversight impacting Regeneron’s research and clinical programs and business, including those relating to patient privacy; determinations by regulatory and administrative governmental authorities which may delay or restrict Regeneron's ability to continue to develop or commercialize Regeneron's products and product candidates; competing drugs and product candidates that may be superior to Regeneron's products and product candidates; uncertainties relating to market acceptance, competitive position, and commercial success of Regeneron's products and product candidates, such as alirocumab; the ability of Regeneron to manufacture and manage supply chains for multiple products and product candidates; coverage and reimbursement determinations by third-party payers, including Medicare and Medicaid; unanticipated expenses; the costs of developing, producing, and selling products; the ability of Regeneron to meet any of its sales or other financial projections or guidance and changes to the assumptions underlying those projections or guidance; the potential for any license or collaboration agreement, including Regeneron's agreements with Sanofi and Bayer HealthCare, to be cancelled or terminated without any further product success; and risks associated with third party intellectual property and pending or future litigation relating thereto. These statements are made based on management’s current beliefs and judgment, and you are cautioned not to rely on any such statements. In evaluating such statements, shareholders and potential investors should specifically consider the various factors identified under Part I, Item 1A. “Risk Factors” of Regeneron’s Annual Report on Form 10- K for the fiscal year ended December 31, 2013 filed with the Securities and Exchange Commission on February 13, 2014, which could cause actual events and results to differ materially from those indicated by such forward-looking statements. Regeneron does not undertake any obligation to update publicly any forward-looking statement, including without limitation any financial or other projection or guidance, whether as a result of new information, future events, or otherwise.
  4. 4. Agenda 4 PCSK9 Inhibitor Potential Market Opportunity ● Robert Terifay, Senior VP, Commercial, Regeneron Alirocumab Clinical Development ● Jay Edelberg, M.D., Ph.D. VP, Head of the PCSK9 Development & Launch Unit, Sanofi Q&A Session ● Robert Terifay, Jay Edelberg and Bill Sasiela, VP, Program Direction, Regeneron
  5. 5. PCSK9 INHIBITOR POTENTIAL MARKET OPPORTUNITY 5 Robert Terifay Senior Vice President, Commercial Regeneron
  6. 6. Despite Current Therapies, There Exists a Significant Population of Patients at High Cardiovascular Risk 6 Sources: 1) Universe & population growth = US NHANES & Decision Resources 2012; 2) HeFH: Adult prevalence = 1/500 ; 25% of them are diagnosed, 80% are above 70mg/dl; 3) Statin Intolerant: IPSOS Chart Audit, Sept 2012; 4) High Risk: EVD Analysis, Dec 2012; 5) Diabetes Only: EVD Analysis, Dec 2012 31.9 (EU5) 30.2 (US) 5.8 7.6 11.1 11.0 2.7 7.6 11.1 62.1 Statin Intolerant Diabetics 0/1 Risk Factor 35.7 Total Population Adults >70mg/dL On Statins + Statin Intolerant 21.6 Diabetes + 2 Risk Factors with or w/o CV events Secondary Prevention w/o Diabetes Statin Intolerant High CHD Risk HeFH (200K) HeFH (250K) Patient Flow Projections for 2016 (Million Patients) US & EU5(1) Very High CV RiskIncreasing CV Risk 57% Secondary Prevention w/o Diabetes Diabetes + 2 Risk Factors with or w/o CV events
  7. 7. Very High CV Risk 7 11.0M 11.1M ~22M Diabetes Patients With LDL-C >70 mg/dL on Statins Projections for 2016 (Million Patients) US & EU5(1) (1) US (NHANES, OPTUM, IPSOS SI); EU (NHANES, Decision Resources, Cegedim, IPSOS SI) Besides Diabetes and LDL-C: UA, MI, Stroke, PAD, bypass surgery, PCI w/wo stent, diagnostic non-invasive evidence of chronic heart disease such as angiogram, stress echocardiogram or exercise electrocardiogram, chronic kidney disease (CKD), hypertension, retinopathy, neuropathy, microalbuminuria, family history of chronic heart disease (CHD) Diabetes + 0/1 Risk Factors Diabetes + 2 Risk Factors with or w/o CV Events ● 52 year-old male ● Diagnosis: Primary Hypercholesterolemia ● Patient history: Type II diabetes & CHD (stented 2 years ago) ● Current LDL-C: 98mg/dL ● Current treatment: atorvastatin 40mg Illustrative Example Diabetics Represent a Significant Portion of The Population Who Are at High Risk
  8. 8. 8 7.6M Secondary Prevention Patients w/o Diabetes And Not at Goal on Statins Projections for 2016 (Million Patients) US & EU5(1) (1) US (NHANES, OPTUM for PAD); EU (NHANES, Cegedim for PAD) PAD = Peripheral arterial diseases ACS = Acute coronary syndrome Secondary Prevention Patients Are at Higher Risk of Cardiovascular Events ● 58 year-old male ● Diagnosis: Primary Hypercholesterolemia ● Patient history: established coronary heart disease (CHD) and acute coronary syndrome (ACS), hypertension, previous myocardial infarction (MI) at age 46 ● Current LDL-C: 140mg/dL ● Current treatment: rosuvastatin 40mg, ezetimibe 10mg Illustrative Example 44% 31% 16%9% 7.6M Patients With Very High CV Risk History of CHD Diagnosed PAD History of Stroke History of ACS
  9. 9. 250K 200K Significant Number of HeFH Patients Remain Undiagnosed or Far From Desired LDL-C Goals 9 Heterozygous Familial Hypercholesterolemia (HeFH) Number of patients - Projections for 2016 US & EU5(1) (1) PijlmanAH et al. Atherosclerosis 209 (2010) 189–194; Ned RM at al. PLOS Currents Evidence on Genomic Tests. 2011 Jul 1. Edition 1. doi: 10.1371/currents.RRN1238, PCK9 team assumptions, Optum & Cegedim HeFH Patients 750K Treated HeFH Patients ● 44 year-old female ● Diagnosis: Primary Hypercholesterolemia ● Family history of cardiovascular disease ● Sustained LDL-C >190mg/dL ● Current treatment: simvastatin 40mg, ezetimibe 10mg Illustrative Example Diagnosed Undiagnosed ~80% of treated patients are unable achieve LDL-C goal
  10. 10. A Large Number of Statin-Intolerant Patients Are at High Risk For Cardiovascular Diseases 10 3.1M Statin Intolerant High CHD Risk 5.8M Patients Intolerant to Statins Projections for 2016 (Million Patients) US & EU5(1) (1) US: NHANES, OPTUM, IPSOS SI, EU: NHANES, Decision Resources, Cegedim, IPSOS SI Statin Intolerant Patients 2.7M ● 58 year-old male ● Diagnosis: Primary Hypercholesterolemia ● Patient history: Myocardial Infarction two years ago ● Current LDL-C: 125mg/dL ● History of statin intolerance: experienced muscle pains with simvastatin 20mg, and recently had upper back and bilateral leg pains with atorvastatin 10mg ● Current treatment: ezetimibe 10mg Illustrative ExampleVery High CV Risk
  11. 11. Lipid-Lowering Market Sales Are ~$30 Billion 11 (1) Worldwide MAT sales in €bn of dyslipidemia market, IMS MIDAS (2) Niacin, omega-3 therapies FDC = fixed dose combination ● Statins remain the primary treatment option for high LDL-C ● Many hypercholesterolemic patients not at LDL-C goal with statins ● Patients with LDL-C too high at maximally tolerated statin dose ● Patients unable to tolerate a recommended statin dose ● Patients completely statin intolerant ● Approximately 8 million patients worldwide receive ezetimibe(1) (mono/FDC) Others(2) Statins Ezetimibe (mono/FDC) Fibrates Lipid-Lowering Agents(1) Worldwide Sales 2013 60% 8% 16% 15% $30 Billion
  12. 12. Economic Burden From CV Disease Remains Substantial 12 (1) O’Sullivan AK et al. Pharmacoeconomics 2011; 29(8): 693-704 $73,300 $36,000 $71,600 Non-Fatal MI Hospitalizations for Angina Non-Fatal Hemorrhagic Stroke Cost Estimation of Cardiovascular Disease Events in The US(1) Attributable Costs Per Patient Over 36 Months Following Event
  13. 13. Alirocumab: Potential Novel Treatment For Patients at High CV Risk With Unmet Needs 13 ● Fully human monoclonal antibody against PCSK9 ● Binds PCSK9 with high affinity ● Up to 70% LDL-C reduction observed in Phase 2 trial ● Being investigated in a broad Phase 3 program to lower LDL-C and to reduce the risk for CV disease ● Dosing flexibility in terms of dose, titration, and interval ● Patient friendly pen being evaluated in Phase 3
  14. 14. Percent of Physicians Aware of PCSK9 Inhibitor Class And Perceiving New Class as Very or Extremely Innovative High Awareness of PCSK9 Class Among Cardiologists, Endocrinologists, And Subset of PCPs 14 Source: Proprietary survey conducted in U.S. (CARDS=150; ENDOS=152, PCPs=306 and in EU5 (CARDS=379, ENDOS=376, PCPs=379), measured in November-December 2013 Q1: Please name and describe all the potential treatments in development for hypercholesterolemia of which you are aware Q2: In your opinion, how innovative are the following classes of medication (PCSK9 inhibitors, CETP inhibitors and statins) 82% 57% 89% 66% 84% 11% 86% 37% 88% 35% 80% 11% Innovation of Class Awareness Endocrinologists Primary Care Physicians (PCP) Cardiologists
  15. 15. Percent of Physicians Likely or Very Likely to Prescribe For Treating Hypercholesterolemia High Likelihood to Prescribe a Self Injectable Treatment or a Monoclonal Antibody Treatment 15 Source: Proprietary survey conducted in U.S. (CARDS=150; ENDOS=152, PCPs=306 and in EU5 (CARDS=379, ENDOS=376, PCPs=379), measured in November-December 2013 Q1: Based on your experiences and anything you might have heard, how likely would you be to prescribe a self-injected subcutaneous treatment for hypercholesterolemia, if available in the future? Q2: Based on your experiences and anything you might have heard, how likely would you be to prescribe a monoclonal antibody for the treatment of hypercholesterolemia, if available in the future? 52% 52% 51% 53% 27% 29% 40% 50% 41% 48% 29% 31% Monoclonal Antibody Treatment Self Injectable Treatment Endocrinologists Primary Care Physicians (PCP) Cardiologists
  16. 16. Market Development Activities Underway: Unbranded Education And Awareness Campaigns 16 “Looming Threat” of Unmet Need PCSK9 Role in LDL-C Metabolism
  17. 17. ALIROCUMAB CLINICAL DEVELOPMENT 17 Jay Edelberg, M.D., Ph.D. Vice President, Head of the PCSK9 Development & Launch Unit Sanofi
  18. 18. Blocking PCSK9 Lowers LDL-C Levels 18 Sources: (1) Tibolla G et al. Nutr Metab Cardiovasc Dis 2011;21:835-43. (2) Akram ON et al. Arterioscler Thromb Vasc Biol 2010;30:1279-81. (3) Duff CJ et al. Expert Opin Ther Targets 2011;15:157-68. (4) Horton JD et al. J Lipid Res 2009;50 Suppl:S172-7. (5) Cariou B et al. Atherosclerosis 2011;216:258-65.
  19. 19. Key Differentiating Features of The Phase 3 Alirocumab ODYSSEY Program 19 ● 14 studies with primary endpoint evaluated at 24 weeks ● Double-blind for 6, 12, 18, and 24 months ● Solid long-term double-blind exposure (≥5,000 patient years) at completion of studies ● This will allow for a robust characterization of safety and efficacy prior to the data of ODYSSEY OUTCOMES ● Dosing flexibility ● Q2W and Q4W dosing regimens ● 75mg and 150mg doses ● Up-titration “treat to target” approach provides physicians the ability to tailor therapy to suit individual patient needs ● Several key patient populations studied ● Patients with HeFH (largest cohort of such patients) ● Hypercholesterolemic patients at high CV risk and poorly controlled LDL-C despite standard of care treatment ● First PCSK9 Phase 3 trial in statin intolerant patients with a re-challenge arm Phase 3 Program (1) Q2W = Every two weeks dosing (2) Q4W = Every four weeks dosing
  20. 20. ODYSSEY Phase 3 Clinical Trial Program: 14 Studies Including More Than 23,500 Patients 20 Statin Intolerant High CV Risk Recent CV Event Patients receiving statins Patients not receiving statins HeFH FH I (n=471) FH II (n= 250) HIGH FH (n=105) OLE (Open-Label Extension, n≥1,000) High CV Risk MI, Stroke, T2D, CKD COMBO I (n=306) COMBO II (n=660) OPTIONS I (n=350) OPTIONS II (n=300) CHOICE I (n=700, 300mg Q4W) LONG TERM(1) (n=2,100) OUTCOMES (n=18,000) Monotherapy CHOICE II(2) (n=200, 150mg Q4W) MONO (n=100) ALTERNATIVE (n=250) Except CHOICE I & II, all studies are investigating Q2W regimens: a dose titration scheme (75mg up-titrated to 150mg, based on LDL-C levels at Week 12) or a continuous treatment with 150mg for patients with LDL-C >160mg/dL (HIGH FH) n = Target enrollment (except for ODYSSEY MONO for which results are already reported). Chronic Kidney Disease (CKD) (1) LONG TERM includes a subset of FH patients (2) CHOICE II includes some patients on additional non-statin lipid-lowering therapy
  21. 21. Lipid-Lowering Trials: Double-Blind for 6, 12, 18, and 24 Months(1) 21 Double-Blinded Efficacy and Safety Evaluation Solid long-term double-blind exposure data (≥5,000 patient years) at completion of studies MONO (n=100) OPTIONS I (n=350) OPTIONS II (n=300) CHOICE II (n=200) 24 Weeks COMBO I (n=306) CHOICE I (n=700) 52 Weeks COMBO II (n=660) 104 Weeks FH I (n=471) FH II (n= 250) HIGH FH (n=105) ALTERNATIVE (n=250) LONG TERM (n=2,100) 78 Weeks (1) Does not include ODYSSEY OUTCOMES (event-driven) and ODYSSEY OLE (open label safety study; up to 120 weeks), ODYSSEY ALTERNATIVE will have an indefinite open label extension Primary Endpoint Evaluation at Week 24
  22. 22. ODYSSEY Program Evaluates Multiple Options to Personalize Dosing Regimen ● Q2W dosing ● 75mg Q2W as the starting dose • Possibility to titrate up to 150mg Q2W if needed ● Alternatively, 150mg Q2W as a starting dose for patients with high baseline LDL-C ● Q4W dosing ● 150mg Q4W for patients not receiving statins ● 300mg Q4W for patients receiving statins 22 Flexible Model Baseline LDL-C Values Patient CV Risk Profile Background Lipid- Lowering Therapy Patient Preference Looking to Flexible Dosing Based on Patient Needs Dosing Regimens Evaluated in Phase 3
  23. 23. ODYSSEY MONO(1): ~50% LDL-C Reduction Achieved With 75mg Q2W at 12 Weeks; Sustained Over 24 Weeks 23 LDL-C % Change From Baseline -70 -60 -50 -40 -30 -20 -10 0 0 4 8 12 16 20 24 Alirocumab 75/150mg Q2W 86% of patients stayed on 75mg from W12 to W24 Week –20.4% –17.2% –53.2% –54.1% Difference vs. ezetimibe: -36.9%. P<0.0001 Ezetimibe 10mg QD ● Percent of patients reporting TEAEs ● 78.4% with ezetimibe ● 69.2% with alirocumab ● Most common class of AEs ● Infections (39.2% with ezetimibe vs. 42.3% with alirocumab), included nasopharyngitis, influenza, and upper respiratory tract infection ● Injection-site reactions in <2% of patients in both groups ● Muscle-related adverse events (3.9% patients treated with ezetimibe vs. 3.8% with alirocumab) (1) Roth et al. 2014 ACC Abstract #1183/125 TEAEs = Treatment-emergent adverse events Up-titration if needed
  24. 24. Clinical Study Supports 150mg Q4W Dosing in Patients Not on Statins ~48% LDL-C Reduction Maintained Over 28-Day Dosing Interval(1) 24 (1) Rey et al. 2014 ACC Abstract #1183/131 (2) Patients received placebo, ezetimibe or fenofibrate alone (w/o alirocumab) -70 -60 -50 -40 -30 -20 -10 0 10 -29 -1 8 15 22 29 57 64 71 78 85 99 120 Alirocumab sc Study Day Alirocumab 150mg Q4W - Alirocumab + placebo (N=24) - Alirocumab + ezetimibe (N=24) - Alirocumab + fenofibrate (N=24) Run-in(2) Follow-up(2) 4 W 4 W 4 W LDL-C%ChangefromD-29Baseline
  25. 25. ● Patient-friendly single-use, disposable pen being evaluated ● Small injection volume of 1ml (75 or 150mg) ● Allows quick injection ● Interchangeably injected in the abdomen, upper arm, or thigh(1) ● >90% compliance in Phase 2 open label extension(2) Delivery Options Evaluated in ODYSSEY Program 25 (1) Lunven et al. 2014 ACC Abstract #1183/132 (2) Stein et al. 2014 ACC Abstract #1183/126 Both options have been included in studies intended for registration Option 1 ● Ready-to-use pre-filled syringe ● Small injection volume of 1ml (75 or 150mg) ● Self-injection at home in clinical studies Option 2
  26. 26. Alirocumab Generally Well Tolerated in Completed Studies(1) 26 ● DMC for the lipid program and DMC for the CV outcome trial ● DMCs meet every 3 months to review unblinded data ● Safety assessment includes ● Injection site reactions ● Immunogenicity ● Hypersensitivity reactions ● Neurocognitive disorders ● DMC review of Phase 3 and CVOT data (March 2014) detected no signal for neurocognitive adverse events ● Injection site reactions ● Diarrhea ● Fatigue ● Headache ● All above events were of mild intensity Most Frequent TEAEs From Pooled Phase 2 Studies ODYSSEY Program Overseen by Two Data Monitoring Committees (DMC) (1) Three Phase 2 studies ( Stein EA et al. Lancet 2012;380:29-36; McKenneyJM et al. J Am Coll Cardiol 2012;59:2344- 53; Roth EM, N Engl J Med 2012;367:1891-900) and ODYSSEY MONO (Roth et al. 2014 ACC Abstract #1183/125)
  27. 27. ODYSSEY OUTCOMES: Large CV Outcomes Trial Initiated in November 2012 27 (1) High intensity statin therapy include atorvastatin 40/80mg or rosuvastatin 20/40mg (2) Patients can also qualify with apoB>80mg/dL or non-HDL-C > 100 mg/dL (3) Primary endpoint is a composite endpoint of coronary heart disease (CHD) death, non-fatal myocardial infarction (MI), fatal and non-fatal ischemic stroke, and unstable angina requiring hospitalization N=9,000 Run-in period Randomization must be 4-52 weeks after index event Screening visit: Initiate high dose statin therapy(1) Double-blind treatment period (minimum of 2 years) Qualifying visit: LDL-C must be >70mg/dl(2) R Patients with recent ACS >40 years of age Alirocumab 75mg SC Q2W Up-titration at Week 12 if needed Placebo SC Q2W N=9,000 Primary Endpoint(3) A composite of major CV endpoints + Diet (NCEP ATP III TLC or equivalent diet) Continued high dose statin 49 countries/ 1,110 sites expected to participate Primary Endpoint(3) A composite of major CV endpoints
  28. 28. Q&A 28