Amgen Investor Event 2014 ACC Scientific Session March 30, 2014 - - PowerPoint PPT Presentation

Amgen Investor Event 2014 ACC Scientific Session

March 30, 2014

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Provided March 30, 2014 as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.

Safe Harbor Statement

This presentation contains forward-looking statements that are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and assumptions that could cause actual results to differ materially from those described. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including, estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission (SEC) reports filed by Amgen, including Amgen’s most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and Form 8-K. Please refer to Amgen’s most recent Forms 10-K, 10-Q and 8-K for additional information on the uncertainties and risk factors related to our business. Unless otherwise noted, Amgen is providing this information as of March 30, 2014 and expressly disclaims any duty to update information contained in this presentation. No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Our results may be affected by our ability to successfully market both new and existing products domestically and internationally, clinical and regulatory developments (domestic or foreign) involving current and future products, sales growth of recently launched products, competition from other products (domestic or foreign) and difficulties or delays in manufacturing our products. Discovery or identification of new product candidates cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The length of time that it takes for us to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and we expect similar variability in the future. We develop product candidates internally and through licensing collaborations, partnerships, joint ventures and acquisitions. Product candidates that are derived from relationships or acquisitions may be subject to disputes between the parties or may prove to be not as effective or as safe as we may have believed at the time of entering into such relationship. In addition, sales of our products are affected by reimbursement policies imposed by third-party payers, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and healthcare cost containment as well as U.S. legislation affecting pharmaceutical pricing and

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• ur competitors. We depend on third parties for a significant portion of our manufacturing capacity for the supply of certain of our current and future

products and limits on supply may constrain sales of certain of our current products and product candidate development. In addition, we compete with

• ther companies with respect to some of our marketed products as well as for the discovery and development of new products. Our products may

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• suppliers. Our business performance could affect or limit the ability of our Board of Directors to declare a dividend or our ability to pay a dividend or

repurchase our common stock.

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Provided March 30, 2014 as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.

Agenda

Introduction

Sean Harper

Evolocumab Phase 3 Overview

Scott Wasserman

Q&A

All

Amgen Investor Event 2014 ACC Scientific Session

Sean E. Harper, MD Executive Vice President, Research and Development

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Provided March 30, 2014 as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.

On average, 47,000 people die

• f CVD each day, an average of

1 DEATH EVERY 2 SECONDS1

There are an estimated

17,300,000

deaths each year from CVD worldwide1

The Global Impact of Cardiovascular Disease (CVD)

CVD is the

LEADING CAUSE

• f morbidity and mortality

worldwide1

Cost of CVD estimated in 2010 to be

$863 BILLION PER YEAR2

• 1. Cardiovascular diseases fact sheet. World Health Organization. http://www.who.int/mediacentre/factsheets/fs317/en/.

Accessed February 2014; 2. World Economic Forum: The Global Economic Burden of Non-communicable Diseases. Harvard School of Public Health.

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Provided March 30, 2014 as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.

CVD Remains the Leading Cause of Death in Males and Females in the US

22k 35k 61k 80k 293k 392k 36k 44k 53k 67k 270k 421k 100,000 200,000 300,000 400,000 500,000

Alzheimer's disease Diabetes mellitus Chronic lower respiratory disease Accidents Cancer Cardiovascular disease # of Deaths Women Men

Causes of Death in the United States—2011

Source: Roger, Circulation (2011) 123:e18-e209.

60% of cardiovascular disease deaths are directly attributable to coronary heart disease

Alzheimer’s disease

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Provided March 30, 2014 as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.

LDL-C = low-density lipoprotein cholesterol Source: Ross, NEJM (1999) 340:115-26.

High LDL-C Is a Major Contributor to Coronary Heart Disease

Development of Atherosclerosis Leads to an Increased Risk of Cardiovascular Disease

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Provided March 30, 2014 as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.

LDL-R = LDL receptor

Evolocumab: A Human Monoclonal Antibody That Inhibits PCSK9

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Provided March 30, 2014 as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.

Human Genetics Strongly Supports Pursuing PCSK9 Inhibition

PCSK9 Variant LDL-C CHD Risk

Gain of function mutations >300 mg/dL2 Premature CAD1,2 R46L ↓ 15%3 ↓ 47%3 Y142X or C679X ↓ 28-40%3,4 ↓ 88%3

1 Haddad L, Day INM et al. J Lipid Res. 1999, 40:1113-1122; 2 Abifadel M, Varret M, Rabes JP et al., Nat Genet. 2003, 34:154-

156; 3 Cohen JC, Boerwinkle E, Mosley TH, Hobbs HH., N Engl J Med. 2006; 354:1264-1272; 4 Cohen J, Pertsemlidis A, Kotowski IK, et al., Nat Genet. 2005, 37:161-165

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Provided March 30, 2014 as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.

Evolocumab Phase 3 Program Findings

• PCSK9 inhibition with evolocumab consistently reduced

LDL-C > 50% vs placebo

– In different populations – In combination with existing therapies – Over 12–52 weeks of therapy

• Evolocumab LDL-C lowering was superior to ezetimibe
• 140 mg Q2W and 420 mg QM dosing resulted in clinically

equivalent efficacy with similar AE profile

• Adverse events were similar between arms, irrespective
• f dose

Q2W = every other week; QM = monthly AE = adverse event; CK = creatine kinase

Amgen Investor Event 2014 ACC Scientific Session

Scott M. Wasserman, MD, FACC Executive Medical Director, Clinical Development

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Provided March 30, 2014 as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.

Our Evolocumab Global Phase 3 Program Evaluates LDL-C, Effect on Atherosclerosis, and CV Outcomes

Combination therapy Statin intolerant Monotherapy HeFH Long-term safety and efficacy Open-label extension HoFH Secondary prevention Vascular imaging

Phase 2 (N = 629) Phase 3 (N = 1,896) Phase 2 (N = 406) Phase 3 (N = 614) Phase 2 (N = 157) Phase 3 (N = 307) Phase 2 (N = 167) Phase 2/3 (N = 58) Phase 3 (N = 250) Phase 2 (N = 1,324) Phase 3 (N < 3,800) Phase 3 (N = 901) Phase 3 (N = 22,500) Phase 3 (N = 950) Phase 3 (N = 329)

CV = cardiovascular; HeFH = heterozygous familial hypercholesterolemia; HoFH = homozygous familial hypercholesterolemia

Phase 3 (N = 100)

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Provided March 30, 2014 as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.

Monthly Dosing

Automated Mini-Doser

N = 164

Evolocumab Phase 3 Program Supports a Broad LDL-C Lowering Global Filing Plan

*Include ezetimibe comparator

Without Statins* With Statins ± Ezetimibe Every 2 Week and Monthly Dosing MENDEL-2 Monotherapy

N = 614

LAPLACE-2 Combination Therapy

N = 1,896

GAUSS-2 Statin Intolerant

N = 307

RUTHERFORD-2 Heterozygous FH

N = 329 Monthly Dosing

DESCARTES Monotherapy and Combination Therapy

N = 901

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Provided March 30, 2014 as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.

We Are Developing Devices for Every Other Week and Monthly Dosing

Autoinjector/Pen

(1.0 mL)

Automated Mini-Doser

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Provided March 30, 2014 as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.

Evolocumab Phase 3 Program LDL-C Lowering Clinical Endpoints

• Primary Endpoints*

– Percent change from baseline in LDL-C

• Key Secondary Endpoints

– Change from baseline in LDL-C – LDL-C response (LDL-C < 70 mg/dL [1.8 mmol/L]) – Percent change from baseline in:

• Non-HDL-C, ApoB, total cholesterol/HDL-C ratio, ApoB/ApoA1

ratio, Lp(a), triglycerides, HDL-C, VLDL-C

• Tertiary Endpoints

– Percent change from baseline in ApoA1

• Exploratory

– Adjudicated cardiovascular endpoints

HDL-C = high-density lipoprotein; VLDL-C = very low-density lipoprotein *Co-endpoints were at week 12 and mean at weeks 10 and 12 for MENDEL-2, LAPLACE-2, RUTHERFORD-2, and GAUSS-2; DESCARTES assessed endpoints at weeks 52 and 12

Efficacy and Safety of Evolocumab (AMG 145) Monotherapy Compared With Ezetimibe and Placebo in Hypercholesterolemic Subjects: A Phase 3 Randomized Clinical Trial

Michael J Koren,1 Pernille Lundqvist,2 Michael Bolognese,3 Joel M Neutel,4 Maria Laura Monsalvo,5 Jingyuan Yang,5 Jae B Kim,5 Rob Scott,5 Scott M Wasserman,5 Harold Bays6 for the MENDEL-2 Investigators

1Jacksonville Center for Clinical Research, Jacksonville, FL, USA; 2Center for Clinical and Basic

Research, Ballerup, Denmark; 3Bethesda Health Research Center, Bethesda, MD, USA;

4Orange County Research Center, Tustin, CA, USA; 5Amgen Inc., Thousand Oaks, CA, USA; 6L-MARC Research Center, Louisville, KY, USA

March 29, 2014, Featured Clinical Research Session 400 American College of Cardiology, Washington DC

MENDEL-2: Evolocumab Primary Endpoint Biweekly Dose

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–30 –40 –50 –60 BL Week 2 Week 8 Study Week Week 10 Week 12 –20 –10 10 Biweekly SC administration Day 1 Week 4 Week 6 Mean Percent Change in LDL-C from Baseline

BL, baseline. Vertical lines represent the standard error around the mean. Plot is based on observed data with no imputation for missing values. P values are multiplicity adjusted. Placebo (N = 76) Ezetimibe (N = 77) Evolocumab biweekly (N = 153)

0.1% –18% –57%

MENDEL-2: Evolocumab Primary Endpoint Monthly Dose

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–30 –40 –50 –60 Study Week –20 –10 10 Mean Percent Change in LDL-C from Baseline

Placebo (N = 78) Ezetimibe (N = 77) Evolocumab monthly (N = 153)

–1% –19% –56%

Monthly SC administration

BL, baseline. Vertical lines represent the standard error around the mean. Plot is based on observed data with no imputation for missing values. P values are multiplicity adjusted.

BL Week 2 Week 8 Week 10 Week 12 Day 1 Week 4 Week 6

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MENDEL-2: Safety and Tolerability

*Reported in ≥3% of patients in one or more treatment arms. †Reported using high-level term grouping, which includes injection site (IS) rash, IS inflammation, IS pruritus, IS reaction, and IS urticaria. ‡Standard MedDRA Queries. §Binding or neutralizing.

Adverse Events (AEs), n (%) Placebo (N = 154) Ezetimibe (N = 154) Evolocumab (N = 306)

Treatment-emergent AEs 68 (44) 70 (46) 134 (44) Common treatment-emergent AEs* Headache Diarrhea Nausea Urinary Tract Infection Constipation Nasopharyngitis Upper Respiratory Infection 4 (3) 6 (4) 1 (1) 2 (1) 4 (3) 3 (2) 4 (3) 5 (3) 3 (2) 3 (2) 3 (2) 1 (1) 6 (4) 5 (3) 10 (3) 9 (3) 8 (3) 7 (2) 6 (2) 6 (2) 5 (2) Serious AEs 1 (1) 1 (1) 4 (1) AEs leading to study drug discontinuation 6 (4) 5 (3) 7 (2) Deaths 0 (0) 0 (0) 0 (0) Potential injection site reactions† 8 (5) 7 (5) 16 (5) Muscle-related SMQ‡ Myalgia Musculoskeletal pain 6 (4) 3 (2) 2 (1) 5 (3) 3 (2) 1 (1) 8 (3) 3 (1) 3 (1) Neurocognitive AEs 0 (0) 0 (0) 0 (0) CK > 5 x ULN 2 (1) 0 (0) 2 (1) ALT or AST > 5 x ULN 2 (1) 0 (0) 1 (0.3) Anti-evolocumab antibodies§ NA NA

A Phase 3 Double-blind, Randomized Study to Assess Safety and Efficacy of Evolocumab (AMG 145) in Hypercholesterolemic Subjects Unable to Tolerate an Effective Dose of Statin

Erik Stroes1, David Colquhoun2, David Sullivan3, Fernando Civeira4, Robert S. Rosenson5, Gerald F. Watts6, Eric Bruckert7, Leslie Cho8, Ricardo Dent9, Beat Knusel9, Allen Xue9, Rob Scott9, Scott M. Wasserman9, and Michael Rocco8

for the GAUSS-2 Investigators

1Academic Medical Center, Amsterdam, Netherlands; 2Wesley Medical Centre, Auchenflower, Australia; 3Royal Prince

Alfred Hospital, Camperdown, Australia; 4Hospital Universitario Miguel Servet, Zaragoza, Spain; 5Icahn School of Medicine at Mount Sinai, NY, USA; 6Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Australia; 7Hopital Pitié-Salpêtrière, Paris, France; 8Cleveland Clinic, Cleveland, OH, USA; 9Amgen, CA, USA

March 30, 2014, Joint ACC/JAMA Late-breaking Clinical Trials Session 402 American College of Cardiology, Washington DC

GAUSS-2: Evolocumab

Primary Endpoint Biweekly Dose

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BL Week 2 Week 4 Week 6 Week 8 Week 10 Week 12

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Study drug administration Biweekly SC

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Day 1 Mean Percent Change in LDL-C from Baseline

–18% –56%

1: Ezetimibe (N = 51) 2: Evolocumab 140 mg Q2W (N = 103) Study Week

BL, baseline. Vertical lines represent the standard error around the mean. Plot is based on observed data with no imputation for missing values. P value is multiplicity adjusted.

GAUSS-2: Evolocumab

Primary Endpoint Monthly Dose

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Study Week 1: Ezetimibe (N = 51) 2: Evolocumab 420 mg QM (N = 102) Study drug administration Monthly SC Mean Percent Change in LDL-C from Baseline

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BL Week 2 Week 4 Week 6 Week 8 Week 10 Week 12 Day 1

–15% –53%

BL, baseline. Vertical lines represent the standard error around the mean. Plot is based on observed data with no imputation for missing values. P value is multiplicity adjusted.

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GAUSS-2: Safety and Tolerability

Adverse Events (AEs), n(%) Ezetimibe (N = 102) Evolocumab (N = 205) Treatment-emergent AEs 74 (73) 135 (66) Common treatment-emergent AEs (≥5% of patients in either treatment arm) Headache Myalgia Extremity pain Muscle spasms Fatigue Nausea Diarrhea Paresthesia 9 (9) 18 (18) 1 (1) 4 (4) 10 (10) 7 (7) 7 (7) 5 (5) 16 (8) 16 (8) 14 (7) 13 (6) 9 (4) 9 (4) 5 (2) 2 (1) Serious AEs 4 (4) 6 (3) AEs leading to study drug discontinuation 13 (13) 17 (8) Deaths Potential injection site reactions* 8 (8) 6 (3) Muscle-related SMQ† 23 (23) 25 (12) Neurocognitive AEs†† Anti-evolocumab antibodies‡ NA

*Reported using high-level term grouping, including IS - rash, inflammation, pruritus, reaction, urticaria. †Standard MedDRA Queries.

††Searched HLGT terms: Deliria (incl confusion); Cognitive and attention disorders and disturbances; dementia and amnestic

conditions; disturbances in thinking and perception; mental impairment disorders. ‡Binding or neutralizing; data missing for one patient. NA = not applicable

The LAPLACE-2 Trial: A Phase 3, Double-blind, Randomized, Placebo and Ezetimibe Controlled, Multicenter Study to Evaluate Safety, Tolerability and Efficacy of Evolocumab (AMG 145) in Combination With Statin Therapy in Subjects With Primary Hypercholesterolemia and Mixed Dyslipidemia

Jennifer G. Robinson,1 Bettina S. Nedergaard,2 William J. Rogers,3 Jonathan Fialkow,4 Joel M. Neutel,5 David Ramstad,6 Ransi Somaratne,7 Jason C. Legg,7 Patric Nelson,7 Rob Scott,7 Scott M. Wasserman,7 and Robert Weiss,8 for the LAPLACE-2 Investigators

1College of Public Health, University of Iowa, Iowa City, IA, USA; 2Center for Clinical and Basic Research,

Aalborg, Denmark; 3University of Alabama Medical Center, Birmingham, AL, USA; 4Herbert Wertheim College

• f Medicine, Florida International University, Miami, FL, USA; 5Orange County Research Center, Tustin, CA,

USA; 6Hampton Roads Center for Clinical Research, Suffolk, VA, USA; 7Amgen Inc., Thousand Oaks, CA, USA; 8Maine Research Associates, Auburn, ME, USA

March 30, 2014, Late-Breaking Clinical Trials Session 402 American College of Cardiology, Washington DC

LAPLACE-2: LDL-C Response at Mean of Weeks 10 and 12

25 All treatment differences versus placebo and ezetimibe were statistically significant (P < 0.001). Vertical lines represent 95% CIs. No notable differences were observed between the mean of weeks 10 and 12 and week 12 alone. LDL-C, low-density lipoprotein cholesterol; Q2W, biweekly; QM, monthly.

Placebo Q2W Placebo QM Ezetimibe QD + Placebo Q2W Ezetimibe QD + Placebo QM Evolocumab Q2W Evolocumab QM

Evolocumab Q2W & QM: 63 to 75% reductions in LDL-C versus placebo Ezetimibe: 19 to 32% reductions in LDL-C versus placebo

Atorvastatin 10 mg Atorvastatin 80 mg Rosuvastatin 5 mg Rosuvastatin 40 mg Simvastatin 40 mg

Mean Percent Change from Baseline in LDL-C and 95% CI

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LAPLACE-2: Safety and Tolerability

n (%) Any Statin + Placebo (N = 558) Atorvastatin + Ezetimibe (N = 221) Any Statin + Evolocumab (N = 1117) Treatment-emergent AEs 219 (39) 89 (40) 406 (36) Most common AEsa Back pain Arthralgia Headache Muscle spasms Pain in extremity 14 (3) 9 (2) 15 (3) 6 (1) 7 (1) 7 (3) 4 (2) 5 (2) 6 (3) 3 (1) 20 (2) 19 (2) 19 (2) 17 (2) 17 (2) Serious AEs 13 (2) 2 (1) 23 (2) AEs leading to study drug discontinuation 12 (2) 4 (2) 21 (2) Positively adjudicated CV events 2 (0.4) 2 (0.9) 5 (0.4) CK > 5 x ULN 2 (0.4) 0 (0) 1 (0.1) ALT or AST > 3 x ULN 6 (1) 3 (1) 4 (0.4) Potential injection site reactionsb 8 (1) 2 (1) 15 (1) Neurocognitive AEsc Disturbance in attention Cognitive disorder Disorientation 0 (0) 0 (0) 0 (0) 1 (0.5) 1 (0.5) 1 (0.5) 0 (0) 0 (0) 1 (0.1) Post-baseline binding antibodies NA NA 1 (0.1)d

a Top 5 in evolocumab treatment group. b Reported using high-level term groupings including IS - rash, inflammation, pruritus, reaction, urticaria. cSearched HLGT terms: Deliria (incl confusion); Cognitive and attention disorders and disturbances; dementia and amnestic conditions;

disturbances in thinking and perception; mental impairment disorders. dBinding antibody was present at baseline and at the end of study. No neutralizing antibodies were detected. NA: Not applicable

The Addition of Evolocumab (AMG 145) Allows the Majority of Heterozygous Familial Hypercholesterolemic Patients to Achieve Low-density Lipoprotein Cholesterol Goals – Results from the Phase 3 Randomized, Double-blind, Placebo-controlled Study

Frederick Raal,1 Robert Dufour,2 Traci Turner,3 Fernando Civeira,4 Lesley Burgess,5 Gisle Langslet,6 Russell Scott,7 Anders G. Olsson,8 David Sullivan,9 Gerard K. Hovingh,10 Bertrand Cariou,11 Ioanna Gouni-Berthold,12 Ransi Somaratne,13 Ian Bridges,14 Rob Scott,13 Scott M. Wasserman,13 and Daniel Gaudet15 for the RUTHERFORD-2 Investigators

1Carbohydrate & Lipid Metabolism Research Unit, University of Witwatersrand, Johannesburg, South Africa; 2Institut de Recherches Cliniques

de Montreal, Universite de Montreal, Quebec, Canada; 3Metabolic and Atherosclerosis Research Center, Cincinnati, OH, USA; 4Hospital Universitario Miguel Servet, Zaragoza, Spain; 5TREAD Research, Cardiology Unit, Department of Internal Medicine, University of Stellenbosch, Parow, South Africa; 6Lipid Clinic, Oslo University Hospital, Oslo, Norway; 7Lipid and Diabetes Research Group, Christchurch, New Zealand; 8Linkoping University and Stockholm Heart Center, Stockholm, Sweden; 9Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Camperdown, Australia; 10Academisch Medisch Centrum, Vascular Medicine, Amsterdam, The Netherlands; 11Institut du Thorax, Nantes University Hospital, Nantes, France; 12Center for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Cologne, Germany; 13Amgen Inc., Thousand Oaks, CA, USA; 14Amgen Ltd, Uxbridge, United Kingdom; 15ECOGENE-21, Dyslipidemia, Diabetes and Atherosclerosis Research Group, Department of Medicine, Université de Montréal, Chicoutimi, Québec, Canada

March 29, 2014, Featured Clinical Research Session 400 American College of Cardiology, Washington DC

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RUTHERFORD-2: Mean % Change in LDL-Ca from Baseline to the Mean of Weeks 10 and 12, and Week 12 Alone

Weeks 10 and 12

aDetermined by the Friedewald formula with reflexive testing via preparative ultracentrifugation when calculated LDL-C was < 40 mg/dL or

triglyceride levels were > 400 mg/dL

bP < 0.001; placebo-adjusted treatment difference analyzed using repeated measures model which included treatment group, stratification

factors (from IVRS), scheduled visit and the interaction of treatment with scheduled visit as covariates LDL-C, low-density lipoprotein cholesterol; Q2W, biweekly; QM, monthly; SE, standard error

Adjusted Mean Percent Change ± SE from Baseline

Placebo Q2W (N = 54) Placebo QM (N = 55) Evolocumab 140 mg Q2W (N = 110) Evolocumab 420 mg QM (N = 110)

–1% –60%b –61% 2% –64% –66%b –60%b –61%b –1% 5% –56% –61%

Week 12

RUTHERFORD-2: Safety and Tolerability

Adverse events (AEs), n (%) Placebo (N = 109) Evolocumab (N = 220) Treatment-emergent AEs 53 (48.6) 124 (56.4) Most common AEs in Evolocumab Patientsa Nasopharyngitis 5 (4.6) 19 (8.6) Headache 4 (3.7) 9 (4.1) Contusion 1 (0.9) 9 (4.1) Back pain 1 (0.9) 8 (3.6) Nausea 1 (0.9) 8 (3.6) Arthralgia 2 (1.8) 8 (3.6) Serious AEs 5 (4.6) 7 (3.2) AEs leading to discontinuation of study drug 0 (0.0) 0 (0.0) Deaths 0 (0.0) 0 (0.0) Potential injection-site reactionsb 4 (3.7) 13 (5.9) Neurocognitive AEsc 0 (0.0) 0 (0.0) Muscle-related SMQd 1 (0.9) 10 (4.5) Anti-evolocumab antibodies,e % NA 0.0

aOccurring in ≥ 3.5% of evolocumab-treated patients bReported using high-level term grouping, which includes injection site (IS) rash, IS inflammation, IS pruritus, IS reaction, and IS urticaria cSearched HLGT terms: Deliria (incl confusion); cognitive and attention disorders and disturbances; dementia and amnestic conditions;

disturbances in thinking and perception; mental impairment disorders.NA = not applicable

dStandard Medical Dictionary for Regulatory Activities (MedDRA) Queries. eBinding or neutralizing

RUTHERFORD-2: Key Laboratory Results

ALT, alanine aminotransferase; AST, aspartate aminotransferase; CK, creatine kinase; ULN, upper limit of normal

Laboratory Results Placebo (N = 109) Evolocumab (N = 220) ALT or AST > 3 × ULN at any post-baseline visit, % 0.0 0.0 CK > 5 × ULN at any post-baseline visit, % 1.8 0.0 CK > 10 × ULN at any post-baseline visit, % 0.9 0.0

Long-term Tolerability and Efficacy of Evolocumab (AMG 145) in Hyperlipidemic Subjects: A 52 Week Phase 3 Double-blind, Randomized, Placebo-controlled Study

Dirk Blom*, Tomas Hala, Michael Bolognese, Michael J Lillestol, Phillip D Toth, Lesley Burgess, Richard Ceska, Eli Roth, Michael J Koren, Maria Laura Monsalvo, Kate Tsirtsonis, Jae B Kim, Scott M Wasserman, Rob Scott, Christie M Ballantyne, and Evan A Stein, for the DESCARTES Investigators March 29, 2014, Featured Clinical Research Session 400 American College of Cardiology, Washington DC

*Division of Lipidology, University of Cape Town, South Africa

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DESCARTES: % Change in UC LDL-C from Baseline at Week 52

Error bars represent standard error for treatment difference Treatment difference are least squares mean derived from a repeated measures model

Evolocumab Placebo Treatment Difference

Overall Diet Alone Atorvastatin 10 mg Atorvastatin 80 mg Atorvastatin 80 mg + Ezetimibe 10 mg

DESCARTES: Treatment Emergent Adverse Events

n (%) Placebo N = 302 Evolocumab N = 599 Any Treatment Emergent Adverse Event 224 (74.2) 448 (74.8) Serious 13 (4.3) 33 (5.5) Adjudicated atherosclerotic CV events 2 (0.7) 6 (1.0) Death 0 (0.0) 2 (0.3) Leading to discontinuation of study drug 3 (1.0) 13 (2.2)

Treatment emergent adverse events are adverse events occurring between the first dose of Study Drug and End of Study

DESCARTES: Treatment Emergent Adverse Events II

n (%) Placebo N = 302 Evolocumab N = 599 Most Common Treatment Emergent AEs Nasopharyngitis 29 (9.6) 63 (10.5) Upper respiratory tract infection 19 (6.3) 56 (9.3) Influenza 19 (6.3) 45 (7.5) Back pain 17 (5.6) 37 (6.2) Neurocognitive AEs* 2 (0.7) 1 (0.2) Amnesia - Short-term memory loss 0 (0.0) 1 (0.2) Dementia With Lewy Bodies 1 (0.3) 0 (0.0) Encephalopathy 1 (0.3) 0 (0.0)

Treatment emergent adverse events are adverse events occurring between the first dose of Study Drug and End of Study * Searched HLGT terms: Deliria (incl confusion); cognitive and attention disorders and disturbances; dementia and amnestic conditions; disturbances in thinking and perception; mental impairment disorders

DESCARTES: Hepatic and Muscle Safety

n (%) Placebo N = 302 Evolocumab N = 599 Liver function tests ALT or AST > 3 × ULN* 3 (1.0) 5 (0.8) ALT or AST > 5 × ULN* 1 (0.3) 3 (0.5) Muscle TEAEs and Laboratory Results Myalgia 9 (3.0) 24 (4.0) CK > 5 × ULN* 1 (0.3) 7 (1.2) CK > 10 × ULN* 1 (0.3) 3 (0.5)

* At any visit post baseline, TEAE = Treatment emergent adverse event

DESCARTES: Glycemic Parameters

Change from baseline at week 52

Placebo Evolocumab Diet alone A 10 mg/d A 80 mg/d A 80 mg/d + E10 mg/d n 273 63 225 131 114 Glucose, (mg/dL); mean (SE) 0.4 (0.9)

• 0.5 (1.5) 1.7 (1.2) 0.3 (1.0) 2.6 (1.9)

n 273 64 227 129 115 HbA1C, (%); mean (SE) 0.00 (0.03) –0.09 (0.04) 0.04 (0.02) –0.02 (0.03) 0.09 (0.04)

A = Atorvastatin E = Ezetimibe

DESCARTES: Injection Sites and Antibodies

• Potential injection site reactions
• Evolocumab 34 (5.7%)
• Placebo 15 (5.0%)
• Antibodies to evolocumab
• 2 patients (allocated to evolocumab) had binding

antibodies prior to evolocumab exposure

• One patient on evolocumab developed transient

binding antibodies during therapy

• No neutralizing antibodies detected throughout study

38

Provided March 30, 2014 as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.

Summary

• Evolocumab administered Q2W and QM consistently reduced

LDL-C in subjects with a wide range of cardiovascular risk

• Evolocumab treatment also resulted in favorable changes in
• ther lipoproteins
• 140 mg Q2W and 420 mg QM results were clinically equivalent

in efficacy with similar AE profile

• Treatment-emergent AEs, CK, and ALT/AST elevations, and

neurocognitive AEs were similar between arms

• No detection of neutralizing Abs
• > 3,000 subject-years of evolocumab exposure across all

doses in development program to date

ALT = alanine aminotransferase; AST = aspartate aminotransferase

39

Provided March 30, 2014 as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.

Amgen Cardiovascular

• Evolocumab

– Phase 3 data support global filing plan – 22,500 subject outcomes study currently enrolling

• Ivabradine

– Will help establish Amgen’s US cardiovascular footprint – Robust clinical program conducted by Servier in heart failure (HF) and angina:

• > 70 clinical studies involving > 43,000 subjects

– US heart failure filing anticipated in Q2 2014 – CAD outcomes data (SIGNIfY) expected in 2014

• Omecamtiv Mecarbil

– Phase 2 study with IV formulation completed in acute HF – Phase 2 study with oral formulation ongoing in chronic HF

CAD = coronary artery disease; IV = intravenous

Amgen Investor Event 2014 ACC Scientific Session

March 30, 2014