1. An Academic Research Organization of Brigham and Women’s Hospital and Harvard Medical School LAPLACE-TIMI 57 Primary Results A Double-blind, Randomized, Placebo-controlled, Dose-ranging Study to Evaluate the Efficacy, Safety, and Tolerability of a Monoclonal Antibody to PCSK9 in Combination with a Statin in Patients with Hypercholesterolemia Robert P. Giugliano, MD, SM, FAHA, FACC TIMI Study Group, Cardiovascular Division Brigham and Women’s Hospital Harvard Medical School, Boston, MA Supported by research grant from Amgen, Inc.

2. Brown MS, et al. Proc Natl Acad Sci U S A. 1979;76:3330-3337. Steinberg D, et al. Proc Natl Acad Sci U S A. 2009;106:9546-9547. Goldstein JL, et al. Arterioscler Thromb Vasc Biol. 2009;29:431-438. LDL receptor AMG 145, a fully human monoclonal antibody that binds PCSK9, was well tolerated and lowered LDL in phase Ia and Ib studies (Dias CS, JACC published online Oct 17, 2012. http://dx.doi.org/10.1016/j.jacc.2012.08.986) Qian YW, et al. J Lipid Res. 2007;48:1488-1498. Horton JD, et al. J Lipid Res. 2009;50:S172-S177. Zhang DW, et al. J Biol Chem. 2007;282:18602-18612. PCSK9 Regulates the Surface Expression of LDLRs by Targeting LDLRs for Lysosomal Degradation

3. An Academic Research Organization of Brigham and Women’s Hospital and Harvard Medical School Objectives Objectives: To compare 12 weeks of AMG 145 (given SC Q2 or Q4 weeks) vs placebo in stable patients with hypercholesterolemia on a statin ± ezetimibe: –Primary: % change in LDL-C* –Secondary: changes in other lipoproteins pharmacokinetics/pharmacodynamics tolerability and safety * measured using ultracentrifugation in a central core laboratory

4. An Academic Research Organization of Brigham and Women’s Hospital and Harvard Medical School Study Design Kohli P, et al. Clin Cardiol. 2012;35:385-391. 78 centers 5 countries 934 screened631 random.629 treated ( *2 subjects assigned placebo Q4W received no study drug) Screening and Placebo Run-in Period Subcutaneous injection of 6 mL placebo Fasting LDL-C 5-10 days before randomization Maximum 6 weeks Day 1 Visits: Week 2Week 8 Week 12 Week 6Week 4Week 10Week 14 70 mg AMG 145 SC Q2W 79 Subjects 105 mg AMG 145 SC Q2W 79 Subjects 140 mg AMG 145 SC Q2W 78 Subjects Placebo SC Q2W 78 Subjects Q2W: 280 mg AMG 145 SC Q4W 79 Subjects 350 mg AMG 145 SC Q4W 79 Subjects 420 mg AMG 145 SC Q4W 80 Subjects Placebo SC Q4W 77 Subjects Q4W: Primary Endpoint Assessed

5. An Academic Research Organization of Brigham and Women’s Hospital and Harvard Medical School Major Entry Criteria Age 18–80 years Stable dose of statin ± ezetimibe for 4 wks Fasting LDL-C ≥ 85 mg/dL Fasting triglycerides ≤ 400 mg/dL No other prescription lipid lowering therapy No recent ACS, revascularization, stroke No major comorbidities Randomization stratified by:1) Baseline LDL (<130 vs ≥130 mg/dL) 2) Use of ezetimibe at baseline Kohli P, et al. Clin Cardiol. 2012;35:385-391.

6. An Academic Research Organization of Brigham and Women’s Hospital and Harvard Medical School Baseline Characteristics Characteristic Placebo (N=157) AMG 145 (N=474) Age, years, mean (SD)60 (9)61 (10) Sex, female, %54%50% Race, white, % 94%87% LDL, mg/dL, mean (SD)124 (29)123 (27) LDL < 130 mg/dL, %66%65% Ezetimibe, %10%9% Intensive statin regimen*, %25%31% Diabetes mellitus, %11%18% Body mass index (kg/M 2 ), mean (SD)30 (5)30 (6) Coronary artery disease, %27%31% Free PCSK9 (ng/mL), mean (SD) 450 (124)443 (126) *rosuvastatin ≥20 mg, atorvastatin ≥40 mg, simvastatin 80 mg or ezetimibe + any statin P = NS for all comparisons

7. An Academic Research Organization of Brigham and Women’s Hospital and Harvard Medical School Primary Endpoint: AMG 145 Reduced LDL-C at 12 wks NOTE: LDL-C measured using ultracentrifugation in a central core laboratory 70 mg N = 79 105 mg N = 79 140 mg N = 78 280 mg N = 79 350 mg N = 79 420 mg N = 80 AMG 145 Q2WAMG 145 Q4W * p < 0.0001 for each dose vs placebo LDL-C at 12 wks Mean (mg/dL) (SD) 73 (25) 53 (21) 44 (25) 69 (28) 60 (23) 58 (26)

8. An Academic Research Organization of Brigham and Women’s Hospital and Harvard Medical School % Reduction in LDL with Top 2 AMG 145 Doses: Major Subgroups 140 mg Q2W dose of AMG 145 reduced LDL at 12 weeks ranging from 56-74% in key subgroups 420 mg Q4W dose of AMG 145 reduced LDL at 12 weeks ranging from 38-57% in key subgroups Baseline Characteristics UC = Ultra centrifugation * P interaction = 0.048, all others >0.05 * All patients -66% (-71, -61)-50% (-56, -45)

9. An Academic Research Organization of Brigham and Women’s Hospital and Harvard Medical School AMG 145 Q2W Dose Response: % Change in LDL-C Through 12 Wks p < 0.0001 for weeks 2-12 for each dose vs placebo Study Drug Administration Placebo Q2W (n = 78)AMG145 70 mg Q2W (n = 79) AMG145 105 mg Q2W (n = 79)AMG145 140 mg Q2W (n = 78) BaselineWeek 2Week 4Week 6Week 8Week 10Week 12 –100 –90 –80 –70 –60 –50 –40 –30 –20 –10 0 10 Mean % Change from Baseline in Calculated LDL-C number of patients 79 78 76 77 74 77 76 77 75 77 78 76 73 75 76 77 76 77 76 74 73 74 LDL-C calculated using the Friedewald equation

10. An Academic Research Organization of Brigham and Women’s Hospital and Harvard Medical School BaselineWeek 2Week 4Week 6Week 8Week 10Week 12 Study Week –100 –90 –80 –70 –60 –50 –40 –30 –20 –10 0 10 Mean % Change from Baseline in Calculated LDL-C 79 80 77 75 70 69 71 77 78 77 74 72 76 77 76 74 75 74 76 75 78 77 76 number of patients AMG 145 Q4W Dose Response: % Change in LDL-C Through 12 Wks LDL-C calculated using the Friedewald equation p < 0.0001 for weeks 2-12 for each dose vs placebo Study Drug Administration Placebo Q4W (n = 77)AMG145 280 mg Q4W (n = 79) AMG145 350 mg Q4W (n = 79)AMG145 420 mg Q4W (n = 80)

11. An Academic Research Organization of Brigham and Women’s Hospital and Harvard Medical School 70 mg 105 mg 140 mg n = 22n = 7n = 23n = 16n = 22 n = 25n = 11n = 28n = 15n = 28 n = 29n = 16n = 30n = 20n = 27 Study Drug Administration 280 mg 350 mg 420 mg n = 25n = 6n = 25n = 16n = 26 n = 27n = 10n = 26n = 18n = 27 n = 17n = 26n = 19n = 28 Study Drug Administration AMG 145 Dose Response: % Change in LDL-C Wks 8-12 (placebo adjusted) LDL-C calculated using the Friedewald equation –100 –90 –80 –70 –60 –50 –40 –30 –20 –10 0 Week 8Week 9Week 10Week 11Week 12 Percentage Change in Calculated LDL-C vs. Placebo, Mean (SE)

12. An Academic Research Organization of Brigham and Women’s Hospital and Harvard Medical School Secondary Results at 12 Wks with Top 2 AMG 145 Doses P < 0.0001 versus placebo for all parameters Q2W, every 2 weeks; Q4W, every 4 weeks; SE, standard error -43% -33% -61% -48% -44% -32% -48% -36% -56% -42% -53% -43%

13. An Academic Research Organization of Brigham and Women’s Hospital and Harvard Medical School Safety Adverse Events, Patient Incidence, n Q2W Dose GroupsQ4W Dose Groups Placebo N=78 AMG 145 Placebo N=77 AMG 145 70 mg N=79 105 mg N=79 140 mg N=78 280 mg N=79 350 mg N=79 420 mg N=80 Total N=629 Adverse events33415243384548 348 Serious AE4014022215 Lead to drug DC0002*0000 2 Drug related AEs74944679 50 ↑ Lead to drug DC000000000 Injection site rxn2110123111 AST or ALT >3x ULN10000000 1 CPK >5X ULN01110001 4** CV events‡110401108 Death00010000 1 *Both events were reported as non-serious by the investigators. †All 50 were reported as non-serious by the investigator and none led to discontinuation of drug ** All were asymptomatic ‡Acute coronary syndrome, coronary revascularization, TIA, congestive heart failure requiring hospitalization, or death

14. An Academic Research Organization of Brigham and Women’s Hospital and Harvard Medical School Summary & Conclusion In patients with hypercholesterolemia on a stable regimen of statin ± ezetimibe, SC AMG 145 for 12 weeks: Reduced LDL-C (ultracentrifugation) by up to 66% at the end of the dosing interval compared to placebo Reduced calculated LDL-C by up to 85% 1 week post dose Reduced total and non-HDL cholesterol, apo B, TC/HDL, Apo B/A1 Well-tolerated with no dose-related increase in adverse events PCSK9 inhibition with AMG 145 offers a new paradigm for LDL-C reduction that warrants testing in a large, phase III cardiovascular outcomes trial

15. THE LANCET Lancet 2012:380 (online first). Available on line at www.thelancet.com Thank you to our investigators and coordinators, data safety committee members, clinical endpoint committee members, core laboratories, operational teams, monitors, and sponsor