STABILITY Stabilization of Atherosclerotic plaque By Initiation of darapladib TherapY. Harvey D White on behalf of The STABILITY Investigators

STABILITY Stabilization of Atherosclerotic plaque By Initiation of darapladib TherapY Harvey D White on behalf of The STABILITY Investigators

Lipoprotein- associated Phospholipase A 2 (Lp-PLA 2 ) activity: Background native LDL carrier of Lp-PLA 2 Lp-PLA 2 Leukocyte Lumen Atheroma Intima Lp-PLA 2 Sustained Inflammation Necrotic Core Expansion Oxidized LDL substrate for Lp-PLA 2 Macphee, Biochem J 1999; Zalewski and Macphee, ATVB 2005; Shi Atherosclerosis 2007; Kolodgie, ATVB 2006 2

Contrasting histopathological characteristics of a stable versus a vulnerable or ruptured plaque Corson et al. Am J Card 2008;101(Suppl):41F-50F Thick Fibrous Cap Thin Fibrous Cap Modest Lipid Pool Large Lipid Pool Lumen Lumen Lp-PLA 2 Lp-PLA 2 Stable Plaque Low Lp-PLA 2 content (dark staining) May have significant stenosis Thick fibrous cap / high collagen content Modest lipid pool Few inflammatory cells Vulnerable or ruptured Plaque High Lp-PLA 2 content (dark staining) May have minimal stenosis Thin fibrous cap / low collagen content Large lipid pool Many inflammatory cells

Lp-PLA 2 and CHD risk: The Lp-PLA 2 Studies Collaboration; compared with conventional risk factors 79,036 participants from 32 prospective studies RR (95% CI) per 1 - SD higher Lp-PLA 2 activity 1.11 (1.05-1.16) Systolic blood pressure Smoking status * n - HDL cholesterol HDL cholesterol 1.10 (1.00-1.21) 1.34 (1.19-1.51) 1.10 (1.02-1.18) 1.15 (1.06-1.24).9 1 1.1 1.2 1.3 1.4 1.5 1.6 Adjusted for non-lipid and lipid conventional risk factors LSC Lancet 2010; 375:1536 4

STABILITY: Background Association studies EPIDEMIOLOGY Higher Lp-PLA 2 levels predict CV events GENETICS Deficiency in Lp-PLA 2 due to null allele results in decreased CHD PATHOLOGY Up-regulation of Lp- PLA 2 in vulnerable plaques Darapladib is a selective oral inhibitor that decreases Lp-PLA 2 by 60% Intervention with darapladib PRECLINICAL Reduces Lp-PLA 2 in plaque and necrotic core area (pig) HUMAN ATHEROMA Reduces carotid plaque Lp-PLA 2 activity CORONARY IMAGING IBIS-2 Halts progression of coronary artery necrotic plaque core volume

STABILITY Trial Stabilization of Atherosclerotic plaque By Initiation of darapladib TherapY Patients with chronic CHD (prior MI >1 mth, prior coronary revascularization, multivessel CAD) Enrichment criteria: 60 years of age, diabetes mellitus, low HDL, current smoking, significant renal dysfunction, polyvascular disease 15,828 patients randomized Darapladib 160mg Placebo Optimized guideline-mandated treatment median follow-up 3.7 years, 1588 events Primary endpoint: composite of CV death, MI, stroke Secondary endpoints: major coronary events, total coronary events 6

Key Exclusion Criteria Planned coronary revascularization Current liver disease or severe renal impairment Current severe heart failure Poorly controlled hypertension Severe asthma that is poorly controlled History of anaphylaxis, anaphylactoid reactions, or severe allergic responses Concomitant cytochrome P-450 inhibitor use Lp-PLA 2 activity 20.0 nmol/min/ml 7

Recruitment into STABILITY Trial (N=15,828) rth America (25%) USA 3102 Canada 780 Mexico 141 Western Europe (22%) Belgium 202 Denmark 102 France 250 Greece 187 Germany 1089 Italy 256 Netherlands 444 rway 113 Spain 474 Sweden 299 UK 184 Eastern Europe (22%) Bulgaria 222 Cz Republic 774 Estonia 77 Hungary 410 Poland 510 Romania 411 Russia 654 Slovakia 120 Ukraine 353 E & SE Asia China 369 Korea 503 Hong Kong 117 Taiwan 200 Japan 318 South America India 398 Pakistan 250 Thailand 207 Philippines 219 Australia 306 New Zealand 202 Argentina 542 Brazil 384 Chile 195 Peru 78 South Africa 386 Asia-Pacific/Latina (31%) 8

Demographics Placebo (N=7904) Darapladib (N=7924) Age: Median in years 65.0 65.0 <65 years (%) 49% 48% 65-74 years (%) 37% 38% >=75 years (%) 14% 14% Female (%) 19% 18% Race or Ethnic Group (%) White 78% 79% Black 2% 2% Central/South/South East Asian 8% 7% East Asian/Japanese 10% 10% Other 2% 2% 9

Chronic Coronary Heart Disease Qualifying Diagnosis Placebo (N=7904) Darapladib (N=7924) Prior MI 59% 59% Coronary revascularization 75% 75% PCI 50% 50% CABG 33% 33% Multi-vessel CAD 15% 15% 10

Enrichment Criteria Placebo (N=7904) Darapladib (N=7924) Age 60 years 73% 73% Diabetes req. pharmacotherapy 34% 34% HDL < 40 mg/dl (1.03 mmol/l) 35% 33% Current smoker or former smoker within 3 months ( 5 cigs/day) Significant renal dysfunction (egfr 30 to 59 ml/min/1.73 m 2 or urine ACR 3 mg albumin/g creatinine) Polyvascular disease (cerebrovascular disease or peripheral arterial disease) 21% 20% 30% 30% 15% 15% 11

Baseline LDL LDL-C (mg/dl) Placebo (N=7904) Darapladib (N=7924) Median (Interquartile range) 80 (63 101) 80 (63 101) <70 (<1.8mmol/L) 36% 35% 70 100 (1.8-2.6 mmol/l) 38% 39% 100 ( 2.6 mmol/l) 26% 26% 12

Concomitant Medication Usage Time Point Placebo (N=7904) Darapladib (N=7924) Aspirin Baseline Study end 93% 91% 92% 90% Statins Baseline Study end 97% 96% 97% 96% Beta-Blockers Baseline Study end 79% 79% 79% 78% P2Y12 Inhibitors Baseline Study end 34% 27% 34% 27% ACE inhibitor Baseline Study end 56% 54% 57% 54% Angiotensin II receptor blocker Baseline Study end 23% 27% 22% 26% 13

Standard of Care Measures LDL-Cholesterol (mg/dl) Time Point Placebo (N=7890) Darapladib (N=7912) Median (Interquartile range) Baseline Study end 80 (63 101) 79 (62 100) 80 (63 101) 78 (61 99) Blood Pressure (mmhg) Mean Baseline Study end 132/79 mmhg 131/77 mmhg 132/79 mmhg 132/77 mmhg 14

Subject Status Overview Placebo (N=7904) Darapladib (N=7924) IP Discontinuation 26.8% 32.7% Study Withdrawal 273 (3.5%) 278 (3.5%) Complete CV Endpoint Follow-up 7628 (96.5%) 7641 (96.4%) Complete Vital Status Follow-up 7845 (99.3%) 7877 (99.4%) Median follow-up time was 3.7 years for both treatment groups Adherence (> 80%) was 91.3% for placebo and 89.3% for darapladib 15

Primary Endpoint: Time to First Occurrence CV Death, MI, Stroke HR (95% CI)= 0.94 (0.85, 1.03) P-value = 0.199 Placebo events = 819 Darapladib 160mg events = 769 16

Baseline Status Baseline Status Baseline Status Multivessel CHD: Age 60: Darapladib 1.03 (0.82, 1.29) 147 (12.3%) Subgroup Analyses for CV Death, 0.91 (0.80, 1.03) MI, 0.422 477 Stroke (9.1%) Diabetes req. pharmacotherapy: Gender: Male Female HDL-C level <40 mg/dl: Race collapsed: White n-white Favors Smoker: Prior myocardial infarction: Darapladib Age 60: Renal dysfunction: Prior coronary revascularization: Gender: Male Polyvascular Multivessel Disease: CHD: Female Race collapsed: White Pre-Study Diabetes CHD req. Event: pharmacotherapy: n-white Recent Prior myocardial infarction: Remote Statin HDL-C use: level <40 mg/dl: Prior coronary revascularization: Smoker: egfr: <60 ml/min/1.73m 2 Multivessel CHD: 60 ml/min/1.73m 2 Renal dysfunction: Diabetes Baseline req. LDL: pharmacotherapy: <70 mg/dl 70 - <100 mg/dl Polyvascular Disease: 100 mg/dl HDL-C level <40 mg/dl: hs C-reactive protein: <1.0 mg/l Pre-Study CHD Event: Smoker: 1.0-3.0 mg/l Recent >3.0 mg/l Remote Renal Region: Statin dysfunction: use: rth America Eastern Europe Western Europe Polyvascular egfr: Disease: <60 South ml/min/1.73m America 2 60Asia/Pacific ml/min/1.73m 2 Placebo Favors Placebo HR (95% CI) P-value Placebo Darapladib 0.92 (0.82, 1.03) 0.395 672 (10.0%) 620 (9.2%) 0.98 (0.80, 1.20) 0.613 191 (8.8%) 149 (12.4%) 182 (8.6% 0.92 (0.82, 1.03) 628 (10.9%) 587 (10.1% 435 (8.3%) 0.980.92 (0.85, (0.83, 1.14) 1.03) 0.500 342 (12.7%) 670 (10.5%) 334 (12.5%) 624 (9.7% 1.01 (0.80, 1.26) 149 (9.9%) 145 (9.9% 0.94 (0.83, 1.07) 0.951 502 (9.8%) 486 (9.2%) 0.930.90 (0.80, (0.80, 1.10) 1.00) 0.077 316 (11.3%) 675 (10.9%) 281 (10.6%) 610 (9.8% 1.13 (0.90, 1.41) Interaction Number 144 (8.3%) of Events 159 (%) (9.4% 0.99 (0.89, 1.11) 0.044 619 (10.0%) 625 (9.9%) 0.77 HR 0.87 (0.62, (95%(0.74, CI) 0.96) 1.03) P-value 0.295 192 Placebo (11.6%) 314 (9.6%) 140 Darapladib 274 (8.9%) (8.4% 0.98 0.98 (0.80, (0.86, 1.20) 1.10) 0.613 191505 (8.8%) (10.9%) 182495 (8.6%) (10.6% 0.87 (0.77, 0.99) 0.104 482 (8.7%) 420 (7.6%) 1.03 0.920.95 (0.89, (0.82, (0.80, 1.19) 1.03) 1.14) 0.837 337 628 (14.2%) 244 (10.9%) (12.2%) 349 587 (14.5%) 229 (10.1%) (11.6% 0.92 0.93 (0.83, (0.83, 1.03) 1.05) 0.500 670 575 (10.5%) (9.7%) 624 540 (9.7%) (9.1% 0.93 1.01 (0.83, (0.80, 1.04) 1.26) 0.796 626 149 (9.3%) (9.9%) 584 145 (8.7%) 0.92 (0.82, 1.03) 0.395 672 (10.0%) 620 (9.9%) (9.2% 0.96 0.901.03 (0.78, (0.80, (0.82, 1.17) 1.00) 1.29) 193 (16.3%) 0.077 675147 (10.9%) (12.3%) 185 (15.6%) 610149 (9.8%) (12.4% 0.88 1.130.91 (0.72, (0.90, (0.80, 1.08) 1.41) 1.03) 0.4810.422 194 144 (10.2%) 477 (8.3%) (9.1%) 173 159435 (9.1%) (9.4%) (8.3% 0.96 0.87 0.98 (0.86, (0.74, (0.85, 1.07) 1.03) 1.14) 0.295 623 314 (10.4%) 342 (9.6%) (12.7%) 596 274 334 (9.9%) (8.4%) (12.5% 0.79 0.980.94 (0.46, (0.86, (0.83, 1.38) 1.10) 1.07) 0.5440.951 505 29 (13.0%) 502 (10.9%) (9.8%) 495 22 (10.7%) 486 (10.6%) (9.2% 0.94 0.950.93 (0.85, (0.80, (0.80, 1.04) 1.14) 1.10) 0.837 790 244 (10.3%) 316 (12.2%) (11.3%) 747 229281 (11.6%) (9.7%) (10.6% 0.930.99 (0.83, (0.89, 1.05) 1.11) 0.044 575619 (9.7%) (10.0%) 540625 (9.1%) (9.9% 0.90 (0.73, 1.10) 0.575 191 (17.0%) 0.96 0.92 0.77 (0.86, (0.82, (0.62, 1.07) 1.03) 0.96) 0.395 625 672 192 (10.0%) (11.6%) 165 (15.2%) (9.2%) 620 140 604 (8.9%) (9.2%) (8.9% 1.030.87 (0.82, (0.77, 1.29) 0.99) 0.104 147482 (12.3%) (8.7%) 149420 (12.4%) (7.6% 1.03 0.91 1.03 (0.87, (0.80, (0.89, 1.23) 1.03) 1.19) 0.238 0.422 245 477 337 (8.7%) (9.1%) (14.2%) 251 435 349 (9.0%) (8.3%) (14.5% 0.95 0.98 (0.81, (0.85, 1.12) 1.14) 291 342 (12.7%) (9.6%) 278 334 (12.5%) (9.1%) 0.840.93 (0.71, (0.83, 1.00) 1.04) 0.796 281 (13.7%) 626 (9.3%) 240 (11.6%) 584 (8.7% 0.940.96 (0.83, (0.78, 1.07) 1.17) 0.951 502193 (9.8%) (16.3%) 486185 (9.2%) (15.6% 1.00 0.93 (0.83, (0.80, 1.22) 1.10) 0.604 209 316 (11.3%) (7.6%) 209 281 (10.6%) (7.6%) 0.890.88 0.99 (0.75, (0.72, (0.89, 1.05) 1.08) 0.481 1.11) 0.044 283 619 (10.8%) 194 (10.2%) (10.0%) 253 173 625 (9.7%) (9.1% (9.9%) 0.900.96 0.77 (0.75, (0.86, (0.62, 1.08) 1.07) 0.96) 249 192 (13.6%) 623 (10.4%) (11.6%) 225 140 (12.2%) 596 (9.9% (8.9%) 0.90 0.870.79 (0.74, (0.77, (0.46, 1.09) 0.99) 1.38) 0.863 0.104 0.544 213 482 (10.6%) 29 (8.7%) (13.0%) 190 420 (9.5%) 22 (7.6%) (10.7% 0.94 1.030.94 (0.77, (0.89, (0.85, 1.15) 1.19) 1.04) 193 337 (10.9%) 790 (14.2%) (10.3%) 181 349 (10.2%) 747 (14.5%) (9.7% 0.89 (0.73, 1.09) 207 (10.5%) 187 (9.3%) 1.02 0.930.90 (0.74, (0.83, (0.73, 1.41) 1.04) 1.10) 0.796 0.575 626 73 (12.2%) 191 (9.3%) (17.0%) 584 74 (12.3%) 165 (8.7%) (15.2% 1.03 0.96 0.96 (0.81, (0.78, (0.86, 1.31) 1.17) 1.07) 133 193625 (16.3%) (8.6%) (9.2%) 137 185604 (15.6%) (8.9%) (8.9% Pre-Study Baseline CHD LDL: Event: Recent <70 mg/dl 0.881.03 (0.72, (0.87, 1.08) 1.23) 0.481 0.238 194245 (10.2%) (8.7%) 173251 (9.1%) (9.0% 70 - <100 Remote mg/dl 0.25 0.50 1.00 2.00 4.00 0.960.95 (0.86, (0.81, 1.07) 1.12) 623291 (10.4%) (9.6%) 596278 (9.9%) (9.1% 100 mg/dl Hazard Ratio 0.84 (0.71, 1.00) 281 (13.7%) 240 (11.6% Statin use: 0.79 (0.46, 1.38) 0.544 29 (13.0%) 22 (10.7%) hs C-reactive protein: <1.0 mg/l 0.941.00 (0.85, (0.83, 1.04) 1.22) 0.604 790209 (10.3%) (7.6%) 747209 (9.7%) (7.6% 1.0-3.0 mg/l 0.89 (0.75, 1.05) 283 (10.8%) 253 (9.7% egfr: <60 ml/min/1.73m >3.0 mg/l 2 0.90 0.90 (0.73, (0.75, 1.10) 1.08) 0.575 191249 (17.0%) (13.6%) 165225 (15.2%) (12.2% Region: 60 ml/min/1.73m rth America 2 0.96 (0.86, 1.07) 625 (9.2%) 604 (8.9%) 0.90 (0.74, 1.09) 0.863 213 (10.6%) 190 (9.5% Baseline LDL: Eastern <70 mg/dl Europe 17 1.030.94 (0.87, (0.77, 1.23) 1.15) 0.238 245193 (8.7%) (10.9%) 251181 (9.0%) (10.2%

Baseline Status Baseline Status Baseline Status Subgroup 0.94 Analyses for CV Death, 0.93 (0.83, (0.80, 1.07) 1.10) 0.951 502 (9.8%) MI, Stroke 316 (11.3%) HDL-C Age level 60: <40 mg/dl: Smoker: Gender: Renal Race dysfunction: collapsed: Male Female White n-white Darapladib 18 Placebo 0.98 (0.85, HR (95% 1.14) CI) P-value 342 (12.7%) Placebo334 (12.5%) Darapladib 0.98 (0.80, 1.20) 0.613 191 (8.8%) 486182 (9.2%) (8.6% 0.92 (0.82, 1.03) 628 (10.9%) 281587 (10.6%) (10.1% 0.990.92 (0.89, (0.83, 1.11) 1.03) 0.044 0.500 619670 (10.0%) (10.5%) 625624 (9.9%) (9.7% 0.771.01 (0.62, (0.80, 0.96) 1.26) 192149 (11.6%) (9.9%) 140145 (8.9%) (9.9% 0.870.90 (0.77, (0.80, 0.99) 1.00) 0.104 0.077 482675 (8.7%) (10.9%) 420610 (7.6%) (9.8% 1.031.13 (0.89, (0.90, 1.19) 1.41) 337144 (14.2%) (8.3%) 349159 (14.5%) (9.4% Polyvascular Prior myocardial Disease: infarction: Favors Favors 0.930.87 (0.83, (0.74, 1.04) 1.03) 0.796 0.295 626314 (9.3%) (9.6%) 584274 (8.7%) (8.4% 0.960.98 (0.78, (0.86, 1.17) 1.10) Interaction Number 193505 (16.3%) (10.9%) of Events 185495 (15.6%) (10.6% (%) Darapladib Placebo HR (95% CI) P-value Placebo Darapladib Prior coronary revascularization: 0.95 (0.80, 1.14) 0.837 244 (12.2%) 229 (11.6% Age Pre-Study 60: CHD Event: Recent 0.98 0.88 0.93 (0.72, (0.80, (0.83, 1.08) 1.20) 1.05) 0.481 0.613 194 191 575 (10.2%) (8.8%) (9.7%) 173 182 540 (9.1%) (8.6%) (9.1% Remote 0.92 0.96 (0.86, (0.82, 1.07) 1.03) 623 628 (10.4%) (10.9%) 596 587 (10.1%) (9.9%) Multivessel CHD: 0.92 (0.82, 1.03) 0.395 672 (10.0%) 620 (9.2% Gender: Statin use: Male 0.92 0.791.03 (0.46, (0.83, (0.82, 1.38) 1.03) 1.29) 0.544 0.500 670 29147 (13.0%) (10.5%) (12.3%) 624 22149 (10.7%) (9.7%) (12.4% Female 1.01 0.94 (0.85, (0.80, 1.04) 1.26) 790 149 (10.3%) (9.9%) 747 145 (9.7%) (9.9%) Diabetes req. pharmacotherapy: 0.91 (0.80, 1.03) 0.422 477 (9.1%) 435 (8.3% Race collapsed: White <60 ml/min/1.73m 2 0.90 egfr: 0.900.98 (0.80, (0.73, (0.85, 1.00) 1.10) 1.14) 0.077 675 0.575 191342 (10.9%) (17.0%) (12.7%) 610 165334 (9.8%) (15.2%) (12.5% n-white 1.13 (0.90, 1.41) 144 (8.3%) 159 (9.4%) HDL-C level <40 60mg/dL: ml/min/1.73m 2 0.960.94 (0.86, (0.83, 1.07) 1.07) 0.951 625502 (9.2%) (9.8%) 604486 (8.9%) (9.2% Prior myocardial infarction: 0.870.93 (0.74, (0.80, 1.03) 1.10) 0.295 314316 (9.6%) (11.3%) 274281 (8.4%) (10.6% Baseline LDL: <70 mg/dl 0.98 1.03 (0.87, (0.86, 1.23) 1.10) 0.238 245 505 (10.9%) (8.7%) 251 495 (10.6%) (9.0%) Smoker: 70 - <100 mg/dl 0.99 (0.81, (0.89, 1.12) 1.11) 0.044 291619 (9.6%) (10.0%) 278625 (9.1%) (9.9% Prior coronary revascularization: 100 mg/dl 0.95 0.84 0.77 (0.80, (0.71, (0.62, 1.14) 1.00) 0.96) 0.837 244 281 192 (12.2%) (13.7%) (11.6%) 229 240 140 (11.6%) (11.6%) (8.9% 0.93 (0.83, 1.05) 575 (9.7%) 540 (9.1%) Renal dysfunction: 0.87 (0.77, 0.99) 0.104 482 (8.7%) 420 (7.6% Multivessel hs C-reactive CHD: protein: <1.0 mg/l 0.92 1.001.03 (0.83, (0.82, (0.89, 1.22) 1.03) 1.19) 0.604 0.395 209 672337 (10.0%) (7.6%) (14.2%) 209 620349 (7.6%) (9.2%) (14.5% 1.0-3.0 mg/l 1.03 0.89 (0.75, (0.82, 1.05) 1.29) 283 147 (10.8%) (12.3%) 253 149 (12.4%) (9.7%) Diabetes Polyvascular req. pharmacotherapy: Disease: >3.0 mg/l 0.91 0.900.93 (0.75, (0.80, (0.83, 1.08) 1.03) 1.04) 0.422 0.796 249 477 626 (13.6%) (9.1%) (9.3%) 225 435 584 (12.2%) (8.3%) (8.7% Region: rth America 0.980.96 (0.78, 1.17) 193 (16.3%) 185 (15.6% 0.90 (0.74, (0.85, 1.09) 1.14) 0.863 213 342 (10.6%) (12.7%) 190 334 (12.5%) (9.5%) HDL-C Pre-Study level <40 CHD mg/dl: Event: Eastern Europe Recent 0.94 0.88 (0.77, (0.83, (0.72, 1.15) 1.07) 1.08) 0.951 0.481 193 502194 (10.9%) (9.8%) (10.2%) 181 486173 (10.2%) (9.2%) (9.1% Western Europe Remote 0.93 0.890.96 (0.73, (0.80, (0.86, 1.09) 1.10) 1.07) 207 316623 (10.5%) (11.3%) (10.4%) 187 281596 (10.6%) (9.3%) (9.9% Smoker: South America 1.02 (0.74, 1.41) 73 (12.2%) 74 (12.3%) Statin use: Asia/Pacific 0.99 1.030.79 (0.89, (0.81, (0.46, 1.11) 1.31) 1.38) 0.044 0.544 619 (10.0%) 133 29 (8.6%) (13.0%) 625 137 22 (9.9%) (8.9%) (10.7% 0.77 (0.62, 0.96) 192 (11.6%) 140 (8.9%) 0.94 (0.85, 1.04) 790 (10.3%) 747 (9.7% Renal dysfunction: 0.25 0.50 1.00 2.00 4.00 0.87 (0.77, 0.99) 0.104 482 (8.7%) 420 (7.6%) egfr: <60 ml/min/1.73m 2 1.030.90 (0.89, (0.73, 1.19) 1.10) 0.575 337191 (14.2%) (17.0%) 349165 (14.5%) (15.2% 60 ml/min/1.73m 2 Hazard Ratio 0.96 (0.86, 1.07) 625 (9.2%) 604 (8.9% Polyvascular Disease: 0.93 (0.83, 1.04) 0.796 626 (9.3%) 584 (8.7%) Baseline LDL: <70 mg/dl 0.961.03 (0.78, (0.87, 1.17) 1.23) 0.238 193245 (16.3%) (8.7%) 185251 (15.6%) (9.0% 70 - <100 mg/dl 0.95 (0.81, 1.12) 291 (9.6%) 278 (9.1% Pre-Study CHD Event: 100 Recent mg/dl 0.880.84 (0.72, (0.71, 1.08) 1.00) 0.481 194281 (10.2%) (13.7%) 173240 (9.1%) (11.6% Remote 0.96 (0.86, 1.07) 623 (10.4%) 596 (9.9%) hs C-reactive protein: <1.0 mg/l 1.00 (0.83, 1.22) 0.604 209 (7.6%) 209 (7.6% Statin use: 1.0-3.0 mg/l 0.790.89 (0.46, (0.75, 1.38) 1.05) 0.544 29283 (13.0%) (10.8%) 22253 (10.7%) (9.7% >3.0 mg/l 0.940.90 (0.85, (0.75, 1.04) 1.08) 790249 (10.3%) (13.6%) 747225 (9.7%) (12.2% egfr: Region: <60 ml/min/1.73m rth America 2 60 ml/min/1.73m Eastern Europe 2 0.90 0.90 (0.73, (0.74, 1.10) 1.09) 0.575 0.863 191213 (17.0%) (10.6%) 165190 (15.2%) (9.5% 0.960.94 (0.86, (0.77, 1.07) 1.15) 625193 (9.2%) (10.9%) 604181 (8.9%) (10.2%

Cardiovascular and Mortality Endpoints 19

Time to First Occurrence Major Coronary Events (CHD Death, MI, Urgent Coronary Revascularization) HR (95% CI)= 0.90 (0.82, 1.00) P-value = 0.045 Placebo events = 814 Darapladib 160mg events = 737 20

Time to First Occurrence Total Coronary Events (CHD Death, MI, Any Coronary Revascularization, Hospitalization for Unstable Angina) HR (95% CI)= 0.91 (0.84, 0.98) P-value = 0.019 Placebo events = 1269 Darapladib events = 1159 21

Coronary-Specific Endpoints 1 2 2 1 1 - Component of pre-specified composite, but not a pre-specified endpoint 2 - Component of pre-specified composite, pre-specified as an endpoint of interest 22

Diarrhea/Odor Adverse Events Leading to Study Drug Discontinuation Placebo (N=7890) Darapladib (N=7912) n (%) Rate per 100 PY n (%) Rate per 100 PY Diarrhea 60 (0.8%) 0.21 254 (3%) 0.92 Abnormal feces 5 (<0.1%) 0.02 177 (2%) 0.64 Abnormal skin odor 4 (<0.1%) 0.01 174 (2%) 0.63 Abnormal urine odor 1 (<0.1%) <0.01 113 (1%) 0.40 23

Adverse Events n (%) Placebo (N=7890) Rate per 100 PY n (%) Darapladib (N=7912) Anaphylaxis 7 (<0.1%) 9 (0.1%) 24 Rate per 100 PY Any serious adverse event 3448 (44%) 16.02 3369 (43%) 15.53 Any adverse event leading to study drug discontinuation 1067 (14%) 3.98 1569 (20%) 6.25 Asthma 64 (0.8%) 0.23 43 (0.5%) 0.15 Renal Effects Renal failure 89 (1.1%) 0.32 120 (1.5%) 0.43 egfr (ml/min/1.73m 2 ): Mean (SD) change from baseline at end of treatment period 1.7 (14.4) -0.8 (14.1) Treatment difference (95% CI) -2.5 (-3.0, -2.1) Cancer New cancer 529 (6.7%) 508 (6.4%) Adjudicated new GI cancer 105 (1.3%) 102 (1.3%) Liver Events 52 (0.7%) 54 (0.7%)

Conclusions Darapladib in patients with stable CHD followed for 3.7 years on a background of optimal medical therapy Did not significantly reduce the incidence of the primary composite endpoint of CV death, MI or stroke There was no effect on stroke or total mortality Reduced the prespecified coronary-specific secondary endpoints of major coronary events (1% absolute) and total coronary events (1.5% absolute) with nominal significance (p<0.05) 25

Implications The STABILITY trial is the first large scale randomized global trial to test a novel mechanism of inhibition of inflammation in the atherosclerotic plaque Further analyses of the trial results in subgroups based on biomarkers, including Lp-PLA 2 levels, and genetics will explore if darapladib might be useful in specific patient subsets The STABILITY trial results indicate that darapladib warrants further evaluation in other clinical settings 26

Study Acknowledgements We would like to acknowledge all the study investigators, research staff and study patients, without whom this study would not be possible Sponsored by GlaxoSmithKline 27