RP Giugliano MD, SM; MT Roe, MD, MHS; RA Harrington MD; CM Gibson, MS, MD; U Zeymer, MD; F Van de Werf, MD, PhD; KW Baran, MD; HP Hobbach, MD; LH Woodlief, MS; KL Hannan, BA; S Greenberg, PhD; J Miller, BS; MM Kitt, MD; J Strony, MD; CH McCabe, BS; E Braunwald, MD; RM Califf, MD on behalf of the INTEGRITI Investigators Boston, MA; Durham, NC; Kassel and Siegen, Germany; Leuven, Belgium; St. Paul, MN; South San Francisco, CA; and Kenilworth, NJ Combination Reperfusion Therapy With Eptifibatide and Reduced-Dose Tenecteplase for ST-Elevation Myocardial Infarction: Results from the Integrilin and Tenecteplase in Acute Myocardial Infarction (INTEGRITI) Phase II Angiographic Trial

Prior Studies Combining Lytic + GP IIb/IIIa Inhibitors Angiographic Trials –Higher rates of early TIMI 3 flow –Reduced time to restoration of flow –Improved myocardial reperfusion –Less reocclusion / re-elevation of ST Large Clinical Trials –No difference in mortality –Less reinfarction, recurrent ischemia –More bleeding Angiographic Trials –Higher rates of early TIMI 3 flow –Reduced time to restoration of flow –Improved myocardial reperfusion –Less reocclusion / re-elevation of ST Large Clinical Trials –No difference in mortality –Less reinfarction, recurrent ischemia –More bleeding

PRIMARY OBJECTIVE and KEY ENTRY CRITERIA PRIMARY OBJECTIVE To Identify optimal dose of eptifibatide +  TNK: l TIMI 3 flow at 60 minutes l Favorable safety profile PRIMARY OBJECTIVE To Identify optimal dose of eptifibatide +  TNK: l TIMI 3 flow at 60 minutes l Favorable safety profile Typical Entry Criteria for Angio MI Trial ST  MI ST  MI Sx onset < 6 h Sx onset < 6 h Age < 76 yrs Age < 76 yrs Lytic eligible Lytic eligible No prior CABG No prior CABG No cardiogenic shock No cardiogenic shock

Dose Finding Aspirin ST , lytic eligible, < 6 h Reduced dose heparin 50% TNK-tPA (0.25 mg/kg) + eptifibatide (180 / 2 / 90) 75% TNK-tPA (0.375 mg/kg) + eptifibatide (180 / 2 / 90) Part 1 2 TNK doses 50% TNK-tPA (0.25 mg/kg) + eptifibatide (180 / 2 / 90) 50% TNK-tPA (0.25 mg/kg) + eptifibatide (180 / 2 / 180) Part 2 2 EPT doses

ST , lytic eligible, < 6 h Control Dose Confirmation 60 minutes: TIMI flow / ST-Segment Resolution Full-dose TNK-tPA (0.5 mg/kg) ACC/AHA Guideline Heparin (60 U/kg; 12 U/kg/h) No Eptifibatide Experimental Low-dose Heparin (60 U/kg ; 7 U/kg/h) Eptifibatide: Bolus: #1 = 180  g/kg; Infusion: 2.0  g/kg/m Bolus #2 = 180  g/kg 50% TNK-tPA Aspirin

Baseline Characteristics N 418 Median Age 58 years Male 77% Anterior MI 33% Median Time Sx onset ->Tx 2.9 hours Prior MI 13% Diabetes 14% Killip > II 13%

60 Minute Flow (Core lab) Dose Finding % pts PART 1: 2 doses TNK PART 2: 2 doses EPT 50% TNK + ept 180/90 50% TNK + ept 180/90 75% TNK + ept 180/90 50% TNK + ept 180/ TIMI 2 TIMI 3 P=0.02 N=

60 Minute Flow (Core lab) Dose Confirmation % pts Dose Confirmation Dose Finding + Confirmation TNKTNK 50% TNK + ept 180/180 50% TNK + ept 180/180 N: % TNK + ept 180/180 50% TNK + ept 180/180 P=0.15 P=0.17

cTFC in INTEGRITI at 60 m Dose Finding + Dose Conf TNK Eptifibatide N cTFC % pts Median

Median ST-Segment Resolution at 60 min ST res N = % TNK + ept 180/180 Dose Confirmation Dose Find + Conf  TNK 50% TNK + ept 180/180 P=0.08

Myocardial Perfusion Grade 2/3 at 60 min % pts 50% TNK + ept 180/180 50% TNK + ept 180/180 TNK Dose Confirmation Dose Find + Conf N: P= % 50% 54% MPG 3 MPG 2

% pts N: TFG 3 All 3Complete ST Res TMPG Angiographic and ECG Outcomes at 60 min

Hemorrhagic Events Dose Conf DC+DF Dose Conf DC+DF TNK 100% 50% 50% Eptifibatide / /180 # patients TIMI Major, n 3 (3%) 9 (8%) 13 (7%) ICH (2) (0) (1) ICH (2) (0) (1) Spontaneous (0) (3) (4) Spontaneous (0) (3) (4) Instrumented (1) (6) (8) Instrumented (1) (6) (8)

TIMI 3 FLOW - Dose Confirmation SPEED rPA TIMI 14 tPA % pts with TIMI 3 Flow ENTIRE-T23 TNK (UFH) INTEGRITI TNK TIMI 14 rPA Lytic: 60 min90 min Weighted Ave = + 6.6% difference 7581 INTRO-AMI tPA

Summary of INTEGRITI Final Results EPTIFIBATIDE + 50% TNK vs TNK mono 1. Trends towards improved rates of –TIMI 3 epicardial flow and IRA patency –corrected TIMI Frame count –ST resolution –Patent microcirculation 2. Trend towards more major hemorrhage EPTIFIBATIDE + 50% TNK vs TNK mono 1. Trends towards improved rates of –TIMI 3 epicardial flow and IRA patency –corrected TIMI Frame count –ST resolution –Patent microcirculation 2. Trend towards more major hemorrhage

Academic Groups TIMI Study Office Duke Clinical Res Inst Core Laboratories Angio - CM Gibson ECG - DA Morrow Cont ECG - M Krucoff Sponsors COR Therapeutics, Inc Schering-Plough Research Institute Study Organization US 39 Canada 1 Belgium 3 7 Countries, 67 Hospitals Germany 13 France 7 Nether. 3 S Afr 1