INTRO AMI. INTEGRILIN AND. REDUCED DOSE. OF THROMBOLYTIC IN. ACUTE INTRO AMI INTEGRILIN AND REDUCED DOSE OF THROMBOLYTIC IN ACUTE MYOCARDIAL INFARCTION

INTRO AMI Study Design Multi-national, multi-center enrollment Open-label, dose finding phase Sequential dose-escalation design Confirmation phase (planned)

Purpose and Primary Endpoints Integrilin INTRO AMI Purpose and Primary Endpoints To evaluate the incidence of TIMI 3 flow at 60 minutes To evaluate the incidence of TIMI bleeding during acute hospitalization

Integrilin INTRO AMI Other Endpoints: ST segment resolution at 3 hours TIMI frame count in IRA TIMI flow at 90 minutes, if available

Integrilin INTRO AMI Clinical Endpoints Death - cardiovascular or other Reinfarction Stroke (CT or MRI documentation) Hemorrhagic non-hemorrhagic Urgent target vessel revascularization CABG or PTCA, including initial PTCA for TIMI 0-2 flow

INTRO AMI Study Design Acute MI <6 hours duration 60 minute angiography PTCA if clinically indicated 90 minute angiography Rescue PTCA for TIMI 1-2 flow Study drug infusion for 72 hours

INTRO AMI Study Design Heparin 4000 IU IV bolus ASA 325 mg / day 800 IU/hr IV infusion aPTT - 50-70 seconds ASA 325 mg / day PCI at discretion of investigator

Integrilin Intro AMI Study Protocol

Integrilin Intro AMI Patient Enrollment Total Enrolled: 190 Level A (180/1.33) = 35 Level B (180 + 90/1.33) = 37 Level E (180/1.33 + 15/35) = 33 Level F (180 + 90/1.33 +15/35) = 53 Level G (180/2.0 Initial + 15/35) = 32

TIMI Grade 3 Flow at 60 Minutes 33 30 31 30 48 Integrilin bolus 180 180 180 180/90 180/90 Integrilin infusion 1.33 1.33 2.0 1.33 1.33 tPA bolus 25 15 15 25 15 tPA infusion 35 35 35

TIMI Grade 3 Flow at 90 Minutes 33 30 31 30 48 Integrilin bolus 180 180 180 180/90 180/90 Integrilin infusion 1.33 1.33 2.0 1.33 1.33 tPA bolus 25 15 15 25 15 tPA infusion 35 35 35

Bleeding events Site adjudication Level A (N=35) Moderate - 2 pts. Severe - 3 pts. Level E (N = 33) Moderate - 5 Severe - 2 Level G (N = 32) Moderate - 1 pts. Severe - 0 pts Level B (N=35) Moderate - 6 pts. Severe - 2 pts. Level F (N = 53) Moderate - 5 Severe - 0

Preliminary Results - OVERALL TIMI Major Bleeding Events Single bolus Integrilin Level A = 3/35 CABG related = 1 Level E = 3/33 Level G = 6/32 CABG related = 2 12/100 4 CABG related Double bolus Integrilin Level B = 6/35 CABG related = 3 Level F = 7/53 CABG related = 4 13/88 7 CABG related

Integrilin INTRO AMI Summary and Conclusions Efficacy The combination of Integrilin and reduced dose rt-PA achieves enhanced TIMI 3 flow at 60 and 90 minutes. Greatest increase in TIMI 3 flow results from a double bolus of Integrilin and with half-dose rt-PA (15/35mg). Safety There appears to be a clinically acceptable increase in bleeding related primarily to femoral access site.

Integrilin INTRO AMI Conclusions The use of Integrilin in combination with low dose fibrinolytics is a promising therapeutic strategy in acute myocardial infarction. Large scale clinical-outcome studies will be required to further assess the benefits of this strategy.