UA/NSTEMI Ranolazine IV to PO Placebo Matched IV/PO RANDOMIZE (1:1) Double-blind Follow-up Q4 mo (Avg 8-12 mo) Holter at enrollment x 7d Follow-up Visits: Day 14, Month 4, Q4 Months Primary Endpoint: CV death, MI or Recurrent Ischemia Final Visit N = ~ 6500 ETT Month 8 MERLIN – TIMI 36 Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes Morrow DA, Am Heart J 2006;1186:1-9

TIMI 37A STEMI within 12h w/ planned 1° PCI INO-1001* IVB x 1 CONTROL IVB x 1 RANDOMIZE (3:1) Single-blind F/U at 14 & 30 days Endpoints/Measures Pharmacokinetics Pharmacodynamics CK-MB, cTn, BNP Death/CHF/dysrhythmia Endpoints/Measures Pharmacokinetics Pharmacodynamics CK-MB, cTn, BNP Death/CHF/dysrhythmia ASAStandard Rx *Dose Escalation Dose #1 x 1 (N = 10) Dose #2 x 1 (N = 10) Dose #3 x 1 (N = 10) N = 40 37A Primary PCI Samples for PK/PD/Biomarkers A Dose Ranging Trial of the Poly (ADP-ribose) Polymerase (PARP) Inhibitor INO-1001 to Reduce Reperfusion Injury After Primary PCI

TITAN Double-blind ACS (STEMI or UA/NSTEMI) & Planned PCI ASA PRASUGREL CLOPIDOGREL 1 o endpoint: CV death, MI, Stroke 2 o endpoints:CV death, MI, Stroke, Re-ischemia CV death, MI, UTVR Median duration of therapy - 12 months N= 13,000 TRITON – TIMI 38 A Comparison of Prasugrel and Clopidogrel in Acute Coronary Syndrome Patients Who Are To Undergo Percutaneous Coronary Intervention Wiviott SD, Am Heart J 2006;152:627-35

TITAN 10,500 Patients with > 2 of the following: 1.  MB or Tn 2. New STD > 1mm 3. Age > 60 Eptifibatide 180/2/180Matching Placebo Angiography > 12 Hrs Later Optional Study Drug in Cath Lab Blinded Placebo / Eptifibatide Primary Endpoint: D/MI/UR/TBO at 96h Secondary Endpoint: D/MI at 30 days n=10,500 EARLY ACS – TIMI 39 Early (<8h) Eptifibatide in Pts with High-Risk ACS Giugliano RP, Am Heart J 2005;149:

ASA + Standard Medical Therapy Simvastatin 40 mg Vytorin 10/40 mg Duration: Minimum 2 1/2 year follow-up (>2955 events) Primary Endpoint: CV Death, MI, Hospital Admission for UA, revascularization (> 30 days after randomization), or Stroke Double-blind Patients stabilized post Acute Coronary Syndrome < 10 days LDL < 125 mg/dL (or < 100 mg/dL if prior statin) N=10,000 Follow-Up Visit Day 30, Every 4 Months IMPROVE IT – TIMI 40 IMProved Reduction of Outcomes: Vytorin Efficacy International Trial

® AZD mg bid (option for 90mg bid) Clopidogrel 300/600mg load: 75mg od V1V2V3V4V5V6 End of Treatment Follow- up Onset of chest pain <24h 1 mo 3 mo 6 mo 6 to 12 mo EOT + 1 mo * N=9000 per treatment arm 9 mo 12 mo PLATO – TIMI 41 A Study of PLATelet inhibition and Patient Outcomes

42 Mod-to-High Risk NSTE ACS w/ Planned Early Inv Strategy Otamix Group 1 (n=450) Otamix Group 1 (n=450) R Aspirin + clopidogrel Bail-out eptifibatide in otamixaban groups if rec. ischemia or thrombotic complic. during PCI Study drug until end of PCI, as clin. indicated, until Day 4 or hospital d/c, whichever comes first 1° EP: Death, MI, Urgent Revasc, Bail-out IIb/IIIa thru 7 d Coronary angiography  PCI (Day 1-3) Otamix Group 2 (n=450) Otamix Group 2 (n=450) Otamix Group 4 (n=450) Otamix Group 4 (n=450) Otamix Group 5 (n=450) Otamix Group 5 (n=450) Otamix Group 3 (n=450) Otamix Group 3 (n=450) UFH + Eptifi. (n=450) UFH + Eptifi. (n=450) at randomization Day 30 Visit, Day 90 Tel f/up, Day 180 Tel. f/up SEPIA-ACS 1 – TIMI 42 Dose Ranging Study of Otomixaban - a Novel, Intravenous, Direct Xa Inhibitor

Standard Medical Therapy Patients post ACS with ↑ natriuretic peptides N= wks End of Study NT- proBNP Blinded Therapy Dose up-titration over 2 wks Aliskiren Placebo Valsartan Combo Rx Dose up-titration of 2 nd agent over 2 wks (placebo in 3 arms and active in Combo arm) NT- proBNP AVANT GARDE – TIMI 43 Aliskiren and Valsartan to reduce NT-proBNP via renin-angiotensin-aldosterone-system blockade 4 wks

Planned Elective PCI Aggregometry and Biomarkers ASA Clopidogrel-naive Clopidogrel 600 mg Prasugrel 60 mg 0.5,hour post-LD Aggregometry and biomarkers Diagnostic catheterization anatomy suitable for PCI Post cath aggregometry n < 180 n = 100 PCI Post-PCI aggregometry, biomarkers Primary Endpoint: Mean IPA (6h) in all treated subjects Additional Platelet Measures, Myonecrosis, Inflammation Planned GP IIb/IIIa prohibited PRINCIPLE – TIMI 44 Phase I: Loading

Prasugrel 10 mg x 14d 14 d clinical events, biomarkers, aggregometry, CROSSOVER Clopidogrel 150 mg x 14d Prasugrel 10 mg x 14d 30 d clinical events, biomarkers, aggregometry Primary Endpoint: Mean IPA (2&4 wks) in all treated subjects Additional Platelet Measures, Inflammation, Clinical Events PCI Clopidogrel 150 mg x 14d Phase II: Maintenance PRINCIPLE – TIMI 44

Enroll within 12 hrs of Angiography Blood Draw for % Platelet Inhibition and Aspirin Responsiveness Day 1 Blood Draw for % Platelet Inhibition Pre-op Day Blood Draw for % Platelet Inhibition Day of CABG Obtain Data from Procedure Post-op Day Follow Course for Complications VERIFY NOW – TIMI 45 Platelet Function Testing for Bleeding Management in Patients Treated with Clopidogrel and Undergoing Coronary Artery Bypass Grafting PRIMARY OUTCOME Correlation of % platelet inhibition immediately prior to surgery to the risk of TIMI major blood loss peri-operatively (fall in hgb > 5 or hct > 15%) Day X Blood Draw for % Platelet Inhibition

Recent ACS Patients Stabilized 1-7 Days Post-Index Event STRATUM 1 STRATUM 2 Primary Endpoint: TIMI Significant Bleeding MD Decision to Treat with Clopidogrel Dose Levels 5, 10, & 20 mg N ~ 1,350 RIVA QD 3 Dose Levels RIVA QD 3 Dose Levels PLACEBO PLACEBO RIVA BID 3 Dose Levels RIVA BID 3 Dose Levels RIVA QD 3 Dose Levels RIVA QD 3 Dose Levels PLACEBO PLACEBO RIVA BID 3 Dose Levels RIVA BID 3 Dose Levels Treat for 6 Months YESNO ATLAS – TIMI 46 STAGE 1: Dose Escalation RIVA = Rivaroxaban

Recent ACS Patients Stabilized 1-7 Days Post-Index Event STRATUM 1 STRATUM 2 Primary Endpoint: Death, MI, Stroke, or Recurrent Ischemia Requiring Revascularization MD Decision to Treat with Clopidogrel N ~ 2,100 RIVA QD RIVA QD PLACEBO PLACEBO RIVA BID RIVA BID RIVA QD RIVA QD PLACEBO PLACEBO RIVA BID RIVA BID Treat for 6 Months NOYES ATLAS – TIMI 46 STAGE 2: Dose Confirmation RIVA = Rivaroxaban

Protocol Design STEMI within 6 hours Eligible for primary PCI ASA mg; Clopidogrel mg UFH; IV Eptifibatide (double bolus and infusion) IC Eptifibatide 90  g/Kg bolus IC Eptifibatide 90  g/Kg bolus N=180 Randomize Baseline angiography Advance wire and balloon without crossing the lesion IC saline bolus IC saline bolus Angiography (assess stenosis, flow and perfusion) PCI Primary Endpoint Improvement in % diameter stenosis pre and post Eptifibatide Primary Endpoint Improvement in % diameter stenosis pre and post Eptifibatide Secondary Endpoint Improvement in pre and post Eptifibatide CTFC Secondary Endpoint Improvement in pre and post Eptifibatide CTFCAngiography (assess epicardial flow and myocardial perfusion) 2 : 1 Intracoronary Treatment with Integrilin To Improve Angiographic Outcomes IC-TITAN – TIMI 47