TUESDAY 19TH OCTOBER2010 CATH LAB PRESENTATION

TAO /ACS study STUDY NUMBER: EFC6204 Randomized, double-blind, triple-dummy trial to compare the efficacy of otamixaban with Unfractionated Heparin + eptifibatide, in patients with Unstable angina/Non ST segment Elevation Myocardial infarction scheduled to undergo an early invasive strategy

3 Inclusion Criteria Patient with non-STE-ACS with ischemic discomfort (ie, ischemic chest pain or equivalent) at rest ≥10 minutes within 24 hours of randomization and One of the two following criteria of non-ST elevation ACS: New ST-segment depression ≥0.1 mV (≥1 mm), or transient (<30 minutes) ST- segment elevation ≥0.1 mV (≥1 mm) in at least 2 contiguous leads on the ECG, OR Elevation of cardiac biomarkers within 24 hours of randomization, defined as elevated troponin T, troponin I, or CK-MB level above upper limit of normal and Planned to have a coronary angiography (followed, when indicated, by PCI) as early as possible (after at least 2 hours of treatment with study drug) and within 36 hours (at the latest on Day 3, if justified) and Informed consent obtained in writing

4 Exclusion Criteria Related to prior or concomitant treatments Patient having received anticoagulant treatment (including UFH, LMWH, or bivalirudin) for more than 24 hours prior to randomization or who have been treated by fondaparinux or abciximab Inability to discontinue current anticoagulation in order to transition to Investigational Products according to the specified transition timing Patients who can not be treated by aspirin and clopidogrel (or any other oral antiplatelet agent) according to their local labeling

Exclusion criteria Related to eptifibatide Patient who cannot be treated with eptifibatide according to the national labeling Related to unfractionated heparin Patient who cannot be treated with UFH according to the national labeling Related to otamixaban Allergy to otamixaban

Otamixaban Characteristics Specific Factor Xa inhibitor  Proximal inhibition of the coagulation cascade Small molecule, direct inhibitor  Allows for inhibition of clot-bound factor Xa, which is inaccessible to large molecule and indirect inhibitors Reversible, short initial half-life (20-30 mins)  Given as wt-based IV bolus & infusion  Eliminated via feces/bile, no significant renal elimination  Permits rapid initiation & d/c of anticoagulation

Discontinued prior anticoagulants R IVR S Signature of ICF Preparation of study drugs Administration of study drugs Transition Timing for Discontinuation of Previous Anticoagulation Delay between discontinuation open label anticoagulant and study drug:  UFH or bivaluridin minutes (unless aPTT < 50 sec)  LMWH 8 hours since last injection  Tirofiban or eptifibatide 4 hours

8 Triple Dummy Design Randomized to Otamixaban Otamixaban Placebo UFH Placebo Eptifibatide Randomized to UFH + Eptifibatide Placebo Otamixaban UFHEptifibatide Otamixaban/pbo ; UFH/pbo ; and Eptifibatide/pbo prepared by Pharmacist or Investigator using study kits PCI start

Study Drug Administration A9

If no PCI is performed Drug A Drug B: monitoring of APTT (blinded) pre PCI and during PCI: target 1.5-2XN Randomization ASA, Clopi, other ADP receptor antagonist As per label and guidelines CK MB and Troponin T (or I) : at 8h and 16h post Randomization Per investigator’s judgment Up to Day 4 maximum

PCI Drug A Drug B: monitoring of ACT (blinded) pre PCI and during PCI: target > 200s Pre PCIPCI start ASA, Clopi, other ADP receptor antagonist As per label and guidelines CK MB and Troponin T (or I) : Pre PCI and at 2h, 8h and 16h post PCI PCI end ACT for sheath removal After PCI Drug C started immediately before PCI start and continued up to 18-24h post PCI or until hospital discharge Within 36h (if possible,  2 hrs after start of study meds), max Day 3 if justified Open-label UFH flushes per operator Bail-out eptifibatide if severe Recurrent Ischemia or thromb PCI complication

TAO /ACS study Flushing of the catheter with UF :  During coronary angiography/PCI: the catheters must be flushed with heparinized serum saline. Thrombotic complications during PCI/angio:  Consider bailout with eptifibatide (+ check ACT and give additional Drug B bolus if <225s)

BLINDED ACT / Hemochron Device  Direct Venous Blood Sample Cannot use “finger sticks” CAN use “buff caps/heplocks/IV starts” MUST be downstream from study drug infusion site  Consider femoral vein sheath Clinical Challenges