1. 1 US Investigator Meeting DIAS-4, Chicago, July 2011 Patient Flow DIAS-3/4

2. US Investigator Meeting DIAS-4, Chicago, July 2011 2 Study Flow Chart BaselineTreatmentFollow up Hours or Days0h (Day 1)0.5-9h12-24h72h7d or discharge30d90d or w/d Visit window±7h±1d±7d±14d Informed consentX In-/exclusion criteriaX Med/Neuro history & social history inc. risk factors X DemographicsX Randomization callX IMP administrationX 72-H safety infoX Clinical examination NIHSSXXXXXX mRSXXXX Physical/Neuro examXX Ht & WtX BP, PRXXXXXXXX TemperatureXXX 12-lead ECGXX

3. US Investigator Meeting DIAS-4, Chicago, July 2011 3 Study Flow Chart BaselineTreatmentFollow up Hours or Days0h (Day 1)0.5-9h12-24h72h7d or discharge30d90d or w/d Visit window±7h±1d±7d±14d Laboratory Assessments HbA1cX Troponin IXX HematologyXXXXXX CoagulationXXXXXX Clinical chemistryXXXXXX PK samplesX Antibody assessmentXXXX UrinalysisXX Pregnancy testX Imaging Assessments Proximal cerebral arteriesX(X) Infarct volumeXX To identify or exclude ICHXX

4. US Investigator Meeting DIAS-4, Chicago, July 2011 4 Study Flow Chart BaselineTreatmentFollow up Hours or Days0h (Day 1)0.5-9h12-24h72h7d or discharge30d90d or w/d Visit window±7h±1d±7d±14d Pharmacoeconomics SF-36XX EuroQOLXX Resource utilizationXX Safety and concomittant treatment Adverse eventXXXXXXXX Concomitant medicationXXXXXXXX Concomitant non-drug therapies XXXXXXXX

5. US Investigator Meeting DIAS-4, Chicago, July 2011 5 Time Window Stroke Onset Time 0 hr IMP 9 hrs Eligibility Clinical assessments Consent Brain imaging IMP preparation Trial data collection & scales completion 3 hrs Recruitment Time Window Triage Laboratory tests

6. US Investigator Meeting DIAS-4, Chicago, July 2011 6 DIAS-3/4 Tool Kit

7. US Investigator Meeting DIAS-4, Chicago, July 2011 7 Standard Stroke Pathway Routine brain imaging, NIHSS, prestroke mRS, PT/INR, aPTT, platelet count, hematocrit, blood glucose done? Grab DIAS-3/4 Toolkit Informed consent DIAS-3/4 & Stroke Pathway DIAS-3/4 Participation Patient seen for acute stroke (A&E, ward, clinic) Triage/clinical assessment rtPA candidate? Onset within 3-8 hrs rtPA protocol Yes No Stroke care Yes No Yes No Yes Eligible for DIAS-3/4?

8. US Investigator Meeting DIAS-4, Chicago, July 2011 8 Standard Stroke Pathway Do PT/INR, aPTT, platelet count, hematocrit, blood glucose, other laboratory tests, EKG (if not yet done) Informed consent DIAS-3/4 & Stroke Pathway DIAS-3/4 Participation Patient seen for acute stroke (A&E, ward, Clinic) Triage/clinical assessment rtPA candidate? Onset within 3-8 hrs rtPA protocol Yes No Stroke care No 1 hour CT/CTA or MRI/MRA IVRS & IMP preparation Data collection & Scales completion Confirm rest of eligibility criteria IMP administration Ineligible

9. US Investigator Meeting DIAS-4, Chicago, July 2011 9 Time 0h IMP 72h BP every 30 min for 6h then every 1h Clinical exams and laboratory assessments Brain image PK X 2 9h Patient Flow after IMP Administration 12h½h24h7d/dc30d90d Adverse events Concomitant medications/non-drug therapies Pharma-eco

10. US Investigator Meeting DIAS-4, Chicago, July 2011 10 Conclusions Easy study – patient management close to normal practice Similar to rtPA in acute stroke setting Longer time window – 3-9 hours Tool kit and worksheets available Single IV bolus of IMP over 1-2 min Potential rate-limiting factors: Brain imaging to document size of stroke and high- grade stenosis/occlusion IMP to be given within 1 hr of completion of scan Careful planning + flexibility

11. US Investigator Meeting DIAS-4, Chicago, July 2011 11 Thank you!!!