1. MIST I & III Studies Andrew J. Dowson Director Headache Services King’s College Hospital London, UK For the MIST investigators

2. Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization listed below. Affiliation/Financial Relationship Company Grant/Research Support NMT Medical Disclosure Statement of Financial Interest

3. MIST I Investigators Cardiologists J De-Giovanni D Hildick-Smith WS Hillis A Khan I Malik L Morrison M Mullen P Wilmshurst Neurologists A Dowson* G Elrington SL Lipscombe K Muir S Nightingale R Peatfield T Rees C Wells DSAEMB H Sievert** E Eeckhout** L Doyal R Kern F Baudet R Taylor L Missault*** *Study chief Investigator ** Chairman of DSAEMB *** Medical monitor

4. Eligible Migraine Patients Contrast Transthoracic Echocardiogram (cTTE) 3 Month Healing Phase PFO Closure with STARFlex ® Sham Procedure MIST I Trial Design 3 Month Analysis Phase aspirin & clopidogrel aspirin & clopidogrel TEE and Randomization Under GA

5. MIST - Outliers Histogram of Total Number of Migraine Headache Days per Month for Each Patient in Analysis Period per Protocol Population Total Number of Migraine Headache Days per Month Number of Patients

6. MIST Study Exploratory Analyses 0 5 10 15 20 25 30 35 40 45 50 % Reduction Implant Sham p<0.027* Total Migraine Headache Days *=2 outliers removed

7. Closure Rate 94% As reported per protocol by implanting cardiologist

8. MIST III Interim Analysis

9. Active Arm Additional 18 month f/u MIST III Trial Design Followed for 6 months Sham Arm Offered PFO Closure with STARFlex® when unblinded Offered PFO Closure with STARFlex® when unblinded Additional 18 month f/u

10. MIST III Demographics ImplantSham # enrolled 5435 Age (mean) 46.246.1 Sex (% female) 89%89% Race (% Caucasian) 98%100% Atrial septal aneurysm 31% Not known

11. MIST III – Headache Days Time (months) Headache Days N 52 52 36 36 40 33

12. MIST III – 50% Responder Rate 3m 6m 9m 12m 15m 18m N 52 52 36 36 40 33

13. MIDAS Total Score Time (months) MIDAS Total Score N 48 46 47 30 27 21 Severe 21+ Moderate 11-20 Mild or infrequent 6-10 Minimal or infrequent 0-5

14. HIT- 6 Total Score Time (months) HIT- 6 Total Score N 48 46 47 45 29 27 21 ≥ 60 – Severe 56-59 Substantial 50-55 Some impact < 50 – Little or no impact

15. MIST III Interim Findings MIST headache-day reductions hold and improve over time. MIST headache-day reductions hold and improve over time. Disability measures improve over time. Disability measures improve over time. Encouraging results need to be replicated in current randomized controlled trials. Encouraging results need to be replicated in current randomized controlled trials.