MASTER Trial 12 Month Results Prof.

MASTER Trial 12 Month Results Prof. Dariusz Dudek Hospital University of Krakow, Poland on behalf of the MASTER Trial Investigators

Disclosure Statement of Financial Interest Grant/Research Support Consulting Fees/Honoraria Major Stock Shareholder/Equity Royalty Income Ownership/Founder Intellectual Property Rights Other Financial Benefit InspireMD No No No No No No Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial Relationship Company

Background Impaired myocardial perfusion after PCI in STEMI is common, and results in increased infarct size, heart failure and mortality. PCI - induced distal embolization of thrombus and/or friable atheromatous debris contributes to impaired myocardial perfusion. Efforts to improve myocardial perfusion with embolic protection devices have failed. Recent results from the INFUSE - AMI and TASTE trials question whether aspiration results in any significant myocardial or clinical benefits.

MGuard stent: designed for embolic protection MGuard is a thin - strut BMS wrapped with an expandable MicroNet mesh, designed to trap, exclude and secure the thrombus and friable atheromatous debris to prevent distal embolization during and post procedure. The mesh is made of a 20 M Polyethylene Terephthalate (PET) fiber. The pores expand to 180 m when deployed. The mesh is expandable for side branch access. The mesh is attached to the proximal and distal edges of the stent only to ensure high flexibility of the stent system.

MGuard & MGuard Prime STENT MGuard MGuard Prime MATERIAL Stainless steel Cobalt chromium STRUT THICKNESS 100 m 80 m CROSSING PROFILE 1.1 - 1.3mm 1.0 - 1.2mm MICRONET MATERIAL PET FIBER DIAMETER 20 M PORE SIZE 150 - 180 M

MASTER Trial design Primary Endpoint: Complete ST - segment resolution at 60 - 90 min Secondary endpoints: TIMI flow, Myocardial blush grade, MACE ( 30 d, 6 m, 12 m) Substudies: Cardiac MRI at 3 - 5 days ( 2 x 30 patients) Angiographic follow - up at 13 months ( 50 patients) 432 patients with STEMI P ain < 12 hrs, de novo lesions Pre - dilatation and/or aspiration TIMI 2 or 3 R 1 : 1 BMS or DES MGuard

Enrollment in participating countries Czech republic (19) Poland ( 166 ) Hungary ( 68 ) Germany ( 45 ) Brazil ( 14 ) South Africa (10) France ( 9 ) Israel (100) Ireland (2)

Main Inclusion / exclusion criteria INCLUSION CRITERIA Symptoms consistent with STEMI within 12 hours of symptom onset 2 mm of ST - segment elevation in 2 leads PCI of a single de novo lesion with RVD 3.0 to 4.0 mm Lesion length 33 mm EXCLUSION CRITERIA LBBB, paced rhythm, etc. (unable to assess ST - segments) Prior PCI within 6 months or prior CABG LVEF 20%, cardiogenic shock or CPR 50% left main stenosis present Infarct lesion ostial Bifurcation with 2.0 mm sidebranch Target vessel or infarct lesion excessively tortuous, angulated or with moderate to heavy calcification Prior stent proximal or w/i 10 mm distal to the target

Baseline characteristics MGUARD (N=217) CONTROL (N=216) Age (years) 60 [52, 68] 58 [51, 67] Male 75.1% 76.9% Hypertension 42.3% 47.4% Hyperlipidemia 27.4% 27.1% Diabetes mellitus 12.0% 18.1% Cigarette smoking 55.3% 46.8% Prior MI 3.7% 8.8% Prior PCI 3.7% 5.6% Symptoms to device, mins 207 [156, 308] 240 [140, 383] Infarct artery = LAD 40.1% 40.3% Baseline TIMI flow = 0/1 66.5% 74.0% Baseline RVD, mm 3.15 [2.87, 3.38] 3.06 [2.87, 3.40] Baseline DS % 100 [85, 100] 100 [88, 100] Stone GW et al. J Am Coll Cardiol . 2012 ; 60 : 1975 - 1984

Procedural characteristics Out of 217 patients, 27 were treated with MGuard Prime Stone GW et al. J Am Coll Cardiol . 2012;60:1975 - 1984 MGUARD (N=217) CONTROL (N=216) P Aspiration performed 65.9% 67.1% 0.79 Balloon pre - dilatation performed 50.2% 44.9% 0.27 Direct stenting 12.0% 10.6% 0.66 > 1 stent implanted 99.5% 100.0% 1.0 Stent type MGuard 96.3% 0.5% <0.0001 Bare metal stent 1.4% 59.7% <0.0001 Drug - eluting stent 2.3% 39.8% <0.0001 Total stent length, mm 19 [15, 24] 20 [15, 24] 0.64 Post stent dilatation performed 36.4% 30.6% 0.20 Maximal device size, mm 3.5 [3.0, 3.5] 3.5 [3.0, 3.5] 0.78 Maximal dilatation pressure, atm 16 [14, 18] 16 [14, 18] 0.02

Epicardial coronary flow 1.8 6.5 91.7 5.6 11.6 82.9 0 10 20 30 40 50 60 70 80 90 100 0/1 2 3 Percent (%) TIMI flow MGuard Control stent P=0.006 P= 0.01 Stone GW et al. J Am Coll Cardiol . 2012 ; 60 : 1975 - 1984

ST - segment resolution Stone GW et al. J Am Coll Cardiol . 2012;60:1975 - 1984 16.7 25.5 57.8 17 38.3 44.7 0 10 20 30 40 50 60 Absent ( 30 %) Partial (>30% - <70%) Complete ( 70%) Percent (%) ST resolution MGuard Control stent P= 0.005 P=0.008 PRIMARY ENDPOINT

Distal embolization Stone GW et al. J Am Coll Cardiol . 2012 ; 60 : 1975 - 1984 4.1 7.0 0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 Distal Embolization Percent (%) MGuard Control stent P= 0.21

Cardiac MRI sub - study at 5 days Stone GW et al. J Am Coll Cardiol . 2012;60:1975 - 1984 MGUARD (N=30) CONTROL BMS / DES (N=29) P Total LV myocardial mass, g 141 [117, 163] 147 [118, 174] 0.41 Infarct mass, g 17.1 [10.0, 30.0] 22.3 [15.7, 30.1] 0.27 Infarct mass (% total LV mass) 13.3 [7.9, 25.0] 16.6 [10.0, 22.6] 0.48 Total MVO, g 0.3 [0.0, 1.6] 1.0 [0.2, 2.8] 0.14 MVO (% total LV mass) 0.4 [0.0, 1.4] 0.8 [0.2, 1.9] 0.39 Abnormal wall motion score 22.5 [20.0, 26.0] 25.0 [21.0, 27.0] 0.48 LVEF (%) 48.3 [44.5, 52.3] 47.3 [42.0, 54.5] 0.79

30 - day clinical results Stone GW et al. J Am Coll Cardiol . 2012;60:1975 - 1984 MGUARD (N=217) CONTROL (N=214) P MACE 4 (1.8%) 5 (2.3%) 0.75 All cause mortality 0 (0.0%) 4 (1.9%) 0.06 Cardiac death 0 (0.0%) 4 (1.9%) 0.06 Reinfarction 3 (1.4%) 2 (0.9%) 1.00 TLR, ischemia - driven 4 (1.8%) 1 (0.5%) 0.37 TVR, ischemia - driven 5 (2.3%) 1 (0.5%) 0.10 Stent Thrombosis Definite or Probable 3 (1.4%) 2 (0.9%) 0.67 Definite 3 (1.4%) 1 (0.5%) 0.62 Stroke 1 (0.5%) 0 (0.0%) 1.00 TIMI Bleeding Major or Minor 4 (1.9%) 4 (1.9%) 1.00 Major 3 (1.4%) 2 (0.9%) 1.00

12 month clinical results NEW RESULTS MGUARD (N=217) CONTROL (N=216) P MACE 9.1% (19) 3.3% (7) 0.02 All cause mortality 1.0% (2) 3.3% (7) 0.09 Cardiac death 0.5% (1) 2.3% (5) 0.10 Reinfarction 1.4% (3) 0.9% (2) 0.66 Death or reinfarction 2.3% (5) 3.7% (8) 0.39 TLR, ischemia - driven 8.6% (18) 0.9% (2) 0.0003 TVR, ischemia - driven 11.0% (23) 0.9% (2) <0.0001 Stent Thrombosis Definite or Probable 2.3% (5) 0.9% (2) 0.26 Definite 2.3% (5) 0.5% (1) 0.10 Stroke 0.5% (1) 1.0% (2) 0.56 TIMI Bleeding Major or Minor 1.8% (4) 2.5% (5) 0.73 Major 2.4% (5) 0.9% (2) 0.26

Propensity score matching ( TLR / TVR ) HORIZONS - AMI BMS N=443 MASTER MGuard N=191 P MACE 7.5% (33) 9.2% (17) 0.54 TLR, ischemia - driven 6.0% (26) 8.7% (16) 0.26 TVR, ischemia - driven 6.9% (30) 10.3% (19) 0.18 Propensity Score Adjustment on the following covariates (3 - 1 caliper = 0.35 ): Age, BMI, Male, Hyperlipidemia, Diabetes, Prior Angina, Prior MI, Symptom to Balloon time, stent length, baseline RVD, LAD vs RCA vs LCX, Baseline TIMI 0/1/2 vs TIMI3

Death Time - to - Event curve NEW RESULTS Death (%) 0 1 2 3 4 5 Months 0 1 2 3 4 5 6 7 8 9 10 11 12 217 214 209 206 126 216 210 209 207 123 Number at risk: MGuard BMS/DES P= 0.09 HR: 0.28 [ 95 % CI: 0.06 , 1.36 ] 1.0% 3.3% MGuard BMS/DES

Cardiac Death Time - to - Event curve Cardiac Death - 12 months (%) 0 1 2 3 4 5 Time in Months 0 1 2 3 4 5 6 7 8 9 10 11 12 217 214 209 206 126 216 210 210 207 124 Number at risk: MGuard BMS/DES P= 0.099 HR: 0.20 [ 95 % CI: 0.02 , 1.69 ] 0.5 % 2.3% MGuard BMS/DES NEW RESULTS

Death or MI Time - to - Event curve DEATH/MI (%) 0 1 2 3 4 5 Months 0 1 2 3 4 5 6 7 8 9 10 11 12 217 212 207 205 125 216 209 208 206 123 Number at risk: MGuard BMS/DES 2.3% 3.7 % MGuard BMS/DES P= 0.39 HR: 0.62 [ 95 % CI: 0.20 , 1.89 ] NEW RESULTS

13 Month angiographic sub - study follow - up Enrollment into the angiographic sub - study started after the study enrolled 100 patients, and occurred in pre - specified sites. 48 consecutively enrolled patients randomized to the MGuard were consented to return at 13 months for an invasive angiographic follow - up. 38 patients underwent the angiography (79.2%) 4 patients refused 1 patient was not available during the visit window. 2 patients exited the study before the follow - up period 1 patient died before the follow - up period 1 patient had an illness, and could not have the angiography 1 patient was lost to follow - up

13 Month angiographic sub - study follow - up ENTIRE SUBSTUDY COHORT (N=36)* SINGLE MGUARD STENT (N=31)** Average 95% CI Average 95% CI Late loss (in stent) 0.99 0.80 [0.73,1.26] 0.88 0.70 [0.63,1.14] Late loss (in segment) 0.82 0.75 [0.57,1.06] 0.72 0.65 [0.48,0.95] Binary Restenosis (in stent) 23.7% [11.4%, 40.2%] 19.4% [7.5%, 37.5%] Binary Restenosis (in segment) 31.6% [17.5%, 48.7%] 29.0% [14.2%, 48.0%] * Of the 38 patients, 36 lesions were analyzable ** 31 patients were treated with a single MGuard stent NEW RESULTS

Limitations The MASTER trial was powered for ST - segment resolution, and not for infarct size or clinical events. Endpoints other than ST - segment resolution should be considered exploratory and hypothesis - generating. The control arm in MASTER consisted of a mixture of patients treated with DES and BMS, and randomization was not stratified by stent type. The trial was open label, and some degree of bias cannot be excluded. Angiographic follow - up was not performed in the control arm.

Conclusions Among patients with acute STEMI undergoing emergent PCI, MGuard EPS resulted in superior rates of TIMI3 and complete STR. A trend towards reduced mortality was present in the MGuard arm at 30 days, which persisted throughout 12 month follow - up. No significant differences in reinfarction or stent thrombosis were present at 12 months between the MGuard and control groups. The 12 month TLR rate in the MGuard arm were higher than in the control, but were comparable to those expected from a BMS. The 13 month angiographic analysis demonstrates LLL and binary restenosis rates for the MGuard stent which are comparable to other BMS.

MASTER - II IDE study design BMS or DES MGuard Prime Randomization 1 : 1 STEMI patients for primary PCI 1114 patients at 35 US and 35 non - US sites Infarct size assessed by cardiac MRI In - stent late lumen loss (LLL) at 13m (BMS) Complete ST - segment resolution at 60 - 90 min All - cause death or TV - reinfarction at 365 days 1 endpoints Powered 2 endpoints