Meital Mazor Ph D PI-136107 -AA Jan 2013

Meital Mazor, Ph. D PI-136107 -AA Jan 2013 -final 0 of 26 The Boston Scientific Vessix™ Renal Denervation System

Meital Mazor, Ph. D Within the past 12 months, I have had a financial interest/arrangement or affiliation with the organization(s) listed below. Vessix Vascular, Inc. Employee and stockholder Boston Scientific Employee

Significantly more nerves in hypertensive patient vs. normotensive subjects Normotensive Patient 32 renal arteries were harvested from 16 pts The number of nerves per mm 2 within the 0. 5 mm ring area from the adventitia was 2. 5± 1. 8 in N vs. 3. 5± 1. 4 in H (p<0. 04) while no difference were detected above 0. 5 mm (1. 5± 0. 9 in N vs. 1. 2± 0. 7 in H, p=0. 3). Giuseppe Sangiorgi et al. J Am Coll Cardiol. 2012; 60(17_S) PI-136107 -AA Jan 2013 -final 2 of 26 Hypertensive Patient

PI-136107 -AA Jan 2013 -final 3 of 26

Vessix™ Renal Denervation System* Overview • Over-the-wire balloon with mounted RF electrodes • Balloon sizes 4 – 7 mm • 30 second denervation time • All electrodes deliver energy simultaneously • RF electrodes automatically deactivated when not in contact with the artery wall • Algorithm controls temperature at precisely 68°C • One button operation • CE marked and TGA approved *The Vessix™ Renal Denervation System is not available for sale in the US. RF=Radiofrequency PI-136107 -AA Jan 2013 -final 4 of 26 • Bipolar technology obviates the need for a grounding pad

Vessix™: Occluding RF Balloon Catheter for Renal Denervation • Low pressure non-compliant balloon (3 atm) mitigates barotrauma • Offset helical pattern of electrodes is optimized for delivery of thermal energy to adventitia Balloons to accommodate 3 mm - 7 mm • Temperature sensors at each electrode allows precise renal artery diameters – ability to treat measurement and independent full range of vessel diameters including titration of power based on accessory renal arteries temperature *The Vessix™ Renal Denervation System is not available for sale in the US. PI-136107 -AA Jan 2013 -final 5 of 26 • Gold electrodes – good thermal and electrical conductivity and each electrode is visibly radiopaque on angiogram

V 2 Catheter Features • 8 F guiding sheath compatible • Working length – 90 cm PI-136107 -AA Jan 2013 -final 6 of 26 • 0. 018” guidewire compatible

PI-136107 -AA Jan 2013 -final 7 of 26 Apposition Algorithm

Apposition Algorithm Apposition detection based upon impedance. Represented by rings in color: • Grey - High impedance…electrodes in open air • Purple - Low impedance…electrodes are in blood • Yellow - Borderline apposition PI-136107 -AA Jan 2013 -final 8 of 26 • Green - Good apposition!

70 65 Temperature Profile Temperature Control 55 50 45 40 35 0 5 10 15 20 Time (seconds)30 seconds Target Temperature: 68 °C, 25 30 PI-136107 -AA Jan 2013 -final 9 of 26 Temperature (°C) 60

Vessix™ Occluding RF Balloon Catheter • Electrodes that are unapposed to vessel wall are automatically deactivated. For more moderate length arteries, 1. 5 treatments can be applied • For longer length renal arteries, 2 treatments (one distal, one proximal) can be applied *The Vessix™ Renal Denervation System is not available for sale in the US. RF=Radiofrequency PI-136107 -AA Jan 2013 -final 10 of 26 • RF treatment can be tailored to length of the artery landing zone

Small diameter renal arteries, such as accessory renal arteries, can not be treated with monopolar RF, due to insufficient blood perfusion to cool the catheter. These small arteries can be treated with the smaller diameter Vessix™ catheter. Images of Case 05 -007 REDUCE HTN. Results from case studies are not predictive of results in other cases. Results in other cases may vary. *The Vessix™ Renal Denervation System is not available for sale in the US. RF=Radiofrequency PI-136107 -AA Jan 2013 -final 11 of 26 Bipolar RF Technology on a Balloon for the treatment of smaller arteries

Renal Denervation Preclinical Program Preclinical Study Timeline 2010 – 2011 Verification testing of final Vessix™ RDN System Sep-Mar Apr - Jul Aug Sep Oct Initial animal 18 animals 20 animals 32 animals 18 animals studies confirming with kidney NEPI to confirm NEPI, to confirm final GLP Safety Study Final Confirmatory depth of comparison histo & angios dose 28, 60, 90 days Study penetration to establish with final balloon NEPI, histo & with angiograms efficacy at 7, 14, catheter design, angios. Compare and histology 28 days. and final unilateral to Angiograms and candidates for bilateral histology to temperature treatments, confirm lack of control algorithm surgery, shams flow limiting and endogenous stenosis in renal levels artery at 28 days Dec 11, Feb 12 22 animals 180 day GLP Safety 128 animals studied Margolis, TRENDS 2012 *The Vessix™ Renal Denervation System is not available for sale in the US. GLP=Good Laboratory Practices; NEPI=Norepinephrine; RDN=Renal Denervation; RF=Radiofrequency PI-136107 -AA Jan 2013 -final 12 of 26 Development and iterative phase employing various designs of RF balloon catheter for renal denervation with new treatment algorithms

Significant reduction in norepinephrine at 7, 14, 28, 90 through 180 days post treatment 74% NEPI Reduction = 77% NEPI Reduction Vessix™ Treatment, 68°C, 30 sec (n=19) Margolis, TRENDS 2012 *The Vessix™ Renal Denervation System is not available for sale in the US. Surgical Denervation (n=3) PI-136107 -AA Jan 2013 -final 13 of 26 Swine model results not necessarily indicative of clinical performance

Vascular Safety in Treated Swine Renal Arteries is Demonstrated through 180 Days 7 days 90 days • • • effect on surrounding tissue All treated arteries were patent No dissections, aneurysms, or changes in blood or urine chemistry Endothelialization by 7 days Vessix™ data on file *The Vessix™ Renal Denervation System is not available for sale in the US. PI-136107 -AA Jan 2013 -final 14 of 26 • Histology confirms no adverse Swine model results not necessarily indicative of clinical performance

Patent Lumen in Swine 180 Days post procedure 180 Days Post Treatment Balloon Location Vessix™ data on file *The Vessix™ Renal Denervation System is not available for sale in the US. PI-136107 -AA Jan 2013 -final 15 of 26 Pre Treatment Swine model results not necessarily indicative of clinical performance

Barotrauma is prevented by using noncompliant balloon Histology of sham treated arteries were confirmed to have completely no affect on the arterial wall, with identical histology scores as untreated arteries. PI-136107 -AA Jan 2013 -final 16 of 26 Non-compliant balloon inflation (with no RF) has no effect on the renal artery wall

Balloon inflation does not cause artery stretching Pre-Treatment PI-136107 -AA Jan 2013 -final 17 of 26 90 Days Post Treatment Balloon Location (6 mm Diameter)

Is balloon over sizing a problem? Pre-treatment In the REDUCE trial few patients were treated with balloon diameter larger > 1. 5 mm from MLD: 4. 39 mm the renal artery diameter. RVD: 4. 86 mm No complication occurred in any of the cases, V 2 Balloon diameter: 7 mm Post-treatment No dissection No aneurysm No thrombus No spasm No embolization No perforation No staining PI-136107 -AA Jan 2013 -final 18 of 26 (according to Synvacor core lab analysis): Arteries are patent at 6 months following treatment according to MLD: 4. 34 mm DUS (Duplex Ultrasound) RVD: 5. 35 mm Vascore lab analysis Patient 06 -004 MLD: Minimal lumen diameter, RVD: Reference Vessel Diameter

PI-136107 -AA Jan 2013 -final 19 of 26 Clinical Data

Vessix™ Clinical Program REDUCE-HTN Clinical Study Overview Postmarket surveillance clinical study for medication-resistant hypertension • Single cohort, international, multi-center, prospective • Up to 150 subjects at 25 clinical sites in EU, AU, and NZ • Efficacy Endpoint – Reduction of systolic blood pressure and diastolic blood pressure at six months post procedure compared to baseline. Measured by office-based blood pressure and ambulatory blood pressure monitoring • Safety Endpoint – Absence of flow limiting stenosis in the renal artery at six months post procedure *The Vessix™ Renal Denervation System is not available for sale in the US. PI-136107 -AA Jan 2013 -final 20 of 26 • Adults with systolic blood pressure > 160 mm. Hg on three or more antihypertensive drugs at maximum tolerated doses

REDUCE-HTN Interim Analysis at Six Months PI-136107 -AA Jan 2013 -final 21 of 26 Systolic Diastolic Margolis, TCT 2012. *The Vessix™ Renal Denervation System is not available for sale in the US.

Vessix™ Renal Denervation Pre Treatment Vessix™ balloon treatments with electrodes visible Images of Case 05 -007 REDUCE HTN. Results from case studies are not predictive of results in other cases. Results in other cases may vary. *The Vessix™ Renal Denervation System is not available for sale in the US. Proximal PI-136107 -AA Jan 2013 -final 22 of 26 Distal

Vessix™ Renal Denervation Absence of Spasm and Continued Patency Post Treatment Images of Case 05 -007 REDUCE HTN. Results from case studies are not predictive of results in other cases. Results in other cases may vary. *The Vessix™ Renal Denervation System is not available for sale in the US. PI-136107 -AA Jan 2013 -final 23 of 26 Pre Treatment