Lutonix® Paclitaxel-Coated Balloon to Treat Obstructive Lesions in the Superficial Femoral and Popliteal Arteries Preliminary Six-Month Results from the SAFE-DCB Study Nicolas W. Shammas, MD, MS and Edward Y. Woo, MD for the SAFE-DCB Investigators

Nicolas W Shammas, MD, MS, FACC, FSCAI Disclosures Nicolas W Shammas, MD, MS, FACC, FSCAI  Relevant Conflict of Interest Research Support Bard Boston Scientific  Consultant/Honoraria

Primary Patency (KM) at 365 Days Background: LEVANT 2 Randomized, Controlled Trial Comparing the Lutonix® DCB to Standard Balloon Angioplasty in Femoropopliteal Arteries LEVANT 2 resulted in: Superior Primary Patency to PTA at 12 Months Comparable Safety compared to PTA^ Numerically, but not statistically, lower TLR rate (12.3% Lutonix DCB vs. 16.8% PTA at 12 months)* 73.5% 56.8% Primary Patency (KM) at 365 Days P = 0.001 ^Freedom from primary safety event at 365 days (86.7% Lutonix DCB vs. 81.5% PTA) *TLR was a secondary endpoint. LEVANT 2 was not powered to detect TLR differences

There is a need for real-world data with the Lutonix Balloon Background: LEVANT 2 LEVANT 2 included: 92.1% claudicants (Rutherford 2 & 3) Mean lesion length: 62.8±41.0mm 97.8% TASC II A & B lesions LEVANT 2 excluded: Rutherford 5 & 6 Lesions > 15 cm in length Patients that were likely to require provisional stent placement: Patients with a major flow-limiting dissection and > 70% residual stenosis after pre-dilation were treated per standard of care Note: The bail-out stent rate was low in LEVANT 2 (2.5% Lutonix DCB vs. 6.9% PTA) Use of atherectomy, laser, cryoplasty, or scoring/focal-force balloons There is a need for real-world data with the Lutonix Balloon

LEVANT 2 vs. LEVANT Global Registry

LEVANT Global Registry* LEVANT 2 vs. LEVANT Global Registry LEVANT Global Registry* LEVANT 2# (DCB Group) 12-Month TLR Rate^, % (n/N) 6.4 (41/639) 12.3 (35/285) Freedom from TLR**, % [95% CI] (365 days) 94.2 [92.2, 95.8] 89.7 [85.7, 92.7] 12-Month Primary Patency Rate^, % (n/N) 82.5 (484/587) 65.2 (172/264) Primary Patency**, % [95% CI] (365 days) 85.1 [82.0, 87.7] 73.5 [68.0, 78.2] *Interim analysis of the Global Registry (May 2016) #Rosenfield et al. N Engl J Med 2015;373:145-153. ^Proportional-based analysis **Kaplan-Meier estimate of survival Primary Patency is defined as the absence of target lesion restenosis and freedom from target lesion revascularization (TLR).

SAFE-DCB Registry Objective: Assess the Lutonix Drug-Coated Balloon (DCB) to Treat Obstructive Lesions in the Superficial Femoral and Popliteal Arteries in a “Real World” US Patient Population Prospective, single arm, multicenter registry enrolled 1006 patients in 74 U.S. centers First patient enrolled: April 2015 Last patient enrolled: September 2016 Co-Principal Investigators: Nicolas Shammas, Edward Woo Oversight committee and medical monitor reviewed safety events Preliminary 30-day and 6-month outcomes are being presented today. Primary endpoint analysis at 12 months Ongoing follow up through 3 years

SAFE-DCB Recommended Procedure Steps Adequately prepare the vessel (determined by the treating physician) Recommended Procedural Step: Transit time < 30 seconds Inflation time ≥ 120 seconds Pressure > 7 atm Final Residual Stenosis < 20% Dual antiplatelet therapy: Pre-Procedure: According to current medical standards After Procedure: Minimum of 4 weeks Prolonged antiplatelet therapy (at the discretion of the physician)

Patients N = 1006 602 currently with 30-day follow up 200 currently with 6-month follow up (discrete cohort at 6 months) Indication: Obstructive de novo or restenotic lesions up to 150 mm in length in the superficial femoral or popliteal arteries (reference vessel diameters of 4-7 mm) Study requirements were broad to allow for a real-world, heterogeneous patient population Inclusion: The patient fits within the above indication for use, is willing to comply with follow-up procedures and visits, and provides written informed consent Exclusion: The patient is unwilling or unable to comply with the follow-up procedures or visits The patient has another medical condition, or is in another clinical study, that may confound the SAFE-DCB data or may prevent the patient from complying with the study requirements

Baseline Demographics 30-Day Group 6-Month Group Number of Patients 602 200 Age, years + SD 68.8 + 10.1 69.2 + 9.7 Male/Female, % 56.5/43.5 54.5/45.5 Rutherford Category, % (n/N) Category 1 1.0 (6/602) 0.0 (0/200) Category 2 13.1 (79/602) 9.0 (18/200) Category 3 42.9 (258/602) 41.5 (83/200) Category 4 15.5 (93/602) 17.0 (34/200) Category 5 14.1 (85/602) 15.0 (30/200) Category 6 3.5 (21/602) 2.5 (5/200) Unknown* 10.0 (60/602) Mean Lesion Length, mm + SD 78.5 + 53.3 74.8 + 51.9 *Not reported/not standard of care

Endpoint Definitions Primary Effectiveness: Freedom from target lesion revascularization (TLR) at 12 months defined as the first revascularization procedure (e.g., PTA, stent) after the initial study procedure Primary Composite Safety: Freedom from device- or procedure-related perioperative death (< 30 days), target limb major amputation (above the ankle), and target vessel revascularization Secondary Endpoints: Acute Device & Procedure Success: < 30% residual stenosis of the target lesion after the index procedure and no peri-procedural complications (e.g., death, stroke, MI) prior to hospital discharge Major Flow-Limiting Dissection TLR & Target Vessel Revascularization (TVR) Device- and procedure-related serious adverse events (SAEs) 12-Month Primary Patency: Freedom from restenosis (> 50%) determined by DUS (PSVR < 2.4) and/or no TLR (DUS & angiographic core lab) Presented Today

Results 30-Day Group 6-Month Group Acute Device & Procedural Success, % (n/N) 91.9 (552/601*) 91.5 (183/200) Major Flow-Limiting Dissection^, % (n/N) 4.3 (26/602) 5.0 (10/200) TLR, % (n/N) 0.5 (3/595) 4.3 (8/188) TVR, % (n/N) 0.7 (4/595) 5.9 (11/188) Device-Related SAE#, % (n/N) 2.4 (14/597) 1.6 (3/190) Procedure-Related SAE, % (n/N) 5.7 (34/597) 6.8 (13/190) Periprocedural (< 30 Days) Death, (n/N) 1.2 (7/602) -- All Cause Death, (n/N) 3.3 (20/602) 6.5 (13/200) *Denominator based on evaluable patients-did not discontinue before 30 Days or have an event before discontinuation ^ Dissection Types D-F per the National Heart, Lung, and Blood Institute (NHLBI) # Serious Adverse Events

Subset Analysis: Vessel Prep (30 Days) Vessel Preparation POBA only Atherectomy Specialty# Number of Patients 195 280 77 Lesion Length, mm + SD 68.8 + 46.1 83.7 + 56.5 70.7 + 55.3 Acute Device & Procedural Success, % 91.8 93.2 84.4 Major Flow-Limiting Dissection^, % (n/N) 1.0 (2/195) 4.6 (13/280) 0.0 (0/77) TLR, % (n/N) 0.5 (1/192) 0.7 (2/277) 1.3 (1/77) TVR, % (n/N) 1.1 (3/277) 2.6 (2/77) Device-Related SAE, % (n/N) 0.0 (0/192) 2.2 (6/278) Procedure-Related SAE, % (n/N) 3.7 (7/192) 4.7 (13/278) Periprocedural (< 30 Days) Death, (n/N) 1.5 (3/195) 1.1 (3/280) #Cutting, scoring, and focal-force balloons *Denominator based on evaluable patients-did not discontinue before 30 Days or have event before discontinuation ^ Dissection Types D-F per the National Heart, Lung, and Blood Institute (NHLBI)

Subset Analysis: Diabetic (30 Days) Non-Diabetic Number of Patients 314 288 Lesion Length, mm + SD 75.2 + 48.9 82.1 + 57.6 Acute Device & Procedural Success, % 92.0 91.7 Major Flow-Limiting Dissection^, % (n/N) 3.8 (12/314) 4.9 (14/288) TLR, % (n/N) 0.7 (2/314) 0.4 (1/288) TVR, % (n/N) 1.0 (3/314) Device-Related SAE, % (n/N) 1.9 (6/314) 2.8 (8/288) Procedure-Related SAE, % (n/N) 5.2 (16/314) 6.3 (18/288) Periprocedural (< 30 Days) Death, (n/N) *Denominator based on evaluable patients-did not discontinue before 30 Days or have event before discontinuation ^ Dissection Types D-F per the National Heart, Lung, and Blood Institute (NHLBI)

Case Study This is the Kaplan-Meier survival analysis of primary patency. At 6 months the lines separate at the time of follow up ultrasound. This time to event analysis shows superior patency in the Lutonix DCB group and the difference is sustained through 12 months. The difference between arms at 12 months was significant, with a log rank p-value of less than 0.001.

Summary Preliminary data from the SAFE-DCB US registry demonstrate high procedural and device success with low TLR and TVR and low device-related SAE 30-Day Results (602 patients): Acute Device & Procedural Success: 91.9% TLR: 0.5% TVR: 0.7% Device-Related SAE: 2.4% 6-Month Results (200 patients): With a limited amount of data available at 6 months, acute device & procedural success remains high while TLR (4.3%), TVR (5.9%), and device-related SAEs (1.6%) remain low Confirmation of these early results await long-term, more complete data and analyses. Additional follow up is ongoing. This is the Kaplan-Meier survival analysis of primary patency. At 6 months the lines separate at the time of follow up ultrasound. This time to event analysis shows superior patency in the Lutonix DCB group and the difference is sustained through 12 months. The difference between arms at 12 months was significant, with a log rank p-value of less than 0.001.

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