Hiroshi Ando, MD Kasukabe Chuo General Hospital Saitama, Japan

Hiroshi Ando, MD Kasukabe Chuo General Hospital Saitama, Japan

Disclosure Hiroshi Ando, MD Kasukabe Chuo General Hospital I have the following potential conflicts of interest to report: Consulting Employment in industry Stockholder of a healthcare company Owner of a healthcare company Other(s) I do not have any potential conflict of interest

Difficult to Avoid Restenosis after Balloon Angioplasty J-BEAT Angio Multicenter prospective registry 101 infrapopliteal lesions (63 CLI patients) 3M-Restenosis = 69% Schmidt A, et al. CCI 2010;76:1047 1054 3M-Restenosis = 73% Iida O, Soga Y, et al. EJVES 2012 Courtesy of Dr. Soga

Time to Wound Healing OLIVE registry J-BEAT Angio Median: 97±10 days Iida O, Nakamura M, et al. Circ Cardiovasc Interv. 2013 Median: 117±79 days Iida O, Soga Y, et al. EJVES 2012 Courtesy of Dr. Soga

Time to Wound Healing To complete wound healing for dialysis pts, we spend too much time!! Median 9M!! N. Azuma et al. Eur J Vasc Endovasc Surg. 2012 Courtesy of Dr. Soga

Time to Wound Healing is longer than Time to Restenosis Wound healing 3-4M > restenosis 3M (dialysis 9M!) Repeat balloon angioplasty is often needed to achieve complete wound healing. Courtesy of Dr. Soga

6 and 12 month follow up data DES trials ACHILLES SES/PTA YUKON- BTK SES/BMS DES > BMS > PTA DESTINY EES/BMS DESTINY II EES PES BTK -70 selfexpanding BVS everolimus -eluting Patients(n) 99 82 78 60 70 22 Rutherford (CLI) 3 to 5 2 to 5 (51.2%) LL(mm) MLL±SD(mm) 26.9±20. 9 4 to 5 4 to 5 (96.7%) 31±9 15.9±910. 2 30-100 47.4 19.7 CTO(%) 81.3 15 53.3 14.3 4 to 5 3 to 6 (60%) 5-50 20.2 P.P(%) 75 80.6 85.2 75.4 72.6 94.4 TLR(%) 10.0 9.2 8.7 15.1 20.9 5.6 Death(%) 10.1 22.4 18.1 10.7 10.6 4.6 P.P: primary patency Limb salvage(%) 86.2 97.4 94.8 96.6 100

Atherectomy Devices to CLI Treatment Device study Patient Mean L.L (mm) Procedure success(%) Limb sulvage( %) MAE (%) Diamondback Calcium 360 25 91 93.1 88/12M 6.7 Laser LACI 145 110 86 92/6M 18 TurboHawk Definitive LE 201 72 83 95/12M 9.5

The Global Lutonix DCB BTK Registry Study Design Study Design Objective Number of patients/sites Inclusion Criteria Exclusion Criteria Study Design Prospective, Multicenter, Single Arm, Real-world Registry To demonstrate safety and assess the clinical use and outcomes of the Lutonix DCB for treatment of stenosis or occlusion of native below-theknee arteries in a heterogeneous patient population in real world clinical practice Study Design 371 subjects enrolled from 26 international sites Rutherford Class: 3-5, 70% stenosis lesion, target vessel(s) reconstitute(s) at or above the ankle with inline flow to at least one patent (<50% residual stenosis) inframalleolar outflow vessel Neurotrophic ulcer or heel pressure ulcer or ulcer potentially involving calcaneus (index limb) Primary Endpoints Follow-up Safety: Freedom from BTK MALE+POD at 30-days Efficacy: Freedom from TLR at 6 months 1, 6, 12 and 24 Months

Study Centers PI Name Prof. Willfort-Ehringer Dr. Loewe Prof. Brodmann Prof. Hausegger Dr. Lerut Dr. Lansink Dr. Clemens Dr. Zech Dr. Giménez-Gaibar Dr. Alves Prof. Sapoval Dr. Lichtenberg Study Co-PI Dr. Thieme PI Name Prof. Scheinert Study Co-PI Prof. Eckstein Dr. Sunderdiek Prof. Tepe Dr. Perez Delgado Prof. Zeller Prof. Karnabatidis Prof. Brountzos Dr. Rossato Dr. Cioppa Dr. Tolva Dr. Butterfield Dr. Rana

Pre-Procedure Procedure Post-Procedure 30 Day 6 Month 12 Month 24 Month Patient Follow-up EVENT Visit Window Inclusion/Exclusion Criteria Informed Consent Medical History ±2 Weeks ±1 Month ±1 Month ±2 Months Routine Physical Exam ¹ ¹ Current Medication Rutherford Classification ¹ ¹ Adverse Event Monitoring Wound Healing Assessment ¹ ¹ ¹Required only if clinical visit occurs

Demographics / Baseline Characteristics Description BTK Study Registry (N=364) Age (Years), Mean ± SD (n) 73.6 ± 9.5 (364) Gender, % (n/n) Female Male 28.0% (102/364) 72.0% (262/364) BMI 30 kg/m², % (n/n) 23.7% (85/358) Hypertension, % (n/n) 86.8% (316/364) Dyslipidemia, % (n/n) 62.4% (227/364) Diabetes 64.0% (233/364) Current/Previous Smoker, % (n/n) 50.5% (184/364) Rutherford Category 3 4 5 RCC 5 65.8% (239/363) 23.7% (86/363) 10.5% (38/363) 65.8% (239/363)

Lesion Characteristics Description BTK Study Registry (N=364) Lesion Location¹ Popliteal Tibioperoneal Trunk Anterior Tibial Posterior Tibial Peroneal 6.9% (25/364) 20.6% (75/364) 51.1% (186/364) 22.3% (81/364) 22.8% (83/364) Total Target Length (mm), Mean ± SD (n) 121 ± 97.9 (364) Average RVD (mm), Mean ± SD (n) (min, max) Calcification, % (n/n) Severe Calcification, % (n/n) TASC C/D 31.1% (113/363) 2.7 ± 0.52 (361) (1.7, 4.5) 64.3% (279/434) 23.9% (83/348) TASC A B C D Unknown 25.3% (92/363) 26.2% (95/363) 16.8% (61/363) 14.3% (52/363) 17.4% (63/363) ¹Subjects may be in more than one category.

Freedom from Primary Safety Events 6M: 94.9% 12M: 92.8% Time N 1 % [95% CI] Survival 2 Month 1 (30 Days) 346 98.6% [96.6%, 99.4%] Month 6 (183 Days) 250 94.9% [91.6%, 96.9%] Month 12 (365 Days) 144 92.8% [88.5%, 95.6%] ¹Subjects ongoing without an event at the beginning of the visit window ²Primary safety response estimate based on Kaplan-Meier estimate Freedom at 30-Days from the composite of all-cause death, above-ankle amputation or major re-intervention, i.e., new bypass graft, jump/interposition graft revision, or thrombectomy/thrombolysis of the index limb involving a below-the-knee artery.

Additional Safety Profile - 12 months Freedom From N¹ Survival² % [95% CI] All Cause Death Survival 150 86.5% [81.2%, 90.4%] Major Amputation 145 94.8% [91.0%, 97.0%] Re-intervention for Thrombosis/Thrombolysis 141 91.5% [86.3%, 97.4%] Re-intervention For Distal Embolization 150 100.0% [NA, NA] TVR 117 75.0% [68.1%, 80.6%] Unexpected Device or Drug Related Event 150 99.6% [97.2%, 99.9%] ¹Subjects ongoing without a failure at the beginning of the visit window ²Survivor rate based on Kaplan-Meier Estimate

Freedom from TLR 6M: 90.6% 12M: 76.0% Time N 1 % [95% CI] Survival 2 Month 1 (30 Days) 344 98.9% [97.0%, 99.6%] Month 6 (183 Days) 237 90.6% [86.4%, 93.5%] Month 12 (365 Days) 117 76.0% [69.2%, 81.5%] ¹Subjects ongoing without a TLR failure at the beginning of the visit window ²TLR-Free response estimate based on Kaplan-Meier estimates

Rutherford Category Shift 12 months Description BTK Study Registry (N=144) Improved by 5 Levels Improved by 4 Levels Improved by 3 Levels Improved by 2 Levels Improved by 1 Levels No Change Worsened by 1 Levels 23.6% (34/144) 9.7% (14/144) 26.4% (38/144) 11.1% (16/144) 6.3% (9/144) 20.1% (29/144) 2.8% (4/144) 77% Improved by >1 RCC 60% Improved by >3 RCC

12 Month Conclusions Only BTK Multi-Center On-going Registry Study Freedom from TLR 76.0% at 12 months Low Amputation Rate 5.2% at 12 months ~60% Improvement by >3 Rutherford Classifications at 12 months ZERO Re-interventions for Distal Embolization at 12 months Promising Treatment Effect in Below-the Knee Arteries Safety Outcomes Consistent with the Strong Safety Profile of the Lutonix DCB in PAD

Hiroshi Ando, MD Kasukabe Chuo General Hospital Saitama, Japan