Slide 1: Twelve-month Safety and Efficacy of CGuard MicroNet-covered Embolic Prevention Stent
TCT 2016 Featured Research Innovation in Vascular Disease Twelve-month Safety and Efficacy of CGuard™ MicroNet-—covered Embolic Prevention Stent Routine Use to Perform Carotid Revascularization: PARADIGM All-Comer Prospective Academic Study P. MUSIALEK?, A. MAZUREK?, M. TRYSTULA?, A. BORRATYNSKA?, A
Slide 2: Disclosure Statement of Financial Interest
Disclosure Statement of Financial Interest Within the past 12 months, | or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial Relationship Company * Grant/Research Support + Abbott * Consulting Fees/Honoraria + Abbo
Slide 3: The Problem of Conventional Carotid Stents
The Problem of Conventional Carotid Stents Human carotid artery treated using)a conventional stent; OCT AJ mE & tct2016 poreaptual nae ib, Unser ae TCT 2016 Featured Research
Slide 4: Post-procedural Embolization with carotid stents
Post-procedural Embolization with carotid stents DW-MRI post CAS Mean total lesion area 3,5h 18h Schofer J et al, JACC Cardiovasc interv 2008 otct2014
Slide 5: Timing of neuro-embolic events after CAS
Timing of neuro-embolic events after CAS Embolic Events 34 Neuro / Imaging evaluations i ' = x) Neurological events Procedural Post-procedural 40-80% 1 *stroke timing with CAS T in CAPTURE and CREST 1 haan D. McCormick TCT 2012, modified
Slide 6: Timing of neuro-embolic events after CAS
Timing of neuro-embolic events after CAS > = Neurological events Procedural AG o o a t Post-procedural 40-80% *stroke timing with CAS T in CAPTURE and CREST D. McCormick TCT 2012, modified
Slide 7: PARADIGM
PARADIGM *CEA excludes the plaque & tct2016 TCT 2016 Featured Research
Slide 8: PARADIGM
PARADIGM *CEA excludes the plaque *In CAS, the stent should exclude the plaque too & tct2016 TCT 2016 Featured Research
Slide 9: An unmet clinical need
IN an unmet clinical need tct2016 TCT 2016 Featured Research
Slide 10: Anti-Embolic Carotid Stent
Anti- Embolic Carotid Stent Plaque protrusion may lead to early and late distal embolization iaate —... otct24 J. Schofer, P. Musialek et al. TCT 2014 aiea\iak renin
Slide 11: CGuard embolic prevention system
CGuard™ embolic prevention system
Slide 12: CGuard-Carotid Embolic Prevention System
CGuard™-—Carotid Embolic Prevention System Stent type Nitinol—self expanding Micronet aperture size 150-180 um Guidewire 0.014” Sizes - Diameter 6-10mm - Length 20-60mm CE Mark—March 2014 © Specific, carotid-dedicated design Vv
Slide 13: CGuard-Carotid Embolic Prevention System
CGuard™-—Carotid Embolic Prevention System Stent type Nitinol—self expanding Micronet aperture size 150-180 um Guidewire 0.014” Sizes - Diameter 6-10mm - Length 20-60mm CE Mark—March 2014 ©
Slide 14: CGuard CAS
— CGuard™ CAS: — - « ~*~
Slide 15: CGuard CAS
“CGuard™ CAS: - Intra- “procedural cerebral embolization is minimize &S tct2016 J.Scl Interv 20152015;8:1229-1234
Slide 16: Intra-procedural cerebral embolization is minimized
Intra- -procedural cerebral embolization is minimize Post-procedural procedural cerebral embolization i is Pal -elit tl N) eS tct2016 |. Scho! lek, et al. JACC Interv 20152015;8:1229-1234
Slide 17: JACC: Cardiovascular Interventions 2015 CARENET trial publication
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 8, NO. 9, 2015 © 2015 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION ISSN 1936-8798/$36.00 PUBLISHED BY ELSEVIER INC. http://dx.dol.org/10.1016/).jcin.2015.04.016 A Prospective, Multicenter Study of ® a Novel Mesh-Covered Carotid Stent The CGuard CARENET Tri
Slide 18: The Power of DW-MRI
The Power of DW-MRI... 48h after LICA-CAS M. Urbanczyk, P. Banys, Dept. Radiology, JP2 Hospital, Krakow, Poland tct2016
Slide 19: CARENET DW-MRI analysis
CARENET DW-MRI analysis — DWAMRI analysis @ 48 hours CARENET _ PROFI (all) Icss* (n=27) (n=62) (n=56) Incidence of new ipsilateral lesions 37.0% 66.2% 68.0% Average lesion volume (cm?) 0.039 0.375 Maximum lesion volume (cm?) om J >10-fold reduction in cerebral lesion volume * External Core Lab analy
Slide 20: CARENET DW-MRI analysis
CARENET DW-MRI analysis All but one peri-procedural ipsilateral lesions RESOLVED DW-MRI analysis @ 30 days* Incidence of new ipsilateral lesions 1 Average lesion volume (cm?) 0.08 + 0.00 Permanent lesions at 30 days 1 * External Core Lab analysis (US) J. Schofer, P. Musialek et al. JACC Intv 2015;8:
Slide 21: CARENET DW-MRI
~ CARENET DW-MRI demonstrated CGuard™ EPD MicroNet E b | i E t i urtesy Dr Joan Rigla, MD PhD Lab, Univerity of Barcelona J. Schofer, P. Musialek, et al. JACC Interv 20152015;8:1229-1234 CGuard EPS Image Cot Perceptual Imaging:
Slide 22: A Prospective, Multicenter Study of a Novel Mesh-Covered Carotid Stent
A Prospective, Multicenter Study of ® & a Novel Mesh-Covered Carotid Stent The CGuard CARENET Trial (Carotid Embolic Protection Using MicroNet) Joachim Schofer, MD,” Piotr Musiatek, MD, DPu,{ Klaudija Bijuklic, MD,” Ralf Kolvenbach, MD, N Marist Tystla, MD, Zbigniew Shak, MD, Hest Seve, MD S E78 Tn
Slide 23: A Prospective, Multicenter Study of a Novel Mesh-Covered Carotid Stent
A Prospective, Multicenter Study of & a Novel Mesh-Covered Carotid Stent ) The CGuard CARENET Trial (Carotid Embolic Protection Using MicroNet) MD," Ralf Kolver e large for routine DW-MRI at 3 time points in relation to CAS ¢ uderpowered for clinical endpoints or any potential device-related events
Slide 24: The PARADIGM study
Prospective evaluation of All-comer perRcutaneous cArotiD revascularization In symptomatic and increased-stroke-risk asymptomatic carotid artery stenosis using the CGuard™ MicroNet — covered embolic prevention stent system: The PARADIGM study CAROTID PARADIGM REVASCULARIZATION —— y tct2016 6 Feature
Slide 25: PARADIGM Objective
PARADIGM Objective e to evaluate feasibility and outcome of routine anti-embolic stent system use in unselected, consecutive patients referred for carotid revascularization (‘all-comer’ study)
Slide 26: The PARADIGM study consecutive CAS pts / 12mo
The PARADIGM study 100 consecutive CAS pts / 12mo* & tct2016
Slide 27: PARADIGM Study questions
PARADIGM PARADIGM aa Study questions: (1) feasibility of routine use of CGuard MN-EPS in ip) an all-comer carotid stenosis requiring revasc. : (2) CGuard EPS device/procedure acute success rate ? (3) safety clinical efficacy @30-days and @12 months ? (4) proportion of all-comer carotid stenosis pati
Slide 28: PARADIGM Methods
PARADIGM |g Methods: academic cardio-vascular centre investigator-initiated study not industry-funded all-comer inclusion (target = 101 consecutive patients) no exclusion critera, all referrals tracked routine consultation and management pathways qualitative and quantitative lesion & stent evaluatio
Slide 29: PARADIGM Methods (cont'd)
PARADIGM PARADIGM oan Methods (cont’d): : : e ASYMPTOMATIC patients treated interventionally only if at /stroke risk e established lesion-level increased-risk crieria used: — thrombus-containing — documented progressive — irregular and/or ulcerated — contralateral ICA occlusion/stroke — asymptomatic
Slide 30: PARADIGM Methods: The CAS Procedure
PARADIGM ee Methods: The CAS Procedure = : e EPD use mandatory; EPD selection according to the ‘Tailored CAS’ algorithm* e Liberal postdilatation accepted in order to maximize potential for ‘endovascular full reconstruction’ (minimizing residual stenosis) NB. 1. DWI evidence of effective MicroNet pr
Slide 31: PARADIGM: investigator-independent
PARADIGM gi | PARADIGM: investigator — independent | e external source data verification J KCRI Excellence in clinical research Core Imaging Analysis eexternal angiographic analysis a4 KC RI Laboratory
Slide 32: PARADIGM Study endpoints
PARADIGM gil Study endpoints: a e PRIMARY a composite of death, stroke (major/minor) and MI in the peri-procedural period, at 30 days, and up to 12 months e SECONDARY (1) acute study device success defined as ability to treat the index carotid lesion using the study device (CGuard MN-EPS) successful
Slide 33: PARADIGM study: referrals flow chart
PARADIGM study: referrals flow chart PARADIGM 139 carotid stenosis patient referrals i y — Neurologist Neuro Vascular Team — Interventional angiologist — Vascular surgeon = = Cardiologist for carotid NOT for carotid revascularisation revascularisation 108 patients 31 patients n=24: increased stroke
Slide 34: PARADIGM study: revascularisation flow chart
PARADIGM study: revascularisation flow chart|@plitanc 108 patients for carotid revascularisation : oe (93%) (1%) (6%) CAS CAS+CEA CEA in n=100 in n=1 in n=7 patients patient patients (bilateral in 5) eee n=l eGRF 14 — no contrast Se TE Sie n=2 hostile access ooo n=1 major ICA kink/loop n=1 severe ao
Slide 35: Table 1. Clinical characteristics of the study patients
Table 1. Clinical characteristics of the study patients (n=101). PARADIGM Age, mean+SD (min-max) 6947 (51-86) > Male, % (n) 70% (71) Symptomatic, % (n) 55% (55) Symptomatic <14 days, % (n) 22%* (12) Acutely symptomatic (emergent CAS), % (n) 14%* (9) Index lesion (CAS), % (n) RICA 51% (52) LICA 49% (
Slide 36: Table 1. Clinical characteristics of the study patients
Table 1. Clinical characteristics of the study patients (n=101). Age, mean+SD (min-max) PARADIGM 6947 (51-86) > Male, % (n) 70% (71) Symptomatic, % (n) 55% (55) Symptomatic <14 days, % (n) 22%* (12) Acutely symptomatic (emergent CAS), % (n) 14%* (9) Index lesion (CAS), % (n) RICA 51% (52) LICA 49% (
Slide 37: Table 2. Quantitative lesion characteristics
PARADIGM Table 2. Quantitative lesion characteristics (n=106), NPD type, CGuard MN-EPS in situ characteristics. All (n=106 | Symptomatic |Asymptomatic lesions) n=51 Before CAS PSV, m/s 3.7+1.2 3.7411 3.741.2 0.964 EDV, m/s 1.2+0.5 1.140.5 1.2+0.5 0.268 : : external Diameter stenosis % (QA) 8349 80+9
Slide 38: Table 2 (cont'd) CGuard MN-EPS in situ characteristics
Table 2.(cont’d) CGuard MN-EPS in situ characteristics. PARADIGM All (n=106 | Symptomatic |Asymptomatic lesions) n=51 p-value Stent length (QA, CoreLab)* We Nominal 30 mm 29.8240.68 | 29.83+0.76 29.8040.59 . ' external (min-max) (27.83-32.62) | (27.83-32.62) | (28.83-31.89) Corelab | analysis Nomina
Slide 39: Table 2 (cont'd) CGuard MN-EPS in situ characteristics
Table 2.(cont’d) CGuard MN-EPS in situ characteristics. PARADIGM All (n=106 | Symptomatic |Asymptomatic lesions) n=51 p-value Stent length (QA, CoreLab)* We Nominal 30 mm 29.8240.68 | 29.83+0.76 29.8040.59 (min-max) (27.83-32.62) | (27.83-32.62) | (28.83-31.89) Nominal 40 mm 39.8940.59 | 39.80+0.70
Slide 40: PARADIGM
PARADIGM Eurointervention 2016;12:e658-70 & tct2016 TCT 2016 Featured Research
Slide 41: PARADIGM: CEA-like effect of CAS
PARADIGM CEA-like effect of CAS TCT 2016 Featured Research
Slide 42: PARADIGM procedural results
PARADIGM (ge © CAS feasibility using the study-tested MicroNet-covered embolic prevention stent system | 100% CAS |(n= 106) (ie, no cross-over to other stents or other carotid stent use during the whole study period) © Device success 99.1% — (n=105)* e Procedure success 99.1% (n=105)* e Transient do
Slide 43: PARADIGM Clinical Results (MACNE)
PARADIGM Ph Clinical Results (MACNE) © 0 peri-procedural death/major stroke/MI 0% © 1 peri-procedural minor stroke* 0.9% e0 new clinical events by 30 days 0% (100% follow-up, independent neuro evaluation) jht-hemispheric stroke 2 months prior to CAS), had hypotonia and transient, patient had additio
Slide 44: Novel Min Carotid Revascularization: Clinical & Duplex US Outcome Data @ 12 months
Novel Min Carotid (iia Revascularization: SSSI Clinical & Duplex US Outcome Data TCT 2016 @ 12 months & tct2016 TCT 2016 Featured Research
Slide 45: CGuard EPS Carotid PARADIGM Study 12mo Clinical Outcome Data
CGuard™ EPS Carotid PARADIGM Study 12mo Clinical Outcome Data : 12month data * 106 index arteries / 101 study subjects * no patient withdrawals by 12 months * 100% -clinical - neurological 12 month follow up - Duplex US & tct2016 2016 Featured Research
Slide 46: CGuard EPS Carotid PARADIGM Study 12mo Clinical Outcome Data
CGuard™ EPS Carotid I ADIGM Study 12mo Clinical Outcome Data 12month data * 106 index arteries / 101 study subjects * no patient withdrawals by 12 months * 100% -clinical - neurological 12 mont - Duplex US ‘ollow up ZERO Stroke Deaths ZERO Strokes @12mo Per-Protocol independent neurological evaluati
Slide 47: CGuard EPS Carotid PARADIGM Study 12mo Clinical Outcome Data
CGuard™ EPS Carotid F Vl Study 12mo Clinical Outcome Data 12month data * 106 index arteries / 101 study subjects * no patient withdrawals by 12 months * 100% _ -clinical - neurological 12 month follow up - Duplex US ZERO Stroke Deaths ZERO Strokes 30d-12mo Per-Protocol independent neurological evalu
Slide 48: CGuard EPS Carotid PARADIGM Study 12mo Clinical Outcome Data
CGuard™ EPS Carotid PARADIGM Study 12mo Clinical Outcome Data = : 12month data °0% stroke °0% TIA (1) in n=101 /stroke-risk patients "0% MI li (55% symptomatic) between 30 days and 12 months & tct2016 2016 Featured Research
Slide 49: PARADIGM 12month data
= PARADIGM 12month data 12 months eNO device-related adverse events eNO procedure-related events & tct2016 016 Featured Research
Slide 50: 12mo Duplex Ultrasound Data
CGuard™ EPS Carotid PARADIGM Study 12mo Duplex Ultrasound Data 2 z 8 12month data n=106 arteries 7 in 101 patients Qe iy E a ~ 5 a > es a 4 ¥o Pa | The 2 xs 2 3 ° aoe. . , 1 % 3 6 _ : baseline 30 days 12 months & tct2016 2016 Featured Research
Slide 51: 12mo Duplex Ultrasound Data
CGuard™ EPS Carotid PARADIGM Study [g\awifeny 12mo Duplex Ultrasound Data 8 12month data n=106 arteries 7 in 101 patients @ 6 2 E 5 > n a4 + <— 1 asymptomatic ISR (treated with PTA+DEB) 3 2 . we. me : . : Sy aS = 0 o baseline 30 days 12 months ct2016 2016 Featured Research
Slide 52: 12mo Duplex Ultrasound Data
CGuard™ EPS Carotid PARADIGM Study 12mo Duplex Ultrasound Data 2 12month data n=106 arteries 7 in 101 patients Q iS Belge PSV (m/s) + <—— 1 asymptomatic ISR (treated with PTA+DEB) Ww Set aye wfhts 2S nN State baseline 30 days 12 months ct2016 016 Featured Research
Slide 53: 12mo Duplex Ultrasound Data
CGuard™ EPS Carotid PARADIGM Study 12mo Duplex Ultrasound Data 2 12month data 8 n=106 arteries 7 in 101 patients @ 6 wt E . ~ 5. 2 > es 24 | ¥ me uf. 3 ‘fe xs 2 3 1 . 7 1 clinically-silent carotid laryngeal cancer relaps bifurcation occlusion™ S-session radioTx course 0 3 months after CAS baseline 3
Slide 54: 12mo Duplex Ultrasound Data
CGuard™ EPS Carotid PARADIGM Study 12mo Duplex Ultrasound Data = z 8 12month data n=106 arteries 7 in 101 patients ECA* patency @ 6 - 2 E 5 > n a4 3 2 . we on . 7 7 1 z % ag 4 0 o baseline 30 days 12 months ct2016 * patient alive, target CCA and ICA patent 2016 Featured Research
Slide 55: 12mo Duplex Ultrasound Data
CGuard™ EPS Carotid PARADIGM Study 12mo Duplex Ultrasound Data 8 12month data n=106 arteries 7 in 101 patients ECA* patency @6E - a E 5 > n a4 3} 2 . . ee es: & # baseline 30 days 12 months 97.09 97.09 96.99 sil Satsee > tct2016 T 2016 Featured Research
Slide 56: 12mo Duplex Ultrasound Data
CGuard™ EPS Carotid PARADIGM Study 12mo Duplex Ultrasound Data 8 n=106 arteries 7: in 101 patients @ 6 on 2 “t ~ 5 oe ‘ ts @yee) ° NO in-stent restenosis issue Ee NO CGuard ECA patency concern 1 & & ® . baseline 30 days 12 months > tct2016 16 Featured Research
Slide 57: MAY
MAY tct2016 TCT 2016 Featured Research
Slide 58: Slide 58
Slide 59: 12-month Data Conclusions
CGuard™ EPS Carotid PARADIGM Study 12-month Data 2 Conclusions & tct2016 TCT 2016 Featured Research
Slide 60: 12-month Data Conclusions
CGuard™ EPS Carotid PARADIGM Study 12-month Data ~. Conclusions eln the increased-stroke-risk population, including >50% symptomatic patients, CGuard™ EPS demonstrated effective and durable protection against stroke & tct2016 TCT 2016 Featured Research
Slide 61: 12-month Data Conclusions
CGuard™ EPS Carotid PARADIGM Study 12-month Data ~. Conclusions eln the increased-stroke-risk population, including >50% symptomatic patients, CGuard™ EPS demonstrated effective and durable protection against stroke in absence of any device-related adverse events by 12 months & tct2016 TCT 2016 Feat
Slide 62: 12-month Data Conclusions
CGuard™ EPS Carotid PARADIGM Study 12-month Data ~. Conclusions eln the increased-stroke-risk population, including >50% symptomatic patients, CGuard™ EPS demonstrated effective and durable protection against stroke in absence of any device-related adverse events by 12 months e12-month Duplex Ultras
Slide 63: Impact on clinical practice
Impact on PARADIGM clinical practice pees th With this novel technology, The ENDOVASCULAR route of carotid stenosis management in PRIMARY and SECONDARY Stroke Prevention is ° Viable V e Safe and effective Vv e Applicable to routine practice of CAS Vv ¢ Applicable to >90% of all-comer patients Vv e D
Slide 64: Endovascular for All-Comers
Endovascular for All-Comers See Endovascular of the Carotid Bifurcation Prevention of embolism, Optimal radial force, Conformability
Slide 65: Endovascular Solution for All-Comers
Endovascular Solution for All-Comers routine © CEA-like effect of — Endovascular Reconstruction of the Carotid Bifurcation Prevention of embolism, Optimal radial force, Conformability
Slide 66: This concept has been desired. And it works.
This concept has been desired. And it works. tct2016 TCT 2016 Featured Research
Slide 67: This concept has been desired. And it works.
This concept has been desired. And it works. tct2016 TCT 2016 Featured Research
Slide 68: This concept has been desired. And it works.
This concept has been desired. And it works. tct2016 CT 2016 Featured Research
Slide 69: Carotid Artery Revascularization for Stroke Prevention: A New Era
Carotid Artery Revascularization for Stroke Prevention: A New Era Piotr Musialek, MD, DPhil', and Silke Hopf-Jensen, MD? Keywords atherosclerosis, carotid artery stenosis, carould artery stent, double-layered stent, embolic prevention stent, MicroNet: covered stent, mesh-covered stent, stroke Caroti