Emerging Programs of DES with Biodegradable Polymers Biodegradable Polymer DES Programs Emerging Programs of DES with Biodegradable Polymers Ricardo A. Costa, MD, PhD Institute Dante Pazzanese, Sao Paulo, Brazil Monday, Feb. 20th 2017 – 11:24 to 11:32 am (8 minutes) Empire Ballroom – The Omni Shoreham Hotel Washington, DC, USA

Disclosure Statement of Financial Interest 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 Grant/Research Support Consulting Fees/Honoraria Major Stock Shareholder/Equity Royalty Income Ownership/Founder Intellectual Property Rights Other Financial Benefit Company Names

Conflict of Interest Statement Ricardo A. Costa, MD, PhD   Research grant/consulting fees from Meril Life Sciences

Potential Advantages Avoid problems related to temporary or permanent polymeric residue (late/very late recurrences, ST) Optimize vascular healing Maintain stent surface integrity (as opposed to webbing/delamination seen with durable polymers) Shorten DAPT post-implant; thus, avoid bleeding complications without compromising safety Maintain efficacy at inhibiting NIH

Emerging DES with BP Abluminus (Envision Scientific, India) Alex (Balton, Poland) BioMime (Meril Life Sciences, India) FireHawk (MicroPort, China) Inspiron (Scitech, Brazil) BuMA (SinoMed, China)

Emerging DES with BP Abluminus (Envision Scientific, India)

Antiproliferative agent: sirolimus Combination of DES and BEB Biodegradable polymer matrix Completed released by 180 days 45” inflation time to ensure complete drug delivery

en-ABL 1 Clinical Trial - QCA Results* Variable (40 pts/56 lesions) Baseline Final 6-Month Lesion length, mm 19.8±14.2 - Reference diameter, mm 2.46±0.45 2.61±0.43 2.53±0.43 MLD, mm 0.71±0.39 2.40±0.40 2.17±0.54 %DS 71.8±14.6 6.9±6.7 14.1±14.4 Late lumen loss, mm 0.24±0.30 *Cardiovascular Research Center, São Paulo, Brazil

Sammer Dani @ TCT 2016

Sammer Dani @ TCT 2016

Sammer Dani @ TCT 2016

Sammer Dani @ TCT 2016

Sammer Dani @ TCT 2016

Emerging DES with BP Abluminus (Envision Scientific, India) Alex (Balton, Poland)

Alex Sirolimus-Eluting Stent Cobalt-chromium platform – 70 µm (Alex Plus – new design) Bioabsorbable polymer coating – 5 µm (PLGA, absorbed in ~8 weeks) Wide range of sizes (2.0-4.5 mm diameter; 8-40 mm length)

Dariusz Dudek @ TCT 2016

Dariusz Dudek @ TCT 2016

Dariusz Dudek @ TCT 2016

Dariusz Dudek @ TCT 2016

PI: Dariusz Dudek (Krakow, Poland)

Emerging DES with BP Abluminus (Envision Scientific, India) Alex (Balton, Poland) BioMime (Meril Life Sciences, India)

*Cardiovascular Research Center, São Paulo, Brazil

BioMime Morph Registry – Kuala Lampur 222 patients with diffused CAD treated with Morph during Apr 2015 – September 2016 Baseline Characteristics N = 222 (%) Age, ≤ 60 Years 144 (64.9%) Age, > 60 Years 78 (35.1%) Diabetes Mellitus (DM) 56 (25.2%) Hypertension(HTN) 48 (21.5%) DM + HTN 104 (46.7%)

Procedural Information Variable N = 222 (%) Vessel Treated with BioMime Morph LAD 127 (57%) LCx 10 (5%) RCA 84 (38%) Sizes N = 222 (%) Diameters of BioMime Morph 3.50 – 3.00 mm 68 (30.0%) 3.00 – 2.50 mm 135 (60.8%) 2.75 – 2.25 mm 19 (9.2%) Lengths of BioMime Morph 30 mm 19 (8.0%) 40 mm 105 (47.5%) 50 mm 34 (15.5%) 60 mm 64 (29.0%) Dilatation N = 222, n (%) Pre-Procedure 219 (98.7%) Post-Procedure 222 (100.0%) Antiplatelet Drugs N = 222, n (%) Aspirin + Clopidogrel 20 (54%) Aspirin + Ticagrelor 17 (46%)

6 Months follow-up data 1 & 6 months clinical follow-up data At Procedure (N = 222) 1 month f/up 6 month f/up (N = 215) Death No Complications 222 (100 %) 100 (100 %) 215 (96.8 %) Stent Thrombosis Bleeding

Emerging DES with BP Abluminus (Envision Scientific, India) Alex (Balton, Poland) BioMime (Meril Life Sciences, India) FireHawk (MicroPort, China)

Key Components Co-Cr stent with abluminal grooves D,L-PLA absorbed after 9 mo and recover to metallic surface Printing technology Sirolimus 1/3 of drug dose of Cypher

Stent Design - Isolated Abluminal Grooves One of the main components of Target Eluting Technology. Only in the straight parts of the strut. The grooves designed on the outer surface of the stent allows targeting release of the drug to coronary vessel wall. The depth of groove is about 1/3 of the strut, and the thickness of coating stored in the groove is about 10 microns (0.00039”)

TARGET Clinical Program FIM Enrollment n=21 TARGET I Trial Enrollment n=510 TARGET II Registry Enrollment n=730 Workhorse Stent * Randomized Trial n=460 Long FIREHAWK (33 and 38mm) Registry, n=50 4mo Angio (95%) and OCT (70%) F/U XIENCE V n=230 FIREHAWK n=230 9mo Angio F/U (>=80%) 9mo Angio F/U (>=80%) 1-Year Clinical F/U (>=95%) and Annually up to 5 Years (n=1,010) Primary Clinical Endpoint: Device Oriented Composite of Cardiac Death, TVMI, or iTLR (Target Lesion Failure, TLF) at 1-Year (Objective Performance Criteria)

Early healing proved by 4m OCT from Target FIM study Analyzed: 14 Stented Segments Every 0.3mm (1084 Cross-Sections), 11551 Struts 2.2% 1.6% Optical Coherence Tomography, OCT 11108, 96.2% 0.1%

TARGET All Comers – Clinical Trial Design Open label, non-inferiority trial All patients with symptomatic CAD eligible for DES implantation (no lesion/vessel limitations) 1,656 patients, 20 sites (Europe) Subsets: QCA 176 pts; OCT 50 pts 100% monitoring Firehawk Stent n = 828 Xience EES n = 828 Clinical/TLF 30d 6mo 12mo 13mo 2yr 3yr 4yr 5yr Angio/OCT 50 Pts OCT Subset 176 Pts QCA Subset Primary Endpoint: TLF (ARC defined) = Cardiac Death, Target Vessel MI, ID-TLR @ 12mo Secondary Endpoint (powered): in-stent late loss @ 13mo; uncovered stent strut rate @ 3mo Secondary Endpoints: TLF @ 30d, 6mo, 2 - 5 yr; Composite (all death, all MI, any revasc) at each FU time point; QCA parameters @ 13 mo; OCT parameters @ 3 mo Drug Therapy: ASA and thienopyridine > 6 months (per guidelines)

Emerging DES with BP Abluminus (Envision Scientific, India) Alex (Balton, Poland) BioMime (Meril Life Sciences, India) FireHawk (MicroPort, China) Inspiron (Scitech, Brazil)

Inspiron SES Thin-Strut Plataform CoCr – L605 Abluminal Coating Biodegradable Polymer Low Drug Sirolimus Cronus Plus™ 75 μm strut thickness PLA + PLGA Abluminal only 5 μm layer thickness Complete degradation in 6-9 months Low dose Inspiron™ 3.5 x 13 mm Cypher™ 3.5 x 13 mm 56 μg 129 μg

6-month angiographic and IVUS outcomes INSPIRON I Trial 6-month angiographic and IVUS outcomes EuroIntervention 2014;9:1380-1384 In-Stent late loss* IVUS % NIH Obstruction P < 0.001 P <0.001 26.5 ± 11.4 0.84 ± 0.45 7.8 ± 7.1 0.22 ± 0.17 *Primary EP *Cardiovascular Research Center São Paulo, Brazil

DESTINY Trial Study Design (Multicenter in 10 Brazilian Institutions) 170 patients (194 lesions) Up to 2 de novo lesions Vessels 2.5 – 3.5 mm Single stent per lesion (up to 29 mm) Primary EP IS LL at 9 months Non-inferiority Randomization 2:1 Inspiron (n=110 pts) Biomatrix (n=55 pts) IVUS substudy* (n=60 pts / 66 lesions) 9-month angiographic follow-up* (164 pts [96.5%] / 187 lesions [96.4]) OCTsubstudy* (n=21 pts / 25 leions) *Cardiovascular Research Center, São Paulo, Brazil

DESTINY Trial 9-month QCA (in-stent) . Inspiron Biomatrix P N 127 60 MLD, mm 2.44 ± 0.44 2.55 ± 0.40 0.09 DS, % 11.2 ± 11.3 9.7 ± 6.6 0.26 Late loss, mm* 0.20 ± 0.27 0.15 ± 0.20 <0.001 (NI) Binary restenosis 3.2% (4) 1.7% (1) 0.56 *Study primary endpoint

DESTINY Trial OCT Safety endpoints Total of 8,944 struts analyzed [SES: 5,801; BES: 3,143] P = 0.021 P = 0.198 2.38 ± 2.20 0.51 ± 1.00 0.28 ± 1.06 0.53 ± 0.81 Uncovered Struts Malapposed Struts

INSPIRON (N= 111 Patients) BIOMATRIX FLEX (N= 55 Patients) DESTINY Trial Clinical events (up to 270 days) INSPIRON (N= 111 Patients) BIOMATRIX FLEX (N= 55 Patients) P-value MACCE 7/111 (6.30) 4/55 (7.30) 0.672 MACE Death 0/111 (0.00) 0/55 (0.00) NA Emergent CABG MI 5/111 (4.50) 3/55 (5.45) 0.803 TLR 3/111 (2.70) 1/55 (1.82) 0.690 TLR / TVR 6/111 (5.40) 0.269

Inspiron Registry Baseline Clinical Characteristics (n=371 pts) Male 63.3 Age, years 62.9 ± 10.6 Diabetes 50.7 Insulin-requiring DM 14.6 Acute coronary syndrome 39.6 Multivessel disease 69.2 2-vessel CAD 35.8 3-vessel CAD 33.4 Heart failure 15.6 Previous coronary treatment 48.5 Previous PCI Previous CABG 18.1 Numbers are average ± standard deviation or percentages CABG = coronary artery bypass graft surgery; CAD = coronary artery disease; DM = diabetes mellitus; PCI = percutaneous coronary intervention

Inspiron Registry Clinical Outcomes (n=371 pts; K-M estimates) Mean 1.6 stents/pt (34.3 mm length) 30 days 180 days Overall death 0.8 1.6 Myocardial infarction Peri-procedural 4.0 - Non-peri-procedural 1.3 Target vessel revascularization 2.8 Any major cardiac adverse event 4.6 9.0 Stent thrombosis 0.5 Possible Probable Definite

Emerging DES with BP Abluminus (Envision Scientific, India) Alex (Balton, Poland) BioMime (Meril Life Sciences, India) FireHawk (MicroPort, China) Inspiron (Scitech, Brazil) BuMA (SinoMed, China)

Conclusions New emerging DES with biodegradable polymer technology incorporate advanced thin cobalt-chromium platforms, abluminal coating and relatively low drug dose (mainly sirolimus) Overall, all systems have demonstrated high efficacy on inhibiting NIH and low event rates Comparative, non-inferiority studies evaluating their performance and clinical impact in complex, real world scenarios comparison to current gold standard DES

Thanks!