Bioresorbable scaffold: the advent of a new era in percutaneous coronary revascularisation Clinical Data Update Ron Waksman, MD, FACC Director, Cardiovascular Research & Advanced Education Associate Chief of Cardiology, Washington Hospital center, Professor of Cardiology, Georgetown University Washington DC

Disclosure Consultant : Biotronik, Medtronic, Boston Scientific. Abbott Vascular Speaker Biotronik BSC, Medtronic, Abbott Vascular Research Grants: Biotronik, Medtronic, Boston Scientific, GSK, Medicine Company, Abbott Vascular

ABSORB A - 5 Year Clinical Results Hierarchical 6 Months 30 Patients 12 Months 29 Patients* 4 Years 5 Years Ischemia Driven MACE, %(n) 3.3% (1)* 3.4% (1)* Cardiac Death, % 0.0% MI, %(n) Q-Wave MI Non Q-Wave MI 3.3% (1)** 3.4% (1)** Ischemia Driven TLR , % by PCI by CABG No new MACE events between 6 months and 5 years *One patient withdrew consent after 6 months **This patient also underwent a TLR, not qualified as ID-TLR (DS = 42%) followed by post-procedural troponin qualified as non-Q MI and died from his Hodgkin’s disease at 888 days post-procedure. Serruys PW, Onuma Y: 5-year Cohort A and 2-year Cohort B results: Integrated insights. In: Transcatheter Cardiovascular Therapeutics. San Francisco, CA November 08 2011.

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Postmarketing Surveillance All-comers Multi-Center RC Trial Global Postmarketing 10,000 PTS ABSORB STEMI Registry

Bioabsorbable magnesium scaffolds: novel experimental and clinical results - Biotronik’s DREAMS program

AMS (2004) The first generation bare magnesium scaffold Where we come from: A bare magnesium scaffold with favorable mechanical properties Mechanical parameters High radial strength (~0.8 bar) Low recoil (<5%) Scaffold Backbone WE43 Mg-alloy Excellent biocompatibility 165µm strut thickness Delivery system Lekton RX catheter Design & Manufacturing Laser cut and polished surface Sizes used in studies 3.25/3.5 x 16 6F compatible

AMS Product Evolution AMS 2004 4 mo n = 63 12 mo n = 60 Cardiac death MI Scaffold thrombosis TLR (clinically driven) 23.8% 26.7% Late loss (mm) 1.08 ± 0.49 - Learnings from AMS Device is safe and feasible Effectiveness required optimization IVUS findings showed lumen loss was due to loss of scaffolding area and NIH 7 year follow-up: no additional MACE between 12 months and 7 years Need for longer scaffolding support and addition of antiproliferative drug Erbel et al. Lancet 2007; 369: 1869–75.

DREAMS device evolution Drug-eluting AMS (DREAMS) Refined alloy with slower absorption rate Reduced strut thickness 6-crown design PLGA polymer carrier Paclitaxel drug elution Used in BIOSOLVE-I study AMS DREAMS 165µm 80µm 130µm 120µm AMS 28-day histology DREAMS 28-day histology

BIOSOLVE-I study design DESIGN: Prospective. multi-center. FIM. single de novo coronary artery lesions between 3.0-3.5 mm and ≤ 12 mm long PRIMARY ENDPOINT: Cohort 1: TLF at 6 months Cohort 2: TLF at 12 months PRINCIPAL INVESTIGATOR: J. Koolen. MD. Catharina Ziekenhuis. Eindhoven. Netherlands 46 patients with de novo coronary artery stenosis Cohort 1 (n = 22) Cohort 2 (n = 24) Mandatory 6mo: Clinical FUP (n = 22) Imaging FUP (n = 201) Optional 6mo: Clinical FUP (n = 24) Imaging FUP (n = 16) Optional 12mo: Clinical FUP (n = 202) Imaging FUP (n = 13) Mandatory 12mo: Clinical FUP (n = 232) Imaging FUP (n = 201) Mandatory 24mo: Clinical FUP (n = 202) Mandatory 24mo: Clinical FUP (n=24) 1 5 pts withdrew consent for imaging FUP (2 at 6-month and 4 at 12-month FUP) 2 1 pt died a non-cardiac death (Cohort 1). 2 pts withdrew consent (1 Cohort 1 and 1 Cohort 2) Mandatory 36mo: Follow-up ongoing Source: M Haude. et al. Lancet 2013; 381:836-44. 37

BIOSOLVE-I study design Prospective, multi-center, first-in-man trial, single de novo coronary artery lesions with RVD between 3.0 and 3.5 mm and lesion length ≤ 12 mm Primary Endpoint Cohort 1: TLF1 at 6 months Cohort 2: TLF1 at 12 months 46 patients with de novo coronary artery stenosis Cohort 1 (n=22) Cohort 2 (n=24) 6-month FUP Clinical (n=22) Imaging (n=202) Clinical (n=24) Imaging (n=16) 1 Composite of cardiac death, target vessel myocardial infarction and clinically driven TLR 2 A total of 5 pts withdrew consent for imaging FUP (2 at 6-month and 4 at 12-month FUP) 3 1 pt died a non-cardiac death (Cohort 1), 2 pts withdrew consent 12-month FUP Clinical (n=203) Imaging (n=13) Clinical (n=233) Imaging (n=202) Bold: Mandatory endpoint Italic: Optional endpoint 24 and 36-month FUP QCA and IVUS are mandatory imaging follow-ups, while OCT is optional

BIOSOLVE-I study results 6-and 12-month late lumen loss (LLL) 6-month LLL 0.64 ± 0.50 mm 12-month LLL 0.52 ± 0.39 mm LLL of the bare AMS in the PROGRESS study at 4-month: 1.08 ± 0.49 mm Cumulative Frequency (%) In-scaffold LLL (mm) Source: M Haude. et al. Lancet 2013; 381:836-44. 39

BIOSOLVE-I study results Six to 24-month clinical follow-up Device success 100% (47 / 47) Procedure success 100% (46 / 46) Clinical results 6-month1 12-months1 24-months Cohort 1 & 2 Cohort 1&2 TLF 4.3% (2/46) 6.8% (3/44) Cardiac death 0.0% MI2 2.3% (1/44) Scaffold thrombosis TLR (clinically driven)3 4.5% (2/44) Device Success: successful delivery of the scaffold to the target lesion, appropriate deployment, successful removal of delivery system. Procedure Success: device success plus attainment of a final residual stenosis of <50% of the target lesion. absence of MACE during the hospital stay up to 7 days. 1 M Haude. et al. Lancet 2013; 381:836-44. 2 Target vessel peri-procedural MI. 3 TLR occurred during 6M FUP, both pts had angina. 1 pt received an additional DREAMS during the initial procedure due to a flow-limiting bailout. 40

BIOSOLVE-I study results Vasomotion results at 6-month (N=26) Relative Change in mean lumen diameter % Proximal Segment Scaffolded Segment Distal Segment -12.91 ±17.93% 9.34 ± 12.88% -10.04 ± 20.30% 8.69 ±10.05% -10.51 ±22.05% 9.66 ±9.33% Mean ±SD ACH NTG -80 -60 -40 -20 20 40 60 ACH concentration Low: 0.36 µg/mL Medium: 3.6 µg/mL High: 18 µg/mL Nitro concentration 200 µg/mL Acetylcholine (ACH): Presents the % change in mean lumen diameter between pre-and post-Acetylcholine (ACH) at the highest response Nitroglycerine (NTG): Presents the % change in mean lumen diameter between post-ACH and Nitroglycerine

DREAMS product evolution 1st generation DREAMS 2nd generation Refined WE43 alloy with slow degradation 3-link design with 120 µm strut thickness PLGA polymer carrier Paclitaxel drug elution analog to Taxus Used in BIOSOLVE-I study in 2010 Optimized scaffold design and process for Better bending flexibility Increased deployment diameter 6-crown 2-link design Radiopaque markers at both ends PLLA drug carrier polymer, same as ORSIRO Sirolimus drug elution, same drug dose density as ORSIRO

DREAMS summary DREAMS First Generation demonstrates an excellent safety profile up to 24 months TLF rate remains stable up to 24-month follow-up DREAMS demonstrated significantly improved efficacy at 12 months compared to the bare AMS: Reduction in LLL of 61% compared to the 4-month data of the bare AMS (1.08mm vs. 0.52mm) Reduction of TLR rate by 82% (26.7% vs. 4.7%) DREAMS second generation improved scaffold properties and utilizing Orsiro DES coating PLLA and Sirolimus BIOSOLVE –II will start in Q3 2013 using second generation DREAMS 43 43

BRS VERSUS BMS and DES

BRS TECHNOLOGY PROJECTION Second and third generation BRS will be disruptive technology with improved deliverability and reduced cost The Bioabsorbable DES is most likely non-inferior to the best in class DES of today and may be superior within 5 years of follow-up The perception of patients and physicians is strong and will drive high usage of BIORESORBABLE DES to become the gold standard for PCI

Bioresorbable scaffolds have been called “the Fourth Revolution” in PCI FIRST SECOND THIRD FOURTH Balloon angioplasty 1977 Bare metal stents 1990s Bioresorbable Drug- eluting stents 2006 Drug-eluting stents 2000’s