Everolimus-eluting Bioresorbable Vascular Scaffolds in Patients with Coronary Artery Disease: The ABSORB III trial Dean J. Kereiakes, MD, Stephen G. Ellis, MD, D. Christopher Metzger, MD, Ronald P. Caputo, MD, David G. Rizik, MD, Paul S. Teirstein, MD, Marc R. Litt, MD, Annapoorna Kini, MD, Ameer Kabour, MD, Steven O. Marx, MD, Jeffrey J. Popma, MD, Robert McGreevy, PhD, Zhen Zhang, PhD, Charles Simonton, MD and Gregg W. Stone, MD for the ABSORB III Investigators

Modest Consulting Fees Significant Consulting Fees Major Stock Shareholder/Equity HCRI Boston Scientific Abbott Vascular Svelte Medical Systems, Inc. Janssen Research & Development LLC Sanofi-Aventis U.S. LLC Ablative Solutions, Inc. Affiliation/Financial RelationshipCompany 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.

Everolimus/PDLLA (1:1) matrix coating Everolimus/PDLLA (1:1) matrix coating 7 µm7 µm Conformal coatingConformal coating Controlled drug release similar to Xience CoCr-EESControlled drug release similar to Xience CoCr-EES PLLA Backbone PLLA Backbone Semi-crystallineSemi-crystalline Circumferential sinusoidal rings connected by linear linksCircumferential sinusoidal rings connected by linear links Strut thickness 150 µmStrut thickness 150 µm Platinum markers in each end ringPlatinum markers in each end ring FullyBioresorbable Absorb BVS

Drug Elution Mechanical Support Mass loss Oberhauser JP et al. EuroInt 2009;5:F RevascularizationRestoration Resorption Months Phases of Absorb Functionality

1 Atherosclerosis 2014;237:23e29 2 Images courtesy of S Windecker, ABSORB Cohort B 5 Yrs Metallic DES 1 Absorb-Treated Artery 2 Metallic DES vs. Absorb BVS Representative Human images at 5 Years

Absorb Program Objectives A Series of Randomized Trials Designed to: Demonstrate similar (non-inferior) results with ABSORB BVS compared to Xience CoCr-EES at 1 yearDemonstrate similar (non-inferior) results with ABSORB BVS compared to Xience CoCr-EES at 1 year Demonstrate superior results with ABSORB BVS compared to Xience CoCr-EES between 1 and 5 yearsDemonstrate superior results with ABSORB BVS compared to Xience CoCr-EES between 1 and 5 years

7 30 d6 mo12 mo24 mo36 mo48 mo60 mo Clinical follow-up: Prospective, multicenter, single-blind, trial ~2,000 patients randomized 2:1 Absorb BVS vs. Xience CoCr-EES ABSORB III Study Design No routine angiographic follow-up

U.S. Australia 193 Enrolling Centers

1. Dr. Metzger (76) Holston Valley Wellmont Medical Center 8. Dr. DeGregorio (38) Englewood Hospital and Medical Center 15. Dr. Waksman (26) MedSTAR Washington Hospital Center 2. Dr. Caputo (52) St. Joseph's Hospital Health Center 9. Dr. Cannon (36) Northern Michigan Hospital 16. Dr. Abbas (24) William Beaumont Hospital 3. Dr. Rizik (49) Scottsdale Healthcare 10. Drs. Cambier & Stein (35) Morton Plant Hospital, 17. Dr. Zidar (24) Rex Hospital, Inc 4. Dr. Teirstein (45) Scripps Green Hospital 11. Dr. Newman (34) WakeMed 18. Dr. Dearing (24) Thomas Hospital 5. Dr. Litt (42) Baptist Medical Center 12. Dr. Feldman (31) Munroe Regional Medical Center 19. Dr. Williams (23) Presbyterian Hospital 6. Dr. Kini (41) Mount Sinai Medical Center 13. Dr. Broderick (28) The Christ Hospital 20. Dr. Choi (23) Baylor Jack and Jane Hamilton Heart and Vascular Hospital 7. Dr. Kabour (41) Mercy St. Vincent Medical Center 14. Dr. Jain (28) Washington Hospital, Fremont, CA 21. Dr. Moses (23) Columbia University Medical Center Top Enrollers (N patients)

Principal Investigators  Dean Kereiakes, MD, The Christ Hospital, Cincinnati, OH  Stephen G. Ellis, MD, Cleveland Clinic, Cleveland, OH Study Chairman  Gregg W. Stone, MD, Columbia University Medical Center, NY, NY Clinical Events Committee  Cardiovascular Research Foundation, New York, NY Steven Marx, MD, chair Angiographic Core Laboratory  Beth Israel Deaconess Medical Center, Boston, MA Jeff Popma, MD, director Data Safety Monitoring Board  Axio Research, Seattle, WA; Robert N. Piana, MD, chair Sponsor  Abbott Vascular, Santa Clara, CA Study Leadership

Primary Endpoint: Target Lesion Failure (non-inferiority) Cardiac death, or Myocardial infarction attributed to the target vessel (TV-MI), or Peri-procedural MI: CK-MB >5x ULN w/i 48 hours Ischemia-driven target lesion revascularization (ID-TLR) Powered Secondary Endpoints (superiority) Angina All revascularization Ischemia-driven target vessel revascularization (ID-TVR) Major Endpoints at 1 Year

Non-inferiority analysis for TLF at 1 year with the following assumptions:  1-year TLF rate of 7%  Non-inferiority margin of 4.5%  “Putative placebo”, preserving ≥ 50% of the treatment effect of Xience vs. BMS  1-sided alpha of (equivalent to 2-sided 0.05)  95% 1-year follow-up  2000 subjects → 96% power Maximum observed difference in order to pass non-inferiority = 2% Primary Endpoint Statistical Design

>18 years old Evidence of myocardial ischemia (stable/unstable/post- infarction angina or silent ischemia) No elevation of CK-MB 1 or 2 de novo target lesions in up to 2 native coronary arteries (max 1 lesion per artery) Diameter stenosis ≥50% and <100% with TIMI flow ≥1  If <70%, abnormal functional test (including FFR ≤0.80), unstable angina or post-infarct angina RVD ≥2.50 mm and ≤3.75 mm (site-determined) Lesion length ≤24 mm (site-determined) Key Patient Eligibility Criteria

Randomized 2:1 N=2008 (ITT) ABSORB N=1322 ABSORB N=1312 Xience N= % Complete 98.7% Complete N=4 lost to follow-up N=6 withdrew consent N=6 lost to follow-up N=3 withdrew consent Xience N= month Follow-up Study Flow and Follow-up

Characteristic Absorb (N=1322) Xience (N=686)p-value Age (mean)63.5 ± ± Male70.7%70.1%0.80 Race (Caucasian)87.1%88.3%0.44 Current tobacco use21.3%20.7%0.77 Hypertension84.9%85.0%0.95 Dyslipidemia86.2%86.3%0.97 Diabetes31.5%32.7%0.60 Insulin-treated10.5%11.2%0.60 Prior MI21.5%22.0%0.79 Prior coronary intervention38.7%38.0%0.75 Stable angina57.3%60.8%0.13 Unstable angina26.9 %24.5%0.25 Silent ischemia10.0%10.2%0.88 Single vessel disease69.5%67.2%0.29 Baseline Characteristics

Characteristic Absorb (N=1322) (L=1385) Xience (N=686) (L=713)p-value ACC/AHA lesion class B2/C68.7%72.5%0.08 # of target lesions treated1.0 ± One95.1%96.1%0.32 Two4.8%3.9%0.36 Target lesion LAD44.5%42.2%0.31 RCA29.2%27.2%0.35 Circumflex26.2%30.6%0.03 Lesion length, mm12.60 ± ± RVD, mm2.67 ± ± RVD <2.25 mm18%19%0.39 MLD, mm0.92 ± ± %DS65.3 ± ± Baseline Lesion Characteristics (QCA) N= number of subjects L= number of lesions

Characteristic Absorb (N=1322) (L=1385) Xience (N=686) (L=713)p-value Per Subject Bivalirudin use60.7%58.7%0.39 GP IIb/IIIa inhibitor use10.1%12.4%0.11 Only unassigned devices implanted4.4%0.6%<0.001 Unplanned overlapping devices6.2%8.5%0.06 Post-dilatation performed65.5%51.2%<0.001 Intravascular imaging guidance11.2%10.8%0.81 Procedure duration (min)42.2 ± ± 20.9<0.001 Per Lesion Total study device length (mm)20.5 ± ± Max device/balloon diameter (mm)3.18 ± ± Max device/balloon to vessel diameter ratio 1.21   Maximum device/balloon pressure (atm.)15.4 ± ± Procedural Characteristics N= number of subjects L= number of lesions

Measurement Absorb (N=1322) (L=1385) Xience (N=686) (L=713)p-value RVD2.70 ± ± In-Device MLD2.37 ± ± 0.40< Acute gain1.45 ± ± 0.44< %DS11.6 ± ± 8.91< In-Segment MLD2.15 ± ± Acute gain1.23 ± ± %DS20.0 ± ± Post-procedural QCA N= number of subjects L= number of lesions

Absorb (N=1322) (L=1385) Xience (N=686) (L=713)p-value Device Success94.3%99.3%< Procedural Success94.6%96.2%0.12 Device Success (lesion basis) Device Success (lesion basis)  Successful delivery and deployment of study scaffold/stent at intended target lesion  Successful withdrawal of delivery system and final in-scaffold/stent DS <30% (QCA) Procedure Success (patient basis) Procedure Success (patient basis)  Successful delivery and deployment of at least one study scaffold/stent at intended target lesion  Successful withdrawal of delivery system and final in-scaffold/stent DS <30% (QCA)  No in-hospital (maximum 7 days) TLF Acute Success

Absorb (N=1322) Xience (N=686)p-value At index procedure P2Y12 inhibitor99.0%98.8%0.70 Clopidogrel62.6%64.7%0.34 Prasugrel21.8%19.5%0.24 Ticagrelor14.8%14.9%0.94 Aspirin99.3% 1.00 At 30 days P2Y12 inhibitor99.0%99.1%0.81 Clopidogrel68.3%72.0%0.09 Prasugrel20.7%17.5%0.08 Ticagrelor11.8%10.6%0.44 Aspirin usage98.6%99.0%0.43 At 1 year P2Y12 inhibitor94.4%95.0%0.55 Clopidogrel67.5%72.2%0.03 Prasugrel17.9%14.0%0.03 Ticagrelor9.0%8.9%0.94 Aspirin usage95.8% 0.94 Antiplatelet Agent Usage

Non-inferiority margin = 4.5% = 4.5% Difference = 1.7% [-0.5%, 3.9%] P NI = % Difference (ABSORB - Xience) Primary Endpoint 1 Year TLF 1-Year TLF ABSORB vs. Xience 7.8% (102/1313) vs. 6.1% (41/677)

No. at Risk: Absorb TLF (%) Xience Months Post Index Procedure 20% 100% 80% 60% 40% 0% Absorb BVS (n=1322) Xience CoCr-EES (n=686) Diff [95% CI] = 1.7% [-0.5% to 3.9%] P superiority = %15% 10% 5% 0% % 6.0% 12 Target Lesion Failure

Subgroup Absorb (N=1322) Xience (N=686) RR (95% CI) Relative Risk (95% CI) p-value (interaction) Age ≥64 years8.1%5.9%1.37 ( ) 0.69 Age <64 years7.4%6.2%1.19 ( ) Female8.5%7.4%1.16 ( ) 0.68 Male7.4%5.5%1.36 ( ) Diabetes10.7%9.1%1.18 ( ) 0.68 No diabetes6.3%4.6%1.38 ( ) Unstable angina/recent MI6.5%6.6%0.98 ( ) 0.35 Stable CAD8.3%5.8%1.42 ( ) Single TL/TV treated7.7%5.8%1.32 ( ) 0.50 Dual TL/TV treated9.4%11.5%0.81 ( ) Clopidogrel8.0%6.8%1.17 ( ) 0.43 Prasugrel or ticagrelor7.1%4.3%1.63 ( ) ACC/AHA class A or B16.8%2.2%3.05 ( ) 0.07 ACC/AHA class B2 or C8.2%7.5%1.10 ( ) Lesion length <11.75 mm7.9%4.8%1.64 ( ) 0.23 Lesion length ≥11.75 mm7.7%7.3%1.06 ( ) RVD <2.63 mm9.8%7.8%1.27 ( ) 0.90 RVD ≥2.63 mm5.7%4.3%1.34 ( ) Favors Absorb Favors Xience 1-Year TLF: Subgroup analysis 1.0

1-Year TLF Components P=0.16 P=0.29 P=0.18 P=0.50

P=0.18 P=0.35 P=0.31 P=0.28 P=0.56 P=0.40 Myocardial Infarction to 1 Year

CK-MB threshold Absorb (N=1322) Xience (N=686)Differencep-value >3x ULN6.8%6.6% >5x ULN (protocol)3.0%2.8% >8x ULN1.3% >10x ULN0.9%1.2% SCAI definition*0.9%1.2% Peri-Procedural MI by Definition *>10x ULN or >5x ULN with new Q waves or new persistent LBBB J Am Coll Cardiol 2013;62:

Absorb (N=1322) Xience (N=686)p-value Device Thrombosis (def*/prob)1.54%0.74% Early (0 to 30 days)1.06%0.73% Late (> 30 to 1 year)0.46%0.00% Definite* (1 year)1.38%0.74% Probable (1 year )0.15%0.00%0.55 *One “definite ST” in the Absorb arm by ITT was in a pt that was treated with Xience Device Thrombosis to 1 Year

1-Year Device Thrombosis Subgroup Absorb (N=1322) Xience (N=686) RR (95% CI) Relative Risk (95% CI) p-value (interaction) Age ≥64 years1.8%0.6%3.22 ( Age <64 years1.2%0.9%1.33 ( ) Female1.6%2.0%0.79 ( ) 0.07 Male1.5%0.2%7.21 ( ) Diabetes3.2%1.4%2.34 (0.67-8,13) 0.78 No diabetes0.8%0.4%1.79 ( ) Unstable angina/recent MI1.0%0.6%1.88 ( ) 0.91 Stable CAD1.7%0.8%2.16 ( ) Single TL/TV treated1.6%0.8%2.09 ( ) n/a Dual TL/TV treated0.0% - Clopidogrel1.8%0.7%2.69 ( ) 0.33 Prasugrel or ticagrelor0.8%0.9%0.96 ( ) ACC/AHA class A or B10.8%0.6%1.36 ( ) 0.67 ACC/AHA class B2 or C1.9%0.8%2.32 ( ) Lesion length <11.75 mm1.4%0.9%1.58 ( ) 0.56 Lesion length ≥11.75 mm1.7%0.6%2.82 ( ) RVD <2.63 mm2.3%0.9%2.65 ( ) 0.48 RVD ≥2.63 mm0.8%0.6%1.28 ( ) Favors Absorb Favors Xience

Absorb (N=1322) Xience (N=686)p-value Angina18.3%18.4%0.93 All Revascularization9.1%8.1%0.50 ID-TVR5.0%3.7%0.21 Powered Secondary Endpoints

ABSORB III eligibility criteria included vessels with RVD 2.5 mm – 3.75 mm (visual estimation) The thicker struts of ABSORB may be of particular concern in very small vessels Subgroup analysis was therefore performed in vessels with QCA RVD <2.25 mm vs. ≥2.25 mm (correlates with visual estimate ~2.5 mm) ~19% of patients had a target lesion with RVD <2.25 mm by QCA ABSORB III Very Small Vessel Analysis

RVD <2.25 mm (median 2.09 mm) 1-Year Events (%) Median based on pooled Absorb and Xience RVD ≥2.25 mm (median 2.74 mm) Outcomes by QCA RVD 2.25 mm # Events: # Risk: TLF: P int diff = 0.31 ST: P int diff = 0.12

ABSORB III enrolled patients with stable ischemic heart disease and stabilized ACS, and excluded specific complex lesions (e.g. CTO, LM, large bif); results may therefore not be generalizable to higher- risk patients and more complex disease Underpowered for low frequency events Results should be viewed in context that Xience was the control device which has been associated with the lowest rates of ST and other events BVS is a first generation device and was used for the first time by most operators within this trial Limitations

ABSORB BVS was non-inferior to Xience CoCr- EES for TLF at 1 year (primary endpoint met) TLF components (cardiac death, TV-MI, ID-TLR) were not significantly different between devices Angina, all revascularization and ID-TVR were similar between devices No statistically significant differences in device thrombosis were present Summary and Conclusions (1)

The ABSORB III trial has demonstrated safety and efficacy of Absorb BVS at 1 year in patients with stable CAD and stabilized ACS Longer term evaluation is ongoing to determine if ABSORB improves late outcomes compared to Xience Summary and Conclusions (2)