Elixir Medical Novolimus Elution from A Biodegradable Polymer CRT 2012 Elixir Medical Novolimus Elution from A Biodegradable Polymer Alexandre Abizaid, MD, PhD On behalf of the EXCELLA BD Investigators International (OUS) Use Only

Alexandre Abizaid, MD, PhD Consulting Fees: Abbott Vascular BSC

Innovating Vascular Restoration Pharmacological Agent Limus Family ↓ Drug dose ↑ Spatial distribution ↑ Residual tissue conc. Controlled Release Biocompatible Polymers Durable Bioabsorbable ↓ Polymer load Stent Platform Cobalt Chromium Alloy ↓ Strut thickness ↑ Flexibility & Deliverability ↑ Vessel coverage Stent Scaffold Fully bioresorbable ↑ Sustained clinical performance ↑ Vasomotion

Novolimus known safety profile Active metabolite of Sirolimus Binds to FKBP12 forming an immunosuppressive complex mTOR inhibitor Known Safety Profile Patients treated with Sirolimus orally or via DES implantation exposed to significant amount of Novolimus Potent anti-proliferative Inhibition of proliferation of hSMC IC50 = 0.5nM Formula: C50H77NO13 MW: 900 Drug Concentration  Systemic Novolimus Exposure after oral Sirolimus Elixir Novolimus DES & Scaffold Not to scale Oral Sirolimus Sustained performance with low drug dose (5 ug/mm stent length for all product platforms) Time 

Controlled Release Technology DESyneTM (Durable Polymer) and DESyne BDTM (Biodegradable Polymer) DESyne and DESyne BD Cypher Xience / Promus Resolute BioMatrix Synergy Strut Thickness (µm) Polymer Thickness (µm) Drug Load (µg) 5

DESyne™ and DESyne BDTM Novolimus-eluting DES Features DESyneTM Durable polymer drug release over 12 weeks Workhorse DES with sustained clinical performance through 2 years Platform features Cobalt chromium alloy stent 81 µm thickness Novolimus drug dose of 5 mcg per mm stent length Thin polymer matrix No primer coating < 3µm coating thickness DESyne BDTM Biodegradable polymer degrades in 6-9 months, drug release over 4 weeks Workhorse DES that leaves behind bare metal surface

Elixir clinical programs running in parallel across three platforms Pharmaceutical Novolimus Products DESyneTM DESolveTM FIM completed* DESyneTM BD FIM completed FIM completed FIMs CE Studies EXCELLA II RCT Completed EXCELLA BD RCT Completed DESolve Nx Enrollment Ongoing IDE Studies EXCELLA III Pending *Myolimus

EXCELLA II Randomized Clinical Trial RANDOMIZED (2:1), SINGLE BLIND, MULTI-CENTER CLINICAL TRIAL Principal Investigator: P. W. Serruys, MD, PhD Co-Principal Investigators: A. Abizaid, J.Ormiston Angiographic Core Lab: Cardialysis IVUS Core Lab: Stanford University CEC/DSMB: Cardialysis Data Management: Cardialysis Single/Multiple De Novo Native Coronary Artery Lesions (A-B2) Vessel Diameters: 2.5-3.5 mm Stent Diameters: 2.5-3.5 mm Lesion Length: ≤24 mm Stent Lengths: 14 - 28 mm Pre-Dilatation required / Post-Dilatation at physicians discretion Cobalt Alloy Stent + Durable Polymer + Novolimus @ 5µg per mm Stent Length ENDEAVOR DES Control n= 71 Geography: New Zealand, Australia, Europe and Brazil EXCELLA DES n= 139 30d 6mo 9mo 12mo 2-5yrs Clinical Follow-up Angiographic/IVUS (Subset) Follow-up Clinical Follow-up This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) Primary Endpoint: In-Stent Late Lumen Loss at 9 months (QCA) Device and Procedure (Clinical) Success Device-oriented composite endpoint (Death, MI, or TLR) Key Secondary Endpoints: at 1, 6, 9, 12mo and 2-5 yrs Clinically driven TLR, TVR and TVF at 1, 6, 9, 12mo and 2-5 yrs Stent thrombosis rates at 1, 6, 9, 12mo and 2-5yrs ABR, LLL and % volume obstruction at 9 months Anti-Platelet Therapy for 12 months 8

Angiographic and IVUS Results 9 months In-Stent Analysis Novolimus Zotarolimus P value RVD (mm) N(L)=154 N(L)= 75 Post-procedure 2.84±0.43 2.91±0.38 0.20 At 9-months 2.82±0.44 2.70±0.42 0.06 MLD / Late Lumen loss (LLL), (mm) Acute gain 1.36±0.40 1.47±0.36 0.047 Acute gain (%) 46.48±11.65 47.51±11.13 0.53 MLD post-procedure 2.48±0.39 2.57±0.37 0.10 MLD at 9-months 2.36±0.48 1.95±0.48 < 0.001 LLL at 9-months 0.11±0.32 0.63±0.42 Diameter Stenosis (%) 12±5 11±5 0.34 16±12 28±14 Binary Restenosis (%) 1.4% (2/138) 7.6% (5/66) 0.037 Volumetric Analysis N(L)=34 N(L)=15 %Neointimal volume obstruction (%) 4.5±5.1 20.9±11.3 <0.001

EXCELLA II Randomized Clinical Trial Cardiac Events at 1 and 2 years This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 10

EXCELLA BD Randomized Clinical Trial RANDOMIZED (3:1), SINGLE BLIND, MULTI-CENTER CLINICAL TRIAL Co-Principal Investigators: A. Abizaid and S. Verheye Angiographic Core Lab: CRC IVUS Core Lab: Stanford University CEC/DSMB: CRC Data Management: CRC Single/Multiple De Novo Native Coronary Artery Lesions (A-B2) Vessel Diameters: 2.5-3.5 mm Stent Diameters: 2.5-3.5 mm Lesion Length: ≤24 mm Stent Lengths: 14 - 28 mm Pre-Dilatation required / Post-Dilatation at physicians discretion Cobalt Alloy Stent + Bioabsorbable Polymer + Novolimus @ 5µg per mm Stent Length ENDEAVOR DES Control n= 31 Geography: Belgium, Germany and Brazil DESyne BD DES n= 115 Clinical Follow-up Angiographic/IVUS (Subset) Follow-up 30d 6mo 9mo 12mo 2-5yrs Primary Endpoint: In-Stent Late Lumen Loss at 6 months (QCA) Device and Procedure (Clinical) Success Device-oriented composite endpoint (Death, MI, or TLR) Key Secondary Endpoints: at 1, 6, 9, 12mo and 2-5 yrs Clinically driven TLR, TVR and TVF at 1, 6, 9, 12mo and 2-5 yrs Stent thrombosis rates at 1, 6, 9, 12mo and 2-5yrs ABR, LLL and % volume obstruction at 6 months Anti-Platelet Therapy for 12 months Clinical Follow-up This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 11

Patient Flow and Follow-up 151 patients (NL=168) enrolled and randomized 1 Deregistered 3 Withdrew consent 3 no study stent 1 Deregistered Novolimus-eluting stent N=115 pts (NL=127) Zotarolimus-eluting stent N=31 pts (NL=38) 30-day clinical FUP N=115 pts 9-month clinical FUP N=31 pts Clinical FUP 100% 6-month clinical FUP N=113 pts 6-month clinical FUP N=31 pts Clinical FUP 98.6% 6-month angio FUP N=107 pts (NL= 119) (NIVUS = 35) 6-month angio FUP N=31 pts (NL= 38) (NIVUS = 16) Angio FUP 94.5% Intention to treat analysis Pts, patients; NL number of lesions; NIVUS number of IVUS

Baseline Patient Characteristics % (n) unless stated DESyne BD (N=115 patients) ZES (N=31 patients) Age, years (± SD) 65.0±9.3 60.4±10* Male 63.5% 77.4% Diabetes mellitus 28.7% 25.8% Current Smoker 18.3% 29.0% Hypercholesterolemia 72.2% 80.7% Hypertension 80.9% Previous myocardial infarction 25.2% 32.3% Previous CABG 5.2% 0.0% Previous PCI 20.0% Unstable angina 10.4% 9.7% *p=0.028; all others p=ns

Angiographic Results 6 months In-Stent Analysis Novolimus Zotarolimus P value RVD. mm N(L)=119 N(L)= 38 Post-procedure 3.00±0.37 3.08±0.35 0.31 At 6-months 2.95±0.37 2.99±0.38 0.67 MLD / Late Lumen loss (LLL), (mm) Acute gain 1.87±0.42 2.01±0.43 0.09 MLD post-procedure 2.76±0.37 2.90±0.34 0.04 MLD at 6-months 2.64±0.39 2.22±0.53 <0.001 LLL at 6-months (in-stent) 0.12±0.15 0.67±0.47 < 0.001 Diameter Stenosis (%) 8.5±44 6.2±4.5 0.002 11.0±6.6 25.6±15.1 Binary Restenosis (%) (in-stent) 0.0% 7.9% 0.003

Primary Endpoint Analysis: 6-month In-Stent Late Lumen Loss Novolimus 0.12 Zotarolimus 0.67 DELTA* (Upper 1-sided 95% CI) -0.55 (-0.44) Non-inferiority P value <0.001 Superiority *Least square means Zone of non-inferiority Pre-specified margin=0.20mm Zone of Superiority Zone of non-inferiority Zone of inferiority Superior -0.60 -0.50 -0.40 -0.30 -0.20 -0.10 0.00 0.10 0.20 0.30 0.40 Upper one-sided 95% CI Met Primary Non-Inferiority Endpoint and Superiority Endpoint

DESyne BDTM Neointimal Obstruction Optimal neointimal coverage with low neointimal volume obstruction Neointimal volume obstruction by IVUS at 6 months (%) 4-6 month results for similar trials* TM TM TM TM 4-8 month results for similar trials* *ResoluteTM from RESOLUTE at 4m, Xience VTM from SPIRIT II at 6m except SPIRIT III at 8m for neointima free ratio (not available from SPIRIT II), Biomatrix from STEALTH at 6m, Synergy from EVOLVE at 6m (IVUS results not available)

Clinical Results – 6 months 0 to 270 days, % (n) DESyne (N=112) Endeavor (N= 31) P-Value HIERARCHICAL EVENTS DEVICE ORIENTATED COMPOSITE 2.7% 3.2% 1.00 CARDIAC DEATH 0.0% -- TARGET VESSEL MI 0.9%         Q-WAVE MI         NON-Q- WAVE MI CLINICALLY-INDICATED TLR 1.8% 0.52 CI-PCI CI-CABG Modified Intention to Treat (patients who received a study stent)

Stent Thrombosis per ARC 0 to 180 days, % (n) DESyne BD (N=115) ZES (N= 31) P-Value Definite Stent Thrombosis 0.0% - Probable Stent Thrombosis

Conclusions The EXCELLA BD Trial demonstrated both non-inferiority and superiority of the Elixir DESyne BD Novolimus eluting stent compared to the control Zotarolimus eluting stent for the primary endpoint of in-stent late lumen loss at 6 months Angiographic binary restenosis for the DESyne BD stent was significantly lower compared to the control stent (0.0% vs. 7.9%, p=0.003) The Elixir DESyne BD Stent demonstrated significantly greater inhibition of neointimal hyperplasia and uniform coverage measured by IVUS compared to the control Device-oriented composite endpoints (cardiac death, MI and TLR) out to 6 months were similar between both groups demonstrating clinical safety of the Elixir DESyne BD stent There were no reported stent thromboses through 6 months for either study group

Comparison of Event Rates Significant reduction p=0.045