1. Meredith ● EVOLVE Primary Endpoint ● TCT 2011 ● San Francisco, CA Slide 1 Meredith ● EVOLVE overview ● TCT 2010 ● Washington, DC Slide 1 Clinical and Angiographic Outcomes of the EVOLVE Trial: A Randomized Evaluation of a Novel Bioabsorbable Polymer-Coated, Everolimus-Eluting Coronary Stent Ian T. Meredith, Stefan Verheye, Christophe L. Dubois, Joseph Dens, Jean Fajadet, Didier Carrié, Simon Walsh, Keith G. Oldroyd, Olivier Varenne, Seif El-Jack, Raul Moreno, Anita A. Joshi, Dominic J. Allocco, Keith D. Dawkins

2. Meredith ● EVOLVE Primary Endpoint ● TCT 2011 ● San Francisco, CA Slide 2 Introduction Durable polymer coatings on drug-eluting stents have been associated with chronic inflammation and impaired healing. Reduced Polymer Load Short-term Polymer Exposure Reduce DAPT duration Reduce risk with DAPT interruption Decrease stent thrombosis may Potential advantages of bioabsorbable polymer stents:

3. Meredith ● EVOLVE Primary Endpoint ● TCT 2011 ● San Francisco, CA Slide 3 SYNERGY Stent Bioabsorbable polymer (PLGA) Applied only to the abluminal surface (rollcoat) Thin strut (0.0029”) PtCr Stent Durable Permanent Polymer + Drug 360° Around Stent PLGA Bioabsorbable Polymer + Everolimus on Abluminal Side of Stent Abluminal Bioabsorbable Polymer Current Durable Polymer Abluminal Bioabsorbable Polymer

4. Meredith ● EVOLVE Primary Endpoint ● TCT 2011 ● San Francisco, CA Slide 4 SYNERGY Polymer Mass Polymer resorption is complete within 4 months PLGA mass assessed in explanted stent and adjacent tissue Time (Days) Polymer Mass Remaining (%)

5. Meredith ● EVOLVE Primary Endpoint ● TCT 2011 ● San Francisco, CA Slide 5 EVOLVE Trial Primary Objective –To compare the bioabsorbable polymer SYNERGY Everolimus-Eluting Coronary Stent System to the permanent polymer PROMUS Element Stent for the treatment of de novo atherosclerotic lesions Test Devices –SYNERGY (everolimus dose and release profile similar to PROMUS Element) –SYNERGY ½ Dose (half the everolimus dose and similar release profile to PROMUS Element) Control Device –PROMUS Element

6. Meredith ● EVOLVE Primary Endpoint ● TCT 2011 ● San Francisco, CA Slide 6 EVOLVE Study Design Randomized 1:1:1 at 29 sites (EU, Australia, New Zealand) SYNERGY N=94 SYNERGY ½ Dose N=99 PROMUS Element N=98 Single-blind, noninferiority design Primary Clinical Endpoint: TLF (TV-CD, TV-MI, or TLR) at 30 days Primary Angiographic Endpoint: In-stent late loss at 6 months Patients with de novo native coronary lesions ≤ 28 mm in length, RVD ≥2.25 mm ≤ 3.5, %DS>50 (excluded LM disease, CTO, AMI or recent MI)

7. Meredith ● EVOLVE Primary Endpoint ● TCT 2011 ● San Francisco, CA Slide 7 Sample Size & Power Calculation Expected rate for both groups = 0.14 ± 0.47 mm* Non-inferiority margin (Δ) = 0.20 Test significance level (  ) = 0.048 (1-sided) Power (1  ) = approximately 0.85 Expected rate of attrition = 20% N = 291 patients (97 per group at 1:1:1 ratio) * From SPIRIT III (9-month endpoint) If the P value from the one-sided Student test is <0.048, it will be concluded that SYNERGY is non-inferior to PROMUS Element Primary Angiographic Endpoint: 6-month in-stent Late Loss

8. Meredith ● EVOLVE Primary Endpoint ● TCT 2011 ● San Francisco, CA Slide 8 EVOLVE Trial Support Co-Principal Investigators Core Labs Clinical Events Committee Data Monitoring Committee

9. Meredith ● EVOLVE Primary Endpoint ● TCT 2011 ● San Francisco, CA Slide 9 Top 10 Enrolling Sites EVOLVE Centers

10. Meredith ● EVOLVE Primary Endpoint ● TCT 2011 ● San Francisco, CA Slide 10 Patient Flow 6-Month Follow-up Clinical: 99.9% (97/98) Angio: 96.9% (95/98) SYNERGY (N=94) PROMUS Element (N=98) No 6-Month f/u (n=1) Withdrew consent: 0 Missed 6 mo visit: 1 6-Month Follow-up Clinical: 98.9% (93/94) Angio: 93.6% (88/94) No 6-month f/u (n=1) Withdrew consent: 0 Missed 6 mo visit: 1 6-Month Follow-up Clinical: 97.0% (96/99) Angio: 88.9% (88/99) SYNERGY ½ Dose (N=99) No 6-month f/u (n=3) Withdrew consent: 0 Missed 6 mo visit: 3 All Patients Randomized (N=291)

11. Meredith ● EVOLVE Primary Endpoint ● TCT 2011 ● San Francisco, CA Slide 11 Baseline Demographics SYNERGY ½ Dose N=99 SYNERGY N=94 PROMUS Element N=98 P value Intent-to-treat; P values are versus PROMUS Element; * medically treated

12. Meredith ● EVOLVE Primary Endpoint ● TCT 2011 ● San Francisco, CA Slide 12 Baseline Lesion Characteristics SYNERGY ½ Dose N=99 SYNERGY N=94 P value Lesion characteristics evaluated by QCA. Intent-to-treat; P values are versus PROMUS Element PROMUS Element N=98

13. Meredith ● EVOLVE Primary Endpoint ● TCT 2011 ● San Francisco, CA Slide 13 Procedural Characteristics SYNERGY ½ Dose N=99 SYNERGY N=94 PROMUS Element N=98 P value a Study stents in target lesion only b Defined as %DS<30 with TIMI flow 3 and no in-hospital MI, TVR, or cardiac death c Defined as successful delivery and deployment of the study stent to the target vessel without balloon rupture or stent embolization Intent-to-treat; P values are versus PROMUS Element

14. Meredith ● EVOLVE Primary Endpoint ● TCT 2011 ● San Francisco, CA Slide 14 Post-Procedure Angiographic Characteristics SYNERGY ½ Dose N=99 SYNERGY N=94 PROMUS Element N=98 P value *By QCA Values are mm or percent Intent-to-treat; P values are versus PROMUS Element

15. Meredith ● EVOLVE Primary Endpoint ● TCT 2011 ● San Francisco, CA Slide 15 Late Loss at 6 Months SYNERGY ½ Dose Late loss, mm SYNERGY SYNERGY ½ Dose Difference (SYNERGY – PROMUS) Late Loss at 6 MonthsDifference and 95.2% UCB Noninferiority Threshold Noninferiority is proven because the upper 95.2% confidence bound of the difference in 6-month late loss is <0.20 for both SYNERGY stents P<0.001 P=0.19* P=0.56* PROMUS Element SYNERGY Intent-to-treat; *P values for superiority comparison

16. Meredith ● EVOLVE Primary Endpoint ● TCT 2011 ● San Francisco, CA Slide 16 SYNERGY ½ Dose N=99 SYNERGY N=94 PROMUS Element N=98 P value Assessed by QCA Values are mm or percent Intent-to-treat; P values are versus PROMUS Element Angiographic Outcomes at 6 mo In-stent values

17. Meredith ● EVOLVE Primary Endpoint ● TCT 2011 ● San Francisco, CA Slide 17 Death and MI at 6 Months Patients, % All P=N.S. All Death Cardiac Death Noncardiac Death All MI Q-WaveNon-Q- Wave PROMUS Element SYNERGY ½ Dose SYNERGY The cause of the noncardiac death in the SYNERGY group was a motor vehicle accident at 191 days post-procedure. Intent-to-treat; P values are versus PROMUS Element (Fisher exact test)

18. Meredith ● EVOLVE Primary Endpoint ● TCT 2011 ● San Francisco, CA Slide 18 Revasc and ST at 6 Months Patients, % All P=N.S. Intent-to-treat; P values are versus PROMUS Element (Fisher exact test) TVRTLRNon-TLR TVR Stent Thrombosis PROMUS Element SYNERGY ½ Dose SYNERGY

19. Meredith ● EVOLVE Primary Endpoint ● TCT 2011 ● San Francisco, CA Slide 19 Target Lesion Failure PROMUS Element SYNERGY SYNERGY ½ Dose Patients, % P=1.00 P=0.72 Intent-to-treat; P values are versus PROMUS Element (Fisher exact test) PROMUS Element SYNERGY SYNERGY ½ Dose Patients, % 30 days6 Months P=0.49 P=0.25

20. Meredith ● EVOLVE Primary Endpoint ● TCT 2011 ● San Francisco, CA Slide 20 Limitations The study only included patients with relatively simple de novo lesions –Patients with AMI, stroke, CTO, bifurcation, LMCA lesion, SVG lesion, ostial lesions, or lesions with thrombus or excessive tortuosity or angulation were excluded The study was not powered to detect differences in clinical event rates The study was not designed to assess the risk of thrombosis or the required duration of dual antiplatelet therapy with SYNERGY –Two additional studies planned with adequate power to Assess clinical event rates Assess long vs short duration of DAPT

21. Meredith ● EVOLVE Primary Endpoint ● TCT 2011 ● San Francisco, CA Slide 21 Conclusions In this prospective, randomized, multicenter, First Human Use trial, the two dose formulations of the SYNERGY stent were non-inferior to the PROMUS Element stent for the primary angiographic endpoint of in-stent late loss at 6 months. –Clinical events were low and comparable with no stent thromboses in any group. These results support the safety and efficacy of the novel abluminal bioabsorbable polymer SYNERGY everolimus-eluting stent for the treatment of patients with de novo coronary artery disease. Additional research is needed to evaluate clinical event rates and the potential for dual antiplatelet therapy reduction with this novel stent.

22. Meredith ● EVOLVE Primary Endpoint ● TCT 2011 ● San Francisco, CA Slide 22 Thank you to the EVOLVE Site Investigators