EXCELLA BD Randomized Trial12-month Results

••••••••Elixir Medical Confidential

Ricardo Costa, MDOn behalf of the EXCELLA BD Investigators

Elixir Medical DESyne BDTM Novolimus Eluting Coronary Stent System

Platform features• Cobalt chromium alloy

stent 81 µm thickness

• Thin polymer matrix No primer coating < 3µm coating

thickness• Novolimus drug dose of 5

mcg per mm stent length• Active metabolite of

Sirolimus

DESyne BDTM

• Biodegradable polymer degrades in 6-9 months, drug release over 4 weeks

• Workhorse DES that leaves behind bare metal surface

Co-Principal Investigators:A. Abizaid and S.VerheyeAngiographic Core Lab: CRCIVUS Core Lab: Stanford UniversityCEC/DSMB: CRCData Management: CRC

RANDOMIZED (3:1), SINGLE BLIND, MULTI-CENTER CLINICAL TRIAL

EXCELLA BD Randomized Clinical Trial

Single/Multiple De Novo Native Coronary Artery Lesions (A-B2)Vessel Diameters: 2.5-3.5 mmStent Diameters: 2.5-3.5 mmLesion Length: ≤24 mmStent Lengths: 14 - 28 mmPre-Dilatation required/ Post-Dilatation at physicians discretion

Cobalt Alloy Stent + Bioabsorbable Polymer + Novolimus @ 5µg per mm Stent Length

Clinical Follow-up

30d 6mo 9mo 12mo 2-5yrs 30d 6mo 9mo 12mo 2-5yrsClinical Follow-upAngiographic/IVUS (Subset) Follow-up

ENDEAVOR DES Control n= 31

Geography: Belgium, Germany and Brazil

DESyne BD DES n= 115

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 monthsAnti-Platelet Therapy for 12 months

EXCELLA BD Study Organization

Principal Investigators• Alexandre Abizaid• Stefan Verheye

Steering Committee:• Alexandre Abizaid• Stefan Verheye• Peter Fitzgerald

DSMB• Otavio Berwanger• Adriana Moreira• Ricardo Pavenello

Clinical Event Committee• Aurea Chaves• Dimytri Siqueira• Sergio Braga

Angiographic Core Lab• Cardiovascular Research Center, Sao

Paulo, Brazil

IVUS Core Lab• Stanford University – Peter Fitzgerald

Date Coordination Center • Cardiovascular Research Center, Sao

Paulo, Brazil

EXCELLA BD Investigators

J. SCHOFER HAMBURG - GERMANY 42A. ABIZAID SAO PAULO, BRAZIL 28R. BOTELHO UBERLANDIA, BRAZIL 24S. VERHEYE ANTWERPEN - BELGIUM 23K.E. HAUPTMANN TRIER - GERMANY 13M. PERIN SAO PAULO, BRAZIL 6H. CASTELLO SAO PAULO, BRAZIL 6M. WIEMER BAD OEYNHAUSEN -

GERMANY5

C. DUBOIS LEUVEN - BELGIUM 3M. WAINSTEIN PORTO ALEGRE, BRAZIL 1

Novolimus-eluting stentN=115 pts (NL=127)

Zotarolimus-eluting stentN=31 pts (NL=38)

1 Deregistered3 Withdrew consent

3 no study stent

6-day clinical FUPN=115 pts

Intention to treat analysisPts, patients; NL number of lesions; NIVUS number of IVUS

151 patients (NL=168)enrolled and randomized

Angio FUP 94.5%

6-month clinical FUPN=113 pts

9-month clinical FUPN=31 pts

6-month clinical FUPN=31 ptsClinical FUP

98.6%

Clinical FUP 100%

Patient Flow and Follow-up

6-month angio FUPN=107 pts

(NL= 119) (NIVUS = 35)

6-month angio FUPN=31 pts

(NL= 38) (NIVUS = 16)

1 Deregistered

Baseline Patient Characteristics

Patient Characteristics 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% 80.7%

Previous myocardial infarction 25.2% 32.3%

Previous CABG 5.2% 0.0%

Previous PCI 20.0% 25.8%

Unstable angina 10.4% 9.7%

*p=0.028; all others p=ns

Baseline Lesion Characteristics

Lesion Characteristics DESyne BD

(N=127 lesions)ZES

(N=38 lesions)

Target Vessel

Left anterior descending 43.3% 39.5%

Left Circumflex 27.6% 21.1%

Right coronary artery 29.1% 39.5%

AHA/ACC Lesion class C 16.5% 21.1%

Lesion Length, mm (± SD) 14.59±5.53 15.30±5.29

Reference Vessel, mm (± SD) 2.94±0.38 3.01±0.46

Ostial Lesion 3.1% 2.6%

Moderate to Heavy Calcification 34.6% 36.8%

Thrombus 0.8% 0%

Bifurcation 7.9% 5.5%

p=ns for all characteristics

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 (%)

Post-procedure 8.5±44 6.2±4.5 0.002

At 6-months 11.0±6.6 25.6±15.1 < 0.001

Binary Restenosis (%) (in-stent) 0.0% 7.9% 0.003

Zone of Superiority

0.40-0.50 -0.40 -0.30 0.300.00 0.10 0.20-0.60

Upper one-sided 95% CI

Zone of non-inferiorityPre-specified margin=0.20mm

-0.20 -0.10

Novolimus

0.12

Zotarolimus

0.67

DELTA*(Upper 1-sided 95% CI)

-0.55 (-0.44)

Non-inferiority P value

<0.001

Superiority P value

<0.001*Least square means

Primary Endpoint Analysis: 6-month In-Stent Late Lumen Loss

Met Primary Non-Inferiority Endpoint and Superiority Endpoint

Zone of non-inferiority

Zone of inferioritySuperior

Clinical Results –12 months

0 to 360 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% 0.0% --

TARGET VESSEL MI 0.9% 0.0% 1.00

CLINICALLY-INDICATED TLR 1.8% 3.2% 0.52

Definite/Probable Stent Thrombosis 0.0% 0.0% --

Modified Intention to Treat (patients who received a study stent)

Cardiac Events at 12 months

DESyne BD 12m Endeavor 12m0.0%

0.5%

1.0%

1.5%

2.0%

2.5%

3.0%

3.5%

0.0% 0.0%

0.9%

0.0%

1.8%

3.2%

2.7%

3.2%

Cardiac Death TV-MICI-TLR MACE (TLR, Cardiac Death, MI)

Conclusions

• The EXCELLA BD trial demonstrated both non-inferiority and superiority of the Elixir DESynetm BD Novolimus eluting stent compared to control for the primary endpoint of in-stent late lumen loss at 6 months

• Angiographic binary restenosis for the DESyne BD stent was significantly less compared to control (0.0% vs. 7.9%, p=0.003)

• The composite endpoint of cardiac death, TV-MI and CI-TLR remains low and unchanged from 6 months for both groups demonstrating clinical safety of the Elixir DESyne BD stent

• There was no reported stent thrombosis through 12 months