12-MONTH DATA RELEASE

Trial

NewRandomised Comparison of Titanium-Nitride-Oxide

Coated Bio-Active-Stent (OPTiMAX™-BAS) vs. Bioabsorbable Polymer Everolimus Eluting Stent (SYNERGY™-DES) in Acute Coronary Syndrome1

1. Colkesen EB et al. TIDES-ACS Trial 2017.

INNOVATIVE SOLUTIONS FOR CARDIOVASCULAR HEALTH

Having launched their 1st coronary stent in the late 90’s, HEXACATH has been committed to developping a complete range of high-technology products in the field of angioplasty. These cutting-edge devices are the fruit of their long-standing partnerships with key opinion leaders, laboratories, and physicians from around the world.

Late Breaking Trial TITAX-AMI

Randomised Trial (TiNO stent

vs. PES)

R&D collaboration programme established

Manufacturing facility inauguration in

Morteau, France

Late Breaking Trial BASE-ACS

Randomised Trial (TiNO stent

vs. EES)

Late Breaking Science TIDES-ACS Randomised Trial

(TiNO stent vs. EES latest gen.)

ESC CONGRESS 2017

Launch of TiTAN™ Bio Active Stent

Launch of TiTAN2™

Bio Active StentLaunch of OPTiMAX™

TiNO coated3rd generation Stent

HEXACATH created in the Paris area

of France

Launch of HELISTENT™ Bare

Metal Stent

HEXACATH’s research and development programme is dedicated to bringing the most innovative solutions for patients’ cardiovascular health.

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OPTiMAX™: THE LATEST GENERATION IN SURFACE NITRIDE-OXIDE STENT TECHNOLOGY

The important role of stent surface material

Despite the advances that drug-eluting stents have brought to interventional cardiology, their use has presented some constraints for patients including the requirement to take aspirin/clopidogrelto reduce the risk of late stent thrombosis, loss of vasomotion, hypersensitivity reactions, and risk of late restenosis. Research reveals that stent surface material importantly affects neointimal hyperplasia and thus restenosis1.

The New OPTiMAX™ surface -particles stent+ 70% TiNOX coating Enhanced PVD technology allows thicker titanium-nitride-oxide coating

Reinforced structural design Helical coil with added connectors

Thinner struts by 20% Cobalt chromium alloy reduces strut thickness from 90 to 75 microns versus steel alloy TiTAN2™

Improved delivery catheter Superior navigation and push capacities

1. Windecker S, Billinger M, MD and Hess OM. Stent coating with titanium-nitride-oxide for prevention of restenosis. EuroInterv 2006;2:146-148.2. Zhang et al. In vivo investigation of blood compatibility of titanium oxide films. J Biomed Material Res A 1998;42(1):128-133. 3. Zhang et al. Behaviour of MEVVA metal ion implantation for surface modification of materials. Surf Coat Technol 1996;83(1-3):280-283.4. Steinemann SG. Metal implants and surface reactions. Injury 1996;27(suppl 3):SC16-22. 5. Yeh HI et al. Comparison of endothelial cells grown on different stent materials. J Biomed Mater Res A. 2006;15;76(4):835-41.

Benefits of surface -particles

Previous investigations have shown that NO prevents platelet aggregation and reduces proliferation of smooth muscle cells1.

Stent coating with titanium-nitride-oxide is associated with -particles on the stent surface promoting1-5:

• Prevention of platelet aggregation and fibrinogen binding• Reduced proliferation of smooth muscle cells• Minimised risk of thrombus formation• Reduced risk of late luminal loss and restenosis

SURFACE NO STENT: A SAFE ALTERNATIVE TO DES?

Why the TIDES-ACS Trial?

Early generation drug-eluting stents have reduced restenosis, but have been associated with an increased risk of late stent thrombosis

Titanium-Nitride-Oxide coating has been shown to decrease inflammatory reaction as well as platelet aggregation and is associated with accelerated re-endothelialisation, thus reducing neoinintimal

formation as well as thrombotic risks1

Larger trial was required to better assess the benefits of Titanium-Nitride-Oxide (TiNO) on the endothelial healing process post angioplasty

NON-INFERIORITY RANDOMISED TRIALS WITH TiNO coated stents vs. DES

TITAX-AMI2,3

Demonstrated non-inferiority at 12 months and significantly less MI or Cardiac Death and Stent Thrombosis at 24 months of TiTAN2™ vs. TAXUS™ LIBERTÉ™

BASE-ACS4,5

Demonstrated non-inferiority at 12 months and significantly less MI or Cardiac Death and Stent Thrombosis at 60 months of TiTAN2™ vs. Xience V®-EES

TIDES-ACS6

Comparing OPTiMAX™ to the latest bioabsorbable polymer Everolimus Eluting Stent

1. Limacher A et al. Clinical long-term outcome after implantation of titanium nitride-oxide coated stents compared with paclitaxel-or sirolimus-eluting stents: propensity-score matched analysis. EuroIntervention. 2012;7(9):1043-1050.

2. Karjalainen PP et al.Titanium-nitride-oxide coated stents versus paclitaxe leluting stents in acute myocardial infarction: a 12-month follow-up report from the TITAX AMI trial. EuroInterv 2008;4:234-241.

3. Karjalainen PP et al. Two-year follow-up after percutaneous coronary intervention with titanium-nitride-oxide-coated stents versus paclitaxel-eluting stents in acute myocardial infarction. Ann Med. 2009;41(8):599-607.

4. Karjalainen PP et al. A prospective randomised comparison of titanium-nitrideoxide-coated bioactive stents with everolimus-eluting stents in acute coronary syndrome: the BASE-ACS trial. EuroIntervention 2012;8:306-315.

5. Karjalainen PP et al. Long-term clinical outcome of titanium-nitride-oxide-coated stents versus everolimus-eluting stents in acute coronary syndrome: Final report of the BASE ACS trial. Int J Cardiol. 2016;1(222):275-280.

6. Kervinen K. Comparison of Titanium-Nitride-Oxide coated Bio-Active-Stent (OPTiMAX™) to the Drug (Everolimus) - Eluting Stent (Synergy™) in Acute Coronary Syndrome (TIDES-ACS trial) Euro PCR 2017 Presentation.

TIDES-ACS: OPTiMAX™ vs. SYNERGY™

Comparison of Titanium–Nitride-Oxide coated Stent (OPTiMAX™-BAS) versus

Bioabsorbable Polymer Everolimus Eluting Stent (SYNERGY™-DES)6

This prospective, randomised and multicenter trial compared the clinical outcome in patients presenting with ACS, treated with PCI using OPTiMAX™ versus SYNERGY™.

OPTiMAX™-BASTitanium-Nitride-Oxide Coated Stent 989 Patients

SYNERGY™-EESEverolimus Eluting Stent with

Bioabsorbable Polymer 502 Patients

Primary Endpoint:

MACE at 12 months:the composite of cardiac death, myocardial infarction (MI) and target lesion revascularisation (TLR) during 12 months of follow-up (non-inferiority).8.5% (α = 5%; b= 90%; delta [non-inferiority margin] = 3.5%)

iInclusion CriteriaAcute coronary syndrome adult patients with:• Non ST-elevation acute coronary syndrome (NSTE-ACS)• ST-elevation myocardial infarction (STEMI)• Unstable angina

TIDES-ACS

Patients presenting withAcute Coronary Syndrome

(ACS)

12 international SitesRandomisation 2:1

Clinical Follow-up

30 days 6 months 12 months

Clinical Primary Endpoints

OPTiMAX™: demonstrated non-inferiority vs. 3rd generation Drug-Eluting Stent1

MACE at 12 months with OPTiMAX™ stent vs. SYNERGY™ stent1

1. Late breaking Science ESC CONGRESS 2017 TIDES-ACS Trial.

OPTiMAX™ stent met the primary endpoint of non-inferiority to platinum-chromium-based bioabsorbable-polymer EES for MACE at 12 months1

i

6.3% OPTiMAX™

(n=989)

7.0% SYNERGY™

(n=502)

VS.

(HR 1.12; 95% CI 0.73 – 1.72; pnon-inferiority

<0.001, psuperiority

=0.66)

Favours OPTiMAX™ Favours SYNERGY™3.5

Non-inferiority zone Pre-specified margin = 3.5%

-3.0 -2.0 -1.0 1.0 2.0 3.0 4.00

Mean age of randomised patients was 63 years old with 76% being males1. Analysis conducted in intention-to-treat population; 12-month follow-up available in 99.3% of patients1.

Reduced incidence of cardiac death and MI with OPTiMAX™ vs. SYNERGY™ 1

MACE event rates and Definite or Probable ST at 12 months1

1. Late breaking Science ESC CONGRESS 2017 TIDES-ACS Trial.

OPTiMAX™ demonstrated statistically signficant safety advantages for patients with acute cornary syndrome1i

“When you look at the individual components of the primary endpoint in this study, the OPTiMAX™ stent comes with a lower rate of cardiac death and myocardial infarction compared to SYNERGY™, which is outbalanced by a higher rate of ischemia-driven target lesion revascularisation for OPTiMAX™. In other words, with the OPTiMAX™ stent hard clinical endpoints like myocardial infarction and cardiac death are less frequent in ACS patients than with SYNERGY™, at the cost of a, probably less important, higher rate of repeat intervention.” announced Dr. Pim Tonino. (Heart center Catharina Hospital, Eindhoven, the Netherlands).

OPTiMAX™ SURFACE NO STENT: Optimising Performance, Maximising Safety1

OPTiMAX™: demonstrated

NON-INFERIORITY to 3rd generation

Drug-Eluting Stent1

OPTiMAX™ and TiTAN2™ are registered trademarks of Hexacath.Xience V® is a registered trademark of the Abbott Group of Companies.SYNERGY™ and TAXUS™ LIBERTÉ™ are registered trademarks of Boston Scientific and its affiliates.

1. Late breaking Science ESC CONGRESS 2017 TIDES-ACS Trial.

As EFFECTIVE with a stronger SAFETY profile1

TIDES-ACS key results at 12 months: OPTiMAX™ stent met the primary endpoint

of non-inferiority to SYNERGY™ 1

OPTiMAX™ demonstrated a reduced incidence of cardiac death, myocardial infarction, Definite or Probable ST with a significantly lower

duration of DAPT (P=0.007) vs. SYNERGY™ 1