The Aptus™ Endovascular Repair System: Independent Fixation and Implications David H. Deaton, MD Chief, Endovascular Surgery Georgetown University Hospital

David H. Deaton, MD DISCLOSURES Consulting Fees Honoraria Aptus Endosystems, Inc., ROX Medical Honoraria m2s, Inc. Grants/Contracted Research Boston Scientific Corporation, Terumo Medical Corporation I intend to reference unlabeled/ unapproved uses of drugs or devices in my presentation. I intend to reference the published data from FDA sanctioned trials of devices that have not been approved yet. I will describe these devices and how they are physically different from current devices.

EVAR in 2010 Nearly 20 years of development 11 years of widespread use A variety of grafts with different approaches to longitudinal graft fixation No techniques for radial fixation (i.e. dilating disease) Deficiencies Migration Long-term follow-up Access and catheter crossing profile Precision control and operator creativity

EVAR’s “Dirty Little Secrets” Radial force (stents) in a dilating pathophysiology No way to understand whether fixation elements (barbs, hooks) remain intact or are failing until the graft migrates (exception: Ancure, no longer available) “Mandatory follow-up” necessary for success…but compliance highly variable

February 2009 April 2007 20 mm migration Over 22 months

Long-Term Failure Modes Disease related Progression of aneurysmal disease Device related Acceleration of dilitation at attachment site Longitudinal migration and loss of aneurysm exclusion (i.e. late Type I) Late Type III – limb disjunction; stent fracture graft perforation

Aptus System Approach Separation of Endograft Exclusion and Fixation Staples capable of reproducing “surgical” degree of fixation Reduction in catheter crossing profile Discrete fixation under physician control EndoStaple augments endograft seal Smaller crossing profile without compromises in: Stent design to accommodate fixation elements Material durability or deployment control to achieve lower crossing profile

Aptus™ Endovascular AAA Repair System Aptus™ AAA Endograft Highly flexible endograft Short Neck Treatment Range Modular Components Positive-Interlocking Limbs Aptus™ Endograft Delivery Systems Lowest Crossing Profile Product Line in the Market (16Fr & 18Fr) Aptus™ EndoStapling System Proprietary technology EndoStapling emulates surgical sutures Discrete radial fixation enables Endograft design optimization – a system approach Aptus Endograft Aptus Endograft Delivery Close up of endostaples in graft 18Fr 20Fr 14Fr 16Fr Aptus EndoStapling System Aptus Future Aptus Current Commercial Current

Irregular neck: Focal seal Short proximal stent allows independence of adjacent aortic anatomy Conformation of unsupported body to irregular aortic neck

Initial Phase Staple Implantation Completed Staple Implantation Staple delivery withdrawal Pressure felt and stent deflection seen as staple applier positioned for implantation

Aptus EndoStapling System Aptus™ Endovascular Repair Kit (Strengthen and/or Repair of Commercial Products) Aptus™ Aortic Cuff Provides additional proximal length Augments fixation and/or seal Used in primary or secondary procedures Aptus™ EndoStapling System Aptus™ Steerable EndoGuide Aptus™ EndoStaple Applier EndoStaple Cassette Aptus Aortic Cuff Aptus EndoStapling System Medtronic Talent Gore Excluder

STAPLE-2 Clinical Primary Results The STAPLE-2 clinical trial completed patient enrollment in Jan 2009 One year follow up to be completed in Feb 2010 Subject Accountability Discharge 1 Mo 6 Mo 12 Mo 155 154 144 102* Primary Safety Endpoints Goal: Less than 13% Major Adverse Event at 1 mo follow-up Results: 1.9% (3 out of 154 patients) Death (1), Myocardial Infarction (2) Primary Efficacy Endpoints Goal: Greater than 80% composite success at 12 mo follow-up Results: 96.1%* (4 patients out of 102 patients) Delivery failure (2), Type I and III Endoleaks requiring intervention (1 Type I, 1 Type III), Conversion to open repair (1) * 12 month follow has not been completed for all patients

STAPLE-2 Clinical Data Performance Comparisons Technical and Performance Success at 12 Mo* Talent Excluder Zenith Powerlink Aptus Migration (> 10 mm) 0.8% 2.3% 0.0% 0.7% Migration (> 5 mm)** NA 2.5% 4.4% Endoleak (I, III, IV) 6.6% 1.0% 1.4% AAA Rupture AAA Mortality 2.1% 0.5% Device Integrity 2.7% 0.6% 2.0% All data from core lab or SSE data sheets except were noted EndoStapling System Delivery Success at 1 mo = 100% EndoStaple Device Integrity at 12 mo* = 100% *12 month follow has not been completed for all Aptus patients ** Internal data evaluation for Aptus

STAPLE-2 Clinical Data Performance Comparisons Aneurysm Size Change at 12 Mo* Talent Excluder Zenith Powerlink Aptus Reduction (> 5 mm) 34% 14% 68% 62% 61% Enlargement (> 5 mm) 2% 7% 1% No Change (0 - 5 mm) 64% 79% 30% 36% 38% All data from core lab or SSE data sheets Pre-Op Post-Op (30-days) Post-Op (6-months) Post-Op (1 Year) * 12 month follow has not been completed for all Aptus patients

12% STAPLE-2 patients with Proximal Neck lengths ≈ 12mm 17% Proximal Neck Zone STAPLE-2 patients with Proximal Neck lengths ≈ 12mm 17% STAPLE-2 patients with Proximal Neck lengths ≈ 10mm 12% Type I Endoleaks* 0% * 12 month follow has not been completed for all Aptus patients

Radial Fixation: Case Example STAPLE-1 Patient 12 mm neck 7.5 cm AAA Post Op: Type II endoleak Refused treatment AAA growth to 10 cm No Migration No Type I Endoleak No Proximal Neck Dilation

STAPLE-2 Clinical Data: Thrombotic complications Patients with Thromboembolic Events (12 mo)* Talent Excluder Zenith Powerlink Aptus Limb Occlusion 3.6% 1.0% 4.0% 1.3% 12% Lower Limb Embolic Event NA** 15% Data from core lab and reported clinical studies All studies had greater than 40 patients and minimum one-year follow-up Patients that have experienced an event were treated via increased surveillance, anticoagulation and secondary interventions The therapies used have been successful and to date no patient has experienced any tissue loss *12 month follow has not been completed for all Aptus patients ** Clinical data on the number of patients with lower limb embolic events not reported

Where is the thrombus forming? CT Images Show: Irregular thrombus in the Main Body docking zone Thrombus loosely connected and extending downstream Small diameters and rough surface in the docking zone Main Body Docking Zone CT Reconstruction and Image of Irregular Thrombus

Why is the thrombus forming? Small Docking Lumens Finished Main Body docking lumens were sewn undersized (2.3 mm) Small and Rough Lumen Surface Undersized Main Body docking lumens led to small and rough lumen surfaces Thrombus Formation Small and rough lumen surfaces led to high fluid shear stress and irregular thrombus

Shear Stress Induced Platelet Aggregation Stagnant: Red blood thrombus may form at very low shear stress levels (0-5 dyne/cm2) Physiologic: Neither coagulation nor intravascular thrombus normally forms (5- 100 dyne/cm2) Pathologic: Excessive platelet activation and aggregation occurs (200-4000 dyne/cm2) Platelets deposit rate as high as 10x greater than physiologic levels

Computational Fluid Dynamics (CFD): Confirmed small docking lumens had high shear stresses Confirmed comparable shear stress among competitors and Aptus device (nominal dimensions) CFD Fluid Shear Results CFD Analysis (Small Docking Lumens)

STAPLE-2 Device Explant: One patient had a surgical conversion during the STAPLE-2 study for thrombus Explanted device confirms the connection Small Docking Lumens Small Rough Lumen Surface Thrombus Formation Explanted Small Main Body Docking Lumens Cast Model Small Main Body Docking Lumens

CFD Fluid Shear Results Manufacturing and Quality Improvements: Sewing procedures, operator training, manufacturing and inspection tooling Design Improvements: New sewing technique, optimize lumen flow characteristics New Graft Old Graft CFD Fluid Shear Results New Docking Lumen Small Docking Lumen

Stapling ….a new Endovascular Capability The ability to attach one object to another with a device independent of the objects being attached Faithful reproduction of fundamental vascular reconstruction Transmural interrupted suture Fixation Enhanced and scalable longitudinal fixation; potential equivalence to open sutured anastomosis Radial – potential to resist aneurysmal degeneration Discrete Control Radial - location, concentration, number Temporal - application of staple(s) at any time Fixation - degree with number of staples Sealing - Ability to use fixation to address seal in irregular anatomy

Thank you