Opportunities to Study Valve Iterations and Modifications in the US Rhonda J. Robb Medtronic

Rhonda Robb, MBA Employee: Medtronic

The Challenge: TAVR is Novel ….

The Opportunity Developing, and innovating a platform that is well characterized technically and advances clinical outcomes

Transcatheter Valve Requirements US FDA Requirement ISO Requirement

Computational Modeling CoreValve Testing Computational Modeling Bench Testing Material Properties Hydrodynamic assessment Structural Performance Delivery System Requirements Simulated Use Usability/Human Factors Pre-Clinical In-Vivo Assessments Clinical Assessments Bench Testing Animal Studies

> 5,000 Patients in CoreValve® US Pivotal Medtronic CoreValve US Pivotal Trial Up to 687 790 Extreme Risk Screened High Risk Screened N=737 N=995 No Yes Up to 200 487 395a 395 CoreValve Transfemoral CoreValve Non-Ilieofemoral CoreValve SAVR Pivotal N=470 N=150 N=390 N=357 Alternative Access Continued Access CoreValve ER CAS CoreValve HR CAS N=1623 N=1034 Primary Endpoint: All-cause mortality or major stroke @ 12 months (compare to perf goal) Primary Endpoint: All-cause mortality @ 12 months

CoreValve Clinical Results Extreme Risk Study support the safety and efficacy of this therapy who are deemed unsuitable for surgical aortic valve replacement Survival at 1 year was superior in patients that underwent transcatheter replacement with CoreValve at high risk for surgery 2 year results at ACC LBCT

Significant Global TAVR Evidence Base More than 70,000 Patients Enrolled Globally in Pivotal Trials, National and Industry Registries Int’l

Delivery Systems Portfolio Next Generation Valve Systems Building on Proven Foundation w/>75,000 implants Self-Expanding Nitinol Porcine Pericardium Delivery Systems Portfolio

Evolut R Building on Proven Foundation Reduced Outflow Height Fit in angulated anatomy Supra-annular Valve Porcine Pericardial Tissue Conformable Seal Optimized oversizing /radial force, extended skirt Recapturable Delivery System Ergonomic handle, 1:1 response, self-centering, with 14Fr Inline Sheath

Evolut R IDE Now Enrolling in the US PURPOSE Assess safety and efficacy of CoreValve Evolut R system in patients with severe symptomatic aortic stenosis who are considered high through extreme risk for SAVR DESIGN Single arm, non-randomized, multi-center up to 25 sites with follow-up through five year DEVICES Evolut R TAV (sizes 23, 26 & 29mm), EnVeo R delivery catheter system with InLine sheath SCOPE Minimum of 150 implanted subjects, up to 250 implanted subjects ENDPOINTS Safety: 30-day all-cause mortality, disabling stroke Efficacy: Device success rate (VARC II), percentage subjects ≤ mild AR @ early echo Feb 2015: FDA approval received for the addition of Evolut R Into the SURTAVI Trial

Dramatic Difference on Time to Approval CoreValve Extreme Risk FDA Approval Jan 2014 CoreValve CE Apr 2007 CoreValve High Risk FDA Approval July 2014 2007 2014 2015 2016 ~ 7 Years CoreValve Evolut R CE Jan 2015 Est FDA Approval < 1 Year 2015 2016 Evolut R

Future Considerations Early feasibility path offers a very innovative mechanism for study of new concepts (e.g. pulmonic, mitral) Need to assess future pathways for studying future patient populations given increased challenges to randomize (e.g., lower risk, bicuspid, pure AI)

Summary CoreValve self-expanding platform has established a solid foundation of safety and effectiveness data System design modifications can be evaluated: Using refined bench test and pre-clinical models to be more predictive of human outcomes Through clinical studies with lower patient numbers, shorter term data (e.g. Evolut R) and novel clinical trial constructs By incorporating into ongoing longer term studies (e.g. addition of Evolut R to Surtavi)

Thank You