1. The Process of TAVR Development
Stanton J Rowe
CEO
NXT Biomedical

2. Disclosure Statement of Financial Interest
I, Stanton Rowe, DO have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation.
Edwards Lifesciences shareholder, stock options

3. OK, you and your friends have looked into the future, and believe that you have the next big idea in TAVR…

4. 2008 slide on 17 TAVR Technologies 4/18 on the market

5. What Problem Are You Solving vs. Current Offerings

6. Virginia Cardiac Services Quality Initiative database.
(2009 to 2011) (2012 to 2015)
Virginia Cardiac Services Quality Initiative database.

7. Areas to Improve Vascular complications Prolonged ventilation
Profile and vascular closure devices
Prolonged ventilation
General anesthesia, COPD
Atrial fibrillation
Age related incidence; higher age in TAVR
Discharge to facility
Multifactoral
Durability
How would you prove better durability with the least clinical implant duration?

8. Similarities and Dissimilaries Surgical versus TAVR Valves
12/9/15
Similarities and Dissimilaries Surgical versus TAVR Valves
Similarities
Exposed largely to the same boundary conditions
Slight differences in removal of calcium in surgery
Expectations of durability are largely the same
Surgical valves tend to be placed in younger patients
VinV has changed the implications of late valve degeneration
TAVR tissues and SHV tissues are similar
Flow dynamics requirements are the same
Host response to implants are the same (early leaflet thickening)

9. Tissue Validation Fixation Chemistry
Mechanical methods applied during Chemical Fixation
Testing techniques to assess Biomechanics
Uniaxial
Biaxial
Tensile stress/strain and bending properties
Crimp
Characterize the condition of leaflets, skirt, and attachment after loading, tracking, and deployment. In the clinical setting, crimp duration can vary therefore these studies should consider worst case crimp durations.
All testing for valve performance should be conducted on devices which have been crimped prior to testing.
What is even more critical is that the three leaflets have the same mechanical properties. Historically we have focused on matching tissue thickness within any given valve to reduce the chance that one leaflet would stretch more than the other leaflets reducing the coaption length. In fact the thickness of the leaflets is less important that the elasticity of the leaflets. If one leaflet will stretch more than the other leaflets coaption will suffer.

10. Fatigue Testing: Accelerated Wear and Dynamic Failure Mode
200x106 cycles to simulate five years of valve implant duration
Peak closed valve pressure difference of /-0 mmHg for Aortic valves
Peak closed valve pressure difference of /-0 mmHg for Mitral valves
Pressures differences should be continuously monitored throughout the duration of the test
Assessments:
Hydrodynamic assessments at intervals throughout the test to determine changes in performance
Visually examined every 25 x 106 cycles, or until failure
Macroscopic damage:
Abrasion, holes, tears, delamination, fraying, coaptation, dehiscence.

12. Hydrodynamic Testing
Pulsatile Flow Pressure drop and Pulsatile Flow Regurgitation
Annulus shape, under-deployment must be accounted for in the assessments of flow performance.
Broad range of cardiac conditions expected in the patient population (i.e. varied flow rates, pressures and beat rates)
Flow Visualization
Assess the flow characteristics of the valve using flow visualization or turbulence measurement techniques to characterize any induced jets, flow stasis, leaflet kinematics which might lead to early deterioration in-vivo. not recognized through standard pulsatile flow testing.

13. Delivery Systems A low delivery catheter profile = <14Fr OD
Atraumatic tracking = optimum tracking and flexibility through the vasculature
Cost effective
Re-capturability and Re-positionability, for self-expanding frame based technologies
Ability to orient the rotational alignment with native commissures (Clocking)
Intuitive design = ease of use
Clear/smart position signaling
Marker-bands / clear visual markers under fluoroscopy
Stability during deployment
Ergonomic
Deployment time < 1min
Efficient or minimized loading (into Delivery system) process required for delivery of the device
Material stability
Shelf life > 2 years
Guide-wire compatibility
Smart packaging e.g. work with the delivery system for TAV loading

15. Animal Studies

16. Regulatory IDE First in Human (FIH) Early Feasibility Study (EFS)
Traditional Feasibility
Pivotal Clinical Trial (TAVI vs TAVI)
(CE Mark)
Pivotal Trial (CE Mark)
Design Dossier

17. Conclusion TAVR has changed the treatment paradigm for aortic stenosis
It is a growing attractive space for development
However, the window for improving TAVR is narrow, the development time and cost are extensive, and established companies continue to raise the bar
The pathway is well established