1. The REVA Tyrosine Polycarbonate Bioresorbable Stent: Lessons Learned and Future Directions Robert K. Schultz, PhD

2. Disclosures
President, REVA Medical, Inc.
2/22/2010
REVA Medical, Inc.

3. About REVA
R&D company focused primarily on development of a novel bioresorbable stent
Strong stent design and polymer expertise
Solid IP position (stents and polymers)
Quality investment partners
Additional product opportunities
2/22/2010
REVA Medical, Inc.

4. Potential Benefits of Bioresorbable Stents
Non-permanent treatment option
Treatment of multi-vessel, prolific disease
Decrease of late adverse events
Late thrombosis, hypersensitivity
Allows arterial remodeling
May lead to better healing outcomes
May allow for earlier discontinuation of Plavix
2/22/2010
REVA Medical, Inc.

5. Goals of the REVA Program
To develop a stent that provides the benefits of metal without the permanency
Strength
Maintain acute lumen gain
Maintain support throughout remodeling process
Performance
Expansion range to accommodate “real world” clinical use
Visibility
Visualize entire stent during and after deployment
2/22/2010
REVA Medical, Inc.

6. Challenges of Working with Polymers
Inherently weaker than metal
Less amenable to deformation
Lack radiopacity
2/22/2010
REVA Medical, Inc.

7. Unique Stent Geometry Unique Material
The REVA Approach
Unique Stent Geometry Unique Material
From the beginning, REVA took a unique approach, to fully integrate both a novel design and material, to develop a stent that provides the benefits of metal without the permanency.
2/22/2010
REVA Medical, Inc.

8. Improved performance with no change to clinical practice
Design: Slide & Lock
Steel-like performance in a polymer stent
Exceptional radial strength
Negligible recoil
Expansion range to accommodate “real world” clinical use
Extremely flexible design
Deploys (expands) in artery with sliding, locking parts rather than material deformation
Improved performance with no change to clinical practice
2/22/2010
REVA Medical, Inc.

9. Material: RESORB™ Bioresorbable Polymer
Tyrosine-derived polycarbonate
Optimized for stent performance
Inherently radiopaque, x-ray visible
Resorption time can be modified
Biocompatible
MRI/CT compatible
Radiopacity of the REVA Bioresorbable Coronary Stent shortly after implant in a porcine animal model.
Desired features for optimal polymer stent performance
2/22/2010
REVA Medical, Inc.

10. Positive Signals from Early FIM First Generation Device
Strength
ACUTE GAIN
Pre-
Post-
MLD (mm)
0.88 ± 0.39
2.76 ± 0.36
DS (%)
70%
5.9%
Lesion Types
Type A 16%
Type B1 48%
Type B2 28%
Type C 8%
MAINTAIN GAIN: RESISTING VESSEL RECOIL
Implant
Follow up
EEL (mm2)
15.5±4.0
15.3±3.1
Performance
3.0 mm device targeted to treat 2.9 to 3.4 vessels
(Actual treatment of 2.7 to 3.3 mm vessels in FIM)
2/22/2010
REVA Medical, Inc.

11. Challenges to Overcome
TLR Rate:
Higher than anticipated between 4-6 months post-implant
Key Learnings:
Probable failure mode primarily related to polymer performance
More predictive bench and preclinical tests required for polymer stenting
Tests and standards developed for metal stents do not yield enough insight to polymer stent performance in the clinical environment
2/22/2010
REVA Medical, Inc.

12. Polymer Stents Model for Potential Failure Modes
Regime I: Stent deployment
Possible brittle fracture upon high-frequency deployment
Regime II: Early stages after deployment
Change in material properties due to rapid plasticization
Onset of physical aging
Regime III: Later stages
Possible low frequency fatigue failure
2/22/2010
REVA Medical, Inc.

13. REVA Polymer Enhancements Post FIM Polymer Evaluation
Regime I
No changes to material properties required
Regime II
Reduction of aqueous plasticization
Minimize physical aging
Regime III
Improve fatigue resistance: Most clinically relevant
2/22/2010
REVA Medical, Inc.

14. Performance of Modified Polymer
Stent Deployment
Like FIM polymer - robust deployment
Ductility
Elongation at break is 7 times higher (350%)
Water sorption
Lower water sorption and no sharp change in material properties
2/22/2010
REVA Medical, Inc.

15. Method to Evaluate Polymer Formulations
DMA Multi-Frequency Stress Mode
Metal stent collapses at cycling force 0.4N
Test Parameters
Oscillating force 0.3N
Temperature 37ºC
Water
Frequency 1.2 Hz
Monitored Parameters
OD of the stents
Amplitude
Stiffness
Storage Modulus
2/22/2010
REVA Medical, Inc.

16. Regime II: Improved Dimensional Stability From Modified Polymer
2/22/2010
REVA Medical, Inc.

17. Regime III: Material Robustness In Vivo Accessing “real life” fatigue performance
FIM Polymer
Modified Polymer
1 month time point
In-vivo partial stent overlap test. Polymeric stents were deployed into porcine coronary arteries followed by the partially overlapped deployment of a metal stent. One-month results demonstrated the modified polymer’s ability to maintain structural integrity under harsh in vivo conditions.
2/22/2010
REVA Medical, Inc.

18. Structural Robustness
Rigorous Testing of Overall Structure
2/22/2010
REVA Medical, Inc.

19. Optimized for Commercial Success Features of the ReZolve™ Bioresorbable Stent
Radiopaque polymer with improved material robustness
Minor modifications to meet clinical demand
Spiral slide & lock design
Optimized for commercial performance
Elution of a –limus drug
done
2/22/2010
REVA Medical, Inc.

20. Preclinical Evaluation
Bare vs. Drug-Coated
Overstretch study
One-month results demonstrated drug effect
No apparent catch up at 3 months.
30-day OCT (bare)
30-day OCT (drug-eluting)
2/22/2010
REVA Medical, Inc.

21. ReZolve™ Bioresorbable Stent Restore. Remodel. Resorb.
Anticipate Clinical Re-Entry 2010
2/22/2010
REVA Medical, Inc.

22. End
2/22/2010
REVA Medical, Inc.