The REVA Tyrosine Polycarbonate Bioresorbable Stent Lessons Learned

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

Disclosures • President, REVA Medical, Inc. 2/22/2010 REVA Medical, Inc. 1

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. 2

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. 3

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. 4

Challenges of Working with Polymers • Inherently weaker than metal • Less amenable to deformation • Lack radiopacity 2/22/2010 REVA Medical, Inc. 5

The REVA Approach Unique Stent Geometry Unique Material 2/22/2010 REVA Medical, Inc. 6

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. 7

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. 8

Positive Signals from Early FIM First Generation Device Strength ACUTE GAIN MLD (mm) DS (%) Pre- Post- 0. 88 ± 0. 39 2. 76 ± 0. 36 70% 5. 9% MAINTAIN GAIN: RESISTING VESSEL RECOIL EEL (mm 2) • Implant Follow up 15. 5± 4. 0 15. 3± 3. 1 Lesion Types Type A 16% Type B 1 48% Type B 2 28% Type C 8% 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. 9

Challenges to Overcome • TLR Rate: • Higher than anticipated between 4 -6 months postimplant • 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. 10

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. 11

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. 12

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. 13

Method to Evaluate Polymer Formulations DMA Multi-Frequency Stress Mode Metal stent collapses at cycling force 0. 4 N Test Parameters • • Oscillating force 0. 3 N Temperature 37ºC Water Frequency 1. 2 Hz Monitored Parameters • • 2/22/2010 OD of the stents Amplitude Stiffness Storage Modulus REVA Medical, Inc. 14

Regime II: Improved Dimensional Stability From Modified Polymer 2/22/2010 REVA Medical, Inc. 15

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. 16

Structural Robustness • Rigorous Testing of Overall Structure 2/22/2010 REVA Medical, Inc. 17

Optimized for Commercial Success Features of the Re. Zolve™ 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 2/22/2010 REVA Medical, Inc. 18

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) 2/22/2010 30 -day OCT (drug-eluting) REVA Medical, Inc. 19

Re. Zolve™ Bioresorbable Stent Restore. Remodel. Resorb. Anticipate Clinical Re-Entry 2010 2/22/2010 REVA Medical, Inc. 20

End 2/22/2010 REVA Medical, Inc. 21