EX-99.1 2 a14-13120_1ex99d1.htm EX-99.1

Exhibit 99.1

 

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Vascular Safety of Bioresorbable Scaffolds Made from Biomaterials Designed for Use In Interventional Cardiology Dr. Marian Rippy Rippy Pathology Solutions, Inc. Woodbury, Minnesota

 


Potential conflicts of interest Speaker's name: Marian Rippy, MS, DVM, PhD, Diplomate, ACVP I do not have any potential conflict of interest  I have the following potential conflicts of interest to report: Consultant: REVA Medical, Inc.

 


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REVA’s Bioresorbable Coronary Scaffolds RESORB Trial 2007 Fantom™ 2014 and beyond ReZolve RESTORE I Trial 2011 ReZolve2 RESTORE II Trial 2013 Each Therapy is Based on the Unique Radiopaque Polycarbonate Polymers 7 Fr. / Bare 6 Fr. / DES 5 Fr. / DES

 


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Key Compounds in REVA’s Polycarbonate Polymers Iodinated Desaminotyrosine (I2DAT) Tyrosine & Analogs Covalently bound iodine enables x-ray visibility of the entire scaffold I2DAT and the tyrosine/analogs are benignly cleared from body

 


ReZolve I2DAT I2DAT TY ReZolve2 Tyrosine I2DAT I2DAT Tyrosine Ethyl-Ester RESORB PEG PCL I2DAT Tyrosine Ethyl-Ester I2DAT TY PLx I2DAT Fantom™ Polycarbonate Polymer Evolution and Resorption Profile 5 Years 4 Years > 5 Years 3-4 Years Resorption

 


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A Comprehensive Approach to Preclinical Safety Evaluations Study Type Material Safety ISO-10993 Tests of Polymer and Catheter Materials Device Performance and Biocompatibility  Scaffold Implants in Porcine Coronary Arteries Degradation and Resorption Porcine Coronary Arteries Rabbit Subcutaneous Disc Implants Absorption, Distribution, Metabolism and Excretion

 


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ISO-10993 Testing Each Generation of Material Consistently Showed Biocompatibility Polar and nonpolar extracts were tested, where applicable. IS0 - 10993 Test Type of Test Test Conclusion 10993 - 3 Genotoxicity Bacterial Reverse Mutation Study Non - Mutagenic and Non - Geneotoxic Mouse Peripheral Blood Micronucleus Study Non - Geneotoxic In Vitro Chromosomal Aberration in Mammalian Cells Non - Geneotoxic 10993 - 4 Interactions with Blood ASTM Hemolysis study Non - Hemolytic C3a Complement Activation Assay Non - Activator SC5b - 9 Complement Activation Assay Non - Activator ASTM Partial Thromboplastin Time Minimal Activator 10993 - 5 Cytotoxicity ISO Elution Method Non - Cytotoxic 10993 - 10 Sensitization ISO Maximization Sensitization Study Non - S ensitizing 10993 - 10 Irritation Reactivity ISO Intracutaneous Study in Rabbits Non - Irritating 10993 - 11 Systemic Toxicity ISO Systemic Toxicity Study in Mice Non - Toxic

 


Methodology to Assess Biocompatibility of Treated Coronary Vessels Light Microscopic Parameters % Endothelialization Injury Inflammation Multinucleated Giant Cells Residual Erythrocytes Fibrin Deposits Neovascularization Calcification Medial and Adventitial Necrosis/Hemorrhage (acute) Medial and Adventitial Fibrosis (chronic) Adventitial/Perivascular Inflammation Scanning Electron Microscopic Parameters Endothelialization Coverage Over Struts Between Struts Endothelialization Maturity Over Struts Between Struts Thrombus Inflammatory Cells

 


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Polycarbonate Polymer Scaffolds Heal Safely 1 Month 12 Months 3 Months Demonstrated Biocompatibility and No Adverse Tissue Response to the Iodine-Containing Polymers All H&E images at 12.5x Mag.

 


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Gradual Replacement of Polymer with Artery Tissue * Residual struts 400x Mag. H&E stain 12.5x Mag. at 46 Mos Toluidine blue stain 100x Mag.at 12 Mos * * 2500x Mag.

 


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Degrading and Resorbing Struts (SEM Time Lapse) Non-Degraded >90% Resorbed Highly Degraded & Resorbing Proximal Staple Time ~ 4.5 Years Generalized Polymer Curves 0 - 3 Months 6 -24 Months 36 - 48 Months

 


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Scaffold Resorption Confirmed by X-ray and Micro-CT Non-Degraded 90+% Resorbed Highly Degraded & Resorbing T=0 4.5 Yr 4 Yr

 


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Summary of Polycarbonate Polymer Biocompatibility Feature Outcome Material Biocompatibility ISO-10993 tests demonstrate polymer safety Vascular Healing Biocompatible in porcine arteries throughout material life cycle Degradation & Resorption Safe and predictable Clinical Performance Polycarbonate therapies evaluated in patients are free of any iodine sensitivity

 


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Introducing Fantom™

 


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Fantom™ Breakthroughs Reinforced polymer enables 5Fr compatibility with thinner struts Maintains visibility of the entire scaffold Maintains material safety I2DAT TY PLx I2DAT Fantom™ I2DAT TY PLx I2DAT

 


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Fantom™ Sirolimus-Eluting Bioresorbable Scaffold The next advance in bioresorbable scaffolds Micro-Computed Tomography Images of Scaffolds Still Inside the Porcine Coronary Arteries Thinner Radiopaque Struts Conformable to Vessel Geometry

 


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Fantom™ 3-Month Tissue Response Struts well apposed to the artery wall Stains: Hematoxylin & Eosin (left) and Elastic Trichrome (right) 20X Mag.

 


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Fantom™ 3-Month Tissue Response Stains: Hematoxylin & Eosin (left) and Elastic Trichrome (right) 100X Mag. No adverse reaction and elastic lamina well preserved

 


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I2DAT TY PLx I2DAT Fantom™ Fantom™ Breakdown Products and Resorption Safe Clearance with No Accumulation of the Degradation Products in Vital Organs Radiolabel ADME study shows I2DAT is excreted Naturally occurring in olive oil and excreted Safely Metabolized I2DAT TY PLx I2DAT Resorption 3-4 Years Mechanism Hydrolysis

 


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Summary REVA Material Safety 10 year history of safe vascular use Demonstrated biocompatibility Benign tissue response through full degradation REVA Materials Provide full x-ray visibility Enable reduced strut profile with high flexibility Are easily modifiable for application-specific degradation

 


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Collaborator / Pathology Lab Analysis Fred J Clubb DVM, PhD Director, Cardiovascular Pathology Laboratory