Challenges in Bioresorbable Vascular Scaffolds Syed Hossainy Ph

Challenges in Bioresorbable Vascular Scaffolds Syed Hossainy, Ph. D. Director, New Business Ventures and Volwiler Fellow Abbott Vascular Santa Clara, CA USA 1

Potential Conflicts of Interest Speaker’s name: Syed Hossainy I have the following potential conflicts of interest to report: Research contracts Consulting Employment in industry (full-time employee of Abbott Vascular) Stockholder of a healthcare company Owner of a healthcare company Other(s) I do not have any potential conflict of interest 2 AP 2931569

Acknowledgements • • James Oberhauser, Ph. D. , Manager, BVS Polymer R&D, Abbott Vascular Richard Rapoza, Ph. D. , Divisional Vice-President, BVS, Abbott Vascular Not to be reproduced, distributed or excerpted. BVS is currently in development at Abbott Vascular. Not available for sale. AP 2931569 3

Perceived Challenges of Bioresorbable Vascular Scaffolds (BVS) Not to be reproduced, distributed or excerpted. BVS is currently in development at Abbott Vascular. Not available for sale. AP 2931569 4

Challenges Create Opportunity: Hypotheses: • Vessel does not require scaffolding in the long term. • Time to complete mass resorption is not essential factor. • Relevant time constants to evaluate BVS function include: 1) Time of radial strength loss < time of structural discontinuity < time of mass loss. 2) Time of BVS immobilization by tissue in-growth < time of structural discontinuity. 3) Time of maximum mass loss rate – for faster resorbing materials. • Returning the BVS treated segment to an unconstrained state allows for restoration of a response to physiological stimuli. • The loss of scaffolding characteristic of a BVS may lead to a new therapeutic description: vascular restoration therapy (VRT). Not to be reproduced, distributed or excerpted. BVS is currently in development at Abbott Vascular. Not available for sale. AP 2931569 5

Simulated Arterial Model (SAM) Exited Model MORE Deliverable (Ave. Curves Reached) Deliverability Lesions LESS Deliverable ML VISION Diffuse Disease PVA Vessel BVS Cohort B BVS New SDS XIENCE V Not to be reproduced, distributed or excerpted. BVS is currently in development at Abbott Vascular. Not available for sale. Tests were performed by and data are on file at Abbott Vascular. 6 AP 2931569

Acute Radial Strength Acute radial strength of BVS Cohort B PLLA implant is consistent with that of other metallic DES products. Tests conducted using circumferential radial strength test on 3. 0 x 18 mm (or 3. 0 x 20 mm) units. Sample size is 5 per group. Not to be reproduced, distributed or excerpted. BVS is currently in development at Abbott Vascular. Not available for sale. Tests were performed by and data are on file at Abbott Vascular. 7 AP 2931569

In vitro resorption testing at 37°C and p. H 7. 4. Sample size is 6 per group. Flat-plate radial strength testing. Sample size is 6 per group. • Hydrolysis of PLLA breaks amorphous tie chains linking crystalline domains. • Loss of radial strength occurs when a sufficient number of tie chains have been broken. • Degradation rate and loss of radial strength are coupled. Tie chains Not to be reproduced, distributed or excerpted. BVS is currently in development at Abbott Vascular. Not available for sale. Tests were performed by and data are on file at Abbott Vascular. 8 AP 2931569

BVS Resorption Rates in Healthy Porcine Model 1 month 18 months 1 4 4 6 months 1 2 3 5 10 X Magnification 2 years 2 5 1 year 3 Models derived based on Prabhu S and Hossainy S, J. Biomed. Mater. Res. , Pt. A 2007; 80: 732. Not to be reproduced, distributed or excerpted. BVS is currently in development at Abbott Vascular. Not available for sale. Tests were performed by and data are on file at Abbott Vascular. 9 AP 2931569

BVS Resorption Rates in Healthy Porcine Model Porcine Coronary Artery Model Inflammation Score (0 -4) 4 3 2 1 0 3 Mo 6 Mo BVS 12 Mo 18 Mo 24 Mo 36 Mo Cypher Inflammation score ≤ 1 = background Not to be reproduced, distributed or excerpted. 10 BVS is currently in development at Abbott Vascular. Not available for sale. Tests were performed by and data are on file at Abbott Vascular. AP 2931569

BVS Resorption Rates in Healthy Porcine Model % Granuloma BVS % Giant Cells 100 80 80 60 60 40 40 20 20 Cypher 0 0 3 Mo 6 Mo 12 Mo 18 Mo 24 Mo 36 Mo Not to be reproduced, distributed or excerpted. 11 BVS is currently in development at Abbott Vascular. Not available for sale. Tests were performed by and data are on file at Abbott Vascular. AP 2931569

Strut Coverage: ABSORB Cohort A 6 -Month OCT Results Strut Coverage – 6 Mos. F/U 1% 99% N = 13 devices, 671 struts Complete Ormiston, J, et al. Lancet 2008; 371: 899 -907. Incomplete Not to be reproduced, distributed or excerpted. BVS is currently in development at Abbott Vascular. Not available for sale. AP 2931569 12

Resorption Phase Restoration of vascular integrity in porcine coronary artery model At 36 months, SMCs are well organized and phenotypically contractile Not to be reproduced, distributed or excerpted. 13 BVS is currently in development at Abbott Vascular. Not available for sale. Tests were performed by and data are on file at Abbott Vascular. AP 2931569

ABSORB Cohort A Vasomotor Function Testing Serruys, P, et al. Lancet 2009; 373: 897 -910. Not to be reproduced, distributed or excerpted. BVS is currently in development at Abbott Vascular. Not available for sale. AP 2931569 14

Conclusions Acute performance challenges of a BVS may be addressed by: • Polymer selection • Optimal implant geometric design • Optimal polymer structure-property design achieved via processing Long-term safety challenges of a BVS may be addressed by: • Loss of radial strength after vessel revascularization is stable. • Loss of structural continuity after stabilization by tissue in-growth. • In vivo inflammation at acceptable level through different stages of resorption. Therapeutic potential (VRT) of a BVS may be influenced by: • Organized SMC assembly that mimics anisotropicity of natural vessel. • Restoration of vasomotor function in treated segment. Not to be reproduced, distributed or excerpted. BVS is currently in development at Abbott Vascular. Not available for sale. AP 2931569 15