Bioresorbable Scaffolds: State of the Field and Lessons Learned Chuck Simonton MD, FACC, FSCAI CMO, DVP Medical Affairs Abbott Vascular Santa Clara, CA, USA FDA Town Hall, CRT 2017

Presentor Disclosures Chief Medical Officer Divisional Vice President, Global Medical Affairs Abbott Vascular Santa Clara, CA, USA

AGENDA 1 Innovations in PCI Over Time Absorb built on XIENCE technology Absorb – The New Goal Potential Benefits – Not Possible with a Metallic Implant What did it take – Development History Absorb Development Timeline – The Path from Concept to Commercial Product Key Takeaways 2 3 4 5 6 7

Innovations in PCI Over Time 1977 Balloon Angioplasty (PTCA) 1988 Bare Metal Stents (BMS) 2001 Coronary Drug Eluting Stents (DES) TODAY Absorb GT1™ (Absorb™) Fully Bioresorbable Vascular Scaffold (BVS) Innovations in PCI

Absorb – The New Goal Revascularization Restoration Resorption with Transient Support 1 Restoration of Physiological Environment (shear stress, multidirectional motion, morphology) Benign Resorption 2 3 For Absorb, the goal is to provide temporary vessel support and then resorb, allowing for natural vessel movement and remodeling.

Absorb: 1st Fully Bioresorbable DES, Built upon XIENCE Technology Material / Design XIENCE Absorb Drug / Elution Everolimus Stent / Scaffold Design MULTI-LINK Design Delivery System MULTI-LINK SDS Stent / Scaffold Material Cobalt Chromium Poly (L-lactide) Coating Material Fluorinated Copolymer Poly (DL-lactide) …Absorb, the first COMPLETELY BIORESORBABLE drug eluting stent, represents a significant advancement in the field of interventional cardiology. We designed Absorb to perform like a DES by building upon Xience technology. In this regard, Absorb utilizes the same drug, everolimus, as well as the well-known multi-link design and balloon delivery system used for Xience. [CLICK] The design features unique to Absorb are in the scaffold and coating materials. Rather than a cobalt-chromium metallic frame, the scaffold itself is made from poly L-lactide, a bioresorbable polymer well-characterized and used in medical applications, including VASCULAR applications, for over 40 years. The coating is also made from polylactide, but a slightly different form, called poly D,L-lactide, which contains the drug everolimus. In this form, the polylactide is “AMORPHOUS” or absent of any crystalline structures, making it ideal for drug elution.

Potential Benefits - Not Possible with a Metallic Implant Restoration of Vasomotion Late Lumen Gain* Unjail Side Branches Long-term Plaque Regression* Non-Invasive Imaging Preserves Native Anatomy *PW Serruys, First Report of the Three Year Clinical and Multi-Modality Imaging Results of the ABSORB Trial Evaluating the Absorb Everolimus Eluting Bioresorbable Vascular Scaffold in the Treatment of Patients with De Novo Native Coronary Artery Lesions; ACC 2013

What Did It Take – Development History

Key Insight into Development of a Novel Product Novel Technology + New Regulatory Questions + Evolving Regulatory Requirements = Steep Learning Curve for Sponsor and FDA

Novel Technology leads to New Questions Underlying Question Is the standard metallic approach appropriate for testing conducted? Any new considerations due to change from metal to polymer? Length of Pre-clinical Safety & Resorption Profile? Assessment of Biocompatibility over degradation? Additional requirements with use of polymers instead of metal? Do we need to assess lot to lot variability of the polymer material? (manufacturing)

A Change in Development Paradigms – Science Drives The Timeline Parameter DES BRS In vivo safety 6 months after implant 6 months after full resorption Biocompatibility Initial – T=0 Through the course of degradation Radial strength At T=0 At T=0 and throughout required support period , in physiological conditions Aging Data/Shelf-Life Data Product aging can be accelerated Limited ability to accelerate due to scaffold materials Data Requirements gated by Polymer Science/Degradation kinetics

New Questions from a Clinical Perspective What additional information is valuable from Clinical perspective? Parameter DES BRS Lumen Stabilization 3 months Similar to DES- 3months Strut Coverage 6 months 6 months and confirm this occurs before the device resorption process begins Assessment of Resorption Not Applicable Clinical data – imaging assessment through resorption process Safety and Efficacy (TLF) 1 year Long Term Outcomes Well understood Data being generated Lumen stabilization and Strut coverage are originally assessed through pre-clinical but confirmed with Clinical Especially important when assessing a new resorbable technology Safety and Efficacy – to show non-inferior to current standard– required for approval However, a critical aspect is long term outcomes of this new technology- which will continue well beyond the 1 year time point- for differentiation Flip the rows.. Add a 5th row.. Long term Outcomes ( well under stood) – BRS – Data still coming

Cohort B- Complete Resorption First, this slide will illustrate a series of OCT images from a representative patient with an Absorb scaffold, showing full resorption and lumen preservation at long-term follow-up. At baseline, you can see the appearance of the scaffold after acute implantation, depicted by the small black boxes along the luminal surface of the vessel. [CLICK] At 6 months, the struts are now covered by an expected layer of neointima and by about two years, the struts are resorbing and there is less appearance of struts. [PAUSE] Then by the time you get to 5 years, there are no visible struts because they are fully resorbed and you can see a more normal-appearing artery with a well-preserved lumen. Data/analysis not submitted or reviewed by FDA

Absorb Clinical Program 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2011 ABSORB Cohort A N=30, First-in-Man 5Y ABSORB Cohort B N=101, First-in-Man 1Y 2Y 3Y 4Y 5Y ABSORB Extend N=812, Registry Enrollment and Follow-Up 1Y 2Y 3Y ABSORB II N=501, International RCT Enrollment and Follow-Up 1Y 2Y 3Y 4Y 5Y ABSORB III N=2,008, U.S. Pivotal RCT Enrollment and Follow-Up 1Y 2Y 3Y 4Y 5Y ABSORB Japan N=400, Japan Pivotal RCT Enrollment and Follow-Up 1Y 2Y 3Y 4Y 5Y With this technology, we embarked upon an extensive clinical program made up of the following studies: [CLICK] - Cohort A, a 5-year first-in-man study which was completed in 2011. - Cohort B, with 101 patients finishing 5-year follow-up last year. - ABSORB EXTEND, an international registry which completes 3-year follow-up this year - ABSORB II, the first international randomized trial. - ABSORB III and IV, both randomized trials in the US, with ABSORB III being the pivotal approval trial with a 1-year endpoint. ABSORB III showed Absorb is non-inferior to Xience and was the basis of approval in IS Beyond 1 year, the ABSORB III data remains blinded to be combined with the ABSORB IV data for an analysis of long-term outcomes at 5 years. - and randomized clinical trials for regulatory approval in Japan and China, both of which met their primary endpoint. Today, the primary focus is the 1-year data from the pivotal ABSORB III trial, ALTHOUGH we will discuss the available longer-term data beyond 1 year from some of the studies started prior to ABSORB III. ABSORB China N=480, China Pivotal RCT Enrollment and Follow-Up 1Y 2Y 3Y 4Y 5Y ABSORB IV N~3,000, U.S. RCT Currently Enrolling 1Y 2Y 3Y 4Y

Absorb Worldwide Commercial Usage at Time of FDA Panel Over 125,000 patients treated in over 100 countries It is important to note that, commercially, more than 125,000 PATIENTS have been treated with Absorb to date in over 100 countries. What this represents is a lot of experience with Absorb that has accumulated outside of the U.S. that has led to a broad knowledge about the optimal techniques for Absorb implantation, and which can be leveraged in the U.S.. Approved

ACC-1 year Cohort B data – 2010 Commercial Launch in CE Abbott Begins Commercial Launch of the Absorb Bioresorbable Stent World's first drug-eluting bioresorbable vascular scaffold has potential to revolutionize treatment of coronary artery disease                                                                                                                                                                                                                                                                                                                                 September 26, 2012 — Abbott Vascular this week began its international launch of the Absorb coronary stent, the world's first drug-eluting bioresorbable vascular scaffold (BVS). Absorb Development Timeline The Path from Concept to Commercial Product 2003-2005 2006-2008 2009-2010 2011-2013 2014-2016 BVS Program was established R&D Team grows 2010– CE approval 2012- CE Launch July 2016 – US approval and Launch Absorb Bioresorbable Vascular Scaffold (BVS) 1st BVS implants – Cohort A March 2006 Cohort A results 2007 101 patients enrolled – Cohort B-2009 ACC-1 year Cohort B data – 2010 Commercial Launch in CE Sept 2012 US PMA Filing – July 2015 US Panel – March 2016 Early, Often and Transparent Communication with FDA 2009- First Meeting with FDA to discuss new technology clinical results well before the IDE On going collaboration - leveraging Pre- Submission meetings to discuss testing strategy; clinical plan and leveraging of data Proactive communication of Clinical Data from on going clinical studies 1st FDA meeting March 2009 IDE Trial initiates 2013 ~200,000 Patients treated WW

Key Takeaways 1 Timeline for a novel technology is driven by science; understanding the product and the technology Novel devices raise new questions for both sponsor and FDA Submission timing is dependent on understanding the technical and clinical questions, and generating the required data (level of evidence) that addresses both safety and effectiveness Early, Often and Transparent communication with FDA can enable a smooth review process Leverage the pre-submission process , start the collaboration as early as possible 2