1. 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

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

3. 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

4. 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

5. 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.

6. 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.
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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.

7. 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

8. What Did It Take – Development History

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

10. 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)

11. 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

12. 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

13. 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.
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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.
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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

14. 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:
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- 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

15. 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

16. 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
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

17. 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