1. Bioresorbable scaffold: the advent of a new era in percutaneous coronary revascularisation Clinical Data Update
Ron Waksman, MD, FACC Director, Cardiovascular Research & Advanced Education Associate Chief of Cardiology, Washington Hospital center, Professor of Cardiology, Georgetown University Washington DC

2. Disclosure
Consultant : Biotronik, Medtronic, Boston Scientific. Abbott Vascular
Speaker Biotronik BSC, Medtronic, Abbott Vascular
Research Grants: Biotronik, Medtronic, Boston Scientific, GSK, Medicine Company, Abbott Vascular

7. ABSORB A - 5 Year Clinical Results
Hierarchical
6 Months
30 Patients
12 Months
29 Patients*
4 Years
5 Years
Ischemia Driven MACE, %(n)
3.3% (1)*
3.4% (1)*
Cardiac Death, %
0.0%
MI, %(n)
Q-Wave MI
Non Q-Wave MI
3.3% (1)**
3.4% (1)**
Ischemia Driven TLR , %
by PCI
by CABG
No new MACE events between 6 months and 5 years
*One patient withdrew consent after 6 months
**This patient also underwent a TLR, not qualified as ID-TLR (DS = 42%) followed by post-procedural troponin qualified as non-Q MI and died from his Hodgkin’s disease at 888 days post-procedure.
Serruys PW, Onuma Y: 5-year Cohort A and 2-year Cohort B results: Integrated insights. In: Transcatheter Cardiovascular Therapeutics. San Francisco, CA November

21. 21

22. 22

24. Postmarketing Surveillance
All-comers Multi-Center RC Trial
Global
Postmarketing 10,000 PTS
ABSORB STEMI Registry

33. Bioabsorbable magnesium scaffolds: novel experimental and clinical results - Biotronik’s DREAMS program

34. AMS (2004) The first generation bare magnesium scaffold
Where we come from: A bare magnesium scaffold with favorable mechanical properties
Mechanical parameters
High radial strength (~0.8 bar)
Low recoil (<5%)
Scaffold Backbone
WE43 Mg-alloy
Excellent biocompatibility
165µm strut thickness
Delivery system
Lekton RX catheter
Design & Manufacturing
Laser cut and polished surface
Sizes used in studies
3.25/3.5 x 16
6F compatible

35. AMS Product Evolution AMS 2004
4 mo n = 63
12 mo n = 60
Cardiac death MI
Scaffold thrombosis
TLR (clinically driven)
23.8%
26.7%
Late loss (mm)
1.08 ± 0.49 -
Learnings from AMS
Device is safe and feasible
Effectiveness required optimization
IVUS findings showed lumen loss was due to loss of scaffolding area and NIH
7 year follow-up: no additional MACE between 12 months and 7 years
Need for longer scaffolding support and addition of antiproliferative drug
Erbel et al. Lancet 2007; 369: 1869–75.

36. DREAMS device evolution
Drug-eluting AMS (DREAMS)
Refined alloy with slower absorption rate
Reduced strut thickness
6-crown design
PLGA polymer carrier
Paclitaxel drug elution
Used in BIOSOLVE-I study
AMS
DREAMS
165µm
80µm
130µm
120µm
AMS 28-day histology
DREAMS 28-day histology

37. BIOSOLVE-I study design
DESIGN: Prospective. multi-center. FIM. single de novo coronary artery lesions between mm and ≤ 12 mm long
PRIMARY ENDPOINT: Cohort 1: TLF at 6 months Cohort 2: TLF at 12 months
PRINCIPAL INVESTIGATOR: J. Koolen. MD. Catharina Ziekenhuis. Eindhoven. Netherlands
46 patients with de novo coronary artery stenosis
Cohort 1 (n = 22)
Cohort 2 (n = 24)
Mandatory 6mo: Clinical FUP (n = 22) Imaging FUP (n = 201)
Optional 6mo: Clinical FUP (n = 24) Imaging FUP (n = 16)
Optional 12mo: Clinical FUP (n = 202) Imaging FUP (n = 13)
Mandatory 12mo: Clinical FUP (n = 232) Imaging FUP (n = 201)
Mandatory 24mo: Clinical FUP (n = 202)
Mandatory 24mo: Clinical FUP (n=24)
1 5 pts withdrew consent for imaging FUP (2 at 6-month and 4 at 12-month FUP)
2 1 pt died a non-cardiac death (Cohort 1). 2 pts withdrew consent (1 Cohort 1 and 1 Cohort 2)
Mandatory 36mo: Follow-up ongoing
Source: M Haude. et al. Lancet 2013; 381: 37

38. BIOSOLVE-I study design
Prospective, multi-center, first-in-man trial, single de novo coronary artery lesions with RVD between 3.0 and 3.5 mm and lesion length ≤ 12 mm
Primary Endpoint
Cohort 1: TLF1 at 6 months
Cohort 2: TLF1 at 12 months
46 patients with de novo coronary artery stenosis
Cohort 1 (n=22)
Cohort 2 (n=24)
6-month FUP
Clinical (n=22)
Imaging (n=202)
Clinical (n=24) Imaging (n=16)
1 Composite of cardiac death, target vessel myocardial infarction and clinically driven TLR
2 A total of 5 pts withdrew consent for imaging FUP (2 at 6-month and 4 at 12-month FUP)
3 1 pt died a non-cardiac death (Cohort 1), 2 pts withdrew consent
12-month FUP
Clinical (n=203)
Imaging (n=13)
Clinical (n=233) Imaging (n=202)
Bold: Mandatory endpoint
Italic: Optional endpoint
24 and 36-month FUP
QCA and IVUS are mandatory imaging follow-ups, while OCT is optional

39. BIOSOLVE-I study results 6-and 12-month late lumen loss (LLL)
6-month LLL
0.64 ± 0.50 mm
12-month LLL
0.52 ± 0.39 mm
LLL of the bare AMS in the PROGRESS study at 4-month: 1.08 ± 0.49 mm
Cumulative Frequency (%)
In-scaffold LLL (mm)
Source: M Haude. et al. Lancet 2013; 381: 39

40. BIOSOLVE-I study results Six to 24-month clinical follow-up
Device success
100% (47 / 47)
Procedure success
100% (46 / 46)
Clinical results
6-month1
12-months1
24-months
Cohort 1 & 2
Cohort 1&2
TLF
4.3% (2/46)
6.8% (3/44)
Cardiac death
0.0%
MI2
2.3% (1/44)
Scaffold thrombosis
TLR (clinically driven)3
4.5% (2/44)
Device Success: successful delivery of the scaffold to the target lesion, appropriate deployment, successful removal of delivery system.
Procedure Success: device success plus attainment of a final residual stenosis of <50% of the target lesion. absence of MACE during the hospital stay up to 7 days.
1 M Haude. et al. Lancet 2013; 381: Target vessel peri-procedural MI. 3 TLR occurred during 6M FUP, both pts had angina. 1 pt received an additional DREAMS during the initial procedure due to a flow-limiting bailout. 40

41. BIOSOLVE-I study results Vasomotion results at 6-month (N=26)
Relative Change in mean lumen diameter %
Proximal Segment
Scaffolded Segment
Distal Segment
±17.93%
9.34 ± 12.88%
± 20.30%
8.69 ±10.05%
±22.05%
9.66 ±9.33%
Mean ±SD
ACH
NTG
-80
-60
-40
-20 20 40 60
ACH concentration
Low: µg/mL
Medium: 3.6 µg/mL
High: 18 µg/mL
Nitro concentration
200 µg/mL
Acetylcholine (ACH): Presents the % change in mean lumen diameter between pre-and post-Acetylcholine (ACH) at the highest response
Nitroglycerine (NTG): Presents the % change in mean lumen diameter between post-ACH and Nitroglycerine

42. DREAMS product evolution
1st generation
DREAMS
2nd generation
Refined WE43 alloy with slow degradation
3-link design with 120 µm strut thickness
PLGA polymer carrier
Paclitaxel drug elution analog to Taxus
Used in BIOSOLVE-I study in 2010
Optimized scaffold design and process for
Better bending flexibility
Increased deployment diameter
6-crown 2-link design
Radiopaque markers at both ends
PLLA drug carrier polymer, same as ORSIRO
Sirolimus drug elution, same drug dose density as ORSIRO

43. DREAMS summary
DREAMS First Generation demonstrates an excellent safety profile up to 24 months
TLF rate remains stable up to 24-month follow-up
DREAMS demonstrated significantly improved efficacy at 12 months compared to the bare AMS:
Reduction in LLL of 61% compared to the 4-month data of the bare AMS (1.08mm vs. 0.52mm)
Reduction of TLR rate by 82% (26.7% vs. 4.7%)
DREAMS second generation improved scaffold properties and utilizing Orsiro DES coating PLLA and Sirolimus
BIOSOLVE –II will start in Q using second generation DREAMS 43 43

44. BRS VERSUS BMS and DES

45. BRS TECHNOLOGY PROJECTION
Second and third generation BRS will be disruptive technology with improved deliverability and reduced cost
The Bioabsorbable DES is most likely non-inferior to the best in class DES of today and may be superior within 5 years of follow-up
The perception of patients and physicians is strong and will drive high usage of BIORESORBABLE DES to become the gold standard for PCI

46. Bioresorbable scaffolds have been called “the Fourth Revolution”
in PCI
FIRST
SECOND
THIRD
FOURTH
Balloon angioplasty 1977
Bare metal stents 1990s
Bioresorbable Drug- eluting stents 2006
Drug-eluting stents 2000’s