1. Update on the BIOSOLVE Clinical Trial Using DREAMS Absorbable Magnesium Scaffold
Ron Waksman, MD, FACC, FSCAI
Professor of Medicine, Georgetown University,
Associate Chief of Cardiology,
Washington Hospital Center, Washington DC

2. Ron Waksman, MD Consulting Fee Abbott Laboratories Biotronik, Inc.
Boston Scientific Corporation
Medtronic, Inc.
Merck and Company, Inc.

3. Honoraria
Abbott Laboratories
Boston Scientific Corporation
Medtronic, Inc. Consulting Fee
Merck and Company, Inc.

4. AMS is a metallic stent with favorable mechanical properties
Design & Manufacturing
Based on Finite Element Analysis
Laser cut and polished surface
San Pellegrino:
Mg: 53.5 mg/l
Mechanical parameters
Low bending stiffness
Low crossing profile (1.2 mm)
Low recoil (<5%)
High radial strength (~1 bar)
Clinical effects
Good trackability and device success rate of 99.4%*
Good stent apposition

5. AMS allows non-invasive imaging of the stented vessel
Headline
IVUS/OCT stent visibility
MRI
16 MSCT
Erbel et al, Herz 32 · 2007 · Nr. 34
Left pictures: Coronary magnesium stent implantation into segment 1 of the right coronary artery and visualization by intravascular ultrasound. The stent was not visible by magnetic resonance imaging, but the invisible stent allowed free imaging of the coronary lumen of the artery despite coronary stenting.
Right picture: 16‑slice computed tomography of a magnesium stent in segment 6 of the left coronary artery. The magnesium stent is not visible allowing a free imaging of the artery lumen
MRI/MSCT
No stent artefact
Optimal vessel lumen imaging
* …
Source: …
Source: Erbel et al, Herz 32 · 2007 · Nr. 4
* …
Source: …

6. Degradation product composition in vivo
Magnesium of the AMS scaffold is completely replaced with conversion products
The polymeric drug coating is fully degraded
Degradation process and conversion product composition in clinical and preclinical use is similar
5 months after AMS 1.0 implantation
Staining indicates a nearly complete replacement of magnesium (pediatric).
Elemental composition of conversion product
Residual magnesium core, degradation products in the surrounding conversion zone (minipig).
Sources: J. Riedmüller; Yucatan Minipig, 42 days FUP // Zartner P. First Successful Implantation of a Biodegradable Metal Stent Into the Left Pulmonary Artery of a Preterm Baby. Catheterization and Cardiovascular Interventions 66:590–594 (2005))

7. Previous bare AMS devices demonstrated safety, but…
IVUS
OCT
Perfect in growth of AMS
Safe in human coronary and peripheral arteries (150 patients)
No death, no MI, no scaffold thrombosis, no distal embolization, no excessive inflammation
Device success rate of 99.4%
Absorbed as intended in several months
Fully CT/MRI compatible
Source: Courtesy Dr Di Mario: PROGRESS AMS-1, long term results (15 months) showed perfect ingrowth

8. Lessons learned from the AMS
PROGRESS-I showed the bare AMS concept to be safe and feasible
Post implantation
4 month follow-up
Contribution to lumen loss
Loss of scaffolding area
In-stent
neointima
53%
47%
Results of PROGRESS* (AMS I FIM): LLL 1.08 mm; TLR 23.8%
Optimization of device with prolonged scaffolding time and an anti-proliferative drug
* Erbel R. et al., Lancet 2007;369: , Waksman et.al, JACC Cardiovasc Intervent 2009;2:

9. From bare AMS to DREAMS Bare AMS DREAMS Histology at 28 days
PROGRESS-I
DREAMS
BIOSOLVE-I
Prolong scaffolding time and inhibit cell proliferation
80x165µm
130x120µm + 1μm coating
Strut Geometry
Alloy Refinement
Drug/polymer matrix added with Paclitaxel
Histology at 28 days
Scaffold design

10. DREAMS: DRug-Eluting Absorbable Metal Scaffold - Design Overview -
Drug carrier
1 µm bioabsorbable PLGA Polymer
Scaffold Backbone
Proprietary Mg-alloy
Excellent biocompatibility
120µm strut thickness
Drug
Paclitaxel
Proven elution behaviour
Delivery system
Modified PRO-Kinetic Energy
Sizes used in FIM
3.25/3.5 x 16
6F compatible

11. DREAMS provides scaffolding and paclitaxel release up to 3 months
acute
3 months
6 months
9 months Mg
Scaffolding
Paclitaxel release
Mg + 2H2O  Mg(OH)2 + H2
Soft Hydroxyapatite
Biodegradation
Bioabsorption
Mg degradation completed
Drug release completed
Degradation of polymer ongoing
Conversion of degradation product completed
Drug carrier layer degradation completed
Beginning of structural disintegration
Mg alloy
Mg degradation product
Polymer

12. First generation DREAMS shows in vitro elution behavior comparable with Taxus
DREAMS drug elution
Cumulated
DREAMS
High stability of paclitaxel allows to control processes in this system comprising a degradable backbone and a degradable drug carrier
Based on preclinical tests, elution time in-vivo elution is estimated at 3 months
Taxus Liberté
DREAMS
Source: in vitro measurements, data on file

13. DREAMS shows low inflammation scores - comparable to Taxus
Comparison between DREAMS and Taxus Liberté control shows low inflammation scores at 28, 90 and 180 days
Minor increase of inflammation at 28 days seen in the DREAMS arm due to degradation of base materials
Inflammation Score [28/90/180d]
Histopathology, Mean Values
4.0
3.0
2.0
1.0
1.31
0.65
0.66
0.56
0.70
0.38
0.0
DREAMS
Taxus Liberté
n=8/8/8/4
n=6/6/6
Source: AccelLAB preclinical studies, data on file

14. DREAMS late lumen loss is comparable to Taxus
Taxus Liberté
N=6/6/6/6
DREAMS
N=8/8/8/8
Source: AccelLAB preclinical studies, data on file

15. Histological Images at 28 days show fast healing of DREAMS
Reference
(Taxus)
Source: AccelLAB preclinical studies, data on file All photos same magnitude and scale

16. 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: TLF* at 6 months
Cohort 2: TLF* at 12 months
46 patients with de novo coronary artery stenosis
Cohort 1 (n=22)
Cohort 1 (n=22)
Cohort 2 (n=24)
Cohort 2 (n=24)
6-month FUP
Clinical (n=22)
Imaging (n=20**)
Clinical (n=24) Imaging (n=16***)
* Composite of cardiac death, target vessel myocardial infarction and clinically driven TLR
12-month FUP
** 2 pts withdrew consent for imaging FUP at 6 months
*** 16 pts from cohort 2 consented for the optional 6-month imaging FUP
Clinical (ongoing)
Imaging (ongoing)
Clinical (ongoing) Imaging (ongoing)
QCA and IVUS are mandatory imaging follow-ups, while OCT is optional
24 and 36-month FUP
mandatory
optional

17. Baseline clinical characteristics
Cohort 1+2
N=46
Age (mean ± SD)
65.3 ± 9.7
Men (N/%) 34
73.9 %
Hypertension 40
87.0 %
Hyperlipidemia 41
89.1 %
History of MI 15
32.6 %
Previous PCI 27
58.7%
Renal Insufficiency 12
26.1%
Congestive Heart Failure 7
15.2%
Diabetes
Smoking 6
13.0%
History of stroke of TIA 3
6.5%

18. Baseline angiographic characteristics
Pre-Procedure (N=46)
RVD (mm)
2.73 ± 0.48
MLD (mm)
1.21 ± 0.52
% Diameter stenosis
56.0 ± 17.1
Mean lesion length (mm)
10.69 ± 4.5
Procedure (N=46)
Scaffold length used (mm) 16
Scaffold diameter used (mm)
3.25 / 3.5

19. Procedural and primary endpoints for both cohorts up to 6 months%
Device success* 46
100
Procedural success**
6-month clinical results
TLF 2
4.3
Cardiac death
0.0 MI
Scaffold thrombosis
TLR (clinically-driven)***
* Defined as:
successful delivery of the scaffold to the target lesion site in the coronary artery
appropriate scaffold deployment
successful removal of delivery system after release of the scaffold
safe removal of the device in case of deployment failure
** Defined as:
device success plus attainment of a final residual stenosis of < 50% of the target lesion
absence of a major adverse cardiac event during the hospital stay to a maximum of first seven days post procedure
*** TLR occurred during 6 M FUP, both pts had angina, 1 pt received an additional DREAMS in the target lesion during the initial procedure because of a flow-limiting bailout situation 19

20. Comparison of angiographic LLL between bare AMS and DREAMS
BIOSOLVE-I
6-month FUP
0.64± 0.50 mm
-41%
Cumulative Frequency (%)
PROGRESS
4-month FUP
1.08 ± 0.49 mm
LLL (mm)

21. OCT evaluation: few malappositions post-procedure and at 6 months
Scaffold Strut Apposition – Baseline
Scaffold Strut Apposition – 6 Mo FUP
3.6%
6.4%
1.1%
5.3%
93.6%
90.0%
Apposed
ISA
Apposed
Persistent ISA
Late Acquired ISA
Resolved ISA
N=4 scaffolds, 3,226 struts
Apposed
N=4 scaffolds, 3,226 struts
ISA – Incomplete Strut Apposition
Koolen J. et al; TCT 2011

22. Six-month follow-up evaluation of OCT images shows 100% strut coverage
Scaffold Strut Coverage – 6 Mo FUP
0.0% (0 struts)
100.0% (9,487 struts)
Complete
Incomplete
N=15 scaffolds, 9,487 struts
Koolen J. et al; TCT 2011
Complete

23. Vasomotion result-cohort 1
Proximal Segment
0.5
4.0
4.5
5.0
3.5
3.0
2.5
2.0
1.5
1.0
Mean lumen diameter (mm)
Pre-ACH
Post-ACH
Nitro- glycerine
Mean
Scaffolded Segment
Distal Segment
P=0.515
2.55______2.25______ p= p=0.012
P=0.493
2.40______2.25______ p= p=0.006
P=0.959
2.37______2.08______ p= p=0.012

24. Koolen J. et al; Poster Presentation, TCT 2011
Case presentation 1
Pre
Post
6 Mo FUP
BEL
76 yrs old female
Hyperlipidemia, LBBB, aortic valve stenosis,
De novo lesion in the mid LAD
Pre-dilatation with 3.0/ 12mm balloon, treatment with 3.5/ 16 mm Dreams
No signs of angina at 6 month follow-up
Post
6 Mo FUP
Koolen J. et al; Poster Presentation, TCT 2011

25. Koolen J. et al; Poster Presentation, TCT 2011
Case Presentation 2
6 Mo FUP
Pre
Pre
Post
Post
6 Mo FUP
6 Mo FU
NLD
72 yr-old male with hypertension, renal insufficiency
De novo lesion in the mid LAD
Pre-dilatation with 2.5/ 12mm balloon, treatment with 3.5/ 16 mm DREAMS
Stable angina class II at 6-month follow-up
Post
Koolen J. et al; Poster Presentation, TCT 2011

26. Future Development
BIOTRONIK is evaluating the option of adding a Limus compound to improve patient outcome
in vitro drug release kinetik of DREAMS vs. Sirolimus-eluting ORSIRO
(Fast Release Method) 10 20 30 40 50 60 70 80 90
100
in vitro
elution time [h]
Total release [% LC]
Reference. ORSIRO Sirolimus-eluting stent
DREAMS Sirolimus-eluting Absorbable Metal Scaffold 26

27. In development
Radiopaque markers will be added to improve x-ray visualization 27

28. Conclusions
The DREAMS device demonstrates an excellent safety profile without death, MI, or scaffold thrombosis at 6 months
A TLF rate of 4.3% at 6 months after DREAMS implantation is comparable to permanent DES
DREAMS demonstrated significantly improved efficacy compared to the bare AMS:
Reduction in LLL of 41% (1.08 vs. 0.64mm)
Reduction of TLR rate by 82% (23.8 vs 4.3%)
Future Directions continued improvement in design, markers and moving to a limus drug
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