1. Development of a Drug-Coated Scoring Balloon Preliminary Results from a FIM Study
Gary Gershony, MD, FACC, FSCAI, FAHA, FRCPC
Interventional Cardiologist, John Muir Cardiovascular Institute, Concord, CA
Co-Founder and Chief Medical Officer, AngioScore, Fremont, CA

2. Disclosure Statement of Financial Interest
Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship Company
Grant/Research Support
Consulting Fees/Salary Support AngioScore, Inc.
Major Stock Shareholder/Equity
Royalty Income
Ownership/Founder AngioScore, Inc.
Intellectual Property Rights
Other Financial Benefit
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3. POBA Inadequacies – “Unmet Clinical Need”
DES/BMS pre-dilatation (geographic miss, inadequate stent expansion/wall apposition)
Heavily calcified/hard lesions
ISR (balloon slippage/geographic miss, tissue recoil)
Diffuse/small vessel disease (poor acute results)
Bifurcation side branch ostial lesions
Unpredictable results and high rate (≥40%) of uncontrolled dissections requiring bailout stenting
High rate of restenosis (30-50%)

4. AngioSculpt – Coronary/Peripheral+ =
2 component system
OTW or rapid exchange semi-compliant balloon
Laser cut nitinol spiral scoring element ( ” struts)
Available in mm diameter, mm length

5. AngioSculpt – Mechanical Forces
Edges lock in
~15-25x force
1x force

6. AngioSculpt – Mechanism of Action
Acute histopathology specimen of a patient post-POBA demonstrating extensive dissection and laceration (yellow arrows)
Post-AngioSculpt scoring of porcine ISR (yellow arrows)
Human IVUS demonstrating scoring post-AngioSculpt (yellow arrows)

7. OCT of RCA Lesions Post-AngioSculpt
De Novo (E) and ISR (F) Lesions Post-AngioSculpt
OCT of De Novo Lesion Post-AngioSculpt demonstrating scoring (white arrowheads)
OCT of ISR Lesion Post-AngioSculpt demonstrating scoring (white arrowheads)
Takano et al, Int J Cardiol 2008, doi: /j.ijcard

8. Proposed AngioSculpt Benefits
Prepare Vessel for DES/BMS
Non-slip (avoid “geographic miss”)
Full stent expansion/apposition at lower balloon pressures
Calcified & Fibrotic Lesions
More optimal lumen expansion at lower balloon pressures
Less trauma/dissection leading to more predictable results
Bifurcation Lesions (AGILITY Trial)*
Less elastic “recoil” in ostial side-branches or plaque-shifting
Lower rate of dissection and need for second stent in side-branch
Non-slip
Overcome “stent jail” of side-branch
*CAUTION Investigational Device. Limited by Federal Law to Investigational Use*
Costa et al, Am J Cardiol 2007;100: Mooney et al, Am J Cardiol 2006;98;8:121M Moses et al, CCI 2011;77;6:S43

9. Proposed AngioSculpt Benefits – cont’d
Small Vessel Disease (≤ 2.5 mm diameter)
Less dissections/more predictable results
Avoid stenting (“full metal jacket”)
In-Stent Restenosis (ISR)
Non-slip (avoid “geographic miss”)
Less tissue “recoil”
More optimal re-expansion of original stent
Ostial Lesions
Overcome calcification and elastic recoil of these complex lesions
Allow use of thin strut stents with less radial strength (e.g. Xience)
More accurate placement and avoid slippage
Fonseca et al, J Inv Cardiol 2008;20: Mooney et al, Am J Cardiol 2006;98;8:121M

10. AngioSculpt for PAD
Highly effective as primary therapy in a broad range of complex lesion morphologies (“stent-like” angiographic results)
Very useful in peripheral lesions where stenting should be avoided (ISR, popliteal, CFA, profunda, A-V dialysis graft/fistula)
Emerging role for renal artery stenosis (pre-dilatation, ISR)
Avoids “geographic miss” due to device slippage
Preliminary data suggest a favorable limb salvage rate in patients with CLI and a favorable long term patency rate in femoro-popliteal disease compared to historical data with POBA (MASCOT Trial)
Safe with a very low complication rate (low dissection rate, very rare perforations or device malfunctions)
Longer length AngioSculpt devices (≥ 100mm) may extend the usefulness of this technology to more complex & diffuse lesion subsets
Scheinert et al, CCI 2007;70:
Bosiers et al, Vascular 2009;17(1):29-35

11. ......but no proven benefit in reducing restenosis compared to POBA

12. Why Consider a Drug-Coated AngioSculpt?
Results with drug-coated POBA (e.g., Paccocath) are very promising
May be able to deliver drug more effectively with a scoring element
Better acute luminal results with AngioSculpt compared to POBA
Lower rate of dissection with AngioSculpt compared to POBA
No slippage or “geographic miss” with AngioSculpt
May be able to avoid adjunctive stenting
All of the above may allow a drug-coated AngioSculpt to provide “stand alone” therapy for a wide range of coronary and peripheral arterial lesions with a significantly lower restenosis rate than POBA or allow the use of BMS/BVS rather than DES

13. PTX-Coated AngioSculpt (SEM)
Drug Coating Project
Earlier collaboration with Elazer Edelman at MIT & Renu Virmani at CV Path using PTX without carrier
Current new collaboration using PTX with excipients
PTX-Coated AngioSculpt (SEM)

14. PTX-Coated AngioSculpt

15. Pre-Clinical Studies: Pharmaco-Kinetics
Porcine coronary overstretch model (8 pigs, 24 vessels)
Coatings are non-polymers used in other intra-vascular clinical applications
Dose of paclitaxel is ~3 µgm/mm2 (similar to Paccocath)
AngioSculpt 3.5 x 20 mm balloons used without stents
Loss of drug during transit was low (2-15%, depending on coating)
8-11% of initial drug was delivered to vessel wall acutely 10-30’ post-treatment) during 60 second inflation
Residual drug on AngioSculpt was 11-18%, depending on coating

16. Gary Gershony, Bruno Scheller, Ulrich Speck, Bodo Cremers
Successful Inhibition of Coronary Neo-Intimal Hyperplasia in Swine Using a Novel Paclitaxel-Coated Scoring Balloon Catheter
Gary Gershony, Bruno Scheller, Ulrich Speck, Bodo Cremers
John Muir CVI, Concord, CA, Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany, Abteilung für Radiologie, Experimentelle Radiologie, Charité, Universitätsklinikum, Berlin, Germany
J Am Coll Cardiol 2011;57;E1662

17. Pre-Clinical Studies: Chronic Efficacy
Porcine coronary overstretch ISR model (~1.2:1)
30 pigs, 60 vessels (LAD, LCx)
BMS (“Bx Velocity”) ~14 mm length
5 treatment arms: PTX-coated POBA, “bare” AngioSculpt, PTX-coated AngioSculpt (3 versions), all 3.5 x 20 mm
PTX dose/balloon ~900 µgm (~3 µgm/mm2)
Follow-up QCA & quantitative histomorphometry at 30 days
3 animals died during f/u (1 control, 1 Paccocath & 1 coated ASC)

18. QCA Summary Results: 30-Day
Bare ASC
PTX-POBA
Coated ASC 1
Coated ASC 2
Coated ASC 3
P-Value
LLL (mm)
1.43±0.65
0.50±0.35
0.44±0.56
0.27±0.24
0.23±0.22
0.001
DS (%)
43.9±24.9
11.5±15.9
0.6±23.5
-2.1±18.3
-6.6±24.2
ASC = AngioSculpt
DS = diameter stenosis
LLL = late lumen loss
“Negative” values for DS mean that the initial stent overstretch is maintained and not compensated by neo-intimal proliferation

19. In-Stent 30-Day Late Lumen Loss

20. LVEF at Baseline & 30-Day F/U
P=NS

21. Histomorphometry Summary Results: 30-Day
Bare ASC
PTX-POBA
Coated ASC 1
Coated ASC 2
Coated ASC 3
P-Value
Neointimal Area (mm2)
4.46±1.49
3.26±0.78
2.95±1.22
2.47±0.86
2.80±0.73
0.001
Media Area (mm2)
4.20±2.56
1.77±0.48
1.41±0.75
1.56±0.71
1.44±0.52
Injury Score
2.53±0.53
2.52±0.30
2.57±0.36
2.52±0.28
2.66±0.26 NS
Inflammation Score
2.37±0.75
2.55±0.42
2.71±0.32
2.56±0.41
2.60±0.59

22. In-Stent 30-Day Histomorphometry

23. Control Treatment – “Bare” AngioSculpt
Baseline
30-day f/u

24. PTX-Coated AngioSculpt
Baseline
30-day f/u

25. Pre-Clinical Dose-Ranging & Safety Study
Porcine coronary overstretch/ISR model
Dose range of 1.5 – 12 µgm/mm2 (groups c-g)
Bare AngioSculpt control (groups a-b)
Total of 35 swine (5 animals and 10 vessels per group)
Follow-up QCA & quantitative histomorphometry at 28 d
Histopathology of distal myocardium (including RV)

26. In-Stent 28-Day Late Lumen Loss

27. Histomorphometry – 28 Days

28. Conclusions: Drug-Coated AngioSculpt
Coating an AngioSculpt with paclitaxel is technically feasible
Use of specific excipients in the coating is essential to provide the correct device-drug adhesiveness, release characteristics and tissue pharmaco-kinetics
Animal studies demonstrate that a drug-coated AngioSculpt is at least as effective as the clinically proven Paccocath for inhibiting neo-intimal proliferation post-stenting
A wide range of drug dosages is associated with safety & efficacy
No evidence of local drug/carrier toxicity or adverse myocardial effects (EF)

29. FIM Study Design Coronary bare metal stent ISR
Randomized controlled trial: PTX-Coated AngioSculpt vs. Bare AngioSculpt
60 patients, 3 sites (Germany and Brazil)
Primary endpoint: 6 month angiographic LLL (in-segment)
Secondary endpoints: TLR, MACE, ST and other QCA and clinical data
Independent QCA core lab and statistical analysis
First patient enrolled 12/13/2011 (Saarland University, Homburg, Germany)

30. 78 Year Old Male, BMS-Restenosis in LAD,
EF 75%, Two-Vessel Disease (LAD and RCA)
PTCA 3.0 / 20 mm
High pressure balloon
3.0 / 10 mm 25 atm
Before PCI
After predilatation

31. 78 Year Old Male, BMS-Restenosis in LAD,
EF 75%, Two-Vessel Disease (LAD and RCA)
AngioSculpt 3.0 / 20 mm
Randomization Group B
Final Result

32. 62 Year Old Male, BMS-Restenosis in RCA,
EF 60%, Two-Vessel Disease (LAD and RCA)
PTCA 2.0 / 20 mm
PTCA 3.0 / 20 mm
Before PCI

33. 62 Year Old Male, BMS-Restenosis in RCA,
EF 60%, Two-Vessel Disease (LAD and RCA)
AngioSculpt 3.0 / 20 mm
Randomization Group B
Final Result