1. Development of a Drug-Coated Scoring Balloon Preliminary Results from the PATENT-C FIM Study
Gary Gershony, MD, FACC, FSCAI, FAHA, FRCPC
Director of Cardiovascular Research,
Education & Technology
John Muir Health and Cardiovascular Institute,
Concord, 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/Honoraria
Major Stock Shareholder/Equity
Royalty Income
Ownership/Founder
Intellectual Property Rights
Other Financial Benefit
AngioScore, Inc.

3. POBA Inadequacies – “Unmet Clinical Need”
DES/BMS/BVS 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/BVS*
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
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
* Caution - INVESTIGATIONAL DEVICES, LIMITED BY FEDERAL LAW TO INVESTIGATIONAL USE

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
Effective as primary therapy in a broad range of complex lesion morphologies (“stent-like” acute 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
More optimal re-expansion of original stent in ISR treatment
Lower rate of dissection with AngioSculpt compared to POBA
Minimal 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. Paclitaxel-Coated AngioSculpt (SEM)
Drug Coating Development
Earlier collaboration with Elazer Edelman at MIT & Renu Virmani at CV Path using paclitaxel without carrier
Current collaboration using paclitaxel with excipients
Paclitaxel-Coated AngioSculpt (SEM)

14. Paclitaxel-Coated AngioSculpt

15. Pre-Clinical Studies: Pharmaco-Kinetics
Porcine coronary overstretch model (8 pigs, 24 vessels)
Coatings: non-polymers used in other intra-vascular clinical applications
Dose of paclitaxel: 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)
*PTX = paclitaxel

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
PTX-POBA = paclitaxel-coated conventional balloon
“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. Control Treatment – “Bare” AngioSculpt
Baseline
30-day f/u

23. Paclitaxel-Coated AngioSculpt
Baseline
30-day f/u

24. Pre-Clinical Dose-Ranging & Safety Study
Porcine coronary overstretch/ISR model
Paclitaxel dose range: 1.5 – 12 µgm/mm2 (4 groups)
Bare AngioSculpt control (2 groups)
5 animals and 10 vessels per group
Follow-up QCA & quantitative histomorphometry at 28 d
Histopathology of distal myocardium (including RV)

25. In-Stent Late Lumen Loss: 28-Day

26. Histomorphometry at 28-Days

27. 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, histopathology)

28. FIM Study Design Coronary bare metal stent ISR
Randomized controlled trial: PTX-Coated AngioSculpt vs. Bare AngioSculpt
60 patients, 5 sites (4 in Germany and one in Brazil)
Primary endpoint: 6 month angiographic LLL (in-segment)
Secondary endpoints: TLR, MACE, ST and other QCA and clinical data (patients will be followed for 2 years)
Independent blinded QCA core lab & statistical analysis (CRF)
Overall Study PI: Bruno Scheller, MD
Chair of Steering Committee: Martin B. Leon, MD
Current enrollment – 52 patients (February 22, 2013)

29. FIM Study Sites
Universitätsklinikum des Saarlandes, Homburg/Saar, Germany (Bruno Scheller - PI)
Dante Pazzanese Cardiology Institute, Sao Paulo, Brazil (Alexandre Abizaid)
Herzzentrum Leipzig, Germany (Sven Möbius-Winkler)
Ernst von Bergmann Klinikum, Potsdam, Germany (Klaus Bonaventura)
Vivantes, Berlin, Germany (Stefan Hoffmann)

30. Key Inclusion Criteria
Clinical evidence of stable or unstable angina or an abnormal functional study demonstrating myocardial ischemia due to the target lesion(s)
Patients with ≤ 2 primary in-stent restenosis (ISR) lesions
≥ 70% diameter stenosis
lesions located entirely within previously placed bare metal stents (BMS) in native coronary arteries*
Stabile oder instabile Angina pectoris Symptomatik oder positiver Stress-Test
*Treatment of one additional lesion in a non-target vessel (non-ISR lesions), is permissible if the lesion is treated prior to the target lesion (ideally ≥24 hrs) without any evidence of post-procedural MACE

31. Key Exclusion Criteria
Target lesion within a previously placed drug-eluting stent (DES)
Reference vessel diameter (RVD) < 2.5 mm
Target lesion stented segment length ≥ 30 mm (lesion should be located entirely within the stent)
Intended treatment of more than 2 ISR lesions or a total of more than 3 lesions (including native vessel disease) per patient
Acute myocardial infarction (MI) within the past 72 hours
Left ventricular ejection fraction < 35%
Women who are known or suspected to be pregnant

32. 78 Year Old Male, BMS-Restenosis in LAD,
EF 75%, Two-Vessel Disease (LAD and RCA)
Before PCI
After pre-dilatation

33. 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

34. 62 Year Old Male, BMS-Restenosis in RCA,
EF 60%, Two-Vessel Disease (LAD and RCA)
Before PCI

35. 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