The Invatec Program Features and Clinical Trials Bruno Scheller, MD Klinische und Experimentelle Interventionelle Kardiologie, Universität des Saarlandes, Campus Homburg Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes Homburg / Saar, Germany

Bruno Scheller, MD, PhD DISCLOSURES Honoraria B. Braun Vascular Systems, Invatec SRL Grants/Contracted Research B. Braun Vascular Systems Ownership Interest (Stocks, Stock Options or Other Ownership Interest) InnoRa GmbH I intend to reference unlabeled/ unapproved uses of drugs or devices in my presentation. I intend to reference Drug Eluting Ballon, CE-approved but not FDA-approved.

Conflict of Interest Affiliation/Financial Relationship Company Grant/Research Support B.Braun Vascular Systems, Berlin, Germany Speaker Honoraria B.Braun Vascular Systems, Berlin, Germany Invatec Technology Center GmbH, Frauenfeld, Switzerland Ownership, Shareholder InnoRa GmbH, Berlin, Germany

Drug Coated Balloon Drug Eluting Stent Drug Coated Balloon Slow release Persistent exposure ~ 100 - 200 µg dose Polymer Stent mandatory Drug Coated Balloon Immediate release Short-lasting exposure ~ 300 - 600 µg dose No polymers Premounted stent optional Scheller, Circulation 2004; 110: 810-4 Scheller, Heart 2007, 93: 539-41

DEB + stent - porcine coronary model EEE Paclitaxel Ac Paclitaxel Iopromide Circulation 2004; 110: 810-4

Scheller, New Engl J Med 2006, 355: 2113-24 PaccocathTM Scheller, New Engl J Med 2006, 355: 2113-24 Tepe, N Engl J Med 2008; 358: 689-99

Waksman, Circ Cardiovasc Intervent. 2009; 2: 352-8

The Design Requirements for a Successful Drug Coated Balloon Combination of Drug and Additive Coating method (homogeneity, reproducibility) Drug transfer to the tissue Biological efficacy, dose dependency Balloon inflation time, safety in overdosing Clinical efficacy (reproducibility in RCT‘s and different indications) So far, the only technology fulfilling all these requirements: PACCOCATH®

Invatec DCB Program Four DCB platforms Coronary Peripheral In.Pact Falcon, PTCA, 0.014“ Peripheral In.Pact Pacific, PTA SFA, 0.018“ In.Pact Admiral, PTA SFA, 0.035“ In.Pact Amphirion, PTA BTK, 0.014“

Invatec FreePacTM DCB Technology proprietary hydrophilic coating formulation paclitaxel (3 μg/mm2 balloon surface) urea hydrophilic additive natural degradation product of protein synthesized in the liver one of the most common substances in human serum (100- 500 mg/liter) low toxicity, no hypersensitivity reactions undisclosed solvents

FreePac Pharmacokinetics Paclitaxel in coronary artery segments at various time points B. Kelsch, submitted for publication

FreePac – Porcine Coronary Stent Model Neointimal area 28 days Control (no drug) FreePac™ coating (3 μg paclitaxel/mm2) Ac= Paccocath™ coating B. Kelsch, submitted for publication

No aneurisms, even in the high dose groups! Drug Coated Balloon - Dose Finding Histomorphometry – Porcine Coronary Stent Model No aneurisms, even in the high dose groups! B. Kelsch, submitted for publication

Clinical Plan 2010 Study PI Indication type 1° Endpoint Status IN.PACT CORO I F.Burzotta C.Trani de-novo PILOT 3 arm RCT DCB pre- vs post-dilat vs BMS (30 pts) 6m neo-intimal area by OCT Enrolment ongoing BELLO A.Colombo A.Abizaid small vessels RCT multicenter EU DCB vs Taxus (182 pts) 6m LLL Enrol start Q1 2010 IN.PACT CORO ISR B.Scheller ISR Single arm single center (23 pts) Enrolment completed IN.PACT DEEP I.Baumgarner T.Zeller D.Scheinert BTK (CLI) RCT multicenter EU DCB vs PTA (357 pts) 12m LLL 12m TLR IN.PACT BTK Registry Leipzig (CLI, Claudic.) DCB vs PTA (100 pts) 6m Rest. Rate FAIR H.Krankenberg SFA (ISR) RCT multicenter EU DCB vs PTA (118 pts) IN.PACT SFA I G.Tepe (de-novo) RCT multicenter EU DCB vs PTA (120 pts) 6m MAE 12m Prim. Patency Enrol start Q3 2010 IN.PACT SHUNT P.Pattynama Hemodialysis Shunts RCT multicenter EU DCB vs PTA (136 pts)

In.Pact Falcon – treatment of ISR ISR CX In.Pact Falcon 3.0 20 mm Final result 6 months

IN.PACT BTK Registry Leipzig preliminary results (LINC 2010) Prospective registry of patients with BTK-lesions In.Pact Amphirion paclitaxel-coated balloon Angiography after 3 months Clinical FU 3, 6 and 12 months 102 pts. treated with In.Pact Amphirion 3 months FU available in 64 pts. 2 pts. died 1 cardiac death, 1 major amputation 15 pts. did not come to the 3-months FU Schmidt A, LINC 2010

IN.PACT BTK Registry Leipzig preliminary results (LINC 2010) Angiographic FU in 48 pts. Diabetes mellitus 41 / 48 (85 %) Lesions treated with In.Pact Amphirion De-novo 28 (58 %) Restenosis 15 (31 %) In-stent restenosis 5 (11 %) Mean lesion-length 170 ± 76 mm Total occlusion 28 (58 %) Schmidt A, LINC 2010

IN.PACT BTK Registry Leipzig preliminary results (LINC 2010) Rutherford categories before and at 3 mo FU Schmidt A, LINC 2010

IN.PACT BTK Registry Leipzig preliminary results (LINC 2010) In.Pact Amphirion paclitaxel-coated balloon 3 months angio Restenosis 15 / 48 (31 %) focal restenosis 8 / 15 (53 %) whole treated segment 7 / 15 (47 %) Comparison with 3-months angio after POBA of long BTK-lesions 58 CLI-pts. / 62 limbs mean length 183 mm Restenosis after 3 months: 68.8 % Schmidt A, LINC 2010

IN.PACT BTK Registry Leipzig preliminary results (LINC 2010) Schmidt A, LINC 2010

The Invatec Drug Coated Balloon Program DCB based on the PaccocathTM technology fulfill all requirements for a successful DCB (including positive RCT‘s) Preclinical data show a similar biological response after experimental injury in the porcine model with the FreePacTM and PaccocathTM coating Promising first clinical experience with the FreePacTM coating (coronary ISR and BTK) RCT‘s are underway