EffPac-Trial CoreLab Dr. Ulrich Beschorner, corelab Bad Krozingen GmbH, Germany Data Management and Safety Board (DMSB) Dr. Michael Werk, Martin Luthe

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1 Department of Radiology EffPac - Trial: Effectiveness of LUMINOR DCB versus POBA in the SFA: primary endpoint and 6 months results Teichgräber U, Aschenbach R, Scheinert D, Zeller T, Brechtel K, Thieme M, Blessing E, Treitl M, Lichtenberg M, von Flotow P, Vogel B, Werk M, Riambau V, Wienke A, Lehmann T, Sixt S NCT Teichgräber et al. Trials (2016) DOI /s x

2 EffPac-Trial CoreLab Dr. Ulrich Beschorner, corelab Bad Krozingen GmbH, Germany Data Management and Safety Board (DMSB) Dr. Michael Werk, Martin Luther Krankenhaus, Berlin, Germany Dr. Vicenc Riambau, Hospital Clinic de Barcelona, Spain Prof. Dr. Wienke, University Halle-Wittenberg, Germany Monitoring and SAE Reporting (VascuScience GmbH)!!!!!!!!!!!!Dr. Christin Ott and Lars Mahler, Leipzig, Germany Project Management Tabitha Heller, Nicole Brillinger, Cornelia Eichorn, Dr. Andrea Rößler, University Hospital Jena, Germany Producer of the Investigational Product Life Vascular Devices Biotech, S.L., Barcelona, Spain CIRSE Copenhagen 2017 U. Teichgräber et al. EffPAC Trial 6 months results 7

3 11 Participating Sites 01 Jena PD Dr. R. Aschenbach, University Hospital Jena 02 Leipzig Prof. Dr. Dierk Scheinert, University Hospital Leipzig 03 Bad Krozingen Prof. Dr. Thomas Zeller, Heart Center 04 Hamburg Dr. S. Sixt, Angiologikum 05 München PD Dr. M. Treitl, University Hospital 06 Berlin Prof. Dr. K. Brechtel, Ihre Radiologen 07 Sonneberg Dr. M. Thieme, Medinos Clinic 08 Karlsbad Prof. Dr. E. Blessing, SRH-Clinic 09 Heidelberg Dr. B. Vogel, University Heidelberg 10 Arnsberg Dr. M. Lichtenberg, Clinic Arnsberg 11 Krusel Dr. P. von Flotow, Westpfalz Clinic CIRSE Copenhagen 2017 U. Teichgräber et al. EffPAC Trial 6 months results 8

4 Flowchart CIRSE Copenhagen 2017 U. Teichgräber et al. EffPAC Trial 6 months results 9

5 Distribution 171/172 subjects enrolled Randomization 1:1 Recruitment completed on 31. Dec POBA N= 86 Luminor35 N= 85 LTFU N= 9 LTFU N= 9 6 month - FU N=77 6 month - FU N=76 Data Lock Point for 6 month-fup on CIRSE Copenhagen 2017 U. Teichgräber et al. EffPAC Trial 6 months results 11

6 Baseline Patient Characteristics LUMINOR POBA Age - yr!!"#$&'#()"(*!"#+&"#")"!* Male -"!#$&'!!$#$,)(+-"(*!.#",)!$-"!* Diabetes mellitus (!"!#$&'! /!#(,)/+-"(* 0$#',)/(-"!* Hypertension (!"!#$&'! "'#+,)'0-"(* "0#.,)'/-"!* Hyperlipidemia (!"!#$&'! '$#!,)!$-"(*!"#!,)(.-"!* CIRSE Copenhagen 2017 U. Teichgräber et al. EffPAC Trial 6 months results 12

7 Baseline Patient Characteristics LUMINOR POBA Rutherford Clinical Category! : + $,)$-"(* $,)$-"(* 194;<6=; : > +(#/,)+/-"(* >+#>,)+"-"(* Severe claudication / "+#>,)!.-"(* ''#!,)!!-"(* Ischemic rest pain 0 >#0,)>-"(* +#>,)+-"(* 12:9<8??7;39?? ( +#>,)+-"(* $,)$-"(* 16@9<8??7;39??! $,)$-"(* $,)$-"(* ABI (treated leg)! $#'/&$#>/)!.* $#'0&$#>/)!.* CIRSE Copenhagen 2017 U. Teichgräber et al. EffPAC Trial 6 months results 13

8 Baseline Angiographic Data LUMINOR POBA p value )*+,$!)*$-./!#01'! (#.&0#/)"0* (#!&/#.)"!* $#'/+ 2.34!50046+,$! >$#>,)+'-"0* >(#!,)>>-"!* $#0!" 7340,8039$! $#$.0 :9:;-A234 (0#>,)0(-"/* 00#>,)/"-"!* A94;<6=; 0>#>,)/(-"/* 00#>,)/"-"!*?;B;<; /#!,)/-"/* ++#!,)+$-"!* :,31*.*;!<.*$+,+!#"'! ""#$&.#")"(*.$#+&"#")"!* $#+.+ =*>*;*$0*!?*++*4!:,31*.*;!#11'! (#0&$#!)"(* (#0&$#')"!* $#/++ $ $,)$-"(* +#>,)+-"!* + >>#0,)+.-"(* >>#+,)+.-"!* > 0+#>,)/(-"(* /+#0,)>'-"!* / /!#(,)/+-"(* 0(#/,)/.-"!* CIRSE Copenhagen 2017 U. Teichgräber et al. EffPAC Trial 6 months results 14

9 Procedural Characteristics LUMINOR POBA p value?*++*4!c;*c3;39$d! A;*(E,43.39$!C*;>;1*E! +$$,)"0-"0*."#",)"(-"!* +#$$$ :,++*09$! /'#!,)/>-"(* 0$#',)/(-"!* $#'(( <.*$.!;3.*! +(#/,)+/-"(* +"#",)+!-"(* $#!" CIRSE Copenhagen 2017 U. Teichgräber et al. EffPAC Trial 6 months results 15

10 Efficacy: Late Lumen Loss - LLL * LLL = difference between the diameters (in mm) at 6 months follow-up minus postprocedure LUMINOR POBA Difference, 95 CI (LUMINOR vs. POBA) p value )))!FG!#11'H! $#+0CDEFG$#/"H$#!'I +#$!CDEF$#(0H+#(.I G$#.>CDEFG+#/!HG$#0.I J$#$$+ * Estimated LLL (MeanK.(,DE) from linear mixed model adjusted for center CIRSE Copenhagen 2017 U. Teichgräber et al. EffPAC Trial 6 months results 16

11 Efficacy: Late Lumen Loss - LLL <.6EI! LMNOPQRL;S;;=63#>$$" T655956=U5968:V W59W<=EL<263X26;=63#>$+! Y<5U24)W59=;5* KLLAM7!!NOPQ! )61,$;!#,?3+0643;'! RWOZQR[67?\65];=63#>$+' R6:V;<PD[ ^Q_WOLE`5U;2:;<=;=63#>$+0 ^7=9:2a)[6<4* [EY^NbTGEL<263`5U;2:;<=;=63#>$+( T6??;9G+"^7a)[29=<9:2]* cq1twdd;<];=63#>$$" T655956=UPD[ DYO`QeNQOL>$+' `;e7;:=t3;6?;)[#[<67:* :;6-(03.*E!J344$! F!1!)))!#11'! 7$.;4! F!1!)))!#11'! )))! :,B*;*$0*!#11'! $#0&+#> +#'&+#" G+#/ $#$(&$#'/ +#+(&$#". G+#+ O&PR!S7TD!(O&UVW!O&FQX! P&OF!S7TDO&YRW!P&YZX! (O&ZN! G$#+!&$#.. $#'!&+#0 G$#.> $#0!&+#+/ +#$.&+#$' G$#!/ $#(+&$#'> +#$0&+#$ G$#(/ $#(&+#+ +#$&+#+ G$#( $#/(CDEF$#+.H$#'.I $#'>CDEF$#!"H+#>>I G$#/' CIRSE Copenhagen 2017 U. Teichgräber et al. EffPAC Trial 6 months results 17

12 Efficacy: Improvement of Rutherford after 6M Improvement of Rutherford Stages LUMINOR POBA :*.*;,;39$!>!P!+.3-*! +#0,)+-'0* $,)$-">* [!,1C;\*1*$.! +/#(,)+$-'0* >(#$,)+"-">* T1C;\*1*$.!>!P!+.3-*! +>#>,).-'0* >$#",)+(-">* T1C;\*1*$.!>!N!+.3-*+! >"#0,)>+-'0* >!#0,)+.-">* T1C;\*1*$.!>!U!+.3-*+! 00#!,)//-'0* >'#",)>$-">* Significant higher improvement of LUMINOR compared to POBA (p=0.021) CIRSE Copenhagen 2017 U. Teichgräber et al. EffPAC Trial 6 months results 18

13 Efficacy: Target Lesion Revascularization (TLR) LUMINOR POBA Relative Risk, 95 CI (LUMINOR vs. POBA) Number needed to treat (NNT) p value 2)=!!FG!#"'!! +#/)+-'!* +'#+)+/-'!* $#$">CDEF$#$+>H$#(!$If ' J$#$$+ *Relative Risk Reduction (RRR) = 91.8, Cochran-Mantel-Haenszel estimate, adjusted for center CIRSE Copenhagen 2017 U. Teichgräber et al. EffPAC Trial 6 months results 19

14 Efficacy: Target Lesion Revascularization (TLR) <.6EI! KLLAM7!!NOPQ! )61,$;!#,?3+0643;'! :7]! F!1!2)=!#"'! P&U!#P^QF'! 7$.;4! F!1!2)=!#"'! PQ&P!#PU^QF'! LMNOPQRL;S;;=63#>$$" T655956=U5968:V W59W<=EL<263X26;=63#>$+! Y<5U24)W59=;5* cq1twdd;<];=63#>$$" T655956=UPD[ 0#>)>-0"* /'#$)>$-(0*!#+)!-..* /"#")/"-."*!#')/-0(* //#/)+0-0>* DYO`QeNQOL>$+' `;e7;:=t3;6?;)[#[<67:* "#.)'-'"* /$#')>/-'(* RWOZQR[67?\65];=63#>$+' R6:V;<PD[ (#!)0-'+* +>#$)0-/0* [EY^NbTGEL<263`5U;2:;<=;=63#>$+( T6??;9G+"^7a)[29=<9:2]* /#")+->!*f 0#>)+->0*f *Kaplan-Meier estimates, clinically driven TLR CIRSE Copenhagen 2017 U. Teichgräber et al. EffPAC Trial 6 months results 20

15 Efficacy: Target Lesion Revascularization (TLR) Censored Luminor 0.75 Freedom from TLR POBA Follow-up (Days) Treatment DEB POBA CIRSE Copenhagen 2017 U. Teichgräber et al. EffPAC Trial 6 months results 21

16 Efficacy: Patency LUMINOR POBA Relative Risk*, 95 CI (LUMINOR vs. POBA) Number needed to treat (NNT) p value A3.*$0I!#"'!!.0#')'>-'!* '(#$)('-'!* +#>!CDEF+#+$$H+#00/I! J$#$$+ * Interpretation: Relative chance for patency is increased by 26 in the LUMINOR group Primary patency: Freedom from restenosis (determined by duplex ultrasound PSVR <2.5) and freedom from TLR at 6 months CIRSE Copenhagen 2017 U. Teichgräber et al. EffPAC Trial 6 months results 22

17 Efficacy: Patency <.6EI! ^Q_WOLE`5U;2:;<=;=63#>$+0 ^7=9:2aPD[ :7]! F!1!A3.*$0I!#"'! '+#")>"-/.*ff 7$.;4! F!1!A3.*$0I!#"'! 0+#0)+'-0+*ff RWOZQRG`cW>$+' R6:V;<PD[ "'#$)!>-'+*!$#$)>$-/0* KLLAM7!!NOPQ! )61,$;!#,?3+0643;'! ZR&Q!#QN^QF'! QY&O!#YQ^QF'! cq1twdd;<];=63#>$$" T655956=UPD[./#()>.-/+*.0#+)/>-/0* * Interpretation: Increase of relative chance for patency DCB vs. POBA ** Patency based on freedom from target lesion revascularization and restenosis, restenosis by angiography (>50DS) at 6M CIRSE Copenhagen 2017 U. Teichgräber et al. EffPAC Trial 6 months results 23

18 Safety: Adverse Events LUMINOR POBA p value G,$;!M1C6.39$!#"'!! $)$-"(* +#>)+-"!* +#$$$ G3_;!M1C6.39$!#"'!! $)$-"(* $)$-"!* +#$$$ :*3./!#$.!;*43.*E`!"'!! $)$-"(* >#/)>-"!* $#0.' CIRSE Copenhagen 2017 U. Teichgräber et al. EffPAC Trial 6 months results 24

19 Conclusions The LUMINOR Paclitaxel-coated balloon catheter demonstrates to be clinical highly effective and safe in inhibiting restenosis compared to POBA The innovative coating technique matters and is shown not only in the patency, LLL and TLR data, but also in an improvement of the Rutherford stage The results of the study allow direct comparison to other already-completed RCTs applying Paclitaxel-coated DEB from different manufacturers in the same target vessel CIRSE Copenhagen 2017 U. Teichgräber et al. EffPAC Trial 6 months results 25