Nanoparticle Based Stents - FOCUS np (Envision Scientific) Program Update. Dr Ashok Seth Escorts Heart Institute & Research Center, New Delhi INDIA

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1 Nanoparticle Based Stents - FOCUS np (nvision Scientific) Program Update Dr Ashok Seth scorts Heart Institute & Research Center, New Delhi INDIA

2 Disclosure Statement of Financial Interest I, Ashok Seth, DO NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation.

3 Nanocarrier Based Drug luting Stent - FOCUS np DS Nanotechnology at the fore front in Cardiology devices like Stents and Balloons Has unique application to address / eliminate various known issues with current treatment Issues like: Delayed Healing / Thrombosis / Restenosis / DAPT Therapy duration NANO CARRIRS

4 Nanocarrier Based Drug luting Stent - FOCUS np DS ARAS OF SOM CONCRN WITH DS 1. HALING - DLAYD Healing delayed with poor ndothelialization Inflammatory response in Coronary Arteries 2. ACUT / SUB-ACUT / LAT THROMBOSIS Occurrence of Acute / Sub-Acute or Late Thrombosis in Coronary Arteries 3. RSTNOSIS Restenosis is not completely eliminated still an area for some improvement Usually FOCAL or DG ( drug deficiency or blank spots??) 4. DUAL ANTIPLATLT THRAPY DURATION DAPT is an area of concern with current drug eluting stents. Complications related to Bleeding event and other surgical procedures are seen

5 Nanocarrier Based Drug luting Stent - FOCUS np DS ADVANTAGS with Nano carrier based technology Increased Drug concentration & presence Increased Bio-availability at target site More Permeability in the sub-mucosal layers Substantial increase in Intra cellular uptake nhancing properties & altering Pharmacokinetics of drugs with encapsulation Prolonged residence time of drugs at site Improves Stability because of encapsulation

6 Nanocarrier Based Drug luting Stent - FOCUS np DS DSIGN DTAILS OF NANOCARRIR LUTING STNT (Polymer free drug delivery) Pre Crimped stent coating (Abluminal Surface) Active Coating on Balloon & Stent nhance NP Delivery to tissue by increasing Drug delivery area Protect drug by encapsulation during transit and release at target area Target based drug delivery

7 Nanocarrier Based Drug luting Stent - FOCUS np DS DSIGN DTAILS S S S S S ncapsulated Structure xcipient based drug delivery (Polymer Free) ncapsulated drug nano particle created Drug carrier properties enhance Drug Delivery Sirolimus encapsulated in xcipient 1 and xcipient 2

8 Nanocarrier Based Drug luting Stent - FOCUS np DS DSIGN DTAILS S S S S S xcipient 1 Lipid Bilayer based component Hydrophilic head with two lipophilic tails ncapsulated Structure

9 Nanocarrier Based Drug luting Stent - FOCUS np DS DSIGN DTAILS S S S S S ncapsulated Structure xcipient 2 Ca/P based component nhances haemocompatibility Readily absorbed by vasculature Drug released on ph change

10 Pre Clinical Work XTNSIV PR CLINICAL WORK DON PRINCIPAL INVSTIGATOR Prof. Wim Van der Giessen MD PhD & Heleen van Beusekom, PhD rasmus MC, Thoraxcenter xperimental Cardiology Study I (n=12 Porcine): Pre Clinical evaluation of a stent releasing Sirolimus from a non-polymeric nanocarrier 5, 28 & 90 days FU Study II (n = 36 Procine + 16 Rabbit) Pre Clinical evaluation of a stent releasing Sirolimus from a non-polymeric nanocarrier 5, 28 & 90 days FU

11 Pre Clinical Work XTNSIV PR CLINICAL WORK DON Injury score 1/4 390±104 μm nvision stent MLD LLL = 0.45 vs 0.47, NS Day 28 Day 90 Pre SS Post SS Follow-up SS LLL SS Pre BIO Post BIO Follow-up BIO LLL BIO

12 Pre Clinical Work OCT valuation Study Dr Pedro Lemos OCT Study to evaluate FOCUS np 28 days in porcine model (Randomization of FOCUS np with BMS, BMS+DCB and Biolimus DS) BMS (n=7) BMS + DB (n=6) DS (n=8) Biomatrix (n=6) NIH thickness, mm 0.19 (0,11 0,29) 0.16 (0,13 0,46) 0.09* ( ) 0.15 ( ) Lumen area, mm² 5.73 (5,25 7,02) 6.18 (3,72 7,17) 7.30 ( ) 5.79 ( ) Stent area, mm² 8.34 (6,97 8,73) 7.85 (7,35 8,64) 8.29 ( ) 7.68 ( ) NIH area, mm² 1.85 (1,18 3,60) 2.05 (1,31 3,92) 0.99 ( ) 1.43 ( ) Perc NIH, % 24.1 (14,1 40,1) 24.3 (13,4 52,1) 11.8 ( ) 20.1 ( ) Numbers are median (interquartile range) or percentage *p=0.048 versus BMS p=0.06 versus BMS p=0.08 versus BMS

13 Pre Clinical Work OCT valuation Study Dr Pedro Lemos

14 NANOACTIV FIM-IN Study Study Design DSIGN: Prospective, Nonrandomized, Multi Center Indian clinical trial ( 6 Centers) NANOACTIV FIM-IN STUDY N = 100 Subjects to be enrolled in Cohort A (N = 55) & Cohort B (N = 45) OBJCTIV: Study to assess performance and safety of FOCUSnp Sirolimus based nano carrier eluting coronary stent system PI : Dr Ashok Seth - Fortis scorts, New Delhi Co-PI : Dr Sameer Dani Life Care Hospital, Ahmedabad CRO & Core Lab Cardialysis B.V. Rotterdam The Netherlands COHORT A nrollment completed (N=55) Clinical follow-up at 6 months in % (3) Angiography followup at 6 months in 82% (10) COHORT B nrollment Ongoing ( N= 15) OCT valuation at 6 months will be done Grube. et al, Am Journal Cardiol 2006; in press

15 NANOACTIV FIM-IN Study Cohort A has completed enrollment and data is sent to CRO for evaluation Clinical Follow up done in 96.55% subjects Angiographic Follow up done in 82% subjects Cohort B is currently ongoing nrollment status : 15 subjects enrolled OCT evaluation will be performed to evaluate

16 NANOACTIV FIM-IN Study nrolled Follow Up Check Angio OCT COHORT A n = 55 Subjects COHORT B n = 45 Subjects

17 NANOACTIV FIM-IN Study * NS Unpublished data

18 NANOACTIV FIM-IN Study ( Treatment & 6 months FU) - 01

19 NANOACTIV FIM-IN Study ( Treatment & 6 months FU) - 02

20 NANOACTIV FIM-IN Study ( Treatment & 6 months FU) - 03

21 NANOACTIV FIM-IN Study ( COHOT B OCT Images)

22 Conclusion Results are expected to be published at URO PCR 2013 FOCUS np - Sirolimus based nano carrier eluting stent system is a novel polymer free approach which has all the characteristics to change the future course of treatment Results from study will help in understanding it better, can help in reducing DAPT durations Further Clinical studies planned to evaluate performance in various clinical settings