1. ReoPro ® in NSTEMI and STEMI Trials Harald Vangerow, MD Clinical Research Physician Eli Lilly UK

2. Company Confidential Copyright © 2006 Eli Lilly and Company Limited MY CONFLICTS OF INTEREST ARE : Lilly Employee

3. Company Confidential Copyright © 2006 Eli Lilly and Company Limited Agenda ReoPro ® in STEMI Recommendations of the ESC Overview of ReoPro ® in Primary PCI trials ReoPro ® in NSTEMI Recommendations of the ESC 1 year results of the ISAR-REACT II Trial

4. ReoPro ® for primary PCI in STEMI patients

5. Company Confidential Copyright © 2006 Eli Lilly and Company Limited What are the recommendations? Silber et al., EHJ (2005) 26, 804-847 ESC guidelines for PCI: Recommendation Grade IIa A for ReoPro ® in Primary PCI (…) abciximab, as adjunctive therapy to PCI reduces mortality, TVR and MACE at 6 months after STEMI. The long term benefits of abciximab administred (…) in patients with STEMI require more investigation.

6. Company Confidential Copyright © 2006 Eli Lilly and Company Limited ReoPro ® in Primary PCI Trials: 30-Day results for primary Endpoint Patients [%] 10 5 15 0 20 RAPPORT 1 CADILLAC 2 ISAR-2 3 ADMIRAL 4 ACE 5 30 days D/MI/UTVR 30 days D/MI/TVR/stroke 30 days D/MI/TVR 30 days D/MI/UTVR 30 days D/MI/TVR/stroke Placebo+PTCA (n=242) Abciximab+PTCA (n=241) PTCA or Stent (n=1030) Abciximab+PTCA or Stent (n=1052) Usual care+Stent (n=200) Abciximab+Stent (n=201) Placebo+Stent (n=151) Abciximab+Stent (n=149) Stent alone (n=200) Abciximab+Stent (n=200) 11.2 5.8 p=0.03p=0.01p=0.038p=0.01p=0.023 7.0 4.6 10.5 5.0 14.6 6.0 10.5 4.5 Adapted from: 1. Brener SJ, et al. Circulation 1998;98:734–741. 2. Tcheng JE, et al. Circulation 2003;108:1316–1323. 3. Neumann F-J, et al. J Am Coll Cardiol 2000;35:915–921. 4. Montalescot G, et al. N Engl J Med 2001;344:1895–1903. 5. Antoniucci D, et al. J Am Coll Cardiol 2003;42:1879–1885.

7. Company Confidential Copyright © 2006 Eli Lilly and Company Limited Trial Characteristics TrialYearnShock 2 [%] 30 day 1 † (control / abciximab) ISAR II20004017.74.5 / 2.0 ADMIRAL20013008.36.6 / 3.4 ACE20034009.34.0 / 3.5 RAPPORT1998483excl.2.1 / 2.5 CADILLAC20021036excl.2.35 / 1.9 1 Silber et al., EHJ (2005) 26, 804-847 2 Montalescot et al., EHJ (2007) 28, 443-449

8. Company Confidential Copyright © 2006 Eli Lilly and Company Limited Primary Endpoint Death/MI up to 3 years  37% RR  6.1% AR NNT=19 ReoPro ® in Primary PCI – European Meta-analysis on Individual Patient Data (n=1101) with Long-Term Follow-up of ACE, ADMIRAL, ISAR-2 Montalescot et al., EHJ (2007) 28, 443-449

9. Company Confidential Copyright © 2006 Eli Lilly and Company Limited Death of any cause after 3 years 15 0 10 5 14.3 [%] 10.8 p=0.052 Placebo Abciximab Montalescot et al., EHJ (2007) 28, 443-449 n=1101

10. Company Confidential Copyright © 2006 Eli Lilly and Company Limited Summary ReoPro ® is the only IIb/IIIa receptor antagonist that is licensed for the use in the cathlab 1. For STEMI patients undergoing Primary PCI the ESC recommends the use of ReoPro ® (level of evidence IIa A) 2. A recently published analysis of pooled data showed a significant reduction in Death and MI in patients undergoing PCI and receiving abciximab compared to placebo for up to 3 years 3. 1.SPC ReoPro 2.Silber et al., EHJ (2005) 26, 804-847 3.Montalescot et al., EHJ (2007) 28, 443-449

11. ReoPro ® for PCI in NSTEMI patients

12. Company Confidential Copyright © 2006 Eli Lilly and Company Limited ESC guidelines for NSTEMI: Recommendation Grade Ia A for ReoPro ® in High-Risk NSTEMI patients undergoing PCI. What are the recommendations? Bassand et al., EHJ(2007)Jul;28(13):1598-660

13. Company Confidential Copyright © 2006 Eli Lilly and Company Limited High-risk ACS patients randomized after pretreatment with 600 mg of clopidogrel (N=2022) Aspirin p.o. or i.v. according to local standards Heparin bolus of 70 U/kg Abciximab group (N=1012) Bolus of 0.25 mg/kg + Infusion 0.125  g/kg/min for 12 hrs Placebo group (N=1010) Additional heparin of 70 U/kg Placebo infusion for 12 hrs Clopidogrel 2x75 mg/day until discharge but maximum 3 days followed by 75 mg day for at least 6 months; Aspirin 200 mg/day indefinitely Treatment Schedule – Double-Blind ISAR-REACT 2 Adapted from Kastrati et al. JAMA 2006; 295: 1531-1538

14. Company Confidential Copyright © 2006 Eli Lilly and Company Limited P=0.03P=NSP<0.05 Primary Endpoint % of Patients Adapted from Kastrati et al. JAMA 2006; 295: 1531-1538 Efficacy Analysis: 30-Day Endpoints ISAR-REACT 2 P=NS -25%

15. Company Confidential Copyright © 2006 Eli Lilly and Company Limited ISAR-REACT 2 Safety Analysis P=NS P=0.008P=NS Adapted from Kastrati et al. JAMA 2006; 295: 1531-1538

16. Company Confidential Copyright © 2006 Eli Lilly and Company Limited 1 Year Follow-Up of the Primary Endpoint Survival free of MI and TVR Months after randomization Placebo % Patients Abciximab RR 0.80 [0.67-0.95] P=0.012 ISAR-REACT 2 Ndrepepa et al., EHJ (2007) Dec 23; [Epub ahead of print] doi:10.1093/eurheartj/ehm562

17. Company Confidential Copyright © 2006 Eli Lilly and Company Limited ISAR-REACT 2 Troponin Level and Benefit with Abciximab Kaplan-Meier analysis of the cumulative incidence of D/MI/Urgent TVR for both treatment groups in the subsets with and without elevated Troponin levels (>0.03 mcg/L) Adapted from Kastrati et al. JAMA 2006; 295: 1531-1538

18. Company Confidential Copyright © 2006 Eli Lilly and Company Limited Months after randomization 50 60 70 80 90 100 01 2 3456789101112 % Patients Survival free of MI and TVR Troponin Level and Benefit with Abciximab after 1 Year ISAR-REACT 2 Adapted from Seyfarth et al. Oral presentation ESC 2007 [http://www.escardio.org/NR/rdonlyres/B3A43A7C-D894-4390-BCC0-FDB5CE55A390/0/706011_Seyfarthctu1.pdfhttp://www.escardio.org/NR/rdonlyres/B3A43A7C-D894-4390-BCC0-FDB5CE55A390/0/706011_Seyfarthctu1.pdf (Accessed 02 Jan, 2008)]

19. Company Confidential Copyright © 2006 Eli Lilly and Company Limited Summary The significant benefit from ReoPro ® in NSTEMI patients undergoing PCI is maintained for at least one year. The benefit from ReoPro in NSTEMI patients is not only confined to those with higher troponin levels – there is a clinical benefit, even though nonsignificant, also for those with lower troponin levels.

20. Thank You !