1. Surfactant Replacement Therapy: Beyond RDS Steven M. Donn, MD, FAAP Professor of Pediatrics Chief, Neonatal-Perinatal Medicine C.S. Mott Children’s Hospital University of Michigan Health System

6. Surfactant and MAS

8. Alveolus Dilute Surfactant Dilute Surfactant Lavage

10. But…what about LAVAGE? Lavage: [French, from the Latin lavo, to wash]. The washing out of a hollow cavity or organ by copious injections and rejections of fluid. Portique de lavage

12. *Wiswell TE, et al. Pediatrics 2002;109:1081-1087. Instill Surfaxin ®

16. … but we can deal with it!

18. Carl Bose and Matthew Laughon University of North Carolina, Chapel Hill, NC Fernando R. Moya New Hanover Regional Medical Center, Wilmington, NC Judy L. Aschner Vanderbilt University Medical Center, Nashville, TN Steven M. Donn University of Michigan Health System, Ann Arbor, MI Robert Segal, Carlos Guardia, and Genzhou Liu Discovery Laboratories, Inc., Warrington, PA for the Surfaxin ® BPD Study Group Late Treatment with a Synthetic Surfactant for the Prevention of Bronchopulmonary Dysplasia * Lucinactant (Surfaxin®) is an investigational product not approved by the US FDA.

21. Risk for BPD Relative to Oxygen Therapy From Laughon et al. PAS abstract # 7935.9, 2007

25. Derivation of Patient Population

29. Patient Characteristics by Group Characteristic S-90 S-175 Placebo Number 47 45 44 GA (wks; median) 25 26 26 BW (g; mean) 734 773 753 Gender (% male) 64* 53 39 Race (% white) 64 80 70 FiO 2 at entry (median) 0.35 0.35 0.36 * p =0.016 vs. placebo

30. Supplemental Oxygen Requirement First Dose

31. Peri-dosing Events DOSE 1 S-90 S-175 Placebo Dose interruption (%) 13 20 0 Desaturation* (%) 60 51 9 Bradycardia** (%) 21 13 0 * Desaturation = SaO 2 < 75% for more than 30 seconds **Bradycardia = HR < 100 bpm for more than 30 seconds

32. Outcomes of Interest S-90 S-175 Placebo BPD (%) 49 47 50 (O 2 at 36 wks PMA) Death (%) 30 11 16 Death or BPD (%) 79 58 66

33. 4.9 4.3 1.7 1.8 0.8 0.5 0.3 0.3 1.9 1.5 0.7 0.7 0.1 1.0 10 S-90 vs. Placebo Unadjusted Adjusted* Odds Ratio Unadjusted Adjusted* S-175 vs. Placebo Odds Ratios for Death or BPD * adjusted for gestational age, birth weight, and gender

34. Number of Doses by Group S-90 S-175 Placebo 1 dose (%) 100 100 100 2 doses (%) 87 89 89 3 doses (%) 72 73 77 4 doses (%) 60 60 66 5 doses (%) 55 44 66

41. Got Surfactant!