1. Summary of InFUSE ™ Bone Graft Preclinical and Pilot Clinical Studies with Interbody Spinal Fusion Devices Scott Boden, M.D. Professor of Orthopaedic Surgery Director, The Emory Spine Center Emory University School of Medicine

3. rhBMP-2/ACS vs Autograft Model: Single level interbody fusion with titanium cage in sheep model Duration: Six months Study Groups: (n) Cage & autograft 8 Cage & rhBMP-2/ACS 6 Sandhu, Dawson et al., Spine, In Press 2002

4. rhBMP-2/ACS vs Autograft

5. Autograft Control rhBMP-2/ACS

6. Biomechanical Test Results rhBMP-2/ACS = Autograft

7. rhBMP-2/ACS vs Autograft Model: Single level interbody fusion with titanium cage in goat model Duration: Six months Study Groups: (n) Cage & autograft 21 Cage & rhBMP-2/ACS 21 Zdeblick et al., Spine, 1998

8. rhBMP-2/ACS vs Autograft

9. Biomechanical Test Results No statistical difference in stiffness between autograft and rhBMP-2 fusionsNo statistical difference in stiffness between autograft and rhBMP-2 fusions rhBMP-2/ACS = AutograftrhBMP-2/ACS = Autograft

10. Rabbit Posterolateral Fusion Model Autograft 42% fusion rhBMP-2/ACS 100% fusion Schimandle, Boden, et. al., Spine 1995

11. Strength of Bone Generated with rhBMP-2/ACS vs Autograft Relative to adjacent unfused level Schimandle, Boden, et. al., Spine 1995

12. rhBMP-2/ACS vs Autograft in Non-Human Primates Model: Rhesus monkey, single level interbody fusion Duration: Six months Study Groups: (n) Allograft bone dowel + autograft 3 Allograft bone dowel + rhBMP-2/ACS 3 Fishgrund, Herkowitz et al., Spine,1999 Fishgrund, Herkowitz et al., Spine,1999

13. Preclinical Study Results (3 months) Fishgrund, Herkowitz et al., Spine, 1999 rhBMP-2/ACS Control

14. Control(50%) Preclinical Study Results (6 Months) Preclinical Study Results (6 Months) rhBMP-2/ACS(100%) Fishgrund, Herkowitz et al., Spine,1999

15. rhBMP-2/ACS in Non-Human Primates Model: Rhesus monkey, single level interbody fusion interbody fusion Duration: Six months Study Groups: (n) Cage + buffer/ACS 2 Cage + 0.75mg/mL rhBMP-2/ACS 2 Cage + 1.50mg/mL rhBMP-2/ACS3 Boden, Sandhu et al., J. Spine Disorders, 1998

16. 6 Month Fusion Results (%) Control (0%) (0%) 0.75 mg/mL rhBMP-2/ACS (100%) (100%) 1.50 mg/mL rhBMP-2/ACS (100%) Boden, Sandhu et al., J. Spine Disorders, 1998

17. Collagen Sponge only (6 months) Collagen Sponge + rhBMP-2 (6 months) Boden, Sandhu, et al., J. Spinal Disorders 1998

18. Collagen Sponge + rhBMP-2 (6 months) Boden, Sandhu, et al., J. Spinal Disorders 1998

19. InFUSE™ Bone Graft/LT-CAGE™ Pilot Clinical Study Design 4 Investigators Study Groups: (n) LT-CAGE & InFUSE™ Bone Graft 11 LT-CAGE & Autograft 3 Boden, Zdeblick, Sandhu, and Heim, Spine, 2000

22. InFUSE™ Bone Graft/ LT-CAGE™ Device Human Pilot Study Results Fusion rate InFUSE™ Bone Graft 11/11 (100%) Autograft 2/3 (66%) Boden, Zdeblick, Sandhu, and Heim, Spine, 2000

23. InFUSE™ Bone Graft/LT-CAGE™ Device Pilot Study - Oswestry Results Boden, Zdeblick, Sandhu, and Heim, Spine, 2000

24. Serial CT Review-Autograft Patient RightCageLeftCageCoronalView

25. RightCageLeftCageCoronalView

26. Serial CT Review-InFUSE ™ Bone Graft Patient RightCageLeftCageCoronalView

27. RightCageLeftCageCoronalView

31. Goals of rhBMP-2/ACS Device Safety - no bone formation away from the cagesSafety - no bone formation away from the cages EffectivenessEffectiveness –eliminate bone grafting morbidity –equal or better healing success Goal of rhBMP-2/ACS is to make bone!Goal of rhBMP-2/ACS is to make bone!

32. Conclusions - rhBMP-2/ACS has success >95% in 4 preclinical studies, substantially better than control ( 95% in 4 preclinical studies, substantially better than control (<50%) Bone formed is normal and biomechanically equal to autograftBone formed is normal and biomechanically equal to autograft CT scan analysis correlates well with histology of rhBMP-2 bone formationCT scan analysis correlates well with histology of rhBMP-2 bone formation The concentration of rhBMP-2 successful in rhesus monkeys produced same 100% success in human pilot clinical trialThe concentration of rhBMP-2 successful in rhesus monkeys produced same 100% success in human pilot clinical trial