1. Updates on Sickle Cell Disease

2. This program will include a discussion of data that were presented in abstract form. These data should be considered preliminary until published in a peer-reviewed journal.

3. Outline

4. US Sickle Cell Disease Population

5. SCD and Mortality in the United States

6. Distribution of SCD Population in the United States

7. Pathophysiology Overview

8. Pathogenesis of SCD

9. Old View of SCD

10. Adhesion in the SCD Microvasculature

11. Molecular Pathophysiology

12. Pain in Sickle Cell Disease

13. Pain in Sickle Cell Disease (cont)

14. Hospital Visits of Variable Frequency

15. The Iceberg Proportion of Days in Pain, Crisis, Utilization

16. SCD Is a Multi-System Disease

17. Clinical Manifestations of SCD

18. Barriers to Care

19. Negative Attitude and Stigma

20. Barriers to Care in Sickle Cell Disease

21. Hydroxyurea Mainstay of SCD Therapy

22. Blood Transfusion Management in SCD

23. L-glutamine Recently FDA-Approved for SCD

24. Targets for Improvement

25. Targets for Improvement

26. Targets for Improvement

27. Targets for Improvement

28. Targets for Improvement

29. Selectins Mediate WBC Adhesion, Rolling

30. Crizanlizumab Background

31. SUSTAIN Trial

32. SUSTAIN Trial Time to First SCPC Significantly Increased

33. Rivipansel

34. Nitric Oxide in SCD

35. Nitric Oxide in SCD (cont)

36. Voxelotor

37. Voxelotor HOPE Study Part A

38. Stem Cell Transplant

39. Sickle Cell Disease Is Potentially Amenable to Gene Therapy

40. Overview of Gene Therapy for SCD

41. Lentiglobin Gene Therapy Overview in Patients With SCD

42. What About Gene Editing

43. Abbreviations