1. The Science of Gene Therapy for Hemophilia

2. This program will include a discussion of investigational agents not approved by the FDA for use in the US, and data that were presented in abstract form. The abstract data should be considered preliminary until published in a peer-reviewed journal.

3. What Is Gene Therapy?

4. Early Clinical Gene Therapy Trials: Late 1990s-2005

5. Delivery of AAV Into a Cell

6. First Successful Study Was in Hemophilia B

7. rAAV Challenges: Dose-Dependent Capsid Immune Response

8. Factor VIII and IX Breakthroughs: Improved Vector Design, Higher Doses

9. FIX Clinical Trials

10. AAV-FIX Padua Vector

11. Sustained FIX Activity Levels With SPK-9001

12. FVIII Clinical Trials

13. Vector Genome Schematic of Valoctocogene Roxaparvovec

14. Mean FVIII Activity Levels for Valoctocogene Roxaparvovec: 6e13 vg/kg Dose

15. Treated ABR and Mean FVIII Use Starting From 4 Weeks Postinfusion: Valoctocogene Roxaparvovec 6e13 vg/kg Dose

16. Characteristics of AAV Vectors Dictating Biological Behavior

17. Sequence Identity Matrix of Representative Primate AAVs

18. Mammalian AAV Evolution

19. Seroprevalence and AAV Tissue Tropism

20. Safety Concerns: Transient Liver Damage

21. AAV Safety

22. Clinical Care Questions for Patients and Healthcare Providers

23. Abbreviations