1. Evolving Science of PAH Treatment

2. Program Goals

3. Paradigm Shift in PAH Treatment

4. Earlier PAH Clinical Trials

5. 6-Minute Walk Test

6. Meta-Analysis of 22 RCTs

7. Changes in PAH Trials Over Time

8. Spectrum of PAH Double-Blind RCTs to Date Study Durations and Sizes

9. PAH Clinical Trials Evaluating Morbidity and Mortality Endpoints

10. Clinical Efficacy/Safety SERAPHIN Trial[a,b]

11. Clinical Efficacy/Safety GRIPHON Trial

16. GRIPHON: Primary Composite Endpoint

23. SERAPHIN Placebo vs Macitentan 3 mg vs Macitentan 10 mg (1:1:1)

25. Treatment Algorithm for PAH

26. Rationale for Combination Therapy

28. Expert Consensus Recommendations for Combination Therapy Have Improved With Increasing Experience

29. An Evolving Paradigm From Sequential to Initial Up-Front Combination Therapy

30. Case Study 29-Year-Old Woman, Referred for Abnormal Echocardiogram May 2015

31. Case Study (cont)

32. Case Study (cont)

33. Treatment Goals

34. Case Study (cont) Plan

36. Case Study (cont)

37. Case Study Intensification of Therapy?

38. Conclusion

39. Abbreviations

40. Abbreviations (cont)

41. Abbreviations (cont)

42. Abbreviations (cont)