1. Late-Breaking Data on LDL-C Reduction

2. LDL Control in High-Risk Patients

3. Even in Clinical Studies Using High Intensity Therapy, Many Do Not Reach Goal

4. 2019 ESC Dyslipidemia Guidelines

5. Goals of 2019 ESC Dyslipidemia Guidelines

6. Targeting PCSK9

7. FOURIER Trial Design

8. FOURIER: LDL-C

9. FOURIER Outcomes

10. ODYSSEY OUTCOMES: Study Design

11. ODYSSEY OUTCOMES: Primary Efficacy Endpoint

12. Safety

13. Effect of the Combined Measure of Adherence x Intensity on LDL-C Reduction

14. Effect of the Combined Measure of Adherence x Intensity on Cardiovascular Risk

15. Estimate of the Benefit from Optimal Adherence and Intensity on Cardiovascular Events

16. Challenge is to Achieve Chronic Sustained LDL Reductions LDL-C Variability Common, Associated With Worse Outcomes

17. Therapeutic Approaches to Reducing LDL-C via the LDL Receptor: Small Molecules, Mabs, siRNA

18. Inclisiran Efficacy: One Dose Starting Regimen Robust, Sustained LDL-C Reductions – 300 mg Optimal

19. Efficacy: Two Dose Starting Regimen Robust, Sustained LDL-C Reductions – Optimal Start Regimen

20. Efficacy: Two Dose Starting Regimen Individual Patient Responses (%) at Day 180

21. ORION-11

22. ORION-11: Study Design Eighteen Months Treatment and Observation

23. ORION-11: Patient Disposition High Proportion of Patients Completed 18-Month Study

24. ORION-11: Patients Representative High Risk Cohort Balanced by Randomization

25. ORION-11: Efficacy Highly Significant Lowering of LDL-C Relative to Placebo

26. ORION-11: Efficacy Durable, Potent, and Consistent Effect Over 18 Months

27. ORION-11: Safety and Tolerability Adverse Event Profile Similar to Placebo

28. ORION-11: Safety and Tolerability Injection Site AEs Localized, Mostly Mild and Transient

29. ORION-11: Safety and Tolerability No Evidence of Liver, Kidney, Muscle, or Platelet Toxicity

30. ORION-11: Safety and Tolerability No Difference in Serious Adverse Events

31. ORION-11: Exploratory Endpoint Adverse Cardiovascular Events

32. ORION-4 Design

33. Abbreviations