Late-Breaking Data on LDL-C Reduction

LDL Control in High-Risk Patients

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

2019 ESC Dyslipidemia Guidelines

Goals of 2019 ESC Dyslipidemia Guidelines

Targeting PCSK9

FOURIER Trial Design

FOURIER: LDL-C

FOURIER Outcomes

ODYSSEY OUTCOMES: Study Design

ODYSSEY OUTCOMES: Primary Efficacy Endpoint

Safety

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

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

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

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

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

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

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

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

ORION-11

ORION-11: Study Design Eighteen Months Treatment and Observation

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

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

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

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

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

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

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

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

ORION-11: Exploratory Endpoint Adverse Cardiovascular Events

ORION-4 Design

Abbreviations