Study of Evinacumab (REGN1500) in Participants With Persistent Hypercholesterolemia

The inclusion/ exclusion criteria below, include, but are not limited to, the following:

Key Inclusion Criteria:

1. Men and women, ages 18 through 75 at the screening visit

2. Diagnosis of primary hypercholesterolemia, either HeFH or non-HeFH with clinical ASCVD

3. A history of clinical ASCVD, for those patients who are non-HeFH.

4. Receiving a stable maximally tolerated statin (± ezetimibe) for at least 4 weeks at
screening

5. Receiving alirocumab 150 mg SC Q2W, OR evolocumab 140 mg SC Q2W or 420 mg SC Q4W for
at least 8 weeks prior to the screening visit

6. Serum LDL-C ≥ 100 mg/dL at screening (1 repeat lab is allowed)

7. Provide signed informed consent

Key Exclusion Criteria:

1. Known history of homozygous FH (clinically, or by previous genotyping)

2. Presence of any clinically significant uncontrolled endocrine disease known to
influence serum lipids or lipoproteins

3. Newly diagnosed diabetes (within 3 months prior to screening)

4. Use of thyroid medications (except for replacement therapy which has been stable for
at least 12 weeks before screening)

5. Laboratory findings during screening period (not including randomization labs):

1. Triglycerides > 400 mg/dL (> 4.52 mmol/L) for patients without a known history of
diabetes mellitus; OR Triglycerides > 300 mg/dL (> 3.39 mmol/L) for patients with
a known history of diabetes mellitus

2. Positive test for Hepatitis B surface antigen and/or Hepatitis C antibody
(associated with a positive HCV ribonucleic acid [RNA] polymerase chain reaction)

3. Positive serum beta-human chorionic gonadotropin or urine pregnancy test in women
of childbearing potential

4. Estimated glomerular filtration rate < 30 mL/min/1.73 m^2

5. TSH > 1.5 x ULN

6. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 x ULN

6. Systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg at screening
visit or time of randomization

7. History of heart failure (New York Heart Association [NYHA] Class II-IV) within 12
months before screening

8. History of MI, unstable angina leading to hospitalization, CABG surgery, PCI,
uncontrolled cardiac arrhythmia, carotid surgery or stenting, stroke, TIA, carotid
revascularization, endovascular procedure or surgical intervention for peripheral
vascular disease within 3 months prior screening

9. History of cancer within the past 5 years (except for adequately treated basal cell
skin cancer, squamous cell skin cancer, or in situ cervical cancer)

10. Having received LDL apheresis within 2 months before screening

11. Pregnant or breast-feeding women

12. Women of childbearing potential who are unwilling to practice a highly effective birth
control method

13. Sexually active men unwilling to use acceptable birth control.