Randomized Study to Evaluate the Effect of Obicetrapib on Top of Maximum Tolerated Lipid-Modifying Therapies

Inclusion Criteria:

• Females may be enrolled if all 3 of the following criteria are met:

• They are not pregnant;

• They are not breastfeeding; and

• They do not plan on becoming pregnant during the study;

• Have underlying heterozygous familial hypercholesterolemia (HeFH) and/or a historyof established ASCVD

• Are on maximally tolerated lipid-modifying therapy as an adjunct to a lipid-loweringdiet and other lifestyle modifications, defined as follows:

• A statin at a maximally tolerated stable dose for at least 8 weeks prior toScreening

• Atorvastatin 40 and 80 mg; and

• Rosuvastatin 20 and 40 mg;

• Ezetimibe with or without maximally tolerated statin for at least 8 weeks prior toScreening

• Bempedoic acid with a maximally tolerated statin for at least 8 weeks prior toScreening

• A PCSK-9 targeted therapy alone or in combination with other lipid-modifying therapyfor at least 4 stable doses prior to Screening

• Have a fasting serum LDL-C at Screening as follows:

• Fasting serum LDL-C ≥ 55 to < 100 mg/dL (≥1.4 to <2.6 mmol/L) OR non-HDL-C ≥85 mg/dL (≥2.2 mmol/L) to < 130 mg/dL (<3.4 mmol/L) with at least 1 of the following riskenhancers at Screening;

• Recent MI (> 3 and < 12 months prior to Randomization);

• Type 2 diabetes mellitus;

• Current daily cigarette smoking;

• Age of > 60 years;

• High sensitivity C-reactive protein (hsCRP) ≥2.0 mg/L (≥19.0 nmol/L) at Screening orwithin 6 months prior to Screening

• Fasting triglycerides (TG) > 150 mg/dL (>1.7 mmol/L);

• Fasting lipoprotein (a) > 30 mg/dL (>70 nmol/L); and/or

• Fasting HDL-C < 40 mg/dL (<1.0 mmol/L); OR

• Fasting serum LDL-C ≥ 100 mg/dL (≥2.6 mmol/L) or non-HDL-C ≥130 mg/dL (≥3.4 mmol/L)

• Fasting triglyceride (TG) < 500 mg/dL (<5.7 mmol/L) at Screening; and

• Have an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73m2 at Screening

Exclusion Criteria:

• New York Heart Association class III or IV heart failure or left ventricularejection fraction < 30%;

• Hospitalized for heart failure within 5 years prior to Screening

• Major adverse cardiac event (MACE) within 3 months prior to Screening;

• Uncontrolled severe hypertension, defined as either systolic blood pressure ≥ 160mmHg or diastolic blood pressure ≥100 mmHg prior to Randomization;

• Formal diagnosis of homozygous familial hypercholesterolemia (HoFH);

• Active liver disease;

• HbA1c ≥10% or a fasting glucose ≥270 mg/dL (≥15.0 mmol/L) at Screening;

• Thyroid-stimulating hormone >1.5 X upper limit of normal (ULN) at Screening;

• Creatine kinase > 3 X upper limit of normal (ULN) at Screening;

• History of malignancy that required surgery (excluding local and wide localexcision), radiation therapy, and/or systemic therapy during the 3 years prior toRandomization;

• Known history of alcohol and/or drug abuse within 5 years prior to Randomization

• Received treatment with other investigational products or devices within 30 days ofScreening or 5 half-lives of the previous investigational product, whichever islonger;

• Are taking gemfibrozil or have taken gemfibrozil within 30 days of Screening

• Planned use of other investigational products or devices during the course of thestudy;

• Participated in any clinical trial evaluating obicetrapib; or

• Known allergy or hypersensitivity to obicetrapib, placebo, or any of the excipientsin obicetrapib or placebo

• Any condition that, according to the Investigator, could interfere with the conductof the study