A 4-week, Randomized, Placebo-Controlled, Double-Blind, Efficacy and Safety Study of HS-25 in Adults With Primary Hypercholesterolemia

This is a 4-week, randomized, double-blind, placebo-controlled study designed to assess the
effects of the cholesterol absorption inhibitor HS-25 on LDL-C levels in adults who have
untreated LDL-C levels ranging from 130-189 mg/dL and fasting triglyceride levels < 350
mg/dL. Eligibility is restricted to 18-65 year old men or women who are using a highly
effective birth control method or are not of childbearing potential. Patients with
diabetes, a history of myocardial infarction or other clinical evidence of atherosclerotic
vascular disease are not eligible for participation in the study.

Inclusion Criteria:

- Men, or women using a highly effective birth control method or not of child-bearing
potential, who are 18 to 65 years of age at Visit 1 (screening visit).

- LDL-C 130 to 189 mg/dL (inclusive) on a cholesterol lowering diet but no lipid
modifying drug treatment for at least 6 weeks. A qualifying LDL-C value must be
obtained at the beginning and end of the placebo run-in (Visit 2 and Visit 3) and the
Visit 3 value must be within 15% of the value at Visit 2, higher or lower; the
average of both qualifying values must be in the range of 130 to 189 mg/dL
(inclusive) for inclusion in the study.

- TG ≤ 350 mg/dL on a cholesterol lowering diet but no lipid modifying drug treatment
for at least 6 weeks and TG levels must be ≤ 350 mg/dL at both Visit 2 and Visit 3

- Compliance of 80% to 120% with assigned study drug regimen during a 2 week placebo
run-in phase.

Exclusion Criteria:

- Women who are pregnant or breast feeding.

- History of stroke, myocardial infarction, unstable angina, heart failure or any
arterial revascularization procedure (eg, carotid, coronary, aorta, peripheral
arterial).

- History of diabetes or glycosylated hemoglobin (HbA1c) > 6.5.

- History of moderate to severe lactose intolerance (eg, unable to drink a glass of
milk).

- History of hospitalization for treatment of a major psychiatric disorder.

- History of drug or alcohol abuse as defined by the Diagnostic and Statistical Manual
(DSM-5) within the prior 12 months.

- History of regular alcohol consumption exceeding 7 drinks/week for females or 14
drinks/week for men (1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of
hard liquor) within 6 months prior to screening.

- Hospitalization for a duration > 24 hours for any reason within the prior 3 months
that, in the opinion of the investigator, may affect adherence to study procedures.

- History of a positive test for human immunodeficiency virus, hepatitis B or hepatitis
C.

- History of cancer with the exception of well-treated basal cell or squamous cell
carcinoma of skin, or in-situ cervical carcinoma.

- Presence of any condition which, in the opinion of the investigator, is likely to
compromise completion of this trial or not be in the best interest of the subject.

- History of intolerance to ezetimibe.

- Participation in a prior study of HS 25.

- Participation in a study of an investigational drug or device within the prior 3
months unless subject has documentation of placebo administration in a
placebo-controlled drug treatment trial only.

- Treatment with a fibric acid derivative (eg, fenofibrate, gemfibrozil), probucol,
warfarin, systemic corticosteroid, cyclosporine or other immunosuppressant agent
within the prior 12 weeks.

- Anticipated need or frequent use of acetaminophen (> 2 gm/day, that is required >
4x/week).

- Vitamins, herbal and dietary supplements must be discontinued at screening unless
subject has been on a long-term daily regimen and agrees to continue this regimen
during the study.

- Alanine aminotransferase (ALT) > 1.0 × upper limit of normal (ULN) at Visit 1, Visit
2 or Visit 3.

- Aspartate aminotransferase (AST) > 1.0 × ULN at Visit 1, Visit 2 or Visit 3.

- Unexplained (not due to exercise or strenuous activity) creatinine kinase increase >
2 × ULN at Visit 1, Visit 2 or Visit 3.

- Estimated glomerular filtration rate (Modification of Diet in Renal Disease) < 60
mL/min/1.73m2 at Visit 1, Visit 2 or Visit 3.

- Thyroid stimulating hormone outside of the normal range.

- Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for
treatment of either a psychiatric or physical disease (eg, infectious disease) must
not be enrolled.

- Any other laboratory abnormality considered by the investigator to be clinically
significant.

- Any subject with an electrocardiogram (ECG) having a QTc interval ≥ 450 msec, or any
other abnormality considered by the investigator to be clinically significant at the
end of placebo run-in (Visit 3) should not be enrolled.