Screening Protocol for a Gene Therapy Trial in Subjects With Homozygous Familial Hypercholesterolemia

Homozygous Familial Hypercholesterolemia (HoFH) is a rare genetic metabolic disorder
characterized by markedly elevated LDL-cholesterol (LDL-C) levels, resulting in severe
atherosclerosis often leading to early onset of cardiovascular disease. The most frequent
cause is mutation in the LDL receptor gene (LDLR). LDL-C levels remain frequently above
acceptable levels despite treatment with multiple existing lipid lowering drugs and/or LDL
apheresis. Thus, the functional replacement of the defective LDLR via AAV-based
liver-directed gene therapy may be a viable approach to treat this disease and improve
response to current lipid-lowering treatments. The purpose of this protocol is to identify
and screen potential candidates for future enrollment in a gene therapy clinical trial. No
study drug will be administered in this screening study.

Inclusion Criteria:

- Males and females ≥ 18 years of age

- Clinical presentation consistent with homozygous FH

- Subjects must be able to comprehend and willing to provide a signed IRB approved
Informed Consent Form

Exclusion Criteria:

- Known to carry confirmed mutations in genes affecting LDL receptor functionality other
than the LDLR gene

- History of cirrhosis based on documented histological evaluation or non-invasive
imaging

- Documented diagnosis of any of the following liver diseases: Hepatitis B or C;
Biopsy-proven nonalcoholic steatohepatitis; Biopsy-proven alcoholic liver disease;
Autoimmune hepatitis; Primary biliary cirrhosis; Primary sclerosing cholangitis;
Wilson's disease; Hemochromatosis; alpha1 anti-trypsin deficiency

- History of immunodeficiency diseases, including a positive HIV test result

- Previous organ transplantation

- Serious or unstable medical or psychological conditions that, in the opinion of the
investigator, would compromise the subject's safety or successful participation in the
study

- Inability to participate