Phase 1 Follow-on Study of AAV2-hRPE65v2 Vector in Subjects With Leber Congenital Amaurosis (LCA) 2

The study is a follow-on to a Phase 1 dose-escalation and safety study (closed to enrollment
as of June 2009). Up to twelve adults and children with a molecular diagnosis of biallelic
RPE65 mutations, who have participated in the earlier Phase 1 study, and who meet all study
eligibility criteria, will receive AAV2-hRPE65v2 vector in the previously uninjected,
contralateral eye to evaluate the safety of bilateral, sequential subretinal administration
of AAV2-hRPE65v2.

Inclusion Criteria:

- Prior participation in Phase 1 study with unilateral, subretinal administration of
AAV2-hRPE65v2.

- Visual acuity equal to or greater than light perception.

- Sufficient viable retinal cells in contralateral, previously uninjected eye, as
determined by non-invasive means, such as optical coherence tomography (OCT) and/or
ophthalmoscopy. Must have either: 1) an area of retina within the posterior pole of >
100 µm shown on OCT; 2) ≥ 3 disc areas of retina without atrophy or pigmentary
degeneration within the posterior pole; or 3) remaining visual field within 50 degrees
of fixation.

- Willingness to adhere to protocol and long-term follow-up as evidenced by written
informed consent or parental permission and subject assent (where applicable).

Exclusion Criteria:

- Unable or unwilling to meet requirements of the study.

- Participation in any other study of an investigational drug within the past six
months.

- Use of retinoid compounds or precursors that could potentially interact with the
biochemical activity of the RPE65 enzyme; individuals who discontinue use of these
compounds for 18 months may become eligible.

- Prior intraocular surgery within six months.

- Known sensitivity to medications planned for use in the peri-operative period.

- Pre-existing eye conditions, such as glaucoma, or complicating systemic diseases that
would preclude the planned surgery or could interfere with the interpretation of
study. Complicating systemic diseases would include those in which the disease itself,
or the treatment for the disease, can alter ocular function. Examples are malignancies
whose treatment could affect central nervous system function (for example: radiation
treatment of the orbit; leukemia with CNS/optic nerve involvement). Subjects with
diabetes or sickle cell disease would be excluded if they had any manifestation of
advanced retinopathy (e.g. macular edema or proliferative changes). Also excluded
would be subjects with immunodeficiency (acquired or congenital) as there could be
susceptibility to opportunistic infection (such as CMV retinitis).

- Individuals of childbearing potential who are pregnant or unwilling to use effective
contraception for four months following vector administration.

- Any other condition that would not allow the potential subject to complete follow-up
examinations during the course of the study and, in the opinion of the investigator,
makes the potential subject unsuitable for the study.

- Subjects will NOT be excluded based on their gender, race, or ethnicity.