Safety and Efficacy Trial of AAV Gene Therapy in Patients With CNGB3 Achromatopsia

This will be a non-randomized, open-label, Phase 1/2 study of the safety and efficacy of
rAAV2tYF-PR1.7-hCNGB3 administered to one eye by subretinal injection in individuals with
achromatopsia caused by mutations in the CNGB3 gene. The primary study endpoint will be
safety and the secondary study endpoint will be efficacy.

Subjects will be enrolled sequentially in four groups. Subjects in Groups 1, 2 and 3 will be
at least 18 years of age and will receive a lower, middle or higher dose of study agent.
Subjects in Group 4 will be at least 6 years of age and will receive the maximum tolerated
dose identified in Groups 1, 2 and 3.

Safety will be monitored by evaluation of ocular and non ocular adverse events and hematology
and clinical chemistry parameters. Efficacy parameters will include visual acuity, light
discomfort testing, color vision, static visual field, ERG, adaptive optics retinal imaging
and OCT.

Inclusion Criteria include:

1. Retinal disease consistent with a diagnosis of achromatopsia and documented mutations
in both alleles of the CNGB3 gene;

2. At least 18 years of age for Groups 1, 2 and 3 and at least 6 years of age for Group
4;

3. Able to perform tests of visual and retinal function;

4. Visual acuity in the study eye not better than 55 ETDRS letters (Snellen equivalent
20/80) based on the average of two examinations at the baseline visit;

5. Acceptable laboratory parameters;

6. For females of childbearing potential: A negative pregnancy test within 2 days before
administration of study agent.

Exclusion Criteria include:

1. Refractive error of ≥ -8.00 diopters (spherical equivalent) of myopia in the study
eye;

2. Evidence of degenerative myopia regardless of the refractive error in the study eye;

3. Pre-existing eye conditions that would contribute to vision loss in either eye or
increase the risk of subretinal injection in the study eye.