A Phase 2/3 Trial to Assess the Efficacy and Safety of OCU410ST for Stargardt Disease

Name of Investigational Product: OCU410ST Name of Active Ingredient: Adeno-associated viral vector 5 human RORA (AAV5-hRORA)

Title of Study: A PHASE 1 STUDY TO ASSESS THE SAFETY AND EFFICACY OF OCU410ST FOR STARGARDT DISEASE AND PHASE 2/3 PIVOTAL CONFIRMATORY CLINICAL TRIAL TO ASSESS THE SAFETY AND EFFICACY OF OCU410ST FOR STARGARDT DISEASE

Study Center(s): Approximately fifteen study centers in the US.

Background: Stargardt disease is an eye disease that causes vision loss in children and young adults. It is an inherited disease caused by faulty genes that cause buildup of fat deposits in the eye. Currently, there is no approved treatment available for Stargardt disease.

OCU410ST Product Information:

OCU410ST is an Adeno-Associated Virus serotype 5 containing human RORA for the treatment of Stargardt disease. Dysregulation in lipid metabolism, oxidative stress, and anti-inflammatory mechanisms are critical for pathogenesis and progression of Stargardt disease. The role of hRORA in regulating these gene pathways strongly suggests OCU410ST could restore homeostasis in the eye and thereby serve as a therapeutic candidate for Stargardt disease.

Phase 2/3 Pivotal Confirmatory Clinical Trial is a randomized, outcome assessor-masked, multicenter study.

A total of fifty-one (51) subjects will be enrolled in a 2:1 ratio to either the treatment group (n=34 subjects) or to an untreated control group (n=17 subjects).

Treatment group: 34 subjects. Subjects will receive a single subretinal injection of 200 µL OCU410ST in concentration of 1.5×10E11 vg/mL.

Control group: 17 subjects. Subjects who are enrolled in the untreated control group of the study will not receive any treatment. They will be followed according to the same treatment schedule as the treated subjects.

Note: Data will be collected for the untreated eye at Screening, 4-month, 8-month, 12-month, four (4) long-term safety follow-up visits, and early termination visit (if applicable).

Data will be collected for the treated eye at Screening, treatment Day 1, Day 2, Day 15, 4-month, 8-month, 12-month, four (4) long-term safety follow-up visits, and early termination visit (if applicable).

Enrollment in the Phase 1 study is complete. Phase 1 enrolled a total of nine subjects in low, medium and high dose cohorts.

Low Dose Cohort (3.75×10E10 vg/mL):

Three (3) Subjects received a single subretinal injection of 200 µL OCU410ST in low dose concentration (3.75×10E10 vg/mL).

Medium Dose Cohort (7.5×10E10 vg/mL):

Three (3) Subjects received a single subretinal injection of 200 µL OCU410ST in medium dose concentration (7.5×10E10 vg/mL).

High Dose Cohort (2.25×10E11 vg/mL):

Three (3) Subjects received a single subretinal injection of 200 µL OCU410ST in high dose concentration (2.25×10E11 vg/mL).

Phase 2/3 Inclusion Criteria (applicable for both adult and pediatric subjects):

• Males or females aged ≥5 years at the time of consent.
• Subjects who have confirmed clinical and CLIA certified or equivalent genetic diagnosis of Stargardt disease (including ABCA4 related retinopathies).
• Adult subjects who have BCVA of 75 letters or less in the study eye (20/32 Snellen equivalent) and Pediatric subjects who have a BCVA of 35 letters or better in the study eye (20/200 Snellen equivalent).
• The study eye should have at least one well-demarcated area of atrophy with a minimum diameter of 300 microns, and total lesion size must add to less than or equal to ≤ 18 mm^2 (approximately 7-disc areas).
• Have detectable outer nuclear layer (ONL) in the macular region

Phase 2/3 Exclusion Criteria (applicable for both adult and pediatric subjects):

• Participation in ongoing antiretroviral therapy treatment.
• Participation in any investigational therapy study or receipt of investigational treatment within 60 days prior to screening or 5 half-lives (whichever is longer).

Any ophthalmic history of gene therapy, stem cell therapy, surgical implantation of prosthetic retinal chips, intravitreal or subretinal injections, or participation in an Alkeus ALK-001 study within the past 6 months.

• Macular atrophy secondary to any disease other than Stargardt Disease (STGD).
• Presence of genetic mutations that mimic Stargardt Disease like ELOVL4, or PROM1.
• Contraindication to subretinal injection or use of anesthesia (local and/or general).

Phase 1 was a multicenter, open-label, dose-ranging/dose escalation study. Enrollment is complete for Phase 1