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

Overview

Phase 2/3 Pivotal Confirmatory Clinical Trial is a randomized, outcome assessor-masked, multicenter study, that will enroll fifty-one (51) subjects. 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). Phase 1 is complete and closed for enrollment. It was a multicenter, open-label, dose ranging/dose escalation study that enrolled 9 subjects. OCU410ST Phase 1- Retinal Structure and Visual Function Data Results * Safety: Favorable safety and tolerability profile No SAE deemed related to OCU410ST including intraocular inflammation, exudation, endophthalmitis, anterior ischemic optic neuropathy (AIONs) or vasculitis. * Primary Endpoint: Structural Improvement Atrophic lesions grew slower by 48% at 12M in evaluable treated eyes when compared to untreated eyes * Secondary Endpoint: Visual Function (BCVA) 100% evaluable treated eyes demonstrated stabilization or improvement when compared to untreated eyes in visual function OCU410ST Phase 1- Structural and Functional Outcomes at 12M Data Results * The GARDian3 clinical trial for ABCA4- related retinopathies including Stargardt disease builds upon encouraging results and positive data from the Phase 1 GARDian trial, which demonstrated 48% slower lesion growth at 12-month follow-up in evaluable treated eyes compared to untreated eyes * Additionally, evaluable treated eyes showed a statistically significant (p=0.031) and clinically meaningful improvement of nearly 2-line/9-letter gain in best corrected visual acuity (BCVA) at 12-month follow-up when compared to untreated eyes.

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).