Clearside Biomedical (CLSDQ) Study Result summary

Study design and patient population

• ODYSSEY was a 36-week, randomized, double-masked, multicenter Phase IIb trial in wet AMD, enrolling 60 participants with active disease confirmed by an independent reading center, all previously treated with anti-VEGF therapy.

• Participants were randomized 2:1 to receive CLS-AX (1 mg) via suprachoroidal injection or aflibercept (2 mg) via intravitreal injection, with strict inclusion criteria and rapid enrollment across 32 sites.

• All participants received three aflibercept loading doses before randomization.

• The trial allowed flexible, as-needed redosing of CLS-AX based on disease activity, with a mandatory redose at week 24.

• The median duration of wet AMD diagnosis was 9.9 months, indicating participants were early in their treatment journey.

Efficacy and durability results

• The primary endpoint, mean change in BCVA from baseline to week 36, was met, with stable visual acuity and central subfield retinal thickness maintained throughout the trial.

• CLS-AX demonstrated durable efficacy: 100% of participants went 3 months, 90% went 4 months, 81% went 5 months, and 67% went 6 months without additional treatment before mandatory redosing.

• Injection frequency was reduced by approximately 84% compared to the pre-study period.

• BCVA remained within two letters of baseline at both week 24 and week 36 in the CLS-AX arm.

• Intervention-free rates were higher if only reading center-confirmed disease activity was used for retreatment decisions.

Safety and tolerability

• CLS-AX showed a positive safety profile, with no ocular or treatment-related serious adverse events, endophthalmitis, retinal vasculitis, or systemic drug/procedure-related SAEs reported.

• Four cases of intraocular inflammation were all mild and resolved by or before week 36; two were potentially related to drug administration.

• Only one instance of injection pain was reported among 84 CLS-AX injections.

• Discontinuation rates were low and similar between treatment arms, mainly due to patient withdrawal of consent.

• CLS-AX was well-tolerated after repeat dosing, with no cases of vasculitis, chorioretinitis, or posterior pole involvement.