Clearside Biomedical, Inc. announced that key data from the Phase 1/2a OASIS clinical trial were presented at The Retina Society 56th Annual Scientific Meeting. The results of the trial demonstrate the key benefits of Clearside?s patented suprachoroidal delivery platform and its lead drug candidate, CLS-AX (axitinib injectable suspension) being developed for the treatment of neovascular age-related macular degeneration (wet AMD or nAMD). The presentation, entitled, ?Safety and Tolerability of CLS-AX via Suprachoroidal Injection in nAMD Patients with Persistent Activity Following Anti-VEGF Therapy?

was delivered by David M. Brown, MD, Retina Consultants of Texas. CLS-AX is a proprietary suspension formulation of the tyrosine kinase inhibitor (TKI) axitinib that provides high potency pan-VEGF inhibition delivered via Clearside?s proprietary SCS Microinjector®. Based on the data from OASIS, CLS-AX is currently being investigated in a Phase 2b clinical trial entitled ODYSSEY.

Dr. Brown?s presentation summarized the promising data from Clearside?s 3-month Phase 1/2a OASIS clinical trial and Extension Study through 6 months. Axitinib was described as a highly potent, pan-VEGF TKI to treat wet AMD which has shown 10x more potency than other TKS in preclinical studies. The advantages of suprachoroidal delivery directly targeting the site of disease at the back of the eye were featured through multiple preclinical studies comparing equivalent doses of axitinib injected suprachoroidally versus intravitreally.

In the OASIS and Extension Study, participants with wet AMD who were sub-responders with active disease at screening were followed for up to 6 months after CLS-AX treatment. This patient population is important because enrolling difficult to treat anti-VEGF sub-responders allowed observation of possible signs of biologic effect while minimizing false signals. The studies demonstrated an excellent safety profile at all doses and timepoints with no serious adverse events (SAEs), no dose limiting toxicities, and no adverse events (AEs) from inflammation.

In addition, signs of biologic effect with stable mean best corrected visual acuity (BCVA) and stable mean central subfield thickness (CST) to the 6-month timepoint were observed. Importantly, CLS-AX exhibited early signs of durability and reduction in treatment burden with a 77-85% reduction in injection frequency at higher doses in cohorts 3 and 4. OASIS was an open-label, single dose-escalation Phase 1/2a trial in wet AMD participants to assess the safety and tolerability of a single dose of CLS-AX administered by suprachoroidal injection via Clearside?s SCS Microinjector®. Eligible participants were those who demonstrated stable visual acuity following two or more previous injections with an intravitreal anti-VEGF agent.

All enrolled participants underwent diagnostic imaging on screening, followed by masked reading center confirmation of persistent active disease. OASIS was a 3-month trial, followed by a 3-month Extension Study. The trial included four cohorts at the following doses: Cohort 1 at 0.03 mg; Cohort 2 at 0.1 mg; Cohort 3 at 0.5 mg; Cohort 4 at 1.0 mg.

Participants from Cohorts 2, 3 and 4 who rolled over into the Extension Study were followed for a total of 6 months after a single dose of CLS-AX. Participants enrolled in OASIS were heavily anti-VEGF treatment experienced with active disease at screening, which was confirmed by an independent reading center. Safety and Tolerability Results in All Cohorts in OASIS (n=27) and Extension Study (n=14): No serious adverse events (SAEs), no treatment emergent adverse events (TEAEs) related to study treatment, and no dose limiting toxicities.

No adverse events related to inflammation, vasculitis or vascular occlusion. No vitreous ?floaters? or dispersion of CLS-AX into the vitreous.

No retinal detachments, endophthalmitis, or adverse events related to intraocular pressure. Durability shown in Extension Study through 6 months in Cohorts 3 & 4 at the higher doses (n=12): 77% - 85% reduction in treatment burden was observed compared to the average monthly injections in the six months before CLS-AX administration. Participants not requiring additional therapy: = 3 Months: 11/12 (92%), = 4 Months: 10/12 (83%), = 6 Months: 8/12 (67%), > 6 Months: 6/12 (50%).

Biologic Effect in Extension Study through 6 months in Cohorts 3 & 4 (n=12): CLS-AX showed signs of biologic effect with stable mean BCVA and stable mean CST to the 6-month timepoint. On Optical Coherence Tomography (OCT) images, anatomical signs of TKI biologic effect were observed in anti-VEGF treatment experienced sub-responders. About the ODYSSEY Phase 2b Clinical Trial: ODYSSEY is a randomized, double-masked, parallel-group, active-controlled, multi-center, Phase 2b clinical trial in participants with wet AMD.

A total of 60 participants are expected to be treated for 36 weeks and will be randomized to either CLS-AX (1 mg) or aflibercept (2 mg) with a 2:1 randomization schedule (40 participants in CLS-AX arm and 20 participants in aflibercept arm). CLS-AX will be administered by suprachoroidal injection via Clearside?s SCS Microinjector, and aflibercept will be administered via intravitreal injection. Eligible participants will be treatment-experienced and will undergo diagnostic imaging at their screening visit followed by masked reading center confirmation of persistent active disease.

The primary outcome measure is the mean change from baseline in best corrected visual acuity. Secondary outcome measures include other changes from baseline in visual function and ocular anatomy, the need for supplemental treatment, and treatment burden as measured by total injections over trial duration. Additional information about the Phase 2b trial can be found on clinicaltrials.gov (NCT05891548).