Clearside Biomedical, Inc. announced that enrollment has opened in ODYSSEY, its Phase 2b clinical trial of CLS-AX (axitinib injectable suspension) using suprachoroidal delivery in neovascular age-related macular degeneration (wet AMD). ODYSSEY is a randomized, double-masked, parallel-group, active-controlled, multi-center, Phase 2b clinical trial of 36 weeks duration. Number of Participants: 60 total participants with 2:1 randomization.

40 participants in CLS-AX arm and 20 participants in aflibercept arm. Key inclusion criteria: Diagnosed with wet AMD within 36 months of screening. History of 2 to 4 anti-VEGF treatments in the 6 months before screening.

History of response to anti-VEGF treatment for wet AMD. Reading center confirmation of persistent active disease. Best corrected visual acuity (BCVA) of 20 to 80 letters Treatment Protocol:   Loading Doses: Participants in both arms will receive three monthly aflibercept (2 mg) loading doses.

At the second loading dose (Baseline visit), participants in the CLS-AX arm will receive one dose of CLS-AX (1.0 mg). Disease Activity Assessments (DAA): Conducted monthly in both arms at Weeks 12 through 32 to determine if there is a need for supplemental treatment. Aflibercept arm (per approved label): Participants will receive aflibercept on a fixed dosing regimen every 8 weeks.

If needed based on DAA, aflibercept may be given at the 4-week interval as supplemental treatment. CLS-AX Arm: Participants will receive CLS-AX at Week 24, if they have not received a second dose since the Baseline visit. If needed based on DAA, CLS-AX may be given 12 weeks after the last dose.

If less than 12 weeks, aflibercept may be given as supplemental treatment. Supplemental treatment criteria (based on measurement changes due to wet AMD): BCVA reduction of >10 letters from Baseline. Increase in central subfield thickness (CST) of >100 microns on SD-OCT from Baseline.

BCVA reduction of > 5 letters from Baseline AND increase in CST of >75 microns on SD-OCT from Baseline. Presence of new or worsening vision-threatening hemorrhage. Primary outcome measure: Mean change in BCVA from Baseline to Week 36.

Secondary outcome measures: Other changes in visual function and ocular anatomy, such as CST. Need for supplemental treatment. Treatment burden as measured by total injections over trial duration.

CLS-AX (axitinib injectable suspension) is a proprietary suspension of axitinib for suprachoroidal injection. Axitinib is a tyrosine kinase inhibitor (TKI), currently approved as an oral tablet formulation to treat advanced renal cell carcinoma, that achieves pan-VEGF blockade, directly inhibiting VEGF receptors-1, -2, and -3 with high potency and specificity. Clearside believes this broad VEGF blockade may have efficacy advantages over existing retinal therapies by acting at a different level of the angiogenesis cascade and may benefit patients who sub-optimally respond to current, more narrowly focused anti-VEGF therapies.

Suprachoroidal injection of this proprietary suspension of axitinib has demonstrated meaningful potential in preclinical studies in multiple species and in a Phase 1/2a wet AMD clinical trial in which CLS-AX was well tolerated and demonstrated an excellent safety profile. With suprachoroidal administration of axitinib, there is the potential to achieve prolonged duration and targeted delivery to affected tissue layers while limiting drug exposure to the front of the eye. Clearside is developing CLS-AX as a long-acting therapy for the treatment of retinal diseases.

Age-related macular degeneration causes a progressive loss of central vision and is the most common cause of legal blindness in individuals over age 55. Neovascular AMD (Wet AMD) is generally caused by abnormal blood vessels that leak fluid or blood into the macula, the part of the retina responsible for central vision, and accounts for the majority of vision loss in patients with this disorder. In the U.S., approximately 11 million patients are living with AMD1, and about 10% have the wet form2.

Current treatments require life-long, frequent injections to maintain efficacy. This treatment regimen tends to cause a treatment burden for patients resulting in reduced compliance and under-treatment leading to potentially limited outcomes. In the U.S., the total economic impact of late-stage AMD is estimated to be approximately $49 billion, with the majority of costs attributed to lower productivity related to job loss or job reduction due to the condition.

Clearside's patent protected, proprietary suprachoroidal space (SCS®) injection treatment approach offers unprecedented access to the back of the eye, where sight-threatening disease often occurs. The Company's unique platform is inherently flexible and intended to work with established and new formulations of medications. Clearside's patented SCS Microinjector® can deliver a wide variety of drug candidates into the suprachoroidal space, providing targeted delivery to potentially improve efficacy and compartmentalization of medication to reduce or eliminate toxic effects on non-diseased cells.

The SCS Microinjector system comprises a syringe, a custom-designed hub, and two 30-gauge hollow microneedles of varying lengths, each less than 1.2 millimeters, optimizing insertion and suprachoroidal administration of drugs.