Efficacy and Safety Study of Squalamine Ophthalmic Solution in Subjects With Neovascular AMD

Phase 3 Study of the Efficacy and Safety of Squalamine Lactate Ophthalmic Solution 0.2%
Twice Daily in Subjects with Neovascular Age-Related Macular Degeneration Methodology: Phase
III, multicenter, randomized, double-masked, placebo-controlled study conducted in 2 periods
(Year 1 and Year 2).

Year 1 (Screening/Baseline to Week 52): Patients will be randomly assigned to one of 2
treatment groups in a 1:1 ratio:

- Squalamine lactate ophthalmic solution, 0.2% BID (Years 1 and 2) + ranibizumab every 4
weeks (Year 1) and PRN ranibizumab (as needed, Year 2)

- Placebo ophthalmic solution BID (Years 1 and 2) + monthly ranibizumab every 4 weeks
(Year 1) and PRN ranibizumab (Year 2), based on optical coherence tomography
(OCT)-guided re-treatment criteria

Inclusion Criteria:

- Age ≥ 50 years

- A diagnosis of choroid neovascularization (CNV) secondary to AMD with CNV comprising
at least 50% of the total lesion area on fluorescein angiography (FA)

- Central subfield thickness (spectral domain (SD)-OCT central 1 mm) of ≥ 300 μm

- Best-corrected visual acuity (BCVA) 20/40 to 20/320 (73- to 24-letter score on the
Early Treatment of Diabetic Retinopathy Study [ETDRS] chart)

Exclusion Criteria:

- Neovascularization secondary to any other condition than AMD in the study eye; Blood
occupying greater than 50% of the AMD lesion, or blood > 1.0 sq. mm underlying the
fovea

- Pigment epithelial detachment (PED) without associated subretinal fluid and/or cystic
retinal changes

- Clinical evidence of diabetic retinopathy or diabetic macular edema in the study eye

- Confounding ocular conditions in the study eye which will affect interpretation of
OCT, VA or assessment of macular appearance (e.g., cataract, epiretinal membrane,
retinal vascular occlusive disease)

- Fibrosis or atrophy, retinal epithelial tear in the center of the fovea in the study
eye or any condition preventing VA improvement

- Uncontrolled glaucoma in the study eye, or currently receiving topical glaucoma
medication in the study eye