Efficacy and Safety Study of iSONEP With & Without Lucentis/Avastin/Eylea to Treat Wet AMD

The study will be conducted in subjects who qualify as "sub-responders" to Lucentis, Avastin
or Eylea meaning that each subject has (i) residual subretinal or intra-retinal fluid
observed on Cirrus or Spectralis SDOCT, (ii) leakage on FA, and (iii) an average central
subfield thickness of ≥250 μm. Additionally, each subject will have previously received a
minimum of 3 IVT injections of Lucentis, Avastin or Eylea within the 12-month period prior
to screening. Screening must occur between 28 and 65 days from the subject's last Lucentis
or Avastin treatment or between 42 and 79 days from the subject's last Eylea treatment.
Subjects must be dosed within 14 days of screening, and as of the day of initial study
treatment (Day 0), meet the following criteria: (i) ETDRS BCVA of ≥25 and ≤73 letters
(approximately 20/320 and 20/40 on the Snellen scale), (ii) residual subretinal or
intra-retinal fluid observed on Cirrus or Spectralis SDOCT, and (iii) leakage on FA.

Inclusion Criteria:

- ≥50 years of age with a diagnosis of wet AMD

- Subjects who have received 3 injections of Lucentis or Avastin or Eylea within 12
months prior to screening

- Active subfoveal CNV secondary to AMD (leakage on FA)

- Presence of residual subretinal or intraretinal fluid on Cirrus or Spectralis SDOCT

- SDOCT in the 1 mm central macular subfield on the retinal map analysis of ≥250 μm at
screening

- ETDRS BCVA of ≥25 and ≤73 letters (approximately 20/320 and 20/40 on the Snellen
scale) at screening and on Day 0

- In the fellow eye, ETDRS BCVA of 20/400 or better

- Subject with serous PED (any part of which may be subfoveal) with intraretinal and/or
subretinal fluid may be included

Exclusion Criteria:

- Most recent IVT injection of Lucentis or Avastin fewer than 28 days and more than 65
days prior to screening

- Most recent IVT injection of Eylea fewer than 42 days and more than 79 days prior to
screening

- Previous PDT or Macugen® at any time point

- Focal thermal laser or grid laser within 3 months prior to Day 0

- Use of IVT, subtenon or subconjunctival steroids within 3 months prior to Day 0

- Use of topical ophthalmic corticosteroids 2 weeks prior to Day 0

- Intraocular surgery, including cataract surgery, and / or laser of any type within 3
months prior to Day 0 or anticipated need for ocular surgery or ophthalmic laser
treatment during the study period

- Subjects previously treated with, or are currently receiving treatment with another
investigational agent or device for neovascular AMD in the study eye

- Retinal total lesion size >12 disc areas (30.5 mm2), including blood, scars and
neovascularization as assessed by FA in the study eye

- Presence of a fibrovascular PED extending underneath the center of the fovea

- Presence of RAP (retinal angiomatous proliferation) lesions

- Presence of PCV (if suspected, ICG should be performed at the discretion of the
Investigator)

- Subretinal hemorrhage in the study eye if any of the following is true: (i) the
subretinal hemorrhage represents 50% or more of the total lesion area; (ii) subfoveal
blood is 1 or more disc areas in size (iii) subfoveal blood where the fovea is
surrounded by less than 270 degrees of visible CNV on FA

- Scar or fibrosis making up >50% of total lesion area in the study eye

- Anatomic damage to the center of the fovea including fibrosis, scarring or atrophy

- History of a retinal pigment epithelial tear

- History of vitreous hemorrhage within 4 weeks prior to screening in the study eye

- Clinical evidence of diabetic retinopathy, diabetic macular edema or any other
vascular disease affecting the retina, other than AMD, in either eye

- Uncontrolled glaucoma defined as: (i) as intraocular pressure ≥25 mmHg despite
treatment with anti glaucoma medication in the study eye or (ii) by the Investigator

- Prior trabeculectomy or other filtration surgery in the study eye (prior laser
trabeculoplasty is allowed)