Safety and Tolerability Study of AAV2-sFLT01 in Patients With Neovascular Age-Related Macular Degeneration (AMD)

A new treatment for neovascular age-related macular degeneration (AMD) is being investigated.
Neovascular AMD is sometimes referred to as the "wet" form of AMD. The purpose of this Phase
1 clinical research study is to examine the safety and ability of an experimental study drug
to treat a complication of the disease which leads to vision loss. The name of the study drug
is "AAV2-sFLT01." This experimental study drug uses a virus to transfer a gene (genetic code)
into cells within the eye. The gene codes for a protein that is intended to diminish the
growth of abnormal blood vessels under the retina. The duration of the gene's effect is
currently unknown, but might last for years.

This clinical research study will look at the safety of a single administration of
AAV2-sFLT01 injected directly into the eye. There are 2 parts to this study, but patients
will take part in only one of them. In the first part of the study, 4 different doses of the
study drug will be studied in 4 separate groups of patients. Patients in the first part of
the study will not be randomized. In the second part of the study, the highest dose that was
safe and well tolerated will be studied in 10 more patients. Patients in this part of the
study may have a ranibizumab (Lucentis®) injection 26 weeks after their AAV2-sFLT01 injection
to verify their responsiveness to anti-VEGF therapy, if they have not demonstrated a response
to AAV2-sFLT01. The initial two parts of this protocol are expected to be completed in July,
2013.

All patients injected with AAV2-sFLT01 will be asked to participate in an Extended Follow-Up
(EFU) program for up to an additional 4 years. Participation is voluntary but strongly
encouraged as it allows for the long term collection of safety information as well as
information about the potential long term effects of the study drug. Study visits will take
place at the site every 6 months.

Up to thirty-four (34) patients at multiple centers will take part in this study in the
United States.

Inclusion Criteria:

- Choroidal neovascular membrane (CNV) secondary to AMD, as confirmed by the patient's
medical history and a documented diagnosis of CNV.

- Distance BCVA of 20/100 or worse in the study eye.

- The fellow eye must have distance BCVA of 20/400 or better.

- The study eye, i.e., the eye that receives investigational product, has the worst CVA
(As compared to the fellow eye).

- Subfoveal disciform scarring in the study eye for the first part of the study (the
dose-escalation part). Patients may or may not have macular scarring in the study eye
for the second part of the study (MTD phase). In addition, patients enrolled in the
second part of the study must have demonstrated responsiveness to an anti-VEGF therapy
within 12 months prior to screening and after the patient's most recent treatment of
anti-VEGF therapy.

- Noted presence of intra- or sub-retinal fluid.

- Adequate dilation of pupils to permit thorough ocular examination and testing.

- Must be willing to have samples of anterior chamber fluid collected from the study
eye.

Exclusion Criteria:

- CNV in the study eye due to any reason other than AMD.

- History of conditions in the study eye during Screening which might alter visual
acuity or interfere with study testing.

- Active uncontrolled glaucoma.

- Had any intraocular surgeries in the study eye within 3 months of enrollment or are
known or likely candidates for intraocular surgery (including cataract surgery) in the
study eye within 1 year of treatment.

- Acute or chronic infection in the study eye.

- History of inflammation in the study eye or ongoing inflammation in either eye.

- Any contraindication to intravitreal injection.

- Received Photo Dynamic Therapy in the study eye within 60 days, or laser
photocoagulation within 14 days prior to Screening.

- Currently using or have used ranibizumab (Lucentis®), bevacizumab (Avastin™), or
pegaptanib sodium (Macugen®) within 1 month prior to Screening.

- Currently using or have used Aflibercept (Eylea®) within 4 months prior to Screening.

- Currently using any periocular (study eye), intravitreal (study eye), or systemic
(oral or intravenous) steroids within 3 months prior to Screening.

- Any active herpetic infection, in particular active lesions in the eye or on the face.

- Any significant poorly controlled illness that would preclude study compliance and
follow-up.

- Current or prior use of any medication known to be toxic to the retina or optic nerve.

- Previous treatment with any ocular or systemic gene transfer product.

- Received any investigational product within 120 days prior to Screening.