AAVCAGsCD59 for the Treatment of Wet AMD

This is a Phase 1, multi-center, open label study to assess the efficacy and safety of a
single dose of the adeno-associated viral vector serotype 2 (AAVCAGsCD59) expressing sCD59
administered via intravitreal injection seven days after a single intravitreal injection of
anti-VEGF. All patients considered for enrollment in this study must have treatment naive wet
AMD, adequate pupillary dilation to permit a thorough ocular exam, and best corrected
distance visual acuity in the study eye of 20/25 to 20/400 using the Snellen eye chart.

Written informed consent will be obtained from each study patient prior to his/her
participation in any study related procedures. Screening will determine patient eligibility
for the study according to written inclusion and exclusion criteria, which include both
general medical and AMD-specific criteria. Patients will be enrolled into the study upon
verification that they fulfill all eligibility criteria and after completion of all screening
assessments.

This study consists of a screening and injection of anti-VEGF (Day 0), injection of
AAVCAGsCD59 (Day 7), and a monthly follow-up period (Month 1 through Month 12) where enrolled
patients are treated as needed with intravitreal anti-VEGF based on an increase in central
subfoveal thickness of >50 micrometers on OCT from Day 0, new subretinal hemorrhage, or a
decrease in > or equal to 10 ETDRS letters from the previous exam. The purpose of the study
is to evaluate the number of anti-VEGF injections that are required after a single
intravitreal injection of AAVCAGsCD59 at a dose of 3.56 x 10e11vg is administered on Day 7.
Anti-VEGF will be injected at Day 0 to treat the CNV per standard of care and enable the
AAVCAGsCD59 adequate time (up to two weeks) to enter the ganglion cells in the retina and
start producing the transgene product, sCD59. Up to twenty-five (25) patients will be
enrolled at to 2 clinical sites in this study.

Inclusion Criteria:

1. Men or women 50 years of age or older.

2. Treatment naive Wet AMD with no evidence of subretinal fibrosis under the fovea.

3. Presence of intraretinal and/or subretinal fluid on OCT.

4. Best corrected visual acuity (BCVA) Snellen equivalent 20/25 to 20/400 in the study
eye using ETDRS charts at a starting distance of 4m.

5. Adequate pupillary dilation to permit ocular examination and testing.

6. Ability and willingness to return for all scheduled visits and assessments.

7. Understand and comply with the clinical protocol and provide written informed consent
prior to any study-related procedure.

8. All fertile men must be willing to use barrier contraception during the study.

9. Women of childbearing potential must have a negative pregnancy test and agree to use
effective contraception for the duration of the trial. A woman of childbearing
potential is defined as any female who has had menses within the last two years or has
not undergone a hysterectomy or surgical sterilization.

Exclusion Criteria:

1. Wet AMD secondary to non-AMD etiologies.

2. Subretinal hemorrhage that interferes with the ability to adequately measure visual
acuity or follow retinal or subretinal fluid collection on OCT.

3. Serous pigment epithelial detachment (PED) that is >50% of the CNV lesion, >400µm in
any diameter, or presence of a RPE tear.

4. Presence of polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation
(RAP), central serous retinopathy, or symptomatic vitreomacular adhesion.

5. Previous macular laser photocoagulation for CNV, photodynamic therapy (PDT), ocular
radiation, or subretinal surgery for CNV in the study eye.

6. History of conditions in the study eye which might alter visual acuity or interfere
with study testing including clinically significant macular edema, central retinal
vein occlusion, macular branch retinal vein occlusion, and optic neuropathy.

7. Active uncontrolled glaucoma with IOP>30 mmHg despite treatment with glaucoma
medications, cup-to-disc ratio of >0.9, visual field defects secondary to glaucoma
that involve the macula, and optic atrophy from glaucoma.

8. Likely candidate for intraocular surgery (including cataract surgery) in the study eye
during the clinical trial.

9. Acute or chronic infection in the study eye.

10. History of uveitis unrelated to eye surgery in the study eye or opposite eye requiring
treatment with topical corticosteroids or systemic immunosuppression within 24 months
of enrollment.

11. Any contraindication to intravitreal injection.

12. Use intravitreal (study eye) corticosteroids within 3 months prior to screening.

13. Any of the following underlying systemic diseases:

- Unstable or severe cardiovascular disease, e.g., congestive heart failure (New
York Heart Association Functional class III or IV), myocardial infarction within
6 months, ventricular tachyarrhythmias requiring ongoing treatment, unstable
angina, or critical limb ischemia;

- Cerebrovascular disease within 12 months prior to Screening that impairs the
patient's ability to participate in the clinical trial;

- Dementia or neurodegenerative disease (e.g., Alzheimer's disease, Parkinson's
disease) of a level that prevents adequate evaluation of the subject during the
study;

- Has an active malignancy or is currently undergoing treatment for an active
malignancy at Screening, or has a history of malignancy that precludes completion
of this 12-month study;

- Immunocompromised conditions and/or need for immunosuppressive therapy

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

15. Current or prior use of any medication known to be toxic to the retina or optic nerve
including, but not limited, to chloroquine/hydrochloroquine, deferoxamine,
phenothiazines and ethambutol

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

17. Received any investigational product within 120 days prior to screening

18. Any psychological, familial, sociological, geographical, or other condition that would
preclude study compliance and follow-up