RGX-314 Gene Therapy for Neovascular AMD Trial

This Phase I/IIa, open-label, multiple-cohort, dose-escalation study is designed to evaluate
the safety and tolerability of RGX-314 gene therapy in subjects with previously treated nAMD.
Five doses will be studied in approximately 42 subjects. Subjects who meet the
inclusion/exclusion criteria and have an anatomic response to an initial anti VEGF injection
will receive a single dose of RGX-314 administered by subretinal delivery. RGX-314 uses an
AAV8 vector that contains a gene that encodes for a monoclonal antibody fragment which binds
to and neutralizes VEGF activity. Safety will be the primary focus for the initial 24 weeks
after RGX-314 administration (primary study period). Following completion of the primary
study period, subjects will continue to be assessed until 104 weeks following treatment with
RGX-314.

Inclusion Criteria:

1. Patients ≥ 50 and ≤ 89 years with a diagnosis of subfoveal CNV secondary to AMD in the
study eye receiving prior intravitreal anti-VEGF therapy.

2. BCVA between ≤20/63 and ≥20/400 (≤63 and ≥19 Early Treatment Diabetic Retinopathy
Study [ETDRS] letters) for the first patient in each cohort followed by BCVA between
≤20/40 and ≥20/400 (≤73 and ≥19 ETDRS letters) for the rest of the cohort.

3. History of need for and response to anti-VEGF therapy.

4. Response to anti-VEGF at trial entry (assessed by SD-OCT at week 1)

5. Must be pseudophakic (status post cataract surgery) in the study eye.

6. AST/ALT < 2.5 × ULN; TB < 1.5 × ULN; PT < 1.5 × ULN; Hb > 10 g/dL (males) and > 9 g/dL
(females); Platelets > 100 × 10^3/µL; eGFR > 30 mL/min/1.73 m^2

7. Must be willing and able to provide written, signed informed consent.

Exclusion Criteria:

1. CNV or macular edema in the study eye secondary to any causes other than AMD.

2. Any condition preventing visual acuity improvement in the study eye, eg, fibrosis,
atrophy, or retinal epithelial tear in the center of the fovea.

3. Active or history of retinal detachment in the study eye.

4. Advanced glaucoma in the study eye.

5. History of intravitreal therapy in the study eye, such as intravitreal steroid
injection or investigational product, other than anti-VEGF therapy, in the 6 months
prior to screening.

6. Presence of an implant in the study eye at screening (excluding intraocular lens).

7. Myocardial infarction, cerebrovascular accident, or transient ischemic attacks within
the past 6 months.

8. Uncontrolled hypertension (systolic blood pressure [BP] >180 mmHg, diastolic BP >100
mmHg) despite maximal medical treatment.