RGX-314 Gene Therapy Administered in the Suprachoroidal Space for Participants With Diabetic Retinopathy (DR) With and Without Center Involved-Diabetic Macular Edema (CI-DME)

Part 1 (DR without CI-DME):

Inclusion Criteria:

• Patients 25-89 years of age with a diabetic retinopathy (DR) diagnosis ofnonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) secondary to diabetes mellitus Type 1 or 2 for which PRP or anti-VEGFinjections can be safely deferred for at least 6 months

• HbA1c < 12%.

• Best corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score in the study eye of ≥69 letters (approximate Snellen equivalentof 20/40 or better).

• Prior history of CI-DME in the study eye is acceptable.

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

Exclusion Criteria:

• Neovascularization in the study eye from a cause other than DR.

• Presence of any active CI-DME.

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

• Any evidence or documented history of PRP or retinal laser in the study eye.

• Patients who had a prior vitrectomy surgery.

• Women of childbearing potential.

Part 2 (DR with CI-DME):

Inclusion Criteria:

• Patients 25-89 years of age with diabetic retinopathy secondary to diabetes mellitusType 1 or 2.

• HbA1c < 12%

• Macular thickening secondary to DME involving the center of the fovea, CST on SD-OCT (≥ 325 μm)

• Best corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score in the study eye of 78-25 letters (approximate Snellenequivalent of 20/32 to 20/320)

• Participants must have demonstrated a meaningful response to anti-VEGF therapy.

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

Exclusion Criteria:

• Neovascularization in the study eye from a cause other than DR.

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

• Any evidence or documented history of PRP or retinal laser in the study eye.

• Patients who had a prior vitrectomy surgery.

• Women of childbearing potential.

Note: Other inclusions/exclusions criteria apply.