Age-related macular degeneration (AMD) leads to severe and irreversible vision loss, while neovascular AMD (nAMD) accounts for 80-90% of AMD blindness. Current anti-VEGF therapies are the standard of care, but these therapies require life-long repeated intraocular injections. These frequent intravitreal injections increase the risk of complications, including submacular hemorrhage, intraocular hypertension, inflammation, and retinal detachment. Therefore, repeated treatments for nAMD place a substantial burden on healthcare systems, patients, and their caregivers. Additionally, approximately 25-35% of individuals with aggressive nAMD show suboptimal responses to the anti-VEGF therapies, experience treatment-extended failure, or require intensive, frequent intraocular injections, and do not prevent irreversible vision loss.

HG202 is a CRISPR/Cas13 RNA-editing therapy delivered through one single AAV vector to partially knock down the expression of VEGFA and thus inhibit CNV formation in AMD. The long-term, stable delivery of HG202 following a one-time gene-editing therapy treatment for nAMD may potentially reduce the frequent injections and the potential risks of currently available anti-VEGF therapies since it does not rely on the long-term expression of anti-VEGF antibodies.

Inclusion Criteria:

• Males or females ≥ 50 and ≤ 85 years at the time of signing the ICF;
• Active macular choroidal neovascularization (MNV) secondary to nAMD in the study eye;
• Sentinel (1st) subject for each dose cohort must have a BCVA ≤ 20/63 and ≥ 20/400 (≤63 and ≥ 19 ETDRS letters) in the study eye. Following the sentinel subject evaluation, the rest of the subjects in the dose cohort must have a BCVA between ≤ 20/40 and ≥ 20/400 (≤ 73 and ≥ 19 ETDRS letters) in the study eye.
• Able to perform visual acuity and retinal function tests and able and willing to comply with study procedures for this clinical trial.

Exclusion Criteria:

• Retinal or subretinal hemorrhage, scarring, or fibrosis of greater than 50% of the total lesion in the study eye;
• Other ocular diseases that may affect central vision in the study eye;
• Any other cause of CNV than nAMD in the study eye
• Uncontrolled glaucoma in the study eye;
• History or presence of corneal transplant or corneal dystrophy in the study eye;
• History of other intraocular surgery in the study eye within 3 months prior to baseline;
• Prior gene therapy or oligonucleotide therapy;
• Other conditions judged by the investigator as inappropriate for the study.