4D-150 in Patients With Neovascular (Wet) Age-Related Macular Degeneration

• 50 years of age

Individuals eligible to participate in the trial must meet the following inclusion criteria:

1. ≥50 years of age

2. Diagnosed with CNV secondary to AMD (confirmed by reading center)

3. BCVA ≥34 ETDRS letters (~20/200) in the contralateral eye, and BCVA in the study eye:

4. Central subfield thickness (CST) and/or presence of subretinal or intraretinal fluid requiring continued anti-VEGF therapy in the study eye, as assessed by SD-OCT; and confirmed by a reading center):

5. Study eye amenable to IVT injection

6. Ability to perform tests of visual and retinal function and structure, and ability to comply with other protocol-specified procedures

7. Currently receiving anti-VEGF treatment (e.g. ranibizumab, aflibercept, faricimab or bevacizumab) in the study eye AND has demonstrated a clinical response consistent with anti-VEGF activity within 12 months prior to screening:

Note: Day -7 aflibercept will be administered ≥ 4 weeks from last IVT anti-VEGF

8. Subjects receiving 4D-150 agree to use a barrier method (e.g. condom) during intercourse for 6 months after administration of 4D-150 to prevent fluid transmission; sexually active males should not father a child or donate sperm during this period

9. Medical records available to document history of anti-VEGF therapy (dates, drugs, and dosage) for a minimum of 12 months prior to Screening

10. Provide written informed consent.

Contralateral Eye Sub-study-Specific Criteria:

1. Received 4D-150 in study eye-1 at least 6 months prior to Contralateral Substudy Screening Visit NOTE: Subjects who received 4D-150 in study eye-1 as part of the Shedding Substudy are also eligible to participate in the Contralateral Eye Substudy only after biological samples from all matrices were at or below the limit of quantitation for vector genomes in at least 3 consecutive measurements AND at least 6 months has passed since 4D-150 administration to study eye-1.

2. Macular neovascularization (MNV) secondary to AMD in study eye-2 as assessed on historical images at any time by SD-OCT (required) and FA when available or fundus photography when available or at screening based on SD-OCT, FA and fundus photography (confirmed by the reading center)

3. History of at least 1 anti-VEGF injection in study eye-2 within 6 months prior to Screening (last anti-VEGF injection must be at least 28 days prior to Screening) AND has demonstrated a clinical response consistent with anti-VEGF activity by historical OCT at any time point prior to screening with confirmed response by the reading center (Screening OCT can be confirmatory)

4. BCVA between 25 and 83 ETDRS letters, inclusive (20/320 20/25 Snellen) in study eye-2

5. Study eye-2 amenable to IVT injection

6. BCVA ≥34 ETDRS letters (~20/200) in the previously treated study eye-1

7. Ability to comply with protocol-specified procedures and visits, in the Investigator's judgment

8. Agree to use a barrier method (e.g. condom) during intercourse for 6 months after administration of 4D-150 to study eye-2 to prevent fluid transmission; sexually active males should not father a child or donate sperm during this period

9. Provide written informed consent.

Shedding Substudy-specific Inclusion Criteria:

1. ≥50 years of age

2. Diagnosed with MNV secondary to AMD as assessed on historical images at any time by spectral domain optical coherence tomography (SD-OCT) (required) and fluorescein angiography when available or fundus photography when available or at screening based on SD-OCT, FA and fundus photography (confirmed by Reading Center)

3. Best corrected visual acuity (BCVA) between 10 and 83 ETDRS letters, inclusive (~20/640 and 20/25, respectively) in the study eye at Screening

4. BCVA ≥34 ETDRS letters (~20/200) in the contralateral eye

5. Currently receiving anti-VEGF treatment (e.g. ranibizumab, aflibercept, faricimab or bevacizumab) in the study eye; minimum of 1 injection within the last 6 months (last anti-VEGF injection must be at least 28 days prior to screening) AND has demonstrated a clinical response consistent with anti-VEGF activity by historical OCT at any time prior to screening with confirmed response by the reading center (Screening OCT can be confirmatory)

6. Study eye amenable to IVT injection

7. Ability to perform tests of visual and retinal function and structure, and ability to comply with other protocol-specified procedures, in the Investigator's judgment

8. Agree to use a barrier method (e.g. condom) during intercourse for 6 months after administration of 4D-150 to prevent fluid transmission; sexually active males should not father a child or donate sperm during this period

9. Provide written informed consent.