This is a Phase 1 study, first-in-human (FIH), open label study to evaluate the safety, tolerability and identify the maximum tolerated dose (MTD) of PMC-403 and determine the recommended phase 2 dose (RP2D).

In this study, Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) will be carried out in a sequential manner.

- PART 1- SAD

The SAD part of the study will be conducted in a step-wise manner for a total of 4 dose levels (0.7 mg, 2 mg, 3 mg, 4 mg). To each dose group, 3 subjects at minimum or 6 subjects at maximum will be recruited. In the SAD part, dose escalation will be performed up to 4 mg/eye (50 uL/eye) until the MTD is identified.

In the SAD part, a maximum of 24 participants are to be enrolled.

- PART 2- MAD

Upon the end of the SAD part of the study, the MAD part is planned to be conducted in a step-wise manner for a total of 2 dose levels (3 mg, 4 mg).

In the MAD part will begin with dose level 1 (3 mg). Subjects will be given a total of 3 doses of IP at 4-week intervals over a total period of 12 weeks and will be assessed for safety and tolerability according to study procedures. While a total of 6 subjects are to be recruited per dose group in the MAD part. Dose escalation will be performed up to 4 mg/eye (50 uL/eye) until the MTD is identified.

In the MAD part, a maximum of 12 participants are to be enrolled.

Inclusion Criteria:

To be eligible for study participation, subjects must meet all of the following inclusion criteria.

* Criteria for the selection of the study eye

If both eyes meet the criteria, the study eye will be selected according to the following criteria:

1. The eye with lower (severer) best corrected visual acuity (BCVA) at baseline will be selected as the study eye.

2. If both eyes have the same BCVA, the right eye will be selected as the study.

   1. Male and female ≥50 years of age at the time of written informed consent.

   2. Treatment required, based on the judgment of the investigator, due to insufficient therapeutic efficacy despite ≥ 3 repeated doses of anti-vascular endothelial growth factor (anti-VEGF) intravitreal injection (IVT) for nAMD in the study eye, and the subject's agreement to receive the study drug instead of conventional standard therapy

   3. >12 weeks must have elapsed since the last dose of anti-VEGF IVT at the time of screening.

   4. Active subfoveal or parafoveal choroidal neovascularization (CNV)* confirmed by fundus fluorescein angiography (FFA), spectral domain-optical coherence tomography (SD-OCT), and IndoCyanine Green (ICG) angiography.

      *Active CNV (confirmed by the central reading center) is defined as the presence of subretinal fluid (SRF) or intraretinal fluid (IRF) in consequence of vascular leakage.

   5. The size of the entire lesion in the study eye (including blood, atrophy, fibrosis, and neovascularization) must be ≤ 9-disc areas, and the area of CNV in the study eye must account for ≥ 50% of the total area of the lesion, as confirmed by FFA and ICG angiography.

   6. BCVA measured in the study eye must be between ≥ 23 letters and ≤ 78 letters based on the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart (Snellen visual acuity 20/25 - 20/320).

   7. Voluntary written informed consent to study participation.

Exclusion Criteria:

Subjects who meet any of the following exclusion criteria are not eligible for study participation.

1. At the screening visit:

   1. Uncontrolled ocular hypertension (≥ 25 mmHg) despite drug therapy;
   2. Retinal pigment epithelium (RPE) tears involving the macula;
   3. Improvement in visual acuity is not expected due to scars, fibrosis, or atrophy involving the fovea;
   4. Presence of vitreous hemorrhage;
   5. Aphakia or absence of posterior capsule (with the exception of pseudophakic eyes treated with laser posterior capsulotomy);
   6. Presence of any causes of CNV other than nAMD, such as ocular histoplasmosis, trauma, pathological myopia, angioid streak, choroidal rupture, or uveitis; or
   7. Macular pathology that is unrelated to nAMD, but may affect visual acuity or study drug treatment (e.g., macular hole, epiretinal membrane, vitreomacular traction, macular telangiectasia, central serous chorioretinopathy, retinal vascular occlusion, etc.).

2. Any of the following conditions or medical history in either eye:

   1. Current or known history of at least moderate diabetic retinopathy or diabetic macular edema;
   2. Active intraocular or periocular infections or inflammations (e.g., infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, etc.); or
   3. History of idiopathic or autoimmune uveitis.

3. Any of the following systemic diseases:

   1. Unstable or serious cardiovascular disorders such as congestive heart failure (New York Heart Association Functional Class III or IV), ventricular tachycardia requiring continuous treatment, unstable angina pectoris, or critical limb ischemia;

   2. Uncontrolled hypertension with systolic or diastolic blood pressure > 160/100 mmHg;

   3. Stroke or myocardial infarction within 24 weeks prior to screening;

   4. Dementia or neurodegenerative disorders (e.g., Alzheimer's disease, Parkinson's disease) that might affect study results during the study period;

   5. History of malignant tumors within 5 years prior to screening; or

   6. Weakened immunity or requiring immunotherapy.

   7. Clinically significant liver/kidney disease or any of the following hematologic test results:

      • Serum creatinine ≥1.5 x upper limit of normal
      • Aspartate transaminase (AST) or alanine transaminase (ALT) ≥2 x upper limit of normal

4. Treatment with any of the following systemic drug therapy:

   1. Systemic anti-VEGF therapy within 12 weeks prior to baseline;

   2. Systemic corticosteroids for ≥2 consecutive weeks

      • ≤ 10 mg/day prednisolone or equivalent for less than 2 consecutive weeks will be allowed
      • Inhaled, nasal, and topical steroids will also be allowed

   3. Ongoing treatment with any drugs with potential toxicity to the lens, retina, and optic nerves (e.g., deferoxamine, chloroquine/hydroxychloroquine, tamoxifen, phenothiazines, vigabatrin, or ethambutol).

5. Any of the following medical history (surgical or procedural):

   1. Intraocular or periocular injection of corticosteroids (e.g., triamcinolone acetonide, etc.) to the study eye within 24 weeks prior to screening;
   2. Intraocular surgery or laser therapy (e.g., cataract surgery, laser posterior capsulotomy, etc.) to the study eye within 12 weeks prior to screening;
   3. Eyelid surgery within 4 weeks prior to screening;
   4. History of vitrectomy, glaucoma surgery, macular laser treatment, keratoplasty, or retinal detachment surgery; or
   5. History of treatment with radiotherapy around the study eye including radiation retinopathy

6. Any concurrent ophthalmic abnormalities that, based on the judgment of the investigator, may affect the assessment of safety and therapeutic efficacy or may need medical or surgical treatment during the study period (e.g., cloudy ocular media, optic neuropathy, amblyopia, etc.).

7. Hypersensitivity to any of the components of IP or to contrast agents used for FFA and ICG angiography.

8. Pregnant and/or breastfeeding women.

9. Men and women of childbearing potential who are unwilling to use adequate methods of contraception* or who are planning a pregnancy during the study period and for 12 weeks from the last dose of IP

   -Methods of contraception: hormone contraceptives (oral contraceptives, contraceptive patch, etc.), intrauterine device (IUD) (copper IUD, hormonal intrauterine system), double barrier method (both male [condom] and female [diaphragm, vaginal sponge, or cervical cap]), surgical sterilization (tubal sterilization, vasectomy, etc.)

10. Having participated in another clinical trial and treated with an IP within 12 weeks prior to screening

11. Distance vision test result of <0.1 for the fellow eye

12. Other reasons based on which individuals are determined by the investigator to be ineligible for study participation.