This clinical study has two phases: Phase 1 and Phase 2a. Phase 1 is an open-label, single ascending dose (SAD), while Phase 2a is a randomized, single-masked (participant) with a sham control.

This clinical study has two phases: Phase 1 and Phase 2a. Phase 1 is an open-label, SAD study to investigate the ocular and systemic safety and tolerability of two dose levels of PER-001, in participants with advanced OAG. Phase 1 will enroll up to approximately 12 participants.

Phase 2a is a randomized, single-masked (participant) study to further investigate the ocular and systemic safety and tolerability of the two dose levels of PER-001 Intravitreal Implants in participants with progressing glaucoma. Participants who meet entry criteria will be randomized to receive either dose of PER-001 or sham control. In Phase 2a, a total of approximately 24 participants (12 in each Cohort, will be randomized).

Inclusion Criteria:

For Phase 1 and Phase 2a:

• Must be ≥ 18 years of age at the time of signing the informed consent
• A negative pregnancy test for females of childbearing potential at Screening (serum) and Day 1 (urine).
• IOP 6 to 25 mmHg (inclusive) at Screening in potentially eligible eye(s)

Phase 1:

• Best corrected visual acuity (BCVA) LogMAR score 1.0 or better at Screening in at least one eye and prior to randomization at Day 1 in the study eye
• Diagnosis of advanced or severe primary OAG including normal tension, pseudoexfoliation and pigment dispersion

Phase 2:

• BCVA LogMAR score 0.5 or better at Screening in at least one eye and prior to randomization at Day 1 in the study eye
• Primary OAG that is progressing in the study eye

Exclusion Criteria:

• Blood pressure >140/90 mmHg or <90/60 mmHg at Screening
• Any condition which, in the opinion of the investigator, would preclude the participant's ability to comply with study requirements including completion of the study (including but not limited to diagnosis of dementia, Alzheimer's, and/or other neurological disease or physical incapacity)
• Females who are pregnant, nursing, or planning a pregnancy during the study
• Any significant media opacity which precludes clinical evaluation and imaging of the retina
• History of vitrectomy surgery or retinal detachment or macular hole (Stage 3 or 4)
• Retinal laser within 3 months prior to Day 1
• Intraocular surgery, including cataract surgery and Minimally Invasive Glaucoma
• Surgery (MIGS), within 3 months prior to Day 1
• Aphakia or absence of posterior capsule
• Change in IOP lowering therapy within 6 weeks prior to Screening and/or anticipated change in IOP lowering therapy or treatment during the study Worse than mild non-proliferative diabetic retinopathy (Note: stable mild background diabetic retinopathy is permitted)
• Any active uveitis and/or vitritis or history of idiopathic or autoimmune-associated uveitis
• Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis (Note: mild blepharitis is permitted if stable)
• History of recurrent infectious or inflammatory ocular disease
• Central serous retinopathy
• Non-glaucomatous optic neuropathy

Placebo sham