The purpose of this study is to demonstrate the safety and tolerability of ONL1204 Ophthalmic Solution in patients with progressing open angle glaucoma.

ONL1204 Ophthalmic Solution is a first-in-class inhibitor of fragment apoptosis stimulator (Fas) receptor-mediated cell death that has demonstrated protection of multiple retinal cell types in numerous preclinical models of retinal disease. Apoptosis of retinal ganglion cells is associated with progressive glaucoma. Nonclinical data on ONL1204 Ophthalmic Solution suggest that ONL1204 Ophthalmic Solution may inhibit the cell death pathways in these cells.

Inclusion Criteria:

1. Males and females aged ≥18 years old
2. Able and willing to give informed consent and attend study visits
3. Controlled intraocular pressure (IOP) (≤21 mmHg) in both eyes for all previous 3 visits before Screening and at Screening in both eyes
4. Prior to screening, 3 or more Humphrey Visual Field (HVF) tests (with acceptable reliability standards) or 3 or more Optical Coherence Tomography (OCT) studies of the study eye on record
5. Open angle glaucoma that is progressing in the study eye
6. HVF 24-2 at Screening with acceptable reliability standards and MD scores

Exclusion Criteria:

Considerations for either eye

1. Best Corrected Visual Acuity (BCVA) at Screening of ≤64 letters (Snellen equivalent of worse than 20/50)

2. Severe open angle glaucoma

3. Glaucoma due to non-open angle causes

4. Worse than mild non-proliferative diabetic retinopathy

   Considerations for study eye:

5. Visual field results suggestive of another disease (eg, altitudinal field defect)

6. Evidence of macular edema based on OCT imaging and Investigator's judgement

7. Previous intravitreal (IVT) injections, history of retinal surgery, history of retinal laser

8. Cataract surgery within 3 months of Screening or yttrium-aluminum-garnet capsulotomy (YAG) within 4 weeks of Screening

9. Anticipated need for surgical or procedural intervention for glaucoma, cataract, posterior capsular opacity, refractive error, or retinal conditions during the study

   Other general exclusion criteria:

10. The requirement for oral carbonic anhydrase inhibitors to control intraocular pressure

11. Severe, unstable, or uncontrolled cardiovascular, diabetic, renal, or pulmonary disease, based on Investigator's judgement

12. Systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg

13. Women who are pregnant, breastfeeding, or contemplating pregnancy during the study period and men who are contemplating contributing sperm for a biologic child during the study period

14. Participation in other ophthalmic clinical trials or use of any other investigational drugs or devices in either eye or systemically for 3 months before Screening (Visit 1)