A Clinical Trial to Evaluate the Efficacy and Safety of Bevemipretide Ophthalmic Topical Solution in Subjects Who Have Dry Age-Related Macular Degeneration (Dry AMD)

1. Adults ≥ 55 years of age with dry AMD.

   Imaging Conditions - Study Eye (as determined by the central Reading Center at the Screening Visit):

2. GA in the study eye may be multi-focal, but the cumulative GA lesion and size (by Fundus Autofluorescence [FAF]) must be ≥ 0.50 mm2 and ≤ 10.16 mm2.
3. Well-demarcated GA in the study eye that is extrafoveal (≥150 μm from foveal center), assessed by FAF.
4. GA that resides completely within the FAF 30- or 35-degree image.
5. Observable hyper-FAF at the margins of the GA in the study eye.

6. The absence of any retinal pathology in the study eye that prohibits outer retinal quantification and EZ mapping.

   Ocular Conditions - Study Eye:

7. BCVA by Early Treatment Diabetic Retinopathy Study (ETDRS) score of ≥ 55 letters in the study eye.
8. LL BCVA by ETDRS score of ≥ 10 letters in the study eye.
9. LLD (defined as the difference between BCVA and LL BCVA) of ≥ 6 letters in the study eye.

10. Sufficiently clear ocular media, adequate pupillary dilation, fixation to permit quality fundus imaging, and ability to cooperate sufficiently for adequate ophthalmic visual function testing and anatomic assessment in the study eye.

    Note: The fellow eye may have any of the following: no AMD, AMD without GA, AMD with GA, CNV AMD, or foveal GA.

    Systemic and General Criteria:

11. Able to demonstrate ability to administer IMP or have an appropriate designee (i.e., a capable family member or a caregiver) who can demonstrate ability to administer IMP.
12. Able to provide informed consent and willing to comply with all site visits, examinations, daily IMP administrations and dosing diary entries, and other conditions of the trial protocol.

13. Women of childbearing potential must agree to use 1 of the following methods of birth control from the date they sign the ICF until 28 days after the last dose of IMP:

    1. Abstinence, when it is in line with the preferred and usual lifestyle of the subject; Subject agrees to use a highly effective method of contraception should they become sexually active.
    2. Relationships with male partners who have been surgically sterilized by vasectomy (the vasectomy procedure must have been conducted at least 60 days prior to the Screening Visit).
    3. Barrier method (e.g., condom or occlusive cap) with spermicidal foam/gel/film/cream AND either hormonal contraception (oral, implanted, or injectable) or an intrauterine device or system.

    Note: Non-childbearing potential is defined as surgical sterilization (e.g., bilateral oophorectomy, hysterectomy, or tubal ligation or postmenopausal (defined as permanent cessation of menstruation for at least 12 consecutive months prior to the Screening Visit).

14. Male subjects with female partners of childbearing potential must be willing to use a highly effective method of contraception (e.g., abstinence, dual method of contraception) from the date they sign the ICF until 28 days after the last dose of IMP.

Exclusion Criteria:

Ocular Conditions - Study Eye:

1. Presence of atrophic retinal disease of causality other than AMD including myopia-related maculopathy and monogenetic macular dystrophies including pattern dystrophy and adult-onset Stargardt disease in the study eye.
2. Evidence of exudative AMD or CNV in the study eye either by history, or by Fluorescein Angiography (FA) as determined by the Reading Center at Screening.
3. History or presence of retinal vein occlusion in the study eye.
4. Presence of vitreous hemorrhage in the study eye.
5. History or presence of retinal detachment in the study eye.
6. History or presence of macular hole (stages 2 to 4) in the study eye.
7. Presence of an epiretinal membrane in the study eye that may impact visual acuity, in the opinion of the Investigator.
8. Presence of vitreomacular traction in the study eye.
9. Presence of any clinically significant corneal pathology in the study eye, including but not limited to corneal scarring, edema, dystrophy, degeneration, or other corneal abnormality that, in the opinion of the Investigator, could interfere with ocular safety, study assessments, and endpoints.
10. Severe dry eye disease, in the opinion of the Investigator.
11. Inability to obtain Color Fundus Photography (CFP), FAF, and FA of sufficient quality to be analyzed and interpreted.
12. Advanced glaucoma resulting in a cup to disc ratio of > 0.8 in the study eye.
13. Uncontrolled glaucoma in the study eye, in the opinion of the Investigator.
14. History of glaucoma filtration surgery in the study eye. Note: Minimally invasive glaucoma surgeries (e.g., MIGS) are allowable

15. Presence of visually significant cataract OR presence of significant posterior capsular opacity in the setting of pseudophakia, in the study eye.

    Note: Significant cataract is defined as ≥ +3 nuclear sclerosis based upon the scale below or any Posterior Subcapsular Cataract in the study eye. The Sponsor, or its designee, will supply the clinical trial sites with a copy of the standard photographs.

    Grade Description

    • 1 Opacity is absent
    • 2 Opacity is present, but less than Nuclear Standard Photograph #2
    • 3 Opacity is present, and as severe as or worse than Nuclear Standard Photograph #2 Source: (Chew 2010)
16. Presence of significant keratopathy or any other media or corneal opacity that would cause scattering of light or alter visual function in the study eye, especially in low luminance (LL) conditions.
17. Ocular incisional or laser surgery (including cataract surgery) in the study eye within 90 days before the Baseline Visit.
18. YAG laser capsulotomy in the study eye within 30 days before the Baseline Visit.
19. Aphakia or a secondary intraocular lens implant lacking an intact capsular bag, in the study eye.
20. History of vitrectomy surgery, submacular surgery, or any vitreoretinal surgery in the study eye.
21. Prior treatment with Visudyne® (verteporfin) ocular photodynamic therapy, external-beam radiation therapy (for intraocular conditions), or transpupillary thermotherapy in the study eye.
22. History of subthreshold laser treatment in the study eye.
23. Photobiomodulation therapy in the study eye in the past 6 months from the Baseline Visit.
24. Intravitreal drug delivery (e.g., intravitreal corticosteroid injection, anti-angiogenic drugs, or device implantation), except for a complement inhibitor, in the study eye.
25. Oral or intravitreal drug delivery of a complement inhibitor in the study eye in the past 6 months from the Baseline Visit.

26. Concurrent disease in the study eye that could require medical or surgical intervention during the trial.

    Ocular Conditions - Either Eye:

27. History or presence of diabetic retinopathy in either eye (a history of diabetes mellitus without retinopathy is not a criterion for exclusion).
28. History or presence of herpetic infection in either eye.
29. History or presence of uveitis and/or vitritis (grade trace or above) in either eye.
30. History or presence of idiopathic or autoimmune-associated uveitis in either eye.

31. Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye.

    Systemic and General Conditions:

32. History of solid organ transplant.
33. Any disease or medical condition that in the opinion of the Investigator would prevent the subject from successfully participating in the trial or might confound trial results.
34. Current use of medications known to be toxic to the lens, retina, or optic nerve (e.g., deferoxamine, chloroquine/hydroxychloroquine [Plaquenil®], tamoxifen, phenothiazines, ethambutol, digoxin, and aminoglycosides) or causing ocular surface medicamentosa.
35. Women who are pregnant, planning to become pregnant, or breastfeeding/lactating.
36. History of allergy to fluorescein that is not amenable to treatment.
37. Inability to comply with trial or follow-up procedures.
38. Active malignancy or any other cancer from which the subject has been cancer-free for \< 2 years. Localized squamous or non-invasive basal cell skin carcinomas are allowed, if appropriately treated prior to Screening.
39. History of allergic reaction to the IMP or any of its components.
40. Participation in other investigational drug or device clinical trials within 30 days or 5 half-lives (whichever is longer) of Screening; or is currently enrolled in a non-interventional clinical trial that, in the opinion of the Investigator, may be potentially confounding to the results of the current trial.
41. Prior participation in any elamipretide or bevemipretide trial.