ReNEW:Phase 3 Study of Efficacy, Safety & Pharmacokinetics of Subcutaneous Injections of Elamipretide in Subjects With Dry Age-Related Macular Degeneration (Dry AMD)

Inclusion Criteria:

A subject must meet all the inclusion criteria at the Screening and Baseline Visit (unless otherwise specified) to be eligible for inclusion in the trial.

1. Adults ≥ 55 years of age with at least 1 eye with dry AMD with photoreceptor loss,as determined at the Screening Visit by the presence of extrafoveal geographicatrophy (GA), as determined by the Reading Center primarily by fundusautofluorescence (FAF). For this trial, extrafoveal GA is defined as:

2. well-demarcated area(s) of GA

3. All GA lesions must be at least 150 μm from foveal center Note: The fellow eyemay have any of the following: no AMD, AMD without GA, AMD with GA, CNV AMD, orfoveal GA (ongoing treatment with anti-angiogenic therapies and/or complementinhibitor therapies in the fellow eye is allowable) Ocular conditions - Study Eye:

4. GA in the study eye at the Screening Visit may be multi-focal, but the cumulative GAlesion and size (by FAF, as determined by the Reading Center) must:

5. be ≥ 0.50 mm2 and ≤ 10.16 mm2 AND

6. reside completely within the FAF 30- or 35-degree image

7. BCVA by Early Treatment Diabetic Retinopathy Study (ETDRS) score of ≥ 55 letters inthe 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 > 5 letters in the studyeye

10. Sufficiently clear ocular media, adequate pupillary dilation, fixation to permitquality fundus imaging, and ability to cooperate sufficiently for adequateophthalmic visual function testing and anatomic assessment in the study eye Systemic and General Criteria:

11. Able to administer IMP or have an appropriate designee who can administer the IMP (i.e., a capable family member or a caregiver)

12. Able to provide informed consent and willing to comply with all site visits,examinations, daily IMP administrations and dosing diary entries, and otherconditions of the trial protocol

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

14. Abstinence, when it is in line with the preferred and usual lifestyle of thesubject; Subject agrees to use a highly effective method of contraceptionshould they become sexually active

15. Relationships with male partners who have been surgically sterilized byvasectomy (the vasectomy procedure must have been conducted at least 60 daysprior to the Screening Visit)

16. Barrier method (e.g., condom or occlusive cap) with spermicidalfoam/gel/film/cream AND either hormonal contraception (oral, implanted, orinjectable) or an intrauterine device or system Note: Non-childbearingpotential is defined as surgical sterilization (e.g., bilateral oophorectomy,hysterectomy, or tubal ligation) or postmenopausal (defined as permanentcessation of menstruation for at least 12 consecutive months prior to theScreening Visit).

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

Exclusion Criteria:

Subjects who meet any of the following criteria at the Screening and Baseline Visit (unless otherwise specified) will be excluded from the trial:

Ocular Conditions - Study Eye:

1. The absence of observable hyper-FAF at the margins of the GA in the study eye at theScreening Visit by the Reading Center

2. Atrophic retinal disease of causality other than AMD including myopia-relatedmaculopathy and monogenetic macular dystrophies including pattern dystrophy andadult-onset Stargardt disease in the study eye

3. Evidence of exudative AMD or CNV in the study eye by history or FA , as determinedby the Reading Center

4. Presence of retinal vein occlusion in the study eye

5. Presence of vitreous hemorrhage in the study eye

6. History of retinal detachment in the study eye

7. History of macular hole (stages 2 to 4) in the study eye

8. Presence of an epiretinal membrane and/or vitreomacular traction in the study eyethat causes distortion of the retinal contour

9. Presence of any retinal pathology in the study eye that prohibits outer retinalquantification and EZ mapping, as determined at the Screening Visit by the ReadingCenter

10. At the Screening Visit, advanced glaucoma resulting in a cup to disc ratio of > 0.8in the study eye

11. History of glaucoma filtration surgery or uncontrolled glaucoma at Baseline Visit inthe opinion of the Investigator OR currently using ≥ 3 medications (Minimallyinvasive glaucoma surgeries (e.g., MIGS) are allowable) Note: Combinationmedications count as 2 medications.

12. Presence of visually significant cataract OR presence of significant posteriorcapsular opacity in the setting of pseudophakia Note: Significant cataract isdefined as ≥ +3 nuclear sclerosis based upon the scale below or any PosteriorSubcapsular Cataract in the study eye. The Sponsor, or its designee, will supply theclinical 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 StandardPhotograph #2 Source: (Chew 2010)

13. Presence of significant keratopathy or any other media or corneal opacity that wouldcause scattering of light or alter visual function, especially in LL conditions inthe study eye

14. Ocular incisional or laser surgery (including cataract surgery) in the study eyewithin 90 days before the Baseline Visit

15. YAG laser capsulotomy in the study eye within 30 days before the Baseline Visit

16. Aphakia in the study eye

17. History of vitrectomy surgery, submacular surgery, or any vitreoretinal surgery inthe study eye

18. Prior treatment with Visudyne® (verteporfin) ocular photodynamic therapy,external-beam radiation therapy (for intraocular conditions), or transpupillarythermotherapy in the study eye

19. History of subthreshold laser treatment or other forms of photobiomodulation for AMDin the study eye

20. Intravitreal drug delivery in the past 60 days or 5-half-lives from the BaselineVisit of the injected drug whichever is longer (e.g., intravitreal corticosteroidinjection, anti-angiogenic drugs, or device implantation) in the study eye

21. Intravitreal drug delivery of a complement inhibitor in the past 6 months from theBaseline Visit in the study eye

22. Concurrent disease in the study eye that could require medical or surgicalintervention during the trial Ocular conditions - Either Eye:

23. Presence or a history of diabetic retinopathy in either eye (a history of diabetesmellitus without retinopathy is not a criterion for exclusion)

24. History of herpetic infection in either eye

25. Active uveitis and/or vitritis (grade trace or above) in either eye

26. History of idiopathic or autoimmune-associated uveitis in either eye

27. Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in eithereye Systemic Conditions:

28. Has a history of a systemic eosinophilic illness and/or an eosinophil count >1,000cells x106/L (equivalent to >1 cell x 103/μL) at the Screening Visit

29. History of solid organ transplant

30. Any disease or medical condition that in the opinion of the Investigator wouldprevent the subject from successfully participating in the trial or might confoundtrial results

31. 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)

32. eGFR of < 30 mL/min at the Screening Visit (using the CKD-EPI 2021 formula) General Conditions:

33. Participation in other investigational drug or device clinical trials within 30 daysor 5 half-lives (whichever is longer) of Screening; or is currently enrolled in anon-interventional clinical trial that, in the opinion of the Investigator, may bepotentially confounding to the results of the current trial

34. Women who are pregnant, planning to become pregnant, or breastfeeding/lactating

35. History of allergy to fluorescein that is not amenable to treatment

36. Inability to comply with trial or follow-up procedures

37. Inability to obtain CFP, FAF, and FA of sufficient quality to be analyzed andinterpreted

38. Active malignancy or any other cancer from which the subject has been cancer-freefor < 2 years. Localized squamous or non-invasive basal cell skin carcinomas areallowed, if appropriately treated prior to screening

39. History of allergic reaction to the investigational drug or any of its components

40. Prior participation in any elamipretide trial