A Phase 2, Randomized, Placebo Controlled, Multicenter, Masked Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacodynamics of Multidose APL 3007 in Combination With Syfovre/Pegcetacoplan (APL-2) in Patients Diagnosed With Geographic Atrophy Secondary to Age Related Macular Degeneratio

Inclusion Criteria:

• The study eye must meet all inclusion criteria. If both eyes meet the inclusioncriteria, the eye with better normal luminance visual acuity at the screening visitwill be designated as the study eye. If both eyes have the same visual acuity, theright eye will be used as the study eye.

• Aged ≥60 years

• Clinical diagnosis of GA of the macula secondary to AMD in one or both eyes, asdetermined by the investigator and confirmed by the reading center

• NL-BCVA of 50 letters or better using early treatment diabetic retinopathy study (ETDRS) charts (approximately 20/100 Snellen equivalent)

• Adequate clarity of ocular media, adequate pupillary dilation, and fixation topermit the collection of good quality images in the study eye as determined by theinvestigator

• Prior treatment for GA in the study eye using Syfovre at 6-8 weeks interval for atleast 6 months but no more than 24 months. Participants will be included if theparticipant has had at least 2 Syfovre injections in the last 6 months beforescreening.

• The GA lesion in at least 1 eye (designated as the study eye) must meet thefollowing criteria as determined by the central reading center's OCT based RPEassessment of imaging at screening:

• Total GA area must be ≥2.5 and ≤17.5 mm2 (1-7 disk areas [DA])

• If GA is multifocal, at least 1 focal lesion must be ≥1.25 mm2 (0.5 DA), withthe overall aggregate area of GA as specified above in 7a

• The entire GA lesion must be completely visualized in the field of view of theOCT, with the GA RPE lesion border >500 µm from the edge of the imaging windowor any areas of peripapillary atrophy.

• Nonsubfoveal lesion with border of GA lesion not encroaching center of thefovea. Distance of GA RPE lesion from center of the fovea >0 based on OCTimaging.

• Presence of any pattern of hyperautofluorescence based on FAF imaging in thejunctional zone of GA. Absence of hyperautofluorescence (ie, pattern = none) isexclusionary.

• Documented evidence of vaccination within 5 years prior to screening, or willing toinitiate vaccinations at least 14 days prior to dosing against:

• Streptococcus pneumoniae (with a pneumococcal conjugate vaccine 15 [PCV15] or 20 [PCV20] or with pneumococcal polysaccharide vaccine 23 [PPSV23]),

• Haemophilus influenzae (type B) (with Hib vaccine),

• Neisseria meningitidis types A, C, W, and Y (with a quadrivalent meningococcalconjugate vaccine [eg, Menactra or MenQuadfi]), and

• Neisseria meningitidis type B (with a meningococcal serogroup B vaccine [eg,Bexsero])

Female participants must be:

• Women of non-childbearing potential (WONCBP), or

• Women of childbearing potential (WOCBP) with a negative serum pregnancy test atscreening and must agree to use protocol defined methods of contraception for theduration of the study and refrain from breastfeeding for the duration of the study (see Section 10.9.5.1)

Male participants must be surgically sterile or must agree to use highly effective contraception from screening through the duration of the study

Willing and able to provide informed consent and adhere to the study visit schedule and other protocol requirements

Exclusion Criteria:

1. Uncontrolled, clinically relevant history of any gastrointestinal, renal, hepatic,bronchopulmonary, neurological, psychiatric, cardiovascular, endocrinological,hematological or allergic disease, metabolic disorder, or cancer

2. History or presence of hepatic cirrhosis or other liver disease that may increasethe risk of drug-induced liver injury

3. History or presence of systemic autoimmune disorders, with the exception of wellcontrolled Hashimoto's thyroiditis

4. History of allergy, hypersensitivity, or serious adverse reaction to siRNA therapyor related compounds, or allergy to any of the components of the study drug

5. Clinically meaningful abnormalities on diagnostic and laboratory testing must beadjudicated by the sponsor's medical monitor and include:

6. CardiacSustained resting heart rate outside of range of 40 to 100 beats/minute, or aheart rhythm that is not sinus rhythm, confirmed on repeat testing within amaximum of 30 minutes, at screeningHistory or evidence of hereditary short QT syndromeFridericia's corrected QT interval (QTcF) >480 milliseconds, or the PR intervaloutside the range of 120 to 220 milliseconds, confirmed on repeat testingwithin a maximum of 30 minutes at screeningAny clinically relevant features of acute coronary syndrome (unstable angina,myocardial infarction)Any other ECG parameters outside of age-adjusted normative range

7. HepaticAST or ALT >1.3 × ULNTotal bilirubin >1.1 × ULNAny 2 LFTs >1.1 × ULNAny other LFT parameters outside of age-adjusted normative range

8. Renal Estimated glomerular filtration rate of less than <45 mL/min/m2 as calculated by theChronic Kidney Disease-Epidemiology Collaboration (CKD- EPI) creatinine equation foradults Any other renal function parameters outside of age-adjusted normative range

9. History or presence of malignancy (except history of basal or squamous cellcarcinoma of the skin) that has not been successfully treated ≥1 year prior toenrollment

10. History or presence of recurrent or unexplained infections, HIV infection, hepatitisB, hepatitis C, or meningococcal infection

11. Participants with fever (defined as temperature >100.4 °F/38 °C) or any acuteinfection (including COVID-19 infection or infection requiring antibiotic treatment)within 30 days of screening until dosing

12. Evidence of ongoing drug or alcohol abuse or dependence, in the opinion of theinvestigator

13. Intention to donate sperm during this study or within 90 days after the last dose ofstudy drug

14. Prior administration of APL-3007

15. Participation in an investigational product or medical device study within 5half-lives of the investigational product before the screening visit

16. Has poor peripheral venous access or any abnormal skin conditions or potentiallyobscuring tattoos, pigmentation, or lesions in the area intended for SC injectionthat would interfere with SC injections or assessments of injection localtolerability

17. Any condition which could interfere with, or the treatment for which might interferewith, the conduct of the study or which would, in the opinion of the investigator ormedical monitor(s), unacceptably increase the participant's risk by participating inthe study

18. Has received a live vaccination (excluding seasonal flu vaccination) within 30 daysprior to the first dose administration

19. Women who are pregnant or breastfeeding

20. Medical or psychiatric conditions that, in the opinion of the investigator, makeconsistent follow-up over the treatment period unlikely, or would make theparticipant an unsafe study candidate Ocular specific exclusion criteria apply to the study eye only, unless otherwisespecified.

21. GA secondary to a condition other than AMD such as Stargardt disease, cone roddystrophy or toxic maculopathies like plaquenil maculopathy in either eye

22. Any history of CNV (active or nonexudative/quiescent) in the study eye associatedwith AMD or any other cause, including any evidence of RPE rips, double layer sign,or evidence of neovascularization anywhere based on SD-OCT imaging and fluoresceinangiography as assessed by the reading center

23. Presence of an active ocular disease that, in the opinion of the investigator,compromises or confounds visual function, including but not limited to, uveitis,other macular diseases (eg, clinically significant epiretinal membrane, fullthickness macular hole or uncontrolled glaucoma/ocular hypertension); benignconditions in the opinion of the investigator such as peripheral retina dystrophyare not exclusionary.

24. History of IVT injection in the study eye within 3 months prior to the screeningvisit, with the exception of IVT Syfovre

25. History of any previous investigational product for GA treatment in either eyewithin 3 months (or 5 half-lives of the investigational drug, whichever is longer)prior to the screening visit

26. History of laser therapy in the macular region

27. Any ocular condition other than GA secondary to AMD that may require surgery ormedical intervention during the study period or, in the opinion of the investigator,could compromise visual function during the study period