Author’s Disclosure Block: Raman Tuli: Bayer, Roche, Apotex, Membership on an advisory panel, standing committee or board of directors; Jeffrey Heier: consultant: 4DMT, AbbVie, Adverum, Affamed, AGTC, Akouos, Alimera Sciences, Allgenesis, Alzheon, American Genomics, Annexon, Apellis, Asclepix, Aviceda, BioCryst, Bionic Vision, Biovisics, Boehringer Ingelheim, Caeregen, Clinical Trials Research Group, Cognition, Complement Therapeutics, Curacle, Daiichi Sankyo, Digital Surgery Systems, Emmecell, Frontera, Genentech, Gyroscope, InflammX, IvericBio, Janssen Pharmaceuticals, jCyte, Kriya, Nanoscope, NGM, Notal Vision, Novartis, Oculis, Ocuphire, Ocuterra Therapeutics, ONL Therapeutics, Osanni, Outlook, Oxular, Perceive Biotherapeutics, Ray Therapeutics, Regeneron, Retina Force, Retinai Medical AG, RevOpsis, Sanofi, Stealth Biotherapeutics, Supernova, Thea, Therini, Tilak, Unity Biotherapeutics, Vanotech, Vinci, Visgenx, Xequel; speaker: Annexon, Apellis, Asclepix, Bayer, Curacle, Genentech, IvericBio, Janssen Pharmaceuticals, NGM, Notal Vision, Novartis, Perceive Biotherapeutics, Regeneron, Stealth Biotherapeutics; stock and stock options: Adverum, Alzheon, Aviceda, Caeregen, jCyte, Manistee, Ocuphire, RevOpsis, Vinci, Vitranu; Chief Scientific Officer: Ocular Therapeutics; Nathan Steinle: consultant: AbbVie, Alimera, Allergan, Apellis, Bausch and Lomb, Biogen, Genentech, Novartis, Ocular Therapeutix, Opthea, Oyster Point Pharma, Regeneron, Regenxbio, Vortex Surgical, Zeiss; independent research: Genentech, Novartis, Regeneron, Regenxbio, Zeiss, Ocular Therapeutix, Opthea; speaker bureau: Alimera, Apellis, Bausch and Lomb, Biogen, Evolve Medical, Genentech, Novartis, Regeneron, Vindico Medical; stock and stock options: Vortex Surgery; David Boyer: consultant: 4DMT, Abbvie, Adverum Biotechnologies, Aerpio, Alcon, Alkahest, Allegro, Allergan. Allgenesis, Amgen, Annexon, Apellis, AsclepiX, Bausch+Lomb, Bayer, Biogen, BioMotiv, Boehringer Ingelheim, Cell Cure, Chengdu Kanghong, Clearside, Coda Therapeutics, Daiichi Sankyo, Duet, Everads Therapy, EyePoint, Galimedix, Genentech, GenSight, Glaukos Corporation, Grifols, Horizon Healthcare Group, Iconic Therapeutics, InflammX, Interface Biologics, Ionis, IvericBio, Jcyte, Kala Pharmaceuticals, Kyowa Kirin, Lumithera, Nanoscope, Neurotech USA, NGM, Notal Vision, Novartis, Ocugen, Ocular Therapeutix, Ocuphire Pharma, Opthea, Optos, Ora, Orbit Biomedical, Oxurion, Perceive, Perfuse, Ray Vision, Reazolute, RecensMedical, Regeneron, Regenxbio, Regulus, Samumed, Santen, SciFluor, Semathera, Smilebiotek, Stealth Biotherapeutics, Sun Pharmaceutical Industries, Thea, Unity; speaker: Novartis, Ocular Therapeutix; stock and stock options: InflammX, Ocugen; Ashkan Abbey: consultant: Alimera Sciences, Alcon, Eyepoint, Outlook Therapeutics, RecensMedical, Bausch; speakers bureau: Apellis, Genentech, Regeneron, Iveric Bio, Biogen, Coherus; research grants: AllerganonebbVie, Eyepoint; David Eichenbaum: consultant: Alimera, Allergan, Amaros, Annexon, Apellis, Astellas, Bausch & Lomb, Coherus, CorEvitas/Vestrum, Crinetics, EyePoint, Genentech, Kodiak, Novartis, Ocular Therapeutix, Ocuphire, Opthea, Outlook, RecensMedical, Regeneron, Regenxbio, ReVive, Roche, Samsara; speaker: Allergan, Apellis, Astellas, Bayer, EyePoint, Genentech, Regeneron; investigator: 4DMT, Aerie/Alcon, Alexion, Allegenesis, Annexon, Aviceda, Bayer, EyeBio, EyePoint, Gemini, Genentech, Gyroscope, Ionis, Janssen, Kodiak,
Mylan, NGM, Novartis, Ocular Therapeutix, OcuTerra, Opthea, ONL, RecensMedical, Regeneron, Regenxbio, Roche, Unity; equity/stockholder/options: Amaros, Boston Image Reading Center, Janssen, Network Eye, ReVive, US Retina; founder: Network Eye; Frank Holz: research grants and consulting fees: Acucela, Allergan, Apellis, Bayer, Biogen, Bioeq/Formycon, Roche/Genentech, Geuder, Heidelberg Engineering, Iveric Bio, Pixium Vision, Novartis, and Zeiss; consulting fees: Alexion, Alzheon, Annexon, Astellas, Boehringer-Ingelheim, Grayburg Vision, Janssen, LinBioscience, Stealth BioTherapeutics, Aerie, Oxurion, and Oculis; Mathew MacCumber: consultant/advisor: AbbVie, Alimera Sciences, Apellis Pharmaceuticals, Astellas, Bausch+Lomb, Cardinal Health, EyePoint Pharmaceuticals, Genentech, Novartis, Ocular Therapeutix, Regeneron; private equity/stockholder: Covalent Medical; Caroline Baumal: employee and stockholder: Apellis Pharmaceuticals; Charles Wykoff: consultant: 4DMT, AbbVie, Adverum, Aerie, Alcon, Alimera, Annexon, Apellis, Ascidian, Aviceda, Bausch+Lomb, Bayer, Boehringer Ingelheim, Cholgene, Clearside Biomedical, Curacle, Eyebiotech, EyePoint, Genentech, Gyroscope, IACTA, InGel, IvericBio, Janssen, Kiora, Kodiak, Merck, Nanoscope, NGM, Novartis, Ocular Therapeutix, Ocuphire, OcuTerra, ONL, Opthea, Oxular, PerceiveBio, Perfuse, Ray Vision, Regeneron, Regenxbio, Resonance, Roche, Sanofi, Stealth Biotherapeutics, Surrozen, Sylentis, Thea, Therini, TissueGen, Valo Health; speaker: 4DMT, Adverum, Affamed, Alexion, Alimera, Alkahest, Allgenesis, Amgen, Annexin, Annexon, Apellis, Aviceda, Bayer, Boehringer Ingelheim, Chengdu Origen, Clearside Biomedical, Curacle, Eyebiotech, EyePoint, Gemini, Genentech, GlaxoSmithKline, Gyroscope, Ionis, IvericBio, Janssen, Kodiak, Kyowa Kirin, Nanoscope, Neurotech, NGM, Novartis, Ocugen, Ocular Therapeutix, Ocuphire, OcuTerra, Opthea, Oxular, Oxurion, PerceiveBio, Pykus, Regeneron, Regenxbio, Rezolute, Roche, Sandoz, Senju, Shanghai Henlius, Skyline, Valo Health; stock and stock options: InGel, ONL, Panther, Polyphotonix, Recensmedical, TissueGen, Visgenx, Vitranu

Abstract Body
Purpose:To report 36-month efficacy and safety of pegcetacoplan in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Study Design: Patients who completed the 2-year pivotal phase 3 OAKS (NCT03525613) and DERBY (NCT03525600) studies, which evaluated intravitreal pegcetacoplan treatment for GA secondary to AMD, could enroll in the GALE 3-year open-label extension study (NCT04770545). Methods: Following the phase 3 OAKS/DERBY trials, patients could enroll in the GALE 3-year open-label extension. Pegcetacoplan-treated patients in OAKS/DERBY continued the same regimen, monthly (PM) or every other month (PEOM). Patients receiving sham crossed over to pegcetacoplan at the samedosing interval: sham monthly to PM or sham every other month to PEOM.Both subfoveal and nonsubfoveal GA were included. Safety and efficacy data over 36 months are reported. Results: Overall, 83% (n=782) of patients who completed OAKS/DERBY entered GALE and 92% completed the first 12 months. Between Months 24 and 36, pegcetacoplan reduced GA growth vs projected sham in nonsubfoveal GA by 42% with PM (p<0.0001) and 28% with PEOM (p=0.0015), and in the overall population by 35% with PM and 24% with PEOM (both p<0.0001). In microperimetry,eyes treated with PM for 36 months had fewer new absolute scotomatous points compared to the pooled sham crossover arm (-2.9, confidence interval [CI] -5.3, -0.6, p=0.0156).Conversion of all 4 central macular loci to absolute scotomas occurred in 54 (34.8%), 59 (38.8%), and 64 (43.8%) patients in the PM, PEOM, and sham pooled arms, respectively. PM and PEOM significantly delayed occurrence of absolute scotomas vs sham in the central macular 4 loci (PM: HR vs sham: 0.66 [34% risk reduction]; 95% confidence interval [CI]: 0.46, 0.96; p=0.0282; PEOM: HR vs sham: 0.64 [36% risk reduction]; 95% CI: 0.45, 0.92; p=0.0164) and in a second analysis of 16 loci (PM:
HR vs sham: 0.57 [43% risk reduction]; 95% CI: 0.33, 0.96; p=0.0361; PEOM: HR vs sham: 0.52 [48% risk reduction]; 95% CI: 0.32, 0.85; p=0.0084).The safety profile in the first 12 months was consistent with OAKS/DERBY. The estimated rate of post-marketing events of vasculitis remains ~1/4,000 per injection (>330,000 injections through June 2024) in the real-world setting; this appears to bea first injection phenomenon. Conclusions: Pegcetacoplan long-term efficacy and safety were demonstrated in patients with GA.GALE is the largest long-term extension inGAand these 36-month results highlight the benefit of C3/C3b complement inhibition with pegcetacoplan.