Treatment of age-related macular degeneration and other eye diseases with apolipoprotein mimetics

Abstract

The present disclosure provides apolipoprotein (apo) mimetics useful for the treatment of age-related macular degeneration (AMD) and other eye disorders. The apo mimetics can be peptides/polypeptides that mimic, e.g., the lipid-clearing action of apolipoproteins such as apoA-I and apoE. The apo mimetics can exert other beneficial effects, such as reduction of inflammation, oxidative stress and neovascularization. The apo mimetics can be used to treat any stages (including the early, intermediate and advance stages) of AMD, and any phenotypes of AMD, including geographic atrophy (GA) (including non-central GA and central GA) and neovascularization (NV) (including types 1, 2 and 3 NV). The apo mimetics can be used alone or in conjunction with other therapeutic agents, such as a complement inhibitor and/or an anti-angiogenic agent, to treat AMD, including atrophic AMD and neovascular AMD, and other eye disorders.

What is claimed is: 
     
         1 . A method of treating age-related macular degeneration (AMD), comprising administering to a subject in need of treatment a therapeutically effective amount of an apolipoprotein (apo) mimetic, wherein the apo mimetic is administered locally to, into, in or around the eye in a dose from about 0.1 or 0.3 mg to about 1.5 mg per administration, or in a total dose from about 0.5 or 1 mg to about 10 mg over a period of about 6 months. 
     
     
         2 . The method of  claim 1 , wherein the apo mimetic comprises, or is, an apoA-I mimetic. 
     
     
         3 . The method of  claim 2 , wherein the apoA-I mimetic comprises, or is, 4F or a variant or salt (e.g., acetate salt) thereof. 
     
     
         4 . The method of  claim 3 , wherein the apoA-I mimetic comprises, or is, L-4F or D-4F, each optionally having a protecting group at the N-terminus and/or the C-terminus [e.g., Ac-DWFKAFYDKVAEKFKEAF-NH 2  (SEQ. ID. NO. 13)]. 
     
     
         5 . The method of any one of the preceding claims, wherein the apo mimetic comprises, or is, an apoE mimetic. 
     
     
         6 . The method of  claim 5 , wherein the apoE mimetic comprises, or is, AEM-28-14 or a variant or salt thereof. 
     
     
         7 . The method of any one of the preceding claims, wherein the apo mimetic (e.g., L-4F) is administered locally in a dose of about 0.1-0.5 mg, 0.5-1 mg, 1-1.5 mg, 0.1-0.3 mg, 0.3-0.5 mg, 0.5-0.75 mg, 0.75-1 mg, 1-1.25 mg or 1.25-1.5 mg (e.g., about 0.1-0.5 mg or 0.5-1 mg) per administration (e.g., per injection). 
     
     
         8 . The method of any one of the preceding claims, wherein the apo mimetic (e.g., L-4F) is administered locally in a total dose of about 0.5 or 1-5 mg, 5-10 mg, 0.5 or 1-3 mg, 3-5 mg, 5-7.5 mg or 7.5-10 mg (e.g., about 0.5-3 mg or 3-5 mg) over a period of about 6 months. 
     
     
         9 . The method of any one of the preceding claims, wherein the apo mimetic (e.g., L-4F) is administered locally in a total dose of about 1 or 2-20 mg or 5-15 mg for the whole treatment regimen. 
     
     
         10 . The method of  claim 9 , wherein the apo mimetic (e.g., L-4F) is administered locally in a total dose of about 1-5 mg, 5-10 mg, 10-15 mg, 15-20 mg, 1-3 mg, 3-5 mg, 5-7.5 mg, 7.5-10 mg, 10-12.5 mg, 12.5-15 mg, 15-17.5 mg or 17.5-20 mg (e.g., about 1-5 mg or 5-10 mg) for the whole treatment regimen. 
     
     
         11 . The method of any one of the preceding claims, wherein the dose per administration, the total dose over a period of about 6 months, and the total dose for the whole treatment regimen are per treated eye. 
     
     
         12 . The method of any one of the preceding claims, wherein the apo mimetic (e.g., L-4F) is administered locally by injection (e.g., intravitreal, subconjunctival, subretinal or sub-Tenon's injection), eye drop or implant (e.g., intravitreal, intraaqueous, subretinal or sub-Tenon's implant). 
     
     
         13 . The method of  claim 12 , wherein the apo mimetic (e.g., L-4F) is administered locally by injection (e.g., intravitreal, subconjunctival, subretinal or sub-Tenon's injection). 
     
     
         14 . The method of  claim 13 , wherein the apo mimetic (e.g., L-4F) is administered locally by injection (e.g., intravitreal injection) in a dose concentration from about 1, 2, 3, 4 or 5 mg/mL to about 12 or 15 mg/mL. 
     
     
         15 . The method of  claim 14 , wherein the apo mimetic (e.g., L-4F) is administered locally by injection (e.g., intravitreal injection) in a dose concentration of about 1-4 mg/mL, 4-8 mg/mL, 8-12 mg/mL, 1-5 mg/mL, 5-10 mg/mL, 10-15 mg/mL, 1-3 mg/mL, 3-5 mg/mL, 5-7.5 mg/mL, 6-8 mg/mL, 7.5-10 mg/mL, 10-12.5 mg/mL or 12.5-15 mg/mL (e.g., about 1-5 mg/mL, 5-10 mg/mL or 6-8 mg/mL). 
     
     
         16 . The method of any one of  claims 13  to  15 , wherein the apo mimetic (e.g., L-4F) is locally administered by injection (e.g., intravitreal injection) in a dose volume of about 50-150 μL or 50-100 μL. 
     
     
         17 . The method of  claim 16 , wherein the apo mimetic (e.g., L-4F) is administered locally by injection (e.g., intravitreal injection) in a dose volume of about 50-75 μL, 75-100 μL, 100-125 μL or 125-150 μL, or about 50 μL, 75 μL, 100 μL, 125 μL or 150 μL (e.g., about 100 μL). 
     
     
         18 . The method of any one of  claims 13  to  17 , wherein the apo mimetic (e.g., L-4F) is locally administered by injection (e.g., intravitreal injection) once every month (4 weeks) or 1.5 months (6 weeks). 
     
     
         19 . The method of any one of  claims 13  to  17 , wherein the apo mimetic (e.g., L-4F) is locally administered by injection (e.g., intravitreal injection) once every 2 months (8 weeks), 2.5 months (10 weeks) or 3 months (12 weeks). 
     
     
         20 . The method of any one of  claims 13  to  17 , wherein the apo mimetic (e.g., L-4F) is locally administered by injection (e.g., intravitreal injection) once every 4, 5 or 6 months. 
     
     
         21 . The method of any one of  claims 13  to  20 , wherein the apo mimetic (e.g., L-4F) is locally administered in a total of about 15 or less, 12 or less, 9 or less, 6 or less, or 3 or less injections (e.g., intravitreal injections). 
     
     
         22 . The method of  claim 21 , wherein the apo mimetic (e.g., L-4F) is administered locally in a total of about 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4 or 3 (e.g., about 3-6 or 7-10) injections (e.g., intravitreal injections). 
     
     
         23 . The method of any one of the preceding claims, wherein the apo mimetic (e.g., L-4F) is administered locally (e.g., by intravitreal injection) in a higher dose and/or more frequently in the early phase of treatment. 
     
     
         24 . The method of any one of the preceding claims, wherein the treatment regimen with the apo mimetic (e.g., L-4F) lasts for about 36 months or less, 30 months or less, 24 months or less, 18 months or less, 12 months or less, or 6 months or less. 
     
     
         25 . The method of  claim 24 , wherein the treatment regimen with the apo mimetic (e.g., L-4F) lasts for about 6-12, 12-18, 18-24, 24-30 or 30-36 (e.g., for about 6-12 or 12-24) months. 
     
     
         26 . The method of any one of the preceding claims, wherein the apo mimetic (e.g., L-4F) is administered at least in the advanced (late) stage of AMD (e.g., to treat central geographic atrophy [GA] and/or to prevent or forestall neovascular AMD, and/or to treat neovascular AMD). 
     
     
         27 . The method of  claim 26 , wherein the apo mimetic (e.g., L-4F) is administered locally by injection (e.g., intravitreal, subconjunctival, subretinal or sub-Tenon's injection) once every about 4-8 weeks or 4-6 weeks, in a total of about 8-12 injections or more, in a dose up to about 1-1.5 mg per injection, or in a total dose up to about 15-20 mg for the entire treatment regimen, or any combination or all thereof, in advanced AMD. 
     
     
         28 . The method of any one of the preceding claims, wherein the apo mimetic (e.g., L-4F) is administered at least in the intermediate stage of AMD (e.g., to treat non-central GA and/or to prevent or forestall central GA and/or neovascular AMD, or administered in the initial phase of intermediate AMD to prevent or forestall non-central GA). 
     
     
         29 . The method of  claim 28 , wherein the apo mimetic (e.g., L-4F) is administered locally by injection (e.g., intravitreal, subconjunctival, subretinal or sub-Tenon's injection) once every about 4-12 or 4-8 weeks, in a total of about 4-8 injections or more, in a dose up to about 0.5-1 mg or 1-1.5 mg per injection, or in a total dose up to about 10-15 mg or more for the entire treatment regimen, or any combination or all thereof, in intermediate AMD. 
     
     
         30 . The method of any one of the preceding claims, wherein the apo mimetic (e.g., L-4F) is administered at least in the early stage of AMD (e.g., to prevent or forestall non-central GA). 
     
     
         31 . The method of  claim 30 , wherein the apo mimetic (e.g., L-4F) is administered locally by injection (e.g., intravitreal, subconjunctival, subretinal or sub-Tenon's injection) less frequently (e.g., an injection every about 3, 4 or 6 months), in a smaller total number of injections (e.g., about 1, 2 or 3 injections) or in a higher dose per injection (e.g., about 0.5-1 mg or 1-1.5 mg per injection), or any combination or all thereof, in early AMD. 
     
     
         32 . The method of any one of the preceding claims, wherein the apo mimetic (e.g., L-4F) is administered locally (e.g., by intravitreal injection) more frequently (which can result in a greater total number of administrations) and/or in a higher dose (higher dose per administration and/or higher total dose for the entire treatment regimen) the later the stage of AMD or the more severe the AMD condition. 
     
     
         33 . The method of any one of the preceding claims, wherein the apo mimetic (e.g., L-4F) is administered locally (e.g., by intravitreal injection) in a fixed-routine regimen, an as-needed regimen or a treat-and-extend regimen. 
     
     
         34 . The method of any one of the preceding claims, wherein the apo mimetic (e.g., L-4F) is administered locally via a composition comprising about 75-95% (e.g., about 90%) of the apo mimetic and about 5-25% (e.g., about 10%) of the corresponding apolipoprotein (e.g., apoA-I) or an active portion or domain thereof by weight or molarity relative to their combined amount. 
     
     
         35 . The method of any one of the preceding claims, wherein the apo mimetic (e.g., L-4F) is administered locally as a composition comprising one or more excipients that inhibit peptide/protein aggregation, increase peptide/protein solubility, reduce solution viscosity or increase peptide/protein stability, or any combination or all thereof. 
     
     
         36 . The method of any one of the preceding claims, wherein the apo mimetic (e.g., L-4F) is administered locally via a sustained-release composition. 
     
     
         37 . The method of any one of the preceding claims, further comprising administering one or more additional therapeutic agents. 
     
     
         38 . The method of  claim 37 , wherein the one or more additional therapeutic agents are selected from the group consisting of anti-dyslipidemic agents, PPAR-α agonists, PPAR-δ agonists, PPAR-γ agonists, anti-amyloid agents, inhibitors of lipofuscin or components thereof, antioxidants, neuroprotectors (neuroprotectants), apoptosis inhibitors, necrosis inhibitors, C-reactive protein (CRP) inhibitors, inhibitors of the complement system or components (e.g., proteins) thereof, inhibitors of inflammasomes, anti-inflammatory agents, immunosuppressants, modulators of matrix metalloproteinases (MMPs), anti-angiogenic agents, and RPE cell replacement therapies. 
     
     
         39 . A method of preventing, delaying the onset of, slowing the progression of or reducing the extent of vision impairment or loss associated with age-related macular degeneration (AMD), comprising administering to a subject in need of treatment a therapeutically effective amount of an apolipoprotein (apo) mimetic according to any one of  claims 1  to  38 . 
     
     
         40 . The method of  claim 39 , wherein the AMD is atrophic AMD (including noncentral and/or central geographic atrophy) or neovascular AMD (including types 1, 2 and/or 3 neovascularization). 
     
     
         41 . A method of treating age-related macular degeneration (AMD), comprising administering to a subject in need of treatment a therapeutically effective amount of an apolipoprotein (apo) mimetic according to any one of  claims 1  to  38  and a therapeutically effective amount of an anti-angiogenic agent. 
     
     
         42 . The method of  claim 41 , wherein the apo mimetic comprises, or is, an apoA-I mimetic (e.g., L-4F or D-4F) and/or an apoE mimetic (e.g., AEM-28-14). 
     
     
         43 . The method of  claim 41  or  42 , wherein the anti-angiogenic agent comprises, or is, an agent that inhibits the action of a vascular endothelial growth factor (an anti-VEGF agent), and/or an agent that inhibits the action of a platelet-derived growth factor (an anti-PDGF agent). 
     
     
         44 . The method of  claim 43 , wherein the anti-VEGF agent is selected from the group consisting of squalamine, PAN-90806, anti-VEGF antibodies and fragments thereof (e.g., bevacizumab [AVASTIN®], ranibizumab [LUCENTIS®], ESBA1008 and ESBA903), anti-VEGF aptamers (e.g., pegaptanib [MACUGEN®]), anti-VEGF designed ankyrin repeat proteins (DARPins) (e.g., abicipar pegol), soluble receptors for VEGFs (e.g., VEGFR1), soluble fusion proteins containing one or more extracellular domains of one or more VEGFRs (e.g., aflibercept [EYLEA®] and conbercept), and combinations thereof. 
     
     
         45 . The method of  claim 44 , wherein the anti-VEGF agent comprises, or is, aflibercept, bevacizumab or ranibizumab, or any combination or all thereof. 
     
     
         46 . The method of any one of  claims 41  to  45 , wherein the anti-angiogenic agent (e.g., an anti-VEGF agent) is administered in a frequency less than the conventional or recommended dosing frequency, and/or in a dose less than the conventional or recommended dose, for the anti-angiogenic agent in the absence of treatment with the apo mimetic (e.g., L-4F). 
     
     
         47 . The method of  claim 46 , wherein the anti-angiogenic agent (e.g., an anti-VEGF agent) is administered (e.g., by intravitreal injection) at least about 1.5, 2, 3, 4, 5 or 6 (e.g., at least about 2) times less frequently than the conventional or recommended dosing frequency for the anti-angiogenic agent in the absence of treatment with the apo mimetic (e.g., L-4F). 
     
     
         48 . The method of  claim 46  or  47 , wherein the anti-angiogenic agent (e.g., an anti-VEGF agent) is administered (e.g., by intravitreal injection) in a dose at least about 10%, 20%, 30%, 40%, 50%, 60%, 70% or 80% (e.g., at least about 20%), or about 10-30%, 30-50% or 50-70%, less than the conventional or recommended dose for the anti-angiogenic agent in the absence of treatment with the apo mimetic (e.g., L-4F). 
     
     
         49 . The method of any one of  claims 46  to  48 , wherein treatment with the apo mimetic (e.g., L-4F) reduces the total number of times (e.g., the total number of injections) the anti-angiogenic agent (e.g., an anti-VEGF agent) is administered. 
     
     
         50 . The method of  claim 49 , wherein the anti-angiogenic agent (e.g., an anti-VEGF agent) is administered (e.g., by intravitreal injection) no more than about 20, 18, 15, 12 or 10 times. 
     
     
         51 . The method of any one of  claims 46  to  50 , wherein treatment with the apo mimetic (e.g., L-4F) and the anti-angiogenic agent (e.g., an anti-VEGF agent) has a synergistic effect. 
     
     
         52 . The method of any one of  claims 46  to  51 , wherein:
 the anti-angiogenic agent comprises, or is, aflibercept (EYLEA®); and 
 aflibercept is administered (e.g., by intravitreal injection) in a dose of about 1-1.5 mg or 1.5-2 mg once every 3, 4, 5 or 6 months, optionally after being administered in a dose of about 1-1.5 mg or 1.5-2 mg once every month for the first 1, 2 or 3 months or once every 6 weeks for the first 1.5 or 3 months,
 compared to the conventional or recommended dose and dosing frequency for aflibercept of 2 mg administered by intravitreal injection once every 2 months after administration of 2 mg once every month for the first 3 months in the absence of treatment with the apo mimetic (e.g., L-4F). 
 
 
     
     
         53 . The method of any one of  claims 46  to  51 , wherein:
 the anti-angiogenic agent comprises, or is, aflibercept; and 
 aflibercept is administered (e.g., by intravitreal injection) in a dose of about 1-1.25 mg, 1.25-1.5 mg or 1.5-1.75 mg in a frequency substantially similar to or the same as the conventional or recommended dosing frequency for aflibercept in the absence of treatment with the apo mimetic (e.g., L-4F). 
 
     
     
         54 . The method of any one of  claims 46  to  51 , wherein:
 the anti-angiogenic agent comprises, or is, ranibizumab (LUCENTIS®); and 
 ranibizumab is administered (e.g., by intravitreal injection) in a dose of about 0.2-0.3 mg, 0.3-0.4 mg or 0.4-0.5 mg once every 2, 3, 4, 5 or 6 months, optionally after being administered in a dose of about 0.2-0.3 mg, 0.3-0.4 mg or 0.4-0.5 mg once every month for the first 1, 2 or 3 months or once every 6 weeks for the first 1.5 or 3 months,
 compared to the conventional or recommended dose and dosing frequency for ranibizumab of 0.5 mg administered by intravitreal injection once every month in the absence of treatment with the apo mimetic (e.g., L-4F). 
 
 
     
     
         55 . The method of any one of  claims 46  to  51 , wherein:
 the anti-angiogenic agent comprises, or is, ranibizumab; and 
 ranibizumab is administered (e.g., by intravitreal injection) in a dose of about 0.2-0.3 mg or 0.3-0.4 mg once every month. 
 
     
     
         56 . The method of any one of  claims 46  to  51 , wherein:
 the anti-angiogenic agent comprises, or is, bevacizumab (AVASTIN®); and 
 bevacizumab is administered (e.g., by intravitreal injection) in a dose of about 0.5-0.75 mg, 0.75-1 mg or 1-1.25 mg once every 2, 3, 4, 5 or 6 months, optionally after being administered in a dose of about 0.5-0.75 mg, 0.75-1 mg or 1-1.25 mg once every month for the first 1, 2 or 3 months or once every 6 weeks for the first 1.5 or 3 months,
 compared to the conventional or recommended dose and dosing frequency for bevacizumab for the treatment of AMD of about 1.25 mg administered by intravitreal injection once every month in the absence of treatment with the apo mimetic (e.g., L-4F). 
 
 
     
     
         57 . The method of any one of  claims 46  to  51 , wherein:
 the anti-angiogenic agent comprises, or is, bevacizumab; and 
 bevacizumab is administered (e.g., by intravitreal injection) in a dose of about 0.5-0.75 mg or 0.75-1 mg once every month. 
 
     
     
         58 . The method of any one of  claims 46  to  51 , wherein the anti-angiogenic agent (e.g., an anti-VEGF agent) is administered (e.g., by intravitreal injection) once every 2, 3, 4, 5 or 6 months. 
     
     
         59 . The method of any one of  claims 41  to  58 , wherein the anti-angiogenic agent (e.g., an anti-VEGF agent) is administered locally to, into, in or around the eye, such as by injection (e.g., intravitreal, subconjunctival, subretinal or sub-Tenon's injection), eye drop or implant (e.g., intravitreal, intraaqueous, subretinal or sub-Tenon's implant). 
     
     
         60 . The method of any one of  claims 41  to  59 , wherein the anti-angiogenic agent (e.g., an anti-VEGF agent) is administered to treat or slow the progression of neovascular (wet) AMD, including types 1, 2 and 3 neovascularization. 
     
     
         61 . The method of any one of  claims 41  to  60 , wherein the anti-angiogenic agent (e.g., an anti-VEGF agent) is administered at least in the advanced (late) stage of AMD to prevent, delay the onset of, or slow the progression to neovascular AMD. 
     
     
         62 . The method of any one of  claims 41  to  61 , wherein the apo mimetic (e.g., L-4F) is administered at least in the advanced stage of AMD. 
     
     
         63 . The method of  claim 62 , wherein the apo mimetic (e.g., L-4F) is administered to treat central geographic atrophy, and/or to prevent, delay the onset of, or slow the progression of neovascular AMD (including types 1, 2 and 3 neovascularization). 
     
     
         64 . The method of any one of  claims 41  to  63 , wherein the anti-angiogenic agent (e.g., an anti-VEGF agent) is administered in a fixed-routine regimen, an as-needed regimen or a treat-and-extend regimen. 
     
     
         65 . The method of any one of  claims 41  to  64 , wherein the apo mimetic (e.g., L-4F) and the anti-angiogenic agent (e.g., an anti-VEGF agent) are administered in separate compositions. 
     
     
         66 . The method of any one of  claims 41  to  64 , wherein the apo mimetic (e.g., L-4F) and the anti-angiogenic agent (e.g., an anti-VEGF agent) are administered in the same composition. 
     
     
         67 . A method of treating age-related macular degeneration (AMD), comprising administering to a subject in need of treatment a therapeutically effective amount of an apolipoprotein (apo) mimetic according to any one of  claims 1  to  38  and a therapeutically effective amount of a complement inhibitor. 
     
     
         68 . The method of  claim 67 , wherein the apo mimetic comprises, or is, an apoA-I mimetic (e.g., L-4F or D-4F) and/or an apoE mimetic (e.g., AEM-28-14). 
     
     
         69 . The method of  claim 67  or  68 , wherein the apo mimetic (e.g., L-4F) and the complement inhibitor are administered to treat geographic atrophy (GA). 
     
     
         70 . The method of  claim 69 , wherein the apo mimetic (e.g., L-4F) and the complement inhibitor are administered to prevent, delay the onset of, or slow the progression of central GA and/or non-central GA. 
     
     
         71 . The method of  claim 69  or  70 , wherein the apo mimetic (e.g., L-4F) and the complement inhibitor are administered at least in the advanced (late) stage of atrophic (dry) AMD to treat or slow the progression of central GA, and/or to prevent or delay the onset of neovascular AMD. 
     
     
         72 . The method of any one of  claims 69  to  71 , wherein the apo mimetic (e.g., L-4F) and the complement inhibitor are administered at least in the intermediate stage of AMD to treat or slow the progression of non-central GA, and/or to prevent or delay the onset of central GA and/or neovascular AMD. 
     
     
         73 . The method of any one of  claims 69  to  72 , wherein the apo mimetic (e.g., L-4F) and the complement inhibitor are administered at least in the early stage of AMD or the initial phase of intermediate AMD to prevent or delay the onset of non-central GA. 
     
     
         74 . The method of any one of  claims 67  to  73 , wherein the complement inhibitor is selected from the group consisting of anti-complement factor B (CFB) antibodies and fragments thereof (e.g., TA106), anti-CFD antibodies and fragments thereof (e.g., lampalizumab), C3 inhibitors (e.g., compstatin and derivatives thereof [e.g., POT-4], mycophenolic acid-glucosamine conjugates, and soluble forms of proteins or fragments thereof [e.g., CR1, decay acceleration factor and membrane cofactor protein]), anti-C3b/iC3b antibodies and fragments thereof (e.g., 3E7), anti-05 antibodies and fragments thereof (e.g., eculizumab and LFG316), anti-05 aptamers (e.g., ARC1905 [Zimura®]), other C5 inhibitors (e.g., Coversin), C5a receptor antagonists (e.g., JPE-1375, JSM-7717, PMX-025, PMX-53, and anti-05aR antibodies and fragments thereof [e.g., neutrazimab]), inhibitors of the alternative complement pathway (e.g., sCR1, TT30 and zinc), inhibitors of the classic complement pathway (e.g., sCR1), inhibitors of the lectin complement pathway (e.g., inhibitors of mannose-associated serine proteases [MASPs], such as anti-MASP antibodies and fragments thereof [e.g., OMS721]), inhibitors of membrane attack complex (MAC) formation (e.g., zinc, CD59 and modified CD59 having a glycolipid anchor), and analogs, derivatives, fragments, salts and combinations thereof. 
     
     
         75 . The method of  claim 74 , wherein the complement inhibitor comprises, or is, lampalizumab, LFG316 or ARC1905, or any combination or all thereof. 
     
     
         76 . The method of  claim 75 , wherein the complement inhibitor comprises, or is, lampalizumab. 
     
     
         77 . The method of  claim 76 , wherein the subject has a mutation in the gene encoding complement factor I (CFI). 
     
     
         78 . The method of any one of  claims 67  to  77 , wherein treatment with the apo mimetic (e.g., L-4F) and the complement inhibitor (e.g., lampalizumab) slows the progression of central GA and/or non-central GA (e.g., reduces the rate of GA progression, or reduces the GA lesion area or size) by at least about 10%, 20%, 30%, 40%, 50%, 60%, 70% or 80% (e.g., by at least about 20% or 40%), or by about 20-40%, 40-60% or 60-80%. 
     
     
         79 . The method of any one of  claims 67  to  78 , wherein treatment with the apo mimetic (e.g., L-4F) and the complement inhibitor (e.g., lampalizumab) slows the progression of central GA and/or non-central GA (e.g., reduces the rate of GA progression, or reduces the GA lesion area or size) at least about 10%, 20%, 30%, 50%, 100%, 150%, 200% or 300% (e.g., at least about 20% or 30%), or about 10-30%, 30-50%, 50-100%, 100-200% or 200-300% (e.g., about 50-100%), more than treatment with the complement inhibitor in the absence of treatment with the apo mimetic. 
     
     
         80 . The method of any one of  claims 67  to  79 , wherein the complement inhibitor (e.g., lampalizumab) is administered in a frequency less than the conventional or recommended dosing frequency, and/or in a dose less than the conventional or recommended dose, for the complement inhibitor in the absence of treatment with the apo mimetic (e.g., L-4F). 
     
     
         81 . The method of  claim 80 , wherein the complement inhibitor (e.g., lampalizumab) is administered (e.g., by intravitreal injection) at least about 1.5, 2, 3, 4, 5 or 6 (e.g., at least about 2) times less frequently than the conventional or recommended dosing frequency for the complement inhibitor in the absence of treatment with the apo mimetic (e.g., L-4F). 
     
     
         82 . The method of  claim 80  or  81 , wherein the complement inhibitor (e.g., lampalizumab) is administered (e.g., by intravitreal injection) in a dose at least about 10%, 20%, 30%, 40%, 50%, 60%, 70% or 80% (e.g., at least about 20%), or about 10-30%, 30-50% or 50-70%, less than the conventional or recommended dose for the complement inhibitor in the absence of treatment with the apo mimetic (e.g., L-4F). 
     
     
         83 . The method of any one of  claims 80  to  82 , wherein treatment with the apo mimetic (e.g., L-4F) reduces the total number of times (e.g., the total number of injections) the complement inhibitor (e.g., lampalizumab) is administered. 
     
     
         84 . The method of  claim 83 , wherein the complement inhibitor (e.g., lampalizumab) is administered (e.g., by intravitreal injection) no more than about 20, 18, 15, 12 or 10 times. 
     
     
         85 . The method of any one of  claims 80  to  84 , wherein treatment with the apo mimetic (e.g., L-4F) and the complement inhibitor (e.g., lampalizumab) has a synergistic effect. 
     
     
         86 . The method of any one of  claims 80  to  85 , wherein:
 the complement inhibitor comprises, or is, lampalizumab; and 
 lampalizumab is administered (e.g., by intravitreal injection) in a dose of about 4-6 mg, 6-8 mg or 8-10 mg once every 2, 3, 4, 5 or 6 months, optionally after being administered in a dose of about 4-6 mg, 6-8 mg or 8-10 mg once every month for the first 1, 2 or 3 months or once every 6 weeks for the first 1.5 or 3 months,
 compared to the conventional or recommended dose and dosing frequency for lampalizumab of about 10 mg administered by intravitreal injection once every month in the absence of treatment with the apo mimetic (e.g., L-4F). 
 
 
     
     
         87 . The method of any one of  claims 80  to  85 , wherein:
 the complement inhibitor comprises, or is, lampalizumab; and 
 lampalizumab is administered (e.g., by intravitreal injection) in a dose of about 3-5 mg, 5-7 mg or 7-9 mg once every month (4 weeks) or 1.5 months (6 weeks). 
 
     
     
         88 . The method of any one of  claims 80  to  86 , wherein the complement inhibitor (e.g., lampalizumab) is administered (e.g., by intravitreal injection) once every 2, 3, 4, 5 or 6 (e.g., once every 2) months. 
     
     
         89 . The method of any one of  claims 67  to  88 , wherein the complement inhibitor (e.g., lampalizumab) is administered locally to, into, in or around the eye, such as by injection (e.g., intravitreal, subconjunctival, subretinal or sub-Tenon's injection), eye drop or implant (e.g., intravitreal, intraaqueous, subretinal or sub-Tenon's implant). 
     
     
         90 . The method of any one of  claims 67  to  89 , wherein the apo mimetic (e.g., L-4F) and the complement inhibitor (e.g., lampalizumab) are administered in separate compositions. 
     
     
         91 . The method of any one of  claims 67  to  89 , wherein the apo mimetic (e.g., L-4F) and the complement inhibitor (e.g., lampalizumab) are administered in the same composition. 
     
     
         92 . The method of any one of  claims 67  to  91 , wherein the apo mimetic (e.g., L-4F) and the complement inhibitor are administered at least in the advanced stage of AMD to prevent, delay the onset of, or slow the progression of neovascular AMD, including types 1, 2 and 3 neovascularization. 
     
     
         93 . The method of  claim 92 , further comprising administering a therapeutically effective amount of an anti-angiogenic agent. 
     
     
         94 . The method of  claim 93 , wherein the anti-angiogenic agent comprises, or is, an anti-VEGF agent (e.g., aflibercept [EYLEA®], bevacizumab [AVASTIN®] or ranibizumab [LUCENTIS®], or any combination or all thereof) and/or an anti-PDGF agent (e.g., E10030 [FOVISTA®]). 
     
     
         95 . The method of any one of  claims 92  to  94 , wherein the complement inhibitor comprises, or is, ARC1905 (ZIMURA®) or LFG316. 
     
     
         96 . The method of any one of  claims 67  to  95 , wherein the complement inhibitor (e.g., lampalizumab, ARC1905 or LFG316, or any combination or all thereof) is administered in a fixed-routine regimen, an as-needed regimen or a treat-and-extend regimen. 
     
     
         97 . A method of treating age-related macular degeneration (AMD), comprising administering to a subject in need of treatment a therapeutically effective amount of an apolipoprotein (apo) mimetic according to any one of  claims 1  to  38  and a therapeutically effective amount of an antioxidant. 
     
     
         98 . The method of  claim 97 , wherein the apo mimetic comprises, or is, an apoA-I mimetic (e.g., L-4F or D-4F) and/or an apoE mimetic (e.g., AEM-28-14). 
     
     
         99 . The method of  claim 97  or  98 , wherein the antioxidant is selected from the group consisting of anthocyanins, benzenediol abietane diterpenes (e.g., carnosic acid), carnosine, carotenoids (e.g., carotenes [e.g., β-carotene], xanthophylls [e.g., lutein, zeaxanthin and meso-zeaxanthin], and carotenoids in saffron [e.g., crocin and crocetin]), curcuminoids (e.g., curcumin), cyclopentenone prostaglandins (e.g., 15d-PGJ 2 ), flavonoids (e.g., flavonoids in  Ginkgo biloba  [e.g., myricetin and quercetin]), prenylflavonoids (e.g., isoxanthohumol), retinoids, stilbenoids (e.g., resveratrol), uric acid, vitamin A, vitamin B 1  (thiamine), vitamin B 2  (riboflavin), vitamin B 3  (niacin), vitamin B 6  (e.g., pyridoxal, pyridoxamine, 4-pyridoxic acid and pyridoxine), vitamin B 9  (folic acid), vitamin B 12  (cobalamin), vitamin C, vitamin E (e.g., tocopherols and tocotrienols), selenium, zinc (e.g., zinc monocysteine), inhibitors and scavengers of lipid peroxidation and byproducts thereof (e.g., vitamin E [e.g., α-tocopherol], tirilazad, NXY-059 and XJB-5-131), activators of nuclear factor (erythroid-derived 2)-like 2 (NFE2L2 or NRF2) (e.g., OT-551), superoxide dismutase (SOD) mimetics (e.g., OT-551), and analogs, derivatives, salts and combinations thereof. 
     
     
         100 . The method of  claim 99 , wherein the antioxidant comprises one or more vitamins (e.g., vitamin B 6 , vitamin C and vitamin E), one or more carotenoids (e.g., xanthophylls [e.g., lutein, zeaxanthin and meso-zeaxanthin] and carotenoids in saffron [e.g., crocin and crocetin]), or zinc, or any combination or all thereof, such as an AREDS or AREDS2 formulation, an ICAPS® formulation, an Ocuvite® formulation or Saffron 2020™. 
     
     
         101 . The method of any one of  claims 97  to  100 , wherein the antioxidant (e.g., vitamins and/or carotenoids) is administered in a dose less than the conventional or recommended dose, and/or in a frequency less than the conventional or recommended dosing frequency, for the antioxidant in the absence of treatment with the apo mimetic (e.g., L-4F). 
     
     
         102 . The method of  claim 101 , wherein the antioxidant (e.g., vitamins and/or carotenoids) is administered in a dose at least about 10%, 20%, 30%, 40%, 50%, 60%, 70% or 80% (e.g., at least about 20%), or about 10-30%, 30-50% or 50-70%, less than the conventional or recommended dose for the antioxidant in the absence of treatment with the apo mimetic (e.g., L-4F). 
     
     
         103 . The method of  claim 101  or  102 , wherein the antioxidant (e.g., vitamins and/or carotenoids) is administered at least about 2, 3, 5, 7 or 10 (e.g., at least about 2) times less frequently than the conventional or recommended dosing frequency for the antioxidant in the absence of treatment with the apo mimetic (e.g., L-4F). 
     
     
         104 . The method of  claim 103 , wherein the antioxidant (e.g., vitamins and/or carotenoids) is administered once every two or three days compared to the conventional or recommended dosing frequency for the antioxidant of at least one time every day in the absence of treatment with the apo mimetic (e.g., L-4F). 
     
     
         105 . The method of any one of  claims 97  to  104 , wherein the apo mimetic (e.g., L-4F) and the antioxidant (e.g., vitamins and/or carotenoids) are administered at least in the advanced (late) stage of AMD to treat or slow the progression of central geographic atrophy (GA) and/or neovascular AMD (including types 1, 2 and 3 NV), and/or to prevent or delay the onset of neovascular AMD. 
     
     
         106 . The method of any one of  claims 97  to  105 , wherein the apo mimetic (e.g., L-4F) and the antioxidant (e.g., vitamins and/or carotenoids) are administered at least in the intermediate stage of AMD to treat or slow the progression of non-central GA, and/or to prevent or delay the onset of central GA and/or neovascular AMD. 
     
     
         107 . The method of any one of  claims 97  to  106 , wherein the apo mimetic (e.g., L-4F) and the antioxidant (e.g., vitamins and/or carotenoids) are administered at least in the early stage of AMD or the initial phase of intermediate AMD to prevent or delay the onset of non-central GA. 
     
     
         108 . The method of any one of  claims 97  to  107 , wherein the antioxidant (e.g., vitamins and/or carotenoids), and optionally the apo mimetic (e.g., L-4F), are administered at least in the early stage of AMD. 
     
     
         109 . The method of any one of  claims 105  to  108 , wherein treatment with the apo mimetic (e.g., L-4F) and the antioxidant (e.g., vitamins and/or carotenoids) slows the progression of central GA and/or non-central GA (e.g., reduces the rate of GA progression, or reduces the GA lesion area or size) by at least about 10%, 20%, 30%, 40%, 50%, 60%, 70% or 80% (e.g., by at least about 20%), or by about 20-40%, 40-60% or 60-80%. 
     
     
         110 . The method of any one of  claims 105  to  109 , wherein treatment with the apo mimetic (e.g., L-4F) and the antioxidant (e.g., vitamins and/or carotenoids) slows the progression of central GA and/or non-central GA (e.g., reduces the rate of GA progression, or reduces the GA lesion area or size) at least about 10%, 20%, 30%, 50%, 100%, 150%, 200% or 300% (e.g., at least about 20% or 30%), or about 10-30%, 30-50%, 50-100%, 100-200% or 200-300% (e.g., about 50-100%), more than treatment with the antioxidant in the absence of treatment with the apo mimetic. 
     
     
         111 . The method of any one of  claims 101  to  110 , wherein treatment with the apo mimetic (e.g., L-4F) and the antioxidant (e.g., vitamins and/or carotenoids) has a synergistic effect. 
     
     
         112 . The method of any one of  claims 97  to  111 , wherein the antioxidant (e.g., vitamins and/or carotenoids) is administered systemically (e.g., orally), or locally to, into, in or around the eye (e.g., by injection [e.g., intravitreal, subconjunctival, subretinal or sub-Tenon's injection], eye drop or implant [e.g., intravitreal, subretinal or sub-Tenon's implant]). 
     
     
         113 . The method of any one of  claims 97  to  112 , wherein the apo mimetic (e.g., L-4F) and the antioxidant (e.g., vitamins and/or carotenoids) are administered in separate compositions. 
     
     
         114 . The method of any one of  claims 97  to  112 , wherein the apo mimetic (e.g., L-4F) and the antioxidant (e.g., vitamins and/or carotenoids) are administered in the same composition.