ASRS 2026 and the reshaping of advanced AMD
AMD is increasingly better understood as one disease with two late-stage phenotypes: neovascular AMD (nAMD), driven by pathologic choroidal neovascularization and exudation, and geographic atrophy (GA), characterized by confluent loss of retinal pigment epithelium, photoreceptors and choriocapillaris. In practice these phenotypes frequently overlap, even within the same eye, now leading retinal clinics to manage a continuum rather than two isolated diseases.
At the 2026 American Society of Retina Specialists Annual Meeting (ASRS 2026), early nAMD innovation, beyond gene therapies, was defined less by “longer anti-VEGF” alone and more by attempts to improve vascular stability, anatomical drying and durability through new biology. For GA, the field is further behind in therapeutic maturity. Although disease-modifying therapies may dominate the next five years, Key Opinion Leaders (KOLs) added that the field would eventually need treatments capable of restoring vision. ASRS 2026 reflected this shift by focusing on improving durability and disease control today, while stablishing the foundations for tomorrow’s restorative therapies.
“Things are starting to move quickly in GA. We’re seeing data for therapies that are really slowing lesion progression, so anatomically really slowing down GA’s progression. While these sorts of therapies may dominate in the next 5 years or so, I think we’ll eventually get treatments that can restore vision.” – US KOL, NY
“Really it’s vision restoration, that’s the next frontier for GA. Sadly progression of the disease leads to blindness, so interventions that stall progression are good, but something that restores vision is what is really needed.” – US KOL, FL
Emerging nAMD treatments beyond gene therapy
Anti-vascular endothelial growth factor (VEGF) therapy remains the backbone of nAMD care, with current standards including intravitreal (IVT) ranibizumab (Lucentis), aflibercept (Eylea) and faricimab (Vabysmo) among others. Although anti-VEGF therapies have revolutionized nAMD treatment, frequent IVT injections remain a major burden and may limit long-term adherence. As a US specialist notes: “What I hear day-in, day-out from my nAMD patients, particularly the poorly-controlled ones, is why do I have to get so many injections? That’s by far the main complaint I hear from patients.” Adeno-associated virus (AAV)-based gene therapies currently in development, such as 4D-150 by 4DMT, Ixo-Vec by Eli Lilly/Adverum and ABBV-RGX-314 by RegenXBio/AbbVie, seek to provide sustained intraocular anti-angiogenic activity after a single treatment. Yet insights from ASRS 2026 indicate that the physicians and patients still want more options.
OLN324 (also known as IBI324) appears positioned as one of the most competitive of the early non-gene therapy entrants. It is a next-generation IVT VEGF/Ang2 bispecific antibody, with higher Ang2 potency, a higher molar dose, and a smaller molecular size than faricimab, the current SoC multi-pathway inhibitor. According to Ollin Biosciences, in the randomized Phase 1b JADE trial, more than 160 US patients with either nAMD or DME received three monthly doses of OLN324 2 mg, OLN324 4 mg or faricimab 6 mg, followed by protocol-defined retreatment during off-treatment follow-up. In the nAMD cohort, OLN324 produced retinal drying comparable to faricimab through Week 20, but with numerically greater Best Corrected Visual Acuity (BCVA) gain, including a +2.2-letter advantage for OLN324 4 mg at Week 20, and faster, roughly 50% greater reduction in pigment epithelial detachment thickness at Week 12. Safety was clean, with no intraocular inflammation, retinal vasculitis or occlusive vasculitis reported with OLN324. Clinically, OLN324 is not being positioned against gene therapies, but rather against the efficacy ceiling of current bispecific anti-VEGF/Ang2 therapy.
TH103, from Kalaris, is mechanistically different. It combines VEGF receptor-1 ligand binding with heparan sulfate proteoglycan anchoring, with the aim of improving intraocular retention while maintaining potent VEGF blockade. In the first-in-human, multicenter, open-label Phase 1 single-ascending-dose study in treatment-naïve nAMD, 13 patients completed 6 months of follow-up in the initial cohorts, later expanded to 17 treatment-naïve and 3 treatment-experienced patients. A single TH103 injection yielded a mean BCVA gain of 10 letters and a mean central subfield thickness (CST) reduction of 129 µm at Month 1. An ongoing repeat-dose Phase 1b/2 study should determine whether the single-dose durability signal survives a standard loading paradigm.
Tiespectus, Merck’s MK-8748, is the most advanced programme among the therapies described here. It is a bispecific antibody that directly agonizes Tie2 while inhibiting VEGF, aiming to stabilize retinal and choroidal vasculature rather than only suppress leakage. The two-part Phase 1/2a RIOJA trial included nAMD in addition to other exudative retinal diseases, namely branched retinal vein occlusion (BRVO) and diabetic macular edema (DME) At ASRS 2026, the public dataset highlighted the BRVO arm: after three monthly injections, mean BCVA improved by 16.7 letters and CST fell by 157.8 µm at Week 12, with improvements seen as early as Week 1 and no drug-related safety concerns or rescue therapy. Merck has already initiated the pivotal MALBEC Phase 2b/3 trial in nAMD and scheduled a second registrational study, both versus aflibercept 2 mg (Eylea). These efforts signal Tiespectus rapidly advancing in its attempt to become a next-generation biologic SoC before gene therapy fully matures commercially.
“The main trend you’re seeing with these new agents is this dual-pathway targeting. We’ve seen how strong Vabysmo (faricimab) uptake has been, and a major reason for that is its dual-action MoA. OLN324, TH103, and others are taking the next step there… I think if we’re going to see even further expansion of treatment durability, it will be through therapies like these targeting multiple pathways” – US KOL, CT
Against gene therapy, these pharmacologic agents offer a different value proposition. Whereas 4D-150 and ixo-vec are already in Phase 3 and compete on one-time or near one-time durability, OLN324, TH103 and Tiespectus remain dose-adjustable, reversible and operationally familiar for retina clinics. That may matter if physicians prioritize controllability over maximal durability, especially early after launch.
Emerging GA treatments
The current approved GA landscape remains narrow. In the United States, pegcetacoplan (Syfovre) is approved for GA secondary to AMD with dosing every 25 to 60 days, and avacincaptad pegol (Izervay) is approved as a monthly intravitreal injection; Astellas subsequently secured an expanded label removing the prior 12-month dosing limitation. Mechanistically, both therapies target components of the complement system – Pegcetacoplan inhibits C3, while avacincaptad pegol inhibits C5 – complement overactivation contributes to chronic inflammation and retinal cell damage that characterizes GA. While both treatments aid the clinical management of GA, neither reverses atrophy, and both still require chronic injection-based care, placing significant burden on patients and retinal practices. Similar to sentiments expressed for nAMD, a US specialist noted: “the main thing we hear from GA patients is whether they have to keep coming in for injections”. Consequently, future therapies are expected to be judged not only by anatomical outcomes and preservation of functional vision, but also by their ability to reduce treatment burden.
The next GA wave is broader mechanistically. K8, a quarterly bioerodible intravitreal implant delivering a dual inflammasome inhibitor, reduced lesion-growth rate by 54% in the 0.7 mg cohort over 6 months and showed a 4-letter BCVA advantage in eyes with extrafoveal lesions, with no drug-related serious adverse events; a Phase 3 programme is planned. ASP7317, a subretinal human embryonic stem-cell-derived retinal pigment epithelial (RPE) cell therapy, was featured at ASRS 2026 with preliminary Phase 1b trial results suggesting possible visual improvement, anatomical stabilization and patient-reported benefit in advanced GA. Apellis’ APL-3007, a systemic C3 siRNA, is already being tested in a Phase 2 trial in combination with pegcetacoplan. Regeneron’s SIENNA Phase 3 trial is exploring systemic C5 suppression with subcutaneous cemdisiran (small interfering RNA) alone or with pozelimab (anti-C5 monoclonal antibody), an interesting approach aiming to decouple complement control from monthly intravitreal dosing. Sanofi’s SAR446597 adds another one-time gene-therapy approach, which is currently under investigation in a Phase 1/2 trial.
According to some specialists, gene therapy represents “probably the most exciting area of research”. Although the development remains early, investigators suggested that “gene therapies could begin emerging as clinical options within the next few years”. Stem-cell therapies are also seen as promising, by replacing cells that have already been lost. At ASRS, a US specialist noted that “stem cell therapy could be very beneficial, especially for people with more advanced disease aiming to stop progression all-together. However, they also noted that “any stem-cell therapy would have to be used alongside something that slows the progression like gene therapy because the stem-cell based therapy would replace the damaged retinal cells, but these cells themselves won’t stop the underlying disease”. Thus, in the interim, current complement-targeting therapies are expected to remain important as they slow disease progression, which may offer a ‘substrate’ for future gene- and cell-based therapies to exploit.
“Gene therapy is probably the most exciting area of research. The hope is that a one-time treatment will provide lasting effects so patients wouldn’t need to keep coming in for frequent visits… It is very early on but we may see them as an option in the next 3 years. So, for now we just continue with the ongoing treatments while we wait for more evidence from these newer ones… but definitely something to look out for is gene therapies.” – US Retina Specialist
Over the next 3–5 years, the GA market is therefore likely to evolve along several tracks. First, lower-burden platforms such as systemic complement inhibition, quarterly implants and one-time gene therapy will try to solve the adherence problem that chronic IVT therapy creates in an often elderly, and oftentimes initially asymptomatic population. Second, the field will increasingly favor programs that can connect anatomical slowing to functional preservation, because GA trials still struggle with the lag between structural progression and patient-perceived visual decline. Finally, the expanding GA landscape may become segmented by treatment profile, with the promise of convenience-driven options, such as oral or topical treatments; durability-oriented approaches, such as gene therapies; and rescue or later-stage treatments, such as IVT therapies. As these options begin to emerge, current standards of care are likely to face increasing competitive pressure.
Advanced AMD as one disease with two end stages
The practical implication for clinicians is that nAMD progresses faster, threatens vision through leakage, and therefore uses short-term functional and OCT-fluid endpoints such as BCVA, CST and retinal fluid resolution. GA often progresses more insidiously, especially before foveal involvement, so trials have relied on lesion-area enlargement while the field searches for more patient-relevant functional endpoints. That difference explains why nAMD innovation is primarily a durability-and-efficacy race, whereas GA innovation is still trying to prove both biological effect and meaningful visual preservation.
Viewed together, the innovation showcased at ASRS 2026 suggests that nAMD and GA are beginning to converge around a common therapeutic ambition. While nAMD development is increasingly focused on maximizing durability without sacrificing efficacy, GA is progressing beyond first-generation complement inhibition towards therapies designed to reduce treatment burden, preserve visual function and, ultimately, regenerate damaged retinal tissue. The next decade is therefore likely to see advanced AMD managed less as two distinct diseases and more as a continuum, with treatment tailored according to disease stage but united by the shared objective of reducing the treatment burden on patients all the while preserving – and hopefully restoring – vision.
