Blake Hauser, MD, PhD and Sandra Hoyek, MD
Massachusetts Eye and Ear, Boston, MA
Friday morning at ASRS 2026 kicked off with back-to-back age-related macular degeneration (AMD) symposia: Innovations in nAMD, moderated by Drs. Manjot Gill, Dimitra Sondra, and Geeta Lalwani, and Emerging Therapies in Geographic Atrophy, moderated by Drs. Allen Ho, Ghassan Ghorayeb, and Danny Mammo.
In the first session focused on neovascular AMD (nAMD), Dr. Joel Pearlman opened with first-in-human data on TH103, a biologic which targets both VEGF and heparan sulfate proteoglycans. In a Phase 1a clinical trial, investigators tested TH103 across four ascending doses in 20 patients enrolled. TH103 produced a mean best-corrected visual acuity gain of 9.2 letters after one month. This occurred with plasma concentrations that were markedly lower than comparator anti-VEGF agents. A total of 29% of patients required no retreatment through six months, and 41% went four months or longer between treatments. Three patients developed intraocular inflammation, two of which were successfully controlled with topical steroids. Otherwise, there were no significant safety signals.
Dr. David Almeida followed with Phase 1 results for CG-P5, a peptide-based topical medication that includes an anti-VEGF segment that is eight amino acids in length. CG-P5 was tested against sham drops and intravitreal aflibercept in treatment-experienced patients. CG-P5 achieved a comparable anti-exudative effect to aflibercept, with a notably higher intraretinal fluid-free responder rate and reduction in hyperreflective foci. However, in contrast to aflibercept, full clinical effect was achieved at approximately 30 days. The discussion centered on the possibility of using topical medications, such as CG-P5, as an adjuvant to injectable anti-VEGF agents in order to extend the intervals between treatments.
The focus then turned to geographic atrophy. Dr. Arshad Khanani presented the 1-year Phase 2 results from the ArMaDa trial of OCU410. OCU410 is a subretinal AAV-mediated gene therapy engineered to deliver the retinoid-related orphan receptor alpha gene. In the medium dose arm, there was a 34% reduction in GA lesion growth versus the control group at 12 months. A post-hoc analysis using alternative lesion criteria also showed 31% efficacy. However, the high dose failed to show benefit. Dr. Khanani attributed this to a bell-shaped dose-response curve, and there was considerable audience discussion around this point. A global Phase 3 program using the medium dose is planned for later this year.
Additional insights came from Dr. Jay Chhablani who added structural details from the same OCU410 program and its Stargardt counterpart, OCU410ST. Dr. Chhablani reported a 23% reduction in ellipsoid zone (EZ) loss and a 41% reduction in retinal pigment epithelium (RPE) atrophy at the 1-year timepoint. The strongest benefit was seen in patients with smaller baseline lesions. In the Stargardt cohort, nearly half of treated eyes maintained EZ integrity.
Next, Dr. Mathew MacCumber presented Phase 1 data on APL-3007, a subcutaneous N-acetylgalactosamine (GalNAc) small interfering RNA that aims to reduce C3 production. The two highest dose cohorts showed C3 reduction up to 91.5% versus 14.6% with placebo. These pharmacodynamic effects were sustained for several months. In light of these results, the investigators are planning a Phase 2 study in combination with intravitreal pegcetacoplan.
Closing the session, Dr. Jayakrishna Ambati reported Phase 2 results for K8, a dual inflammasome inhibitor. K8 is delivered via a sustained release biodegradable implant in 24-gauge injector, and each dose lasts approximately 3 months. Treatment with K8 reduced GA lesion growth by 54% compared to the control group. This is roughly four times the rate of growth reduction reported previously for FDA-approved complement inhibitors. Dr. Ambati also reported a BCVA benefit in extrafoveal lesions. A phase 3 trial of K8 is currently in the planning stages.
During the discussion portion, panelists debated methods for measuring lesion growth (mm² versus square-root-transformed units). Several presenters noted growing interest in microperimetry as a functional counterpart to structural endpoints in GA clinical trials. Dr. Ambati closed by framing geographic atrophy as a multi-pathway disease, noting that no single therapeutic approach is likely to halt progression alone. In his opinion, combination strategies will likely define the field’s next phase.
