ASRS 2026: First-in-human trial shows TH103 improves vision and reduces fluid in wet AMD

Study design

TH103 is a fully humanized recombinant fusion protein designed as a dual-targeting biologic: it combines VEGF receptor-1 ligand binding—the mechanism behind aflibercept (Eylea; Regeneron Pharmaceuticals)—with a heparan sulfate proteoglycan (HSPG)-anchoring domain intended to extend the drug's residence time in ocular tissue. Napoleone Ferrara, MD, a co-author on the study, contributed to the molecule's design.

The multicenter, open-label, Phase 1 single ascending-dose trial enrolled adults with active, treatment-naive neovascular age-related macular degeneration (nAMD) and central subfield thickness (CST) greater than 325 µm. Participants received one intravitreal injection of TH103 at 1 of 3 escalating doses—0.5 mg, 1.5 mg, or 2.5 mg—with safety review preceding each dose escalation. Thirteen patients completed 6 months of follow-up.

Efficacy and durability

At month 1, TH103 produced a mean best-corrected visual acuity (BCVA) gain of 10 letters and a mean CST reduction of 129 µm, corresponding to an approximate 95% reduction in central intraretinal fluid volume across all dose levels. Pearlman said these anatomic and functional changes were consistent with aflibercept's known effect and persisted through the first month.

Using protocol-defined retreatment criteria over the 6-month trial, Pearlman reported that 41% of patients required their first retreatment at month 4 and 35% required it at month 5; per the study abstract, 31% of patients received no additional anti-VEGF treatment through month 6. Pharmacokinetic sampling showed plasma Cmax values 27- to 51-fold lower than published values for approved anti-VEGF agents, supporting greater intraocular retention of TH103 relative to systemic drug exposure.

Safety

TH103 was generally well tolerated, with no dose-limiting toxicities, treatment-related serious adverse events, retinal vasculitis, vascular occlusion, cataract progression, or clinically significant intraocular pressure elevation. Two patients in the 2.5-mg cohort had transient mild-to-moderate intraocular inflammation, potentially related to host cell protein impurities; the inflammation resolved with topical therapy, and no additional cases occurred after the manufacturing process was optimized.

Looking ahead

Pearlman said the results support continued evaluation of TH103 in an ongoing Phase 1b/2 repeat-dose study, with the goal of reducing treatment burden for patients with nAMD if efficacy and durability hold up in larger trials.

Reference:

1. Pearlman J, Lally D, Alfaro DV, Gonzalez V, Wong R, Ferrara N. First-in-Human Evaluation of TH103, a Novel Dual-Targeting VEGF/HSPG Biologic: Phase 1 Single Ascending-Dose Study in Treatment-Naive Neovascular AMD. Presented at: American Society of Retina Specialists (ASRS) 44th Annual Meeting; July 15-18, 2026; Montreal, Quebec, Canada.