Kalaris Therapeutics recently reported positive phase 1a results for TH103, an investigational anti-VEGF fusion protein, in treatment-naïve patients with neovascular age-related macular degeneration (nAMD), with early data showing improvements in visual acuity and retinal anatomy after a single injection.

The single ascending dose study included 13 patients who received 1 intravitreal injection of TH103 at doses ranging from 0.5 mg to 2.5 mg. At 1 month, patients demonstrated a mean gain of 10 letters in best-corrected visual acuity, along with a 129 µm reduction in central subfield thickness and an approximately 95% reduction in retinal fluid.

TH103 was generally well tolerated. No dose-limiting toxicities or treatment-related serious adverse events were observed. Two cases of transient intraocular inflammation at the highest dose were attributed to host cell protein in the drug product; no additional cases were reported after manufacturing modifications.

Pharmacokinetic analysis showed plasma Cmax levels 27- to 51-fold lower than those reported for currently available anti-VEGF agents, suggesting increased intraocular retention. In addition, 31% of patients required no supplemental anti-VEGF therapy during 6 months of follow-up.

In September 2025, Kalaris began enrolling patients in a phase 1b/2 dose-finding study, which replaces the part 2 design of the phase 1a study. Preliminary data is expected in the second half of 2026.