AbstractPurposeWhile effective for corticosteroid sparing, systemic anti‐tumor necrosis factor‐alpha (TNF) therapy is associated with potentially serious side effects. Intraocular anti‐TNF therapy offers the possibility to reduce systemic safety concerns, improve patient compliance and enhance efficacy. EYS606 is a novel non‐viral gene therapy that induces ciliary muscle cells to express a potent anti‐TNF fusion protein in the eye. Herein, we present the results from Part 1 of a first‐in‐human study investigating EYS606 in patients with NIU.MethodsThe EYS606‐CT1 study is an ongoing, 24 week, multicenter, open‐label, phase I/II study investigating the safety and tolerability EYS606 administered using a proprietary electrotransfection system. In Part 1, end stage NIU patients were assigned to treatment with one of three escalating EYS606 doses, while in Part 2, patients with less severe, active NIU will receive the maximally tolerated EYS606 dose. The primary outcome is the assessment of adverse events (AEs) after treatment administration.ResultsNine patients (3 per cohort) with refractory posterior or panuveitis were enrolled and treated in Part 1 of the study. The majority AEs occurring within 4 weeks of EYS606 treatment were mild in severity, ocular in nature and related to the treatment administration procedure. No serious adverse events related to EYS606 were reported. Despite the advanced disease stage, clinically significant improvements from baseline were observed in 3 patients including >10 ETDRS letter gain in visual acuity in one and reductions in macular edema in two treated in the highest dose cohort.ConclusionsThese results suggest that EYS606 could be a safe and effective local treatment for NIU that avoids the safety concerns and inconveniences of systemic NIU therapies. Treatment of active NIU patients in Part 2 of study will further clarify the risks and benefits of sustained TNF inhibition in the eye.