Aviceda Therapeutics announced topline results from its phase 2b SIGLEC clinical trial evaluating AVD-104 in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

The primary endpoint analysis showed no statistically significant difference in the rate of change in GA area between AVD-104 and the active comparator, monthly avacincaptad pegol. Aviceda noted that imbalances in key baseline lesion characteristics across treatment arms contributed to the lesion-growth outcomes. Despite this, treatment with AVD-104 demonstrated clinically meaningful reductions in GA lesion-growth rates compared with historical sham and natural history data, sustained visual acuity gains, and a favorable safety profile, including a low rate of conversion to neovascular AMD.

In the monthly 1 mg AVD-104 treatment arm, the study demonstrated an approximate 31% reduction in GA lesion growth rate compared with sham and expected natural history rates. Participants treated with AVD-104 also experienced sustained improvement in mean best-corrected visual acuity (BCVA) throughout the study period, with a gain of +0.6 letters at Month 12—an outcome not previously observed in other GA clinical trials.

Categorical BCVA gains of at least 5, 10, and 15 letters were achieved by 28.9%, 16.9%, and 4.8% of participants, respectively. The rate of choroidal neovascularization (CNV) conversion was low, with only 2% of participants developing neovascular AMD. No drug-related serious adverse events were reported, and the most common treatment-emergent adverse event was vitreous floaters.

“The SIGLEC study represents the first clinical validation of glycoimmune checkpoint therapy to modulate macrophages and microglia to treat geographic atrophy,” said Jeffrey Nau, PhD, MMS, Chief Executive Officer of Aviceda Therapeutics. “These results reinforce our belief that AVD-104 can provide meaningful functional vision benefit while reducing lesion progression, and has the potential to become a differentiated therapy addressing a significant unmet medical need for patients living with GA.”

David Callanan, MD, Chief Medical Officer of Aviceda Therapeutics, added, “We are encouraged by the magnitude of visual acuity gains, including protection from significant vision loss, reduction in lesion growth relative to historical sham and expected natural history, and the compelling safety profile observed with monthly AVD-104, in this first-ever multi-dose trial of AVD-104. We believe AVD-104 is poised to address critical gaps in current GA therapies, including the lack of functional vision benefit and safety concerns related to neovascular AMD conversion.”

Next Steps in Clinical Development

Aviceda said it expects to present detailed data from the phase 2b SIGLEC trial at medical congresses in 2026. The company plans to advance AVD-104 into two randomized, sham-controlled phase 3 confirmatory studies. Final trial design is underway and will be informed by additional analyses of OCT-based baseline lesion characteristics and ongoing global regulatory interactions, with trial initiation anticipated in 2026.

AVD-104 is a poly-sialic acid–coated nanoparticle designed to engage sialic acid–binding immunoglobulin-like lectins (SIGLEC) receptors 7, 9, and 11 on macrophages, microglia, and monocytes in the retina. These immune cells have been shown to localize to areas of retinal atrophy in patients with GA secondary to AMD. Binding of AVD-104 to SIGLEC receptors inhibits pro-inflammatory cytokine release, reduces phagocytosis, and limits differentiation of monocytes into pro-inflammatory M1 macrophages.

About the SIGLEC Trial

SIGLEC is a randomized, multicenter, double-masked, active comparator–controlled phase 2b clinical trial comparing the safety and efficacy of AVD-104 with avacincaptad pegol in patients with GA secondary to AMD. The study enrolled 300 patients at investigational centers across the United States. Participants had an average age of 79 years and a mean baseline visual acuity of 58.5 ETDRS letters.

Patients were randomized to receive 2 mg AVD-104 every other month (n=100), 1 mg AVD-104 monthly (n=100), or 2 mg avacincaptad pegol monthly (n=100) for 24 months, with a prespecified interim analysis at 12 months. The primary endpoint was the rate of change in GA lesion growth from baseline, measured by fundus autofluorescence. Secondary and exploratory endpoints included multiple visual function measures, such as changes in ETDRS BCVA, contrast sensitivity, and low-luminance best-corrected visual acuity.