Aviceda Reports Topline Phase 2b SIGLEC Data for AVD-104 in GA

Aviceda Therapeutics has reported topline results from the phase 2b SIGLEC trial evaluating AVD-104 for geographic atrophy (GA) secondary to age-related macular degeneration. The study’s primary endpoint did not show a statistically significant difference versus monthly avacincaptad pegol, but Aviceda highlighted visual acuity gains, lesion-growth reductions versus historical data, and a favorable safety profile.

SIGLEC Trial Design and Patient Population

The SIGLEC study evaluated safety and efficacy of AVD-104 versus an active comparator in GA secondary to AMD.

• Design: Randomized, multicenter, double-masked, active comparator–controlled phase 2b trial
• Sites: Investigational centers across the United States
• Enrollment: 300 patients
• Average age: 79 years
• Mean baseline visual acuity: 58.5 ETDRS letters
• Treatment arms (n=100 each):
  • 2 mg AVD-104 every other month
  • 1 mg AVD-104 monthly
  • 2 mg avacincaptad pegol monthly
• Duration: 24 months, with a prespecified interim analysis at 12 months
• Primary endpoint: Rate of change in GA lesion growth from baseline measured by fundus autofluorescence
• Secondary/exploratory endpoints: Visual function measures including ETDRS BCVA, contrast sensitivity, and low-luminance best-corrected visual acuity

Primary Endpoint: No Satistically Significant Difference vs Active Comparator

The primary endpoint analysis did not show a statistically significant difference in GA area change between AVD-104 and monthly avacincaptad pegol. Aviceda stated that imbalances in key baseline lesion characteristics across treatment arms contributed to the lesion-growth outcomes.

Lesion-growth and Visual Acuity Findings Highlighted by Aviceda

Aviceda emphasized lesion-growth reductions versus historical datasets and visual acuity improvements in the monthly 1 mg arm.

• Monthly 1 mg AVD-104: Approximately 31% reduction in GA lesion growth rate compared with sham and expected natural history rates (as described by the company)
• BCVA (mean): Sustained improvement throughout the study period, including a +0.6-letter gain at Month 12
• Categorical BCVA gains at Month 12 (monthly 1 mg arm):
  • ≥5 letters: 28.9%
  • ≥10 letters: 16.9%
  • ≥15 letters: 4.8%

Safety and Neovascular AMD Conversion

Aviceda reported a favorable safety profile for AVD-104, including a low rate of conversion to neovascular AMD.

• CNV conversion: 2% of participants developed neovascular AMD
• Serious adverse events: No drug-related serious adverse events reported
• Most common treatment-emergent adverse event: Vitreous floaters

Company Perspective and Clinical Rationale

Aviceda positioned the SIGLEC results as supportive of its approach in GA.

• “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.
• “We are encouraged by the magnitude of visual acuity gains… and the compelling safety profile observed with monthly AVD-104,” said David Callanan, MD, Chief Medical Officer of Aviceda Therapeutics.

How AVD-104 is Described to Work

AVD-104 is described as a poly-sialic acid–coated nanoparticle designed to engage SIGLEC receptors 7, 9, and 11 on macrophages, microglia, and monocytes in the retina-immune cells that have been shown to localize to areas of retinal atrophy in GA secondary to AMD. Aviceda stated that binding to SIGLEC receptors inhibits pro-inflammatory cytokine release, reduces phagocytosis, and limits differentiation of monocytes into pro-inflammatory M1 macrophages.

Next Steps: Data Presentations and Planned Phase 3 Studies

Aviceda said it expects to present detailed SIGLEC data at medical congresses in 2026 and plans to advance AVD-104 into two randomized, sham-controlled phase 3 confirmatory studies. The company said 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.

Conclusion

In topline results from the phase 2b SIGLEC trial, AVD-104 did not demonstrate a statistically significant difference on the primary endpoint versus monthly avacincaptad pegol. Aviceda highlighted lesion-growth reductions versus historical sham and natural history data in the monthly 1 mg arm, sustained BCVA gains through Month 12, and a low CNV conversion rate alongside a favorable safety profile.