Aviceda Therapeutics has released topline results from its phase 2b study, SIGLEC, evaluating AVD-104 in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
AVD-104 is a polysialic acid-coated nanoparticle in which the polysialic acid ligands present on the surface of the nanoparticle interact with sialic acid-binding immunoglobulin-like lectins (SIGLEC) receptors -7, -9, and -11 found on macrophages, microglia, and monocytes in the retina. Furthermore, the binding of AVD-104 to SIGLEC receptors 7, 9, and 11 inhibits pro-inflammatory cytokine release and phagocytosis and reduces monocyte differentiation into M1 macrophages.
SIGLEC (NCT05839041) is a randomized, multi-center, double-masked, active comparator-controlled clinical trial comparing the safety and efficacy of AVD-104 to avacincaptad pegol. For the trial, a total of 300 patients were enrolled with the average age of 79 years. Average baseline visual acuity for those enrolled was 58.5 letters.1,2
In the trial, patients were enrolled to receive either an intravitreal dose of 2 mg AVD-104 every other month (n=100), 1 mg AVD-104 monthly (n=100), or 2 mg avacincaptad pegol (n=100) for a treatment period of 24 months. The primary outcome of the trial was the rate of change from baseline in GA measured by fundus autofluorescence at month 12.1,2
According to the company, 12-month results showed that there was approximately a 31% reduction in GA lesion growth rate versus growth rates in sham and natural history rates. Additionally, a sustained improvement in mean best-corrected visual acuity (BCVA) was seen over the entire study period (+0.6 letters at month 12), which, according to the company, has not been seen in other GA trials to date.
In BCVA, gains of ≥ 5, ≥ 10, and ≥ 15 letters were achieved in 28.9%, 16.9%, and 4.8% of participants, respectively. A low CNV conversion rate was seen as well, with only 2% of patients developing neovascular AMD.
Jeffrey Nau, PhD, MMS, CEO of Aviceda Therapeutics, commented on the trial results in a press release from the company, saying, “The SIGLEC study represents the first clinical validation of glycoimmune checkpoint therapy to modulate macrophages and microglia to treat geographic atrophy. 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, CMO of Aviceda Therapeutics, added, “AVD-104 demonstrated a favorable safety and tolerability profile, with a low rate of neovascular AMD conversion and no serious drug-related adverse events, including no retinal vasculitis. We believe AVD-104 is poised to address critical gaps in current GA therapies that limit adoption, such as the lack of functional vision benefit and the safety limitations of neovascular AMD conversion.”
The company noted that it plans to advance AVD-104 into 2 randomized, sham-controlled phase 3 confirmatory studies. The final design of the clinical trial is underway, and the trial is expected to begin in 2026.
References:
Aviceda Therapeutics Announces Phase 2b SIGLEC Results for AVD-104 in Geographic Atrophy. Published December 15, 2025. Accessed December 15, 2025.
https://www.businesswire.com/news/home/20251215245453/en/Aviceda-Therapeutics-Announces-Phase-2b-SIGLEC-Results-for-AVD-104-in-Geographic-Atrophy A Multiple Dose Study of AVD-104 for Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (AMD) (SIGLEC). NCT05839041. Accessed December 15, 2025. https://clinicaltrials.gov/study/NCT05839041?tab=table
