Aviceda Therapeutics recently reported new phase 2b clinical findings from the ongoing SIGLEC trial evaluating its investigational therapeutic for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
Let’s begin with this therapeutic.
Its name: AVD-104.
What it is: A glyco-immune therapeutic (GIT) and sialic acid-coated nanoparticle designed using Aviceda’s proprietary nanotechnology platform.
Its purpose: To target a specific area of the innate immune response relating to AMD (see how it differs from other GA treatments).
- To note: It’s also under clinical development for diabetic macular edema (DME).
Tell me more about that nanotech platform.
Dubbed HALOS, this platform utilizes glycobiology (see here if you’re not familiar) to modulate the innate immune system in order to develop immuno-oncology-focused therapeutics.
- Click here for more details on how the technology works (hint: it involves siglecs, located on the immune cells’ surface).
Alrighty, now to the SIGLEC trial.
The two-part study was first initiated in 2023 after the FDA granted Aviceda an investigational new drug (IND) approval. Its setup is divided as follows:
- Part 1 (2a) experimental: Multicenter, open-label safety, and dose escalation
- Part 2 (2b) active comparator: Multicenter, double-masked, randomized
To note: The study is evaluating AVD-104 against avacincaptad pegol (IZERVAY).
- See here for a more in-depth look at each part’s design—and their respective primary outcomes.
And in this instance, we’re focusing on Part 2 of the trial, right?
Correct. But before we talk about the new data, the company previously reported (in 2023 and 2024) two separate sets of positive topline findings from the first 3 months of Part 1.
The gist of the most recent data:
- AVD-104 demonstrated continued safety, with no drug-related or serious adverse events (AEs)
- No evidence of any significant dose-limiting toxicities (or reports of other potential complications)
Noted. Now to the latest topline findings.
We’ll start with its primary endpoint analysis, which showed “no statistical difference in the rate of change in GA area” between AVD-104 compared to monthly avacincaptad pegol injections.
Imbalances were also observed in key baseline lesion characteristics across treatment arms (causing lesion-growth outcomes), with the study demonstrating that AVD-104 use resulted in:
- Clinically meaningful GA lesion-growth rate reductions (versus natural history)
- Sustained visual acuity (VA) gains
- A favorable safety profile with a low rate of wet AMD conversion
Talk numbers.
Aviceda reported that the GA lesion growth rate indicated an estimated 31% reduction compared with both the sham and natural history cohort growth rates.
A sustained improvement was observed in the mean best-corrected VA (BCVA) throughout the entire study period, with +0.6 letters at Month 12.
- This reportedly “has not been observed in other GA clinical trials to date” according to Aviceda.
And while we’re on the subject of visual outcomes …
Major category BCVA gains were achieved in the following percentage of patients:
- ≥ 5 letters in 28.9% of patients
- ≥ 10 letters in 16.9% of patients
- ≥ 15 letters in 4.8% of patients
What else? Any adverse events?
A low rate of choroidal neovascularization (CNVA) was observed, with 2% of patients developing wet AMD.
And as for AEs: There were no reports of drug-related serious AEs. However, the most common treatment-emergent AE noted was floaters.
Let’s talk big-picture significance.
Of this study, or AVD-104? Nevermind — we’ll give you both.
For the study: CEO Jeffrey Nau, PhD, MMS, stated that SIGLEC represents “the first clinical validation of glycoimmune checkpoint therapy to modulate macrophages and microglia to treat [GA].”
- He added that these Part 2b results reinforce the company’s belief in AVD-104’s ability to “provide meaningful functional vision benefit while reducing lesion progression.”
- Also, keep an eye out for this data to be presented at future medical congresses later this year.
As for AVD-104 itself: The therapeutic has the potential to be the first GA therapy to target key upstream pathways, including macrophage inhibition and complement cascade amplification.
Lastly: What’s next?
With a major source of financing secured last year, Aviceda plans to advance AVD-104 into two randomized, sham-controlled phase 3 confirmatory studies.
Per the company: The final design for this clinical development program is currently in progress.
As for a timeframe: Trial initiation is reportedly expected to begin sometime this year.
As always, stay tuned!