AAO 2023: AVD-104 and the results of the phase II/III part 1 SIGLEC trial

Mohammed Genead, MD, CEO of Aviceda spoke with the Ophthalmology Times team about the company's Phase II/III SIGLEC trial part 1 results, which were shared at this year's American Academy of Ophthalmology meeting.

Video Transcript

Editor's note - This transcript has been edited for clarity.

David Hutton:

The American Academy of Ophthalmology is holding its annual meeting in San Francisco. During the Eyecelerator event, Aviceda CEO, Mohammed Genead made a presentation on a new patient case study. Thank you for joining us today to tell us about this presentation.

Mohammed Genead, MD:

Thanks so much, David, you know, for the opportunity to give more background about our clinical asset AVD-104, but before I will do that, with just quick enough background. We're Aviceda. Aviceda is a private, late clinical-stage biotech company based in Cambridge, US, we have a technology platform called HALOS, High-Affinity Ligands of Siglecs, with a lead asset AVD-104 targeting patients was GA, geographic atrophy secondary to age-related macular degeneration, and also diabetic macular edema. AVD-104, the lead asset, which we're going to give you some key data highlights today about, it's a very promising intravitreal therapy. It's a sialic acid coated nanoparticle was a dual mechanism of action. This acid was designed to modulate the over activation of critical inflammatory celluar and complement pathway, which we knew it's highly implicated in patients was GA, secondary to AMD. And the way the drug works, AVD-104 is inhibiting and repolarizing, the overly activated retina immune cells to the resolution states, as well [as] enhance the activity of complement factor H to regulate the over amplification of the alternative complement cascade.

I would love to highlight about the clinical trial. The clinical trial called SIGLEC. It's a Phase II/III ongoing, US-based clinical trial. The AVD-104 is being going after a patient was GA second to the AMD as well as the diabetic macular edema. The highlight of my presentation at the Eyecelerator at the American Academy of Ophthalmology will be focusing on the SIGLEC trial for GA. Some critical insights the dual [inaudible] of AVD-104, as I mentioned before, targets the retina inflammation by modulating the immune cell over activation through targeting the repolarization of the macrophages to the resolution state and also activating the CFH activity to normalize the complement over amplification. I'm very excited to share the part 1 of the phase II/III trial the roll is completely done. This was happening over the last, you know, few weeks. We had a press release around it, and the ongoing phase II/III part 2 is active and starting to roll patients in the next few weeks for the second randomized portion of the study. What we're going to present and we will show, we will show preliminary part 1 data, and the highlight of the data showed sustained efficacy of AVD-104. In patient with GA, for the first time, we began to see in the majority of the patients some BVCA gain, best-corrected visual acuity using the etdrs chart, and also we saw stabilization and some patient also regression in the GA lesion over time.

As I said before part 2 of the study, which will be a multicenter, double-masked randomized trial to evaluate the treatment effect of AVD-104 in patient was GA against sham and active-control is active and enrolling patient the next few weeks. [There] will be close to 219 patient and the study going to be in US. One of the key data points I want to highlight and I will present in my talk during the American Academy of Ophthalmology will be the part 1 data we have generated thus far. What I can report, and I'm very excited about it as a retina specialist physician, we didn't have we didn't see any drug-related severe adverse events, either ocular or systemic. And we didn't see any evidence of those limits associated in any patient in any cohort in part 1 of the SIGLEC Phase II/III trial. Of interest, and also we look at this very carefully, we didn't see any drug related ocular inflammation, no retinal vasculitis, or neovascularisation infection for optic nerve abnormality in any patient in any eyes in your cohort in the phase, in the part 1 of the phase II/III SIGLEC trial. Also I can report, and I will report, no patient lost 15 letters or or more best-corrected visual acuity over 3 months.

However, not the, one of the key and and also the early efficacy data we have generated showed up to 80% in the majority of the patients analyzed thus far have reported best-corrected visual acuity gain after a single injection with AVD-104. And this was very clear dose response with the higher the dose, the more gain you see in these patients. Also initial data on the GA lesion hyper autofluorescence area, which was graded by a masked third party greater reading center, suggests stabilization and/or regression of the leading edge of the GA lesion.

So, in summary, we're very excited about the safety profile of AVD-104 in the clinic, that patient is, the drug looks very well-tolerated and safe at this moment was this early efficacy data is shown for the first time in GA space BCVA gain in patient was GA secondary MD and stabilization of the GA lesion is quite exciting, and we're very intrigued. And we're going to continue the development to the part 2, which is actively enrolling right now. And we will report more data in the upcoming clinical meetings or medical conferences in the next few weeks and the beginning of 2024.