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This PER On Air - Ophthalmology Times podcast examines the new treatment paradigm for patients with geographic atropy, following the introduction of complement-targeting therapies. In this podcast, experts, Dr Cecelia Koetting and Dr Talia Kaden review some of the key highlights from the live satellite symposium, Community Practice Connection™: Mastering the New Treatment Paradigm in Geographic Atrophy – From Detection to Intervention presented at the 2024 EnVision Summit in Ophthalmology.

Northwell Health and the Manhattan Eye, Ear and Throat Hospital (MEETH)

University of Colorado School of Medicine

This PER On Air - Ophthalmology Times podcast examines the new treatment paradigm for patients with geographic atropy, following the introduction of complement-targeting therapies. 

Mastering the New Treatment Paradigm in Geographic Atrophy – From Detection to Intervention

 EyePod podcast, Mandeep S. Singh, MD, PhD, speaks with Mark S. Humayun, MD, PhD, to learn about the advancements for a novel stem cell patch developed by a team of researchers at USC for the treatment of advanced dry age-related macular degeneration.

Dr. Humayun talks about the inspiration behind the patch, how his expertise in both ophthalmology and biomedical engineering has been crucial, and insights gained from a Phase 1/2a study. Dr. Humayun also outlines the upcoming steps for a multisite Phase 2b clinical trial and envisions the potential future role of the stem cell patch in the treatment of geographic atrophy.

Associate professor of ophthalmology and genetic medicine at the Wilmer Eye Institute at Johns Hopkins University School of Medicine in Baltimore, Maryland

Recipient of the 2023 Andreas C. Dracopoulous Professorship in Ophthalmology

Co-Director of the Genetic Eye Diseases (GEDi) Center and principal investigator at the Center for Stem Cells and Ocular Regenerative Medicine (STORM)

University Professor of Ophthalmology, Keck School of Medicine of USC in Los Angeles, California

Cornelius J. Pings Chair in Biomedical Sciences

Director, USC Ginsberg Institute for Biomedical Therapeutics

Received the National Medal of Technology and Innovation from President Barack Obama in 2016 for his innovative work and development of the Argus II.

In this Ophthalmology Times EyePod podcast, Mandeep S. Singh, MD, PhD, speaks with Mark S. Humayun, MD, PhD, about the progress made by a team of USC researchers on a novel stem cell patch for treating advanced dry age-related macular degeneration.

Innovation Series: A stem cell patch for treating advanced dry AMD

 EyePod podcasts focusing on innovation in ophthalmology. Throughout this series, we'll be hearing insights from various stakeholders including those in clinical practice, academia, and industry. The overarching message in this podcast is intended to be informational and not promotional. Today, our host Ehsan Sadri, MD, engages in a conversation with Jeffry Weinhuff, who is managing partner of Visionary Ventures. And just a quick note: the thoughts and opinions expressed are those of the speakers and do not necessarily represent the opinions of this publication.

 in Newport Beach, California, and is board-certified, fellowship-trained in treating LASIK, cataract, and glaucoma surgeries. He is a co-founder of Visionary Ventures Fund and a consultant to Tarsus.

, a series of venture capital funds which is a leading investor in drugs and devices for the eye. Visionary has current financial interests and serves on board of directors of the following companies: Aurion Biotech; Centricity Vision; CorneaGen; IanTrek; ONL Therapeutics; Orasis Pharmaceuticals; Pelage Pharmaceuticals; Re-Vana Therapeutics; Surface Ophthalmics; Sydnexis; Surface Ophthalmics; TearClear.

Explore cutting-edge ophthalmology innovations in this new series on the Ophthalmology Times EyePod podcast. Throughout this series, we'll hear insights from various stakeholders in clinical practice, academia, and industry. In this episode, host Ehsan Sadri, MD, engages in a conversation with Jeffry Weinhuff, managing partner at Visionary Ventures, exploring trends and offering advice for individuals driven by an entrepreneurial mindset.

(EyePod) From idea to impact: Navigating ophthalmic innovation

Sanaregen Vision Therapeutics invites investors to reserve shares as it prepares for an equity crowdfunding campaign to advance retinal disease treatments.

Sanaregen Vision Therapeutics invites prospective investors to reserve stock shares

New findings reveal RG6501 cell therapy shows promising long-term visual improvements for geographic atrophy patients

36-month results from phase 1/2a clinical study of RG6501 released

Assistive devices empower patients with central vision loss to regain independence, enhancing daily activities and reducing reliance on low vision centers.

Q&A: Meeting the need for low vision services with wearable tech

The trial treated 9 patients in 3 sequential, ascending dose-level (DL) cohorts.

Eyestem completes phase 1 study of Eyecyte-RPE in patients with geographic atrophy

A study reveals attrition rates in patients with geographic atrophy on complement inhibitor therapies, highlighting the need for improved treatment adherence strategies.

Q&A: Deepak Sambhara, MD, discusses real-world follow-up for patients with GA

Dilsher Dhoot, MD, on the evolution of geographic atrophy therapy: where are we now?

Dilsher S. Dhoot, MD, FASRS, provided an update on the current treatment landscape for geographic atrophy (GA) in a recent interview with the Eye Care Network. “Geographic atrophy causes progressive and irreversible vision loss,” he noted, emphasizing the clinical urgency given that the median time to foveal involvement is approximately 2.5 years from diagnosis.

Dhoot is a retina specialist with California Retina Consultants and an adjunct clinical assistant professor of ophthalmology at the Keck School of Medicine at the University of Southern California in Los Angeles. 

The year 2023 marked a significant shift with the FDA approvals of pegcetacoplan, a complement C3 inhibitor, and avacincaptad pegol (ACP), a complement C5 inhibitor. Both therapies target dysregulation in the innate immune system’s complement pathway, with the aim of slowing GA lesion progression. “We’re regulating complement and thereby allowing these GA lesions to grow slower,” he said.

Dhoot reviewed key data from the pegcetacoplan program, including the OAKS and DERBY phase 3 trials and the GALE open-label extension. Over 48 months, pegcetacoplan showed increasing benefit: “We saw in the last 24 months... a 28% reduction in GA growth,” compared with 19% to 18% in the initial 24 months. The most notable tissue preservation occurred in nonsubfoveal lesions, with up to 3.16 mm² of preserved area by month 48.

ACP’s efficacy was demonstrated in the GATHER 1 and 2 trials, which enrolled only nonsubfoveal patients. “We see again a reduction in the growth of the GA lesions,” Dhoot said, highlighting a 35.4% reduction in GATHER 1 and 17.7% in GATHER 2 at 12 months.

Safety profiles were generally favorable, he noted. Pegcetacoplan has a low incidence of injection-related vasculitis (1 in 4000), and both agents show a dose-dependent risk of choroidal neovascularization.

Dhoot emphasized patient education: “These drugs don’t improve vision… They just slow them down.” He also noted the need for more durable and effective therapies, adding, “We’re just at the beginning of the evolution of GA treatment.”

Dhoot D. Update on current treatments for geographic atrophy. Presented at: Sonoma Eye 2025 Meeting; March 20-23, 2025; San Diego, CA.

Videos

A look at current therapies, clinical trial results, patient education, and emerging options for managing this progressive retinal disease.



Dilsher S. Dhoot, MD, FASRS, on the landscape of geographic atrophy therapy

ARVO 2025 Roger Goldberg

At ARVO 2025, in Salt Lake City, Utah, Roger Goldberg, MD, MBA, talked about his presentation on the effect of AREDS vitamins in geographic atrophy.

Editor's note: The below transcript has been lightly edited for clarity.

Hi, I'm Roger Goldberg from Bay Area Retina Associates in Walnut Creek, California. And it's great to be here at ARVO 2025 in Salt Lake City, Utah. Today, I had the pleasure of presenting data on the effect of AREDS vitamins in geographic atrophy.

We know that the original AREDS studies, AREDS1, which kind of ran over the 1990s and was published in early around 2001 and then AREDS2, which made some slight tweaks to the formulation, ran the 2000s, and was published, I think around 2012/2013. Those showed a reduction in the progression to advanced AMD. But if you look closely at the data, that reduction in progression of advanced AMD from stage 3 or 4, kind of intermediate AMD, was largely driven by reducing the conversion to wet macular degeneration or neovascular AMD. And not really on the development or progression of geographic atrophy.
Recently, just earlier this year, there was a paper published a posthoc analysis of AREDS1 and AREDS2 that looked at, again, kind of a sub group analysis of patients who either developed GA over the course of AREDS1 and AREDS2 or who had some incipient GA and how did it progress over time. And in that posthoc analysis, which is a couple 100 patients, a couple 100 eyes, there is some suggestion that although it didn't slow the overall growth rate of geographic atrophy, and didn't have an effect on visual acuity, that perhaps it slowed the progression towards the fovea. And ultimately, when we think about treating our patients with geographic atrophy, that's the direction we really want to slow down, because we know that foveal anatomy is the most important real estate in the retina, and where the patients kind of fine central vision is located. So that was a really impactful and interesting posthoc analysis of the AREDS1 and AREDS2 studies–could just vitamins alone slow growth of GA towards the fovea.

And we said, well, let's go and look at another data set of GA patients. And can we replicate that same result? And of course, a medicine pegcetacoplan, or SYFOVRE, ran about a 1200 patient phase 3 clinical program called the OAKS and DERVY study. And about a third of those patients didn't get injections, they had sham treatment. And of course, all those patients had fellow eyes, some of whom had geographic atrophy at baseline. So here we have a relatively large population of patients who didn't receive any treatment in the OAKS and DERBY study, and we could follow them over two years. And this is with really advanced imaging, unlike AREDS, which was color fundus photography, kind of assessed on an annual basis. This was OCT and fundus autofluorescence, so really detailed reading center confirmed analyzes. And in OAKS and DERBY, about half of patients were on either AREDS1 or AREDS2. And we looked to see, does AREDS have any impact on the progression of geographic atrophy or growth towards the phobia? And the short answer is no. There is no difference between either sham or fellow eyes, so untreated population, whether they were on AREDS1 or AREDS2 or not taking any vitamin supplementation.

So in this other analysis now, also a posthoc analysis, we did not replicate the result that was seen in the AREDS1 and AREDS2 posthoc analysis. We also then looked at, well, what about in the pegcetacoplan, treated eyes? Could AREDS have any impact on those eyes. And it turns out that, again, when we look over a two year period, no difference, whether the patient was on vitamins or not in terms of pegcetacoplan,'s ability to slow geographic atrophy. Those two populations, overlap perfectly. Finally, we looked at exudative AMD, we know that the AREDS vitamins–I think, that is well established, slow or reduce the risk of developing neovascular or exudative AMD. We also know that these GA medicines, including pegcetacoplan, have an increased risk of exudative AMD development, could AREDS therapy be helpful in driving that down further, and unfortunately, we did not see any difference. So whether the patients were taking AREDS1 or AREDS2, there was really no impact on the development of Exudative AMD.

So obviously these are both the Keenan paper from AREDS1 and AREDS2, and this analysis is posthoc in nature. Lots of limitations that come with that, but we were not able to replicate that finding from AREDS1 and AREDS2. I didn't know what this–I thought would be interesting, actually, if we were able to replicate the results in the Keenan paper. Unfortunately, we weren't. I think really, what was the most interesting is really digging in on the AREDS1 and AREDS2 post hoc analysis and how frankly, confusing it is. Because in AREDS2, there was no population that didn't receive treatment. Everybody got some variation of AREDS1 plus or minus lutein and zeaxanthin or plus or minus beta carotene. So there was no real placebo or control group in AREDS2 so you sit there and scratch your head to say, well, how did they show an effect if, in that AREDS2 population, there was no control group. So I think kind of the further and deeper I got into the AREDS data, frankly, the more confusing I found it.

ARVO 2025: Analysis of AREDS oral micronutrient supplementation on geographic atrophy growth

Arshad Khanani, MD, MA FASRS discusses data from GATHER 2 Trial

Sydney M Crago, the editor of Modern Retina, talks with Arshad M Khanani, MD, MA, FASRS, about the expanded efficacy data from the GATHER 2 trial for geographic atrophy (GA).

- This transcript has been edited for clarity.

Hi, I'm Sydney Crago with modern retina and I'm here today with Dr Arshad Khanani to speak about his presentation at the upcoming meeting. He'll be talking about the 2-year expanded efficacy data of the GATHER 2 trial. Dr. Khanani, can you tell us a bit about your presentation?

Thank you, Sydney. So my talk at Angiogenesis 2024 virtual meeting is, is about the expanded efficacy of avacincaptad pegol, or ACP. As you're aware that ACP is a small pegylated RNA aptamer that is designed to be a specific inhibitor of complement C-5. Based on the 2 positive pivotal, GATHER-1 and GATHER-2 studies, ACP received FDA approval in August of last year. In my talk, I'm actually sharing the expanded efficacy data, and there are a few things [that] I wanted to highlight from my presentation. First thing, we know that ACP monthly and every other month reduce GA growth versus sham in GATHER-2. As you recall, gather to is a multicenter, international randomized study where patients receive either monthly ACP in the first year, or sham, and then they were really randomized to receive either monthly or every other month dosing while the sham group continued with the sham injection. 

So, the idea was to see if every other month can result in comparable efficacy as monthly, and that's what we saw. The other thing we notice is the treatment effect, we know that the treatment effect with ACP starts as early as 6 months. And what we saw was the treatment effect, more than doubled at over 2 years, compared to over 1 year with ACP, 2 milligram compared to sham. And then we also looked at the pooled analysis from GATHER-1 and GATHER-2. As you recall, GATHER-1 was a phase 2/3 pivotal study, and it was 18 months. So we wanted to see how pulling the data from GATHER-1 and GATHER-2 in terms of efficacy will give us more information about the treatment effect because we know that the GA is a very variable disease, and it's a multifactorial disease. So what we saw was, we saw robust efficacy of ACP in that analysis, and we saw an almost doubling of treatment effect every 6 months in the 18 months pool analysis with an overall reduction of 19% in GA growth compared to sham. Again, this is a postdoc analysis. And lastly, I presented the first time results of a match-adjusted, indirect comparative analysis or called medac analysis. And these analysis are done when level 1 evidence is missing in a head-to-head study. So we know that pegcetacoplan, which is also another drug that's approved for the treatment of GA. 

That trial enroll patients with central and non-central point involving GA, well, patients in the ACP study, in all, were enrolled with non-centerpoint involvement. So, there are different baseline characteristics of each trial, but what we can do is we can match the baseline BCVA and GA lesion growth across trials and then look at the efficacy. So, we took all the publicly available data for pegcetacoplan DERBY and OAKS study, and then we matched the parameters of bcva GA and other parameters using the data from pivotal GATHER-1 and GATHER-2 studies. And then we ended up with a population that was actually very well matched. And again, this is not level 1 evidence this is done for for payers and regulators, especially when level 1 head-to-head evidence is missing. So what we saw was, we saw greater directional doubling of treatment effect with ACP monthly compared to pegcetacoplan monthly. So I think that is something very informative for the field that if we have similar baseline characteristics, we are comparing the efficacy so we saw a reduction over 12 months of 26% with ACP, in GA growth versus sham, and we use the same in sham from the same study. So we're not comparing the sham from a different study. While we saw a 14% reduction with pegcetacoplan in the similar group. 

So we took all the data from DERBY and OAKS. And then we matched the patients from ACP in this analysis. So this was very important to find that with the match medac analysis, we saw greater benefit with ACP compared to pegcetacoplan. Of course, keeping all the caveats in mind about the limitations. 

And the other thing we looked at which matters most for our patients is vision. So we looked at visual acuity in the sham group, and the match group for ACP. And then we looked at visual acuity in Derby and oaks with every month and every other month. And we saw that ACP monthly demonstrated greater vision preservation verus a sham compared to pegcetacoplan versus sham. So when you look at the data, there is 47% greater preservation of vision compared to share with ACP. And when you look at pegcetacoplan, in the monthly group, there is 17% less vision preservation. And in the every other month group, it's 65% less vision preservation. So this was another interesting finding that patients treated with ACP had greater vision preservation, which is obviously the ultimate goal of treating these patients long term with these therapies. 

So I hope this summary of my talk was helpful to you and thank you for inviting me to share the summary of my talk.

Angiogenesis 2024: Expanded efficacy data from the GATHER 2 trial for geographic atrophy

CEO of Aviceda shares results from Phase II/III part 1 SIGLEC trail

AAO 2023: SIGLEC Trial Results

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.

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.

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.

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

Our team spoke with several researchers and industry professionals at the 2023 American Society of Retina Specialists meeting in Seattle, Washington. We asked them, "What research here do you find exciting or interesting?" Here's what Paul Hahn, MD, PhD, Kerrie Brady, BPharm, MBA, MS, and Michael Singer, MD had to say!

You know, one of the best things about these meetings is that you get, you get to learn about different things that are coming. And, you know, we hear about different mechanisms of treatment for geographic atrophy, different mechanisms of treatment for wet AMD, different methods of delivery, gene therapy, and so forth. And, you know, it's really learning more about these at these types of meetings really, what's, what's innovative.

Yes, we're particularly excited about the growth and expansion of AI and machine learning to enable diagnosis. And so with that, with the machines getting smaller, getting more into the community, we are looking forward to being able to detect more patients at earliest stages in their disease. And with a product such as OTT-166, begin early active treatment sooner in their disease process.

I am excited about the possibility and when I looked at patients who were being treated in a high dose Eylea trial, that you're able to get a significant number of patients, 44%, to essentially go 20 or 24 weeks. Even though it's a clinical trial, I think it really potentially has real ramifications to our patients in practice.

We asked, "What research at ASRS 2023 do you find exciting or interesting?" Here's what Paul Hahn, MD, PhD, Kerrie Brady, BPharm, MBA, MS, and Michael Singer, MD had to say!

ASRS 2023: Attendees share most interesting topics from annual meeting

Carl Regillo, MD, FACS, FASRS, spoke with our team following the annual ASRS meeting in Seattle, Washington to share insights from his presentation titled, "Modulation of Macrophages and Complement Dysfunction in Non-exudative AMD utilizing novel, sialic-acid coated nanoparticles."

I'm David Hutton of Ophthalmology Times. The American Society of Retina Specialists is hosting its annual scientific meeting this year in Seattle. Joining me is Dr Carl Regillo to talk about his presentation at this year's conference. Thank you so much for joining us. Tell us a little bit about your presentation.

Thanks, David. [I'm] happy to be part of this. My presentation titled, "Modulation of Macrophages and Complement Dysfunction in Non-exudative AMD utilizing novel, sialic-acid coated nanoparticles." Now, that's a lot. So [it] really describes a new mechanism of action of a therapeutic that's now in clinical trials for the treatment of geographic atrophy from AMD, in particular. 

So, what does all this mean? Well, we know that complement intubation has shown a reduction in GA lesion growth rates. We also know that the C3 C5 blockers that have been successful through Phase 3 trials have shown efficacy that have been rather modest. Plus, there's the side effect of secondary corneal neovascularization, which does appear to be a class effect. With a modest or limited degree of efficacy, it points to the fact that there's got to be another mechanism that is driving geographic atrophy. And indeed, there is evidence to suggest that the cellular arm of the innate immune response, namely macrophages, activated macrophages, play a role. 

So, there is evidence to show. Just like we're familiar with the deposition, or abnormal deposition, of complement in and around [inaudible] geographic atrophy and histopathologic studies. These studies also show an increased amount of macrophages, and there have been labeling experiments that show that these are actually pathologic or activated, so called activated macrophages. Macrophages exist in several forms, pathologic types, M1 [and] M2 for example, and then there's resolution resting or non pathologic types. 

The whole concept here with this therapeutic, called AVD-104, [is that] it's a cyanuric-acid coated nanoparticle. The nanoparticle is a bar-resorbable PLGA core, and it's injected individually. What happens is the sialic-acid binds to receptors on activated macrophages called siglecs. So when you bind the siglec on an activated macrophage it deactivates it, or so called polarizes it or cause it to resolve. The mechanism of action here is, in essence, to inhibit activated macrophages. There's another mechanism of action that was discovered in preclinical testing, which was ABD104, [It] also binds complement factor H, enhancing its inhibitory nature, and therefore dampening the alternative pathway. 

So, we got to do mechagnomes action, anti macrophage, and also blocking compliment to some degree. There's been a whole host of preclinical studies, in vitro human macrophages that show decreased macrophage cytokines like TNF-alpha and interleukin-12. It's shown to have an anti-complement activity in hemolytic assay. It's also been shown to reduce inflammatory retinal damage in a variety of animal models such as the light damage mouse model, and also decrease Mac formation in the laser induced CNV model. All this with good tolerability injected in variety of species, including non human primates, that is an individual injection. 

That leads us into where we are now, with AVD-104. It's in a Phase 2 3 clinical study called the SIGLEC trial. It's a 2-part study. Part 1 is a single dose escalation, individual injection for safety, with 3 months of follow up. Patients are being enrolled with multiple doses. We have data to suggest already that it's well tolerated, at least in the low and mid dose cohorts. We have patients that have been enrolled in these dose cohorts that have been followed up to 2 months and have not shown any problems with adverse events or serious adverse events. Once we're done with this dose escalation part 1 phase, part 2, the larger scale prospective, randomized clinical trial with ABD104 will start. We think that we're likely to get that started by the end of the year. So that's a 2 year, Phase 2 3 clinical study with both a sham and an active comparator control. This is a superiority study with the primary endpoint being the rate of change in geographic atrophy from baseline to 12 months as measured by fundus autofluorescence, which is the typical GA profile. 

So, in summary, we've got this very novel, unique therapeutic called AVD-104. It's a salic-acid coated nanoparticle with this dual mechanism of action that's performed well in preclinical studies, and is now in the early dose escalation part 1 of a 2-part, larger Phase 2 3 clinical trial.

Carl Regillo, MD, FACS, FASRS, spoke with our team following the annual ASRS meeting in Seattle, Washington to share insights from his presentation titled, "Modulation of Macrophages and Complement Dysfunction in Non-exudative AMD utilizing novel, sialic-acid coated nanoparticles." Aviceda Therapeutics is unlocking the proteogenomic code of AMD to target proteins and pathways linked to macular degeneration.  

ASRS 2023: Insights on AVD-104, a sialic-acid coated nanoparticle therapeutic for geographic atrophy

Paul Hahn, MD, PhD, spoke with our team about comparing the relative efficacy of pegcetacoplan versus avacincaptad pegol in patients with geographic atrophy at the 2023 ASRS annual meeting.

My name is Paul Hahn. I'm a retina specialist at New Jersey Retina. The purpose of this project was to try to compare relative efficacy of pegcetacoplan versus avacincaptad pegol. It's really an interesting time. 

We went from having no treatments for geographic atrophy, to having one approved treatment. Now, [we have] the possibility of another approved treatment for geographic atrophy all within the span of less than a year. So how do we decide which of these drugs to use? Well, in the absence of a head to head comparison, 1 thing that might be tempting is just to look at the top line data between the 2 trials. That, of course, is not something that you should do. 

A better way to do it is an analytical method called the anchored matched-adjusted indirect comparison. In this approach, called the MAIC, you try to match and balance the patient populations between the 2 different groups. So, you apply the inclusion and exclusion criteria from 1 trial to the other trial. Then you match or balance the populations by propensity score weighting to try to get as similar of a population between each group as possible. 

So in this trial, or in this study, patients from the pegcetacoplan studies, OAKS and DERBY, were filtered out to identify the same inclusion, exclusion criteria as from the avacincaptad pegol trial, called GATHER 2, only including patients that had non-subfoveal atrophy excluding patients with fellow eye, CNV, et cetera, and then balancing key characteristics like vision, lesion size, multifocal, et cetera. In the end, we found that when we compared pegcetacoplan monthly to avacincaptad pegol monthly, we found a statistically significant greater reduction with pegcetacoplan compared to avacincaptad pegol in OAKS, not in DERBY. But in a combined analysis, we also found a statistically significant greater reduction by 30% of pegcetacoplan monthly compared to avacincaptad pegol monthly when we compared pegcetacoplan every other month, in other words, less frequent dosing. 

Compared to avacincaptad pegol monthly, we found that although all the trends favored pegcetacoplan every other month, there was no statistical difference suggesting comparable efficacy. So, the overall conclusion of our study was that pegcetacoplan monthly appeared to show a better efficacy profile than avacincaptad pegol monthly in non-subfoveal GA patients. Every other month, or less frequent, dosing with pegcetacoplan appeared to show comparable efficacy profile to avacincaptad pegol.

ASRS 2023: Pegcetacoplan vs avacincaptad pegol in patients with geographic atrophy

Tarek Hassan, MD, spoke with our team about a novel glyco-mimetic nanoparticle for the treatment of geographic atrophy at the 2023 ASRS annual meeting.

Hi, I'm Tarek Hassan. I'm a partner of Associated Retina Consultants in Royal Oak, Michigan. I'm here at the American Society of Retina Specialists meeting in Seattle. 

Very excited to be here and present some of our early data using a new novel treatment paradigm, using glycobiology, glycoimmunology to try to treat geographic atrophy from dry AMD.

We are using a new compound that harnesses the body's own natural immune system to try to modulate the immune cells that directly are at the site of action of where the damage occurs in geographic atrophy. In our bodies, all of our cells are coated with things called sialic acids. They are sugars, and they're all over every cell. And those sugars are the immune model, immune identifiers to the actual immune cells. All different immune cells that have receptors that identify all of our cells in our body as either self or non-self; They're good or bad. So when these receptors on, for example, macrophages OR microglia, the immune cells that cause the damage and dry AMD, recognize damaged retina cells from the disease of macular degeneration, it turns on a whole process of inflammation, where the phenotype of macrophages that causes geographic atrophy turns on, and we figured out a way to present a drug to the eye that has sialic acids that mimic your own good sialic acids. So when the receptors come in, they meet our drug, and all the macrophages sort of stand down. They go from the activated state to the resolution state. And that happens for the phenotype of macrophages that causes dry AMD, and the phenotype of that causes wet AMD. The receptors, which are called siglecs, you'll hear that, you're going to hear that word more because it's the name of our clinical trial. Siglecs are simply the name of the receptors on all immune cells that recognize those sialic acids.

So our drug is a sialic acid mimetic. And by using it, we've been able to show in vitro and in vivo in multiple species of animals, great efficacy at reducing inflammatory cytokines, because we believe macular degeneration to be largely an inflammatory mediated disease, and also increase resolution cytokines. And we've been able to show significant efficacy, all the way up to now, hopefully, our human trials. So, we've introduced this siglec trial. It's phase 2/3 First, part 1 is enrolling now across the United States. It's a dose escalation study to determine our dose and biomarkers, and PK. We look to start enrolling our phase 2, or part 2 trial in the late part of this year, hopefully at the latest.

We have seen no safety signals whatsoever. There's no sign of inflammation in any animals that have been done in multiple species of multiple doses. We've seen no safety signals in the early clinical data that we've seen from the part 1 of the study, which was shown in a wonderful presentation by Carl Regillo, here at this meeting as well. So, we look forward to getting to talk to you more about siglecs, the receptors and silac acids in this new paradigm of glyco-immunology, using our own body's immune system, and the way it modulates inflammation, but we want to do it better with drugs that we can introduce into the eye.

ASRS Live: A novel glyco-mimetic nanoparticle for the treatment of geographic atrophy

Ursula Schmidt-Erfurth, MD, spoke with our team to share information on the GALE extension study at the 2023 ASRS annual meeting.

My name is Ursula Schmidt-Erfurth. I'm the Chairman of the Department of Ophthalmology at the Medical University of Vienna. I'm also the director of the Vienna Reading Center, and leading the ophthalmic Image Analysis Group, which is a computer science. 

Here at the ASRS, I will report about the extension of the OAKS and DERBY study, which are Phase 3 studies using pegcetacoplan treatment to limit the progression of GA [geographic atrophy] disease. There is an extension that has now started, the GALE study, which will continue up to 60 months. At the moment, we have the first 6 months of this extension available. The group of patients that is of highest interest for us [are] patients that were in the sham group over the 2 previous years of the Phase 3 study. These are lesions with very active disease. They have advanced quite substantially, and now they are rolled over to active treatment. 

Geographic Atrophy

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