Good morning, everyone, and thank you for joining H.C. Wainwright's fourth annual Ophthalmology Conference. My name is Max Martin. I'm an analyst on the corporate access team here at H.C. Wainwright. H.C. Wainwright is a full-service investment bank, which includes providing corporate finance, strategic advisory, and related services to public and private companies across multiple sectors and regions. We have a total of 24 publishing senior analysts and 640 companies covered across all sectors. Please visit hcwco.com for more information. From a logistics standpoint, please make sure to reference your virtual conference online portal that provides your individual links to your meetings and all presentations. Please join us for the panels that will be available live and streaming on Thursday, August fifteenth. With that said, have a productive and enjoyable day. I'd like to introduce our first presenter.
I'd like to welcome Frédéric Guerard from Opthea Limited.
Thank you, Max, and I'd like to thank H.C. Wainwright for inviting us today to present our story and data. We're a public company, listed on ASX in Australia and Nasdaq in the U.S., and I will be making some forward-looking statements. You can find our disclosure on our website under the Investor section. So, our lead asset is called sozinibercept. It has the potential to become the first drug in close to 20 years to improve visual outcomes in patients suffering from a disease called wet AMD, age-related macular degeneration. This is still the leading cause of vision loss in the Western world.
Around 3.5 million patients between the U.S. and Europe suffer from this disease, and they receive anti-VEGF-A therapy, which have been around for more than 15 years, but still suffer from vision loss despite these very good drugs. Our technology is the first-in-class VEGF-C and -D trap that is intended and developed to be used in combination with existing anti-VEGF-A standard of care. We have good IP with composition of matter, IP protection all the way to 2034 and beyond. And we have a very strong phase IIb trial that has demonstrated statistical superiority when sozinibercept been used in combination with a standard of care compared to standard of care alone.
That superiority was not only on anatomy, but more impressively, even on function of the eye and on vision, acuity of the eye. And we have that potential, unique potential to improve the vision of these millions of patients around the world suffering from wet AMD. We're in the middle of our pivotal program. We have two very large pivotal trials ongoing. The first one is called COAST, and I'll come back later in the deck to show you the design of this trial. COAST has been fully enrolled with close to 1,000 patients in February of this year. And SHORE, which is our second trial, was fully enrolled in May of 2024.
We anticipate the top-line data of COAST early in the second quarter of next year, whilst the top-line data for ShORe should be coming in the middle of next year. This is a multibillion-dollar market. I will say a bit more about this, and we anticipate this market to keep on growing in volume because of the aging of the population. And we are developing the drug to be used with any anti-VEGF-A currently approved in, on the market, and therefore not really competing with anyone there. It's really a combination play, and we can basically play with anyone that has been already launched.
The market has gone from being a rare disease 20 years ago to become a $15 billion+ growing global market, dominated by three drugs: Eylea with close to $10 billion of sales; Vabysmo, which is a new drug that has been launched 2 years ago by Genentech and has already recorded last year $2.8 billion of sales worldwide; and Lucentis, which is probably still around a couple of billion dollars , also by Genentech and Novartis ex-US. So these are the drugs that are already on the market. What sozinibercept is doing is adding to these existing drugs and, you know, improving vision.
It fits in the clinical practice of the physicians treating these patients, the retina specialists treating these patients around the world. As I said before, we are targeting a broad label to be used with any anti-VEGF-A, and as you can imagine, the market is extremely large. This is our team. I'd like to highlight a few people here. Our Chief Medical Advisor, Dr. Arshad Khanani, is one of the leading retina specialists in the world, has participated to over 100 clinical trials, very often as principal investigators, and he has accepted to join us part-time to be our chief medical advisor. We also have two lead investigators.
We have Charles Wyckoff, who is actually the principal investigator for our COAST trial, and Tim Jackson, who is the chief investigator for the SHORE trial. So the medical need remains despite these amazing drugs. Anti-VEGF-A drugs launched more than 15 years ago. Close to half of patients do not achieve significant vision gains. More than half of them have persistent fluid in the back of the eye, and 25% have further vision loss after a year, and more than that, after two years. The majority of patients fail to achieve 20/40 vision, and that vision is important because you need to have at least that level of vision in one eye to be able to drive in the U.S.
And because the vision loss happens in the center of the eye, when your vision does not recover, you basically cannot perform daily activities such as driving, reading, or even recognizing the faces of your family members. The unmet medical needs are very clear. Efficacy remains one, and a number of drugs have been launched, and here we have on this graph on the left, the data coming from the latest large clinical trials with faricimab, which has had a fantastic commercial success over the last couple of years. But as you can see, these drugs do not really deliver additional efficacy compared to historical standard of care.
It's compared to Eylea low dose, and you can see that patients gain vision shortly when they get injected very frequently at the beginning of their treatment for the first 3 or 4 injections in these trials, and then there is a plateau or even a decline over time of vision. So what we are trying to do with sozinibercept is basically to gain more vision at the beginning and maintain it longer. When you ask clinicians whether they will tell you improved vision remains a very, very important unmet medical need. But more importantly, when you ask the patients suffering from this disease, they will overwhelmingly tell you that for them, this is the most important thing, is to preserve as much vision or regain as much vision as possible. We are the only company working on superiority outcomes for the patients.
A number of our colleagues in other biotechnology or large pharma companies are working on longer durability, basically spacing out injections, but with no hope of bringing better efficacy. They're just trying to be non-inferior to very frequent anti-VEGF-A injections. So we stand alone as being the only asset being developed for superiority in that competitive landscape. So the way, the way our drug, sozinibercept or OPT-302, works is by trapping circulating VEGF-C in the eye, therefore offering a complete blockage of the VEGF pathway.
All the existing drugs on the market today are either anti-VEGF-A or A, B, or PLGF blockers, trap or anti-VEGFs, but they leave wide open VEGF-C and D that are binding to the second and third VEGF receptors, and therefore stimulating angiogenesis and vascular permeability, which are basically resulting in the damages in the back of the eye, which lead to visual impairment. So what do VEGF-C and D do in the back of the eye? So very much like VEGF-A, they stimulate angiogenesis, and you can see here in this knockout animal model, when you basically remove VEGF-C, you have limited angiogenesis, limited neovascularization of the back of the eye. When suddenly VEGF-C is present, you see these abnormal blood vessels basically multiplying and growing in the retina.
They also promote vascular permeability in a very similar way to anti-VEGF-A, which results in fluid accumulation and photoreceptor damage in the back of the eye. What's known now is that when you have AMD, you basically have a natural upregulation of VEGF-C. But furthermore, when you start injecting the patients with anti-VEGF-A, there is another and further upregulation of the VEGF-C pathway, which leads to this vascular permeability and angiogenesis. So, as much as our drug would be probably efficient or effective as a standalone, as you can see here on the graph on the right-hand side in this mice model, OPT-302 alone reduced the choroidal neovascularization area, which is a biomarker of the disease in this animal model. But clearly, the magic happens when you combine it with...
In that particular study, it was combined with Eylea, aflibercept, and you can see here the marked improvement in response when you combine the two the drugs together. So what we are trying to do is not to compete with any of the existing drugs on the market. It's really to be combined to all of them and deliver better vision, which will be the first time in close to 20 years. This is our pipeline. So we are currently developing sozinibercept in wet AMD.
We will prepare for a pivotal program in diabetic macular edema, which is an indication which is very large as well, and for which we have a lot of clinical and mechanistic belief that the sozinibercept combination with an anti-VEGF-A could also be beneficial in these patients. We're also doing feasibility work on a co-formulation to have in the same vial, co-formulated, a form of sozinibercept with an anti-VEGF-A, which would improve the easiness of use for the drug. We have conducted a very large phase IIb trial in wet AMD naive patients. These patients, it was 366 patients, randomized 1:1:1 in three arms.
All of these patients were getting Lucentis as per label every 4 weeks for 6 months and were either receiving a sham injection every 4 weeks, or they were receiving a low-dose sozinibercept or a high-dose sozinibercept. As you can see here, the inclusion/exclusion criteria were very standard, with the exception of best-corrected visual acuity at baseline. Patients were carefully selected to have a lower vision than what is normally seen in these trials, simply to be able to show and see a differentiation between the monotherapy arm and the combination therapy arm. The primary endpoint was mean change from BCVA from baseline at week 24. The key secondary endpoints were a mix of functional and anatomical endpoints.
Very interestingly, subtypes of patients were pre-specified in the trials based on their anatomical findings and the type of lesions they were presenting at enrollment. Those are the baseline characteristics of the patients. Nothing exceptional here, with the exception of the BCVA, as I said before, which was around 50 letters across the arms. You can see here the breakdown of the lesion types of these subjects that were enrolled, very balanced across the arm. And the CST here, the mean central subfield thickness was over 400 micrometers, and this is a biomarker of disease activity, showing the patients where had a active wet AMD disease.
The combination of sozinibercept, 2 milligram, demonstrated statistical superiority in the overall population compared to Lucentis monotherapy, as you can see here, with a 3.4 letter additional gain over monotherapy. The low-dose sozinibercept combined to Lucentis was not statistically different on visual outcomes. More interestingly, looking at this patient population, which is harder to treat, and that patient population has been identified close to 20 years ago during the pivotal program of Lucentis. When Lucentis was developed, 2 trials were run, ANCHOR and MARINA, on different patient population, and it's occult and minimally classic lesion patients were clearly not responding as much to Lucentis monotherapy as the classic lesion patients population. And here, it is harder to treat patients.
You can see the gap between the monotherapy, Lucentis, and the combination of Lucentis and sozinibercept 2 milligram, was even, broader and, with a 5.7 letter gain over standard of care for the combination arm. And this, this population represents the vast majority of patients presenting in clinics, when diagnosed with wet AMD. A question we get very often is: Is that gap of 5.7 letter driven because the control arm did something, special or unexpected? And the answer is no. I was referring before to a trial done 20 years ago by Genentech for Lucentis, the MARINA trial, and if you compare the MARINA trial on this same patient population, the patient gained at 6 months, 6.5 letters of vision in MARINA.
Where in our control arm, in our phase IIb, our patients gained 10.3. Now, they started from a slightly lower vision, so, that needs to be accounted for, but even if that is corrected for a lower vision at baseline, our control arm in the phase IIb did not underperform, and certainly did not underperform compared to historical data, that is available to us. So you can see this 5.7 letter gain, is based on a very well-performing, control arm. Not only we showed a statistical superiority on function in the phase IIb, but we had a consistent signal of better, anatomical control. As you can see here, we had a better reduction of, central subfield thickness, which is one of the biomarkers, of, disease activity.
We had less patients presenting with subretinal fluid, intraretinal cyst, which is a sign of better disease control. We had a reduction, marked reduction of the lesion, the total lesion area, as well as a CNV area, and all trending in a direction showing benefit from the combination therapy over the monotherapy with Lucentis. In especially hard-to-treat patient population, called PCV, patients, the polypoidal choroidal vasculopathy patients, they are so hard to treat that some of them still get laser in the back of the eye to control the disease. We had actually even a better improvement in the combo arm compared to the monotherapy arm, with a 6.7-letter. And the p-value, despite the patient population being quite small, around 20 patients per arm in this trial.
We are enrolling these patients in our phase III trial, so we should be getting more data on that, especially hard-to-treat patient population. I want to say the PCV lesions are not rare. They're extremely common in Asia. They are actually the majority of the lesions in Asia. They're also not rare for Caucasian patients. The safety from all our clinical work, it's pooled data here, is very much in line with the safety observed with anti-VEGFAs. Nothing particular, whether it's in ocular safety or non-ocular safety, it seems to be very much in line with what is expected from this class of drugs.
If you zoom on inflammation, which is always a concern in the eye, you can see here that the rate of intraocular inflammation was pretty similar in all arms, and as well as the severity of the inflammation that was observed. So our phase III program is ongoing. We have a very strong clinical program that was designed to win. We have the primary analysis is actually conducted first on this high-responding patient population we've identified in the phase IIb minimally classic and occult patient population. And that's the primary endpoint first tested on that patient population and then tested on all comers. We have two trials ongoing. One is comparing sozinibercept combination with Lucentis. The other one is comparing the sozinibercept combination with Eylea.
And that should allow us to get a broad label with the FDA, not linking sozinibercept to a particular anti-VEGF-A, but basically opening us to the whole class. So this is the design. It's around 1,000 patients per trial. The patients are randomized one-to-one to one. They were all naive patients, so the patient population enrolled is the exact same as in phase 2B, with the exception of RAP patients that we eliminated to maximize probability of technical success. This RAP patient population are responding really well to standard of care, so removing them increases the probability of technical success. The trials are powered at 90%, and which is very well-powered.
Our primary endpoint is mean change from baseline in best-corrected visual acuity at week 52, which is a very standard visual function endpoint. Then our key secondary endpoints are a mix of anatomical and functional endpoints. This is the trial design. The patients were randomized in all trials. So the first one is COAST. The three arms, more than 300 patients per arm, and patients are receiving aflibercept as per label, so 3 loading doses, and then aflibercept given every 8 weeks for 2 years. The trials are a 2-year duration.
And the patients were either receiving a sham injection every four weeks, or they are receiving a sozinibercept injection every four weeks, for the duration of the trial, or every four weeks for the first three loading doses, and then every eight weeks for the duration of the trial. The second trial is a ShORe. On ShORe, all patients receive Lucentis every four weeks for the duration of the trial, and they, on top, either get a sham injection every four weeks, or they get sozinibercept every four weeks, or they get sozinibercept every four weeks for the dosing, the loading phase, and then every eight weeks for the rest of the two years of the trial.
The primary endpoint is at week 52, but we will keep on collecting the data for the second year, primarily for safety purposes for the BLA filing. So we are now clearly in the middle of these pivotal programs. The top-line data is expected for COAST in the early second quarter of 2025, and for ShORe, in the middle of the year 2025. We are very busy manufacturing at commercial scale, which is required for the BLA filing. We need 3 consecutive process validation batches at commercial scale for the BLA filing, and these activities are currently ongoing and ongoing well. And of course, we are preparing for not only the FDA submission.
We have a fast track designation, which should allow quick turnaround from the FDA, but we're also preparing for commercial readiness and hire the team of ophthalmology experts to join us over the last few months. So to summarize, we are addressing a very large unmet medical need in $15 billion+ market. We would be the first and only therapy over the last 20 years to have demonstrated superiority to the original standard of care, which was Lucentis. We are preparing not only the wet AMD program, but also to be ready with a DME pivotal program after we read out the wet AMD data.
And this is a market where a biotech company can actually execute a launch, especially in the U.S., where the prescriptions are incredibly concentrated in a low number of high-volume clinics. It's actually a very elegant almost business-to-business model, Medicare Part B model in the U.S., which we can actually execute that launch with a lean organization. Thank you very much for your time.
Fred, thank you for leading a very informative and productive discussion here at H.C. We truly appreciate the effort and time that you put into putting this together, you and your team. So, thank you so much for that.
You're most welcome. Thank you, Max.