A biopharmaceutical company developing novel therapies to address the unmet need of progressive retinal diseases, including wet AMD. Dr. Guerard?
Thank you, Jane, and I would like to thank H.C. Wainwright for inviting us today to present the Opthea story. We're a public company in Australia and in the U.S., and I will be making forward-looking statements. You can find our disclaimer on our website under the investor section. Our drug is called sozinibercept, and sozinibercept has the potential to be the first product in close to twenty years to improve visual outcomes of patients suffering from wet AMD or wet age-related macular degeneration. This is still the number one cause of vision loss in the elderly in the developed world, and that is despite the use of a class of drug called anti-VEGF-A, which appeared around twenty years ago and has really transformed the care of these patients.
Our drug, sozinibercept, is a first-in-class VEGF-C and -D trap that we intend to use, and we have developed in combination with a standard of care anti-VEGF-A. This is a new molecule. We have composition of matter and method of use IP at least through 2034, and opportunities to extend beyond that. We have a very large phase II-B trial that demonstrated superiority in combination with standard of care, compared to standard of care alone, with a very satisfactory safety profile. We are very excited because we have the opportunity to improve the vision of millions of patients around the world. We are in the middle of our pivotal program. We have two trials ongoing. The first one is called COAST. COAST has been fully enrolled since February of this year.
Both trials enrolled around 1,000 patients each. And SHORE, the second trial, has been enrolled since May of this year. We expect that the top-line data of COAST a little bit before SHORE, early Q2 of 2025, whilst SHORE will be in the middle of 2025. This is a significant commercial opportunity. This is a multi-billion-dollar market, and we do not have any competitor near the stage where we are at in the clinical development. We are developing the drug to be combined with any drug on the market or any drug coming to the market, not to be used against any drug on the market.
So just to recap, the market, if you don't know the size, it's around $15 billion a year, dominated by very few players. The most used drug is still Eylea, which recorded close to $10 billion of sales last year. Vabysmo is a new drug launched by Genentech Roche, which recorded close to $3 billion last year in its second year of launch, which demonstrate the appetite for this class of drug or this category for innovation, and the fact that even incremental innovation in the anti-VEGF standard of care class picks up very quickly. And retina specialists are really willing to evolve their practice of medicine.
In our case, we're a VEGF-C and -D trap, as I said, first in class, and what we are trying to do is to fit into the clinical practice of these retina specialists. And we would develop the drug, and we would be approved, assuming our trials are positive, for use with any anti-VEGF-A already approved. This is our team. We were very lucky to be joined this year by Dr. Arshad Khanani, who decided to dedicate some of his time to the company as a chief medical advisor. And we since have built a very prestigious medical advisory board.
We also have a clinical advisory board with Charles Wyckoff, who is the chief investigator of the COAST trial, and Tim Jackson is the chief investigator of the SHORE trial. Jason Slakter runs the centralized reading center for all images taken in the COAST and SHORE trials. Despite incredibly effective anti-VEGF-A therapies, it is now well documented that the majority of patients fail to achieve the 20/40 vision when they are under treatment. The 20/40 vision is important because that's the limit one needs to have in one eye to be allowed to drive in the U.S. Most patients cannot resume routine daily activity such as reading, driving, recognizing faces, watching TV.
The vision loss appearing in the center of the eye, it impacts the finest and the most precise part of the eye. So despite these wonderful drugs that are currently available, the most patients still have disease activity, do not achieve significant vision gains, and a quarter of them have further vision loss a year after they've been initiated on these drugs. And that is very well documented. The TENAYA LUCERNE trial is a trial done on faricimab, which is Vabysmo, the latest drug that was launched in this space. And as you can see, patients gain vision rapidly when they are initiated on the drug, and then slowly but surely, these vision gains erode over time.
What we are trying to achieve here is to maximize efficacy, gain even more vision short term, and help the patients protect that vision long term. So we are the only company working on a drug delivering better vision outcomes. All our competitors work on better durability. Their objective is to extend the injection intervals between two injections, so that patients can have non-inferior outcomes to standard of care with less injections. And this is very, very interesting approach. We are going really the other way, which is we believe listening to patients, that what they want is actually better vision outcomes, and therefore, we are going for maximum efficacy, not for convenience or better durability. Our drug, sozinibercept, or OPT-302, is the first-in-class VEGF-C and -D trap.
As you can see here, the benefit of this approach is the complete blockage of the VEGF pathway. This pathway has been very well known for decades, targeted by this list of drugs you have on the slide here, whether it was LUCENTIS, which is the original standard of care, or subsequent drugs being launched, and all these drugs block VEGF-A, or A and B, and PLGF, but basically leave wide open the VEGF-C and -D pathway to activate the second and third receptor of the VEGF pathway. Our solution is to bring sozinibercept, trap VEGF-C and -D, and reduce the stimulation of these receptors. It's been well published over the years that VEGF-C and -D have a very similar effect to VEGF-A.
VEGF-C stimulates angiogenesis, as you can see here, with promoting these abnormal blood vessels in the back of the eye, leading to vascular permeability and leakage of these blood vessels, resulting in fluid accumulation in the back of the eye. When one has age-related macular degeneration, there is a natural elevation of production of all sort of VEGF, but certainly VEGF-C is massively increased, as you can see here, and there is a further upregulation when patients get treated with VEGF-A. The graph at the bottom here shows the effect of bevacizumab given monthly on the level of VEGF-C in human eyes that have been initiated on bevacizumab. You see this, therefore, there is this counter-mechanism in the eye. When you block VEGF-A, there is a regulation, upregulation of VEGF-C in the eye.
Our drug, sozinibercept, works as a standalone, and with that control in that animal model, the area of choroidal neovascularization, in a very similar way to aflibercept or Eylea. But the magic really happens when you combine these anti-VEGF-A and -C and -D blockers together. You can see a much better control of the disease, and this is what we are doing in clinical practice. As I said before, there hasn't been any innovation, any drug since LUCENTIS, that has demonstrated superiority to LUCENTIS in terms of vision benefits. Some of these drugs require less injections than LUCENTIS, but none of them deliver better vision, so that's what we are trying to do here.
Our pipeline is the following: We have our lead asset is in wet AMD currently, and this is the COAST and the SHORE trials I mentioned before. We are planning to initiate a diabetic macular edema phase III program after the top-line data in wet AMD, so we are currently preparing for this trial. And we're also working on a co-formulation, a fixed co-formulation of sozinibercept and an anti-VEGF-A inhibitor. That would improve the easiness of use and would be a convenience offer for the clinics. We will still keep on developing sozinibercept as a standalone because we want to give the clinics the flexibility to use whatever anti-VEGF-A they want as an underlying treatment, whether it's a branded product or one of the numerous biosimilars on the market.
That flexibility, we think, will be welcome in some cases. Other clinics indicated that having a fixed-dose combination would make it easier for them, so we're working on that now. Our phase II-B data was very strong. The trial that was run was run on naive patients that had never been treated for their wet AMD. Very standard inclusion/exclusion criteria, with the exception of vision at baseline, and I'll come back to this. 366 patients were randomized into three arms, in a one-to-one-to-one randomization. They all got LUCENTIS every four weeks, as per label, for six months, and they were either getting, on top of LUCENTIS, a sham injection, or a low-dose sozinibercept injection, or a high-dose sozinibercept injection for six months, monthly for six months.
Around a hundred and twenty patients finished the trial. The primary endpoint was mean change from baseline in best-corrected visual acuity at week twenty-four. Secondary endpoint were a mix of functional and anatomical endpoint. Very interestingly, the pre-specified subgroups were set in the protocol. It's been known for a very long time that actually some lesions respond better to anti-VEGF-A than others, and therefore, the point of the phase II-B was not only to do a dose ranging of sozinibercept, but also look at are the patients benefiting better or benefiting more from the combination as opposed to others? And we have the answers now, which I will share with you. The baseline characteristics were very ordinary for this type of trials, as you can see, so disease of the very elderly patients.
They were close to 70 years-80 years of age. We had patients that were the disease was active. There were presence of fluid in the retina. Their retina was the retinal thickness was elevated with 410 micrometers-420 micrometers of retinal thickness. What was different in that trial was the baseline, the best corrected visual acuity, which was around 50 letters across the three arms, and that was by design. It was an inclusion criteria that we wanted patients with a lower vision to allow these patients to gain more than they would in a trial if the patients had perfect vision.
Simply with the idea here to be able to see separations of the arms between the monotherapy and the combination therapy, which we have seen, that I will show you. Finally, lesion types were identified so that patients and patients were very well-balanced between the arms. The idea, again, was to see if some groups would benefit more from the treatment. The primary endpoint was on the overall population, and you can see here a delta of 3.4 letters at six months between the combination of sozinibercept, high dose with LUCENTIS or ranibizumab, compared to ranibizumab alone, with a very good P value. The low-dose sozinibercept did not perform differently to ranibizumab alone, and therefore, our phase III program continues with the two-milligram dose, which is the dose we selected.
So the dose selection worked. We now have our winning dose. When looking at what you call the biomarker-positive patient population, which is these patients in which we've known anti-VEGF-As tend to not deliver results as good as they do in classic lesion patients, for instance. These patients are normally suffering from occult and minimally classic lesions. And in that patient population, that was pre-specified, you can see here a difference, an additional benefit of 5.7 letters for patients receiving sozinibercept 2 milligram on top of LUCENTIS compared to LUCENTIS alone, with a very strong P value. And that is the patient population on which in our phase III trials, we will be running the primary analysis on all the endpoints.
This is the majority of the patient population in clinical practice, and it's around three-quarters of the patients that the clinics see on a regular basis. So it's not a niche population at all, but clearly the ones that benefited the most from the combination treatment. Sorry, I'm struggling with my slide. Here we go. We always look at functional endpoints in retina trials. We want to see if patients can see better, but to support these visual benefits, anatomy is important because the correction of the anatomy leads to these better vision outcomes, and you can see here for all parameters, the combination arm overperformed the monotherapy arm with LUCENTIS.
Whether it was in the mean change in central subfield thickness, or the proportion of patients presenting subretinal fluid, or the proportion of patients presenting intraretinal cyst, all endpoints trended in favor of the fixed combination of sozinibercept with ranibizumab. Looking at the lesion area of these patients, so the surface of blood, fluid and blood vessels in the back of the eye, you can see here a much stronger reduction in the case of patients receiving the combination treatment compared to monotherapy, and same was observed in a choroidal neovascularization area, basically the abnormal blood vessels in the back of the eye. You can see a stronger effect of response with the fixed combo.
Very interestingly, in these very hard-to-treat patients, these polypoidal choroidal vasculopathy patients, it's a very common type of wet AMD in Asia. It's actually not rare in Caucasians. We had close to 20% of our patients who were Caucasian in this phase II-B trial presented with these lesion types. You can see here that in the control arm, these patients benefited less from LUCENTIS, only 6.9 letter gain, as opposed to an average of over 10 letters for the overall population. But the combination arm had a massive improvement compared to monotherapy in that especially hard-to-treat lesion types. That alone is probably a billion-dollar indication.
These patients still receive laser because they are so hard to treat that sometimes anti-VEGF-As alone is not enough. So we will have these patients in our phase III, and probably more patients because we enroll patients from Asia as well in our global trials. Safety, I'll go fast here. Nothing exceptional was discovered. It's either the safety profile of these sozinibercept injections is very similar to the safety profile of anti-VEGF-A, so it doesn't seem that having two injections on the same day in the same eye created any sort of additional safety concern compared to ranibizumab or aflibercept injected alone. Same on inflammation, which is something we always of interest in the eye.
As you can see here, there hasn't been a trend in any type of inflammation of a higher risk for the combination compared to the monotherapy. So moving to the phase III trial, our trials are well advanced. As I said before, fully enrolled, there are close to two thousand patients in total. They are multi-center global trials. We run them in a large number of countries, double masked, randomized one-to-one to one. There are three arms. And they are also studying treatment-naive wet AMD patients. Each trial has a different comparator. COAST has Eylea or aflibercept as a comparator, and LUCENTIS is the comparator on SHORE. And these trials are very well powered to detect a difference between monotherapy and combination.
The primary endpoint of these trials is mean a change of BCVA versus baseline at week 52. The primary endpoint is at one year, and then we have the same type of functional and anatomical endpoint as a secondary endpoint. The design is the following: they are very similar. COAST is using aflibercept, as I said before, as a comparator, use as per label, so three loading doses, and then aflibercept given every eight weeks for the duration of the trial. The trials are two-year duration, with a primary endpoint at week 52.
Patients are randomized in the COAST trial, and they all get aflibercept as per label, and then they get either a sham injection every four weeks, or they get sozinibercept two-milligram injections every four weeks, or they get sozinibercept two milligrams every four weeks for three injections, and then they get them every eight weeks. The SHORE trial is a similar principle using LUCENTIS as a comparator. LUCENTIS is given as per label every four weeks for two years. Sozinibercept is given, and patients are randomized. They either get a sham every four weeks, or they get sozinibercept every four weeks for two years, or they get sozinibercept three times as a loading phase every four weeks, and then sozinibercept every eight weeks for the duration of the trial.
Patients are followed up for, after week 52 for another year, and this is mainly to collect additional safety data, and that data is part of the BLA filing. We've made a lot of progress. Not only we have fully enrolled, and we are now in the middle of these two trials, but we've also made very good progress in manufacturing. We need to be able to produce three commercial-scale batches, to validate our process of manufacturing for the BLA filing, and we are making very good progress there. We also have fast-track designation from the FDA, which will allow us to file modules as they go, as well as potentially assuming our data comes out positive, potentially have a faster review and faster approval from the FDA.
Finally, we are building the team to not only deliver the BLA and the approval from multiple health authorities, but also to prepare for commercial launch, building up our commercial and market access capabilities. In a nutshell, to summarize, it is a very large market, large unmet medical need, over $15 billion a year market. We will be the first and only therapy to demonstrate superior visual outcomes if our trials come out to be positive, and the only ones over the last 20 years to improve visual outcomes of the patients. We are the only company working on such an approach. As I said, we are not disrupting any sort of prescribing protocol.
We are just sliding in a very well-oiled machine that is currently delivering these standard of care anti-VEGF injections around the world, and finally, this is a very concentrated market. A few hundred retina centers in the U.S. prescribe the majority of these injections, and therefore, it is a very interesting biotech play for us if we were to commercialize the drug ourselves in the U.S. Thank you very much for your time.
Thank you so much, Fred, for that fantastic presentation. The wet AMD space is definitely something very exciting to be in these days, I think. I'd also like to extend a quick thank you to all of our presenters this year, as well as everyone who took the time to watch this presentation. I hope you have a great rest of your conference.