Good afternoon. My name is Frederic Guerard. I'm the CEO of Opthea. Opthea is a publicly listed company in the U.S. and Australia, and I will be making some forward-looking statements. You can find our disclaimer on our investor section on the website. We are working on a drug called sozinibercept, which has the potential to be the first drug in the last almost 20 years to demonstrate superiority in terms of vision for patients affected by wet age-related macular degeneration. The standard of care has been established in 2006 when Genentech launched a drug called Lucentis, which changed really the destiny of these patients who before were all going blind after some time.
Now, millions of patients around the world get these injections in the eye of anti-VEGF-As. Lucentis was the first drug, others followed, and this market has become around $14 billion a year just for wet AMD around the world. This is still the most prevalent cause for loss of vision in Western countries. Despite the drugs, patients still lose vision. Sozinibercept is a first-in-class VEGF-C and D trap. It's an extremely potent molecule, and basically, we are developing the drug to be combined with existing standard of care. It's in addition to existing drugs. This is a new molecular entity.
We have composition of matter IP at least until 2034, and potentially beyond in the US with biologic exclusivity we will get here. We have a positive phase IIb trial that demonstrated superiority in combination with Lucentis, standard of care, compared to standard of care alone, and the safety profile was acceptable, and I'll go through this data in a minute. We believe we have the potential by adding sozinibercept to existing drugs to improve the vision of a patient, which is for the patients, the only thing that really matters is their ability to navigate life and operate, drive, see their family, and read. We are in the middle of our pivotal program. We enrolled two large trials.
The first one is called COAST, and I'll go back later on the design of it. That enrollment was completed in February of this year, and we announced last week the full enrollment of SHORE, which is also now ongoing. These trials need to read out at week 52. So we expect the top-line data from both trials in the middle of next year. So the market grew from being a rare disease, wet AMD was not, the treatments were either suboptimal or people were not getting access to them, so people were diagnosed with this disease and were going blind in a matter of weeks.
And now, after 20 years of these drugs and this green bubble being used, these patients actually can maintain some sort of vision, at least for some time. And this market has grown from nothing to being around $15 billion a year now. So what we do is we do not want to disrupt this market. We want people to keep on using the drug they want as an anti-VEGF-A. It's only one class of drug that is being used, all, they are all anti-VEGF-As. And we just want to add our drug on top.
We want to make sure we fit into the practice of the clinicians around the world, not disrupting the way the drugs are used or the way the drugs are reimbursed. We are developing the drug to have a broad label so that we can be used with any anti-VEGF-A, not a particular one, but basically the entire market. This market is transforming very fast. Biosimilars of Lucentis have been already launched in the U.S., available and used quite extensively. Eylea biosimilars have been approved last week by the FDA. There are two of them approved. They can't launch quite yet. New drugs like Eylea high dose and Vabysmo have been launched recently.
Vabysmo around two years ago, Eylea high dose last year, and these drugs start to grow. Vabysmo registered $2.8 billion of sales last year, which was their first year of full year of sale was last year. This is our team. We were very lucky to get Dr. Arshad Khanani to join us earlier this year. He's one of the most published and most researched retina specialists in the world. He's working now part-time with us, so a day a week, still practicing medicine. He sees around 100 patients a day, but he's still advising us a day a week. And then we have a raft of clinical and medical advisors that are helping us.
So despite these fantastic drugs, and they really changed the destiny of these patients by allowing them to regain some vision and stabilize that vision over time, most patients on anti-VEGF-A cannot go back to driving level of vision. So they can still operate in life, but they certainly cannot operate as before. They still have fluid in the back of the eye, so a healthy retina is dry. You have no abnormal blood vessels. You have no leakage from these blood vessels in the back of the eye. So as soon as you still have some fluid, it means there is some disease activity. The majority of patients do not get rid of this fluid in the back of the eye despite the use of these very good drugs. So that's where—this is where we play.
We are basically offering with a VEGF-C and D trap with sozinibercept, a more complete blockage of this VEGF pathway, which we know is the number one driver of the disease. All the drugs on the market block VEGF-A or A and B and, PlGF, but basically leave wide open the third receptor of the pathway for, binding with, VEGF-C and D. So the combination with sozinibercept allow this complete blockage of this pathway, which is responsible for neovascularization and vascular permeability in the, in the eye. So this is what the market looks like. So, Lucentis clearly improved the standard of care 20 years ago. All the drugs that have been launched since then are all non-inferior to each other in terms of visual, benefits.
None of them has demonstrated any statistical superiority to any of each other. But what they provide, some of them provide a slightly better anatomical control or a longer duration of action. So patients do not need to be injected as often as they were when they were using Lucentis or Avastin. The market leader until recently was actually off-label Avastin, which was recompounded in the U.S. from oncology drugs. That was around 60% of the injections in the U.S., 40% was branded. That is changing a little bit now with the biosimilar entry of Lucentis. But as you can see, nothing much happened in the market for 20 years.
So what we are going to do is to come with sozinibercept and make the step change in the standard of care of the patients. We are developing the drug first in wet AMD. We also will go into the diabetic macular edema, which is another disease where our mechanism of action can benefit the patients. We're also working now on a fixed-dose co-formulation of sozinibercept with an anti-VEGF-A to have the two drug mixed in a vial, and therefore, ready to inject. This is a feasibility study which is currently ongoing. So this is the phase IIb design. So first, this is another slide of all the trials that were done with the drug.
As you can see, a large number of patients have been injected with sozinibercept over the years. I'll go back to the phase 3 design before. The design of the phase 2b was the following: so it was a 366-patient trial. The patients were randomized into three groups. They were all getting Lucentis every four weeks for six months, and they were getting on top a sham injection every four weeks, or a low dose of sozinibercept every four weeks, or a high dose of sozinibercept. The patients that entered the trial were naive. They had never been treated for the disease before. The inclusion/exclusion criteria were very standard for these trials, with the exception of vision, which by design was targeted to be lower at entry.
The point being that if you want to show the superiority of a combination of drugs, you need to make sure the patients have enough room to improve over standard of care. So we took patients that had a slightly lower vision at baseline, and the patients were followed for six months. The primary endpoint was mean change from baseline in best-corrected visual acuity at week 24. This was a 24-week trial, and we had a whole raft of secondary endpoints looking at functional and anatomical benefits. We had predefined the subgroups based on the lesion type of these patients. So disease is not uniform. You have different types of blood vessels that grow in the back of the eye. They all have different characteristics, and they all respond differently to existing standard of care.
So, these lesions were predefined, and I will, I'll come back to this. These, those are the baseline characteristics of the patients, nothing exceptional, an average of 77 years old, which is common for this disease. The only thing which was a bit different compared to other trials was the baseline, the best-corrected visual acuity, which was at around 50-51 letters, which as per design and as per inclusion criteria. The patients were classified per their lesion type, and as you can see, the majority of patients had minimally classic or occult lesion, which is what's happening in the market, in clinical practice, with a minority of patients having classic or predominantly classic lesions.
And then we had a number of patients on top of these lesions having PCV or RAP lesions, and I'll come back to this. And the patients had disease activity. They had fluid present in the back of the eye. So on the all-comers overall population, we demonstrated with a high-dose sozinibercept in combination with Lucentis, a 3.4-letter improvement in vision at week 24 compared to Lucentis alone. The low dose of sozinibercept did not deliver a statistically significantly different benefit in terms of vision. It did benefit in anatomy, but not in terms of vision. So that was for the all-comer population with a very good p-value. On the harder to treat patient population, so we know the classic lesion patient population respond better to anti-VEGF-A.
So when you exclude these patients, and it was all predefined in the phase IIb, and you focus only on the harder to treat patient population, the occult and minimally classic lesion patients, you can see here we demonstrated a 5.7-letter improvement between the standard of care and the combination with sozinibercept high dose. This is the patient population on which we will conduct the primary analysis of the pivotal program, the exact patient population here on the slide. So 5.7 letter is more than a line of vision. We use a different vision chart than what you see at the optometrist. It's called the ETDRS.
A vision chart is basically five letters per line, so a line is considered to be extremely significant, and here we have 5.7 letters. And as I said before, this is the majority of the patients in clinical practice. So this is what the lesions look like. So depending on the type of lesion you have, you have deeper penetration of the blood vessels, the abnormal blood vessels in the retina. And as I said before, the classic lesions on the right are highly responsive to existing treatment, so we do not expect these patients to benefit much from the combination with sozinibercept, but the majority of the patients are occult and minimally classic, and these people showed very good, very good results.
We looked at the anatomy of the retina, which is not completely correlated to vision, but certainly is a biomarker of disease activity and drug activity, obviously, or drug effectiveness. The patients had a reduction in the central retinal thickness. They had less presence of subretinal fluid in the eye, less presence of intraretinal cyst. They also had a reduction in the lesion area of the eye, which is a measurement of the leakage of the blood vessels in the back of the eye, as well as a reduction of the choroidal neovascularization, which is basically a measurement of the abnormal blood vessels in the back of the eye.
So all of this is trending in a reduction of the disease activity, and that probably explain how it translated into better vision for these patients on the combination. Specifically, how to treat patient population is the PCV patients. These polypoidal choroidal vasculopathies are very common in Asia, and very hard to treat with standard of care anti-VEGF-A. So here, we almost double the vision benefit on these patients, and these patients will be enrolled in our or have been enrolled in our pivotal programs, already. We're gonna get this subgroup analysis from the pivotal trials. The safety was unremarkable, very similar for the combination of sozinibercept alone, very similar to anti-VEGF-A therapies. Whether it was systemic or ocular safety and... Sorry, I'm pressing the wrong button. And same for inflammation.
We had no particular signal of inflammation, that would point to a different safety profile to anti-VEGF-A. The ongoing pivotal program is the following: We are, the program is designed to first test every endpoint, primary and secondary endpoint, on the biomarker-positive patient population, which is this minimally classic and occult patient population. RAP absent, we excluded the RAP from the trial. Those are two very large, phase 3 program. One is using Lucentis as a comparator, the other one is using Eylea, and that is to basically allow us to get a broad label of combination with any anti-VEGF-A, not to be linked to one in particular. Sorry, I keep on pressing the wrong button. So the trials are designed as follow.
We reported last week, we have enrolled 1,984 patients in the phase 3 program. We expect the top-line data by mid-calendar year of next year. These two trials look very similar. I'll show you the design in a minute. 330 patients per arm. It's a 1:1:1 randomization, and people get either the standard of care or the standard of care and sozinibercept every two month, or the standard of care and sozinibercept every month. So that's the design, and we are very well powered. We have a 90% power to detect a 4.7-letter difference between the control and the active arm. The primary endpoint is very standard in wet AMD, so mean change from baseline BCVA at week 52.
The trials are two-year trials. We, you know, the efficacy is at 1 year, and then we collect the second year for safety purposes for the FDA. But we can file with the 1 year, the 1-year data. And the secondary endpoint are a mix of functional and anatomical endpoints. So people gaining 3 lines of vision, 2 lines of vision, or any sort of anatomical benefits will be tested in the plan. So this is what the trials look like. We use both comparator drugs as per label, which is, for wet AMD, everyone gets monthly injections for the first 3 months, and then, if you're on aflibercept, your intervals are extended to every 8 weeks.
If you're on Lucentis, you stay every 4 weeks for the whole duration of the 2 years of the trial. And then the patients either get sham, or as I said, they get sozinibercept every 4 weeks or every 8 weeks. Primary endpoint at week 52. So this is where we are now. So the trials are fully enrolled. We have certainty about when the trials are gonna read out next year. We are so very busy manufacturing the drug at commercial scale, which is required for. We are required by the FDA to test the process of manufacturing at commercial scale. So we are running 3 consecutive batches at commercial scale. So that's happening now, and that will be part of the BLA filing.
We have a fast track designation from the FDA, which would allow us potentially a faster review than normal, and we are allowed to submit the modules whenever they are ready, so a preclinical, manufacturing, and so on. We don't have to wait for the clinical data to get the process started, so we have hired a team of experts to do that for us. And finally, we are preparing the BLA filing as well as manufacturing and commercial readiness in the organization. So I'd like to thank you and take questions if you have any.
Thank you. Thank you for a great discussion, and if I may. So for the second injection, could you walk us through the logistic steps of how the second injection of OPT-302 is performed in the clinical practice? And what's the typical wait time after first injection, and also, how should we think about the reimbursement, any reimbursement complexity because two separate injections?
Yeah, very good question. So, the injection in the clinical trial design, patients get injected on the same day with either two actives or two shams or one active and one sham, depending on the arms and the frequency of injection they are in. Our drug is 50 microliters, and anti-VEGFAs are also 50 microliters. So the two, when you inject the two on the same day, you basically inject 100 microliters in the eye. Drugs have been approved already by the FDA with that volume of injection. So we know that volume does not create an issue of increase intraocular pressure in the eye. That's been well demonstrated by drugs in geographic atrophy.
So, the way the drug will be used in clinical practice, the patients will present exactly as they do now to get their anti-VEGF-A. They normally get a reading chart, a test, they get a scan of the back of the eye called OCT, and the physicians will normally inject on that day these patients. What will happen is they get the first injection, they stay in the chair, and immediately after, they can get the second injection. So there is no mandated waiting time between the two injections. In the context of the clinical trial, because we want to collect safety, we actually ask the physician to measure the intraocular pressure after the first injection and only inject when the intraocular pressure has returned to normal.
In clinical practice, we know today drugs with 100 microliters are being injected, so it's not gonna be mandated by the FDA in the label. It's highly unlikely. On the reimbursement. So, sorry, I want to add one thing. It's no additional burden for the patients because what takes an awful amount of time for the patients is to drive to the clinic, get all the exams, get the eye prepared for the injection, wait, get injected. From there, adding another drug takes 30 seconds. So for the patient, it's actually no additional burden. All the burden is for the first injection, not for the second one. Reimbursement, so all agencies around the world, US and ex-US, pay on vision benefits.
So our primary endpoint is exactly what the payers want to see around the world, which is additional vision gains, and there is a depending on the country, there are different methods for pricing the drugs, but basically it's a, it's a price per pair, number of letters you gain versus, versus baseline. So we do not expect any sort of exotic requirement from payers. The other benefit is we are doing our trials using Lucentis and Eylea, and both these drugs are considered to be standard of care. So that means the payers will have the data they need to make a decision on pricing.
Okay. Maybe one more question as to what AMD treatment landscape is evolving with Vabysmo and a high-dose Eylea, both approved, and Eylea biosimilar is also approved. How do you see these new therapies shape the wet AMD landscape in near future, and how should we position OPT-302?
Yeah.
in this market?
So all patients have individualized treatment. They basically get diagnosed, get the 3 monthly injections, as I said before, and then they get evaluated every visit, and the intervals of injections between visits are decided by the clinical specialist at that time. What we know in clinical practice is that this new high-dose drug, like, Eylea high dose or Vabysmo , seem to be lasting in clinical practice around a week, 1 week longer than Eylea or Lucentis. So the way we were told our drug will be used is physicians will use whatever anti-VEGF they want as a baseline therapy, and then they will inject our drug in the same, using the same intervals of injection. So it could be every 4 weeks for some patients, it could be every 10, every 12 weeks for others.
It's always all individualized at patient level. So these drugs are not gonna change the way they practice medicine. We've seen biosimilars making big inroads, which is great for our case because payers are gonna make some savings on the biosimilars. And therefore, it will create the space for them to pay for our drug, which will be used on top of these biosimilar drugs. So it's all benefit for us.
Terrific. Thanks again. That's a wrap up for the session.
Thank you.