Good afternoon. Welcome to the H.C. Wainwright Virtual Fireside Chat with Dr. Pravin Dugel, Executive Chairman, President, and CEO of Ocular Therapeutix. Thank you for joining us, Pravin.
Yi, thank you for the opportunity. It's a pleasure to be with you today.
Thank you. My name is Yi Chen. I'm an Equity Research Analyst at H.C. Wainwright. For the audience, please note that you can submit your questions via the Q and A link, and we will address your questions at the end of this session. Pravin, I understand Ocular is preparing to submit an NDA for AXPAXLI as a treatment for wet AMD based on the SOL-1 phase III trial data alone. Have you received any explicit feedback from the FDA regarding the requirement of only one pivotal trial data for the approval?
Yi, thanks for that question, and obviously this is very important for us, for the company, for doctors, and most importantly for patients. Our intention is not just to have the best in class, but also the first in class. We have known for quite a while from the leaders of the FDA, Dr. Makary, and others, that the intention was to have a single trial approval, and this was cemented in their editorial first in The New England Journal of Medicine. Since then there have been several other communications that have also emphasized that. What's really important to state is that two things.
One is that this is a default position that the FDA intends. It's not an option, it's a default position, and that's a really important statement. That's been stated very consistently. The second thing which has become clear from not just the editorial, not just the communications that they've had, but also the communications that we've had formally with the FDA, is that they view this not as a lowering of their standards, but actually a raising of the bar, a raising of their standards. What they want is an extremely well-designed, well-masked, well-controlled study that's properly powered.
They really want a perfect study. We believe that if any such drug is gonna be approved based on one study, it's going to be this drug, AXPAXLI. We have a SPA, as you know. We've met a superiority threshold that nobody else has with a very robust p-value of 0.0006. We satisfied all the requirements.
We have stated publicly that we have begun the process of formal discussions with the FDA. We are very, very happy with the way that the discussions are going, and, obviously as others, we don't detail our discussions with the FDA publicly. Suffice it to say that if they weren't productive, and if they weren't collaborative, and if we weren't happy, and if they weren't happy, we wouldn't be continuing to have these discussions. When appropriate, we certainly will detail you and the street as well.
Got it. Would you be able to provide the estimated timing of the submission? Is it going to be this quarter or third quarter?
Yeah. Again, great questions. We're not prepared to answer that as yet. When appropriate we'll detail that. Just realize that again, if we weren't, and if they weren't happy with the discussions, you know, we wouldn't be saying what we're saying. We're following the guidelines of the FDA to a t. We've checked all the boxes, and we're very happy with the direction of the discussions.
Got it. Thank you. I understand the primary endpoint of SOL-1 is the proportion of subjects who maintain visual acuity at week 36. The results are 74% in AXPAXLI arm maintained vision versus about 56% in the aflibercept with about 18% risk difference. Do you believe the FDA will need to see other efficacy endpoints before granting approval? If so, what are those endpoints?
Yeah. You know, look, I don't wanna speak for the FDA, but I have worked with the FDA in my other capacity for over 30 years. What I do know is that the FDA, at least our ophthalmic division, is extraordinarily collaborative and extraordinarily consistent. We have a SPA. We have designed this trial according to their requirements and according to their guidelines, which were issued in February 2023, and this again was validated with a SPA. All of our interactions thereafter have been absolutely aligned and consistent with us doing everything according to the guidelines.
As you recall, there have been a number of modifications that we've had in this study, as well as with SOL-R. And everything that we did, everything we've done has been completely aligned with the FDA. Realize that even with the modifications we've had with SOL-1, the SPA has never been jeopardized. This speaks to the collaborative relationship that we have with the FDA.
My understanding from having worked with the FDA in general, and this is from a very high level, is that what the FDA wants is a study that proves that a drug has an acceptable and excellent safety profile, which we do. SOL-1 clearly has a safety profile that we're very proud of, and one that has robustly met statistical significance. Obviously we have to a very robust extent in a study that is well-masked. Again, we're well-masked. There is no sham here at all. That follows the FDA guidelines, again, formalized by a SPA.
We believe that we have everything that the FDA needs and wants for a single trial approval. Again, I don't wanna speak for the FDA, but suffice it to say, that we're very grateful for the collaborative discussions that we're currently having.
Thank you. How do you view the risk of the FDA requiring a second pivotal trial for approval given the superiority trial design of SOL-1 versus the historical non-inferiority precedent for anti-VEGF agents?
This company made a strategic move in saying that what we want is the potential to have the first and only superiority label, and the reason is very clear. As you see, in drugs that are already in the market and drugs that are being developed, they're all me-too drugs. They're all non-inferiority drugs. If you are fortunate enough to get a superiority label, it provides you the potential of being in a different orbit altogether and the potential of protecting you not only from a price point of view, but also from things such as step therapy, et cetera.
It's for that reason that we strategically made that decision to do everything possible per the FDA guidelines for a superiority track. We did. We achieved it. This is the first drug to ever succeed in a superiority endpoint ever, that I know of in retina. We also understand that the primary endpoint is one that the FDA desired, which is a separation of 15 letters. That's something the FDA has been very consistent with. We also recognize that that doesn't necessarily reflect, how clinicians treat on a day-to-day basis. The way they treat is really based on the OCT.
We've done a lot of things here in the last two months since the card turn to give a enormous amount of information that shows that this is the best drug that we think that has ever been studied based on disease control and based on the OCT findings. At the end of the day, I believe what the FDA cares about is that this is a safe drug that has met its primary endpoint to a statistical robustness that they desire and one that has been conducted with proper masking and proper power.
Yeah. Can you tell us what exactly drove the superiority of AXPAXLI over aflibercept in SOL-1? Is it visual acuity, durability, rescue rates, or patient selection?
Well, you know, again, we're not in labeling discussions as yet with the FDA as must be said. However, our expectation and our hope is that we will have the first and only superiority label to an anti-VEGF. Now how that is written is something that we still have to negotiate with the FDA. I believe that we're in a very good position to obtain the, again, the first and only superiority label.
Yeah. Is the superiority label meaningful to retinal specialists treating patients, or are they just looking for a more durable treatment option that is non-inferior to Lucentis?
Yeah. It's a great question. You know, if you were to ask me, and somebody pointed this out, you know, some months ago when I was in my previous life, you know, as a practicing physician. If someone was to ask me, "Hey, look, does the label matter?" My answer, and I bet if you call your KOLs they'll give you the same answer, is, "You know, I don't care about a label. I never look at a label, so it means nothing to me." You know, that's the wrong question to ask physicians. The right question to ask physicians is the following. Do you care that you get to choose the drug that you want the patient to be on from day one?
Do you care that you don't have to wait and see your patient fail in a drug that's inferior and then have to petition for the drug that you wanted in the first place? Do you care that the ASP is as high as possible? All of those questions will be answered with a resounding yes. It just depends on the question that you ask. Is a superiority label potentially important to the physician and the patient? Absolutely it is. In a way that is the way that I described, which is that there's a potential now not to be a me-too non-inferiority product.
There's a potential to be in a different orbit where one can be immune from step therapy, where pricing can be protected as a premium drug. All those things asked in the right way matter to physicians and matter to patients.
Got it. Does AXPAXLI's performance differ in treatment naive versus previously treated patients?
Well, you know, here's the thing. It's very, I don't know if it's unique in retina or not, but it certainly stands out in retina. As a retina physician who's practiced for 30 years, I can speak to this, which is that there's not a single drug out there that is used per label or per clinical trial. You know, as you know, all of us do treat and extend. There is no treat and extend in any label. There is no phase III study on treat and extend. What will happen with this drug, I believe, is what has happened with every other drug. Our job is to get this approved. This is a safe and effective drug with the best disease control that we've ever seen.
It doesn't require any change in the physician's workflow. It doesn't require any extra overhead. The experience is exactly the same for the physician as with everything else. It's simply a better product. I think what physicians will do is to go ahead and use this based on what is best for the patient. Now, some may start out as a treat and extend that's extended further and further, others may go ahead and jump right into, say, Q6-month dosing. That's to be seen. There's no reason that this drug, it can't be used in treatment-naive patients as well as previously treated patients.
That is something that will be, I'm sure, studied by others. As you know, this trial was done in patients who were previously treated and loaded with EYLEA. These were treatment-naive patients that went through a loading phase, both in SOL-1 as well as in SOL-R. The reason for that was patient selection. The reason for that was to make sure that we have an enriched patient population suitable and bespoke to each trial. It wasn't, at least in my opinion, based on the requirement biologically to have an anti-VEGF to load and then maintain with a long-acting TKI.
However, if that is the case, if I'm wrong and that is the case, that's okay. I mean, it's perfectly fine to have a couple of EYLEA injections and then to have a TKI for the next, you know, 10, 15, 20 years. It doesn't really change the projection of this potentially being the most impactful drug ever in this field.
What I base my opinion on that this is a first-line drug are a few patients and admittedly these are a few patients in the study in Australia who received this drug as first-line therapy, and these patients were treatment-naive. The response that we saw were what one would expect for commercial-grade Lucentis or EYLEA. Those studies will be done once this drug is out in the community. I look forward to those studies. I think that's exactly what physicians should do. Again, our job here is to get this drug approved as quickly as possible and put in the hands of retina physicians to the benefit of their patients.
Yeah. Thank you. Ocular recently reported post-hoc analyses on durability metrics through week 52, including central subfield thickness increases, visual acuity gains, and BCVA changes in the rescue-free subjects. Are these results more meaningful for FDA approval or for market adoption by physicians?
Yeah. Again, I don't want to speak for the FDA, but, you know, having dealt with them, look, these are clinical trialists and superb biostatisticians in the FDA. What they will look at, as I've said before, is this drug safe? Did this drug meet the primary endpoint with robust statistical significance? Clearly we did, validated by a SPA. The rest of the analyses are really done in order to make sure that physicians and others understand how effective this drug is for clinical adoption.
We've said from the very beginning that the primary endpoint is very important from a regulatory point of view, but it's not necessarily what physicians do on a day-to-day basis. They don't wait for 15-letter loss. We recognize that. What physicians do is they look for disease control, and the barometer for disease control is very, very clear. It's the OCT. What we did was we provided data that nobody else has provided to show the level of stability and disease control that one gets with this drug.
A single injection of this drug at nine months will provide disease control that's within 30 microns of stability in a majority of patients, and that's absolutely unheard of. If somebody said that that was going to happen some months ago prior to the card turn, one would just laugh because that level of disease control has never been achieved.
What we've done with the results of SOL-1 and the analyses thereafter is not only satisfy the FDA's requirement for a superiority endpoint, but provide several endpoints that are very, very important. The most important one, in my opinion, being the OCT endpoints, which show disease control that are absolutely relevant to the day-to-day practicing retina specialist.
Yeah. Thank you. Looking at AXPAXLI safety profile, how does it compare to Lucentis, EYLEA, and Vabysmo?
First, let me say that if you're ever going to even think about having a drug that's going to supplant the current anti-VEGFs, you know, Lucentis, EYLEA, Vabysmo, EYLEA HD, the safety profile has to be absolutely superb. It's an absolute no-go if it is not, because these drugs have a superb safety profile. What we did when we saw the SOL-1 results is we said our safety profile absolutely meets those criteria. This is as good as any of the anti-VEGFs that are commercially available.
To prove that, what we did was something that nobody else has done, which is to show everybody everything from day one up to the patient level. Nobody's ever done that. We showed every single IOI. We showed absolutely everything because as clinicians, as you know, in this company we have more retina experience per capita than any other company on the planet. We looked at the safety profile and said, "Look, I would adopt this tomorrow," 'cause the safety profile was that good. We showed everything. You know, there are companies that show everything that's above 5%.
There are others that show everything that's above 2%. We showed everything at the patient level. Yes, there were questions that were raised, questions that quite honestly we did not expect. For instance, the floaters question is a question that was raised. Well, what are these? Why is the floater rate, you know, so higher? And recall that the floater rate was in the twenties in the phase III Lucentis studies. We never thought that this was an issue at all, but it became an issue. We didn't anticipate it, but it became an issue. We said, "Look, it's very simple what these are. These are drug."
We asked physicians to look for this. It's way out in the periphery. Patients didn't see this. Physicians saw this. We asked them to code it as floaters because the MedDRA classification had no other coding. It will after the summer because of us, but to this point, it doesn't. It's really nothing that troubles the patient and we showed all the data supporting that, including the fact that these floaters came when the drug was supposed to come, went away, and had no impact on the visual acuity whatsoever.
I think what we've done from a safety point of view is to show everything to prove that this drug absolutely is in a position to compete with the anti-VEGF based on the safety profile, and now also based on the efficacy. I think every question here has been answered at the level of the patient. Again, this type of scrutiny, this type of transparency for safety, I don't think has ever been provided at a patient level this early, and this transparently.
Thank you. Comparing AXPAXLI to DURAVYU developed by EyePoint, what are AXPAXLI strengths or weakness, if any? What is the current status of the ongoing litigation?
Well, look, it's not appropriate for me to talk about other companies, but what I will tell you is that there are certain things that are scientifically very obvious and are factual, which is that we have two different TKIs. Not all TKIs are the same. We believe that we have a TKI that's far more potent, far more sensitive to VEGF. We also believe, as we've stated over and over again, that the TKIs at a physiologic level inhibit VEGF, which is what they should do. We don't think that they do everything as others have claimed.
I think we've been very transparent in terms of what they do and provided a lot of scientific evidence, and that's out there in public from third parties to show exactly what TKIs inhibit. We also have a format for long-term release that has been proven previously. As you know, this hydrogel is FDA approved, as is the TKI. Our safety profile shows that we have no cases of endophthalmitis. We have no cases of ischemic or non-ischemic vasculitis. This is very much in contrast to other TKIs and other formats. We believe that this is the safest and most effective drug there is.
We have demonstrated superiority nobody else has. We have demonstrated a level of disease control that nobody else has, and we look forward to providing further data. I think we're very distinguished from other companies in that regard.
Thank you. Can you tell us how do retina specialists who are actually treating wet AMD, wet AMD patients interpret SOL-1 data versus competing drugs?
Yeah. Again, excellent question. We recognized a long time ago that this trial result would require quite a bit of communication, quite a bit of explanation because it's the first of its kind. Realize the job of this company, first and foremost, is to make sure that we follow the FDA guidelines, and if we believe that this drug is safe and effective as we do, that we get this drug approved. That's our job. We also need to educate, and that takes some time because this trial is the first of its kind. There's no anti-VEGF trial of this kind that can be compared with. It's taken some time to educate everybody.
We are there at this point, and it's only been a couple of months. What the doctors talk about now, which is great, is not whether this drug will be in their hands or not. They all do believe that it'll be in their hands. What they talk about is how they will start using this. Will they use it directly in a fixed fashion every six months? Will they do a treat and extend and extend that? That's the discussion, and that's great. I don't think that there's any doubt as to the drug's ability to control the disease.
Again, we recognized also that the endpoint was one that may not be entirely clinically applicable, but we went out of our way to give a ton of information in regards to disease control. The durability of this drug is very well known. The disease control of this drug is very well known. The safety profile is very well known. I dare say that in a matter of two months, we've given more information about this drug than most sponsors do.
Got it. Assuming the FDA is okay with the SOL-1 data alone, how would positive SOL-R data expand the label or reimbursement positioning, even if it's not required for initial approval?
Yeah. Thank you for that question, and it's really important to know as happy as we are, as encouraged as we are with our communication with the FDA for a single trial approval with SOL-1 alone, please realize that SOL-R still goes on as efficiently, as effectively as it ever did. SOL-R is going great. We're not doing anything to SOL-R. We're not opening up SOL-R. We're not disbanding SOL-R. We're not changing SOL-R. We absolutely will run SOL-R as efficiently as it's being run right now, and it's doing extremely well. We're very happy with the execution of SOL-R. What SOL-R will provide is additional information.
We still believe that it won't be required for approval based on our interactions thus far. However, we believe that it will provide some very important information from a clinical point of view. We don't think that that's information that's necessary for doctors to adopt this drug. We believe that SOL-1 alone contains all the information that one needs for doctors to adopt this drug. However, having SOL-R run and having the SOL-R data will certainly help and provide additional information that will be very important as well.
Got it. Can you also tell us the current status of the SOL-X trial, what it brings to the regulatory process or future market positioning of AXPAXLI?
Yeah. Thank you for asking that as well. SOL-X is very important. As you know, it's the extension trial. There are a number of things that SOL-X will answer. The most important thing that SOL-X will answer is the long-term outcomes. You know, we always talk about the fact that the purpose of this drug, of AXPAXLI, is twofold. The first goal is easy, and that's really what we spend our all our time talking about right now, which is sustainability or durability of the drug. That's the easy thing that people look at. The other one that people tend to forget about is that of better long-term outcomes.
As we've always mentioned, look, it's not just a tragedy from a human point of view, from a social impact point of view, that now almost four decades after the miraculous benefit that we see from the anti-VEGFs, in this country alone, 40% of patients in the first year drop out, and all of these patients go blind. Nearly half the patients go blind after dropping out in the first year despite having a drug like this. That's the first goal that AXPAXLI aims to cure.
The second goal is that even those patients who come in religiously to get their injections, after about three to five years, they inevitably end up losing vision and getting worse than baseline. They do so not by rebleeding, which is what we had assumed in the beginning, but they do so with fibrosis, and with atrophy. We know why. It's because the pulsatile nature of our injections. You know, we inject every month, so there's a massive amount when it goes away, or every other month, there's a massive amount that goes away.
The back of the eye gets thick and thin and thick and thin, and because it's neural tissue, it's akin to having multiple concussions, and that's why you get scarring, and that's why you get atrophy. There's a great amount of evidence to show that if you can suppress on a near zero-order basis where you can keep suppression continuous, and you don't have these pulsations, you reduce the risk of having fibrosis and atrophy and thus get better long-term outcomes. We believe that SOL-X will demonstrate that. Remember, in SOL-X, patients are crossed over after two years of pulsatile treatment.
We don't think those patients will ever catch up. Remember that you can start seeing atrophy and fibrosis by OCT, and this is not necessarily vision-threatening fibrosis, but fibrosis on OCT nonetheless, as early as 90 days following pulsatile treatment.
We believe that after two years of pulsatile treatment, when these patients cross over, they will already have enough fibrosis, already enough vision-threatening fibrosis and atrophy that they'll never catch up to those who are on AXPAXLI to begin with. Not only will we be able to demonstrate the durability and disease control and sustainability of this drug, but with SOL-X, we'll also be able to demonstrate the better long-term outcomes of this drug. There'll be more information, by the way, about SOL-X and about where we stand with SOL-X in our upcoming Investor Day.
Got it. AXPAXLI has the potential to be the first TKI approved for wet AMD. What real-world evidence or market research supports the willingness of retina specialists to adopt a TKI-based intravitreal hydrogel with potentially fewer injections?
Well, you know, look, what we know from history is the absolute thirst there is for anything that lasts incrementally longer and has a comparable safety profile to previous to our current anti-VEGFs. We've seen this in history and over and over again, and let me give you a couple of examples. I'm old enough to remember Lucentis as an absolute miraculous drug, and Genentech still as one of the finest scientific companies there is. Remember Genentech and Lucentis had a seven-year head start, and that's an infinity in our field. Then came Regeneron, a company we'd never heard of, with EYLEA.
Arguably, EYLEA bought us an extra week or maybe two weeks. After seven years of dominance, Regeneron took over the entire market with EYLEA. Now we have history repeating again. If you look at Vabysmo and high-dose EYLEA, maybe that buys you another couple of weeks. That incremental increase is a huge amount of market share. What we believe will happen with AXPAXLI is that it'll be in a different orbit altogether. We're not talking about an extra week or two weeks. You know, we're talking about two-thirds of patients with a single injection not being rescued for a year.
And that's very, very impressive, specifically with the disease control that I mentioned within 30 microns in a majority at nine months. That's what physicians look for. They also look to make sure the workflow is not disturbed. There's not a single piece of new equipment to buy. There's no new workflow that's gonna be present. There's no steroids to be given. There are no carcasses left floating around. There's no surgery to go to. The doctors simply put their hand out and get a better drug. The patients are happier, the doctors are happier, and I dare say the payers are happier because fewer patients are going blind.
One may be concerned if you talk to your KOLs that, you know, well, I'll be giving less injections. You know, they actually won't be giving less injections. They'll actually be giving more injections if they want, just not to the same patient over and over again because there'll be fewer patients dropping out, and the catchment will be much greater. I mean, just think about the potential impact of this on society.
If we reduce the dropout rate by even 10%, which can easily be done, 250,000 fewer patients will go blind in this country alone. That's impactful. That's a statement that should really resonate. Doctors will be able to inject as much as they want with a better drug, without potentially needing to go through step therapy with a higher ASP, with happier patients because the retention will be greater and the drug is better. That's just with wet AMD. That doesn't even include the other topic that we haven't talked about, which is a field that's 3.5x bigger than wet AMD, which is diabetic retinopathy.
Assuming a six to 12 months durability label for AXPAXLI, how would you model peak sales of AXPAXLI?
Yeah, you'll hear more about that, in our investor day as well. You know, we obviously have a very fine commercial team. We're very lucky to have a commercial team led by David Robinson, who's the person that has led the most successful launch ever in our field, which is the launch of EYLEA. We're also fortunate to have a commercial team that is already selling a product, which is DEXTENZA. That team is almost completely built out right now. We have the sales force in hand. We have all the folks that we need in specialty care, et cetera, already enhanced.
We're ready to go with that, and we have great leaders leading that right now.
Could you give us a very short preview of the size of the targeted sales force and structure?
Yeah, great question. You know, what I will tell you is, at the height of the sales for Lucentis, you may be surprised to know that their sales force consisted of 55 people, I believe it was. So it's not what you're used to in oncology or rheumatology, where there are hundreds and hundreds of people. We already have that, and we have more than that, you know, based on DEXTENZA alone. So we already, you know, really almost every piece of the puzzle is already here.
Got it. Yeah. Can you comment on the pricing strategy that you're considering relative to current branded anti-VEGF such as EYLEA and Vabysmo? Do you believe the market adoption of biosimilar EYLEA could have an impact on your pricing strategy?
No, we don't. Not if it's done properly, and we'll do it properly because, again, that's the advantage of having a drug that will potentially have a superiority label. It puts us in a different orbit altogether, so we're not a me-too drug that's competing with a whole bunch of other me-too drug where they are susceptible to these kind of pricing pressures. The simple fact is that we're in a wonderful position of being in a win-win-win situation. We have payer boards on a constant basis. We've had a number of them. And payers love this. And why do payers love this drug? Because of the cost of blindness.
As I said earlier on, in this country alone, 40% of patients drop out in the first year. All of those patients end up going blind. You know, I've been on a couple of payer boards, and payers are actuaries, you know, much like your life insurance companies. As actuaries, they look at the cost of each disease, and the most expensive disease by far is blindness. It's not cancer, it's not heart attacks, it's not stroke, it's blindness. The reason is simple. The mortality doesn't change, but the use of resources skyrockets. If we can decrease that dropout rate, again, as I said earlier, by 10%, 250,000 fewer patients will go blind.
It's not just the human impact of that, the societal impact of that, but the economic impact of that on payers. There's a significant amount of cost savings on not having these patients go blind, which can be then translated into premium pricing for the drug, which potentially is immune from competition with other me-too drugs and step therapy. We haven't had obviously any pricing discussions. It'd be too early for that. We certainly have a very clear robust pricing strategy that is being built.
Yeah. Do you expect any potential reimbursement and prior authorization hurdles during commercialization?
I'm sorry, any reimbursement? What do you mean?
Yeah, reimbursement or hurdles like prior authorization by the physician.
Yeah, you know, again, it'd be a little early to know that at this point. You know, again, we continue to study payers and get advice from payer boards a lot. We are in deep discussions with them in terms of the logistics of how this will come out. We've got a group that's very familiar with buy-and-bill. We think that we have a great commercial strategy and reimbursement strategy that we will detail when appropriate.
Yeah, can you talk about your assumptions for market share uptake in year one to year three post-market launch, including conversion from existing anti-VEGF patients versus treatment-naive patients?
Yeah, it's a great question. Again, look, I think you will get more detail on our commercial strategy in our investor day. But let me say this, in the 30 years or so that I've been on the other side as a PI and as a practicing, you know, retina specialist, there has never been a drug, there's never been a drug that has done better in the community than it has done in clinical trials. That makes sense, right? What you wanna do in clinical trials is have the most enriched patient population to have this drug do as well as possible. That's how you design the trial.
When this drug goes to the community, and now you're exposed to patients of all types, the performance may still be great, but still it's not gonna be as good as the clinical trials. This will be the first drug that does better in the community than in the clinical trial, and that's a profound statement, right? What we did was we designed a clinical trial per the FDA's guidance, and the sole purpose of that was to be in a superiority trial. We looked at patients deliberately who were designed to lose vision, right? We took the most VEGF-dependent patients we could find in SOL-1.
Then we went ahead and stopped treating them and waited for them to lose 15 letters of vision once before they were rescued. That's the design that we got the SPA for, that was per the FDA's guidelines to the t, right? Arguably these were the most difficult patients to treat. Now, what will happen in the community? The bar for success will be so much lower in the community, and this drug will perform so much better.
Let me explain how. If you go to a retina doctor, today or tomorrow, they may see 50 patients. Of those 50 patients, one or two will be treatment-naive patients. The vast majority are gonna be previously treated patients. This doctor's gonna talk to Mrs. Jones and say, "Mrs. Jones, I know I've put you on EYLEA every other month for two years now, and I know that you're getting tired of that and you're frustrated with that.
What I have here in my hand is what I believe is a better drug, and I'm using it for the first time. I believe it may work better. Let me go ahead and give you that, and I still want you to come back in two months because I wanna see how it works with you. Here's the patient who's being treated every two months, and then the doctor may say in two months, "Wow, you're looking great. Now come back in four months or so." "You're looking great," and may treat, may extend that patient further and further. The bar for success for that patient is just a little bit more time. It's just durability.
That's the kind of patient that this drug will initially be used in, and the bar for success will be very, very low. For that reason, this drug will actually perform a lot better in the community than it ever did in the SOL-1 study with arguably very difficult patients. I think this drug will be very easily adopted, and this drug will impress physicians and patients alike based on that reasoning.
To that point, what percentage of retina specialists, I mean, in your view, could switch their stable patients with existing treatment options to AXPAXLI? Or is it rather a decision by each individual patient's payer?
Well, you know, look, if this is launched the way we believe it will be launched, and there's no reason to not have every patient, you know, switch to this and to not have every doctor adopt this. I mean, when you think about this, why wouldn't they? This is exactly what happened after seven years of Lucentis with EYLEA because of an extra week. If you were to be able to reliably tell a patient, "Look, you know, this drug with a single injection will carry you through for nine to 10 months," why would you not do that? It wouldn't make any sense not to do that, you know, based on the efficacy and safety profile we have now.
Our expectation is that this will be adopted universally.
Got it. Okay. So, are you currently considering any partnerships or co-promotion deals for the ex-U.S. markets for [inaudible]?
Yi, I can tell you the definitive answer is no. The only reason that people would consider partnerships is if they needed expertise or capital. We're in no need of either. We're in fantastic shape right now. We're scaling up very, very well. As I keep saying, we're very happy with our regulatory pathway forward. This is a global drug. We believe that our discussions outside the U.S. with regulatory agencies are also going very well. We have absolutely no reason whatsoever to partner.
Now, having said that, and maybe this is where your question is going next, you know, my job from the day that I came here is to make sure that I keep a network that's open for everybody. I'm fortunate enough to have been in this business on both sides for a very long time and developed a very good robust network of folks who are strategics and others. Look, I communicate with them all the time, and the level of interest has certainly gone up significantly since the card turn. I continue to communicate with strategics, and that is my job, and that is what I should be doing.
However, having said that, we're building a standalone company. It's really important to say that again, we're building a standalone company. We're building this product to launch this product ourselves and get it in the hands of retina specialists and to our patients. Now, we're a public company like any other public company, we're for sale every single day. That's not the intent. The intent is to build a standalone company. Having said that, my job is also to make sure that I communicate with everybody that's appropriate.
If anything happens, to make sure that I make shareholder value the primary concern here. As said, in building a standalone company, the advantage that I have here that I haven't had before is that I've got a fantastic commercial team, experienced commercial team. I have a situation where we don't rely on anybody outside the company to build this product and to scale up. As you know, we manufacture this ourselves, so we have complete quality control.
Both of the components of this drug are already FDA-approved, which allows us to submit on a 505(b)(2) basis. It also gives a great deal of familiarity with the FDA upon submission. There are a lot of those levers that we have that allow us to scale up and be very efficient and very self-contained. At this point, that's exactly what we're doing.
Yeah. Could you provide an update on the strengths and duration on of the IP portfolio protecting [inaudible]?
Sure, yeah. Our IP, publicly stated and publicly known and available, goes till 2044. We think we have a very robust IP. We are filing further IP based on our scale-up, which involves automation, et cetera, for materials and methods which we believe will provide extra moats of protection. We're very comfortable with our IP, but publicly, what we stated is that we believe that we're ironclad till 2044.
Got it. How do you assess competitive threats from other long-acting agents in wet AMD or DR, such as gene therapies or bispecific agents?
You know, I mean, look, I wish them all well. Again, it's not appropriate for me to talk about others. What I will say is, again, what I said before, it's important to understand that for almost four decades, we've had anti-VEGFs, which have proven to be absolutely miraculous drugs, when patients are able to take it as prescribed, which unfortunately is approximately half the patients. I say this because in order to go ahead and supplant an anti-VEGF, there are several boxes that have to be checked. No matter what your product is, again, whatever it may be, including us, those boxes have to be checked sequentially.
If you don't check one, you can't go to the other. The first box and the most important box is safety, right? There's no way of getting around that. These anti-VEGFs are extraordinarily safe drugs. Your inflammation rate, your endophthalmitis rate, you know, has to be virtually nonexistent. That's really important. It's not just the rate of inflammation, it's the predictability of inflammation. You can't have inflammation that is unpredictable because that really means the doctor has to be watching the patient all the time, which defeats the purpose, right?
I mean, if you have inflammation three months later or five months later, and you don't know if it's gonna happen or not, there's no way. Again, people oftentimes don't think of this, it's not just the rate, it's when the inflammation occurs. Well, if you know that there's some inflammation that occurs in three months or five months, how often do you see this patient? You know, you kinda defeat the purpose of reducing the treatment burden if you're gonna have to keep watching for inflammation.
I mean, nobody's ever said, you know, "Look, Ms. Jones, you know, your next EYLEA is in two months, but I wanna see you in two weeks because I wanna make sure that you don't have that inflammation." That conversation has never happened. It can't happen if you wanna supplant an anti-VEGF. That's the first box that has to be checked. The second one is efficacy. I mean, look, the anti-VEGFs work. Unless you've got the diagnosis wrong, they work in every single patient. They may not work as well as you want them to work, but they work. Then the third box that has to be checked is that of economics and workflow.
You know, we're used to a certain type of workflow. We're used to seeing patients in a certain way. You know, we have large offices. We have big throughput. To ask patients or ask doctors now to leave and go to the operating room or go ahead and give an extra drug such as a steroid or watch for other things becomes very difficult. I think for anybody looking to supplant an anti-VEGF, those three boxes have to be looked at sequentially and very carefully, and those three boxes have to be checked, and only then I think do you stand a chance against the current anti-VEGFs because these are really, really good drugs.
Thank you for that. Next, could you comment on whether Ocular could reliably manufacture hydrogel-based products at scale? Can you comment on what is the anticipated timeline for securing permanent J-codes?
Yeah. Again, the J-code part, I mean, it's a little bit too early to comment on that now. We certainly will advise you when appropriate. As far as scaling up is concerned, we absolutely believe that we're in a position to scale up. You know, we still are a small company. What I've done when I first came in here is to really concentrate this company to have a single product and have an identity. Obviously we kept DEXTENZA going because it was really important for us to keep that product, the hydrogel manufacturing, as well, very importantly as the commercial team.
Other than that, we have other things in our pipeline such as PAXTRAVA, which is the glaucoma product that is kind of frozen at this point simply because we're concentrating entirely or as much as we can on AXPAXLI. The potential certainly is there to expand the use of the hydrogel to other products by scaling up as we are with automation facilities, et cetera.
Got it. My next questions are about the diabetic retinopathy. For the HELIOS-3 NPDR trial, what enrollment progress has been made since initiation? And what percentage of NPDR patients are realistically treatable?
Yeah, look, I'm so glad you asked this, Yi, because I think, because wet AMD has taken such center stage, this has been, you know, a bit forgotten. Realize what we have here. What we have here with the HELIOS study is albeit a fairly small study, but in patients who have moderate to severe diabetic retinopathy, to have a study like that and the results as definitive as we have seen is absolutely remarkable. What we saw in patients, the control patients, was a progression to vision-threatening complications of 30%-40%, which is what is reflected in natural history. They behaved as one would expect to behave.
However, with a single injection of AXPAXLI, what we saw after a year is that the rate of vision-threatening complications was literally reduced to zero. I mean, when you let that sink in as a clinician, it is absolutely remarkable. We know that giving anti-VEGFs to these patients works really well. If you've ever given an anti-VEGF to a patient with a non-proliferative diabetic retinopathy, what you see within a matter of 24-48 hours is almost miraculous. The blood vessels look a bit better, that there's less blood there. Everything looks better. It's like a new eye. Nobody's treated for two reasons.
One is because of sustainability. Nobody's gonna come in who's asymptomatic, and these are working age people. They're mailmen or lawyers or accountants, and they're not gonna come in once a month, you know, for an injection when they're completely asymptomatic, even though they have a bit of a time bomb in their eye. The other reason is because if they don't come in, you can have a rebound effect. You can actually leave them worse, which is another reason that they're not treated. What we have here is a single injection that will reduce the risk of a blinding complication potentially to zero.
You can sit with a patient and say, "Mr. Jones, if you can come to see me but once a year like you go to your dentist for teeth cleaning or like you go get a flu shot, I can reduce your risk of going blind back to zero." I mean, that is sustainable. That can be done. Who's it gonna be used in? Well, look, the clinical trial is gonna be done in patients with moderate to severe non-proliferative diabetic retinopathy, as you know. However, we expect a label that's going to be broad and wide to include all of diabetic retinopathy.
Remember, the clinical trial is also gonna include patients with non-fovea involving diabetic macular edema. Our expectation is that the label is going to be another superiority label because we have a superiority trial with a SPA that will include all of diabetic retinopathy, all of diabetic retinal disease, including diabetic macular edema. Now, why do I say that? Well, let's talk about each one. As far as diabetic retinopathy is considered, as you know, with the current anti-VEGFs, they also did trials with moderate to severe non-proliferative diabetic retinopathy.
If you look at their label, it's all of diabetic retinopathy. There is no restriction. We expect the same thing for us. The same thing is true with macular edema. In my last company, we didn't treat a single patient with fovea involving geographic atrophy, right? With IZERVAY, as you know, the label is not restrictive at all. It's for all of geographic atrophy, fovea involving or non-fovea involving. Our division of the FDA has always said that the label will be given for the disease, not for the clinical trial, but for the disease. That's exactly what they've done over and over again. You go all the way back to ANCHOR and MARINA.
There were patients with only poor vision that were enrolled. The label for Lucentis has no restriction. The same thing for PANORAMA, which is a diabetic retinopathy study. The same thing for IZERVAY. We expect the same thing. We expect the label to cover all of diabetic retinal disease, and we don't expect to ever have to do another diabetic retinopathy study ever again to cover all of diabetic retinal diseases.
Got it. I understand, you know, as you mentioned, the injection burden for the NPDR patients. Fewer than 1% of the patients are currently treated because of the burden. If let's assume AXPAXLI has a once every 12 months treatment burden, do you think the symptomatic but stable patient would automatically accept this treatment option? Or do you still need to convince them to accept it?
You know, I mean, look, I totally understand that not everybody will come in, but the market is enormous. It's 3.5x bigger than wet macular degeneration. Even if you capture 5% of that market, I mean, you've got an enormous amount of patients. Look, it'll be a lot more than 5% if you know, if people can go for teeth cleaning, they can certainly go to see an ophthalmologist or a retina specialist to prevent them from going blind. I think that's a very makeable argument. By the way, who's gonna push this? It's gonna be the payers.
As I said earlier on, blindness is the most expensive thing they have, and the cost of treating a patient with macular edema that's losing vision, the cost of treating a patient with vitreous hemorrhage or traction retinal detachment is enormous. If this can reduce the rate to zero, the driver is not just gonna be the patient, it's gonna be the payers. I know this because I used to manage the ophthalmic part network of a very large payer system called Banner Health in Arizona. They were very farsighted. This is 15-20 years ago. They actually put non-mydriatic fundus cameras in the offices of primary care doctors.
They used to take pictures. The pictures were sent to my office, and my staff used to look at them, or the doctors used to look at them and say, "Yep, this patient needs to come in, you know, right away," or, "This patient can wait for another three months," or whatever it is. Banner did that because they recognized the cost savings they would have of preventing patients from losing vision and going blind.
Not only will patients with proper education come in once a year, which is very, very doable, but I really believe the biggest driver for this will be the payers, because the amount of money that they will save, the cost savings and the impact on society from not losing vision, not going blind. These patients, by the way, who are in the most productive part of their life and who are young, is huge.
Got it. Question about DEXTENZA. Is it a legacy product that you wish to divest in the future?
No, it really is not. The reason for having DEXTENZA, again, it's part of our system right now because the hydrogel is one that we produce. The other reason it's really important for me is that it gives us a ready-made commercial team. We are able to continue to expand with AXPAXLI the way we have. A lot of the reason is because we have a commercial team. It's really as I found out in my previous company, you can't just, you know, turn on a switch and get a commercial team. I told you how few salespeople were required for Lucentis sales.
If you've got 50 or 60 people that are salespeople that are boots on the ground, they better know ophthalmology and specifically retina. They better be well-connected. They better be well-taught. It's when you have that few, a number of patients representing you, it's really important that they be the best that you can possibly get, and that's what we have with DEXTENZA, and that's one of the main reasons that we still keep DEXTENZA, and we'll continue to do so.
Thank you, Pravin. I think we have one question from the audience. Could you please outline your goals for the June Investor Day?
Well, if I gave you the goals, then nobody would attend. We do have a lot of information that we're gonna give you. We certainly will, you know, talk about what's very obvious, the regulatory path. We'll talk about where we are with our commercial strategy, where we are with our extension studies and diabetic retinopathy studies. I think what you'll find is a lot of information in our Investor Day, and I hope all of you are able to attend.
Thank you very much for the update. I wish you all the best luck and success in your regulatory, clinical, and commercial efforts. Thank you.
We thank you so much for having me here. It's an honor and a privilege to be here, and I really appreciate the opportunity. Thank you again.
Thank you.