Fireside chat started here, guys. Again, welcome. We're shifting from gene therapy to wet AMD. I am proud to be joined by Dr. Pravin Dugel, Executive Chairman, President, and CEO of Ocular Therapeutix. In February, Ocular reported SOL-1, the first trial in which a novel agent beat an approved anti-VEGF on a superiority endpoint in wet AMD. The company has since cleared both a Type C and pre-NDA meeting with FDA and is targeting an NDA submission this quarter. Plenty to cover. Pravin, thank you for joining us. For the generalists in the room, for those who are not familiar, give us the two-minute version of SOL-1. What did AXPAXLI show, and why does it matter for how retina specialists will actually use it?
Andreas, first of all, thank you for having me here. It is an honor to talk with you, and thank you all for being here. I think you first start out with a need here. We have had a very, very effective and safe class of drugs, the anti-VEGFs, now for almost four decades. Yet, in this country alone, in the first year, there is a 40% dropout rate. That is not just tragic, it is intolerable really. All of these patients who drop out, almost half of them end up going blind. So there is a great need for sustainability of treatment so that the dropout rate decreases. We know that is the case historically.
The other part of this is also that because of the pulsatile nature of injections, even in those patients who are able to stay through the therapy, the majority of them, after two to five years, end up losing vision because of atrophy and fibrosis. So what we are trying to do is to solve both of those problems. We have a tunable hydrogel with a TKI called AXPAXLI. We have shown superiority. We have hit a superiority endpoint versus an anti-VEGF for the first time ever. We are very proud of the results. We think the results are terrific, and we have got a single trial approval pathway formalized with the FDA.
Fantastic. Just so everyone knows, we write these scripts ahead of time, and then things happen where we have to modify. So I am bouncing around on the script here, and I think it is actually important that we do so given some news that came yesterday. EyePoint missed its non-inferiority primary endpoint in its second straight phase III trial. Is that a TKI class signal or product specific, and how do you position AXPAXLI against DURAVYU, high-dose aflibercept, and faricimab?
That's a great question. Look, I think it goes without saying to this audience that we're in a very, very tough field. Nine out of 10 drugs fail, and it has an impact on everything, including a lot of employees, their families, and everything else. That's the first thing to be said. There's no joy in seeing somebody else fail. The way that I look at this is there are lessons to be learned here, and we'll talk about that in detail, and these are really important. I'll take a little bit of time. In terms of the overview, we had one competitor in our field, which is that we have a maintenance drug. We don't have a bolus injection. Everything else that you hear about, which are non-inferiority studies, are in a morass of bolus injections.
There are really, as far as we're concerned, two drugs competing for maintenance. One is us and one is EyePoint, and now it's only us. I think there's a clear path forward for us without any kind of competition whatsoever. Now let me get to this really important topic, and this really applies to anybody who's an analyst, who's an investor looking at chronic retinal diseases. One thing that is absolutely misunderstood, in my humble opinion, outside of the retina community, is the variability of our diseases. Let's look at macular degeneration, but quite honestly, it's true for diabetic macular edema, for RVO, for diabetic retinopathy, all of those things. The bottom line is that we are at least 75 years behind oncology and rheumatology and immunology. We have absolutely no idea about disease stratification.
If I were to come to you, Andreas, and say, "Look, I have a drug for colon cancer," you'd just look at me like I was from Mars. You'd say, "Well, what kind of colon cancer? What stage? What grade?" I come to you and say, "Look, there's a drug for wet macular degeneration or diabetic macular edema," and nobody pays mind. They go, "Okay, that's great." We know there's an enormous amount of variability. We know that even with the regular Lucentis, there are patients that require treatment every two weeks. There are patients that require treatment every six months. So the selection of patients and clinical trial design is absolutely key. We're not doing 2,000, 3,000-patient large studies anymore that would negate this, perhaps, or mitigate this at least, like Genentech and Roche and others did. We're doing smaller studies.
Great attention has to be paid to patient selection. Because we don't have any biomarkers of disease. We don't have any genetic markers of disease. What we have done is very, very thoughtfully gone through patient de-risking that in a bespoke manner for each of our studies. It's an entirely different patient population and an appropriate one that we have selected for SOL-1 versus the stable patient population for SOL-R. This is why we're so confident in succeeding with SOL-R. It has nothing to do with retreatment criteria. It's got everything to do with clinical trial design and proper patient selection. I think now EyePoint themselves are actually admitting to that now following the failure. I think you saw some of that news this morning and yesterday.
We emphasize that. I think the reason for their failure is not only what we said earlier on, which is that we believe it's a weaker TKI, but one of the very, very big reasons is the patient selection. Now, it's easy to enroll trials when you allow everybody to come in as they did. They mixed previously treated patients with treatment-naive patients. They randomized, and then they loaded. We're doing the opposite. We're only using treatment-naive patients. We're making sure that we load first, and the loading for us is not necessarily biologic. It's to select the right patient population, and only then are we randomizing. That is the key to why we are so confident in the success and why this is different than what happened with LUGANO and LUCIA.
Yeah. That was great. Maybe we'll keep it on the competitor side of things. Talk about Kodiak quickly. They reported the DAYBREAK data in wet AMD. tarcocimab was non-inferior to aflibercept, 54% of patients on six-month dosing. Wall Street reacted very favorably. Any thoughts on the results? How would tarcocimab compete with AXPAXLI if both are approved?
Well, look, I wish them well. I don't see them as our competitor for reasons that I mentioned earlier on, which is that they're a bolus injection. I think it's important to separate bolus injections from maintenance drugs. We're a maintenance drug. As I said earlier on, our competitor was EyePoint, and now it's only us. Whatever bolus injection one uses, if one feels the need to use that prior to using a maintenance drug, really doesn't matter to us. It could be Avastin, it could be Vabysmo, it could be Lucentis, it could be the Kodiak drug if it makes it that far. But it's the maintenance drug category that we're in. So it's not the same thing. It's important to separate, and we don't consider them competitors at all. Having said that, I think there are a lot of questions to be answered.
Who were the patients that actually lasted six months? Where were they? Were they after six bolus injections? Were they in the beginning? Do they have to be retreated? How many injections did they actually get? We haven't seen the total number of injections. These are just really basic questions. It's a PRN arm versus an on-label arm. I don't know what the regulatory pathway is for a PRN arm. As far as AEs are concerned, I think we, at best, may have seen 25% of the AEs. I think there's a lot more to be seen. So look, I wish them well. There's a lot of data that we'd still like to see from a clinical trialist point of view. I'm sure that'll be forthcoming. I hope that'll be forthcoming. But again, we don't consider them our competitors.
They're competing with the Lucentis, Avastin, and Vabysmo of this world as a bolus injection. We're a maintenance injection.
I have to say, I do appreciate not just how specific and thorough you are, but how quick you are. Because I know this clock keeps running and it's-
Yeah, I'm looking at it.
It's giving me. We'll move right along here. If we have to go over a little bit, that's fine.
Sure.
Just a couple minutes. You plan a Q4 NDA under a 505(b)(2) based on one adequate and well-controlled trial plus confirmatory evidence. Both the May Type C and September pre-NDA meetings went your way. What remains before submission, and what are the residual risks, whether CMC, size of safety database, or potential advisory committee?
Yeah, let's talk about the regulatory path. Look, this is not something that we just thought of. This is not something that we said after a failed study and said, "Look, how about one study?" This is something that has to be planned out for years in advance, and the entire trial has to be planned out that way for a single trial submission. We're in constant contact with the FDA. The FDA has been very collaborative, very supportive, and we've checked all the boxes. All the evidentiary standards have been checked. Remember, we have a robust trial. Their definition of robustness is a p- value less than 0.001. Ours is less than 0.0006. We've hit a superiority endpoint for the first time in the history of the planet. We said that we would have a pre-NDA meeting in the third quarter. We did. We've got the minutes back.
We are very happy with the FDA minutes. We're absolutely in lockstep with them. We've said that we would submit the full package in the fourth quarter, and we're certainly on schedule for that. We're very pleased with our interaction with the FDA. We couldn't be more grateful to them, and we're absolutely on schedule for a single trial submission.
I was trying to catch all that. Did you mention anything about a potential advisory committee?
Again, it's a little early to be talking about that at this point.
Sure.
In my opinion, and this is just my opinion, there should be no reason for that. That's usually reserved for something that's a brand-new mechanism, a brand-new treatment, and this is not. We're suppressing VEGF, which is what anti-VEGFs have done for 40 years, and we don't see any reason for an AdCom at all.
You amended SOL-1 to add a key secondary of superiority versus aflibercept 8 mg at week 96 and extended masking, which moved top line from Q1 2027 to Q1 2028. Critics say you're pushing the trial that tests repeat dosing against the on-label control past the potential approval. It was the right trade.
Well, look, it's an absolutely correct strategic decision because what we didn't want was we didn't want a major amendment in the middle of a review. A card turn of any kind would have been a major amendment because who wouldn't want to see the card turn? Who wouldn't want to see the results? Of course, everybody would. As soon as you get a major amendment, you lose the time advantage that you've had. We're on an accelerated path, right? We've got a 505(b)(2), so we're in an absolutely accelerated path. Our goal is to go ahead and get this approved as quickly as possible, and as cleanly as possible, and there's no reason to go ahead and be off track by having a major amendment which would then turn back the clock and start all over again.
From that point of view, we think that it was the right strategic decision.
Fantastic. I'm going to ask one financial question, and then we'll be close to time. Cash was almost $600 million at June 30th with runway to 2028, but guidance explicitly excludes the full cost of commercializing AXPAXLI. How much incremental capital does a U.S. launch require, and what is the preferred funding mix, equity, debt, royalty, or ex-U.S. partner?
Look, our goal is to go ahead and launch this product. We're absolutely on track to do that. We've got the right team. We've scaled up to be able to do that. We're more confident than ever in being able to do that very well. We're by retina, for retina. That's all we know, and we know how to do that extremely well. Having said all of that, our guidance has not changed. We're well capitalized into 2028. We haven't guided you as to what is needed for the launch. But as you can imagine, as we get closer, if that is necessary, there are all kinds of flexible ways that one can go ahead and get capital without being diluted.
Fantastic. Thank you, Pravin. That was a quick one, guys. That was very efficient, so I appreciate that again, Pravin. Everyone, please stay seated. Opus Genetics joins us right now. We're behind a little bit, but we'll-
Andreas, thank you for the opportunity.
We'll make it work. Thanks, everyone.
Thank you very much.