Our next presenting company with us, sitting next to me from Ocular Therapeutix, is Pravin Dugel, who is Executive Chair, President, as well as CEO. Pravin, thanks for flying over to the West Coast for us today.
Thank you, Tizine. Thank you for having us again in this wonderful conference. Really appreciate it.
I've been starting off with macro questions for my companies, which is a new one for me. You guys are not yet commercial, so most of these won't apply to you, but I will ask you for your updated thoughts as it relates to any potential changes that you've noticed at FDA, let's say over the last one or two months with your division, people that you talk to, the timelines for how things are getting done, etc.
You know, luckily, nothing at all. And I really do mean that. The FDA is very consistent, very, very collaborative, and nothing has changed. The people are exactly the same, other than Wiley Chambers retiring. Bill Boyd has taken over now, but everybody beneath that is exactly the same, the same people that have been there for decades and decades. You know, what I will tell you is there are some things that have happened that reflect that, both to us and outside. You know, what I would point to are two things, and let's use them as an example because I think there are quite a few, but two things. You know, one is the CRL that was recently received by Regeneron, for instance.
I think that is absolutely consistent with what the FDA has been saying all the time, which is that they want studies to be well designed, well masked, etc. I think that's right in line with what we have with, given our SPA and given our Type C validation. The second thing that I'll tell you is our amendment that we recently announced in the SOL1 and SOLAR studies. The fact that we received that amendment without jeopardizing our SPA at all shows you the collaborative relationship that we have with the FDA and the fact that we are following their guidelines to a T. Nothing has changed. Our collaboration and consistency remains.
Okay. When I said you were not commercial, I meant as it relates to AXPAXLI, you are not commercial. Let us talk about AXPAXLI. You are developing it for treatment of wet AMD. Some initially might have asked, is not that a crowded market? You have got a lot of drugs that are currently available. You have got a recent generic launch. You are a retina specialist, so you are an end user of these products. Can you talk to us about, I guess, number one, what differentiates AXPAXLI? Just to give everybody a reminder, you came out of, I guess, retirement to take this job. You do have another side gig. I think it is winemaking now. Clearly.
I'm old.
Could take all of your time if you wanted to. What was it about the profile of this company that made you decide that this was the right time to be CEO of a company in the process of becoming commercial again?
Yeah. As a segue from the macro questions, let me also add that, look, with AXPAXLI, also nothing has changed in this macro environment. Our entire manufacturing, all the products are in the U.S., our IP is in the U.S., and we feel that we're in great position, particularly with the SPA and the Type C validation. As far as my journey is concerned, yeah, you're right. I was retired for all of three months, very happily retired, wasn't looking really for a job. As a retina specialist who's practiced for 30 years, as miraculous as these drugs are, and I really do mean miraculous, you know, I am old enough to remember when we used to sit in front of patients and what we could do was to predict or try to predict when they were going to go blind so their affairs were in order.
That's when I started practicing. Not only that, but the standard of care at that time was to literally laser the fovea and actually blind the patient. Somebody would be coming in at 20/60 vision who would say, "Look, I'm going to go ahead and laser the center of your vision because your blind spot will be smaller in two years than it would have been if I didn't laser you." That is where I started my training. To come and see what Lucentis and Eylea have done, and especially with macular degeneration being in my family and my father, for instance, being treated, is truly miraculous. However, we've had the same treatment now for almost four decades, right? You have got to kind of step back.
I do not mean to be critical of this, but it's truly unacceptable and tragic that 40 years later, in this country alone, in the very first year, there's still 40% of patients that drop out of treatment, 40% that end up going blind in this country because the treatment is simply not sustainable. We have a known target, we have a known solution, and the next thing that we need is a sustainable treatment option. Because of the opportunity out there and because of the personal interactions that I've had and the career that I've had, it was a no-brainer for me to come here and run this company. I'm extremely glad that I did, that I am as confident as I was when I came in. I'm manyfold more confident in the success of this trial now that I'm seeing the trial conduction itself.
Obviously, we're masked, but what we're seeing in SOL1 makes me manyfold more confident than I've been even before I came here.
Okay. Let's talk about the advantages of less frequent dosing. Going back to your practicing days, what kind of a time commitment or what kind of burden is it for patients to be able to come to a doctor's office to get an injection, whatever it was, once every four weeks, six weeks, eight weeks, whatever? How is this really paradigm shifting, basically, by allowing patients less frequent dosing? Can you talk about the dosing that you're looking for?
Yeah, let me just tell you typically what happens. I mean, you all talk to your KOLs and you ask them, "Look, how long does it take to inject a patient?" They'll all give you the same answers, as I did for 30 years. I'd say, "It takes me a second." It takes the doctor a second, but you should follow the patient's journey, right? The patient is oftentimes an elderly patient, usually needs a caretaker, takes, I don't know, 20 minutes to find a parking spot in my office. They all have to go there and do a pre-authorization check because insurances change and it's an expensive drug. That takes another 40 minutes. You go through, you have the vision exam, you have the IOP check, you have OCT, you have dilation, you have consent.
Now they're already in there for like two, three hours. They see the nurse or the PA and they basically say, "Oh, you know what? You need an injection." You go back through the whole thing with the consent. You see the doctor, you get an injection, you get the anesthetic and everything else, and you get the IOP checks to make sure everything's okay. You go home. The patient is a whole day affair and the caregiver as well. Typically what ends up happening is that, and this happened to me all the time, a patient comes in and the whole family is there.
I look at the patient and the family and say, "You know, if we met a few years ago, there would be nothing to give you, but I'm very happy to tell you that we have a treatment now that'll save you from going blind. However, you have to come in every month or every other month." Immediately, the entire family says, "Absolutely. You know, Jenny will bring Granny and then John will bring Granny and so on and so forth." Three or four visits later, the patient is tugging at me saying, "You know, Jenny's about to lose her job. She can't take any more days off. Is it okay if I skip a visit or two visits or anything else?" Pretty soon they drop off. This happens all the time. There are two problems we're trying to solve, right? That's one.
That is the obvious one, which is the 40% dropout rate in this country alone. The other problem that people do not think about is that even the people that remain, and this is the other sad part, almost inevitably end up getting worse than baseline after about three to five years. Now think about that. Even if you come in religiously to get these injections, in three to five years, you end up getting worse than baseline. We used to think that was because patients re-bled, but actually re-bleeding is very rare. The reason for that inevitably is because of fibrosis, scarring, atrophy. The reason that that happens is because of the episodic way in which we treat the back of the eye because there is fluid and it is all neural tissue, gets thick and thin and thick and thin.
It's like having multiple concussions over and over and over again. It's not surprising that you get scarring and atrophy. That's how patients end up going blind. The second problem we're treating is that because we have a sustained delivery drug, instead of having these episodic on-and-off periods of suppression and loss of suppression and suppression, we have a constant suppression that continues. There's very, very good evidence that once you do that and you don't get this thickening and thinning and thinning, you don't get the fibrosis and the atrophy that you would get. One problem that we're solving is that of sustainability. The second problem that we're solving is that of better chronic long-term outcomes.
Okay. It is not simply about dosing. It is about an overall better profile for the patient.
Exactly.
You're in phase three now. You've mentioned SOL1 and SOLAR. Can you talk to us about the differences between those two studies, why you're running these and in the sequence that you're running them?
Yeah. Look, this is not any credit to me. I've got the most, and I just say this freely, phenomenal retina team ever assembled on this planet, and I'm very, very, very proud of them. They put this together. What everybody does, at least in my field, everybody that I know is kind of a no-brainer, is they repeat the same trial again, right? Because you need two trials that are successful to be approved. Everybody's done that, you know, Anchor, Marina, V1, V2, Hawk, Harrier, even trials going on now. We didn't do that. The reason we didn't do that is because when you think about it, although the second trial validates the first trial and allows for approval, it doesn't provide any further information. I mean, it's a real opportunity that's lost. What we did was we did two complementary trials.
One is a superiority trial called SOL1, and the other is a non-inferiority trial called SOLAR. They are absolutely complementary. They have worked beautifully. We can go into detail about that. What we have done in each of these trials, which I am also very proud of, is that we have gone through a loading phase. The loading phase before randomization is to super select an enhanced and de-risked patient population. What people do not realize is that macular degeneration is about as variable as colon cancer or lung cancer or bladder cancer. If I went in to talk to you and said, you know, I have got a drug for colon cancer, you would not just allow me to talk away. You would say, "What do you mean colon cancer? What kind of colon cancer? What stage? What grade?" AMD, wet AMD is equally variable.
The problem is we're 50 years behind oncology, at least. We don't have a genetic marker. We have no anatomic biomarkers. We have no way of knowing how patients will respond to treatment. That's why we do something called treatment extent, which is we kind of play it by ear, right? We treat and we say, "This patient can go for four weeks. This patient can go for six months." That is fine in a clinical setting. When you have clinical trials like we do and you want predictability in the patients that you're enrolling, we have gone out of our way to have a very, very thoughtful and bespoke loading phase as a ramp to specifically select the kind of patients that we need for each trial. Each is different.
For the SOL1, which is a superiority study, what we've done is to select patients that have the most amount of VEGF receptors, and we've tested them to be responsive. This is a superiority study where we load twice. We require that patients improve by 10 letters or more or get to 20/20. We load them up and we allow them to fail once. It is a perfect design for a superiority study. On the other hand, for SOLAR, which is a non-inferiority study, we want absolute stability. We've got three loading phases, and then we have something that nobody else has ever had before, really quite unique, which is we have two opportunities to observe the patient. What we're observing for is any kind of instability.
Once we ensure that patients that are unstable or VEGF dependent are weeded out, we have two more loading doses, and only then do we randomize. It is not just about recruiting patients. It is about recruiting the right patients for the right study in a bespoke manner. I think our team has done that very thoughtfully.
How do both of these studies together help with what ultimately would be the pitch that a field force person would make to a retinal specialist?
Look, it helps in many, many ways. I'm glad you said both studies because remember, neither study will ever be looked at alone, right? You need two successful studies. That affords us a huge amount of advantage logistically, commercially, and from a regulatory point of view. Let me just talk about each separately. Logistically, we never lost a patient. That's really important because what we did was when we had SOL1 going, we started SOLAR. SOLAR, the non-inferiority study, what I required of that was that it not only not cannibalized from the recruitment of SOL1, but that it actually helped the recruitment of SOL1. That's exactly what it did because everybody had to go through SOL1 first. If they screen failed, then they went to SOLAR. We didn't lose anybody.
Nobody had to say to a patient, "Look, you don't qualify." That helped greatly because in January, we were able to say, "Look, we already have 311 patients enrolled in SOLAR." This was just bolused on from SOL1. Logistically, it helped a great deal. More recently, with the amendment that we may talk about, we're able to reduce the size of SOLAR because we're able to extend SOL1. That worked beautifully. From a logistic point of view, it worked perfectly. From a commercial point of view, look, we have the potential to have the finest label, the best label that this field has ever seen.
What would that be?
A superiority. And this, again, we're not in labeling discussions. I want to make that very, very clear. These are all hypothetical discussions, and this is potentially the best label. I want to make that clear as well. It'd be a superiority label, the first and only one in its field based on SOL1. It'll be a label that allows the flexibility of treatment of every six months based on SOLAR to every 12 months based on SOL1, and also repeatability based on SOLAR. Additionally, from a commercial point of view, it also allows us to discuss the numeric analyses that we could do with high-dose Eylea. Remember, we don't have any sham as per the FDA's guidelines because sham is at risk. We've never taken any risks. We need a masking arm in SOLAR. For that masking arm, we deliberately chose high-dose Eylea.
That's not for statistical analysis. That's for numeric analysis. We will be able to leverage that data to our advantage from a commercial point of view. Finally, the third part that this affords is a regulatory advantage because nobody's going to see one study alone. When somebody sees, for instance, the number of rescues, say, in SOLAR, they will see that in the context of a positive SOL1, knowing that this drug can last for 9-12 months. From a logistic point of view, from a commercial point of view, from a regulatory point of view, this trial design, this complementary trial design gives us an enormous advantage.
I'll also point out that enrollment rate, certainly for SOL1, was much faster than anyone expected, and I suspect also for SOLAR. For SOL1, you will be releasing top-line data in the first quarter of next year?
Correct. First quarter of 2026.
That's right. First quarter of next year.
Yep.
Okay.
That's right.
I thought for a second, am I in the right year? What would be good data on that study?
Look, again, at the end of the day, our goal is to hit the primary endpoint, right? The primary endpoint requires a separation of delta of 15%. Remember, the primary endpoint is at month nine. The primary endpoint is the percentage of patients who maintain vision. That's our goal. We believe that we'll beat that. There'll be many other analyses that will be, we think, very favorable to us in SOL1. It will also be viewed in the context of SOLAR. Let me just say a few things here. The goal really is at the primary endpoint. Let me just say, as I've described in detail, this is not a typical patient population in either study by design. This is not the patients that walk in the door of somebody in Nevada or Idaho or New York.
These are specifically de-risked patients in SOL1 that are designed to fail. We are very, very happy with the rescue rates and the cadence of rescue and the fact that the rescues are vastly on protocol. We're seeing this in a masked fashion. Really, we feel very confident, more confident than ever with what we see that will hit that delta and exceed that delta. That would be success, of course. In SOLAR, we'll gain even more information. We'll find out how this drug does in a non-inferiority context versus what is the standard of care, Eylea 2 milligram. We'll also have the numeric analysis based on high-dose Eylea. I think we'll have a lot of information for doctors and patients and payers. I will repeat again, I couldn't be happier. I just want to make this very, very clear.
The primary goal of this company right now is the conduct of SOL1. We're going to deliver an extraordinarily clean study, SOL1 and SOLAR to the FDA. Extraordinarily clean. The primary goal here and what we assess ourselves at in terms of how we assess our success under masking is to look at three things. We look at the number of rescues under masking in SOL1. We look at the cadence of those rescues, and we look to see whether those rescues are on protocol or not. This is all under masking, and we're thrilled with what we see. I couldn't be more confident of the results of SOL1 today. I was confident coming into this company. I'm manyfold more confident today.
Yeah. And since you made the changes to SOL1, you did not have to enroll as many patients into SOLAR. That study will presumably read out a bit faster than what we might have been thinking before. Can you lay out timelines for us? SOL1 reads out in the first quarter of 2026. What then needs to happen after that in order to be ready to apply for approval?
Yeah. I'll talk about the amendment separately because that's a really important thing. We haven't given you guidance as to the card churn in SOLAR as yet. We will when appropriate. The reason is we just want to give you good data, you know, obviously. It's a pretty long ramp, as you know, by design, as we've discussed, for de-risking purposes. Let me just talk about the amendment and why. The bottom line is there are two takeaway messages from the amendment. One is the fact that we will get to the finish line much faster and much cheaper. The second goes back to an earlier question, which is, you know, the relationship that we have with the FDA by following every one of their guidelines. Let me just tell you what happened.
The team before us, to their credit, obtained a SPA for SOL1. However, SOL1, the superiority study, ended at month nine. It ended when the primary endpoint was met. The FDA requires not just from us, but from everybody, a certain number of patients, about 300, to be followed for two years only for safety purposes, not for efficacy, only for safety. Because that study ended and we had a SPA at month nine, we needed to overweight the SOLAR study with 825 patients to satisfy that requirement. Not for powering, but to satisfy that requirement. That was one. The second thing that happened also with that is our PIs came to us and said, "Hey, look, you put me in a really difficult position because once the study is positive at month nine, I'm going to have to go to my patients and say, 'Look, you're done.
I can't do anything for you because you're going to have to wait until this drug is approved.' That is a really difficult discussion to have. They are right. The second thing is that we saw with the Vabysmo label that the threshold for getting something on the label for durability was fairly low. They got a four-month label, but there are actually a minority, a small number of patients that actually reached that mark. We were certain that many more would be able to cross the 12-month threshold with AXPAXLI. That was a really important thing for us or an opportunity for us. The third thing, and this was the gating item, all of us having the experience we have in Retina have never seen patient retention as good as we are seeing in SOL1. We have just never seen it.
Putting these three things together, we went to the FDA and said, "Look, we do not want to jeopardize our SPA. Can we extend our SOL1 study to year two and treat every six months with AXPAXLI to maximize the exposure to satisfy your safety requirement?" They said yes. If so, then can we decrease the size of SOLAR now that we can use those patients by a third? Instead of 825 patients, now we just need 555 patients. They said yes. We stayed masked, right, until week 52 because now we have the potential of getting 12 months on the label by staying masked. We gave up nothing. That is really important to note. We did not change our statistics, our powering. We did not change our primary endpoint. Our primary endpoint is still at month nine.
We have the potential of having a superb label with great commercial advantage. Again, this speaks to the fact that with this amendment, we will get to the finish line much faster, much cheaper. It also speaks to the kind of collaboration we have with the FDA simply because we have followed every one of their guidelines and done everything they've asked us to do and taken no risk whatsoever.
Okay. Thanks for that deep discussion about the reasons for the changes. You mentioned getting 12 months on the label. You talked about it a few minutes ago, about the patients and their journey and making it as convenient for them as possible. As you think now, this is thinking a little bit ahead about how doctors would think about a product where a patient may not need to have a new insert put in until, you know, 12 months after the first one. How does that change the way they treat patients? Do you think that they will still ask patients to come in to be examined? How does that work into the way they like to practice?
It's a great question. The beauty of this is that this will be adopted the day after it's approved. I mean, there is no barrier to adoption here whatsoever. Nothing changes. The doctor's offices don't change. The workflow doesn't change. Everything remains the same. They simply reach out and get a better drug. The doctors will be happier. The payers will be happier, and the patients will be happier. Let me just explain. As I mentioned earlier on, there is a 40% dropout rate in this country in the first year. Those patients end up going blind. It's tragic, but it's also extremely costly. They don't drop out of the payer system. They drop out of coming in to see the doctor. A blind patient is very, very, very expensive. There's a huge amount of resources they use, and mortality doesn't change at all.
If we can decrease the dropout rate by even 10%, that's a quarter million less patients that will go blind in this country alone. That's a huge impact. That's also huge cost savings. We are very, very happy not just to have that impact, but we think it'll translate into a higher premium for the drug. We think that this will be a situation where the doctors will be able to also inject many, many more patients, just not the same patients over and over again because there'll be fewer patients dropping out. We think they'll be happier as well. Obviously, the patients will be happier. We haven't even talked about the better long-term outcomes. There's not a single piece of new equipment they have to buy. There are no changes they need to make in the office. The workflow is exactly the same.
The other important part is the experience is the same. Now, remember, what we do know is the doctors want to be able to make sure that when they inject, that injection wound heals completely and closes completely. We know what threshold that is for that. And we know that that threshold is at least 23 gauge. We know this from the surgical experience. In our case, it's going to be much more than that. We have a 25 gauge needle. There is no doubt that the experience is going to be the same, that the wound is going to close by itself. Nothing changes. I think it'll be adopted very, very easily into the workflow. I think in the beginning, doctors will still do treat and extend, quite honestly, because that's what they're used to doing. The needle will be shifted very much to the right.
A patient that may have required, say, Eylea every month may now require AXPAXLI every eight months. And someone that may have required it every two months may now be every year, what have you. But after a while, because we're very comfortable seeing patients every six months, I think what we will do is what all of the rest of medicine does, which is to treat on a fixed basis. That's what's done in oncology. That's what's done in rheumatology everywhere. I really believe that what will happen with this drug, which has a great safety net because it'll last for 9-12 months and is perfectly safe, there's been no safety issue whatsoever, I think this drug will simply be given on a fixed basis every six months.
Okay. How does that tie with sort of the economics of how doctors are compensated?
You know, doctors are compensated based on ASP, of course, as you know. Again, we're not in pricing discussions whatsoever, so I don't want to assume that anybody should assume that we are. We believe that we'll be able to make a very good case for premium pricing based on what I've just mentioned. I mean, just think about 10% less of a dropout rate, having a quarter million more patients that you can say are not going to go blind. I mean, that's a great impact. Again, this is a known target. This is a known population. We believe that the encachment of patients will be massive. This is just in wet AMD. This doesn't even include the other disease that we haven't talked about that we will be going after, which is non-proliferative diabetic retinopathy and diabetic macular edema.
We also know that in the history of our field, every single anti-VEGF that has worked in wet AMD has also worked in diabetic retinopathy, diabetic macular edema, retinal vein occlusion, PCV, ROP, on and on. The impact, the potential impact of this drug is massive. Now, we're a small company, and we're laser-focused on one thing. What we're doing is, as I said, the number one thing that everybody talks about in this company, everybody is to do one thing and one thing only right now, which is to make sure that SOL1 is successful. We're well on track for that.
Okay. Last question maybe is to spend one minute. That's all we have left. It deserves more on NPDR. Talk to us about where you are in development there
Look, we're in great discussions with the FDA. We're having fantastic discussions. We couldn't be happier. We're absolutely going to pursue that target. We obviously have no competition whatsoever. We have the capital to do so, and we will do so. The impact is going to be enormous. We are trying to be as responsible as possible in this unstable environment. We're taking a bit of a pause to make sure that there's some stability because at the end of the day, we're doing everything we can to be fiscally responsible and respectful of our shareholders. The whole idea here is to maximize shareholder value. That's what I think about from the moment I wake up to the moment I go to sleep.
Okay. With that, we're just about out of time. Pravin, thanks again for coming. Everybody that joined in the room, appreciate your attendance. We'll talk soon.
Thank you, Tizine. Thanks for having us.