Good morning, and welcome to the H.C. Wainwright 26th Global Investment Conference. This morning I have the pleasure of having a chat with Dr. Pravin Dugel, Executive Chairman, President, and CEO of Ocular Therapeutix. Welcome, Doctor.
Thank you. Thank you for having us here.
So I know recently FDA accepted your phase III SOLAR trial as a registration-enabling study. So how significant is this to the company's overall development plan for especially for the treatment of wet AMD?
Yeah, thank you for the question. It's absolutely critical. What it does is several things. So what we asked the FDA for was a Type C meeting.
Mm-hmm.
What they said to us was that they would provide a written response, which is a great thing, because this is not subject to interpretation. It's not minutes. It's actually on paper. It's written by them and signed by the current team, and that's very important. What it stated very clearly is the following, that SOLAR qualifies as a registrational study. It also says that the combination of SOLAR and SOL-1 is sufficient for approval-
Mm-hmm.
So no other study needs to be done. The third thing that it says, which is really important, has been our stance from the very beginning, that we told the Street in terms of what the FDA wants, what they consider to be properly masked and not properly masked, and why we designed our trials.
Mm.
the way we designed it. So in writing, the FDA states, in writing, that sham is not recommended.
Mm-hmm.
Sham does not constitute proper masking.
Mm-hmm.
If a study is done under sham, it is subject to review, which is what we've been saying all along.
Mm-hmm.
That's why we've designed our study without any sham whatsoever.
Mm-hmm.
The Type C response in writing has just validated our position.
Got it. Is this the first time that the FDA would accept a superiority trial together with a non-inferiority trial for drug registration?
Not at all. If you remember ANCHOR and MARINA, one was started out as a superiority study and the other as a non-inferiority study.
Mm-hmm.
However, they both obviously ended up being superior to, at that time, the standard of care. In fact, what the FDA has said is they actually prefer having two different designs of studies-
Okay
... reach the same conclusion, for obvious reasons. So, the way we've designed these two studies is not just to satisfy the regulatory requirement, but to give us, I believe, a huge advantage from a commercial perspective as well.
Yeah. Got it. So could you give us a brief description of the SOLAR trial versus SOL-1?
Yep. So SOL-1 is a superiority study.
Mm-hmm.
With SOL-1, we have followed the guidelines of the FDA, per their requirement, of a superiority study to a T, and we've obtained a spot. SOLAR is a non-inferiority study. In SOLAR, what we want to do is to enroll patients who are stable. What we have is a very unique design, where we have three loading doses, and we have two opportunities to observe the patient.
Mm.
What we're observing for are fluctuations in the OCT, because what we don't want is patients that are what we call anti-VEGF addicts-
Mm-hmm
... and who are unstable and require anti-VEGFs on a very, very regular basis, and then, once we screen those patients out, we have two other opportunities to load the patients, so five loading doses and two opportunities to observe the patient before randomization. What you'll notice is that in each of these trials, the patients are randomized only after the loading dose, only after loading phase, I should say.
Mm-hmm.
So that means that these trials and the patients that we enroll in these trials after randomization are about as de-risked as they can be.
Okay, got it. So I noticed that the SOLAR trial have five aflibercept 2 mg loading doses, compared to three loading doses indicated on the label, right? So are five loading doses actually being used in real-world practice? And the non-inferiority demonstrated, let's say, by five loading doses, is equivalent to non-inferiority demonstrated by three loading doses? I don't know.
Yeah, so there are two separate questions. So one is, what-- how will physicians use it in real life-
Right, right
... right? And, somewhat facetiously, I'll tell you that there's not a single drug in my field that physicians use per label.
Mm-hmm.
What we do is we personalize the drug according to what the patient needs.
Mm.
I tell people that macular degeneration, wet macular degeneration, as well as a lot of other things that we treat, are highly variable and varied diseases, and the only way we can personalize this is by using a method called treat and extend.
Mm-hmm.
It's not per label anyway.
Mm-hmm.
The second part of the question is, what are we doing to de-risk the study?
Mm
... remove the variables that are inherent in this disease.
Mm-hmm
... and make sure that we maximize the chance of success.
Mm-hmm
... in a study that's approved by the FDA?
Mm.
And that's what we're doing in this non-inferiority study, and I think we've done it in a very thoughtful way-
Mm-hmm
... as I said, with five loading doses and two-
Mm
... opportunities to observe.
Mm-hmm.
The most important thing is that the entire thing has been validated now in writing by the FDA.
Got it, got it. So, what is the enrollment status of the SOL-1 trial, and what's the estimated timeline for data readout?
Yep. So what I will say is one of the, one of the very thoughtful things we did in designing SOLAR is to make sure that it actually increased the recruitment of SOL-1, because remember, patients have to go through SOL-1-
Correct.
and not qualify.
Mm-hmm.
Usually because they don't improve quite by 10 letters, maybe a little bit less than 10 letters.
Mm.
And then they're eligible for SOLAR. So we fully expect, and we have seen, that the traffic in SOL-1 has actually increased. It already was recruiting incredibly well. SOL-1 was, as you remember what we said on June 13th-
Mm.
and that's merely eight weeks after this team got together.
Mm.
Eight weeks afterwards was that we had enrolled-
Mm
... 151 patients, and that's remarkable.
Mm.
And that's record time. As you know, in a trial like this, or in any trial, there's a linear component, and then there's a critical mass of enrollment-
Mm
... and then it becomes exponential.
Mm-hmm.
We're certainly in the exponential phase. We are enrolling with a cadence that is absolutely historic.
Mm.
I can guarantee you, there's no trial in my field that has ever enrolled this quickly.
Mm, mm.
We haven't given you further details. Our original guidance still stands.
Mm.
We haven't changed that.
Mm
... which is that we expect enrollment to be complete by the end of the first quarter of 2025. Now, we certainly believe that it'll be earlier than that, but at this point, it's a little bit too early still. Things are moving very, very quickly-
Mm, mm
... but really, it's really quite early still, that we haven't revised that guidance yet.
Okay, okay. So, what about the SOLAR trial? I mean, will it complete enrollment somewhere around maybe mid-2020?
Yeah, we haven't guided you to that either.
Okay.
But here's what I will tell you. It's not just that we're thrilled with the enrollment in SOL-1, and I want to say absolutely thrilled with the enrollment in SOL-1. The second part of what I said in our Investor Day is that we are very happy that the screen failure rate-
Mm-hmm
... for SOL-1 is lower than we expected-
Okay
... and lower than we modeled.
Wow.
What I will tell you right now is that that still stands.
Mm.
And what that means is, not only are we getting a lot of patients, we're getting really good patients.
Mm-hmm.
And I will tell you that, given the design that we have, where in the beginning, everybody has to go through SOL-1, and then if they screen fail, then they go to SOLAR. Given the fact that that failure rate is low, we firmly believe that the vast majority of patients eventually-
Mm-hmm
... in SOLAR will not be coming from SOL-1, for the reasons that I mentioned.
Mm
... but rather than from the outside.
Mm-hmm.
Remember, the way that it's designed is that we control that switch. In other words, SOLAR will never, ever cannibalize SOL-1. In fact, it'll always help the recruitment of SOL-1.
Mm-hmm.
Once we see that SOL-1 is either fully enrolled or about to be fully enrolled, we can turn that switch. We control that switch to say, "Okay, now you no longer need to go through SOL-1." We can take patients from the outside to be enrolled-
Mm
... in SOLAR.
Got it. So based on, 'cause you talk about, the FDA would like to see that you have two different trial designs reaching the same conclusion. So based on the existing clinical evidence, do you believe SOL-1 and SOLAR trial will reach the same conclusion?
Oh, absolutely. I mean, that's why I'm here.
Mm.
And it's not just that I believe that, it's that we have gone out of our way to make sure the studies are designed and the patients are randomized in a way that it absolutely increases the chance of success.
Mm
... by decreasing the variability-
Mm
... of the patients who are going to be randomized.
Mm-hmm.
Again, I repeat that. It's very important to understand that the variability is oftentimes what adds the risk in these trials. In some cases, patients are randomized in other trials before they're loaded.
Mm-hmm.
In some cases, patients who are treatment-naive.
Mm
... and previously treated are mixed.
Mm-hmm.
We're doing none of that.
Mm.
We're using treatment-naive patients. We have them go through a process of loading that is very well thought out-
Mm
... as I explained, and then we randomize. So the variability is decreased, and I really do believe that the chance of success with these trials are greatly increased.
Got it. Thank you. So, is there going to be any additional clinical or non-clinical work required for regulatory submission for AXPAXLI?
I can answer that very definitively, and the answer is no.
Mm-hmm.
Now, we have it in writing-
Mm
... from the FDA, that all we require are these two trials.
Mm.
There's gonna be a SOL-1, and there's a SOLAR. There won't be anything else required.
Mm-hmm
... for approval.
Got it, got it. So, when AXPAXLI eventually reaches the market in the future, I expect it could face competition from generic Eylea, Eylea HD, Vabysmo, and potentially candidates currently being developed by EyePoint or Clearside. How do you plan to position AXPAXLI in the treatment paradigm?
Here's what I would say.
Mm.
Again, this is the thoughtfulness that has gone into these trials.
Mm-hmm.
With the success of these two trials, we potentially have the only drug that will have a superiority label-
Mm-hmm
... based on SOL-1. We'll have the flexibility of dosing every six months to every nine months, based on SOLAR and SOL-1-
Mm-hmm
... and we'll have repeatability, based on SOLAR.
Mm-hmm.
As you know, we have three arms-
Mm-hmm
... in our SOLAR trial. We specifically picked high-dose Eylea-
Right
... 'cause we wanna go up against it.
Mm.
We're certainly not at all concerned about our results with that.
Mm.
Now, remember, that HD Eylea arm is purely for masking-
Mm
... not for statistical analysis, but purely for masking. We control that data. I'm saying this because we're not concerned about any other drug that's going to extend the durability as high-dose Eylea and Vabysmo are by a week or two weeks or three weeks.
Yeah.
We're talking about ten months, nine to 10 months. We're in a completely different orbit than they are, and I'm very, very convinced that what will happen is physicians will look at this and say, "Now I've got something that is much more sustainable." Remember, we've got a huge market right now.
Mm.
But we're only seeing half the market because there's a 50% patient dropout.
Mm.
Right? Because they can't tolerate this schedule that they have to be on. So physicians are gonna look at this and say, "I'll have a much larger market of patients." Patients aren't gonna be dropping out as much. If we reduce that dropout by even 10%-
Mm.
-that market is humongous now. So physicians are gonna see healthier patients, they're gonna have a larger catchment of patients, they're gonna have a much more sustainable treatment regimen, and they don't have to change their workflow.
Mm-hmm.
It's not like they have to close down their offices or to go to surgery or anything else. It's the same workflow.
Mm.
It'll be adopted and adapted very, very easily.
Mm
... and very quickly. This is the easiest adoption of a medication that you'll see.
Mm.
What I'll also say, and this isn't—this hasn't been talked about a lot, but it's really important to mention, is that it's not just about durability. We're achieving two goals here. Durability is obviously very important because of the sustainability and the fact that more patients are gonna be treated.
Yeah.
But the long-term outcomes are also really important.
Mm.
There's a great deal of evidence now that our pulsatile nature of injection, where the back of the eye gets thick and thin and thick and thin, is what causes fibrosis and atrophy, much like having multiple concussions. And if you have a sustained suppression, as this drug will provide-
Mm
... the chronic outcomes will certainly be better as well.
I see. Thank you. So, could you comment on the patent- I mean, the intellectual patent portfolio for AXPAXLI? What are the expiration dates?
Yeah. We are very happy with our patent situation. We're very confident with multiple patents that we're absolutely protected until 2044.
Okay, got it. So Ocular is also developing AXPAXLI for the treatment of diabetic retinopathy. What is the observed efficacy so far for DME patients?
Yeah, so that probably is one of our strongest study-
Mm
... if not our strongest study-
Mm
... demonstrating the effectiveness of AXPAXLI.
Mm.
What we had was a small study that was started by the previous administration-
Mm
... based purely on safety. This is the most variable disease we treat.
Mm-hmm.
We reached the primary endpoint in a masked fashion. We could see there were absolutely no safety issues. At that time, we decided, look, we'll go ahead and unmask this, because we felt that it was gonna be all over the place.
Mm.
There were 13 patients who received the drug. This really wasn't well-controlled at all for high blood pressure or blood sugar-
Mm
... or anything else like that, and what we saw was truly remarkable. What we saw was that every single metric, every single parameter was aligned in favor of the drug.
Mm.
That was at week 40.
Mm.
We had data till week 48, and the data just got-
Mm
... better and better and better.
Yeah.
In the meetings that are coming up, the Retina Society, EURETINA, as well as Academy, we'll be showing more and more data regarding what we see here, in terms of the diabetic retinopathy data.
Mm.
Because what it shows is that there's no doubt whatsoever that this drug is present-
Mm
... effective, and safe at week 48.
Mm.
Again, every single parameter is aligned in favor of the drug. What that means to us is that there's a whole new target, which is huge, where effectively there is no drug-
Mm
... because nobody uses Eylea or Lucentis-
Mm
... label in these patients. There's a huge market that's open for us. There's no competition because others have thrown in the towel.
Mm.
The other thing that it says to us is it gives us a huge amount of data-driven confidence for SOL-1 and SOLAR, because, as I say, the drug is absolutely there, it's absolutely safe, and it's absolutely effective.
Mm.
This is a really important piece of data for us.
Mm
... and it clearly, it gives us an enormous amount of confidence-
Mm
... for the success of SOL-1 and SOLAR.
Mm-hmm. So what are the next steps for the DR program, and will DR patients receive the same dose of AXPAXLI as wet AMD patients?
Yes. So, what we said we would do is that we will go to the FDA-
Mm-hmm
... and we will sit down with them and discuss what the trial design should look like-
Mm
... and what the path forward is for approval.
Mm.
We definitely will do that.
Mm-hmm.
But I also want to be very clear, our first priority, we're still a fairly small company, our first priority is SOL-1 and SOLAR. So this comes as a third priority. We will see what the FDA says, and we'll strategize accordingly in terms of the path forward. But I'll tell you what the clinicians say. The clinicians look at the data.
Mm
... and say, "In this small, uncontrolled study, what we see there is absolutely sustainable and viable in the clinic.
Mm.
What we see, the most important parameter here is the vision-threatening complications.
Mm.
Because at the end of the day, we don't want these patients going blind.
Right.
The risk of blindness is 20%-30% year upon year upon year, which is exactly what our control arm had. The risk of vision-threatening complications in the treatment arm was literally zero.
Mm-hmm.
Zero. Every patient with diabetic macular edema resolved-
Mm
... when under the treatment arm. That's absolutely remarkable. I mean, nobody progressed. That's absolutely remarkable. So from a clinician's point of view, one can sit with a patient and say-
Mm
You know, your risk of going blind is 20%-30% year upon year. If you come to see me once a year - as you would go to your dentist for teeth cleaning, your risk of going blind is literally zero. Literally zero. That is, that is sustainable.
Got it. So, as you mentioned that the Lucentis Eylea has little adoption by DR patients in real-world practice, do you believe DR patients who experience no symptoms would accept an injectable therapy every six to nine months?
Again, it's not every six to nine months-
Okay.
It's every year.
Every year.
That data is 48 weeks-
Okay.
and even then, it was in a study that was small, not necessarily designed for this, and we don't have data to go further than that.
Okay.
It may well go much further than that because the data just gets better and better.
Mm-hmm.
Absolutely, it's sustainable. As I said, you know, people go to the dentist once a year.
Mm-hmm.
People go for teeth cleaning once a year.
Mm-hmm.
Here, these patients are sick. They know they're gonna go blind.
Mm-hmm.
It's just that they can't come in every month.
Yeah.
These are usually young patients that may be accountants, lawyers, doctors, et cetera, but it's absolutely reasonable to say to them, "Come in once a year, and your risk of going blind is literally zero.
Mm-hmm. Got it. So what is the company's plan for non-retinal disease assets?
Yeah. So we have several. We are very, very fortunate to have a commercial arm-
Mm.
-with DEXTENZA. We have a phenomenal commercial team. It is very important for us to be able to say we know how to commercialize products, and we're doing it successfully. There's a great deal of overlap because of multi-specialty clinics and so forth-
Mm
... between the anterior segment and retina.
Yeah.
This team will be very valuable to us.
Mm
... as we start our commercialization process-
Mm
-in retina as well. So we have every reason to value Dextenza.
Mm.
The same thing with PAXTRAVA. We believe that glaucoma data is superb.
Mm-hmm.
So there are assets that we believe that we can develop, but most of what we'll be doing will be entirely retina-focused.
Okay. Got it. So could you give us a brief overview of the upcoming catalysts within the next 12 to 18 months?
What you'll see in these meetings, as I mentioned, is more and more data regarding the diabetic retinopathy study, which again will give us a great deal of confidence.
Mm-hmm.
The other ones obviously are that we're moving very, very quickly in terms of SOL-1. We will update you based on the comp-
Mm
... the recruitment of SOL-1, as well as SOLAR-
Mm
... appropriately.
Got it, and I believe the company is well-funded into 2028 , correct?
That is correct.
Mm.
It is well-funded into 2028.
Do you have any last comment or any key takeaway message for investors today?
Yeah, I think the most important thing that I'll say is two things. You know, one is, I promise you that there will never, ever be, and there never has been-
Mm
... the kind of recruitment that we are performing right now in SOL-1.
Mm.
It is absolutely historic. We're recruiting at a pace that nobody's ever seen. It's not just that we're recruiting a lot of patients, it's that we're recruiting really good patients-
Right
... based on their low screen failure rate, and we're thrilled with it. That's the first thing. The second thing that I would say is, when you look at new medications in a field such as ours, the bar for success is very high-
Mm
... because of Lucentis and Eylea. We've achieved that. We will achieve that bar for success, but we'll have the durability, and most importantly, we'll have the adaptability. This will be adopted like that tomorrow.
Mm. Mm.
The workflow doesn't have to change, the physician's office doesn't have to change. Nothing has to change. It's simply a better drug.
Mm-hmm.
The market size out there is far, far bigger than people realize. What they're seeing is just the 50% of the market, because 50% of patients drop out. If we decrease that dropout rate by even 10%, as we will, if not more, that market size is humongous, and that's just for wet macular degeneration. That doesn't include diabetic retinopathy, retinal vein occlusion, ROP-
Mm
... on and on and on.
Mm.
All the things where VEGF suppression works, that we know-
Mm
... works scientifically. So the potential for this drug is huge, and we will make sure that we do absolutely everything we can to get this to patients as quickly as possible.
Got it. Thank you very much for an informative chat, and best wishes to your clinical-