Good afternoon, everybody. Thanks for joining day one of the Citizens JMP Life Sciences Conference. My name is John Wolleben. Pleased to have Ocular Therapeutix here joining us, and I guess how many are you—we on months now or weeks?
We're on months now, but couple of months.
CEO Pravin joining us here to talk a little bit about. You know, you guys have a lot of data recently. You're gonna have a new strategy and focus at the company, but maybe, you know, talk to us at a high level about, you know, why you joined the company, and then what do you think the vision is moving forward?
Great. So John, first of all, thank you for allowing us to be here. It's really an honor and a pleasure to be here, and then thanks to all of you for being here as well, and your interest. Well, to be honest, I really had no plans to come back after Iveric Bio. I was very happy making wine in Napa. And this opportunity kind of crossed, and it was just one of those things that I just couldn't pass up. To make a long story short, you know, it was a trial design that was really intriguing because it was clear that this is the path that the FDA wanted.
We're talking wet AMD.
Wet AMD, now. Yep. And, it was exactly down the middle of what the FDA wanted, validated by a SPA. I also looked at the, the primary endpoint itself, and I said: "You know, if we can go ahead and communicate properly, and we can recruit properly for this trial," which we will do, that it was about as de-risked as I've seen. And then finally, it had immediate application. There, there's nothing that needs to change in the workflow of my colleagues to adopt this, and the market size is enormous. You know, people look at the market size and say: "Well, it's Lucentis plus Eylea plus Avastin if it was Lucentis or Eylea." But that's just the tip of the iceberg. Realize that that's the market size with half the patients missing, right? Because only half the patients actually stay on this regimen.
Mm-hmm.
Now, if the dropout rate can be less than 50%, it can be less than by even 5% or 10%, that market size is expansive, and that's just wet AMD, and there's no drug that has suppressed VEGF that's worked in wet AMD that hasn't worked in diabetic retinopathy or diabetic macular edema or retinal vein occlusion, et cetera. So that market size is even bigger. So, the fact that all of these things were together in one place, and that it was so undervalued, was very attractive to me.
That's and that's why I came, and I thought, if I can put together the very best retina team the planet has ever seen, and have enough capital to have this happen, this is really gonna impact the way patients are treated, and I believe that we're in a very, very good direction in a very short period of time for that.
Obviously, you joining got a lot of folks very excited. The market loved what you guys have done so far in terms of wet AMD. Can we focus there for a bit, and then we'll touch on-
Of course
... some of the other programs and expansion. AXPAXLI, a long-acting TKI. Can you talk about the dropouts today that you're seeing in the marketplace? What, you know, why are people stopping taking the drugs, and what is the unmet need, and does AXPAXLI address that?
Yeah, so again, we have a treatment in the anti-VEGFs that was absolutely miraculous, and I'm old enough to remember when we had nothing, right? We just watched patients go blind. And when the Lucentis ANCHOR and MARINA trials came in, it was just unbelievably remarkable. It was miraculous. We all felt that there was no way that you could actually put a needle in the eye on a regular basis. Now, obviously, we're wrong about that, but what we're not wrong about is patients coming back. If you talk to a physician, and again, I practiced for 30 years, right, before I came here. If you talk to a physician and say: "What is it like to, you know, to be a wet AMD patient?" They'll say: "Ah, it takes two seconds.
You know, they come in, we stick a needle in, and they're gone.
This is no exaggeration. How many injections does an average ophthalmologist do?
Maybe 40-80, depending.
Yeah.
But on the other hand, when you actually look at the patient and you say: "What does it take?" It's a whole different story. You know, they've got to take a day off from work. They oftentimes have to have a caregiver with them, find a parking spot in my office, wait for authorization, wait another two hours to get dilated and looked at and everything else, and then after that, be decided whether they're gonna get injected or not, and then they have to wait, and then go. It's a whole day for them, and patients simply cannot do this. I mean, they just cannot do this. This is for wet AMD. I know we haven't talked about diabetic retinopathy, but let alone diabetic retinopathy, where it's even a bigger burden.
But having something there where there won't be a 50% dropout, where you know it works, it'll be adopted without any change in workflow whatsoever. Now, that's the convenience part and the sustainability part, which is what everybody talks about, which is really important. The part that is equally important in my mind as a physician that people don't talk about is the outcome, and let me explain. What we do right now, and again, this is an equally important part for all of us because the... I'm convinced that the outcome eventually will be better, okay? What we do right now is a pulsatile treatment. You know, we inject a lot, and it goes away. We inject a lot, and it goes away. If you look at the OCT, the OCT expands and decreases, expands and decreases.
It's like there's a concussion in the back of the eye on a regular basis. There's clear evidence now that that pulsatile injection, you know, cadence, causes fibrosis, causes atrophy, and eventually, that's how patients go blind. You know, patients go blind not because of rebleeding, from atrophy and from fibrosis. If you have a suppression as we will, where there's a decreased suppression, and there's none of this bouncing back and forth, and it just suppresses on a regular basis, I think, we're all convinced that the final outcome will be better as well. It's not just convenience, but it's also the outcome.
Yeah, that'll be fascinating to see how that plays out long term, because I think that is a very good argument for a better outcome long, long term. Can you talk about the data that you've seen so far that gives you confidence that, you know, this is possible long term?
Yeah, so, three studies, and again, you want a wet AMD, but I'll also include diabetic retinopathy in that, okay? So, the first one I would say is in Australia, and the significance of that study is that it's the first time that I've seen a sustained delivery TKI used entirely naked, and what I mean by that is monotherapy in treatment-naive patients, so there's absolutely nothing else. And what we showed there were OCTs that would be comparable, and really identical, in my opinion, to what you would see with commercial-grade Eylea or Lucentis. So there was no doubt in my mind when I looked at that, that this medicine worked, because it was seen completely naked without anything else. The second one was a study that was done in the U.S. with Eylea as a control, and that...
This really showed durability, where what we're able to show was that with a single injection at 10 months, over 70% of patients required no rescue versus on-label Eylea. That's the second piece of evidence. The third actually is this diabetic retinopathy study, and here, and we have talked about this, but there were 13 patients, literally 13 patients, that received the drug. We expected the results to be all over the place. Instead, every single metric was aligned in favor of the drug. Everybody that improved had the drug. Everybody that decreased didn't have the drug, and we'll show more data in our investor day on June 13th to support the fact that there's no doubt whatsoever that this drug is active, despite only 13 patients getting this, that this drug is absolutely active at week 40.
So put all that together and look at the design of SOL- 1, which is a loading phase, right?
Mm-hmm
... of Eylea, followed by maintenance, really, just we watch the patient thereafter. I think it's a de-risk study.
Can you talk a little bit about the profile that you guys have shown and that you're targeting versus what is out there today? Because what I think what's an interesting dynamic that we keep talking about is, we have Eylea, Lucentis, off-label Avastin, but we also had Vabysmo launched, I guess, 15 months ago, give or take.
Mm-hmm.
It's taken 22% of the market-
Yep
... with the profile it has. So-
Right
... what does that tell you about, you know, that profile versus your profile? And then I'll stop there, but-
So, John, I, I'm old, so I can go back... It's a great question. I can go back to Eylea and Lucentis, right?
Mm-hmm.
So you go back to Eylea and Lucentis, Genentech had a 7-year head start with a fantastic drug, right? Then comes Eylea from a company at that time that nobody had heard of, right? Well, and Eylea sort of captures the market, and you've got to ask yourself, "Well, why did that happen?" I mean, what—there was no safety issue with Lucentis whatsoever. It's because Eylea reduced the number of injections by maybe 1, 1.5 a year.
Mm-hmm.
And now fast-forward, you know, why hasn't Vabysmo captured the market, and why high-dose Eylea? It's because it reduces the injection maybe by 1 or 2 a year, and what does that tell you? That tells you the thirst and the market opportunity there is for, for decreased injections and increased sustainability of this treatment. It's out there, and people are dying for this.
Mm-hmm.
We're not talking about one or two weeks here. We're talking about a drug that lasts nine or 10 months, which is exactly what you need for the perfect cadence. The perfect cadence is every six months. Every physician will tell you, "I want to see my chronic patients every six months. I'm not comfortable having them go longer than that." So if you want to see them every six months just to have a safety net, patients might get sick, doctor may be on vacation.
Mm-hmm
... what you really need is a 9-10-month drug, and that's exactly what we have.
Get some wiggle room.
Yep.
Vabysmo high dose, so there are some patients get to every four months.
Now, some patients may get to every four months, right? But again, that's the max.
Yep.
Here, we're talking about the max being 9-10 months.
Yep.
There's a big, big difference between the two.
But you're not the only long-acting TKI in development. Can you talk about which... you know, how you differentiate from other players and also gene therapies in development? You know, is there a place for those and, you know, how does Ocular fit in?
So regarding other players, you know, in the TKI world, look, it's not appropriate for me to comment about competitors or anything like that, but I will give you some facts. The first fact is that we, I believe, are the only drug that has a match between the PK and the PD. So when the drug is gone, the infrastructure, the hydrogel is gone. There is no stacking issue. This is one injection, one filament, not two or three. So there's no stacking issue whatsoever, and that's just a fact. The second fact is that we believe we have an entirely de-risked regulatory pathway. We're following the guidelines of the FDA to the T. We have a SPA to validate that. We're in constant touch with the FDA.
We have been very recently, and we're absolutely, and I repeat, absolutely convinced that the SPA is in alignment with their current thinking, and nothing has changed. Okay, so that's number 2. Number 3 is this is the only drug that I know of that has a pathway that gives it the potential to get a superiority label. In 2027, you may have a whole bunch of drugs out there, you know, biosimilar, so on and so forth, but this one is the only potential to have a superiority label. So I think those three things are just facts, and they're really important, and as I said, we're convinced, even with the diabetic retinopathy study, or especially with the diabetic retinopathy study, that this drug will last for 40 weeks.
Now, as for gene therapy and cell therapy, and so on and so forth, you know, look, I think there are major challenges that they have. There are- there's a whole change in workflow. There are challenges they have to overcome in terms of inflammation, in terms of a surgical administration, et cetera. We have no such challenges. There's no workflow change that's required. If this drug was available tomorrow, physicians would use it tomorrow without changing anything.
Mm-hmm.
That's the advantage.
We've talked about SOL in passing. Tell us about that design and how it's different than what's out there or what's typically done, and what it is.
Yeah, so the FDA has made it very clear that what they want are specific guidelines to have a de-risked trial for non-inferiority and superiority. It's about as clear as can be... Here's the trial design, and here's what we want you to do if you wanna de-risk your study. The FDA will allow you to do any trial design, as long as it's ethical, at risk.
Yes.
There are companies, as you know, that have gone forth at risk. There are others that have hit their primary endpoint and have been told, "Look, you can't be approved because you've gone at risk. You'll have to do another trial." We didn't wanna take that path. We wanted the most efficient path as possible to approval. So what we did was did exactly what the FDA wanted in terms of their new guidelines, which is very clear. This was validated with a SPA agreement. That's what we have. And the trial design is really quite straightforward and simple. It's that, you have a pool of patients that have good vision...
By the way, typically, these patients have no clinical trial to go to, and that's why there's really no competition for us in recruiting these patients, which is 20/80 or better. These patients then go ahead and are enrolled. They go through 2 Eylea injections as a loading phase. If they improve at least 10 letters of vision or get to be 20/20, those patients are then randomized to receive an additional single injection of Eylea, which is the control arm versus the TKI. And those patients are watched on an every 4-week basis. The primary endpoint is at month 9.
Mm-hmm.
The primary endpoint is the proportion of patients who maintain vision.
It, it almost seems like an unfair design. Talk about what you saw. So we talked about durability in the previous studies. What did you see about proportion of patients that lost those 15 letters in the previous studies at nine months?
Well, you know, our modeling is such that, you know, first of all, I'll push back a little bit on lost 15 letters of vision. It's really important to say that it's a net of at most 5 letters of vision. Okay, so from baseline, patients are given the Eylea injections, and they will improve at least 10 letters of vision.
I see. Okay. Okay.
So the net actually-
Sure
... is at most five letters of vision. And what I would argue is, look, we do treat and extend on a regular basis. We... Treat and extend means that we give an injection, and we wait for the efficacy of that injection to go away.
Mm-hmm.
We do this on a repeated basis until we find the proper cadence for that patient. Here, we're doing it once-
Mm-hmm
... with a net of at most five letters of vision, just once. Once those patients are rescued, then they're on Eylea from that point on.
Mm-hmm.
It's very, very important to understand that, that we've got two world-famous medical monitors to make sure those patients are managed properly and, and, and are not harmed. We have every reason to believe that those patients, after rescue, will do very well, just as well as, as, as, as any other patient would do.
Sure. I guess, asked another way, what, what do you expect for an effect size for AXPAXLI on the primary endpoint in SOL1?
Yeah, so our modeling is such that with Eylea, the-
'Cause that's the other big swing factor, is you're enrolling patients who could... What happens if you just treat them and let them go on Eylea, too?
Yeah. So, there's a lot of historic evidence on Eylea. It's a great question, and we know that it's about 20% or less of patients with Eylea that will maintain vision at nine months. With AXPAXLI, we know from the studies in the U.S. that I described, it'll be north of 70%.
Mm-hmm.
So there's a 50% delta, and we know that we need a 15-15% delta to be statistically significant, so we're very confident in the de-risking of the trial design.
Yeah, it's a very low clinical risk.
Yeah.
I guess the question then becomes execution, and you mentioned these patients don't have any other options. How hard is it to find these patients in the real world? Do they want to go on a trial, or do they wanna wait to see vision loss before they go into a study? You know, can you talk a little bit about the difficulty or not in finding them? And then also, I guess enrolling is one thing, but also getting them randomized through that, you have to gain as well.
Yeah, it's a great question. So I think the big thing that people don't realize unless they're practiced is patients don't come in with 20/200 vision anymore. It's not like they come in saying, "My God, I can't see anything. I have a blank spot." Those days are gone. I mean, those are the anchor and marina patients.
Mm-hmm.
Those days are gone. Patients... If, if you talk to a retina specialist in Idaho or Iowa or New York City and say, "Who are your patients that come in, de novo, with wet AMD?" They're patients that'll come in and say, "You know, I was watching TV, and I see a little weird line there," or, "I see a little spot over there." And you look at their vision, they're 20/20, or they're 20/30, or they're 20/40. That's the vast majority of patients, and those patients are absolutely symptomatic. If you doubt that, you can just put, like, a little Scotch tape on your... Well, you don't have glasses, but I do. But you can put Scotch tape on your glasses. You can't work.
Mm-hmm.
I mean, those patients are absolutely symptomatic, but in an artificial setting, they may test for 20/20. They absolutely do want to go on a trial, but there's no trial for them to go in because most trials, you know, don't want a ceiling effect. Ours is the opposite.
Mm-hmm.
So we think, and we've got good, excellent feedback with this all-planet team, recently talking to physicians and our colleagues, is that there's a great deal of activity that has happened, positive activity in terms of recruitment, as long as soon as we communicate exactly what I said to you, which is say, "This is the trial design.
Mm-hmm.
The best thing we can do for patients and for the community is to have an efficient up-down answer. This is a really simple, simply designed trial. It's got a SPA. It's validated by the FDA. We will have a binary answer, and that's the best thing we can do for patients in the community. And once physicians see that, and they realize, "Look, we do this on a regular basis, it's a net of at most five letters"-
Mm-hmm
... then there's immediately, I think there'll be great adoption to this trial.
You guys recently started enrollment. Have you talked at all about, or internally, you know, what's your metrics for timing of completing enrollment, randomization, and potentially data, or-
Yeah-
... tbd?
We have guided to... Look, this team just got together, you know, a few weeks ago, really, and we said it's probably gonna be about, you know, 12 months or so.
Mm-hmm.
We haven't given absolute milestones at this point... and I think what you will see is we have Investor Day coming on June 13th here in New York City. Our goal there is to give, you know, people a line of sight into the activity that's going on-
Mm-hmm
... in this very short period of time that this team has been together.
An interesting wrinkle I don't think we've discussed is retreatment.
Yeah.
So you're testing one dose.
Yep.
Then, you know, it's not just gonna be one dose in the real world, so how do you bridge what you're doing in SOL-1 to commercially what eventually you wanna be, which is, you know, you're getting treated once a year, whatever it may be, with AXPAXLI?
Yeah, it's a great question, and you're right, you know, obviously. But we think we have a great advantage there because of the biodegradability, right? Again, as I said earlier on, the PK and the PD are perfectly matched. When the drug is gone, the hydrogel is gone, so it's actually a perfect drug for retreatment. There's no stacking issues whatsoever. You're right. That's top of mind for us, and you'll be hearing more about that very shortly.
June 13th.
Very shortly.
You guys have said previously that you plan on potentially starting a second phase III study as soon as third quarter. Interesting then if you're answering that question in that study, or is it gonna be rinse and repeat of SOL-1? You know, anything you can tell us about that second study?
Yeah, I don't mean to be cryptic, but I really do.
June 13th.
Very shortly.
You've referenced the MPDR data-
Yeah
... that you guys recently reported. Tell us kind of the highlights there, and then I'll have a couple follow-ups.
Yeah, so John, let me just tell you how it happened. This is a new team, as you know, and we went to... We said, "Look, we're gonna do a deep dive here. We're gonna have a silent period. We'll look at and see what the company has," because it was new for us. You saw some of the personnel changes. When we looked at, you know, at the, at, in the company, we saw a very small study, and I emphasize very small, that was entirely for safety, okay? Entirely for safety. Only 13 patients received the drug, okay? This... We looked at it in a masked fashion, and the safety endpoint had been met.
There was no safety issue whatsoever, and the study protocol allowed us to unmask if the primary endpoint had been met, and it had been met. We had also... The previous administration had also committed, and it was in our filings, that we would present the data in a major meeting in the summer. I looked at this and said, "There's nothing more to be learned from this," and it's 13 patients, and unfortunately, people extrapolate a tiny safety study for efficacy.
Mm-hmm.
We decided that we're just gonna go ahead and rip the Band-Aid off and just show everybody everything that we had. I mean, nobody would design an efficacy study with 13 patients in diabetic retinopathy, which is the most variable disease we treat.
Mm-hmm.
But yet, people extrapolated and said, "You know, well, this is not PANORAMA." Well, of course, it's not PANORAMA. PANORAMA was designed for diabetic retinopathy and had more than 400 patients, and logically, to extrapolate 13 patients to more than 400 patients makes no sense. My prediction was that these 13 patients, that were pretty much all comers, would be all over the place. The take-home message from this, which was more impressive than anything to us physicians and the PIs, is that despite having all comers in this tiny, tiny study, every single metric aligned in favor of the drug. Everybody who gained had the drug. Everybody who lost didn't have the drug, and on June 13th, we're gonna show you even more evidence that this drug is absolutely active at week 40.
So we're more convinced than ever.
Based on what I saw, I think there's clearly evidence that the drug is active. I think the question maybe from investors is, is it active enough to cross the typical regulatory hurdle? Since you guys reported data, we had data from another competing long-acting TKI that showed no response.
Right.
Can you talk me, I mean, how... Does that give you more or less confidence? Is, is that a trial difference? Is it a drug difference? You know-
Yeah, so John,
Does that change your opinion based on when you guys?
Yeah
... had your data?
Look, it's a very appropriate question, and again, it would be inappropriate for me to comment about a competitor's trial design or results, so I won't do that. But let me tell you the other pushback, and I think that this may be where you're getting to, and this is fair as well. What people have said is they say, "Oh, you've shown me that your drug is now a maintenance drug. It's really not an initiation drug." I don't care. That's perfectly fine with me.
Just as on the trial-
Well, I mean, you know, at the end of the day, the only evidence I have are the patients that I told you about in Australia, right?
Mm-hmm.
Who basically got this naked, who had monotherapy in treatment-naïve patients?
Yep.
That's the only evidence I have. I actually don't care if it's a maintenance drug. I'm not gonna fight that fight at all. I mean, what do I care if people have two injections of EYLEA and then 25 years' worth of our drug?
Yeah.
I mean, it doesn't really matter. But here's what I'll tell you. Every single anti-VEGF study on this planet, every single, has a loading phase. Would I ever have designed or anybody on my team design a 13-patient study? The answer is no, absolutely not. Who would? Right? Makes no sense. What I can also tell you is every study we design will have a loading phase.
Interesting. Okay.
So we will not fight that fight at all. I have no problems having a maintenance drug, and if you think this is a maintenance drug, you would love the SOL-1 study design.
Yeah.
The SOL-1 study design is designed exactly for that. It has a loading phase, and then you watch.
Does that complicate the paradigm between wet AMD and DR, though, where patients in wet AMD are getting treatment with VEGF versus MPDR, where they have more-
Not at all. I mean, not at all. I mean, look at the PANORAMA study design, right? There are 3-5 loading doses. Again, there's no VEGF, anti-VEGF study without a loading phase. So, I mean, when this goes to market, think about the conversation that a physician would have with the patients.
Oh, I think if it gets to market, it'll be used a ton.
Yeah. Right.
It's "getting it there" is the key question.
Well, you're right.
Yeah.
So, that's a conversation with the FDA.
Mm-hmm.
And we said, you saw in the press release, I said that we're gonna go to the FDA because we're absolutely bullish about diabetic retinopathy. We are even more bullish now that we've seen more of the data.
Mm-hmm.
We will go to the FDA. It's a huge market there. Now, what we will come out of that with, design-wise, I don't know, because that depends on the FDA conversation. But we will not do a study without a loading phase of any kind. There's no reason to have that variable introduced whatsoever.
Okay, and in the last minute or so, you also had glaucoma data. Recently, it looked really good. You have DEXTENZA selling, post-cataract surgery inflammation and pain. But your focus is on retina. Those aren't quite retina. You know, how do those fit into the long-term strategy?
Yeah, they aren't quite retina, but, you know, what I'll say is we've got great deal of confidence in DEXTENZA as well as PAXTRAVA. But this is, you're right, a retina-focused company. Strategically, what you'll see is that everything we do in this company, every resource that we have in this company, is going to be designed to have SOL-1 recruited as efficiently as possible.
Perfect. Well, I know we're a little bit over. Just one last question: cash on hand, and how long does that get you guys?
Yeah, so we've guided the street to at least 2028. We are, we-
That's quite a long time.
We are 20-
Into '28.
Into 2028.
Into 2028.
Into 2028, and we have raised a PIPE , as you know.
Mm-hmm.
and we're very comfortable with our cash position at this time. Certainly, the studies that I mentioned will get completed.
Well, ourselves and everyone else, I think, are very much looking forward to June 13th.
Fantastic.
Pravin, thanks for joining us.
John, thank you for this opportunity. It's an honor to be here. Thank you.
Thank you.