Great. First, welcome to Jay Ducker and George Elfton from iPoint Pharmaceuticals here at the 47th Annual Goldman Sachs Healthcare Conference. Welcome, gentlemen.
Thank you very much.
For those in the audience and listening who may be newer to the story, can you start at a high-level overview of iPoint today, core clinical programs that are advancing, and key milestones that should be on Investor's Raiders?
Sure. Happy to answer that question. And again, we really appreciate the invitation. So iPoint is a drug delivery company for the back of the eye. We hope to improve patients' lives who have serious retinal diseases. Our lead product is called Duraview, or EYP1901. It's a combination of a small molecule tyrosine kinase inhibitor called virolinib in our proprietary bioerodible delivery system. Virolinib is a bit unique because it has activity against all the VEGF receptors. Again, it is a receptor-based treatment. as well as PDGF, and we also block the JAK1 receptor, which means we have an anti-inflammatory effect, which does appear to be important in retinal diseases. We are currently in phase three in the two largest retinal indications, wet age-related macular degeneration and diabetic macular edema. The wet AMD trials are called Lugano and Lucia. They are traditional non-inferiority trial endpoints, and the first trial, Lugano, is on target to read out sometime in August of this year. The Lucia trial is about two months behind, and therefore will read out approximately two months after that. The diabetic macular edema trials are still currently enrolling, and as of last week, they were two-thirds enrolled. They are simultaneous, identical, non-inferiority trials called COMO and COPRI. And they should be fully enrolled in the third quarter of this year. Given that their endpoint is 56 weeks, the top-line data should be out in the fourth quarter of 2027. So we have some really exciting milestones coming up in the next year and a half.
Maybe dig in a little bit deeper in terms of kind of your view of the differentiation. So at a high level, where do you see the key differentiation versus standard of care from both as well as other emerging clinical agents?
So at a high level, what we can provide is sustained release anti-VEGF effect for six months or longer with a single injection. We have some excellent biologics that are direct ligand blockers that are approved. We have multiple biologics. And while some of them have extended duration, they really don't have, in my opinion, the only true sustained release that's approved is the port delivery system. But the differentiator there is port delivery requires surgery for placement. And our medications are injected in the office for vitriol injection procedure. And I might add, we do come in a pre-filled room temperature, which is not a major differentiator, but we believe commercially the fact that we don't need to be refrigerated or frozen will prove to be an advantage should we be approved. So I think the durability, obviously, is the big high-level differentiator. Now, the next issue around durability, of course, people talk about reduction in treatment burden. How many fewer injections or visits will that provide? And while that's important, what we believe, and I think the retina community is coming to believe, that durability with sustained release means in the long term, and that's really what we're trying to accomplish. The reduction in treatment burden, let's call it a beneficial side effect of that, but that's not our true value. We believe the true potential value here is better vision in the long term. So that's the high level. I think also I mentioned that we do appear to have activity against the JAK1 receptor, which means we should reduce the downstream effects of IL-6, which is an inflammatory pathway that's been implicated in both DME and in wet AMD. That, again, is a differentiator for us. If we're approved with an every-six-month label and we provide both anti-VEGF activity and anti-inflammation activity, I think that has the potential to set us apart from the current therapies and, frankly, from the other therapies that are currently in study.
Yeah. Let's dig a little bit deeper there. When you talk about, especially some of your recent ARVO work around IL-6, JAK1, et cetera, can you talk a little bit more detail on why you see the anti-inflammatory potential benefit as differentiated? Specifically, how is that going to translate to meaningful clinical benefit or eventually commercial?
Sure. Great question. And let me kind of start at the beginning in what prompted this discovery that we were not only anti-VEGF, but we were anti-inflammatory. I'd like to go back and review a little bit of our phase two DME trial, which is called the Verona trial. And in the Verona trial, we recruited it meant that they had fluid and they had decreased vision. We optimized either to receive a single ILEA injection or an ILEA injection 30 minutes later with EYP 1901. If you look at the week four result, the earliest time point, the eyes that received our drug were already four to five letters better than the eyes that received a single dose of ILEA. And they're about 40 to 50 microns drier on OCT. Now, we believe we have a very good anti-VEGF drug. When we looked at that data, I said to the R&D team, I don't think we're that much better than ILEA. There must be something else active here. And that's when we went back and did a further kind of analysis and discovered that the IC50 for virulative in the JAK1 receptor is about 80 NM, which means that the doses we're using in humans, we should be active against the receptor. Subsequently, we did some cell-based studies, including a study where IL-6 was applied to cells and virulinib was able, at doses that were equivalent to what we're using in humans, reduce the downstream activity. At Arvo, just recently, we reported another trial, cell-based, which essentially looked at leakage. If you then add an anti-VEGF, they'll leak less. If you add an anti-IL-6, they'll leak less. If you add both, you get minimal leakage. We then added virulinib at approximately the dose we can get into humans, and we were essentially this leakage reduction as the IL-6 blocker and the anti-VEGF. So there's additional data to suggest that the anti-VEGF. I want to mention a couple other things from the Verona trial. I mentioned the rapidity of onset and also the rapidity of the dryness. But if you look at the eyes in Verona, and it was over 70% in the high dose that did not get rescued, they just received our drug for six months, those eyes improved over 10 letters. Now, again, cross-trial comparison is difficult, but if you look at the improvement in a previously treated population, We've designed the trial to show this difference at week four. We're dosing our drug at day one. And at week four, we can replicate the findings that we had in the phase two. I think that even in the end, if we're non-inferior to ilea, but we can get the patients to see better faster and get them drier faster, that means, I think, potentially a huge commercial. Back to Verona, one other data point here. Leakage in eyes can be measured quantitatively by fluorescein angiography, and a reading center that's independent can rate the leakage, and that's a sign of inflammation. And in a dose-dependent fashion, EYP-1901 reduced the leakage more than ILEA did, another data point that suggests that this anti-inflammatory effect is real.
We're going to get into what AMD and DME in a little bit more detail shortly, but before doing so, can you talk about the delivery platform and how that is part of the story in addition to active?
Sure. Again, a great question. Just to remind people, iPoint has been in the sustained drug delivery to the back of the eye space for almost 30 years. We've had four FDA-approved products with sustained delivery. All of them, however, prior were not bioerodible. The way they were designed is you had the drug admixed with the matrix, and then the drug disc or cylinder was then an impermeable plastic that was inert, and the plastic was open. There were essentially pores at either end, and that allowed the drug to diffuse out. And the reason you needed that is if you had a very soluble drug, like a corticosteroid or gancyclovir, for example, without that reduction in the surface area, the insurids wouldn't last very long. So that matrix, though, is very similar to the matrix that we're using in the current version of EYP-1901, and it's been in tens of thousands of patients safely. uh the uh difference here is we removed that uh impermeable plastic we want the whole surface area of the inserts to be able to release the drug because we wanted to get higher levels number one and number two we didn't want any residual uh long-term plastic to be remaining in the eye given that on average wet empty patients can live over a decade uh requiring treatment uh and so we really didn't think there was any reason to keep that design. So in effect, the current inserts have less excipients than the four that were FDA approved. In addition, what our scientists were able to do with the latest version, the payload of the drug, our inserts are now 94% verolinib, only about 6% matrix. That gives each insert a payload of about 1.34 milligrams of drug. which means we're able to achieve high tissue levels with two inserts in a single injection. And our injector actually can hold up to three inserts, which, again, down the road, one could then potentially see the possibility of using multiple drugs, which is something that we look forward to studying in the future.
Moving on to, I guess, digging in a little bit deeper on what I'm doing, You talked a little bit about Verona and some of the prior data there. Can you talk about Davio-2 and how that underpins plans within wet AMD?
So Davio-2 was our phase 2 study in wet AMD. It enrolled approximately 160 patients, and they were randomized to either receive 3 milligrams of our drug versus 2 milligrams versus on-label ilea control, 2 milligram ilea. The patients all were previously treated, and in order to enter the study, we only wanted to enroll patients that had responsive to an anti-VEGF. So they had to receive an anti-VEGF two weeks to five weeks prior to screening, and they had to show a response, and then they were enrolled. The primary endpoint was at month eight, and eyes were not re-injected with our drug. So they only received a single injection. And at month eight, we were statistically non-inferior to ILEA. And the actual numerical difference in the vision was only 0.3 in the 2-milligram arm and 0.4 in the 3-milligram arm. So that's 0.3 letters. Those of you who've been to the eye doctor, you know, you read a line, that's five letters on a line. So there's less than half a letter difference, which is, again, statistically equivalent. Equally important is we found that the safety was quite good, and we really had no safety signals that were identified in that trial. There were no ocular systemic SAEs that were attributed to our drug or inserts. So we're quite pleased with the safety, and we've reported safety on over 190 patients from the Phase II and Phase I trials, and again, the safety. From the perspective of, for example, the anatomic results, we measure anatomy using the device called the OCT. Normal anatomy on OCT is up to 325 microns in thickness. And anatomic control is important because in wet AMD, what's been shown is if you allow patients to gain fluid and have more leakage, even if you get it back under control, if that cycle continues, you can lose vision and get fibrosis as a result. So our maintenance of the anatomy was quite good in W-2. In the higher dose, the 3-milligram dose, there was about a 5-micron difference in the end between us and ILEA, which is, more importantly to the doctors, having the fluid go up and down in a sawtooth pattern is something that they really don't like to see, and our fluid control is quite good through the whole study. And that's, again, important. If you look at the eyes in W-2 that were unrescued, meaning they only got our drug, there was straight anatomic control all the way through. What that tells you is that the drug was working until the end because you would expect if the drug started to run out at month 7 or 8 or 9, you would start to see an increase in fluid, and we didn't see that. So it gives us confidence that we truly have a six-month or longer drug. Reduction in treatment burden was about 80%. and about two-thirds of the eyes were free of a rescue up to month six. And even though we didn't re-inject the drug, at one year, about 50% of the eyes in the Durabu arms were unrescued. So we had quite a good durability. That gives us quite a lot of confidence going into the Phase III about the results, and we've obviously used what we learned in the Phase II.
So good transition to Phase III. Can you remind investors of study design and, in particular, why you chose non-inferiority versus there's certainly other approaches out there? And then, additionally, could it occur?
So non-inferiority, the way the last five approvals have been in wet AMD have been using a non-inferior approach. So it's a de-risked approach. There's a lot of risk in this business. And our belief is that any time you can reduce the risk without harm to patients or harm to your label, you should. And so obviously we're taking a de-risked approach. Non-inferiority, again, the doctors understand it. They've seen it before. And our control arm, 2-milligram ILEA, know the treatment of choice of a lot of doctors out there. And so when the data comes in, if we're non-inferior to that 2-milligram on label, I think the doctors are going to understand very well where we fit into their paradigm. So non-inferiority, again, to us is a de-risking, and it's the way to get to FDA approval, we believe, the fastest. So the study design is very similar to W2, except in a few ways. First of all, we enrolled the majority of patients who are actually treatment-naive. about 75 percent treatment naive about 25 percent previously treated and we believe the addition of the treatment naive patients if approved will not only help us on the label but also de-risk the trial what i mean by that is in w-2 we had a very tough to treat population on average in the united states patients get about six injections a year and w-2 if you looked at the prior year and normalize the number of injections, it was about 10. And that makes sense because those are the patients we call the frequent flyers who need a lot of treatment. We got very few easy to treat patients in W2. And our hypothesis is if you have a patient who can go three or four months on any of the anti-VEGFs between injections, they should do really well with our drug. And we think the addition of the naive patients allows us to get a proportion of those easy to treat patients. So we think that's going to actually improve the end result. The second difference I mentioned already is we're re-injecting every six months over two years because we'd like an every six-month label. We didn't re-inject endavio-2 at all. The third difference is we altered the supplement criteria. We studied the supplement criteria endavio-2 and found out that three of the criterias that we used did not result in an improvement in vision after supplementation, And therefore, you could call it a waste and supplement. And so we didn't include those in the pivotal trial. So ultimately, we think with positive data, doctors will know exactly how to use this, and our labels should be very...
When you think about what does good look like, how should investors frame BCVA in the context of non-inferiority?
Sure. That's a really good question, and one that's very pertinent, given that our data is coming soon. So I think the way to look at our data from the top line from the phase three is really quite simple. The first is we need to hit non-inferiority. We need to be statistically non-inferiority. That's obvious. That's the primary endpoint. But I'd also argue that the exact numerical difference probably doesn't matter. This is, again, a piece of data to share, but if you look at the wet AMD study of high-dose ilea that got it approved, the high-dose ilea arm was 1.4 letters worse than the 2-milligram arm. It doesn't stop us retina specialists from using it at all. It's a great drug because that amount of vision we believe is inconsequential to the patient. And frankly, the agency believes that too. That's why the non-inferior margin. So I would argue that the exact numerical difference probably doesn't matter. We need to hit the primary endpoint. point i'm going to reverse myself though and say there's a chance we could be superior and we're able to test for that without penalty if we hit the non-inferiority margin obviously not guiding to this but we could be statistically superior even numerically superior and i think obviously either of those if we hit it would be very beneficial to us commercially now the second piece of data you should look for uh at the top line of safety and uh those of you who follow retina companies, you know safety is of paramount importance. The good news for us is I've already mentioned the safety in the prior studies, and we've talked about this publicly. A few weeks ago, we had the DSMC meet, and they see not only the unmasked safety, and they didn't recommend any changes in the protocol or the trials, which is of a relief. We see, as we've reported publicly, the mass safety looks very similar to what we have seen in the prior 190 plus patients that we've already reported on. So while the studies are not over, anything can happen. I'd also like to remind everybody that most of the safety events occur at or just after the time of injection. And this last look at the safety, all the patients in Lugano and Lucia had received their second dose of our drug, and about a third of them had received the third dose. The third thing to look for at the top line is reduction of treatment burden, and we believe this may be the easiest bar for us to hit, and the reason is that it's a, and we only need to be 8% less than the control arm to be statistically. Now, the way treatment burden is going to be measured in this trial was a little different than prior. And I do want to go into a little detail about it so investors and analysts can understand. Because both arms of the trial get the three-injection ilea load at the beginning. Those injections don't count for treatment burden. In the Duraview arms, all eyes will receive two. In the ilea arms, all patients will receive five ileas. So if there were no supplements and everybody follows protocol, the most reduction in treatment burden you could possibly see would be 60%. We know there's going to be some supplements, probably in both arms. But if you then look at W2 and you say, what if you had the same supplement rate in W2 as you do in the Phase 3s? It would be about a 35% reduction in treatment burden, which we believe would be excellent. If you talk to the KOLs, and we've talked to a lot of them, and you ask them, what's your floor for using a TKI, they'd like to see at least a 20% reduction, which, again, remember in a real-world situation, using a supplement is not a failure for physicians. That the idea of using two MOAs may be beneficial to patients, and therefore just the idea of using a ligand blocker with a TKI may be an acceptable way to go. So that's really the three things that I think are most important. I think we will likely talk about the anatomy and also talk about the percentage of patients that are rescue-free through the entire first year. While I'd argue also, given that the agency's interest seems to be more in reduction in treatment burden, that figure is probably not as important. but I would hope that we could do at least as well as we did in Davia 2 where we were 50% rest.
Switching gears a little bit to the commercial side, obviously a little premature, still need to get to the data, but to the extent data plays out as you expect, where do you see it fitting into the current?
So I'm going to first of all say it's never too early to think about that. I think that companies need to start to think about it even when they're designing their phase one trial because this is a large continuum. We're focused on the clinical outcome because that's coming up and it's easy to get focused on it. But we haven't just been laser focused on that. We're focused on CMC because we know that that's where most of the CROs come from. And we're focused on commercial success because ultimately what we're trying to do is improve patients' lives, which means we need to be able to get the drug to them. So it's not just how it fits into the paradigm. We need to be able to make enough inserts to satisfy what we hope to be a demand. But how it fits in, I think our data will help dictate that. But if you just look at us, we provide an additional benefit, a visual acuity benefit, or let's say we can show we're anti-fibrosis. I think doctors will accept then that in the long term, if we can reduce fibrosis, we will reduce vision loss, and they may choose to use us. And this is backed up by what we've heard on the podium by KOLs recently, where they have the tolerable. We use a TKI in 80% of our patients. So I think at the beginning, it will be most likely used in the patients who require very frequent treatment. But I think once doctors get comfortable with it, if our clinical profile is what we hope, I think it's going to be used in the majority of patients.
Switching gears to DME, let's focus on Coma and Campari. Can you talk a little bit more detail or give a little bit more detail on study design, specifically learnings from Verona? You already mentioned a few, but anything more specific there, as well as what investors should be looking for on balance of the year as you march towards full enrollment?
Sure. So I would say that the study design in the DME trials is very similar to the wet-empty trials. 75% naive, 25% previously treated. The N of the trials are less, only 240 patients in each. The reason we were able to use a lower N is that we will have the results of the wet-empty trials when we submit DME. And the agency has allowed us to inform the safety of the DME trials. So we don't need to hit the safety numbers in DME that we would have otherwise. So the two big differences, we are dosing our drug on day one, and there is a secondary endpoint of vision and ad. We hope to replicate in the phase three what we showed in the phase two. Because if we do, and we can show as early as week four that we're better than a single dose of ilea, Even in the end, if we're non-inferior and we're the same as ILEA, or even a half a letter, let's say, or a letter worse, but we're non-inferior, but we achieve the vision faster and we achieve dryness faster, I think the majority of retina specialists will choose to use this in almost all their DME patients because what patient wouldn't want to see better or faster? I think they would. So that's the first difference. The second difference is a little bit more subtle, which is the label for ilea, 2 milligrams, in DME is a 5-injection load, which is what we're doing. The agency really insists on use on-label Lucentis or on-label 2-milligram ilea as your control. That's mandated. But we don't believe the 5-injection load is necessary with DuraVue, and therefore we're only doing a 3-injection load. So very similar studies to wet MD.
In terms of mechanistic rationale in DME, anything additional that you think the profile fits DME specifically?
I think I mentioned this already, that we do have data with some supporting clinical data from Verona that we have an anti-inflammatory effect. And so we expect to see that in the phase 3 trials. And if we can show it, the combination of an anti-VEGF that's anti-inflammatory, that's given every six months, delivered in the office, shipped and stored at ambient temperature, I think that has the potential to have us stand heads above everybody else.
From a, I guess, mentioned earlier, commercial, and I guess never too early to start thinking there, can you talk a little bit about the commercial and medical affairs readiness as well as manufacturing readiness that you're doing in advance of, hopefully, good data?
I'm going to let George answer that. So let's start with manufacturing. We have our own state-of-the-art facility, so we do drug development at iPoint. So this facility was started four years ago. We have registration batches already on stability, and we are scaling up and preparing not just for building commercial supply but also being prepared for a pre-approval inspection. The team has really done a remarkable job there, and we are just as prepared for that section of the NDA as we are for clinical data. So that is well underway, and we will continue to push that, especially through 2027. you know interestingly on our medical affairs team you know we we have a robust msl group that we actually retained we had commercial products several years ago which we transacted but we kept the msl team and they were really instrumental in helping us get our trials enrolled quickly building relationships with the kol community and we've continued to add to that so that group is already on the ground as part of a more robust medical affairs team which we think is very important not just for wet amd and dme but also for commercial readiness and then on the commercial side we have a new chief commercial officer mike campbell who joined us probably two months ago now patient access and that's really going to be key and part of our launch and so while we have a a small footprint right now on a commercial team they're doing a lot of the leg work to be prepared on the other side of our data release starting this summer. And obviously, you know, with positive data, we'll be looking to scale that team up. We are planning to launch this product in the United States ourselves, and we will be ready for that. From a payer perspective, we've had initial discussions and have gotten very good feedback from payers as we think about where does Duribu position versus the current standard of care. And I think importantly, you know, we're not another anti-VEGF. We're actually bringing a new MOA. And so we're really looking to position this program commercially in that same effect. And I think the other interesting thing, and Jay touched on this a little bit, our products shipped and stored at room temperatures, and some of our interactions with the larger practice groups and the private equity groups, the message is don't slow us down. And I think what's really unique about this program is we're shipped and stored at room temperature. We're not taking up refrigerator space. And because it's a pre-filled syringe, there's really no change in practice. So there's a lot of work between now and a potential commercial launch, but we've got the right team and right infrastructure in place, and there'll be more to follow.
Briefly on balance sheets, can you remind investors, Current Cash Runway, what does it fund and what does that include?
So our cash guidance has been unchanged for quite some time, and it's into Q4 of 2027. That includes all four ongoing phase three trials and their readouts, along with commercial scale-up for our facility and NDA filing. Obviously, the commercial launch, I touched on this earlier, the commercial launch and scale-up would obviously come on the other side of data. But as we look out over the horizon, we've got the two phase threes reading out this year, and wet AMD will have the DME trials reading out next year, NDA filing. So we have a catalyst-rich upcoming 12 months that we're going to be in a position to transact and fund the company. And we suspect it's going to be some combination of equity structure. And, you know, there's been a lot of interest from all of those groups on the other side of our data.
Great. Final little bit of time, maybe just in closing. What do you think is the most underappreciated part of I-Point that investors don't appreciate as much as you think they do?
I don't think there's a single thing other than the whole story. We are a de-risk, we believe, very good phase two data going into the two largest anti-VEGF markets, total of almost $13 billion in the United States alone, with data readout coming very soon. We remain quite confident and quite optimistic in the results, and we think we can make a difference for patients. And so I think as people dig in and turn their attention to us, they're going to realize how underappreciated we are right now.
Fair enough. Good place to leave it. Well, thank you so much for your time, and best of luck. Thanks so much for inviting us.