Conference Transcript - EYPT 2026-06-03

Pastor Karsheed, Analyst — Jefferies

All right. Good afternoon, everyone. Thank you for those of you in the room and those on the webcast sticking through as we get word to the tail end of the day here. My name is Pastor Karsheed. I'm one of the senior biotech analysts here at Jefferies. We are live at the Jefferies Global Healthcare Conference in New York. Really pleased to have with us today the management team of iPoint Pharmaceuticals. We have Jay Duker, CEO, George Elston, CFO, and Ramiro Ribeiro, CMO. So with that, Jay, why don't I pass it off to you to just start with introducing the company a little bit.

Jay Duker, CEO

Thanks very much for the invitation. We're really delighted to be here, and thanks for those of you in the audience who have come stay till the end. So iPoint is a drug delivery company, and we try to improve patients' lives with serious retinal diseases. Our lead product is EYP1901, also known as Duraview. DuraVue is a small molecule tyrosine kinase inhibitor called virulinib, which is patent protected. It is in our proprietary delivery system that we call DuraCert-E. DuraVue is currently in four phase three trials, two in wet age-related macular degeneration, two in diabetic macular edema. The wet AMD trials are fully enrolled, and we'll be reading out this year. The first trial, Lugano, we expect to read out sometime in August, with the second trial, Lucia, about two months later. Lugano and Lucia are identical. The primary endpoint is non-inferiority change in visual acuity at week 52, week 56, averaged against an on-label 2-milligram ILEA control. We did a robust phase 2 study in wet AMD called the DAVIO-2 study. Our two doses were both highly statistically non-inferior to the control group, giving us quite a bit of confidence in the Phase III results. With respect to DME, we have two, again, simultaneous trials. COMO and CAPRI are their names. They are actively enrolling, and we're delighted to report today that both trials are now nearly two-thirds enrolled. First patient was enrolled in late February, so these trials are enrolling very rapidly. There's a lot of reasons for that, which we can get into if you like, but we expect that the last patient should be enrolled in Q3 of this year, giving us top-line data in diabetic macular edema in approximately a year after that.

Pastor Karsheed, Analyst — Jefferies

Got it. Excellent. So definitely a very exciting time for the company with these four Phase III readouts coming up. on the horizon. So let's start with Lugano and Lucia. So for the phase three wet AMD program,

Jay Duker, CEO

what does good look like? Well, I'd rephrase it probably in a different way. I think there are three things that we should be looking at as the outcome. And the first, obviously, is the primary outcome of non-inferiority change in visual acuity against the control group. Provided we are non-inferior statistically, I don't actually believe the actual number difference between us and ILEA matters much. And the reason is in the community, in the retina community, a letter or two is not really a measurable amount that is meaningful to patients. Again, we have some data on that. high-dose ilea arm in their phase 3 trial was 1.4 letters worse than the 2 milligram arm. Nobody remembers it. Nobody in the retinal community ever stopped to say, I'm not going to use that drug because of the difference. So the most important thing is that we're statistically non-inferior. Number two, and probably just below the primary endpoint, of course, is safety. Safety in retinal trials is really important. And the good news is we've had a really good safety track record. We've done four trials that we've reported, one phase one and three phase two trials, and the safety has really been quite good in those trials, and there's been no safety signals reported and no ocular systemic SAEs due to our drug. With respect to safety in the phase three we are monitoring the mast safety and we also have a data safety monitoring committee that has now met three times most recently a few weeks ago and they were the report was no change in the protocol necessary but we've talked about publicly is that on a mast basis the safety that we're seeing in the wet amd phase three is really no different than what we've seen in the prior trials. So we are confident and comfortable in the safety that we've seen so far. And I like to remind people in a wet MD trial that the number one cause of safety events is the actual injection. And so in the phase three trials, the injections of our drug was done at week eight and week 32 in the first year. So at the time that the last the SMC meeting occurred, all the patients in both trials had received their second injection of drug, and about a third of the patients had received their third injection of the drug. And again, so far, so good with respect to safety. The study's obviously not over. We've got the last patient visit coming in approximately a month, but we're quite comfortable at this point with the safety that we're seeing on a mass basis. Now, the third thing to look for is the reduction in treatment burden. What that refers to is how How many injections did the control group get versus how many injections did the study group get? The way that's calculated for the Phase III trial is, for those of you who don't know, all the patients in the trial receive what's called a load, which means monthly ilea times three. The count starts after the load, which means for the DuraVue arm, there will be two DuraVue injections. For the ilea arm, that's five ilea injections. So if there were no supplemental injections given the study, that would be a 60% reduction in treatment burden. But the way we're going to report it is on a statistical superiority basis, we are going to do a statistical analysis of superiority of the dervue arm against the control arm. And because the N of the trials are so large, we only need an 8% difference to be statistically superior. So we believe that's a bar that's easily achievable based on the data that we've seen from the phase two. From a clinical perspective and commercial perspective, I think the answer is slightly different. I think if you talk to KOLs and they'll say, well, what type of treatment reduction burden would you want to see in a study like this? The number we're hearing is about 20%. And I think we've got some real-world evidence of that. if you look at the real-world usage of, for example, Babismo, it's approximately a 17% reduction in the treatment burden. So even a relatively, let's call it modest, reduction in treatment burden can result in a very successful and well-used drug. Now if you apply the percentages of rescues that occurred in the DAVIO-2 trial and apply them to the pivotal trials, we'd have about a 35% reduction in treatment burden. So going back, with respect to treatment burden, the numbers are going to look different because of the way they're calculated from our trial, our previous trial, and any of the other trials that you might see. But we would expect and hope for a 20% reduction or more. We only need 8% to be statistically

Pastor Karsheed, Analyst — Jefferies

superior. Got it. And then what about in terms of injection-free rate? Is that a metric, or can Can you characterize the extent to which that metric matters to you? Because I think that's something that investors kind of anchored to a little bit.

Jay Duker, CEO

Yeah, I think that there is interest in that. And what I'll remind people is in DAVIO2, the number of patients who were rescue-free up to month 9 after the drug went in, which was month 8 of the study, is about two-thirds. And at one year, 50% of the eyes were rescue-free in the Duraview arm, and that's without a re-injection. Those patients only got one injection. So presumably by month 12, most of the inserts were devoid of drug at that point. So we expect that the number of eyes that are rescue-free up to month 12 would be higher than that. But it's not a metric per se that we think is really crucially important to either the agency or to the doctors. A supplemental injection in the real world is not a failure. And in fact, based on what KOLs are telling us, they may take advantage of two MOAs. Remember, DuraVue has a new MOA. It's a receptor blocker. It's not a ligand biologic blocker. And doctors may choose to use both a ligand blocker and a receptor blocker together to take advantage of both MOAs. The other way to think about it is if you have a patient who, let's say, is getting six injections of a biologic a year. And Duraview is approved, and it's safe, effective, and tolerable. And that doctor switches the patient to Duraview, and they get two Duraviews over the next year. But they also get two biologics. Is that a failure? I would argue that's a resounding success. That patient's gone from six injections to four injections, a one-third reduction in their treatment burden. And now they only have to come in four times a year, not six times a year. So again, the idea of reduction in treatment burden and supplement-free, while I think there's value to it, doctors individualize therapy in the real world. And that means that they're going to look at the individual patient and ask the question, how is this drug doing for this patient? I also want to emphasize what we're trying to do here in the long term is preserve vision. The reduction in treatment burden we're all interested in, And we do believe that's going to be a benefit. But that's not the primary thing we're trying to do. We believe, and I think there's now increasing evidence, that if you can suppress VEGF constantly, long-term, you will get better visual acuity in these patients. And so ultimately, that's what we're trying to show.

Pastor Karsheed, Analyst — Jefferies

Got it. And then if you take us through, like, how this works in a real-world setting, how often are these patients coming to the clinic anyways? And is there a worry? Because one pushback that I get from investors is that if the patient still has to come in every X amount of time to get checked for a potential need for a supplement injection, does that reduce the value proposition of a drug like Duraview? Is that fair, or how should people be thinking about that?

Jay Duker, CEO

I don't think that that's the way the real world is going to exist at all. So on average in the United States, patients after the load get about six injections per year, although it diminishes to eventually about four injections, and that's partially because some of the patients just drop out. They just can't keep up with the visits. You know, the studies obviously suggest that more injections are better than fewer injections, and pretty much every study has shown that in the real world. So what's going to happen? I think that once approved or if approved, I think you're going to see the doctors use Duraview the same way they started to use any of the anti-VEGFs, which is basically there's three strategies that we use. The first and most commonly used right now is called treat and extend. So I think you're going to see that. In other words, you'll see patients get their three monthly injections at the beginning. Doctors will put a Duraview in and then maybe see them back in six weeks, if they look good, they'll give them another biologic. See them back in eight weeks, they'll look good, give them another biologic. See them back in 12 weeks, and if it's time to give them another DuraVue, they'll give them another DuraVue, and they'll continue out until they hit six months. Now, remember, if at month three or month four they show fluid again, I don't think doctors will have any problem just saying, okay, you're going to need a biologic every other visit and a DuraVue every other visit and just go from there. I think as needed, which is PRN and how some of the investors are saying that may not be an advantage, right now there are not a lot of doctors who do that. And the reason is if you're allowing the fluid to come back in the long term time and time again, we believe that that results in decreased vision. But I think you may see it at the beginning before doctors really get used to how the drug works. And finally, the third way is put patients on a schedule. Now, if you look at that, we individualize therapy in general and that the number of patients, for example, when Lucentos was approved, they used it monthly, which was on label, was about 5%. So it happened, but it was low. But if our Phase II data holds, and one can extrapolate it to Phase III and then to the real world, if you look at the number of eyes that after they got a derivative in Phase II needed either zero or one supplement, it was about 90%. So a priori, if this holds, then one could imagine that you could take about 90% of the wet MD population and treat them every three months, alternating a biologic with our drug, and not have any recurrences. Now, you might argue, Jay, aren't you over-treating some of them? We would rather

Pastor Karsheed, Analyst — Jefferies

over-treat than under-treat. Yeah, and Jay, just to be clear, so you're saying that the real-world setting, the way that you envision it, could actually work in a fundamentally different way than the trial, where instead of waiting to see a trigger for a rescue, it's actually the total opposite, where they intensify treatment and de-intensify thereafter? Correct. So to me, this strikes me as a disease area where somehow the investor bar is way, way higher than the clinician bar. Is that fair?

Jay Duker, CEO

Yeah, it's an interesting observation. You know, the key opinion leader title that people get, you know, and I always thought when I was a key opinion leader, we'd tell the investors is what I think, and they'd write it down and believe it. So this actually, it's an interesting observation because this actually started with our phase two. prior to the phase two data you asked kols well how much vision would you be willing to sacrifice in your patients to get durability of six months or longer and they were zero two or three letters oh i don't care about two or three letters you talk to the investment community and they were oh my goodness two or three letters so yeah there is a dichotomy here but you know what ultimately this is the data is going to uh you know guide usage and and the doctors are going to figure it out. And that ultimately, if the belief is sustained release is going to give me better vision in the long term, then that's what doctors are going to choose. And whether they choose to use a second MOA on top of it, I think some will. Interesting. Okay. And then, like, obviously,

Pastor Karsheed, Analyst — Jefferies

there's, like, the, you know, what will ultimately matter and what the bar is, per se, for the medical community. There's investor expectations. But in your opinion, based on your conversations with any potential strategic partners, how do the kind of larger companies or companies interested in this space, sort of think about what is a compelling value proposition?

Jay Duker, CEO

Well, I think the first answer to that question is they're viewing it as a very large opportunity. You know, right now, you know, it's, some would argue, over $10 billion in the United States alone. DME, you know, we haven't talked about Diabetic Bank or DME much. It's about a $3 billion opportunity right now in the U.S. alone. So I think that strategics understand that this is an area that can really help patients because it really helps preserve sight, and so that there's quite a bit of interest in the results and what will ensue after that.

Pastor Karsheed, Analyst — Jefferies

Got it. And then you spoke a bit about some of the benchmarks and observations from your Phase 2 Davio 2 study, but with Lugano and Lucia, you have a couple of differences. with respect to both the characteristics of the enrolled population and the rescue criteria as well. Can you talk about the push and pull on rescue dynamics that you'd expect from that?

Jay Duker, CEO

Yes. So we're expecting lower rates of rescue in the phase three for several reasons. The first you touched on is that the population we enrolled in the phase three wet AMD is 75% naive and 25% previously treated, approximately. And we expect that the addition of the naive patients will improve the results. And the reason is, if you ask a retina specialist how many of your naive patients are easy to treat, meaning I can give them three injections and they can go many months without another shot, or I could give them any anti-VEGF every three or four months and they'll do fine, they'll answer about 30% approximately. Some will answer even up to a third. Well, we got very few of those patients in our Phase II. We expect enrolling a naive population, we'll get quite a few of them in the Pivotals. And I think our hypothesis is that our drugs should do very well in those patients. So that's a dynamic we expect to be a positive. You asked about the rescue criteria, and perhaps I'll ask our Chief Medical Officer, Dr. Romero DiBero, to comment on the rescue criteria changes and why we made them.

Ramiro Ribeiro, Analyst — CMO

Yeah, so when we look at our phase two study, which was relatively large, 160 patients, on that study we had five different criterias. And we just, we look at the rate of rescue, but more important than that, we look at the outcomes of those injections. So did the patients actually gain vision after the supplement injection? And out of those five criterias, only two made a big difference. and they were either the presence of hemorrhage or if a patient on the same visit had decreasing vision and increasing fluid. So for our phase 3 study, we only included those two criterias. So we do not have, for example, vascular discretion in the phase 3 study. We don't have if a patient only lost vision but no anatomy. So we only have those two criterias.

Pastor Karsheed, Analyst — Jefferies

Got it. And then based on the observations that you've seen on a blinded basis in Lugano and Lucia, are the rescue rates in line with your expectations?

Jay Duker, CEO

We are not viewing the mass rescue rates.

Pastor Karsheed, Analyst — Jefferies

Got it. Okay. And then in terms of the inclusion of the naive patients, and you spoke about some of the reduction in treatment burden that you saw from Davio2, would including the naive patients blunt the effect of that, given that you have on the control arm as well patients that may be better controlled on just ilea alone?

Jay Duker, CEO

Sure, but remember the control arm gets every other month ILEA whether they need it or not. And so you'd argue that there's some eyes in the control arm that are being over-treated. But over-treated doesn't show improved vision. In fact, if you look at the ILEA control arms in the last couple of studies that got approval, after week 12, the control arm is pretty much flat visual acuity. But also remember, about 20% of wet AMD eyes have to be treated monthly. And so when you shift one of those patients after the load to every other month, they're undertreated. And so what will that result in? Well, it may result in some rescues. We saw that in Davio 2 in the control arm. But it also may result in just some drop in vision that doesn't quite meet rescue criteria. And that's, you know, certainly possible to see as well. So, yes, so the fact that those easier-to-treat patients will be in both arms certainly doesn't

Pastor Karsheed, Analyst — Jefferies

hurt us and may in fact help us got it okay uh and then from a uh from a safety perspective can you um talk to us about what gives you um confidence on the safety side and you know i think the history of the company is pretty important here as well well i i may be repeating

Jay Duker, CEO

myself a little bit but uh you know in the uh over 190 patients in the four trials that we've reported the safety has really been quite good uh again there have been no in those trials ocular systemic SAEs associated with our drug, and there are no trends toward any safety issues. We also have really good preclinical data. We've put doses of aerolinib into rabbits that are 10 times scaled higher than what we've ever put into a human, and we've not found a maximally tolerated dose of aerolinib. We've actually had up to six inserts simultaneously in an eye of a rabbit with no toxicity. So, we're comfortable, again, from a preclinical, and, you know, obviously, the FDA has seen or will see that data as well. From the mask safety, you know, again, I'll turn it over to Romero. He's the one monitoring this. Any other comment on the mask safety from the Phase 3s?

Ramiro Ribeiro, Analyst — CMO

Yes. So, internally, we review the mask safety data as an ongoing basis, and then also we have a DMC every six months that review the data on a mask fashion. So what we're seeing so far in terms of the type of adverse events, the frequency of the adverse event, is very similar to what we saw in our Phase II study. And as Jay mentioned before, our DMC met last month. They saw the data, both for our wet AMD study as well as for our DME study, and they recommended no changes to the protocol or no safety concerns.

Pastor Karsheed, Analyst — Jefferies

Great. And then as you think about the competitive landscape, there's a lot of development happening in wet AMD. We'd love to hear your thoughts on how DuraVue is positioned relative to the plethora of things in development, including novel mechanisms, other TKIs, and gene therapy.

Jay Duker, CEO

Maybe I'll ask our CFO, George Elston, to answer that question.

George Elston, CFO

I think, you know, as we look at the competitive landscape and, you know, I think what's important as you think about DuraVue versus other programs is we are not another anti-VEGF biologic. We're bringing in new MOA. We block all VEGF isoforms intracellularly. We've blocked PDGF, and we've published data recently that suggests that we meaningfully block JAK1, which gives us this inflammatory benefit as well. And so we've never viewed the biologics as our competition because historically the message was each biologic is the same MOA, and the message was we last longer, use us, don't use the MOA. Our message is very different. It's really use both. And because we are bringing this second MOA, we can last six months or longer, which a biologic can't do. You know, gene therapy that we see is a different category. They're producing the same biologics. And, you know, even the biosimilar space, you know, they're competing with the VEGFs, which we don't see as direct competition.

Jay Duker, CEO

One other advantage we have, which may prove to be very beneficial commercially, is we're shipped and stored at room temperature. All the biologics and the other competitors either have to be refrigerated or frozen. And given the number of anti-VEGFs that are proved out there, you can imagine retina specialists have huge refrigerators already. I think it will be nice for them to just put us into the closet and not have to put us into a refrigerator or a freezer. And that, again, I think it will prove to be a commercial advantage if we're approved.

Pastor Karsheed, Analyst — Jefferies

Got it. And then just shifting over to DME, can you talk to us about expectations for that study and the evidence base that's supporting it?

Jay Duker, CEO

Well, so I think if you talk to retina specialists, they're likely to tell you that the need for sustained release is even more important in DME than it is in wet MD for several reasons. I think one of the reasons is it's generally a younger patient population who are generally working. They have multiple doctor's appointments. And you don't get what I call the wow factor with an anti-VEGF and DME typically, meaning if you treat a wet MD patient with an anti-VEGF, usually in a week or two, they know they're better. even if their visual acuity hasn't improved, and most of them will come in four weeks and say, please give me another one that worked really well. DME takes longer to work, probably because it's more of a multifactorial disease, and sometimes it can take four, five, six injections before the patient realizes that they're improving, which means after one or two or three, if they're not feeling like it's worth it, it's very easy for them to drop out of treatment. The real-world data suggests that on average in the first year, DME patients are getting three injections, they should be getting 11. So there's a need for sustained release. Now looking at our data, one of the things that really struck us when we looked at our Verona Phase II data is the four-week result. The only difference between our drug and the control group was our drug at week four. There was no supplements obviously given that early, but yet we were already in the high dose four to five letters better and we were 40 to 50 microns drier at week four now we've designed the phase three trials to try to show that as well so we do have a secondary end point about week four vision and fluid so even if in the end we're non-inferior and we're equivalent to ilea but we can show that we get there better and faster then i think we will get quite a bit of the market. And once again, the idea of being able to give somebody sustained release if they miss visits, I think is going to be very attractive to patients and retina specialists

Pastor Karsheed, Analyst — Jefferies

should we be approved. Great. And talk to us about the overall market size and growth outlook for

Jay Duker, CEO

vascular retina diseases. Well, again, I think in the U.S., which is the over 50 percent of the worldwide market, it's approximately 13 billion next year. Year-over-year growth rate is high single digits, aging population. And remember also that about 40% of wet AMD patients stop treatment after a year or so. That's another portion of the population that we may be able to capture with sustained release. That if they're not feeling the benefit of monthly or bimonthly injections, if the doctor says, well, I can switch you to twice a year, they may stay under treatment under those circumstances. So we think that this isn't a zero sum. This isn't taking from one and adding to the other. I think that all the sustained release, if approved, are likely to grow

Pastor Karsheed, Analyst — Jefferies

the market. Great. And then in terms of how the market has performed, there was the kind of patient foundation disruption last year. Just for investors' benefit, can you recap what happened there and if that's kind of all set now?

Jay Duker, CEO

Well, again, there is several funds that are funded typically by the companies that have approved products, and that's to help with patients who have a large co-pay. And these are all, 1MD is almost all Medicare, obviously. And as I believe about two years ago, the companies chose not to continue the funding. which left some patients unable to afford their branded drugs. We believe that that hopefully will be solved, and as a company, again, we're really dedicated to patients, and should this need arise, that we will be doing what we can to make sure that patients can get our drug. We think, though, the value will be there. Again, I can look at the success of the VABISMO launch during that time also, quite successful because they offered a benefit to patients. If you poll retina specialists in the ASRS PATS survey, it's called Done Every Year, the number one unmet need still in wet AMD and DME is for sustained release longer duration. And so we believe that if we can provide that, then the payers will compensate.

Pastor Karsheed, Analyst — Jefferies

Excellent. And then, you know, assuming these two phase threes later this year read out positively, it could be in a situation where second half of 27, you're transitioning towards a commercial stage company. How are you preparing for that transition, and are you engaging in any partnership discussions as well? MR.

Jay Duker, CEO

And, George, why don't you take it there?

George Elston, CFO

So, we've, you know, we do drug development. I point, we prepare in advance. So, we recently announced the appointment of a new chief commercial officer who has brought in several key hires, including someone focused on hub services and someone focused on market access. You need to have that in place and ready well before. And we have a rollout plan, obviously, on the other side of data to be prepared for I think another important part of this is CMC. So we have our own manufacturing facility in Northbridge, Massachusetts. We are well aware that most CRLs happen on CMC, and we've been planning for this for years. We've got a great team there. We're focused on we have registration batches on stability, and we're focused on being prepared for a pre-approval inspection. And so as we get into next year, assuming good positive data, we'll file the NDA and scale up the commercial side in parallel. both on the manufacturing front and the commercial team as well.

Pastor Karsheed, Analyst — Jefferies

Got it. And is the goal of the company to be a kind of like fully integrated company?

George Elston, CFO

Yeah, so our plan is to launch DuraVue in the United States ourselves. I think the beauty of Retina is you can do that with a fairly limited commercial footprint. We've got long established relationships in that community. Remember, we've had 200 plus sites in the wet AMD trial and slightly fewer in the DME trial. So we've already got established relationships. And it's a market where you can address as a small company in the United States. You know, I think from a strategic perspective, we are – there's certainly been a lot of strategic interest, but, you know, we are well-positioned and prepared to launch in the U.S. ourselves. Ex-U.S., I think we'll see. Our trials should support a regulatory filing in the U. And we'll see what happens with most of your nation pricing, because what we don't want to do is affect the U.S. market. with a small deal in Europe that may impact our operations here excellent

Pastor Karsheed, Analyst — Jefferies

makes sense well thank you so much I think that's all we have time for but really appreciate you J George and Romero for joining us thank you for

Jay Duker, CEO

inviting us