Good afternoon, everyone. My name is Balaji Prasad. I'm the Senior Analyst for the Specialty Pharmaceuticals sector. Continuing our Spec Pharma track for the day, we have with us the management team from EyePoint. We have Jay Duker, the CEO, and George Elston, the CFO. Jay and George, thank you so much for joining us today. I know you had multiple meetings since morning, and I hope it's been a productive day for you.
It has.
Yeah.
Thank you very much for the invitation.
Great. Maybe just kick-start the proceedings. Could I request you to provide an overview of the company and, background, a bit of background on the technology?
Sure.
Yeah.
EyePoint is the leader in drug delivery to the back of the eye with four FDA-approved products using our Durasert technology. Our lead product is called DURAVYU. DURAVYU is the small molecule tyrosine kinase inhibitor, vorolanib, in our Durasert E technology, E for erodible. Unlike the four prior approved products, the products in Durasert E are fully bioerodible. DURAVYU has been in four trials so far, including a very positive phase II wet AMD trial that was called DAVIO 2. That trial, and its success in trial design, has really guided our current phase III protocols. We are two active phase III protocols, identical, global trials that are near simultaneous and are actively enrolling in wet age-related macular degeneration.
In addition, we have data from diabetic macular edema phase II that we recently reported that we're very excited about, because our drug DURAVYU showed excellent visual acuity improvement, concomitant anatomic improvement.
Mm-hmm.
Interestingly, and most exciting, is the improvement occurred very early within four weeks of administration of the drug. We are very excited about the potential of DME, which is another potential multi-billion dollar indication.
Thank you, Jay. Great to hear that. Maybe starting with wet AMD, the larger market, help us understand the design of the wet AMD registration trials, both the LUGANO and the LUCIA studies, and what are the primary endpoints you're seeking to demonstrate?
Sure. Wet AMD is about a $10 billion market currently in the United States and growing. There are multiple ligand blockers that are biologics that are approved. Longevity is important to both patients and doctors. The ability to successfully go longer between visits and injections without risking vision is important. That's really our value. DURAVYU should last a minimum of six months in virtually all patients. Studies indicate that by nine months, the drug is really fully eluted from our insert. The pivotal trials are designed around a non-inferiority endpoint. Non-inferiority is the way the last five approvals in wet AMD have been achieved. It's a tried-and-true approach to FDA approval. The primary endpoint is non-inferiority change in visual acuity against an on-label Eylea 2 mg control group.
The study is enrolling both previously treated wet AMD patients and treatment naive wet AMD patients. The ratio's gonna be at the end about 75% naive. All patients have to have active wet AMD, which means they have to have decreased vision. They can't have perfect 20/20 vision to be enrolled. They have to have signs of exudation, which means they have to have fluid on this OCT examination that's done. Patients are then randomized on day one to either DURAVYU 2.7 mg dose or the Eylea control. All patients then receive a full load of Eylea, which means monthly injections starting on day one.
Mm-hmm.
Week four and week eight. At week eight, 30 minutes after the Eylea, they either receive their first dose of DURAVYU 2.7 mg or they receive a sham injection for masking. Patients are then evaluated monthly. Every other month, the Eylea arm gets another Eylea.
Mm-hmm.
At that same time, the DURAVYU arm will get a sham injection for masking. At six months after the initial DURAVYU, the DURAVYU arms will get a second injection. The primary endpoint is non-inferiority change in visual acuity between day one and weeks 52 and 56 averaged.
Mm-hmm.
That will be sufficient at that point for us to put in our NDA. The FDA has allowed the one-year submission of the data, but our studies will both go on for two years for safety. In the second year, nothing changes in the sense of the treatment protocols. They will be the same. The first trial is called the LUGANO trial. The second trial is called the LUCIA trial. Again, they are essentially identical trials. First patient dosed in the LUGANO trial was dosed in October, and we are now 60% enrolled in the trial. First patient dosed in LUCIA was about six or seven weeks later. That trial is ramping up nicely, and the curve of enrollment looks very similar to what we have been achieving with LUGANO. There has been really outstanding patient and investigator interest in this trial.
We set a very high bar for enrollment, and we're breaking through the bar. And so.
Wow.
We're literally enrolling at rates so far in LUGANO that we haven't really seen before in wet AMD trials. We're guiding to have full enrollment in both trials by the second half of this year, which gives us top-line data in the second half of 2026, both trials. I certainly think as you look at our enrollment, it's possible that LUGANO will finish enrollment prior to the second half of the year, but we will certainly keep updates going to inform when we have a little more daylight on exactly when the enrollment will be complete. The feedback has been great from patients and from the investigators, and we're just very pleased about how these trials are enrolling.
Got it. Great. Those are excellent updates. As you commented upon the enrollment, let's start there. You saw that you announced a 30% enrollment in January.
Yeah.
50% in February. I would have asked you if you had not mentioned it as to what it is at mid-March. We are at 60% now.
We are.
What's driving this rapid enrollment?
A lot of things, and I don't think I could name them all, but I'll name some of the big ones. I think the primary thing is that we did a very large phase II trial, and it showed both safety and efficacy. That's really what gives doctors comfort in getting a patient to enroll in a trial, that there is a good chance that the drug, if assigned to that drug arm, will work. Also, there's been really no safety signals at all. We've injected over 190 patients with our drug so far with no ocular or systemic SAEs reported due to the drug. There really are no trends of any kind of AEs that would be not unexpected from an injection. The safety looks really good.
The other, in general, you know, reasons why we're doing well is that we did a very comprehensive phase II trial. We had 70 centers in that trial. We had a great deal of doctors who knew about our drug, knew about the trial, and were very easy to get them to roll into the phase III. We learned a lot of lessons about how to enroll a wet AMD trial in the phase II.
Mm-hmm.
We got a lot of good feedback, and we've taken a lot of those lessons to heart. I think that really has made the trial very attractive to both doctors and patients. I think the historic enrollment that you're seeing, though, I'd like to say it's all due to our great drug and great data.
Mm-hmm.
There is another reality out there, which is there are a lot of very professional retina centers throughout the United States and throughout the world that know how to enroll trials now.
Mm-hmm.
I don't think that was true six, seven years ago, but it's certainly true now. I think there are a lot of very high-volume enrolling centers that we're taking advantage of.
Got it. As you speak about the retina centers, remind us how many clinical sites have been activated across the trials, versus your oral trial?
Yeah. Across the two trials, it's about 130 centers now have been activated. They're all currently just in the United States.
Okay.
We would expect OUS centers, the first ones, to come on in another month and a half or so. But this has all been done in the United States so far.
As for the trial protocol, how many do you plan to activate OUS?
Oh, we could activate up to 220 sites worldwide.
Mm-hmm.
The way things are enrolling, we may not get there because we may be fully enrolled.
Right.
Before we have a chance. It is a competitive trial. There's no preset numbers on where the patients need to come from, region or country.
Okay.
So that when we're done, we're done.
Got it. Help us understand what the non-inferiority margin as endpoint is.
Yeah. The non-inferiority margin for wet AMD trials in the United States has been traditionally - 4.5 letters as the lower limit, which means statistically, when you do a non-inferiority trial, you have an actual numerical difference between your drug and the control group.
Mm-hmm.
In addition, there's margins, superiority and non-inferiority margins.
Mm-hmm.
that, you know, above and below that are determined by the, the size of the trial and the standard deviation. And as long as your lower limit of the non-inferiority margin doesn't cross - 4.5 letters, then your trial's been successful to the primary endpoint. We have that - 4.5 margin, given to us by the FDA at our end of phase II meeting.
Got it. Assuming things proceed well this year and next year between the enrollment and the top line, and eventually we see a commercial product, what kind of market opportunity or revenue opportunity are you looking at from the drug particularly?
Yeah. That's a great question. We've started to do and have been really for the last two years, doing early development of the market.
Mm-hmm.
We have a pretty good idea now, if we were to roll the drug out now, how that would be. You know, we've, you know, queried doctors with a TPP that actually was worse than the TPP that we got from the phase II trial. And in that initial, re-querying of doctors, we got between 25% and 40% market penetration with our drug. Now our TPP from the phase II looks even better than that, and we're repeating that quantitative data.
Mm-hmm.
To see. I would say that last week we heard at a couple of TKIs at another meeting say that if the TKIs are approved, they would use it in 80% of their wet AMD patients. I think the idea that doctors are getting comfortable with is having a sustained-release option that's safe, effective, repeatable.
Sure.
Running in the background in most of their wet AMD patients. If occasionally a patient gets fluid and needs a ligand blocker in between, there's nothing wrong with that.
Mm-hmm.
To supplement them. I think based on our phase II data, it looks like we should be able to take at least two-thirds of the wet AMD population out six months or longer with our drug alone.
Mm-hmm.
Again, it's not an either/or situation. Because we're a second mechanism of action, I think you can look at our DME data especially and say that may be advantageous, and doctors may want to take advantage of two MOAs in this disease. I think that would be acceptable to patients, doctors, payers, especially if we can show advantages in using both an MOA of a ligand blocker extracellularly and a receptor blocker intracellularly.
Got it. And I remember hearing on your call, one of your calls earlier that you mentioned that you have around $370 million, $400 million in cash and cash equivalents. It clearly looks like you have cash on way till 2027. What is embedded in the guidance now other than DURAVYU and wet AMD for the survey?
Oh, go ahead, George.
Yeah. So our cash guidance includes completion of the ongoing phase IIIs.
Mm-hmm.
In wet AMD. That's really our focus. When we had our earnings call last week, you know, we guided that, number one, we're not going to the equity capital markets this year. We're really conserving our cash and focusing the organization on completing those phase III's in wet AMD, which are really critical. As Jay noted earlier, we'll complete enrollment second half of this year, and we'll have the data readout roughly 13, 14 months later. Our cash guidance is well into 2027, you know, approximately a year on the other side of data.
Got it. Also, could you talk about whether you currently have a plan to initiate a phase III in DME at this point, or at some point in 2026?
Yeah. It's gonna be a 2026 event.
Mm-hmm.
We are preparing, certainly from a regulatory perspective, to meet with the FDA in the second quarter of this year to gain alignment.
Mm-hmm.
On the details of the DME pivotal program, we will be doing some things behind the scenes. We have that in the budget to do that. As George said, we have no thoughts and interest in tapping the equity markets this year. Therefore, we're planning on initiating the pivotal trial or trials. We'll see what the agency says for DME in 2026.
Got it. Also, as I look at the top-line data and phase II results from the VERONA program, I think there's something which you're discussing with the team. Seems like you removed one outlier in your supplemental analysis, and BCVA improvement at 24 weeks was 10 letters now.
Right.
Help us understand the rationale of this.
I wouldn't say we removed the patient.
Mm-hmm.
We showed all the patients, all the patients in the trial, with 27 patients finished the trial. We showed the complete data set.
Mm-hmm.
At the end of the trial, week 24, all three arms of the trial, the high dose of DURAVYU 2.7 mg, low dose of DURAVYU 1.3 mg, and the Eylea control all ended up with a seven-letter improvement. Embedded in that, however, was a single outlier. At week 20, the DURAVYU arm had about a 10-letter improvement, but at week 24, it dropped to seven letters because of this one outlier lost.
Got it.
23 letters. Turns out the outlier actually missed the 20-week visit, and what should have been their 20-week visit ended up being a 24-week visit. We did not eliminate from the full analysis, but what we wanted to show was without that outlier, our drug did really well. Ten letters improvement in the studies that got Eylea approved for DME, there was about an eight-plus letter improvement. Without that outlier, the improvement in our group in the high dose was terrific. The improvement was seen right away at week four, unlike Eylea in DME, which takes months to show the improvement.
Mm-hmm.
By month eight, it was a full 10, week eight, sorry, it was a full 10 letters. That remained throughout the study. There was no drop-off towards the end, showing again that for most patients, we do have a six-month-plus drug. The other important thing in this evaluation was the anatomy, the how drying effect did we show, what kind of drying effect on OCT. Even with the outlier, the drying effect on OCT was superior in the 2.7 mg arm to the control group. We also did a subgroup analysis.
Mm-hmm.
Of the eyes that made it the whole study in all three groups without any supplement. Again, without supplement, the unsupplemented eyes in the 2.7 mg arm gained over 10 letters compared to just three letters in the control group. More evidence that when our drug worked in DME, it worked really well, and that potentially showing visual improvements, perhaps even a little bit better than what you might see in Eylea on label. Now, if in fact we do a non-inferiority trial design, we do not have to beat Eylea.
Mm-hmm.
We only have to tie them or come close to tying them for the non-inferiority margin. Obviously, if we can show rapidity of action, if we can show the same visual improvement in four weeks that it takes four or five months for Eylea to achieve.
Mm-hmm.
I think that would put us in a very, very good spot in the marketplace.
Maybe it's a good point, good time to also just remind our audiences to what were the results with high-dose Eylea or Vabysmo in similar studies and what their non-inferiority looked like, versus what you see, what you saw here.
Yeah. The non-inferior margin for high-dose Eylea versus regular Eylea in their wet AMD trial, the high-dose Eylea was 1.4 letters worse than regular Eylea. It's not something that obviously the company or even the KOLs make a big deal about. The reason is non-inferiority is non-inferiority. The drug is approved. There is an important point there, which is patients don't really notice one or two-letter loss.
Mm-hmm.
As a result, doctors for more longevity are willing to sacrifice that level of vision. Hence their use of, you know, of Vabysmo and high-dose Eylea, where, clearly if you use these drugs monthly, you're gonna get a little better visual result. It's just not practical to bring patients in that often. Even with an every-two-month regimen, too many patients are lost to follow-up. Too many patients lose vision because they can't complete what they need to do. Therefore, a sustained-release option with forced compliance over six to nine months we think will be a really, really good innovation.
Got it. You help me understand the non-inferiority and the endpoints on the LUGANO side. With the VERONA study, at least 43% of patients had achieved absence of DME,
Mm-hmm.
By week 24. Help us understand how do you define the absence of DME here?
Lack of DME for that study was defined as 325 microns on the OCT or less.
Mm-hmm.
Normal spectral domain OCT thickening of the macula is about 300 microns. Anything more than two standard deviations, which is about 320, would be abnormal.
Mm-hmm.
Anything below 325 was considered to be no DME. That was a pre-specified endpoint. And for the, as you said, for the eyes that had no rescue.
Yeah.
About half of them in the DURAVYU arm ended with no DME. None of the unrescued eyes in the control group had no DME.
Got it. With this data that you have on hand, how are you thinking about the path forward in DME, and what are your plans to meet the regulators both in the U.S. and ex-U.S.?
The path forward, I think, we know what we'd like to see, and again, that would be a single trial. I think we have some precedent to now suggest that in the second indication of DME, the agency may be agreeable to just one trial. Traditionally, it's been two trials.
Mm-hmm.
After the first two indications. That would obviously be very helpful to us. We are still internally debating the structure of the trial that we wanna run, whether it would be a non-inferiority trial or perhaps even a superiority trial based on the results. The other thing that we learned is our drug, we knew from in preclinical that our drug worked fast. I go back to the four-week results. With a single injection of Eylea and our drug, we got excellent results within four weeks. We could consider doing a non-inferiority trial against.
Mm-hmm.
On-label Eylea 2 mg, but not do a full load in the DURAVYU arms, maybe just one injection. That would again highlight the rapid improvement if it's there, which we would think it should be, and also allow us to do a shorter trial.
Got it. The other thing which is happening in the, in the world of the, both AMD and DME is many of these will see waves of biosimilars.
Correct.
How does that influence your program and both commercially and also as you speak to payers, how does it influence it?
It doesn't really influence us at all.
Mm-hmm.
Because we can do something none of them can do, which is last six months or longer in the majority of eyes.
Sure.
In some ways, the more the merrier. You know, again, for doctors out there who are doing these injections, it gets very confusing. How many, how many anti-VEGFs can you stock in your refrigerator? And, and so the biosimilars right now are less than 5% of the market.
Right.
With the price they're charging without rebate and the prices now of Lucentis and 2 mg Eylea approaching those, it's not clear in the end how much of a market biosimilars will have in the space. That's really up to the makers of those other branded drugs. Regardless, we've had meetings with payers, and the payers are clear that if in fact we get a label, they will pay for our drug. Certainly the mathematics around reduced injection frequency, reduced costs related to that, I think will add into what our average selling price will be.
Mm-hmm.
I think if we show that we're neuroprotective, which is possible, if we show we're anti-fibrotic, we have, you know, improved visual acuity, not just tie, but do better. Those are all reasons why we'd be able to get even more of a premium price. We think we're gonna be in a very good position with both the market and payers.
Got it. That's an excellent update. Jay, thank you so much for your.
Of course.
Responses. Look forward to future updates on this and wish you the best.
Thank you.
Hope you have a productive day at the conference too, George.
Thanks very much.
Thank you.
Thank you. Bye-bye.
Thank you.