All right, welcome to the management team of 4DMT. Thank you guys so much, Julian, Kristian, and Chris, for joining us today. We're going to get into the weeds, I'm sure, on both of your major programs here. But before we get started, I'd love to open the floor up to you guys. What is most exciting? For the remainder of the year, I can guess the answer, but what's most exciting for you as we look forward into 2026? Yeah, thanks, John. It's great to be here. Thanks for the invitation. So a couple of things. First of all, we're excited with the data we just recently released. We can cover that, I'm sure, in a few questions. We showed long-term data on our 4D-150 program out to two years in our most severe patient population, which we think is very encouraging and consistent. We're deep into phase III, and both of our 4FRONT-1 and 4FRONT-2 programs are enrolling at a pace that's highly encouraging to us. We just passed the halfway point on 4FRONT-1. We announced that about a month or so ago, and the pace of enrollment continues to accelerate. So we're thrilled about where we are. And then, of course, in 2026, we hope to finish the enrollment on both of those programs and provide an update on that. And Julian can speak more too. We will provide an update and data on our CF program here in a few weeks as well. We're excited to see that. Certainly, we'll get to that. But I'd love to start with wet AMD and 4D-150. This is a landscape that has evolved dramatically over the years, and the next generation of therapies seems to be headed in a pretty wide array of different possible directions. And I hear from everybody that there always is the best way, but I'd love to hear from you guys your view of the competitive landscape as it stands. What is the real bar for success, and what are you hearing from physicians in terms of what they want to see from a product? Yeah, no, great question. So I can take that, and then Julian and Kristian can feel free to pile on. So quick history. I've been in retina on the commercial side since 2013. So coming up on 16 years, I was working on the Lucentis brand at Genentech when it was Lucentis, Eylea, and off-label Avastin. So to your point, the world has changed a lot. But what's been really consistent and interesting, we think, is that every new innovation that's come to this space has continued to pursue the biggest unmet need in the space, which is increased durability. And I think for most that are familiar with the area, that makes perfect sense because the current mode of delivery for this space, being an anti-VEGF therapy delivered via a needle in the eye, arguably is quite barbaric when you think about how that gets delivered. Right? Here we are 16 years later, and patients are still getting six, seven, eight needles in the eye in a given year. So if you can reduce that without sacrificing, certainly, safety or the efficacy of these drugs, which are arguably very efficacious, if you can reduce that treatment burden, it's incredibly meaningful for physicians, but more so for patients. So the space has become more competitive because we are all trying to make meaningful changes and effects in reducing that treatment burden. So everything in development, even the newer drugs that were recently launched, we had Vabysmo or Eylea HD, provide an incremental value, incremental benefit in durability measured by a week or two. Yeah? And we've seen that even with that incremental benefit of durability of a week or two, brands like Vabysmo have become multi-blockbuster for Roche, I think probably $4 billion this year projected. We at 4DMT, with our 4D-150 asset, we're not looking to make an incremental gain of a week or two or even a month or two. We actually think with a sustained genetic medicine approach, we can provide treatment burden reduction and relief that's measured in years for patients. So we're looking to try and make a real meaningful change and shift the paradigm in treatment. And physician feedback and patient feedback on our program and our data so far has been highly validated and highly encouraging. So I can speak more to that. But yeah, again, that treatment burden reduction is still the biggest unmet need in this therapy area. Yeah, makes sense. We recently saw that recent longer follow-up data from the phase I/II study that you mentioned just a moment ago. It seems like in the newly diagnosed cohort, where we're most mirrored to PRISM, one additional patient started to need supplemental injections after a year, between a year and a year and a half. Can you remind us what you're seeing in patients that are more likely to end up needing supplemental injections, and what's the current thinking about how long a patient might need regular follow-up before they're confident that they're going to be stable wherever they are on treatment? Yeah, it's a really good question. So first of all, it's really hard to predict. So it's a very heterogeneous disease. It's dynamic. What we have seen is that there are no markers that we can tell at this point in our data set. Maybe with time in a commercial setting, you can maybe start to see that more clearly. But there are no markers that say, "Hey, this patient is going to need supplementation at X frequency." We don't know of that data. By the way, similarly, with the current bolus therapeutics, there's no data that says, "Hey, you're going to be a Q8 or a Q12 or a Q16 patient." This is why treat and extend these treatment paradigms have evolved in retina, because physicians, in their hands, on a patient-by-patient basis, figure out what is the right frequency for retreatment. We expect it would be similar for us. To your point, you do see patients in our PRISM data set. At differing time points, some patients will need a supplemental therapy, a rescue therapy. What we think is remarkable is that when that happens, it's very rare that that then puts a patient back on a frequent treatment path. Right? A lot of these patients, for example, our phase I/II severe patient population, they were getting an average of 10 injections in the year prior to 4D-150. The average in the year following that was about 1, so 1.9, I think. We took that treatment burden down by about 80%. Those patients that needed rescue, quite often when they needed a supplementation, they were good for a period of time, so they weren't back on a monthly retreatment schedule. Now we've seen that data out to two years, and that remarkable treatment burden reduction of 80% that we saw at 52 weeks was visible at the 18-month time period and was also visible at pretty much the same rate at the two-year time period. So that consistency of treatment burden reduction has continued, even with occasionally a patient needing a supplement at a certain point. So we hope at a future time point, maybe there's enough data that says, "Hey, this is what would indicate a patient that would need a higher rate of retreatment." The data, I don't think there's enough on it right now to kind of give you an indication there. Fair enough. Fair enough. Obviously, we're excited to continue to see long-term follow-up data from those phase I/II as we wait for the phase III. At this point, what's the most important incremental learning we can get from additional follow-up of these same patients? First and foremost, it's safety. Right? So again, the continued efficacy treatment burden reduction, we think it should continue to resemble what we've seen already, partly because what we reported continues to be very consistent. It's kind of boring, actually. There's nothing major that showed up. For a patient population, reduce the treatment burden by 80% at year one. You saw the same thing in relative terms at 18 months, and you saw it in the severe patient population at two years. I think what the community, the physician community, continues to want to pay attention to, understandably, is what's the long-term safety data for gene therapy. Efficacy is clearly important, but efficacy doesn't get you there unless the safety is at least as strong as what they have today with their existing standard of care. What we've seen with 4D-150 is a safety profile that pretty much resembles standard of care, actually. The intraocular inflammation, the IOI rate is almost identical to what you saw with Eylea in their phase III program. Procedure-related. The IOI, yes. Maybe it's injection. It's related to the procedure itself rather than. Right, and the two cases of IOI that we did see in our PRISM data occurred by week 28, and we shared this in our most recent update, and we had no cases of intraocular inflammation after that time point, so the safety profile in the long-term data continues to be very strong. Okay. So let's talk about translation into the phase III then. So the phase III design is a non-inferiority design, which notably, to my eyes, the gene therapy arm, the experimental arm, allows rescue, while the control arm, Q8 week Eylea, does not allow supplemental injection. So it seems that on non-inferiority and BCVA, at any rate, this should be a very hittable trial, to my eyes. Am I reading that correctly? And if I am, doesn't it imply that the most important endpoints are not going to be that primary registrational endpoint, but something down the chart? Yeah. So an important, I think, nuance. We do allow for rescue in the Eylea arm in our phase III program. So you can get supplementation if you're in the control arm. But that said, the point that you make is absolutely correct. We think we've de-risked this trial as much as you can. So a couple of things that make us say that, first of all, the patient population in our phase III program is a newly diagnosed patient population. And if you look closely at our PRISM data, you see that those patients that were most recently diagnosed is where we had the most pronounced efficacy benefit, like over 90% of treatment burden reduction. So we are selecting a completely naive patient population for our 4FRONT-1 program. In addition to that, there's entry criteria to get into the study. First of all, you have to show at least a 15% response in CST thickness to get randomized into the trial. You can't come in with a CST over 500 microns. The reason for that is you weed out patients that could be unresponsive. The 15% response criteria is to ensure that patients that are enrolled in a lifelong gene therapy are responsive to VEGF therapy. We think those things, in addition to the fact that it's a naive patient population, de-risk the trial as much as we think we can for our phase III program. Fair enough. But I guess the second part of my question is, if the trial is successful on a BCVA endpoint, on a non-inferiority endpoint, I would expect that somewhere down the secondary endpoints would be the key levers on a commercial opportunity, on the adoption in the real-world setting. So what is it there that physicians are most focused on? Yeah, absolutely right. So obviously, you've got to hit your non-inferiority endpoint. Right? You have to have a safety profile that physicians are comfortable with. But beyond that, the key efficacy data set is going to be the effect on treatment burden reduction, which is a proxy to the first part of our conversation for durability. So if we can show a treatment burden reduction at the 52-week time period, 70%-80%+, we think that's highly compelling. Do you think that the newly diagnosed population is the population most likely to be early adopters of a gene therapy-like regimen? It's a great question. So what we've learned in our 4FRONT program, so we went into this program, we started 4FRONT-1 at the end of March, and the question was, are you going to be able to enroll a naive patient population in gene therapy? We heard anecdotally from the community that they thought they would, but not until you start the program. What we're thrilled by is our pace of enrollment has been far exceeding our expectation, and we've reported that publicly. That said, so we ultimately do believe, yes, you will get naive patients on a 4D-150 profile. However, I've launched a couple of medicines in this space, and I think other new launches would say the same. The first patients that you will get tested on in a commercial setting are those patients that have the highest unmet need. So it's the patients that are on a monthly or every six-week bolus therapy. So the first patients that are likely to be considered the early adopters are actually less of a naive population. It's going to be more of a treatment experience. Yeah. It It would be my expectation as well. When I think about the commercial launch dynamics and the potential competitive landscape at that time, this is a space where docs have their favorite products, and they can be very entrenched and have very strong opinions about it. What are the strategies to educate the retina specialists to sort of crack open the egg, as it were, on folks that might have very strong opinions about the landscape here? Yeah, and we have them in retina, for sure. I feel like I put that in my opinion. Yeah. There are a few people out there with strong views on a lot of things. Here's the thing. So that's a very true statement. There's a lot of education work to be done. But I will tell you, again, as someone who's launched drugs in this space, this community can be very fast adopters. And we've seen that with other medicines as well. And yes, there's things they have to go through. They have to get validation of real-world safety. They need to see evidence of reimbursement, for example. But even with those hurdles that you would expect to have, the community, I think, by and large, is a very fast adopting community for new therapeutics. So we would expect the pace of adoption for 4D-150 to be strong. But there are some things we're going to have to spend time educating on. Of course, that actually seems very counter to what we typically expect, not in retina specifically, but in gene therapy space, where the expectation is for very slow adoption across the board. Exactly. And I think that goes exactly towards some of the education that we need to do. So yes, we are gene therapy, but we're not a rare disease. We won't be a hyper-expensive gene therapy. We're going after a mass market. I think another way to think about 4D-150 is that it's actually a biologically based, we think, very sophisticated sustained expression platform. We are expressing aflibercept, otherwise known as Eylea. So we think unpacking what gene therapy is or is not in this context is going to be really important. I think educating physicians and, as appropriate, patients in that regard is going to be important as well. And I think, honestly, our approach will have an effect on the current practice patterns and practice economics. So you've got to educate on that as well. Let's talk about those economics for a second. You mentioned that you're not going to price at a super orphan, ultra-high gene therapy price point. This seems to be a point of, well, a point of contention amongst your competitors and maybe a point of confusion in the market sometimes. What is the pricing strategy, if not the exact price, but what's the strategy here? And how can you assure folks that the true cost per year isn't a multimillion-dollar therapy? Yeah. I see a couple of things. First of all, the strategy for us starts with what we believe is our vision for what 4D-150 can be. So we say consistently, we think we see a world in the future where you have a backbone therapy like a 4D-150 in place. And when patients need supplementation, the great news is that there's a broad assortment more on the way of highly efficacious bolus therapies that can be used in supplementation. But a backbone therapy approach with other things used in supplementation, we think makes sense. We think it makes sense for a practice and how they run their practice. So the reason I start with that is I think it's hard to have that vision and then price in a way as if you're a niche product. Right? So if you're going to have that vision, you're going to have to, I think, take into consideration how pricing and other factors need to support that and allow for mass market adoption. So that's our philosophy, first of all. So that certainly doesn't, again, it's way premature to get into specific price point conversations, but that takes you away from pricing in the multi-hundreds of thousands, for example. I don't think you can do that and say, "Hey, most patients should [crosstalk]. Everybody should be on this. Right. Exactly. And the other factor that's, I think, really beneficial for us is we have massive flexibility. I mean, our cost of goods is, we've said publicly, less than $1,000. So how you ultimately set price is going to be determined by a lot of factors: the competitive environment, what payers are going to tolerate, what physicians are going to tolerate. It's a buy-and-bill model. So how much you price it, it's going to have to consider what they're comfortable with paying upfront. And we'll weigh all those factors in. But at the end of the day, our philosophy is to price this so that the majority, as many patients as possible, can get access to it. Okay. Now, we have a couple of minutes left, and I want to make sure we get to the CF data, because that is coming up very shortly. And I know you can't tell me probably too much about it, but remind us, what are you going to share with us? What should we be looking for? What are the key metrics in these upcoming releases? Yeah. Julian, you want to start? Yeah. Thanks for the question. Thanks for letting us get this in, but I think at a high level, first of all, we haven't talked about this program, really updated it for over a year now, so the key objective really here is to update the work that we've been doing on dose ranging, and as a reminder, the phase I portion of our study is really to study safety as well as pick a dose for phase II. We have nine patients now at the lower dose. That's kind of new data that we've kind of followed out through varying levels of follow-up, and we'll kind of share the safety data there. We expect safety to continue to be strong as we've lowered the dose now, and then in terms of efficacy measures, we're looking at newer endpoints now that the street is not as familiar with. So lung clearance index is very well accepted by the European regulators as a primary endpoint for lung function. It's a more sensitive and reproducible measure, so less variability, more ability to detect subtle changes in lung disease, because the CF disease actually starts in the outer lungs and then builds its way into the medium and large airways, where FEV1 is more measuring impact. So we think that with this more sensitive measure, we can detect improvements in disease at an earlier stage and a more subtle effect. And so we'll start sharing some of that data. An earlier stage of disease, you mean in patients with less severe lung deficits at baseline, or you mean with fewer number of patients? Both, actually. Yeah. So that's the benefit of it. Okay. Good. Can we talk about updated thoughts on the eventual development path here? Obviously, we're talking about monotherapy in patients who are unavailable for correctors at all, but you've also mentioned patients with inadequate response to correctors. So can you remind us what the relative sizes of these markets are, how many patients you think fall into that bucket, and what the development path looks like? Yeah. That's really important to clarify that. We're first starting the patients with the highest unmet need without access to the Vertex modulators. So that's roughly 15% of the population. They either aren't eligible, so they can't receive them, or they're intolerant to the side effects. But the overall vision for this program, if successful there, is to be number one, redosible within that population, as well as also be variant agnostic, so it can be applied to the suboptimal responders you mentioned. So it's too early to say exactly when we'll go into those plans, but this release will kind of maybe update our thinking on redosing when that may happen, and then longer term, we'll still have ongoing discussions on the modulator combination. Okay. You mentioned redosible there. I know in the past you've talked about the possibility for possibly maybe annual redosing. But what's the current thinking on redosing timeline, and have you been redosing patients in the phase I? Yeah. So the data is still emerging to understand exactly when the right time to redose is. We want to see, first of all, the durability of expression. So that's going to be an update we'll share on this release. Then with that data in hand, we can look at, is there signs of waning clinical activity as well? So we have to establish both those things before we can then come up with a well-thought-out redosing plan. But you haven't been redosing anybody yet. Yeah. Yeah. Exactly. Makes sense. All right. Well, we are unfortunately fully out of time and moved into the passing period. But thank you guys so much for all the commentary. I really appreciate you coming out. Thanks for having us. Thank you for having us.