Good afternoon, everyone. Welcome to the UBS Global Healthcare Conference. Thank you very much for joining us in person today. Very happy to have Unity Biotechnology here with us presenting, and we'll open it up for a fireside chat as well. Joining us from Unity is Anirvan Ghosh, CEO. With that, I'll turn it to you. Thanks, Eliana. Thanks for having me here. I thought I would just kind of provide a very brief overview of where we are and our near-term data readouts. It's a very exciting year for us. As you know, when we chatted last week, I mentioned that we have a you know number of important readouts between now and Q1 of next year. I just wanted to kind of tee those up, and then we can talk about the background science, the details of what we learned in the phase I study and what's coming up. Yeah. You know, this slide just provides you an overview of our therapeutic approach and the diseases we're targeting and the near-term milestones. The company is focused on developing a new class of drugs called senolytics. Senolytics are drugs that target senescent cells. These are cells that are dysfunctional cells in the tissue that can lead to disease progression. We've identified a number of molecules, including the lead molecule, UBX1325, that can selectively eliminate senescent cells. By doing that, change the pathophysiology of disease and lead to improved outcomes. The lead program is UBX1325, which is a BCL-xL inhibitor, and is being developed for two major indications in the eye, wet AMD and diabetic macular edema. Just recently completed a phase I study in advanced patients, and in both cases, we found evidence of improved vision and structure following treatment with UBX1325 in patients who were no longer responsive to anti-VEGF. They had either stopped taking anti-VEGFs, they had not been on anti-VEGF for at least three months, which is the standard of care. We're really excited to see that fast response. I'll show you some of those examples. While the lead program is directed at two eye diseases, the biology of senescence crosses many other diseases. We see this as an important proof of concept to potentially expand into other areas. The last thing to highlight are the data readouts that we have coming up. Following the phase I study, we initiated two phase II studies, one in DME and one in AMD. We recently announced that we had completed the enrollment of the DME study. In the DME study, we expect to have 12-week data around the middle of the year and 24-week data before the end of the year. We also started a wet AMD study, and that study has started enrolling patients, and we expect to have up to 16-week data from that study by the end of the year and up to 24-week data in Q1 of next year. These are really where all of our focus is, and we'll talk a little bit about what those studies would look like. I should also point out that behind this lead program, we have a Tie2-VEGF bispecific molecule that is fairly close to a development candidate nomination. This gives an overview. I'm just gonna maybe just tee up the studies in this slide, and we can start talking and discuss various elements of this. This provides an overview of our completed and ongoing studies. At the top, you see the phase I study, which we've completed. It was a single ascending dose study in patients, you know, primarily looking at safety and tolerability. We're introducing a new mechanism to the eye, but also it allowed us to see whether or not there was an improvement in vision or structure in these patients. Most importantly, in that study, what we found was that the drug was very well tolerated and had no adverse effects that would prevent further development of the molecule. Importantly, we saw evidence of early efficacy as I mentioned. It also shows the next two studies. The DME study first and then the AMD study. The DME study is called BEHOLD. It's a phase II study. You can see in that study, we expect data around mid-year. The first data set, 12-week, 24-week data by the end of the year. We also added a long-term extension to the study, so we can follow patients all the way through about a year. We'll have that data near the middle of next year. The ENVISION phase II study is the wet AMD study. In that study, you can see the first data readout comes toward the end of this year and continues into next year. I think, you know, this gives you a bit of an overview of where the various studies are. I think for us, what's really important, exciting is the opportunity to introduce a completely new therapeutic approach in these diseases where the standard of care anti-VEGF has been around for 10-15 years. As you know, a significant fraction of patients don't get full benefit from EYLEA. We think that with a new mechanism, we could target those patients and potentially provide a better vision beyond what anti-VEGFs achieve. The other major potential differentiation is the durability of effect. Everything I mentioned is after a single injection of UBX1325. These patients come, they get a single injection, we follow them over time, compared to standard EYLEA regimen, which is every other month dosing. I think there's a possibility of big impact with this drug. Absolutely. Did you have more slides or I can dive into questions? You can ask some questions. I'll go to the slides as needed. Okay. Maybe just before we get into some of the data, can we first talk a bit about the mechanism of action and understanding how this is additive on top of or instead of VEGF? Sure. Let me go to a slide couple slides to illustrate the mechanism of action. You know, I would say in the last 10 years, this is one of the, frankly, one of the most exciting discoveries in biology. Which is that at the root cause of many aging-associated diseases is the accumulation of cells in tissues that can secrete factors that will damage the tissue, right? You know, we are all aware of the fact that there's inflammation. Inflammation is bad, that can lead to disease. When you wonder, like, where is it coming from, a lot of it is because of embedded cells in our tissues. We have learned a lot about these cell types and how they accumulate, when they accumulate, what they do over the, you know, past decade. This illustrates the basic idea of a senescent cell. A senescent cell is a cell that's essentially under some level of stress. Either it's accumulation of DNA damage over time in the course of a lifetime, or it can be acute stressors, as in diabetes, for example. It's you know, hyperglycemic stress. It's the stress that's driving the cell into a senescent state. When the cell enters that state, it stops dividing, but it's metabolically very active and can secrete a number of factors, as shown on the right-hand side. They include inflammatory factors like TNF-α, IL-1α, many pro-fibrotic factors, inappropriate expression of growth factors. In your tissues, you have these cells now scattered that are secreting factors that can damage the neighboring cells, and eventually those cells can also turn senescent. It's like this kinda progressive mechanism. We know that during aging, we'll get to a point maybe about 5% or so of your cells would be senescent in any given tissue. What we find in disease context is a significant increase in that senescence burden. In the eye, for example, the senescent cells accumulate in the vasculature of the eye and the blood vessels. There's significantly higher levels of senescent cells in AMD and DME eyes compared to what you would see in an age-matched control, right? The accumulation of senescent cells in diseases is quite clear. Now, the therapeutic approach is shown here. Going from left to right, we're looking at a representation of accumulation of senescent cells over time. Those blue cells represent the senescent cells, and you can see by the time you get to the middle panel, they have drawn in a lot of, you know, other cells, immune cells, often into that region, and it's secreting factors that can drive local inflammation. Our goal is to develop a class of drugs that will go and eliminate those blue senescent cells. Once that happens, you should stop that entire process. You're not drawing in macrophages anymore. You're not secreting growth factors. Ideally, at least arrest the progression of disease. What's shown on the right-hand side is the possibility that the regenerative mechanisms present in the body might then allow the tissue to heal and actually improve function. The early data we have is kinda consistent with this, with this idea. Maybe I'll just jump to a preclinical slide just to kinda illustrate what this looks like. With this in mind, we developed molecules that would selectively eliminate senescent cells and not affect normal cells. I just wanna go to a preclinical data slide. Actually, this is helpful. This kind of shows at least how, where in the pathway the drug is supposed to act. This is an illustration of what happens in diabetic eye disease. You see the cell is under stress, ends up in a senescence state and then secretes a number of factors shown in that gold circle. The standard of care is anti-VEGF, shown on the left. You can see VEGF is one of the factors that is elevated in this inflammatory state. UBX1325, as far as we can tell, could affect disease in two ways. One is by its direct effect on senescent cells, eliminating those cells at the top, preventing inflammation. You also see a pretty rapid effect on reduction in vascular permeability, as these are the mechanisms that we are really interested in. I just wanna highlight this one slide that illustrates what the drug does in an animal model and what we're looking to achieve in people. This slide shows the pharmacology of UBX1325 and shows the effect in retina in a mouse model of retinal disease called oxygen-induced retinopathy or OIR. On the top left, you see that the drug has a very nice dose-dependent inhibition of BCL-xL, and you see that both in OIR eyes and in normoxic eyes. If you go right below it, what you notice is in the OIR eyes, you see a strong activation of caspase, but you don't see it in the normal eyes. This is at the core of why we believe the drug selectively affects senescent cells and not other cells, right? The effects are then shown on the right-hand side. You see a very sharp reduction in neovascularization, the abnormal growth of blood vessels in the eye that drive disease, and a significant reduction in the avascular area. The images on the right, I think, capture it probably more effective than any bar graph. In the disease model, what you see in a flat mount of the retina, which is kind of what you see as like kind of expanded butterfly, is right in the middle, you see those ischemic areas, you know, the dark areas near the middle of the retina. That's where the blood vessels have dropped out. If you go further out, you see abnormally structured blood vessels, as shown in the inset on the top right. These are the blood vessels have grown into the retina. They're leaky in that state. When you treat with UBX1325, what you see is shown on the bottom right, which is a significant reduction in the ischemic area of the eye and really nice, pristine blood vessels. This latter part is very important because it's one of, I say, the most obvious differentiators compared to anti-VEGF, because while anti-VEGFs reduce neovascularization, they do not reduce ischemic areas in the eye or restore healthy blood vessels. Yeah, it's very interesting. Maybe just taking a step back and thinking about the unmet need. VEGF are widely used in the treatment of wet AMD, DME, to a lesser degree diabetic retinopathy. You know, before we dive into the data, maybe can you help us understand sort of the unmet need remaining from VEGF and particularly, you know, what proportion of patients in each disease that this affects? Yeah, absolutely. I'm gonna go back a couple of slides and illustrate some kind of background data that is very helpful. First of all, just to get everyone on the same page, anti-VEGFs, you know, inhibit, essentially an antibody injected into the eye every other month, inhibits all the VEGF that is present in the eye, and that's a driver of neovascular growth. At a very high level, the main limitations of the current treatment is that a significant fraction of patients, about 40% of the patients, have very little gain in vision. This slide kind of illustrates that. You can see, this shows a DME study looking at an anti-VEGF Lucentis over time. It breaks down the number of patients who are getting good vision improvement versus not. The top line, the blue line is where patients wanna be. They wanna see a strong improvement of 10 letters or more starting at a naive condition. But about 40% of the patients have less than a five-letter improvement, you know, from beginning. They're getting very limited vision improvement, but that's the only option that's available to them, so they'll still take it, and that's limitation and improvement in vision. I think is one big unmet need. The other is around, you know, in this high patient burden and in that they have to get an injection every other month. They're pretty. Depending on which drug you're taking, it's either every month or every other month. Frankly, what ends up happening after the first year, patients start not coming in as often and start losing vision, and they're, you know, down to often where they started. You know, the top things that we hear from patients and physicians is a novel mechanism that would provide improvement in vision beyond what an anti-VEGF does and can have durable effect. Like, that's kind of the benchmark, right? Now, I'm just gonna highlight a comparison here for you to really put our drug in context. This shows the profile of aflibercept, which is the standard of care right now, an anti-VEGF. This shows the profile of faricimab, which is a drug that just got approved earlier this year. The third column are some kind of still clinical-stage molecules looking to extend durability of VEGF in the eye. This slide I think illustrates that what we don't have, we have a significant number of patients who do not respond well to anti-VEGF, and we believe UBX1325 could hit those patients, and the phase I study was in those patient populations. We'd like to get patients out to six months or less frequent treatment, which would be a huge differentiator. Finally, the ability to restore health in the eye and improve blood vessels and reduce ischemia. Mm-hmm. Interesting. Certainly, seems like a very high unmet need in terms of both efficacy as well as extending the duration between doses. Maybe can you tell us a little bit more about the phase I data and what we've learned from the clinical profile so far? Absolutely. Let me move forward to the clinical design. The phase I study was carried out in advanced AMD and DME patients who had been off of an anti-VEGF for at least three months. Most of them had previously been on anti-VEGF and had, you know, failed to respond or were no longer responding. That's the patient. All of them had residual fluid in the eye, which is kind of a measure of active disease. The study design is shown over here. It was a single-ascending dose study with both DME and AMD patients. DME shown in blue, AMD shown in green. Eventually, we added another AMD cohort at the high dose so that we would have enough AMD patients in the study. I'm just gonna highlight. I'm just gonna show a couple of examples because I think that those are the most striking things. This is a summary of the DME data from that study. What we're looking at is change in best-corrected visual acuity or BCVA from baseline in terms of numbers of letters gained shown on the Y-axis, and on the X-axis, you see time through 24 weeks. It's a 24-week study. The patients got a single injection at time zero, and then we're following them out. In green and blue, you see the patients treated at the high doses, the five and 10, and blue being all patients. In gray, you see the fellow eye, the untreated eye. In this case, one eye was treated. What you can see is that we get a very rapid and significant improvement in vision shortly after treatment, you know, within less than a week, frankly. Beyond that, you can see that after about two or four weeks, the gain is maintained, right? Patients who gain that, they are able to maintain that all the way through 24 weeks, which is when the study stops, so potentially longer than that. You see that on the fellow eye, there's virtually no change in letters. It makes a couple of important points. One is that the speed is consistent with the mechanism of action. We know that we eliminate senescent cells within one to two days following an injection of a BCL-xL inhibitor. The effect is happening at the time course that you expect it to have an effect. The durability is also consistent with our understanding of the mechanism, right? Because once you eliminate the senescent cells, the eye should be in a better state and kinda maintain that, and the vision gain reflects that. In the DME patients, we also saw improvements in retinal structure. Most of them had, you know, improved CST thickness, but that's kind of the main vision gain in DME. I could also speak to the AMD data, if you'd like. Should touch upon the AMD? Yeah, absolutely. Let me just quickly go through. Sorry, I'm just gonna go back here and show you a couple of important points. Before I jump to AMD, I wanted to also show you that in DME patients, we also look to see how long can they go without needing rescue. Big measure of durability is how far do they go before they need an anti-VEGF. In this first study, that injection was at the discretion of the physicians. It was not defined in terms of a very specific change in thickness or vision in the patients. What you can do is we can look at all the patients and ask how many patients would have hit a rescue criteria that is normally used in phase II or phase III studies. The normal rescue criteria is an increase in fluid of 75 μm or a loss of vision of 10 letters from peak. What this shows, if you look at all our phase I DME patients over time, you can see that over half the patients, about 60% of the patients, go out to six months without hitting those rescue criteria. Now, this we think is really important because we can compare that with what the latest approval looks like. In the bottom left box is just a reminder of the data from the YOSEMITE and RHINE DME studies that were recently conducted, and about half the patients can go three to four months without needing retreatment. The main value proposition of faricimab is durability, right? Even in this early and difficult to treat population, we're seeing strong evidence of durability and in a less severe patient population might be even better than this. This is the CST data that I was alluding to, and you can see that shortly after treatment, there's a reduction in CST thickness, and then it stays pretty stable like 12-24 weeks out. This is a measure of the improvement in fluid in the eye. We're seeing quite a bit of consistency between vision improvement, CST improvement, and durability. Now moving to the AMD patients. Once again, we're looking at change in BCVA measured in ETDRS letters over time. What you notice is, again, a pretty sharp increase in vision shortly after treatment that is then maintained out through 24 weeks. The general pattern is the same in terms of having, you know, nice durable effect. There are two things I should point out here. One is that there is one outlier patient that is not in this average graph and is shown in the inset. That patient was unusual in that they had a pretty rapid decline in vision. They got two injections of anti-VEGF at eight and 12 weeks, and then they had an improvement in vision, but their trajectory was very different from most of them, so we show them separately. A number of patients had an anti-VEGF injection at the physician's discretion between 12 and 24 weeks. However, in those cases, the anti-VEGF did not have any significant effect on vision after that treatment. Which is consistent with the idea that, you know, we took in patients who were advanced, who are not responding to anti-VEGFs, and that most of the gain you're seeing here is because of UBX1325. The AMD CST change is shown over here, so you can see that the trajectory looks somewhat different, but once again, you see an improvement in CST out through 12 weeks, and that is maintained through 24. Again, it highlights the fact that people who did get a rescue between 12 and 24 did not have any additional impact on CSTs. Again, the primary effect we're seeing is because of the drug. Once again, in the analysis similar to what I showed in DME, looking at how many patients would hit a rescue criteria, it's actually even more impressive. Here you can see in up to 12 weeks, about 80% of the patients are going after a single injection without having gain in fluid or loss in vision that would normally meet a rescue criteria. Do you wanna see a, an image of the eye of what it looks like after treatment? Yeah, that'd be great. All right. I'm gonna start with This is to remind us of what the normal eye looks like in an OCT image. This has really transformed the treatment of eye diseases because you can assess the eye more precisely than just about any system in your body, literally like in a micron resolution. This is a little part of the retina right near the central, near the foveal area. You see this little dip in the middle? That's the area of high acuity vision. That's where, you know, you only have cones there. All the other cells are pushed to the side. A healthy eye would look like this. What happens in diseased eye, normally you have fluid accumulation. As a result of it, you end up losing that dip, and often you have, you see, pockets of fluid, which you don't see over here. Here's an example of one of those eyes. This is from a patient with wet AMD, and you can see in top left what their eyes looked like when they came in. You see that the surface of the retina is highly curved and not normal. You see that pocket of fluid in a... In the subretinal space, the dark area near the middle of the field. Then you see these bright speckles around it, which are called hyperreflective foci. They are associated with disease pathophysiology. When you go see an ophthalmologist, they'll see this, they'll take an OCT scan, they'll see fluid in the eye, and this will be key to having a wet AMD diagnosis, right? The wet part comes from that fluid that's in there. Now, when you treat this patient and follow them through four weeks, shown below, and 12 and 24 to the right, you see at four weeks, maybe there's a bit of a change, not a whole lot on the fluid. By the time you go to 12 and 24 weeks, you see that the fluid is largely resolved in that area, and then the anatomy of the eye is getting better. Compared to the undulation you saw at the top left, it's a, you know, much more normal-looking retina by the time you get to the bottom right. You know, these kinds of examples, you know, give us confidence that the drug can have an effect in retinal fluid. We also have their BCVA at the bottom left and their CST at the bottom right in those graphs. You can see this patient had a gain of about, you know, five to eight letters in that six-month period and had a CST improvement during that period, right? This is kind of, in a way, like ideal kind of patient data set that you would like to see. You see improvement in vision, you see reduction in fluid and so on. Anyway, those are the highlights of the phase II data. Awesome. So very helpful background on the data. Maybe, in thinking about what to look for in the upcoming data in DME and wet AMD, including the DME data guided for mid this year, can you tell us a little bit more about these study designs and maybe starting with DME since that's coming first, what would be good data in your mind and what you're looking to see? Sounds good. Let's go to the study designs and then, I'll provide some historic context in terms of what we would be looking for. As I mentioned that we have these two studies ongoing, the DME study and the AMD study. This is the design of the DME study. There are some differences in the two studies, so worth highlighting. First of all, in terms of the patients who come into the study, in contrast to the phase I study where they were very advanced patients and were not on anti-VEGF, in this study, these are patients who are on anti-VEGF and require pretty heavy dosing with anti-VEGF to maintain vision. These patients have had at least three anti-VEGF injections in the prior six months, and even then, they have residual fluid of over 300 μm, right? These are in that bucket that I showed early on, like the essentially the sub-responder kind of category, right? Poor responders, but being given a lot of anti-VEGF so that they don't lose vision. Once they come into the study, they get randomized to a UBX1325 arm or a sham arm, and dosed at the 10 microgram dose, which is the dose that I showed the data for earlier. After the single injection, we'll follow them out to 12 weeks. That's the first data cut. At that point, we will have aggregate data. We expect to have group data for the sham arm and for the treated arm. We will not have individual patient data at that point because we want to maintain the integrity of the study through 24 weeks, which is the next data point. We'll have the first read at 12, and then we'll follow them out to 24, to see whether or not there's a change in BCVA. What does their CST look like? There's also a number of other measures of, like, vascular health. OCT angiography is a method that allows you to see blood vessels really, you know, clearly. We're gonna do that. Fluorescein Angiography, another measure of vascular health. That's the DME study design. I'll move forward and talk about kind of historic expectation, and then we can go to the AMD design. This slide shows the trajectory of patients coming into the study, or what would be expected of them coming to the study who have been on aflibercept for at least six months. This data set is taken from the registration approval study of aflibercept. What you see is in treatment-naive patients, there's a fairly rapid improvement in vision, up to about 10 letters that happens within the first six months. Beyond that, you see that there is relatively little improvement in vision after that. There's an arrow showing where the BEHOLD patients come in, right? They're coming in after at least six months of treatment. At that arrow or to the right of it, and that's expanded on the right graphic. Just to illustrate what the trajectory of the patients would be if they were to remain on anti-VEGF. The expectation from that point forward would be that, ideally, that they would maintain vision and maybe with a slight improvement, right? The standard of care would give you a letter improvement in the vicinity of about a letter. You can see they're fluctuating between zero and one letter. That would be their natural history trajectory. Then it shows in dotted lines the two assessments we'll make at 12 and 24 weeks. We've been thinking about what, where our data might lie and what it would tell us with regard to the profile of this new drug. Following treatment, we're gonna look to see how the patients do in terms of BCVA gain compared to historical aflibercept, and that's an important benchmark for us. You can see that, you know, if you end up in that zone of about a letter or essentially vision stability, then you're achieving what aflibercept would achieve for these patients. They have switched, and they have now gone, frankly, longer than the aflibercept duration, which is every eight weeks. They've gone 12 weeks and maintaining vision. That would be essentially a non-inferiority measure compared to historic aflibercept. And we will be looking to see whether the patients meet that bar as well as possibility of gaining more vision. Now, if you look at the top zone that's shown in green, which would be superiority to historic anti-VEGF, that if you're out in the zone where you're looking at, you know, two, three, four, five letters, now you have clearly differentiated the trajectory from what anti-VEGF would be doing for them, right? Because you're in a vision improvement trajectory. Those are the two things we'll be looking for. That's the initial evidence of, you know, efficacy that would be comparable. As you know, this is important because a registration study in this area would be a non-inferiority to aflibercept. Like, that would be the path for approval. That was the path for approval for Lucentis, for example. On the right-hand side, the 24-week data point is also really important because that, I think, will provide the best evidence of durability. Mm-hmm. If you have a drug that gives you vision improvement, that's as good as aflibercept, for example, but you can go six months and maintain vision, maybe longer. Now you've completely changed the treatment paradigm because now the patient comes in twice a year. The 24-week, we'll be mainly looking for durability and then see whether or not it is comparable to historic anti-VEGF or whether it is superior, right? We'll have a sense of like, Do you have a drug that as a monotherapy is meeting or beating historic aflibercept, right? That's kind of the zone that, we're focused on, along with various assessments of retinal health, possibility of changing the trajectory of disease progression, you know, modifying disease. That's the focus of the next data set. I think anywhere in the aflibercept historic zone or better would be something that would be, I think, very exciting. I guess when we think about endpoints like BCVA, what's the numerical range that you'd say, "Oh, this looks better," versus just being similar? Yeah. The way we've designed it is to kind of rely on statistical analysis, you know, as a way of kind of showing what level of confidence we have in the study. As you know, the statistics in an earlier-stage study is usually has a higher P value than a registration study, which is typically several hundred patients, because that goes down as the square root of the number of patients, right? We will be looking at statistical significance separation, I think, as maybe the primary thing that gives us a sense of kind of the meaningfulness of that effect. In terms of letter gains, I mean, we've had a number of KOL discussions in the last few weeks to talk about what they would think is exciting. Frankly, nobody thinks that people can beat, you know, meet or beat anti-VEGF. Nothing has beaten anti-VEGF. That hasn't happened. As I told you, we showed in these patients who had failed anti-VEGF, we saw improvement in vision. I think this is in the realm of possibility that you could have a strong improvement, which would be very exciting. For them, anything that ends up in that zone above historic anti-VEGF would be really exciting because they would know that here's the new drug that is having biological effect and could potentially become a new standard of care. The last thing that they talk about also is about, you know, the possibility of combining with anti-VEGF, right? You have a patient. Let's take a patient like this. They come in, they've gotten some gain with EYLEA over the first six months or so, but then they've plateaued. Like, every ophthalmologist essentially has patients, that's what they look like, right? Now, at that point, the anti-VEGF is still helping them maintain fluid, but if I can put another drug in and then give them greater benefit, then that would be really exciting, right? The combo idea has a lot of, you know, a lot of pull. Mm-hmm. Understandably. Yeah, that's gonna be my next question, which I guess we'll get to quickly, because I also wanna hear about what you're looking for in the wet AMD study. Just in terms of the development pathway as well as the regulatory hurdles, how are you thinking about the decision between monotherapy versus potential combination, albeit even if you are able to show monotherapy activity or non-inferiority? Yeah. How are you thinking about the strategic decision? Right. I think that for a monotherapy, you need to have a differentiation on one of these axes, right? I think for it to be a viable drug, either on the durability axis or on the efficacy axis, right? If it is a monotherapy profile that looks very much like anti-VEGF, you're getting it every other month and you have the same vision, I don't see how that becomes a strong monotherapy product, right? You say that I have vision improvement like anti-VEGF, but I can go six months, then I have a strong monotherapy product, right? Because I've changed the treatment paradigm. If I have a product that's giving me greater vision gain, then I have a strong monotherapy product, right? Those are the two things that we would be looking for in terms of monotherapy placement. If it turns out that it's in the world where it looks quite similar to anti-VEGF, then I think in terms of, like, how much you might need in terms of treatment, then I do think that the combo study or some combination effect becomes more interesting, right? Because maybe you're getting a certain gain with anti-VEGF, maybe a similar gain with our maintenance with thirteen twenty-five, and if I have a way of, you know, sequencing them, I might get a better gain, right? That would be the way we would think of it, depending on the readout that we see here. Mm-hmm. Makes sense. Yeah, what are you looking to see in your wet AMD study? All right. Let me tell you about wet AMD. Presumably similar in that you're looking to improve upon VEGF, but curious if you want? Yeah. You know, this study has an element that I think is particularly interesting in that, it's a head-to-head comparison with aflibercept, right? Mm-hmm. In the wet AMD study, they come in like the DME study, in that they have had at least three injections of anti-VEGF in the past six months. They have residual fluid in the eye and when they come to the study, we give them all a benchmarking aflibercept dose, shown on the left, so they all start at the same anti-VEGF prior treatment. They get randomized to either UBX1325 or to aflibercept. In the UBX1325 arm, they get two injections of UBX1325, and then we follow them out to 16-24 weeks. Aflibercept, they are on every other month aflibercept, which is standard of care. We do a second injection in this because you might remember that in the AMD study, I saw the patients waning a little bit in their effect as they approached 12 weeks. Giving a second injection at that four-week point might give me an additional bump. The data set here could be really strong because, you know, head-to-head aflibercept actual data compared to historic data is a really strong bar. Because if we hit non-inferiority of aflibercept in this study, then you know that you have the kind of data set you need to go into, you know, into pivotal study with high confidence. That's what we would be looking for. This comes towards the end of the year, right? I think the first one would give us a sign of what it would look like in DME. This will tell us, I think, in AMD, whether the drug has an effect and it's a bigger population, more severe patients. We're excited about this study. Yeah, maybe can you tell us a little bit more about what you would expect on BCVA from the EYLEA comparator arm, just in terms of thinking about expectations and what the bar would be? Yeah. It turns out that the trajectories are quite similar in that in AMD as well, after about 12 weeks, you see fairly minimal gain in AMD. The AMD patients are more severe, and they, you know, eventually start progressing more than the DME patients do. Any gain beyond what you see at that 12-week point, I think would be a win, would be really exciting if you see something that's comparable or better. I think, you know, based on the early data that we had in very severe patients, I think that having significant letter gain is entirely in the realm of possibility. In that study, we had, like, you know, eight, 10-letter gains in DME, you know, five, six letters i n AMD. Those would all be beyond where that graphic ended, right? There's always a possibility of that slam dunk result. Frankly, anything better than historical aflibercept or comparable or better, I think would be really, really exciting in the field. Cool. These are some exciting readouts. We very much look forward to seeing the data. Unfortunately, I think we're out of time, but thank you so much for sharing about the story and we look forward to seeing these data readouts. Well, thank you for your time.