Good morning. Welcome to the Unity Biotechnology conference call and webcast. At this time, all attendees are in a listen-only mode. A question-and-answer session will follow the formal presentations. As a reminder, this call is being recorded and a replay will be made available on the Unity website following the conclusion of the event. I'd now like to turn the call over to Lynne Sullivan, Chief Financial Officer of Unity Biotechnology. Please go ahead, Lynne. Thanks, Sarah. Good morning, thank you for joining Unity Biotechnology's conference call to review the 24- week data from Part A of the phase II ENVISION study of UBX1325 in patients with wet AMD. With me on today's call is Anirvan Ghosh, the CEO of Unity Biotechnology, Jamie Dananberg, our Chief Medical Officer, myself, Lynne Sullivan, the Chief Financial Officer, and we are fortunate to have Dr. Arshad Khanani, Managing Partner and Director of Clinical Research at Sierra Eye Associates, joining us for today's webcast. Before turning the call over to Anirvan, I'd like to remind you that during today's call, we'll be making forward-looking statements which are subject to risks and uncertainties, including those described in our latest Form 10-K filed with the SEC. Actual results may differ materially from today's forward-looking statements, we don't assume any obligation or intent to update them except as required by law. With that, I'll hand the call over to Anirvan to start the discussion. Thank you, Lynne, and welcome everyone to our conference call today. I am pleased to share with you results from Part A of our phase II ENVISION study in patients with AMD. Part A of ENVISION is a head-to-head study of UBX1325 versus aflibercept in patients with active disease who had visual acuity deficits and subretinal and intraretinal fluid after having been on anti-VEGF therapy for at least six months. Patients were given a run-in injection of aflibercept four to eight weeks before being randomized to the UBX1325 or aflibercept arms. In this study, UBX1325 monotherapy did not achieve non-inferiority to aflibercept through 24 weeks, due in part to an unexpected 3.5- letter gain in the anti-VEGF control arm. UBX1325 maintained visual acuity in patients with ongoing active disease through 24 weeks with less than 1- letter mean decrease from baseline. 52% of UBX1325-treated patients did not require anti-VEGF treatment through 24 weeks. UBX1325 was well-tolerated with no instances of intraocular inflammation. Additional analysis suggests that a single dose of run- in aflibercept may not have been sufficient to get patients entering the study to anti-VEGF BCVA plateau. UBX1325 may be more effective in patients with longer disease duration who may have greater senescence burden. Before I hand over the call to Dr. Khanani to go through the data, I wanted to briefly review the senolytic therapeutic hypothesis and our clinical development plan. Our therapeutic concept is motivated by the fact that there is an accumulation of senescent cells in AMD that may contribute to disease progression, and elimination of these cells may lead to a change in disease trajectory. On slide 5, we see an example of senescent cell burden in the eye of a patient with advanced AMD. In this cross-section of the retina, senescent cells are shown in purple. You can see significant accumulation of senescent cells in several parts of the retina. There is a cluster of senescent cells in the RPE layer shown on the right side of the image, close to an area of damage to the photoreceptor layer. We also see some senescent cells right below that zone in the choroidal vasculature, as well as, in this case, in the nerve fiber layer near the top of the image. Slide 6 summarizes our analysis of senescence burden in patients with DME and AMD. The image on the left shows accumulation of senescent cells near the RPE layer. On the right, we see that there is greater burden of senescent cells in more advanced disease. The senolytic therapeutic hypothesis is shown on slide 7. We know that in the course of disease, there's an accumulation of senescent cells in the eye, including in the vasculature. On the left, we see a representation of an AMD eye showing accumulation of senescent cells in the choroidal vasculature, which can lead to vascular leak and loss of vision. Based on preclinical experiments, we believe that elimination of senescent cells with the BCL-xL inhibitor, such as UBX1325, should lead to a reduction in vascular leak, improvement in vascular perfusion, and ultimately improvement or stabilization of vision. We're testing this hypothesis in the phase II ENVISION study in AMD patients. Slide 8 shows our clinical development plan. We have been exploring the potential role of senescence in retinal disease across studies in DME patients and AMD patients. We have previously shared phase II data from our BEHOLD study in DME patients, where through 24 weeks, we found compelling evidence of improvement in vision and stabilization of retinal structure. We're expecting 48- week data from that study at the end of April. Today, we'll be sharing 24 week data from the ENVISION study. This was a head-to-head study against aflibercept, intended to determine non-inferiority to aflibercept in part A of the study. In part B of the study, we will be exploring the potential benefit of combination with anti-VEGF. Before reviewing the data from the ENVISION study, I wanted to remind you of the trajectory of AMD patients on anti-VEGF. Slide 10 shows data from the VIEW 1 and VIEW 2 registration studies of aflibercept in AMD patients. What you'll note on the left is that most of the benefit from anti-VEGF takes place over the first 16-24 weeks. If you look at the expanded graph on the right, you'll see that there is relatively little change in visual acuity from 24-48 weeks, with patients staying within about a letter despite getting every eight weeks of aflibercept. In the ENVISION study, we enrolled patients who had been treated with anti-VEGF for at least six months. We expected that the aflibercept arm would have shown relatively little change in visual acuity based on prior data. As you will see, as I highlighted at the start of the presentation today, there was an unexpected response to aflibercept of about 3.5- letters right after the first injection, which led to a maintained gain in BCVA such that the UBX arm did not achieve non-inferiority despite maintaining visual acuity. With that, I'm going to hand it to Dr. Khanani to go through the study design and top-line results. Thank you, Anirvan. Good morning, everyone. It's a pleasure today to be here to share with you the top-line results of the phase II ENVISION study. I'll be sharing with you the 24-week data. As Anirvan said, ENVISION is a two-part study in patients who were treatment-experienced with neovascular AMD. This is a phase II study. In the first part, we are looking at non-inferiority of UBX1325 to aflibercept, and in the second part, we are looking at the benefit of combination of anti-VEGF with UBX1325 to aflibercept alone. Looking at the detailed design of the Part A that I'll be sharing the data today for, this is a proof of concept study. There are a few questions we were asking when we were designing the study. Number one, is there a biological activity of UBX1325 in patients with neovascular AMD? Number two, what is the durability we can get with UBX1325 in previously treated patients who are high need with active disease? One thing I want to highlight is that these are patients with active disease. They had to have active CNV with intraretinal fluid or subretinal fluid. They were required to have minimum of two anti-VEGF injections in the preceding six months. Actually, they received four anti-VEGF injections in the prior 6 months. BCVA had to be between 70 to 20 letters, and the actual mean BCVA in this study was 60 letters. As I said, these are high-need patients who require frequent treatment. The CST at baseline was actually 370 microns, showing that these patients had significant amount of fluid coming into this trial. At screening, all patients receive aflibercept run-in injection. They were randomized to receive either UBX1325 or aflibercept. In the UBX1325 arm, patients received two injections, one at zero or baseline and one a month later. They were allowed to receive supplemental aflibercept throughout the course of the study. In the aflibercept group, patients received every eight week aflibercept, and the primary endpoint was at 24 weeks looking at safety and efficacy. Some of the endpoints we are looking at, obviously, this is a proof of concept first in human in terms of neovascular AMD patients, looking at safety and tolerability, and then of course, BCVA change from baseline, CST change from baseline, and other parameters that are listed. Looking at demographics at baseline, I want to highlight a few things here. Number 1 is the mean visual acuity. It was 62.4 letters in the aflibercept group compared to 58 letters, there is a mismatch there. In terms of CST, that was comparable around 370 microns, the mean duration of neovascular AMD about four years prior to entering the study. Safety is important. This is a new molecule with a new mechanism of action. I'm happy to report that we did not see any cases of intraocular inflammation, endophthalmitis, retinal artery occlusion or vasculitis. You can see most of the treatment-emergent adverse events are comparable, these are mainly related to the injection procedure. Let's look at the top-line data in terms of visual acuity. This is change from baseline in BCVA excluding post-rescue data. I want to spend a little bit time here so everybody can understand what we are seeing. As I said, these are treatment-experienced, high-need patients requiring frequent injections. As you can see in the aflibercept group, we see that unanticipated increase in visual acuity after the first injection, while in the UBX arm, we can see that we are maintaining visual acuity. That initial gain, which we usually don't see in previously treated patients, we expect to maintain visual acuity. You can see that there's a mismatch after the first aflibercept injection. When I look at this data, I see that UBX1325 patients maintain BCVA through 24 weeks. We did not meet the non-inferiority margin. As you can see at week 24, patients had increase of 3.1-l etter in the aflibercept group compared to -0.8 letters in the UBX group. If you look at the average, you can see patients in aflibercept group had 2.9- letter increase compared to -1.9 in the UBX group. Again, here patients in UBX group were dosed at zero and four weeks, and aflibercept at zero, eight, and 16 weeks. This is change from baseline in BCVA, including the post-rescue data. So the last slide was excluding any post-rescue. Here you can see again that initial unanticipated increase in these prior treated patient that was maintained essentially in the aflibercept group, led to a non-inferiority margin not being met. Looking at CST to look at disease activity, this shows change from baseline in CST excluding the post-rescue data. You can see patients in UBX1325 group have increase in CST up till week 12. After that, they have decreasing CST, and this is excluding post-rescue data. What we are seeing is that there is a delayed impact on CST with UBX1325, which is consistent with the potential time course of senolytic mechanism to exert effect. At the end, at week 24, there was an increase of 87.3 microns in the UBX group compared to 30.5 micron in the aflibercept group. You can see actually in the aflibercept group, we see that fluctuation, the sawtooth, fluctuation with every eight weeks of aflibercept that we usually see in clinical trials with the aflibercept every eight weeks. This has changed from baseline in CST, including the post-rescue data. You can see that anti-VEGF rescue appears to improve CST in UBX1325-treated patients. Now, there are other questions we were asking. What is the patient population that can benefit the most with UBX1325? Here we are seeing the impact of neovascular AMD diagnosis on BCVA response. Again, this excludes the post-rescue data. We're looking at patients who have had disease longer than two years and less than two years. When you look at the patients who have diagnosis over two years, you can actually see that we see a better treatment effect in terms of comparable outcomes. Here you can see that when we are looking at BCVA change in patients with neovascular AMD with diagnosis greater than two years, again excluding post-rescue data, the data is actually similar between UBX1325 and aflibercept-treated group. Now, durability is important for clinicians and patients. Looking at durable effect of UBX1325, you can see on the left that majority of the patients went 24 weeks without requiring anti-VEGF injections, that 52% of the patients. You can see 24% required one treatment, and the other 24% required two injections or more. On the right, you can see the maximum anti-VEGF-free interval in the study where 44% went 24 weeks or greater without requiring anti-VEGF. You can see the 16 weeks, there's greater than or equal to 16 weeks. Looking at durability, that's 56% of patients. As I said earlier, these are patients requiring frequent injections before coming into the study. Here you can see the history of anti-VEGF use in the prior timeframe before getting into the study in prior six months or so. You can see that these are high-need patients with active disease requiring anti-VEGF treatment approximately every six weeks. As I said earlier, the CST actually is quite thick in these patients, about 370 microns in both treated groups. What happens after patients were randomized in the UBX1325 group? You can see that in these high-need patients requiring frequent injections, UBX treatment led to 52% of patients without requiring any anti-VEGF rescue. We are clearly decreasing the treatment burden in these patients who were requiring very frequent anti-VEGF injections. In conclusion, in the first part of the ENVISION phase II study in patients who were high need requiring frequent injections for neovascular AMD, what we have seen is that UBX1325 was well-tolerated with no intraocular inflammation. UBX1325 maintained visual acuity through 24 weeks in these patients, but there was a 3.5- letter gain in aflibercept group at two weeks, and non-inferiority to aflibercept was not met in this trial. We expect patients who were previously treated to maintain vision rather than gain vision, as we have seen in other trials looking at patients who were treatment experienced. UBX1325 allowed 52% of patients to avoid any anti-VEGF treatment for at least 6 months. As a reminder, these were patients who were receiving injections on average every 6 weeks prior to entering into this trial. What we have learned from this study that UBX1325 may have a greater treatment effect in patients with a neovascular AMD diagnosis greater than two years based on the post-hoc assessment. We are waiting to see the part B of the ENVISION study, which is exploring the benefit of UBX1325 in combination with anti-VEGF. Now I'm going to pass it back to Anirvan Ghosh. Thank you, Arshad. You can see, there was an early and unexpected response to aflibercept in this study. The run in aflibercept injection was intended to get patients to a BCVA plateau before randomization, it appears that a single aflibercept run in dose was not sufficient to achieve that. UBX1325 was effective in maintaining visual acuity through 24 weeks did not achieve the non-inferiority margin given the early response to aflibercept. We see maintenance of visual acuity in UBX1325 arm as evidence of treatment effect are encouraged by the durability which show that over half the patients could go 24 weeks without requiring anti-VEGF injection. It is noteworthy that UBX1325 may have performed better in patients with longer disease duration, which is also associated with greater senescence burden. The maintenance of BCVA in AMD patients is in contrast with significant gains in BCVA we had observed in the DME BEHOLD study. These differences may be related to distinct pathophysiologies in the two diseases. We're looking forward to sharing 48-week BEHOLD data in the weeks to come and intend to advance UBX1325 to a phase IIb study in DME in the second half of the year. Thank you again for your interest in the program. With that, we will be happy to take questions. Great. Thank you, Anirvan. At this time, we'll be conducting a question-and-answer session with our speakers. Please hold for a brief moment while we pull for questions. Our first question comes from Salim Syed from Mizuho. Please go ahead, Salim. Hey, guys. Good morning. Thanks for the question. A few if I can, and my sympathies to the team. I know this is not the data folks wanted to see. I guess on the, you know, if we're trying to figure out what happened in this trial, I mean, you pointed out a few things here. One is the aflibercept of, you know, one injection just wasn't enough. It looked like the baseline stats were more or less similar between arms. And you kind of pointed out this less than two years and over two years as perhaps another reason is, I guess, you know, in terms of if we're looking for other baseline characteristics here, it was kind of minimal on the slide. Is there anything else you guys can point to as to why maybe you're seeing this result, or is it really just that these patients who were thought to be deemed, you know, no longer benefiting from anti-VEGF, there was something wrong with that particular part of the design of the trial? Salim, let me start, and then I might have Arshad add too, based on his experience. You know, the first point you made was with regard to whether the run-in was enough. I think it did not have as intended effect, right? The design was that the aflibercept run-in would allow patients to get to their peak state, and then from that point on, they would be steady. Interestingly, you'll note that at the eight and 16-week injections in the aflibercept arm, that is in fact what happens, right? Those subsequent injections do not lead to a bump. The response in that first injection is indeed unexpected and unusual even within this study, right? That injection has an effect. It might have something to do with them switching from whatever their previous treatment was coming into aflibercept treatment. They were pretty, you know, advanced patients with active disease. Overall, the baseline characteristics were pretty or were well-balanced. We don't believe that there's a significant imbalance effect that would account for it. The, the period effect is noted, you know, both in patients over two years and over three years. The three-year and greater analysis was pre-specified, and again, in that group, we had saw comparable effects in UBX and aflibercept arms. The two-year analysis was post hoc, and there again, we saw that patients over two years performed pretty similarly. Maybe with that, I'll hand it to Arshad to comment a little bit on your experience of the patient's prior treatment and then moving into aflibercept and how that might have related to the early effect. Yeah. Thanks, Anirvan. I think that's a very good question about that initial gain in vision after receiving on study aflibercept. You know, when you look at the data we have from the Port Delivery System, from the TKI trials, and even gene therapy trials, we don't see these patients gaining, you know, 3.5- letters of vision or three letters of vision right getting into the study. That was a surprise for me as a clinician participating in multiple clinical trials with the different agents looking at treatment experience, patient population. Obviously, we need to dive in more into, this is just the top-line data, to see if there is any individual patients that are driving this, but that initial gain is unexpected. What I feel like is that we wanted to see a biological activity in this trial. That's why patients were required to have active CNV, were required to have intraretinal and/or subretinal fluid. Many other trials, when you look at them, they just have to have a history of neovascular AMD and anti-VEGF injections. Many of them don't require active fluid. I think here the bar was higher because patients had to have active disease. What it appears that, you know, many of the patients, gain, you know, vision after receiving aflibercept. We didn't require them to have aflibercept historically. Jamie can give you more information about how the treatment history looked like for these patients. You want me to chime in on that? Yeah, Jamie, you can briefly comment on their previous anti-VEGF history. Yeah. Most of the patients coming into this study were on aflibercept. There's a variety of regimen, some on more than one drug. The majority of patients on aflibercept were already on aflibercept, roughly 70%. It's a little perplexing the frequency of aflibercept injections was roughly the same throughout, even into the run-in period. Again, as Arshad pointed out, the bump we saw in the aflibercept group was indeed unexpected. Thanks, Jamie. Thanks, guys. If I can, just a quick follow-up. On the DME study that you plan to start in the second half of the year, I noticed in the press release it says phase IIb. Is that still pivotal? Salim, we're gonna be finalizing the design of that next study over the coming weeks. We'll share details of the design. The one element that we can comment on is that we expect it to be a head-to-head study against aflibercept. We'll share details of design most likely after we get to the 48-week data. Okay. Any comment from the team or maybe Dr. Khanani on whether these AMD results, you know, increase or decrease? It sounds like parts of this, you guys seem encouraged, parts of this data set, you guys seem discouraged. Just curious how you're thinking about, maybe directed to Dr. Khanani, how this influences your probability of success for DME. Well, I think when I look at this data and the DME data, I think we need to understand that these are very different diseases and they're different patients. You know, in DME, there's a large number of patients that have suboptimal response to anti-VEGF, and there are other cytokines that are leading to active disease. I think senescent cells play an important role in that based on the positive data we have seen. In neovascular AMD, this is a proof of concept study. We didn't know if the mechanism of action will show any biological activity. It's nice to see that we are actually seeing some biological activity. I think the learning from this trial is to figure out what is the patient population that may benefit in neovascular AMD, or is this a drug that needs to be given in combination with anti-VEGF. The delayed effect we saw, Salim, in terms of CST reduction shows that it does take time for this drug to work. I think the learning goes on, but I think based on the data I have seen for DME versus neovascular AMD, I think there's high likelihood that senesce plays a role in DME. These are different diseases. I think I cannot speculate, I cannot translate one data into another disease state, but I think all we can say is as clinical investigators trying to look for, you know, a new mechanism of action, the bar is very high. Looking at the data, we hope that we can see positive data that continues in the DME space. Got it. Thanks so much, guys. Thanks, Salim. Thanks for the question, Salim. Our next question comes from Carly Kenselaar from Citi. Please go ahead, Carly. Great. Thanks. Hi, team. This is Carly on for Yigal. Thanks for taking our questions. First on the Eylea arm. Sorry if I missed this earlier, but we were just curious if the 3.5-letter gain was driven by maybe a few outliers that had significant BCVA improvements or if you saw a fairly consistent improvement across all the patients in that arm. Thanks, Carly. We did do some sensitivity analysis and that 3.5-letter gain was not driven by outliers. Okay. Okay, got it. That makes sense. Second question is on the CST profile for UBX1325. Just curious if you can maybe elaborate a little bit on what you make of the initial rise in CST followed by a decline. I know you mentioned this may be consistent with the MOA, but just curious if you can kind of elaborate a little bit on that. Well, let me start and then I'll hand it to Arshad to add additional commentary. you know, what we observe is that when patients are taken off of their anti-VEGF, and these patients coming in with a significant amount of fluid in the eye, about 370 microns or so, that, with that withdrawal of anti-VEGF, there is a fairly kind of rapid accumulation of fluid that you see over the first, 12 or so weeks in the UBX arm. Beyond that, at least in this dataset, one sees a, the beginning of a decline. As Arshad pointed out, that could be evidence of a delayed effect. I think we have to be careful about interpreting exactly what is driving the dynamics of CST, but I think that the profile would suggest something like that. I think importantly as we go into the second half of the study, part B of the study, it'll be interesting to see how those patients fare because those patients in part B of the combination arm will be getting into the aflibercept dose with their CST relatively well controlled. Arshad, maybe you can comment a little bit. I mean, maybe your expectations about like withdrawal of anti-VEGF, how that relates to what we see in the CST and the potential delayed effect. Absolutely. I think, we see that clinically also that patients who are very high need, that are requiring frequent injections, if they miss an anti-VEGF injection, there is a rapid increase. I just wanna remind everyone, this was a proof of concept study. You know, going head-to-head with anti-VEGF is a very high bar, especially picking a patient population that has very active disease. You know, presence of fluid, active CNV, not just the history of neovascular AMD on treatment. I think the learning here is that, you know, when you stop the anti-VEGF, these are anti-VEGF addicts, meaning requiring a lot of anti-VEGF, and there is an initial increase in CST right away. You actually see the increase in CST with every fluctuations with every 8 week of aflibercept where, you know, 8 weeks after the injection, the CST is increasing. The question is, what is the learning from this in terms of how if we design future studies would be to give more run-ins? You know, we have seen that in the TKI space, that we are loading patients with multiple anti-VEGF depends on the trial before or after giving the TKI. I think the learning here is that because of the delayed effect of UBX1325, patients with anti-VEGF, if we could have stayed on anti-VEGF for 2 or 3 more injections, that could have changed the course. I think again, this was learning in a proof of concept study, and I think we have gained a lot of information from this trial. We do see the biological activity of UBX1325, where we saw greater than 50% of patients not requiring supplemental aflibercept. That's the good news here. Thanks, Arshad. Super helpful. Thank you. Thanks for the questions, Carly. Our next question comes from Brandon Folkes from Cantor Fitzgerald. Please go ahead, Brandon. Hi. Thanks for taking my questions this morning. Maybe just following on the other side of an earlier question, just can you talk about the individual patient responses in the UBX1325 BCVA response curve? Just was it pretty consistent across patients, sort of any outliers there? Maybe just following on, as we look to part B of this study, how do you now think about sort of what's gonna be deemed success or maybe what you're paying more attention to in light of today's data? Thank you. Thanks, Brandon. We did look at individual patient curves in the UBX arm, in both arms, actually. They are quite consistent. If you look at patients in the UBX arm, across the board, typically, patients kind of maintain vision as you saw in the overall average. That's the first part, so that there does not seem to be great differences in kind of the overall trajectory of patients on UBX through the duration of 24 weeks. With regard to part B, I think there are a couple of things that are important. The first is kind of in the original design, it's really designed to address the question of whether adding UBX to aflibercept might provide greater benefit than aflibercept alone. We will get that answer from that study because now we have, we already have that data on the aflibercept alone arm and know that they're coming into part B with very stable BCVA. If there is an additional treatment benefit of UBX, we'll be able to detect that. Noting that this is an orthogonal mechanism, these patients, you know, still have sub-optimal vision even with that aflibercept treatment. It's worth noting that, you know, we have been highlighting this early aflibercept bump, but it's a pretty modest bump. It's not really that significant with about a 3-letter gain. These patients still have significant visual acuity deficits going into part B. We have an opportunity to learn about the potential benefit of combination treatment. The other things come really from, I would say, hypothesis generated from the first half. One has to do with kind of how the UBX arm would perform when patients that come in with more stable BCVA and CST into the study. Going into part B, those patients we know will be coming in with stable BCVA and well-controlled CST. At that point, when you add UBX, we'll see how that translates into durability. It's an opportunity to kinda confirm the findings from the first study overall in terms of seeing what effects we see in the subsequent 24 weeks both in terms of durability and efficacy. I do think it's worth highlighting the durability benefit. These patients were coming in with getting aflibercept about every six weeks or anti-VEGF every six weeks. They're very, you know, aggressive, active disease patients. To go from there to having over half the patients go without any anti-VEGF for six months, I think is a pretty noteworthy result. Thanks. One follow-up, if I may. Just on that point, if we look at sort of today's data, obviously it's very early stage. You know, you're gonna do a lot of work. We're gonna look at part B. You know, how would you characterize sort of maybe your willingness to continue to pursue AMD versus making the sort of go, no-go decision? Sort of what is that bar and when is that made? Yes, I think when I look across what we know so far from the DME and AMD data, clearly the visual gains we saw in DME and stabilization of CST, I would characterize it as a very strong result, and that drives our confidence in moving that forward to the next study. On AMD, this data is all really fresh and we have just been analyzing it for a couple of days. There's additional imaging data that we'll have in the weeks to come. Of course we'll have data from the part B. I expect that, you know, once we have the totality of the AMD data, we would be in a better position to determine how best this could be advanced or explored in AMD. As Arshad pointed out, we believe that maintenance of visual acuity is a sign of biological activity. Of course, we need to see and continue to look for where the areas of differentiation would be with current standard of care. If there's evidence of disease modification, that would be interesting. If there's evidence of add-on benefit to anti-VEGF, that would be interesting. I think we need to see those data sets and then determine what a future study in AMD might look like. Great. Thanks very much. Thanks, Brandon. Thanks for the questions, Brandon. Our next question comes from Andreas Argyrides from Wedbush. Please go ahead, Andreas. Hi, good morning, team. Thanks for taking our question here. Just a quick follow-up from the rest of the questions. Could you just help us, you know, contextualize the rescue-free rates that you've seen here? I mean, it seems UBX1325 performed as expected, you know, in terms of maintenance of visual acuity, and considering the high unmet need population here. How should we think about, you know, maybe a little bit more context around the rescue-free rates? Thanks. Yeah, absolutely. First, the observation that over half the patients go without rescue, we find to be quite impressive in terms of potential treatment effect of UBX1325. If you look at the BCVA trajectory and the CST trajectories, one would infer that the rescues most likely were driven by CST. We don't have that individual causal data yet, but I think that if you look at the trajectories, that's probably what's driving it. That does relate to the point that Arshad made about potential future trial designs. I think this is a very important point when you're switching from one treatment onto another. We have to think carefully about what is the optimum handoff, if you will. In this case, there are two things that I think kind of stand out from the data we have. One is about how you make sure that you've gotten the patients to a plateau effect before you switch to UBX. Arshad pointed out that given the potential somewhat delayed effect of UBX kick in, which we also saw in the DME study, that it might benefit to have a couple of additional aflibercept injections post-UBX before just handing over to UBX alone. So that we expect would have an effect of clamping down the CST and might provide even greater durability benefit. All right. Thanks. Yeah. I'll step back in the queue. Thanks, Andreas. Thank you, Andreas. This concludes the question and answer session for today. I'll now turn it back over to Anirvan for closing remarks. Thanks, Tara. Thanks everyone for your attention. Thanks Dr. Khanani for joining us today and helping us understand the data. I think examining it in multiple ways, we find a pretty consistent theme here about the fact that UBX is able to maintain BCVA through 24 weeks, which we find encouraging in terms of potential treatment effect in AMD, as well as the observation that this early and unexpected increase in BCVA in response to aflibercept most likely accounted for UBX not achieving non-inferiority. We are looking forward to the DME 48- week data, which is right around the corner. We expect to have that data before the end of April. We'll share that with you and that I think together with the prior DME data will inform the design of the next DME study, which will most likely be the next study that we initiate with UBX1325. With that, I'll conclude the call and thank you all. Thank you.