Good morning and 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. Good morning, and thank you for joining the Unity Biotechnology Conference Call to discuss the 24 and 36-week results from our ASPIRE study, a Phase 2b head-to-head study of UBX1325 in patients with diabetic macular edema against the standard of care of Aflibercept. I'm Lynne Sullivan, the Chief Financial Officer of Unity Biotechnology, and with me on today's call is renowned retinal specialist Dr. Robert Bhisitkul, a Professor of Ophthalmology and Director of the Retina Fellowship at University of California, San Francisco. Anirvan Ghosh, the CEO of Unity Biotechnology; Federico Grossi, our Chief Medical Officer; and Alicia Tozier, our Chief Strategy Officer. On today's call, Anirvan will begin with an overview of the senolytic therapeutic hypothesis for DME and the results of the ASPIRE Phase 2b study. Alicia will briefly discuss how UBX1325 could fit in the competitive landscape before handing it to Dr. Bhisitkul to discuss his physician perspective of the data and potential use in real-world practice. Lastly, we'll go back to Anirvan for closing remarks, and we'll wrap up the call with a Q&A. 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 10-K filed with the SEC on March 7th. Actual results may differ materially from today's forward-looking statements, and we do not assume any obligation 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 thanks everyone for joining our data review of the 24 and 36-week results from the ASPIRE Phase 2b study in patients with DME. This is a head-to-head study against aflibercept. What we find is that patients on UBX1325 gained a little over five letters at both weeks 24 and 36. UBX1325 was non-inferior to aflibercept at nine out of ten time points through 36 weeks. The one point where it did not meet non-inferiority was the average analysis of weeks 20 and 24. About 40% of the patients did not need supplemental anti-VEGF through week 36. We find that UBX1325 generally outperformed aflibercept in subjects who had less aggressive disease. We also see that patients with poor vision who switched from prior aflibercept to UBX1325 had the most consistent gains in BCVA and less variable CST. We continue to see a very favorable safety profile with UBX1325, with no instances of inflammation or other severe retinal or ocular adverse events. We feel that UBX1325 could provide an important treatment option for patients with DME with poor vision who are not receiving optimum benefit from their current anti-VEGF standard of care. Before going into the Phase 2 results, I'm going to briefly review with you the senolytic therapeutic hypothesis and the mechanism of action of UBX1325. UBX1325 is a BCL-XL inhibitor that is designed to eliminate senescent cells that we believe drive disease progression. On the left-hand side of this slide, you're seeing an illustration of a DME retina highlighting the vasculature and illustrating the senescent cells in blue. What we have found over the course of the last several years is that in the course of disease, senescent cells will stop dividing, and they are highly inflammatory and secrete a number of factors that can damage the local microenvironment. They also do not form tight junctions with their neighboring endothelial cells, which can lead to vascular leak and accumulation of fluid. Our therapeutic hypothesis is that with a BCL-XL inhibitor, we should be able to selectively remove the senescent cells from the vasculature, thereby reducing the local inflammatory drive as well as reducing the increased vascular leak that should lead to improved perfusion through the blood vessels and eventually improvement in vision. Let me now move to results from the ASPIRE study. This slide shows you the design of the study, and I will walk you through the inclusion criteria for the study and our primary outcomes. The inclusion criteria is shown on the bottom left. In the study, we enrolled patients who had a diagnosis of DME for at least six months and had had three anti-VEGFs during that period. They also needed to have poor vision, so they came in with less than 70 letters of vision and had to have a CST of over 325 microns. Just as a reference, I'll mention that 70 letters of vision is what driving vision is, so they all had less than driving vision coming into the study. When they came into the study, they were taken off of their prior anti-VEGF treatment and given three run-in injections of Aflibercept a month apart before being randomized to an Aflibercept arm or a UBX1325 arm. On the Aflibercept arm, they received every eight-week Aflibercept for the first three doses through 16 weeks. In the UBX arm, they received UBX1325 for those first three doses at 0, 8, and 16 weeks. You'll note that in the first treatment with UBX1325, they also received an aflibercept. This was based on our prior BEHOLD study where we have seen an early accumulation of fluid in some of those patients, and this was meant to stabilize those patients. You'll also see that beyond week 16, there are no further planned injections all the way through week 36. Moving now to the baseline characteristics of the patients. You'll see that the baseline characteristics are fairly well-balanced. They were about the same age. You'll see their A1C is fairly similar. They came in with BCVA of about 62 letters, so fairly poor vision, and with CST between 370 and 400 microns. You also see at the bottom their prior anti-VEGF use. I'll note that there are a couple of areas where there was an imbalance such that it appears that there were somewhat more severe patients in the UBX1325 arm. With regard to duration of diabetes, you see that the UBX patient came in with about 21 years of diabetes compared to about 14 years in the Aflibercept arm, a DME duration of about 4.7 years in the UBX arm compared to three and a half years in the Aflibercept arm. I'll note that in our previous BEHOLD study, the duration of diabetes was about three and a half years. Additionally, you'll note that in the prior anti-VEGF use, we have about a similar number of patients on the Aflibercept and Avastin, which are the two drugs that were used most in the period prior to being enrolled in our study. I will note that there's an imbalance in faricimab such that about 25% of our patients had been on faricimab previously and about 7.5% in the aflibercept arm. There were about 10% Lucentis patients in the aflibercept arm and none in the UBX arm. Let us now move to the primary analysis of BCVA change from baseline through week 36. In these slides, UBX treatment is shown in blue and the aflibercept shown in gray. You'll note that beginning at week zero, when they get randomized, there is a fairly rapid increase in vision in both arms. On the UBX arm, you see a gain that is at about five letters or so at 24 weeks that continues through 36 weeks. You see on the aflibercept arm, the vision is similar at most of the time points. You'll note that at several of the time points, UBX has a numerical advantage to Aflibercept, and there's one time point, which is week 20, when Aflibercept has a numerical advantage. In describing the data, I will present them both excluding post-rescue data as noted at the top right or including post-rescue data. This data set is excluding post-rescue such that if any patient during the study received a supplemental injection of anti-VEGF, all data beyond that point for that patient is excluded. What you're seeing over here is a clean UBX1325 effect indicating largely a non-inferior curve ending with a slight numerical advantage at week 36. If you look at the data including post-rescue, this has all of the patients and including any anti-VEGF they received, the shape of the curves is largely similar. Once again, you see a gain in both arms, and at multiple time points, they're fairly similar with a few time points where UBX1325 has a numerical advantage, one time point where aflibercept has a numerical advantage, and they both end with about a five and a half letter gain in BCVA from the time that they started. Let me now turn to an overall summary of the data highlighting the BCVA in the UBX1325 arm and the aflibercept arm and various predefined analyses, including the primary analysis. You'll see on the left-hand side, the first four rows are analyses done at week 24 data, and at the last four, you see analysis done at week 36 data. I should also note in this analysis, we have all of the subjects represented from the week 24 data set, and at week 36, we have a majority of the subjects that have already completed that week 36 treatment. When you look at the two columns, it shows the BCVA at that time point. A green highlight indicates that in that particular analysis, the UBX1325 arm or the aflibercept arm had a numerical advantage. I'll draw your attention to the fourth line, which is the average of 20 and 24 weeks, including post-rescue data. That is the analysis that we had defined previously as our primary analysis. Looking at the right-hand side, you'll note the confidence interval of these various analyses. In all of these analyses, you see a fairly high confidence of achieving the non-inferiority margin of negative 4.5 letters. In most of these analyses, it exceeds a confidence interval of 90%, which was our predefined threshold. You'll see two time points, which is the average of 20 and 24, where it barely missed the 90% confidence interval to end with an 88% confidence interval of meeting a negative 4.5 letter non-inferiority margin. Let me now turn to the patients where we see the effects of UBX1325 generally outperforming Aflibercept. When you looked at the data, I noted earlier that the UBX1325 patients were generally a bit more severe than the Aflibercept patients coming in. We had a pre-specified analysis of looking at patients who had CST less than 400 microns at baseline. These are patients who still have fluid in the eye, but not as severe as the worst CST patients. In that group, you'll note that starting at zero and going all the way to 36, at most of the time points, UBX1325 had a numerical advantage, and a couple of time points, it was similar to Aflibercept. In this analysis, it met non-inferiority at all of the time points. This data set here is excluding any post-rescue data. When you look at this data set including post-rescue data, you see a result that is fairly similar. Once again, you see that in the majority of the time points, UBX has a numerical advantage to Aflibercept and one time point where it is fairly similar. Once again, at each of the time points, it was non-inferior to Aflibercept based on the analysis. A second analysis that we had done was in patients who had CST less than 400 microns at their run-in. In this analysis, once again, you see UBX1325 numerically outperforming Aflibercept at most of the time points, with a couple of time points where it is fairly similar but ending with a significant letter advantage by the time you get to week 36. If you look at this data including post-rescue data, you see once again that at most of the time points, UBX has a numerical advantage over Aflibercept and a significant separation when you get to week 36. Let me now turn to the CST data and the need for supplemental anti-VEGF. When you look at the CST curves shown in blue for UBX and gray for Aflibercept, you note that the Aflibercept arm largely performs as you would expect for patients who have plateaued on their Aflibercept treatment. The CST stays fairly close to zero on those patients all the way through 36 weeks. I'll just remind you that in this analysis, those patients had injections at zero, eight, and sixteen weeks and no injections planned after that point. You'll note that in the UBX1325 arm, there is an increase in CST overall at the sixteen and twenty-week time points, which led to a number of patients needing supplemental or rescue anti-VEGF. Once they receive that treatment, the CST goes down to baseline and then is maintained all the way through thirty-six weeks. They end at thirty-six weeks with CST that's fairly similar to the aflibercept arm. We have been analyzing what drove those CST increases in the sixteen to twenty-week window. This analysis is a pre-specified analysis that indicates a particular subgroup that was driving most of the CST increase. As I mentioned, there was a subset of patients that were imbalanced in the UBX arm, which were the previous faricimab patients, about 25% of our patients. You'll see the line with the highest CST, the dotted line represents those faricimab patients. These are the patients we expect to be the most severe because typically, a patient would get into faricimab after having tried other anti-VEGF therapies and needing fairly aggressive anti-VEGF treatment. You can see that those patients had the highest CST gains starting at week 16 and most likely drove the need for the rescues. When you look at the patients who are previously on aflibercept or on Avastin, these are the patients which represent about 75% of our patient population. You see that generally speaking, their CST remains fairly steady throughout the study duration, although some of them might have needed rescue as well. Let me now move to safety. Overall, the safety of the molecule tends to be very favorable, as we have seen in previous studies. There were no instances of intraocular inflammation, endophthalmitis, or other severe retinal or ocular adverse events. The other line I'll draw your attention to are treatment-related ocular AEs in the study eye that are fairly balanced across the Aflibercept and UBX1325 arms and did not require any additional interventions. I'll also note that you'll see in the ocular AEs on the study eye, not related to treatment, there is a slight imbalance where there are more of those AEs in the UBX1325 arm. Those were mainly related to either procedure because the UBX1325 arm so far has had a few additional injections because of those Aflibercept supplements or to gain in fluid in that eye. None of those required additional intervention on the patients on behalf of the physicians. To summarize these data sets then, we find a data set that is largely consistent with what you have seen in BEHOLD with regard to the UBX1325 arm such that the patients on UBX1325 gained over five letters through 36 weeks in a difficult-to-treat patient population. We find that overall, the vision gains in the two arms are fairly similar. However, there are some patients where UBX1325 seems to provide perhaps an added benefit, most prominently in the group that has CST less than 400, which are, I'd say, better managed fluid patients. We see a trend of UBX1325 outperforming Aflibercept in those patients. We also see that patients who have switched from Aflibercept to UBX1325 show the most consistent and durable vision gains as well as greater stability in the CST. We feel, based on this data, that we're beginning to understand the patients who are most likely to benefit from UBX1325 going forward. I feel that we are in a position that we should be able to design the right subsequent studies to really highlight where UBX could be beneficial to patients who are not getting an optimum treatment with their prior anti-VEGFs. I would now like to turn the discussion to where the unmet need in DME is and where UBX1325 might fit in the current treatment paradigm. With that, I'm going to hand the call over to Alicia Tozier to discuss those elements. Thank you, Anirvan. We just discussed the clinical data to date and what's on the horizon for UBX1325. Now we'd like to pause and take a moment to discuss why this matters so much for patients. In this section, we'll be walking through the current unmet needs within DME and the existing treatment paradigm. As we look at the current DME landscape today, several factors are worth noting. As you can see over to the left, this is a large and growing patient population. As of last year, there were over 30 million patients worldwide in key markets that were working through a DME diagnosis and seeking treatment, and 1.7 million within the US alone. Let's remember that when we think about these patients, a third of the time, these patients have bilateral disease, which means that they would require distinct treatment for both eyes. Let's double-click into what's happening with these patients as they seek treatment. We know that anti-VEGFs have been available for 15-plus years and really been a game changer for many patients. While there are so many mature products on the market, one might think that it's a mature marketplace. What we may not realize is that according to an analysis of the IRIS database as of last year, 50% of patients discontinue treatment within DME by six months. While some patients may respond well to therapy, there is still a large portion of patients who still have an unmet need. Underpinning this disease are four dynamics at play that we believe are worth noting. As you look here to the bottom right, you can see the non-responders. There are about a third of the time patients who do not respond to anti-VEGF therapy. We also know that there is a large portion of patients that receive a suboptimal response. Maybe they get a few letters, but perhaps not enough in terms of BCVA. The third dynamic at play we know in the real world is that while patients may fortunately see vision improvement initially, by about the 24-month mark, vision starts to decline over time. Last, but certainly not least, is dosing frequency. We hear a lot about durability within this space, and that's because about a third of the time, patients are having to come in monthly still for injections. What this creates is the passion for companies, including Unity, to create new products and MOAs. In other words, anti-VEGF continues to play an important role, and there's more to be done. In this slide, what we wanted to illustrate are how all these dynamics come together. Let's take a look at the current treatment paradigm today. We know that for treatment-naive patients to date, patients have begun on anti-VEGF, and we expect for that to continue. However, we know that when patients initiate therapy, one of two things can happen. Either they respond to therapy or they get a suboptimal vision outcome. For those who do see a BCVA improvement and maintain that vision over time, we expect for them to continue on that therapy. However, we also know that for a portion of those patients, as we just discussed, vision may decline over time, and UBX1325 has the opportunity to benefit those patients. Now, over to the left, we want to call out another very important category. Those are the patients who are getting a suboptimal response to vision. For those patients, we believe another option could offer a benefit. Either these patients may not be responding to anti-VEGF at all, or these patients may be getting a suboptimal vision outcome. In either case, we believe UBX has the opportunity to offer a benefit for those patients. In summary, we believe an unmet need exists for patients who are suboptimal responders to current therapy, and there is an opportunity for a new option like 1325 to offer a benefit. With that, I'll pass it back over to Anirvan. Thanks, Alicia. As you can see, even with the current treatments, there is a very significant need in patients who have DME who are getting an inadequate response to anti-VEGF. I wanted to turn the discussion now to a conversation with Dr. Bhisitkul, who has followed the program since the very beginning, who is very familiar with the data, and understands how a drug such as UBX1325 might be used in a clinical setting. Thanks, Bob, for joining our call today. You have seen this program from the very beginning, and you're seeing the latest data set. You've had a chance to review it. As we shared, we see vision gains in the UBX arm that are fairly similar to what we have seen in prior studies and maybe certain populations where it might be helping a bit more than what you had seen on the Aflibercept arm. As I understand it, patients come in and initially get on a treatment, and at some point, maybe they switch to other anti-VEGFs. Can you speak a little bit to maybe what the normal course of treatment is for patients who come in with DME, and what do you typically end up doing for patients who are not receiving an optimum outcome? Yes. For the current standard of care for diabetic macular edema, we're basically doing the same thing that we've been doing for the past 15 years with anti-VEGF therapies. These are successful therapies for a large portion of the patients. We recognize that these therapies are incomplete or suboptimal for many of our patients. Right now, the treatment algorithm really is a step therapy or a switch therapy. We start with one anti-VEGF, say it's Avastin, and we might give that for three, four months. If we are seeing the patients in that category where they're having a suboptimal response, we only have a choice to switch to a different anti-VEGF drug. Maybe we switch to aflibercept. Three or four months go by, and we might switch to another anti-VEGF or switch to Vabysmo or switch to one of the biosimilars that are available to us now. It really is just cycling through different anti-VEGF treatments. What's exciting about the ASPIRE data and the BEHOLD data before that is now we have something that is with a novel mechanism. When we make a switch, we can switch not from an anti-VEGF to another anti-VEGF, but from a drug from an anti-VEGF to something with a different mechanism of action. We're seeing signs that this switch may even provide visual gains in this patient population as well. I think that's really interesting in just highlighting the value of having other maybe drugs based on different mechanisms compared to things that are just anti-VEGF-based, which we know all have fairly similar vision outcomes. Let me ask you a practical question. One of the things we saw that I highlighted that in a group of patients that had fluid in the eye but were, I would say, moderately managed, the CST less than 400 micron group, those are the patients, at least in our initial analysis, it seems like UBX1325 might be able to give them some vision gain compared to where they were compared to what they might get if they had just continued on the aflibercept. Tell me about these kind of moderately controlled patients. Is that something that would be, say, potentially practical to implement if you said that, look, if you were to treat patients for some period of time, you have moderate fluid control, and then use a CST-like criteria or maybe some similar thing to decide that you maybe decide to switch to UBX1325 instead of continuing on aflibercept or another anti-VEGF? Yeah. I think you're hitting it on the head. This subpopulation analysis is very interesting to me as a clinician because it really represents my typical DME patient. Okay? My typical DME patient is on aflibercept already. My typical DME patient does not have severe macular edema. They fall, for the most part, within that range of 300 microns of central subfield thickness to 400 microns of subfield thickness. That subgroup of patients under 400 microns on aflibercept, that kind of represents the bulk of the patients that I'm currently following. To see the more pronounced effect in that group of patients, including some of those time points are getting close to 10 letters of visual gain. That's two lines of vision improvement. That really is something that would be applicable to a large portion of patients that are currently under treatment. All right. Thanks, Bob. I really appreciate your time and your insights. Let me wrap up this part of the call so that we can go to any questions on the line. Why are we doing this? Several years ago, we embarked on this journey to see whether we could develop new treatment options for patients who are inadequate responders. For over 10-15 years now, the way these patients have been treated has been by treating them with anti-VEGFs. This is a very active area of innovation. There have been more recent approvals in the space. I would say largely, they mainly help patients who are already doing well on an anti-VEGF agent. If it's a longer durability agent, for example, where there has been a lot of attention, maybe you take a patient who's responding well but needs frequent treatment and perhaps reduce the treatment frequency. I think none of that addresses the need of patients who do not get an optimal response to an anti-VEGF. I think, as Alicia mentioned, that is a very sizable group. There are about half the patients who are walking around who get a diabetes diagnosis. They go to an optometrist every year. At some point, they start losing vision. Patients like the ones in our study, they cannot drive. They are very dependent and have poor quality of life. For them, I think being able to deliver or develop an alternate treatment option that could give them a line or two of vision, take a patient who's not being able to drive to be able to drive, I think is a very meaningful benefit. We look forward to continuing to advance UBX1325 to define the patients who might benefit most and hopefully bring a new treatment option eventually to patients. With that, I will hand the call back to Tara to go to Q&A. 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 Yigal Nochomovitz at Citi. Please go ahead, Yigal. Hi. Thank you. Could you comment a little bit more, please, on the go-forward path? Obviously, the data and the patients with the sub-400-micron CST seems to be the place to focus. Is that going to be the source of the way to design the next study? Could you just give us a little more insight there, please? Thank you. Yeah. Hi, Yigal. Yeah. I would say the goal of a Phase 2 study like the one we just ran is to understand the patient population that is most likely to benefit from the treatment you're developing. In our case, I think from the ASPIRE study results, what we see is the emergence of that population that is the less than 400-micron population, that's moderately severe patients. You'll see that that was about 60% of the patients in our study. A sizable patient population, as Dr. Bhisitkul mentioned, a lot of his patients are of that kind. I would say that is the group where we would have the highest probability of success in running a pivotal study. From where I sit right now, what I see is that there is a group of patients. People might start on aflibercept or Avastin. If they fall into a poor responder category and they have a pretty well-defined threshold of about 400, then enrolling those patients into a pivotal study gives us a very high probability of being able to show, hopefully, at least a numerical advantage over aflibercept, as we're seeing over here, and ideally, kind of overall, maybe reduced treatment burden. Maybe Dr. Bhisitkul, you could comment on if you had a pivotal program like that, is that something that you'd say would generate valuable data to support a product in the future? Yeah. I think with this study, one of the things that's really come out of this study is identifying the target population that is both a very common target population and also had, very interestingly, robust responses to UBX1325. And that's that population that has that less than 400 microns of CST and is on aflibercept or standard drug. I think that will make a whole lot of sense to make that the target population for the next study. Okay. Thank you. Thanks for the questions, Yigal. Our next question comes from Salim Syed at Mizuho. Please go ahead, Salim. Thanks, guys. I appreciate the color on today's call. I guess a few from me, if I can. One, can you comment on the prior therapy groups and if there was any difference in BCVA gains? If so, how would you account for that in a go-forward trial? Number two, the Faricimab patients that you had referenced that had a CST increase, could you clarify that they also have a notable BCVA decline? What was it? Number three, just lastly, on your secondary endpoint of gaining 15 letters, 10 letters, 5 letters, just any color there, what was the extent of benefit that you saw with 1325 in this study? Were there any patients that actually were able to achieve those thresholds? Thank you. Thanks, Salim. First, talking about those subgroups by prior treatment. We had patients who had previously been on Avastin, Aflibercept, or Faricimab. We had pre-specified analysis to see how those subgroups performed once they got on study. What I showed you in the presentation was that the group that was on prior Faricimab had the biggest CST gains, whereas the ones with prior Aflibercept and Avastin had less so. Our understanding of that is that patients who have gotten into Faricimab probably as their second or third-line treatment have already kind of passed to another anti-VEGF and probably not responding well and need something like Faricimab to manage fluid. What we see is that those kinds of patients tend to have the biggest maybe rebound effects. That is also the group where we see the biggest vision drops. I'll first of all mention that, yeah, the vast majority of those Faricimab patients were patients who got rescue injection. Also, those are the ones that had the biggest drop at that week 20. The week 20 dip you see is quite related to those patients. When we look at the other subgroups, for example, the Aflibercept group, which is the largest subgroup that we have, we see a consistent vision improvement. We do not see that drop at week 20. Those patients end with a little over 6 letters of vision gain by the time they get to week 36. With regard to your other question, we also analyzed the 5, 10, and 15-letter gainers across the two groups. Overall, in the overall study population, they look very similar. We do not have that analysis for the subgroup of less than 400. As we get that, maybe as we get towards the 36-week data, of course, we will share that. Great. Thanks so much. Thanks for the question, Salim. Our next question comes from Matthew Caulfield at H.C. Wainwright. Please go ahead, Matthew. Hi. Thank you, guys. For future development considerations, can you speak to prospectively using the AND rescue criteria for the gain of CST and the drop in vision? Just thinking about the importance there in terms of best setting up 1325 for possible pivotal success based on these learnings. Thanks a lot. Thanks, Matthew. Yeah, an important point. Just as I said, part of the goal of a Phase 2 study is to understand which patient population would be the right one for the next study. It is equally important to have a dataset that creates high probability of success in a future study, in a pivotal study. In our case, that is informed both by the design of the ASPIRE study, which is going to be very similar to what we expect in a, which is very similar to what we expect in a pivotal study, as well as the type C interaction we had with the FDA that provided clarity on their expectations of a pivotal study with UBX1325. To your point, the two things that they noted was that in a pivotal study, the aflibercept arm would have to be dosed per label, which is very similar to the treatment regimen we used in ASPIRE. They indicated that we should use an AND criteria for rescue, which is something along the lines of a gain of 75 microns in fluid and a 10-letter drop in vision. It's a good reminder for me to say that in this study, we had an oral rescue criteria. They could be rescued if they either had a CST increase or vision drop. Virtually all of the rescues were because of CST increase. As you saw, the vision was actually really good in the UBX patients. Moving forward, and to your question, we did an analysis to ask how many of our patients would have hit that AND rescue criteria in ASPIRE. Only 2 out of 26 patients in each of the arms hit that criteria. Very few patients. Overall, 90% of the patients would not have hit that rescue criteria. Going forward, I think when you think about a pivotal study, there's one element about selecting the right patients to optimize response, which in our case would be the 400-micron cut. The second is that if you were to run a study with an AND criteria, we'd expect that would lead to significantly fewer rescues in that arm and maybe provide an opportunity to show vision improvement with limited numbers of interventions. Understood. Thank you very much, guys. Thanks, Matthew. Thanks for the questions, Matthew. Our next question comes from Brandon Folkes at Rodman & Renshaw. Please go ahead, Brandon. Hi. Thanks for my question. And congrats on the totality of data. Maybe just one from me. Were you surprised by the aflibercept group curve of this study? Given that sort of we're looking at suboptimal non-responders, they seem to continue benefiting here versus the plateau that maybe one may expect from suboptimal responders. As we move forward into additional studies, should we be thinking about maybe a similar aflibercept or anti-VEGF comparator curve here? Do you think you can control that arm curve going forward so we do not see the magnitude of gains we saw here either through patient selection or run-in phase? Just any color on the overall aflibercept group response in this trial would be great. Yeah. Thanks, Brandon. An important point. Going into the study, we would have expected that the aflibercept arm would not have as much of a gain because they, like you said, have been on prior treatment. We had the three run-ins before coming to the study. As you saw, the UBX1325 arm broadly performed the way it had in the BEHOLD study. I was surprised to see that gain in the aflibercept arm. There are not very many studies like this where there are previously treated patients who are essentially being put back on kind of the initial treatment regimen. I think what we saw here is that they can continue to gain vision for some time when they're put back on an intense aflibercept regimen. What you will notice, the first couple of injections, at least, of aflibercept continues to look a bit like an aflibercept growth curve, right? You see a bit of an increase at the zero-week injection and the eight-week, but maybe not after that. That would indicate that the amount of pretreatment they got did not fully bring them to that plateau. I think there's lots of data that indicates eventually they will plateau, but maybe not with just three injections. The FDA guidance on the pivotal is that they should be dosed per label, which would be five run-in aflibercept injections before going to every eight weeks. That might further stabilize that arm. You can kind of eyeball it. If you were to take the aflibercept curve we have and move it a couple of time points to the left, you kind of get a sense of maybe what an aflibercept more stable curve might have looked like. I would expect something like that in a pivotal study. I think there is a learning here that even in this patient population, when you bring them back on a per level of aflibercept, there can be some gains. It's important to make sure they have an adequate run-in that brings them close to plateau before you start comparing them with another arm. Great. Thanks very much. That's all from me. Thanks, Brandon. Thanks for the questions, Brandon. Our next question comes from Daniil Gataulin at Chardan. Please go ahead, Daniil. Yeah. Hi. Good morning, guys. Thank you for taking my questions. First, as you think about the new study, would you consider enrolling newly diagnosed patients? Would you say there is a potential for increased benefit in the less treatment experienced patients? One. Then two, given UBX1325 mechanism of action, would you expect the effect to deepen over time as senescent cells would have a chance to get cleared and replaced with healthy cells? Thank you. Thanks, Daniil. I think with regard to the study population, I said the data that we've generated so far, it's most relevant for patients who have been on a prior anti-VEGF and are receiving a suboptimal response. Having said that, something we have mentioned in the past, there's nothing about the mechanism that indicates that a prior anti-VEGF is needed for UBX to have an effect. As we think about the next study, we'll certainly consider whether or not it makes sense to have some patients who might be new patients. You might be familiar that in some prior studies, there's been a design where you have a fraction of the patients who are, let's say, treatment naive and then others who are previously treated. If we were to do something like that, we would, of course, not want to create a lot of uncertainty in the possibility of success in the next study. In a larger study, of course, you have a little bit more room. Maybe having some patients who are newly diagnosed could make a difference. I think related to that, there might be a point of not having patients who have had a very long diagnosis. I mean, I think one thing that we see, I showed you that we had some really long DME diagnosis patients in our study. When we look at the data, we've just looked at some of the scatter plots, you do see kind of more variability and less predictable course in the patients who have very long duration at that point. The treatment effect might be harder to predict. We might have an outer bound on how long the disease duration might be so that you are in a phase of early active disease where the patients might benefit the most. The second thing is about how the response might change over time. You're right that the mechanism indicates that once you have eliminated senescent cells, you should get fairly long and durable benefit. I've said first glance, that pattern seems to be true both in BEHOLD and ASPIRE. The drug is on the eye just for a couple of days. You're largely seeing a PD-driven effect. In this study, we had given them a couple of extra UBX1325 injections compared to BEHOLD to see whether that might lead to any additional vision gain. You'll note that what we see here is that most of the gain happens after the first injection. Maybe there's a little bit of benefit in the second, but certainly not beyond that. We don't see a reason to continue treatment after maybe the two injections if you were to design a pivotal study using this data. You get pretty long durable benefit to the very end. As in BEHOLD, you don't see a waning effect. As the eye gets healthier, whether that reduces the need for rescue or the stability, those are things I think we'll need to continue to learn. I mean, I think one of the useful things in the upcoming data, I want to say the full 36-week data, there are a few important things. First of all, we have to make sure that the effects that we're seeing here continue to be true in the full dataset. We have a majority of 36-week. We want to see if that's true. We'll also see whether are we seeing more vision stability by the time you're getting to that point, to your question. Also, 36-week data is very important in being able to give us confidence in achieving non-inferiority in a pivotal study. Based on the FDA feedback we have, starting with that first UBX injection, we would need to go out about 40 weeks for that first non-inferiority analysis. The 36, we believe, would be quite predictive of that. I think there will be a little bit more to learn from the 36-week, but I think there's a possibility that we continue to see good vision out to that point. Great. Thank you for the questions, Daniil. This concludes today's Q&A session. I'll now turn it back over to you, Anirvan, for closing remarks. Thanks, Tara. Thanks, everyone, for joining the call. This has been a long journey for us to try to see if we can develop alternate treatments for patients who are not responding well to the current standard of care. While everybody would like to have a dataset where you can clearly show improvement across the board compared to something like aflibercept, aflibercept is a good drug that's been around for 15, 20 years and helps a lot of patients. It is a very high bar. I would say having a dataset that shows with a new mechanism of action providing comparable vision benefit is an important achievement. We will continue to look into the data and understand how we optimize the next study to identify patients who would most benefit from UBX as a potential future treatment. In closing, I would just like to thank all of our physicians, our advisors, our patients who have participated in the study and in our prior studies who have helped us understand the potential benefits of UBX. We continue to learn from that. Also to our incredible team that did an excellent job of executing on the study as consistent, delivered, clean, and interpretable data so that we can continue to find the best path forward for this program and develop better drugs for patients in the future. Thank you.