Good day, and thank you for standing by. Welcome to the Unity Biotechnology conference call. At this time, participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star one on your telephone. Please be advised that today's conference may be recorded. I will now hand the conference over to your speaker today, Lynne Sullivan, Chief Financial Officer. Please go ahead. Good morning, everyone. Thank you for joining Unity Biotechnology's conference call this morning to discuss the phase I results from our UBX1325 program. With me on today's call is Anirvan Ghosh, the CEO of Unity Biotechnology, Jamie Dananberg, the Chief Medical Officer of Unity Biotechnology, and myself, Lynne Sullivan, the Chief Financial Officer. Before turning the call over to Anirvan, I'd like to remind you that during today's call, we will be making some forward-looking statements, which are subject to the risks and uncertainties, including those described in our latest 10-Q 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. Good morning to all those joining us on the call today. I'm really excited to share our data from the phase I single-ascending dose study of UBX1325 in patients with advanced diabetic macular edema and age-related macular degeneration. As you know, these are devastating diseases that rob patients of their vision and independence. While anti-VEGF therapies have been the standard of care for about 15 years, they pose significant patient burden, and many patients do not respond optimally to these treatments. This morning, we will share data that show that UBX1325 leads to improvement in vision as well as structural improvements in the retina of DME and wet AMD patients. While a limited number of patients with DME and wet AMD were treated in this phase I safety study, we have shared the data with key experts in the field who find the results highly encouraging. We believe that UBX1325, which works by a completely new mechanism of action to restore vascular integrity and retinal health, could provide a powerful disease-modifying alternative to the current standard of care. Before we go into the phase I data, I would like to highlight a few elements that we consider particularly important. First, we will present data which show that for the first time that a senolytic molecule is not only well-tolerated, it also has clear positive impact on defined clinical endpoints in patients with advanced disease. These clinical data show improvements in visual acuity as well as evidence of reduction in fluid in the retina in DME and AMD patients. Second, we believe that UBX1325 could be a disease-modifying treatment for DME and neovascular AMD patients by targeting a root cause of disease progression and provide a much-needed alternative to the standard of care. There has not been a novel treatment for AMD or DME in over a decade, and we feel that there is an urgent need for a new class of therapies that go beyond anti-VEGF variants. This requires breakthrough innovation, and our early data suggest that senolytic medicines could provide that opportunity. Based on the initial efficacy data in advanced DME and neovascular AMD patients, UBX1325 could be powerful as a monotherapy, as adjunctive combination treatment, and provide a treatment option to patients who no longer benefit from the standard of care. Finally, our data provide important evidence in support of the senolytic therapeutic hypothesis. Unity's core platform targets senescent cells, which accumulate during the course of aging and can drive disease progression across organ systems. Early clinical evidence we have generated indicates that selectively targeting senescent cells can not only slow disease progression, it might reverse the underlying pathophysiology and restore tissue health. This is quite remarkable and has broad implications for age-related diseases such as DME and AMD, as well as diseases in other therapeutic areas, a possibility that we are actively exploring. Since some of you may be new to Unity, in the next few slides, I'm going to introduce our core therapeutic approach and then hand it to Jamie to go over the UBX1325 phase I data. At Unity, we are focused on developing therapies that slow, halt, or reverse diseases of aging. The primary biology we're targeting is cellular senescence, and the diseases that we're mainly interested in are in ophthalmology and in neurology. In ophthalmology, our focus is in DME, diabetic retinopathy, and AMD, and we'll share data on DME and AMD this morning. Slide six provides an overview of senescence biology, which we believe is an important driver of disease progression and aging. As our tissues age, there are certain cells that enter a state where they stop dividing and undergo cell cycle arrest in response to stress factors. These cells continue to be metabolically active and can secrete factors that can be damaging to the local microenvironment. These include inflammatory factors, pro-fibrotic factors, and certain growth factors that can drive disease progression. You'll see this list of factors includes VEGF, one of the factors that is known to contribute to disease progression. UBX1325 targets senescent cells, which are upstream of these factors and thereby might exert a broader effect on the underlying pathophysiology. Slide seven illustrates the senolytic approach. Our goal is to develop a set of therapeutics that will selectively eliminate senescent cells, thereby reducing the inflammatory response in diseased tissues and ultimately restore tissue health. I mentioned that as tissues age, there's an accumulation of senescent cells, shown in the slide as those blue cells, which accumulate as we move from left to right. These cells can secrete factors that can be damaging to the tissue. Our candidate therapies were designed to selectively eliminate senescent cells to remove the destructive signals and allow the healthier cells to repopulate that tissue and eventually change the trajectory of disease. Moving now to the senescence disease hypothesis in the eye, we have focused our attention in particular to vascular pathology and inflammation. As you know, DME and AMD are characterized by vascular leak and pathological growth of blood vessels that eventually lead to fluid accumulation, aberrant repair with structural damage, and increased fibrosis, all leading to loss of vision. We have generated preclinical evidence over the past several years that indicate that there is a high senescence burden in the eye in relevant disease models. Based on this research and clinical evidence we'll share with you today, we believe that UBX1325 has the ability to selectively eliminate senescent cells in the vasculature, significantly improve vascular health and tissue repair, and ultimately lead to improvement in patient outcomes. It is worth highlighting that UBX1325 targets the node that is upstream of VEGF, which is the target of the current standard of care. As you know, eye diseases are a major complication of diabetes. We believe that accumulation of senescent cells in diabetes leads to upregulation of a number of inflammatory factors and growth factors that drive disease progression. One of those factors is VEGF, which is a major growth factor that leads to neovascularization and vascular leak. While anti-VEGF therapies have an important role to play in the treatment of DME, these agents do not target other inflammatory factors, nor do they remove senescent cells. By targeting senescent cells, UBX1325 could have a broad impact on disease progression, driven by numerous factors, including VEGF, pro-inflammatory factors, and pro-fibrotic factors, which should lead to better outcomes. Although we are at early stages of our clinical program, we believe that UBX1325 provides the opportunity for a transformative best-in-disease therapy. This slide highlights some of the key attributes we are exploring that could differentiate UBX1325 over the standard of care. UBX1325 can lead to rapid elimination of senescent cells and thereby has the potential to provide a faster effect than what we see with standard of care. Because of its mechanism of action, UBX1325 could restore retinal health and provide long-lasting benefits to those patients. As previously mentioned, UBX1325 targets a novel mechanism of action that acts upstream of anti-VEGF therapies. You may be familiar with other programs that are variants of anti-VEGF, but those programs typically cannot provide benefit to patients who have not responded well to anti-VEGF in the past. By targeting a new mechanism and a new pathway, UBX1325 might not only benefit naive patients, it may also provide benefit to those patients who are not responding well to anti-VEGF and could provide an add-on benefit beyond what they've received from anti-VEGF therapies. Finally, our preclinical evidence suggests that UBX1325 and senolytics can lead to healthy vascular growth in ischemic areas of eyes and thereby restore health in the eye in ways that anti-VEGF would be unable to do. We're excited by the potential of senolytics to change the trajectory of disease and the potential of UBX1325 to reshape how we treat age-related diseases of the eye. At this point, I'm going to hand over the presentation to Jamie, who will go over some of the key clinical data. Thank you, Anirvan. It's a pleasure to have the opportunity to share the first data from our initial studies of UBX1325. I'll start with a summary of the overall clinical development plan for UBX1325, which includes our phase I and phase II studies, as well as a proposed phase II AMD study that is under consideration. As we've previously disclosed, we've completed dosing in the first 12 patients in the phase I study and have initiated the phase II DME study. For today's call, we're discussing the phase I single ascending dose study, which evaluated four cohorts with doses up to and including 10 mcg intravitreally. In each cohort, we enrolled two patients with diabetic macular edema and one patient with neovascular age-related macular degeneration for a total of 12 patients in this first-in-human study. The patients in this study had advanced disease and, in the earliest cohorts, poorer vision. Additionally, these were patients for whom the investigator believed anti-VEGF treatment would no longer be beneficial. As such, they had not received any anti-VEGF or steroid treatments for a minimum of three months prior to enrollment. Now onto the top-line results. First and foremost, UBX1325 met the key objectives of this phase I SAD study. UBX1325 demonstrated itself to be well-tolerated with a favorable acute safety profile supporting further development. There were no dose-limiting toxicities, and two non-drug-related adverse events were reported throughout the entire study phase. Importantly, we saw strong evidence of biologic activity in well-established and defined endpoints of disease improvement in this small advanced stage patient population, as measured by best corrected visual acuity, or BCVA, and central subfield thickness, or CST. With respect to changes in BCVA, we observed a rapid increase in visual acuity in the majority of our patients, 10 of 12, within two weeks or less, an effect that persisted in nine of 12 patients at four weeks. In those patients who received the two highest doses of 5 mcg and 10 mcg of UBX1325, all six patients showed a gain in ETDRS letters of visual acuity at two weeks and five of six at four weeks. We observed a change in the CST of patients as measured by spectral domain optical coherence tomography, or OCT. There was a decrease in the CST in six of 12 patients at two weeks and in five of 12 patients at four weeks. Amongst the high-dose patients, four of six patients showed a decrease at two weeks, and half of the patients, three of six, showed a reduction from baseline at four weeks. Amongst the AMD patients, we observed a clear reduction in both subretinal and intraretinal fluid in three of the four patients, including those at the lowest doses. I'd like to remind everyone that the patients who participated in this study were those with advanced disease and for whom anti-VEGFs were not considered beneficial by the investigator. We and a number of leading retinal experts with whom we review these data believe that the structural changes that were identified on OCT and the association with functional BCVA changes were clear indicators of disease-relevant biologic activity, and that such activity should coincide with improved visual outcomes in larger clinical trials studying patients with less advanced disease. Now let's explore each of these summarized points more deeply, starting with our safety and tolerability assessment. As you can see in the summary table, there was no evidence of acute inflammation or infection, nor were there changes in intraocular pressure. Indeed, we have been notified of two adverse events in total, as I noted in the top-line summary, both of which were considered consistent with ongoing progression of disease in those patients and both determined to be non-drug related. This slide shows the change from baseline in best-corrected visual acuity over the first eight weeks of the study in patients from the two highest dosing cohorts. The doses that we had modeled and predicted to be the most likely to fall in the efficacious exposure range. In this graph, we show the data from each individual patient. The violet colors represent data from patients from the 5 mcg cohort, and the gold represents those from the 10 mcg cohort. The dashed lines are those patients with neovascular AMD. As you can see, there was a rapid increase in the visual acuity in most patients very shortly after treatment. Additionally, changes in visual acuity appeared to stabilize at week four and maintain through week eight, despite having received only a single dose of UBX1325 at week zero. Of course, we continue to obtain data from these patients as they progress in the study through week 24. Although overall the data are consistent with a positive impact on BCVA, there was a single patient in the study that had a reduction in visual acuity, as noted on the figure by week eight. This patient represents one of those patients with a reported non-drug-related adverse event describing progression of disease. This patient received anti-VEGF rescue, and we will continue to follow them closely. Although not part of this study in a direct head-to-head comparison, we've provided some context to the BCVA changes that were observed in this study. Plotted in the X circles are data derived from the aflibercept VISTA study following dosing with this anti-VEGF agent every four weeks. Again, while not intended to be a direct comparison, these data of BCVA change from baseline demonstrate that UBX1325 has a favorable impact on visual acuity even after a single injection in patients with advanced disease and for whom anti-VEGF therapy was determined by the investigator to not be beneficial. On slide 18 are the data for the change in baseline of the central subfield thickness from baseline to week eight when available, measured by OCT and assessed by the central reading center for the study. Although changes were modest, there was an overall trend towards reduction of central subfield thickness across the study. In a number of patients, the reduction in CST was coupled to an increase in BCVA. However, after review of the OCT data from these patients, in some cases, we believe the CST measure underrepresents the degree of observed response that occurred in retinal regions outside the central subfield. This is best depicted by reviewing images of patients that responded well to UBX1325. As a safety study in patients with advanced disease, we believe that this is the best mechanism to determine whether UBX1325 demonstrates relevant pharmacologic activity in these patients. Now let's review some of the key image data from the study. For context, this title slide depicts an OCT image from an individual with a normal retina. Notice the concave nature of the retina at the macula, and the smooth linear layers of the retina itself without evidence of inclusion bodies, hyper or hypoechoic regions or streaks, or other abnormalities. Slide 20 includes images taken from a patient with diabetic macular edema who received 5 mcg of UBX1325. Before diving into the slide details, notice the inset on each image depicting the registration mark defining the retinal location of the slice. The two images are taken from near identical parts of the retina. To the OCT image itself. The image on the left was taken at the patient's first visit prior to receiving UBX1325. You notice that there is a large fluid-filled central cyst. This cyst is flanked on both sides by numerous large pockets of fluid in the subretinal space. The image to the right is the same patient now four weeks after treatment with a single dose of UBX1325. This image demonstrates a clear reduction in the central cyst, as well as a reduction in subretinal fluid on each side of that cyst. The lower right-hand graph shows how this fluid reduction was captured as a reduction in CST by the reading center. Finally, it is important to note that the reduction in CST is coupled to the increase in BCVA shown in the lower left-hand graph. The next images are taken from another patient with diabetic macular edema, who also received 5 mcg of UBX1325. In the baseline image on the left, you'll notice a complex fluid-filled structure in the retina, as shown by the red arrow. At this same location, four weeks after treatment with a single dose of UBX1325, there was a clear reduction of fluid in this cystic structure. This fluid reduction is also captured as a reduction in the CST as shown in the graph in the lower right. This reduction in CST was also coupled to an improvement in the BCVA for this patient. Finally, also noted for this patient was a decrease in a number of the hyperreflective foci, the white dots, one of which is shown by the white arrow as well. While the exact nature of these foci are not fully known, the resolution of these foci are considered a positive indicator of UBX1325 action. Now I'd like to show you an image of a patient with age-related macular degeneration. The image on the left represents the baseline retinal state for this patient. The red arrow identifies a significant amount of subretinal fluid that is depicted, and one hyperreflective foci is shown by the white arrow. In the right-hand image, by week eight, the fluid has nearly completely resolved. In addition, the hyperreflective foci have also resolved in this patient by the same time point. These are also examples of images demonstrating improvement in the retina in an area outside of the central subfield. Nevertheless, this patient also had a reduction in CST, as shown by the lower right graph, and an improvement in BCVA, as shown by the graph in the lower left. Now let's review images from our last patient with AMD that we'll be sharing today. The image to the left shows a pocket of subretinal fluid depicted by the green arrow, just to the right of a large central fibrotic region in the retina. This patient received 5 mcg of UBX1325. The image to the right shows the same region four weeks after treatment. We observed a significant reduction in the fluid in this region that was also manifested by a reduction in the CST as shown in the graph on the lower right. Importantly, this patient also showed a parallel increase in BCVA over the course of the first eight weeks of this study. In summary, what I shared with you is, number one, the fact that UBX1325 was well-tolerated with a favorable safety profile that supports further development of the molecule in patients with both diabetic macular edema or age-related macular degeneration. Overall, there was an improvement in best-corrected visual acuity in the majority of patients, with a larger proportion of patients in the highest dose cohorts with letter gain, and with overall increases showing stability through eight weeks. We also observed a trend towards improvement in the central subfield thickness in patients with both DME or AMD, as well as clear reductions in both subretinal and intraretinal fluid in patients with AMD. Finally, in a number of patients with clear structural evidence of pharmacologic effect, this study also demonstrated a parallel improvement in function as measured by visual acuity. In summary, we and many of the retinal experts with whom we've consulted believe UBX1325 as having biologically relevant activity in patients with advanced neovascular AMD and DME in a manner that both supports the further investigation of the molecule in future clinical trials, but also could represent a significant future therapeutic opportunity for patients with these devastating diseases. With that, I'd like to turn it back to Anirvan Ghosh. Thank you, Jamie. As you can see, these are very compelling findings for a phase I safety study that was not designed or powered to detect efficacy. You can understand why we are enthusiastic about the initial data we have seen with UBX1325. For us, the improvements in vision and CST are highly encouraging, and the initial data we observe is consistent with the aspiration we have for this drug and its potential to change the treatment paradigm in these diseases. I will remind you that this was a safety and tolerability study done in very advanced patients who are no longer expected to benefit from anti-VEGF treatment. They had not been treated with an anti-VEGF in the prior three months, and many of them had major structural damage. Frankly, we had no expectation that these patients would benefit from UBX1325, and many of them have major complications such as macular fibrosis or pigment epithelial detachments, which would make improvement in vision exceedingly challenging for any agent. To see improvement in such advanced patients is pretty remarkable, and we would expect greater therapeutic benefit in patients at earlier stages of disease, which we'll explore in our phase II-A study. I would also note that all of the data are in patients who are not concurrently receiving anti-VEGF, indicating that UBX1325 might be effective as a monotherapy. Based on the mechanism of action, we believe that this could evolve into a disease-modifying treatment by reversing the underlying pathophysiology and restoring tissue health and provide a novel treatment option for DME and AMD patients. We have initiated our phase II study in DME patients and look forward to sharing data from that study in the first half of 2022. We also shared earlier that based on the initial signals we have seen in AMD patients, we're enrolling additional AMD patients into the phase I study to further inform our decision on proceeding with a parallel phase II study in patients with neovascular AMD. We look forward to updating you on the progress of the two studies in the coming months. Many of you have followed the Unity story since the beginning. Others have joined our journey recently. It is not easy to introduce new therapeutic approaches, but we believe it is essential that we explore new frontiers to develop the next generation of transformative treatments. Unity embarked on a journey to develop a new class of therapeutics to target the root cause of disease by eliminating senescent cells. We have presented clinical data today that this senolytic approach can lead to improved vision and reverse the core pathophysiology of disease. We're excited about our journey ahead, and I'm optimistic that we are on the verge of developing a new class of therapeutics that could transform the lives of patients. With that, we'll be happy to take questions. Thank you. As a reminder, to ask a question, you'll need to press star one on your telephone. To withdraw your question, press the pound key. Our first question comes from Brandon Folkes with Cantor Fitzgerald. Your line is open. Hi, thanks for taking my questions, and congratulations on the data. Two quick ones from me maybe. The data looks very good. Looks very clean. Maybe just with no dose-limiting toxicities, do you expect to explore higher doses from here, or are you comfortable you have the right doses? Secondly, can you just remind us on the patient inclusion criteria for the phase II-A? You touched on disease severity, but just any other significant differences there we should be aware of as well. Thank you. Thanks, Brandon, this is Anirvan, I'll start off, I'll hand it to Jamie to elaborate on it a bit. As you saw, we see a very favorable safety profile of the drug, both at 5 mcg and 10 mcg is well tolerated. At this point, we don't see a reason to go to additional high doses. We predict that at this point, we get the exposure that we would need to fully engage the mechanism. We're seeing biological activity in very advanced patients, that's quite promising. We started out with a pretty severe patient population. We'll be moving to a more typical patient population and look at impact in a broader patient population as we move to the phase II studies. Jamie, I'll hand it to you to maybe elaborate on our rationale of 10 mcg as the top dose and inclusion criteria for the phase II study. Yeah. Thanks, Anirvan. Thanks, Brandon. Great question. We did a fairly substantial amount of modeling of exposures that were likely to achieve relevant pharmacology in humans, and those models were relatively conservative. That is, we used conservative estimates on all the parameters for the models and predicted that doses at or above around 2 mcg intravitreally would be effective. That we're able to escalate up to 10 mcg, as well as having observed biologically relevant findings in humans, gives us a lot of confidence in terms of the dose we've selected. We also want to make sure that we maintain the proper safety margins that continue the safe profile that we've observed so far. 10 mcg is likely to be the top dose that we'll be exploring. That said, we will be, in our later-stage studies, exploring dosing regimen as well to make sure that we're optimizing therapies for patients. All we're sharing today are those associated with a single dose. In terms of the phase II-A study that we have already started, you are correct. We're going to be studying patients with less advanced disease. There's not a ton of other details that we can share today that you can't find in clinicaltrials.gov to show the inclusion/exclusion criteria for that study. For the most part, we're looking at patients with diabetic macular edema across a range of disease states and advancements so that we can explore more broadly the effect of 1325 in that patient population. Great. Thank you very much to both of you, and congratulations again. Thanks so much. Thank you. Our next question comes from Salim Syed with Mizuho. Your line is open. Hi, this is Bennett on behalf of Salim. Congrats on the data, thanks for taking our questions. In the phase I, did you experience any challenge recruiting AMD patients? We were wondering, when do you anticipate having data for this possible second phase II-A in AMD? Also, if you could remind us, please, that those being tested in the phase II, I mean, understanding it's 10 mcg, since, if I'm not wrong, this 10 mcg dose was introduced a bit later in the phase I. Are you anticipating any delays in the data readout timing for the phase II-A? Thank you. Hi, let me comment on it, and Jamie can add if there's anything I miss. With regard to the first study, as Jamie covered in that 12 patients with eight DME patients and four AMD patients. It was designed to include both DME and AMD patients. It is with a goal of initiating a phase II study in DME, which we have recently initiated and announced the dosing of the first patient in that study. With regard to AMD, it is not a matter of any particular difficulties recruiting AMD patients. I would say to some extent, what was remarkable is that although we had only four AMD patients in that study, in three of the four patients, we saw evidence of fluid reduction and paying attention not only to the CST but also to adjacent areas and looking at subretinal fluid. That was seen as being particularly striking by many of the experts we spoke to and the KOLs we spoke to, and frankly encouraged us to explore the possibility of accelerating an AMD study as well. As we shared earlier, we have been recruiting additional AMD patients into the phase I study so that we can generate a bit more AMD data that will inform our decision as to whether we want to initiate a parallel phase II study in AMD as well. We're super excited about the AMD data, along with the DME data that we shared. With regard to the dosing of patients in the phase II, everything is on track as previously communicated. We indicated that we would go in with a 10 mcg dose, and we do not anticipate any issues with enrollment of that study. Jamie, is there anything else that I might have missed you can add to? Those might have been the main questions we had here. I think that's good, Anirvan. I think you covered all the questions unless there was additional. Okay. Thanks, team. Thank you. Thank you. Our next question comes from Matthew Harrison with Morgan Stanley. Your line is open. Great. Good morning. Thanks for taking the questions. I guess a few from me. Can you talk about dose selection? Obviously, you're looking at a higher dose in phase II. Can you talk about how this data informed that dose selection? I guess second question is about your thoughts on multiple doses, or perhaps, maybe this goes to the higher dose, but it looks like sort of in the four to eight-week time period, there was some rebound in a handful of patients. I realize there could be also noise here, but just curious about multiple doses. Then third question is more broadly on OCT. Maybe just for some context, you put some data on OCT for the patients there. Just in terms of improvement in retinal thickness, how does that compare what you guys are seeing compared to traditional VEGF therapy? Thanks. Thanks, Matthew. I'll lead off, and I'm sure Jamie will have additional details to add. First of all, with regard to dose selection, we had gone into the phase I study with the anticipation of 5 mcg and 10 mcg being in the predicted therapeutic dose. Based on all the preclinical data we had modeled that at that level, we would have target engagement of 90% or greater, and that if we were to achieve that dose, we would move forward to the phase II study with the maximum dose if it achieved. Based on that, we were able to clear both the 5 mcg and 10 mcg doses. Since 10 mcg was the highest dose we had in the study, and it was predicted to engage the target as required, that's the dose that we have advanced to the phase II study. Your question about multiple doses is really important. A reminder again that all of the data we saw today is single-dose data. As you'll remember from the early days of anti-VEGF therapies, the single anti-VEGF treatment provides single efficacy at about one month. That is largely gone by about two months. That led to the evolution of the current treatment paradigm, which involves an initial loading phase, followed by a maintenance phase. With leading anti-VEGF therapies today, as you know, there's typically a once-a-month loading phase for the first three months. Patients will move into once every other month regimen. There's a lot of interest in understanding that beyond the initial loading phase, what kind of durability one might achieve. In our case, the single-dose data look quite favorable to us compared to previous anti-VEGF studies. We are very interested in maximizing treatment value and are in the middle of tox studies that will enable multiple dosing studies in patients. I expect that when we move to the phase II-B study, we'll be able to explore both the impact of single injection as well as an initial loading regimen, and then extending to see what kind of durability we might achieve. It might well be the case that with initial few doses, that might provide even greater benefit than what we're seeing here. I'd also note that everything we're seeing here are in very advanced patients for whom anti-VEGF was believed to no longer provide benefit, and we expect that as you go to a more moderate patient population, we might have greater benefit. Finally, with regard to the OCT data, I'll have Jamie comment on it more. I think one thing that we noticed is, of course, we see these initial signs of CST changes. I recall, we had a number of calls with the KOLs and experts before we were having this call. They were particularly focused on a couple of things. One was around patients in whom you see this concordant change of improvement in vision and a change in CST. You recall in patients like patients nine, 13, seven, 12, we would in most of the field separately plot BCVA and CST data. We see many examples where we see these reciprocal changes, which I think give us confidence about the biology we're observing. I'll hand it to Jamie to maybe comment on other parts of the imaging data that I might have missed. Thanks, Anirvan. Thanks for the question, Matt. I don't have a lot more to add. A couple of key things, I think, just to provide a little more color. In terms of how this compares to standard of care, you'll recall, as Anirvan just mentioned as well, that these were patients for whom the attending physicians for these patients no longer felt anti-VEGF would be of benefit. As well as the fact that these are advanced patients, we did not have a priori expectation that we're going to see any biologically relevant pharmacology here. Yet we're finding both improvements in structure by OCT and concomitant improvements in BCVA. Those changes taken together are very encouraging. We are, as well as Anirvan mentioned, many of the experts with whom we've consulted are both highly supportive of moving this molecule into further studies to help us clarify the overall benefit over time. The other thing, you mentioned that there might have been some rebound at around four, eight weeks. It's hard to call that out from these data sets. There's just so few patients, and there is some noise in the system. Yet, what is also clear as I've stared at these data is that the data between four and eight weeks appear to be pretty stable. It does call in the possibility that an initial response could be sustained for a longer period of time. That's why it's going to be so important to your multiple dose question, why it's going to be very important in our later stage studies to explore beyond a single dose, especially in the loading phase, the induction phase of treatment. We do want to ensure that if 1 dose is optimal, that we have proven that. If we need two or three loading doses prior to a strongly durable response, that would be okay as well. Those need to be studied, and that's our intention as we continue progressing the program. I'll stop there and see if you have any follow-ups. Nope, that's great. Thank you very much. Thank you. Our next question comes from Yigal Nochomovitz with Citigroup. Your line is open. Great. Thank you very much for taking the question. Obviously, the therapeutic hypothesis relies on eliminating senescent cells. With that in mind, have you developed an assay for measuring the senescent cell burden in the retina to confirm that 1325 is having the desired effect in eliminating senescent cells? If you have such an assay, what has it shown so far? Thanks. Hey, thanks, Yigal. A very important question. Just as a reminder for others on the call, the core therapeutic hypothesis here is that with UBX1325, a BCL-xL inhibitor, you would be able to eliminate senescent cells in the vascular endothelium. Our confidence of this mechanism really comes from a wealth of preclinical data, where in disease models where we can create an increased senescent burden in the vasculature, we find that this mechanism selectively eliminates senescent cells while leaving the healthy cells nearby unaffected. That was the basis of our selecting those for the human study. As you alluded to, there is not an established way of detecting senescent cells in the eye. While this is something that we would love to have down the road, in our case, we felt that the best biomarker we could use to understand whether we're impacting the disease was to study the impact on the biology that should be driven by the senescent cells. Based on our hypothesis, we predicted that that should lead to a reduction in fluid accumulation and reduction in central subfield thickness. That data that we see an effect on the biology that's predicted through the senescent is encouraging to us. We are in the process of exploring really getting new tools to see whether we can detect cells undergoing apoptosis, whether those can be adapted to the human eye. As you know, it takes a long time and a lot of work to get a validated imaging biomarker like that in the eye. We are continuing to work, and I'm optimistic that over time, we will also develop those tools. Thank you, Yigal. Okay. Thanks. I just had one specific question on patient 0009, the DME patient. They had a pretty sharp drop in BCVA between weeks two and four, but the central subfield thickness continued to decrease from weeks two to four. I'm just wondering if you have any more granular thoughts on what might be going on with that patient that showed a continued decrease in thickness but did not have a concordant increase in BCVA over that timeframe. Yeah. Maybe I'll start out, and then I'll have Jamie comment. I'll start out by reminding everyone that these two measures that are widely used, BCVA and CST, while as a population level, they've been found to be very important in the measures of a treatment effect. At the individual patient level, the correlation is not very good. There's some really excellent publications with regard to the anti-VEGF literature that will show that a relatively small part of the improvement in vision is accounted for by changes in CST. One needs to be careful about how much one can interpret from an individual data change in CST and BCVA. I'd also note that when we reviewed these data with our experts, they were paying quite a bit of attention to not only what is happening in the CST, but also in other areas of the eye, including fluid in adjacent areas. Here you can see that we show a CST measure, but there's also additional fluid in adjacent areas where you see a decrease. Not all of that is quantified in this particular graph. Some of the other changes beyond the CST could also be contributing to improvement in vision. For us, I think that the totality of data indicates that there's an improvement in the structure in the retina. We're quite encouraged to see the improvement in vision in this particular patient. I'm not sure that just the CST BCVA connection at a given time point would best describe what might be driving the improvement in the patient's vision. Jamie, I don't know if you want to add anything to it. Hopefully, that addresses the primary points. I think that covers most of it. I just would add one small piece to this is, especially in diabetic macular edema, diabetic eye disease in general, we know that there's a number of things that impact visual acuity in patients with diabetes outside of just the fluid in the retina. There's enough noise looking at single individual patient data that sometimes it's expected that there's going to not be a perfect relationship between CST and BCVA. Overall, we find the improvement in patient nine that you described to be convincing as well as really encouraging us to continue to pursue this drug. Patient nine, we think had a response that is indicative of improvement of the overall health of the retina and with an initial significant improvement of BCVA, quite substantial. This is the kind of patient that we would love to continue to explore over time and eventually go to multiple dose regimens in the future. For us, these are all encouraging data. Maybe I'll just add one thing that your question triggered, which is that. We're all kind of used to focusing on the CST largely based on our previous anti-VEGF data. In this particular case, we're coming into the eye with a completely new mechanism. Another thing that I would say that a lot of our experts found quite remarkable to have an orthogonal mechanism that exerts biology and also urging us to explore or understand where else the biology might be exerted. As I mentioned a little while ago, we believe that much of that is probably in the vasculature of the eye. Even if one is not able to image senescent cells in the vasculature, there are sensitive ways of imaging overall vascular health and vascular dynamics. One of the things that we are looking forward to in the phase II-A study is to gather additional data on the vasculature in the eye that I hope will complement what we see with the BCVA and CST measures. Thanks. Got it. Thank you very much. Thank you. We have a question from Elemer Piros with Roth Capital Partners. Your line is open. Yes, good morning. I just wanted to confirm, Anirvan Ghosh, if the phase II-A study would be a single dose and at what point would you have enough toxicity data to introduce multiple doses? Hi, Elemer. Yes, this is to confirm that the phase II-A study is a single-dose study in DME patients. That is a placebo-controlled, sham-controlled study. It is really designed to better understand the efficacy in a broader patient population to help optimally design the phase II-B study. We expect some data from the study in the first half of next year. We also expect the tox data during that period that would enable a multiple dosing study in a phase II-B study after that. I would expect that by the end of the first half of the year, we would both have the data on the phase II-A study as well as the tox that would inform the phase II-B study. Thank you. You also mentioned that there was one patient that was given a rescue anti-VEGF treatment. Did that make a difference for the patient? Yes. I'll hand this question, Jamie, for you to address with regard to the one patient that received an anti-VEGF rescue. There were actually two patients that received rescue in this study. As I told you, there were two adverse events that were considered progression of disease. The one patient that I showed the data for, it's too early to be able to report any impact of the anti-VEGF. In the other patient, who is in one of the much lower dose cohorts, that anti-VEGF did have a response to that patient, though they continued to progress in terms of visual acuity. Thank you so much. Thank you. I'm showing no other questions in the queue. I'd like to turn the call back to management for any closing remarks. Thank you. Thank you for all the questions, and thank you for joining the call this morning. I hope that you understand why we are very enthusiastic about this early data set in a study that was designed primarily to be a safety and tolerability study in very advanced patients. To see signals of efficacy is quite heartening. We look forward to sharing additional data both from this study as well as the phase II-A study in the months to come. Thank you very much. This concludes today's conference call. Thank you for participating. You may now disconnect. Everyone, have a great day.