Good day, ladies and gentlemen, and welcome to Unity Biotechnology, Inc. conference call. At this time, all participant lines are in a listen-only mode. Later, we will conduct a question and answer session, and instructions will be given at that time. To ask a question, you will need to press star then one on your telephone. As a reminder, today's call is being recorded. If you require any further assistance, please press star then zero. I would now like to hand the conference over to your host today, Lynne Sullivan, Chief Financial Officer. Please go ahead. Good morning. Thank you for joining the Unity Biotechnology conference call this morning to discuss the 12-week results from our phase I study of UBX1325. With me on today's call is Robert Bhisitkul, Professor of Ophthalmology and Director of the Retina Fellowship at University of California, San Francisco, a renowned retinal specialist. 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'll be making some forward-looking statements, which are subject to 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, and we do not 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 everyone joining us on the call today. We're excited about the progress we're seeing in the phase I single ascending dose study of UBX1325 in patients with advanced diabetic macular edema and age-related macular degeneration. Today, we are reporting data from these patients 12 weeks following a single intravitreal injection of UBX1325, the first senolytic treatment being explored for these indications. We previously reported improvement in vision and retinal structure at eight weeks following treatment. We are pleased to see those responses sustained through 12 weeks, an important time point in the management of these diseases. As I've mentioned before, DME and neovascular AMD 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. We've invited Robert Bhisitkul from UCSF to join us again today. He's a retina specialist who has had the opportunity to review the phase I data in detail, including the previously reported data at eight weeks in addition to this latest 12-week data. We will share his perspective on the data on the call today. I will begin with a brief background on Unity and the role of senescence in certain age-related eye diseases, and then hand it to Robert to go over the data. Our CMO, Jamie Dananberg, will discuss the phase II-A development plan for UBX1325 before closing remarks and Q&A. On to slide four. At Unity, we are focused on developing transformative medicines to slow, halt, or reverse diseases of aging. The primary areas we are focused on are in ophthalmology and in neurology, and the primary biology we are targeting is cellular senescence. I am going to go over briefly about what senescent cells are and why we believe they contribute to disease progression. I will also discuss our senolytic approach to target that biology and how we are applying it to DME and AMD. On slide 5, we highlight key upcoming milestones. Today, we are reporting 12-week data from the phase I SAD study of UBX1325 in patients with DME and AMD. Still ahead, we expect to share 24-week data from the SAD study, as well as report eight -week data from an additional cohort of neovascular AMD patients from the UBX1325 phase I study before the end of the year. Our phase IIa proof of concept study in DME is underway. The first patient was dosed last June. 12-week safety and efficacy data are expected in the first half of 2022. Additional programs in our pipeline are advancing well. Our Tie2 monoclonal antibody program and our alpha-klotho programs are projected to enter IND-enabling studies in 2022. On slide six, you see our pipeline, which highlights the novel mechanisms we're advancing as alternatives to the standard of care in ophthalmology. BCL-XL inhibition, Tie2 activation, and a dual Tie2-VEGF bispecific are promising modalities for patients with these diseases. Our neurology programs are advancing in early preclinical development, and we hope to have more to report on these programs in the coming year. Now on to slide seven. UBX1325 is the first senolytic agent to be taken into eye diseases and show potential as a disease-modifying therapy. phase I data indicates that it has a favorable safety and tolerability profile. Initial review of the data indicates that after a single dose of UBX1325, we see rapid improvement in vision in a number of patients, as well as improvements in retinal structure. Importantly, analysis of the eight-week data and the 12-week data sets indicate sustained response following a single treatment. We're particularly excited about that potential as it begins to signal how this treatment could provide a differentiated treatment option from the current standard of care. As we think ahead about the need for treatments like UBX1325, it is important to note that it is a mechanism that is distinct from anti-VEGFs, and therefore, we believe that it would work as a monotherapy or together with anti-VEGF agents. By reversing the pathophysiology of disease, it could lead to a disease-modifying treatment option. Taken together, the data support targeting senescent cells as the root cause of many diseases and as a new approach to improve outcomes. In the past, we have shared our research showing how senescent cells are found in a number of other diseases and a number of other indications, and we're excited to explore the impact of this approach in other diseases as well. On slide eight, you'll see what cellular senescence is and why we believe it contributes to disease progression, and how we're attempting to target that biology to improve patient outcomes. We can see going from left to right, the progression of disease illustrated here, we see that over the course of disease, there's an accumulation of cells that are dysfunctional, often generated by stressed conditions. These cells stop dividing but are metabolically active and can secrete factors that can damage the local microenvironment. These cells are called senescent cells, and we have generated extensive data that indicate that if you're able to eliminate senescent cells, you can alter the trajectory of the pathophysiology that characterizes the disease. With that in mind, we have been developing senolytic medicines that can target and eliminate those cells. On slide 9 nine we show you the senescence disease hypothesis in the context of eye disease. In AMD and DME, there's an accumulation of fluid in the retina, and that is accompanied by loss of vision and creates disability. We believe that as the disease progresses, there's an accumulation of senescent cells in the blood vessels indicated in the lower part of the slide. Those senescent cells can secrete factors that lead to an inflammatory environment in the eye and can also lead to vascular leak. Our goal is to develop agents that will remove those senescent cells and restore blood vessels to a healthier state and change the course of disease progression. On slide 10, you see how UBX1325 acts upstream of anti-VEGF therapies. UBX1325 acts in a cascade that we believe leads to disease progression. In the context of diabetic eye disease, the cellular stresses that the eye and the vasculature face leads to an accumulation of senescent cells in blood vessels, which in turn leads to accumulation of a number of inflammatory factors shown in the lower part of the slide. You're all familiar with drugs that target VEGF, which is one of those factors. Factor, when targeted, leads to considerable benefit in patients with DME. With UBX1325, we are targeting a node that is upstream of these factors, and we believe that this could lead to a greater benefit and greater durability of effect. On slide 11, we show preclinical data from a recently published paper in Cell Metabolism. On the top left, we see the biochemical activity of UBX1325, a BCL-XL inhibitor. Here we're seeing effective reduction in BCL-XL activity in both normal eyes and in an OIR mouse model of retinopathy. Importantly, when you look at the bottom left graph, you see that in the OIR model, the treatment leads to a rapid and significant increase in caspase activation, which is the mechanism by which cells are eliminated. However, in the normal eyes, you do not see caspase activation, and this is what protects normal eyes from being affected by the treatment. On the top right graph, you see the consequences of the treatment. We see very significant reduction in neovascularization and significant reduction in the avascular areas of the eye. On the right, you see images from retinal flat mount from this mouse model. On the top right are examples of the diseased eye, where you see that near the middle of the field, there's a large ischemic area, and near the periphery, you see aberrant neovascular growth. In eyes that have been treated with UBX1325, you see a reduction in the ischemic areas, indicating growth of healthy blood vessels, and in the periphery, you see healthy vasculature restored by UBX1325. This slide shows the aspiration profile of UBX1325, which we believe could provide a superior option than the current standard of care. We believe UBX1325 could have a rapid effect on improvement in vision and structure and could lead to greater durability than the standard of care. It is a novel mechanism with favorable pharmacology, because of that, it could act either as a monotherapy or in combination with anti-VEGFs. We see effect of the drug in patients who are no longer eligible for anti-VEGF therapy and therefore could provide an important treatment option for patients who are not responding well to the current standard of care. Our preclinical data show the possibility that this drug could lead to improved vasculature and regrowth of blood vessels into ischemic areas of the eye, which anti-VEGFs cannot achieve. This could be an important differentiation in diseases like diabetic retinopathy and diabetic macular edema. We also see that because we are targeting a fundamental disease mechanism, that it is a truly disease-modifying option for patients suffering from AMD and DME. The next slide, we summarize our clinical development plan. The phase I study of UBX1325 is ongoing. We have completed the single ascending dose phase in advanced patients with DME and AMD. Based on what we saw in these initial patients, we are enrolling additional AMD patients and expect to report eight-week data from those patients by the end of the year. We have also recently initiated a phase IIa DME study. This is a sham control study where we'll follow patients following a single dose of UBX1325, and we expect to share 12-week safety and efficacy data from that study in the first half of 2022. We're also exploring the possibility of starting a parallel phase IIa study in neovascular AMD that could also generate data in the first half of 2022. I should mention that we're looking forward to sharing the 12-week data very soon and in today's call that the 24-week data is not far behind, and we'll be sharing that before the end of the year. I'd like to hand over the call to Dr. Bhisitkul to review with you the 12-week results from the phase I study of UBX1325. Thanks, Anirvan. This is the inclusion criteria and exclusion criteria for this phase I single ascending dose study. The inclusion criteria for patients with diabetic macular edema were that the patients were older than 18 years of age and had center-involved diabetic macular edema with a central subfield thickness of greater than or equal to 350 microns. For the patients with neovascular AMD, it was required that they be greater than or equal to 50 years of age, and that they had evidence of active choroidal neovascularization on the fluorescein angiogram with the OCT showing intraretinal and/or subretinal fluid indicating active disease. For the visual acuity in the study eye, it was required to be 20/80 or worse through the first 2 drug cohorts, and after that, it was 20/40 or worse. This is the design of the study. It's a single ascending dose trial, starting at the lowest dose of 0.5 micrograms and going up to 10 micrograms. There were three patients in each cohort, and there was first a sentinel patient. When safety was determined with that patient, it went on to include the remaining patients in that dose cohort. When that cohort was found to be safe, it was to go up to the next ascended dose there, all the way up to 10 micrograms. A couple things to point out about the study population. These are advanced patients, both with severe diabetic macular edema and with the neovascular AMD. The patients were determined by their treating physicians to no longer be receiving a benefit from standard of care anti-VEGF. The non-responder or incomplete responder population for both of these diseases was enrolled into this study. This is, I think, a critical point as well. The design of the study required a washout period. Before entering into the study, the patients had to cease their anti-VEGF therapy for three months preceding enrollment, and that also included any treatment with ocular steroids as well. As we noted, the patients with DME had to have greater than 350 microns thickness on the OCT, and the AMD patients had to show evidence of subretinal or intraretinal fluid. The summary of the results is that the drug was safe and well-tolerated. No dose-limiting toxicities were seen, and there were two non-serious, non-drug related adverse events through the first 12 weeks. In terms of vision, there was a gain in the ETDRS letters from baseline. Overall, eight of the 12 patients in the study showed some gain at eight weeks and at 12 weeks. In the two higher dose cohorts, five of the six patients showed a gain of vision at these two time points. In terms of anatomy and retinal structure, the OCT showed that there was a central subfield thickness decrease from baseline, and this was seen in eight of the 12 patients overall at eight weeks and eight of the 10 patients at 12 weeks. This same decrease in improvement in the OCT was seen in the higher dose cohorts in five of the six patients at eight weeks and three out of the five patients at 12 weeks. This is a list of the adverse events that were noted, and as I mentioned before, there were no serious adverse events that were seen, nor were there any drug-related events that were seen. Overall, there was good safety and tolerability to advance UBX1325 to further clinical studies. This shows the data through 12 weeks for the patients with diabetic macular edema, and they are coded according to the drug dose that the patients received from 0.5 micrograms to 10 micrograms. As a comparator, the aflibercept results from the registration trial VISTA are shown as the red crosses here for a cross-trial comparison. From this, we can see that the majority of the patients are above the line. That is, they have visual improvement compared to the baseline. Previously, we discussed the results at eight weeks. We can see here that there's a sustained improvement or sustained benefit of that effect from 8 weeks to 12 weeks, again, indicating that there's some durability of the effect here with the UBX1325 treatment. This is showing the visual acuity data over 12 weeks for the patients with neovascular AMD. Again, we see patients who have an improvement in vision compared to baseline. For these patients with the improvement that we saw at eight weeks, it appears to continue on its benefit to 12 weeks, showing that sustained effect. Point out that one patient here required rescue because of visual acuity loss. This is a patient in the 10 microgram dose. We had our KOLs do a deep dive on this patient, and it was found that the patient had some questionable things about the diagnosis. Possibly this patient had polypoidal choroidal vasculopathy, and in future, these patients will not be included in the UBX1325 trials. This 10 microgram dose will be further explored in an additional seven patients with neovascular AMD in a study subset that is now ongoing. We'll have more data for these neovascular AMD patients at the highest dose forthcoming. Here we're looking at just the two higher doses of UBX1325. Again, we see favorable results with above the line vision effects that are sustained out to 12 weeks for the majority of the patients at both of these doses, both for the DME patients overall and for one of the two neovascular AMD patients that are shown in this study. The final analysis is shown here. This is looking at the OCT and the central subfield thickness through 12 weeks. Here for the two higher doses, we see in a number of the patients that there is a decrease in the central subfield thickness. That is an improvement in terms of the macular edema and the fluid, and this is sustained for these patients out to 12 weeks as well. Next, we'll go through some individual patient cases, both patients with diabetic macular edema and with neovascular AMD. We'll show one case here of a patient with diabetic macular edema. Again, as a retina specialist, I'd look at this OCT here for the patient at baseline and see that this is a severe case of diabetic macular edema, one of the most severe that we would encounter in clinic, with these large chronic appearing cysts here, as well as diffuse intraretinal fluid. We can see after a single dose of UBX1325 on the right, we see improvement both in the macular thickness and in reduction in the size of that chronic cyst. Not complete resolution, but definite reduction in the fluid. That can be seen here on the graph showing the central subfield thickness as well. This patient enjoyed a visual acuity gain over this time period as well. Here's a second DME patient, again with severe chronic macular edema, and after a single dose of UBX1325, we see noticeable improvement and reduction in those cysts and fluid. That's associated with a visual acuity gain that can be seen on the graph in the lower left-hand corner. Turning now to patients with neovascular AMD. This is a patient showing at baseline the typical reflective material underneath the retina, which indicates probably the choroidal neovascular membrane itself. Then overlying this, we see that black subretinal fluid and some thickening of the overlying macula. After a dose of UBX1325 on the right, we can see that the subretinal fluid is resolved, and there's some improvement in the overlying macular thickness as well. That's associated with a visual acuity improvement here with the patient over the time period, as well as that reduction in the central subfield thickness. We can also point out that there are some hyperreflective foci at baseline that with a suggestion that those intraretinal hyperreflective foci are resolved after UBX1325 treatment. Here's a second patient with wet AMD. Again, we see that hyperreflective SHRM underneath the retina. Alongside this are two areas of subretinal fluid, that more obvious one pointed out by the green arrow, and then a more subtle area on the left slope of the lesion, showing those little dots of subretinal fluid underneath there. Again, after UBX1325, we see some improvement in this with reduction in that subretinal fluid on the one side and complete resolution of that very subtle fluid along the left slope of the lesion. Again, this is associated in the patient with visual acuity improvement, and over time, we see reduction in the overall central subfield thickness in this patient as well. I'll turn this back over to Jamie. Thank you, Bob. I'd like to summarize the data that was just presented. It's extremely helpful to hear the review and insightful observations from someone who treats patients with ocular disease every day, and that was very helpful. Thanks again, Bob. I'd like to recap the data that was just presented of the phase I results for 12 weeks. UBX1325 was well-tolerated with a favorable acute safety profile, further supporting additional development. There were no dose-limiting toxicities up to the highest dose of 10 micrograms. There were no serious adverse events. There were no adverse events attributable to UBX1325. With respect to visual function, we identified a rapid and relevant increase in best-corrected visual acuity in most patients at 12 weeks. Amongst patients in the higher dose cohorts, all but one showed letter gain from baseline to 12 weeks. Structurally, there was a trend to decrease CST from the baseline, a relevant correlate to the gain in visual function. Most patients demonstrated such a decrease in CST at both eight and 12 weeks, and within those patients in the higher dose cohorts, again, all but 1 had a decrease in CST that was maintained through 12 weeks. Not only are we encouraged by the gains in letters and the improvement in structure, but we're also encouraged by the sustained responses out to 12 weeks following a single administration of UBX1325. These data support our decision to proceed to a phase II proof-of-concept study in patients with diabetic macular edema, a study we started earlier this summer. I'd like to share some of the design elements and endpoints of that study. These patients with DME less advanced than what was studied in our phase I SAD study. The patients are currently receiving their regular scheduled anti-VEGF treatment and have had at least three consecutive anti-VEGF injections in the past six months and still have residual structural edema with a CST of at least 350 microns. At the time of what would have been a consecutive anti-VEGF injection, they will instead receive either UBX1325 or sham injection, and we'll be following these patients for both safety and efficacy endpoints out through 12 weeks, with an additional follow-up through 24 weeks. This study design allows us to explore a number of elements for these patients to help us understand the activity of 1325 in a set of patients who are earlier in their disease course compared to those enrolled in the phase I study and for whom we believe 1325 could represent an important therapeutic option. Shown here is a summary of the endpoints being evaluated in the phase IIa proof-of-concept study. We will continue to evaluate the safety and tolerability of 1325. In addition to standard measures of safety, we'll also be assessing improvements in visual function by BCVA and retinal structure by CST and DRSS score, and the proportion of patients who require rescue with anti-VEGF agents as well. We'll also explore the ability of UBX1325 to improve capillary non-perfusion, a potentially important differentiating feature of this new investigational agent. I'll now hand it back to Anirvan Ghosh for final comments. Thank you, Jamie. We believe that UBX1325 could have a best-in-disease treatment profile. It shows potential for rapid effect with greater efficacy and durability than what patients are currently receiving with the standard of care. We believe that it's important to note that it is a novel mechanism of action with a favorable pharmacology and safety profile. It means that the drug could be used as first-line therapy, it could be used in combination with anti-VEGF treatments, and finally, it could be used in patients for whom anti-VEGF agents failed to demonstrate ongoing efficacy. We believe that it could have unique properties, such as improvement in retinal and choroidal vasculature, which could strongly change the trajectory of disease for these patients and make it truly a disease-modifying agent. Therefore, for us, this represents a unique and extremely important opportunity that could greatly impact the trajectory of patients with AMD and DME. In closing, we see a lot of momentum building behind the UBX1325 program, both in the clinic with investigators as well as with the physician community. Ahead of us, we expect to share eight-week data from the additional neovascular AMD cohort before the end of the year. We also expect to share 12-week data from the phase IIa DME study in the first half of next year. I also mentioned that we expect to have 24-week data from the SAD study before the end of this year. You see that we have a lot to be excited about at Unity with this data flow coming up, and we appreciate your continued interest and support. I'd like to close by thanking Bob for the time that you took to go through the data carefully. I'd also like to thank Jamie for sharing the design of the phase IIa study. The enthusiasm that we see within the KOLs community and the investigator community is truly contagious, and we're very excited about advancing new treatment options for patients. That concludes our formal remarks. We'll now open the call up for questions. Thank you, to ask a question you will need to press star then one on your telephone. To withdraw your question, please press the pound key again that is star then one, if you would like to ask a question. Our first question comes from the line of Brandon Folkes with Cantor Fitzgerald. Your line is now open. Hi. Thanks for taking my questions, and congratulations on the data. Maybe just two high-level ones from me. Just firstly, for the Unity team. Yeah, the data's looking very good. I'd love to get some context in terms of what you're seeing in the data to date. How does that compare with your hypothesis? Any surprises at this stage to the upside in the data, compared to, I guess maybe what you're expecting. Just for the KOL, granted it's early stage, similarly in this data set that you see, any subsets of patients that you think UBX1325 could really benefit beyond what we're studying in this inclusion criteria? Thank you very much. Thanks, Brandon. Let me take the first part of the question, and then I'll hand it to Dr. Bhisitkul to address the second part about subsets of patients. Brandon, with regard to the mechanistic hypothesis, as you know, with the senolytic mechanism, we expect the drug to clear senescent cells fairly soon after treatment. In preclinical models, we see those effects within a couple of days. One of the things that's exciting about this mechanism is that the PD effect is expected to last longer than the PK of the drug, so that drug should get clear from the eye relatively quickly. Since you've eliminated the source that might be driving vascular leak and vascular pathology, the effect of it should last much longer. That is what we had seen in the initial animal models. What was hard to predict from the animal studies is the durability of effect when we moved to patients. I think what is really exciting for me in this data set is that not only did we see fairly rapid improvements in vision and improvements in various aspects of retinal structure in many patients soon after treatment, which we had shared, when we shared the eight-week data. Now when we look out to 12 weeks, I think the sustainability and stability of it is really quite striking. If you look at that data set with BCVA at four weeks, eight weeks, 12 weeks, you see the people who have a gain at four and eight really continue to maintain the gain. That's really important, right? I think with most therapies or drugs out there, even under investigation, there is a need for repeat dosing at some level. It's fairly high frequency often. Standard treatment paradigm would be two to five repeat doses in the beginning, followed by some duration, maybe every other month dosing. What we see as a sustained effect after a single injection out to 12, it begins to suggest that we might really be getting to the kind of durability we were hoping for when we started the mechanism. I think, at least to my eyes, the upside is that in this first study and in very advanced patients, we see the sustainability and, of course, we continue to follow the patients, and we'll have 24 week data from these patients, in the coming weeks to months. For us, that's really quite exciting. I will hand it to Bob for the second part of the question. Brandon, you might need to elaborate, but Bob, you might have caught the essence of it. Yeah. I think the second part of the question was, is there a subset of. Sorry, I don't know if you're asking me, but because you cut out. Yeah, Brandon, sorry. Dr. Bhisitkul, your audio might be cutting out a little bit. I don't know if we don't hear you, then Brandon would have you repeat the question, then maybe Jamie might be able to take it. Brandon, would you mind repeating the question, and then we can have maybe Jamie address it? No problem at all. The context was just trying to sort of think about the overall patient population. When I look at this inclusion criteria, we see very, very strong data in this patient, this subset of patients. Just wondering as we sort of, not to get too far ahead of our skis, but think about a broader patient population in practice that KOLs could get excited to use this drug, based on the data we've seen to date beyond just this patient population. Got it. Jamie, maybe you could take that, if Bob is able to reconnect on his phone, he could add to it. Yeah, that'd be great. Thanks, Brandon Folkes. This population, as you remember, to be reminded, is a rather advanced patient group who no longer have been considered no longer benefiting from anti-VEGF therapy, so they've been off all therapy. The initial patients were all pretty severe in terms of their visual acuity. As we advance into later-stage studies, we'll be exploring significantly broader populations of patients, more typical patients who are either on anti-VEGF or benefiting from anti-VEGF or much earlier in their disease. We believe there's a reasonable likelihood that those patients will also show similar, significant benefits in visual acuity, after treatment with, in this case, just a single dose of UBX1325. We believe that given the orthogonal nature of the mechanism of action of UBX1325 relative to standard of care, it's certainly possible that this agent could be used on its own, in naive patients. It could be used in combination with anti-VEGF, as a supplement or Ability to potentially resensitize patients to that action or to be used in patients who failed anti-VEGF therapy, giving us multiple patient populations for whom this could be beneficial. Jamie, I'm back on the call now. Okay. Thanks, Bob. Okay, thanks. Good to hear. Bob, I don't know if you wanted to add anything to that. We just couldn't hear the first part of your audio. Yeah. Just the patient populations question. Here we're looking at very severe advanced disease that's anti-VEGF non-responders. I think this is an interesting population, but another interesting population might be looking at patients that are in earlier stages of their diseases, where the UBX therapy could have even preventative effects or halt the advance of the disease to these more stages of disease where we don't expect to see a big turnaround. Thanks, Bob. Can I just underline one additional piece that emphasizes Bob's last point is that is the possibility of 1325 being truly disease modifying. That is, change the trajectory of the course of these diseases. What we're seeing in this study is the ability of a single injection to both improve BCVA and stabilize it. That is not the normal course of disease in these patients, especially not these advanced patients. We would assert that's true in even less advanced patients. As we know, for example, in AMD, these patients lose a letter a month without treatment. These patients have been off anti-VEGF for at least six months after showing you the 12-week data because they were off anti-VEGF for a minimum of three months prior to this. The fact that we're able to both improve vision and maintain it suggests that 1325 has a disease-modifying activity, which we think is quite unique and could be transformational in terms of treatment of these diseases. Thank you, Jamie. Thank you. Our next question comes from the line of Salim Syed with Mizuho. Your line is now open. Great. Thanks so much guys for all the color and congrats on the data. Just a couple from me, for Dr. Bhisitkul, perhaps. Dr. Bhisitkul, when I look at the BCVA chart, we just look at the lowest dose, which is the blue line, the highest dose, which is the orange line, it says 0.5 micrograms and 10 micrograms. It seems like they overlap quite a bit, I'm wondering what your view is and what could explain that. The second question is, just on the CFT measure here, subfield thickness. I don't think you guys had shown the lowest dose here in the slides, the half a microgram. I was curious if, since you're seeing the increase on visual acuity, I'm wondering if you're seeing a decrease in the lowest dose cohort as well on CFT. Thank you. Okay, great. Thanks. To answer your second question first. We've long recognized in clinical trials with looking at both visual acuity and the OCT macular thickness, that there really is not a predictable correlation between the two. It's counterintuitive, but the changes that we see on OCT don't necessarily correlate to changes in vision and vice versa. Sometimes the vision improvements occur while the subfield thickness changes are either lagging or not in sync with that. I'm not surprised to see any mismatch between the BCVA and the OCT. On your question, in the lowest doses, we could go back and look at what the OCT changes were in the patients in those low doses that had the visual acuity gains. Now to your first question. It's really a dose response question, yes, that will be important to demonstrate dose response data for this drug. In this phase I study, we really have such a small number of patients in each cohort, three patients in each drug cohort. Really for the diabetic macular edema patients, there's only two patients in each drug cohort. It's, I don't think to be expected that we would see a reliable dose response pattern yet at this early clinical development stage. Particularly, we don't expect to see that in a disease that's fairly variable in terms of the vision. We know that when we treat patients with DME or wet macular degeneration, during the course of treatment, there's going to be a fair amount of bounce up and down in the visual acuity over that treatment course. I think the future studies will give us a more firm picture of what the dose response picture is for UBX1325. Do you mind if I ask a quick follow-up? Go ahead, Salim. Oh, sorry. I'm sorry to interrupt. I didn't mean to interrupt if you didn't finish the comments on that question. Sorry, everyone. Oh, no. Not at all. Yeah. Salim, let me just add one thing to what Dr. Bhisitkul said, and then we'll be happy to take another question from you. I just wanted to point out one additional thing about that particular data set that you pointed out. One is you did point out that at the very low dose, there's just 1 patient who seems to be up there. I just want to point out that patient is really the worst patient we had in the entire set. That patient started out with zero letters of ETDRS when they were first screened for the study. They are quite an outlier in others. They started at a very bad place, and then you see some gains. The other patients were more in the middle zone of starting and end points that you would find typically in these groups. There, we find it quite encouraging that you'll see that at the 10 microgram cohorts, the two patients are up there by about 10 letter gains, and then you see roughly five-six letter gains in the 5 microgram. Those clusters seem both are relevant doses and give us confidence about the 10 microgram going forward. You had a follow-up question, Salim? Yeah, thanks, Anirvan. Dr. Bhisitkul, given your comments then, I'm just curious, since we don't have the dose response curves shown as maybe we would like to see them just yet, just curious if you can characterize your overall level of confidence in this asset right now in terms of ultimately becoming a commercial drug in the market. What else do you need to see in order to be convinced, or maybe you're already convinced, just curious to get your thoughts on that. One part is we're looking at this very difficult population, these anti-VEGF non-responders. Again, in the clinic, we've had a washout period with these patients, and now we're at 12 weeks where the patients have had anti-VEGF withheld. In clinic, you would expect a steady decline in these patients. No question. If you just stop treatment on a patient with DME or neovascular AMD, for example, during the pandemic, we saw this. Quite predictably, you're going to see a decline in vision. In these patients, we're seeing the opposite. We're seeing a gain in vision, which is surprisingly positive to me, especially from this single dose. What we'll need to see is, of course, controlled data, longer follow-up period, greater number of patients. We'll need to refine and make decisions about what the dosing regimen is going to be for this drug. We'll need to also see secondary endpoints, such as how many patients need to receive anti-VEGF rescue, what the vascular perfusion effects are going to be in the eye, all those secondary endpoints. At least from the primary endpoints that we're looking at now in terms of vision and the signal that we're getting from the OCTA, I'm seeing things that I wouldn't have expected in a small study like this in severe patients. I'm getting a positive feeling about this as being something that would be useful for retina specialists to use in the clinic, especially with the different mechanism. Does that answer the question? That's super helpful. Thanks so much for all the color and congrats again on the data, guys. Thanks, Salim. Thank you. As a reminder to ask a question, you will need to press star then one on your telephone. Our next question comes from the line of Yigal Nochomovitz with Citigroup. Your line is now open. Yeah. Hi. Thanks for taking the question. It's a question for Dr. Bhisitkul. I'm curious what you think about the relative timing of delivering a senolytic such as UBX1325 with anti-VEGF. What I'm wondering more specifically is, do you think that these two mechanisms should be administered concurrently? Given that UBX1325 works upstream of VEGF, isn't there perhaps some advantage to clearing out the senescent cells first with the senolytic and then following perhaps a few weeks later with the anti-VEGF as a mop-up operation? Yeah, that's going to be the critical question for how we use this in the clinic. Will UBX1325 be a monotherapy, or will it be a combination therapy with standard of care? Right now, what you're suggesting is start with UBX1325 as sort of a senolytic therapy that stabilizes the cellular composition in the retinal vessels and in the retina, and then follow that with mop-up injections of anti-VEGF to handle any residual macular edema or incomplete response. That's quite rational. I think in a clinical trial it'll be the opposite, because, as in the case of this clinical trial, we have a standard of care out there with the anti-VEGF drugs, and it's difficult to make a decision to withhold that treatment unless the patients have first failed or had incomplete response to the anti-VEGF treatment. We're doing the opposite. We're starting with the anti-VEGF, then we're coming in with the senolytic therapy with UBX1325. I agree with you. I think it might be more interesting to intervene earlier with something that will stabilize the cellular composition of the retina. I think all of these options should be explored in the future clinical trials, both as a monotherapy to look at non-inferiority to anti-VEGF, then as a combination therapy with anti-VEGFs that would be compared to monotherapy anti-VEGF as a superiority comparison. Many different parameters on how to use this drug. I think earlier intervention and initial intervention with this one does make a lot of sense, as you're suggesting. That's a very helpful perspective. Thank you. Thank you. There are no further questions at this time. I will now turn the call back to Anirvan Ghosh for closing remarks. Thank you very much. I just wanted to wrap up with a couple of comments. First of all, thank you again, Dr. Bhisitkul, for joining the call, sharing your view of the data, and then taking many of the questions from the analysts we have on the call today. I think you see why we're quite excited about the data we're seeing at 12 weeks. When you share the data at eight weeks, it is not clear how sustained those gains would be. To see really stable gains going out to 12 weeks is very encouraging, particularly in a very severe patient population, these advanced AMD and DME patients. In many of the patients, we see changes in retinal structure as well. So far, we have shared 12-week data from the BEHOLD study. As you know, the study is ongoing, and we're looking forward to sharing with you 24-week data in the coming months, as well as data from this additional cohort of AMD patients that Dr. Bhisitkul alluded to. We have seven additional AMD patients at 10 micrograms, and that will really fill out that data set before the end of the year. Looking forward to sharing all of that data with you. Thank you again for your interest and attention, and I'll close the call with that. Thank you. Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.