Good morning, everyone, and thank you for joining the H.C. Wainwright Fourth Annual Ophthalmology Virtual Conference. My name's Arabella, and I'm an analyst on the corporate access team. H.C. Wainwright is a full-service investment bank dedicated to providing corporate finance, strategic advisory, and related services to public and private companies across multiple sectors and regions. We have a total of 24 publishing senior analysts and over 650 companies covered across all sectors. If you would like more information, go check out our website, hcwco.com. From a logistics standpoint, please make sure to reference your virtual conference online portal that provides your individual links to meetings and all presentations. With that said, have a productive and enjoyable day, and I'd like to introduce Anirvan Ghosh, who is the CEO of Unity Biotechnology. Thank you, and thank you for the invitation to participate in the H.C. Wainwright Annual Ophthalmology Virtual Conference. I'm Anirvan Ghosh, CEO of Unity. Before I get started, I'd like to note that during today's presentation, I'm going to be making some forward-looking statements. I encourage you to review our SEC filings, including the most recent 10-Q filings, for a more detailed overview of Unity Biotechnology as a company. At Unity, I am supported by an incredibly talented and experienced leadership team, as shown over here. I'd like to make special note of the fact that the most recent addition to our team is Alicia Tozer, who joined as Chief Strategy Officer about a month ago. Alicia comes with deep product and commercial experience from her time at Genentech and Astellas. As we start planning our transition from a phase II to a phase III company, Alicia's input will be invaluable. We also have a very strong steering team and advisory team, which includes several KOLs that you would be familiar with, many of which who have presented Unity data at prior meetings. At Unity, we are developing a new class of therapeutics called senolytics. Senolytics are agents that target cells that can lead to disease progression, cells that are called senescent cells, and by targeting and eliminating those cells, we believe we can alter the trajectory of disease. Our primary focus is in ophthalmology, especially in the back of the eye, with the lead program being in diabetic macular edema. The senolytic approach is also relevant for other retinal diseases, such as diabetic retinopathy and geographic atrophy, which could be opportunities for indication expansion. The core differentiator for us is the development of a class of therapeutics called senolytics. Senolytics are small molecule agents, in our case, the lead program being a Bcl-xL inhibitor, that selectively targets and eliminate disease-causing senescent cells. Over the past several years, we have generated compelling preclinical and clinical data indicating that senolytics can be valuable to alter disease trajectory for retinal diseases. Importantly, last year, we completed our first phase II study examining Bcl-xL inhibitor UBX1325 in patients with DME, and we reported that patients who had plateaued on their anti-VEGF treatment got significant improvement in vision beyond that with UBX1325. Right now, we're excited about executing on our phase IIb ASPIRE study. This is a head-to-head study comparing UBX1325 to aflibercept, and we just recently achieved our enrollment target. We are on target to share our 24-week primary endpoint efficacy data in the first quarter of 2025, and 36-week data in the second quarter of 2025. The emerging profile of UBX1325 indicates that we have a potential product in our hand that could be well-differentiated from the current standard of care and other evolving treatments. The standard of care in the field for some time has been aflibercept, which is a VEGF trap, and the most recent entrant in this field is faricimab, which targets VEGF and Ang-2. The emerging data from UBX1325 indicates that we might be able to provide benefit to patients who might not be optimally receiving benefit from aflibercept or faricimab. Importantly, we believe that UBX1325 could be valuable for all patients, including those who are suboptimal responders to anti-VEGFs, and by definition, other anti-VEGF agents, like aflibercept or faricimab, cannot provide them with added benefit. Durability is important in the field. Standard-of-care treatment is about an injection every other month. Our target profile is to have an agent that can be given every six months or less frequently. Our initial data from BEHOLD is consistent with that profile. Finally, I'm really excited about the potential for UBX1325 to lead to healthy vascular growth in ischemic areas of the retina, something that we see in our preclinical models and something that has not been reported for anti-VEGFs. Let me spend a couple of minutes now to introduce you to the senolytic therapeutic hypothesis. This slide shows you an illustration of the diseased eye on the left and the state of the eye potentially after being treated with a senolytic agent. DME, as you know, is a vascular disease that is characterized by a lack of vascular integrity and vascular leak that leads to edema in the eye. We know that the vasculature of the eye includes senescent cells, shown here in blue, and these cells secrete a number of inflammatory factors, such as IL-8, IL-1 beta, TNF-alpha, and they also do not form tight junctions with their neighboring cells.... Our preclinical data indicates that treatment with a Bcl-xL inhibitor will lead to the selective elimination of senescent cells, thereby reducing the inflammatory drive, reducing vascular leak, improving perfusion, and eventually leading to improved retinal function and vision. Looking a bit more deeply into the vasculature, this slide illustrates the cross-section of the blood vessel in the eye, illustrating a senescent cell shown here in blue. In this illustration, you can see that that cell is a highly inflammatory cell that leads to secretion of inflammatory factors around the vasculature. With a senolytic agent such as UBX1325, we expect those cells to be eliminated, for the inflammation to be resolved, for the growth of healthy vasculature in its place, and eventually improved perfusion and retinal function. This is supported by both our preclinical and clinical data. I'll show you a couple of examples of important preclinical experiments. This slide shows data from a diabetic mouse model, the STZ mouse model, in which you end up with a hyperglycemic state, and eventually you have retinal pathology. In this experiment, after inducing diabetic retinopathy, we give the mice two injections of a Bcl-xL inhibitor and then assess the inflammatory state and vascular integrity. On the bottom left, you see that a number of inflammatory markers, including IL-1 beta, IL-6, and TNF-alpha, are highly elevated in vehicle-treated animals. However, after treatment with the Bcl-xL inhibitor, there is very marked resolution of the inflammation. On the bottom right, you see an image showing leakage from the retina, which is indicated by albumin in the tissue. There's high levels of tissue albumin in vehicle-treated animals, but with the Bcl-xL inhibitor, you see nice resolution of that, indicating restoration of vascular integrity. Perhaps more impressively, we see remodeling of the retinal vasculature, as shown in these flat mounts. These are images from an oxygen-induced retinopathy model. We're looking at images of two major forms of vascular dysregulation: neovascularization, shown on the top, and ischemia, shown at the bottom. After treatment with the UBX1325, we see that the neovascularization is significantly resolved, so we get beautiful, normal-looking capillary beds, and the areas of ischemia significantly reduced, all of which indicate that UBX1325 could be a disease-modifying option for patients with DME. Let me now move to our clinical development plan. I'm going to spend some time reviewing our data from the phase 2 BEHOLD study in patients with DME, and I'm going to wrap up with the study design and current state of the phase 2b ASPIRE study, where we're examining UBX1325 against aflibercept. An overview of the studies is shown over here. Late last year, we completed 48-week data from the phase 2 BEHOLD study, where we showed that in patients who had reached their plateau with anti-VEGFs, we got significant improvements in vision and durability of effect. Following that, we initiated the ASPIRE study, which is a phase 2b study, where we're examining UBX1325 head-to-head against aflibercept. We just recently hit our enrollment milestone, and we expect to have 24-week data from that study in the first quarter of 2025, and 36-week data in the second quarter of 2025. To provide some context to the data that I'll share today, I'll remind you that even on an anti-VEGF, patients reach their plateau efficacy at about six months of treatment. These are data from the pivotal study of aflibercept, the VISTA study, showing that after about 6 months, there's no additional gain in vision in patients, even if they continue to stay on anti-VEGF. And we know from historic data, even at this point, there are significant number of patients who do not have 20/20 vision or 20/40 vision and have significant fluid in the eye. Our goal is to examine whether a new mechanism, such as UBX1325, can lead to improvement in vision beyond the anti-VEGF plateau. We first explored that in the BEHOLD study, the design of which is shown over here. The patient population are suboptimal responders to anti-VEGF. In this study, we recruited patients with DME who had been on anti-VEGF for at least 6 months and had to have at least 2 injections in the prior 6 months. In actuality, on average, they had 4 injections in the prior 6 months, indicating that they were getting an anti-VEGF every 6 weeks before being enrolled in our study. They needed to have at least 300 microns of fluid. In actuality, the enrolling population had about 440 microns, indicating there are a lot of patients who have a lot of fluid in their eye, even after anti-VEGF treatment, and their vision needed to be 73 letters or worse. In reality, their average vision was 61 letters, once again indicating that for a significant patient population, even after anti-VEGF treatment, there is visual acuity deficit. This was a 48-week study, with the primary endpoint being at 24 weeks, and we had enrolled a total of 65 patients in this study. The study was well-balanced, as shown over here. Importantly, I'll note that with regard to incoming BCVA, they were right around 61 letters. Their fluid was between 425 and 450 microns, and they were also balanced with regard to the prior anti-VEGF they had been on, with about an even split between aflibercept and Avastin or bevacizumab. The first insight that we had from this study was a significant reduction for the need of anti-VEGF once they were switched to UBX1325. In this slide, in this Kaplan-Meier curve, we're showing the rescues as downward notches, and in gray is the sham-treated patients, and blue are the UBX-treated patients. You'll note that over time, the sham patients continued to require anti-VEGF treatment, such that by the time you get to 48 weeks, about 80% of the patients have needed an anti-VEGF rescue. In contrast, right from the beginning, there's a rightward shift on the UBX arm, indicating those that need rescue need it later than the sham patients. Perhaps most importantly, after about 18 weeks, there are very few additional injections needed in the UBX arm, such that over half the patients go without any anti-VEGF injection for a whole year. I remind you that before this study, they were getting an injection every six weeks. The rescue criteria are shown in the bottom left graphic here. Moving now to some efficacy data. The first output that we paid attention to was the change in visual acuity, as measured in BCVA change from baseline. The analysis specified 24 weeks and 48 weeks as the primary points of analysis. And you can see here in blue, show the UBX effects, at both at 24 and 48 weeks, we see significant vision gains, such that those patients have about a 6.5-letter improvement in vision compared to what their anti-VEGF plateau was. In gray are the sham-treated patients, and you can see that there's no improvement in vision in that arm. I should also note that in this analysis, we have excluded all data after any rescue that happened, and you'll recall that the sham patients had a lot of rescues in that arm. As a result, to some extent, these patients at the end represent the best of the sham patients. Another way of looking at this data, which keeps all of the data in the analysis, is called last observation carried forward, so that the last observation data point before rescue is concluded in the final dataset. Here, the difference becomes even more evident. You can see that in the sham patient, sham line, the patients continue to lose vision, such that they have lost significant vision by the time they get to 48 weeks. In contrast, you see the gain in vision with UBX treatment that is then maintained all the way through 48 weeks. And the difference here is about 7.5 letters of vision by the time you get to week 48. Turning now to fluid in the eye. An important measure is to see how well we control additional fluid accumulation. When you take patients off of anti-VEGF, in the sham arm, as you might expect, there's a rapid accumulation of fluid shown in the gray bar over here, and this is what leads to much of the rescue that happens over the first 24 weeks in this patient population. That added fluid is largely maintained through the duration of the study. In contrast, in UBX-treated patients, you can see that there is hardly any fluid accumulation beyond where they started, and between eight and 48 weeks, there's a gradual decline in the amount of fluid. So with a single injection of UBX1325, we are managing edema quite effectively. Another way of looking at this data is the last observation carried forward analysis. Once again, you see significantly greater fluid accumulation in the sham arm compared to UBX1325, which accounts for fewer rescues in the UBX arm. An important analysis, of course, is the need for rescue. The field is quite focused on treatments that will give you - that'll allow patients to go longer without needing anti-VEGF treatment. In our study, on the left-hand side, you see that with UBX1325, over half the patients went without needing any anti-VEGF rescue, compared to only 20% of the sham patients who could go rescue-free for the entire duration. Safety is a very important feature of any new treatment under development, and here you can see that we have a very favorable safety profile. It's been in many patients, both DME and AMD patients now over the last couple of years, and importantly, we see no instances of intraocular inflammation, endophthalmitis, retinal artery occlusion, or vasculitis in this patient population. The other adverse events are balanced across sham and UBX, and there are no other treatment-related adverse events of note. Based on all of these observations, we're very encouraged by the potential of UBX1325 to provide benefit to DME patients. We see that through week 48, in patients with a single injection of UBX1325, there is about a 6.5-letter gain from baseline compared to no significant change in the sham arm. We see that over half of the patients are able to go through a whole year without needing anti-VEGF rescue, representing a significant reduction in treatment burden. We find that with anti-VEGFs, we maintain retinal integrity and do not significantly accumulate fluid, and we see a favorable safety profile. All of these are consistent with UBX1325 being a potentially valuable treatment option for patients going forward. Based on that study, we recently initiated the ASPIRE phase 2b study, and I'm going to close my presentation here by reviewing that study design and when we expect data from that study. ASPIRE is a head-to-head study of UBX1325 against aflibercept in patients with DME who have reached their plateau response with an anti-VEGF. The study design is shown over here. This study takes in a patient population that is very similar to what we had in the BEHOLD study. Importantly, we're recruiting patients who have been on anti-VEGF for at least six months and have had three anti-VEGF injections in that period. To be eligible to enter the study, despite anti-VEGF, they need to have a visual acuity deficit within a range of 30-70 ETDRS levels. They also need to have fluid accumulation in the eye of at least 325 microns. So we're recruiting patients that are quite similar to those that we had recruited in BEHOLD, and frankly, this reflects the unmet need in the field. The study is evenly distributed between patients who are treated with aflibercept or UBX1325, and we intend to enroll 50 patients, with about 25 per arm. Let me now speak to the study design and a couple of features that are somewhat different from the BEHOLD study. You'll note that once these patients come into the study, they get 3 injections of aflibercept before being randomized. This is critical for us to get the patients to their anti-VEGF plateau before randomization, because we want to avoid any potential unexpected gain in these anti-VEGF treated patients because of aflibercept. Our goal is to show a benefit above and beyond the anti-VEGF plateau. Based on these injections, we know that when they get randomized to the aflibercept arm, we expect no additional gain in vision on the aflibercept arm. They'll get 3 injections of aflibercept at 0, 8, and 16 weeks, and we expect that these patients to maintain a BCVA of about no change from baseline. On the UBX arm, you'll note that compared to a single injection of UBX in the BEHOLD study, in ASPIRE, they'll get 3 injections of UBX1325 that are matched with the aflibercept injections to allow us a fair comparison of treatment. It also allows us to maximize the benefit of UBX1325. We saw very impressive gains after a single injection of UBX, but this study will allow us to determine whether a second or third injection might provide even greater benefit. Lastly, I'll point out that in the very first injection, the patients received both a UBX injection and an aflibercept injection. This is because we noted in the BEHOLD study that it took about 8 weeks for the UBX mechanism of action to kick in, to eliminate senescent cell, to... and to lead to improvement in metrics of vision and fluid. When you take patients off an anti-VEGF, there is an initial accumulation of fluid. By giving an initial anti-VEGF injection, we expect to clamp that fluid accumulation during that period until the anti-VEGF effect has fully taken hold. We believe this study is optimized us to show the differentiation of UBX efficacy versus aflibercept. The primary endpoint of this study is going to be at 24 weeks. We expect that data in Q1 of 2025. Recently, we extend this, the study to 36 weeks so that we can also generate some durability data in the study. The 36-week data is now expected in Q2 of 2025, and this will allow us to generate data about how long patients can go through week 36 without needing any anti-VEGF treatment. We believe that collectively, this will provide us a strong data set to optimally design a pivotal study to show differentiation of UBX1325 compared to aflibercept as a new treatment option for patients in DME. Over the coming months, we expect to update you on our phase 3 design and study plans and additional data readout details. Thank you very much for your attention. Thank you so much, Anirvan, for the super interesting presentation, and we really appreciate the time and effort that went into putting it together. We're really glad to have you present at the conference, and thank you again from the whole H.C. Wainwright team. Thank you.