Great. Good morning, everybody, again. I'm Matthew Harrison, one of the biotech analysts here, and very pleased to have Unity with us for our next session. Before I get started, I just need to read a quick disclosure statement. Please note that all important disclosures, including personal holdings disclosures and Morgan Stanley disclosures, appear on the Morgan Stanley public website at morganstanley.com/researchdisclosures. I thought maybe just to kick us off and get us started, we could talk about the recent data and sort of the implications and outlook for that. Then we can jump into some more detailed Q&A. Thank you, Matt. Great to be here. As you know, we're developing therapeutics to address aging-related diseases, with our lead program being in ophthalmology. Just as a reminder for those dialing in, the lead program is UBX1325, which is being developed for DME and AMD. That is currently in a couple of studies, a phase I study and a phase II-A study. Recently, we shared some data from the single ascending dose phase of the phase I study, which was in fairly advanced AMD and DME patients. These are patients who have been off of anti-VEGF for at least three months and are not expected to benefit from additional anti-VEGF treatment. In that study, and that was 12 patients in that group. Majority of patients, this is at eight weeks, showed improvement both in vision and structure. We were really pleased to see that. It's kind of unexpected as a safety study, and our primary goal was to understand the safety and efficacy and tolerability of the drug. It was very well-tolerated. No severe adverse events. Seeing initial signs of efficacy was really exciting to us and happy to talk more about that. Okay, great. Good. I thought maybe just a good place to back up just for a second, because maybe not everybody's familiar with the platform so much. Maybe we just talk about what's the thesis behind the mechanism of sort of the development program broadly and the overarching sort of vision of the company in terms of how you're picking these molecules. Sure, Matt. Our broad goal is to develop therapeutics to slow, halt, or reverse diseases of aging. The fundamental motivation there has been that over the last 10-15 years, we have learned a lot about the fundamental biology that drives aging-associated diseases. As you know, aging is the primary risk factor for a number of diseases. The question has been, what are the fundamental biological mechanisms that cut across organ systems that increases risk of disease? One biology that we have found particularly compelling is cellular senescence or the accumulation of cellular senescence in tissues as we age. A feature that is universal, certainly among vertebrates and mammals, is that as we age, our tissues will accumulate cells that have accumulated damage over the course of a lifetime. They have DNA mutations or other stressors in the environment. That places the cells in a senescent state where typically they stop dividing, but they're metabolically very active and can secrete factors that can damage the local environment. In the normal course of aging, there's some accumulation of these cells, probably contributes to the normal aging process. In aging-associated diseases, we see evidence of increased accumulation of senescent cells. A number of experiments from several labs indicate that if you're able to target and eliminate the senescent cells, you can bring the tissue back to a healthier state and alter the trajectory of disease pathology. That central idea is frankly what brought me to Unity that we're very excited about. Our goal now for several years has been to identify molecules that can safely and selectively eliminate senescent cells while not affecting the neighboring cells. With that in mind, we decided to kind of focus initially on compartments where we can locally affect cellular senescence as opposed to a system-wide treatment. In the case of eye diseases, that's a great place to explore this because it's a closed compartment. That led to the identification of our lead senolytic target, which is Bcl-xL. What we find that targeting Bcl-xL will eliminate senescent cells and not non-senescent cells. The preclinical data support suggested that in a number of disease models, doing that reduces elements of vascular pathology in the eye, things that we believe are important driving diseases in human. That drove us to move this program to our phase I study and now a phase II study as well. Okay, perfect. Good. I guess the next question is just in a phase I study is in a small number of patients, I think investors probably struggle to figure out how much stock to put in the fact that you did see some anatomic benefits, and you saw some clinical outcomes. What to make of that, and how you guys internally think about how robust that signal is at this point. Yeah. Let me provide a little bit of context about kind of where the treatment of AMD and DME stands today. Because I think that context is important in terms of thinking about what a new therapeutic would need to look like to really provide superiority to the standard of care. The standard of care in this field for many years, 15 years or so now, has been anti-VEGF treatment. Anti-VEGFs are approved for both DME and AMD. The standard treatment regimen tends to be monthly dosing anywhere from two to five months, after which they'll go generally to a once every other month regimen. A good number of patients will respond to it, but there's a sizable fraction that are sub-responders or non-responders. Anywhere from maybe 15-30 people do not respond well to anti-VEGFs. They have some response, but they have significant residual visual deficit or structural deficit. Over time, if you just look at their population studies, you can see that beyond the first year, because of a combination of disease progression, people not staying on that fairly tight regimen of treatment, their vision will continue to decline. The field has been quite focused on thinking about what are the next generation treatments that's really going to move the needle. That has really two dimensions. One is around durability and the other is around greater efficacy. I think that those are the things that collectively we're focused on as a community. With a senolytic agent, our aspiration is to develop a treatment that has very long durability by virtue of its mechanism of action. By changing the fundamental biology of vascular disease, you should get durable effect. Because it is a mechanism independent of anti-VEGF, we expect that it should work in patients who do not respond well to anti-VEGFs or could work on top of anti-VEGFs. Right. Those are the things that we'd be looking for. With that in mind, what did we see and how should investors put that in context? In our study, although a small number of patients, and it's very important to remember that, hence the phase II-A study that we have started. We're looking at the response after a single injection. We're looking at a few different doses, a single injection of UBX1325, and then we're following those patients out to 24 weeks. So far, we have shared 8-week data, but we expect to share 12-week data and 24-week data in the coming months before the end of the year. What we found that after a single injection, the vast majority of patients showed improvement in vision and in structure, and particularly in the two high doses. The therapeutically active doses were predicted to be five or 10 microgram. In the five and 10 microgram cohorts, you see most of the people showing vision improvement and structural improvement. All of them showing improvement out to 8 weeks, which is how far we've shared the data and will go beyond that. As it is, it already starts to peel away from historic anti-VEGF single injection data. Those kinds of data sets almost don't exist because for most agents now, they lead in with that multiple dose start, right? It'll go back to look at single injection data for the initial anti-VEGF, and you'll see this respond by a month, and by about two months it starts to wane. Hence this treatment paradigm developed with multiple injections in the beginning. The first signal that we might get some durability is that at up to eight weeks we're seeing fairly good responses, and we will be looking to see whether we see some evidence that can be maintained through 12 weeks or beyond. That gives them a sense of what the durability might look like. These are patients that are very advanced patients, as I mentioned, and patients who have failed anti-VEGFs or are not considered eligible for anti-VEGF. The fact that we're seeing responses in that population also supports the hypothesis that this might help people who are not anti-VEGF responders. The efficacy data, I think we'll need additional data to understand. Certainly, we do not have a combination study here to know whether it might provide benefit over anti-VEGF. So far, compared to historic data, the gains in letters is quite impressive. Okay. Good. Maybe just the comment on durability. I guess the first thing is from a mechanism standpoint, your hope is you remove, I'm going to use sort of a non-technical term, but you remove the offending cells and therefore that gives you longer durability. Would you think this would come most in durable on vision, or you think some of the OCT and some of the more anatomic things is where you might start to see that, just given the smaller number of patients, and we know how BCVA can bounce around a little bit? Right. Just for the audience, let me just double-click on where we think the senescent cells are in vascular disease of the eye and how that might turn into durability. What we found was that in the context of eye disease, most of the burden of senescent cells is in the vasculature of the eye, which is also where we see the pathologies. That was one of the first reasons that got us quite excited, seeing that we see accumulation of senescent cells in the same place where we know the blood vessels are going to become leaky and eventually lead to disease progression. In preclinical models, we had found that if you eliminate senescent cells, then we reduce vascular leak. We're hoping that that will translate as we move into people. The idea would be that we've restored blood vessels to a healthier state, and that is now allowing the retina to continue to function better over a longer period of time. It's also important to remember that we believe, and there's evidence that the factors that senescent cells secrete include VEGF, which could be one of the local offending factors, right? We know anti-VEGFs work quite well. It's not the only source of VEGF in the eye, but certainly in terms of areas of pathology, the local senescent cell-derived VEGF would be quite important. I think in terms of durability, and this does get to an important point about where will one eventually see the biological effects. We've been measuring BCVA and CST because historically those have been areas that have been most important. As you know, BCVA is the approval endpoint, so eventually you have to have vision gain. Without that, there's not a drug. The field has been also looking at other areas where you might see change that might tell you that the drug is doing what you expect it to do. The two places where in, again, in a small number of patients, but we've seen fairly convincing evidence is 1 is in the reduction in CST thickness. As well as a reduction in fluid pockets in AMD patients which are parafoveal. Areas that are next to the fovea, we can see there's fluid reduction. Those are very encouraging. I think that the additional element that we'll probably learn in future studies is going to be about vascular dynamics and vascular health. These are kind of indirect measures that says if your blood vessels are leaky, you might accumulate fluid, and that's what you see. In the next study, the phase II-A study that's now ongoing, we expect to have significant number of patients where we have OCTA measurements, as well as wide-field fluorescein angiography, which would give us a sense of vascular flow and vascular integrity. I think that is probably where we'll see some of the durable effects that you're talking about. In the meantime, I think the fluid accumulation CST thickness provide evidence that it's exerting biology in the eye. As you know, at an individual patient level, even for historic approved agents, the correlation between CST change and vision change is not that tight. It doesn't have, I think, a predictive value that one might want in an ideal biomarker. Okay. You touched on the phase II-A. The first thing is, it's in DME, talk about why you picked that over AMD as sort of the first more robust study. The second is just maybe outline the phase II for people and what you think is sort of a key piece of information you're going to get out of that study. Right. We believe the biology is relevant to both DME and AMD in that in human tissue, we see evidence of increased senescence in both these diseases. The preclinical data set was more heavily weighed towards models of DME. There are models where we believe you can model diabetic eye disease in an animal model and then show that you're reversing that trajectory. In AMD, as you know, there's not a really good true disease model of AMD. They're kind of like vascular damage model, if you will, in laser ablation models. They're not driven by the same biology that might be driving AMD. That gave us more confidence that DME might be a place because the same biology is driving disease, and we see effect of the drug. As a result of that phase I study of 12 patients is weighed towards DME patients. There were eight DME patients and four AMD patients in that study. Most of the data we have really is from DME patients. There we see initial signals that look promising. Based on that, we have started this phase II-A study in DME. That study now is a sham control study. As opposed to the first study, which is only different doses, only treatment. It allows us to generate data in a well-controlled study to really get a better sense of what effect size we might expect in terms of vision improvement. We'll look at structural changes, vascular integrity, et cetera. Also importantly, this goes into a broader and more moderate patient population. The first study, because this is the first time we had taken a senolytic in the eye, we needed to be super careful. I think you're familiar with a number of other programs where safety or tolerability issues have really been a big challenge and have slowed down programs. For us, the primary goal is to make sure that we believe that we have a safe drug we can inject into the eye, and therefore, we also entered very severe patients. This phase II-A study goes into a more typical patient population. These people will have had more recent anti-VEGF treatment. They still are not great responders in that they have residual fluid by the time they get into the study. We'll generate data in this sham control study. We'll measure BCVA CST as well as other measures of disease progression. In that study, we expect to share a kind of first look at that data will be the 12-week safety and efficacy data that'll be in the first half of next year. Coming back to AMD, that's an area we're also very interested in. Although we only had four patients, what is interesting is that several of the patients showed letter gain as well as reduction in fluid. This gets to your question about what people pay attention to. In the KOL community, and we spoke to multiple experts in the field before we shared our data and since then, that they have great confidence having seen thousands of patients that at the individual patient level because it's a time course essentially that can tell you whether or not this is a potential drug effect. They were quite impressed by the initial AMD data. Encouraged by that, we decided to add additional AMD patients to that phase I study. In the last few months, we have added a number of AMD patients, and to essentially create a deeper data set of that phase I AMD patient group. Based on that, we'll make a decision whether to advance a parallel phase II AMD study. Okay, perfect. As we think about expectations for the phase II DME study, I guess at 12 weeks, given what's available on the market now, a 12-week endpoint will tell something a little bit about competitive durability, but clearly, there are agents that are looking at three, four, and five months also out there. I guess the question would be, so maybe you could define a little bit how you think what we're going to know about durability from a controlled setting at that point. It sounds like you feel like we should have a much clearer read on efficacy and what that looks like from a competitive standpoint. That's right. I think in terms of durability, and again, it's worth pointing out this next study is also a single-dose study, right? The phase II-A study is really to kind of generate a more robust data set about what a single injection of UBX1325 can achieve, and we'll look out to three months and six months, right? This study is a 24-week study. We'll get three month and sixmonth data after a single injection. I think it will give us a better sense of what durability you might expect after a single injection. Also, possibly a better sense of are there patients who respond better or poor that could help select future studies. Now, I'll point out that, and you pointed out that I think other programs are looking at three to six month durability. That's kind of where the field is. I think there isn't an agent that I'm aware of that where significant majority of patients see durability to six months. They start dropping off between three and six months. It's fraction of patients that show durability to three and six months, obviously, will be quite important. I'd also mentioned that generating also this kind of data with a non-anti-VEGF mechanism is very important because with the other mechanisms being explored that are anti-VEGF based, there is no reason to believe that they would provide any superiority or benefit to people who are not responding well to anti-VEGFs. The treatment paradigm, often we talk to physicians, they'll say, well, they'll put the patients on anti-VEGF, and if they respond well, they'll stay on, and if they don't respond well, there are not a lot of other options right now. I think that generating that kind of data might really give confidence saying that, "Here's going to be a completely orthogonal treatment mechanism that could be quite valuable." Certainly, with regard to the mechanism, it's possible that one might have durability even beyond six months, right? There's this element because of the nature of the treatment that would be quite exciting to explore. I should also point out that the reason we have this call, this as a phase II-A study, then a phase II-B study afterwards, is in part to kind of move towards what the optimum treatment paradigm might be. Of course, we might get a significant durability or efficacy after a single injection, but in the field it's quite common to have two or three initial doses and then look at what the durability looks like. That's the standard design right now. In the phase II-B study, we'll be able to explore that more clearly, because when you look at the patients right now, we don't really know whether if you were to come back at the second month or third month, could we get an additional bump beyond what we're seeing with a single injection? Whether that might then lead to even greater durability, right? I feel that beyond the single injection data, which I think will give us evidence as to does the drug have the possibility of being a useful treatment? It'll set up the stage for what a repeat dose might look like, right? If you see that, we're seeing this thing, but between three and six months, some of the patients wane, in the next study, we might decide that we'll work it into the protocol so that they can get another dose at that point to see, can we bump up the level and get greater durability. I think we'll learn a lot in this first study, but certainly the data sets going out to three and six months will be quite important. Yeah. We'll also learn a lot about structure as well as vascular flow, et cetera, which will allow us to see what biology we're impacting. Okay. Got it. Maybe just two other questions about how you think about the development pathway. In addition to more than one dose, is there any reason to think that combination with VEGF is something that's worth exploring or not? The way we see this molecule, one can anticipate that it could be beneficial in a few different treatment regimens. We've talked quite a bit about what the monotherapy arm might look like, the possibility after a single dose getting durable effect. It's very reasonable to anticipate that it might also combine with anti-VEGF to provide maximum benefit, if you will, because you're going to hit certainly a known driver of disease, which is VEGF with an anti-VEGF. On top of that, you can have this thing that gives you much greater durability. One can anticipate that 1325 and an anti-VEGF gives you really great efficacy, the 1325 action to reverse disease pathology at the core would then give you much greater durability than you would have gotten with an anti-VEGF, right? That's a very interesting possibility and something that we're thinking about how we can begin to explore in the phase II-B study and beyond. I think that there's this element of defining the patients who might be best positioned to switch from an anti-VEGF treatment to UBX1325. Having worked in other areas like in MS when I was at Biogen, et cetera, this understanding what the right switch is is very important to manage patients. I think what we're really excited about is having an option that allows you to switch to a completely different mechanism of action where you really have the possibility of having benefit, where moving to another anti-VEGF related molecule might not really make sense. Got it. Okay, good. Maybe in the last couple minutes, you obviously have a pipeline behind this drug. Maybe you could just briefly touch on some of the work you're doing in sort of next generation ophthalmology and then what you're looking at in CNS. Yeah. With regard to ophthalmology, and as we touched upon today, is that we're very excited about UBX1325, but we also see how it could work maybe in combination with other agents as we look ahead. We've been paying a lot of attention to other fundamental biologies in eye disease that we believe are important target that could provide independent approaches and might benefit certain patients and might be the right treatment for them. In that vein, we're very excited about our Tie2 programs. As you know, Tie2 is a receptor tyrosine kinase involved in regulating vascular integrity. That pathway has had some recent validation with data that has come from aflibercept, which targets VEGF and Ang-2 and the VEGF pathways. As you noted, we're still in a world where we really don't have a slam dunk drug that just gives you very long durability. We're still playing at the edges a little bit, extending it out a bit. We are really looking for what those transformative drugs might be. In the Tie2 pathway, that receptor has two agonists, two ligands, Ang-1 and Ang-2. The approaches have been to kind of have an Ang-2 antagonist and rely on endogenous Ang-1 to activate the receptor. Now, Ang-1 levels vary a lot from eye to eye. You're not getting reliable, consistent activation of receptor if you just take that mechanism. What we have developed is an agonistic antibody that binds to the receptor and allows us much greater control over receptor activation. You can really tune up the signaling that you would like. What is not on the pipeline slide yet, we're also working on a bispecific, that's a VEGF Tie2 bispecific, that I think could be a really exciting program that's going to hit those two pathways. Beyond the eye, we're very excited about our neuroscience program, I'm a neuroscientist by training. We have been generating, I think, fairly deep data on understanding senescence biology, senescence burden across neurological indications. We spent much of the last couple of years, I think, building a really strong platform in neurology. That has revealed that, again, not only is there increase in senescence burden over age in the brain, in certain diseases, and this is interesting. It's not a uniform increase in senescence across all of neurology. We're getting insight into which particular diseases and what phase of disease do you get increase in senescence burden. We see a lot of that increased burden in astrocytes and microglia, and we're developing tools much the way we did it in the eye to target those cells and expect that those will be strong next-gen programs for us. Okay. Great. Good. Maybe in the last minute then, just sort of remind people of key milestones in the next six to 12 months and where you are from a funding perspective. Absolutely. In terms of near-term data readout, and we expect this to kind of start beginning at about ASRS, which is in October, and through the end of the year. First, we're going to be looking at the additional data coming from the phase I study that's really going to be the near-term data readouts, the 12-week safety and efficacy data, and then the 24-week safety and efficacy data in the phase I SAD cohort. We also expect to share data from the additional AMD study patients that we have enrolled in the phase I study. We'll have a deeper AMD data set, and those will be coming up fairly soon. We have started the phase II-A study in DME, and so as we move into next year, in the first half of next year, we expect to share 12-week safety and efficacy data initially from DME patients. We will be looking at the right timing for a potential parallel AMD study, which we have not triggered yet, the two phase II study. Depending on when we started, that data could also come in the first half of next year. Those are things that are on the horizon. Okay. Awesome. Good. Well, thank you for being here. Appreciate the time, and nice to see you. Thanks very much. Great to see you again, Matt. Take care.