Hello, everyone. Thank you for your time and attention today. I'm very happy to present to you Sensei Bio's conditionally active antibodies for immuno-oncology. First, I just wanna thank Oppenheimer for inviting us to the conference and for their continued support. Oppenheimer played an important role in Sensei Bio's IPO 2 years ago. As you can see from our cover slide, we are an immuno-oncology company developing conditionally active antibodies, and we're gonna talk about what conditionally active antibodies are throughout the presentation. Before I get started, I will be making forward-looking statements here today, and this is our disclaimer. At Sensei Bio, we're particularly focused on one of the key challenges in immuno-oncology, and that is that many antibodies fail because of off-tumor binding. Systemically delivered immuno-oncology drugs are developed in a fairly canonical way and are developed to bind to targets both in the tumor and in the periphery. This creates, in our view, some major problems for immuno-oncology agents, including target-mediated drug disposition resulting in poor pharmacokinetics and toxicities such as CRS. Our strategy has been to focus on developing conditionally active antibodies. What that means is antibodies that bind only in the tumor and avoid binding in the periphery. It's that feature that essentially enables the drug ability to a whole range of promising oncology targets. This isn't just a pie in the sky idea. We've actually gone out and done this, and we have a lead program called SNS-101. We'll be filing an IND for that program very soon, on or before April of 2023. SNS-101 is a pH-sensitive antibody targeting the VISTA receptor. We'll talk about what VISTA is in a moment. We have a very strong financial position. We ended the third quarter with over $100 million in cash. That gives us cash runway into the second half of 2025. Plenty of runway to continue developing our pipeline. Now, I wanna expand on the real challenge that we face in the industry because it informs the way we've gone about building our platform. In our view, conventional or canonical antibodies are really the source of a major problem in immuno-oncology. In most cases, I think we've done a pretty good job as an industry of selecting the right drug target, we haven't always done a good job of selecting the right antibody. Conventional antibodies bind their targets both in the tumor and in normal tissues, that has several downstream implications for drug development. One of those is that this creates a pharmacological sink effect that drains the antibody from the body and requires higher and more frequent dosing that often results in dose-limiting toxicities due to on-target but off-tumor binding. Both of those together conspire to create suboptimal activity. Our solution is to develop conditionally active antibodies that only bind target in the tumor, and that results in lower and less frequent dosing requirements, little or no toxicity due to the selective action on target and on tumor, and powerful activity. Now, as you can see from the chart below, the selection of conventional antibodies has resulted in very few drug approvals. In 2011, I think the world, the oncology world was excited by the approval of ipilimumab. We followed up later with pembrolizumab targeting PD-1. That's been a huge commercial success. It took 8 years before the approval of LAG-3. Why has it taken so long to get more immune checkpoint drugs approved? Our central hypothesis, the reason for Sensei's existence, is to solve this problem. To solve it, we really needed to reinvent the drug discovery process. We built our platform around a central hypothesis. That is that the discovery, development, approval, and I would say ultimately the commercial success of IO antibodies can be dramatically improved by screening out off-tumor binders very early in the drug discovery process. What I mean by that is that in a typical antibody drug discovery process, one optimizes around binding, such as KD or receptor blocking, very early in the process. Then you follow up with a. looking at developability, in vivo efficacy, picking a lead, scaling up, etc., before you look at PK and tox issues. Those issues come later, and by that time, you're typically a year into the drug discovery process. That's quite a commitment. We really rethought this process, and we thought about PK, and we thought about toxicities early. We built a different kind of process where we're screening in antibodies that bind selectively in the tumor microenvironment and screening out antibodies that bind in the periphery. That has dramatic downstream consequences for drug development because you've largely de-risked PK and tox issues at that point. This is a little bit of a visual to give you a sense of what I'm talking about. The image on the left, you can see our antibodies binding at the tumor. One of the features we really exploit here to take advantage of tumors that bind selectively is pH. It was about 100 years ago when Otto Warburg described a phenomenon in which tumors metabolize nutrients differently. It's a process more akin to fermentation than traditional human metabolism. That results in a lower pH. As you can see, the pH in the tumor is around 6.1, and the pH in the blood is around pH 7.4. We've developed antibodies that only bind and recognize target at pH 6.1 and avoid binding at pH 7.4. The downstream effect of that is that you alleviate many of the undesirable properties of traditional antibodies, like dose-limiting toxicities and poor pharmacokinetics, and you bolster the specific activities of your antibody that you want to preserve. We think this process is broadly applicable and will eventually unlock previously undruggable immune targets across the IO space. That's a really important feature of what we're doing here today. Now, we've applied this process to a pipeline, and we have several programs in development. Our most advanced is our SNS-101 program targeting VISTA. As you can see, we're very close to filing our IND. That is that the discovery, development, approval, and I would say ultimately the commercial success of IO antibodies can be dramatically improved by screening out off-tumor binders very early in the drug discovery process. We've also announced a very important collaboration with the largest research cancer institute in the world, the National Cancer Institute. The goal of that effort is to explore combination therapy beyond PD-1. We're very excited to explore these collaborations. We're developing two other programs right now as well. One of them is SNS-102, targeting VSIG4, a more novel target with many of the same challenges as VISTA in that it's broadly expressed in the periphery, as well as SNS-103, targeting CD39, a better-known target with many challenges that we think is perfectly suited to the TMAb platform. Let me expand a little bit on SNS-101. If you're not familiar with VISTA, let me spend a moment telling you about this very interesting immune checkpoint target. VISTA is a B7 family member, and it's established that it suppresses T-cell function and plays a role in T-cell quiescence. When VISTA engages with its T-cell receptor PSGL-1, the result is T-cell suppression. It's very akin to the process that takes place between PD-1 and PD-L1. Unlike PD-L1, VISTA is expressed primarily, not exclusively, but primarily on myeloid cells, and that gives it a very different role within the tumor microenvironment. By disrupting the interaction with VISTA and PSGL-1 with an anti-VISTA antibody, you unleash T-cell proliferation and activation. Let's zoom in on that for a minute. One very important feature of VISTA that we've taken advantage of with our conditionally active platform is the fact that VISTA itself is activated at the low pH of the tumor microenvironment. At low pH, certain amino acids, such as histidines, circled in green, accept an extra proton, and that subtly changes the charge and the shape of the epitope. That change within VISTA enables the binding to PSGL-1 that when sulfonated allows PSGL-1 and VISTA to interact. That's a very important interaction that we aim to disrupt with SNS-101. PSGL-1 isn't the only putative receptor for VISTA. There are others, we've looked at all of them. As you can see here, one of the remarkable features about PSGL-1, it has the greatest degree of differential binding to VISTA between pH 6, where it's very strong interaction, and pH 7.4, where it's very weak. All the other receptors share that property to some degree. It's a very interesting molecule that's selective for low pH, and it's that feature that we used to develop SNS-101. We developed SNS-101 to be exquisitely selective for VISTA at pH 6 over pH 7.4. As you can see here, the KD for VISTA at pH 6 is sub-nanomolar. While at pH 7.4, there's essentially no binding. We confirmed that recently with the co-crystal structure of SNS-101 and VISTA. As you can see here, SNS-101 interacts with the epitope as depicted in red, which was predicted by our epitope mapping process. We're very excited. Soon we'll be sharing soon the multi-dose PK and toxicology data in the first half of this year. First, we're very focused on preparing to submit our IND on or before April of this year. I touched on the epitope for SNS-101, and it's a very important epitope because it seems to interact with a number of different receptors. As you can see here, SNS-101 inhibits strongly the VISTA-PSGL-1 interaction, but it also inhibits all the other putative receptors that we've looked at. We're very focused on the PSGL-1 interaction, but we think that it's a good feature that these other putative receptors are also blocked. Why is all that important? That's shown here. As I mentioned earlier, VISTA is expressed fairly broadly in the periphery, specifically on myeloid cells of myeloid lineage. If you have a canonical antibody, such as those depicted in yellow or blue, you can see that the binding of these antibodies occurs broadly in monocytes, neutrophils, and NK cells where VISTA is broadly expressed. There's very little VISTA on T-cells, that curves shift to the right less so. Now look at SNS-101 down below depicted in pink. That curve barely shifts, indicating that SNS-101 avoids binding to VISTA in the periphery at physiological pH. This point was made even more clear to us when we looked at our pharmacokinetic work. Let me focus your attention first on the left side of the screen. This was a very innovative PK study that we did in mice. First, look at the black line. The black line are mice where essentially there is no target. These are wild-type mice with mouse VISTA, to which our antibody does not cross-react. Over a 4-week period, you see the gentle and gradual disposition of the antibody in the blood. Now look at the blue line. These are genetically engineered mice that have been engineered to express the human version of VISTA, to which our antibody binds, but only at low pH. In these mice, because there's no tumor, there's no binding, and so the PK of the antibody is very similar to the mice in which there's no target. What happens when we implant a tumor in those same genetically engineered human VISTA-knockin mice? That's depicted in red. For about the first week, as the tumor grows and becomes more established, it tracks with the blue. As the tumor grows, it requires more nutrients. That means metabolism changes and the pH of the tumor drops. That enables the binding of our antibody, and it's at that point you see the disposition of the antibody occur at a more rapid pace. This exciting result continues to confirm the mechanism of action of this antibody. Now, on the right side, you see our PK study in monkeys. At three different doses of SNS-101, we observed linear dose elimination kinetics, which was really nice to see. We went a step further, and we also looked at a canonical clinical stage anti-VISTA antibody, and that's depicted in red. As you can see, within about 48 hours, that antibody is undetectable. We're really excited for the possibility, and we think that this antibody, SNS-101, is going to be the first to truly test the VISTA axis due to these properties. One of the important things we wanted to look at early in development was cytokine release. That's important because prior clinical stage VISTA antibodies have had cytokine release as a toxicity in the clinic. We compared SNS-101 to clinical stage antibodies across a variety of different CRS assays. This is the most sophisticated CRS assay that we're aware of, in which blood from patients is kept in continuous circulation. As you can see across a range of different cytokines and a range of different doses, SNS-101 consistently shows a much lower degree of cytokine release compared to a clinical stage VISTA antibody. Note that the axis on the y-axis is in log scale, so these are massive differences. Now, I've shown you a lot about what SNS-1 doesn't do. How about what SNS-1 does? We've looked at SNS-101 in a range of preclinical models. Here you can see in an MC38 model really nice evidence of SNS-101 deepening the anti-tumor response to PD-1, in which SNS-101 and PD-1 appear to work synergistically. We also looked at a clone of MC38 which had become insensitive to PD-1, and that's depicted on the right. Here you can see while PD-1 no longer works or is effective, SNS-101 results in some really nice tumor growth inhibition. The same is true for the combination. We're really excited to report single agent and combination activity. In some of these models, we also dig a little deeper and look at the immune markers that are associated with the response. In this MC38 model, you can see a dose-dependent increase in CD8 T cells for both SNS-101 monotherapy and in combination with PD-1. Last but not least, we've also looked at a sarcoma model. While we're not particularly focused on sarcoma for development, we view this model as a very important level of validation preclinically. Why is it important? We did this study in combination with Bob Schreiber's lab at Wash U. As you know, Bob Schreiber is one of the authors of cancer immunoediting. This sarcoma line was developed because while it initially responds to PD-1 after about 20 days, eventually these mice become, in a sense, refractory. The regrowth occurs. However, the combination of SNS-101 results in markedly better tumor growth inhibition. Moreover, when you look at percent survival, the combination of SNS-101 and PD-1 results in a dramatic increase in essentially complete responses in these mice. We look at these models as ways to help us understand areas for further development of SNS-101. Of course, we'll also be looking to the clinic. In the clinic, we'll be running a fairly traditional phase 1 dose escalation study as monotherapy, and then also roughly in parallel, begin to look at the phase 1 combination dose escalation. Once we have found and identified a recommended phase II dose for both monotherapy and in combination, we will then move rapidly to expansion cohorts, where we will begin to select patient populations based on not only the preclinical data, but also the clinical data that we'll be looking at. This is going to be a very data-rich study looking at biomarkers across a range of different markers. We'll be able to use that information to help us select patients in the phase two cohort expansions. Clinically, SNS-101 won't be alone. There are four other drugs in phase I currently. While we'll be the fifth, we believe SNS-101 will be the first to really meet all the requirements that we view as imperative to effectively block VISTA as an immune checkpoint. Those features include blocking PSGL-1, blocking it in a pH-sensitive way, and having an active Fc. We view these features as important because we have a long history with VISTA. Myself and other members of the team have been working with VISTA or VISTA antibodies for over 10 years. There's a wide body of literature to support this view. We're very excited to get started clinically. Now let me transition to our 2 other programs. I'll start with VSIG4. VSIG4 is a target you may not have heard of before. It is an immune checkpoint. It's an immunosuppressive receptor. It has similar on-target, off-tumor challenges to VISTA. VSIG4 is also expressed on cells of myeloid lineage. That means it's often expressed on Kupffer cells of the liver, a particular challenge. That appears to drive significant TMDD and clearance with VSIG4 antibodies. Now within the tumor, VSIG4 plays an important role. It's expressed on tumor-associated macrophages, and it correlates with an immunosuppressive M2 phenotype that inhibits T-cell activation. We think VSIG4 plays an important role within the tumor microenvironment in terms of suppression. We've set about to develop TMAb antibodies because we think VSIG4 is a prime TMAb platform target. To date, we have identified eight parental antibodies, and we've optimized them, and we're currently in the process of testing those progeny antibodies. These antibodies are pH sensitive. This was the second program in which we were able to achieve a differential between low pH and physiological pH. Because VSIG4 is very novel, another important milestone for this program is the identification of novel VSIG4 receptors on T-cells. We've made some incredible progress on this front. We recently announced some of this progress. We're looking forward to using this information because I think it will give us a leg up when it comes to selecting a VSIG4 lead antibody, and we plan to do that this year. How about CD39? CD39 is a target you may have heard of before. It's a very important target because it really plays an important role in the production of adenosine, which has been shown to be immunosuppressive. CD39 is an important enzyme because it's the rate-limiting enzyme in the production of adenosine. However, it's been challenging to create effective antibodies targeting CD39 because it's expressed broadly on various immune cells, both in tumors and in normal tissues. We believe that to date, the lack of activity that's been seen with clinical CD39 molecules is due to the expression in normal tissues, thus thwarting the attempt to truly test the CD39 axis. We believe SNS-103 will be the first to do so. As with our VSIG4 program, our CD39 program has been initially successful in identifying antibodies in which there is pH selectivity, and we've selected eight of them for further optimization. While slightly behind our VSIG4 program, we also believe we'll be in a position to select a lead product candidate in 2023. Looking ahead, let me summarize. Our program milestones are as follows. For SNS-101, we will be discussing our multi-dose non-human primate tox PK data in the first half of this year. We're very excited to announce an IND filing on or before April of this year. For both 102 and 103 programs, we look forward to selecting a product candidate. We have a very experienced team, and we look forward to sharing more information with you in the coming months. Thank you very much.