Good day, and thank you for standing by. Welcome to the BTLA Agonist R&D event. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Dan Faga, Interim CEO of AnaptysBio. Good afternoon. Welcome to AnaptysBio's R&D event, focused on ANB032, our BTLA agonist. Today's presentation contains statements about our current plans that are forward-looking. Joining me from AnaptysBio are Dr. Paul Lizzul, our Chief Medical Officer, and Dr. Martin Dahl, our SVP of Research. We're going to cover a significant amount of exciting new data and information, followed by Q and A. This will include an overview of checkpoint agonists, including deeper insights into ANB032's mechanism of action targeting BTLA. We'll present translational preclinical data supporting the rationale to pursue development of a BTLA agonist to treat atopic dermatitis. We will also review our recently initiated phase IIb study and insights into why we are excited about the potential benefit ANB032 may bring to patients living with moderate to severe disease. We're thrilled to have Dr. Emma Guttman join us as well. Guttman is a professor of dermatology and immunology and chair of the Department of Dermatology at the Icahn School of Medicine at Mount Sinai. She'll cover the disease pathology and unmet patient need in atopic dermatitis. AnaptysBio is striving to transform patient health by treating autoimmune and inflammatory disease through the development of antibodies that directly modulate immune cells. Our portfolio of three immune cell modulators include two clinical-stage, best-in-class checkpoint agonists: ANB032, which we are focused on today, and rosnilimab, our PD-1 agonist, with two planned phase II trials initiating this year. The first for rheumatoid arthritis, beginning in the next few months, with top-line data expected by mid-2025, and a second trial in a yet to be disclosed indication that will initiate by year-end. Our third immune cell modulator is ANB033, an anti-CD122 antagonist, on track to file an IND in the first half of next year. The history of AnaptysBio has led us to today's well-capitalized position, with cash runway out through year-end 2026, allowing us to design an optimal multi-year execution plan for the development and continued research of our immune cell modulator portfolio. Over the past 18 years, the AnaptysBio business model has evolved while remaining focused on discovering differentiated antibodies. All of our programs have been discovered internally at AnaptysBio by our research team. The company originated as a research stage out-licensing engine, discovering antibody candidates directed at high-value immunological targets. In 2016, we began the clinical development of a single cytokine blockers, including imsidolimab, an anti-IL-36 receptor antagonist, in a registration-enabling phase III trial for the treatment of generalized pustular psoriasis, or GPP, with top-line data expected in the fourth quarter of this year. Dating back 12 years ago, AnaptysBio outlicensed first-generation variants of a PD-1 agonist to Celgene. These variants were in the early stepping stones relative to the field's advancements and understanding of both checkpoint agonism and the pathology of inflammatory diseases. Both of AnaptysBio checkpoint agonists in development today have significantly benefited over a decade of our company's cumulative expertise and leadership in this field. Over the last 12 months, since I've joined this company, this is where we have refocused. Our approach to clinical development and translational research has been refined. We have also significantly augmented our organization to further complement the exceptional talent that was already here. We are moving forward with conviction to maximize our return on equity by enabling broad clinical development of our best-in-class checkpoint agonists, as well as continue to leverage our research platform to generate differentiated immune cell modulators. Immune cells have extracellular receptors called checkpoints that serve as both markers and regulators of immune cell activation and proliferation. We are all familiar with the many PD-1 checkpoint antagonists developed for the treatment of cancer. These antibodies block the ability of a checkpoint receptor to bind with its natural ligand on an opposing cell. In the context of cancer, this allows the immune cell to operate unchecked and proliferate. Said simply, a checkpoint antagonist releases the brakes on immune cells, allowing them to remain activated to target a tumor. On the flip side, a checkpoint agonist antibody should be non-blocking and bind on a checkpoint receptor near the immune cell surface to facilitate the natural intracellular machinery that downregulates or tunes down an activated immune cell. In the context of autoimmune and inflammatory disease, a checkpoint agonist hits the brakes on runaway inflammation to restore immune balance. BTLA is one of these key checkpoint receptors. BTLA is expressed predominantly on activated immune cells, including T cells, B cells, and dendritic cells that drive inflammatory disease. ANB032 is a non-depleting antibody that binds to the BTLA checkpoint receptor and inhibits activated T cell proliferation, reduces inflammatory cytokine secretion, and modulates dendritic cell function, including inducing Tregs, both in inflamed tissue and in the periphery. By interacting in the periphery, ANB032 prevents further migration of pathogenic T cells into the inflamed tissue. ANB032's broad cellular reach holds promise for the treatment of systemic inflammatory diseases where the BTLA pathway is dysregulated, including areas such as dermatology, rheumatology, and gastroenterology. In atopic dermatitis, multiple immune cells, including Th1, Th2, Th17, Th22, and dendritic cells, contribute significantly to disease pathogenesis. The standard of care, dupilumab, as do most other development-stage therapeutics, block the signal of Th2 cytokines, addressing only a part of this heterogeneous disease biology of AD. Despite this limitation and unmet patient need, the atopic dermatitis market overall is expected to grow to greater than $16 billion by 2030. This biology driving AD matches well with the mechanism of action of ANB032, providing a strong rationale to develop our BTLA agonist to treat patients with moderate to severe atopic dermatitis. In the remainder of today's presentation, you're going to hear a deep dive on the mechanism of action of a BTLA agonist antibody, as well as the drivers of inflammation in atopic dermatitis. We'll share why ANB032, supported with translational, preclinical, and phase I safety data, has the potential to drive deep responses across a broad patient population in AD, as well as share our excitement to execute our recently initiated phase 2B trial towards delivering top-line results expected in the next 18 months. I'll turn it over to Dr. Martin Dahl, our Senior Vice President of Research. Thank you, Dan. In this section, I'm going to walk through why checkpoint agonism is an exciting approach to target for the treatment of inflammatory diseases, and how to achieve maximum agonistic activity. Our rationale for focusing on BTLA, and how we've optimized ANB032 to target this key node in the immune system, and present comparative data from a GvHD model that reinforces ANB032's in vivo potency and best-in-class potential. When the immune system is challenged, a normal inflammatory response ensues. It progresses through a staged process of initiation, amplification, and ultimately, resolution when the immune system completes its task of addressing the challenge. Checkpoint receptors and their ligands are actively involved in this process. However, in many diseases, the inflammatory response often is sustained through self-reinforcing cycles. This dysregulation prevents resolution, ultimately resulting in inflammatory disease with significant risk factors and comorbidities. Put simply, with dysregulation and chronic activity, the immune system may lack the ability to hit the brakes like it would normally. Therapeutically blocking cytokine signaling can inhibit the inflammatory response, providing some degree of symptom relief. Most inflammatory or autoimmune diseases involve numerous immune cell types and numerous downstream mediators that are difficult to target with cytokine signal blockers, thus making it challenging to fully resolve the inflammatory cycle. By therapeutically targeting and leveraging natural immune regulatory mechanisms to modulate the many immune cells that are driving the inflammatory disease, there's an opportunity to dampen the inflammatory cycle and restore immune balance. Checkpoint agonists have the potential to offer differentiated safety and efficacy. There are some diseases, like psoriasis, where a simple cytokine blockade can deliver significant efficacy across most patients, for most autoimmune and inflammatory disorders, there's substantial remaining unmet need that can't be met by blocking a single cytokine. Checkpoint agonists have the potential to act upstream and more broadly than cytokine antagonists to modulate multiple types of activated immune cells, which are the drivers of dysregulation. JAK inhibitors have shown us that broader mechanisms can drive broader and deeper clinical responses. However, there are safety risks and toxicity associated with these small molecule approaches. By targeting immune cells specifically, agonist antibodies will potentially have at least equivalent or superior efficacy as JAK antagonists, but without the potential toxicity. There are T-cell modulators that have already demonstrated the safety of this approach, as abatacept, which broadly targets all T cells, haven't demonstrated significant carcinogenic risk over decades of use. To date, the checkpoint antagonist class, including AnaptysBio checkpoint agonists, has been well tolerated in human trials. We believe targeting checkpoint agonism has the potential to drive broader and deeper responses for autoimmune and inflammatory diseases with substantial unmet need. As Dan outlined, checkpoint receptors are regulators of immune cell activation and function. This regulation occurs by signaling through intracellular domains called ITIMs, that when phosphorylated, recruit downstream signaling modules that turn off immune cell activity. In an unbound state, checkpoint receptors are generally held in a steady state of neutral activity, intermittently signaling when phosphorylated by a kinase and turned off by phosphatases like CD45, which are broadly expressed by immune cells. Agonism occurs when a ligand binds to the checkpoint receptor and drives phosphorylation of the ITIM, resulting in downstream signal transduction that hits the brakes in the immune cell. Importantly, the agonistic signal is amplified when an opposing cell creates a close immune synapse with the checkpoint-expressing cell, driving clustering of the checkpoint receptors and exclusion of large phosphatases like CD45, to bias the state of these ITIM motifs towards elevated or prolonged phosphorylation. With more than a decade of experience in the checkpoint agonist space, we've dialed in the most important characteristics contributing to maximal agonism and how these characteristics work together to create the optimal antibody. One way to achieve activation of the checkpoint receptor is through direct binding with a checkpoint agonistic antibody. As you can see in the left graph, this excludes CD45 and focuses kinase activity. I'll show you data shortly that simply binding independently achieves a modest level of checkpoint agonism. The key factor to driving optimal checkpoint agonism is the enabling of a tight immune synapse, in which the agonist antibody binds to a membrane-proximal domain of the checkpoint receptor and simultaneously binds to an FC receptor on an opposing cell. As demonstrated in the graph on the right, the tight synapse is important because it drives enhanced agonistic activity by physically excluding large phosphatase molecules, such as CD45, resulting in robust and sustained downstream signaling. AnaptysBio checkpoint agonists, like ANB032, are best in class because they optimize inhibitory signaling by enabling tight immune synapse formation, leveraging optimal binding properties on the checkpoint receptor and simultaneously optimal binding properties on the FC receptor. BTLA, or B- and T-lymphocyte attenuator, is an inhibitory checkpoint receptor that regulates T cells, B cells, and dendritic cell function. It's expressed only on immune cells and preferentially on activated immune cells. If you're familiar with PD-1 and its interaction with its ligand, P1, to induce potent inhibition of T cell activity, you'll appreciate that BTLA works in a very similar manner, interacting with its ligand, HVEM. Both PD-1 and BTLA are phosphorylated upon binding their respective ligands, and both recruit SHIP family phosphatases as part of their agonistic signaling cascade that inhibit activation signals downstream of antigen presentation and co-stimulation. As a reminder, T cells require both antigen presentation to the T cell receptor, accomplished through interactions between the MHC and the TCR, and co-stimulation, accomplished through CD80 or CD86 binding to CD28. This is really important. When these interactions are inhibited, T cells can't be effectively primed to expand and differentiate into inflammatory T cells. One of the reasons that makes BTLA agonism so powerful is because BTLA can also be expressed on the dendritic cell side, and its ligand, HVEM, can also be expressed on the T cell side. This allows for BTLA agonism on the dendritic cell in addition to that on the T cell. Inhibition of these signals is the basis of checkpoint agonism. As I said, inhibiting antigen presentation and co-stimulation leads to less effective priming of T cells, which prevents T cell expansion and cytokine secretion. Importantly, it can also contribute to the induction of regulatory T cells or Tregs. Because BTLA is such a key node in the immune system, dysregulation of the BTLA pathway has serious consequences, accelerating disease onset or exacerbating existing disease. There are many published examples that demonstrate how dysregulation of the BTLA pathway accelerates disease onset or exacerbates inflammatory disease. Here's one example where dermatitis is being studied in mice. On the left, you can see what happens when BTLA is knocked out. When an immune stimulant is painted onto the ears of mice, they develop an exacerbated inflammatory response, measured by an increase in the thickness of ear skin, as well as greater infiltration of T cells. These T cells are secreting more inflammatory cytokines than wild-type mice. This demonstrates that BTLA is a critical node in negative immune regulation. On the right, normal mice with BTLA are treated with the same immune stimulant used in the experiment on the left. After administration of a mouse-specific BTLA agonist, it was reduced disease severity in the ears, reduced T cell infiltration, and reduced inflammatory cytokine secretion compared to untreated animals. This provides us with evidence that modulation of BTLA signaling can have a powerful effect on inflammatory responses. On one hand, literature documents that when there's insufficient BTLA agonism alone, there's dysregulation of immune cells, resulting in accelerated inflammatory disease onset or increased severity of disease. On the other hand, BTLA signaling has proven to be a highly potent modality in preclinical models for reducing inflammatory disease by reducing T cell expansion, migration into tissues, and inflammatory cytokine secretion. We developed ANB032, a BTLA agonist antibody that has the potential to modulate all phases of pathogenic inflammatory responses, including initiation, amplification, and resolution. ANB032 binds to a membrane-proximal epitope of BTLA and maintains the potential to engage FC receptors, which we believe optimizes overall agonistic signaling and has resulted in a best-in-class profile. As Dan highlighted, BTLA is expressed across many immune cells implicated in inflammatory diseases. Here's how ANB032 works. First, ANB032 has a wild-type IgG4 FC domain, which enables FC receptor engagement while avoiding depletion of BTLA-expressing cells. Second, on T cells, ANB032 inhibits activated T cell proliferation and reduces inflammatory cytokine secretion from Th1, Th2, Th17, and Th22 cells. Third, it's also a potent modulator of dendritic cell maturation and function, reducing both antigen presentation by MHC and expression of costimulatory molecules. These properties contribute to the enhanced ability of ANB032-treated dendritic cells to induce more Tregs. These three properties together are complementary to driving toward immune resolution. The data on this slide highlight what we believe is one of the key characteristics that differentiates ANB032 from in-class competitors. I walked you through the framework for why engaging an opposing cell to exclude phosphatases was so important for potentiating agonistic signaling. The data here explains why. This assay measures SHP-2 recruitment to phosphorylated BTLA, which is a key mechanism through which BTLA exerts its agonistic activity. In the green curve on the left, simply binding BTLA with ANB032 induces an increase in SHP-2 recruitment. This level of agonism is similar to that of the brown curve, induced when BTLA is engaged by a stabilized, soluble form of HVEM, its natural binding partner. However, when we introduce into the assay an opposing cell expressing an FC receptor, to which ANB032 can simultaneously bind and generate an immune complex, we see a dramatic potentiation in SHP-2 recruitment, with both a left shift in potency as well as a magnitude shift. I want to highlight the importance of this characteristic for agonistic potency, because the FC receptor binding profile of ANB032 is differentiated relative to Lilly's BTLA agonist, currently in a phase II study in SLE. In short, ANB032 has superior FC receptor engagement, and I'll show you in the next slide how that translates to greater biological effect in a disease setting in vivo. Now we get to see how a BTLA agonist and ANB032's best-in-class profile translates in vivo. We've run an experiment comparing ANB032 to Lilly's BTLA agonist in a humanized murine model of GVHD, a T cell-dependent disease model where human PBMCs are transplanted into a mouse. The human T cells drive a GVHD phenotype due to T cell expansion, infiltration into tissue, secretion of inflammatory cytokines, and ultimately, death of the animal. First, let's look at the Kaplan-Meier survival curves on the left. This is a severe model of disease. Death is a key endpoint in this GVHD model. 100% of the animals treated with an isotype control, which is to say, placebo, succumbed to disease and died by day 32. Animals were treated with the same dose of antibodies biweekly for only the first 28 days. You'll see that even during the treatment period, some of the animals treated with Lilly's BTLA agonist succumbed to disease. Notably, all of the ANB032-treated mice survived well beyond the treatment period. Furthermore, at the end of the study, there was a clear differentiation in the survival benefits of ANB032-treated animals versus the Lilly-treated cohort. Looking at the body weight graph, mice treated with the ANB032 gained more weight than those treated with Lilly's agonist and sustained this weight through the end of the study, showing robust, durable response even after the cessation of bi-weekly dosing. We also measured the engraftment and expansion of the human T cells at a midpoint in the study, at day 18, when there was still enough isotype-treated animals for comparison purposes. These are the T cells that expand, infiltrate tissue, secrete inflammatory cytokines, and ultimately lead to death in this model. ANB032 inhibited T cell expansion to a greater degree than Eli Lilly and Company's BTLA agonist. We believe these exciting data demonstrate the potent in vivo capacity of ANB032 to drive deep, durable responses, even in a model as severe as GVHD. I just covered a lot of ground, so let me review the key points from this section. First, modulating immune cells through checkpoint agonism represents a promising approach to leverage a natural pathway for immune regulation to safely drive differentiated outcomes for a broad range of patients. Second, BTLA is a key checkpoint molecule that modulates the activity of broad populations of T cells, B cells, and dendritic cells. Third, our head-to-head comparison in a GVHD model demonstrates that ANB032 is the best-in-class BTLA agonist with the potential to deliver durable responses and restore immune balance. We expect ANB032 to be broadly applicable to the treatment of a variety of autoimmune and inflammatory diseases, starting with atopic dermatitis. It's my great pleasure to introduce Dr. Guttman, who will speak about atopic dermatitis, disease pathology, and current unmet needs for people with this disease. Hi, everyone. My name is Emma Guttman. I'm the Waldman Professor of Dermatology and the Assistant Chair of the Department of Dermatology at the Icahn School of Medicine at Mount Sinai. I'm also the immediate past president of the International Eczema Council. I'm really happy to talk today about the unmet needs in patients with atopic dermatitis and our need for additional targets. Atopic dermatitis is a very common disease, more common than we used to think. It's in fact the most common inflammatory skin disease as we know now. 7% of the adults in the United States by several studies, and around 15% of children, and in some countries in Asia, it may be even more. Up to a third of the patients will have moderate to severe disease. Of course, still, the majority will have mild to moderate disease. There is a very large unmet need still for long-term disease control. Yes, we do have treatments for atopic dermatitis already. Still we have a large unmet need for better long-term disease control. However, the therapeutic drought for atopic dermatitis is finally nearing an end due to a lot of research and increased knowledge in this field. Let's review: What is the impact of moderate to severe atopic dermatitis? Atopic dermatitis is one of these diseases that has a lot of impact on quality of life. First of all, we see it, right? Patients have erythematous patches that are really not comfortable, and the more patches you have, of course, the more discomfort you will have. Body surface area is really important. When you have more than 10% body surface area involved, and many patients will have much more than that, you are really feeling a lot of discomfort. What does discomfort mean? It disrupts education of a patient, both children, adolescents, and adults. It disrupts them to do their job, right? Because they cannot sleep. They itch all the time, including at nighttime. They itch during the day. Some patients, all they can think about is just thinking about their eczema. It gets them to have anxiety, depression, low self-esteem, interferes with their relationships, interferes with their jobs, gets them to have an interference with their personal relationship or interpersonal relationship, marriage problems, financial problems. They cannot exercise. It's really painful for them to exercise because of sweating. And sometimes any water contact can be painful for these patients. Really major interference with the quality of life of patients and parents of children with atopic dermatitis, particularly again, when extensive body surface areas are involved, more than 10% body surface area for moderate to severe atopic dermatitis. As I hinted, a greater understanding of the pathogenesis of atopic dermatitis is now really enabling and facilitating to develop better and better treatments and novel targets, finding novel targets. Now we know that atopic dermatitis is a complex disease that involves abnormalities in multiple cells, and those cells are T cells, they are dendritic cells, and they are B cells. When we are talking about the T cells, we have many flavors of these T cells, and unlike psoriasis, that is really focused on the Th17 and IL-23 biology. In atopic dermatitis, we have a much more complex picture, where the main cell is Th2 cell that produces many molecules. It has multiple cytokines that are associated with it, such as IL-13, IL-4, IL-31. There are other T-cells that are also important, such as Th1 with the leading cytokine Interferon-gamma, Th17, the leading cytokine is IL-17, and Th22, that the leading cytokine is IL-22. To complicate even more, there is some irrelevance for B-cells and eosinophils in the disease, as well as a regulatory cell called Treg. We need to understand that dupilumab really revolutionized the way we are treating atopic dermatitis, because before dupilumab, we had immune suppressants that really targeted everything. They were really nonspecific and induced some side effects because of that. Dupilumab narrowed it down to target only IL-4 and IL-13, because it is an IL-4 receptor antagonist. IL-4 and IL-13 are involved in the barrier disruption in atopic dermatitis, including the differentiation abnormalities such as filaggrin, as well as tight junctions, lipids, and many others, because the barrier is abnormal in patients with atopic dermatitis. Not only they have abnormalities in immune responses, but the barrier of patients with atopic dermatitis is not normal. The results of dupilumab are very good when you look at in several metrics that we are using for assessing the improvement in the disease without any additional treatment, which is called a monotherapy study. This was a 16-week study, not allowing topical steroids, and we assessed EASI-50, EASI-75, and EASI-90. What are these metrics? EASI-50 means how well you managed to get 50% of the disease resolved. It was a secondary endpoint. EASI-75, how well you get 75% of the disease resolved. EASI-90 means almost clear. You are not at EASI-100, which is full clearance, so you are almost clear, and that was at 32.8%. What does it tell us? When EASI-75 is only half of the patients, 50%, and EASI-90 is around a third of the patients, that the majority of patients are still not clear. We can still do better, even though this treatment really revolutionized the way we are viewing atopic dermatitis treatment, but still we have a way to improve upon this treatment. This is also reiterated by assessing quality of life of patients, how they assess their improvement in sleep, control of disease, itch and pain-free periods, and how treatment is either meeting their expectations or exceeding their expectations. Pay attention that less than 25% of the atopic dermatitis patients say that they are completely satisfied with their treatment. What it means, again, that we can still do better and much better. We, again, are at a good point, but we can be at a much better point, so we still have a while to improve. Why is that? That stems from the fact that atopic dermatitis, while it is focused on Th2 biology, as I said, Th2 is very central to the disease, with the leading cytokines, IL-4 and IL-13. Atopic dermatitis, unlike psoriasis, is a highly heterogeneous disease that involves multiple immune cytokines, depending on multiple factors, such as age of onset of atopic dermatitis, the duration of the disease, the chronicity of the disease, the ethnicity of the patient. Patients that are Asian may have a different phenotype with increased Th17, whereas African American, for example, do not have Th1. Children have also increased Th17. All of these are resulting in really heterogeneous presentation. In fact, we just recently published a paper on patients that have atopic dermatitis much later in life, and this is a phenotype that we see increasingly more often than previously recognized. They have greater Th1 activation compared to those with the disease starting in childhood. It's about 15% of the population that start having atopic dermatitis later in adulthood, of the population of eczema patients, obviously. There are many factors that vary between patients, and that relates also to differences in treatment. These factors are IgE status, different triggers. I already told you, sweating plays a role, but not only, exercise, contact with water, and many others. All of these will have differences in the impact on itch, sleep, and quality of life. The exciting news is that the pipeline for atopic dermatitis is growing. We now have multiple things in the pipeline targeting some of them. The majority may focus on Th2 targets, such as IL-13. There are several going into the disease. There is another IL-4 receptor antagonist that targets a different epitope than dupilumab. There is an IL-13 receptor antagonist as well. There is an itch-aimed related cytokine that is being targeted, nemolizumab, IL-31 antagonist, and there is an IL-22 receptor antagonist. They also come into play because Th22 cells are also really important in atopic dermatitis. There are some cells targeting activated T-cells or dendritic cells that are linked to these activated T-cells, so either OX40 or OX40 ligand antagonist, that are in a relatively advanced stages. there is an S1P receptor modulator, etrasimod, that is also in phase III. we now have a new molecule that is being targeted, that is a different class, a BTLA agonist, ANB032, that is now moving into phase IIb. Now, another important concept when we are considering treatment of patients with moderate to severe atopic dermatitis is the idea that we cannot treat them just with topicals. Why is that? We and many others showed that these patients will have systemic inflammation. The inflammation is more than skin deep. That is a concept that in psoriasis was well established, but in atopic dermatitis, this was built just quite recently. It was built by many publications showing increases in blood of patients of activated T cells, also activated in B cells, and there are also dendritic cells in the circulation of these patients, and also increases in circulatory cytokines and cardiovascular-associated markers. Importantly, that came exactly at the same time when several population-based studies showed increased cardiovascular risk or disease in atopic dermatitis patients in very high number of patients. Now we can say with confidence that in patients with moderate to severe disease, atopic dermatitis is a systemic disease and needs to be treated with systemic treatment to really be able to control the disease long term so that it doesn't fluctuate and it prevents flares. I also have a lab that focuses, among others, on atopic dermatitis, and I'm studying biomarkers. To really understand the phenotype of atopic dermatitis and also to understand the effect of the given treatment, we really need to integrate in our understanding a model that will incorporate both lesional skin and non-lesional skin. That uninvolved skin of atopic dermatitis patients is also important because it will have a partial disease phenotype as well, likely because of the systemic inflammation we have in these patients. We also need to bring into account the systemic inflammation of these patients and the markers they have in blood. We really need to account for the involved skin, the uninvolved skin, and the circulatory abnormalities that we have in patients with atopic dermatitis when we are considering a trial. This is really important because this is really the way we are facilitating the therapeutic development in atopic dermatitis. It starts from bench studies of pathogenesis, in which we are trying to understand the profile of these patients in their skin and in their blood, and in the skin, remember, both lesional but also non-lesional skin. That helps us to really narrow down some hypothesis or some disease targets. Then we follow up with clinical trials with targeted agents that also have skin and blood profiling, and that gets us to biomarkers of therapeutic response. Multiple cycles will get us to new treatments. Of course, you know, along the way, there are successes, but there are also failures, but both are really important to help us frame the pathogenic concepts and the therapeutic directions. Again, the atopic dermatitis disease biology is really heterogeneous, and that's where a BTLA in targeting agent fits really well this a mechanism of action, because the pathogenesis of atopic dermatitis is really linked broadly to multiple cells and multiple T cells. It depends on the phenotype of atopic dermatitis, like we said, depending on ethnicity, the age of the patient, and many others. It's been broadly linked to Th2, but also to Th1 and Th17, Th22, and also dendritic cells are important. BTLA-expressing cells, Th1, Th2, Th17, Th22, B cells and dendritic cells, are validated drivers of disease in atopic dermatitis across its phenotypes. It is exciting to now see new targets, such as this BTLA agonist antibody, that now is coming into clinic in clinical trials. Why is this important? Because it may target additional patient populations, because it targets T cells, B cells, and dendritic cells. When we are talking about T cells, remember, it goes after Th2, but also Th1 and Th17 and Th22. It has some function also on dendritic cells and Tregs, potentially allowing additional benefit for our patients. Because, remember, I bring you back to the idea that still the majority of our patients are not fully controlled with current monoclonal antibodies, and we need better disease control, particularly long term or particularly for chronic use. We see that in practice. We see also patients that are on a treatment, they are controlled for a while, and then they stop being controlled. We still need to improve the way we are treating our patients, and we need additional novel mechanisms of actions. This offers potentially for our patients a novel mechanism. With that, thank you so much for your attention. Thank you, Dr. Guttman. So far today, we've discussed checkpoint agonism, including deeper insight on ANB032's mechanism of action targeting BTLA. Dr. Gutman has provided a great overview of atopic dermatitis biology, as well as clarity on what's still driving the unmet need in this disease. In this section, I'm going to show you some translational and some preclinical data that are the foundation for our strong belief that targeting BTLA with ANB032 has significant potential in atopic dermatitis. As Dr. Guttman discussed, while blockade of IL-13 signaling has provided options for patients, there's emerging evidence that targeting additional cell types can be as efficacious or more efficacious than currently available treatment options. We now understand that atopic dermatitis is a systemic disease rather than localized only to the tissue, and it's driven by the involvement of broad T cell-driven pathways, including Th1, Th2, Th17, Th22, and dendritic cells. In early-stage studies, we're now seeing supporting evidence of the potential for immune cell modulators to go broader and to drive meaningful outcomes. I'll lay out in the following slides that BTLA agonism has the potential to be a broader and more potent immune cell modulator that can drive differentiated outcomes for both biologic, naive, and experienced patients. BTLA is expressed broadly across the T cell substance that are drivers of atopic dermatitis, but what's particularly exciting is that BTLA is also expressed on dendritic cells, which are less frequently discussed due to the lack of therapies that directly impact them, and these fees are critical upstream orchestrators of T cell activation. There's a common analogy used in immunology that while T cells are the soldiers, dendritic cells are the generals, and data demonstrate that dendritic cells are significant contributors to atopic dermatitis pathophysiology. BTLA agonism modulates dendritic cell function, which further impacts T cell inflammation and may be key to delivering resolution of inflammation that could result in durable outcomes. On this slide, you can clearly see in these images from a paper published by Dr. Gutman as far back as 2011, that there's an enrichment of T cells and dendritic cells in the skin of atopic dermatitis patients, supporting the understanding that T cells and DCs are hallmarks of AD skin. In the next few slides, I'll focus on answering three key questions related to T cells and dendritic cells. First, what does BTLA pathway dysregulation look like in atopic dermatitis? Second, how does BTLA agonism by ANB032 affect T cell function in atopic dermatitis? Third, how does BTLA agonism by ANB032 affect dendritic cell function? We're going to discuss the effect of ANB032 on both T cells and DCs. Using both published clinical and AnaptysBio generated preclinical data, I'll share our rationale for why ANB032 has the potential to deliver differentiated outcomes in atopic dermatitis. First, we reanalyzed existing data from Dr. Guttman, published in The Journal of Allergy and Clinical Immunology in 2018, looking at BTLA and HVEM expression in skin samples from healthy donors and patients with atopic dermatitis. In the graph on the left, BTLA expression is elevated in biopsies taken from lesional skin of atopic dermatitis patients compared to healthy skin. Likewise, you can see in the graph on the right, HVEM expression is reduced compared to healthy skin, so the receptor is up and the ligand is down. As I presented earlier, this profile of dysregulation in the BTLA pathway, where there's insufficient ligand presence to engage BTLA agonism, have been reported to drive aberrant inflammation in both murine disease models and in patients with BTLA or HVEM polymorphisms, and may be a significant driver of atopic dermatitis pathology. In addition to looking at BTLA and HVEM expression in lesional AD skin samples, we also looked at them in blood samples, as AD is known to be a systemic disease. In the periphery, we see the same BTLA pathway dysregulation. In the left graph, BTLA expression on CD4 and CD8 T cells in the periphery in atopic dermatitis patients is higher than BTLA expression in healthy donors. On the right, you see the same pattern as we saw in the skin, with HVEM expression reduced on the CD4 and CD8 T cells of AD patients compared to healthy donors. These data reinforce that atopic dermatitis is not just driven by a local dysregulation of inflammation in the skin, but is a systemic inflammatory disease characterized by BTLA dysregulation. We expect that a BTLA agonist will have therapeutic effects both peripherally and locally in the tissue, addressing skin cell types and key factors driving this disease. Just one final slide on this BTLA dysregulation. The data on the left demonstrates BTLA expression in the skin before treatment, and the data on the right demonstrates BTLA expression after dupilumab treatment. On the right, in orange circles, which represent incomplete responders to dupilumab, BTLA remains consistently elevated in the skin. In black circles, which represent complete responders to dupilumab, BTLA expression is reduced almost back to the levels seen in healthy skin. Back to my first question: What does BTLA pathway dysregulation look like in atopic dermatitis? In atopic dermatitis patients, BTLA is bumped and its ligand, HVEM, is down. Supplementing BTLA signaling with a BTLA agonist through this pathway may be a potent way of restoring immune balance. To the second question: How does BTLA agonism by ANB032 affect T cell function in atopic dermatitis? Depicted in this illustration, BTLA agonism should result in broad, direct, and potent inhibition of the pathologically activated T cells. Coming slides, I'll highlight ANB032's inhibition of T cell proliferation, resulting in a reduction of cytokine secretion in atopic dermatitis patient PBMCs. Start by looking at T cells. As we've previously demonstrated, we see clear gene expression patterns demonstrating the presence of Th1, Th2, Th17, and Th22 phenotypes in skin biopsies of atopic dermatitis patients. Our goal is to address as many of these T cells as possible with one therapy. To determine the impact on T cell function, we assessed ANB032's impact on both T cell proliferation and associated cytokine secretion. We stimulated atopic dermatitis patient-derived peripheral blood cells in the presence of ANB032 and assessed proliferation using CFSE. Shown in the graph on the left, ANB032 inhibits T cell proliferation in a concentration-dependent manner. An example of the inhibition of T cell proliferation in a single AD patient sample is shown on the right. Now, let's look at ANB032's impact on cytokine secretion from different T cell subsets. As you can see in these four graphs of PBMCs derived from AD patients, direct BTLA agonism with ANB032 consistently reduces inflammatory cytokine secretions across Th1, Th2, Th17, and Th22. This broad modulation is statistically significant at concentrations that we would expect to achieve in a clinic. Furthermore, patient-level data, which we're not showing here, demonstrate this modulation is consistent across donors. This activity across multiple Th subsets highlights that ANB032 could be applicable to a broader patient population than those responding to a single cytokine antagonist. Before discussing how ANB032 modulates a BTLA-expressing dendritic cell, let's first review the biology of dendritic cell maturation. Dendritic cells largely exist in two states, immature and mature. Why does this matter? In the figure on the left, immature DCs express low levels of MHC and costimulatory molecules, and because of this, they're inefficient at priming T cells. They also express a low level of BTLA. When dendritic cells encounter stimuli, such as LPS, they mature by upregulating expression of MHC and costimulatory molecules. Mature DCs become highly efficient at turning naive T cells into inflammatory T cells. The right graph demonstrates that BTLA is highly expressed on mature dendritic cells that we can target and modulate with ANB032. An ideal therapeutic molecule should prevent the maturation of DCs or reduce the maturation state of DCs, thereby preventing T cell priming or the generation of inflammatory T cells. This is super important and leads us to our last question: How does BTLA agonism by ANB032 affect dendritic cell function? As I've described, mature dendritic cells act earlier in the inflammatory cycle to educate and stimulate naive T cells and turn them into pathologically activated T cells. BTLA agonism by ANB032 uniquely modulates these dendritic cells, in addition to the direct activity on T cell function that we saw earlier from agonism. This may serve to cut the inflammatory cycle by reducing the capacity of these DCs to stimulate T cells to proliferate and secrete inflammatory cytokines. I'll show that BTLA agonism by ANB032 inhibits expression of antigen presentation and costimulatory molecules on DCs, which are themselves validated targets for immunology drugs. I'll show that when ANB032 modulates dendritic cells, it results in the generation of FoxP3-positive Tregs, which could happen even in a highly inflammatory environment. In the figure on the upper left, we stimulated the dendritic cells with LPS in the presence of an isotype antibody or ANB032. LPS induced an increase in the number of mature dendritic cells, which ANB032 clearly inhibited, as demonstrated in the graph on the upper right. As demonstrated in the graph on the lower left, ANB032 also inhibited the amount of MHC expressions by DCs. On the bottom right, ANB032 inhibited co-stimulatory molecule expressions by DCs. This is the signature we see from ANB032-driven BTLA agonism of dendritic cells. These two mechanisms, direct agonism of T cells and direct agonism of dendritic cells, are synergistic in preventing the generation and proliferation of inflammatory T cells. Particularly exciting is our last set of data demonstrating ANB032 modulation of dendritic cells induces FoxP3 positive Tregs. Tregs, or regulatory T cells, play a critical role in balancing our immune system. Tregs express the transcription factor FoxP3 and suppress activation, proliferation, and cytokine production of CD4 and CD8 T cells. Dendritic cells were co-cultured with naive T cells. Compared to DCs previously treated with isotype, the DCs previously treated with ANB032 generated significantly more FoxP3-expressing Tregs. This is a unique and potentially highly potent mechanism through which ANB032 may contribute to resolution of inflammation and result in durable immune balance in numerous inflammatory diseases. This could be a key driver of differentiated outcomes for ANB032 in atopic dermatitis. ANB032 inhibits T cell and DC-mediated inflammation, which are both validated drivers of AD pathogenesis. Specifically, we've shown the BTLA pathway is dysregulated in both the tissue and the periphery, demonstrating that atopic dermatitis is a systemic disease. Second, BTLA is broadly expressed on T cells and dendritic cells. Third, as shown in our preclinical data, ANB032 directly inhibits proliferation of, and cytokine secretion from, AD patient-derived pathogenic Th1, Th2, Th17, and Th22 cells. Also, in our preclinical data, ANB032 directly modulates dendritic cells, which, together with the direct effect on T cells, provides a synergistic mechanism to further drive the inhibitory effect on T cells. Furthermore, ANB032-treated DCs can induce Tregs. Because of this, we're very excited to move this molecule into phase two. Let me hand it over to my colleague, Dr. Paul Lizzul, our Chief Medical Officer. Thank you, Martin. Now, I will walk you through our clinical development rationale for ANB032 in atopic dermatitis, focusing on a few key points, including, first, a framework for clinical differentiation compared to other agents already on the market or in development. Second, ANB032's phase I healthy volunteer trial results. Finally, our development plan, translational medicine strategy, and operational execution plan for our recently initiated phase IIb trial in atopic dermatitis. To understand the evolving treatment landscape, it is important to recognize that despite approvals over the past five years of first-generation, single-cytokine-targeting biologics to treat atopic dermatitis, there remains significant headroom to improve upon existing treatment options. Dr. Guttman also talked about that in her presentation earlier. We see a parallel between where atopic dermatitis therapeutic development is today to where psoriasis development was over a decade ago. Similar to what has been realized for psoriasis patients, there is a true unmet need and tremendous opportunity to achieve superior and truly clinically meaningful levels of efficacy beyond the first generation of biologics that have been approved. In 2004, the first anti-TNF therapy was approved in psoriasis, which was truly innovative for the time, but it had relatively modest efficacy. This was followed by tremendous advancements in the understanding of disease biology and a series of incremental approvals with biologics targeting the key pathways involved in psoriasis pathogenesis. These novel agents provided deeper efficacy for many patients, even pushing the efficacy bar to achievement of clear to almost clear skin in a large proportion of patients. Now let's take a look at atopic dermatitis. Similar early progress has been made with the approval of the first-generation IL-13 targeting therapies, followed by incremental approvals in the same pathway as was just covered by Dr. Guttman. Other single cytokine-targeting agents, with the exception of IL-4 or IL-13, have either largely failed to provide meaningful efficacy or have not provided additional clinical benefit over dupilumab to date. Therapies targeting a broader range of cytokines, such as the JAK inhibitors, have improved on the efficacy benchmark set by single cytokine-targeting agents. On mechanism but off-target activity has raised legitimate and rational safety concerns for this class of medications that have black box warnings, limiting JAK inhibitors from dosing to their full efficacy potential. Other immune cell modulators are being evaluated in mid- and late-stage studies in atopic dermatitis and hold some promise of enabling broader immune modulation, but without the off-target toxicities associated with the small molecule JAK inhibitor class. For example, OX40 ligand antagonists that target a co-stimulatory checkpoint pathway observed efficacy in preliminary proof-of-concept studies, which appear to minimally equal what is seen with the Th2 or IL-13 targeting standard of care agents, such as dupilumab, supporting the potential of an immune cell modulator to expand treatment options beyond first-generation biologics. We are excited about ANB032's comprehensive approach to deliver clinically meaningful outcomes that are differentiated, providing broader and deeper responses, but without the safety and tolerability issues seen with the JAK inhibitors. Unlike in psoriasis, where the disease is dominated by one or two key single cytokine pathways, atopic dermatitis is a systemic disease where a broader immune-modulating approach is necessary to drive to optimal results, given the heterogeneous nature of the disease. Altogether, as a whole, or even in segments, this represents a large patient population and unmet need. We estimate that more than 1.2 million atopic dermatitis patients who are not adequately controlled on conventional therapies are eligible for advanced biologic treatment options in the U.S., including those who had experience with an IL-13 targeting agent. There remains significant headroom to improve upon and differentiate versus standard of care and other development-stage programs. There are three ways to consider the opportunity for ANB032, given its mechanism of action. First, to provide a treatment option for a broader population of patients, including the majority of patients who are suboptimal responders to IL-13 single cytokine therapy. Second, the potential to achieve a deeper response for all patients, including the 45%-50% of patients who achieve EASI-75 scores. Third, for any patient to drive to resolution of inflammation that could result in durable outcomes. We recognize that dysregulation of diverse cell types contributes to AD pathogenesis, and ultimately, this results in the clinical signs and symptoms observed in patients. This explains the observed suboptimal clinical responses for the majority of patients when solely targeting a single Th2 cytokine pathway, such as IL-4 and IL-13. The opportunity for a BTLA agonist, such as ANB032, to safely target not only Th2 cells, but also Th1, Th17, Th22, as well as dendritic cells, creates a compelling opportunity and case for a therapy to improve upon therapeutic options for all atopic dermatitis patients. As we have previously disclosed, our Phase I SAD/MAD trial demonstrated safety as well as rapid and sustained target engagement on both T cells and B cells. This was a randomized, double-blind, placebo-controlled, healthy volunteer Phase I trial, where single ascending dose cohorts received subcutaneous or intravenous single doses, while multiple ascending dose cohorts received four weekly subcutaneous doses. ANB032 was generally well tolerated, with no dose-limiting toxicities and no discontinuations due to adverse events, other than one patient quarantined for potential COVID infection. No serious adverse events were reported. Most adverse events were considered to be mild or moderate, of short duration, resolved without sequelae, and occurred sporadically in a dose-independent manner. Importantly, this study confirmed that the pharmacodynamic activity of ANB032 in humans was rapid and sustained target engagement on both T cells and B cells. With these favorable results, coupled with a robust preclinical package, we are excited to have initiated the phase IIb trial in atopic dermatitis. Based on our understanding of BTLA agonism, we believe that ANB032 can address all segments of the population. Our global phase IIb study includes an all-comer population of adult patients with moderate to severe AD, who are either anti-IL-13 treatment, naive or experienced. The dose ranging study has three active arms versus placebo in approximately 160 patients with over 40 sites participating in North America and Europe. We will be assessing both every other week and monthly dosing cohorts. Patients will receive study drugs through week 12, with a primary endpoint assessment at week 14, measuring the mean change from baseline in EASI and secondary endpoints, including IGA clear or almost clear and EASI-75. Patients will then be followed for an additional 12 weeks after treatment to understand longer-term safety, as well as the potential for prolonged and sustained efficacy. From a translational medicine perspective, we will be exploring potential predictive biomarkers to inform not only future atopic dermatitis development and patient selection, but also mapping changes onto potential mechanistic drivers of atopic dermatitis and additional diseases. A major goal of this study is to evaluate biomarkers at baseline that may be predictive of treatment responses. While we are studying an all-comer population, exploration of differences between clinical responders and non-responders, regardless of prior IL-13 treatment, may help to clarify which patients may be the ideal candidates for ANB032. We are excited about applying these learnings to this program, as well as future studies for our BTLA agonist. As we have previously guided, we expect to report top line week 14 data by year-end of 2024. We are pulling on a number of levers to drive quality data and timely enrollment in this trial. We have selected more than 40 well-trained dermatologist investigators with experience conducting atopic dermatitis trials in both North America and Europe. This will support recruitment of both IL-13 naive and experienced patients. Importantly, we have long-standing relationships with top KOLs in the field and are working with expert CROs who have extensive atopic dermatitis experience. In summary, there is a real unmet need for an atopic dermatitis treatment option that delivers improved outcomes for patients. Standard of care or other development stage programs do not adequately address AD disease heterogeneity, falling short on the inhibition of all the diverse contributing cell types, including Th1, Th2, Th17, Th22, as well as dendritic cells. We have initiated our global phase IIb trial with clear and precise endpoints, recruiting across more than 40 high-quality experienced sites in North America and in the EU. We look forward to sharing these top-line data with you in the fourth quarter of 2024. I will now turn the call back over to Dan for closing remarks. Thanks, Paul. We just covered a lot of ground, which supports our conviction in the initial development of ANB032 for the treatment of atopic dermatitis. The understanding of AD pathogenesis has evolved. We know the disease is broadly driven by a range of T cells, including Th1, Th2, Th17, and Th22 cells, as well as dendritic cells. This biology matches well with the mechanism of action of our BTLA agonist, which inhibits activated T cell proliferation, reduces inflammatory cytokine secretion, and modulates dendritic cell function, including inducing Tregs. An estimated 1.2 million patients in the U.S. alone have moderate to severe AD and are eligible to be treated with biologic therapies. This commercial market is only in its early days, projected to generate greater than $16 billion in global sales by 2030. We've shown that ANB032 has the potential to drive deeper responses across a broader patient population in atopic dermatitis relative to existing treatment options. ANB032's phase 2 development is supported with a robust translational preclinical package, safety data in healthy volunteers, as well as compelling PK and PD. We're excited that AnaptysBio's global phase 2B trial is underway, with top-line results expected by year-end 2024. AnaptysBio is a leader in the development of checkpoint agonists, a novel MOA, which can deliver differentiated outcomes while restoring immune balance across autoimmune and inflammatory diseases. In addition to ANB032, our PD-1 agonist, rosnilimab, is in development with two global phase II trials initiating later this year. An additional investor event focused on rosnilimab is being planned in the second half of 2023. Thanks, everyone, for listening, and special thanks to Dr. Guttman for sharing her real-world experience. I also want to thank all the patients and families who participate in the clinical trials to advance our science. Lastly, thank you to the AnaptysBio team for all the work they do every day.