My name is Christie, and I will be your conference facilitator today for Amgen's conference call from EADV Inflammation. All lines have been placed on mute to prevent any background noise. There will be a question and answer session at the conclusion of the last speaker's prepared remarks. In order to ensure that everyone has a chance to participate, we would like to request that you limit yourself to asking one question during the Q&A session. To ask a question, please press star, then the number 1 on your telephone keypad. To withdraw your question, please press the pound key. I would now like to introduce Arvind Sood, Vice President of Investor Relations. Mr. Sood, you may now begin. Thank you, Christie. Good morning, everybody. Thanks for joining us this morning. Over the weekend, we announced positive data from a phase II study of AMG 451 at the European Academy of Dermatology and Venereology. AMG 451, as you know, is a potential first-in-class OX40 fully human monoclonal antibody that's being developed for the treatment of moderate to severe psoriasis. In addition, Christie, there's a little bit of background noise. Okay. All right, let's see if this works. All right, in addition to reviewing this data in some detail, I would like to invite you to engage in a broader dialogue this morning on all the work that we have done and continue to do to develop a broad presence in inflammation. With Enbrel as a backbone, we have amassed decades of functional expertise in this area and have an opportunity to launch many first-in-class molecules and biosimilars over the next several years. Inflammation, as a matter of fact, we think can become a meaningful growth driver for our company going forward. Joining me this morning are Dr. David Reese, our Executive Vice President of R&D, Dr. Rob Lenz, our Senior Vice President of Global Development, and Murdo Gordon, our Executive Vice President of Global Commercial Operations. We should have ample time for Q&A at the end of our prepared remarks. With that, I would like to ask Dave to commence. Dave? Dave, I think you're mute. Thanks, Arvind. Good morning, everyone. As Arvind mentioned, we're going to give you an update, of course, on the OX40 program, which was presented over the weekend, also a broader view into our plans in inflammation, which we feel is one of our meaningful growth drivers in the coming several years, as well as a core of our research strategy. I'll provide some introductory remarks. Rob Lenz, our Head of Global Development, will engage in a data review, Murdo will provide a commercial perspective on the opportunities before us. Next slide. As we've just discussed, we expect inflammation to be a meaningful growth driver in the years to come. This builds on our legacy now of more than two decades of experience from the bench to commercialization. We have a number of potential first-in-class molecules and I would say a wave of activity in the coming year, including both launches and the readout of mid- and late-stage clinical data. Much of this is now built on a foundation of human omics, built around genetics and genomics, but now extending beyond that to allow us to interrogate pathways. In a moment, I'll say a bit more about that. There are a number of key late-stage milestones that are coming up in the next few years. Next slide, please. Regarding those late-stage milestones, just to remind everyone, we have an FDA action date in mid-December for Otezla for a mild to moderate indication in psoriasis, more on that a bit later. Followed by the anticipated launch of tezepelumab in the first quarter in the U.S., also under review in jurisdictions outside the U.S. In the first part of 2023, the launch of one of the next leading molecules in the next wave of biosimilars, AMGEVITA, our biosimilar Humira, that will launch in the U.S. Looking out a bit further, we anticipate the launch of ABP 959, our biosimilar Soliris, in 2025. In parallel to these launches, next slide, please, there will be a wave of clinical readouts, as I mentioned, and clinical activity. In the first half of next year, we anticipate launching a comprehensive phase III program for our OX40 molecule being developed in collaboration with KKC. Rob will speak more about that in just a moment. In addition, there will be key mid-stage readouts from the AMG 714 anti-IL-15 program in celiac disease, two of our lupus programs in the coming few years, as well as phase II and additional phase III studies for tezepelumab. Importantly, I would also point out that next year we should see the completion of three major phase III programs in our biosimilars portfolio, for ABP 654, ABP 938, and ABP 959, representing STELARA, EYLEA, and Soliris biosimilars, respectively. Next slide, please. Before we have Rob commence with the data review, I just wanted to spend a couple slides giving you some insight into our basic research approach to inflammatory diseases. I have an unshakable belief that we are entering a golden age of treatment of these disorders, a real precision medicine, as we've seen in oncology that can now be, I believe, delivered to those with autoimmune diseases in particular. Historically, the traditional approach to inflammatory disorders has been blocking cytokines or cytokine pathways, and we have, of course, molecules that represent that approach. There are now, I think, a variety of mechanisms available that we are pursuing that allow us to customize the approach based on underlying disease pathophysiology. This includes cellular depletion, that's represented by the OX40 program. Tolerization, we know that in almost all autoimmune diseases, there is a dysregulation of T-regulatory cells. Restoring that regulatory balance is now a key goal in some programs. The AMG 592 program represents an attempt to tolerize in the setting of dysregulated T-cells. Then finally, tissue repair. Barrier function, in particular, is often lost in these disorders in the gut, in inflammatory bowel disease, for example, or in the lung in asthma. The Rodeo program that we acquired earlier in the year represents an example of an attempt to restore barrier function in the gut, and we'll have more to say about that program as the preclinical work moves along. Next slide, please. Now, all of this is now built on a foundation of human genetics combined with other omic technologies that you see represented here. We have now chip typed more than 2.5 million individuals in our databases. We have whole genomes on over 300,000. That should be approaching 0.5 million or more by the end of this year. This is really a fundamental approach that we apply to every target now across our portfolio. I believe that this approach in inflammatory diseases, in particular, given that we're entering an era of precision medicine disorders, will be a considerable competitive advantage. More to come on that as we go along. For now, I want to turn things over to Rob, who will present the heart of the material today and review some of the data that came out over the weekend. Go ahead, Rob. Thanks, Dave. Why don't you go ahead and click the next slide and the next one after that. Great. I'll start with AMG 451, which is probably of greatest interest this morning. We're developing that for atopic dermatitis with our partner, Kyowa Kirin. Double click a couple here. One more. Atopic dermatitis, a very common disease in both childhood and adulthood. These are patients who, despite the normal, fluctuating chronic symptoms, things like itch, that leads to impaired sleeping and impaired quality of life. Despite best efforts at avoiding triggers and treatments with topical therapies, many of these patients require systemic treatment. When I'm thinking about the residual unmet need in atopic dermatitis, I find it helpful to sort of juxtapose it to psoriasis. Clearly, we have a lot greater unmet need in atopic dermatitis, and thus the opportunity for new therapies. Next. I'll spend a minute walking through the biology of OX40, as I think it provides some helpful context. OX40 is an interesting target in that it's not constitutively expressed on cells, but rather the expression is actually induced on T cells by various cytokines under a number of inflammatory conditions. Often that upregulation is also spatially limited to the areas of inflammation. OX40 stimulation increases the proliferation and longevity of what we call effector T cells, and that disrupts that balance for immune tolerance that Dave alluded to. OX40 is mostly expressed on CD4 and CD8 T cells, such as the helper TH1, TH2, and TH17 lymphocytes. In terms of its relevance to human disease, increases in OX40 expression have been observed in for example, in the lesions of patients with atopic dermatitis, but not in non-lesional skin. Elevated levels have also been seen in several autoimmune diseases. Interestingly, levels often correlate quite well with disease activity. Obviously we're excited about the mechanism in atopic dermatitis, but I think we're equally as excited about opportunities in other autoimmune diseases. Of course, we're applying these omic strategies that you just heard Dave talk about to understand which diseases would be most amenable to OX40. AMG 451, it's a fully human monoclonal antibody specific for OX40, and it mediates its mechanism and its effects through two different approaches. One is by directly inhibiting the binding of its ligand. The other is because it's an afucosylated antibody, it induces what's called antibody-dependent cellular cytotoxicity, and that leads to cell depletion of the activated pathogenic OX40 positive T cells. This can be relevant in that it could result potentially in a prolonged treatment effect and potentially less frequent maintenance of dosing, which of course is ultimately more convenient and desirable for patients. Next slide. I think probably many of you saw Dr. Guttman present the results from the phase II study of AMG 451 in atopic derm. I won't repeat the presentation, but I'll provide a little bit of additional color on some points. Next slide. This is the study design. It was a dose-ranging phase IIb study that evaluated four doses over a very broad dose range from 150 mg subcutaneous monthly up to 600 mg Q2W. The study was placebo-controlled through week 18, and the primary outcome measure was assessed at week 16. At week 18, the placebo patients then received a high dose of 600 mg Q2W in a blinded fashion. The blind was maintained, and patients continued dosing through week 36. Given the hypothesis that this mechanism of T-cell depletion could result in a more prolonged duration of action, subjects were then followed for an additional 22 weeks after their last dose. Next slide. Okay, the population and baseline characteristics were pretty typical of a moderate to severe AD population, except for one aspect, and that's shown in the bottom row if folks can actually see it. These slides are small for me, but about 14% of patients enrolled had actually been previously exposed to a biologic. The most common biologic they'd been exposed to was dupilumab, then there was a mixture of patients who'd received anti-IL-13s or IL-31s, suggesting that this was a bit of a more recalcitrant patient population than, say, a typical only naive to biologics population. What's interesting is that across the outcome measures that I'll show in the next couple slides, we saw very low placebo rates compared to recently completed atopic derm trials. That to me is further suggestion that this indeed was a bit more of a recalcitrant population. Next slide. The primary outcome was the percent change in EASI score from baseline to week 16. Here you can see all doses resulted in highly statistically significant and clinically meaningful reductions compared to placebo. There was a small trend of increasing effect with increasing exposures, with the 300 mg Q2W here resulting in a 61% reduction in EASI from baseline. The relatively flat dose response relationship suggests that we've likely saturated the target. Importantly, when I look at data like this, seeing the internal consistency of effect that we saw at all the doses on not only the primary but across the secondary measures certainly gives us a lot of confidence in the efficacy that we're seeing in this trial and how that predicts phase III. It's pretty standard in phase III programs in atopic dermatitis. We'll likely explore two doses in phase III. As we'll discuss in a minute, also interrogate different maintenance frequencies forward. Next slide. This slide shows the time course of effect as assessed by the EASI-75, and this is one of the standard regulatorily required outcome measures. I'd highlight just two points. One, if you look on the right, you see that all doses resulted in a highly statistical significant improvement compared to placebo, underscoring again this consistency of effect of the compound. Then the second thing I'd highlight is shown on the time course component on the left, and that's that the treatment effect continues to increase with increasing duration. That's actually quite unique. It's something that we'll be interrogating more formally in phase III. Next slide. Similar slide. This is now you're looking at IGA. This is the other regulatory required outcome measure. You can see again statistical significance at all the doses as well as the continued trend for increasing efficacy with longer treatment. Here's a nice example. If we focus on the gray placebo there on the bottom left, you can see that there was an extremely low placebo rate, especially contextualized relative to other AD trials. Again, suggest that this was a bit more of a recalcitrant patient population. The next slide. Given the mechanism of action that we discussed, it was important to understand what the persistence of effect is. That's important because that can inform us as to the possibility for things like less frequent maintenance dosing. This plot shows the durability of response after stopping treatment. What happened here is we took patients who had achieved an EASI 75 response at week 36, and then we followed them. Recall that their last dose was at week 34. You can see that the vast majority of subjects maintain their EASI-75 response for the duration of the follow-up period. I know the lines are difficult to see, particularly as they're displayed. Let me just pull out one example. A middle dose, the 300 mg Q2W dose, that resulted in 89% of subjects retaining their EASI-75 response through 20 weeks of follow-up, which certainly supports the idea that one could require less frequent maintenance dosing with AMG 451. Next slide. This slide summarizes the safety. I'll just highlight a couple things. One thing worthy of note is that by far, the most common adverse leading to discontinuation is actually atopic dermatitis. Think of it as patients who experience a worsening of atopic dermatitis. You see that that rate is nearly three times higher in the placebo arm there on the right. Similarly, when looking at the Grade 3 adverse events, actually the most common underlying adverse event in that group was atopic dermatitis. Next slide. Of course, it's always important to look at the adverse events, not necessarily at a SOC or System Organ Class level, but really at the preferred term level, and that's what you're seeing here. Fever and chills were the most common adverse event, consistent with what we saw in phase I. Importantly, all of those events were Grade 1 or 2. It's really a first-dose effect. About 75% to 90% of the fever and chills are experienced only after the first dose. Most occur actually the first day of dosing, and then almost all resolve within that same day of dosing or by the next day. One important negative that you don't see here is conjunctivitis, allergic or infectious. We saw that in less than 1% of patients across the active dose groups, and that was half the rate that was seen in the placebo group. Next slide. We're encouraged by the data in this pretty sizable phase II study, as mentioned. Particular areas of interest are the efficacy seen despite having patients who have been previously exposed to biologics. Also, we're seeing this increased trend for efficacy with increasing duration of exposure and this prolonged persistence of effect despite discontinued dosing, how that might support less frequent maintenance. Obviously, we're incorporating those elements into the phase III program quite literally as we speak. All right. Next slide. I'll shift to Otezla and psoriasis. As most of you are aware, we have filed with FDA for the approval of the mild to moderate indication for psoriasis based on the positive phase III trial in that population. Next slide. There are no systemic therapies that are approved for the mild to moderate population. I'd say the mild nomenclature is a bit misleading. Many of these patients experience pretty debilitating symptoms. It's true that many of the mild patients, in particular, are able to be treated with topicals, but many of them have disease involvement in areas that really aren't amenable for topical therapies. These are patients that have substantial hand involvement or genital areas. What you're seeing here is this plot shows patient-reported burden of disease in mild, moderate in the dark blue versus the more severe in the light blue across the various disease areas. You can see that they can really endorse similar levels of burden of disease as patients with the more severe form of the disease. Next. As I mentioned, we recently read out a positive phase III trial. This is a nearly 600-patient trial in mild to moderate psoriasis who were not adequately controlled with topicals, and that trial showed Otezla resulted in statistical significance and clinically meaningful improvements in the primary outcome measure, which is the physician's global assessment in that overall population. Obviously, a major goal of therapy is to reduce the percent body surface area that patients have. This analysis was actually presented in the past few days at the EADV conference, shows that sort of regardless of the baseline severity, Otezla resulted in a significantly greater proportion of patients who could achieve a body surface area outcome of less than 3% compared to placebo, and that overall, more than half the patients were able to achieve that target of less than 3% body surface area involvement regardless of the baseline severity. Let me turn things over to Murdo. Thanks, Rob. As Rob has said, obviously our data now allow Otezla to potentially be positioned across an entire spectrum of our psoriasis patients. As Rob also mentioned, while we are describing these patients as mild to moderate, they indeed have a large unmet need considering the inadequacy of topical therapy for some of their conditions. We see this as a very large opportunity to continue to grow Otezla, and we're preparing accordingly. As many of you know, we've historically positioned Otezla very clearly as a post-topical pre-biologic option for patients. This new data set and potential indication allow us to move even earlier in the continuum of psoriasis. A very exciting opportunity and one that we're preparing for. We have initiated primary care promotion because many of these patients are under the care of a primary care physician, but we've also got very broad dermatology capabilities at Amgen, and I feel that we're well-positioned to make physicians aware of these data rapidly upon approval. Next slide, please. When you look at Otezla, you really see that we have an opportunity to potentially be the first and only systemic oral treatment for the active psoriatic arthritis patient population, as well as mild to severe psoriasis patients. We have a well-established safety profile over many years on the market and hundreds of thousands of patient exposures. No required lab monitoring or pre-screening. In times like these, where we have seen post-marketing surveillance data show some safety issues with the JAK inhibitors, I think this is particularly reassuring for dermatologists as we move into that milder disease setting. The majority, over 90% of commercially insured lives, have biologic step-free coverage for Otezla. This is an opportunity for dermatologists and potentially primary care physicians to use Otezla without a lot of difficulty in terms of insurance coverage for PsA and PsO patients. As I mentioned, over 700,000 patients now have been treated across over 40 countries. The experience database with Otezla is large. We have been able to grow Otezla by expanding geographically and securing additional markets since the acquisition of the product from Celgene. Most recently, we were approved in China, and we anticipate launching Otezla for Chinese patients in the new year. What's the opportunity here? Well, approximately 1.5 million additional patients, and these are the patients that Rob described. This isn't broad, mild patients. These are the patients who have some difficulty achieving relief of their psoriasis symptoms with topical therapies alone. 1.5 million additional patients to address in that mild to moderate psoriasis setting. Really exciting and one opportunity that we're very much looking forward to. I'll hand it back to Rob now. All right. Thanks, Murdo. We're going to turn our focus now to severe asthma and tezepelumab. You can go to the next slide. Despite available therapies, there remains a very significant unmet need for the severe asthma patient population. This slide summarizes some of those areas. Shown in that orange donut plot at the top, even when on available biologic therapies, about half of patients continue to experience one or more exacerbations per year. Often, those require emergency room visits or hospitalizations, or even ICU admissions. On the bottom right, we know that roughly half of severe asthma patients have non-eosinophilic or those who carry eosinophil counts less than 300, and that currently available biologics really have suboptimal efficacy in that population. Clearly, there's a large unmet need there. There's really this growing appreciation within the field that many patients don't really have this sort of purely eosinophilic or purely neutrophilic asthma. A pretty substantial portion, up to 50%, really have both elements of this TH1 and TH2, either simultaneously or temporarily evolving. Having a single therapy that targets both pathways can really be ideal in these patients. Next slide. Severe asthma disease is a huge burden on the individual patient in terms of reducing their functioning, leading to hospitalizations, ICU admissions. It also has profound societal burdens given how common severe asthma is. In aggregate, serious exacerbations require about 1.6 million emergency room visits per year and 180,000 hospitalizations in the U.S. alone. Those severe asthma patients account for roughly half of the asthma-related costs incurred. Clearly, unmet need for these severe patients. Next slide. It's quite nice. The mechanism of action of tezepelumab is really ideally suited to address those patients, exactly those patients we were just discussing, who have the highest unmet need. Just by way of reminder, Tezspire blocks an epithelial cytokine called TSLP. It's unique in that it really sits at the top of that inflammatory cascade. It can drive both eosinophilic as well as non-TH2 inflammation. TSLP has been associated with a number of allergic diseases, of course including asthma. Next slide. These are the pre-specified analyses of the phase III NAVIGATOR study that's been presented previously, and it shows Tezspire resulted in statistically significant reduced exacerbations in patients both with high eosinophils, shown on the left, as well as those with low eosinophils on the right. Of course, the more feared outcome in these patients with exacerbations is ER visits and hospitalizations. The next slide shows the outcomes there, and you see Tezspire resulted in a profound reduction in ER and hospitalization visits by 79%, shown on the left, then resulted in a remarkable 85% reduction in hospitalizations on the right. We look forward to sharing some additional color around those hospitalizations and the nature of those hospitalizations in future scientific congresses. Next slide. Overall, we're enthusiastic about the profile of Tezspire. Again, there's this really nice alignment between where the greatest unmet need is, those patients with low eosinophilic asthma, and then that large segment who have this mixed component of eosinophilic and non-eosinophilic and how that aligns well with where Tezspire was able to demonstrate benefit. As Dave mentioned, we filed to the major global regulatory authorities. In the U.S., we have a due date of Q1 next year. I will note we also have several ongoing trials in other indications, including chronic rhinosinusitis with nasal polyps, which has a reasonable overlap of those patients also having asthma. We did generate some very supportive data in actually the NAVIGATOR phase III trial showing that tezie resulted in an 86% reduction in exacerbations, specifically in those patients who had nasal polyps compared to placebo. We also demonstrated that tezie resulted in meaningful improvements in nasal polyp symptoms that the patients were having. That gives us a lot of confidence in the ongoing phase III trial in those patients. Murdo, back over to you. Thanks, Rob. We are indeed excited about the opportunity that Tezie represents with the ability to treat a broad range of asthma patients. As you can see here from a very simplified look at the epidemiology in severe asthma, you can see asthma prevalence, roughly 26 million patients in the U.S., severe asthma prevalence, roughly 4.2 million of that 26 million. The potential tezepelumab patient target, roughly 1 million patients. These are the patients that are having acute exacerbations of their disease and are in the treatment pool. The eligible pool here in that light blue color also includes patients who have low eosinophilic counts. The low eos patient population represents roughly 50%-60% of that blue triangle. This is a larger population than can currently be targeted today by biologic therapies. We will, in effect, be broadening that pool of patients. Any time that you can come to a severe disease area here, like Rob has described, and offer these patients another treatment option that they currently don't have is obviously an exciting opportunity for any organization and one that we, along with our partners at AZ, are taking very seriously and moving as quickly as possible. If you look at the next slide, we have another opportunity, which is a first and only opportunity. We have the opportunity here to launch a broad product to treat a broad patient population. That requires, of course, the efforts of two fairly large organizations here. We will reflect the best of both approach from AZ and Amgen. We bring to the table 20 years of contracting and access in inflammation as well as sales marketing capabilities across the gamut of inflammatory disease. Our partners at AstraZeneca have 50 years of respiratory disease area experience. Pretty impressive pairing of two companies. We really have looked inside each organization to find the things that we can both bring to the table that we feel are strengths of either organization. We've kind of divided and conquered what you would normally put together as your go-to-market model. On Amgen's side, we'll be covering our patient support programs broadly for this product, and we'll also handle a lot of the market access negotiations. Then on the AstraZeneca side, they'll be taking the lead with HCP communications as well as patient education and communications. We'll co-commercialize in the U.S. and Canada with coverage of both allergists and pulmonologists, and AZ will take the lead in the rest of the world. We are fully staffed in the U.S. and ready to go across both companies, and we've had several joint meetings to ready ourselves for the pending FDA approval. Really, the combined expertise of both companies here is going to be brought to bear to help those patients broadly in that severe asthma category access the innovation that is tezepelumab. Next slide, please. Rob, I think you were going to cover the life cycle. Yeah, I think I covered that already. I think we can jump to the next slide. Thanks. All right. I'll keep things moving here. Just wanted to take a couple minutes to highlight three of our mid-stage pipeline products. I'll move through this pretty quickly so we can get to the Q&A. The first is AMG 714, which is a potential first-in-class molecule targeting IL-15 for celiac disease. Celiac is a really common autoimmune disease. It's due to a genetic predisposition to react to gluten ingestion. This is a disease where there's really a tremendous wide variation in the severity of symptoms. Some have relatively mild disease, and they can be controlled by simply avoiding gluten in their diet. There's about a third of patients who continue to have symptoms despite a gluten-free diet, and they're called non-responsive celiac disease. Many of these patients have pretty significant symptoms, significant diarrhea, abdominal pain, weight loss due to malabsorption. Sometimes they can have systemic manifestations because of that. The driver of the disease is this aberrant activation of cytotoxic T-lymphocytes and natural killer cells, and there's evidence that this is being driven by elevated levels of IL-15. Based on that, as well as we generated some encouraging data in a small phase IIa gluten challenge study, where the clinical symptoms were improved with AMG 714, we've embarked on a phase IIb study in patients with this non-responsive celiac disease, and this study's being conducted in partnership with Provention Bio. Next slide. We also have two mid-stage lupus programs, both of which you see there have completely unpronounceable names. One is efavaleukin alfa or AMG 592. The other is rozibafusp alfa or AMG 570. Next slide. Lupus, relatively common disease, obviously much more commonly manifest in females than African Americans. It's a disease that can manifest in almost any organ or organs in the body. Compared to other rheumatologic diseases, it really hasn't seen that significant therapeutic advances that we've seen in the other. Today, of course, we only have two approved therapies in the last 40 years, resulting in relatively modest benefit. The first program I'll mention, next slide, is our IL-2 mutein program. Next. One of the findings in lupus is this abnormal balance between the regulatory and effector T cells that Dave mentioned. Really specifically in lupus, you see too few of these activated regulatory T cells. It's been shown that if you administer patients low-dose IL-2, it can actually increase the T regs and start to reestablish that fine balance. As you increase the dose of IL-2, you start to also activate the effector T cells, and then that balance gets askew again. efavaleukin alfa, it's basically a mutated IL-2 that preferentially increases the Tregs without increasing those effector T cells. We've shown exactly that it does that in our phase I study. Then we're also going to be presenting data from a multi-dose study in lupus patients later this year. We have started the phase II study. Interestingly, this is a study that was selected by the FDA to participate in this Complex Innovative Design Pilot. This pilot, for those of you who aren't familiar, focuses on applying innovative designs, particularly in trials that could be registration-enabled. This has been a great partnership with FDA. We'll be starting up our phase II dose-ranging study for ulcerative colitis. Importantly, I won't get into it, there's been some pretty encouraging clinical data for both lupus and ulcerative colitis generated with low-dose IL-2, giving us some additional confidence in this mechanism. All right. You can go to the next slide. I'll end the portfolio review by saying a few words about AMG 570. Next. This is an interesting molecule. It's a bispecific antibody that targets ICOS ligand as well as BAFF in order to target both T cells and B cells respectively. Both of these targets have actually generated proof of concept in lupus. Obviously, BAFF inhibition, that's the mechanism of action for BENLYSTA. Inhibition of ICOS ligand was shown to improve symptoms in a small lupus study that was conducted a few years ago with a different molecule that targeted selectively ICOS ligand. The goal here is to drive greater efficacy through dual inhibition, both targets with a single bispecific molecule. That phase II study is well underway. Murdo, back to you. Thanks, Rob. What we've outlined today is predominantly the innovative side of our portfolio and over 20 years of leadership in inflammation. However, we've also got an exciting portfolio of biosimilar products some of which we've already launched and many of which have yet to be launched, particularly in the U.S. Of course, we'd be remiss if we didn't mention the foundation of all of our inflammation work with Enbrel. Between the marketed products, Enbrel, Otezla, AMJEVITA, and AVSOLA, and the to-be-launched side of the equation, we've got a very strong growth profile emerging in the inflammation sector. I think with the mechanisms and the modalities that have been highlighted today position us very well for the continued success of this franchise on a go-forward basis. I'll highlight just some of the capabilities in the biosimilars experience in the next few slides. If we can go to the next slide. The things that we have been able to achieve globally with our biosimilars products have sometimes been achieved despite perhaps a broad view that the biosimilars market was not functioning efficiently in the U.S. One of the things that I think has contributed to our ability to generate good uptake of the biosimilars is the fact that we commercialize those biosimilar products alongside the innovative or branded portfolio that we have. That not only creates a cost-effective selling model, but it capitalizes on existing customer relationships for the biosimilar options that we bring to the market. I think with 40 years of biologics manufacturing experience, Amgen really connotes quality when we are introducing biosimilars to the market. The results of that is, we are now annualizing an over $2 billion franchise globally. We've established ourselves as leaders in Europe, where AMJEVITA, our biosimilar to Humira, is category leading. We have a broad portfolio that complements our branded products, particularly in inflammation, as we're talking about today. It affords us the opportunity to sequentially launch with fairly high frequency over the next long-term growth period. We are addressing a large economic pool. The value of these biosimilars, as I'll show you in a moment, is high. That also allows us to deliver efficiencies to the healthcare system in the form of our lower priced biosimilars that oftentimes creates headroom for additional innovation like Otezla, like tezepelumab, and the earlier assets that Rob described. Really, we see an opportunity for meaningful portfolio growth from additional launches of biosimilars, as well as expanding geographically. We think that working alongside our innovative portfolio really augments our commercial strength in the marketplace. Next slide, please. When you look at the cumulative value of the biosimilar originator products that we are targeting, you look at the Avastin, Herceptin and Rituxan all the way down. We have yet to announce three additional assets. The total originator value as of 2020 for these products was $86 billion. As you can see, there's a concentration in oncology and inflammation. Generally, in the first wave of biosimilars, we have been able to establish ourselves as leaders. That's the case with MVASI, KANJINTI, and as I mentioned, with AMGEVITA in Europe. We expect to be in the first wave with AMJEVITA in the U.S., as well as with EYLEA and STELARA and Soliris. A real opportunity here for our inflammation biosimilar candidates to provide access to a large market opportunity here. Next slide, please. This is the frequency of launch cadence that I was describing. We'll have phase III data soon for biosimilar candidates to STELARA, EYLEA and SOLIRIS. The AMGEVITA anticipated U.S. launch will be in early 2023, and we expect that to be a relatively quick launch in terms of uptake. I know that there are many who think on the pharmacy side of biosimilars that the uptake curves are very modest, and I think we're seeing that change over time with more progressive thinking on the part of the PBMs and payers. Of course, the anticipated U.S. launch of ABP 959, which is our SOLIRIS biosimilar, in the 2025 period. We have a fairly frequent cadence beyond 2025 as well. Really, a nice time for the biosimilars to augment what we're doing on the innovative side of our portfolio. Next slide, please. Biosimilars allow us to also build commercial capabilities in areas that are target areas for indications for the innovative side. That allows us to build commercial and medical capabilities ahead of the innovative launches. That's true of the gastrointestinal world. Dermatology, rheumatology, we already have strength, and of course, respiratory and allergy are areas that will be targeted for pipeline and potentially some biosimilars as well. Our coverage on our innovative portfolio has been very successful in contracting with payers and PBMs. Enbrel, 85% frontline and Otezla even higher at over 90% frontline coverage. These are products that are available to prescribers early in the continuum of disease. We've also augmented our model over the last several years with heavy investment in digital capabilities. That was accelerated throughout the pandemic to make sure that we can still access patients, providers, and of course, payers, in the virtual or remote realm. Our rankings also have been rising in the inflammation market. I think as Robert Lenz's organization continues to invest in clinical trials to develop our pipeline, we continue to invest in clinical trials to develop our biosimilars products, and we expand our commercial footprint in the market to launch new products and new indications. I think you'll continue to see the perception rankings of Amgen rise in the inflammation world, given the breadth and depth of our portfolio. Really exciting. Obviously, two very exciting launch opportunities on our doorstep with expansion of Otezla. Also the launch of tezepelumab is really exciting because these are two potential first and only, and highly differentiated opportunities in the market. That's what gets us up in the morning to help more patients who are currently not adequately treated by existing therapies. In summary, on the next slide, we are really well-positioned to build on our history and our legacy of 20 years in inflammation for the next 20 years. We've got really nice near-term opportunities, but the innovative pipeline is really shaping up with indications beyond what we've described for tezepelumab or Otezla. AMG 451, as Rob characterized, highly differentiated mechanism, potentially many benefits from an efficacy and potentially safety and dosing convenience perspective. That mid-stage pipeline really taking shape now. Of course, last but certainly not least, the biosimilars coming in and representing a very meaningful growth opportunity for the company as we go forward. Thanks for your attention. I'll now turn it back over to Christie and Dave Reese for Q&A. Great. Just a reminder to all our listeners that all the slides have been posted to our website. Christie, why don't you go ahead, please. At this time, ladies and gentlemen, if you would like to ask a question, press star, then the number one on your telephone keypad. In order to ensure that everyone has a chance to participate, we would like to request that you limit yourself to asking one question. We will pause for just a moment to compile the Q&A roster. Your first question will come from the line of Geoff Meacham with Bank of America. Please go ahead with your question. Morning, guys. Thanks for the question. You guys have highlighted a pretty deep I&I pipeline, including OX40, which looks pretty good. I think it's interesting that in hemo combo therapy is by far the standard, but that's not really the case in I&I. The question is, just given all the programs at Amgen, does combining some of your newer mechanisms such as OX40 make sense just to increase effect size or maybe extend durability? I know obviously you first have to de-risk as a monotherapy. Thank you. Thanks, Geoff. I'll take that question. I think that's a great question. As I alluded to in my remarks, I think we're entering an era where precision medicine really will have an impact in inflammatory diseases, not only to be able to tailor therapies to the specific molecular defects that underlie subsets of patients, but also to guide the way towards combination therapy. I think absolutely, what we've done in oncology over the last few decades will be a model here. As you point out, it requires establishing safety and efficacy of the monotherapy components. In the longer term, I think combinations will undoubtedly come here. I like where we're positioned to be able to prosecute combinations based on underlying biology and orthogonal mechanisms of action. Dave, I would just add, that is exactly the approach we're trying to achieve within a given molecule, given our expertise in protein engineering with the bispecific molecules such as AMG 570, where we're targeting simultaneously two targets, rather than two different molecules and a single molecule. There's some nice opportunities there. Great. Thank you. Christie, next question. Your next question comes from the line of Umer Raffat with Evercore ISI. Please go out with your question. Hi, guys. Thanks for taking my question. I had a couple today, if I may, and just wanted to focus in on the OX40 mechanism. Perhaps first, if you could zoom in a little bit on the Dupixent experienced or if there were any Dupixent non-responders in your trial and what the efficacy outcomes look like. Can we assume they're roughly comparable to the other patients or not? That would be very helpful, number one. Secondly, I'm just trying to understand if there's a link or there isn't a link between some of the T helper depletion that is there with your molecule, perhaps not so much with the Sanofi Kymab molecule, but also if it correlates in any shape or form with some of the sores and some of the chills and fever we saw in the trial. Thank you very much. Yeah, great questions, Umer. Let me turn those over to Rob, who's certainly thought quite a bit about both those issues. Yeah. In terms of the, as I mentioned, about 14% of patients in the trial had been previously exposed. Of course, the reason for discontinuation of those would be either intolerability or lack of efficacy. I think it was slightly more than half of those were dupilumab failures, and the rest were mostly IL-13, IL-31, and a smattering of JAK inhibitors. Small data set, but we were, I'd say, quite encouraged by the data that we saw within that population as it relates to the treatment effect that we saw in the treatment naive population. We're certainly encouraged by that and taking that in and incorporating that into our phase III planning. In terms of the mechanistic relevance of the T-cell depletion versus the blocking of the ICOS signaling, I'm sorry, the OX40 signaling, I think it is yet to be determined. It's early days. There's been a relatively small amount of data, particularly on the safety side, that's been. Observed. I don't think that I saw the preferred term level data on the safety from the Sanofi compounds, so it's a little hard to comment on that. Obviously, something we'll be evaluating moving forward with larger trials. I think the key that we saw with the fever and the chills was, again, it was basically a first dose effect. The vast majority of those patients resolved, despite obviously the ongoing therapy, within the first day or two. To date, it seems more like a tolerability issue than a safety issue per se. Great. Thanks. Next question, Christie. Your next question comes from Michael Yee with Jefferies. Please go ahead with your questions. Thanks. Good morning, guys. Thanks for hosting this call. Two-part question. One was following up on the differentiation in the mechanism versus the OX40 that blocks the ligand. Can you just comment hypothetically if you see advantages with blocking T-cells directly? Talk about how you think about the mechanism vis-a-vis the competitor. Secondly, given the data we've seen today, do you anticipate that there are more obvious diseases that this would work in? Are you planning to start additional studies, et cetera? Talk a little bit about that. Thank you. Yeah. Thanks, Mike. In terms of differentiation, I think one of the keys here, as Rob has just pointed out, is the cellular depletion. We think that in addition contributing to the direct effect, this is also contributing to the duration of effect and the prolonged off-treatment effect that was observed, really across all of the dosing arms. That suggests to us that maintenance therapy may be effective, but that intermittent or relatively infrequent dosing in maintenance may be something that we could pursue, and these are avenues that we will explore in the phase III trial. We are quite interested in diseases beyond atopic dermatitis. In fact, the integrated omics approach that I briefly outlined, we have brought to bear. We have ruled out several diseases and have several candidate indications that we believe have promise based on this combined omics analysis. We will talk a little bit more about those additional indications as those programs develop and get ready to move forward. Obviously, the first order of business is atopic dermatitis, but we absolutely do not believe that this mechanism of action will be restricted to atopic dermatitis. We think we have some good insights in terms of where to go next. Next question, Christie. Your next question comes to the line of Jay Olson with Oppenheimer. Please go ahead with your question. Well, thank you for the presentation and for taking the question. I'm curious about how tezepelumab could transform the treatment of asthma. Do you think the availability of tezepelumab will eliminate the need for testing eosinophil levels, or is that still an important diagnostic that physicians will continue to monitor? Yeah. I'll start with that and then ask Murdo to comment. Over time, I think there is the possibility that it makes ascertainment of eosinophil levels less relevant. I'd also like everyone to take a step back. We tend to think of high eosinophil asthma and low eosinophil asthma as binary outcomes. In fact, there's a fair amount of plasticity in the disease, and patients transition between high and low eosinophil asthma. Being able to handle the disorder regardless of eosinophil count, I think is another major advantage of tezepelumab without worrying about those sorts of transitions occurring. Murdo, do you want to speak about how this might play out in the marketplace? Yeah. It's an important question, Jay. We do believe that we can dramatically simplify the average prescriber's treatment pathway for these severe asthma patients. They're looking for, as Dave's described, they're looking for some predictability of effect over time. As the disease waxes and wanes or surges and regresses, you want a product that can cover all of the allergic status or eosinophilic status of that patient's disease. I think we've not only shown that we can go toe to toe with the existing biologics on the market with the efficacy profile and the safety profile we have, but we pull in this unaddressed patient population on the lower EOS site. I think that knowing that this drug works as well in the currently treated population and has the utility of being able to treat the patients that currently can't be treated by biologic therapy is going to fairly dramatically simplify the average prescriber's practice. We will initially see some uptake in the lower EOS population, but our intent is to position the product broadly and to cover that broad population of over 1 million patients fairly quickly. I think it'll take work and an education, but the differentiation of this mechanism will allow us to do that. Great. Thanks. Christie? Your next question comes to the line of Chris Raymond with Piper Sandler. Please go ahead with your question. Hey, thanks. Just a question on the phase III design, and this might be a bit premature here to ask this. David, I heard you say that you're going to look at two doses in phase III, and I also heard, obviously, and looked at the data around the flexibility in terms of maintenance dosing frequency. Maybe just curious if you could provide clarity on those doses that you're thinking about. Also maybe a second part to that question is, the observation period that you'd be thinking about, especially given the deepening of response after week 16. Then if I can maybe, another part to that, do you think you can enroll a similar proportion of patients who are Dupixent naive versus the phase II trial? Thanks. Yeah. All important questions, Chris, regarding phase III design. Regarding clarity on dosing, certainly, as you saw from the data, there were not dramatic differences across the dose range tested. You can expect us to really bookend those dose ranges as we move forward into phase III. We have had very good discussions with regulatory authorities, and based on that, are finalizing phase III designs, and we'll provide details when those trials are ready to launch. In terms of the deepening of response, that is another very important question, and it suggests that you need a reasonably prolonged observation period to understand the totality of the effect on the disease, and the ultimate optimum effect on the disease. You'll see that reflected in phase III design as well. A lot more to come on phase III design, as I said, very good discussions. I think given the activity of the molecule, we've got a lot of ways where we can have a creative program here, that really brings, we hope, meaningful benefit to patients with an orthogonal and differentiated mechanism of action. Next question, Christie. Your next question comes on the line of Yaron Werber with Cowen. Please go ahead with your question. Great. Thanks for taking my question. Maybe David, for you, the conjunctivitis rate you said, I remember, was less than 1%. We are seeing atopic dermatitis, which seems to be on par with upadacitinib and even Dupixent. Can you comment as to maybe how that eczema is the same or different than Dupixent? Secondly, about half the patients in your study are from Japan, understandably. How does the data compare non-Japanese to Japanese in that study? Thank you. Yeah. I'll take Yaron the first parts of those questions and ask Rob to comment on the geographic breakdown of the data. In terms of conjunctivitis, it's again, as Rob Lenz had mentioned, it seems to be quite infrequent. The atopic dermatitis that you see reported is typically a flare of the patient's underlying disease. It's not a new manifestation, but a worsening or lack of control, that is by definition then reported as an adverse event. Rob, do you want to talk about the geographic breakdown of the data? Sure. Yeah. It was a global study. Patients were enrolled in Western and Japanese, so U.S., Canada, Germany, as well as Japan. We did see a consistent treatment effect across the Western and non-Western regions. Yeah. Very important. In fact, the internal consistency of the data across the trial were actually quite impressive. Next question, Christie. Your next question comes from the line of Alethia Young with Cantor Fitzgerald. Please go ahead with your question. Hey, guys. Thanks for taking my question. I appreciate all the color this morning. Can you talk a little bit for Otezla in mild to moderate, like how you're going to try to drive a change in physician paradigm to potentially moving that to maybe first rather than topicals, or at least be a decision they concurrently or an or statement with. Thanks. Yeah, I'll comment very briefly and then ask Murdo to comment about that. Obviously, he and his team are gearing up. One thing I'd like to say is psoriasis is a systemic inflammatory disease. To me, in the coming years, we will view our current treatment paradigm for psoriasis as misguided, and that I suspect the use of topicals will wane over time. These patients have evidence of systemic inflammation even with mild skin involvement. Things like rates of cardiovascular disease are higher. That's an epidemiologic fact that's been appreciated for years, probably driven by underlying inflammation. I believe over time, you're also going to see systemic therapy move earlier in the treatment paradigm. Now we have a very nice data set. Murdo and his teams are getting ready to share that as we look forward to the launch. I'll ask him to comment on the market opportunity. Yeah. Thank you for the question, Alethia. One of the things that we've done in the epidemiology analysis, is to focus in on the patients that Rob was describing in his earlier remarks. These are patients with difficult-to-reach areas, large body surface areas, or just persistent areas of residual symptoms despite topical treatment. That takes that mild to moderate population from a 4 million patient population down to about 1.5 million patients. When we talk about 1.5 million patients, it's a subset of that mild to moderate target opportunity. We're not talking about everybody out there. We're talking about the very focused opportunity. Still large, 1.5 million patients who are currently seeing persistent symptoms despite topical therapies. We think that Otezla plays very nicely there because of its safety and its efficacy profile. The other thing I would say is a lot of the topical therapies that have been launched more recently still have fairly difficult access and reimbursement challenges. I think that's where the ease of prescribing and ease of reimbursement of Otezla can position us very well versus the more novel topical treatments. As Rob showed, we also see some great efficacy data, when you can get over half of these patients to see resolution of their symptoms. Now, the one thing that will be interesting is, do you see patients being treated by a base of Otezla therapy in mild to moderate and perhaps augment with some topical treatment? That's a potential treatment paradigm that you could see for small area disease that is persistent despite Otezla therapy. That's what we're looking at in terms of the marketplace, and as I said, we've got broad dermatology coverage, broad primary care coverage. Clearly, we've got a very extensive customer-facing organization that will allow us to launch fairly rapidly and effectively into this new patient population. Great. Thank you. Christie? Your next question comes on the line of Matthew Harrison with Morgan Stanley. Please go ahead with your question. Great. Good morning. I was hoping you could comment a little bit more on lupus. I think when investors look at that area, we've seen not a lot of significant traction, either commercially or clinically there. Maybe you could just highlight for everybody why you think you have some differentiated products, clearly, and then secondarily, what sort of commercial bar you think is necessary in that market. I'll take the first part, Matt there, and then ask Murdo to comment. As you pointed out, as we noted in our remarks, there have only been two new approvals in lupus in the last 40 years. Significant unmet medical need. This is driven by disease heterogeneity, waxing and waning, and what has been a relative paucity of insights into disease biology. I think that the two approaches we're taking represent the two most promising approaches mechanistically to the disease that we've seen in a while. Number one, restoring some of the T-regulatory function that is clearly very dysfunctional in this disorder with AMG 592. As Rob mentioned, we're participating in a complex, innovative design pilot with the FDA that allows that to potentially be a seamless phase II, phase III trial. So we're looking forward to the first data readouts from that study. The AMG 570 program is a bispecific that targets both critical T and B cell signaling pathways in the disorder. We know there's a complex interplay and interchange between T cells and B cells in lupus, and to my knowledge, this is the first time that anyone is actually trying to tackle both limbs of the immune system that are abnormal in the disease. Murdo, you want to comment on the commercial side here? Sure. Matthew, I actually think lupus sets up well from a payer perspective in that the sequela of the disease obviously costs the system a significant amount of money. We've done some payer research over the years with physicians that treat lupus, and I think there's a high degree of confidence that with the right efficacy and safety profile, despite the fact that the current standards of care are generally generics, there is an appetite for payers, providers, healthcare systems to provide coverage and reimbursement in this disease setting. I think we've just not seen the efficacy profile that people are looking for, and I think given what we've got in our pipeline, we've got a good shot at helping patients. It's probably just an unseen area right now because of the profile of the products that have launched so far. Great. Thanks. Christie? Your next question comes on the line of Geoffrey Porges with SVB Leerink. Please go ahead with your question. Thank you very much, and I appreciate you taking the questions and also the comprehensive presentation. Murdo, on Otezla, I'm sure payers are panicking about the notion of Otezla moving into the mild psoriasis population. Could you give us a sense of where your gross to net is and then what it might have to increase to for you to really access that mild patient population? Perhaps, you could comment also on the TYK2 data from Bristol. That's coming pretty quickly. Are you expecting that to have class JAK labeling, or do you think it's going to be on a more or less equal footing with Otezla in the moderate to severe patients, and affect the market in that way? Yeah, Geoffrey, I'll take the first part. I'll open on the second, turn it over to David, see if he wants to add anything on the regulatory perspective with the TYK2 data. Look, overall, we've had very successful negotiations with payers for Otezla. We're almost through another cycle of negotiating with the PBMs and commercial insurers. We continue to maintain that above 90% covered lives. That's a pretty powerful position in the market. If you'll recall, it took Celgene a long time to establish that. I think with the ability for us to add it to our inflammation portfolio, I think we've strengthened the access. We've actually increased the coverage on Otezla. Many of those contracts allow for the mild to moderate population to be reimbursed. We've been very clear with payers, we're not targeting all mild to moderate. We're targeting a subset. As I was describing to Alethia, it's not 4 million patients, it's the one and a half that we think really require systemic treatment. That's where we're positioning it, and I think that that will allow us to secure good, broad coverage there. I wouldn't say payers are panicking, actually. I think that they see Otezla as a safe and effective treatment option that delivers very strong results in the market, and they're happy with the way in which we've negotiated that coverage. We don't disclose gross-to-nets, but we've been able to do a lot of the coverage expansion without a large increase in gross-to-net erosion. When it comes to deucravacitinib, one of the things that we're watching closely with the TYK2s is obviously how they will be perceived in the market. I'm not talking about regulatory here, just perception in the market, being from that JAK family of products. I think when you talk to dermatologists, there's a degree of conservatism there with that prescribing community about new mechanisms of action and new products. They are paying attention to what just happened in the JAK class with respect to XELJANZ and now the imminent class labeling. I think that that could potentially slow the uptake down of a novel mechanism, particularly a product that comes from the JAK family. As to whether or not deucravacitinib gets class labeling, I'm not going to speculate. Dave can comment. The one thing I would also add is that a lot of people have talked about the efficacy superiority. When you look at POETYK-2, you look at the clinical trial data, roughly five out of 10 patients on the deucravacitinib arm achieved the PASI score endpoint, and four out of 10 on Otezla achieved the PASI endpoint. For an understood safety profile, the hundreds of thousands of patient experience in the real world that we have, the market access coverage and this new mild to moderate indication, I think allows us to continue to think about growth beyond the launch of TYK2, that I think might be more positioned for the more severe patients anyway, not just the moderate, but the more severe patients, and perhaps more competitive to the biologics than Otezla. I'll turn it over to Dave. Yeah. Just briefly, I would add that we saw data from another TYK2 inhibitor presented at the EADV conference over the weekend that did raise some safety concerns. My sense is that it's just going to take a while with prolonged follow-up and a lot of patients to fully understand the safety profile of the TYK2s and whether they may behave like the JAK class or not. I think physician behavior will probably reflect that waiting period. Next question, Christine. Your next question comes from the line of Kennen MacKay with RBC Capital Markets. Please go ahead with your question. Hey, thanks for taking the question and doing the event. In the AMG 451 trial, it looks like you may already sort of be at maximal effect looking at the dose effect there, at least on the EASI impact there. Do you think you are sort of seeing a plateau effect on EASI? As it relates to dosing, are there other endpoints where there's more of a profound dose effect, like on some of the itch scoring, for instance, where those higher doses might be really important? Thank you. Yeah. Kennen, thanks for the question. Yeah. We believe we may have achieved saturation across the dose ranges, at least in terms of the primary endpoint. As we indicated, that's why we anticipate interrogating at least a couple doses in phase III going forward, more on that specific design once we have agreed it with regulatory authorities. Your primary observation is correct there. Next question, Christie. Your next question comes from the line of Robyn with Truist Securities. Please go ahead with your question. Great. Thank you. Quick one. You talked a little bit about the differences you view in OX40 ligand targeting the receptor versus the ligand. What about scientific concerns around long-term toxicity in T cell, influencing some of the T cells and maybe leading to tox down the line? How comfortable are you? Then just quick on business development, you've got a great portfolio. You've got some early-stage and late-stage assets. How are you thinking about some of the early-stage drugs in development that may be more targeted, maybe less risk for safety, that are in development and business development, and M&A around those types of things? What is the bar for you to be interested in for early-stage assets with different profiles that fit very well into your portfolio? Great. Robyn, I can start on these questions and then ask others to chime in if they wish. In terms of the mechanism of action, as we mentioned, we think the cellular depletion is an important component of that. As Rob pointed out, OX40 is really expressed on activated cells, and so we are attempting to target the pathogenic component here that is really the disease driver. In the quiescent state, OX40 expression is quite low, and so one would not hope to see untoward safety effects. Obviously, atopic dermatitis trials are of longer duration to amass adequate safety data. That's something that we will do as part of a broad-based phase III program. Inflammation will be a core area for us in terms of business development. As we've previously discussed, we're open across a range of opportunities from platforms and early-stage molecules through later-stage molecules. Still, despite the broad portfolio that you see here represented today, quite a bit of interest in business development in this area as well. Christie, why don't we move on to the next question? Your next question comes on the line of Salim Syed with Mizuho. Please go with your question. Hi. Good morning. This is Benet from Salim's team. Thanks for hosting the call and for taking the questions. A quick clarification first, if I may. These patients in the phase II for 451 received systemic steroidal immunosuppressants. Following up a little bit on BD, are you planning to pursue additional autoimmune targets? If so, what would be the potential candidates? Thank you. Great. I'll take the latter part first and then ask Rob to comment on the phase II trial and other therapies that may have been permitted. As I just mentioned, Salim Syed, I think we're open across the spectrum in terms of business development, including autoimmune disorders. You can think of it in those four broad disease categories that we outlined in the presentation of being of greatest interest, or areas that would be immediately strategically adjacent to those. We've got well over 20 years of deep experience in immunology at this point, and so we feel we're actually well-positioned to take advantage of scientific insights across a range of diseases. Rob, do you want to comment very briefly on the phase II design and potential concurrent or prior therapies? Sure. Yeah, this was a monotherapy trial. Patients could have received and failed previous either topical or systemic, including biologic therapy. They had to discontinue that, say, within, depending on the molecule, roughly a month before the start of that trial. Great. Thanks. Christie, why don't we take one more question here? Your next question comes on the line of Matt Phipps with William Blair. Please go with your question. Yeah, good morning. This is Rob Andrew on here for Matt Phipps. Thanks for taking the questions too, if I may. Back on the AMG 451 phase III study design. I think there was a clear theme at the Congress over the last few days among the discussions of some of the atopic dermatitis data that physicians are kind of looking for head-to-head data to help them determine the most appropriate treatment approach or sequencing. Are there any plans as part of the phase III program to look at some head-to-heads as we've seen kind of emerging over the last period here for some of the JAKs? Secondly, just on the disease-modifying potential for the OX40, what can you leverage from this phase II outside of more patients, longer follow-up? Are there specific biomarkers you can be looking at to support that? Were punch biopsies taken at all on the study? I think this was mandated at least at baseline on the amlitelimab phase II study. Thank you. Yeah. I'll answer a few of those questions and then turn things over to Rob to wrap things up. Rob, thank you. Yeah. Clearly, atopic dermatitis is a variety of diseases nested under one clinical label, as many autoimmune diseases are. So we will have a comprehensive biomarker program that we enact in the phase III study to try to tease out differences and give us insights into predictors of response and resistance to help optimize the therapy. I think this sort of, again, precision medicine approach, it's a time that has come in autoimmune diseases in general. I think you can expect in the phase III program some element of head-to-head data as well as other design elements. As I said, we're having very productive and active discussions with regulatory authorities right now. We'll give guidance on phase III design details as we have finalized that program in the coming weeks and months. Rob, do you want to comment on the disease-modifying piece here to wrap us up? Yeah, absolutely. It's an interesting concept around disease modification. Certainly, as we saw the persistence of treatment effect, one would expect to see an underlying biologic effect that was of equal long duration. That is what we saw. We actually assessed for something called TARC. TARC is a chemokine whose levels are downstream of OX40, and they're highly correlated with atopic dermatitis symptoms. It's been pretty well established. Similar to the persistent clinical effect, we saw a persistent reduction, significant reduction in TARC levels consistent with that clinical effect. It's a nice sort of cohesive effect that we saw there. There were a number of skin biopsies as well that demonstrated a reduction of OX40 positive cells in the upper dermis, and that persisted in a similar way to the clinical symptoms. It all kind of aligns up quite nicely when we look at the data. Great. Well, thanks, Rob. At this point, we'll wrap things up. I really want to thank everyone for joining us today. We just have tremendous excitement around our inflammation portfolio with marketed products that have been on the market for some time, a wave of innovative products coming as you have seen including the OX40 program, and then biosimilars that will complement this portfolio and really provide additional punch in the years to come. Much more to come here. We wanted to have the opportunity to share our excitement with you in this area. As always, our investor relations team will be standing by for additional questions if you've got them. With that, we'll go ahead and close the session. Thanks everyone, and enjoy your day. Thank you everybody. Ladies and gentlemen, thank you for participating in today's Amgen's conference call from EADV Inflammation. You may disconnect at this time.