Paul Burton. So I know there's a lot to talk about, and you know, last week, there were some new developments in terms of new clinical trial initiations and also new data. So I'm admittedly going to bounce around, but one product I wanted to start with, Paul, if you don't mind, is UPLIZNA. So obviously, you had the label expansions last year, but you did discuss last week plans to initiate phase III studies in autoimmune hepatitis and also chronic inflammatory demyelinating polyneuropathy later this year. So I guess a high- question here. You got a B-cell depleter in UPLIZNA, so maybe talk about your rationale here for moving ahead with these two clinical settings and help us better understand the rationale for B-cell depletion in both of these clinical settings. Great, David, thanks for having us. You know, I think as a company, we have strong experience in B-cell depletion. We have BLINCYTO, which has had data from a number of centers looking at patients with RA as well as systemic sclerosis, showing clinical improvement there. And, you know, we also have a master phase II protocol actually enrolling patients both with SLE or rheumatoid arthritis, looking at both UPLIZNA and BLINCYTO. And so, you know, UPLIZNA is a remarkable medicine, six-monthly dosing, excellent safety profile. And both autoimmune hepatitis, AIH, and CIDP are conditions where pathogenic B-cells seem to play a central role, probably through autoantibody production, but immune dysregulation as well. And so UPLIZNA, being a B-cell depleter targeting CD19, is interesting because it's able to really target a broad spectrum of B-cells, pre-B-cells, mature B-cells, and then plasmablasts. We think, you know, it's this breadth of its activity that is able to bring about, you know, a diverse range of improvement in disease-driving autoantibody conditions. AIH is characterized by liver inflammation- Mm-hmm and that can cause progressive scarring and loss of liver function. CIDP, disabling immune-driven neuropathy that damages peripheral nerves, myelin. And both of these diseases have quite a lot of similarities with IgG4-related disease, as well as generalized myasthenia gravis, where UPLIZNA, because of its B-cell depletion activity, has been able to show durable and really quite profound clinical benefit. So it's really this scientific basis where we've had proven effectiveness of UPLIZNA that makes us think that AIH and CIDP, you know, are really important unmet medical needs where UPLIZNA could play very strongly, and so that's why we're interested now in, in tackling those diseases. And then one more quick question before we kind of move on to, you know, other parts of the, the I&I portfolio. In terms of just how you think about, the sizing of these two populations, just help us better understand, you know, how you think about that, particularly relative to gMG and IgG4-related disease. And I mention IgG4-related disease because our understanding of the population is it looks to be a good bit bigger than, you know, what we thought it might be. So, I'm kind of asking a similar question about these two populations, and how are you thinking about that? Yeah. I think, you know, IgG4-related disease is interesting. When you have a impactful medicine, I think, you know, physicians are more likely to diagnose and to treat, and so that's important. For CIDP, we think the pool in the U.S. is around 35,000 patients, so that would be the prevalent pool, with maybe about 7,000-10,000 incident new cases diagnosed a year. AIH is probably larger than that, but it's difficult to get an absolute number on it. Mm-hmm. But that just gives you a kind of ballpark sense of where we are. Okay. All right, that's helpful. Let's talk about daxdilimab. So you announced, or the team announced last week, positive phase II results in discoid lupus. So just wanted to take a step back here. So daxdilimab, I think it was acquired via the, via the Horizon transaction, if I'm not mistaken. It did fail a phase II study in SLE. Obviously, it worked in a particularly challenging cutaneous manifestation with lupus. So I guess with that in mind, are, you know, as you think about a product like this, a plasmacytoid dendritic cell depleter, are these kind of cells more prominent in cutaneous manifestation of lupus? Or maybe put differently, can you talk to the mechanistic rationale behind the success in discoid/cutaneous lupus, but the failure in SLE? Yeah. So, so as you very rightly say, David, daxdilimab is a first-in-class molecule that targets something called immunoglobulin-like transcript 7 protein, or ILT-7. And it seems that that is involved in driving plasmacytoid dendritic cell function and, in turn, interferon production. So daxdilimab is essentially a plasmacytoid dendritic cell-depleting agent, just like we've talked a little bit about in a different setting with UPLIZNA, which obviously goes after B cells. So SLE is an autoimmune disease. It tends to affect the skin, joints, kidney, the nervous system as well, with autoantibody production, and often you get complement depletion. Discoid lupus is a skin manifestation, so it's similar to lupus, but it has to SLE, but it has a different underlying pathology. It's driven, as I said, you said as well, by plasmacytoid dendritic cells, interferon production in the skin, which, which leads to this dermatitis. And so we think because of that biology and the pathology, that daxdilimab would be a good potential therapy for discoid lupus. And in fact, as you say, we did do a phase 2 study of daxdilimab in those patients with discoid lupus. It met the primary endpoint, which was really a reduction in disease severity index at week 24. And it also met the key secondary endpoint, which was looking at investigator-assessed global assessment of disease activity. We also have a smaller study, a phase 2 study, in just 12 patients with dermatomyositis, where it also showed clinical benefit. So while it didn't show the, the efficacy that we were hoping for, as you say, in SLE- Mm-hmm. We think that this positive phase 2 in discoid lupus, coupled with the biology, coupled with the pathophysiology in that disease, makes us feel confident that we can take this molecule into that setting and hopefully provide some clinical benefit there in these patients with discoid lupus. So we're excited about that. Is the plan to move right to phase 3, and do you evaluate discoid lupus specifically, or do you look at a broader population with cutaneous manifestations of lupus? Yeah, it's a great question, and I would say we're still thinking about exactly that. You know, we want to be very thoughtful. This is a difficult disease with- Yeah few treatment options. We think we have a very attractive asset here. So I think we probably need a little bit more time just to continue to look at the data and plan the phase 3, and then we'll share those plans in due course. Okay, and then looking at daxdilimab more broadly, can you just talk generally about other autoimmune disease settings where you think a product with this mechanism could play a role? And, and maybe just, I'll ask bluntly, are you thinking about other potential indications for daxdilimab regarding its development? Yes, certainly. We'll be, you know, very methodical and very thoughtful in that anywhere where plasmacytoid dendritic cells, interferon production may have a role, we'll obviously think about. But, you know, we're going through that whole process now, so I think we need just a little bit more time- Yeah ... and then we'll be able to comment more on that. Okay. And then I wanted to spend a little bit of time on daxdilimab, which- Yes your CD40-directed treatment. So I believe the enrollment in your pivotals is wrapped up. Before we talk about Sjögren's, which I think is a really interesting space, can you talk to the underlying mechanistic rationale here? Yes, absolutely. So for dazodalibep, the CD40, CD40 ligand axis, you know, there's a common theme here, I think, David, in many of the diseases we've talked about. The CD40, CD40 ligand axis really drives B-cell activation, cytokine production, and there is good evidence that it's active in Sjögren's syndrome. And so dazodalibep is a fusion protein that inhibits CD40 ligand, and by blocking this pathway, we think that we can interrupt the upstream immune activation that contributes not only to autoantibody production, but then in turn as well, the downstream inflammatory cascade that you see in Sjögren's disease, the Sjögren's syndrome. We think that mechanistically, dazodalibep is well suited to Sjögren's disease because it's heterogeneous- Mm-hmm ... and there's frequently immune activation across all of these different disease manifestations in that syndrome. Okay. So I know you're running the two phase threes. Yes. One is moderate to severe systemic disease activity. Yes. The other is a different population, severe moderate. High symptomatic burden. High symptomatic burden, with its low systemic disease activity. They're, you know, they're very different populations. So I guess there's two questions I have here. One is, you know, how are these two different groups managed? And I guess secondly, how could the drug be beneficial in both of these groups, given its mechanism of action? I think the answer to the first part, you know, today, Sjögren's syndrome is really managed symptomatically. Yeah. So you, you know, you have good oral care, tear replacement, analgesia, you know, for the pain, and sometimes you can use glucocorticoids and steroids. So there's really not a good definitive treatment for it. We did publish the results in 2024 of our phase two study, which also looked at these two groups, you know, independently within that study. And we were able to see an improvement in disease activity index as well as patient-reported outcome. And so that gives us confidence that going in now to this phase three study that enrolls those two groups of patients, that if the medicine behaves as it did in phase two, we would hope to see, you know, a successful clinical outcome there. I think, you know, what we know about the disease is that that CD40, CD40 ligand axis is active across both of those types of manifestations of Sjögren's. So I think you can have one therapy that is able to, you know, attack that underlying pathophysiological mechanism and bring about clinical improvement, albeit in two different subsets of the disease. Yeah. Is there a path to approval in one of the two subgroups? Or maybe put differently, do you have to have success in both studies to be in a position to file? You know, I think we would have to wait and see, wait and look at the data and see how compelling it is. Again, you know, we were successful in the phase 2 in both groups- Yeah ... and so we'll be hopeful that we'll, we'll be there as well. Okay, and then on the competitive landscape or potential competitive landscape, because there's a lot of white space here, but what are your thoughts on the FcRn-directed treatment nipocalimab in Sjögren's, and how you think dazodalibep stacks up versus that agent? Yeah. To just remind everyone, we're hoping to have results from our phase 3 study in the second half of this year. Mm. I think obviously, David, we have to wait, you know, it's just around the corner really to see that and then how it compares. I would say that we are the first therapy to demonstrate efficacy in phase 2 in both of those groups that you mentioned, and that we're now studying them definitively in phase 3. Okay. Okay, so let's talk about TEZSPIRE and all things TSLP. Lots going on. So I wanted to start with the label expansion for TEZSPIRE in chronic rhinosinusitis with nasal polyps. So this is a little bit of a, you know, a commercial question and a little bit of a science question, which is how you see the product fitting into a treatment landscape, the treatment landscape relative to IL-4, IL-13-directed treatment, and also the IL-5s. I mean, I guess or maybe asked differently from a mechanistic perspective, you know, how do you see the fit? And also how TEZSPIRE could have an advantage in the nasal polyp indication. Yeah. Okay. So, you know, CRS with nasal polyps is a heterogeneous inflammatory disease. It often coexists with asthma, other respiratory conditions as well. And as you say, most therapies target the single or double downstream Th2 cytokines, IL-4, IL-5, IL-13. But those therapies do not address the upstream drivers like TSLP, which is involved in epithelial dysfunction and immune activation. And, you know, I think we've talked about this in the past. What's so exciting about TEZSPIRE is that it attacks TSLP right at the top of the inflammatory cascade, and so that gives it a differential profile. It's an upstream therapy, can take out multiple inflammatory pathways, not only cytokine production downstream, but also these diseases are often mediated through inflammatory cells, particularly eosinophils being recruited and activated. So if you can control TSLP, you really can control both of those different pathways. I think that mechanism we've seen has given strong adoption and, and confidence among prescribers. You know, just to remind everybody as well, in that phase 3 Waypoint study that underpinned- Yeah ... the approval of TEZSPIRE in CRS with nasal polyps, we were able to show statistically significant, clinically meaningful reduction in nasal polyp severity, almost complete elimination of the need for surgery, and a big reduction in the use of steroids versus placebo. So I'd say in summary, we think we're well positioned to reach more patients due to the differentiated mechanism, upstream mechanism of action. Mm-hmm. It's broadly applicable across multiple different patient phenotypes, and that's, you know, widely appreciated by prescribers today, rather than a single downstream pathway. And one thing we hear a lot about is the extent to which there's a lot of coexisting asthma and nasal polyps. Mm. Is it your view that having nasal polyps in the label is something that actually can enable you to reach more asthma patients with? Yeah ... with TEZSPIRE? Yes. Yes, it is. I mean, we think that about the coexistence of chronic rhinosinusitis and severe asthma is probably about 20%, you know. So the overlap here is large and really highlights a significant overlap between the two diseases' underlying pathophysiology that is both cytokine as well as eosinophilically driven, and really supports the clinical value of TEZSPIRE in these two indications. Yeah. And then just touching a little bit more on asthma, what are your thoughts on the implications of the availability of an ultra long-acting biologic? I mean, we have the, we now have a once or twice a year dupilumab. That product recently is approved. I know it's mechanistically different, but how do you see that impacting TEZSPIRE, if at all? I mean, I think, you know, these newer agents, I think, are going to have to demonstrate safety, durability, and meaningful clinical benefit. And so until we see those data, you know, I think it's, it's difficult to comment on that. Our focus really is on execution. We have, you know, we have approved indications where the medicine is really showing excellent benefit, and we have other indications in development. I think that what I can say is that with low penetration in severe asthma and the recent approval now for CRS with nasal polyps, plus these additional Phase III studies we have underway, COPD, eosinophilic esophagitis. Mm-hmm. We think that TEZSPIRE really has great potential to be a durable growth driver well beyond 2026 into a very large population of patients. So let's talk about EoE. I know that that study is not far away from reading out, but I had a couple of questions here that maybe we can tackle in the five minutes we have left. One is just talk to the nature of the unmet need and specifically biologic penetration here. And I guess where I'm going with the question is, we've got Dupixent available, you know, but there's a lot of corticosteroid management, of course. So just trying to get a better sense of how you're framing the unmet need, the underlying opportunity, particularly given the TSLP mechanism here. Yeah. So for eosinophilic esophagitis, you know, we have not formally characterized the epidemiology of the disease. Yeah. When you look at the literature, you know, here in the U.S., some databases would say that it has a prevalence of about 1 in 700 people. Hmm. I think it does represent an important and high unmet medical need. You know, the therapy today is proton pump inhibitors, surveillance, you know, maybe steroid use as well. So there's not a clear definitive therapy for the disease. And I think the fact that it is clearly eosinophilically driven and the effectiveness and efficacy that TEZSPIRE has shown in those types of diseases that we've just talked about, you know, is very exciting. And so, as you say, the phase III study is enrolled, and we hope to have data being available in the second half of this year as well. I think in terms of comparisons, again, you know, I'd be hesitant until we- Yeah ... see the data to really make comparisons with other agents. But, you know, the data really are just around the corner, second half of this year, and then I think we'll be able to define its profile and compare it to other therapies. Well, one quick follow-up here on just in terms of data, and I know it may be a hard question to answer, but you know, one of the endpoints, a co-primary endpoint, one piece of that is the Dysphagia Symptom Questionnaire. So help us contextualize what kind of improvement here would be considered clinically significant? I mean, I think the other endpoint is eosinophil count. Yes. I'm just trying to better understand on the DSQ, how you think about what would be clinically significant? Yeah. Well, look, again, I think we'll have to see the results of the study. Yeah. And then I think, you know, we're going, we're going to have to talk to regulators- Yeah ... or talk to physicians and groups who are here in the U.S. and around the world. And I think it's, you know, oftentimes with these patient-reported outcome, physician assessments, you know, it's a discussion on the totality of data. Sure ... as you say, the two endpoints together, and really, what do they see as the important difference there? Okay. I wanted to just ask a general question about TEZSPIRE and just TSLP-directed treatments and your plans beyond the core- Yeah ... or what I call the core of asthma, nasal polyps, COPD, and EoE. I mean, those are certainly big populations in the aggregate. But are you thinking even more expansively about your TSLP franchise in other indications? I would say we agree with you. I think they're big populations. Yeah. The medicine's been shown to really provide profound clinical benefit. I think for us now, it's about execution- Yeah ... to build in those populations. As I said, you know, we're still building penetration, and we have a lot of headroom. So we're not pursuing other indications for TEZSPIRE at this time. Mm-hmm. We do have AMG 104- Mm-hmm ... which is an inhaled TSLP antibody fragment, and, you know, that may also have utility. We've tested that in phase II. So we like TSLP, TSLP as a target. We clearly have a great medicine for it. We want to execute there and then think about perhaps the inhaled agent as well. Yeah. So in the minute we have left, I wanted to ask about the inhaled agents. I know the enrollment in the phase II is complete. Yeah ... so potentially another readout this year. But my question here is sort of two-part. One is, your thoughts regarding the challenges of adequately delivering a biologic into the airways, into the lungs, and then how you think you overcome those challenges. And then, you know, I guess the second question is, if you have data that you like and you want to move forward, maybe jumping ahead, where does an inhalable TSLP fit in within the asthma armamentarium? Yeah. So look, I think mechanism of delivery, you know, it's proven- Yeah ... with other agents. We've conducted the phase I. It was, you know, it was a small phase I. It was like 104 patients in the first part, and in the second part of it, 77. But it did show effectiveness, efficacy there, consistent with what, what we've seen with TEZSPIRE. So I think that's encouraging as well. You know, we think that for more severe asthma, inhaled corticosteroids, beta agonists are clearly sort of foundational therapy. Sure. But then something that, again, can attack right at the top of that inflammatory cascade, taking out cells as well as, you know, cytokine mediators, could really have an important role in managing asthma and, you know, delivering a therapeutic right to the site of insult being converted into injury through TSLP production. So, you know, the Phase II is expected to complete in the first half of this year. Yeah. And so we'll have more data soon, and we'll be excited to share this as well. And then just real quick, do you think it's potentially the, the 104 could be another option ahead of injected biologics? I mean, is that one way to think about it? Yes, I think it is. You know, we'll obviously have to see the data- Sure ... think about it with experts, but yes, it certainly has the potential for that. Okay. Well, I wish we had more time, but, but this has been great. Thanks so much, Paul. Thanks, Casey, and thanks to everyone listening in. But yeah, this is a exciting year ahead, in terms of, of readout, so, more to come. But yeah, thanks, thanks again, and really appreciate your time, and, we'll wrap things up. Thanks, David. Thanks, David.