Okay, well, good morning and thanks once again for joining us at the 45th Annual TD Cowen Healthcare Conference. I'm Yaron Werber from the biotech team, and it's a great pleasure to moderate the next panel with Argenx. With us today really needs no introduction. I think you've said this is your eighth or ninth Cowen conference now. Tim Van Hauwermeiren, Founder and CEO. Tim, good to see you. Thanks so much for joining us. And thanks for having us, Jeroen. It's a pleasure. So we're going to talk about, obviously, commercially what's going on, but we're going to reserve a lot of time for the pipeline since there's really going to be a tour de force worth of data this year. So maybe, Tim, the first one is on CIDP. You went pretty quickly from essentially having no patients on therapy to finishing with, you said, about 1,000 patients or so in Q4. I guess my first question, can you just remind us, is that 1,000 patients on drug at the end of the year, or was that sort of 1,000 patients throughout Q4, which means you actually finished probably higher than that? It was closer towards the end of the year. And the surprise that is going so fast actually sits in the access which we created. So we have a phenomenal market access team. And the rate limiting step in such a launch is how fast can you get policies in place? And I think they did, again, a great job, similar to what they did for myasthenia. That means that in just two quarters' time, 90% of the lives were covered with favorable to very favorable policies. And that's really the step you need to take to unlock your patient potential. So I think you saw a nice ramp in function of the policies coming in place. But at the same time, you also very much need pull-through both at the physician and the patient level as well. So that's not trivial at all. And I think you do a few things that other companies don't do. You have patient portals. You have patient outreach. I think that's a little bit more savvy than other companies. And you also have a lot of new prescribers now in CIDP. Can you talk about both of those? I think it's indeed important to do your educational effort on both the physician side and the patient side. We learned from Myasthenia, and we're really leveraging these insights. Our DTC campaign just went live two weeks ago. So you really need to mobilize the patient to stand up and ask for better. I think that that's an important part of the deal here, similar to Myasthenia. Indeed, there is an interesting halo effect going on in the launch. There are some big CIDP practices out in the community, which may also have some MG patients, but that's not really the focus of the practice. And having now seen Vyvgart in their own hands, seeing the success in CIDP makes them also start to prescribe for Myasthenia. So we do see some new prescribers we have never seen before, about 25%, giving us MG patients, which is that nice halo effect, which I think will be typical for the launch that will not continue forever. When you're thinking about the first 1,000 patients, kind of what's the profile of them? Are these patients that were presumably a lot of them are coming from IVIG or steroids, but a lot of them were off therapy and they're coming back? Or are these the very severe ones who are not getting switched? From that point of view, the playbook which we had in mind for the launch is panning out. These are IVIG patients. 85% of those patients actually come from IVIG. They're not doing so well on IVIG either for efficacy reasons or for safety/tolerability reasons, and therefore, they come on Vyvgart, so this was really the first segment of patients which we thought we would be getting, and that's indeed panning out in reality. What's the profile of the other 15%? They can be just patients on steroids or newly diagnosed patients. What's the breakout through both of those? Do you have any sense? Majority steroids. Majority. Okay. When patients are getting on therapy, and it's the question we actually asked on the call as well, I think Karen does a really nice job reminding us that there is sort of an initial 12-week sort of "test period," quote unquote, but physicians are not going to be doing INCATs in a community. So how are they really assessing response? And one would imagine at that point, why wouldn't the majority of them stay on therapy? Yeah, so the 12 weeks is an interesting reference because it's referring to the ADHERE trial where we gave patients 12 weeks' chance in stage A to respond before they could go into stage B. And what you see in practice, because this is such a novel medication, is that physicians will give us 12 months' time, sorry, 12 weeks' time to assess efficacy. That's also how they use IVIG. So they will give the drug 12 weeks to make up their mind. You're right, INCAT is not your routine assessment in daily clinical practice. I think they will rely mainly on clinical symptoms. Are they looking for improvement, or are they looking at stabilization? I think both. But in reality, what we see is a significant portion with regain of function. Remember, this is also what we have seen in the ADHERE trial, where 60% of the patients saw a regain of function, more than 30% saw a significant regain of function. These are also the stories which are reaching us from the real world. I mean, you hear a lot of patients reporting that they can start to resume activities which actually they had stopped doing already years ago on their IVIG. That's also, I think, the nice link we have with the DTC campaign. For the male patient, the number one activity we see them do again or start doing again is playing golf. So that's why the campaign is all about golfing. That's pretty impressive. I kind of need that since I don't play golf, so maybe I should take that. What about when you're looking at the VBAs, are they requiring that 12-week assessment? That's not going into the equation. What the VBA is taking into account is what we think the real-world success rate will be, where we triangulated from the clinical trial, 70% success rate, and then a certain real-world utilization of the drug. Remember, in the controlled randomized portion of the trial, patients were dosed weekly. But then in the open label extension, they can start to space out the medication. And looking at the totality of these data, we could triangulate with the payer what we think the real-world utilization actually would be. And that all feeds into that 450 number. Do you have any sense what% will ultimately go to a Q2 week regimen? We do have a sense from the open label extension study. Stay tuned. We will be talking about OLE data in the upcoming clinical conferences. Okay. We're also expecting data, I think, from the seronegative study sort of late this year, but really more importantly, ocular. And right now, you have a label on 85% of patients, which are generalized. The remaining 15 or so are ocular. The endpoints are the ocular is obviously a little different than generalized. Generalized is a little bit more severe. Ocular is obviously more localized. Can you talk about the differences in the endpoints? And what about what that means to uptake? Ocular is sort of a little bit less of an unmet need there. That's also what we thought, Jeroen, when we looked at MG. If you just look at the scientific and the medical literature, you would assume that ocular MG is somewhat a milder form of MG and that the generalized form is more severe. That's actually not true. When you double-click on that and you talk to patients, the ocular form is very debilitating. The double vision means you cannot drive a car. You cannot work on a screen. You get migraine. There's significant social stigma associated with ocular myasthenia. And then the treatment tool today is just high-dose steroids, which we all know over time is detrimental. So we overlooked the medical need when we came into MG. Now we're going to course correct and really try to serve these patients. You're right, it's about 15% of the MG patient population. The upside to the ocular MG trial is actually the question, can we delay the generalization? Can we stop the generalization? Because I think that would be a real bonus on top of just getting the ocular MG patients into the label. That all feeds into the strategy of the company to try and treat MG patients as early as possible because we know that comes with the best outcomes. So usually when you have an ocular manifestation, you can progress. Do all patients progress or some of them? 85% of ocular MG patients over time will develop generalized myasthenia. Just to finish off on your endpoint question, it is true that the generalized MG endpoint is looking at the total body. And therefore, the eye is just a small representation in that score. We're applying a novel endpoint for ocular myasthenia. It's quite robust. It's quite well described in the literature. But we're the first ones to use it in a clinical trial. But it gives you the full focus on the eye compartment of the disease. Remind us in that study how the actual study is designed and what you need to show for approval. It is a pretty fast study. You know that Vyvgart has a very fast onset of action. You typically will know after one or two cycles whether the drug works. You don't need any longer exposure in order to know that. So that's the pattern which we also follow into ocular MG. In that study, that's a little different. You need to show a statistically significant difference there versus control. That is correct. This is a controlled trial. The control will be placebo on top of pyridostigmine and steroids. Same requirement. The patient needs to be symptomatic despite being on a stable dose of background medication. I'm just going to maybe quickly ask, the PFS PDUFA is coming up April 10th. I mean, it sounds like you are expecting an auto administration in the label. And that's going to be at that point, how do you think about when you launch Hytrulo? I think the price of Hytrulo is the same price as Vyvgart, right, more or less. This is PFS. It's going to be more Part D oriented. It's got its own probably slightly higher gross to net as you approach commercial plans. Is there a reason to have two different price points or that's going to be a bit too confusing for the market? To cut a long story short, you do have some flexibility how you set your price for the PFS. On the other hand, you will have to anticipate some more rebating in your payer dynamic. But the way we think about it conceptually as a company is that physician and patients should be able to make their own choice of what product presentation fits them best without being forced into a certain product from a pricing point of view. So we will try to make it agnostic from an access and a pricing point of view, giving equal opportunity to all three product presentations. Okay. I'm going to move on to the ALKIVIA myositis opportunity. By the way, we're covering that opportunity in two different panels. I think one we have a dermato today. So we'll cover the dermato. And then tomorrow is the rheum panel where we'll talk about myositis, the muscle component. So we'll cover both areas. You've said that you've advanced into all three subtypes. It's the IMNM, it's dermatomyositis, and also the ASyS, which is also a lot of times known as polymyositis, right? Correct. When we talk to KOLs, it really depends what the definition of a KOL and how much they really know the area. Because you got from various feedback from, oh, this is absolutely going to work to, we're very bullish on IMNM because of the passive transfer data and animals to, we're a little bit more skeptical to DM. But then some of the real KOLs are saying, look, IVIG works in the dermato component, so it should work there too. And you've advanced it now into all three components. And a lot of the KOLs, they really know the drug. They're saying that it works very well in all three subtypes, presumably because the phase 2 obviously was not blinded. But this is very anecdotal sort of feedback. Sort of how is your view based on the biology? Where do you think it should work the most? We have done a ton of translational biology work in all three subsets. There are more myositis subsets, but these three clearly have an autoantibody involvement. It's typically more than one autoantibody. It's a panel of autoantibodies, and you're right, the passive transfer model in IMNM, but also in ACES, I think is proving the point, but there are other clues, I think, from B-cell depleting agents, IVIG, et cetera. I think with the phase two, which was a randomized controlled blinded study, what that study really showed us was statistical significance on the primary endpoint, this total improvement score for the total population of the three subsets, and then we looked at each of the three subsets, and we saw convincing signs that the biology is actually in motion, is responding to Vyvgart, and therefore, we advanced all three subtypes into the global registration trial. Okay. And I don't think you've noted, I think, how exactly you power the phase 3? We're not public on powering, but we're pretty conservative on how we calculate sample size and powering of the study. About 70% of the patients have a demonstrable level of autoantibody. In the other 30% of the patients, we think the autoantibody is there, but it's simply not detected because the assay is not sufficiently sensitive. But the powering is taking into account a scenario where actually some of these patients will actually not be antibody positive and may not respond to Vyvgart. So we're leaning towards the conservative side of the equation. And when you're looking at the powering, because it's essentially one study, but it's got three components, right? And each one is actually randomized against placebo within that cohort. The primary endpoint is then run on all patients together, or it's running on, there's a primary endpoint for each one of the three cohorts? Yeah, primary endpoint is on the total population, just like for phase two, using the same endpoint total improvement score TIS, and then, of course, there's a lot of unpacking to be done in the secondary and the exploratory endpoints to really unpack the effect of the drug across the three subsets. Theoretically, if you hit in the total score, you can get a broad label. Presumably, you need to show efficacy in each subtype. That's the going-in assumption. Okay. And again, for the audience, if you have questions, just raise your hand. I'm going to maybe move into Empa next, and there's a lot to unpack. There's going to be a lot of data this year on Empa. I'm actually going to start with, based on upcoming data, I'm actually going to start sort of in a reverse order based on where we get questions. DGF is the phase 2 delayed graft function. It's a 102-patient study versus placebo. Part A is at 12 weeks, and then you go into Part B, which is OLE for another 40 weeks. The primary endpoint is eGFR 24 weeks post-transplant against placebo. What do we know about the role of C2 in delayed graft function? I think it's a textbook example of why C2 is such a clever target choice, because it's sitting at the nexus of the lectin and the classical pathway. If you look at kidney biopsies of patients suffering from delayed graft function due to ischemia reperfusion injury, if you look into the biopsies, you clearly see C4d deposition triggered by both the lectin and the classical pathway. So it's an example of an indication where you need a C2 blocker and a C1 blocker, for example, could not do the job to answer the question on how you differentiate C2 from C1. I think from a biology point of view, it's a very strong rationale, but we felt we had to go through a proper well-designed phase two proof of concept study before we would then venture into phase three. That's going to be eGFR 24 weeks. The secondary is delayed graft function or functional delay and dialysis duration as well. What do you need to see from that data? Is it sufficiently powered at 102 patients to make a decision of phase three? Yeah. This is a sizable phase two. It's a meaningful phase two, and you're looking for proof of biology. I mean, you really need to move the needle on that surrogate endpoint of eGFR, because ultimately, the real value of the drug should and will be judged on graft survival. That's something you need to take care of in phase three. In phase two, I think we have a reliable proxy, which is eGFR. And graft survival would be at a year, or is that? It's something you would follow over a couple of years' time. But that's where the ultimate value of your drug will reside. This is on top of standard of care, is that right? Correct. Okay. So you're also running the, again, continue to kind of go a little bit backwards. The Empasiprubart phase two, this is in dermatomyositis, 42 patients randomized two to one against placebo. The primary endpoint is TIS, but now it's in the dermatomyositis patients. So they're actually the most common. It's about 50% of the myositis patients. And we're expecting that data in the second half, I'm sorry, in the first half of next year. This is patients with dermatologic manifestations, but they do need to have active muscle disease. Maybe again there, so in a way, you're already studying this population, obviously in ALKIVIA. What's the biology now supporting C2 in DM? The difference between the two is that in the basket study, the common denominator across the three subtypes is there needs to be muscle weakness. Muscle weakness is actually a key contributor to TIS. For the dermatomyositis study for complement, we don't have that requirement. There's a subset of dermatomyositis patients where if you look at the skin biopsy, there's a direct deposition and activation of complement. That's the type of patient we're pursuing with AMPA. And so to get enrolled, do you need to have that biopsy? We are taking the biopsies, at least to do the post hoc correlation. In the clinical diagnosis, this is one of the possibilities to get included in the study. It's not the only one, but it's one of the possibilities. Right. Okay. So it sounds like it's maybe from making it kind of simpler in a way, it's an overlapping population, but a little bit less severe in terms of the muscle compromise? Yeah, in terms of muscle compromise, I would agree. I mean, both subsets are equally severe. And I think it's a case where we want the data to speak. Can we triangulate what is a subset of patients, but the complement blocker will really shine. And so ultimately, if it's successful, is this sort of a broad-based therapy for DM, or is this going to be something that goes sort of after IVIG, or do you go up against, head to head against IVIG? The idea is, of course, with our type of innovation, is to go as early as possible in the treatment paradigm. So if you look at the design of the clinical trial, we're not niching the trial into a refractory patient population. Okay. I'm going to maybe now move to MMN. And the Empasiprubart phase 3 is ongoing, 300 patients, right, randomized two to one. So now you're going head to head against IVIG. The primary endpoint is the change from baseline in the MMN-RODS at 24 weeks. Part A is actually powered for non-inferiority initially, but then you have sufficient power for superiority as well. So can you give us a sense about just the thinking, the strategy there? It's an example of how the statisticians in our company are really innovative and adding value to clinical trial design. We like to believe that the way we innovate in trial design is a hallmark of the company. And I think it's your insurance policy. I mean, we feel comfortable to go in with the non-inferiority endpoint first. And then if you hit it, you can immediately go for superiority. And the reason I think that commercially speaking, non-inferiority would work is because MMN patients typically still worsen and they still progress on IVIG. So I think you would be able to get these patients even if you would only show non-inferiority. Of course, we're all hoping for superiority. We have been testing that endpoint on the phase two data sets. And I think the biology would support it. So think of it as a kind of insurance policy. As a minimum, you would have non-inferiority with a clear market opportunity, but we really aim for superiority. And then can you file based on non-inferiority? And if so, why is that the case? This trial design has been vetted with the FDA. Why aren't they requiring superiority? I think they agreed with the non-inferiority. Looking at the shortcomings of IVIG, I think we could document the unmet medical need in support of a non-inferiority trial. Is IVIG actually approved for MMN? It is approved. There's one brand approved for MMN. The brands are basically used in the real world in MMN. There was a clear win for IVIG in MMN, based on which it's actually on label. And I don't think you've said, and correct me if I'm wrong, which dose you took forward into the phase 3. You tested two different doses. The first data that we saw, an impressive 91% reduction in the need for IVIG was actually at a high dose, right? And then you actually lowered the dose. And give us maybe a little bit of a sense. How do you think about dosing? Remember, go back in time with me, Jeroen. The reason we had two distinctly different doses and dosing regimens was because no one actually knows what is the degree of C2 blockade you need to have the maximum clinical benefit in an MMN patient. The purpose of the phase two was to basically populate a PKPD model, so we could triangulate that dose and that dosing cadence. And that was actually very successful. We have not been public yet on that phase three dose and dosing cadence, but I mean, it's very accurately predicted by the PKPD model. It's the type of dose, I think, which will maximize efficacy, but also allow for maximally convenient dosing regimens. The phase 3 dose, is it distinctly the same as the high dose or the low dose, or it could be a hybrid of the two? Could be hybrid. This is an autoinjector that went into, or it's sub Q? We're progressing AMPA, both IV and sub Q. The fastest path to market will be IV, just like we have done with myasthenia, because the unmet need is so big that we think the IV product should not be delayed. But in parallel, we're progressing the sub Q execution. Understood. I'm going to maybe switch now to Vyvgart with the ADVANCE CIDP study. And so this is. We're going to get this data in the second half of the year. This is head to head against IVIG. It's a small study. It's a phase four, right, because it's already approved, 25 patients. You already have approval. So why do a head to head against IVIG now? But are we blending two studies here, Jeroen? What study are we talking about? The 25-patient phase four switch study. It's a phase 4, so it's not a randomized control trial. There is so much work to do in CIDP. I mean, remember, we like to say with the first real innovation in 30 years that there are more questions than you can handle in one study. One of the key questions you need to address is how do you switch? We already know from the IVIG trials where, for example, they switched IVIG patients to SCIG patients, that you need to pay attention on how you do it, because you may lose patients in that switch. So in order to help educate the space and pioneer in such a high medical need area, we decided to trigger that phase 4 study immediately after we had a win in the ADHERE trial. So the question is, at what point in time do you most effectively switch over from IVIG to Vyvgart? That is an open label phase four trial. Yeah. So yeah, I should have qualified. So this is specifically just so you know. This is patients who are controlled on IVIG. They're getting it every three weeks or every six weeks or steroids, and you're switching them. Primary endpoint is percentage of patients who are still on Vyvgart at 12 weeks of those who start Vyvgart within one week of stopping IVIG. The patients who are coming onto the study, do you foresee that they're sort of the mild IVIG, or are they going to be the more severe patients? I think this will be your typical IVIG patients. This does not need to be label enabling, right? This is just informing of how do you switch? Yeah. It serves the purpose to educate and inform the community on how best to switch. It's not going to be the last phase four trial. I mean, there are a number of questions from the field, and we will effectively address them. I think that's our responsibility as a pioneer in this space. So really, from Sanofi is doing phase 3s. We'll get those next year. They're running two different phase 3s. One, again, sort of a head to head against IVIG in patients who are on IVIG and well controlled, and another one, again, head to head in patients who are not doing well or even stopped IVIG. So different strategy from ADHERE. De facto, they're relinquishing the frontline population at that point. And KOLs actually do like that design too, because it tells them to really understand which patients to put on therapy. And I think you're addressing one of them with this study. So it sounds like you're considering doing maybe another study on potentially another head to head? So with Empasiprubart, our C2 blocker, we go head to head against IVIG. I think the days are over that you can offer the type of ADHERE trial, because now there is an approved medication. Patients don't like the prospect of potentially ending up on placebo and worsening. So I think it is attractive to roll out a study these days on both arms you can get on an active therapy. And then based on the data we have seen in MMN, based on some of the translational data which we generated in-house, we think there's a realistic chance we can beat IVIG in a CIDP setting. There's a lot to talk about in the phase 1 pipeline as well, so in the remaining time, we'll focus on that. I actually want to start with ARGX-109, so this is a program that originally sort of argenx made and licensed it out to one company, and then it went to another Chinese company. They ran a couple of phase 1, one in China, one in Brazil, and ultimately, you regain rights, but then you change the master cell line, and you're running a phase 1 now. You said this is a much more potent IL-6 than alternative available approved agents, and I believe also with a longer half-life. Can you talk about the strategy and the differentiation? Yeah. This molecule was built when the company still had its own business model, which was to build molecules for other people to develop. Basically, we were in survival mode, and we didn't have money to do any meaningful clinical development. Luckily, that has changed. So the task which we gave to the scientists in those days was, you make the most potent IL-6 blocker ever. So we have a phenomenal potency, and we go to infrequent dosing. So this molecule has a half-life of 60-80 days in phase one. So it's a best in class. Meanwhile, the understanding of IL-6 biology has meaningfully developed. I think we see potential, which was not seen in the days the molecule was made. Because we were not happy with the cell line in which ARGX-109 was being manufactured, we decided to bite the bullet and go back to the drawing board, make a very high yield cell line, and redo the phase one work, because it's a foundation for a big investment going forward. So IL-6 now is even being explored in autoimmunity or inflammation of cardiac disease as well, right? These are some broad markets as well. Obviously, there's some orphan opportunities as well. How are you thinking? And I know you haven't said much about indications. Yeah, there are new angles to the biology which we simply didn't see when the molecule was made, which gave us the conviction to actually activate that molecule and start to develop it as fast as possible now through phase one, and then you will hear us talk more about the clinical utility the way we see it when we branch out into phase two. Okay. Your IgA degrader ARGX-121 will have phase 1 data in the first half of 2026. I I think that's in healthy volunteers, or are you actually? Correct. It's a proper phase one. Are you looking at PKPD and biomarkers in that study? Yep. PK/PD will be very informative. It's a sweeping molecule. Remember, it's catalytically removing IgAs. All IgAs, by the way, because there are different glycosylation defects within the IgA class, and we want to take them all. And what we have shown in the preclinical data set is that we have a very fast and very deep IgA reduction without touching, of course, the other antibody molecules. And there is a lot of utility for an IgA sweeper. Of course, you have IgAN, but there is an increasing understanding of the role of pathogenic IgA antibodies in autoimmunity. And we think there is, again, a pipeline and a product opportunity right in front of us. Then ARGX-213 is a monthly, essentially alpha VHH, C-terminal alternative version of Vyvgart, obviously a very different profile overall. Same idea, phase 1 ongoing, data in the first half of next year. As you think about then differentiating and looking into different indications, sort of what comes to mind strategically? I think the molecule is going to give us a lot of strategic optionality, because if you study precedents, you could easily imagine following a kind of Soliris Ultomiris playbook, right? So you just roll up your existing indications with the next generation molecule. That is definitely an option. But remember, Yaron, there is so much opportunity which we simply don't tap yet with Vyvgart. We are in 15 indications, but there are many more indications. So another strategic option would be to take it into uncharted terrain with a whole new price point. So we're still weighing these options. We're still doing work on other next gen molecules. So let now the phase data speak, and then we will choose the path forward in phase two and phase three. Right. So this can potentially maybe go into broader markets, lower price points that will take some time to get to market. At that point, Vyvgart also has only several years left on patent, and maybe that's the strategy. Could be. I think you just articulated one of the two options, yeah. Okay. I think we're a little over, but time for one last question. Go for it. Completely not related to the pipeline. Would you consider a stock split at some point? So we did discuss the stock split with the bank several times. Our audience is not really a retail audience. So for the retail audience, a stock split could make sense, also psychologically speaking. For the type of investors we're targeting, when we ask them for them, actually, they're indifferent. So we didn't really see a reason for a stock split. Thanks for the question. Terrific. Tim, great seeing you as always. Thanks so much for coming. We appreciate it. Thanks for having me. Congrats on everything. Thank you. There's a lot of questions in the show. To moderate the next panel with Argenx. With us today, really needs no introduction. I think you've said this is your eighth or ninth TD Cowen Conference now. Tim Van Hauwermeiren, Founder and CEO. Tim, good to see you. Thanks so much for joining us. Thanks for having us, Jeroen. It's a pleasure. So we're going to talk about, obviously, commercially what's going on, but we're going to reserve a lot of time for the pipeline since there's really going to be a tour de force.