argenx SE ADR Stock

Yes, I think we are good to go. Welcome, everyone. I'm Sean Laaman, the Head of SMID-Cap Biotech Equity Research here at Morgan Stanley and welcome to our Global Healthcare Conference. For important disclosures before we begin, please see the Morgan Stanley research disclosure website at www.morganstanley.com/research disclosures. And if you have any questions, please reach out to your Morgan Stanley sales representative.

With that, we welcome Karl Gubitz, CFO from argenx; and An Vandebosch, Head of Development. Thank you both for joining us today.

Thank you. Thank you, Sean. It's great to be here.

Yes. Maybe just to kick off, we've got some more broader question thematically. How is the rise of China innovation changing your competitive positioning, if at all, and your R&D and business development playbook?

Yes. What's happening in China, I think, is exciting. It's exciting for patients, it's exciting for the ecosystem. It creates a lot of new avenues to fund unmet -- to fund biology. I think for us at argenx, it doesn't really change because I think the moat, which we have built is around innovative biology. It's where we find new indications, and we build those indications in our commercial engine.

So the way we think about China is it gives us another avenue to explore biology to find that next molecule. And what we're doing as a company is we're investing in China by -- we've opened an office for this purpose, where we have got a small team to help us hunt for business development opportunities. So no change in strategy. It is just augmenting or adding a geography where we are finding targets for our IIP, our immunology innovation platform.

Thanks, Karl. And moving on to AI. So another hot topic in well, drug development more broadly. But exactly give us a sense of how argenx is thinking about the adoption of AI and impact on your business?

I think all pharma companies, and I think all companies actually are investing in AI. It's clearly a hot topic. And so for us, too. Where we are today, I think it's a journey. Most of our AI initiatives are pilots, proof of concepts and informing our strategy. We've got a clear AI strategy because AI needs to be part of our business. It's not a strategy which stands alone. I think if you want to be -- if you want to be a biology innovator, you also need to innovate along the side of data. And we -- our strategy is built around pillars. We've got a strategy for discovery, helping us find molecules. We've got a strategy around research. We want to use that to help do the clinical studies earlier, finding patients, site selection, so forth. We've got a strategy on tech ops. We've got a strategy on commercial, all about patient interaction.

And then very importantly, scaling argenx way, which is so close to our heart and now we're operating as a company, building AI into our ways of working. So different strategies, but it's a big focus point for us as a company.

Great. And last macro type question before we delve into the heart of argenx. But which policy variable, if any, is it FDA, Medicare negotiations, MFN, global pricing? What matters most to your economics? And what have you changed, if anything, because of it?

I think, I mean, all of those are super important. And as a company, we continue to focus on it and spend a lot of time on it.

Maybe just quickly on the FDA. Our interaction with the FDA has been positive. We didn't feel or see any disruption on any of our -- on our interactions with them.

And in terms of MFN: GLOBE, GUARD, all of those, I will put it all under pricing, if you like. Pricing, of course, is not going to go away. This administration, next administration, it will continue to be an important factor for all drug development biotech pharma. And the only way to address this long term is to innovate.

Society will only pay for innovation. And that is core to our strategy of how we select drugs, what are we trying to do. Novel biology, find those white space indications where we can have a disproportionate impact on patients. And once you're there, you continue to innovate with adding indications, presentations and that's how you deal with it.

On top of that, we do, of course, a lot of scenario play to make sure that we are ready for any change because I think it's a fluid situation.

Sure. Thank you. Now to move on to the heart of the issue, which is company-specific. And I want to structure these questions to really get across the growth message. So maybe -- and I promise that I'll ask some different questions to breakfast. I'll try to at least anyway. But you saw 17% sequential growth in Q2 on Q1. And just to give investors a flavor of how much of that would you attribute to the seronegative label? And how do you think about that as a contributor going forward?

Our key growth driver, of course, continues to be an MG and CIDP. In MG specifically, the growth is driven by biologic expansion. 80% of MG patients are still not on a biologic. So that is where the growth is. And by the way, if you ask 5 docs, 4 of them will tell you, you start with VYVGART. So I think expansion and growing the biologic patient share is the key growth driver. PFS is super critical in that because that's a clear differentiator for us. It helps us to get into the community.

And seronegative, which we've got the label expansion in May, I should say, is an important contributor to that. It gives us the broadest possible label. Nobody else has a label as broad as we do. The triple negative, which is a subsection of seronegative, around half of that it, where we have no other treatment options. So that is where most of our seronegative patients are coming from, and it's an important growth driver.

The growth since launch, 18 quarters has been exceptional. And to maintain that growth, you need new innovation. The new innovation, which we have now is seronegative. So it's an important contributor.

Sure. Thank you. On my estimates, at least, I think, generally, consensus just north of $6 billion revenue for the year is what's being expected. But then I think about some of the opportunities that lay in front of you. We looked at the myositis data going on from the R&D Day into the actual release of the Phase III top line, in my view, probably couldn't have read out better than what it actually did.

But if you look at the IMNM indication, you've got 20,000 patients in the U.S., which is the epidemiology, my estimates of 6,000 to 7,000 patients are seeking treatment for what is a severe disease. So in terms of what we should expect as investors from here in terms of the regulatory path, just on focusing IMNM side, focusing on the regulatory path from here? And how should investors think about the launch given some of those dynamics?

An, do you want to comment on the regulatory part and then I'll comment on the commercial.

Yes. So as you have seen in our -- and as we had out in the call, when we reported the results, we have strong results in IMNM and DM. They're really consistent with stat sig in IMNM and borderline in DM. And that puts us forward in a path forward to have the conversation with FDA on DM. And for IMNM, of course, we will use the data to go forward in that conversation, but it will be a matter of review and discussion with regulator.

And from a commercial point of view, as you said, 20,000 patients in the U.S. It's a prototype argenx indication, completely wide space, no treatment options, severe debilitating disease. So opportunity for patients and for us as a company, of course, is clear.

How quickly we can ramp that launch? Of course, we're looking at different scenarios. But what I will say is that if you look at our history and how we get ready for launch, how we prepare the market and ultimately, the resources we apply to that I mean we're going to play to win. And I think those patients are waiting, and we will -- we hope to make significant inroads into that patient population once we launch.

A big element, of course, will be the payer work which we need to do. It will take a while to get all the payers signed up here. But the value proposition of efgart is well understood, well appreciated. We've done it a few times now with MG and all the label expansions with CIDP. So I think we know how to do it. We have relationships. So we -- I think we are bullish on the long-term opportunity here. In the beginning, of course, we will have to work for all those factors.

Sure. And on the DM side, so I think it's double the number of patients, epidemiology is about 40,000 tests. But if you go back to IMNM, you look at the T-score clinically meaningful TIS score, clinically meaningful on stat sig. Clinically meaningful on DM but not stat sig. But then also in comparison to maybe some of the competitive products out there on DM. How should investors frame the opportunity, given the data that you've seen on DM?

I think -- I mean, of course, brepo will launch before us. I think they're basically already launched. That's JAK/TYK2. It's an oral, of course, that comes with an advantages. But I mean, JAK, of course, also have some safety issues, which I'm sure the Street will be aware of.

But in terms of DM, it's a heterogeneous disease. It's a big patient population. I think it will take more than 1 or even more than 2 innovators to develop that space. And I think each drug will find its place.

An, anything you want to comment on how our drug compares?

Well, what we have seen repeating the results and the data, we have seen quite consistent results between IMNM and DM in Phase II and Phase III. And we will let the data tell and where each patient can play.

Sure. And thinking about the catalysts that we've got coming out. So we've got a pretty catalyst-rich next 18 months. But this year, you've got the Q3 results, we've got the celiac results, but also just to focus on a little bit on empasiprubart in MMN. How are you thinking about translation of the Phase II results into Phase III? How should investors think about the bar for success? And how should we think about the commercial opportunity?

I'll let An talk about answering your question directly. But if I can just quickly add how important empa and MMN is for us as a company. With VYVGART, of course, we all know it's a generational drug, once in a decade type of drug, which builds companies. But that playbook, novel biology, first-in-class, product in the pipeline, continue to innovate with presentations, continue to raise the bar, building the markets. That is the playbook. That is what made argenx successful. And we believe we can replicate that playbook with our C2 with empa. And MMN is, of course, the first indication on deck, and we will get that Phase III data later this year.

Yes. And to continue on your question from the Phase II learning versus Phase III, what we have seen in the Phase II trials is actually when you switch patients from IVIg to placebo, several return back to IVIg. And that is what led us to set up the trial in the way we did as a head-to-head comparison versus IVIg.

If you take the treatment burden into account how long these patients are in the chair when they take IVIg and what we know from empa. We believe that when we demonstrate that we're non-inferior versus IVIg, this is considered a win and success in the trial.

Sure. Sure. Next question is a bit of an algorithm. At least it's for me. But you presented some data back at AAN in treatment-naive patients, CIDP patients who were treatment naive, so hadn't had immunoglobulin. There is a bit of a conception that maybe VYVGART has mandated a second-line therapy here in the U.S., but it's not. It's just that the payers are require the step through.

Exactly.

But how do you anticipate getting more [ trickled ] moving to front line over time, given the bolus of patients is so much greater on immunoglobulin than what was around VYVGART. So long -- lot of runway to growth. So that part of the question.

Second part is when we look to the empasiprubart data head-to-head against Ig in CIDP, how important that is to the story and how much growth that could unlock?

Yes. Expanding VYVGART in CIDP beyond refractory patients, I think that will happen over time. Remember, when we launched in MG, we talked about 17,000 patients being a refractory patient population. That is where most of our competitors are today. VYVGART has moved beyond into the earlier lines. I think that playbook, of course, is not unique to VYVGART and MG. You see that in rare diseases. You typically start with your more refractory patients because that's where the unmet need is. And then you -- hopefully you expand if you have a drug for it. We believe the same thing is going to play out in CIDP.

Today, most of our patients are refractory patients, IgA refractory patients, only around 15% of patients are naive patients. It is -- as you said, it's not -- that's not how the study was done. The study included naive patients. We've got the label. It is the payers who are pushing us there at the moment. I think as physicians, as patients get more experienced, patients who -- physicians will be more willing to add patients and also to move up earlier line. To help support that we need data, and that is some of the data which you've referenced. We will publish -- we will create and publish more data. And over time, I think you will see VYVGART also moving up the treatment paradigm in CIDP.

Sure. And on the RT, as we talked Q3 a little bit, we talked [indiscernible] MMN, but what about the Forte acquisition and the data come out in celiac? How would you frame it to investors on what to expect, what you think the bar for success is and how you think about the commercial opportunity relative to the rest of your business?

Maybe just quickly and then An can comment on the data itself, which we are expecting. Forte again, fits our playbook. Novel biology, first-in-class, product in the pipeline, and gives us the opportunity to replicate the VYVGART playbook. I think when we did the Forte acquisition, it didn't stand on one indication. We don't think of it as we bought an indication. We think we bought a product, which we can put in many indications.

And of course, we are looking forward to a Phase II data and then we'll look at the data, and we'll try to get into Phase III as quickly as possible because we do understand it's a competitive race. And but what we do as a company at argenx is execution. We think that we can execute really well, and we will continue to do that also with FB102.

Anything specific on the data?

Yes. So Forte has already done a Phase I study in celiac which had a positive trend which created excitement. Of course, we will be reading out the Phase II data set later this year. And this is a learning study. So we will look at the data to learn more about the inflammation histology, but also about the symptoms and based on that, determine what appropriate next steps are.

Wonderful. Thank you. Just on the competitive dynamics. So we have some other complement inhibitors sort of coming down the pike. We've got Imaavy, we've got Ultomiris. There's a couple of drugs out there. On the other hand, you've got a very broad label in MG. You've got CIDP, you've established market position. How do you think about the risk of competition? And -- or how do you think about the competitive dynamic moving forward with all those pieces moving?

First of all, competition, of course, is good for patients. Competition helps to build the market. So of course, we welcome all competition.

In terms of how it impacts us and how we've been able to successfully position VYVGART as the first biologic in MG of course, it means that when competition come in, it doesn't really impact us. It actually helps to grow the market. We are the market leaders. We get most of the new patients in terms of biologic patients. So that is one of the success stories. One of the reasons VYVGART is so successful in MG.

And that is also why we should continue to be able to drive growth. I mean it's amazing, but we sit here today, VYVGART was launched 18 quarters ago. And we say, well, it's still the early stages of a launch because only 20% of patients is on a biologic. We are leading that biologic expansion or VYVGART is leading that biologic expansion. And based on our efficacy where we talk about MSE, minimum symptom expression, our safety and tolerability, where we have 20,000 patient years. And on the patient convenience side, where PFS for self-injection is clearly leading with an auto-injector to come. We believe that we will continue to see that growth.

The competition comes in, we get 4 out of 5 patients. The rest of competition is basically very competitive to get the rest. And of course, you also hear competitors say that they get VYVGART refractory patients, but of course, it's true. VYVGART does not work for all patients around 4 out of 5 patients respond to VYVGART, 1 of them don't.

And that is where VYVGART refractory patients, and that is also where some of the competition is getting patients from. But if we look at our data, it's very consistent in terms of hanging on to the patients we believe we should be able to keep, and that is playing out in the real world.

Sure. Sure. The top line growth is often discussed, a lot of debate around that, not so much debate. Everyone recognizes that the growth is there. But I think what is maybe underappreciated in your story, and you do have to invest for growth is you've seen well over a 1,000 basis point expansion in operating margin over the last year. And we look at some benchmarking, you're probably looking at operating margin across larger cap biopharma, somewhere in the 40%, 40% range. So how would you contextualize the balance of investment in the business to sustain the top line growth versus an expanding margin profile?

Thank you, Sean. I love that question. I think in terms of our capital allocation, how we make decisions, we always lead with a science. The science lead. We are a biotech company working for patients and investing in science. That is how we make decisions. We then want to -- we also, in terms of giving guidance and talking about margins and putting ourselves in a box, we're going to be very hesitant to do but because we love the flexibility. If we see science to invest in, we want to invent in that science like we just did in Forte.

And it is not a but, it's an and, and we can give you margin expansion. I think that is a unique position. It speaks to the strength of VYVGART launch and the financial structure of the company. We've got a very flexible operating structure. I keep on reminding the Street, but with a $60 billion market company, we've got 2,000 colleagues only. We outsource a lot. We're working with partners, we collaborate. That is our DNA, that is how we work. And of course, that allows us to be a little bit more flexible. But ultimately, over time, we're going to continue to expand that margin, but following the science.

Sure. And I guess the myositis data takes you into rheumatology. So again, related question. How do you think about the build-out of any commercial infrastructure associated with that TA entry?

Yes. Of course, we've got strong neuro capabilities. And if you think about myositis, including DM and we've talked about what we need to do to get DM on label. It's not if it's when. But we need to -- we will -- for myositis we will need neuro capabilities which we already have, strong neuro capabilities. We will need room and we might need a bit of derm, but that's very small.

In terms of rheumatology capabilities, we will need to go and build the field force. We will need to put those customer-facing organization in place. We've done that before. I think we know how to do it. And the platforms already exist and we can just build on that.

In terms of size, we don't want to talk size now, but I mean, typical orphan disease. I mean, I think most organizations will talk about the reps of around 100, but I'm not saying we're going to hire 100. But just in terms of give you a sense of scale. But we will build that and most of that resources will come online next year. We might -- start adding a little bit of resources now. And in Q3, the earnings call, which we will have in October, I will talk a little bit about expenses for this year because we don't guide as a company, but we gave the Street a rough idea of where expenses will be in 2026.

But now with a Forte acquisition, and with myositis reading out successfully, we need to augment that. And so I'll give you a revised guidance at that date.

Sure. Sure. So increased cost at the moment with Forte going vitiligo, celiac and alopecia. So what are incremental costs associated with that?

Yes. Okay. Thinking about the next wave of FcRn and the pipeline, perhaps. So ARGX-213, phase III ready for monthly dosing. Does that extend the franchise or cannibalize VYVGART? And how do you sequence the 2?

At the moment, people think of -- the Street believe VYVGART -- look at argenx as a VYVGART company. We need to change that to being an FcRn company. VYVGART has got a very long patent life. Matter of composition patent is until 2036. And we're adding patents on top of that, by the way. But eventually, VYVGART will run into its patent -- into its LOE.

We are starting to think about how you build an FcRn capability, and we've got 2 second-generation FcRNs. One is 213, which is once a monthly dosing. It's ready, ready now. We can start Phase III studies, but we have a bit of time because the LOE is so far out, but we will get there. But we first want to see the profile of 124, our second second-generation FcRN that is currently in Phase I and first in human studies. We will get to that data soon enough.

And then we can determine which compound will be used for life cycle planning, which compound will be used for possibly broader indications, possibly at a different price point. That -- and then that should also be augmented with our combo strategy. We have Adapt Forward, where we put VYVGART and our C2 together and currently in an MG study. And of course, we also have our oral program. All of that is designed to build on your current FcRN leadership and to make sure that we maintain and expand that leadership well and throughout the next decade.

Sure. Thank you. Thinking longer term, we wrote quite a large report on your company, I think, 2 weeks or so ago. I'm thinking longer term, like if you're doing this year, just call it, say, $6.5 billion of revenue, whatever it turns out to be, and we're forecasting, I think, $13 billion. So basically doubling of revenue by 2030.

So therefore, if you held the current price to sales multiple, then you're looking at doubling in market cap over that time. And while you don't have control over the price to sales multiple at least the price component, you do have some control over the sales component. So if I think about not extra indications beyond what you have today in the broad cMG label, throw in CIDP, that $6.5 billion revenue and compounded whatever you want to do at 5% to 10%, you're probably landing somewhere around $8.5 billion, $9 billion, something like that.

So to get to the $13 billion, you've got another $3 billion to $4 billion of revenue to add, which may come from your entry into rheumatology. You can get there by mapping it out on 20,000 IMNM patients at 400,000 pop is $8 billion, and then throw in whatever contribution from DM. So am I thinking about it the right way? What's your confidence in those -- while, I'm not asking you necessarily give long-term guidance, just your confidence in those kinds of aspirations?

So Sean, first of all, thank you for that report. I've read it and read it again in detail and circulated with my team, and we're studying it to see what we can learn. So it's a good read. Everybody, please go aware.

In terms of 2030, I think our strategy is very clear. We want to reach 50,000 patients. We want to have 10 on-label indications, and we want to have 5 late-stage programs. That is our vision for 2030. We believe we're going to execute on that, and we are working hard to achieve that. And I think if we can do that, that will, of course, translate into the market cap implications, and we'll -- I'm sure we'll get -- we'll be rewarded for that.

But in terms of that focus on patients, focus on Vision 2030 and doing it by argenx way by being very disciplined in terms of how we invest money, but still let the science lead we believe that is how you build the biotech for the future, and we're going to continue to execute on that strategy.

Wonderful. If I could go all the way back. Thank you, Karl, and thanks for the compliments. But if I could go all the way back to the empasiprubart study in CIDP. So maybe just sort of frame the treatment burden for patients on immunoglobulin that have CIDP versus what would happen if empasiprubart did improve on superiority? Then if you did prove superiority on IVIg, how do you think that melds into the conversation with payers around the different price points?

In CIDP or MMN?

Sorry, moving forward to next year, the CIDP study. Yes.

So moving forward to next year's CIDP study. As we know from IVIg, the burden is long in the chair. There is a safety label and based on that -- and that is something where, of course, we don't have Phase II data in CIDP, but we have Phase II data in MMN, and we don't expect it in the same way. So that is an element to take into account for that study.

And we will have to see how the data turn out at that moment in time. But here, too, we believe that setting up the experiment in a direct head-to-head comparison versus IVIg was the right way to do and we'll learn once we have seen the data. And Karl, maybe you want to comment further.

Yes. I think on the commercial opportunity of VYVGART, of course, is growing is doing really well in CIDP, but we are not able to help all patients. From ADHERE data, 70% of patients responded in -- with VYVGART in CIDP. So 30% did not. In the real world, by the way, we are not -- I think our response rate is slightly better than that. Probably over time, we might get to the 30%. We don't know. We'll see. But there is a segment of patients which are not being helped. And maybe IgM plays a role there. I think we need to do the experiment and let the science speak.

But if a [ deck of cards ] falls our way, having 2 drugs next to each other, we can talk about co-positioning at that date, but that will give us a very strong commercial footprint or foundation, I should say, to be -- to have continued success in CIDP.

Sure. And moving forward another catalyst we're keenly anticipating that next year is in Sjogren's. So again, a standard question. How do you frame the competitive framework? The competitive benchmarks? How do you think about what the bar for success is? And how do you think about the commercial opportunity?

Sjogren's, of course, large indication. I see a lot of data points out there. Our data points suggest around over 300,000 patients in the U.S. And of course, there are other drugs, competition is coming in and some of them are even launching before us.

But in terms of FcRn and specifically around VYVGART, we believe that the VYVGART signature can be very successful in Sjogren's. Think of rapid response, deep and sustained. I think that -- and with our safety and tolerability, where we already have over 20,000 patient years of safety data can give us a really strong position to compete in such a large heterogeneous disease where multiple players will have to work together to build that market. I think longer term, if the [ deck of card ] falls our way, super excited about what we can do for patients here.

We've talked Forte, we've talked empasiprubart, we've talked further expansions of VYVGART. But what in the pipeline that maybe you don't get asked a lot about excites you the most?

I don't know, An, do you want to talk about the pipeline? Maybe you want to talk about Ig?

That's one option. I was going to actually respond what you called out is already quite exciting, right, with especially the Forte acquisition. In that regard and how we then expand our portfolio and pipeline. Of course, the data will have to tell and guide us in that regard. But when you look further down the pipeline, there is, of course, pioneering of biology with adimanebart, although that's in Phase III that's further down the pipeline, I would say, the IgA 121. I believe also, if you show how rapid and how deep we can inhibit the IgA, I believe that's also an exciting molecule to us.

And Sean, if I can add, what makes me excited is not necessarily one specific program. It is the opportunity we have at argenx. We have the short-term growth drivers. We believe we do have the medium-term growth drivers. Think of Sjorgren's, think of FB102, all the other programs in your assets -- in your program.

And then with our financial structure, the strength of our balance sheet, its focus on execution and the way we make capital allocation decisions, let the science lead, let's focus on novel biology, let's find those white spaces, let's develop them. I think that is -- we're building a type of biotech here, which will give you -- which will be durable and provide long-term revenue growth.

I think the opportunity set we have here is what I'm very excited about.

Sure. I think I had you at about $6 billion on cash and balance sheet down to maybe $4 billion-ish post-Forte. Then think about what we correct the numbers. But thinking about what we have just discussed on the pipeline, do you think BD is more organic or inorganic from...

So we had $5.2 billion at the end of the previous quarter when we used around $2 billion, $2.2 billion on Forte. But still a very strong balance sheet. I've talked about how we make decisions in terms of what we spend the capital on, capital allocation or what. Of course, FcRN is a very important pillar, and we talked about next-gen combos, peptide, all of that.

Next to it is the rest of our pipeline. We've talked about empa and how important that is, but there's also a number of other programs in there, which we're very excited about, like the IgA and all the other programs.

And then the third pillar of growth is business development. We've done Forte. You can expect us to do more. You can expect us to look more at earlier stage because the way I describe it is what problem are we trying to solve. We don't really -- it is -- we do have a growth drivers in the medium and the long term.

But if you look forward well into the next decade, VYVGART and FcRn should be a really large franchise, which should generate a lot of revenue. To maintain a good revenue CAGR on that, you will need a number of other successful franchises. And what do we need to do today to build those franchises, which gives us revenues early in the next decade to maintain the forward-looking CAGR we want. And that is where our business development effort is focused on, and you can look forward to us hopefully executing more, but it will follow the same playbook, novel biology, look for those white spaces, where we can be first-in-class and where we can build a product and pipeline opportunities.

Wonderful. Well, we're right at time. Is there anything that I didn't ask that I should have asked?

No, I just want to say thank you to you for inviting us, and thank you to our investors who are supporting us on our journey. Thank you.

Thank you, everyone.

Good morning. My name is Leila, and I will be your conference operator today. I would like to welcome everyone to the call. [Operator Instructions]

I'd like to introduce Beth DelGiacco, Vice President of Corporate Affairs. You may now begin your call.

Thanks, Leila, and welcome to everyone on the call. Earlier today, we issued a press release summarizing positive topline results from the Phase III ALKIVIA study of VYVGART Hytrulo in autoimmune myositis. The press release and the presentation for today's webcast are available on our website.

Before we begin on Slide 2, I'd like to remind you that forward-looking statements may be presented during this call. These may include statements about our future expectations, clinical developments, regulatory timelines, the potential success of our product candidates, financial projections and upcoming milestones. Actual results may differ materially from those indicated by these statements. Argenx is not under any obligation to update statements regarding the future or to conform these statements in relation to actual results unless required by law.

I'm joined on the call today by Karen Massey, Chief Executive Officer; and Luc Truyen, Chief Medical Officer. I will now turn the call over to Karen.

Thank you, Beth, and welcome, everyone. Let's go to Slide 3. Today is an important day for patients living with autoimmune myositis and an important day for FcRn science, an exciting day for the rheumatology community, and it is a proud day for argenx. Based on the strength and consistency of the ALKIVIA data that we shared this morning, I can say that I am personally committed to securing a VYVGART label for patients living with both IMNM and DM. In IMNM, we have breakthrough therapy designation, and we will move with urgency towards submission.

In DM, the data establish a path forward, and we'll move with the same urgency to engage regulators on next steps. This is where the data lead us, and more importantly, it's what patients deserve. For too long, patients with IMNM and dermatomyositis have lived with serious progressive diseases and too few treatment options. For those living with IMNM, the consequences are particularly severe. IMNM progresses quickly, sometimes in a matter of months, leading to irreversible muscle damage yet no approved therapies exist.

In DM, the burden extends beyond severe muscle weakness.

Patients live with debilitating skin manifestations of the disease and many continue to struggle despite available therapies. The ALKIVIA data start to change that picture. Today is also an exciting day for science. 6 years ago, we shared the ADAPT data in gMG, the first registrational study ever for an FcRn. It established VYVGART and the FcRn class as a meaningful new approach in autoimmunity. At the same time, it was a breakthrough for patients and its impact continues today.

Since then, each successful VYVGART study has strengthened our understanding of where pathogenic IgGs are not just bystanders of disease, but rather they are driving it. ALKIVIA is now our sixth positive first-in-class Phase III data set with VYVGART, and it validates that autoimmune myositis is IgG-mediated. It is also an exciting day for the rheumatology community. For years, rheumatologists have cared for IMNM and DM patients without the right tools.

This is our first Phase III data set for VYVGART in rheumatology. And if approved, it will be the first opportunity to integrate an FcRn into their practice of medicine. And because of all of this, it's also a very proud day for argenx. For us, it's not simply about introducing a new medicine. It's about advancing science and changing what patients can expect from their treatment.

Slide 4. With that, let's dive into the results. What stands out most to me is the consistency of the data. We met the primary endpoint in the overall population with VYVGART demonstrating a statistically significant and clinically meaningful improvement in mean total improvement score versus placebo. What is particularly compelling is that this benefit wasn't confined to one subgroup or one aspect of the disease.

We saw a similar magnitude of treatment effect in both IMNM and DM, consistent improvement across all 6 core set measures that make up the TIS, including MMT8, and we saw benefits across both muscle and skin manifestations of the disease. We also saw the profile that has become a hallmark of VYVGART, rapid separation from placebo, deep treatment effect and benefit sustained through 52 weeks. Importantly, all of this was achieved while maintaining the signature safety and tolerability profile of VYVGART.

Slide 5. These results are particularly meaningful when you consider the burden these patients face every day. There is a real urgency to intervene early. Patients can experience severe and rapidly progressive muscle weakness. We heard at R&D Day from Dr. Aggarwal that IMNM patients can go from diagnosis to a wheelchair in a matter of months. Hospitalization is common, irreversible muscle damage can occur if it's not brought under control. Despite the seriousness of the disease, autoimmune myositis has remained largely overlooked by the industry. And that is why these results matter.

VYVGART is the first and only therapy to demonstrate clinically meaningful improvements across both IMNM and DM with benefits that span muscle strength, physical function and other aspects of the disease that directly affect patients' daily lives. In the study, patients maintain their benefit from VYVGART while tapering corticosteroids, which remains an important treatment goal for many patients and physicians. Early KOL feedback has been positive. They see these results as a meaningful step forward for patients who have historically had far too treatment options.

Slide 6. ALKIVIA reflects the playbook that has guided us from the beginning, following biology to areas where we believe we can have transformative impact for patients. Along the way, we have translated FcRn science into meaningful advances for patients with several firsts. We delivered the first major innovation in CIDP in nearly 30 years. And now we've achieved the first positive Phase III results in IMNM ever. VYVGART continues its leadership as the only FcRn medicine approved in more than one indication. And now we have the data to support 7. The potential for FcRn is expansive with an opportunity to transform the treatment paradigm in many more autoimmune diseases and in the process, reshape treatment outcomes for patients.

Slide 7. With these data, we have the opportunity to build on the foundation we have established in neurology and expand FcRn into rheumatology. If approved, VYVGART will be the first FcRn to reach rheumatologists with whom we have a tremendous opportunity to make a difference for patients. As we've engaged with rheumatologists, we've heard many of the same challenges we encountered in our early conversations with neurologists, a need for therapies that work quickly, deliver durable benefit, reduce steroid burden and improve patients' daily lives.

We are also seeing a growing recognition of the role pathogenic IgG autoantibodies play across a number of rheumatic diseases, creating increasing interest in the potential of VYVGART. While our immediate focus is on IMNM and DM, this is just the beginning. Our next major rheumatology milestone is the Sjogren's Phase III readout expected in the second half of 2027. And our Phase II study in systemic sclerosis remains ongoing.

With that, I'll turn the call over to Luc to take you through the ALKIVIA study results. Luc?

Thank you, Karen. Slide 8. I really want to echo your comments. It's an exciting day for the autoimmune myositis community who have waited a long time for meaningful innovation and targeted treatment options. I want to sincerely thank the patients who enrolled in ALKIVIA, the investigators and advocacy leaders who partnered with us and the argenx team whose scientific rigor made this moment possible.

Slide 9. We designed ALKIVIA to reflect what the biology was telling us. Myositis presents differently across subtypes, but IgG autoantibodies are a common driver and muscle weakness is a hallmark clinical feature. That gave us a scientific basis to study IMNM, DM and PM within a single operationally seamless Phase II/III basket trial with mean Total Improvement Score, or TIS, as a primary endpoint to measure muscle strength, physical function and broader disease activity. We included a specific skin measure for DM as well.

We made the decision to continue enrolling all subtype patients in the Phase III portion of the study based on the Phase II results. 175 patients entered Phase III and all patients had to demonstrate active muscle weakness to enroll. The Phase III duration was 52 weeks, allowing us to evaluate the response over a longer time period. We also introduced a mandatory corticosteroid taper from week 16 to 44. It's a core part of the design to pressure test the robustness of the treatment effect. This is especially important as it will provide confidence to taper in real life.

With that context, let me take you through the data, Slide 10. As you see on the left chart, the study met its primary endpoint of mean Total Improvement Score, TIS, at week 52 in a combined study population of IMNM and DM with a p-value of 0.0011. You can see a clear rapid separation of the active versus placebo arm, sustained over the 52-week period and consistent with VYVGART's profile. We saw consistent treatment effect across both IMNM and DM across all core TIS measures, which was consistent with the Phase II data, as you can see on Slide 11.

From the baseline chart on the left side here, you can also see that consistent with Phase II, we did not have a balanced randomization by subtype. This led to a larger percentage of IMNM patients enrolled in the study. So looking at the prespecified subtype analysis for IMNM, efgartigimod met the primary endpoint with a p-value of 0.0048. At week 52, mean TIS was 45.05 in the active treatment arm compared with 30.24 in the placebo arm, resulting in a 14.81 treatment difference.

And I want to pause here to reiterate. This is the first Phase III data set in IMNM, a milestone for the field. In IMNM, where progressive muscle weakness creates real urgency and long-term steroid exposure remains a significant concern, these results are exactly what we aim for. These data form a clear path towards bringing a new treatment to these patients as soon as possible.

Moving to dermatomyositis. Patients treated with efgartigimod showed a clear clinical benefit with an identical magnitude of effect to what we've seen in IMNM. The mean TIS was 51.51 in the active arm versus 36.96 in placebo, demonstrating 14.52 (sic) [ 14.54 ] points of improvement. However, the DM subgroup did not reach statistical significance on the primary endpoint. This is a reflection of the smaller sample size rather than absolute treatment effect.

In addition to muscle, we also saw a clear impact on skin disease in DM. The strength of these data compel us to engage with the FDA with urgency on the path forward. Altogether, we have a rich and compelling data set from ALKIVIA, which we will look forward to sharing with you at a future medical congress.

Slide 12. The safety and tolerability profile observed in ALKIVIA is consistent with the established safety profile of VYVGART, VYVGART Hytrulo as well as from previous clinical trials. The strength and consistency of the efficacy data, combined with a favorable tolerability profile creates a compelling benefit-risk proposition. This strengthens our conviction in bringing this medicine to patients who urgently need better treatment options. And I will now turn the call back to Karen.

Slide 13. Thank you, Luc. We are ready to move forward with urgency to bring VYVGART to patients living with autoimmune myositis. Based on the Phase II and Phase III data and the consistency of treatment effect we observed across both IMNM and DM, we believe we have a compelling regulatory package. In IMNM, where we have breakthrough therapy designation, we intend to move rapidly towards submission. In DM, we have strong conviction in these data and what they mean for patients, and we'll engage with the regulators on a path forward.

Today's announcement reflects the topline results. Our next step is to share the full data set with the medical community at an upcoming congress. We look forward to presenting the depth and consistency of effects across endpoints, including both muscle and skin measures of disease and to engaging the rheumatology community with a data set that has the potential to change clinical practice.

And finally, we're not waiting to prepare for the future. We're advancing our plans for a launch in one or both subtypes, and we continue to invest in the rheumatology capabilities that will support long-term leadership. This reflects our commitment to the myositis community and our ambition to build a lasting presence in rheumatology.

Slide 14. We set a bold ambition to reach 50,000 patients with our medicines, secure 10 labeled indications and advance 5 new late-stage molecules by 2030. Today, the ALKIVIA results strengthen our confidence that we are well on track to achieve that vision. What today's data reinforce is that our strategy is working. We continue to follow biology. We invest in areas of high unmet need and generate evidence that can change how diseases are treated. ALKIVIA is the latest example of this approach in action. As we look ahead, we are building on a strong foundation, continued expansion of VYVGART, a growing late-stage pipeline and an innovation model designed to create lasting impact for patients.

Slide 15. We continue to unlock the full potential of VYVGART. Today, we have data supporting 7 potential labeled indications for VYVGART and a growing opportunity to reach many more patients. Empasiprubart continues to advance through late-stage development with our first Phase III readout in MMN expected later this year. We're also progressing adimanebart and ARGX-121 and looking forward to adding FB-102 to our late-stage pipeline following the close of the Forte transaction.

What you see on this slide is that our growth story does not begin or end with any single molecule. We're broadening the reach of VYVGART today while building the next generation of medicines that can shape the future of argenx. This is why I'm more confident than ever in our ability to continue to bring meaningful innovation to patients and create long-term impact in immunology. I want to say thank you again to the patients, investigators, physicians and Argonauts that help make today's milestone possible.

And we will now open the line for questions.

[Operator Instructions] Our first question will come from Tazeen Ahmad with Bank of America.

Congratulations on the positive update this morning. I was wondering if you could provide a little bit more detail on the steroid tapering benefit that you saw. This has been something that you pointed to as a potential benefit. It looks like you did see that.

How do you think it's going to compare relative to how physicians would want to see benefit? Is it simply lowering the amount of steroid? Or is there a minimal amount that they wanted to see? And do you plan on showing this and other level of data at upcoming medical meetings as well?

Yes, Tazeen, thank you for the question. And in terms of comparing across the different data sets, what I think is actually most compelling about this data set is the consistency of data even with the steroid taper. But maybe, Luc, I can hand it over to you to talk through that steroid taper.

Yes. Thank you, Karen, and thank you, Tazeen, for the question. So the steroid tapering was a real construct within the trial, where as of week 16, patients were depending on their level of steroid use coming in, were tapered until week 44 with a target of 5 milligram or less of steroids. The reason that we wanted to do this in the trial was to see if indeed the treatment effect would be maintained on those conditions. And we achieved that as the robust endpoints show.

There is observation that, in fact, placebo patients, there are several of them had to use rescue. The main goal for us was to make sure that indeed treatment effect is robust. And as I said in the remarks, hopefully, for the field, this will give some confidence that you can taper a patient that is benefiting of VYVGART.

And then, Tazeen, on your last question around medical congress, you can absolutely expect that we will be very transparent and share all of the data in the argenx way at an upcoming congress, and it certainly is a robust data set.

Our next question will come from Derek Archila with Wells Fargo.

Let me add my congrats on the data. So just one question from us. I was wondering if you could better characterize some of the benefits you're seeing on the secondary endpoints in DM and understanding the caveats of cross-trial comparisons, but how might those compare to brepo? Any that you could see VYVGART where they could be differentiated?

Yes, absolutely. I mean I think this is topline results. So we've shared with you what I think the primary endpoint and tried to qualitatively sort of outline for you what we see in the secondary results. And what's important there is the consistency across all of the core set measures that we see. So when we look at those 6 measures within the TIS and when we look at other secondary endpoints that measure also things like impact on skin in DM, then we really see consistent treatment effect and that consistency is across both IMNM and DM. So I'd say we're very pleased with that consistency of the data set.

Our next question will come from Akash Tewari with Jefferies.

By our math, if you group the Phase II and Phase III data sets in DM, VYVGART would have a stat sig data package. Can you confirm that's true? And did you disclose bundling both trials when the FDA modified your original trial design earlier this year?

And if I could sneak in one more. I suspect the effect size approaching 15 on TIS, would have been stat sig in Phase II? What led to the miss in Phase III despite the larger N? It seems like there was a lot of underlying variability here or perhaps steroid rescue imputation?

Yes. Thanks, Akash. Great questions. Let me zoom out for a second. I think what you see, what is clear from the data is that we have a medicine that works across IMNM and DM. And we see that there is, as you call out very well, consistency in the improvements that we see between Phase III and Phase II. Now obviously, there are some differences in the design between Phase III and Phase II. So pooling those wouldn't make sense.

But I think you're really focused on the right thing, which is when you look at these -- the primary endpoints for Phase II and Phase III for IMNM and for DM, it is clear that we have a medicine that works. And it's the first time a medicine has demonstrated positive benefit for both of these patient populations. And I think we have a strong regulatory package to take forward.

Our next question will come from Danielle Brill with Truist.

I'll also add my congrats. So maybe a follow-up on some of the secondary efficacy endpoint measures. I wanted to ask about the TIS 20, 40, 60 threshold specifically. I know many physicians view these as important measures of clinical relevance. Can you comment directionally on how efgar performed across these response thresholds and whether the effect was consistent across IMNM and DM?

Yes. Thanks for the question. Maybe, Luc, you can comment on...

Well, we don't want to give too much detail away given upcoming presentations. What I can say is that we were very pleased with the rates of response to those EULAR milestones you state, TIS 40 in particular, is recognized as an important one, and we had a very robust result there.

Your next question will come from Alex Thompson with Stifel.

Congrats on the data. I wonder if you could talk through kind of your next steps in DM in particular? Do you plan to seek sort of regulatory alignment before filing? Or do you expect to file directly with these data?

Yes, I'll hand over to Luc to comment on the pathways. But what I want to reiterate is where I started the call today, which is we do see that we have a medicine that works in both, and we are committed to getting a label expansion in both IMNM and DM. And as you point out, the paths do look different. So maybe, Luc, do you want to talk to that?

Yes. So from the data set, it should be clear that the path to submission and consideration by the FDA is pretty clear, compelling data set, very robustly significant. And so that's pretty clear. On the DM side, while we are very, very pleased with the results and the magnitude of the effect size, this has to be a discussion as to what they would require to see to be able to grant approval. And it's too early to speculate what that could be. We will engage in the dialogue as soon as we can.

Your next question will come from Samantha Semenkow with Citi.

Let me also add my congratulations on the great results this morning. I have a question on DM. Just given the heterogeneity of this disease, are there any early signals that you can pull out that some autoantibody profiles responded better than others? Or are you seeing a pretty broad magnitude of benefit across patients enrolled?

Yes. I mean I think we've all used that word heterogeneous nature of DM. I think what we see is that there is one common feature, and that's that autoantibodies are driving this disease and IgG autoantibodies. So we see consistent impact across secondary endpoints, across patient populations. And I think it really reinforces the value of VYVGART in that population.

Your next question will come from Sarah Cai with TD Cowen.

Congrats on the amazing data. This is Sarah on for Yaron. The data seems to support filing in DM, as you had noted earlier, but just curious if the conversation with FDA maybe doesn't completely support filing in DM, would you then choose to run a smaller Phase III to have a confirmatory effect in DM? And then separately? Are you thinking about maybe expanding into other subtypes of myositis? We've heard inclusion body myositis, IBM, mentioned as an interesting subtype of myositis that maybe VYVGART could also have an effect in. So just curious to hear your thoughts there as well.

Yes. Thanks for the question. I would agree with you, these are amazing data that we're seeing. So yes, in terms of the path forward on DM, as Luc said, we will very urgently have a discussion with the FDA to be able to share what we see is a very compelling data package. And then I think that we can see that there are a few paths forward, either that we're able to move forward for a label expansion based on the strength of this Phase II and Phase III data package or we can think about the example of what we did with SERON and the seronegative in MG, where the agreement we came to with the FDA was to do a small follow-on study to be able to really demonstrate the benefit in that patient population.

And so we have that as a path forward as well.

Certainly, from my perspective, what I want to impress is that we are working with urgency on this, and we see a real need to get to patients as quickly as possible. They have really limited treatment options today, and this is a severe disease that progresses quickly. So our goal is the fastest path to patients possible. And then maybe, Luc, I could hand over to you to talk about our thinking on the other subtypes.

Yes. Now you mentioned IBM in particular. There, the biology is somewhat more unclear. But you can rest assured that we are very committed with VYVGART or any of our other assets to make an impact for this community with our innovation benefiting their unmet needs. So this is just in our mission.

Your next question will come from Thomas Smith with Leerink Partners.

Let me add my congrats on the data. I know these are just topline results, but anything in the ALKIVIA data that makes you more confident on the opportunities for efgart and Sjogren's systemic sclerosis?

Yes, it's certainly exciting that we are able to establish ourselves in rheumatology through this data before the Sjogren's readout. But maybe, Luc, do you want to talk about your thoughts on...

Yes. Well, I think the -- I would say, other than our commitment to rheumatology, there is not an immediate read-through of these results to Sjogren's. For Sjogren's, we did our own small study, giving us confidence that there is a consistency in the biology that we can follow, but I wouldn't say that these data would further support that.

Your next question will come from Rajan Sharma with Goldman Sachs.

Maybe thinking ahead a little bit, but just on the potential commercial launch, assuming there is an approval. I think in the past, you've always talked about 2 or 3 quarters to get sufficient coverage for VYVGART when there will be new indications. Just given the unmet need in IMNM and potentially even DM, is there any reason that, that could be a faster launch than you may have experienced in other indications?

Yes. Great question. We'll certainly be working as -- to get patient access as quickly as possible. But I think what we'll do is take the same approach that we've taken in neurology. And so it likely will, to your specific question, take a couple of quarters to get that access in place. But we don't see that access will be a major barrier for IMNM or DM. Thanks for the question.

Your next question will come from Gavin Clark-Gartner with Evercore ISI.

This is Yixin on for Gavin. Congrats on the data. So just a question on the Phase III eligibility. Can you remind us -- it looks like muscle weakness was required for each patient, but for the active skin enrollment is not mandatory. It only needs to meet 1 of the 5 criteria. So based on this criteria, can you remind us how the resulting mix is going to compare with the real-world DM patients presented in the practice?

I can answer this. So yes, from the paradigm of a basket trial, we were looking for a dimension that was really common to all, so that we can have a common measure of it. As I've indicated, we included in the specific skin measure, the CDASI. But we didn't really require a specific level of activity on that. Nevertheless, I find -- and what I will say about the CDASI result is that I find them very compelling for a treatment effect.

Your next question will come from Sean Laaman with Morgan Stanley.

Congrats on the results, and I hope everyone is well. Just wondering with competition, why should physicians choose FcRn over JAK inhibition? And is there particular physician segments or patient profiles where FcRn might emerge as the preferred approach?

Yes. Thanks for the question. Look, I think if we zoom out, we can think of neurology as a good sort of playbook of what we can expect in rheumatology here. And what you see in neurology is that VYVGART was the first-in-class FcRn and that argenx was able to establish ourselves as a trusted partner to neurologists. And as a result of those things, along with the fact that VYVGART has rapid, significant sustained efficacy, a clear safety profile with, I think it's now 25,000 patient years of safety that gives those neurologists real comfort and also, of course, the prefilled syringe.

So the convenience factor of a prefilled syringe. That's established VYVGART as the #1 branded biologic in MG. And I think what you'll see in rheumatology is exactly the same. We will be the first, if approved, to launch in rheumatology. So first FcRn in the hands of rheumatologists. I think we have a package of data today that you can see in autoimmune myositis that shows rapid, sustained, significant efficacy with a safety profile consistent of that with what we see in the real world and obviously, the convenience of a prefilled syringe. So I think you'll see some similar uptake and similar impact in rheumatology that you have in neurology.

Your next question will come from Matt Phipps with William Blair.

Congrats on great data here. You talked up a lot the IMNM commercial market opportunity, really CIDP-like in the number of patients. But now with the DM data in hand, how do you see this total myositis opportunity? Could it be as large as MG given now maybe 60,000 patients with these 2 subtypes?

Yes, it's a great question. What we shared at R&D Day is that we see both of these indications as blockbuster indications on their own. So obviously, the dynamics are a little bit different. In IMNM with 20,000 -- about 20,000 patients, we estimate, but no treatment options. So very, very high unmet need. And then in DM, about 40,000 patients, there is an approved therapy. But what we hear from patients and rheumatologists that there is significant unmet need remaining. So as you say, I think that this will be a substantial commercial opportunity. Thanks for the question.

Your next question will come from Suzanne van Voorthuizen with Kempen.

This is Suzanne. Congrats again on the data. Now a lot of the regulatory route focuses on the U.S. and the FDA, but I'm wondering about the ex-U.S. filing strategy. Can you expand a bit on what feedback you've gotten from other health agencies? And I think IMNM is clear, but basically for DM, should we expect that the global path to market resembles whatever the route will be in the U.S.? Or do you see more flexibility already upfront in certain other territories?

I'm glad you asked because it is important for us that we are able to bring VYVGART to patients around the world, not just in the U.S. So maybe, Luc, you can talk to that.

Well, I think given the nature of this data set -- of this whole program, in fact, first the Phase II and now the Phase III with the treatment impact that we've shown, we will most certainly engage with regulators and present them with this data package and discuss the route to approval for both IMNM and DM.

Your next question will come from Leland Gershell with Oppenheimer.

Congrats on the data as well. Just quickly following on to a previous question on the data differences between DM and IMNM. It looks like from the consistency of the data and the effect size, you missed stat sig big on DM by literally just a couple of handful of patients if those patients had produced the same data. Could you just comment on that?

Yes, absolutely. Look, I don't think I've ever said in any topline results where we haven't looked at one piece of data and said, if only, or what could have been? I think what's really important is the strength and consistency of the data that we see across IMNM and DM and that we have a path forward for label indications for potential label expansion, I should say, in both of those indications.

And also just wanted to ask as you move into this new area of rheumatology, I just want to ask if you see any differences in getting uptake amongst this new group of physicians relative to your penetration into the neurology community?

Yes. Thanks for the follow-up question. Look, I think just like when we started out in neurology, it's about establishing argenx as credible and as a partner in providing care to their patients. And so I think we're on that journey with rheumatologists. We'll be investing to become that partner just like we are in neurology. And I think it will take some time, but we'll be able to apply that same playbook that I think has been successful in the past.

Your next question will come from Victor Floch with BNPP.

Congrats for this great milestone. Maybe first one, a quick follow-up to Rajan's question on the launch. And so I'd just like to see if we leave like access on the side for one second, something like the very unmet need that you've done, discussed many times during the call. Should it be fair to assume that the launch could be even faster than what you've seen for MG at the time?

And a very quick follow-up on modeling some maybe like a question for Karen, if I may. In terms of launch readiness and preparations, should we expect like a significant step-up in terms of SG&A? I think consensus has $3.6 billion in OpEx, excluding COGS for this year, $4.2 billion for next year. So does it look fair to you in the context of the IMNM launch later this year or more likely next year?

Yes. Thanks for both of the questions. I can take both of those. So as you said, with our launch, what you can expect, and we have a lot more work and we'll have a lot more opportunity to share this with you is we will go about getting access as soon as possible. That always takes a couple of quarters. But I do think that as you're calling out, there is significant unmet need. And so I do think that patients and rheumatologists will be excited about the opportunity to start using VYVGART in their practice. So we look forward to a successful launch. That's for sure.

In terms of launch readiness, we're already working on it. And -- but in any step-up in SG&A that you can expect because of the expansion into rheumatology will come through in next year's financials. And so we'll be able to share more detail with you at an upcoming meeting.

Your next question will come from Luca Issi with RBC.

Congrats on the data. Maybe, Luc, can you comment on what you're seeing in polymyositis? I know there was obviously just a small number of patients enrolled and you obviously deprioritize that. But how does the p-value look like in the overall trial if you also include polymyositis? I guess what I'm trying to ask is how does the p-value look like in the ITT population as the way the trial was originally designed in case the FDA ultimately decide to do that sensitivity analysis as part of the review process?

Yes, it's a good question. Luc, do you want to...

Yes. So as we indicated during the R&D Day already, we had actually modified our primary analysis already to only focus on the IMNM plus DM population given the very low numbers. So in fact, we don't have the analysis and are not planning to do it as it would not really contribute to our overall effort. And -- but it's an interesting observation how few we actually got, which, again, reflects maybe how that disease picture is moving.

Your next question will come from Douglas Tsao with H.C. Wainwright.

Congratulations. I'm just curious, Luc, we saw in terms of IMNM and almost all the patients enrolled in the study were MSA positive, but we did see a lower proportion in DM. And I'm just curious if you saw any difference in results between those who are MSA positive and those who were not.

Well, thanks for that question, which we, of course, are also looking with interest, but it wasn't part of our topline. And so we are in the process of analyzing that. But again, look at the overall results, very robust.

Your next question will come from Xian Deng with UBS.

Maybe I'll just ask a broader pipeline question, if I may. So I mean, you mentioned so this IMNM could actually be VYVGART's first step into rheumatology. So just wondering in your broader pipeline, of course, you have Sjogren's coming up next year. But other than that, just wondering what are the other non-VYVGART assets that you think could potentially leverage this rheumatology infrastructure that you will be building?

Yes. Thanks for the question. So first of all, let's start with VYVGART. And as you mentioned, we're excited that we also have Sjogren's data that we'll be reading out towards the end of next year. And we have a Phase II study ongoing in systemic sclerosis. So already within our development plans for VYVGART, we have quite a rheumatology footprint. And in fact, that we also have seen that there is biological rationale for the use of FcRn in other diseases treated by rheumatologists as well. So I think this is just the beginning.

Secondly, as you said, if you take a step further back, we are building an immunology innovation company. And many of the therapies that we're developing as pipeline of product assets will have indications that will cross over and be treated by rheumatologists. So I think over time, what you will see is argenx becoming a real leader in the space and transforming outcomes for patients treated by rheumatologists across a number of different diseases. Thanks for the question.

Your next question will come from Andy Chen with Wolfe Research.

Can you talk about whether your previous decision to separate the 2 trial types or the 2 subtypes would have any impact on how the FDA views DM versus an alternative scenario, assuming you never separated the subtypes. So based on the data today, it sounds like argenx really never had to separate the subtypes and your likelihood to obtain approval regardless of whether DM is stat sig.

Yes. And I think -- I'll let Luc comment. But before he does, what I do want to say is this basket trial, I think, has delivered exactly what we wanted it to. And that is that it allowed us to generate data in multiple different subtypes as well as the total population. And as a result of that, we have the opportunity to pursue a label expansion in both IMNM as well as DM. So I think if you take a step back and asking the question, was this the right clinical trial design? My answer to that would be absolutely, and it's put us in a position where we can bring VYVGART to patients across both IMNM and DM.

And to come further. So we actually did this in dialogue with the FDA to look at the individual risk benefits in each subtype. It was actually already planned in the overall trial, but the hierarchy was different. So they just wanted to have the hierarchy focused on the subset rather than the total, but yes. So it was not just an invention of ours. This was in dialogue.

Your next question will come from Qize Ding with Rothschild & Co Redburn.

I have one follow-up question about the potential for other pipeline assets for the DM subtype. If you look at the ARGX-217 (sic) [ ARGX-213], this molecule has a similar mechanism of action to VYVGART. I mean based on the data and learnings from VYVGART in the DM subtype, do you have any thoughts about the potential future clinical development plan for 213 in the DM subtype?

Yes. I think you're referring to ARGX-213, which is one of our next-gen FcRn assets alongside ARGX-124. And what you're calling out is something very important, which is that the space and the biology that we're unraveling with FcRn is very broad. I mean with this data set, this is the sixth positive Phase III registrational data set for VYVGART and there's more to come. So when we look at our FcRn strategy with ARGX-213 and ARGX-124, I think there's opportunities to continue to broaden that indication landscape as well as deepen our leadership within indications as well. So you'll certainly see that in our FcRn strategy moving forward. Thanks for the question.

Your next question will come from Jack Allen with Baird.

Congrats on the update. This is Chris on for Jack. Just a safety question. Can you provide just a little more color on the infection and immunoglobulin reduction profile in these subtypes versus what you've seen in gMG and CIDP, given the sustained 52-week dosing? And then just along those lines, do you plan on providing subtype specific safety data at some point?

Yes. I'm glad you're focusing on safety. It's certainly one of the strengths of VYVGART as well. But Luc, maybe you want to provide some color?

Yes. And to start with your last question, yes, of course, we will be providing at some point the data by subtype. So far, we don't see any differentiation there. In terms of the safety and you talk about infections. So the first thing we have to talk about is the population we're in today in these diseases is heavily pretreated with steroids and immunosuppressants. So that's the background on which this trial is run. And if you look at that and take that into account, it is really consistent with what we've seen before.

On the one hand, there is a slight increase in infection. On the other hand, there is no consistent pattern. So we don't think that this is changing the view on the risk side. And let's not forget, with VYVGART, we have already 25,000 patient years in the real world. So so far, for us, not a real case for concern. Of course, we continue to evaluate. But for me, the main thing is the benefit we've shown really makes for a real robust benefit-risk in this population that's needing new options.

And our final question will come from Mathijs Geerts Danau with KBC Securities.

Congrats on the results. The final question on the IMNM commercialization. Do you actually plan on relying on the existing sales force? Or will you need to have to hire additional people?

Yes. Thanks for the question. Maybe to put the reason why you are asking that question, IMNM is often diagnosed by neurologists and treated by rheumatologists. So it's a really important bridge for us to be able to leverage our strength in neurology into rheumatology. We will be able to leverage a lot of the infrastructure that we have in commercial to, for example, our patient support and that type of thing where we'll provide the same sort of quality and level of support that we do in neurology. But we do foresee an expansion into rheumatology so that we can reach all of the prescribers that we need to. Thanks for the question.

There are no further questions at this time. This concludes our conference call for today. Thank you for participating. You may now disconnect.

The press release can be found on our website, along with a slide presentation that you can follow as you listen to the call. I'm joined today by Karen Massey, Chief Executive Officer; Arjen Lemmen, Vice President of Corporate Development and Strategy; and Peter Ulrichts, Chief Scientific Officer. Karl Gubitz, our Chief Financial Officer, will be available during the Q&A.

Before we begin on Slide 2, I'd like to remind you that forward-looking statements may be presented during this call. These may include statements about our future expectations, clinical developments, regulatory time lines, the potential success of our product candidates, financial projections, upcoming milestones and the anticipated benefits and timing of the proposed transaction.

Actual results may differ materially from those indicated by these statements. argenx is not under any obligation to update statements regarding the future or to confirm these statements in relation to actual results unless required by law.

I'll now turn the call to Karen.

Thank you, Beth, and welcome, everyone.

I'll begin on Slide 3. Today's announcement is an important milestone for argenx and an important investment in our next chapter of growth. It's also an important day for patients and our commitment to raise expectations of what a treatment can deliver in autoimmune disease. We have entered into an agreement to acquire Forte Biosciences, adding FB102, a first-in-class anti-CD122 antibody to our immunology pipeline. FB102 has demonstrated clinical proof of concept in diseases that have lacked meaningful innovation like vitiligo and celiac disease, and we believe there is broader potential across multiple autoimmune diseases.

Before I talk about our conviction in FB102 and recognize the impressive work the Forte team has done to advance the programs through proof of concept, I want to start with our strategy. Our Vision 2030 strategy is well-defined and on track.

Last week, we shared our second quarter results. VYVGART continues to reach more patients around the world as we progress towards our goal of treating 50,000 patients. With the approval of VYVGART in seronegative gMG, we now have four labeled indications on our path to 10 by 2030. And we continue investing in our innovation engine to advance five new molecules to late stage that we believe can become the future growth drivers of argenx and shape the future of immunology. It is the success of this strategy that makes today possible.

Over the last several years, we have built an incredible foundation, pioneering the FcRn class, and we've demonstrated that we can translate promising biology into transformational outcomes and new treatment paradigms for patients. And now we have an opportunity and a responsibility to build on that foundation. Our ambition has never been limited to a single molecule, a single target or a single therapeutic area. Our ambition is to become the leading immunology innovator, building a pipeline across multiple targets and multiple dimensions of the immune system.

The acquisition of Forte fits directly into this ambition and is a continuation of a strategy that has guided argenx from the beginning. Stay close to great science, pursue the best ideas wherever they originate and build conviction through data, all to bring immunology breakthrough to patients. This principle helped create argenx, and this principle brought us to Forte Biosciences. It will continue to guide how we build our next chapter.

Slide 4. At argenx, innovation has never been limited to what happens inside our own walls. We pursue the best science through our immunology innovation program and partnering with leading academic collaborators and research institutions and with biotech partners through partnering deals, strategic investments and now an acquisition. This is how our pipeline has been built and is proof that breakthrough innovation does not happen alone. It is how we discovered and developed efgartigimod. It's how we're advancing empasiprubart and the rest of our pipeline, and it's also how we came to know about FB102. We've been following closely CD122 biology for several years.

And this year, in April, we made a strategic investment in Forte based on our belief in the science. More recently, with the positive Phase Ib data in vitiligo, we saw the opportunity to bring FB102 into argenx. The Forte team has done an impressive job in advancing this program. We believe great science and great people go hand-in-hand, which is why we are excited not only about FB102, but also to continuing to work alongside the team that helps bring the asset this far.

So with that, I'll turn the call over to Arjen to discuss the transaction and why Forte and FB102 are such a natural fit for argenx. Arjen?

Thank you, Karen. Slide 5. When we think about bringing in new pipeline programs, we always start with the same questions. Is the biology and mechanism of action differentiated? Is there evidence that it can translate into meaningful benefits for patients? And can argenx help realize its full potential? FB102 stands out across all these dimensions. What initially attracted us was the combination of novel biology, a targeted mechanism and early clinical validation. We're also attracted to the broader potential of the program to be a pipeline in the product opportunity across vitiligo, celiac disease, alopecia areata and other autoimmune diseases. Just as important is why we believe FB102 is a strong fit for argenx.

First, FB102 complements our existing portfolio. Our strategy as an immunology leader is to play across important pathways of the immune system. For example, we have efgartigimod and ARGX-121 in the antibody compartment targeting FcRn and IgA and empasiprubart addressing complement activation at C2. FB102 add another important dimension, targeting pathogenic T cell and NK cell through activity through CD122 biology while preserving beneficial regulatory T cells.

Second, we believe this is the right moment to bring the molecule into argenx. The program has generated clinical validation in 2 indications, while still leaving meaningful opportunity for us to shape development strategy, expand the indication footprint and build the full value of the program alongside the Forte team.

And third, we believe argenx is uniquely positioned to help realize the full potential of FB102. We are specifically organized to execute and maximize pipeline in product development programs. We have an established product presentation playbook and strategy, and we have demonstrated that when we enter underserved markets, we establish leadership and shape treatment paradigms. We believe these capabilities can expand the impact of FB102 for patients and maximize the opportunity.

Slide 6. Turning briefly to the transaction. Under the terms of the agreement, argenx will commence a cash tender offer to acquire all outstanding shares of Forte for $77 per share, representing a total equity value of approximately $2.2 billion. The transaction is not subject to a financing condition and will be funded entirely from cash on hand. The Board of Directors of both companies have approved the transaction, and we expect it to close in the third quarter, subject to customary closing conditions. This transaction also reflects how we think about investing for the future.

We've always taken a disciplined approach to capital allocation and our priorities remain clear. First, we continue to maximize the opportunity for VYVGART and build the future of FcRn medicines. Second, we continue to advance our broad and growing pipeline. And third, we continue to pursue differentiated biology wherever we find it to strengthen our future growth trajectory and expand what we can deliver for patients. Ultimately, this transaction reflects the simple belief that science should set the pace for investment. Where we find an opportunity of raising the bar for patients and strengthening the future of argenx, we have the flexibility and the conviction to act. We found this with Forte.

Now I'll turn the call to Peter to walk through the science behind the program.

Thank you, Arjen. Slide 7. Building on what you said, our interest in FB102 begins with the biology and as antibody engineers with the quality of the molecule. FB102 is uniquely designed to inhibit IL-2 and IL-15 mediated activation and proliferation of pathogenic T cells and NK cells while sparing beneficial IL-2 signaling on regulatory T cells. The scientific question we seek to answer is whether we can reduce the activity of the cells driving diseases like vitiligo and celiac disease while preventing the immune -- or while preserving the immune regulation we want to keep. At argenx, our goal is not broad immune suppression.

Our goal is to target the underlying drivers of disease in a precise way. FB102 gives us the potential to do that through a differentiated approach leveraging CD122 biology. The clinical data generated to date have been important in building our conviction on FB102. Let me briefly walk through those data before turning the call back to Karen.

Slide 8. First, on vitiligo. In the study, FB102 demonstrates rapid and sustained benefit with statistical significance reached by day 64. Patients continue to show improvement through week 24, 12 weeks after the last dose.

On the slide, I would like to show the week 24 results. 29.6% mean a FAS improvement for FB102 compared with 7.9% for placebo. These data provide early evidence that targeting CD122 may address the underlying immune activity and reinforce our conviction in the mechanism. Celiac disease provides another example. This is a systemic autoimmune disease driven by a T cell-mediated response to gluten.

FB102 has a strong mechanistic rationale in celiac disease because CD122 blockade simultaneously suppresses IL-15-driven epithelial damage and IL-2-driven gluten-specific T cell activation. The slide shows that the Phase Ib study met the primary BCL endpoint and showed fewer gluten-induced GI symptoms versus placebo. FB102 is now being studied in a Phase II trial in celiac disease, which will read out before the end of the year. Together, the biology, the translational evidence and the clinical data provide a strong foundation for continued development of FB102.

And with that, I'll turn the call back to Karen.

Thank you, Peter. Slide 9. The biology Peter described is what first attracted us to FB102. The opportunity to bring that science to patients at scale is what excites us about the future. Vitiligo has too often been misunderstood as a cosmetic condition. It is not. It is a chronic autoimmune disease driven by pathogenic immune activity. Current treatment is limited to a subpopulation, and many patients do not achieve complete or lasting repigmentation with these options. More than 2 million people in the United States live with vitiligo. While awareness of vitiligo has increased and new therapies have emerged, outcomes are far from where patients want them to be.

Celiac disease represents another significant opportunity. More than 2.5 million patients in the United States live with celiac, yet they have no approved treatments beyond a strict gluten-free diet. Even with careful management, many patients continue to experience symptoms and anxiety around accidental exposure. In addition, there are long-term complications beyond the digestive tract and an increased chance of other autoimmune diseases. We believe these are diseases where argenx can play an important role.

We have demonstrated with VYVGART that we can successfully establish leadership and transform underserved markets so that patients can spend less time managing their disease and more time living their lives. That experience gives us confidence not only in the opportunity ahead for FB102, but in our ability to execute, expand its potential and maximize impact for patients.

Slide 10. Before we start Q&A, I want to leave you with 3 key takeaways. First, this transaction is firmly aligned with our strategy. Vision 2030 is on track. Our conviction in VYVGART and our existing pipeline remains unchanged. FB102 builds on that foundation and supports our ambition to be a leading immunology innovator. Second, we believe FB102 is the right molecule. It combines novel biology, a targeted mechanism and an elegant design with potential across multiple autoimmune diseases. Third, these are serious systemic diseases where patients need better outcomes and where argenx can help shape the future standard of care, just as we have done with VYVGART.

Forte has advanced impressive science. Our role is to build on that foundation and work alongside the team as we advance FB102. This is an important milestone for argenx, for Forte and most importantly, for patients.

Thank you for joining us today. And operator, we'll now open for questions.

[Operator Instructions] Our first question will come from Yatin Suneja with Guggenheim Securities.

Congratulations on bringing this important mechanism into your portfolio. Always good to see one of your companies getting acquired by another company that you cover. So the question that I have is mostly around the indication. So if you could frame for us how much weight you are putting on the areas where we've already seen proof of concept like vitiligo, EoE and celiac.

What about other areas that are opening up with this mechanism, whether it's alopecia areata or atopic dermatitis that other companies are going after? And how much visibility you had into some of the ongoing studies that Forte was running. So just basically frame to us the investment you're going to make across the indications that might open up with this indication.

Yes. Thank you for the question. And I like starting with that question because I think it really makes us zero in on the value that FB102 can bring to a broad range of patients and very much aligned with our mission. So one of the things -- the parts of argenx strategy and one of the reasons that this looks like an argenx molecule is that it is a pipeline in a product molecule. We like molecules where we can pursue multiple indications. One of the reasons for that is that it gives us multiple paths to success and multiple paths to growth.

With this molecule, when we looked at it, one of the key ungating factors for us was the recent data -- Phase Ib data in vitiligo and obviously, also the data -- the Phase Ib data in celiac. So those will be 2 of the lead indications. But exactly as you say, we think that this target has the opportunity to open up more indications beyond that. We're not in a position today to share what those indications would be. But what we can say is that we'll take the exact same approach with FB102 that we've taken with our other pipeline product assets like VYVGART. And we have a very clear and disciplined approach to indication selection. So we always start with a strong biology rationale, and we like to see indications that are derisked with preclinical or translational data.

We like it when there's a clear development and regulatory pathway and always use that as a gate. And last but not least, there needs to be a high unmet need and a high commercial potential. So over the coming months, we'll be looking at a broad range of indications for FB102 through these lenses. But as you point out, I think what we'll find is that there's opportunity beyond celiac and vitiligo for FB102. Thanks for the question.

Our next question will come from Tazeen Ahmad with Bank of America.

Karen, I just wanted to get your thoughts about what you mentioned about vitiligo. So Incyte does have a product available currently. They have had a bit of a slower-than-expected launch into that space. Is it your view that it's still because it's viewed as a cosmetic indication as opposed to something that needs medical treatment? And then can you just remind us what specifically gives you confidence at this juncture that this could be differentiated from what's already out there?

Yes. Thanks for the question, Tazeen. I will just to touch on it. I mentioned it in the script. We do not believe that vitiligo is simply a cosmetic skin condition. It is a chronic and systemic autoimmune disease. And I think the opportunity ahead is to make that clear to the health care system and to treating physicians. What we see is that vitiligo impacts quality of life, especially where there's significant body area that's impacted and when symptoms like severe photosensitivity are involved.

So we think that there is a clear opportunity to elevate expectations for patients with that condition. And I think we had some learnings for how we've done that from elevating expectations and transforming markets in some areas with VYVGART. But perhaps, Peter, you could talk to the strength of the data that we see in vitiligo.

Yes. First and foremost, of course, there is the Ib data, which showed the clear effect. And I think also from a biology point of view, the molecule is hitting 2 pathways, which are well established to be active in vitiligo, the IL-15 arm and the IL-2 arm. So that combined with a favorable safety profile, which we've seen to date, which we obviously need to confirm, give us some differentiated angles as compared to what's out there. And that's why we're quite bullish on this biology.

Our next question will come from Derek Archila with Wells Fargo.

Congrats on the transaction. Just wondering if you could discuss your view on FB102's rationale and opportunity in alopecia. And I was wondering if reviewing the blinded data from the ongoing trial was part of the diligence process.

Yes. Look, in terms of when we were looking at FB102, we had the opportunity, obviously, to look at all of the data, the public data. And we look forward to seeing the alopecia data that is for later this year that will also inform our position. And as part of diligence, we were able to work closely with the Forte team.

I would say while I have the opportunity right now that we were very impressed with the Forte team, the quality of the science, the quality of the execution and how they're bringing this asset forward. And so we were able to look at all of the standard types of data that you can look at through due diligence, and that really gave us confidence in this asset and in the data package behind it. Thank you.

Our next question will come from Yaron Werber with TD Cowen.

Yes. Congrats on really a terrific deal based on really good data, especially given this is your first deal. So maybe, Karen, for you, the celiac data, Phase II data is expected to come pretty soon. The Phase Ib, as noted, was really positive. There's going to be even more of a gluten challenge in this Phase II. So the potential to even show more outsized effect. Can you maybe frame kind of your expectations for this data? And maybe give us a little bit of a sense how big do you think celiac is as an indication?

Yes. Thanks for the question. We're looking forward to seeing the celiac data as well. Obviously, with the Phase Ib proof of biology, we have confidence going into that data, but you're always turning a data card. And I think it's important that we note that this is a Phase II study. So Phase II studies are a learning study. So what we'll be looking for alongside the Forte team is to make sure that we can get really good insights into celiac, including, as you said, with the gluten challenge and the impact of FB102 so that we can design a strong Phase III development program moving forward.

And I think the way that the clinical trial is designed, the insights that we'll get, including the primary and secondary endpoints will give us the information that we need to design a good Phase III clinical development program. So let's wait and see. The data from that program will be coming in Q4. And when we turn that data card, we'll be able to share those top line results and what the future program looks like.

Our next question will come from Gavin Clark-Gartner with Evercore.

Congrats on the deal. So you definitely talked through the pipeline and the potential in a lot of detail. If you were to pick one indication where you see the largest commercial opportunity, what would that be? Because from an investor point of view, I think it's celiac at the moment. And I'm curious if you share that perspective.

Yes. I think one of the strengths of this molecule is that it is a pipeline in a product. And what I would say is that we see the opportunity for multiple blockbuster indications. And it's one of the reasons that we like this molecule is that we have multiple paths to success with -- across indications. So like you, we're certainly looking forward to the celiac data, but I wouldn't underestimate the opportunity in vitiligo and some of those other indications as well.

Our next question will come from Samantha Semenkow with Citi.

Congratulations on the deal. I wanted to ask just about these indications being significantly larger than the typical rare disease indications that you've gone after for VYVGART and some of your other molecules. Just how are you thinking about evolving the commercial engine to really work into your playbook for building these meaningful indications?

Yes. Thanks for the question. It's an important part of our consideration when we were thinking about these indications. I mean we do see these indications as very argenx-like indications. They are severe autoimmune conditions, and there is significant unmet need. But as you say, we will need to continue to augment our commercialization capabilities.

I think we've built a strong commercialization engine, and we continue to build that with VYVGART. Of course, we'll start pending positive data with Sjogren's disease, for example, we'll start entering larger markets with FcRn as well. I think the key to that will be to continue on the path that we've been launching our medicines on with our commercial engine that's focused on a patient-centric approach. So what's going to be really important here is making sure that we are empowering patients to expect and to ask more from their medicines. And that's something we already do with VYVGART very actively.

The second piece that will be important is continued evidence generation, even post approval or post launch. These are markets that need to be built and where the real-world evidence needs to be generated to demonstrate the impact of expanding treatment and expanding treatment with biologics. And we have experience also with that most recently in MG, expanding, for example, into ocular MG.

And last but not least, I think in these markets, proven payer execution will be key. And what we've seen is that that's a core capability here at argenx, and we think that we can redeploy that capability indication by indication with FB102 as well. So there's a long way to go before we get to commercialization of this asset, but we think we're well positioned and have the commercialization capabilities to do it.

Your next question will come from Akash Tewari with Jefferies.

So for vitiligo, what's your confidence 102 that data holds up in a larger data set, particularly for patients with less facial involvement? And will those under 0.75 patients be excluded from your further trials? And then can you talk about the delta between the protocol defined versus ITT data and what imputation method you're going to be using in your further studies? And then finally, did Forte measure total vitiligo area scoring, not just facial? And if so, what did that data look like?

Yes. Thanks for the question. So what I will say is the call today, we're focused on the -- our initial insights on the program. And what we'll be working on over the next couple of months is going much deeper with Forte and also being able to define the program in the future. So we'll refrain from commenting on all of the detailed questions that you have. But maybe, Peter, you could share why you have confidence in vitiligo and what you see the benefit of the program.

Yes. Again, I think the biology fits nicely with the pathophysiology of vitiligo. And to comment, we have at least one element on your question, indeed, you do see really great activity at the high end of the disease severity. I think what we're going to do now is indeed take deep dive in all these data and define what potential next steps could be, including the question on which patients to include as or no in future trials.

Your next question will come from Alex Thompson with Stifel.

On the deal. Maybe another question for Peter. Could you talk a little bit about your confidence in the therapeutic index here with sort of the blockade of both T effector and natural killer cell activity and that we're maybe out of the woods for infection risk at this point?

I think that is indeed a concern of the biology of targeting -- a broad targeting of NK cells and some of the T cells. I think first and foremost, based on the current exposure, which is 3 months, we don't see any increase in infectious risk. So, so far, the safety profile looks good. Secondly, it is not a total NK cell depletion and it's a specific subset of NK cells, which are depleted with this mode of action, which gives also some confidence on the safety element. Obviously, we need to see longer-term treatment data to fully explore the risk benefit profile of this molecule. Thank you for the question.

Our next question will come from the line of Suzanne van Voorthuizen with Kempen. Well, we'll return Suzanne later. Our next question will come from Matt Phipps with William Blair.

Congrats on the deal. There was some interesting data at the recent Society for Investigative Dermatology Conference with an IL-15 antibody showing a lot of benefit when combined with UVB in vitiligo patients. Is that something that you would look to explore? Just curious if you're familiar with that data.

Yes. I'll let Peter comment on the data. But I think in general, what you bring up is something interesting in the immunology space, which is combination therapy. And certainly, we haven't started down that path yet, given where we are with FB102. But as you know, it's a key and core part of our strategy in -- with the rest of our pipeline, and I think an area that will continue to emerge of importance in the future. But Peter, I don't know if you want to comment on that.

Yes, I think we obviously are also aware of these data, and it's an element which we are considering or will be considering when drafting plans for the next phases of clinical development.

Our next question will come from Douglas Tsao with H.C. Wainwright.

Just maybe as a follow-up to Samantha's question in terms of this representing a little bit of a shift for the company in terms of its focus on sort of more common prevalent diseases than orphan indications. I guess I'm just curious, is that going to be reflected in the business development strategy and how you're prioritizing things? Or is it going to still be sort of through a lens of biology?

Yes. Thanks for the question, and I'll let Arjen comment in a moment. But I would say, at the highest level, our strategy for building our pipeline and for becoming an immunology -- a leading immunology innovator is to focus on novel biology in areas of high unmet need. And our capital allocation priorities internal as well as business development follow that strategy. But Arjen, maybe you want to talk in a little more detail about how we think about business development within that context.

Yes, absolutely. So partnering has been a fundamental tool in how we've built our pipeline to date. It's how the immunology innovation program works. And we've consistently done that around biology with academic institutions and other biotech companies. I think this represents an ability to also do that at a later stage. And ultimately, our business development strategy will be tailored for the target space for the molecule for its stage of development to do the right thing to augment our Vision 2030 objectives.

And maybe the last thing to add is that what we do like is with these assets is being able to put, let's say, the argenx fingerprint on them. We think we have a differentiated capability in developing these pipeline and product assets, our product presentation playbook, for example, how we go through indication selection, sequencing. And so assets that are early enough in their development that we can still put our fingerprints on them, I think, is an important component to the strategy.

Our next question will come from Sean Laaman with Morgan Stanley.

Karen, strategically or maybe sizing, what role do you expect CD122 biology to play relative to FcRn complement and your other pipeline franchises?

Yes. I mean I think what we're building is a broad immunology portfolio, as you say, that is sort of -- where we have assets across different compartments of the immunology system or the immune system, I should say. And Peter, maybe you want to talk about how you see the strategy of covering different immune targets as we develop our pipeline.

Yes. I think what we like is first-in-class biology on key elements of the immune system. So with FcRn, we're tackling the autoantibodies. With empasiprubart, we're hitting the complement system heart. With 121, it's the IgA element. I think FB102 gives us the opportunity to tackle T cell, pathogenic T cell biology, pathogenic NK cell biology with this molecule. So it really fits that immune portfolio approach, which we are taking and which we continue to build.

Our next question will come from Thomas Smith with Leerink Partners.

This is Brian on for Tom. Just wondering if the team can comment or elaborate on their confidence in the potential regulatory path in celiac given there are currently no FDA-approved treatments.

Yes. And certainly, when I was talking earlier about the fact that we like to focus on novel biology in areas of high unmet need, navigating these types of regulatory situations is not new to us, and I think something that we've demonstrated we can navigate in the past. Maybe, Arjen, you want to talk to some of the due diligence and what we learned around the path forward to celiac.

Yes. Like I said, that really starts with the Phase Ib data and the conviction that we have. From there, you can start to think about different patient populations and a way forward. I think at this stage, for celiac, the next step will really be for the Phase II data card to turn. And from there, we will set the right Phase III plan forward.

Our next question will come from Danielle Brill with Truist.

On the deal. Maybe as a more specific follow-up to an earlier question. Just wondering what specifically makes FB102 differentiated in your view versus other molecules in the pipeline? Are there meaningful differences in the magnitude of CD122 blockade or any other mechanistic attributes that support a best-in-class profile?

Yes. Certainly, I'll hand over to Peter to comment on this. But one thing that we do see is differentiated that is important is that it's on track to be first-in-class. And we know how important that is when launching medicines into areas of high unmet need in competitive spaces. But the potential for best-in-class, Peter?

Yes, there, I think, indeed, based on some in vitro data, but also, of course, as Karen indicated, the clinical data gives us confidence on the potency of the molecule.

Our next question will come from Sophia Graeff with JPMorgan.

One on route of administration. So we've seen argenx be very successful in innovating on route of administration with VYVGART. How important was the possibility of similar innovation for FB102 in terms of the decision to acquire the asset? And how important do you see this innovation given the development of oral JAKs in vitiligo?

Yes. Certainly, when we were looking at this asset and also at what argenx could bring to this asset, the question of product presentation comes to the forefront. So I think what we saw in FB102 was an asset that's complementary to our immunology portfolio, but also an asset where I mentioned earlier, we can put our fingerprints on the development and leverage the experience that we've had with VYVGART in really maximizing the value of the asset.

And as you say, one of those places is through product presentation. So I think with VYVGART, we've seen the playbook of launching with IV, very quickly being able to bring a subcutaneous, a prefilled syringe. Next year, we're launching auto-injector. And you can imagine that we have the opportunity to take that same playbook and apply it to FB102, which will be important, especially in these autoimmune conditions in larger patient populations.

Our next question will come from Victor Floch with BNP Paribas.

Maybe just a quick follow-up on the addressable population for celiac disease. So should we assume that it will be limited to the patient nonresponsive to gluten-free diet? Or are you anticipating that at some point, you should be able to bring that product to maybe earlier lines treatment patients?

Yes. It's too early to comment specifically on the clinical development program. But certainly, what you can look at is the approach that we've taken in -- with other indications in the past as a model. And so what I would think about, for example, in MG, where we started with a clearly defined patient population in the ACHR positive, we were able to, over time, generate the evidence and expand that population.

Now we'll have to make this -- make the strategy specific to each of the indications that we look at for FB102 -- but with the different patient populations within celiac, you can imagine that there could be different ways that we could break down the patient population and align the clinical development program beyond that. But we'll do that work over the next couple of months, and we'll share when it's ready.

Our next question will come from Luca Issi with RBC.

This is Cathy for Luca. Congrats on closing such an amazing deal. This is a follow-up on indication selection. Anti-CD122 mechanism has shown clinical proof of concept in celiac diseases in vitiligo as we've seen. But how broadly do you think this data read through to the other disclosed indications like alopecia areata and type 1 diabetes and your conviction in the rationale for going after these 2 indications. Any thoughts there, much appreciated.

Yes, certainly. Maybe I can hand over to Peter to comment on that.

Yes. And alopecia, I think there is IL-15 data out there showing that [ angle ] is definitely involved in the disease. For type 1 diabetes, there's preclinical data sets out there. Obviously, I think that's the work we are going to start now with the Ib alopecia data, how good are they? And what is then the next step is one element for type 1 diabetes. As for other potential autoimmune indications, we are going to follow the same playbook as we always do, look into biology as number one, then okay, what is the path towards approval there? How does it look like? And is there indeed an unmet need?

Your next question will come from Andy Chen with Wolfe.

This is Jason on for Andy. I just want to ask if you guys have done any evaluations of FB102 against other CD122 programs, maybe like Tregs, for example? And what do you think differentiates on safety, efficacy and maybe Tregs preservation? And do you have any confidence that FB102 will hold against their Cohort 2 and 3 for the Phase Ib data in terms of assessing healing capability for CD122 targets?

Yes. Thanks for the question. So when we look at assets and when we assess them, including FB102, we're looking across a few different parameters. One of them is, do we think that there's a path to a best-in-class asset. And that best-in-class asset can be defined by what do we see as the mechanism of action and the design of the molecule. I think you heard from Peter earlier, we see this as an elegant design and a very elegant mechanism of action. And the design of the molecule is certainly important to us as we selected it.

But then, of course, you need to prove that out with clinical data. And so we see the strongest clinical derisking data for FB102. So of course, we have the vitiligo data as well as the celiac data. And when you look into that, when you look at the efficacy that we've seen, when you look at the safety that Peter spoke to early, we think that we have the potential for a best-in-class asset here. Of course, what contributes to developing a best-in-class asset is, in fact, how you develop that asset. What are the indications you select?

In what order, how do you -- in what sequence, how do you develop things like the product presentations that you'll bring to market. And I think that's where we have the opportunity to really accelerate this asset and put the argenx fingerprints on it to bring our best-in-class asset to market. The last thing that I'll say that was compelling to us and that I think is important, and I've mentioned a few times, is that this is a first-in-class asset. So we'll be acting with urgency because we see that patients are waiting, and we want to bring FB102 to those patients as quickly as possible.

For our next question, we'll return to the line of Suzanne van Voorthuizen from Kempen.

Can you hear me now?

We can hear you now.

Okay. Perfect. Sorry about that. Congrats on the deal. I may be last, but hopefully not least, can you elaborate a bit more on the differentiation of FB102 that you see versus other molecules that are pursuing the same or similar mechanism of action? You mentioned an elegant design. What is it exactly about the molecule that you find holding potential for best-in-class potential?

Yes. Thank you. As I mentioned earlier, there are a number of different reasons that we think this could be a best-in-class asset. But Peter, maybe you want to speak about the elegant design in particular.

I think it is hitting hard on the IL-2 and IL-15 signaling while sparing the Tregs. I think that's an important element in the design of that asset. Ultimately, from a design perspective, it will pan out as compared to other CD122 molecules in development that I think we should wait for clinical data for clinical data to make that comparison.

Our next question will come from Jun Deng with UBS.

So maybe sort of a broader question for the rest of the argenx portfolio. So given this one, it's going to the broad autoimmune diseases where the payer dynamics is quite different from rare disease and rebate war, et cetera. So just wondering, could you highlight any other assets you also plan to go for broad autoimmune diseases, maybe 1 to 4? Yes. Thank you very much.

Yes. Thanks for the question, and it's great to have the opportunity to talk about our pipeline more broadly because it is an exciting pipeline and a broad pipeline. So what I would start with first is within FcRn. So when you look at VYVGART, I mentioned earlier that assets -- that the indications such as Sjogren's and Graves for VYVGART start to make steps into larger patient populations. When we think about our FcRn strategy more broadly, where we have ARGX-213 and ARGX-124 as next-gen FcRn molecules, we also have the opportunity to explore broader and larger patient populations with those assets within the FcRn space.

In addition to that, when you look beyond FcRn into the rest of the pipeline, you can look at ARGX-121 is a molecule that we're moving into Phase II. It's an IgA APRIL-body, first molecule IgAN, but that's also a pipeline in a product with potential for larger indications. And then as you mentioned, we haven't been public on our indications or our target for 124, and we're also moving other INDs forward into the clinic very rapidly this year. And I think what you'll see is a consistent theme that we're expanding the population that we can have impact on and where we can transform outcomes with novel biology. Thanks for the question.

Our final question will come from Henrietta Boeg with Deutsche Bank.

A question for Peter, please. So in celiac disease, we saw Amgen's IL-15 antibody didn't prevent mucosal injury. So it would be good to know what makes you confident on the Phase I data and the proof of concept given that you said IL-15 is a key target? And does that mean IL-2 is more of an important disease driver?

I think there, both pathways are involved in celiac disease. I think with the endpoint, with the composite endpoint, it touches upon gut morphology, but also lymphocyte infiltration and there we saw movement on both of these elements. I think from that aspect, the Ib is quite convincing. Thank you.

This concludes our conference today. Thank you for participating. You may now disconnect.

Good morning. My name is Leila, and I will be your conference operator today. I would like to welcome everyone to the call. I'd like to introduce Beth DelGiacco, Vice President of Corporate Affairs. You may now begin your call.

Thank you. A press release was issued earlier today with our second quarter 2026 financial results and business update. This can be found on our website along with the presentation for today's webcast. Before we begin, on Slide 2, I'd like to remind you that forward-looking statements may be presented during this call. These may include statements about our future expectations, clinical developments, regulatory time lines, the potential success of our product candidates, financial projections and upcoming milestones.

Actual results may differ materially from those indicated by these statements. Argenx is not under any obligation to update statements regarding the future or to conform those statements in relation to actual results unless required by law. I'm joined on the call today by Karen Massey, Chief Executive Officer; Karl Gubitz, Chief Financial Officer; and Sandrine Piret-Gerard, Chief Commercialization Officer. Luc Truyen, Chief Medical Officer, will be available during the Q&A. I'll now turn the call over to Karen.

Thank you, Beth, and welcome, everyone. I'll begin on Slide 3. The team delivered one of our strongest quarters yet, marking our 18th consecutive quarter of growth. This momentum reflects the value VYVGART continues to deliver for patients, the continued expansion of both MG and CIDP markets and our ability to unlock new opportunities for growth, most recently with the seronegative MG approval. The progress we're seeing across the business brings us closer to realizing Vision 2030, our road map for delivering near, medium and long-term growth.

Looking ahead, we have 2 registrational readouts before year-end, which support our goal of achieving 10 labeled indications. Together with our differentiated immunology pipeline, these programs position us to extend our growth well beyond 2030. Our success today creates the opportunity to reinvest in the best science we can find wherever we can find it, fueling the next phase of Argenx growth.

Slide 4, VYVGART continues to change what is possible for patients with MG and CIDP, and we see strong growth across both indications and all regions. We're reaching more patients than ever before, driven by our commitment to bring meaningful innovation to the treatment experience. Last year, we introduced our prefilled syringe, expanding our prescriber base and supporting our goal to reach patients earlier in their treatment journey. This year, we reached another important milestone with the approval of VYVGART for seronegative gMG.

VYVGART is now the first and only treatment approved across all serotypes of gMG, including for triple seronegative patients who previously had no approved treatment option. This is transformational for patients and physicians, removing the need for testing. With ocular MG ahead, we are moving forward in our ambition to make VYVGART the treatment of choice across all MG patients.

Slide 5, we have 2 important readouts ahead that represent the next chapter of our growth strategy, broadening our leadership in neurology with empasiprubart and extending the impact of FcRn into new therapeutic areas, starting with rheumatology. VYVGART has the potential to have a similar impact in rheumatology as it has had in neurology. Autoimmune myositis is our entry point. It represents both a near-term label expansion opportunity and the foundation for long-term leadership. What continues to motivate us is the urgent patient need.

In IMNM, patients can progress from their first symptoms to needing a wheelchair within a matter of months. We heard this at R&D Day, and there are no approved treatments today. This sense of urgency to deliver for patients is what is driving our filing strategy based on the benefit risk of each subtype on its own. We saw a clear signal in both IMNM and DM in the Phase II, and we're on track for a readout this quarter. Myositis is just the beginning.

We believe a first-in-class launch in myositis can establish the foundation for broader leadership in rheumatology with data expected in the second half of 2027. Slide 6. Empasiprubart remains on track to become our second pipeline of products with our first registrational readout in MMN expected later this year. MMN represents one of the clearest unmet needs in neurology. Empasiprubart has the potential to offer a differentiated approach, supported by the efficacy, durability and safety profile observed in the Phase II ARDA study.

We continue to see growing enthusiasm from the neurology community, particularly around the safety profile and the sustained improvement in grip strength observed in the open-label extension. These are outcomes that matter in patients' daily lives. Our ambition extends well beyond MMN. The unique biology of C2 inhibition has the potential to benefit a broader range of patients from our ongoing Phase III program in CIDP to our combination study in MG.

We are focused on unlocking the full potential of this mechanism for patients. Slide 7, it's an incredibly exciting time to be building a company around scientific innovation. Pace of discovery is accelerating, and our job is to find the most promising science that can change outcomes for patients. Our goal is to advance 5 late-stage molecules by 2030 to fuel long-term growth, and we are pursuing this through 2 pathways. We're extending our leadership in FcRn and we're broadening our immunology pipeline. We are already delivering against strategy.

Our future FcRn molecules, ARGX-213 and ARGX-124 as well as our IgA sweeper ARGX-121 are progressing towards late-stage development. And ARGX-118, ARGX-125 and TSP-101 now in Phase I, each represent new pipeline and product opportunities. Together, these investments reflect a disciplined capital allocation strategy, focusing on delivering durable growth over the long term. And with that, I'll turn the call over to Karl.

Thank you, Karen. Slide 8, I am pleased to present the second quarter 2026 financial results in this morning's press release. We continue to increase the number of patients that we treat, resulting in growing revenues. Product net sales for the second quarter were $1.5 billion, representing 60% year-over-year growth and 17% quarter-over-quarter growth. By region, product net sales were $1.3 billion in the U.S., $102 million in Japan, $136 million across the rest of the world and $5 million related to product supply to Zai Lab in China.

Our U.S. market grew by 15% quarter-over-quarter with a gross to net and net pricing similar to prior quarters. In Japan, quarter-over-quarter net product sales growth is 55% or $35 million. Reported sales include a one-off benefit of approximately $25 million due to a change in our distribution model. Next slide, Slide 9. Total operating expenses in the second quarter were $1 billion, representing an increase of $129 million compared to the first quarter.

We have stepped up our combined R&D and SG&A investment to $903 million in the quarter. This increase is deliberate and reflects disciplined investment in multiple mid- and late-stage clinical development programs and commercialization capabilities to support our growing multiproduct portfolio. Operating profit in the second quarter is $494 million, an increase of 146% year-over-year. Tax over quarter is 11% of profit before tax.

We ended the quarter with a cash balance of $5.2 billion, including cash, cash equivalents and current financial assets, an increase of more than $744 million from the beginning of the year. Our capital allocation priority continues to be building durable long-term revenue growth. At the same time, we are well on track to deliver a financial profile that includes increasing operating margins, sustained earnings growth and a significant cash generation. I now turn the call over to Sandrine, who will provide details on the commercial front.

Thank you, Karl. I'll begin on Slide 10. What continues to set Argenx apart is our ability to translate the patient-first approach into execution across the entire treatment journey. From educating health care providers to supporting patients to ongoing care, we are focused on removing friction at every step. And this is an approach that continues to deliver results. More HCPs are choosing to prescribe VYVGART as the preferred biologics for MG and CIDP. More patients are requesting VYVGART and as a result, getting on treatment earlier.

Patients are remaining on treatment because VYVGART continues to make a meaningful difference in how they feel and function in their daily lives. Today, we have patients who started in the very first quarter of launch and remain on therapy 18 quarters later. These strong fundamentals are reflected in our performance this quarter, and they continue to position us well for future growth. Slide 11, this quarter, we continue to see growth driven by both MG and CIDP across all regions with new patient demand remaining at a consistently high level.

The prefilled syringe continues to be an important driver of this demand across both MG and CIDP. Its convenience and flexibility are supporting broader adoption of VYVGART. In the second quarter, approximately 80% of prefilled syringe patients in the U.S. have been new to VYVGART. We also see increasing breadth and depth of prescriptions for VYVGART. Physician confidence in VYVGART is reflected in a repeat prescriber base of more than 5,000 neurologists and increasing use earlier in the treatment journey.

While early into launch, we also saw a contribution to growth from our seronegative expansion in gMG. VYVGART is now the first and only biologic approved across all serotypes of generalized MG, significantly expanding our addressable market in MG by 11,000 patients. Slide 12, our recent approval across all serotypes of gMG, MuSK positive, triple seronegative and LRP4 positive strengthens VYVGART's leadership in MG and advances our goal of reaching the broadest patient population.

We are pleased with the early response to the label expansion with extremely positive patient and HCP feedback. We have established relationship with more than 80% of seronegative MG treaters and see the recent VYVGART label expansion having a halo effect on all gMG prescriptions, also driving increased uptake by prescribers in the seropositive population. On the payer side, we leverage the credibility and relationship we have built to secure policies covering approximately 55% of U.S. commercial lives, all within 10 weeks since launch.

Most plans are removing the serology testing requirement, making it simpler for physicians to prescribe VYVGART as the go-to option in MG. There is also tremendous excitement and hope among patients, particularly triple seronegative patients who previously have no approved therapies available. One of these patients, Zack shared, I cut off my computer and cried. Hope, this is finally real hope from the seronegative community.

As we look ahead in MG, we see significant opportunity to reach patients earlier in the treatment journey and pending approval, expand into ocular MG. These patients continue to face a meaningful burden of disease, underscoring the need for additional treatment options and reinforcing our commitment to serving the full MG community. Slide 13, let's move to the opportunity in CIDP. Within our initial 12,000 patient addressable population in the U.S., we are driving further adoption through physician education and continued evidence generation.

At the same time, we are laying out the groundwork to expand beyond this. Today, approximately 24,000 patients are being treated for CIDP in the U.S. and roughly half are considered well managed on the current therapy. Yet, what we consistently hear is that many have learned to live around their disease, often without realizing how much function they have lost. And this is exactly why generating data that shows meaningful functional improvement matters.

Our [ real-time ] results demonstrate the impact VYVGART can have on outcomes that are important in patients' daily life and meaningful to the physicians treating them. Similarly, we have generated evidence that helps physicians navigate practical treatment decisions, including transitioning appropriate patients from IVIg to VYVGART. We presented recently at PNS the results of a Phase IV switch study showing that 87% of patients on IVIg switched successfully to VYVGART, helping address the question, how do I switch from IVIg to VYVGART.

Finally, we continue to explore the opportunity to reach patients earlier in their disease journey. We see significant potential among the large population of untreated patients where our data suggests that treatment-naive patients may derive meaningful benefits from earlier treatment. Slide 14, looking ahead, we are preparing the organization for the next wave of growth.

We view autoimmune myositis as a strategic entry point into rheumatology with the potential for VYVGART to establish early leadership as the first FcRn. We are augmenting our best-in-class launch playbook in MG and CIDP to be launch-ready for myositis. We are already engaging with 650 KOLs treating autoimmune myositis, advancing disease state education, engaging patient communities and getting ready to expand our field force footprint. With that, let me turn the call back to Karen for closing remarks.

Thank you, Sandrine. As you've heard today, we continue to see strong momentum across the business with significant opportunities ahead for VYVGART and a pipeline positioned to sustain growth well into the future. And while there is much to be proud of in the first half of the year, there is even more ahead.

We enter the second half of 2026 with multiple opportunities to advance innovation and further our mission of transforming the lives of people living with autoimmune disease. I want to thank our team, patients and strategic partners for their continued commitment as we continue this mission together. And with that, operator, we'll open the call for questions.

[Operator Instructions] Our first question will come from Myles Minter. Your line is now open. Please go ahead.

Congrats on the quarter. Looking forward to the myositis data in the third quarter here as well. I'll keep it to one on the commercial business. You've delivered quarter-over-quarter sort of mid-teens percentage growth if you take out the first quarter seasonality. I just had a question on whether that sort of future growth trajectory might change with the launch in the seronegative population here and whether there's any sort of tailwinds that we should think about from the broader population now that most plans are not requiring the serology testing for that population.

Yes. Thanks for the question, Myles. And I would agree with you, it is incredible 18 quarters in that we're still delivering consistent growth quarter-over-quarter. And what I would say related to the quarterly trends, of course, every quarter has its own dynamics. And after Q1 seasonality, we generally see some rebound in Q2, but we expect the shape of the curve for the remainder of the year to look pretty consistent to what you've seen in prior years.

We're off to a strong start, of course, with seronegative, but we've had the same dynamic in prior years with the launch of the PFS and that type of thing. So I would expect to look -- continue to look to grow and to look similar to prior years. Thanks for the question, Myles.

Our next question will come from Derek Archila with Wells Fargo.

Congrats on the quarter here. Excellent results. I just want to understand, so where do things stand with the ocular MG filing? And I guess maybe going to more tailwinds, but assuming approval, I guess, how do you think ocular could be a growth driver? And does that really materially change VYVGART's revenue trajectory?

Yes. Thanks for the question. We're moving forward with urgency on ocular MG filing. I mean there's a big patient unmet need in ocular MG. Of course, there's no advanced therapies approved in this patient population. So we will be the first and only approved treatment in this population. So we're on track with the filing. We'll update you when we have a PDUFA date. But maybe, Sandrine, you could comment a little bit on how you see the outlook if we do have an ocular approval.

So thank you, Karen, and Derek, for the question. So I see the ocular MG potential approval as another way to continue and to support the growth momentum. Over the last 5 years, we basically have had 5 launches when you think about that. So this would give us another launch to continue that growth momentum.

And we are well positioned because many of these patients are being treated by neurologists, and this is already a population of providers that we visit and that have experience with the drug. So I'm very confident that this will be another -- adding another leg to our growth for the long term.

Our next question will come from Tazeen Ahmad with BofA.

So Karen and maybe Sandrine, I wanted to get your thoughts about the competitive landscape. So you're right, you're 18 quarters in and you have commanding share, but there continue to be new launches and upcoming launches and some of the competitors that are talking about what advantages their products might have include comments such as efficacy may not necessarily be where it needs to be with FcRns in general and that patients might be dropping off therapy due to safety observations.

So can you maybe share with us your feedback from the field about what doctors' satisfaction is vis-a-vis their patient commentary on both efficacy? And can you talk to us about dropouts as a result of any safety concerns?

Yes. Thank you, Tazeen, for the question. Let me just comment broadly on competition, and then I'll hand over to Sandrine. But we've had this question a lot. I would say we launched in MG. And I'd like to say that Argenx put MG on the map, and there's been a lot of competition that has followed us into that -- into the space.

And throughout that, we've maintained our leadership in the market. And you can see, for example, 4 out of 5 physicians continue to say that they choose VYVGART before any other biologic. But Sandrine, maybe you want to comment on specifically the efficacy advantage and any other dynamics you see in the market.

Yes. So VYVGART, I mean, like you said, Karen, is being seen and is being used to this earlier than the others. The others are used more in refractory populations, and it's being used in earlier lines. And the reason is that the label supports it, and the data support it. And when you look at the data I wonder if anybody else can demonstrate an MSE that we have. We have 60% of patients that have reached minimal symptom expression.

And then that MSE is sustained over time. So I haven't seen until now other competitors being able to demonstrate MSE or even speak about MSE. And so that's really what stands out when you think about the efficacy of VYVGART. And then if you combine that with its safety over more than 25,000 patient years, I mean, this is a very strong combination of safety and efficacy profile that puts us in a position to be used earlier lines. And that's why until now, we haven't really seen a meaningful impact on our growth trajectory.

Our next question will come from Alex Thompson with Stifel.

Maybe for Karen, could you walk us through sort of what we should expect to see now at the top line for myositis in terms of both primary endpoint clinical data as well as the potential path to filing, particularly in DM?

Yes. Thanks, Alex. We're really looking forward to the readout in Q3, and we're on track. Just to set the stage, what we see as success for myositis is positive readout on the primary endpoint in one or more subset, and that's the data that we'll share. So you'll remember from our myositis Day that we shared that we see both of these indications on their own as potential blockbuster indications.

They both have significant unmet need, and they're both actually strategically important to us. If we proceed with an approval, this will be important because it will be the first-in-class FcRn approval in rheumatology. So we'll be looking for positive data on the primary endpoint in one or more subset. But maybe, Beth, do you want to share a little bit more about what they can expect to see top line results?

Yes. I mean we're still working out the specific details of what the communication will look like. But what we know is that this is an important event with positive data for Argenx. It's our entry into rheumatology, and we'll want to capture that in our communication, and we'll also want to capture the primary endpoint analysis in IMNM and in DM. So the details are still to come, but you can assume that those are the key topics of the communication.

Our next question will come from Akash Tewari with Jefferies.

Can you give a little more color on your stat plan for myositis? Based on your public comments, it seems like there is no alpha split. Basically DM and IMNM are now being run independently as 2 separate trials. Is that the correct read here? And then if the effect size in DM for your Phase II trials was replicated in Phase III, would the trial hit stat or not? And if not, what are some reasons that efficacy could improve from Phase II to Phase III?

Yes. Thanks for the questions, Akash. We have Luc here, so I'll ask him to comment.

Yes. And thanks, Akash. So you are correct. So the way we now approach the analysis of the Phase III is that we will independently analyze the subsets. So each has their own chance to win. As you also know from the research there, of course, the enrollment differs between subsets. So that will affect the intrinsic power.

Nevertheless, the analysis plans are completely in parallel. With respect to your question on effect size, if we see effect size in Phase III in the end, that's what we have observed in Phase II, you could make the assumption that because it's twice as long and twice as big that, that would increase the chance for a statistics difference, which is certainly true, but not a guarantee. We just have to turn the data cards, what we have and then determine our path forward. But whether stat sig or stat negative, we are working on a plan forward in the end.

Our next question will come from Rajan Sharma with Goldman Sachs.

I've actually got one on empasiprubart. Could you just provide a little more color on the DGF update, please? So it seems like you're progressing development, but not in DGF itself. So can you maybe help us understand what the forward path is here in terms of indications and when you may be in a position to move to a pivotal trial and what it was that you saw in the 52-week data that gives you confidence to move forward? And I'm just wondering if there's any additional reassurance into MMN based on what you've seen in the DGF trial. Thank you.

Yes. Happy to have Luc comment on this. Just a reminder, this is a Phase II proof-of-concept study. And what we wanted to do was use it to explore and learn about the use of empa in the transplant setting broadly with a focus on DGF in the particular study. But Luc, maybe you can talk about what we saw on the path forward.

Yes. Thanks, Karen. Thanks for the question. So as already said, this was a relatively small trial. Basically, evaluating hypothesis whether we could influence reperfusion injury with this mechanism. And the transplant situation lends itself to this. And we have chosen as a target DGF, which is a relatively short-term goal.

So when we saw the data at 24 weeks, we found an intriguing signal which made us decide let's continue the exploration of the study up to 52 weeks, which more or less confirmed that there is something in the renal parameters here that is affected, which gives us an interesting perspective on exploring the transplant. However, it does not support DGF, which as I said, is a short-term readout to be continued as an indication.

And maybe just to comment on the second part of your question around MMN read-through. I don't think I would take any read-through for MMN other than we did see some effect of the drug, but in particular for MMN with the readout in Q4. I think the most important data point to look at there was our positive Phase II study, where on the endpoint of grip strength in the -- both in the initial Phase Part A as well as the open-label extension, we saw positive results. Thanks for the question.

Our next question will come from Yatin Suneja with Guggenheim.

Excellent results. So congrats again. So a quick one on the pipeline, specifically on ARGX-121, the IgAN program. Could you maybe talk about a little bit about the profile that you have seen in Phase I that is enabling you to move into Phase II? What level of IgA reduction you saw? How should we think about frequency, all of that?

Yes. Thanks for the question about ARGX-121. We're really excited about 121 and broadening our pipeline with the IgA sweeper. And we had shared data specifically from Phase I from -- and with the profile that showed that ARGX-121 reduces IgA by about 90% within a matter of days, and that reduction is maintained all the way out till day 28 with one single dose. So very impressive data, and we're moving very quickly with urgency into IgAN. And perhaps, Luc, you could share your thoughts on the IgAN program, clinical development program?

Well, with such a signal in Phase I, we are all very excited to keep this really moving fast. When we showed those data with key opinion leaders, they were also very enthusiastic and this speed and depth really puts it aside from -- as we all know, IgAN has quite some efforts going on. But our signature of the drug here really set us apart and is really offering us great hopes for the Phase II and the Phase III that we can bring a meaningful drug to patients.

Our next question will come from Yaron Werber with Cowen.

Congrats on a really nice quarter. Just a question for you on MMN, and thanks for putting that slide into the deck that shows the GRI change from baseline. What we hear from clinicians is that 8 points is clinically meaningful. And I believe the primary noninferiority and then you have superiority. Can you maybe just talk about that Phase III trial design, maybe a little bit of the powering or whatever you can share as to how do you -- what do you expect from baseline?

Yes. Maybe, Luc, I can pass it over to you to talk about the study design.

Yes. And thanks for the question because it allows us to talk to what are we really trying to achieve at Argenx. So with the Phase II data, as you remember, we had like an 81% reduction in the need for rescue with IVIg based for those that received empasiprubart. This to the point where we said if every rescue we need to take forward as on IVIg, we might as well do IVIg head-to-head, which would also provide the most meaningful data for prescribers.

So we designed this trial where after stabilization on IVIg and optimizing that we initiate either a continuation of the IVIg regimen or switch to empasiprubart. The endpoint here is indeed grip strength, which we picked in conversation with actually the agencies because there were quite meaningful data available, which allowed us to define a non-inferiority margin.

And the non-inferiority margin is, I think, pretty relevantly, but we also have the opportunity to go to superiority. And I think based on the Phase II data and what we learned on IVIg that there is, in my opinion, a great chance that we could show that. But the noninferiority at least gives us the ability to at least provide that information.

Yes. Thanks, Luc. And just to wrap it up, what I would say is what we see as success is a positive readout on the primary endpoint, noninferiority and obviously, upside would be superiority. But when we speak to KOLs and prescribers, we certainly hear excitement about the fact that we have a head-to-head versus IVIg. And certainly, with our experience in CIDP, we have some experience competing in that space as well. So I think we're set up for success, assuming a positive readout towards the end of the year with MMN.

Our next question will come from Danielle Brill with Truist.

This is Alex on for Danielle. Congrats on the quarter. Just a question on CIDP as it pertains to the current commercial dynamics as well as the ongoing empa trials. As far as it relates to the commercial read-through of the CIDP launch in the regions where VYVGART is available, who are the types of patients who are enrolling in the empa CIDP trials instead of trialing VYVGART?

Yes. So maybe to start, just to lay out our strategy with CIDP. So we see that CIDP is a heterogeneous disease, and there is significant unmet need. Until VYVGART launched, there hadn't been innovation in the space for 30 years. And we've seen the strong uptake of VYVGART in CIDP. What we know is with the disease heterogeneity that there is also IgMs driving the disease. And so that's why we have the study within empasiprubart where we think we have strong biology rationale.

So our hypothesis is that there are some patients that we have a 70% response rate with VYVGART. So those patients that don't respond to VYVGART might have more IgM-driven disease. And so we think that there's an opportunity for empasiprubart in those patients. There also might be patients where they have sort of multiple drivers of the disease and so an overlap that might be between eligible for both VYVGART and empasiprubart.

So our strategy here is to study empasiprubart. And we're enrolling empasiprubart in a broader patient population so we can understand what the impact of empasiprubart on the disease. And then once we have the data readout, we can analyze that data as well as the VYVGART data and really understand what is driving the best outcome for patients and move forward with the commercial strategy from there. Thanks for the question.

Our next question will come from Thomas Smith with Leerink Partners.

Let me add my congrats on the really strong quarter here. On the pipeline, could you just provide some updated thoughts on how you're thinking about advancement between your next-gen FcRn candidates, 213 and 124? Any additional color on the target profile you're aiming for 124 with respect to IgG lowering or dosing interval or other potential differentiation? And how do you think about indication selection between life cycle management and potential expansion opportunities across those candidates?

Yes. Thanks for the question. Our goal with FcRn is to maintain our leadership and even advance our leadership for decades to come. And we have a few pieces or parts to that strategy. Next-generation molecules, 213 and 124 that you referred to, 213 is we call it Phase III ready. And 124, we're in Phase I at the moment. And by the end of the year, we'll be in a position to move it into late-stage clinical development. So at the moment, we're working with our teams based on that data to assess the 2 molecules.

Of course, ARGX-213, we know has a Q4 weekly dosing schedule. ARGX-124, we're further categorizing the advantages that it will bring over VYVGART at the moment. And then we'll be in a position where we can lay out what the strategy is for the full portfolio between VYVGART, 213 and 124. The other component of our strategy that's really exciting is that we are in development of an oral FcRn, and that program also moves forward quickly at the moment. Thanks for the question.

Our next question will come from Sean Laaman with Morgan Stanley.

Karen, just going back to the seronegative gMG impact. What specific early prescribing trends have most exceeded your expectations? And how should investors think about the revenue contribution from seronegative patients over the next 12 to 24 months?

Yes. Thanks for the question. And I'll hand over to Sandrine in a moment, but I'd be remiss if I didn't just say, first of all, that I'm really proud to see seronegative launch. It really is the Argenx playbook in action. We made a commitment to this patient population many years ago when we launched VYVGART that we would bring this innovation to seronegative patients and to see that happening in the market and be so positively responded to is really exciting. But Sandrine, maybe you could comment a little bit more on the dynamics you're seeing with the launch.

Thank you, Karen, and thank you for asking a question on seronegative because for me, this is a big event in the second quarter. So it's great to have someone asking that question. So I spent time in the field over the last few weeks to listen directly and hear the feedback from prescribers, but also from patients. And although we are only 10 weeks in, so it's still very early, the feedback is overwhelmingly positive. I mean you saw the quote I had in the presentation from the patients.

Many were actually waiting for more solutions because they have been excluded from clinical trials, especially the triple seronegative patients, and they were really waiting for an option. And so a lot of hope, a lot of enthusiasm on the patient side. Some of them are calling the physician to make sure that they have access to the product as soon as possible.

On the provider side, what is interesting is that the -- when you look at what the providers are saying is that they consider now that the fact that we add seronegative to the label is that we now have a fully loaded gMG label and that adds simplicity in decision-making, streamlining decision-making. They quote, I consider VYVGART as the go-to option for all night gMG. And so one of the things we have observed over the first few weeks is that it has really a strong halo effect beyond the seronegative patients onto the positive serotype patient.

And that was something that we were expecting, but it's great to see it confirmed. What we are also very, very happy about is that the payers have been approving quite quickly and endorsing the policy VYVGART in seronegative, where we have roughly 55% of the covered lives yet already, less than 3 months after launch. And I have said that it would take 3 to 6 months to get to roughly 90%, and we are well on track to get there.

And so what is also very important is not just the quantity of coverage, but also the quality and seeing that the majority of the plants are removing the testing requirements for the serotype, it's also making the life of the providers easy. So if I would summarize, it's all about leadership in MG with that approval, but also simplicity of decision-making for the providers. So great feedback.

Our next question will come from Samantha Semenkow with Citi.

Just one on CIDP for me. You outlined in your slides market expansion opportunity. I'm wondering what you're seeing in the data about treatment-naive patients utilizing VYVGART as the first line. Are you seeing a shift towards these patients being treated more frequently? And if so, how should we think about the progression of the launch in that segment going forward?

Yes. Thanks for the CIDP question. Sandrine, maybe you can comment.

Yes. So it's indeed a very big opportunity for us to really make sure that VYVGART is used as early as possible because still the majority of the patients start with IVIg when they start the treatment for CIDP. So we published data, and we are generating more and more evidence to show that if you're prescribing VYVGART for treatment-naive patients, actually, you see clinical benefits. And we presented a study at AAN where we showed that 87.5% of the patients that were treatment naive benefited from a clinical response.

And we are using data to encourage physicians to prescribe VYVGART in earlier line patients, and they are seeing good results. Now it's taking time. It's taking time because we have to change entrenched habits. And you have also to make sure that payers are supporting that because still the majority of them are requiring some kind of experience with IVIg. So that's what we are working on, but you see more and more traction in the treatment-naive population as well as in the patients that are in as well managed, but need some more functional improvement.

Our next question will come from Gavin Clark-Gartner with Evercore ISI.

Just following the recent riliprubart update, are you considering any changes to your CIDP development plans for EPA? And I guess on this point, did this outcome change what you think the likelihood of EPA meeting superiority versus IVIg is in either CIDP or MMN?

Yes. Thanks for the question, Gavin. As a reminder, before I hand it over to Luc, our clinical development program for CIDP for empasiprubart has 2 studies. One is the head-to-head versus IVIg and the other is a placebo-controlled study. And so I think it's around the placebo-controlled study that you're particularly asking for, but also maybe some comments, Luc, on your confidence in the IVIg study as well.

Yes. And what is important to realize CIDP, and we used the term already is a heterogeneous disease also. And therefore, your selection of patients matters. We took particularly in that study to install, for example, that clinical adjudication committee, which now has become the standard. But we continue to exclude possible CIDP patients, for example, is one of the differences.

And then if you then on top of that, go with very refractory patients, you may come in a situation where the disease has burned out more or less. And then what's your ability to change. We, of course, want to learn, and we will be looking more closely at the data and evaluate is there anything we need to do to optimize our studies, but we are continuing with our plans to continue both.

And maybe just one more comment on that, that has made me reflect on is that it's very clear from this that it's not easy to run successful clinical trials in CIDP. And one advantage that we have is that we do have the VYVGART experience, and we've been able to demonstrate that ability. So that gives me additional confidence as well.

Our next question will come from Sophia Graeff with JPMorgan.

One on the upcoming myositis trial. You commented that you currently no longer see a path forward for polymyositis patients. But given the strong evidence that ASyS is autoantibody driven, would there be scope to run an ASyS-specific trial in future? Or is this population still a bit too small to target?

Yes. Thank you for that question. We, of course, want to reach as many patients as we can. But just from a technical point of view in this trial with the enrollment numbers, we just can't get there, but we will learn. And so ASyS is not just confined to PM and polymyositis itself is heterogeneous and has been a bit kind of being more and more allocated to the other subsets as we get to know more. So we will definitely look at the data as they come and determine the plan forward for ASyS.

Our next question will come from Victor Floch with BNPP.

So maybe just one on the PFS. I noticed in your slide that the proportion of PFS patients new to VYVGART actually increased to 80% from 68% in Q1, which is quite impressive. So I was just wondering whether it makes you incrementally more bullish about the auto-injector opportunity and whether there's any chance you can share more details on the remaining development milestone for the auto-injector and the expected launch timing?

Yes. So thanks for the question on PFS. I'll hand over to Sandrine in a moment. But just to confirm, auto-injector is on target or on schedule for 2027 launch. But maybe some of the dynamics you're seeing with prefilled syringe in the market, Sandrine.

Yes. So thank you for your question, Victor. So indeed, I wrote on the slide, 80% of the patients that are on PFS in the second quarter in the U.S. are new to VYVGART. So it's true expansion for us. And you compare it to last time where we said 68%. Last time, 68% was launch to date. So these were the patients since the launch. This time, we should actually adjust for Q2.

If you look at launch to date to compare apples with apples, we would be at 70%. So it's a slight increase, but it's not 80%. 80% is really the last quarter. And it shows that actually more and more of the patients that start on VYVGART actually are truly -- on PFS, sorry, are new to VYVGART. So thank you for the question.

Our next question will come from Andy Chen with Wolfe.

This is Jason taking it for Andy. I just wanted to ask a question in terms of seronegative approval and what its effect on this quarter's earnings. And also, I wanted to ask in terms of the launch curve of seronegative and ocular, would it be similar? Or what might there be in terms of like total differences? And anything to think about when we're looking at the uptake of ocular?

Yes. Thanks for the question. Karl, maybe you can comment on the dynamics of the quarter.

Thank you, Karen, and thank you, Jason, for the question. Yes, as Sandrine already mentioned in the prepared remarks, the quarter was driven by strong fundamentals and PFS was the key driver of growth. However, seronegative, of course, is also a contributor, in particular, the seronegative -- the triple-negative patients where we see the huge unmet need and also the halo effect the seronegative had on the broader gMG market.

So I think what -- and of course, we expect that to also flow into Q3. In terms of ocular, I think as we always said, you need continued innovation to maintain the growth and regular new launches, of course, is what we need. And I think we are very excited that we're going to continue to deliver that for patients. Thank you for the question.

Your next question will come from Luca Issi with RBC Capital Markets.

Congrats on another great quarter. Maybe, Luc, I just want to circle back on the prior question from myositis, you mentioned that IMNM and DM are independent analysis, each of them has change to the stats. But did the FDA still ask you to split the alpha between the 2 trials, given that this was originally structured as an all-comer trial that enrolled both populations together? Or are each trial at this point completely independent from one another and there's absolutely no cross stock between the 2 trials?

I guess the other way to ask the question, are these trials successful if the p-value is below 0.05? Or do you need to hit p-value below 0.025 because again, you're split the alpha between the 2 trials. Any color there much appreciated.

Yes. So I want to stay consistent with how we answered that at the R&D Day, which is we're not going to comment on a specific alpha value because even in these rare diseases, even with alpha that are in between 0.05 and 0.1 even, you can have a conversation. It's not that we go in there, but I'm just saying we're not going to disclose the actual alpha value. And yes, the data card is to be turned soon.

Yes. And maybe just to give you some additional insight and color on the strategy and the filing strategy. So as Luc shared earlier, the analysis plan is independent of each other. So IMNM and then DM separately. So they are 2 separate analysis plans. And our filing strategy and path forward is in IMNM, recall that there are no approved treatments in IMNM. And so we have breakthrough designation with the FDA and have had significant -- and have had those communications based on that with the FDA.

In DM, what we'll be looking for, of course, is statistical significance. And once we have that data, we'll be able to continue discussions with the FDA on what the path forward is there. But what I want to come back to is that with this myositis study, what we've given ourselves the opportunity to do is have 2 opportunities for label expansion, both or each of them individually as blockbuster in potential blockbuster indications, IMNM and DM. So we're on track for Q3. We'll turn the data card, and we'll determine the path forward from there.

Our next question will come from Sebastiaan van der Schoot with Kempen.

Congrats on the excellent quarter. Can you maybe share your latest thinking on your ambitions regarding business development and M&A? What should -- or should we not expect in this aspect for the next 12 to 24 months? And can you maybe describe the profile of assets that you will be looking forward to add to your pipeline?

Yes. Thanks for the question. So our overall capital allocation strategy is very much focused on delivering growth, growth in the short, mid and long term. And in line with that, our capital allocation strategy focuses on, number one, fueling VYVGART growth; Number two, funding and accelerating our internal pipeline that includes our FcRn assets that I was talking about earlier, but also beyond FcRn.

And then, of course, with the strength of our balance sheet, we also have the opportunity to look at business development. Now looking at business development opportunities in order to identify potential new assets is not a new strategy for us.

And always, the approach that Argenx has taken has been to partner to look for novel biology, new mechanisms of action where there's significant unmet patient need. And in the past, we partnered with academic institutions in order to identify that biology and build those molecules.

With the strength of our balance sheet and our continued profitability, we can now widen the lens and also look at biotech companies that are pursuing, but we use the same bar for those business development opportunities as we do for our internal pipeline. And that bar is that it has to be novel biology, and it has to be in areas where there is significant unmet patient need.

So we're -- we hold the bar high. But I can tell you when we find those opportunities where we can have an impact for patients, we will leverage the flexibility of the balance sheet to be able to go after them and continue to build our pipeline. Thanks for the question.

Our next question will come from Douglas Tsao with H.C. Wainwright.

Just I'm curious in terms of the CIDP opportunity and the slide where you indicate the number of patients who are diagnosed but not treated. And I'm just curious if your sense is that those patients aren't being treated just given the sort of tolerability issues related to IVIg. And is VYVGART sort of tolerability become an attractive sort of attribute that you are going to sort of try to sell to clinicians in terms of bringing those patients back into treatment.

Yes. Thanks for the question, Douglas. And I think what you can see from that slide that I find exciting is that it's clear we're just at the beginning of the growth curve for CIDP, and there's a lot of opportunity for continued growth. But maybe, Sandrine, you can share what you're seeing in the market around those patients.

Yes. Thank you, Karen. So indeed CIDP, lots of opportunities for further growth within the addressable market we started with at launch, but also way beyond that. And so what I noticed when I discussed CIDP with patients, but most importantly, with providers is that it's a disease which is not well understood and where there is not really a true dialogue between the patients and the providers where actually the unmet need is underestimated.

And even when a patient is being treated and is thought as being well managed, actually is not the case because there is not this dialogue. And I often use example like you would ask somebody, are you doing your thing, can you brush your hair in the morning? And the person say, yes, I can. And then when you ask all them do that, they say, I'm lying on my best to brush my hair, which shows that there is really a muscle weakness there and that we must show the provider that you can make a difference by putting them on treatment like VYVGART.

And this is the same happening for patients who are not on treatment and that have been diagnosed because they cannot underestimate the level of functional -- how they function every day. They have accommodated their life. They have moved from a house to an apartment. They don't drive anymore.

They have just lowered the bar of what their life should look like, what the quality of life should look like. And what we are trying to do is generate data to show that you can get your life back if you really take that seriously. This takes time. This takes a lot of data generation, and it takes also patients to go and have the discussion with the providers. So that's what we are trying to do.

Our next question will come from Qize Ding with Redburn.

Can I just ask a quick follow-up question on the BD. Are you interested in the assets within the same therapy areas that could further strengthen your existing portfolio? Or are you looking for complementary assets that could broaden your portfolio?

Yes. Thanks for the question. So when we build our pipeline, whether it's with internal assets or through business development, we're focused on immunology assets, but we are focused on diversifying our pipeline beyond FcRn. And so you can see that within our internal pipeline. Of course, we have empasiprubart. We have ARGX-121. We also have molecules in earlier-stage development that are very exciting.

When we look at internal and external molecules, we set the bar as what we're looking for is novel biology, and we need to have clarity on how we can derisk that novel biology to move into patients. And we keep the bar high on that as well as these areas of high unmet patient need where we could be bringing the first-in-class or the best-in-class assets forward for patients. And so that's the strategy that we have for both our internal pipeline as well as business development.

Our next question will come from Xian Deng with UBS.

One on DM, please. So just wondering, there are some studies or evidence kind of suggesting DM is more sort of interferon-driven disease and the role of autoantibodies is not as clear as IM. So just wondering for your DM study, but I think on the other hand, especially in DM, some autoantibodies have very strong predictive power to prognosis and symptoms, et cetera, et cetera. So just wondering, do you see some several subtypes of DM that potentially have a better response? And are you enriching those for the study?

Yes. Thanks for the question. Maybe I can just start by sharing at a high level what we shared at R&D Day, which is we see a clear biology rationale for both IMNM and DM. They are both autoantibody-driven diseases. So maybe you can provide a little more.

Yes. Again, the theme of these diseases are not driven by just one mechanism, which is why we thought that multiple modes of action are moving forward. The molecule clearly is more in the interferon pathway, as you indicate, which we feel is clearly a demonstrated driver mostly in skin pathophysiology, but some in the muscle.

We feel that given the demonstrated level of auto antibodies present in these diseases and their targets that addressing primarily the auto antibodies has a role to play. And in that sense, our Phase II subset data demonstrate that there was a signal in DM, which could not be driven by interferon I. So yes, there's place for more than one approach.

Yes. And that was what I was going to just close out with. I think that's important, Luc. I mean there's been really very limited innovation in the myositis space for many, many years. And so I think if you take -- if you zoom out, there is room for more than one mechanism of action in DM.

And in particular, what I think is going to be important is to look at the muscle involvement and the impact of these mechanisms of action on the muscle because that is the defining feature of this disease, and that's something that we'll be looking for in our Phase III readout. Thanks for the question.

And our final question will come from Niall Alexander with Deutsche Bank.

It's Niall Alexander from Deutsche Bank. So just one on VYVGART pricing and channel mix. It would be helpful seeing if you can provide the actual realized list price per average subcutaneous patient at present. Any color you can give on gross to net pricing and discount? And in addition, it would be great to get a sense of the channel split for VYVGART sales right now.

Thank you. Yes, of course, I mean, the list prices in the U.S. is public information, and we can -- I mean you can also reach out to us if you need help with that. I think what is important is that the gross to net and the net price per patient continue to be stable. It's the same in Q2 as it was in prior quarters.

Over time, you'll see a slight increase in gross to net quarter-over-quarter, and that is because PFS, prefilled syringe for self-injection do have a slightly higher gross to net than the other presentations, but that, of course, is offset by higher adherence. So I think what we can say is that the net prices per patient continues to be stable, and the business is good, and there's nothing really new to say. So thank you for the question.

There are no further questions. This concludes our conference for today. Thank you for participating. You may now disconnect.

Please welcome Beth DelGiacco.

Hi and welcome to our Boston Innovation Hub. It's looking very transformed today. And welcome to our second R&D spotlight event. Today, we're going to focus on autoimmune myositis and the opportunity for Vyvgart to have a meaningful impact on patients' lives. We have a full house today. We have many investors and analysts. We also have our argenx colleagues here. And during that mix and mingle, we encourage you to get to know each other. We also have a lot of people joining on the webcast. So a big welcome to them as well.

Autoimmune myositis. We've actually transitioned from calling this disease or what is really a group of different diseases away from idiopathic inflammatory myopathies, because idiopathic means of unknown origin. And the reality is, today, we know what drives myositis, which is our immune system. And so you're going to hear from us at autoimmune myositis. We're going to be making forward-looking statements, and the details of that are here. This is now -- we've held several of these topical focused events, and it's really core to who we are as a company. We're grounded in science. The patient is our north star. All of this is guiding our future. And what you're going to see today is an agenda that covers the full spectrum of that value chain. We're going to hear from Karen Massey, our Chief Executive Officer. She's really going to connect the autoimmune myositis opportunity to Vision 2030. You're going to hear from Leentje De Ceuninck, the principal scientist on the autoimmune myositis team about the biology rationale of why we selected the subtypes that we selected. You're going to hear from Luc Truyen, our Chief Medical Officer. I've heard the rumors that we're going to have Phase III data today. The update is that we're firmly on track for 3Q, so not today, but we will be able to add context around all the Phase II data we've shown and the path forward. And we have Sandrine Piret-Gerard, our Chief Commercialization Officer, who is going to talk about the evolving view of the commercial opportunity for autoimmune myositis.

We have a great panel of external speakers today, and that's going to be a fireside moderated by Josh Bryson, our Head of U.S. Medical Affairs and evidence generation. They're going to talk about the unmet need, the treatment burden, lack of treatments, and the opportunity for Vyvgart and much more. But what I wanted to flag as I introduce our external speakers is that we have 3 physicians with 3 different specialties. And actually, that is very reflective of myositis autoimmune myositis as a disease. We have Dr. Avery LaChance from Harvard. She's a dermatologist. We have Dr. Arjun Seth from Northwestern. He's a neurologist. And we have Dr. Rohit Aggarwal from the University of Pittsburgh, and he's a rheumatologist. And actually, if any of you who had attended our virtual 2021 R&D Day, when we unveiled myositis as an indication, Dr. Aggarwal was a speaker there as well.

We're going to make it very easy for you today. We know that we're going to share a lot of information. So we like to just start with what you need to know right upfront. First off, autoimmune myositis is a white space opportunity, and it has the attributes that are perfect for an argenx indication, strong biology rationale. We know IgGs are present, and they're also driving disease, and we have data to support that. We also know there's very high unmet need in autoimmune myositis. In IMNM, there are no treatment options approved. In DM, there's been limited innovation. So you're going to hear from Larissa today, she's an IMNM patient. We have an urgent call to action as a company to bring forward our medicines. And we have strong conviction that when we enter these markets, we're going to shape them, and we're going to expand them. And I think this is a playbook that you probably recognize. ALKIVIA enabled us to take a data-rich approach to development, and it's guiding our path forward. Remember, ALKIVIA was designed as a basket trial. We believe that IgGs are driving IMNM, DM and PM. You'll hear from today on the Phase II data. You'll hear about the Phase II enrollment and also how that drove the Phase II response. Enrollment was led by IMNM. We said we enrolled it fast and we did.

We also saw that IMNM drove the statistically significant response we saw and supported our receiving breakthrough designation from the FDA in IMNM. We also saw a clear signal in DM that give us the confidence and the conviction to move forward in this subtype. PM was the smallest contributor to our Phase II enrollment and also a similar smaller contribution to Phase III. And this actually makes sense. Alongside our evolving understanding of PM, PM is continually being reclassified into different subtypes. So today, we no longer see a path forward to approval in DM. So what started as a basket study is now a big opportunity in IMNM and DM. Based on this learning, we're refining our U.S. regulatory filing strategy. We will update the analysis of the primary endpoint. And I just want to say this again. We are not updating the primary endpoint. We are updating the analysis of the primary endpoint. So we're going to assess each indication on its own merits ensuring there is a strong benefit risk profile for approval. Of course, we still have the experiment ongoing. We have to see the data. But if we have positive data, we see a clear path forward for approval in one or more subtypes. IMNM and DM are strategic entry points for argenx and for Vyvgart into rheumatology. We have the opportunity here to be first-in-class. And we know what that means, building long-term relationships with HCPs launching with strong evidence and doing it without other FcRn competition. And that's meaningful. We've seen the power of this position from the MG and the CIDP experience. It also feeds into our Vision 2030.

First, IMNM DM as the foundation, followed by shograns and future indications to come. I think all in all, for number five, we are well positioned to achieve our 2 goals, near-term label expansion and long-term leadership in autoimmune myositis. We have strong Phase II data, clear signals in both IMNM and DM. We've had active collaborative discussions with the FDA for alignment, and we now have a filing strategy that sets us up for the clearest path to approval in 1 or more subtypes. This is what supports that near-term goal, label expansion. We also see this as a foundation for our future leadership in autoimmune myositis. And so that's really about that second goal, long-term leadership in autoimmune myositis.

So with that, let's get the event started. We want to start where we always start, which is with the patient voice. So let's hear from Larissa.

[Presentation]

Please welcome, Karen Massey.

Thank you, everyone. It's great to see you. And I've watched that video, obviously, a few times, but every time I watch it. I mean it's -- when you hear my muscles are dying. Can you imagine the feeling that you have and how she describes, my dreams went poof. And dreams of my husband went poof. Her whole life impacted by this disease. And I think what you hear from Larissa and what we hear from patients is myositis is more than muscle weakness. It takes away people's identity. It takes away their independence. It takes away the ability to live their life that they want to leave -- lead. And for us, as Beth said, that's a call to action, and that's a call to urgency that you'll hear throughout the presentation today and why we're so focused on turning over that data card and hopefully getting Vyvgart to patients as quickly as possible.

By the way, what's also really important to note is that myositis is deadly. Myositis has 3x the mortality rate of the general population. So this is not just about muscle weakness. This is not just about symptoms. This is also about a severe rare disease that is -- has a high mortality. So we have an urgency to act and what we want to share with you today is our clear path forward for autoimmune myositis. So autoimmune myositis is a quintessential argenx opportunity. What do we mean by that? Well, at argenx, we always start with the biology. We always start with the science first. And I want to make sure that it's clear today and what you'll hear from Leentje is we are as -- have as much conviction in the biology for IMNM, for DM, even for PM today, as we did when we started this trial in 2021. It's very clear that pathogenic autoantibodies are driving this disease. And with Vyvgart, we have a targeted option to remove those central drivers of the disease.

Second is we always focus on disease areas that have high unmet need. We just talked about that we just heard from Larissa. But what you'll also hear about today from our KOL panel is health care professionals are frustrated, treating myositis, they feel helpless. Sandrine will share some market research from neurologists, from hematologists that share that they don't feel that they have the tools in their toolbox to treat these patients the way they want to. They have blunt tools they have tools that are not approved for the indications that are not treating the underlying disease. They feel frustrated when they're sitting across from the patient. So the opportunity is clear. We can help these patients and we can provide these tools targeted precision tools to health care professionals. As Beth said, we've prioritized 2 opportunities here, IMNM and DM. That's based, yes, on the biology. It's based on regulatory feedback. It's also based on the Phase II study data. You'll hear more from Luc on that as our path forward. So the opportunity is very clear. IMNM, roughly 20,000 patients, there are 0 treatments approved today. There are no treatments on the horizon.

The unmet need was recognized by the FDA with breakthrough designation, and we believe that IMNM is a blockbuster indication on its own. DM is the second opportunity. It's larger, around 40,000 patients. It's a more heterogeneous disease. There are limited treatment options available here as well. Of course, IVIg is approved, but we know what that comes with, especially in terms of treatment burden for patients. We see DM as another blockbuster indication on its own. So what you'll hear today is that we have prioritized IMNM and DM. We have a clear path forward Assuming positive data, let's turn over the data card and see in Q3. But if we get positive data, we'll be moving as quickly as possible for a faster path -- fastest path to market for both IMNM and DM.

Let's talk about the ALKIVIA trial that set us up for success in myositis. So I'm really proud of the team that designed this study back in 2021. I think it's exactly the right trial and has set us up for success today because it's an adaptive design, it's flexible, and it's allowed us to evolve as the disease and the understanding of the disease has evolved. It's bold and it's innovative. By the way, ALKIVIA is the first study to actively include IMNM patients. And to date, I think it's the only study to actively include IMNM patients. And the Phase II data are very convincing. So you're going to hear more from Luc in -- on the Phase II data, but just at a high level to pull out what I think are some of the most important points. You all already know there were 89 patients. It's a Phase II study. On the primary endpoint, TIS at 24 weeks, the p-value was 0.0004. That is a strong p-value on 89 patients. What you saw in the data is a rapid separation of efcatigamib versus placebo. We published data recently that you see that all the way out to 52 weeks sustained efficacy. That's a classic signature of Vyvgart and that's what these patients need. Of course, the safety reflects what we see in the real world that strong safety leads to a benefit when you're looking at chronic therapies like in autoimmune myositis. That gives the prescribers confidence.

What gives me confidence for Phase III? Well, Phase III is twice the size of Phase II, and it's twice as long. It also includes additional end points that patients and prescribers really care about, in particular, on the steroid tapering. So this seamless Phase II, Phase III design is exactly the right study to lead us to the position that we're in today. It's the right trial, it's the right design, and it's going to unlock the myositis opportunity for us. So what are our goals and what does success look like for argenx and for patients in myositis. So you'll be able to see the playbook in action that we've applied in MG and CIDP as we think about autoimmune myositis. Our filing strategy focused on IMNM and DM gives the clearest path to label expansion. So we're focused on getting there fast and broadening access to reach more patients with Vyvgart got as quickly as possible. The reason that strategy is so powerful, is that this is our first step into rheumatology.

Now remember how we succeeded in neurology. We were first to market we were able to win the loyalty of prescribers based on the innovation that we bought, but also the world-class team behind Vyvgart. We now have the same opportunity to do that in rheumatology. This will be the first-in-class FcRn launching with rheumatology and setting the stage ahead of what we have Sjogren's data reading out later next year. So that combination of first-in-class alongside that world-class team builds a moat that is hard for competitors to penetrate. But in true genic style, the work doesn't stop when we turn over that data card in Q3. We will continue to generate evidence. We will continue to shape the market and we'll continue to expand the market. So just like when we launched Vyvgart in MG or in CIDP, we fully expect that with a new treatment option and a new innovation. The market won't just switch to Vyvgart, the market will expand. We'll start to see earlier diagnosis. We'll start to see earlier treatment. We'll start to see patients staying on therapy longer, and we'll start to see importantly, better outcomes for patients as a result. These 2 strategies in parallel allow us to deliver both short-term leadership in myositis as well as long-term leadership in rheumatology.

So as we get into the details for the rest of the afternoon, one thought that I want to leave you with is that we are confident in our clinical trial. We're very clear on our path forward, and we're very much looking forward to the data readout in Q3. So with that, let me bring to the stage Leentje, who will take you through the biology and our conviction in the biology of autoimmune myositis. Thank you, Leentje.

Thank you. Good afternoon, everyone. In this session, I would like to highlight how 50 years of autoantibody research has transformed our understanding of myositis. Back in time, now almost 50 years old, when the first myositis-specific autoantibody, Mi2 was discovered. It was thought that autoantibodies were just by centers of disease. Over the years, more than 30 different autoantibodies have been identified. And these autoantibodies nowadays are important diagnostic tools for physicians. Over time, we also learned that myositis is not just one disease. In this animation, which is actually a courtesy of Dr. Ku and Dr. Chinoy, it nicely illustrates how evolving classical diagnosis or evolving evaluations of the classical diagnosis has led to a split up of polymyositis and dermatomyositis and actually into splitting out polymyositis even further in newer myositis subtypes, such as IV IMNM, overlap myositis and antisynthetase syndrome.

This actually also nicely reflects that there is not that much left of what was originally identified as polymyositis. Each of these auto myositis subtypes are also associated with specific auto antibodies. And they can also lead to a whole spectrum of clinical symptoms. On the top left, you can see how antisynthetase syndrome auto antibodies, such as Jo-1, but also certain dermatomyositis or IMNM autoantibodies can lead to a higher chance for patients to develop complications of the lung, such as interstitial lung disease, while other autoantibodies are associated with the development of symptoms that are associated with, for instance, the joints, the heart, the skin or the gastrointestinal tract. But what my patients with IMNM, DM and anti-synthetase syndrome have in common? Is this a specific proximal muscle weakness as we also heard from Larissa. And this common feature actually allows to evaluate the therapeutic effect of novel treatments or muscle function across these different myositis subtypes, which we actually did in the ALKIVIA trial.

But the biggest question in myositis was always are these auto antibodies just presence? Are they just markers of the disease? Or are they actually being pathogenic? And well, most of these myositis autoantibodies, actually, all of them, they target autoantigens that are present inside cells, which would argue against the fact that they would be pathogenic. But biometering research from the NIH has shown that the autoantibodies can actually enter muscle cells and skin cells in myositis patients. On top, you can see here the muscle biopsies of some patients, and you see in green IgG autoantibodies lighting up in green inside the muscle cells across the different myositis subtypes, which is not the case in muscle biopsies of healthy patients. Further research showed that when auto antibodies enter muscle cells, they combined to their target antigen and disrupt the normal function of this antigen. And this can, for instance, leads to interferon overproduction, lipid accumulation or disruption of transcription and translation, eventually leading to cellular damage and inflammation.

So yes, autoantibodies are pathogenic. And autoantibodies, they can cause cellular damage in a dual way. As I just showed you, autoantibodies can have this intracellular effects, but autoantibodies can also bind extracellular antigens. This can lead to the formation of immune complexes or activation of the complement system. This triggers interferon and cytokine production, access signaling and inflammatory cell recruitment. But one example of this, for instance, this pathway on top is the clear example of how in IMNM patients autoantibodies and bind to autoantigens that are expressed on the cell surface of muscle cells. This causes the activation of the complement system and leads to perforation of the muscle cells and the leakage of muscle enzymes such as CK. This explains, for instance, why myositis or specifically IMNM patients such as Larissa have these extremely highly elevated muscle enzyme levels of CK.

The clinical success of JAK inhibitors further confirm that suppressing downstream interferon and JAK signaling could dampen autoantibody-driven inflammation. Our hypothesis is that efgartigimod could act one step earlier more upstream and could actually remove the pathogenic IgG autoantibodies that leads to this cellular damage. Importantly, as well on the right, you see that the cellular damage that is caused by the autoantibodies leads to more exposure and more release of autoantigens in the environment which then causes a feedback loop further driving inflammation and damage. Two preclinical models actually support the hypothesis that efgartigimod could break this cycle of damage. When autoantibodies that are isolated from IMNM patients that are positive for an auto antibody are injected in mice. We see that these mice develop muscle weakness and necrosis.

On the left picture, you see in the muscle biopsies of B cells that the device develop necrosis, which is indicated by the black triangle. And this is also clearly reflecting what is seen in IMNM patients. Now when these mice are treated with efgartigimod starting on day 8, which is once the disease established in these mice, the mice show reduced muscle necrosis. And you see we saw this increased muscle generation present by the, I don't know, sorry, -- there is no point there. As you can see by these clusters of regenerating muscle cells indicated by the white stars. We also see on the right that treatment with efgartigimod indicated in green leads to a restoration of the muscle function in these lines compared to non-treated mice which are indicated in black and which keep on having a clear loss of muscle group strength.

In a second model, when we immunized mice with a Jo-1 autoantigen, these mice develop excessive lung fibrosis. On the left picture, you can see accumulation of collagen in the lungs of these mice. So there are clear deposits of collagen, which actually disrupt the architecture and the function of the lungs in these mice. And this picture reflects as well what happens in patients that have Jo-1 autoantibodies, which, as I previously showed can develop severe lung damage such as interstitial lung disease. Now when these mice are treated with an efgartigimod mouse on the look, we saw that these mice had clearly improved lung fibrosis restoring the normal architecture of the lungs. So in the past 2 years, we have had the hypothesis that actually, by reducing the autoantibody levels, we could bring therapeutic benefit to patients. And what was just in beginning just a plausible hypothesis is now supported by more mechanistic evidence by preclinical data and as well by clinically controlled data.

In the ALKIVIA trial, we saw that patients that were treated with efgartigimod showed clear clinical improvements across different myositis subtypes compared to the control group Importantly, in the biomarker data of patients that show a major clinical improvement, we saw that the improvement was also reflected in their biology. We saw that improvement in clinical symptoms and muscle strength was paralleled by reductions in autoantibody levels. And in individual DM patients, we saw also reductions in interferon production and an individual IMNM patients, we saw clear reductions in CK levels. Together, this indicates that targeting autoantibodies underlying the disease holds strong potential for targeted therapy to improve the muscle and extramuscular sentence and the quality of life of patients like Larissa.

I will now hand it over to Luc, who will further elaborate on the Phase II clinical results.

Thank you, Leentje. Isn't science cool? In case you see me limping, it's about new shoes, and I regret it. I want to back. Most of you were at our R&D Day in New York in '24, where we talked about this particular study, and how it for us was an example of the best argenx could do, trying to minimize white space and accelerate our path to patients by utilizing an adaptive study design. We built this on the whole story Leentje has shared with you the biological insight that autoantibodies speak are the drivers, not by standards and that days lead to destruction of muscle, as you could see in these preclinical models.

As we then design this, how do we reveal this biology in patients, we also want to recognize that we need to know what patients care about. We need to know how physicians would assess effect. And so we chose the primary endpoint, the test, which is a composite endpoint that encompasses 6 dimensions relevant to this disease, and I'll go in a bit more detail later, but the core feature is, of course, the muscle strength. As we already have said, at proximal muscle weakness is a core feature across the subtypes. But another very important aspect of these diseases is the high frequency of utilization of steroids. And Larissa, in fact, talks about this, which she said she gained 40 pounds under high steroid treatment. That is the least, I think, of the problem she encounters with this sort of treatment. So we also built in, in the program systematic approach as steroid tapering.

Now where does the another part of the innovation line is that we said, and I said it on the stage there, one of our core approaches we want to minimize white space. In this particular case, how can we do Phase II, III developments as time efficient as possible. And we developed an operationally seamless design. And I will show that more on the slides. And also as a first, and this was already indicated, but repetition is the mother of something. It's the first time that 3 different subtypes were included in the same trial, and that also the first time that IMNM was, in fact, included in any study because it was prior an exclusion. So what does this look like? And this slide now, in '24, there were no numbers in there because, of course, this was ongoing. But here, you can see that in the 90 patients approximately that entered the 24-week Phase II study. And the operation is seamless here, just to be clear, is from when we fulfill screening in Phase II, we started enrolling in the Phase III and the adaptive aspect of this study was that we could stop a subtype should data warranted. That was the adaptive part of this study. And this is maybe relevant for the Q&A later.

As I already said, the TIS tries to capture holistically the impact of this disease and how an intervention could improve it, muscle strength, physical function, patient and physician assessment muscle enzymes and Leentje already showed some of the -- stole my thunder basically. But okay, we measure those and extramuscular activity. These patients in our Phase III trial, we have up to 175 patients we're following for 52 weeks. What is important to realize as we talk about this, is that we on purpose did not have a target per subtype of enrollment because the moment you do that, then you're basically in a convoy situation, where the slowest enrolling cohort determines the overall speed of the trial. And we didn't want that again, speed to patient was essential. Of course, they all had to have active muscle weakness, right? We wanted to have something that could change. The tapering protocol already talked about was actually only executed in Phase II. Why is that relevant? Because the Phase II data I will show you are on top of standard of care, okay? The primary analysis, and this has already been talked about is that we are really going to look at the individual benefit in each subtype and the reasons why will come in the next slide.

You've seen the slides and Leentje just showed it. But to me, it's still remarkable that over 24 weeks, we could see this solar effect on active. As already said, highly robustly significant. But a very simplified way to think about it is that TIS is an improvement score. And it's a derivation of percentages, and I can go in a very complicated explanation. But it goes between 0% and 100%. And over 24 weeks, the patient on active reached 50% improvement from their condition they were at baseline. Pretty neat. I'm very excited about that data. Now where did those data come from? And here is the beginning of the story of the change, which is we didn't have a target enrollments, first come first serve. We saw that we very quickly enrolled IMNM patients to about 2/3 of the study. DM about 1/3, PM quite low. And during the panel, we can come back on some thoughts why that is. But PM, I'm going to say it maybe wrongly, could be going the way of the dodo because as it's recognized that different antibodies are driving, you get more individualized identification and it's no longer just polymerize eyes. You can see steroid dose in Phase II. There was no tapering down age, et cetera. Yes. And then 85% had autoantibodies, 15% were seronegative.

So the majority of this effect you see on the left side, logically was driven by the IMNM subset. And in fact, if you do an analysis, it was statistically significant on its own. DM showed a clear signal, but with that 30% part of the sample, did not reach statistical significance, but a clear signal. Another feature that is common across all the indications of Vyvgart is speed of onset. And this shows you that on actually a responder analysis because if you take the continuous one, it actually starts separating earlier, but this is reaching TIS 20. Another feature depth of response, which we all should care about is that if you take higher and higher thresholds of what you want to achieve, the separation between active and placebo becomes bigger. And in this particular case, TIS over 40 to us is particularly encouraging.

Now the TIS, as I said, is a composite. And here is just a message that each of the composite parts improved. Look at the muscle dimension. It improved significantly. And this is very rewarding for us because this is, again, biology at work. And this just shows you again the fast time it does it. And not only does this MMTA score, the patients feel it right very fast, right? Blue is efgartigimod. From early on, patients feel there's something different. Pretty exciting to see. What are the risks? By and large, the risks are, as we know very well, from our overall safety database. If you look at the event rates per 100 patient years, which is in each column, the first right, there is not really that much difference. We currently have 25,000 patient years of experience. But -- and I was sensitized to this by Dr. Aggarwal is that in these particular indications, infections and serious infections are, of course, always of interest. And there is on the more than Grade 3, 3 patients that had that in the whole study. I think that stands for the known safety profile. And we can discuss this further. But overall, in the context of this does not take away from any benefit observed. This is supported by an extensive database and gives us the confidence that we can have a reliable risk-benefit assessment here. So what have we learned, what are we doing with it? And why does it matter? We have learned that M&M drove the Phase II results.

DM showed a signal but due to low sample size could not reach the significance in the Phase II. We went to the FDA with our data package and talked about breakthrough designation, and they granted it for IMNM. The reasons being, no available treatments and clinically relevant results package in the Phase II. The baseline characteristics of Phase III, I can tell you, without divulging too much, this is an ongoing trial. We don't want to cause any problems before we close the database. But what I can tell you is that the baseline characteristics in Phase III are very close to Phase II. What does that lead us to that we have an emerging strong data package in IMNM and the potential for the strong data package in DM. And so that positions us for, of course, either overall must be positive, but that we can file for at least one of these subtypes with urgency because thinking again about our principal speed to patients. And that's why it matters and the way we designed this program.

So with that, I give the floor to Josh. Thank you.

Thank you, Luc, and good afternoon, everyone. So over the last part of the session here, I think you've heard that we have a really exciting opportunity to impact patients with autoimmune myositis. And so today, we're really fortunate to have 3 leading experts across dermatology, neurology and rheumatology. It's come up here and talk to us about the landscape, the unmet need the treatment paradigms and what's exciting about innovation in the space.

So with that, let's meet our panelists. Our first panelist is Dr. Avery LaChance, who is an Associate Professor of Dermatology at Harvard Medical School, and she is the Director of the connective tissue disorder clinic at that institution. We have Dr. Arjun Seth, who is an assistant professor of Neuromuscular Medicine in the Department of Neurology at Northwestern. Dr. Seth brings deep experience in neuromuscular disease, treating both MG CADP as well as autoimmune myositis and was a site in both Phase I and Phase II. And then we have Dr. Rohit Aggarwal, who joins us. He's a Professor of Medicine at University of Pittsburgh Medical Center, and he's the Co-Director of the UPMC Myositis Clinic. And he's been a key adviser, I think, as you heard earlier on this study and on this program. So we are absolutely delighted and privileged to have this expert panel. I would like to welcome the 3 of you up to join me.

Thank you. Okay. Lovely. Well, so why don't we kick it off with Dr. Seth, and I think we're going to talk a little bit about the disease burden and the unmet need in the space. And I want to start by anchoring to the patient we heard from earlier Larissa, and specifically necrotizing myopathy patients. Can you talk to us a little bit about how these patients come into your clinic and present to you and some of the struggles they go through it.

Yes. That's a great question. I think a lot of the patients come in exactly the same way that you heard Larissa's story, which is they present with the weakness, they're not able to work out or do their normal activities of daily living, so getting up off a toilet, climbing stairs and they go to their primary care providers and explain that they're having symptoms, sort of they're told sometimes that they're just getting a little bit older. And it actually takes a few months to actually end up seeing someone, so a neurologist or a rheumatologist to actually then do this testing to value for CK and then discovering that they actually have an immune-mediated necrotizing myopathy. So that story is very, very common.

Yes. And just a follow-up to that. We've been thinking about her disease course, but the course in IMNM in general, right, is we know it's very aggressive. So could you talk to us a little bit about how you think about the urgency to treat there?

So immune-mediated necrotizing myopathy, in particular, can be quite aggressive as an dermato, but immune-mediated necrotizing myopathy, typically patients progress quite quickly over the first 3 to 6 months and are initially able to just noticed some site difficulty with, let's say, running or getting up out of bed and then over 6 months are really in sort of kind of end up being wheelchairs. And so those are the -- most of the patients that I've ended up seeing have been coming to me basically in wheelchairs and they're not able to get up and walk and ambulate independently. And so that's the sort of burden.

And these patients have a privilege of getting to in a very specialized sort of tertiary center, but I would imagine that could be somewhat disparate depending on where you are and your access to care.

Absolutely. And so most patients actually end up coming into the hospital. So their first admission is actually into the hospital where they end up seeing a specialist then get diagnosed and then initiated on treatment on a hospital.

Excellent. So shifting gears, we'll go to you, Dr. LaChance, and I want to ask specifically a bit about DM. So we know even from some of the science we went through and everything else that this is a very heterogeneous disease. I guess, could you talk a little bit about sort of the variety of presentations that patients come to you with?

Sure. So I think for dermatomyositis, we've really been anchoring and hearing a lot about the impact of muscle on patients we can see a similar thing in dermatomyositis as well, where patients have difficulty walking, getting upstairs, et cetera. But as the dermatologists in the room like the Lorex the trees, I also speak for the skin and say that actually in dermatomyositis, dermato skin, myo muscle, that inflammation in the stim in the muscle is a really big thing to know about in dermatomyositis. And in fact, a lot of our patients, the burn pain, discomfort can keep them up at night and prevent them from sleeping team can have just a bit as big, if not bigger impact for those patients as well. So about 80% of patients with dermatomyositis are going to have skin and muscle involvement where they're battling both and about 20% of patients are going to have in only disease, so amyopathic. And then layered on top of this, this can also be a multisystem disease where we have to think about interstitial lung disease and other internal disease manifestations as well. So this is not really just impacting the muscles but really is a multisystem inflammatory disease state.

Thank you. And Dr. Aggarwal, shifting over to you, thinking about sort of all the unmet need in myositis, I guess, what do you think are the greatest unmet needs today?

Well, I think the biggest unmet need is we need more efficacious treatment that are safe and tolerable. And I would add in today's wall that can limit the use of steroids. So I think we do not have a treatment that encompasses all 3, maybe IVIg in one subset. But overall, in the whole disease, we do not have that. And specifically, we do not have that for IMNM. So there is a huge unit. The reason that you see a lot more IMNM in your trial is because that's what they're telling you that is -- that's the subset has the highest unmet need. So I think, overall, I would say -- overall, IMNM itself needs efficacious, safe and tolerable treatment. But amongst those, IMNM patients have the highest unmet need.

Very helpful. And a question about -- I think Leentje did a really nice job of showing how symptomology has evolved the subtypes over time and how we've learned more about auto antibodies, distinguishing subtypes over time. But I guess how has it evolved from your perspective and you think about pacing in the space?

So in the last 20, 25 years, what has happened is mostly put by the slides that how the DM and PM was combined and then they took a part and how the journey of the myocyte is diagnostically. So all of that has been influenced heavily by autoantibodies to begin with diagnosis and classification has been heavily influenced. We know auto antibodies define a unique clinical phenotype. So we know that for sure. And then lately, we have been using autoantibodies to drive our management itself. But what has happened in the last about 5 to 10 years, we have seen increasing data about pathogenic role of autoantibodies. Largely to multiple scientists across the world, but I would say NIH has really shown convincingly that how these autoantibodies are playing a direct role in pathogenesis, which so far was thought about, but we didn't have a direct proof. So now we really have these direct proofs. So lowering these autoantibodies should get to the improvement even in 10 years ago, when we did studies where the antibody level will go down, disease get better, antibody get -- levels go up, disease get worse. We knew their clinical association. But having a direct pathogenic experimental proof was not there. And I'm really happy to see that coming through now.

Dr. Seth, I want to sort of ask you a similar question, and I guess thinking about how you've seen it evolve and also around auto antibodies in your experience?

I think the auto antibodies, you're absolutely right. It really does help guide sort of our management, especially if we find an HMGCR antibody or an SRP antibody. We know sort of what the phenotype looks like, so what patients will present with in terms of their weakness, there sort of clinical course and can actually change our treatment strategy based on that. There's also a whole subset. These -- the HMG antibody was only discovered 16 years ago. And so there's a lot of these other novel types of immune-mediated necrotizing myopathy , what we call seronegative without known antibodies that probably exists and they present very similarly. So we do send other labs to look for actually different types of novel antibodies that will present in the same way.

And Dr. LaChance, I want to ask you a very similar question in dermato, which we know that auto antibodies depending on your phenotype have found impact on your comorbidity risk and other things. So I'd love to hear your thoughts. .

Yes. I think a couple of things to nail home is that in dermatomyositis. First off, the autoantibodies are not needed for diagnosis. Your diagnosis is really based on what you see clinically for patients. And I think it's a really important thing to know that actually, the sensitivity of some of these assays can really vary by institution and where we send these labs off for. So historically, if you look back at a number of the different studies that have come out, some say X number of patients were -- did not have a positive autoantibody probably if you had a better assay, you are going to detect that autoantibody. And I think now more and more we're realizing. And I think the dermatomyositis kind of curious and experts for a long time have really thought actually those autoantibodies are there, we just need better assays to detect them. So I think that's one thing that's important to nail Home. And secondly, in dermato, although you don't need those auto antibodies for diagnosis exactly as has been mentioned, it can be really critical to help prognosticate what you're going to expect to see for patients in terms of comorbid disease. So some patients their autoantibodies, MDA5, you're going to be very worried about rapidly progressive interstitial lung disease. Their patients may have very NXP2 mild skin disease, very aggressive muscle involvement. And so auto antibodies seeing that they play a role really in driving these heterogenous disease state and the different things that we see in terms of how they present clinically helps us also understand the role of these autoantibodies as truly pathogenic.

Excellent. So shifting a little bit to the treatment landscape and then the FcRn rationale. And maybe this is a question for the group. When we were reflecting on the data we saw in Phase II, and we're going to see in Phase III. It's not a true placebo group, right? These patients are on a background of steroids and DMARDs. And obviously, I know the 3 of you are experts and are doing a lot for complicated myositis. But when we think about the limitations of what's in the toolkit right now. I would love to hear some perspectives, and maybe Dr. Aggarwal will start with you.

Yes. So I think we have been using the toolkit that was prescribed to us from rheumatology per se, which is DMARDs, methotrexate, meclofenamate [indiscernible] these are -- none of these are really proven, and none of them really works on its own. They're all sort of steroid -- they need steroid help in -- steroid plus these modulators would work. But then if you look at the overall outcome in our studies, in our center for 10 years, only 20% of patients had any major outcomes in the past when we didn't have more immunomodulatory therapies. In dermatomyositis, we are fortunate now to have IVIg that does take to the next step. But that said, that's all we have. So I think the unmet need from that standpoint is huge. And I think we have nothing. When our IMNM patient comes in, we know that in 3 months, this patient is going to be wheelchair bound and have nothing to really push the treatment forward other than keep bombarding them with steroid, next immunosuppressive agent, next immunosuppressive agent and nothing else. So I think that's a really significant unmet need that we feel that needs to be fulfilled by hopefully the drugs like FCR and receptor blockers.

Dr. Seth, I don't know anything to add.

That's a great answer. I think I totally agree. I think there has been huge unmet need, no FDA-approved drugs for M&M I think that's where the space and this trial actually fills that space.

So Dr. LaChance, I want to skew slightly differently, right? So these patients are going to be chronically immune suppressed for a long time. So how do you think about that? And specifically, how do you think about steroids and they may have to be on high doses of steroids?

Yes. I think for a really long time, exactly as Dr. Piira mentioned that we've been having to rely on our DMA, so methotrexate, mycophenylate mofetylin and you imagine coming into your doctor and saying, "I can't walk or I have this burning rash and we say, okay, I've got a drug for you, but it's going to take 3 to 6 months to kick in. And then the eyes get wide and you say, okay, but that's going to have -- while that's ramping up, we're going to turn this off really quickly with a fire hose. And that's where the corticosteroids have come in to really turn disease off as we're waiting for those slow ramp-up steroid-sparing agents to kick in. And those steroids, we have to remember, have a really big impact for our patients as well. So there are a lot of risks associated with long-term high-dose steroids. And especially when we're talking about the myositis space, there can be muscle impacts and loss of muscle from those long-term steroids as well. And then over time, you're saying, am I dealing with the steroid myopathy? Are we still having ongoing inflammation? There are these really important things that we need to know that the steroids can do. And so for a while, we've had to layer therapies on, and it's a really exciting time to now have some more targeted quicker-acting agents that we can bring into this space, and that's really needed to have that steroid-sparing effect and prevent long-term damage.

Can I just jump in on that? I feel like sometimes I exchange the disease, give them tons of steroid, make them -- make me feel better that their myositis is better. I show the numbers, the seek is going down, but I'm exchanging a big long-term disease with them, which includes diabetes, cardiovascular disease, bone health, muscle health, kidney. So I feel like I feel better, but I'm not sure I'm really doing a good job by giving them long-term morbidity and mortality risk.

Very helpful perspectives. I guess shifting gears a little bit and thinking specifically, I've heard a lot of your talks in DM and complex DM and then learning from you about how you think about it in your clinic. But we know there's a lot of innovation in this space. And so how do you see the role for multiple MOAs in the DM space in the future?

Yes. I think as a dermatomyositis doctor, it's a very exciting time to be caring for these patients. But actually, it's not like we have just been waiting for the one magic bullet to come through and treat these patients as the only thing. A lot of times, first off, we've heard how these are complex disease entities, and there are multiple pathogenic drivers of disease. And actually, to date, we've been using JAK inhibitors off-label. We've been using IVIg. We've been using our DMARDs. And it's really not uncommon for us to need to layer different therapies together. And in fact, we use DMARDs and IVIg. We use IVIg and JAK inhibitors off-label still currently in combination because exactly like I said at the gut, for dermatomyositis, a lot of these patients, you may control their muscles with one thing, but their skin is still burning or their interstitial lung disease may still be progressing. And it's not uncommon for us to see to layer therapies for patients. And so actually having multiple MOAs, multiple targeted agents, all in the name of getting patients off of steroids is very important, very exciting. And I think we will be using these therapies in combination moving forward.

And so to keep up with that same theme of the last answer we heard from you, Dr. Aggarwal, the way you answer -- finished your answer, Dr. LaChance. Let's talk about the steroid taper in Phase III and sort of how you think about that? What is that going to accomplish? Why could that be meaningful when we see the data?

Yes. I think really, if you think about 10 years ago, we were not doing steroid tapering in myositis trial because at that time, we didn't have any treatment available. There was nothing available. So we said if we do steroid tapering, it may jeopardize the treatment outcome. But now the thinking has evolved. What we are seeing is studies after studying long-term effects of these steroids, specifically in myositis coming out. So doctors are now worried about giving long-term steroids. So I think that's one of the reasons. The clinical reason is so huge because doctors are seeing burden of these long-term steroid when they follow these patients 5 to 10 years down the lane, the myositis might be better by now, but now there's a lot of other problems. So that's the clinical reason. But also from the regulatory standpoint also, the FDA has learned through various of the studies that, look, this is a very critical area for regulatory bodies to make sure the drugs are effective on their own, not because they're on the background steroid because that's what has been happening until now. Now they want neurodrum, novel therapeutics or targeted therapies to be effective on their own, not requiring steroid help and now the steroid has done this much job. Let's move it to here. No, we need that the whole thing has to be travel by that drug so that the steroid can be tapered off to a large extent.

And how do you see FcR inhibition fitting in to that potential?

So I think I expect -- so in Phase II, we did not do steroid tapering because it's more proof of concept. But my expectation is in Phase III, we should see robust steroid decrease in patients who got the drug versus who got the placebo. That's my expectation. That's my hope, and it will bring a lot of hope and excellent outcome for our patients.

Thank you. Dr. Seth, I think you have an interesting perspective here as a neuromuscular physician who has been using efgartigimod in CIDP and MG and have a lot of experience as well as being a trial participant, right, and having subjects enrolled. And I'm curious what is your outlook on sort of the mechanistic rationale here? And how do you think this is going to fit in, specifically in IMNM?

I think it plays -- we know that these are IgG sort of -- we think that their IgG mediated disorders, we have good evidence to say that, I think depleting the IgG and those pathogenic immunoglobulin has -- does play a role. We've seen that in myasthenia quite robustly and also shown steroid-sparing effect, so it reduced the amount of steroids that patients needed CIDP similarly have shown benefit in that. I think the same thing will happen in -- with this study as well. I have 2 patients enrolled in the Phase II, and they have been fine and doing pretty well on their background immune suppression and have tolerated the drug really well.

Very helpful. Thank you.

I just wanted to make one more point. The fact that we have one drug approved, that's going to be all in. It's not -- this is an autoimmune disease. The median age is 50 years. They're going to live another, let's say, 30 years. It's a 30 years of drugs. So a single drug will not going to cut it. We need -- even in DM, I would say we need at least 3 or 4 or 5 drugs to really be able to serve about 90% of our patients. So I think the fact that one drug is approved them, this is a second drug is a wrong understanding. This is not a second or this is an option for the patients that could be even the first line in the future.

Yes. And I know you shared sort of an interesting insight earlier about how we've seen that in some of the more complicated spaces where innovation has taken place in the last decade, like RA.

RA is a perfect example. We have 20 drugs approved in RA and I still struggle with some of my RA patients. These are lifelong diseases, that one drug may work for 1 year, 2 year, maybe 10 years, but it may fail because autoimmune disease evolve and overcome that mechanism of action and you may need a second mechanism of action to counter the disease. So I think this is an autoimmune space is a chronic disease space where these drugs are going to be used for long term.

Very helpful. Okay. So I want to shift gears more towards data impressions, specifically from the Phase II ALKIVIA data. I think we saw some nice details from Luc earlier about some components of that. And Dr. Aggarwal, I'll go ahead and start with you on this. Let's talk a little bit more about the total improvement score because this is a complicated sort of multicomponent score, there's a lot to unpack. So could you tell us a little bit more about how you think about sort of the 6 core attributes and why they're meaningful?

So I think before talking about total improvement score, I want to take you to rheumatoid arthritis because that has been the major disease that revolutionized rheumatology in the last 25, 30 years. And the reason that rheumatology has been revolutionized by the RA field because of these clinical trials that use composite response criteria called ACR 2050 70, some of you may be familiar. So rheumatologists are very familiar with composite response criteria. Why? Because in rheumatology, it's not a single disease is not a single organ, a straight manifestation. It's a complex disease, a heterogenous disease. So we need composite response criteria so that we can hit multiple aspects of our heterogeneous disease. Same in myositis. We need to know how is the patient feeling. We need to know how the physician feeling. We need to know how the biomarker is doing. We need to know how the skin is doing. We need to know how the muscle is doing, how is the function is doing. Then you get a better overall picture. If you use a single outcome we will not be successful in any of these clinical trials because of highly heterogeneous nature of the disease. Some patients are worried about their skin. Some over the lung, some over the muscle. So it's -- so that's the power of the total improvement score encompasses 6 outcome measure that looks holistically the patient. And then because of that improvement, then you're able to see, overall, we feel patient improved. Now there is efficiencies that you see the patient improve overall, you may not be able to say what aspect of the patient improved that led to overall improvement. For that, then you have to look at the core set measure improvement to see what exactly improved that the patient had an overall improvement.

And just to further ask some questions about total improvement score. So I think one thing we've seen across trials is that there can be a very notable placebo rate. So I was wondering if you could give some insight on that than anyone else spoken away as well.

So the placebo rates are not truly placebo rates. So think about this. These are patients on 1, 2 or 3 drugs on the background immunosuppression. So the background immune suppression is going to improve the patient. So that's one aspect. It's not placebo standard of care, okay? The second part I wanted to mention is the moment the patient gets into the trial, they were not taking their methotrexate earlier, they start taking the methotrexate now. They were not exercising, they start exercising now. They were not taking care of their health, they start taking care of their health. So there is a second aspect, which is also not placebo, which is fully treatment. And then the third aspect, which is true placebo, which is the bias that comes in because of the hope of being in a truck. So I think the overall placebo effect would be wrong to say it's about 40%, 45%. It's about 10% to 20%, which is pretty normal in any of the studies. The rest of it comes from standard of care treatment, taking the medication on time, taking care of yourself. So -- and this is not the only study where we have seen this hypo placebo response. Almost all myositis studies, we have seen significant high rates of placebo response. And that also speaks to the extent that if you have a positive study, despite high placebo response, that means that treatment is working really, really well to overcome that placebo response is not an easy. So I think from that standpoint, I believe that this delta of 15 mean this and a delta of 20% to 30% is hugely meaningful.

And I also think added on top of that, that's why it's going to have the steroid taper in Phase III is going to be even more meaningful because I think that's where there will be we've just talked about all the risks associated with steroids long-term steroids. Having that layered on as a real-world thing and also a delta already at 4 weeks, I think, is very important because that doesn't mean we're going to have to wait 6 months to start to take for those steroids.

So I know that when you're just taking care of patients with myositis, they're not part of a trial, you're probably not evaluating a total improvement score, right? You're looking at them. But I do think we saw moderate and major improvement marks there, right, [indiscernible] I was wondering if we could maybe hear across the panel sort of what is that meaningful impact for the patients you see that's representative of that. So Dr. Seth, I don't know...

Sure. I think some of the big things are functional functionality. So getting up off a toilet, climbing stairs. I ask patients that or simple things like rolling in bed. So patients with immune-mediated necrotizing myopathy, have a hard time actually rolling around in bed and getting on their side even to do assessments even for the clinical trial. So those sort of simple things are having to sit up. So these patients when they do come in, they're really weak. And so those are the big questions I initially asked them and then swallowing. So if their swallowing is impacted, they tend to lose a lot of weight because they're not able to keep up with nutrition. And so they tend to lose around like 30 to 40 pounds as they're going through this whole process. So if that's stabilized their weight has stabilized and they're able to swallow. So those are big things in terms of functionality that I look at.

Yes. From my standpoint, what I look at is because we have done studies where sure if you hit this 40, that means your pain is improved, your function is significantly improved, fatigue has improved. If the skin involvement and skin is part of this, then in your skin has improved, so overall, their activity function, pain, fatigue, all the disability part has improved. So it's really meaningful for me TIS 40 is very meaningful. If you ask me, looking at the data, would you tell somebody that 80%, 90% of patients improve because TIS 20 improved, I would say no. I would say 70% patient or 77% patient improved because TIS 40 improves. So for me, TIS 40 is my gold standard that what I evaluate the drug on.

And I think to add in the skin layer as well, what we're looking to see is decreased pain, burn and itch. And there's actually a lot of data out there that itch is as impactful for patients as and that itch and burn in dermatomyositis is a very high impact on quality of life. Patients will say, "I can't sleep. It's all I think about all day and when patients are improving, they say, I feel comfortable in my skin again. And that's really kind of what patients are saying to say, is not just the look and the appearance of the rash, it's how they feel in their skin.

Excellent. And so I want to change direction for sort of the last question here and talk a little bit about the implications of innovation and changing the standard of care in a space and what that really means. And so knowing that you all are at tertiary care centers, you're seeing complex patients. if new innovation is in this space, how do you think that's going to change as far as how patients can access treatment from tertiary centers to the community? And how will it impact the overall amount of patients that are sort of being seen with these diseases. So Dr. Seth, why don't we start with you?

I think you'll -- so the myasthenia work has been outstanding, okay? Honestly, with the odds and everything on TV, patients come out of the work evaluation for their myasthenia. I think the same thing will happen with myositis, patients who are weak or have weakness will end up seeking additional care and with more awareness, they will actually look for and care I think one of the things that we've been doing at least at my institution is like we are trying to disseminate information on myositis and train our trainees and others in the community about inflammatory muscle disease so that people can recognize it more. And so we've done a lot of work on that aspect, at least in Chicago.

Avery?

Yes. I think absolutely the same thing we've seen is targeted therapies are there. We see more patients coming up and even self-diagnosing and recognizing the disease. I think we're going to have to do a really good job of educating our community providers as well, our community dermatologists, our community rheumatologist, but actually, one of the benefits of a subcu therapy in oral therapies is there's an ease of prescribing that's not there with an infusion-based treatment. And actually, we have a lot of our community dermatologists feel very comfortable prescribing a whole multitude of targeted therapeutics and psoriasis atopic dermatitis. So with a clean safety label that's on the dire side, what everyone is always looking for and subcu injectable dosing, those are 2 things that people are getting much more comfortable prescribing. And I think as we can empower people to diagnose and start treatment sooner, more patients are going to come in, and hopefully, we're going to see a dissemination of treatment, not just in tertiary centers as well.

Yes. I agree. I think the education is key because community doctors look at the KOLs for the education, so talking about in state rheumatology societies, ACR, EULAR where you kind of communicate that, look, the treatment paradigm is changing, stop using excessive steroids, stop using DMARDs after DMARDs that are ineffective and you're losing time is muscle you're losing muscle in that time frame. That education has to be communicated to the community doctor. Once they know that, it is very easy for them. They know how to get approval. They know how to get started on treatment. So I'm not worried about that, but only the education part I think, is the most important. But I think I want to also touch upon increasing diagnostic tools. Also another area that the companies like argenx should focus on because there are a lot of misdiagnosis. There are a lot of delayed diagnosis. There are a lot of the patients who don't get diagnosed old age. Once you give parts who comes with milder milder phenotype, you give them a wheelchair you think anybody is going to care about them? No. So I think there is a lot of best diagnosis and undiagnosed cases that diagnostic tools can really cover that growth.

Very helpful. Well, I'm going to close there, and I'm just going to say a profound thank you, 3 of you for spending the afternoon with us. I think your insights are so valuable for everyone here. So thank you very much, and appreciate it.

Thank you.

Thank you.

Thanks.

And now it's my pleasure to welcome Sandrine to the stage to talk about the commercial opportunity. Thank you.

Thank you, Josh, and thank you to our panelists. So I'll bring it home, bringing everything together from the biology and the sand, the unmet need we heard about and then Vyvgart. So yes. So I prepared this slide actually without knowing what our panelists will speak about because I wanted to anchor our discussion on the commercial opportunity on the unmet need. And actively, I think this is a pretty good summary of what we just heard. We heard from Larissa, my muscle are dying. I heard Dr. Aggrawal, you finished by saying time is muscle. We heard patients who have IMNM within 3 to 6 months end up in a wheelchair. So this notion of disability is very, very present. And this can impact the daily work or this can impact them going climbing stairs, going to bed, et cetera. So that's something where there is a huge, huge need. We also heard that the toolbox that is physician disposal right now is far from being sufficient. Many patients need more. Many patients are going to leave 10, 20, 30 years and what is available today is not sufficient. We also heard steroid tapering is going to be critical because long-term steroid good is not good for anyone.

And actually, we saw in some studies that more than 85% of patients that suffer from myositis, use steroids and 60% of them are on those that are as high as 20-milligram per day. So this is not sustainable for the long run, you're adding to the disease beyond myositis. For all these reasons, there is a need for medicines that can bring what you have here on the slide, rapid onset of an efficacy because time is muscle. System efficacy, especially on the muscle we heard for DM, 80% of the patients have both muscle and skin involvement in IMNM. This is mostly muscle involvement. The safety and the long-term safety will be critical and have an established safety profile will be key that allows for steroid tapering. And at the same time, we heard Dr. LaChance finishing convenience could also help. If you have a PFS subcu or oral much better than having had patients that have to come to the hospital for an infusion. So that will be the perfect profile of medicines coming to market to help these patients. So what we know at argenx is that we have a playbook, something that we have been using to make our launch in MG and CIDP successful. And this playbook is based on 3 pillars. High unmet need that I've just described is one of these pillar. The other 1 is very clear biology, and LaChance explain in detail why we believe autoantibodies are really driving the disease and that the biology is very clear. And the last key pillar is that this must be white space. Very little medicines and drugs available, little competition, little opportunities for patients to have actively tools in the toolbox that can make a difference. And if you apply that to IMNM and DM, you see that actively with a perfect argenx indication with these 2 subtypes.

Let's summarize what we heard about IMNM. So the biology very clear. This is the strongest body of evidence we have of autoantibody-driven disease. We also conducted much research since many years, but the most recent one in this first quarter. I looked at it, and there was one quote that stood out for me that one of our providers said is that stop the damage now. So if we have to remember what is the unmet need is that we have to go fast, have a drug that act really fast with a rapid onset of efficacy sustained efficacy, especially on muscle. That's what we saw is the core need for IMNM. And we heard in, there is nothing. Nothing has been approved. Drugs are being used of label, the unmet need and the sense of urgency is high. So this is why when you ask physicians in a market research, which has been blinded. We didn't share the names of the drug and we shared a high-level profile of different drugs, 9 out of 10 rheumatologists who don't know Vyvgart, 9 out of them said that they would use Vyvgart to treat IMNM should it be approved.

So if we move to DM. There, the biology is clear as well, also driven by 2 antibodies, but the spectrum of autoantibody is broader, which leads to more heterogeneity in the disease manifestations. You heard from Dr. LaChance, 80% of the patients have both skin and muscle involvement, and it goes even beyond that. If we have to summarize the unmet need here from this market research we conducted, actually the one I kept here with, help me manage for the long haul. So this is a long-term management, patients will live for long term, and we need multiple options, and we need to make sure that the safety profile of these options is very strong, very established and that we can use it for the very long term. And you know Vyvgart, 25,000 patient years' experience. So the profile of Vyvgart is very strong from a safety perspective.

In IVIg, there is already a treatment approved. IVIg already exists, highly burdensome for patients. As we know, we know that space quite well because in CIDP and MG, this is also drugs that are being used. But we also know that in DM, you will need multiple mechanisms of action, like you were seeing the outlets, you need to layer one after the other, just to make sure that it's fitting the different needs of the patients. So when presented the blinded profile of Vyvgart to rheumatologists, actually 8 out of 10 say that they would use Vyvgart to treat DM in case Vyvgart would be approved for this disease. So this shows that there is truly biology, unmet need and white space, and it all boys together by a strong willingness to prescribe Vyvgart prescribed for these 2 subtypes.

So now the question I often get is how big can it be? So what we have been saying is that there are 20,000 IMNM patients diagnosed in the U.S. This is more than what often you see in literature. But we triangulated this a number using registry using claims data and physician information. We strongly believe that there are at least 20,000 patients diagnosed with IMNM in the U.S. This is more than the total addressable market that we added MG when we launched. MG in 2021, where we said 17,000 patients in the U.S. This is more than the CIDP total addressable market of 12,000 patients. So this is a sizable opportunity. Now we know that there is a high sense of urgency to treat these patients. So the penetration will be fast and high. What we also know is the dosing for this patient is a CIDP dosing, so weekly use. So if you combine all of that, IMNM its own will be a multi-blockbuster opportunity.

Now if you add to that DM, DM, bigger number of patients proxy, we estimate that 40,000 patients diagnosed with DM in the U.S. But as we know, it is a heterogeneous disease, multiple mechanism of action can coexist and will be layered. So there is room for multiple players. And so this is a broader market that we would share. But this will be also a significant opportunity. So 20,000 plus 40,000 is 60,000 patients. This is actually the size for the people who have MG in mind, the total addressable market we have been speaking about is that and patients total addressable market. So this is the size of MG as we define it today.

And then we have to add something else that our panelists mentioned at the end of day 2, which is the biologic market expansion. And this is often something we forget, but systematically, think about MS when there was nothing and more treatment started to come into the market, more noise around optionality, more diagnosed patients coming in, the market grew Same for MG. We put MG on the map and now look at the number of players coming to the market, but also the number of patients being diagnosed and being put in the addressable market. Same for -- we believe this will be the same game for autoimmune myositis where the market itself additives defined today is going to expand. So if you bring that all together, this is an amazing opportunity to make a difference for patients. And this is why we haven't been waiting for approval to start getting ready. What impressed me when I joined argenx 6 months ago was the commercialization engine. What argenx has been able to do since they launched and were approved in MG 4.5 years ago is unbelievable. And there are a few strengths that this team has the commercialization team has. And this strength will be leveraged also for autoimmune myositis.

The first one is our patient support programs. You are in rare disease. These patients need a wide glove approach. And that's we offer. That's what we offer, and this is not going to change for autoimmune myositis. We are going to have this wide growth approach for them as well. We also need extremely strong market access capabilities. For each of our indications, more than 90% of the lives in the U.S. cover Vyvgart, and we are going to leverage that same engine of market access also for autoimmune myositis. We also have an amazing team in the field. MSL, our sales team, actively one provider mentioned to us, I don't only prescribe the molecule. I also prescribe the team behind the molecule. So people who work at argenx are amazing, and we are going to lose these people also to make sure that patients who need Vyvgart, if approved in autoimmune myositis will get it. So of course, we are going to augment this engine with some capabilities towards dermatologists and toward hematologies. This is important. So -- and that's what we have started to do, at least since a couple of years. We have engaged with autoimmune myositis patient advocacy groups, working about education, how important it is to make noise around it. We have been proactively engaged with payers to educate them about the disease so that they are not taken by surprise when we come with a positive trial if the data are positive, we have expanded our MSL team already since a while, and they've been engaged with 650 autoimmune myositis key opinion leaders across neurology, dermatology and rheumatology. And actually, we like market research. So we did a market research to ask them. So of all the MSL you engage within the industry, for auto myositis, which one do you prefer? Argenx came first. So this is great. It means that the quality we have seen in neurology is also seen in rheumatology and in dermatology.

We have also launched a disease education campaign, and we know how important this is because we want to make sure the market expands and that patients are aware that if they feel tired and weak muscle, maybe there is something that we trigger more diagnosis. And then we have planned the sales force expansion into rheumatology and dermatology once the data are positive. We are waiting for that. We can then press the button and make that happen. So all in all, we are getting ready for a successful launch because patients really need it. And if we can avoid as many patients as possible ending it in a wheelchair, it would make me and all my colleagues at argenx so happy.

So with no further ado, I'm going to hand it over back to Karen, our CEO, to close not the meeting because we still have Q&A, and I'm sure there will be questions knowing this audience. And to bring Karen back on stage.

Thank you, Sandrine. That was great. Thank you. Okay. So I want to close giving some of the key messages that you heard today and just recap and then make it link to Vision 2030. So what do we hear today? Number one, conviction in the biology. So you heard from Leentje, it is clear that autoantibodies are driving this disease, and Vyvgart is a targeted therapy that removes those autoantibodies. Number two, I think you heard Clari on the clinical data from Luc. So we're now Phase II data. We had -- in our Phase II study, I should say, we have -- we had strong data, in particular, statistical significance on the primary endpoint, the total population, statistical significance on IMNM and a clear trend or a clear signal in DM. Remember, there was less patients in DM. So we have strong conviction as we go into Phase III. Phase III study is twice as big, twice as long. So we have strong conviction in the potential for a positive outcome in the subtypes of IMNM and DM in the Phase III study.

And you heard from Sandrine, a very compelling commercial opportunity. We see both IMNM and DM individually as blockbuster or as Sandrine said, multi-blockbuster indications. So conviction in the biology clarity on the clinical data and a compelling commercial opportunity. So what's next for myositis. So in Q3, we'll turn over the data card, and we'll see the outcome of the Phase III data. What you heard today is that we have updated our strategy. So in the U.S. We do not plan to analyze and file the data on the total population. The plan is to analyze IMNM, on test and look at the data and based on the strength of the data, have a path to filing in IMNM. We plan to separately analyze the DM population based on the strength of the data, have a path to file for DM. PM, based on the fact that it enrolled in a similar way to Phase II in Phase III. We do not believe we have sufficient -- we will have sufficient data to be able to file.

So hopefully, that provides a clear path forward for iris based on the -- and the compelling opportunity that we have in M&M as well as DM. So with that being said, how does this link to Vision 2030 and the future that we are creating with argenx. As you all know, Vision 2030 is what is our engine for growth and being able to deliver growth in the short, mid and long term. Our goal is that we have 50,000 patients on Vyvgart by the end of the decade. The majority of that will be delivered by MG and CIDP, but myositis, if approved, IMNM and/or DM will also contribute meaningfully to that 50,000 patients. In terms of 10 labeled indications, we have MG, we have CIDP and ITP approved. With the data reading out in Q3, we have the potential to add 2 indications: IMNM and DM to our goal of 10 labeled indications by the end of the decade. And on our goal around 5 molecules in late-stage development by the end of the decade, we are well on track. So at the end of this year, we have our first data readout for Impasapprubat in MMN. That's our next molecule but beyond efgartigimod. That's an exciting moment for the company to start building beyond FcRn. But we have much more coming, and we're well on track to have 5 molecules in late-stage development by the end of the decade. Our goal as a company is not to be an FcRn company. It's to be an immunology innovator and a disruptor in the space. And so we're building the portfolio with the breadth and the depth to be able to deliver. They've got leadership over the long term with our next-generation molecules as well as a broad and deep portfolio beyond FcRn.

So with that, I'm going to close the presentation part of the meeting and bring to stage Beth, Sandrine, Luc and someone who haven't heard from yet today. Peter Ulrichts, our Chief Scientific Officer, come to the stage.

So the good news is we are right on track for Q&A. So we'll be about 30 minutes to go through Q&A, but there's also time afterwards, we have a reception, and so please come and find us.

Yatin Suneja from Guggenheim. And putting this wonderful presentation. So 2 for me. So the first one is, could you maybe talk about how well does IVIg work in IMNM and DM, what is the hypothesis that you would see a bit of a differentiation or differential effect in these 2 subtype, especially for FcRn mechanism, which tends to be a little bit more cleaner and more narrower. And then the second is more on the regulatory front. Any feedback or buy-in from the FDA on these 2 separate path that you are highlighting? And what would be the split of these to subtype in the Phase II study in the Phase III study?

So I suggest, actually, Peter, do you want to talk about the IVIg and IMNM and DM and also Sandrine, you can layer it in Luc, of course, to hear from the filing strategy? .

Yes. I think it's clear that IVIg does have an effect in dermatomyositis as it's approved there. IMNM as the panelists will confirm also is showing benefit in IMNM. On what the mechanism of action of IVIg is in these subsets, it's a bit unknown, whether it's linked to autoantibody reduction or complement inhibition or something else. So I think in IMNM, based on the Phase II data, which we have, I think we saw a very strong single which is definitely competitive as compared to what we see with IVIg in these patients. For DM, I think what we need to understand not only for IVIg, but also for the JAKTC inhibitors is how they will work in that spectrum of autoantibody present in DM. What we do know is that these statements are working. What we don't know yet is how good they're working for the individual subtypes in terms of [indiscernible]. I think that is something which we will learn in the future. and our data from ALKIVIA will help understanding that and will help also positioning the different mode of actions or maybe even show that there's room for combination treatments.

And Luc, the second one was on the regulatory front, feedback or buy-in on the strategy.

Yes. I mean, so this, as we said, we went through our Phase II data set to the agency, discussing the potential to break to designation. They looked at the data package. They picked up the IMNM results as being quite significant, also where the white space is in terms of available treatments and so they selected that one for break to designation. But of course, we discuss the whole package. And it is clear from that, that. And also from our sample size that we talked to has -- you saw the proportion. We see similar proportions in Phase III. So the inherent probability to IMNM is just higher. And they are very interested in the risk-benefit assessment of that. But if the data card is turned over and DM makes it, we evidently will also include that in our filing.

Yes. And maybe just to add, on the question of the engagements with the FDA and related to the subtypes. So yes, obviously, we're engaging with FDA on an ongoing basis, but we -- there is a path to approval for the subtypes based on the analysis.

Andy Chen from Wolfe Research. Just a question on the difference between IMNM and DM. So obviously, empirically, it looks like your data is better in M&M. But is it just -- but we also heard earlier from the experts today that IMNM is a more aggressive disease and doesn't that just make it harder to treat. So why is it that efficacy is now worse or is not better in DM? Is it just because of the sample size is smaller, so you saw maybe an unfavorable swing in the data, is it possible with a Phase III, we're going to see better data on DM just because it might be an easier to treat population.

Yes. I don't know, Karen, if you want to start and then Luc or vice versa.

So I think, in fact, it shows when the speed of enrollment shows that the IMNM as was already said, a very high unmet need and patients came in at times, we could still affect the disease. And that's, to us, very rewarding to see that us opening that door and actually allowing them to create such a benefit. So from my point of view, it's not an inherent more likely to or not between IMNM and DM. It's just we got a much higher influx allowing us to have a better assay sensitivity, if you will, of the trial. Now in the Phase III as was said, double the length, double the size. So even if it's at 30%, it's again going to be a significant sample size on its own. There is a reasonable likelihood that DM can come from a clear signal to a significant signal. It just lower than IMNM inherently.

Alex Thompson from Stifel. I guess again, on the primary endpoints and sort of thinking about the bar for the subsets, I think in the prepared remarks, you talked about a clear path for IMNM and sort of looking at the primary analysis on total TIS? For DM, is there as clear of a path there as you think about it, is it total TIS? Are there sort of the itality of the data? And what is the role of the Phase II data set when you're thinking about filing in DM?

For dermatomyositis, we also took the CDs. So there are multiple readouts we have that this isn't less weighted towards dermatomyositis, if you will, because the derm is only in the assessment of the extramuscular, yes, thank you, domains. So for me, the foundation of the path is the strength of the delta in the sample. And that is dependent on what's the variability in the Phase III that allows -- so is it lower or higher than in Phase II. And we will really only know that once we turn the data card. And that's why you say at least one it's clear because 60% or 2/3 of the sample in Phase III from IMNM, we feel that has a very robust chance of repeating what we saw in Phase II.

Yes. And maybe just to add, if this helps because I think this is an important point. There's no difference in the analysis strategy for IMNM versus DM nor the filing strategy. The only difference is there's more patients in the IMNM group than the DM group. That's the simplest way that I think about it.

Tazeen Ahmad from Bank of America. First of all, for hosting. Second, maybe this is for Karen. So since there's a lot of focus on you provided us a lot of color and also, I think the physician panel was helpful. So I think Dr. LaChance said that 80% of DM patients have muscle involvement. So do you have a sense of the type of patients that got enrolled that were DM that have that? Do you think that they match that 80% of patients who have the muscle involvement. And does that increase as a result of the chance of the portion of the study working, again, assuming that it's a smaller end of patients relative to IMNM, but do you think that as long as that portion of holes does not have a good chance of allowing the study that portion of the study to work?

This too -- so maybe I'll jump in and then Luc at a 2 things that give me confidence on that front. One is that the -- if you look at the baseline characteristics, the commonality across IMNM and DM in the inclusion criteria -- what you'll see in the baseline characteristics is the score of 120, which is the average severity of muscle weakness. And so we have patients from the patient cohort, they have that muscle weakness. So we should be able to see that. And -- sorry, go ahead.

No, I think to answer direct to your question, there's an inclusion criteria, which is demanding for a certain amount of muscle weakness. So I think it will be even more than the 80%. Actually, it will be 100%.

The other important point just to add to that, so there's the inclusion criteria. What's important that Luc pointed out is the significance of demonstrating impact on MMT8, which is the muscle component of the TIS score and that was -- and we saw that in Phase II. That's important because there is muscle weakness present in dermatomyositis. It's not just skin manifestations. And so seeing that significance of that clinical endpoint of MMT8, I think, is a good signal for DM.

David Nierengarten, Wedbush. I was curious on background with steroid use. Is there any differences in general patient benefit for steroids who -- patients with dermatomyositis versus IMNM and therefore, with the steroid taper effect as populations differently in the Phase III?

Maybe the want to talk about the difference in -- from a clinical perspective?

I think what happens is because IMNM is more refractory and you see how many patients were included they tend to have higher steroid use as compared to dermatomyositis, but these patients are entering in the trial, that means they are definitely refractory. So they would also have a significant steroid. There may be a small difference between the 2 -- but overall, I think the median steroid dose was 10 milligrams. And that's the same steroid median steroid dose we saw in IVIg study, which was only dermatomyositis. So I think there may be minor differences and perhaps a little bit more in IMNM or a little bit less in DM, but pretty much both would require steroid because these are refractory patients entering clinical trials.

And specifically linked to the trial, I think we have, of course, set of specific rules in terms of steroid use, stableness and then the tapering, which is identical between the subtypes. So I don't think it's affected there.

Sam Semenkow. So 2 questions for me. So for the M&M and DM subgroups in the Phase III, given we know that they're the same roughly enrollment as Phase II. Just to put a finer question on it, could you maybe speak to the powering that we have in each of these subgroups and then layering on top of that for the placebo arm, now that we have the steroid taper in the Phase III, does this give you more confidence that the DM subject could be positive?

Yes. So we're not going to actually discuss what the actual power is. We just are confident that it's robust enough to be able to complete the mission, which is bring Vyvgart to IMNM patients based on what we learned from the Phase II. Remember, this is still an open database. So I would like everybody to we cannot give answers that might buy us even in this late-stage data outcome. So...

And maybe I can just add something. We saw clear Signal and DM, and what you saw here of the percentage, I mean that was a relatively small population, and this is a heterogeneities. So to see a clear signal is meaningful. And now we have a bigger study, so I do think that you have to kind of think about that and where we'll have the power of the Phase II and the Phase III to kind of make that -- make a compelling case with the FDA once we see the data. Peter, do you -- no, I was going to say, Peter, maybe you want to talk about the steroid tapering.

Yes. On the state of paper, I think we have some precedent with recent trials in DM as well. I don't think it's a factor to the plaza the con for placebo and the powering.

This is Sarah on for Yaron at TD Cowen. Two quick questions from us. Can you share maybe how the TIS subcomponents effects are different between IMNM and DM? And was the overall TIS improvement similar for both subtypes? And then secondly, is there any known autoantibody involvement in skin similar to what you've been able to show in muscle, specifically for the MDA5 or NXP2 auto antibodies?

Yes. So as well -- so relevant and logical question. But for the same reason that I spoke about, we are not giving further details on the subtypes that are. So you see the total population, you saw the movement across all 6 domains, which is encouraging, but we have not -- or nor will we share subtype data at at this moment.

On your question on this is exactly the same metric in IMNM as well as DM. And on your question on skin involvement, in our DM subset in Phase II, we did recruit different types of patients having different types of autoantibody also including MDA5. When we turn the Phase III data card, that will be a sub-analysis. And of course, we will look into specific benefits in all of these different autoantibody patients.

Xian From UBS. Two, please. So just wondering the first question. So you mentioned your enrollment in Phase II also reflects the unmet need. But just wondering how much do you think that might also have the impact that you are the only 1 running the trial in IMNM versus on multiple other companies running trials on I'm just wondering whether that has any impact on how reliable or do you think maybe for DM is you might not be able to detect the true power of Vyvgart just because of the competition of enrollment and et cetera, et cetera. So that's the first question. And second one is, just wondering, is it fair to say that another major difference between Phase II, Phase III is the introduction -- other than a longer, bigger is also the introduction of steroid tapering. So just wondering how do you think that might affect the placebo arm. So just wondering, do you think the placebo arm with all the concomitant medications and start tapering, is that generally quite stable.

And on the first one, I mean, I think there's actually 2 questions there, it's like why do we think that there was a discrepancy in the enrollment. And then I think the powering one we've kind of discussed already, but maybe we want to talk about kind of what we think contributed to the speed at which IMNM enrolled, right, because there's different factors there.

Yes. In my mind, it was more about -- we had a fixed sample size and the file up much faster. And so the room for DM to come in was just so and even less, but I know Dr. Aggarwal as a hypothesis around that. It was just that we think yes, go ahead. I was going to say, I do think to keep it a perspective though, IMNM enrolled very quickly. DM enrolled quickly. I don't think we should take away from this that the DM was slow enrolling. Yes, PM was quite slow enrolling, but also we've been seeing that that's a shrinking part of the population. So I'm actually really pleased. If you look at the speed of how fast we were able to enroll IMNM and actually how fast we were able to enroll DM, so I think we have a good opportunity in both. The other thing I would just add is.

Unmet need, right? There's nothing available, as you said, there's nothing available on IMNM, and there is innovation available and DM, of course, still a lot of room for improvement there. And then the second is also the fact that there are neurologists who may be more frequently treating menu, and they would know Vyvgart well. .

Danielle Bongero from Truist. I have 2 questions as well. Understanding that you're not breaking out subgroup specific data. Maybe broadly speaking, can you just help us understand what our expectation should be around Vyvgart's ability to improve skin manifestations of DM. I believe IVIg clears rash any reason why we shouldn't expect an impact there? And then it sounds like you didn't enroll enough polymyositis patients to meet the regulatory threshold for approval by that subgroup? What is the minimum number of patients that you need to enroll in this subgroup for approval?

So Luc, why don't you take the second one? And then I was thinking about Dr. LaChance, maybe you could answer the first one on the skin manifestations. IVIg works very briefly for the skin in a lot of patients, and it has been very helpful for patients with refractory disease, again, sometimes the skin can be more treatment refractory even than muscle. So it's not uncommon for us need to layer therapies. But IVIg, we do use quite a bit for skin manifestations. And as was alluded to earlier, the role of autoantibodies in driving different manifestations of disease, including the skin is thought to be very high. So patho mechanistically, there -- it would make sense that we'll see the response that we're hopeful response to Vyvgart as well.

I just want to also add, if you see the extramuscular component improved significantly. And in dermatomyositis the extramuscular component, by and large, come from skin. So I think I would say, overall, it looks like the skin would improve.

With respect to PM, I mean, there is not a fixed sample size or percent, it's about they need to be able to figure out what is the actual risk benefit. And that depends on the effect size, a major effect in a small number of patients can be enough and the safety profile. Now in that particular case, safety, we know with Vyvgart is not an issue, but it's about can we reliably measure the benefit.

[indiscernible] JP Morgan. I had a question on -- do you have any estimates in terms of the prevalence of negative IMNM patients? And did you see any differential response in Phase II amongst this subgroup? And if so, is that similar in Phase III in terms of proportion of enrollment. Also on ASIS, just to clarify, are you enrolling ASIS patients across the 3 subgroups in Phase II? Was this concentrated in PM? And did you see a differential response across ASIS patients in the Phase II study?

Peter, do you want to talk about these 2?

Yes. I think on your set of negativity, approximately 20% is seronegative. In the trial, it was a little bit less. We -- and it's a bit the same story as in myasthenia, where there is a fraction of seronegative patients, and we discussed it before in the panel whether it's an asset or an identified autoantibody that remains to be seen. I think the data sets in seronegative IMNM in Phase II is relatively small, but we did see these responses there as well. And then on ASIS, I think there, that was predominantly in the PM bucket, again, data set is a bit too small to give a good answer to your question there.

If you can just come on that.

Sorry. This is Cassie for Luca Issi from RBC Capital Markets. Luc, can I ask you to talk about that again? You mentioned that the primary analysis is now updated to evaluate each subtype, can you expand on that? I appreciate not much you can comment today on powering, but are you splitting the offer between IMNM and DM? If so, should we assume that you're splitting the alpha equally between the 2 subtypes, meaning that you need to hit p smaller than 0.025 in order for the trial to be successful. Any color very much appreciated. And then quickly related to that, is this analysis hierarchical, meaning that you have to formally successful trial in DM first before we can hit IMNM or reverse, et cetera?

Thanks for posing it to me, but they are somebody much more qualified to talk about as [indiscernible], Head of Development.

Formally statistician. So I think that's what brings it to me, sir. We usually do not disclose that much detail on the statistical analysis plan of home. But as Karen and Luc and Beth already explained, we have based on an ongoing dialogue and on the learnings, set up a bat separately for IMNM and DM for success. And we have evaluated what matters for each population, how we evaluate hierarchically the different end points, taking into account the heterogeneity of the disease. And for example, that skin matters, speed of onset matters, the muscle component in setting up our strategy.

Akash at Jefferies. So I just want to make sure I understand this. Like did you want to make -- this is kind of my read, you would not want to split the trial separately if you had your way with the FDA because I can't help but think, like you look at the standard error assumptions, I'm assuming it's probably high teens TIS on IMNM. Probably DM is probably like, let's say, 10, 11 it would make more sense for you to actually have the study combined. And from a powering perspective, it seems it was more at the FDA, the hest for you to actually look at this study separately. Is that the right assumption here? I just want to make sure I'm interpreting that correctly?

So -- and that's why I wanted to bring us back to where we started originally with the basket study, where we bring 3 indications in and the sample size was indeed powered on this over the overall. Then -- but that was on the assumption we would about equally enroll. Remember, there was a question, would you have 38% of each during that. It turns out that wasn't the case. So it was 2/3 basically 60 30, 10. And so that's the data we had in hand. So when we went to the agency with the data package and as to break through designation given all the unmet need, et cetera, they focused on IMNM and said, this is where we think you could make the biggest difference. This is why we assign brick designation to this. If we then take that with where our Phase III is, then we start to say, our fastest surest path to bring to these IMNM patients Vyvgart is to focus and indeed split that study up where IMNM becomes -- and it's not first because then I know what you're going to ask, it becomes its own study within the study, and DM becomes its own part. But if you have 60% versus 30% a priori, our ability to get a positive outcome is going to be higher in M&M. So it was an outcome of the dialogue our own insights and then saying, okay, how do we match this up with speed to patients?

Yes. And I think that final point is really important. If we take a step back, think about what we heard from patients. I mean it was compelling actually that we heard in IMNM, within 3 months, these patients are in wheelchairs. I mean, time is muscle. There is nothing approved. So when we looked at the data and of course, when we engage with the regulatory agencies, the focus is we have this data set on IMNM. We have this opportunity. How can we move as fast as possible to get -- to turn over the data card and get this therapy to patients. And I think what we've been able to do is define a strategy that achieves that leaves a good path forward for DM based on the clinical data that we saw in Phase II. And and allows us over time in the same way to have an MG to be able to build and transform this market. So I think the team has done actually an incredible job of being able to maximize speed as well as breadth and so that we can have leadership in the market.

Okay. That makes sense. And by the way, my read on that is actually, it seemed like the FDA wanted that more than you did, which I would argue as a bullish thing for DM, not a bear thing, but two cents. Okay. So then going to the seronegative example and Karen, you alluded to this before, how can you take -- let's say you generate somewhat of a robust, maybe it's barely stat sig or it misses in DM. How can you combine that data set with another trial in DM? Like what would the timelines be if, let's say, there's a border line result in that population, given we already do have a precedent with seronegative.

Do we want to let -- to answer again.

So we will look at the data. First of all, we have strong conviction in the Phase II data, and we will look at the Phase III data, what the data will tell us in that regard. We are a company that makes decisions based on data and based on the science. So we will indeed look at how can we set up the best possible trial design indeed learning from the data and how can we leverage that data in that trial design in the path forward. how that exactly will look will depend at that moment in time. And if and when we ever have to do that in that scenario. But yes, if we are in that scenario, we will incorporate a strategy that leverages innovative trial design and the data.

Yes. Prioritizing speed.

On a separate topic, sorry. Peter, we were talking about the on it. Like when we look at the ROYVAN study with BEPO and the steroid protocol for people who don't -- who deviate from the protocol, there's a certain imputation penalty that occurs, which actually help them if you look at their trial. Can you comment about your protocol? And how do you deal with patients who actually deviate from your stereo tapering? And then -- what have you seen from a blinded basis about adherence to your steroid tapering protocol in Phase III?

I think it's a similar penalty and the deans is good. So obviously, it's an element which we're controlling or at least look into very, very tightly.

It's Rajan Sharma from Goldman Sachs. Just on DM and not to kind of labor the point, but just a clarity, if you show comparable efficacy signal in the Phase III that you showed in Phase II. Is that enough to hit stat sig? Or is it enough for a regulatory pathway? And then secondly, on IMNM, can you just maybe talk about what you think current diagnosis rates are there? And where you think that can go? I think one of the doctors talked about the job that you've done in myasthenia in terms of growing diagnosis and patient awareness.

Do you want to answer the first one about the benefit -- and then maybe actually, Dr. Seth, you could answer the one on diagnosis. And if there's anything, Sandrine, you want to layer on a market expansion?

Yes. So on the first one, actually, as Luc pointed out, we're still in the process of preparing for a data readout and not disclosing what the data in Phase II look like. At this moment, actually, because of where we are in the trial design, it will be significant or not, right? So we will have to look at what the data tell us. And then based on that determine what the appropriate next steps will be. And also maybe reiterating also the point on the innovative trial design, right? We would not be here today to actually have this conversation if we didn't start based on the biology and with speed as a mission in that regard. So concluding on that, I would say we have a very strong conviction in our Phase II trial data. We had start on IMNM. We had a clear signal on DM, and we will now prepare for database lock in a record center and then wait what the data will tell us what appropriate next steps will be and then execute with speed.

And that was a great question regarding the diagnosis for myositis and immune metacritizing myopathy. I think one of the things there has been a lot of education around this. in myasthenia, I did not -- at my center, we -- I did not expect to see so much myasthenia, and they really after the Vyvgart trial results came out, patients started showing up. And the same thing, I think, has happened with IMNM. And to a certain extent, we set up a myocyte center at Northwestern and patients have been coming. And so I tend to see like 1 to 2 at least news every 2-ish weeks to 3 weeks of immune-mediated necrotizing myopathy. And so there are a lot of primary care providers that are now preferring because of education.

And that's why we believe the market expansion is not something that will just happen -- we see it happening when you have trials when you make noise around it. And that's why in our launch preparation. We already spent time developing disease state education. It's not about a brand. It's about what is IMNM, what is DM and if you start feeling muscle weakness, what does it mean? Working with patient advocacy group started 2 years ago. We just don't come and then leave. We are there to stay until we can really make a difference for patients. So we are in together to shape the market and expand the market in terms of number of patients who can benefit from a treatment.

So I think we have time for one more question.

This is Tracy on for Leland at Oppenheimer. A couple of questions from us. First, given that TIS incorporates multiple core measures, are there any individual components that you're most focused on for Phase III. And would any of those drive your label strategy if TIS were positive, but heterogeneous. And two, for IMNM, given the time of muscle message, how do you expect prescribers to position Efgart-relative to IVIg primarily as a option for those who are dependent or in earlier-line settings.

Yes. Maybe I can take the first one and then Sandrine, if you want to touch on that. So from my perspective, I mean, the TIS is a composite measure. I mentioned earlier, one really important component is the MMT8 because that's the component that focuses on muscle. And it's called myositis, muscle weakness is the hallmark feature across all of the different subtypes. And you've heard from our KOLs here, but that's often what patients present with. So for me, I think focusing, of course, on the total, but MMT8 is going to be a really important one to watch out for. And then in terms of how you think...

Yes, in IMNM, basically, IVIg is actually not approved for IMNM. So when you look at market research, you've heard that I have been looking at quite a lot. And you can discuss with your providers here during the drink. Most of the providers said, if the data reflects what we have seen in the Phase II, I mean, they would be ready to really start as of first line after using some more series, et cetera, directly with Vyvgart. We will have to see the data, and every prescriber is different. But for sure, this will be the first and only approved treatment available.

Thank you. That's all the time we have for Q&A. But we will be around, and so please find us with additional questions. And our excellent KOLs, thank you. They will also be available during the Q&A if you want to continue to get their perspective. Thank you.

Good afternoon, everyone, and thank you for joining. My name is Rajan Sharma European pharma and biotech analyst here at Goldman Sachs. Very pleased to have argenx with us this afternoon for the last fireside of the day. And we've actually got 2 speakers. We're lucky to have two seekers because today, we've got Karl Gubitz, CFO will probably know and then we also have Arian Namen, who is Head of Corporate Development. Maybe just to kick off, Aryan, given that you probably someone that hasn't had as much time with investors, relative to call. Maybe if you could just give a brief introduction of your role yourself and how that's evolved over the years at Argenx.

Yes. No, happy to do so and happy to be here. So my role at Argenx is indeed that I had corporate development and strategy. I've been with the company since 2015. So I joined Argenx when it was just 30 people at the time with a responsibility on our business development deal making, I ultimately evolve my role in a broader corporate development responsibility in the sedan leadership team. So my team focuses on really everything related to third parties and dealmaking. So the business development, the partnerships, the alliances are sourcing with suppliers and corporate strategy as a whole.

So supporting the organization, which countries do we enter, which indications do we prioritize does the overall portfolio make sense? Which molecule do we take into what indication basically?

We'll definitely dive into some details that. But maybe just to start, maybe if we could just start on VYVGART commercials. You obviously had a very solid start to the year, 60% year-on-year growth in Q1. But competition in myasthenia in particular, is stepping up. We've had a couple of recent approvals and potentially 1 coming. Just in that context, how should we think about the growth outlook for firstly, in myasthenia gravis in the near to midterm?

Thank you, Rajan. Yes, MG still has a lot of growth ahead of it. We are now 17 quarters into the launch, but the growth is not slowing down. All the share of biologics, that's Webcor, all the other FcRns, C5s and so forth is only about 20% of a total market. 80% of the market is still on the orals, Mestinon steroids immune suppressants, there's a lot of growth into the earlier lines. And VYVGART is not only the biggest of innovators in that 20% share of biologics, it's also driving the growth because if you ask a doc 4 out of 5 docs will say, you start with Wipro -- and now, of course, we also have a CRO negative, which gives us the broadest possible and able to help with that growth, but at 11,000 patients to take the total addressable market, if you add 0 negative, moving into the earlier lines and also ocular, which we have a data, but not yet the approval to 60,000 patients. .

And one of our key growth drivers continues to be the PFS for self-injection because of a convenience of a 22-second injection, which none of our competitors can do of course, is also driving the growth. So a lot of growth looking forward in MG. And on CIDP, if I can quickly add -- we are in the early innings of a launch there. We still at the bottom of that patient funnel in about 12,000 patients, which are not adequately addressed with standard of care. Slowly over time, we can move earlier line. but both CIDP and MG continues to grow in all markets. So I think we're set for growth over the rest of the year.

And in terms of maybe just to double down on MG for a moment, you said 20% biologic penetration in the indication. Where do you think that can go? And are there any specific analogs that you look to as you think about how a biologic?

It's a great question. Of course, we also debated internally. And the short answer is I don't know what the share of biologics will be in a few years, but it should be multiples of 20%. And it is Webcor who's driving that biologic growth, as I said earlier, because of our efficacy, safety and tolerability and the patient convenience. So I think that we can look forward to expanding that biological growth numbers significantly .

And then just thinking about CRA negative, you're obviously clear that it adds a reasonably significant number of patients. But how should we think about the ramp there? I think at Q1, you talked about being ready to launch there, whereas in previous launches, you've talked to maybe 2 or 3 quarters to get reimbursement in place. Is it different to see your negative?

CRA negative is a little bit different. But typically, when you add a new indication, you have to go back to the payers to do a negotiation. Of course, this is not necessarily here because GMG is on the label, but the payers need to change the way formularies to say that the actually requirement to do a test and to send in the test but cannot be removed. But it's actually removing a bureaucracy or a process at the physician's office. And I think that, of course, is very helpful for them.

Remember that the triple negative -- the negative is 3 subsets and half of that patient population is the triple negatives, which has no options available today. So there are many patients waiting. But in terms of a trajectory of growth 17 quarters in, we continue to show growth quarter-after-quarter and to maintain that growth, you need new innovation. So this is the new innovation which is going to drive growth for this year in mg the 0 negative plus the PFS, which is continuing to drive growth.

Okay. And then obviously, we have the ocular potential as well we've seen that you've hit on the trial. Is that a seamless scenario where it could be a relatively quick uptake?

Yes. On ocular, is an important part of -- I already mentioned our strategy is to be the first-line biologic and to move earlier line. Ocular is earlier lines, if you like. 85% of ocular patients generalize into generalized myasthenia gravis. We think we're going to add around 7,000 patients there, and the unmet need is clear. At the recent medical conference at AAN when we presented the data, it was standing room only. And this is because the unmet need calls out for a new tool in the toolbox to treat these patients. .

And I think that we don't have approval yet from the FDA, of course. But what we're hoping is to change GMG into MG, and that will get you to the 60,000 total addressable market.

And I think the unmet need is very often underestimated in ocular. I think like this short hand has sometimes wrongly been that Ocular is less severe right, because you don't have these generalized symptoms yet. But just imagine how debilitating ocular on its own can still be, I mean, these patients with the double vision they have they cannot work on a computer. They cannot drive a car. It's hard to actually walk anywhere without falling, right? I mean -- so it's overall not a version that is less severe. It's just concentrated in the eye at that stage. And it is indeed typically earlier in the disease manifestation.

Okay. And then maybe just quickly touching on CIDP. Do you have a sense of where penetration is for VYVGART got right now? And you talked about kind of moving to earlier lines. And how do you actually not that do you need more clinical data? Or is it more of a case of physicians becoming more familiar with the product profile?

Yes. Moving earlier line, of course, is, let's call it, a little bit more aspirational. We're going to get there over time because where we are now is still early in the launch. If you just look at the patient numbers, 42,000 patients diagnosed in the U.S., 24,000 of them are treated, half of them not adequately treated with standard of care. What we continue to do is to educate the physicians and to activate the patients.

You'll see in the U.S. all the DTC, the television campaigns because what really helps to get the patient on VYVGART is if a patient go to the dock and ask a dock is VYVGART right for me. So we need to do a lot more work in terms of patient activation, physician education and then over time, we can increase the usage of it. But we're still early in the launch and the penetration is relatively low.

Maybe kind of moving to BD and then potentially M&A. Could you maybe just outline what sort of assets are potentially of interest to argenx. You probably -- I mean, you've done a few smaller deals, whether that's for technology platforms or formulation? And what was the rationale behind those?

I think partnership has really been in the DNA of Argenx right from the start. Actually, 1 of the cultural pillars of the company has been what we call co-creation. -- where we work together with our partners, either a technology partner or an academic partner, and that's how we've been able to create and design the molecules that we have in a differentiated way. And we actually consistently do that. So in our IIP, we do these business development licensing deals in close collaboration with the scientific team identifying the novel biology.

But there is actually not any program in Argenx that get started without some form of partnership at that from day 1. And we do, I think, a multitude of these deals per year. And you've seen if you track carefully the early-stage pipeline, we've systematically added to that early-stage pipeline building up, let's say, the innovation engine for the future. What I think has changed with the company turning profitable is the means to build on that playbook, but also apply it to later-stage opportunities. So what are we looking for? We're looking for opportunities that still fit the Argenx innovation playbook.

So we're looking for novel target biology, first-in-class opportunities. We're looking for opportunities where we can bring our pipeline in a product execution. And we're looking for that in context of neuromuscular and I&I. None of that, I think, by any means, is surprising. I think from a stage point of view, we're looking for opportunities that are IND minus 12 months or a preclinical asset or IND plus 12 months, maybe a Phase II asset -- it could be later if it's the right fit. I don't think that these rules are dogmatic in any way, but just to give you some color.

So at the beginning of the year, you saw us signed this option to acquire Ten Security, which is a Japanese biotech company. They have an antibody molecule against a novel target fn14 -- we believe that, that target biology has applications in multiple muscle wasting disorder. So we can apply our playbook there. It's an option deal. So we actually create a way for us to generate data together based on which argenix can decide to bring it in. And it's an incredibly strong antibody actually the tense -- for those of you that don't know, it's a spinout company out of Astellas. I mean that molecule was actually discovered in the Astellas discovery. So I'm just highlighting it because it's just a good example of what we've been doing. But there's other shapes and forms that potentially could fit.

Okay. And where do you think that you add value as a partner? Is it on the development? Because obviously, Visa's been pretty successful. It's been tested across multiple indications. You've been successful in most of them. Or is it as a commercial engine where, again, you've been pretty successful at commercializing the drug?

Yes. I think it can be both. So clearly, if it's something that fits our commercial organization, there's a way for us to add value. I think from a development execution pipeline in a product there, so there's a way to add value for the earlier stage program on the antibody engineering, there's a way to add value. I think 1 of the precoat is that we have to add value to the deal, right? We cannot only be a financial tool -- in that, we also need to bring capabilities, I think, to these assets that basically allow to either broaden or accelerate the opportunity that the biotech company otherwise would have been able to do.

Okay. And how do you think about capital allocation there? I mean not just from a balance sheet perspective, but then I guess, falls from a P&L perspective because if you're bringing things in, there's an R&D cost that comes with that, are you sort of holding back some of the internal spend in the anticipation that there'll be something external coming?

I think the strength of Webcor is it really is the type of company type of asset which builds companies. If you look at the scale of our revenue, even now and with a lot of growth, as I said, ahead of us, you already see the revenue falling through to profitability. That said, we have a unique opportunity to build the company for the longer run. We are going to invest in building durable growth now. Should give us that growth into the next decade. But after that, we're going to have a large base and to build durable revenues on top of that, you need to invest in innovation now.

And that is what Arion is doing now and what is the strategy of the company. I think that, as I said, we've got growth can afford, but we can do both. But the priority, number one, of course, is revenue growth, and that is where the dollars go first.

Okay. And maybe just on that point of sort of revenue growth dropping down through the P&L, how should we think about that on a forward basis? There's obviously some confusion within the market on the OpEx venture for '26. How do you think that going forward? And do you think the market is in the right place now?

Yes. I mean we were clear at the beginning of the year with the OpEx growth year-over-year and with this combined R&D and SG&A should be around 30%, that should get you to around $3.5 billion on a full year basis. So we wanted to put that market out there. At the end of Q1, we made a $400 million operating profit, which is an operating margin of 30%. We don't want to give targets out there in terms of operating margin because we don't want to box ourselves in. We want to chase the novel biology, as I said earlier on. But over time, of course, we think that we can provide operator -- and we will provide operating leverage. And so you can see that margin improving over time. .

Okay. And then maybe just 1 time, just moving on to pipeline readouts. It's obviously a relatively busy second half of the year. Lots of focus on my site. I'm conscious that you have the event in a couple of weeks. But could you just kind of walk us through the trial there, what population you're studying and how to think about the sort of respective commercial opportunities in those subtypes.

Every site study readout registrational study will be in Q3. In a couple of weeks, we have an R&D day on my side this. It will also be webcast, so please join us. It is a basket study across 3 subsets. dermo myositis, IMNM, immunonemediated myositis and also polymic -- in terms of -- I won't get into all the details here. I think the joint R&D Day. But there's a path to get all the subsets or 1 or 2 of these subsets, it really depends on the data and it depends on the FDA, of course.

The unmet need surely will also play a role. In terms of a commercial opportunity, let's start with IMNM because that's 20,000 patients, and it's a complete white space, but this is probably the best example in the myositis of being a prototype argenx indication, strong biology rationale and clear unmet need. If you take that 20,000 patients with no treatment options, I think we have an opportunity to very quickly transform the lives of those patients.

Very excited about that commercial opportunity. The bigger driver, if you like, is dermo myositis 40,000 patients. But of course, it's -- there will be more competition there. Ajacc2from Roivant, repo, will launch in September this year. It's an oral -- but of course, it's a JAK, which comes to a certain safety considerations. But at the end of the day, dermomystitis is a very heterogeneous disease. So I think over time, each innovator will find its place in that indication and VYVGART also be very excited there. So I think that more to come on the R&D Day. Another Phase III data in Q3, lots to be excited about.

Okay. And maybe just thinking on the OpEx point, it's kind of related here, just assuming that you kind of get the label in all 3 indications, how should we think about that incremental launch costs that come with that because there'll obviously be a new physician group that you'll be targeting?

Yes. So it is -- I mean, of course, argenx playbook is if we launch, we play to win. You've seen that from MG launch. You've seen that from the CIDP launch, and we will play to win. We will put in a field force for rheumatology. Part of my sites is prescribed by Neros, where we already have strong relationships and established capabilities, but we will need a rheumatology field force. We will look at what patient activation strategies which we will put in place.

But because the platform is already in place, I think the launch will be very profitable in terms of P&L. It will not be a drag in operating margin. It will actually support the operating margin. And just to put a sense of scale out there, we launched MG in the U.S. very successfully with 70 reps, 7 0. Just to give you an indication of a size you need for an orphan type of indication in the U.S.

That's super helpful. And then maybe just on the data itself. So we saw the Phase III data, it looked pretty encouraging. We don't know what the subtype split was in that. Is it fair to assume that there was a similar level of efficacy across all of these subtypes.

I mean we didn't provide all the detail, of course. But the only thing I will say is that at the end of Phase II, we had the option to not to continue in 1 or 2 of 3 subsets and we made the decision to continue with all 3. And we will, of course, now get the data in a few months of Phase III data. .

Okay. Perfect. And then maybe just switching to empathy probe as well, which I guess kind of fits with the extended innovation piece as well. How should we think about the commercial opportunity there in the initial indication of MMN?

Yes. MMN is I think it's the kind of indication where, first of all, like in CIDP with discard, there hasn't been innovation in that indication for decades, right? The only available option for those patients is IVIG. But what we've said is that there is about 12,500 patients in the core markets. We think about 6,000 of those in the United States. So that's, I think, the direction to think about. What is also important about -- to note about MMN and its unmet need is that we know that the MMN patients are actually the single highest consumers of IVIG. They tend to use a lot of IVIG, which I think is a testament to the level of need that exists in that patient population.

In terms of a broader context, if I can just add, the bare case on Argenx is that we are -- it's a single asset concentration risk and this is why IMPA and the MMN data, which we'll read out in Q4 is so important for us to show you what we're doing with VYVGART repeatable and scalable because an EMP is currently in 2 Phase IIIs and more indications to come. .

Okay. On that point, how much how much of important sort of readout is in passion in the sense that it de-risks put for you internally? And then is it a scenario similar to VYVGART once you have confidence in the profile that you then explore multiple indications.

Well, I think we're already executing that strategy, right? I think we designed a very strong molecule with Empire. It's highly differentiated in its molecular design. We think C2 is a great target to intervene in the complement system and the intersection of the classical and the lectin pathway. So it has this pipeline and a product potential. So MG and CIDP are leading the way. We've been there with DGF, but we're -- I think we're not done evaluating new indications for this biology.

And then eventually, is that something that you can foresee, again, kind of extending that they've got sort of playbook where you have multiple formulations.

Yes. I think the presentation playbook that we had for VYVGART would also apply to Empa but probably in an accelerated way relative to VYVGART.

Okay. Makes sense. And then you're also exploring the asset in -- how should we think about that coexisting with VYVGART? Is this a combination approach? Or is there a subset of patients that don't respond on VYVGART they need an alternative?

Yes. So we made a couple of important choices there. So first of all, we didn't subordinate our Empire development to VYVGART. So it's not fifthard failures in the EMPA trial. Actually, our strategy is to develop Empire for the broadest possible label, and we will let the data speak on how to think about that. We do know that there it's likely that these molecules target different biology to a certain extent.

In CIDP, it is characterized that IgMs also play a role IGM activates complement. VYVGART would -- biologically, it would not impact an IgM. So could you see that biology is part of the rationale of patients that don't respond on VYVGART it could be. And would these patients potentially have a right to respond to Empire, I think biologically, the answer would be yes. But we're putting that through the test. And basically, what we're doing on the co-positioning is we're generating then we will make a data-driven decision on what approach is based on the label, based on the data sets. We would be the only player in this market that has multiple modes of action. So we are, I think, in a strong position to continue to build out and generate a return on our investments in CIDP.

Makes sense. And then thinking a little bit deeper into the pipeline, you've obviously got a couple of next-generation SCRN assets. Maybe if you think with your sort of thinking about portfolio strategy and how did those exist? And is this the case of wait for the data to mature and then you make a decision on which you take forward?

Yes. I think portfolio is a very important work in that context. So I -- what we are trying to achieve on the next generation is to move our FcRn leadership with VYVGART into potentially a decade-long strategy. So we have -- from that, we created multiple next-generation molecules. And these have differentiated profiles. So we've been public on the profile of argenx 213 -- it's a longer-acting FcRn. It completed early-stage studies. It's ready for late-stage studies -- then we have argenx 124, where we have not been public on its design and its mode of action.

But what we can say is that it's not just another 213, right? It's a different molecule. It's a different profile. That is currently going through Phase I what does that optionality allow us to do, right? It allows us to think about life cycle for VYVGART in a way that still elevated, but it potentially also gives us the cation pipeline even beyond, let's say, the current set of indications. And we do know that there is more evidence being generated for anti-FcRn. There is a multitude of IgG-driven diseases in which we haven't explored yet. So we're creating this portfolio. And that's the second wave in this portfolio. I think at JPMorgan, and Tim also highlighted for the first time I think the third way is on how we think about that with a potential oral formulation in FcRn as well.

Okay. And in terms of time lines, you talked about 213, we know a little bit more about that. Is that potentially ready to go to Phase III? And can you be a bit more aggressive in terms of time lines, given you have the capital and you have the understanding of the mechanism.

I think that is exactly right. It's potentially ready to go to Phase III. It's really about what is the right plan. How to move that forward in the fastest possible way. In addition to that, the 124 data is not far out. We will see that in the second half of this year, and that will really, I think, give us the information to say which molecule is best positioned where, at what pace. So we're doing, let's say, all that scenario, strategic analysis as we speak.

Okay. And maybe just on the point of sort of there are more IgG-mediated diseases that you could target not just with VYVGART, but also with the next-generation assets -- how should we think about pricing? Because you've got Shogan coming next year, which is a potentially larger indication, you also exploring grades disease, which is a much larger indication. So can you maintain sort of orphan-like pricing as you expand into those indications?

Yes. If you think -- if you -- I mean, cogens a very big indication, more than 300,000 patients. But if you think about where the drug might work probably more in a moderate to severe subset of that, which gets you more to an MG like opportunity in terms of patient numbers. So I think, yes, you are right. As we add on more indications, pricing pressure will come surely, -- and maybe we need to adapt our price. But think of that as a very slow decline more than offset with incremental patients over time. .

Okay. Yes, I'm just kind of thinking about the strategy that Alexion or Astra had as they shifted from Soliris to Atomos and there was obviously a price incentive to do that. Is that something that may be rational?

That may be something -- yes, I think, as Aryan said, we want to have multiple next-gen FcRns. One will be life cycle management, and we can look at playbooks we or many successful playbooks out there. [indiscernible] is to automate surely is 1 of them, but then to have a second FCR at a different price point, possibly lower price point, maybe broader indications, we'll see. I think that will be all important aspects to consider. .

Okay. And just on 14 time line, should we expect an update there this year?

Well, we'll have the data this year, allowing us to make that portfolio level strategy decision-making -- to what extent we will communicate that this year. I'm looking at our IR.

We're going to be light and communication. .

I think that's exactly right. I mean there's -- I think in this very competitive environment, we will really want to maximize our position, and we will want to go as fast as we can and then do the communication in a very deliberate and strategic way.

Okay. Well, let's move on before you get in trouble. Maybe on systemic fluorites -- there's obviously a Phase II data readout coming second half of the year. What are you looking to learn from that? And how quickly could you then move to a registrational study? Or would this be 1 of those sort of seamless Phase II to Phase III that you've employed in the past?

I think scleroderma is an indication of a similar size as graphs where there's tremendous unmet need. There is really not that much that works the approved drugs are typically confined to the lung setting and more systemic settings or manifestations of the disease are really lacking treatment options. I think the autoantibodies are well characterized in this biology as a potential driver of the disease. That's really what we're putting to the test in Phase II. Can you intervene, can you see the kind of effect that justifies moving that forward? Can you intervene early enough to have a real benefit.

Okay. And then maybe in the last minute, I think there's building interest on the IGA sweeper. Can you maybe again just talk to the differentiation of that asset relative to everything else that's going on in that space? And maybe if I could ask about time lines there as well.

Yes. That molecule is -- it's a precision tool and it specifically targets IgA and what it does, it reduces IgA deep and fast -- so ultimately, we will roll out an indication development plan across multiple IgA driven diseases. We've communicated IgA nephropathy as the first indication. It's a pretty obvious one. It's also a competitive one. So we have to show, I think, those benefits in our clinical trial approach, where we have to show the benefit of the fast onset of action we have to show the benefit of the depth of the reduction because that's really, I think, what justifies the positioning of that molecule in this competitive treatment paradigm.

Okay. Perfect. I think we're just perfectly at time. So Ari and Karl, thank you so much.

Thank you, and thank you all for listening. Thank you.

Hello, and welcome back to the Bank of America Healthcare Conference. I'm Tazeen Ahmad. I'm one of the biotech analysts here at the bank. Our next presenting company is argenx. Sitting up here on stage with me is the new CEO, Karen Massey, congratulations, Karen, on the recent promotion. We're going to be spending time, I think, focused a little bit on the pipeline because there's a lot going on.

But maybe we can start off by talking about what your vision is for the company now that you're helming all the major decisions and how you think about strategy going forward?

Yes. Thank you so much. It's great to be here and a great conference. And I appreciate the opportunity. I mean I would say we have laid out our growth strategy for argenx, and that's Vision 2030. And so that gets us to 50,000 patients by the end of the decade, 10 labeled indications and 5 molecules in late-stage development. So we have -- I would say, we've had that plan in place, and we continue to execute on that plan. But as I think about my strategy and where we want to take argenx over the decade even beyond that. The vision for argenx has always been to be an immunology innovation company.

And so the first leg of that was building Vive VYVGART and establishing VYVGART. And we've -- and I think we've demonstrated the ability to do that. We want to continue that leadership in FcRn. So the first leg of the next part of the strategy is extending our FcRn leadership for decades to come. So we have 2 next-generation FcRns, and we're investing in an oral. So that's a big part of the vision for the company. But the second part is how do we also build a non-FcRn portfolio that is as meaningfully contributing to argenx as the FcRn portfolio. And that's really all about hopefully, what we can talk about today is the pipeline beyond VYVGART.

Okay. So since you mentioned them, let's maybe spend a couple of minutes on those next-generation assets that you're looking at for the gMG and CIDP indications as well as the oral FcRn. So -- until recently, you were heading up the commercial organization. So you can talk to this in real time. What do you think theoretically would be the benefit of, let's say, having an oral FcRn versus the various different methods that you have of delivery now, everything from IV to Hytrulo to prefilled syringe?

Yes. I mean, our strategy from the beginning with VYVGART and we'll continue with FcRn is that we want to transform these diseases that have significant unmet need. And with VYVGART, what we can -- we believe we can deliver in MG, what we're seeing we deliver also in CIDP is really strong efficacy, but importantly, safety across the broad indications. And then as you said, the convenience for patients. So we launched with the infusion, we brought subcutaneous and then prefilled syringe. Taking that playbook across all of the indications allows us to start to think about patients being treated earlier in their disease. So we're really expanding these indications, expanding these markets.

It's a big part of our strategy and will be a big part of our strategy for future indications. And the oral helps us to do that, so -- as well as our next gen. So 2 on 3, one of the next-gen FcRns moves to every 4-week dosing. So it's a step forward in convenience. And potentially with the oral, you can imagine that's another step forward in convenience, but still maintaining that efficacy and safety profile of FcRn. When you think about FcRn from an MOA, we know that there are many, many indications beyond what we already have approved in MG, CIDP and ITP.

And so we think by having multiple next-generation options, we have the opportunity, yes, to provide more convenience in the indications that will already be approved in, but we can also start to continue to push the boundaries of the biology of FcRn and even further expand those indications beyond.

Yes. So it seems though that you've done a good job of moving patients into front line. I remember, I think our first version of the model when the drug first launched had a much lower peak sales penetration. And I think part of the reason for the constant revision upward is that the company has been able to move higher in the lines of therapy. So as you think about in a world where, let's say, auto-injectors are much more commonly used because of, let's say, the GLP-1s, the company is developing an auto-injector pen. So as you think about the incremental benefit from moving to a prefilled syringe to an auto-injector to an oral, how much of a meaningful impact do you think you're going to be seeing with each of those iterations?

I mean I think for each of these innovations, we do see it as a step forward and driving the majority of our growth. I mean if you think about the step that we took going from subcutaneous to prefilled syringe. And as you said, they continually increasing the revenue and the projections, a lot of that's being driven by prefilled syringe because what you see is that we've been able to expand the prescriber base significantly beyond where we thought it would be when we launched VYVGART significantly expand the addressable market because of the simplicity of being able to use a prefilled syringe at home rather than having to go into -- for an infusion.

So it is a step forward. I think the auto-injector is less of a step change because the big shift was being going from HCP administered to patient administered with the prefilled syringe the auto-injector will still -- assuming approval and we get through the regulatory framework will still be patient administered. It helps because it's easier to handle. It helps because if patients are needle phobic, but it won't be as much as a step forward. But it is -- but it will continue to be a differentiator for us.

And then you can imagine the oral, as you say, I mean, we'll see how it plays out with the GLP-1s. But I think you can imagine that going from an injectable to an oral opens up a different pool of patients for whichever indication you're looking at.

Okay. So maybe let's talk about a couple of the near-term data catalysts that you have upcoming late stage. Let's start with myositis. So just remind us when is that Phase III reading out? And you were looking at 3 different subtypes. I think there's been some questions about what the company thinks is going to be the biggest value drivers. So maybe talk to us about those items.

Thank you. It's exciting. We have the data reading out in Q3. And yes, so we see myositis as our next growth frontier, our next growth opportunity. And we see the addressable market as around 70,000 patients. So to put that in context, that's similar to where we see the MG market addressable market right now. So you can think of it as an MG-like opportunity from that perspective.

There we designed a clinical trial that allows us to explore 3 of the different subtypes. So we have IMNM; we have DM, dermatomyositis; and then PM. And from my perspective, each of the subtypes has a clear biology rationale, and we can go through what that is. I would say we're very disciplined at argenx at always starting with the biology and the science. So we have a clear biology rationale for each.

And we designed a clinical trial that is very thoughtful and that it allows us to look at the overall population, but also the subsets so that we can really explore and we have multiple paths to success depending on data that we see. In terms of the value driver from my perspective, and certainly, as a commercial person, I'm really excited about M&M, and that's what we've been talking about as we've been doing our homework to really understand the commercial opportunity, what you see in IMNM, there's nothing else approved.

This is a completely white space indication. We see there's around 20,000 patients. So that's bigger than the TAM for CIDP. It's bigger than the addressable market when we launched MG and you'll remember that with myositis, it's weekly dosing, so CIDP-like dosing. So being able to go to a space where there is a huge unmet need there is no competition, including the competition on the horizon. And there's also quite a bit of overlap in IMNM. It's -- if you think about the treatment -- the treating physicians, it's more neurology and rheumatology. And obviously, we have strength in rheumatology. So the overall opportunity is a big value driver for us. We have a lot of belief in the biology for all of the different subtypes. But if you had to ask me to prioritize and where I'm most excited about, because of the patient unmet need, I think IMNM is going to be really exciting.

Okay. And to say that you're most excited about is not the same thing as less bullish about DM. Correct?

That's exactly right. I would not say that. I mean I think in DM, it's just a different dynamic. I'm also -- I'm excited about the overall myositis opportunity. In DM, we have a strong biology rationale. The difference from a commercial perspective is just is the dynamics. It's more heterogeneous. So we know that there's more at play in driving the disease and there is more competition, but it's a larger patient population.

We think that that's a 40,000 TAM. So look, I think that's also an exciting opportunity. It's another one where it's bigger than the CIDP TAM at launch. So yes, it's certainly a big value driver. There's a good biology rationale. And I look forward to seeing that actually the data play out for each of the different subtypes because I think they all -- each have their own unique opportunity.

So when you -- when it comes time to showing the data in the press release, like give us a sense of what level of granularity we're expected to see?

Yes I mean at argenx and the style that we have is that we like to be transparent, and we want to share as much data as possible. This is our first entry into rheumatology and some of the medical congresses and conferences with rheumatology are a little more strict. And we want to make sure that we have the opportunity for -- to make a big splash with this data because when it reads out. So we'll definitely share the top line and as much detail on the subtypes as we can. But we'll just have to -- once we see the data, we'll have to determine what the right path forward is there. But we like to be able to give transparency, and we'll be able to give a good sense of where we think we're going with this indication.

Okay. Now because of the different prevalences of the 3 different subtypes, how should we be thinking about the balance of each of the subtypes that finally enrolled into the study?

Yes. So the way that we designed the study, if we maybe just take a step back, it's a seamless Phase II, Phase III. And when -- and we did not cap any of the subtypes. So we let the enrollment run both for Phase II and then also for Phase III. So you can imagine that it's not an equal distribution across all of the different subtypes, but it enrolled based on, I would say, unmet need and as well as the disease characteristics. So we haven't shared the underlying sort of the number of patients across subtypes, but we'll be able to do that, I would say, at top line.

Okay. But there isn't a concern internally that you enrolled too few people in one of the subtypes and therefore, it wouldn't be like strong enough to support an application?

No. I mean the trial -- it's a basket design. So we're able to look at from a statistical analysis plan perspective, the total population as well as the subtypes.

Okay. And one other common question we're getting lately is what are your discussions with the FDA on the subtypes? Like is there flexibility to look at the data and then decide if you want to apply for a full label for all 3 or a subset of them?

Yes. I mean, as always, we're engaged very closely with the FDA on -- especially on such an important study. And as always, it will come down to let the data speak and then it will be a review decision. But I think we have multiple paths forward.

Okay. And then in terms of commercial organization, assuming that you move forward in some capacity with this indication, what changes would you need to make, if any, to the field force?

Yes. So this is our -- potentially our first step into rheumatology. And so we -- with this step and then, of course, we have on the horizon, Sjogren's, another exciting potential rheumatology indication. So we do start to think about expansion so that we can cover more of the rheumatology. It's a different footprint, also potentially different support services for patients so that you can compete in rheumatology versus neurology. So we can leverage a lot of the commercial infrastructure that we have with, let's say, some expansion so that we can make sure to have the reach that is needed to succeed.

Okay. So if this becomes, let's say, another potential vertical for the company, you just mentioned Sjogren's. So maybe let's talk about that. You've got a study underway, which I believe reads out in sometime in 2027. So you wouldn't be alone in looking at Sjogren's. So maybe mechanistically, can you just talk us through why it made sense to invest the money and the time into looking into this?

Certainly. I mean I think one sort of takeaway that I think about with Sjogren's is and some of these rheumatology indications is there was always -- the auto antibodies were generally known. But it was always thought that they were more of a bystander or an outcome of the disease. And I think what the real shift has been is like is that no, in these rheumatology indications, actually, these IgGs could be driving the disease. And I think that's what we've seen in Sjogren's.

So the way we went about Sjogren's is the same sort of disciplined approach that we go about to choose any indication, look at the biology, and that's what we can look at and look at the development path and then what is the unmet need. The way our development plan, I think, was quite innovative and agile and reflects the argenx way.

Our competitor did a big Phase II study. So we were able to leverage the data from that competitor in FcRn that really demonstrated that the biology rationale was there. And what we did was small, very focused Phase II study where we went deep to really understand the drivers of the disease and really understand how to run a clinical trial so that we were able to execute, and I'd say, leapfrog ahead.

And as you say, we have data coming out next year. And it's certainly an exciting indication. In terms of the third category that we always look at Sjogren's, I mean, it's a big patient population, 300,000 patients. But what we see is especially in the sort of around 100,000 more severe patients, there's a real serious unmet need and patient need. It goes beyond just dry eyes, the systemic manifestations of the disease, and that's where we think we'll have the biggest benefit.

Okay. And the investments that you would theoretically be making now into rheumatology would be for all indications. That's right.

That's right.

And with the targeted physicians, we've talked about the overlapping, let's say, of neurologists who treat CIDP and gMG. So when you make the decision into moving into various rheumatology indications, is it too simplistic to say that any rheumatology indication would be something that a community physician of community rheumatologist would be treating? Or are there specializations within that?

I think it will -- we still need to do the work up, but it will be -- I would say it's more -- it will be more specialized than that. Even when you look at neurology, we have over 5,000 neurologists that are writing VYVGART. And so there are a lot of breadth. That's not all of neurology. There are some neurologists that mostly treat migraine. So as an example, so we're not targeting them. It will be the same in rheumatology. And so what we'll be able to do once we have the data and once we -- as part of our launch preparation is really target what's the -- where do we need to focus our energy to get the best return on investment.

Okay. Let's maybe move on to MNM, which is another pivotal study that's going to read out in the fourth quarter, I believe. And it's going to be your first foray of a late-stage study that's not efgartigimod. It's going to be with empa. So maybe talk to us about the excitement that you guys have internally about this particular program because it could open the door to many other indications for this different drug.

Yes, absolutely. We're very excited about empasiprubart. When I talked earlier about the long-term strategy for the company, it is to become a leader in immunology. And so this is our next medicine C2 as the target and MMN as the first indication. And when you look at MMN, I think it's a very argenx-like indication.

It's very clear biology rationale for C2 with MMN a really strong development path that we can unpack a little bit more in terms of a head-to-head versus IVIg based on very strong Phase II data and importantly, a very high unmet need. I mean it's another place that there hasn't been innovation for decades and in MMN. It's a progressive disease.

IVIg is the only option and patients continue to progress even with very high doses of IVIg. So this is a great first indication. But empasiprubart is a pipeline in a product. So we see more indications coming. And one of them that we've announced is obviously CIDP, but there's even more beyond that.

Can you maybe just talk to us about the trial design for MMN and what we should be looking at in particular?

Yes, absolutely. So the trial design is a head-to-head versus IVIg. And the reason for that is because we have such confidence based on the Phase II data that we can design a Phase II study -- sorry, a Phase III study, non-inferiority versus IVIg. The primary -- it's a 24-week endpoint and the primary endpoint is actually is on grip strength. And that's important because what we've learned in CIDP is that grip strength is a really meaningful endpoint to prescribers and to patients, mostly because it's very easy to understand.

I mean if you're losing the ability -- losing nerve function and you can't pick up your coffee cup in the morning, if you can understand as a patient, as a lay person, oh my grip strength is improving. And what we actually saw in the Phase II study is grip strength was able to improve over time, not just slowing the decline. So it's an important endpoint that's meaningful to doctors, understandable to patients and I think really shows functional improvement potential for empasiprubart.

And then what about quality of life? Like maybe talk to -- tell us about what patients feel they need to have that they don't have right now?

Yes. I mean this is another indication where at the very simplest level, a patient's immune system is attacking their nervous system. So they lose the ability to use their hands to walk to -- they lose strength. So from a quality of life perspective, group strength is a good -- is one of the -- is a good endpoint. We also have an endpoint MMN-RODS, which is more holistically looking at various quality of life measures to be able to assess the impact on the disease.

One of the most important data points from Phase II that we saw was when you ask patients to compare how they felt on empasiprubart versus at their peak on IVIg, 9 out of 10 patients said they felt better in empasiprubart. So there's a lot of secondary endpoints also of those qualitative quality of life outcomes.

And what are -- which of those quality of life measures are you looking at? Or will you be looking at?

We have a very long list of secondary endpoints that look at physician-rated quality of life, patient-rated quality of life in MMN-RODS, as I say so. So it's a deep study.

Okay. And then maybe just one more question on mechanism, C2 versus, let's say, C1. On the complement cascade, some might think of are those really that different from each other. But the work that argenx has done, maybe explain why C2 might make more sense?

Yes, absolutely. I mean whenever we look at and identify targets for argenx, we always like to work with world-leading experts to really understand what are the -- what's the best target from an efficacy and safety perspective that's going to be able to open up this pipeline in a product. And for us, C2 is that in the complement cascade. And why is that?

First of all, it's at the intersection between the classic and the lectin pathway. So you're able to capture indications that are driven by both of those pathways while leaving the alternate pathway free, if you will, which has an important safety benefit. You can still mount an immune response to a bacterial infection. But there's also -- the other reason is for C2 in addition to having the indications opened up for the classic and lectin pathway is that we think that it's the safest place to intervene in that complement cascade. And we've seen that with the strong safety and the data that we've generated in Phase II as well.

Yes. So you've focused in on safety, which was going to be my next question. I guess, in particular, is there any reason to think baseline assumption that any kind of black box warning would be part of what a label could theoretically look like?

Yes. I mean, with complement inhibitors, obviously, there's always the consideration of a black box warning around vaccinations and considerations. So in our clinical trials, yes, we do run the clinical trials with vaccination, but we're also working very hard in developing data packages alongside that to demonstrate that you can still mount that immune response and -- so that we can start to work towards. And I think we're relatively confident that we should be able to get to a good place in terms of the vaccination requirement.

Okay. And then same question as before, what to expect at the top line level disclosure?

Yes. I mean here, again, we will be as transparent as we can, and we'll balance that need for making sure that we can -- especially in this indication, I mean, we are first-in-class in this indication, first innovation in decades. You can imagine how much excitement there will be in the medical community. And so we want to make sure that we get a good -- are able to have a good presence at Congress as well as share the top line results when we get them. So we'll be as transparent as we can.

Okay. And what is the specialty that treats MMN?

It's neurology. So it's also a strong overlap with our current footprint.

Okay. So maybe in a couple of minutes we have left, I did want to touch upon IgAN because you will be beginning a program for 121. And I think some people find it interesting that the company wants to invest time and money into this, just considering the view that it's becoming a quickly crowded space given the April and April BAFFs that have launched, will be launching. So just quickly, mechanistically, why do you think there is still room for a new entrant like this?

Yes. Absolutely. So two things. One, when we look at MG, whenever it was, and I remember I was -- when others looked at MG, they also felt like it was a competitive space and there wasn't enough room and look how much that's transformed. And so I think there's plenty of space in IgAN. If we do the same thing as we have in MG, which is provide transformative outcomes. And I think we have the opportunity to do that because our IgA sweeper, what -- it's differentiated because it drops IgAs -- it targets only IgA and it drops them rapidly and sustained. And if you think of kind of this idea of time is nephron, then we think we can provide more rapid efficacy, and that's going to be important for these patients.

And what about on safety? There are some questions about risk of infection for the April BAFFs. And just theoretically, what do you think that profile could look like for 121?

Yes. I mean we'll have to see it play out. But I mean you have people that are walking around and from a genetic perspective, don't have IgA and there's no risk infection. So we think actually targeting IgA is going to actually produce a good safety profile and will allow us to compete there.

Okay. What is the status of the program? It's enrolling?

It's -- no, we're starting the program shortly.

Okay. So not necessarily data this year then?

No data this year. Yes.

Okay. Great. So with that, we're just about out of time. So I'll say thank you for making the trip all the way to Las Vegas. I know you travel a lot. So I'm not even sure where you might have traveled once again here, but thank you. And thanks, everybody, for sitting and listening to the session.

Thank you.

Good morning. My name is David, and I'll be your conference operator today. I would like to welcome everyone to the call. [Operator Instructions] I'd like to introduce Beth DelGiacco, Vice President of Corporate Affairs. You may now begin your call.

Thank you. A press release was issued earlier today with our first quarter 2026 financial results and business update. This can be found on our website along with the presentation for today's webcast.

Before we begin on Slide 2, I'd like to remind you that forward-looking statements may be presented during this call. These may include statements about our future expectations, clinical development, regulatory time lines, the potential success of our product candidates, financial projections and upcoming milestones. Actual results may differ materially from those indicated by these statements. Argenx is not under any obligation to update statements regarding the future or to conform those statements in relation to actual results unless required by law.

I'm very excited to be joined on the call today by Karen Massey, our new Chief Executive Officer. Today is her first official day on the job, marking a very important milestone in the story of argenx. We're also joined by Karl Gubitz, Chief Financial Officer; and Sandrine Piret-Gerard, Chief Commercialization Officer. I will now turn the call over to Karen.

Thanks, Beth, and welcome, everyone. I'll begin on Slide 3.

I want to start by saying what a privilege it is to step into the CEO role at this point in argenx journey. I joined the company 3 years ago for the culture, the science and the opportunity to help build a different kind of immunology innovation company alongside an exceptional team, one that scales innovation through collaboration, delivers meaningful impact for patients and creates lasting value for all stakeholders.

I'm excited to carry forward Vision 2030, our road map for growth and value creation at a moment when we have so much opportunity across the near, medium and long term. Near term, we see continued growth with VYVGART across both MG and CIDP. While we see the typical effect of seasonality, the underlying demand trends remain very strong and continue to point to a business that is both growing and expanding. I'm particularly encouraged by our new patient demand. Q1 was amongst our highest quarters ever.

Our leadership in neuromuscular was on display at AAN last month, where consistently strong efficacy and safety data reinforced why physicians should treat broadly and earlier with VYVGART in both MG and CIDP. Importantly, that growing confidence amongst neurologists positions VYVGART well for the next phase of growth with potential expansion into seronegative, ocular and pediatric MG population based on the strength of ADAPT SERON, OCULUS and Jr.

When I consider the growth over the medium term, we see strong runway of launches ahead, reflecting the scale of our ambition and the depth of opportunity across our pipeline. We're advancing into rheumatology with readouts in autoimmune myositis and Sjogren's. And we expect the first readout and potential launch of our second medicine, empasiprubart in MMN.

Lastly, we're investing in our future. We're building a pipeline by sourcing novel biology relevant in diseases of high unmet need, positioning us to sustain long-term growth and reach thousands more patients.

Slide 4. Our strategy is ambitious, but it's one we know how to execute. Vision 2030 is built on a proven immunology innovation model that has already delivered a strong foundation. Today, we have 5 clinical stage molecules that follow our model, first-in-class against a novel immune target and collectively addressing more than 15 distinct diseases. Empasiprubart is positioned to be the second medicine we bring to patients. Like VYVGART, we built this molecule very intentionally to target C2, leveraging novel biology insights from leading experts in complement biology.

Through empasiprubart's development, we've also unraveled critical insights into MMN biology that position us to fully transform the treatment paradigm. The Phase III readout is expected in 4Q, bringing us closer to launching our second medicine. In MMN, we see a familiar opportunity, build and lead the category, much as we did with VYVGART and MG, transforming the entire disease space. In CIDP, we have the same ambition. We continue to grow our market share with VYVGART and are generating extensive real-world insights as patient experience increases. And now by advancing a second targeted approach with empasiprubart, we will deepen our understanding of the underlying biology, helping us learn which patients benefit most from which treatment and positioning us to secure leadership in CIDP.

Slide 5. Across VYVGART and empasiprubart, we're solidifying our leadership in neuromuscular diseases and amongst the physician and patient communities. One of the most critical therapeutic area expansion for argenx is into rheumatology, and this starts with an important Phase III readout in autoimmune myositis in the third quarter. This is a disease with significant unmet need, defined by progressive muscle weakness that makes basic daily activities really challenging, if not impossible. There are no approved treatments in necrotizing myositis. And in dermatomyositis, where serious symptoms can emerge in the muscle, in the skin and in other organ systems, the complexity of the disease means more innovation is needed.

VYVGART has the potential to be the first truly targeted therapy in this indication, targeting autoantibodies against proteins that are highly expressed in the muscle. In the case of positive data, we plan to take an approach similar to what we've done with MG and CIDP because the myositis opportunity has similar attributes overlapping physician community, long established conventional treatment patterns and our goal to transform patient outcomes and become the #1 prescribed biology.

Slide 6. We've significantly broadened the number of clinical candidates across our pipeline in the last 12 months, and you can expect to see this cadence continue. Adimanebart is in Phase III in CMS. ARGX-121 is in Phase II development in IgAN with more indications to follow. And our long-term FcRn portfolio is taking shape with ARGX-213 ready for Phase III and ARGX-124 to follow.

To expand our pipeline at a cadence that will sustain our long-term trajectory, we need to deliberately expand the ecosystem from which we source novel biology. We'll double down on collaborations and licensing agreements with academic institutions and biopharma companies alongside acquisitions and strategic investments, giving us the flexibility to engage in whatever form accelerates innovation into our pipeline. The establishment of our China entity supports this strategy, building on the clinical and commercial strength of our partnership with Zai Lab and embedding us into the local ecosystem to effectively access emerging innovation, accelerate evidence generation as part of our pipeline and product strategy and ultimately expand our impact in this region.

As I step into this new role, I'm reminded of our purpose as a company, our patients. When we launched VYVGART 5 years ago, we made a commitment to continue raising the standard of care for people living with myasthenia gravis. Today, with 17 consecutive quarters of growth, we continue to see that commitment translate into real-world impact in MG, in CIDP and in ITP. This is what gives me confidence in the opportunity ahead. We're deeply committed to our purpose, we're disciplined in our execution, and we'll be flexible in how we source innovation. With that, I'll turn the call over to Karl to walk through our financial performance and outlook.

Thank you, Karen. Slide 7. Product net sales for the first quarter were $1.3 billion, representing 63% year-over-year growth. By region, we generated $1.1 billion in the U.S., $67 million in Japan, $112 million in the rest of the world and $12 million in product supplied to Zai Lab in China. The 1% quarter-over-quarter growth reflects the impact of Q1 seasonality in the U.S. and is aligned with our expectations. Gross to net adjustments and net pricing in the U.S. remained consistent with the prior quarter.

Next slide, Slide 8. Total operating expenses in the first quarter were $919 million, representing a decrease of $36 million compared to the fourth quarter of last year. Research and development expenses increased by $68 million quarter-over-quarter, principally driven by CMC investments to support the expected launch of a VYVGART subcu auto-injector in 2027, continued development of efgartigimod across several indications and advancing our pipeline assets. These strategic investments will deliver long-term growth through innovation in providing transformational outcomes to patients.

SG&A decreased 17% quarter-over-quarter, reflecting higher discretionary expenses in the fourth quarter of last year. We delivered an operating profit of $394 million in the first quarter and operating margin of 30%, representing 183% year-over-year growth. With revenue growth exceeding operating expense growth, we are on a clear path of continued margin expansion, demonstrating the operating leverage we are building as VYVGART scales and we advance our pipeline.

Tax for the quarter is in line with expectations at 14% of profit before tax. We ended the quarter with a cash balance of $4.9 billion, including cash, cash equivalents and current financial assets, an increase of more than $400 million from the beginning of the year. This strong financial position gives us significant flexibility as we deploy capital to fuel long-term growth. Our capital allocation priorities are clear: maximizing the VYVGART commercial opportunity, advancing our pipeline, strengthening our supply chain and pursuing business development opportunities to source the novel biology that will fuel our long-term growth. With our profitability profile, we are investing from a position of strength to deliver on Vision 2030.

I will now turn the call over to Sandrine, who will provide details on the commercial front.

Thank you, Karl. I'll begin on Slide 9. Over the past several months, I have spent a lot of time with our field teams and meeting with physicians and patients. What stood out to me is how argenx translates differentiated science into execution in the market, from securing access to building physician confidence in VYVGART in MG, CIDP as well as in ITP in Japan and to delivering white glove patient support designed to help patients start and stay on therapy. This level of disciplined execution and building trust among our core stakeholders will be critical as we approach several important growth catalysts. Today, I'll focus on what's driving our performance and where we see the most meaningful opportunities to build from here under Vision 2030.

Slide 10. We continue to deliver on our long-term growth strategy in 2026 with strong momentum across all indications and all regions. Our fundamentals are incredibly strong. Now 4 years into MG and 2 years into CIDP launch, we see no signs of demand slowing. In the first quarter, new patient starts were amongst the highest since launch, and we continue to have an expanding prescriber base, reflecting increasing confidence in VYVGART. We now have over 5,000 neurologists prescribing VYVGART in the U.S.

Since launching in CIDP, we have effectively doubled our prescriber base and each incremental physician meaningfully expands the number of patients we can reach. We are also seeing a change in prescribing behavior. Across both MG and CIDP, we are seeing a clear shift towards earlier use of VYVGART as physicians gain confidence with what it can offer patients. In the U.S., our market research now shows that 4 out of 5 HCPs prefer to start with VYVGART as the first targeted biologic in gMG.

New patient demand continues to build across both indications, driving consistent quarter-over-quarter patient growth. The prefilled syringe has materially changed the demand of VYVGART. By giving patients and physicians more flexibility, it continues to drive earlier adoption across MG and CIDP with 68% of PFS patients being new to VYVGART since launch.

Slide 11. VYVGART is the #1 prescribed biologic in gMG, a market that continues to grow. We still believe the biggest opportunity is ahead of us, particularly given the nearly 80% of MG patients who are not yet on a biologic. We know the VYVGART profile is resonating with physicians in this population and more than 70% of patients starting VYVGART today come directly from oral therapies. This continues to be the focus of our strategy to extend our leadership by reaching patients earlier in their treatment journey and expanding our reach to broader MG populations.

The data we presented at AAN served as an important driver of this strategy, and we were excited by the positive response from neurologists. VYVGART is delivering fast, deep and sustained efficacy and safety across MG patients. This supports our ambition for VYVGART to be the targeted treatment of choice, simplifying decision-making for the HCP and underscoring VYVGART's growth potential. I want to share one patient story that underscores why this matters.

Pam first presented with blurred vision and muscle weakness around her eye, but her ocular symptoms were not taken seriously, and she was unable to access appropriate treatment. As her disease progressed, she ultimately generalized, suffered a serious fall and was hospitalized. When Pam later started VYVGART, the impact was meaningful, helping us regain both mobility and independence. Our experience is a powerful reminder that ocular MG is not an eye disease. It can be profoundly debilitating and disrupt independence in ways that are often underestimated. Our positive ocular MG data, which demonstrated consistent improvements in both total and double vision, bring us closer to extending innovation for these patients.

We are now 3 days away from our May 10 PDUFA date for seronegative. So we are limited in what we can say at this point. A potential approval represents a meaningful opportunity to reach patients without detectable acetylcholine receptor antibodies up to 11,000 additional patients in the U.S. Many of them have been left out of studies or lack access to targeted innovation, and this commitment is what drives us every day.

Slide 12. Turning to CIDP. We continue to see consistently strong patient adds quarter-over-quarter with nearly 80% of new starts coming from direct switches from IVIg. As neurologists gain real-world experience and digest emerging data, they are becoming more thoughtful about when to introduce a targeted therapy like VYVGART and are increasingly considering earlier use. Physicians are citing VYVGART's functional outcomes as a key differentiator, particularly our grip strength data.

When CIDP patients were followed from ADHERE to the open-label extension, mean grip strength continued to improve with weekly treatment up to 96 weeks. While neurologists shared that it is rare to see patients regain function after deterioration, which makes an observed recovery in grip strength especially compelling. We remain focused on understanding how best to serve the broader CIDP population and how we can shape the market for earlier use of VYVGART. We are steadily expanding within our initial 12,000 patient addressable market and are seeing our strategy to work increasingly beyond this. At AAN, we presented the post-hoc analysis of the ADHERE study showing 87.5% response among treatment-naive patients, which continue to support this effort.

As we look ahead, our focus is on repeating what has already proven successful. The commercialization playbook we built in MG and CIDP is repeatable, combining a patient-first access strategy, deep prescriber engagement and disciplined execution. This positions us well as VYVGART expands into new indications and our future medicines, including efgartigimod, move closer to launch. With that, I will now turn the call back over to Karen.

Thank you, Sandrine. Slide 13. Putting patients first is how we define success at argenx. I'm incredibly proud of what this team has accomplished, and I'm energized by what lies ahead. I'm grateful for the trust of our patients, our partners and our shareholders as we continue this journey together. Thank you. And with that, operator, we'll open the call up to questions.

[Operator Instructions]

Your first question comes from the line of Yatin Suneja from Guggenheim Partners.

First, congratulations to Karen on the CFO confirmation. Perhaps 2 questions for me. So I would love to hear -- Karen, would love to hear your perspective on the outlook of argenx as you see it. Once you are fully settled in the role, do you anticipate or should we think about any sort of changes to the company's strategic direction? So that's one.

And then the second one is more around VYVGART. You do have 2 significant label expansion opportunities ahead of you. You probably will have the broadest label for MG across various subsets. How does this change the growth outlook as we head into second half? And how do you expect this differentiation to play out from a competition standpoint?

I appreciate the congratulations on the new role. I'm really excited to be taking on this role at this time for the company. We're in such a position of strength with a really strong quarter and strong momentum, and there's so much opportunity and momentum ahead.

So in terms of the question around strategic priorities, as I step into the role, my priorities are very clear. I mean, I was very much involved with Vision 2030, and there won't be a change in that strategy. For us, Vision 2030 is not just an aspiration, but it's a growth strategy. And so when you look at what we've laid out for that strategy, by the end of the decade, we want to have 2.5 more times patients -- 2.5x patients on VYVGART. We want to have 3x more indications approved and 5 molecules in late-stage development. And those 5 molecules in late-stage development really set us up for the next decade of growth. So there's no change to the strategy, and I'm incredibly optimistic about our future.

In terms of your second question on label expansion, we've laid out a strategy in MG for continued growth by bringing continued innovation to the market. So we have our PDUFA date for seronegative in 3 days. Beyond that, we have ocular MG that we'll be filing quickly, and we're also looking at an expansion into the pediatric population in the future. So as you say, with this, we should in MG have the potential to have the broadest label and be able to reach the broader set of patients. And we see this as a huge differentiator in the market.

What we're already seeing today is that physicians are choosing VYVGART 4 out of 5 times for their early line patients as their first biologic. So we see really strong momentum already and that growth strategy of expanding our label should continue that momentum through this year, but also into the future. Thanks for your questions.

Your next question comes from the line of Tazeen Ahmed from Bank of America.

Okay. So Karen, there's a big second half of the year upcoming for the company with several data readouts. I did want to focus my question on myositis in particular. Can you clarify your view of the likelihood for success for each of the 3 subtypes that you're studying? In particular, do you feel like anyone is more likely to work than the others? I think some people recently have interpreted comments you've made to indicate that you might be less bullish on DM?

Thank you so much, Tazeen, and I appreciate the pipeline question early on in the earnings call. So yes, as you said, the second half of the year is exciting. Myositis is our entry into rheumatology. And we should remember this is a first-in-class opportunity. This is a white space opportunity. And we have a very thoughtfully designed trial that really lets us explore and understand across 3 different subtypes. Each of those subtypes is grounded in a very strong biology rationale. And you'll recall that we had Phase II data in these same 3 subtypes, and we did move forward into Phase III.

So what we see as a win is a positive study in meaning statistical significance on the primary endpoint. More broadly, I think what's important in myositis is that there's significant unmet need across myositis broadly. And we've been talking about IMNM quite a bit recently because we've had some learnings around IMNM. Specifically, as we've been learning about IMNM leading up to the readout and looking into the data in more detail, what you see is that because IMNM is -- those patients have no treatments available, it is severely underdiagnosed and undertreated. So we see that the TAM opportunity in IMNM is bigger than we previously thought. It's around 20,000 patients. That's more similar in size to a CIDP opportunity and with similar dosing.

So that's why we've been focused on IMNM. But of course, the other subtypes, for example, DM also have significant unmet need and with limited treatment options. IVIg is the only treatment option available there. DM is a little bit more heterogeneous, but we still think that there's plenty of room for multiple mechanisms of action, and we think that VYVGART has a good value proposition in DM. So we're looking forward to the data readout in Q3.

Your next question comes from the line of Derek Archila from Wells Fargo.

Let me add my congrats, Karen, to stepping into the CEO role. Just 2 quick questions. So first, just on 2Q '26 VYVGART step-up. Like in the last 2 years, we kind of see that move from 1Q growth to 2Q growth, and we see kind of a nice magnitude of step-up. So I guess, can you characterize what we should expect this year? And then just a follow-up to Tazeen's question on myositis. So my understanding is that it's not powered for the individual subtypes, but will you give any qualitative information on how the subtypes performed in the Phase III?

Thanks, Derek. Yes, let me hand it over first to Karl so that he can give you some comments on the momentum that we have heading into Q2. And then maybe, Beth, you can comment on the primary endpoint and communications.

Thank you, Derek. Nice to hear from you. Every quarter has its different dynamics, of course. I think we need to focus on the underlying dynamics, which, as Karen already said and as we said earlier in the prepared remarks, which are very strong at the moment. Our full year expectations are unchanged. And the shape can look -- and you can look at the shape of the curve, which will be consistent with prior years. Thank you for the question, Derek.

Derek, on the question about what we're going to share on the myositis readout, I think at this point, you know the style on which we communicate. Our plan is, of course, to give the outcome of the primary endpoint. The primary endpoint of the study is the mean TIS score, and that is taken at week 52. But we also understand the importance of contextualizing that subtype performance. How we do that and what that looks like will still to be seen. I think it's important to remember that because this is a new therapeutic space that we're entering, we will need to preserve some of that data for an upcoming medical meeting so that we can inform and generate enthusiasm among the rheumatology community.

Your next question comes from the line of James Gordon of Barclays.

James Gordon of Barclays. I had a question on competition in MG. So I've had some questions from investors about competitors in the U.S., such as Amgen who have been talking about UPLIZNA, so CD19. They're talking about strong uptake in both bio-naive and switch patients even without step through. So are you seeing UPLIZNA being used much in MG? And is it displacing in any patients that could use VYVGART? And also, I think that Amgen has said they're taking into a CIDP trials. So could that be a threat in addition to potentially C1s coming along? And then also from the competitive point of view, Regeneron, they've got cemdisiran, so also hitting C5, but also a potential MG approval later this year in Q4. Do you think that could impact VYVGART in MG?

Yes. Thanks for the question, James. There's a lot in there. I'm actually going to hand it over to Sandrine. She's been spending a lot of time out in the field with customers and at AAN, and I think has probably recent experience to talk from.

Yes. Thank you. Thank you, Karen. Thank you, James. So indeed, competition has come. We have put MG on the map. So there are more and more players in there, and we see that as a good sign. It means there is a lot of potential in that market, but also more option and innovation for patients, which drives the size of the biologic market, which benefits all of us and especially VYVGART as 4 out of 5 providers really prefer VYVGART as the first biologic.

Now going to your question specifically on some more recent entrants. So what is interesting to see is that most of the recent launches are really positioned towards the later lines. So more for refractory patients and after VYVGART. So we see some use but not really directly competing with us. Because what we are trying to do is to go in earlier lines because we know that 80% of the MG market is still not in the hands of biologics. And this is where we see a really big opportunity, and that's our strategy. So some use indeed, but more in later lines and refractory.

So you also mentioned a recent competitor in CIDP. I mean, CIDP, as you know, we have been in the field for now 2 years. We have another product in development, empasiprubart in development. So what we believe is that CIDP is a progressive disease, but very heterogeneous and there is space for multiple mechanism of action. And so with the current profile of VYVGART, we believe we have a very strong value proposition between the PFS, the efficacy, the safety, recent grip strength data where we showed sustained efficacy up to 96 weeks and then we just presented the data at AAN on earlier use where we did a post-hoc analysis. I don't know if you saw that one, where we showed that naive patients had 87.5% clinical efficacy. So we are really trying to extend here the overall market for VYVGART, and this is very great for CIDP patients.

So now for the C5 question, I think Karen wanted to say something. So I'll hand it over back to Karen.

Thank you, Sandrine. I think that's great. And I think you're exactly on point. As we see new competitors coming into the market, C5s and others, they're mostly being used in the refractory space. So thanks for the question.

Your next question comes from the line of Alex Thompson from Stifel.

Congrats to Karen here. I was wondering sort of, to talk at a high level about your appetite for later-stage business development than what you've done historically? And maybe in the context of that, how you're thinking about your Forte equity investment?

Yes. Thanks for the question. Yes, maybe to take a step back, we talked about our ambition earlier with Vision 2030. And over the long term, we want to become a leader in immunology. And what that means is that we're focused very much on building our pipeline. In the past, we've been focused on building our pipeline through partnerships with academic institutions. You all know our Immunology Innovation Program where we've sought novel biology that can provide transformative outcomes for patients through those partnerships with academic institutions.

As we've been developing a stronger cash balance and financial strength, what that allows us to do is broaden our lens a little bit and also look for other opportunities to source novel biology and where we can provide transformative outcomes. So your example that you're calling out of Forte is one example of that where we made a strategic investment in something that we see is novel biology and similar to what you also saw with Tensegrity earlier this year, where we're investing in options in novel biology. So you can expect to see more of this from us as we continue to build our pipeline and continue to leverage our balance sheet. We want to invest in our internal innovation pipeline and source novel biology from wherever we can find it. Thanks for the question.

Your next question comes from the line of Rajan Sharma from Goldman Sachs.

Maybe just on the topic of competition. We saw that J&J are running a head-to-head trial of ImAAVY versus VYVGART in myasthenia gravis, which could read out next year. I was just wondering if you could provide your perspectives on the trial design and expectations here. To what extent is that a risk to VYVGART or not conscious of the different formulation? And then a very quick follow-up for Karl. I heard your comments on operating leverage. Should we expect to see this incrementally quarter-on-quarter as well as on an annual basis?

Yes. Thank you. I'll take your question on competition, and then I'll hand over to Karl for the question on operating leverage. Yes, look, I think Sandrine said it best, we put MG on the map and many competitors are following us, especially as a first-in-class FcRn. And I think what you see is that we've set the standard for efficacy in terms of MSE in MG and have the stronger safety profile and we have all of these innovations. We started with IV, we launched subcutaneous and then we most recently brought PFS to market. And in fact, PFS is driving the majority of our growth at the moment.

And so when you think about that, I think the question to ask about some of these studies and these other competitors is what problem are they trying to solve? And I think what we're really focused on is how do we bring more value to more patients where there is unmet need. And for us, that's focusing on PFS, which is unmatched as well as focusing on that strategy we were talking about earlier, which is broadening the population through seronegative, through ocular and in the future through pediatrics. So with that being said on competition, maybe, Karl, you can talk about our operating margin.

Thank you. Thank you, Rajan, for the question. Yes, I want to start off by reminding we are on an innovation mission. The patient is your North Star. We have a unique opportunity now to invest in innovation and set the company up for the long run to build a long-term sustainable company. That is the capital allocation priorities of the company.

But that said, yes, you are right. The very successful launch allows us to build a P&L where we already have a very good margin structure. Our gross margin is around 90%. Our operating margin is around 30%. We added $400 million of cash this quarter, getting us to $4.9 billion. So yes, you can expect going forward to see margin expansion every quarter year-over-year, and we're going to continue to build on that. But that, of course, is not the objective at the moment, but I think we can do both. Thank you for the question.

Your next question comes from the line of Allison Bratzel from Piper Sandler.

This is Ashleigh, on for Allison Bratzel. Congrats on the quarter and all the progress. So just from us, -- just curious to learn more about the go and no-go decision on the Phase II VARVARA trial in delayed graft function, which is expected midyear. What specific clinical or biomarker signals are you looking to see to justify advancing clinical development? And just more broadly speaking, how are you viewing the commercial opportunity in delayed graft function?

Yes. Thanks for the question on DGF. As I said earlier, it's great to hear these questions on our pipeline. So DGF is an important indication for us for our second molecule, empasiprubart. And we're able to pursue DGF as an indication because of empasiprubart being a C2, so involved in both the classic and the lectin pathways in complement. So that's a differentiator for us.

In terms of the study, it is a Phase II study. So think about it as an exploratory study. And what we wanted to do was see the readout of the data for longer term. So we're following this data out to 52 weeks because in this patient population and what we hear from both patients as well as health care systems and providers is what they care about is the long-term outcomes. So as soon as we have that data, we'll be able to analyze it, and we'll have a go/no-go decision for Phase III. Thanks for the question.

Your next question comes from the line of Daniel Brill from Truist Securities.

This is Alex, on for Daniel. Congrats on the quarter. Another question on myositis. On the placebo response, just curious if you could talk a little bit about what factors are known to drive the placebo response? And do you expect any difference in the 3 subgroups? And then alternatively on the steroid taper, just curious what effects of the steroid tapering you're anticipating in the placebo response? And also, do you have any thoughts on why Roivant steroid tapering did not yield any decrease in the overall TIS endpoint in its placebo arm in its DM trial?

Yes. Thanks for the question. So let me take them one by one. So first, when you think about placebo response, whether across immunology, you see this pretty consistently. We've seen it in MG, in CIDP, you see it in Sjogren's studies and similar in myositis. So I think this is a pretty common phenomenon. And when you're developing an immunology like we are, then you start to get sort of good learnings around how to make sure you're minimizing that placebo response in the trial. And that can include things like training the sites to make sure that they understand how best to use the tools and the measures for the primary endpoint and that type of thing. So in this case, as you said, it's TIS. So I don't think there's anything special across the different subtypes or in myositis there.

In terms of the steroid taper, we think this is actually a benefit of the design of our study because what we've been able to do is build it in late enough in the trial so that you have a systemic steroid tapering, which should actually unmask any placebo response and help us to show a clear benefit on active disease. So we see that -- the way that we've designed it is very elegant, and it should actually help us to uncover the benefit of VYVGART. In terms of Roivant, I would encourage you to ask them. I'm not sure about the details on their steroid taper. Thanks for the question.

Your next question comes from the line of Yaron Werber from TD Cowen.

Congrats, Karen, again. A couple of sort of interrelated questions. One, can you just give us a little bit of a sense? We're kind of thinking that CIDP is around 40% of sales right now, maybe kind of 37%. I don't know if I'm in the right ballpark. And then secondly, for the seronegative study, it was a very wide study with a p-value of 0.1 across all patients, which you hit successfully. And it looks like it was driven by the MuSK and LRP positive patients. In the seronegatives, technically, the endpoint wasn't met, but because just it came together literally at the end, there was a benefit throughout the period. Just trying to get your conviction that you can get a broad approval and not just in the autoantibody positive?

Yes. Thanks for the questions. I'm going to hand it over to Karl to talk about CIDP and how the mix of business is evolving. And then I'll turn it over to Sandrine to talk about seronegative. I want to just make a point that's really important, though, related to the specific question you asked. We're 3 days from our PDUFA date. And so we have to be very careful in how we talk about this. So we're going to keep the discussion very general. And what I want Sandrine to talk about is, in general, how you see the seronegative opportunity in the case of approval so that we don't go into those details. But maybe we can talk about CIDP first.

Yaron, thank you for the question. Yes, both CIDP and MG continue to be growth drivers for us. And of course, CIDP is mainly in the U.S. now, but also in Japan and Germany, other markets we still have to launch. In terms of a percentage breakdown, I don't want to get into that, but I will say that MG is still the majority of our revenues and of course, the majority of our patients, but both still have a lot of growth in them. Thank you for the question. I'm handing over to Sandrine.

So thank you for the question on seronegative. So like Karen said, I will stay very general because we are only 3 days away from the PDUFA date. So if approved in seronegative, as you mentioned, I mean, there is a pool of patients, which we assess at 11,000 patients that would cover potentially these 3 subtypes. And so as we are only 3 days away from PDUFA date, we are obviously ready to launch. I mean the good news is that we are already embedded into MG. There is a big overlap of the prescriber base with more than 80% of the target we already did it that are actually -- that we cover seronegative patients. So we don't need to add any field force.

The prescribers know extremely well VYVGART and the trust, their experience of VYVGART and its efficacy that is deep, fast and sustained. And then we had a good presentation at AAN with lots of questions. So it shows that there is an interest really and that physicians and providers are really waiting for that. So I won't be able to go more into the details, but we should hear in the next few days.

Your next question comes from the line of Thomas Smith of Leerink Partners.

Let me add my congrats to Karen on stepping into the CEO role here. It sounds like the VYVGART auto-injector continues to advance and you're guiding to launch in '27. Can you just provide an update on where you are with this formulation? What are the outstanding gating factors for bringing this to market? And how are you thinking about potential uptake in this form versus the prefilled syringe?

And then if I could, just a clinical follow-up on efgartigimod in Graves' disease. We saw the Phase III design that you recently posted on clinicaltrials.gov. And I was wondering if you could comment on some of the design considerations for this multipart study? How are the patients being handled between Part A and Part B? And how are the background ATDs being managed? And maybe just higher level, like what are your expectations with respect to the primary endpoint registrational path?

Yes. Let me start with the auto-injector question. We're moving into manufacturing stage at the moment, as you say, to get ready for auto-injector launch in 2027. The key ungating factors are really just moving through those different gates of making sure that we're ready for production and approval. In terms of the opportunity that we see with auto-injector, what we saw with prefilled syringe is that it opened up a significantly larger patient population. And actually, and we said earlier, prefilled syringe is driving the majority of the growth for us today.

And so with auto-injector, I don't think it will be as much of a step forward as prefilled syringe. You'll recall that in the U.S., prefilled syringe moved us out of health care administration into at-home administration. But the auto-injector will be a step forward in terms of patient convenience and ease. So I think that's an important consideration for how we compete in MG.

In terms of Graves' disease, clinicaltrials.gov covers all of the details that we want to disclose publicly. But I'm going to hand over to Beth to talk about some of the additional details.

Yes. So we designed the Graves' study, taking into account, of course, precedent studies, and that was aligned with what the regulators wanted. So it's actually going to be 2 studies. You're going to see some kind of similar attributes of this study where we're actually dosing on top of antithyroid drugs. We're looking at patients at the end of the study who are euthyroid off antithyroids. So you're going to see kind of a tapering off that. I think beyond that, we'll get into more details at a later date. But we're really excited about kicking this off. We're focused on moving enrollment along as quickly as possible. And yes, more to come at a later date.

Your next question comes from the line of Akash Tewari from Jefferies.

Karen, congrats on the new role. Very well deserved. Just on your Phase III myositis trial design, will the FDA allow you to file on full data? Or does each subset need to be statistically significant for broad approval? And additionally, can you go over the rationale of your ADAPT Forward trials that look at VYVGART and empa in combination in gMG? What type of signal would you want to see to move that forward in larger studies?

Yes. Thanks for the question. So in terms of myositis, look, the label that we get, that will be a review decision, and we'll have to see how the data unfolds and let the data speak in each of the subtypes. So we look forward to that data in Q3. I'm glad you asked about ADAPT Forward because it's a key part of our combination strategy that I think we're uniquely positioned as argenx to pursue in MG and also in some other of our indications like CIDP.

So ADAPT Forward is a platform study. And what we're looking at is can we dramatically increase the efficacy and outcomes for patients in MG. So what we're looking at is VYVGART as the backbone of therapy and then looking at different combinations, for example, empasiprubart on top of VYVGART and can we increase the number of patients reaching MSE. Over time, we want to -- it's a platform trial. So we will be adding different arms to the trial to explore different combinations of -- that we have in our pipeline so that we can explore which we would want to move forward in Phase III. Thanks for the question.

Your next question comes from the line of Sean Laaman from Morgan Stanley.

Two questions. The first one is your recent data presented at AAN for VYVGART in treatment-naive CIDP patients. How do you see that evolving? Do you see VYVGART potentially moving up into the front line? I think there's a lot of focus on just the cost of drug, but considering you've got just a short injection with VYVGART versus all the [ plough ] that goes on with Ig administration, just to give your view there. And Second question is just on the IMNM opportunity. And I think, Karen, you mentioned a CIDP-like opportunity. But just give us a bit more color on the accessibility of that patient base. Are they readily diagnosed? What do you have to do there to get into that market?

Yes. Thanks for the question. I'm going to hand over to Sandrine to talk about the CIDP data. She was at AAN, and then I'll come back to the question on IMNM.

Yes. So great question. And indeed, in my prepared remarks, I mentioned that post-hoc analysis because I think it's data what we have never presented before, showing that VYVGART can indeed have an impact -- a sustainable impact and fast impact and efficacy on naive patients, truly naive patients. So we are very excited by this data. A few analysts picked that up, and I think this is going to expand the possibilities for VYVGART because if you look at our label in the U.S., we actually could be used first line. So there is actually theoretically no barriers to using.

And so in practice, we see 2 barriers for broader usage in first line. The first one is indeed getting physicians comfortable using it when patients are doing okay. And for that, it's very important to come with convincing data like the one in the post-hoc analysis, but also data like we are showing with the grip strength, where we show really very good efficacy on a sustained basis at 96 weeks. And the second barrier we are seeing is indeed payers, and you mentioned that in your question. So having data like the one we had in the post-hoc analysis allows us to go back to payers and a discussion because ultimately, this is better for patients. So we believe this kind of data will help us move the needle step by step into broadening the market in first line for VYVGART. So I'll hand it back to Karen for your other question.

Thank you, Sandrine. Yes. And in relation to your question on IMNM being a CIDP-like opportunity, so the way that we see it is we size the addressable market as around 20,000 patients. But when you first look at the treated population of IMNM in claims data, it looks more like it's around 6,000 to 7,000 patients. So we think that those are quite easily accessible because there's no treatment options available at the moment.

Beyond that, what we will need to invest in, in the case of positive data is really disease state education to increase awareness and increase diagnosis of this patient population. But what the opportunity that we have is that IMNM is frequently treated by neurologists, and there's quite a lot of overlap with those neurologists with our MG and our CIDP prescribers. So we see the opportunity to build this market in the same way that we've built the CIDP market, we've built the MG market. And I think we'll see, assuming positive data, the same outcome in IMNM. Thanks for your question.

[Operator Instructions]

Your next question comes from the line of Gavin Clark-Gartner of Evercore.

This is [ Yi Zhang ], on for Gavin. Congrats on the strong quarter. So one question about the next-generation molecule 213. We saw now it's become Phase I ready. Just wondering, can you share more details on the time line and how you are thinking about the indication selection? And also for the Phase III, will it be a noninferiority study head-to-head against VYVGART or it's going to be a stand-alone placebo-controlled study?

Yes. Thanks for the question. The strategy that we're laying out for FcRn is to continue our leadership for decades to come. And so as you mentioned, we have ARGX-213, which moves dosing to every 4 weeks and we also have ARGX-124, another next-generation asset in the FcRn space as well as our program focused on developing an oral FcRn.

So we have a portfolio of options here for how we'll continue to build the FcRn space, explore the FcRn biology and deliver value to patients. So we aren't public on our clinical development plan for 213 yet, but it is Phase III ready and we'll be moving quickly. And we see a few different opportunities. One is to advance patient outcomes in the indications we already have approval for with a more convenient -- with 213 being a more convenient option. And we have the opportunity to expand the indications that we have FcRn approval in. So continuing to expand the boundaries, if you will, of FcRn biology. So we're really excited about our full FcRn portfolio, and we think that it will be able to deliver growth for many years to come. Thanks for the question.

Your next question comes from the line of Samantha Semenkow from Citi.

Your next question comes from the line of Jacob Mekhael from KBC Securities.

I have one maybe further down the line on the oral FcRn and your collaboration with UMP. Maybe if you can share a bit more on how that's evolving. And a follow-up on that, we see other disease areas that if you introduce an oral, that could expand the market. So I'm keen to hear your view on the potential impact of an oral FcRn on the overall biologics market in MG and CIDP. Could this lead to further market expansion? Or do you see it more as a tool to prevent the competition from taking existing share?

Yes. Thanks for the question on the oral. Our partnership with UMP is progressing incredibly well. They are great partners. And we've -- we're partnering with them on a number of targets and FcRn being the first one. And exactly, as you said, our strategy here is that we believe an oral FcRn can expand the market. You can imagine there are patients earlier in disease that would prefer to have an oral option rather than an injectable even if it is a PFS that we have with VYVGART. So the strategy here across all of our indications, and as I mentioned on the prior question, even potentially in new indications is that we'll be able to bring more convenient options to patients that continue to deliver the same efficacy and safety standard that we've seen with VYVGART. Thanks for the question.

Your next question comes from the line of Victor Floch from BNP Paribas.

Maybe just a quick follow-up on 213. And I mean, I was looking at the initiation of the Graves' disease Phase III. And I was just wondering how should we think in terms of additional VYVGART Phase III studies in new indication moving forward? Basically, should we assume that the Graves' disease program will be VYVGART's final Phase III for new indication and that any promising signal from the ongoing proof-of-concept studies will instead be pursued with the ARGX-213 due to IP consideration. So any comments on the life cycle management there would be helpful. And maybe if I can just squeeze one on the on CDP. You've mentioned that the penetration of biologics in MG was around 20%. Can you share the same metrics for CDP? And can you discuss like the drivers that you have to further penetrate the market there?

Yes. Let me take the first question, and I'll hand over the question on CIDP to Sandrine. So for Graves' disease, it's -- we're pursuing Graves as an indication for VYVGART. And I wouldn't assume that future indications that we name all are going to 213 or 124 or any of our future pipeline. We still see that we have a lot of runway with VYVGART and a strong development program with VYVGART. So we continue to invest and we'll continue to grow VYVGART. And in parallel, we'll be developing 213, 124 and the oral as well. As I mentioned earlier, we see those molecules as a real expansion opportunity for FcRn. But let me hand it over to Sandrine to talk about the CIDP opportunity and market growth opportunity.

Yes. And I like that you picked that up on the 80% in MG being still among orals, where there is a huge market opportunity. We see something similar with CIDP. So the total number of diagnosed patients for CIDP in the U.S. is 42,000 patients and 24,000 of these patients are treated. That means the remaining are not right now. They have been diagnosed, but they are not treated. Out of these 24,000 patients, 12,000 of them are on IVIg, but are not optimally treated. And these are the one we have been focusing on when we started launching because these are the ones that have a reason to switch to something better and that's why we feel that VYVGART is the answer.

The other 12,000 that are treated and feel optimally treated with IVIg could also potentially switch to VYVGART because could benefit from efficacy like the grip strength data that we -- where we showed strong efficacy. So if you have to compare the 80:20 split of MG with what we see here in CIDP. I would say out of the 42,000, only 24 dozen are treated. The others are not. So there is room there. And then 12,000 feel optimally treated, but there is an opportunity for us to expand the market beyond what we already see today. So still a big potential beyond what we have focused on until now.

Your next question comes from the line of Myles Minte from William Blair.

This is John, on for Myles. Wondering if you could talk a little bit about how you're viewing the evolving CIDP complement development landscape, especially as some of the early [ C1 ] inhibitor data has suggested a potentially best-in-class profile there? And as a follow-up, maybe if you could just talk a little bit about your views on knocking down both the lectin and classical pathway with C2 versus just knocking down the classical pathway?

Yes. Thanks for the question on empasiprubart. It's exciting to be bringing our second medicine potentially to market with our readout -- our first Phase III readout at the end of this year. Certainly, from my perspective, on the competitor data, I see this as a real confidence booster for why we're pursuing empasiprubart in CIDP. It demonstrates that they're in CIDP. IgM is part of the driver of the disease and complement is at play. And so that reinforces why we think empasiprubart could have best-in-class potential in CIDP.

And I think from a company perspective, argenx is very well positioned in CIDP. There hasn't been innovation in CIDP in 30 years. The first innovation was VYVGART. And now as we develop that market, we also, in parallel, are developing empasiprubart. So I think what you'll see is that we have the opportunity between VYVGART and empasiprubart to really shape that market and transform the market. And I think it will look very different in the future from where it looks today as we really raise expectations of patients of what they can get from their medicine. So we're excited for that.

In terms of the classic and the lectin pathway, the reason we chose C2 was very specific. And one of the reasons for that is because there are indications where lectin plays an important -- the lectin pathway plays an important role. I was talking about DGF earlier. And so we think that it gives us better pipeline and a product opportunity by targeting C2 to be able to get the efficacy benefit there, but also the safety benefit of leaving the alternate pathway intact. Thanks for the question.

Your next question comes from the line of Samantha Semenkow from Citi.

Apologies for the technical difficulties. Just wanted to follow up on a couple of the previous questions on combination strategy for both CIDP and MG. How do you think about the market evolving? It seems combo therapies is a growing theme within I&I. And as you start to see some of that data in the platform trials that you talked about, Karen, how do you see the market evolving there and your opportunity to continue being a leader in both indications?

Yes. Thanks for the question, and we had some technical difficulties earlier today as well. So no problem. In terms of our combination strategy, as you see -- as you said, you can see that this is emerging in I&I in a way that it's similar to how it did in oncology as well. So we're at the forefront of that, and we're driving innovation. And I think we're very clear on what we want to achieve. The value proposition for combination therapy has to be that it substantially raises efficacy outcomes for patients. I think that's the bar that we need to see in combination therapy. And you have to be able to deliver that efficacy benefit without a safety trade-off.

So that's what we'll be looking for in the platform studies with the different approaches, the different combinations that we'll be testing. And as I said earlier, the reason we did a platform study is that, that will allow us to test these quite quickly. And then when we see a signal, we'll be able to move quickly into Phase III with the goal that we always have as a company of elevating outcomes for patients. Thanks for the question.

That's all the questions we have time for. I'd like to hand the call back over to Karen Massey for closing remarks.

Thank you, everyone, for the questions and the great discussion, and we'll see you next quarter.

That does conclude our conference for today. Thank you for participating. You may now all disconnect.

Good morning. My name is Rob, and I will be your conference operator today. I would like to welcome everyone to the call. [Operator Instructions]

I'd now like to introduce Beth DelGiacco, Vice President of Corporate Affairs. You may now begin your conference.

Thank you. Two press releases were issued earlier today, one sharing the positive results from our Phase III ADAPT OCULUS study and the other, which outlines our fourth quarter and full year 2025 financial results and business update. These can be found on our website along with the presentation for today's webcast.

Before we begin on Slide 2, I'd like to remind you that forward-looking statements may be presented during this call. These may include statements about our future expectations, clinical developments, regulatory time lines, the potential success of our product candidates, financial projections and upcoming milestones.

Actual results may differ materially from those indicated by these statements. argenx is not under any obligation to update statements regarding the future or to conform those statements in relation to actual results unless required by law.

I'm joined on the call today by Karen Massey, Chief Operating Officer; Karl Gubitz, Chief Financial Officer; Luc Truyen, Chief Medical Officer; Sandrine Piret-Gerard, Chief Commercialization Officer; and Tim Van Hauwermeiren, Chief Executive Officer.

I'll now turn the call over to Karen.

Thank you, Beth, and welcome, everyone. I'll begin on Slide 3. 2025 was an incredible year of execution for argenx. We reached 19,000 patients globally, driven in part by the successful launch of our prefilled syringe for self-injection. We also continue to advance our deep and differentiated immunology pipeline, including 4 new molecules from our IIP, positioning us for sustained long-term growth. This progress is grounded in our commitment to patients to innovate in ways that don't just improve care, but meaningfully change what patients can expect from their treatment.

I'm speaking to you today from our U.S. national team meeting, where hearing directly from patients is a powerful reminder of why our work matters. One moment in particular, stayed with me. We recently received a handwritten note from a patient, thanking the team for the impact VYVGART has had on her life. We later learned that before starting treatment, she had been living with very severe MG symptoms that significantly limited her day-to-day activities. Today, at the meeting, we saw a video of the patient about a year into treatment with VYVGART Hytrulo, sharing an update from a hype she was on. She is thriving. It's one individual story, but it reinforces the real-world difference VYVGART can make.

Slide 4. At the start of the year, we outlined our strategic priorities for 2026 that will guide our next chapter of growth towards Vision 2030. We want to impact more patients globally with VYVGART through broader patient adoption and label expansion. We're shaping the future of FcRn medicines with next-generation molecules, delivery modalities and combination approaches and delivering the next wave of immunology innovation, supported by a strong late-stage portfolio and a goal of at least one new pipeline candidate per year.

Slide 5. VYVGART is leading the growth of biologics in both MG and CIDP, and we're confident that we have the right strategies and milestones ahead to sustain this momentum. Today marks an exciting moment for ocular MG patients with the positive ADAPT OCULUS results, which Luc will discuss shortly. Together with our progress in seronegative MG, we see a meaningful opportunity to broaden VYVGART's reach to patients who have historically had limited or no targeted treatment options. What's guided us here is a long-standing commitment to the MG community and to advancing our understanding of the underlying biology of the diseases we treat. Across MG populations, our data confirm that disease is driven by pathogenic IgGs regardless of antibody status.

In seronegative MG, we demonstrated a clinically meaningful improvement in MG-ADL in the overall population with responses becoming more pronounced with subsequent treatment cycles across all subtypes. In ocular MG, we're seeing that same biology extend to another patient population with VYVGART meeting its primary endpoint and driving clear improvements in ptosis and diplopia.

Our seronegative PDUFA date is May 10. And based on today's results, we see a clear path to expanding our label into ocular MG as well, positioning VYVGART to have the broadest MG label and to reach our target addressable population of approximately 60,000 patients in the U.S.

In CIDP, we're also having a meaningful impact on patients with clinical data showing functional improvement and these benefits increasingly reflected in real-world experience. VYVGART is driving a paradigm shift in CIDP. While there remains significant opportunity within the initial 12,000 addressable patient population, we're also beginning to see expansion beyond that population, a core focus as we build leadership in CIDP. Sandrine will speak more to this later in the call.

Slide 6. Over the next 12 to 18 months, we have multiple avenues for expansion beyond MG and CIDP, including autoimmune myositis and Sjogren's disease, which broaden VYVGART's footprint into rheumatology. In particular, our work in IMNM highlights a significant unmet need with an estimated 20,000 patients and no approved treatment options today. Meanwhile, our upcoming Q4 readout for empasiprubart in MMN marks an important milestone, positioning us to advance a second medicine to patients and extending our neurology footprint with a first-in-class C2 inhibitor. We have an opportunity to address a clear unmet need in MMN with IVIg as the only approved treatment and symptom progression in 60% of patients.

Slide 7. Lastly, we continue to strengthen the pipeline that will shape our long-term future. VYVGART is just the beginning of FcRn leadership that we aim to establish for decades to come. As part of this, we're advancing 2 next-generation assets, ARGX-213 and ARGX-124. We're investing in efgartigimod anchored combination approaches and new delivery modalities like the auto-injector and oral peptide capabilities.

At the same time, we're seeing real momentum across our broader innovation platform, progressing first-in-class molecules like ARGX-121 targeting IgA and ARGX-118 targeting Galectin-10. We are deliberately source agnostic in how we identify new biology drawing from both leading academic research and opportunities emerging within biopharma.

In 2026, we expect to progress 3 Phase I programs, including a program from our Tensegrity collaboration, reinforcing our ability to bring forward high-quality science wherever it originates.

We have an exciting year ahead of us with a strong foundation in place and exciting progress across the pipeline. Let's turn to the data that's shaping our next steps. Luc?

Thank you, Karen. I'm excited to share the positive outcome of our Phase III ADAPT OCULUS study. Our second MG expansion milestone to hit just months after we shared positive seronegative data.

Let's turn to Slide 8. Together with leading global experts, our team designed the first registrational study in ocular myasthenia gravis, filling a long-standing gap for the patient population that has historically been excluded from clinical trials. We leveraged the screening period to ensure patients had a confirmed diagnosis of ocular MG, defined as MGFA Class I, meaning patients had meaningful measurable eye symptoms without evidence of generalized disease.

Patients were also required to be on stable background therapy. 141 patients were randomized 1:1 to VYVGART Hytrulo versus placebo. And in Part A, they received 4 weekly injections. In Part B, participants received multiple cycles of VYVGART Hytrulo. The primary endpoint of the study was a change in MGII patient-reported ocular score from baseline to day 29, a measure focused on the key ocular symptoms of myasthenia gravis, diplopia and ptosis.

Slide 9. The study met its primary endpoints. Treatment with VYVGART Hytrulo led to a statistically significant improvement in MGII patient-reported ocular score at week 4 compared to placebo with a p-value of 0.012. VYVGART-treated patients experienced a mean 4.04 point improvement compared to a 1.99 point improvement on placebo, including clear improvements on diplopia and ptosis. VYVGART was well tolerated, upholding its consistently strong safety profile with no new safety signals. We will present a broader data set at an upcoming medical meeting.

This is a big day for patients. Ocular MG strips people of independence. Many suffer from headaches and the persistent double vision and drooping eyelids don't just affect eyesight, they can take away the ability to drive, work and confidently engage in daily life, often with a heavy psychological burden and stigma. And today, too many patients are still relying on chronic steroids and symptomatic therapy, which comes with an unacceptable treatment burden over time.

For the first time, we are bringing forward a therapy that specifically addresses the underlying pathological mechanism of ocular MG, and that is something we should all be excited about. Based on these results, we plan to file an sBLA with the FDA.

Now before I turn the call over to Karl, I want to sincerely thank the investigator site teams and most importantly, the patients and families who made this study possible. Karl?

Thank you, Luc. Slide 10. The fourth quarter and full year 2025 financial results are detailed in this morning's press release. Product net sales are consistent with our preannouncement in January at $1.3 billion for the fourth quarter and $4.2 billion for the full year, which represents a year-over-year growth of 90%.

Regional breakdown of product revenue in Q4 2025 reflects $1.1 billion in the U.S., $63 million in Japan, $110 million in the rest of the world and $26 million in product supplied to Zai Lab in China. The product net sales in the U.S. grew by 68% from the fourth quarter of the prior year, reflecting solid patient demand and prescriber confidence driven by PFS. The gross to net adjustments and the net pricing in the U.S. are in line with the prior quarter.

Next slide, Slide 11. Total operating expenses in the fourth quarter are $955 million, representing an increase of $149 million compared to the third quarter. Cost of sales for the quarter is $150 million as our year-to-date gross margin remains consistent at 11%.

The combined R&D and SG&A expenses totaled $2.7 billion for the full year, which is in line with our financial guidance for 2025 discussed in our most recent earnings call.

Looking ahead into 2026, operating expenses will continue to grow at a similar percentage as in prior years. SG&A growth will support the significant revenue growth in our current markets as well as expansion into new patient populations. R&D expenses will increase due to our continued commitment to execute on our pipeline.

Our operating profit for the quarter is $367 million and $1.1 billion for the year, which marks our first year of annual operating profitability. Tax for the quarter and full year reflects a net benefit. This is largely due to nonrecurring tax items and favorable foreign exchange movements. Going forward, you should continue to expect an effective tax rate in the low to mid-teens. This brings us to the profit for the fourth quarter of $533 million and $1.3 billion for the full year, respectively.

Our cash balance represented by cash, cash equivalents and current financial assets is $4.4 billion at the end of the fourth quarter, which represents a more than $1 billion increase over the year. The strength of our balance sheet allows us to invest with confidence in growing our commercial business as well as our pipeline.

I will now turn the call over to Sandrine, who will provide details on the commercial front.

Thank you, Karl. Slide 12. I'm thrilled to be joining argenx at such a pivotal moment. What excites me most is the combination of bold science and a deeply patient-driven mission, what I often describe as science with purpose.

I've spent time in the field already, met clinicians and seen firsthand the real impact our science is having on patients' lives. With Vision 2030 as a road map, we have a clear path to meaningfully improve the lives of more than 50,000 patients.

Slide 13. Echoing Karen, we entered 2026 from a position of strength following a year of phenomenal execution. We closed 2025 with approximately 19,000 patients on treatment globally, reflecting consistent growth across all regions and all indications.

We successfully launched the prefilled syringe, which has proven to be a key driver in increased overall VYVGART demand. At the end of the fourth quarter, we had more than 4,700 prescribers, including dozen new prescribers since the PFS launch. This momentum underscores the execution strength of our field teams, the added convenience the PFS brings to patients and the growing confidence in VYVGART among clinicians.

As we highlighted at the start of the year, our next chapter is about applying a proven indication expansion playbook to reach even more patients. MG and CIDP remain the cornerstone of our commercial strength, and we are well positioned to build on that foundation as we scale.

Slide 14. We entered the MG market with strong biology and a first-in-class therapy. Since then, we have redefined what patients and clinicians can expect with the highest MSE and a favorable safety and tolerability profile. As a result, VYVGART is the fastest-growing and #1 prescribed biologics in MG with continued momentum driven by earlier line adoption. 6 out of 10 MG patients starting on biologic start with VYVGART. 70% of VYVGART patients are already coming from orals, and we believe the PFS will continue to help drive near-term growth.

We are now on track to reach 18,000 additional patients through 2 label expanding opportunities, seronegative and ocular MG. Seronegative MG alone has the potential to move us towards the broadest possible MG label with our May PDUFA just around the corner. And ocular MG gives us a chance to be the first to market in a patient group that has had no precision treatment options. What gives us confidence here is that these expansions build on strong relationships we have already established with neurologists, many of whom are confident in VYVGART through experience treating generalized MG.

Slide 15. We are earlier in the CIDP launch trajectory, but are delivering on the same disciplined approach that has led to our successful market expansion in MG. Significant opportunity remains within the 12 dozen patients who are not well managed on current treatment, and our focus today is on continued evidence generation, patient activation and new prescriber adoption.

Clinicians continue to respond to the meaningful functional benefit data and well-characterized safety shown in the ADHERE trial. The prefilled syringe is further driving uptake by reducing the administration burden and offering more flexibility to patients.

Worth noting, we secured an important access win for PFS in Q4 with UnitedHealthcare, broadening our covered lives to over 90%.

CIDP is a highly heterogeneous disease, and we are committed to advancing the science to expand our reach to broader set of patients. Our biomarker program is designed to better define responders and unlock earlier and broader use, and we are advancing empasiprubart in a head-to-head study against IVIg to further explore the bounds of efficacy. Together, these efforts position us to expand the CIDP population we can serve and continue shaping this market over the long term.

Slide 16. Our clinical pipeline continues to broaden and deepen, providing a multiyear runway for commercial growth. I'm excited to join the company at this pivotal moment to help scale the organization thoughtfully and translate this pipeline into even greater patient impact.

With that, I'll now turn the call over to Tim.

Thank you, Sandrine. Reflecting on where we stand, argenx has never been better positioned, and our leadership transition comes at the right moment as we enter our next phase of growth. Karen is the right leader to take this forward. She understands our innovation playbook, leads with patients at the center of every decision and brings the operational discipline needed to continue executing against Vision 2030 and beyond. I have complete confidence that she will nurture what has always made argenx special while driving the next chapter of growth for the company.

My dedication to argenx and to our mission remains as strong as ever. I look forward to supporting Karen and the entire leadership team as we continue to advance meaningful innovation and deliver for patients and shareholders alike.

With that, operator, we will open the call up to questions.

[Operator Instructions] Your first question today comes from the line of Tazeen Ahmad from Bank of America.

First off, Karen, congratulations on the new role. We're looking forward to continuing to work with you. And Tim, what else can I say, but thank you. You've set the example for everyone to follow, and we wish you the best in your new upcoming role as well.

So my first question is going to be on the addition of both seronegative as well as based on today's results, assuming ocular MG to the revenue stream for VYVGART. How should we think about, number one, what the average price would be for each of these subindications? And can you talk to us about what proportion -- you talked to us about how many patients there are. But have you done any market data research to indicate what proportion of those patients are more likely to seek this type of treatment?

Well, thank you, Tazeen, for your comments and also for your question. It's a really exciting day for ocular MG patients and certainly for argenx, as you call out. It's important to think about the fact that we are now the first and only -- or VYVGART is the first and only to have positive data for patients with ocular MG. So a really exciting day for patients.

And as you called out, that, combined with the seronegative data that just read out a few months ago, and we have the PDUFA date in May, really positions us well for continued sustained growth in MG and I think an expansion even further of our leadership position in MG. So we're very excited to share that data today.

I'll let Karl talk to the price in a moment. But just on the second part of your question around the addressable market, we obviously have done quite a bit of market research, and we'll continue to do so to prepare for how best to go to market. But the best numbers to look at are those that we've provided with the seronegative expanding the addressable market by 11,000 patients and ocular by 7,000 patients that we've provided before. That 7,000 patients in ocular MG, that's not the total ocular MG patient population. That's actually the portion that when we've done the research before, we thought would be eligible for VYVGART. So that's the number that I would stick with. And obviously, as we get closer to -- as we unpack the data more, as we get closer to submission and hopefully approval, we'll be able to provide more color on that.

And then maybe, Karl, you could comment on the price.

Thank you, Karen and Tazeen, thank you for the question. Yes, we still have to have the discussions with the players, of course. But I do want to mention that we have a strong capability and market access. It is an enabler of our launch, not a hurdle, and the value proposition of VYVGART is well understood and appreciated by all stakeholders.

At this stage, I will say that we would expect to have broad access also for seronegative and ocular, and we can assume a similar price as MG, i.e., $225,000 the net benefit or a net price to argenx. Thank you for the question.

Your next question comes from the line of Danielle Brill from Truist Securities.

I think I'll ask a question on the CIDP opportunity. Karen, you mentioned in your prepared remarks that you're beginning to see expansion beyond the initial 12,000 patients that you were targeting. Can you elaborate a bit? Are you seeing a step-up in frontline use? And then I think you also mentioned that you secured additional coverage, broadening coverage for PFS to over 90% of covered lives. What impact do you expect this to have on adoption rates in the setting going forward?

Thanks, Danielle, for the question and the interest in CIDP, we're really pleased with the continued growth in CIDP. So, yes, we laid out that the strategy was first to focus on that 12,000 patients that are treated -- that are already treated, but continue to have symptoms. And that is -- continues to be where we see the majority of our patients and the majority of our growth. But you'll recall that our label does allow us to be used in a broader patient population. And there are some payer policies actually that also allow that. So we are starting to see some use of VYVGART beyond just the switch from IVIg.

In general, it's still about at 85% of our patients are being switched from IVIg, but there are some that are coming directly. I think as prescribers and neurologists get more experience with VYVGART and see the impact in the real world, then over time, we'll start to see that expansion even more.

And as you said, continuing to expand access with the recent UnitedHealthcare decision and having 90% coverage, that also helps to contribute to our growth. So I would say what to expect in CIDP is that continued steady momentum. We're still early in the launch. And so I think we still have some quite a bit of growth ahead of us.

Your next question comes from the line of Derek Archila from Wells Fargo.

Congrats on the progress in the Phase III win today. So I had a question on, do you think approval in ocular MG will drive more utilization in the less advanced MG patients? And I guess, is there anything in the data set that you'll present in the future that could demonstrate prevention of progression to more generalized disease?

Yes. Thanks for the question, Derek. I'll comment on the first and then maybe, Luc, I can hand it to you for the data. So certainly, I think that our hypothesis, I mean, we know that in MG, the majority of patients first do present with ocular symptoms and then the majority of those ocular MG patients do transition into gMG. So a big part of our strategy is expanding the use of biologics to earlier line uses of MG.

We are already seeing that. Biologic use is growing in generalized MG. We are driving -- we get 6 out of 10 of those patients that are first use biologics. So we're driving a lot of that earlier use and a lot of that growth. As you say, I think the ocular MG data will help us with that strategy and will provide a halo to that strategy. And then maybe, Luc, you could comment on the data and progression.

Yes. Thanks, Karen, and thanks, Derek, for the question, which is close to my heart. So with the data in hand, we show that we can meaningfully impact the current symptomatology of ocular MG, which is not MG like. It's a significantly debilitating state to be in. But of course, the excitement of continuing to collect long-term data as we are planning to do and compare that to what is known with the natural progression, which, as Karen said, is a high percentage up to 80% will allow us to make some statements on do we delay progression to generalized MG. So I would say stay tuned.

Your next question comes from the line of Yatin Suneja from Guggenheim.

Just with regard to the Q1 dynamics, could you point to us if there are any particular consideration that we should have for Q1 in particular?

Yes. Thanks for the question. And it's important as we're in Q1. So obviously, across the industry, we can see the pattern that there always are Q1 dynamics around reverifications and winter storms, of which we've had quite a few in the last couple of weeks. So argenx and VYVGART are, of course, privy to the same, those same seasonal dynamics. And we saw that last year as well. If you recall, we did have a slowdown in Q1. And then in the end of the year, we delivered 90% full year growth. So I think you can recognize the pattern and expect that. But maybe, Sandrine, you could comment on the underlying dynamics that we're seeing since you've joined.

Yes. Thank you, Karen. And this is something that I looked at before joining argenx, what is the growth we are seeing. And year-after-year, we have been delivering consistent growth, and this is a pattern you can expect this year, full year because the underlying dynamic are very healthy.

I mean when you look at the new patient starts, the provider and the prescriber expansion. When you look at our access, we just mentioned that, but also how strong we are and VYVGART is in leading the growth of the overall biologic market. These are all amazing underlying factors that will help us continue that growth.

And then you have the PFS that was launched less than a year ago that drove a lot of momentum last year, plus the expansion of the labels that we are expecting both for seronegative and later for ocular. So all are good underlying factors that will help us continue that growth, as Karen mentioned.

Your next question comes from the line of James Gordon from Barclays.

James Gordon from Barclays. The question was on VYVGART for myositis. And my question was, what is the efficacy bar you're looking to exceed in the Phase III in myositis in Q3? What's a good result? Is there hope to be more efficacious than [ brepo ] or JAK/TYK and what they did in the VALOR trial? Or is it more -- a good result would be if you had a similar efficacy and you are better tolerated as well? So what's good and what's really good?

And could I also just squeeze in a clarification, not a question, but just normally, there's an OpEx guide, but I didn't see a formal guide this year. Should we assume a similar pace of OpEx growth this year as last year, so '25 similar pace of '26 and maybe more R&D and less SG&A? How do we think about spend this year, please?

Yes. Thanks for the questions there, James. And so I'll open. I'll hand over to Luc to provide some more color on myositis and then Karl on OpEx. But the first thing that I just wanted to frame is when you think about myositis, it's right out of the argenx playbook. I mean there is so little options available to patients here, really limited innovation in the market. And so what we're looking for is a statistical significant benefit coming out of this study. In the DM, in IMNM, there are no approved therapies available. And you heard in the script that there are 20,000 patients with IMNM. So for them, any benefit, I think, is clinically meaningful. But maybe, Luc, you could talk about how we're thinking about the study.

Yes. Thanks and also for laying it up that this is not a singular indication. So this is a constellation of indications that each have somewhat different pathological drivers. We continued our Phase III program based on the strength of a robust Phase II, which gave us the confidence that we could provide meaningful benefit across the 3 subsets. Ultimately, the data will speak once we complete Phase III.

With respect to relative benefit compared to others, of course, studies are hard to compare. And the DM result of brepo certainly is encouraging for the DM patients. But we believe that in DM, multiple modes of actions could play a role. And therefore, we will go on the strength of our own data. In any event, positive data in these diseases is always good for the patient.

Thank you, Luc. And maybe, Karl, a comment on the OpEx.

James, thank you for the question. Yes, in 2025, we spent around $2.7 billion on combined R&D and SG&A. That is around 30%, 3-0 percent increase over 2024. Looking ahead, you can expect the combined R&D and SG&A to grow at a similar rate with most of the growth in R&D because that is where we're going to invest to set the company up for the long run, investing in our very exciting pipeline. So thank you for the question, James.

Your next question comes from the line of Alex Thompson from Stifel.

Maybe on Graves, I was wondering if you could comment on where you're at from a regulatory discussion perspective on starting the pivotal and whether you think that a single pivotal could be sufficient for an sBLA or whether you might need 2 studies.

Yes. Thanks for the question. We're excited about our Graves program, and it's well underway. Luc, do you want to comment on our strategy around the single study?

Well, I mean, the ability to run a single study has sufficient evidence of efficacy and be able to define a benefit risk is actually not new. That always existed, but it was at the discretion of the individual divisions as to how much they accepted that or not. This particular division has asked us at this moment for 2 trials, which we are executing on.

Your next question comes from the line of Matt Phipps from William Blair.

Congrats on the quarter and progress here. Just wondering if you might be able to give us any more details on the auto-injector, how you can position that versus the PFS and maybe if that can just continue the continued expansion you're seeing from that PFS launch across indications.

Yes. Thanks for the question. We're excited about the auto-injector, and I think it just reinforces our innovation playbook, right, just continually bringing more and more innovation as we drive leadership in the MG market. So auto-injector is on track. We have planned for 2027. And the way we've talked about it is it won't be such a step forward in the way that PFS was because if you recall, the big step forward for prefilled syringe was that we moved from HCP administration to patient administration, and that was a meaningful and important step forward for many patients, giving them the freedom to self-inject. So auto-injector doesn't provide that step change, but it does provide an important step, for patients that provides a better experience for those patients and especially those that are needle phobic.

Actually, we mentioned earlier, we're here at the U.S. National Field Meeting. We had a patient just yesterday that was talking to our team, and she was sharing that she wanted to wait for auto-injector because the prefilled syringe needle was something that she was a little nervous about. So it does provide value to patients, but it's not such a step forward that you should think of it as an accelerator in the way that the prefilled syringe was.

Your next question comes from the line of Akash Tewari from Jefferies.

This is Amy on for Akash. Maybe just a quick one on your 2 next-gen FcRns 124 and 213. Are you seeing an accelerated path to registrational study? And can you give us a sense of how you're thinking about the indication and then the size of these trials?

Yes. Thanks for the question and the interest in our future portfolio. Maybe I can start. The way that we think about our leadership of FcRn over the coming decades is that we know there is a lot of opportunity for FcRn, in fact, probably more than we can explore with VYVGART alone. And so we see the opportunity of having 2 next-generation molecules as opening up the opportunity to provide a better patient experience in some of the indications we're already in, but also start to push the biology even further and expand the indications that we can -- that an FcRn is making a difference to patients. So I think that's the strategy that we're planning. We think each of the next-generation molecules brings -- will bring that benefit to patients. Thanks for the question.

Your next question comes from the line of Yaron Werber from TD Cowen.

Congrats on the ocular study. If you don't mind, maybe a couple of questions. For EMPASSION, you switched the primary endpoint to grip strength. In the previous study in ARDA, you gave us sort of the ranges of grip strength. So maybe help us understand how is it powered? Is it superiority sort of head-to-head? What's clinically meaningful?

And then secondly, Karen, we have a huge confidence in you, and congrats on the role. Tim, we're just -- we continue to get questions on the timing. I know, obviously, Peter is retiring as Chair. So maybe give us a little bit of a sense what drove your decision to kind of step up the chair.

Thanks for the questions, Yaron. I'll hand it over to Luc first to talk about EMPASSION. And then, Tim, maybe you can take the follow-up question.

Yes. So in fact, this is a story of growing insights in data as they matured. As we looked at ARDA and ARDA plus, so the Phase IIs, the signal we saw in grip strength gave us increasing confidence that this is really a real and patient-relevant outcome with an increasing separation over time or improvement over time, which in these patients was not seen before. And that's ultimately why in discussion with agency, we started utilizing this endpoint as the primary. You asked about superiority. The study is set up as a non-inferiority study, but with a prespecified option that if noninferiority is met, that we can formally test superiority. The data will ultimately drive that [ tree ].

Thank you, Luc. And Tim?

Thank you for the question. I think we're doing this transition out of a position of strength. I think now is the time to do the transition because the business and the organization is in a very healthy and a very strong state. You have seen the pipeline. You know the profitability, which we achieved during the course of last year, very strong foundation of the business. Also from an internal candidate point of view, we are ready. Karen knows the innovation playbook. She's a very strong carrier of the culture of the company, and she's ready to help us scale into our future because she know new therapeutic areas will come on back relatively soon. So consider this as a proactive move based on a position of strength. Thanks for the question.

Your next question comes from the line of Thomas Smith from Leerink Partners.

I was just wondering if you could provide a bit more color on the Phase IIa results for adimanebart in ALS. Obviously, really difficult indication, very complex biology. But just wondering if there are any learnings from this study that could be applied to the Phase III CMS program or potentially other indications.

Yes, I'll let Luc comment on the data.

Yes. Thanks for that question. Evidently not an outcome we were hoping for. We felt we had the moral obligation to explore ALS as an indication given our mode of action, trying to -- in this disease where there's very, very limited treatment options to see if we could move the dial. From our POC, the data, unfortunately, don't supports progressing, but we learned a lot, not in the least about how novel endpoints could be used, and we hope to share that knowledge with the field.

With respect to impact and learnings on CMS, the context of treatment is fundamentally different. And CMS is directly in the biology of this molecule with the DOK-7 and other mutations affecting the mask receptor. And so that's a much more direct application of this molecule. So we don't think there's a read-through.

And on our SMA program, likewise, there is a backdrop of approved treatments. The gene therapies are very well established. And we are going to evaluate whether we can have an add-on efficacy there, which is a different situation than ALS altogether.

Your next question comes from the line of Rajan Sharma from Goldman Sachs.

I had just a question on VYVGART growth dynamics through 2026. So just thinking about kind of the underlying growth outside of potential new indications, how should we think about growth across the various formulations of the drug? And if you could maybe just comment on competitive dynamics. I realize there's been a recent new approval in myasthenia gravis. Could you just talk to your confidence in the VYVGART profile and to what extent you think you may be impacted by that emerging competition?

Great. Thanks for the question. What -- I'll provide just one comment, which is one of the things that I think is incredible 5 years out from launch for VYVGART is that what we're seeing is continued growth across all indications, all geographies and all product presentations. And I think that's a sign that there's space for all of the different product presentations, and it's important that we're bringing those innovations. But Sandrine, maybe I can hand over to you to talk about the growth outlook for MG and CIDP.

Yes. Thank you, Karen. And I can maybe also help answer the question on the competition but that was a second question. So I think for MG, I mean, we have seen an amazing growth year-on-year. And we have, as I mentioned earlier, healthy fundamentals. I mean, our product, VYVGART is being used earlier and earlier. I mean, as I mentioned in the opening, 70% actually are coming from orals.

And then on VYVGART, when you have 10 patients coming on biologics, 6 of them are actually starting with VYVGART. So this shows that this is the molecule that patients start on when they are starting on biologics. PFS is the one that has been driving and helping us drive strong growth last year. And as Karen just mentioned, we expect to continue to grow across all mode of administration, including PFS. And then the label expansion, of course, is going to help us this year, starting with seronegative.

If you look at CIDP, I mean, we have -- we are still early in launch. So we have launched roughly 1.5 years ago, and we are still have a lot of room within the 12,000 patients that are not fully well managed. And beyond that, we are working very, very hard to lift any challenges either with payers or the inertia of prescribers to start earlier with VYVGART. So overall, very strong dynamics expected for this year like we had in the prior years.

So now going to your question on the competition. Actually, we welcome competition. For me, this is -- and for us, this is a sign of progress, and this is a sign of innovation, and that's great for patients to have multiple options. This expands the overall market and VYVGART benefits from a market expansions. I just mentioned that 6 out of 10 patients starting on biologics go on VYVGART. So the more the market expands, the better it is for us.

And as we are a data-driven company, all the data we have generated support our confidence that VYVGART profile will help us continue leading that category and remain the #1 prescribed biologics in MG from an efficacy viewpoint, and we are the only one that can really show the strong MSE, the robust safety that fosters earlier use, the ability to meaningfully reduce steroids and then as we mentioned, multiple flexibility on either IV subcutaneous or PFS. So when you take that all together, I mean, we believe that we have a very, very strong profile for continuing our leadership there.

Great. Thanks, Sandrine.

[Operator Instructions] Your next question comes from the line of Sean Laaman from Morgan Stanley.

This is Morgan on for Sean. Maybe one on the financials. So with VYVGART delivering $4.2 billion this year in net sales and 90% year-over-year growth resulting in the first year of operating profitability. How should we think about the sustainability of this growth profile as penetration deepens in MG and CIDP throughout this year and next year?

Yes. Thanks for the question. Karl, maybe you want to talk about the growth profile?

Yes. I think what we're building here is a long-term sustainable business, as Sandrine already mentioned, we see a lot of growth in MG and CIDP going forward. And the way we look at the financials long term is that revenue growth should exceed OpEx growth, which basically will return operating margins, which will increase over time. That in itself, of course, is not the objective of the company. We have very clear capital allocation priorities, and we're executing on those priorities. But what we should see is that we're going to build on our very strong balance sheet. We currently have $4.4 billion of cash in the bank. And going forward, that number should increase. So I think you can look forward to a long-term sustainable and profitable business. Thank you for your question, Morgan.

Your next question comes from the line of Sophia Graeff Buhl Nielsen from JPMorgan.

So just on the Phase III readout for VYVGART in myositis, could you clarify, would you have data to support approval by subgroup? Or will this largely be dependent on the overall data? I think you've been very clear on that the high unmet need within IMNM and the large patient population that could be addressed there and also the heterogeneity within DM. Given these dynamics, would you see these as relatively equally sized commercial opportunities despite the differences in addressable TAMs you've highlighted?

Yes. Thanks for the question. Maybe, Luc, you can talk to the basket trial and our approach, and then I can comment on the commercial opportunity.

Yes. So the Phase III setup is indeed that we can make statements on all 3 subsets. And of course, the ultimate reflection of that in label will be connecting the data with the regulatory discussion. But in principle, all 3 could be in scope.

Thank you, Luc. And then in terms of the commercial opportunity, the way I think about it, I mean, the total myositis population that we're studying, we think about in terms of it being an MG-like opportunity. But obviously, there are other subtypes. And I like to think about the 2 bookends of the subtypes.

So we talked -- you mentioned IMNM. So IMNM, there are no other approved treatment options. There's about 20,000 IMNM patients. So what you can imagine there is that from a commercial perspective, you could imagine that we'll be able to gain a high portion of those patients because there are no other treatment options and the biology is so clear.