Thank you, James. Every year, it's a pleasure to be kicking off the year together at this J.P. Morgan conference, and a very warm welcome, ladies and gentlemen, to the argenx presentation. A couple of seconds paying attention to the forward-looking statements. So, ladies and gentlemen, at argenx, we are on a mission. We are on a mission of innovation. Actually, we are acutely aware of the fact that the only reason we exist, the only reason we have the right to exist, our raison d'être, is because we innovate. But innovation as such has no meaning unless it's providing real benefits to patients, and today, I would like to start with one of our CIDP patients.
This is a 19-year-old young woman diagnosed with CIDP last year, very quickly progressing to a wheelchair, not responding to IVIG, giving up classes in college, and actually seriously considering a feeding tube because of the weakness in her arm. Around Thanksgiving, she came on VYVGART Hytrulo, and just after one month's time, this person could walk again independently, planning again to go back to college, and perfectly able to feed herself. This is not a miracle. This is transformative innovation. It's the type of innovation we're trying to build at the company. We have a playbook of how we build innovation. And actually, the early molecules, including VYVGART, helped us to crystallize the playbook. We think this industry badly needs novel biology. We have too many new hammers hitting on the same old nails. We need transformational biology.
It's the type of biology we find in academic centers with whom we collaborate, trying to identify these foundational immune targets. And once we have such a target, we co-create with these academic researchers the molecules which we built so they're very difficult to beat for followers. And we only take a program forward into development if we have the conviction the molecule can play across multiple indications. Pursuing novel biology is risky. A way to spread your risk and a way to create disproportionate returns on investment is by having these pipelines in a product. So you hear us talk a lot about a pipeline in a product concept, which definitely VYVGART is. Let's see if you bring this type of innovation to a marketplace what it can do.
If you look at our MG space, our MG market, for our VYVGART patients, you have an eight out of 10 chance to reach an ADL of five or lower, meaning you're no longer eligible for any clinical trial. You have a more than 50% chance in the real world to achieve minimum symptom expression. That means you're living your life with no or minimal symptoms. Actually, if we would fill in an ADL score, we would typically end up at a zero or a one. In the CIDP space, what it means for patients is that in seven out of 10 cases, they develop a meaningful clinical response. More than 60% of our CIDP patients in the clinical trial regained function, and actually one out of three regained substantial function on the drug. Now, ladies and gentlemen, patients don't talk about an ADL scale.
They don't talk about an INCAT scale. The testimonials which we get every day in the company are stories of patients telling us they're getting their life back. It's a transformative event. Being able to live again your life the way you had it before you were diagnosed with the disease, that's what matters. And that is transformative innovation. So once you have these molecules, once you disrupt markets by setting a whole new goalpost in these markets with your product, you can get rewarded with an attractive commercial success. This is my opportunity at the beginning of the year to thank the entire U.S. Commercial Organization and global U.S. Commercial Organization for the very strong performance they gave us in 2024. Q4 gave us $737 million revenue, totaling the total revenue for 2024 to $2.2 billion.
We ended the year with a bigger cash position than we started the year, which means we're on a path to profitability, but my commitment here today is that we're not going to lower the bar on discipline. We will stay disciplined in the way we allocate capital, and we will stay disciplined in the way we scale our company. Looking forward into 2025, we have three simple priorities. Priority number one is to reach more patients. Patients are waiting, and there are many of them, and we believe that the prefilled syringe is going to be a key enabler in that goal to reach more patients. Second priority is to fuel the pipeline. This year, argenx will be executing 10 phase III clinical trials and 10 phase II clinical trials, but it doesn't stop there.
Priority number three is that we're going to expand the next wave of innovation with four new molecules entering phase I clinical trials. So let's unpack priority number one, reaching mor patients with VYVGART. I would like to applaud the TechOps team for giving us this beautiful piece of innovation, this prefilled syringe. It's a beautiful product because it was co-created with Halozyme to give us this low viscosity, very high product concentration, and exclusively equipped formulation with ENHANZE technology, which allows patients to inject, self-inject the product in as fast as 20 seconds. We co-created a container with Vetter. It's a pretty remarkable container. And we think this product is on track for the PDUFA date of April 10 here in the United States, and in total on its way to four global decisions on approval in 2025.
We're also working in the background on the next generation of innovation, which is the autoinjector, which we're co-creating with Ypsomed. Reaching more patients in myasthenia gravis. We are already the market leader with the number one branded biologic for gMG. I just showed you that we have nice, consistent quarter-on-quarter growth. And I also showed you that we have put the bar very high. Now, guys, we have a ton of work in front of us. The total addressable market today is 17,000 patients, and we're going to elevate it into the 60,000 patients we have been talking about during last year's R&D day. Three ways to do it. The prefilled syringe will help us to continue to move upstream in the treatment paradigm, expanding the TAM.
We're currently executing two phase III registrational trials, which should be label enabling, one in Seronegative MG and one in Ocular MG. We have the technical right to win in Seronegative MG because we already have that on label in Japan. We have an overwhelming body of evidence from Europe, and now it's a matter of landing that registrational trial for which we have an agreement with the FDA, and that trial is actually enrolling while we speak, but let me talk today about Ocular MG. I'm very excited about this opportunity. First of all, the ocular form of MG is a significant unmet need. It comes with a very high disease burden. Imagine you have double vision, drooping eyelids. It basically means you're not able to work. You're not able to work on a screen. You're not able to drive.
You're not even able to participate in normal social activities. It comes with a high treatment burden. The only real option these patients have on top of Mestinon is a chronic high dose of steroids. And I do not need to explain to this audience what it means long term in terms of detriment. So here is the opportunity to pioneer and transform, and just like we did in gMG, set a whole new standard for these patients. Technically, we have the right to succeed in Ocular MG. The ocular muscle domain scored as well as all other muscle domains in our ADAPT trial. And we have an increasing number of case reports from the real world where Ocular MG patients are doing really well on drug. Actually, there is nice upside to the Ocular MG indication because that's typically how MG starts and then spreads into generalized MG.
Just imagine that we can demonstrate that we can slow down the generalization of MG. Ladies and gentlemen, that's a big deal. So I'm very proud today to announce Oculus. It's live. It's enrolling. It's the first and only study in MG, Ocular MG. How do we reach more patients living with CIDP? Well, we need to continue the momentum. We created a very nice momentum back in 2024. Let's continue it in 2025. We have more than 1,000 patients on therapy. Most of them are actually IVIG experienced, as expected. My turn to applaud the market access team for doing a phenomenal job in securing the policies. We have more than 90% of lives covered here in the United States with policies which we think are favorable or highly favorable. The halo effect of being able to market CIDP next to MG opened up new prescribers to us.
25% of our prescribers were never seen before at argenx. This year, in 2025, you will see a continued global expansion in CIDP. Let's talk about strategic priority number two, fueling the pipeline. I did talk about the pipeline and the product concept. We have three pipeline products in development: VYVGART , empasiprobart, and ARGX-119. And here we visualize the indication footprint of these three molecules. You see a very nice neuro segment shaping up, flanking the approved indications of MG and CIDP. With myositis, we have a nice foot in the door with rheumatology and a very big indication coming with Sjögren's. And then in the third segment, you see some real big indications with Thyroid Eye Disease next to the approved indication of ITP, and a nice growing cluster of kidney indications with AMR, LN, and DGF.
On this slide, you can see that empasiprobart starts to populate the field. We already see four indications. So I would like to double-click on this molecule. Empasiprobart is now a phase III asset. It's coming directly from the argenx Innovation Playbook. We think C2 is a great target. Clean safety profile, both on a theoretical ground and on a very robust phase I data ground. Very nice scope of opportunity by nailing both the classical and the lectin pathway, but leaving the alternative pathway intact. Together with the world experts on C2, we co-created a molecule which will be difficult to beat from a potency or a dose inconvenience point of view. And again, we see the pipeline and the product shaping up. This year, we will be running two phase III clinical trials, registrational trials, one in MMN and one in CIDP.
We have two robust proof-of-concept trials ongoing in delayed graft function and dermatomyositis. Personally, I'm very excited about MMN, multifocal motor neuropathy. Ladies and gentlemen, this is a bad disease. It's so bad that often it's misdiagnosed as ALS initially. These patients are progressing rapidly, ending up in disability in 20% of the cases. The only drug out there today is IVIG. Remember the phase II data which we presented in 2024? I've never seen more black-and-white data than this phase II ARDA trial. But what I'm most convinced about and most excited about is the right-hand panel where patients talk to us. Patients were asked how they feel on EMPA compared to the best they felt on IVIG. 94% of the patients feel better or much better than how they felt at their best on IVIG. That's a big deal.
EMPA in 2025 will be in two head-to-head trials, registrational trials with IVIG. The MMN trial is called Empassion. That study is actively enrolling. And what I'm very excited about is the fact that we are also flanking that study with a natural history study, where we had the bold ambition to enroll 150 MMN patients. And look at this. More than 400 MMN patients raised their hands and participated in the trial. That tells us something about the unmet medical need. Also, in CIDP, we decided to go head-to-head against IVIG. Now we have an opportunity to shape the CIDP market with two innovative molecules. Last year, during the R&D day, we spoke about how the MS market was built by innovation. Today, I already told you how we're building the MG market with innovation.
I think there's another market to be built, which is the MMN market with our type of innovation, which ultimately brings much better outcomes for many more patients. Quick look at ARGX-119. You see the playbook. MuSK is an exciting novel target. It's a key organizer of the neuromuscular junction responsible for the development, the maturation, and the functioning of the junction. Together with the world experts on MuSK, we've built a very rare antibody called ARGX-119, an agonistic antibody, and you already see that we're active in three indications. There are two proof-of-biology indications already in play with Congenital Myasthenic Syndrome and ALS, and we just announced today that we're venturing into a third indication based on solid translational biology data called SMA. Let's talk about the third strategic priority: expanding our next wave of innovation. This year, we will see four molecules start their clinical career.
I mean, they will all start phase I clinical development. When I will be on this podium next year, they will have either concluded their phase I clinical trial or will be very advanced in their phase I clinical trial. All four molecules are clever pieces of antibody engineering. All represent a pipeline and a product opportunity with multiple indications which we have been vetting in the antibody selection. The way this is all coming together, the way it's all summing up, I think is a world-class pipeline. Two approved products, 10 phase III trials, 10 phase II trials we're running in 2025, four phase I molecules, and a lot of interesting stuff cooking in the immunology innovation kitchen. But this is the point where I also want to call out bullous pemphigoid.
Bullous pemphigoid is no longer on this slide because the data which came in at the very end of last year did not demonstrate the transformative capacity of VYVGART in this indication, and that brings me all the way back to the disciplined capital allocation. We will only deploy capital, not because we can, but because we think we can have a transformational impact on our patients. The news flow originating from such a pipeline, I think, is significant. All eyes in the first half of this year will be on our prefilled syringe, PDUFA date, hopefully multiple approvals. Venturing then in the second half of the year, we will see interesting data for VYVGART from the phase IV, the phase III, and the phase II front, some earlier stage work happening, importantly with argenx- 119, hopefully showing proof of biology in CMS and 119 delivering phase I data.
It then goes crescendo into 2026 with a ton of phase III work, a lot of phase II work across multiple molecules. In summary, in the coming period, we will be seeing four decisions on approval, six phase III data readouts, six phase II data readouts, and four new molecules in phase I clinical development. The way this is designed is to create this nice cadence of launches. Remember, we have a bold goal to reach 50,000 patients by 2030. This is the ramp-up we believe into 50,000 patients. And that 50,000 patients should sound familiar because it's actually embedded in our Vision 2030. Remember, by 2030, we want to have five times more impact than we had in 2024. We want to reach 50,000 patients with 10 label indications and five new molecules in phase III. For me, this is a very humbling moment.
When we founded the company back in 2009, we had no idea we would be building this type of company. But one thing has not changed. That is the relentless commitment to innovation. That's why we continue to be loyal to our innovation mission. And with that being said, James, I would like to thank everyone for your attention. And we can move over to the questions.
Just as a reminder, you can ask questions by using the application if you know how to do that. You can also raise your hand to ask some questions. And we've got Karen Massey with us as well, who's COO. Does anyone have any questions they'd like to start with? Otherwise, you're going to get one starting with me. I think we've got one over there.
Thank you for the talk. That was very inspiring.
You have a really ambitious goal, which is to reach 50,000 patients. It's within reach, but I would like to ask you about your manufacturing strategy to get there. Thank you.
and maybe if you could repeat the question before answering.
Yeah, thank you for the question, and I would agree. It's an inspiring mission, and we are committed to innovation. The question was around our manufacturing strategy to deliver on all of this innovation, and I would say that the tech ops team has a clear strategy in place and we've been investing to ensure that we can deliver on our commitment to patients and to deliver to that growth. Our manufacturing strategy, we partner with Lonza, and so we have a strong partnership with Lonza. We're also expanding with Fujifilm.
We started with small scale and have been investing in expanding that scale, including to larger sites within the U.S., as well as beyond Singapore, where we are today. So I'm confident that we have the supply and the manufacturing strategy in place to continue to supply all the way up to our 50,000 patients.
To the person with the hand raised there.
Thank you. Very nice talk. So for your second-generation FcRn compound, you mentioned monthly dosing. Do you worry about infection risk?
No, we don't worry about infection risk at all. We now have 8,000 years of patient safety data. There is no real signal of infection, and actually, we understand that. We do clear IgG antibodies very effectively. Remember, we don't clear them 100%. There's a safety cushion which is left behind.
And very importantly, and totally differentiated from some other molecules, we're not touching the B cells. The little manufacturing plants of these IgGs are perfectly intact and able to respond. Actually, we have gone way above and beyond this theoretical rationale and the safety data. We did deliberately vaccination studies where we have shown that actually patients, regardless whether they're in between cycles or on a VYVGART cycle, they can perfectly respond to the typical commercial vaccines, including the COVID vaccination.
Thank you for the question. Question there.
Thank you. I know it's early days, but can we fairly expect some kind of halo effect from the CIDP launch on the other indication for VYVGART, like a stronger endorsement of the drug? You mentioned the 25% new prescribers. Do you have any early sign of that in the prescription trends, for example?
Yeah, yeah. Thanks for the question.
We are seeing what we call a halo effect from CIDP and the uptake of CIDP onto MG. So you'll recall that the majority of prescribers overlap between MG and CIDP. Having said that, there are more prescribers in the community for CIDP. So we expanded our target list with the CIDP launch. We also expanded our field team. What we've seen going out into the community with more targets is that there are 25% of the CIDP prescribers are new to VYVGART Hytrulo. Some of those prescribers have started their first patient on CIDP and now have started also a patient on MG. We are seeing that halo effect and that spillover, if you will, of being able to demonstrate both the efficacy as well as the safety for both of those indications with prescribers that have patients with both those indications.
Maybe a question I've had today, which has been so the sequential growth in VYVGART was quite a big step up. It would appear that most of that is CIDP, but could there be a one-off factor there, a bolus of patients that were waiting to go on therapy? Or is that a clear trend? Did you add more than $100 million on CIDP in Q4?
Yeah.
$100 million. Sorry, yeah.
Yes. No, thanks for the question, so we are very pleased with the Q4 results. And I would say the results that we're seeing are a reflection of continued momentum and continued growth in MG in line with our strategy to move into earlier lines of treatment. And we're seeing that play out. We also saw a strong uptake in CIDP, as you mentioned.
We're seeing that based on the back of that 90% favorable coverage that allows us to get patients started. And there also is this halo effect that we're seeing in Q4, where we did see that strength in MG growth as well. So I would say the growth reflects our continued momentum in both indications. And I think you can expect us to continue to see that in this coming year.
And then I'll say the gentleman with the question here.
Yeah. So with the new form factors that you have, do you have an estimate?
We should just wait for the mic, actually. Sorry.
Yeah. So with the new form factors that you have, do you have any estimates on how much better you could do on therapeutic adherence or patient retention relative to the competing drugs?
Yes.
So in terms of adherence, so what we said for MG, we have seen since launch around an average of five cycles. We don't expect that to change with prefilled syringe, with self-administration, if we get self-administration. We believe patients are being treated to their symptoms, and that will continue. In CIDP, since with launch, we have weekly dosing. And we believe that that will continue with prefilled syringe as well. Certainly, having self-administration will help those patients rather than having to come into their office every week. So we believe that the adherence and retention rates will remain consistent with prefilled syringe.
Thank you. On the theme of the prefilled syringe, how will it work in terms of doctors getting paid and in terms of how much money you'll make on a patient?
So are there different considerations in terms of this being an outpatient product if people can use it at home?
Yeah, absolutely. So assuming we get self-administration, the prefilled syringe would be a Medicare Part D for Delta, so through the specialty pharmacy. We haven't shared the pricing strategy yet, but I think it's fair to say that it will be consistent with how we've approached it in the past, which is we don't want the consideration to be made around the choice to be made based on price.
What we want is for the patient and the prescriber to be able to have a conversation about what makes most sense for that patient, what's going to provide the best patient care and outcome, and that they're empowered to be able to make that decision based on the price that's been set and the access that we've been able to negotiate. So we'll get more into it into details as we get closer, but that's certainly the strategy and the commitment of the company.
And so when you think about prefilled syringe, so this could potentially be for someone to use at home, but I believe at the moment, VYVGART Hytrulo do have a first monitoring or initial monitoring requirement. So how would that work? Would someone initially have to get the product in a doctor's office and after a period of time could transition?
Yes.
First of all, the monitoring requirement, there's many self-administration products that have a monitoring requirement, and they're dealt with in different ways. You'll recall that outside of the U.S., we already have self-administration in Europe, in Japan. In that case, for MG, how it works is the first four administrations are with the HCP, and that's when the patient is being trained. The first of the second cycle is generally with the HCP, and then assuming that the doctor sees that the patient can do it, then they're able to take the medication at home as self-administration. You can imagine something similar like that would be the case in the U.S. Obviously, it's a review decision what that actually looks like.
Thanks.
Question here.
Yeah, just a big picture question on margin. You're transitioning into, I guess, comfortable, profitable growth in 2025.
Can you give us more color about the R&D spending? To what extent it can, let's say, blur the, let's say, step up in margin from the 2025 baseline?
So the only guidance which we have given is that the operating expenses for 2025 will be in the order of magnitude of $2.5 billion. From a margin point of view, the gross to net is constant for our Medicare Part B products. It's around 11%-12%, expected to be stable. For the Medicare Part D product, the prefilled syringe, which needs to come online, stay tuned. I think we'll be talking more about it when things get clearer right now.
Yep, exactly right.
And so if you are a profitable company, as you've now suggested, and you're sat on quite a pile of cash as well, what are you going to do with the money?
I think, James, if you look at the plan, there's a hell of a plan. I mean, this is not going to be cheap. It's going to take a very significant and very substantial investment, which, remember, we will do in a very disciplined way. But remember, these are all pipelines in the products which are coming online. Each of these four phase I molecules, if successful, will unfold into opportunity across multiple indications. So this is a big wave of indications coming, which will be capital intensive. So I think the way to look at profitability is and the cash position, this company will be able to execute on a very ambitious innovation agenda on its own dollar. Okay.
I just have a quick commercial question. I'm just curious how much seronegative as well as Ocular MG is commercial today.
I'm just curious on the physician feedback, either from the academics or the community physicians on off-label use.
Yeah.
If you could repeat the question as well.
Yeah. So the question was, in terms of seronegative and Ocular MG, how much of our commercial patients coming from those today and what's the neurologist feedback? So seronegative and ocular are not on label today. So the majority of our patients are our on-label MG patients, generalized MG patients. And certainly, that's what we promote too. Certainly, the feedback that we hear from neurologists is that there is a significant unmet need for treatment options for seronegative. They don't feel that they have the treatment options available, and they ask us consistently based on what they know about VYVGART in those seronegative population in the registrational trials, as well as the real-world evidence. They also ask us a lot about Ocular MG.
There's a significant unmet need. Tim already reviewed the fact that steroids are the only treatment option available, and neurologists are frustrated that there isn't more available. So I think there's a significant unmet need, both in terms of the patient burden as well as neurologists looking for treatment options. There's significant, I would say, loyalty to VYVGART that we're building as the number one prescribed advanced biologic in gMG. So I think there's significant opportunity in those label expansions.
While we're on seronegative, so you have tested VYVGART before in some seronegative patients, but you don't have that U.S. label at the moment. Why would you be successful with a trial that's come up this year where the previous trial wasn't there? And can you also remind me, what is it you need to show? I think it's a lower threshold in terms of the significance level.
Yeah.
So pretty overwhelming evidence. The question is, how do you design your registration trial in such a way that you can differentiate from that very high placebo effect which we picked up in ADAPT? I think we have refined the inclusion-exclusion criteria. I think we work with an independent adjudication committee, which has proven a successful filter. Remember the CIDP trial. And you're absolutely right that in dialogue with the FDA, based on the amount of evidence available, they allowed us to run a trial with a somewhat relaxed p-value. So the typical p-value you would see for a successful clinical trial would be 0.05. We have a p-value agreed with the FDA on 0.1.
Could we talk about, so EMPA, you're going to have potentially two products with CIDP. So are you going to be competing with yourself or the different segments?
Why does it make sense to go for one disease with two drugs? And how is that going to fit together?
Yeah. So look, VYVGART has shown the highest ever response rates in a proper clinical trial in CIDP with 70% response rate. Still, there's about 30% of patients who do not seem to be responding to the drug, at least in this clinical setting. So the question is, what's happening there from a biology point of view? We have some hypotheses. We did some translational biology work. We have also seen the Sanofi phase II results for a complement C1 blocker. It looks like complement is in play. And maybe the answer for that subset of patients to be seen. So instead of proactively niching EMPA into a kind of VYVGART refractory patient population, we decided to give EMPA its full chance to shine.
So we're testing head-to-head against IVIG in a broad CIDP patient population. And I think the data will hopefully guide us to understand when does EMPA make sense, when does VYVGART make sense. It's a big space. There's a ton of innovation which needs to come into that space. So we feel comfortable moving forward with both molecules.
And could they even make sense together? Would that ever be an approach?
It is an interesting question, which could be the question for a number of our indications. It's too early to answer that question today. The only thing I can say is that both molecules are compatible. I mean, they would both be able to recycle through FcRn. They would be compatible in the endosome, unlike a wild-type IgG.
And if you're taking some confidence from Sanofi's complement targeting molecule, does that mean you think that product does also have a fair chance of working in CIDP? And if that worked, would that be a problem?
Well, first of all, if the drugs would be fantastic for patients because they have the problem. And I think their phase II data look interesting. It's, of course, their trial. We have only a view on the public data. But I think there's a plausible data set out there highlighting the impact of the classical pathway upstream of C3.
We're probably going to have one or two more questions. Maybe one more for me, which would be just competition in MG, what you're seeing at the moment from FcRns and more FcRns coming. And I know you've got some next iterations for your products, but could things get a bit tougher?
Are you seeing any more competition?
Yeah. I mean, I think the way we think about innovation, whether it's our innovation, whether it was just talking about Sanofi, or whether it's innovation coming into the MG space, we see it as a positive for patients. And we think that more innovation builds markets and transforms outcomes for patients. And I think we're seeing that play out in MG in a similar way that we've seen in the past in MS, where it really expands the treated population and improves outcomes for patients. So what we're seeing in MG is that as more innovation comes to market, more and more patients are being treated with an advanced biologic.
VYVGART, as the number one advanced biologic in the market, with, I would say, the best value proposition in terms of over half of patients reaching MSE, that consistent, say, an established safety profile. And of course, how we continue to up the differentiation in terms of the route of administration, we're seeing that VYVGART is benefiting from that. You'll recall that we updated the TAM for MG from 17,000 to 60,000. 25,000 of that increase is because of the expanded use of biologics. And that's being driven by all this innovation coming into the market. And that is fantastic for patients.
What about myositis? So you announced a phase III go towards the end of last year. Are we going to see some data from the clinical data from phase II this year? Where might we see that?
And what should we look out for there?
Yeah. So in the style of the house, we will be public about our data. And at a clinical conference to be announced, it's internally decided, but to be announced, we will actually be showing the data from the phase II proof of concept study, which I think was a very robust and a very convincing study based on which we already are well advanced now in the phase III registrational trial. So stay tuned. We will be public about the exact date and conference.
And the scale of the opportunity there, like number of patients with myositis, if you did work in all three subsets, say, versus where you are now in MG, how big an opportunity is this?
Roughly speaking, I would bin myositis in the same place as MG.
We're talking about the same cumulative number of patients here in the United States. Very importantly, in equally high unmet medical needs. In IMNM, in ASyS, there's virtually nothing. In DM, there is IVIG approved. But there's a ton of work to do for these patients. It's a very bad disease. It can be a fatal disease. And I'm looking forward to the phase III data.
Thank you. Are there any further questions from the audience? In that case, thank you very much. Brilliant.
Thanks, James.
Thank you.
Thanks, James.