Well, good morning everybody, thank you once again for joining us for the 46th annual TD Cowen Health Care Conference. I'm Yaron Werber from the biotech team, it's really a great pleasure to moderate the next fireside chat with argenx. With us today for the first time as an incoming CEO is Karen Massey from argenx. I know we have many members of the team here. I see Alex, I see Tim as well in the audience, among others. If anybody has any questions at any point, raise your hand. We'll be very happy to take it on your behalf. Karen, thank you for joining us.
Thank you for having me.
We appreciate it. Lots to talk about. Maybe the first one is you think about your vision and sort of your mandate now, and what you wanna sort of accomplish, let's say in the next 12 to 24 months. Maybe give us a sense how you're prioritizing, you know, argenx 2.0.
Yeah. Absolutely. I think what you can think about with argenx 2.0 is similar to argenx 1.0, and that is that it's a growth story. Our focus is on growth and our focus is on innovation. Specifically to me and what I'm focused on and I think the strategic agenda, I mean, I've been involved very closely, obviously alongside the team with Vision 2030. That doesn't change. Our portfolio and our focus doesn't change. We're continuing to execute against getting to 50,000 patients by the end of the decade, 10 labeled indications and 5 molecules in late-stage development. That links directly to our growth story.
Because we have clear paths to growth in the short term, and we'll unpack this a little bit more, but in the next 12-24 months, we have readouts in myositis. We have readout for VYVGART for MMN, so our second molecule empasiprubart, as well as into next year, you can start to think about Sjögren's and in the future CIDP for empasiprubart. We have clear path for growth in the short term. In the midterm, we have our FcRn strategy to continue the growth in the FcRn platform, with 2 next-generation molecules, as well as an oral. We have an expanding pipeline beyond FcRn. Really that next act for argenx that continues to broaden our opportunity, our pipeline, our opportunity for growth.
In the long term, we have really exciting early-stage programs as well. We just announced the deal at JP Morgan as an example with Tensegrity. We're expanding where we're looking for novel biology as well. I think the story doesn't change for argenx. It's a story about growth.
You mentioned that there's a lot to unpack there. Myositis data, Sjögren's data, which we're obviously fairly attuned to. The two FcRns and an oral.
Yeah.
One of the FcRns, I believe the 213 is potentially phase 3 ready.
Yep.
You have another one right behind it. ARGX-213 I believe you said is monthly. The next one you haven't said as much about that one. Maybe give us a little bit of a sense from a differentiation perspective, obviously, you have a long-acting component. Maybe you have an injectable volume advantage, may or may not, and obviously a potential for differential pricing in another indication set. I don't know what you can share about how to think about all that.
Yep. I think you're thinking about all of the right levers that we have to play with. Our goal over the long term is to continue to lead in the FcRn space. I mean, I would say we have the world-leading experts in FcRn. We're leading the space with VYVGART. And having two next-generation molecules gives us the opportunity to explore both, yeah, how do we look at the indications that VYVGART is already in and extending there, bringing different value to patients, for example, every four-weeks dosing. Also expanding. We know that there's more indications that VYVGART or that FcRn biology plays a part. We can also start to expand to different indications at different price points.
We have those options by having multiple next gens. Part of the strategy, and we're working on it at the moment, we're students of the industry in the past, and you can look at a lot of different examples of successful generational strategies and leadership. I think we're on track with our approach of having these two molecules. As we progress through the year, we'll have more data in humans for ARGX-124, and the other molecule. We'll be able to lay out exactly how we want to leverage both ARGX-213 and ARGX-124, and that's even, not even mentioning how we'll get to the oral, which is a little bit further out.
The oral is a small molecule or oral is another version of the biologic?
On, an oral peptide, so we're working with UMP, on that.
Yeah. You mentioned you're students, and so you're learning from the past. Are there some examples of franchise sort of long-term duration assets that come to mind?
Yeah. I mean, one of the ones we've been looking at recently is. Well, we're always obviously looking at ULTOMIRIS and SOLIRIS. That's close to home for us, so that's an important one. HUMIRA is another good one to look at. Obviously with SKYRIZI and RINVOQ and the approach there. A lot of good learnings that we can take from that. I mean, if you look at where I came from with Rituxan, Ocrevus and the strategy there. I think there's good learnings from each and every single one of those. What we can take away from it, I think, is, how do we apply that playbook to FcRn, which is a unique space, and we have actually a unique leadership position in.
Are you waiting for the one to four data to decide to whether to advance ARGX-213 forward and prioritize?
What we wanna do is get the one to four, get the next step in one to four, and then we have various scenarios. Obviously, the scenarios are different depending on whether you have one next gen or two. We believe we have two. We have one more step forward to de-risk that, and then we'll be able to lay out the. Pull the trigger on the different scenarios that we've been working on.
Okay. Maybe let's focus a little bit on Q1. There's usual, you know, Q1 dynamics with some seasonality. You mention a lot, think about Q1 as a year-over-year growth not necessarily a quarter-over-quarter growth. You've been coming off some very strong quarters, and then usually we see an uptick in Q2. You know, should we assume growth in Q1? How are you thinking about it?
Look, I think across the industry that we've seen the pattern before, you know that Q1 growth is impacted by re-verifications and by winter storms. We've had a couple of winter storms this quarter. Look, we had this exact same conversation last quarter. I remember that very well. What did we deliver? We delivered 90% year-on-year growth for the full year last year. The message at the time at that moment is exactly the same message as we're giving now, which is the underlying fundamentals of for VYVGART are very strong. Across MG, across CIDP, whether you look at new patient starts, new prescriber adds, the number of cycles, discontinuations, everything is on track. I think for us, that's the more important measure.
Just zoom out and look at the big picture. We're five years from the launch of VYVGART and still delivering consistent growth, consistent momentum, and we expect that to continue. I think the more interesting piece of information or insight that people are missing is we have a PDUFA date in May for seronegative for the seronegative MG patients. We got the priority review. We got the notification from the FDA the day after our presentation at JP Morgan, so it was a little bit lost in the noise then. Then this at this earnings that we just had last week, we had positive ocular MG news, so it got a little bit lost there as well. If you ask.
I think what people are missing when they're focused on the Q1 seasonality is, hey, zoom out. We continue to bring innovation to the market. We're expanding with seronegative. We have positive ocular MG data. I think we're well-positioned to continue to grow.
Maybe you mentioned CIDP. You reached blockbuster status in Q3 last year. We're estimating that CIDP is probably around 35% of sales right now. I know you can't comment too much. Based on our surveys, which we've been running every quarter, you're sort of in the mid-teens market share. Am I roughly in the ballpark?
Yeah. I mean, what I would say is you're exactly right. We reached $1 billion in sales. The last time we had provided the update, we said we had 2,500 CIDP patients, which is, you know, just over a year from approval. I think is an outstanding job by the team. What that has driven off of is we have great access for our patients. We have payer policies that allow patients to get started with any trial on IVIg. We're still seeing the majority of patients come from IVIg. I think what you're seeing is a very successful launch. We're still at the beginning of that launch, and I think there's still a lot of room to grow.
Okay. seronegatives, you mentioned May 10th. you know, there are other FcRns that are approved for seronegatives. How much of a tailwind is this gonna be? Is this gonna be a conversion story? Is this gonna be, you know, a new patient add story, or is this gonna be there's an entrenched population you can go into?
Yeah, I mean, let's see what label we get, but don't forget we are the only that has the triple seronegative. There are some with the MuSK and the LRP-4. Look, when you speak to physicians in market research, what they tell you is, you know, I mean, this is a simplicity story. VYVGART is already the number one written biologic or prescribed biologic in MG. We're getting 6 out of 10 of the new biologic patients already. We're driving market growth. What this means for physicians is now I can reach for VYVGART regardless of antibody status. I don't even have to think about antibody status anymore. I think if we get that broadest label, it's about removing friction from the system for those prescribers. I think it really sets us up well, to expand our position as the number one prescribed.
The 4 out of 10 patients who go on an alternative new biologic, why are they going to the alternatives?
That's the question I asked my team. We were just with the sales team last week and asking the same question. I mean, I think that's the work that we have to do. What you hear about, from physicians about VYVGART is that what they appreciate is the rapid onset, the dosing, the fact that you have dosing, different options for dosing they appreciate and the strong access. I think the expanding into the seronegative population will help grow that market.
The line share of the 4 out of 10 are C5?
No. I mean, what we're seeing is FcRn is very clearly positioned front line, for MG patients. I would say the C5s are very are more used later line. You have IVIg, don't forget, in that population as well, which sometimes can be used as a, yeah, as whether you wanna call it a rescue or whatever, or whatever it is.
Okay. It looks like it's more IVIg and then C5 potentially.
The way that we're seeing the market play out is very clearly FcRns are being used first, as first line, and then the C5s and some of the other therapies are really being saved for the refractory patient. I think the opportunity and the big when we think about growth, how is VYVGART set up to grow within that? We just had the Ocular MG study readout. Which the majority of patients first show up, first present with ocular symptoms, and then progress to generalized MG. 80 to 85% of them progress to generalized MG.
Our positioning of VYVGART is that we should be used as the first biologic, and we're seeing that first biologic that we are in that first biologic position and that FcRns are. With Ocular MG, that positions us even earlier and certainly with being the first and only with that Ocular MG data, it really squarely says that you should start with VYVGART.
Yeah. The data you showed us was still early, so to speak. It was up to three cycles.
On Ocular MG, it was actually just one cycle.
It was after the first cycle. Thanks for the corrections. You have two more cycles that you've done.
Yep.
Which we have not seen yet.
That's right.
We'll see that, you know, at some point soon. Even after 1 cycle, you showed 4-point difference.
Yep.
Improvement in the MGII endpoint, and placebo-adjusted was about two.
Two.
It sounds like I think you made a comment that it might continue to deepen.
Yep.
We'll see that once the three cycles are out. We look at sort of what's clinically meaningful on that scale, a lot of times you hear 3 points, 2-3, depending on what exactly. Is it diplopia? Is it, droopiness of the eyelids, ability to drive? Can you maybe talk about what you've seen and, you know, how clinically meaningful is it in ptosis as well?
Yeah. I mean, I think it's very clinically meaningful data there because First of all, it's the first and only data, and that in itself makes it clinically meaningful. These patients have nothing available other than steroids. This is meaningful data. What's important, and as you say, we only showed the top line. You can see the continued, the typical what you see with VYVGART, where more cycles, you continue to see benefit. We're also really zeroing in on making sure that we could see impact on both the drooping, as well as double vision. Drooping and because those are important to patients. Indeed, as we unpack the data, you'll see that there is consistency across endpoints.
This is clinically meaningful and important to patients. The biggest piece of work that we have to do now is convincing neurologists that it's important to treat these patients and that these symptoms have a huge impact on their quality of life. Sometimes you'll hear neurologists say, "Yeah, it's just Ocular MG. It's just the eyes. It's not that big of a deal." Well, when you speak to patients, they say, "Because of my Ocular MG, I completely lose my independence. I can no longer drive. I can't work." The impact on their quality of life is large. The majority of them within 18 months progress to generalized MG as well.
If they're not progressing, they're on incredibly high doses of steroids, and we all know the impact that that can have on patients. There is a huge unmet need here and this is a clinically meaningful difference.
You're the leader in gMG, and despite that it was an established market, you've really put it on the map.
Yeah.
Now there's competition coming behind, and each one of them comes in and talks about that there is a, quote-unquote, "a big unmet need in gMG because the cyclical dosing require patients to relapse." You do have the ADAPT-NXT data.
Yep.
That shows dosing Q 2 weeks, is as good as cyclical dosing. I don't think you're actively marketing it.
Yeah.
That's something the MSLs and in corporate and medical affairs can talk to physicians about. I guess my question is, how much of an unmet need is it to have chronic therapy? You have a sense what patients are on doing Q 2 weeks. Finally, does it make sense to formally develop a Q 2-week study for the label?
Yeah. Yeah. First of all, I think what's interesting is when competition goes to an advantage being a dosing advantage that actually is nonexistent. I think when we talk about from competition, what we should be looking at is where is the MSE data? VYVGART what's most important is, are we getting MG patients into MSE, Minimal Symptom Expression? VYVGART has the highest efficacy and the demonstration of that. Similarly, safety. If you look at the over 10,000 years of patient safety, VYVGART has the safest profile and has been on the market for the longest. Okay. Now we get to convenience, which is the third thing that you wanna compete on. VYVGART has an IV option.
W e also have subcutaneous and for self-injection. Um, in terms of the cyclic dosing, which is where, you know, eventually, okay, uh, let's try and find a way to, to differentiate. Actually, patients, uh, do not need to, um, worsen or relapse, uh, when they're on, on VYVGART. What the label will-- says is that the patie- that the doctor should prescribe based on clinical symptoms, um, and, uh, that they can treat as frequently as needed, including with, uh, with ADAPT-NXT. So I don't think we need an additional study, uh, to, to do that. I, I think pa- prescribers, and if you speak to prescribers, they know, uh, they can, they can treat, they should treat to the symptoms, uh, and they can treat as proactively as needed. Uh, and, and that's what we see in the real world.
Okay. All right. Let's move to myositis and the ALKIVIA study and the, the first phase 2 portion of the study was 90 patients randomized one-to-one to based on subtype. It's the three subtypes, each one of them needed 30 patients. Based on that, you showed it was 15 points as a mean, 12 points as a least- squares mean. The reason I bring that up is 'cause that's relevant for the primary endpoint at the phase 3. This was of course 24 weeks. There was no real steroid tapering. phase 3 is 48 weeks with a steroid taper. My understanding from our discussions is that you didn't need to enroll equally based on each subtype.
That's right.
Can you talk about that and why is that important?
Yeah. I mean, I think what's most important around the myositis trial that we have this reading out in Q3, is that we do have data. It's a basket trial. We have data from all three subtypes, the way that we design the study is that we can look at the overall population as well as the subtypes, to be able to see where do we demonstrate clinical benefit, and therefore, that we have a path to approval based on which which subtypes we see efficacy in. The study is designed in that way to enable us the flexibility to do that.
The biggest component in terms of prevalence is DM, right? It's about 40,000 patients. MMN is I think the second biggest with twenty.
About 20,000 patients.
ASyS or polymyositis.
Is s maller patient population. Yep.
You know, you Based on the passive transfer data, based on the biology, I think sounds like you've had very high confidence in MMN, so do KOLs. I think I would say probably DM was probably the second area that you had a lot of confidence in. As you prioritize enrollment, should we assume that's sort of how you prioritize enrollment in the phase 3?
Yeah. I mean, I think that's a fair characterization across all. The way we see it, in IMN, yeah, the biology rationale is crystal clear. There is a huge unmet need. I mean, nothing is approved in IMN. The reason we updated that 20,000 patient number is because we've been doing our homework, if you will, leading up to the clinical trial, to characterize these patients. What you find, because there are no approved therapies for IMN, you can't just rely on the claims data to look at the patient population. When you go out and you speak to neurologists, when you go out and do primary research, you find that there are a lot more patients out there. Exactly as you said, DM I would say is the next patient population. More heterogeneous. There's also more competition there, followed by PM and Antisynthetase Syndrome.
As you mentioned, it's essentially all subtype study.
Yep.
It will support a broad label.
Yep.
If it's driven by one or two of the subtypes, do you still get a broad label? If it's driven by one of the subtypes, do you still get a broad label?
I mean, I think we'll have to let the data speak, because there's so many different scenarios of how you can see it play out. Yeah, we're looking forward to the data.
Okay. The next one that I'm just staying on VYVGART, that we've been doing a lot of work on is Sjögren's.
Yep.
Your data actually looked fairly comparable to IMAAVY. Excuse me. Which we thought was really encouraging. You're looking at systemic patients with an ESSDAI endpoint in patients who are moderate to severe, and we'll see that data I believe first half 2027 or so.
Would you.
Second half, you said.
Second half 2027. Would you consider doing a study in symptomatic patients as well?
Yeah. I mean, look, first of all, we're doing a big program. I'm actually just to say I'm really proud of the team on and excited about Sjögren's. The way we went about the clinical development program I think is very much in the argenx style. We've been able to. J&J went ahead and did a large phase 2 study. As you say, the data was impressive, which we see as a good thing. We did a smaller phase 2 study where we were able to go deeper on each of the patients and then as a result go really fast and actually catch up. I think we've caught up to and may even end up being ahead. Let's see.
I don't wanna jinx ourselves on Sjögren's, for bringing VYVGART to market. That's really exciting. The way we're looking at this is, let's get that data, let's see the readout. Then in true argenx fashion, we have a number of additional evidence generation ideas that are lined up. Once we have a positive readout, then we can pull the trigger and go.
Let's shift to EMPA and the Empassion study with MMN, which is reading out Q4.
Q4. Yep.
You switched the endpoint to grip strength.
Yep.
F rom, you know, the previous endpoint, which is gonna be a secondary now. As you think about powering that endpoint, how did that come about?
Yeah. It was actually a good switch, in the endpoint, and it was in discussions with the FDA. You'll recall grip strength was what we used in our phase 2 study. During discussions with the FDA, the endpoint changed to MMN-RODS. Then there was a change back to grip strength. We're pleased with the endpoint going back to grip strength. That actually means that we can leverage the data from phase 2. It's also an important endpoint because grip strength, you can imagine, is much more meaningful to patients and also prescribers. It's not a composite endpoint, it's a grip strength. It's easy to understand. We can all any layperson can understand, hey, if my grip strength improves, then I must be seeing improvement. We're happy with that as an endpoint and look forward to the data.
Part of your data from the long-term extension really shows continued improvement in grip strength.
Exactly.
IVIg, based on our search in literature, improves grip strength by about 30%. Does that make sense to you? You know, so as you think about powering, you know, take that into account?
I mean, so we use the obviously all of the literature available. What we know from IVIg is in MMN is two things. One is that MMN patients continue to progress, even when they are on IVIg, and the other is the, let's say the cyclical nature. Patients that you can see it in our phase 2 study, patients' symptoms go up and down on IVIg with MMN. Whereas with empasiprubart, what you can see is consistent improvement and consistent response. I think based on those two things, we should be well-positioned.
Right now it's a Q4-week IV. Is there a chance to make it subQ?
We will be applying the argenx playbook, which is that we always wanna continue to bring innovation, more innovation, more innovation to patients. You can imagine the exact approach that we took with VYVGART, we'll be applying that playbook.
Okay
T o EMPA.
Maybe let's move to the study EMVIGORATE and ENERGIZE.
Yep.
CIDP, which is clever. In this sense what you've done now, is you're going head-to-head against IVIg.
Yeah.
Same, same playbook. You've learned from really and both going for experience and refractory, but then you kinda zoomed out and said, "We'll do an ADHERE-like and also bring in the naives. You're gonna cover essentially both segments. When we've spoken with clinicians about Riliprubart essentially because we have to admit at that point it was anecdotal feedback, but it's supported by the data. They said that they believe the C1s is probably a little bit more potent or fast than let's say VYVGART. They might want to use it in sort of the more advanced patients or rapidly progressors. The way really it's getting tested is obviously in the more refractory setting now. They're, you know, obfuscating the frontline market. You're going for the frontline market too. I guess the question ultimately with the assumption you beat IVIg, where does EMPA get used?
Yeah. Well, I think if you take a step back and look at it as an argenx strategy, our strategy in CIDP is to completely transform outcomes for patients and transform the market in the way we, in a similar way that we have with MG. Although here we have two molecules. First we bring VYVGART, the first innovation in 30 years. By the way, we have a ton of data, biomarker data from that clinical trial, which is the largest done, and we continue to generate evidence and continue to generate biomarker data to really deeply understand these CIDP patients and what is driving their disease. We come with the second, which is empasiprubart, and we can take the same approach. We have two large trials.
We're going deep in terms of the biomarker study data. What we'll be able to do is we'll let the data speak. We're giving empasiprubart just the equal shot in CIDP as you said with naive patients as well. Let's see how the 2 molecules play out. We will make the best decision based on what's best for the patient and what's best based on the scientific understanding. I think what we're seeing, we published data on this last year, is that you can see in CIDP it's a heterogeneous disease. There are some patients that are more IgG driven. There's likely some patients that are more IgM- driven. There is some overlap. We are uniquely positioned. We have multiple molecules. I think we can shape this space and lead this space, and lead to truly transformative outcomes for patients.
Okay. You're also doing the combination study.
Exactly. What we've announced is the combination study in MG. That's a platform study, where we can look at different combinations in MG. You can imagine we can take the same approach, that same playbook, as we start to look at different indications, and it would make sense that CIDP would be the next.
That's a broad MG or is that a generalized MG strategy?
That is a generalized MG strategy at the moment. Yeah. With each different arm, because it is a platform study that's set up, you, we can, we have the flexibility.
Okay. Any questions from the audience? Before, I'll go into my favorite pipeline product, which is the IgA sweeper.
Yes.
I think of it literally as a little broom that says IgA on the bottom. Just that's how I remember it. Works for me. The phase 1 data was fairly profound. I mean, 1 dose to 28 days can be a monthly dosing, you're now moving into an IgAN in phase 2, you could potentially even go into a broader development pathway. Why choose IgAN first? I mean, obviously it makes sense, it's also fairly competitive. In terms of differentiation.
Yeah. Obviously IgAN, huge unmet need. The biology is really clear. I mean, IgA is in the name of the disease, I think that's pretty clear. It is competitive, but we think we can get there fast, and we think we have a differentiated value proposition. You know, there's obviously a lot of the BAFF/ APRIL are going into IgAN. What we hear is, you know, likely that there will be patients that don't respond to BAFF April or maybe there's ADAs. There is need for a different mechanism of action.
Being able to have our IgA sweeper, and I like the image of the that you bring up, have an IgA sweeper as a different mechanism of action in what is emerging to be a very large market, I think is important. There's the value proposition as you mentioned with IgA, with bringing down the IgA so rapidly, so deeply, and with 28-day dosing in such a targeted effect, what you can think about is does that actually provide a differentiated efficacy and safety profile that as we see this play out. I think there's plenty of room for more than one mechanism of action in IgAN, and I think our IgA sweeper one-to-one is really well-positioned.
What are potentially next indications for that? Is it RA or other things coming?
Yeah. I mean, the next one that we're looking at is IgAV, IgA vasculitis, but then as you say, there is a number of different indications that we could be looking at for that for argenx one-to-one and you should stay tuned. There'll be more to come.
Okay. Terrific, Karen. Great to see you. Really appreciate it.
Thank you so much.
Congrats.
Thank you for the questions.
We're.
Great
We're all believing.
Thank you.