argenx - Q4 2023

Transcript

Operator (participant)

Good morning. My name is Rob, and I will be your conference operator today. I would like to welcome everyone to the call. At this time, all lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question-and-answer session. If you would like to ask a question during this time, simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question, again, press the star one. Thank you. I'd like to introduce Beth DelGiacco, Vice President, Global Head of Corporate Communications and Investor Relations. You may now begin your conference.

Beth DelGiacco (VP, Global Head of Corporate Communications and Investor Relations)

Thank you. A press release was issued earlier today with our full-year financial results and recent business updates. This can be found on our website along with the presentation for today's webcast. Before we begin, I'd like to remind you on slide two 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 those statements in relation to actual results unless required by law. I'm joined on the call today by Tim Van Hauwermeiren, Chief Executive Officer, Karl Gubitz, Chief Financial Officer, and Karen Massey, Chief Operating Officer. I will now turn the call over to Tim.

Tim Van Hauwermeiren (CEO)

Thank you, Beth, and welcome, everyone. I'll begin on slide three. It has been another year of incredible execution by the argenx team, setting us up to build on this momentum for the year ahead. At the core of everything we do is our mission to transform the lives of patients suffering from autoimmune diseases. Today, we are in a better position than ever to deliver on this mission, reaching more patients globally with our first-in-class innovation and bringing hope to the autoimmune community on what a novel treatment can offer. We see multiple opportunities to expand our patient impact this year and are investing across our business to do so. These innovation horizons serve as a roadmap for how we will build long-term value by expanding the VIP card opportunity, advancing our pipeline, and bringing the next wave of R&D candidates into the clinics.

On today's call, I would like to highlight recent news and walk through upcoming milestones in the context of these horizons. slide four. Let's start with the VYVGART opportunity. We had an incredible second year of launch driven by the ambitious strategies and seamless execution of our commercial and medical teams. We are still at the beginning of what we hope to achieve. First and foremost, the launch trajectory demonstrates the significant unmet need that still exists with gMG and the opportunity for an innovation like VYVGART to deliver differentiated outcomes for patients. As a part of our commitment to the broader MG community, we will initiate a registration trial in seronegative patients this year, which, if positive, could allow us to reach the 15% of gMG patients who are not served by our current label.

Beyond MG, we continue to demonstrate the breadth of possibility for FcRn across autoimmune indications, and we have launch preparations underway ahead of anticipated regulatory decisions in ITP in Japan in March and in CIDP in the U.S. in June. We will be ready to tackle these anticipated opportunities as we leverage our key learnings from our launch playbook to best position ourselves for success. slide five. VYVGART continues to make headway in the clinics. The phase III TED study is ready to start this quarter and will be the first to utilize our pre-filled syringe from the onset. We are expecting readouts from 5 phase II studies, including in Sjögren's, post-COVID POTS, and 3 subtypes of myositis.

We expect to provide an update on our plans in bullous pemphigoid later this year once the team has had the opportunity to analyze the data from patients who enrolled in BALLAD Stage A. This is part of our commitment as a learning organization and our ongoing work to double-click on the clinical feasibility of current and future advancing mode studies based on key insights from ADAPT-SC and ADDRESS. This will be another year where we learn more about the broad potential of SCRN through our next wave of indications, advancing our leadership of the class, and unraveling important findings about the underlying biology of these autoimmune diseases. Today, we will focus on our expectations of success around Sjögren's as that will be the first of the five. The RHO study has a target enrollment of 30 moderate to severe patients randomized to one.

The study is not powered for efficacy, so we will rely on the depth of data we will gather from each patient, looking at various endpoints, including CRESS, ESSDAI, ESSPRI, and biomarkers across patients. We have a few objectives with the signal finding study. First, to confirm the role of IgG autoantibodies in mediating disease in children. Second, to evaluate a combination of efficacy and biomarker data to gain sufficient confidence to move forward in this indication. And third, to inform potential patient selection and endpoints to design a winning registration trial to amplify any signal we observe in phase II. We plan to employ a similar approach in our evaluation of POTS, looking at the depth of data across the enrolled patients to make an evidence-based decision to move into a phase III study.

With myositis, we have a seamless phase II/III design, which will expedite the transition from the first 30 patients of each subset into a registration study of one or more of the subsets where proof of concept has been established. Wrapping up on efgartigimod, I'm very proud of all that we have accomplished in pioneering this new class of medicines. Proof of concept has now been demonstrated in nine out of nine indications across FcRn, and we believe this is still just the beginning of the broader opportunity. slide six. Turning attention to our next horizon of innovation, I want to briefly touch on our pipeline progress. Empasiprubart is our second pipeline in a product opportunity from which we have shown compelling and interim data from the first patient cohort earlier this year.

This is a program that emerged from our IIP and perfectly demonstrates how we like to build opportunity from our discovery engine into our pipeline and now towards a registration trial in its first indication. In collaboration with Professor Eric Hack, we built what we believe is the first-in-class and best-in-class sweeping antibody against C2 and have conducted translational work to highlight where targeting C2 could have the most impact. Out of this, we identified that complement activation in MMN happens upstream in the complement cascade. We designed an innovative trial, and in the first cohort, we demonstrated a 91% reduction in the need for IVIG rescue compared to placebo. We are now awaiting the results of the second cohort to inform the final design of the registration trial and look forward to sharing the full phase II data set this year.

The opportunity fits perfectly within our expanding capabilities in neurology, as does ARGX-119, our third pipeline program. This molecule will come more into focus this year as we move beyond healthy volunteers into CMS and ALS patient studies. Of note, we recently initiated natural history studies in both CMS and to engage each of their respective patient communities. This falls in line with our strategy to better understand the real-world experience of patients and will help us identify potential participants in upcoming studies. slide seven. Finally, and core to our sustainable growth, is our third innovation horizon, our immunology innovation program. The track record of success of our IIP goes well beyond advanced TED and MPA with nine programs tested in humans since inception.

We demonstrated the efficiency of this pipeline engine by nominating four new molecules last year, all on track to be filed as INDs by the end of 2025. We will continue to invest in our internal discovery engine and technical capabilities, combining our antibody engineering and clinical development expertise with the knowledge of leading scientific collaborators as we advance our next wave of molecules. I will now turn the call over to Karl

Karl Gubitz (CFO)

Thank you, Tim. slide eight. The fourth quarter 2023 financial results are detailed in the press release from this morning. I will highlight the key points here. Revenue in the fourth quarter totaled $418 million. This reflects $374 million in product net sales and $43 million in other income and collaboration revenue. Our collaboration revenue includes a $30 million milestone payment from AbbVie for advancing ARGX-115 to phase II, as well as royalty income from Zai Lab of $0.7 million for VIP card sales in China. The breakdown per region of $374 million in product net sales is $326 million in the US, $17 million in Japan, $24 million in EMEA, and $7 million in China. Globally, we saw growth of 14% or $45 million in our product net sales from Q3 2023 to Q4. Operating expenses in Q4 were $556 million.

This is an increase of $136 million over Q3 2023, driven primarily by the recognition of a priority review voucher we submitted with the sBLA filing for CIDP. This impact of a PRV was $102 million and brings total R&D cost for the quarter to $306 million. Net loss for the quarter was $99 million, bringing the full year loss to $295 million. We continue to have a strong balance sheet with $3.2 billion in cash, cash equivalents, and current financial assets at the year end. The financial guidance for 2024 is as follows. Based on our current operating plans, we expect the combined research and development and selling general and administrative expenses in 2024 will be less than $2 billion.

We expect to utilize up to $500 million of cash in 2024 on our anticipated operating expenses, as well as working capital and capital expenditure, including investment in our supply chain. I will now turn the call over to Karen, who will provide details on the commercial front.

Karen Massey (COO)

Thanks, Karl. slide 10. Echoing Tim, I'm thrilled with the impact VYVGART is having on patients and their loved ones. With over 6,000 patients on therapy, the response from the patient community has been tremendous, and we have set the bar high for what a novel gMG treatment can offer. I want to first thank the team because the success of our launch can only be achieved through tireless dedication and a firm commitment to our mission to transform the lives of autoimmune patients. Today, I would like to focus on three key areas which I believe will advance VYVGART's leadership and maximize the impact we can have on patients globally. One, reaching new gMG populations with VYVGART. Two, leveraging our know-how from gMG as we prepare to potentially launch in CIDP and ITP.

And three, building a commercial engine that can reliably and repeatedly maximize value creation and patient impact. slide 11. Let's begin with our gMG launch. We closed out 2023 with $1.2 billion in revenues, including over $1 billion in the U.S. alone, which is a remarkable feat in just our second year of launch. Importantly, this tells us that patients place a high value on innovative treatments such as VYVGART to meet the demand for safe and effective treatment alternatives in the gMG treatment space. We continue to see double-digit quarter-over-quarter growth, and we contribute this momentum to several factors, including a broader prescriber base, the continued shift to patients earlier in the treatment paradigm, and additional regulatory approvals and launches in our ex-U.S. markets. We see consistent growth of our prescriber base, having breadth and depth amongst neurologists and further reach into community centers.

Prescribers are becoming increasingly comfortable with the efficacy and safety of VYVGART, which is supported by a body of real-world evidence demonstrating the consistent value VYVGART can deliver to patients. As an example, we see rates of minimum symptom expression in the real world that mirror the data from our clinical trial, indicating that patients have the potential to achieve quality of life scores that are comparable to healthy populations. We have over 4,000 patient years of safety follow-up with advanced TED, which continues to support our consistent safety profile. With physicians, this is a key differentiator. We are observing increased utilization of both VYVGART and VYVGART Hytrulo in early line therapy, with an impressive 55% of patients coming to VYVGART directly from orals. We only expect this trajectory to continue.

Although VYVGART still comprises the majority of prescriptions, we are seeing more traction with Hytrulo, likely supported by access dynamics, favorable payer policies that mirror VYVGART and a dedicated J-code in place. We are committed to innovating on the patient experience even further by advancing the development of our prefilled syringe or PFS this year. The PFS will allow us to introduce VYVGART to a new patient population with an increasingly easy-to-use interface. It is our goal to make a prefilled syringe available for both MG and CIDP. Importantly, we believe this will move us one step closer to the possibility of self-administration in the U.S. slide 12. The momentum ex-U.S. has been strong, with multiple launches and approvals already underway for 2024.

The majority of our current sales are still in the U.S., but over time, we expect global markets to make increasingly larger contributions to total revenue, especially as the speed at which we bring VYVGART into new territories is picking up. I'm very proud of the team in Europe who's been working hard to secure reimbursement at a record pace in Germany, Italy, Spain, and recently Belgium, with patients receiving access to VYVGART in half the average time historically needed by orphan drugs. We're also seeing incredible uptake in China through our partnership with Zai Lab, driven by our recent inclusion on the NRDL. We are still at the front end of reaching patients who could benefit from VYVGART, and we remain committed to deliver on our promise of reaching the broadest set of MG patients possible.

We also know that the MG opportunity continues to expand, with competition and innovation driving growth of the overall market. With a robust knowledge of FcRn and one of the most expansive sets of clinical and real-world data generated to date, we are in a position of strength to continue to lead this market. slide 13. We're excited by the opportunity to expand our patient impact beyond MG this year with two upcoming regulatory decisions in ITP and CIDP. Today, we're going to focus on the CIDP opportunity. CIDP is a debilitating disease and one where patients continue to face significant burden, both from the symptoms of the disease but also the demands of the available treatments. Our strategy will be to leverage the learnings and infrastructure we built with MG and apply them to the unique dynamics of the CIDP market to best position ourselves for success.

The key learnings and overlapping strategies between MG and CIDP give us more confidence in the long-term potential of VYVGART Hytrulo as a transformational treatment in CIDP. But we also recognize there will be some unique challenges that may impact launch trajectory. First, as standard with most launches, we will need to wait approximately 2 quarters for payer policies to come into place. Second, IVIG is well entrenched and on label for CIDP patients. CIDP is a progressive disorder with many patients fearful of symptom regression who may not want to change from their existing therapy. Having said that, we're very motivated by the strength of our ADHERE data to bring a new treatment option to the CIDP community, which would be the first real innovation in decades. And we will be prepared with thoughtful strategies at the time of the FDA's decision on our submission. slide 14.

Before I turn the call back to Tim, I want to talk about the commercial engine we're building as we think ahead on how we can reliably and repeatedly maximize the value we offer to autoimmune patients. We continue to learn about the unique challenges and resulting gaps in treatment that patients suffer with autoimmune diseases. Most notably, there's an overall lack of innovation. Old entrenched therapies are considered sufficient. Patients take a long journey to get to diagnosis, and often that diagnosis does not result in clear answers. Finally, there are high barriers to access, even when innovative treatments become available. At argenx, we're making a long-term commitment to these communities that we hope extends well beyond the treatments we can deliver.

Some of the areas of focus for us include generating awareness of the disease and the challenges that patients and their supporters face, whether through online communities, our DTC campaigns, or our advocacy efforts. We want to raise the bar on treatment expectations. Our goal is not just to replace old treatments but to reset expectations. We want to move the goalposts so that patients aim to regain function or go back to things they enjoyed before their diagnosis. We want to drive innovation beyond the molecule and on the patient experience in the form of new product presentations and a best-in-class support system. And we're delivering on our commitment by providing broad and simple access to patients.

These are the types of investments we want to make as we grow and expand into new patient populations because we're in the business of transformation and advancing beyond incremental change. We're making a long-term commitment to deliver repeatable, sustainable, comprehensive value to patients, their care teams, and to the broader autoimmune community. With that, I'll turn the call back to Tim.

Tim Van Hauwermeiren (CEO)

Thank you, Karen. We laid out an ambitious plan for the year. At two months in, we are already in a great position to deliver on our goals. We are energized by the incredible cadence of opportunities that remain ahead and will continue to approach the argenx way with relentless execution. Before we turn the call over to Q&A, I want to take a moment to thank the individuals who drive our success. We would not be where we are today without the tireless efforts of the argenx team. I also want to thank all the patient communities and physicians who inspire our efforts to bring better outcomes to those suffering from autoimmune diseases. Thank you, and we look forward to your questions.

Operator (participant)

At this time, I would like to remind everyone, in order to ask a question, press star, then the number one on your telephone keypad. We ask that you please limit yourself to one question and then rejoin the queue for further questions. Your first question comes from the line of Tazeen Ahmad from Bank of America. Your line is open.

Tazeen Ahmad (Managing Director)

Hi. Good morning. Thanks for taking my questions. Just a couple based on your prepared remarks. Regarding the CIDP launch, if we assume that it launches, let's say, in early July, you've talked about taking a couple of quarters to really get full insurance reimbursement. So just directionally, how should we be thinking about any type of contribution from CIDP sales in calendar year 2024? And then I have a follow-up.

Karen Massey (COO)

Thanks for the question, Tazeen. It's great to hear from you. So maybe I'll provide a few thoughts on CIDP launch and what we're learning. And Karl, if you want to make any comments from the financial perspective. So we're in launch preparations, as you mentioned, for CIDP. And the more that we learn through market research, I would say the more confidence we have in the value that we're going to bring to patients in this market. It's a debilitating disease, and there certainly is a very high unmet need in this patient population. So we're very confident. As you said and as we shared in the prepared remarks, there's a few things that will impact the uptake this year. There's the payer policies getting in place and the fact that this is a debilitating disease, a progressive disease.

So there's some what we call stickiness, likely, of the patients remembering that IVIG is on label for those. So we're not expecting a rapid uptake in the latter part of the year. But Karl, do you want to comment on any further than that?

Karl Gubitz (CFO)

No, I think you've said it all. I think the payer contracts, which will take a quarter or two to put in place, will definitely delay some of those revenues into 2025.

Tazeen Ahmad (Managing Director)

Okay. Thank you. And then also a comment from your press release about price decrease in Germany. I know historically in Europe, there's just naturally price deterioration. But are you calling out this particular decrease because it's a bigger price decrease than you would have normally expected? Just to give a little bit of color. Thanks.

Karl Gubitz (CFO)

Yeah. So thank you. We had a really successful launch in Germany, and we, of course, had a really good price in Germany. That actually meant that we exceeded the threshold for the classification of an orphan drug, which automatically triggers a price renegotiation with the German authorities. We have now entered into that negotiation, and we have to assume a lower price. We don't know what that price will be. We're negotiating it. We will only know in the beginning of 2025, Q1 2025. But we will be accruing for that lower price from 1 January 2024, as the difference between old and new price will have to be a rebate back to the government. So Tazeen, I mean, this is because we were so successful and exceeding that threshold of $30 million, which is an orphan drug designation.

Tazeen Ahmad (Managing Director)

Okay. Thank you.

Karl Gubitz (CFO)

Thank you for your question.

Operator (participant)

Your next question comes from a line of Derek Archila from Wells Fargo. Your line is open.

Derek Archila (Managing Director and Senior Equity Analyst)

Hey. Good morning and thanks for taking the questions. Yeah, just two from us. So I just wanted to understand the percent of the 2,300 prescribers for MG that currently treat CIDP patients. And then also, I guess you had a comment in the prepared remarks around new patients that you'll be able to access with the prefilled syringe. So I just want to understand who those patients are specifically that you can't really access right now with IV and Hytrulo. Thanks.

Karen Massey (COO)

Thanks for the question. I'll take them one by one. So what we're learning as we look into the CIDP market is that there is significant overlap between the prescribers, as you said, the 2,300 prescribers that are prescribing VYVGART for MG and potential future prescribers for CIDP. CIDP is treated much more in the community, is what we're learning. And as you well know, one of our strategies for MG and one of the things that we're seeing is that out in the community, we're seeing a lot more confidence with using VYVGART for MG based on the real-world efficacy. We're seeing real-world efficacy that reflects the clinical trial efficacy, the safety that continues to hold up. We have over 4,000 years of patient safety data now. So there is significant overlap in that prescriber base.

In terms of the new patients that you asked about with the prefilled syringe, I would say this just continues the momentum towards our strategy of moving earlier into the treatment line. So in MG, we've stated that the goal is that we believe MG should be used after orals. We're seeing 55% of our patients coming directly from orals. The IV, having the subcutaneous Hytrulo option and then moving into the prefilled syringe will just allow us to continue to execute on that strategy. Thanks for the question.

Derek Archila (Managing Director and Senior Equity Analyst)

Thank you.

Operator (participant)

Your next question comes from a line over at Rajan Sharma from Goldman Sachs. Your line is open.

Rajan Sharma (Managing Director and Equity Analyst)

Hi. Thanks for taking my question. I'm just looking ahead to thyroid eye disease where you're initiating the phase III. I realize that we'll probably see the clinical trials entry relatively soon. Could you perhaps just talk about how you're thinking about positioning relative to incumbents in that market? Maybe related to that, could you just comment on what underpins your confidence in moving to phase III? We've obviously seen some competitive proof of concept data, but just wondering if there's anything beyond that that is driving the decision here. Thank you.

Tim Van Hauwermeiren (CEO)

Yeah. Thank you. So I will take this question. The conviction in TED, of course, is driven by biology. That's done based on the internal homework but also peer-reviewed data from another player in the FcRn class. There are now nine indications out of nine for the class where we have seen successful proof of concept. TED is one of them. So we're marching based on that combined conviction. And differentiation, we hope, will come from different modes of action. So we are convinced TED is an IgG orphan antibody-driven disease. We think that by lowering these orphan antibodies, we could have the most profound effect on the disease. But we also, of course, can leverage a very clean safety profile and a very competitive way of presenting the product. So these are the three pillars to try and be competitive in the TED markets. Thank you for the question.

Operator (participant)

Your next question comes from a line of Yatin Suneja from Guggenheim. Your line is open.

Yatin Suneja (Senior Managing Director and Biotechnology Analyst)

Thank you for taking the question. I have a question on the Sjögren's disease. Could you just talk about the disclosure that you expect to make? And given the composite nature of CRESS, will you decide to move forward even if you don't see a strong signal or even if you just see a signal on other domains? And then maybe along the same line, from a regulatory standpoint, is there a well-defined regulatory path here, or is there an endpoint of choice from a registration standpoint? Thank you.

Tim Van Hauwermeiren (CEO)

Yeah, Yatin, this is a great question. Thank you for asking it. And I want to call out that Sjögren's is a signal-finding study where we will look at the totality of data across multiple clinical endpoints, not just CRESS but also ESSDAI, actually ClinESSDAI and ESSPRI, and then a string of biomarkers, which we're carefully monitoring. And what we want to see is consistency between the clinical endpoints and the biomarkers in order to get conviction and march forward. From a regulatory point of view or endpoint point of view, we will need to have, of course, an interaction with the regulators. But mind you that there are a number of phase III registration trials running where actually the primary endpoint is ESSDAI. So we assume this is the endpoint the FDA would like to see. CRESS is relatively new.

Stay tuned if and when we would have positive signal data. We would entertain a conversation with the FDA on this topic and afterwards communicate. Thanks for the question.

Operator (participant)

Your next question comes from a line of Yaron Werber from TD Cowen. Your line is open.

Yaron Werber (Managing Director, Senior Biotechnology Analyst)

Right. Tim, maybe just a follow-on on Yatin's question also on Sjögren. So your study is 36 patients, J&J ran three arms, you have two, and they obviously had 163 patients. So they obviously had a much bigger study. It sounds like it was that sick, as you mentioned. The endpoint's a little different, but you have a composite that includes their endpoint. So I guess my question is, it's a pretty good trial design. Give us a little bit of a sense. Is it completely underpowered to show any statistics at all? And is there a certain threshold of an effect that you want to see that you consider to be positive to move forward? Thank you.

Tim Van Hauwermeiren (CEO)

Yeah. I want to call out there's an overlap between our endpoints and the J&J endpoint. The reason, of course, they're doing three arms is because they still need to sort out the dose, which is not something which we have to do. You know that you can dose VYVGART at full power without paying a safety penalty. We will look at consistency of data. So it is defined what a clinically meaningful improvement is on an ESSDAI score, on a CRESS scale, on an ESSPRI scale. And then, of course, we want to see the biomarkers move in the right direction. The biomarkers are a combination of biomarkers from the circulation but also from the biopsy. And it is important to see the needle move on a clinical endpoint.

But we're going to pay special attention to what's happening in the biomarkers section, what's happening in the biopsies, and are these moving in a consistent fashion. So conviction on biology. We have also stratified for high and low IgG levels. About 50% of Sjögren's patients have high IgG types, 16 grams per liter or more. I think it's a very interesting stratification factor. The other way we look at the data is looking for patients which are positive for the Ro antibody or not. So I think it's going to be a small sample but a very deep look into patients and a very rich look, so way beyond a p-value on an endpoint. Thanks for the question.

Operator (participant)

Your next question comes from a line of Allison Bratzel from Piper Sandler. Your line is open.

Allison Bratzel (VP and Senior Research Analyst)

Hey. Good morning. Thanks for taking my question. Just to follow up on some of the discussion on the prefilled syringe, could you just expand on the expected cadence of updates on that this year and just what gives you confidence in potential approval of the prefilled syringe in 2024? Then just more broadly, given competitive updates in this field, how important do you see self-administration via syringe or autoinjector in determining your competitive positioning in a market with multiple FcRn agents approved? Thanks.

Tim Van Hauwermeiren (CEO)

Thanks, Allison. Thank you for the question. I'll take the first one, and I will hand over to Karen to explain how we seek to continue to lead the space also from a patient convenience point of view. But first, a prefilled syringe. It is high on the strategic agenda of the company this year. You know that we decided to launch the first generation subQ as fast as we could with the patient in mind. This is our second generation of prefilled syringe. And there are two important datasets we need to collect in order to be ready to submit the dossier with the FDA. The first dataset is a bioequivalence study. The second dataset involves a human factors study.

We're on track to give you an update during the first half of this year in terms of the progress we're making with collecting these data points. But it is of high priority for the company to be in a position to submit this year with the FDA. And maybe, Karen, you can continue on part two of the question, please.

Karen Massey (COO)

Yeah. Absolutely. I'm really excited for the prefilled syringe and the potential to bring that to patients. Look, we talked earlier about there's a significant unmet need in this market, and we can see that patients are looking for innovation. And I think our revenue last year demonstrates that in just our second year of launch. MG patients want to get their lives back. And PFS and self-administration help them to do that. So I think that's the real reason that the innovation of PFS is important. And I think for us, from a VIP card perspective, it just reinforces our leadership in the market. So first-in-class FcRn. I talked earlier about how we're demonstrating that real-world efficacy, continued safety. And then this just brings another product presentation potentially to the market. So we're confident that we're bringing the innovation to the market that patients really need.

Operator (participant)

Your next question comes from a line of Vikram Purohit from Morgan Stanley. Your line is open.

Vikram Purohit (Executive Director and Equity Analyst)

Hi. Good morning. Thank you for taking our questions. We had two. First on Bullous Pemphigoid. We're just curious, for the decision you're contemplating internally, what are some of the key considerations at play right now? And what do you see as the potential scenarios that could result from the update you're planning on providing us later this year? And then secondly, based on market research you might have done for MMN, I was curious to see how you segment this patient population and which segment of the patient base you think efgartigimod could be. I'm sorry, empasiprubart could be a viable therapy for. Thanks.

Tim Van Hauwermeiren (CEO)

Yeah. Thanks, Vikram. Karen was taking question two on our MMN patients. For bullous pemphigoid, I think the data analysis is ongoing, as we said. The key consideration is going to be, what is the impact of the background medication on the disease-causing autoantibodies? And is there a clinical trial design conceivable where actually efgartigimod can still shine because it is knocking down autoantibodies like hell? But are you still able to show a delta over the background medication? And there you need to thread the needle between what we want to achieve as a company and what regulators actually will want to see as a minimum background therapy. So I think we're well advanced with the homework. We will do, again, consultancy with our experts during AAD in the coming weeks.

I think we will be ready to think through a couple of scenarios based on that feedback. So stay tuned. This is an important discussion internally for the company. We believe the unmet need in BP warrants very thoughtful considerations. Thank you.

Karen Massey (COO)

Yeah. And on the topic of MMN, MMN is the type of disease, I think, that we say that we like at argenx because it's characterized by the fact that there's an enormous unmet need in these patients. There's been limited innovation. These patients continue to progress despite treatment today. So of all of the diseases that we're studying, we get the most calls from MMN patients that are asking for innovation to come to the market. These are the types of diseases that we like because we think we can really raise expectations and reframe what patients can expect. And we think we'll do that with empasiprubart. In terms of what the market research is telling us, beyond that, we're not breaking down our clinical trial design as yet. But rather just thinking about what's the broadest patient benefits that we can create.

Tim Van Hauwermeiren (CEO)

Vikram, remember that in MMN, at least 85% of the patients share that pathogenic autoantibody, that IgM autoantibody against GM1. We actually think that 100% of the MMN patients have that autoantibody, the disease-causing antibody, the sensitivity detection issue. So we think that the underlying biology is pretty much unifying for all MMN patients. So I think we're in a good position. Thanks for the question.

Operator (participant)

Your next question comes from a line of Joel Beatty from Baird. Your line is open.

Joel Beatty (Managing Director and Senior Biotechnology Analyst)

Hi. Thanks for the question. Are you seeing or anticipating any meaningful differences in the frequency of dosing between IV and subQ and then soon prefilled syringe and eventually autoinjector?

Karen Massey (COO)

Oh, thanks for the question. No, we're not seeing any differences between the formulations. It's really about product presentation for patient convenience.

Operator (participant)

Your next question comes from a line of Danielle Brill from Raymond James. Your line is open.

Speaker 22

Hey, guys. This is [Allison] for Danielle. If I recall correctly, it looks like you updated prevalence estimates for CIDP, which are higher than your previous projections. Just curious what factors you saw that are attributed to the TAM growth as it pertains to diagnosis rates, treatment rates, and potentially life expectancy. Thanks so much.

Tim Van Hauwermeiren (CEO)

Yeah. I wouldn't read too much into it. I think previously, we shared a number from official sources specifically for U.S. and EU5. We now gave you the accurate number, what we think is accurate for the key markets in which we play. But our view on prevalence actually has not really changed. We try to feed you with as much accurate information as we can, representing the markets in which we play. Okay? Thank you.

Operator (participant)

Your next question comes from the line of Simon Baker from Redburn Atlantic. Your line is open.

Simon Baker (Head of Global Biopharma Research)

Thank you for taking my question. If I can go back to Sjögren's, please. I'm not sure if I missed the answer, but I just wanted to check if you did say what the form of the disclosure of that phase II data would be. I'm guessing it would be an announcement that the study has worked and you will proceed, followed by disclosure at a clinical conference. But I just wonder if you could confirm that and suggest a potential conference where that would be disclosed. Just putting the cart before the horse a little and thinking about phase III design, Tim, I think you mentioned the likely regulatory endpoint is changes in ESSDAI score. It also looks like 48-week duration looks like a typical length for phase III study in the indication. From other studies, it looks like three to 400 patients is a typical size. Can you comment on the legitimacy of those assumptions? Thanks so much.

Tim Van Hauwermeiren (CEO)

Yeah. Thanks for both questions. So yes, we're looking for the signal. And of course, when we see it, we will share it with some level of detail surrounding the go decision or the no-go decision. And assuming a go decision, you're correct in your understanding that then we would show more detailed data at the need for a medical need. So that understanding is correct. From a phase III assumptions point of view, I think you're spot on. This is indeed what you can see from other phase III registration trials in Sjögren's.

There are not many. But I think it's going to be subject of the conversation with the FDA. With the data in hand, we will need to go with our proposal into an end-of-phase II meeting and basically triangulate expectations for that phase III. For the time being, I would also build on your assumptions looking at the other registration trials. Thank you.

Simon Baker (Head of Global Biopharma Research)

Thanks so much.

Operator (participant)

Your next question comes from a line of Suzanne van Voorthuizen from VLK Kempen. Your line is open.

Suzanne van Voorthuizen (Head of Life Sciences Equity Research)

Hi, Tim. This is Suzanne from Kempen. Thanks for taking my question. I wanted to ask if you can speak a bit about your early-stage molecules, specifically the ones with the disclosed targets, the IL-6 targeted 109 and FcRn targeted 213. What can you tell us at this moment about these two molecules, and how do you think about development from here? Thank you.

Tim Van Hauwermeiren (CEO)

Yeah. Thank you, Suzanne. That's a great question to put the spotlight on the four IND candidates which are on the way to IND before end of 2025. ARGX-109 is a best-in-class IL-6 antibody. It has spent the most importance with a half-life of at least 60 days. So it's equipped with our proprietary technologies. That is, I think, a phenomenal antibody. But we were always a little bit questioning what is the central role of IL-6 biology in certain diseases. The reason that we gave that molecule the goal is because we have seen several indications where we think we see now a clear involvement of IL-6 biology as the driver of disease, not just a bystander, but really driving the disease. There are a couple of indications which we like. They would fit the franchises we're building.

They would basically also be the size of indications which we think we can master very well. On that second FcRn antagonist, people have been asking us, "What's wrong with VYVGART? What are we trying to improve?" It's very difficult to improve upon VYVGART. But what we see is that there is just more opportunity than we can handle with one molecule. I mean, VYVGART will have an ending life either from an IRA point of view and/or an LOE point of view. And we just want to make sure we have a second very competitive molecule in the race to take on all the abundance of opportunity which we see in front of us. And therefore, we think about the long-term presence in the class, a long-term leadership role in the class. And that's exactly what that molecule will serve. Thanks for the question.

Operator (participant)

Your next question comes from a line of Alex Thompson from Stifel. Your line is open.

Alex Thompson (Managing Director and Senior Biotechnology Analyst)

Yeah. Great. Thanks for taking the question. On CIDP OLE data, I wonder if you could talk a little bit about expectations around when you will present that data. And then how much of it so far has been included in your filing with the FDA? And is there a chance that anything around every other week dosing would be included in that filing? And if not, at this point, could that potentially delay any timelines here? So thanks.

Tim Van Hauwermeiren (CEO)

So for CIDP, we said that these are such important data that we wanted to showcase them as one of the major upcoming neurology indications. So stay tuned. That announcement is waiting for us around the corner. It's an important presentation, of course, because it's the first real innovation in CIDP for a very long time. Secondly, I think the question number two relates to, I think, a review issue with the FDA. We will need to see how they look at the data. It is true that the randomized controlled portion of the trial was weekly dosing. In the open label extension, we do have every other week dosing. But whatever is going to show up on the label, I think ultimately, this will be a conversation with the payers.

There you have to expect that agencies will take a position, similar position to what we did for MG. We will want to price transparently and responsibly and aim for broad access for patients to this innovation. Stay tuned. We will be talking about it in the near future.

Alex Thompson (Managing Director and Senior Biotechnology Analyst)

Great.

Operator (participant)

Your next question comes from a line of Samantha Semenkow from Citi. Your line is open.

Samantha Semenkow (VP and Senior SMid Biotech Equity Research Analyst)

Hi. Good morning. Thanks for taking our questions. I think you recently kicked off a direct-to-consumer advertisement for CIDP in preparation for the launch. I'm wondering if you could characterize how you expect this to impact the early launch for CIDP based on your learnings from the MG launch. And then just secondly, I think you're targeting dermatomyositis with two assets, efgartigimod, of course, in one of the ALKIVIA cohorts, and then EMPA in a phase II study. Can you just talk through the rationale for each drug in DM and how you're thinking about the types of patients that could be addressed with each mechanism of action? Thank you.

Tim Van Hauwermeiren (CEO)

Thank you. Well, I'll be taking question two. I think Karen is best coming to talk about our recent DTC campaign.

Karen Massey (COO)

Yeah. Absolutely. Thanks for the question. As I said, we're getting more and more confidence in the unmet need in CIDP as we approach launch and the more that we learn about this market. And certainly from a perspective of preparing for that launch, as you said, we recently launched an unbranded campaign to really raise the awareness of the burden of CIDP in the community. And that campaign is ongoing. It leverages the learnings that we had in the MG launch, that to educate patients and to activate patients is incredibly important in these autoimmune diseases that are underserved, underdiagnosed, and undertreated. And that's the real goal of the campaign. Thanks for the question.

Tim Van Hauwermeiren (CEO)

Thank you, Karen. For dermatomyositis, this is a very high medical indication, pretty complex biology. When we did the homework on the biology, including studying the skin biopsies, you see two distinct subsets of patients. There is one subset of patients where you clearly see the involvement of pathogenic autoantibodies of the IgG type so that this actually perfectly fits for an FcRn. There's also a subset of patients where you see in the skin biopsy direct complement deposition and activation without the role of recruiting autoantibodies. So we think both modes of action deserve the short-term goal in the end. And I think the way we do the studies is there's a ton of biomarker data involved. So maybe we further unravel the disease biology, and we learn how to triage patients based on the driving disease biology which is relevant to them. Thanks for the question.

Operator (participant)

Your next question comes from a line of Gavin Clark-Gartner from Evercore ISI. Your line is open.

Speaker 21

Hi. This is [Yasha] on for Gavin. Thanks for taking our question. We were just wondering what you make of the Ultomiris discontinuation in dermatomyositis and if you see any read-through to your ongoing trial. And then I have one follow-up.

Tim Van Hauwermeiren (CEO)

Yeah. It wouldn't be unusual to see a C5 blocker fail in an indication where then other complement intervention works. Complement is not one-size-fits-all. Complement is a very complex system. There are multiple pathways involved. And depending on the disease, different arms of complement are involved and at different stages. So MMN, for example, is a case in point. C5 blockade failed in MMN. C2 blockade is a home run. So the same, I think, is valid for DM. It's not because a C5 blocker fails that an upstream complement blocker effector would fail. So we did our homework on the biology. We think the complement activity is upstream of C5. And therefore, I think we need to do this experiment with our own proprietary C2 blocker. Thanks for the question.

Speaker 21

Awesome. And then one quick follow-up. Could you comment on any relative design differences between your phase II and phase III and then the Ultomiris trial, if you happen to know?

Tim Van Hauwermeiren (CEO)

Yeah. We don't have enough details about the Ultomiris trial to really do a head-to-head comparison between study details. We don't have that information. I'm not in a real position to comment on that, [Jessa.] Thanks for the question.

Operator (participant)

Your next question comes from a line of Myles Minter from William Blair. Your line is open.

Myles Minter (Senior Biotechnology Analyst)

Hey. Thanks for taking the question. Just back on the RHO study, I think we've seen 50% ESSDAI response rates in prior Sjögren's trials at phase II on placebo. Just wondering whether that's the expectation for the 12 patients that you have on placebo in that trial. And then also, how important is it to show efficacy on the totality of data at the 24-week endpoint versus efficacy over the entirety of the trial? Again, just pointing to recent trials in the space that have shown variability between 20 and 24 weeks on efficacy. Thanks very much.

Tim Van Hauwermeiren (CEO)

Yeah. It's an excellent question, Myles. So yes, we have been studying precedent trials. There is some consistency in placebo response. It's about a 40% response. You have an outlier study, but we think we understand why there is an outlier. So I think you do see a reasonable consistency in historical placebo responses. And that was the ingoing assumption for our trial II. In terms of endpoint, we have an endpoint to choose. Well, we're actually looking at multiple endpoints, okay? So it's a 24-week study, but we have multiple time points where we will basically assess the patients and look at the dynamic evolution of their disease symptoms and the biomarkers. So it's not just going to be a photo finish at week 24. We will look at the evolution of the data over time. Thanks for the question.

Myles Minter (Senior Biotechnology Analyst)

Very helpful. Thank you.

Operator (participant)

Your next question comes from a line of Xian Deng from UBS. Your line is open.

Xian Deng (Executive Director and Equity Analyst)

Hi. It's Xian from UBS. Thank you for taking that question. So I have a question on 119 in ALS, please. I was just wondering if you could elaborate a bit more about the biological rationale for ALS, please. I mean, given ALS is a very complex disease, I mean, there's protein degradation, autoimmune, genetic factors involved. So just wondering, for 119, are you coming from the angle that MuSK is sort of a key factor in neuromuscular synapse formation? And if that's the case, I'm just wondering, are you after disease modification here, or it's more sort of like a symptom relief, a bit like levodopa in Parkinson's? Thank you.

Tim Van Hauwermeiren (CEO)

Yeah. It's an excellent question. So MuSK is a very interesting target. It's not just organized in the formation and the maturation and the functioning of the neuromuscular junction. And the signal also goes in the other way. So MuSK can signal through LRP4 back to the neuron. And one of the hallmarks of ALS is that in the initial stage, we go to a phase which we call a phase where you have repeated denervation and renervation. And there must be communication between the nerve cell and the muscle cell in that process. And we think that happens through retrograde signaling MuSK to LRP4 to the neuron. So if you can keep the innervation longer through activating MuSK, we think that could have a meaningful impact on ALS patients. So there's quite some biology thinking going on behind the program.

We do realize ALS is high risk, but also high reward. Therefore, there's a ton of translational biology going into the ALS thinking. Also, the way we set up the initial clinical experiment is such that we will have a very deep look into these patients. Almost happens on that innervation-denervation process. Stay tuned. It's an exciting experiment. We're looking forward to seeing the first data.

Operator (participant)

Your next question comes from a line of Joon Lee from Truist Securities. Your line is open.

Speaker 23

Good morning. This is [Asimon] for Joon. Thanks for taking the questions. On the TED trial, I believe it was previously slated to begin in the fourth quarter last year. So just wondering what was behind the delay. And then my other question is on the prefilled syringe, just wondering if you could just provide some details on your manufacturing capacity or your preparations. Thank you.

Karen Massey (COO)

Yep. For the TED trial, thanks for the questions. For the TED trial, we made a decision to wait to start that trial so that we could use the PFS. And that trial is on track now. For the second question, we've invested in manufacturing capacity and are confident in the manufacturing capacity for IV subcutaneous and PFS at this stage.

Operator (participant)

Your next question comes from a line of Douglas Tsao from HC Wainwright. Your line is open.

Douglas Tsao (Managing Director and Senior Healthcare Analyst)

Hi. Good morning. Thanks for the questions. I'm just curious in terms of how you're thinking about reimbursement in CIDP or just sort of contracting with payers. I suspect you've had some early conversations. Just given the fact that IVIG is already on label, the dosing frequency is greater in CIDP, do you see the same opportunities to have access that you do the same success with access that you've had in MG? Will it sort of have different outlines and same opportunities for value-based reimbursement? Thank you.

Karen Massey (COO)

Yeah. Thanks for the question. We think a lot about how do we maximize access for patients to our innovation. We're thinking deeply about it for the CIDP launch. What I can share is that we'll take the same approach that we did with the MG launch. We'll be transparent once we have a decision. We'll make responsible decisions that really give patients the greatest access to our innovation that we can. More to come. Thanks for the question.

Operator (participant)

Your next question comes from a line of Andy Chen from Wolfe Research. Your line is open.

Andy Chen (Director and Senior Biotechnology Analyst)

Hey. Thank you for taking the question. Can you talk about empasiprubart a bit and the sequencing of indications? I know you have named three indications, but how were these chosen and prioritized? Are these the best indications commercially, or are they the best indications scientifically given the mechanism and disease pathogenesis? And obviously, what are the key decision-making factors when you choose the next few indications? Thank you.

Tim Van Hauwermeiren (CEO)

Yeah. This is the typical way our argenx works. We always start from the biology. So we're not going to force-fit biology with what looks like a great commercial opportunity to then fail in the clinical trial. So we follow biology. And the three indications we pursue for MMN, for which we showed recently data, where we believe the pathogenic IgM autoantibody is actually the driver of the disease and actually the activating complement. And we have shown we can block that very effectively. The second indication is delayed graft function. That is actually in the kidney transplant setting. And there's, again, very compelling evidence. The classical and the lectin pathway is in play if you look at the kidney biopsies.

And therefore, C2, which is at the nexus of both pathways, is an ideal target to block delayed graft function, which actually leads to significant kidney loss in the transplant setting. So the value of that organ is very high. It's a higher medical need with an effective commercial setting. And then the third indication is dermatomyositis, which we already touched on. We have more indications in the works, but we always start from biology. Then we will actually look at the ability to do a clinical trial experiment in terms of availability of clinical endpoints, approvable endpoints, ability to enroll the trial, also ability to show the signal despite background medication.

And then finally, of course, we take a careful look at unmet medical needs and the ability to shape the treatment paradigm, which are two pillars to formulate the commercial rationale. All three indications have been carefully selected based on these filters. More indications are underway. We think this is our next pipeline in the products.

Operator (participant)

This ends our question and answer period and does conclude today's conference call. Thank you for your participation. You may now disconnect.