argenx SE
XBRU:ARGX
Earnings Call Analysis
Q4-2023 Analysis
argenx SE
Argenx commences with a vibrant vision to transform lives in the autoimmune community by strategically enhancing the reach of its first-in-class innovation, VYVGART, and building long-term value with a focus on expanding opportunities and introducing new treatments for seronegative patients and across different autoimmune diseases. With a firm commitment to its mission and an array of innovation horizons, Argenx foresees a robust roadmap for enduring growth.
Having carved a commendable niche within its second year of launch, VYVGART's trajectory speaks to the substantial unmet needs of patients suffering from generalized Myasthenia Gravis (gMG). With the ambition to traverse beyond gMG, Argenx sets its sights on leveraging VYVGART's success to address other indications, notably launching preparations for regulatory nods in ITP in Japan and CIDP in the US. The company's readiness to expand underscores a tactical approach, cementing its position in the market and preparing to conquer forthcoming opportunities with a finely honed strategy.
Argenx's devotion to clinical excellence is evident in its progress with multiple Phase 3 and Phase 2 studies. By delving into various subtypes of myositis and post-COVID afflictions, and advancing plans in bullous pemphigoid, the company aspires to break new ground in understanding autoimmune diseases. This relentless pursuit of broader treatment potential echoes Argenx's innate drive to lead through innovation and furnish pivotal insights into the underpinnings of autoimmune biology.
Argenx showcases its pipeline prowess with promising prospects such as Empa, a derivative of the company's Immunology Innovation Program (IIP), which has already demonstrated exceptional results in Multifocal Motor Neuropathy (MMN). The company's continued pipeline development, encompassing translational and registrational work, exemplifies a methodical progression from discovery to potential registration trials. Argenx's foray into nurturing molecules like ARGX-119 for CMS and ALS patient studies further solidifies its commitment to neurology and the overarching aim of unveiling transformative treatments.
The Immunology Innovation Program stands as the bedrock of Argenx's sustainable growth. With a formidable legacy of launching multiple programs into human testing, the company affirms its innovation tenacity. The nomination of four new prospective molecules for advancement echoes Argenx's strategic intent to deploy its expertise in antibody engineering and clinical development, in partnership with notable scientific collaborators, thus promising a new horizon of treatment solutions.
The fiscal discipline and astuteness displayed in the fourth quarter of 2023, with revenues of $418 million and net loss trimmed to $99 million, underscore Argenx's financial resilience. Bolstered by a robust balance sheet, Argenx projects its R&D and SG&A expenses for 2024 to be beneath $2 billion, with a cash utilization of up to $500 million for operating, working capital, and capital expenditures, delineating a clear financial trajectory steered towards judicious investments and fiscal prudence.
With over 6,000 patients under VYVGART's wing, Argenx revels in the remarkable progress and plans to enlarge its footprint across gMG populations while paving the way for potential CIDP and ITP treatment launches. Boilerplating its success in bringing innovative treatments like VYVGART to market, Argenx maintains a growth narrative that hinges on strategic commercial acumen, a diversified prescriber base, and unwavering dedication to revolutionizing patient experiences.
Argenx feels the pulse of a burgeoning global market, emboldened by the uptick in sales and the accelerated pace at which VYVGART gains traction outside the States. The company's forward momentum is palpable, with reimbursement headway and strategic partnerships, most notably exemplified in Europe and China. These advancements bode well for the company's vision of being a global leader in the autoimmune therapy market and eroding the dominance of U.S. sales with a more balanced global revenue footprint.
Poised at the threshold of expanding its patient impact, Argenx eyes CIDP, a crippling ailment crying out for innovative treatment. Capitalizing on the insights gleaned from VYVGART's MG battleground, the company is gearing up to navigate the complex CIDP therapy landscape. Although anticipating challenges, the team's enthusiasm is buttressed by robust ADHERE data, driving their motivation to introduce a groundbreaking therapeutic option and prefacing strategic preparations for FDA submissions.
Argenx sets its stakes high with an overarching commitment to redefining treatment paradigms in autoimmune diseases. By fostering disease awareness, raising therapy expectations, and pushing the envelope of innovation beyond pharmaceuticals, the company showcases its dedication to lasting impact. Argenx's vision straddles the responsibility of providing comprehensive, valuable, and accessible solutions to improve the lives of patients and caregivers alike.
Finally, with a strategy grounded in steadfast execution, Argenx concludes its narrative on a note of gratitude, acknowledging the efforts of its team, the patient communities, and the physicians. The company's drive, catalyzed by these collaborations, continues to fuel its quest to achieve superior outcomes for individuals grappling with autoimmune diseases. This collective spirit of determination and thanks serves as a poignant testament to Argenx's ethos and its unwavering allegiance to its mission.
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Good morning. My name is Rob, and I will be your conference operator today. I would like to welcome everyone to the call. [Operator Instructions] 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.
Thank you. A press release was issued earlier today with our full year financial results and recent business update. 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 2 that forward-looking statements may be presented during this call. These may include statements about our future expectations, clinical development, regulatory time lines, the potential success of our product candidates, financial projections and upcoming milestones. Actual results may differ materially from those indicated by these statements. Argenx is not under any obligation to update statements regarding the future or to conform those statements in relation to actual results unless required by law.I'm 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.
Thank you, Beth, and welcome, everyone. I will begin on Slide 3. 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. And 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 VYVGART opportunity, advancing our pipeline and bringing the next wave of IND candidates into the clinic. On today's call, I would like to highlight recent news and walk through upcoming milestones in the context of these horizons.Slide 4. Let's start with a VYVGART opportunity. We had an incredible second year of launch, driven by the ambitious strategy and seamless execution of our commercial and medical teams, and 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 registrational 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 launched 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 better position ourselves for success.Slide 5, VYVGART continues to make headway in the clinic. The Phase 3 TED study is ready to start this quarter and will be the first to utilize our prefilled syringe from the onset. We are expecting relapse from 5 Phase 2 studies, including insurance, post-COVID POTS and 3 subtypes of myositis. And 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 involved in pilot 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 efgartigimod studies based on the impact from ADVANCE-SC and ADDRESS. This will be another year where we learn more about the broad potential of FcRn 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 children as that will be the first of 5. The RHO study has a target enrollment of 30 moderate-to-severe patients randomized [indiscernible]. The study is not filed for efficacy, so we will rely on the depth of data we will gather from each patient looking at various endpoints, including crest, SDAI, [indiscernible] 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 registrational trial to amplify any single we observed in Phase 2.We plan to employ a similar approach in our evaluation of cost, looking at the depth of data across the enrolled patients to make an evidence-based decision to move into a Phase 3 study. With myositis, we have a seamless Phase 2/3 design, which will expedite the transition from the first 30 patients of each subset into the registrational 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 9 out of 9 indications across the FcRn and we believe this is still just the beginning of the broader opportunity.Slide 6. Turning attention to our next horizon of innovation, I want to briefly touch on our pipeline progress. Empa is our second pipeline in a product opportunity from which we have shown compelling MMN 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 registrational trial in its first indication.In collaboration with Professor Erik Hack, we've built what we believe is a first-in-class and best-in-class sweeping antibody against C2 and have conducted translational work to highlight what 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 registrational trial and look forward to sharing the full Phase 2 data set this year.The MMN opportunity fits perfectly within our expanding capabilities in neurology and plus ARGX-119, our third pipeline program. This molecule will go 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 MMN 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 7. 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 efgartigimod and empa with 9 programs tested in human since inception. We demonstrated the efficiency of this pipeline engine by nominating 4 new molecules last year. All are on track to be filed with 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.
Thank you, Tim. Slide 8. 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 a $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 2 as well as royalty income from Zai Lab of $0.7 million for VYVGART in China.The breakdown per region of $374 million in product net sales is $326 million in the U.S., $17 million in Japan, $24 million in EMEA and $7 million in China. Globally, we saw growth of 14% or $45 million in your 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 costs 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, and we expect to utilize up to $500 million of cash in 2024 on our anticipated operating expenses as well as working capital and capital expenditures, including investment in our supply chain.I will now turn the call over to Karen, who will provide details on the commercial front.
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 3 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 MG 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 population. And we have over 4,000 patient years of safety follow-up with efgartigimod, which continues to support our consistent safety profile and with physicians, this is a key differentiator. We are observing increased utilization of both VYVGART and VYVGART Hytrulo in earlier lines of therapy, with an impressive 55% of patients coming to VYVGART directly from orals, and 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. And 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 broader 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 set 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 2 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 demand 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 treatment but to reset expectations. We want to move the goal post so that patients aim to regain function or going 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.And with that, I'll turn the call back to Tim.
Thank you, Karen. We laid out an ambitious plan for the year and at 2 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 we'll continue to approach these, 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 Instructions] Your first question comes from the line of Tazeen Ahmad from Bank of America.
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 '24? And then I have a follow-up.
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, do 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'd 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 really -- 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 could -- 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?
No, I think you've said it all. I think the payer contracts, which will take a quarter or 2 to put in place, will definitely delay some of those revenues into 2025.
Okay. 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.
Yes. 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 renegotiating it. We will only know by the -- 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 -- back to the government. So Tazeen, this is because we were so successful and exceeding that threshold of $30 million, which is orphan drug designation.
Your next question comes from the line of Derek Archila from Wells Fargo.
Yes, just 2 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?
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 we -- so there -- 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 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 like Hytrulo option and then moving into the prefilled syringe will just allow us to continue to execute on that strategy.
Your next question comes from the line of Rajan Sharma from Goldman Sachs.
Just looking ahead to thyroid eye disease, where you're initiating the Phase 3, and I realize that we'll probably see the clinical trials entry relatively soon. But could you perhaps just talk about how you're thinking about positioning relative to incumbents in that market? And maybe related to that, could you just comment on what underpins your confidence in moving to Phase 3. 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.
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 9 indications out of 9 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 autoantibody-driven disease. We think that by lowering these autoantibodies, 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 3 pillars to try and be competitive in the TED markets.
Your next question comes from the line of Yatin Suneja from Guggenheim.
I have a question on the Sjogren's disease. Could you just talk about the disclosure that you expect to make? And given the composite nature of [ crest ] 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, like from a regulatory standpoint, is there a well-defined regulatory path here? Or is there an endpoint of choice from a registration standpoint?
Yatin, this is a great question. Thank you for asking it. And I want to call out that children's is a signal finding study, where we will look at the totality of data across multiple clinical endpoints, not just crest, but also SDAI, actually [indiscernible] and then a string of biomarkers, which we are 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. And 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 3 registration trials running where actually the primary endpoint is SDAI. So we assume this is the endpoint the FDA would like to see. And crest is a relatively new, so stay tuned, if and when we would have positive signal data and we would entertain a conversation with the FDA on this topic and afterwards communicate.
Your next question comes from the line of Yaron Werber from TD Cowen.
Tim, maybe just a follow-on on Yatin's question also on Sjogren. So your study is 36 patients, J&J ran 3 arms, you have 2, and they obviously had 163 patients. So they obviously had a much bigger study. It sounds like it was [indiscernible] as you mentioned. The endpoint is 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. And so 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?
Yes. I want to call out there's an overlap between our endpoints and J&J endpoints. The reason, of course, they're doing 3 arms is because they still need to sort out a dose, which is not something which we have to do. You know that you can dose VYVGART at a full power without paying a safety penalty. We will look at the consistency of data. So it is defined what a clinically meaningful improvement is on an SDAI score, on a [indiscernible] scale, on an SP 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 that either 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 biopsy -- 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 children, 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 raw 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 the p-value on an endpoint.
Your next question comes from the line of Allison Bratzel from Piper Sandler.
So just a 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? And then just more broadly, given competitive updates in the field, how important do you see self-administration via syringe or auto injector in determining your competitive positioning in a market with multiple FcRn agents approved?
So 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, at prefilled syringe, it is high on the strategic agenda of the company this year. You know that we decided to launch the first-generation subcu as fast as we could with the patient in mind. This is our second generation of prefilled syringe and there are 2 important data sets we need to collect in order to be ready to submit the dossier with the FDA. The first data set is the bioequivalent study. The second data set involves a human factor study, and we are 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 that it is a 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 2 of the question, please?
Yes. 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 a 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 then -- and I think for us, from a VYVGART perspective, it just reinforces our leadership in the market.The first -- 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 the patients really need.
Your next question comes from the line of Vikram Purohit from Morgan Stanley.
We had 2, first on bullous pemphigoid. I was just curious for the decision you're contemplating internally. What are some of the key considerations that play right now? And what do you see as the potential scenario 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?
I'll take question 2 on our MMN patients. For bullous pemphigoid, I think the data analysis is ongoing, as we said. And 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 health, but are you still able to show a delta over the background medication. And there you need to thread a needle between what we want to achieve as a company and what regulators actually will want to see as 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. And 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. And we believe that unmet need in BP warrants a very thoughtful consideration.
Yes. 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 and these patients continue to progress despite treatment today. So they are -- 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. So 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 beyond that, but rather just thinking about what's the broadest patient benefits that we can create.
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 to disease-causing antibody, it's a sensitivity detection issue. So we think that the underlying biology is pretty must unifying for all MMN patients. So I think we're in a good position.
Your next question comes from the line of Joel Beatty from Baird.
Are you seeing or anticipating any meaningful differences in the frequency of dosing between IV and subcu and then soon prefilled syringe and eventually auto injector?
Thanks for the question. No, we're not seeing any differences between the formulations. It's really about product presentation for patient convenience.
Your next question comes from the line of Danielle Brill from Raymond James.
This is [ Alex ] on 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?
Yes, 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.
Your next question comes from the line of Simon Baker from Redburn.
If I can go back to Sjogren'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 2 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. And just putting the cart before the horse a little and thinking about Phase 3 design.Tim, I think you mentioned the likely regulatory endpoint is changed in clinical SDAI score. It also looks like 48-week duration looks like a typical length for a Phase 3 study in the indication. And from other studies, it looks like 300 to 400 patients is a typical size. Can you comment on the legitimacy of those assumptions?
Yes. 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 logo decision. And assuming a go decision, you're correcting your understanding that then we would show more detailed data at the unmet medical need. So that understanding is correct. From a Phase 3 assumptions point of view, I think you're spot on, this is indeed what you can see from all the Phase 3 registrational trials in children's, there are not many. But I think there'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 2 meeting and basically triangulate expectations for that phasing. So for the time being, I would also build on the other assumptions, looking at the other registrational trials.
Your next question comes from the line of Suzanne van Voorthuizen from VLK Kempen.
This is Susanne with Kempen. 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 target of 109 and FcRn target of 213. What can you tell us at this moment about these 2 molecules? And how do you think about development from here?
That's a great question to put the spotlight on the 4 IND candidates, which are underway to IND before end of 2025. ARGX-109 is a best-in-class IL-6 antibody, it has [ phantom ] order potency with a half-life of at least 60 days, so it's equipped with our proprietary technologies. And that is, I think, a phenomenal antibody, but we've got always a little bit questioning, what is the central role of IL-6 biology in certain diseases?The reason that we give 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 the bystander, but really driving the disease. And they are the type of indications which we like to know, they would fit the franchisees we are building and they would basically also be the size of indications which we think we can master very well.On that second argenx 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 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 a long-term presence in the class, a long-term leadership role in the class and that's exactly what that molecule will serve.
Your next question comes from the line of Alex Thompson from Stifel.
On CIDP or [ lead ] 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 dosing -- every other week dosing would be included in that filing? And if not, at this point, could that potentially delay any timelines here?
For CIDP that these are such important data that we wanted to showcase them as one of the major upcoming neurology indications. So stay tuned. This announcement is waiting for us around the corner. And 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 #2 relates to I think, review issue with the FDA. We will need to see how they look at the data. It is through the randomized controlled portion of the trial, it was weekly dosing. In the open label extension, we do have [ every other ] redosing, but whatever is going to show up on the label, I think ultimately this will be a conversation with the payers. And then you have to expect that argenx 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. So stay tuned, we will be talking about it in the near future.
Your next question comes from the line of Samantha Semenkow from Citi.
I think you recently kicked off a direct-to-consumer advertisement for CIDP in preparation for the launch. I'm wondering if 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 2 assets, efgartigimod, of course, is one of the [indiscernible] cohort and then empa in a Phase 2 study. Can you 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?
I'll be taking question 2. I think Karen has best comment to talk about our recent DTC campaign.
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 and 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, under-diagnosed and undertreated. And that's the real goal of the campaign.
For dermatomyositis, look, this as a very high [ medical ] lead indication, pretty complex biology. When we did the homework on the biology including studying the skin biopsies, you see 2 distinct subsets of patients. And there is one subset of patients where you clearly see the involvement of pathogenic autoantibodies of the IgG type, so that is actually perfectly fit for efgartigimod.There is also a subset of patients that you see in the skin biopsy, direct complementary position and activation without the role of recruiting autoantibody. So we think both modes of action deserve the shot on 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 this disease biology and we learn how to triage patients based on the driving disease biology which is relevant to them.
Your next question comes from the line of Gavin Clark-Gartner from Evercore ISI.
This is [indiscernible] on for Gavin. 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.
Yes, it wouldn't be unusual to see a C5 blocker fail in an indication but 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 an example in case C5 blockade failed in MMN, [ D2 ] blockade is a homer. So the same, I think is valid for DM. And it's not because a C5 blocker fails that an upstream complement blocker defector would fail. So we did the 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 [indiscernible].
And then one quick follow-up. Just could you comment on any relative design differences between your Phase 2 and Phase 3, and then the Ultomiris trial, if you happen to know?
Yes, we don't have enough details about the Ultomiris trial to really do a head-to-head comparison between study details. So we don't have that information. And I'm not in a real position to comment on that.
Your next question comes from the line of Myles Minter from William Blair.
Just back on the RHO study. I think we've seen, like, 50% SDAI response rates in prior Sjogren's trials at Phase 2 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.
Yes, 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 will be the incoming assumption for our trial, too. In terms of endpoint, we have what endpoint to choose? Well, we are 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.
Your next question comes from a line of Xian Deng from UBS.
Hi, it's Xian from UBS. 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. Giving ALS is a very complex disease, there's like, protein degradation, autoimmune, genetic factors involved. So we're just wondering for 119, are you coming from the angle that mask 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.
Yes, it's an excellent question. So MuSK is a very interesting target. It's not just organizing the formation and the maturation and the functioning of the neuromuscular junction, the signal also goes in the other way. So MuSK can signal through LRP4 back to the neuro. And one of the hallmarks of ALS is that in the initial stage, we go through a phase which we call a phase where you have repeated denervation and reinnervation, 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 neuro. So if you can keep the innovation 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, and therefore there's a ton of translation 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 innovation to innovation process. So stay tuned. It's an exciting experiment and we're looking forward to seeing the first data.
Your next question comes from a line of Joon Lee from Truist Securities.
This is [indiscernible] on for Joon. 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?
Yes. 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. And 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.
Your next question comes from the line of Douglas Tsao from H.C. Wainwright.
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 and 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, the same success with access that you've had in MG? And will it sort of have different outlines and same opportunities for value-based reimbursement?
We think a lot about how do we maximize access for patients to our innovation and 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, and we'll make responsible decisions that really give patients the greatest access to our innovation that we can. So, more to come.
Your next question comes from a line of Andy Chen from Wolfe Research.
Can you talk about empasiprubart a bit and the sequencing of indications? I know you have named 3 indications, but how were these chosen and prioritized? Are these the best indications commercially or are these 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?
Yeah, this is the typical way 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 3 indications we public on are MMN, which we showed recently data where we believe the pathogenic IgM autoantibody is actually the driver of the disease and actually recruiting 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 Galectin 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 high unmet medical needs, so an attractive 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 need and the ability to shape the treatment paradigm, which are 2 pillars to formulate the commercial rationale.So all 3 indications have been carefully selected based on these filters and more indications are underway. So we think this our next pipeline in the product.
This ends our question-and-answer period and does conclude today's conference call. Thank you for your participation. You may now disconnect.