argenx SE (ARGX) Q4 2020 Earnings Report, Transcript and Summary

Good morning. My name is Andrew, and I will be your conference operator today. Welcome to the argenx Full Year and Fourth Quarter 2020 Financial Results Conference Call. At this time, I would like to welcome everyone to the call. All lines have been placed on mute to prevent any background noise. After the speakers’ remarks, there will be a question-and-answer session. [Operator Instructions] Please note this conference is being recorded. Thank you. I'd like to introduce Beth DelGiacco, Vice President of Corporate Communications and Investor Relations. You may begin your conference.

Thank you. A press release was issued earlier today with our full year 2020 financial results and the 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; Eric Castaldi, Chief Financial Officer; and Keith Woods, Chief Operating Officer. I will now turn the call over to Tim.

Thank you, Beth, and good morning to everyone on the call. We appreciate your joining. I'm proud of the exceptional progress we made in 2020 despite many unexpected global challenges. We believe we are closer than ever to reaching patients and strongly positioned to create long-term sustainable value for our shareholders. I'd like to briefly highlight some recent milestones and then provide updates on our deep and differentiated pipeline. First, as we announced earlier this week, we are pleased that our BLA was accepted for review by the FDA. This decision is an achievement for us as a company, but more importantly, we are thinking about what this means for our patients. We see the very real unmet needs of people living with MG. We hear about it from patients directly and from their supporters, and we are hopeful that efgartigimod may provide a new treatment option for this community. The acceptance of our BLA serves as another gating event on our path to our first commercial launch, and we remain sharply focused on execution at every level of the organization. Between now and the potential approval of efgartigimod, we will be working in collaboration with the FDA to answer their questions and coordinate site inspections. I can tell you that we are planning to be ready well ahead of our December PDUFA date because we know that patients are waiting. Still, these are exceptional times with much uncertainty ahead. We are proactively planning for a launch in various scenarios, fully virtual for one or now that we have more time for the COVID vaccine program to be implemented, only partially virtual. We continue to make progress in engaging with a large proportion of our target stakeholders in a digital environment, which Keith will discuss later in the call. With that said, we would welcome the opportunity for our field force to hold meetings in person. Regardless of scenario, we plan to use every day we have until launch to further implement these important campaigns. The U.S. remains our priority for our first launch and our largest market, but we are also well underway with preparations in Japan where we expect to file our marketing application in the first half of 2021. This sets us up for a potential additional approval shortly after the U.S. In the European Union, we are seeking scientific advice in the first half of this year with plans to file our marketing authorization in the second half. Our European General Manager is very experienced in market access and is working on a strategic reimbursement plan in the highest priority countries. Secondly, we recently announced a goal decision to continue enrollment in the registrational ADHERE trial evaluating subcu efgartigimod in CIDP. With this update, efgartigimod now has four out of four successful proof-of-concept trials under its belt. This further emphasizes the breadth and potential before with efgartigimod and validates our careful indication selection process and innovative trial design. We will continue to leverage the same comprehensive strategy with future indications, which we believe will strengthen our leadership in the FcRn class overall. Third, argenx has a history of raising capital on the back of strong data, and the recent financing was no different. The 1.1 billion in gross proceeds strongly position us for the launch and will facilitate the expansion of our diversified pipeline and the growth of our team. On that note, I would like to take this opportunity to thank and recognize the outstanding argenx team. We have grown to over 450 colleagues over the past year and plan to increase to approximately 750 in 2021 across our four offices. In particular, I would like to thank our Chief Financial Officer, Eric Castaldi, who has been with argenx since 2014. As stated in the press release from this morning, we have started a planned transition process to recruit a U.S.-based successor for Eric. This is part of our evolution to a commercial stage company and will all happen in close coordination with Eric, our executive leadership team and the argenx board. We are very grateful for Eric's long tenure with the Company and for his invaluable contributions. Moving on to the pipeline update, starting with efgartigimod. We continue to believe that we have a first-in-class and potentially best-in-class FcRn antagonist. The structure and mechanism of action of efgartigimod are depicted on Slide number 4, and you can see that efgartigimod is unique due to our close collaboration with Dr. Sally Ward, efgartigimod is the only IgG1 smart fragment, which binds to FcRn in a way that mimics the natural items and preserves the PH dependent binding of endogenous IgG to FcRn. In our studies, we have not observed effects on other serial radians like IgM, IgA or a reduction of human serum albumin. To date, over 350 subjects have been dosed with efgartigimod, and we continue to observe a favorable tolerability profile, which has been observed to be consistent across indications. On Slide number 6, we also see a consistent PD effect across trial that has translated into promising clinical benefits. The Phase III ADAPT trial demonstrated a response rate of almost 80% across two treatment cycles, a fast onset of action, depth of response and the potential for individualized building. The consistent PD effect also enabled our ongoing subcu bridging strategy for MG, as seen on Slide number 7. This study is a registrational non-inferiority trial, which compares the pharmacodynamic effect of 1,000 milligram subcu efgartigimod with 10-milligram per kilogram IV efgartigimod and is expected to enroll approximately 50 patients. The primary endpoint will be taken at day 29 and that after we will continue to build a safety database to support the filing of the subcu BLA. Slide 8. CIDP is the second efgartigimod indication within our neuromuscular franchise and the fourth established proof-of-concept indication. I covered the GO decision earlier in the call, so I will just mention a few key points. We believe we designed a very innovative trial with ADHERE using screening criteria to identify patients with an active confirmed diagnosis of CIDP. We also included a planned interim analysis before committing valuable time and resources to running a registrational program. We wanted to be confident of the role of the auto antibody in the disease pathophysiology. We set the bar high using precedent trials to define our thresholds, and we match the criteria. We can now move forward with confidence as we open new trial sites for enrollment in this registrational trial. CIDP is an indication where there has been little innovation, and we are advancing the program as quickly as possible. Next, we are enrolling patients in our ITP trials as well as our PV trial, which can be seen on Slides 9 and 10. For ITP, we have brought forward our subcu strategy based on feedback from patients and physicians and are running two concurrent ADVANCE trials, one with IV and one with subcu. We expect these trials will support registration of both formulations. In pemphigus, we are evaluating subcu efgartigimod in the ADDRESS registrational trial and as part of this, are specifically evaluating the ability to taper patients off steroids. We listen to patients describe the ongoing burden of current treatments and incorporated this evaluation into our trial design. As you can see, we take a forward-thinking approach when designing our trials based on feedback from physicians and patients. We will continue to infuse that feedback into future trial designs so that we are optimally positioning efgartigimod within current treatment paradigms. This is true for our fifth and sixth indications, which we will disclose closer to the start of clinical trials. Turning to Slide 11. We believe that there is a broad landscape of IgG-mediated severe autoimmune diseases, for which efgartigimod may provide clinical benefit to patients. We will continue to roll out indications ourselves and will also expand and accelerate the pace of efgartigimod development globally through our strategic agreement with Zai Labs. Our MG launch in the U.S. is just the beginning. Beyond efgartigimod, we look forward to sharing the first set of clinical data from ARGX-117, our second pipeline candidate, with broad potential in severe automotive. We remain on track to provide data midyear from a Phase I healthy volunteer study from both IV and subcu formulations of ARGX-117. We expect to provide information on safety and tolerability, PK and PD effects, bioavailability and the selected Phase II dose and dosing regimen based on three C2 levels. Slide 12. The first indication we have highlighted for ARGX-117 is multifocal motor neuropathy, or MMN, which fits grade into our neuromuscular franchise. You can see our neuromuscular focus taking shape with MG, CIDP, our fifth efgartigimod indication, ARGX-117 and ARGX-119. We know that the investments we are making now in both neuromuscular and other franchises will benefit us over time as the franchises grow. Slide 13, quickly on cusatuzumab, for which we have a strategic collaboration with Janssen. We have shifted our priority for this program to the ELEVATE trial, evaluating a triple combination of cusatuzumab, venetoclax and azacitidine. This was based on one interim Phase II data from the CULMINATE trial; and two, the shifting treatment landscape for newly diagnosed elderly AML patients, where venetoclax has emerged a standard of care. In evaluating ELEVATE data, we will look at overall response rate, durability of response and safety and tolerability to consider where cusatuzumab could address unmet needs in this indication. With ELEVATE and the future of the program overall, we will continue to make data-based decisions on the path forward for cusatuzumab, as we do with all our clinical trials. Slide 14. We will not spend time on our broader pipeline today, but we are committed to providing updates as necessary. Investing in our Immunology Innovation Program continues to be a core part of our pipeline strategy. As we look towards commercialization, we seek to create optionality within our pipeline, whether through wholly owned candidates, pilot programs or asset-centric spin-off companies. We believe this is an important part of our growth story as we transition into an integrated immunology organization. I will now turn the call over to Eric for our financial results.

Thank you, Tim. On Slide 15, you will find our full year 2020 operating results, which are detailed in today's press release and regulatory filings. Operating income decreased by €28.1 million for the year ended December 31, 2020, compared to €54.5 million compared to €82.6 million for the year ended December 31, 2019. The decrease was due to the milestone payments we achieved in 2019 for the start of the first-in-human clinical trial under our AbbVie collaboration partly offset by revenue recognition of the transaction price related to the Janssen collaboration and the increase in other income. R&D expenses increased by €127.8 million for the year ended December 31, 2020, to €325.5 million compared to €197.7 million for the year ended December 31, 2019. The increase in 2020 resulted from higher external research and development expenses primarily related to our efgartigimod, cusatuzumab and other clinical and technical programs. Furthermore, the personnel expenses increased due to the increased head count as planned. SG&A expenses totaled €149.4 million for the year ending December 31, 2020, compared to €64.6 million for the year ended December 31, 2019. The increase primarily resulted from higher personnel expenses and consulting fees related to the preparation of a possible future commercialization of efgartigimod. For the year ended December 31, 2020, financial expenses amounted to €1.4 million compared to a financial income of €14.3 million for the year ended December 31, 2019. Financial expenses correspond mainly to the decrease in net asset value of money market funds following the impact of the COVID-19 outbreak on the financial markets. Based on our current operating plans, we expect our cash burn rate to increase significantly in 2021, approximately doubling compared to 2020. This will support our transition to an integrated immunology company, including the build-out of global infrastructure and -- product inventory ahead of our first expected commercial launch, the advancement of our clinical stage pipeline and our continued investment in the Immunology Innovation Program. I will now turn the call over to Keith to discuss our commercial preparations in more detail. Keith?

Thank you, Eric. Slide 16. I would first like to take a moment to highlight an important event for the MG community that occurred over this past weekend, Rare Disease Day. Its purpose is to raise awareness of the challenges that the rare disease community faces each day and to demonstrate our solidarity alongside them, including people living with MG. We at argenx are united by our common purpose to pursue a better tomorrow alongside the MG community. We know that the best way we can do this is by listening and learning. We hear directly about the significant unmet need that still exists, the symptoms, treatment burden, strain on relationships and mental health and struggles these patients face just to manage day-to-day activities. These stories motivate us every day in the work that we do. Slide 17. With this in mind, we are very excited to hear from the FDA this week that our BLA has been accepted for review we are now working towards a PDUFA date of December 17, 2021, and I can assure you that we are working hard to be ready for a potential commercial launch well ahead of that time. We have been building out our commercial capabilities and personnel for almost two years, and we know what we have to do to prepare in these next several months. We also announced the opening of our preapproval access program this week. We have been getting requests for efgartigimod from physicians, and we want to accommodate them, where possible, as part of our commitment to MG patients and their supporters. We also want to honor our commitment to the patients that participated in our global registration trial to keep them on therapy as long as possible. More than 75% of patients who entered our open-label extension are still on study, some for over two years now. Slide 18. With the acceptance of our BLA, the clock has started, and we are accelerating preparation across multiple fronts, building out our field team, including the sales force, engaging with patients, physicians and payers and ensuring appropriate physicians and payers and ensuring appropriate commercial drug supply at the time of launch. Let's start with our team. We now have over 100 colleagues working out of the Boston office or in the U.S. field, including medical research liaisons, thought leader liaisons and reimbursement account directors. We have launched a hiring process of our sales force with the plan of being fully staffed at least four months prior to the anticipated launch. Based on the interest and experience level we are seeing from candidates, we are confident we will have the right team in place. Moving to our patients. We launched several patient-centric efforts last year, including MG United, which is our digital platform to engage with the MG community and provide clear credible information. We now have over 20,000 patients and caregivers who have opted to receive information from us on MG. We also launched a real-world evidence study, MyRealWorld MG, where we have over 1,000 participants enrolled. We collaborated with global patient advocacy groups in launching the study with a goal to better quantify the real-world burden of MG, including hospital visits, loss of productivity, direct and indirect medical costs, treatment side effects and psychological implications. Moving to our physician education and engagement efforts, which we are rolling out through disease state awareness campaigns and CME programs, this will be critical to our launch success because FcRn as a target in MG is not yet well understood. Specifically, details on our multichannel approach include: the launch of our disease state awareness campaign called gMG cycle. The purpose of this campaign is to educate health care professionals on the role of the antibody in MG and on FcRn as an integral pathway to disease. We have had significant engagement from this campaign, reaching 62% of the target physician audience to date. We are also planning peer-to-peer marketing programs to start once we launch. We have been learning from our peers who have had precedent launches in a COVID environment, and they emphasize the growing importance of this channel. Physicians are faced with new challenges, treating patients virtually. And because of this, there's an increasing reliance on input from peers and neurology thought leaders for new treatment considerations. In planning for our various launch scenarios, we are also using market research to learn more about physician preferences and to tailor our engagement approach. With our December PDUFA date, we may have the option to offer both virtual and in-person engagement with health care professionals because even in a post-COVID environment, we know that not one size fits all. efgartigimod being a first-in-class FcRn antagonist, which means we have the opportunity to be a thought leader to the health care community on this new modality, but it also means we may face a more gradual uptake as our education efforts take effect. In terms of payers, we continue to have valuable discussions with both national and regional payers. We know that at launch, we will not have a permanent J-code and that payers will not have a dedicated policy in place for efgartigimod. We are working on building out the patient support system to help patients and providers navigate the complexities of the reimbursement environment. We still know that early in the launch, reimbursement challenges will be a potential hurdle to adoption. We have a strong manufacturing strategy in place with our best-in-class partner, Lonza, we currently have facilities in the U.K. and Singapore and have plans to open a third site in the future to accommodate growth from our planned expansion into new territories and indications. In addition, we have partnered with -- for fill and finish and Cardinal Health for third party logistics. We recognized ahead of the global pandemic that ramping up supply chain efforts would be prudent given the broad potential of efgartigimod and our plans to open a preapproval access program. We are glad that we did so, particular as we've seen continued pressure on the global supply chain in supporting the vaccination campaign. We are in full preparation mode for our launch, and we plan to use every day that we have to further engage with our stakeholders and build out our inventory. On Slide 19, before I hand the call back to Tim, I would like to reemphasize the point that we made earlier on the call. MG is just the beginning. We are building a solid foundation, which we can leverage across indications and molecules in the future. This will allow us to benefit from certain economies of scale as the resources we are investing in today and relationships we are building now will be advantageous for the rest of our pipeline and in the long term. With that, I will now turn the call back over to Tim. Tim?

Thanks, Keith. Turning to Slide 20. In summary, 2020 has been an outstanding year for argenx, and we look forward to building on our accomplishments in 2021. We are proud of what we have achieved, including the acceptance of our BLA for efgartigimod in MG; demonstrated proof-of-concepts in four indications; and an ambitious global development plan for efgartigimod; a second autoimmune asset from which we will show the first set of clinical data this year; continued expansion of our differentiated pipeline through our IIP; and our team, which continues to grow across our four global offices to support our success. 2021 stands to be another pivotal year for the Company and we are strongly positioned to create long-term shareholder value. As we continue to grow, we aim to stay true to what makes us argenx. We are firmly rooted in groundbreaking immunology research, which enables us to innovate. We are committed to growing through co-creation because diverse opinions and experience challenge us to do better. And our patients humble us and are at the core of all we do. With that, I would like now to hand back the call to the operator to begin the Q&A.

We will now begin the question-and-answer session. [Operator Instructions] The first question comes from Yaron Werber of Cowen. Please go ahead.

This is Brendan on for you Ron. Thanks very much for taking the question and congrats again on a great quarter and on great progress. Just a couple of quick ones from us, I guess the first on ITP. The study is ongoing here. Can you just give us kind of a quick update on your thinking for the expected treatment regimen? Obviously, the two Phase III support registration from both, but are you kind of thinking of induction dosing with IV and then transitioning to subcu? And do you think any additional studies would be required for that? And then I think just quickly on AML, can you give us a sense of where you're thinking the bar is for improvement with the triple -- the combo treatment over the double that would kind of encourage you to expand development?

Thank you, Brendan. Thank you for joining us today. I'm going to hand over question number one to my colleagues, Keith. Just for clarification, we streamlined the Phase III global registration campaign to now run an IV-only study next to a subcu only study. Remember the two -- which we did last year and full quarter time. So these two studies together, I think, have the right to qualify for registration. Keith, can I invite you to comment on our views on the treatment regimen, which we have in mind, please?

Sure, happy to do so, Tim. The subcu study that we're running in ITP is utilizing the halozyme-enabled subcu. So it is the same dose that we use in the CIDP trial. And remember that 1,000 milligram flat dose is non-inferior to 10-milligram per kilogram IV. So there's no induction dose needed. The one trial was pure IV with 10 milligram per kilogram, and the other one is subcu with 1,000 milligram flat dose. So we expect both of them to be able to stand alone and be registration-enabling.

Thank you, Keith. And then on the AML question. I think there's a firm new -- by the VALE study. I think the study tested the combination of venetoclax and azacitidine. And what we saw was approximately 37% CR rate with 66.7% cumulative CR rates and an overall survival going up to 15 months. So we believe this is the new standard of care in the newly diagnosed elderly AML population, which is unfit for intensive chemotherapy and bone marrow transplant. So this is the part to beat. And of course, the other dimension, which is important in this study, is safety, can we safely add cusatuzumab on top of a combination of two drugs which, of course, come with some significant safety burden for the patient. Thank you.

The next question comes from David Nierengarten of Wedbush. Please go ahead.

I had a question. Now that you have additional experience, growing experience with patients on the open-label extension, could you describe the number of treatment cycles that you're beginning to see in some of the patients who have been treated the longest? Thank you.

David, you're right. I mean as Keith alluded to, more than 75% of the patients are still in the open-label extension study, which I think is very exciting. And we start to see the shaping of what is likely going to be the real-world distribution of the dosing cadence. So in the first portion of the open-label extension, we have patients which still followed the mandatory cycles of the ADAPT study with the ability to taper background medication, and in the second portion that we alluded to, the hands -- and we can see the real-world utilization of the product. It's too early to comment on what we've seen, but we are planning on regular updates at clinical conferences and at the open-label extension study. So stay tuned. Information is on its way this year.

The next question comes from Matthew Harrison of Morgan Stanley. Please go ahead.

This is Max Skor on for Matthew. Thank you for taking our questions. We were wondering if the FDA provided any rationale with a standard review in their letter. And do you expect the agency to hold an advisory committee meeting? Thank you.

Max, good to hear from you, thanks for joining us today. So no, we can only guess what the modification was of the FDA. However, if you look at the overall landscape, I think it's fair to say that this is a reasonable outcome of an FDA, which is, of course, heavily burdened and focused on the COVID pandemic. I think in the letter the FDA states that they're currently not planning on a panel, which we think is encouraging. Of course, the FDA will always reserve the right to organize the panel each and when they deem necessary during the review of the file. So, so far, so good, but we stay cautiously optimistic. Thank you.

The next question comes from Tazeen Ahmad of Bank of America. Please go ahead.

Tim, just wanted to ask you, just given on the back of your announcement that you will be moving forward with CIDP, we saw that a competitor, UCB, decided to discontinue their program. So obviously, it's good in the sense that there is less competition imminently. Are there any other obvious conclusions to come to with their decision to discontinue their program in terms of superior profile of your product perhaps to theirs?

Thank you, Tazeen. Thanks for joining us today. Look, I believe that in their press release or earnings call, UCB alluded to the fact that they would disclose the data of the Phase II CIDP trial later this year. So that's something which we will be eagerly awaiting. You know that we like to study data and make data-based decisions. Now first of all, I think both molecules are, of course, fundamentally different. I think there's a distinctly different design, molecular design between efgartigimod and the full-sized high -- monoclonal antibody. But we also believe that our innovative study design really contributed to a strong positive GO decision in our case. So we're confident in our data. We're confident in the path forward, and of course, we're going to study the data if and when they become available.

The next question comes from Danielle Brill of Raymond James. Please go ahead.

Can you just remind us what is required in terms of data for subcu filing? Beyond showing PK/PD equivalent what types of data are gating, any long-term safety requirements or that sort of thing? Thank you.

Hi, Danielle, thanks for joining us today. I think this forum, and as you can see from the disclosure today, primary endpoint is taken on day 29, and that constitutes a percentage of IgG reduction at that point in time. So that's relatively straightforward. The getting data, of course, from a timing point of view, will be the safety data. What we have been saying publicly there is that you know, we were quite pleased with the outcome, with the expectations of the FDA on the size and magnitude of the safety database, but we have not given any further detail there. So stay tuned, but that is maybe news we will disclose later.

The next question comes from Graig Suvannavejh of Goldman Sachs. Please go ahead.

Good morning. Good afternoon. Thanks for taking my question. If I could maybe squeeze in two; the first, maybe this is for Keith. Keith, I think, on the last call, you seem to be walking down launch expectations. And I just wanted to get a sense of where you are in the process of building awareness for efgartigimod. You clearly walked through the different initiatives that you've got going. But maybe to use a baseball analogy, like what inning do you think that organically in terms of building up awareness for not only the FcRn mechanism of action but also for efgartigimod itself? And then maybe a second question is maybe for Eric, if I could ask a financial question. But given the doubling of cash burn expected this year, could you perhaps provide some comments around is that equally distributed between R&D and SG&A? Is that more heavily weighted towards R&D, given that you've got so many late-stage trials that are ongoing? And in terms of CapEx, what should the expectation be for 2021 relative to 2020?

Great, Graig. Thank you for the question. And what I want you to first know that my overall view on efgartigimod in treating MG patients has not wavered. We believe that of the 65,000 patients in the U.S., 20,000 of them will be appropriate patients for efgartigimod. But what we do believe, and I've said, is a gradual, steady launch and the reason being is this is a first-in-class mechanism of action. And this is a mechanism of action that really has been -- hasn't been taught in medical school, and so many of the physicians that treat MG were not previously familiar with FcRn. So we've got a great deal of health care professional education to do. I think that we also look at this happening during COVID times, where a lot of the education was taking place virtually. I'm actually quite encouraged with our PDUFA date that we may have the opportunity to launch, as I said in the prepared statements, not only virtually but also in-person. So I think that benefits our ability to be able to get this message across. It's also going to benefit patients being able to see their physician in-person because, as we spoke the last time, so many of these calls are taking -- so many of these appointments are taking place via telemedicine with physicians. So look, remember, at the beginning, we will not have a J code. There will not be policies in place at most of the payers. And so this will take a little bit of time as far as what inning for your baseball analogy. All I can say is that I think we feel pretty fortunate that J code is no longer something that you apply for once a year, and now you can on a quarterly basis. And so I'd expect this to be really hitting our groove here sometime in towards that six to seven months when we get that J code. Eric?

Yes. So with regard to your question on the distribution between R&D and SG&A and commercial expenses, clearly, in 2021, we will continue to see a step increase in R&D expenses. We're going to have seven treatment trials and then. So clearly, I mean, this is going to be impacting directly the operational expenses. And obviously, with the preparation of the launch, commercial expenses also are going to increase significantly. What we gave as an indication in the burn rate for 2021 is going to double compared to last year. So last year, we had the rate of about $400 million. So we could expect something around $800 million for this year. In terms of capital expenditure, this is not going to be important, and we don't plan to invest a lot in CapEx. What we're going to have [indiscernible] on the balance sheet is inventory for efgartigimod. Already at the end of 2020, we have an amount of $20 million, and this is going to increase significantly as we prepare the launch of efgartigimod.

The next question comes from Yatin Suneja of Guggenheim. Please go ahead.

This is Eddie on for Yatin. Thanks for taking my question and congrats on the year. Can you give us your thoughts on the lipid changes that we're seeing with one of your competitors? And if it's possible if the FDA might require some sort of monitoring for that class? And did you provide any data to them to, like, convince them that you're confident that you won't need any monitoring? And then just quickly for the pre-approval access program that you just initiated, can you give us a sense of how many patients you expect to be on that by the time you launch commercially? Thanks.

Thank you for the question. So I'm going to get the question to my colleague, Keith. But let me start with the first one. Let me repeat that with all FcRn antagonists are made equal. I think they have distinctly different molecular designs. The face of an antibody FcRn complex is fundamentally different as we have published, and we also see an emerging differentiated clinical profile between the molecules. So in our BLA file, there's an extensive data set discussing all these parameters in detail and the FDA will be able to look at the data and make data-based observations and Q&A. We do not think this is a class effect. We also did not get any specific comment or question on that so far. So let it continue to be a data-based conversation, but we are confident in our own data set. Keith, would you mind taking question number two on number of patients?

Sure. I'm happy to. We're really excited to announce our preapproval access program because we have been getting requests from physicians if they could get access to efgartigimod to treat their MG patients. So we're really pleased to be able to do so. At this point, we have set aside a certain amount of clinical supply to be able to treat those patients. But for me to speculate with an actual number of what I think the number of patients we will enroll between now and the PDUFA date, it would be a guess. So that wouldn't really be valuable to you. The one thing that I do want to call out is this preapproval access program is for patients in the U.S. and also in Europe. So we're really excited for the patient who will be able to benefit from efgartigimod.

The next question comes from Akash Tewari of Wolfe Research. Please go ahead.

This is Amy Li on for Akash. So first, on the MG launch, how much interests have you gotten in your preapproval program? And how quickly can you convert these patients on top of any patient currently in your open-label extension trial to commercial patients upon approval? And then another one, just wanted to hear your thoughts on the kidney disease market for anti-FcRns, specifically in conditions like ANCA-associated renal vasculitis, where we see a relatively large patient pool. The disease is predominantly IgG autoantibody-driven, and we've seen recently promising efficacy data from complement inhibitors. And then finally, would love to hear the current in-house take on what's causing the albumin drop in competitors? And if immune advanced LDL increases are due to albumin drops, are specific to thyroid eye disease or if there's another reason? Thank you so much.

Thank you, Amy. And Keith, why don't you take question number one on the preapproved program, and then I will continue with the question on kidney opportunities and the albumin story, okay.

Happy to do so, Tim. So first of all, this week is the first time we've actually gone public with the preapproval access program. I can tell you that the request that we have had over -- in the past have been from physicians that most of them participated in our trials because they're the ones that are educated about the FcRn and the mechanism of action and how efgartigimod really works as well as they have -- some of them have seen firsthand experience of how efgartigimod has benefited their patients. Now since we put this out publicly, and I can tell you that the patient advocacy organizations are aware of this program that the increase of the number of physicians reaching out to us has gone up, but we're in early days here. So again, I don't want to make any projections but there definitely is an unmet medical need in MG, and our ADAPT trial data has been pretty impressive. So, I expect to get quite a bit of attention towards this. Thank you.

I think with regards to opportunity, we believe there's a vast opportunity in front of efgartigimod. So, we continue to talk about at least 10 to 15 high-conviction indications, high conviction meaning, solid biology rationale -- feasibility running clinical trials and registration trials based on known clinical endpoints and approvable endpoints and then, of course, a substantial commercial opportunity. So, we're not going to comment yet on where we think the indication sits in the priority list. We will be disclosing fifth and sixth indications for efgartigimod this year. And you also remember that in the Zai Lab collaboration, Zai is now going to join us in adding new indications in an accelerated fashion. So you will see the strategy going forward on how we have been prioritizing indications. But I agree with you that it's substantial opportunity, including in the kidney area. On the albumin drops and we have consistently told you that we do not see any drops in serum albumin we have also published that. And we have also in our Phase I manuscript disclosed an experiment where you can clearly see under the microscope and infectious experiment that efgartigimod is mainly deciding in the recycling endosome in the recycling loop and is able to leave the cells to exit the cells. So, efgartigimod is basically mimicking wild-type IgGs through the citing pathway and is, therefore, not fundamentally impacting the face of FcRn or driving FcRn into the lysosome. But that explains, we believe, why serum albumin levels are intact upon dosing even the high doses of efgartigimod. That is fundamentally different, I believe, from the high-affinity monoclonal antibodies. And look at the cholesterol data and only correlate to the indication of [indiscernible] being aggregated by drops in serum albumin, as seen by some of the competitors, but that remains to be seen. We need to wait for that data. And when we remind the literature, you will see that serum albumin levels inversely correlated cholesterol levels. I mean, albumin is a very important carrier for many things, including cholesterol. So, there could be a combination of both forces, both factors here. But let's wait for the data before we make further comments on that. Thank you

The next question comes from Lenny Van Steenhuyse of KBC Securities.

Some questions as well on the pre-approval access program, which is, of course, great news for patients and an opportunity to also invest in market share by sponsoring therapy before the official starting on as fired. I was just wondering if there's a material cost as well related to the [indiscernible] given the fact that it will likely run for roughly nine months in the U.S. and likely longer in Europe? Thank you.

Keith, could you take this question, please?

Yes. In regard to the -- we are working with a corporate partner, Clinigen, to be able to run this program. So, our material costs are involved with the contract that we have with Clinigen and them handling this as well as the cost of goods sold. So, yes, it's nine months, but in the long run, this is a commitment to patients that we think is the right thing to do for them.

The next question comes from Yanan Zhu of Wells Fargo. Please go ahead.

Thanks for taking my question. It's mainly related to the pemphigus program. In the Phase III IV study, the population is moderate to severe, which is different from the mild to moderate population in Phase II, I believe. So could you comment on what have contributed to the change in the patient population in Phase III? And also, what about the IV dose, I don't think you have disclosed that will be used in the Phase III study and whether that could be compatible with future subcutaneous strategy? Thank you.

Thank you, Yanan. So you're right, the Phase III trial for pemphigus is done with the subcu product. Patients in the patient panels were very excited about the ability to access subcu products for treating pemphigus. You're also right in observing that the patient population is brought in the Phase III. We aim for a broad label. It's a moderate to severe patient population. It's the bulk of the patients. That definition has shifted a little bit. If you look at the [PPI] cutoffs to define what is mild, what is moderate, what is severe, actually, in our Phase II study, we have patients which you would qualify today has actually severe pemphigus patients. So the patient populations overlap to a certain degree. And based on the PD efficacy data we have seen, we feel confidence that efgartigimod will be able to make a difference in this broader patient population.

The next question comes from Alex Cogut of Kempen. Please go ahead.

I have a question about your PIP indication. If I look on the slide where you -- there's two opportunities, it looks like there are just a handful of indications that would fit number five. So I think the question is, will you keep with the strategy you're going for orphan indications? Or does it mean that it could also be a larger indication?

Keith, would you mind commenting on that question for open versus larger?

Yes. I would say, at this time, we continue on our path, which was our strategic plan that we -- when we select indication, it's based on the biology rationale. That is the first hurdle that we need to get through, and we work on this with academic experts. And we have indeed, again, for this fifth indication to determine it as our target. We do like to work in orphan and rare disease. And so we continue down that path, and that is part of the plan. It's sticking to this formula that has allowed us to hit four for four on our proof of concept. And so we're going to stick with that plan. In the event that there comes a time later that we need to expand outside of rare disease and orphan, we will cross that bridge when we get there.

Got it. I guess the follow-up question is out of the bigger indications you have listed on the slides, which ones do you see the most compelling biology for?

Yes, some of them do have a relatively compelling biology. And I would be also very careful it's concluding that it's going to be open versus big indications. So some of these larger indications, which we list on the slide, you will probably find the slide, you will probably find subtypes of the subsegments of patients where the pathogenic IgG is really driving the disease, for example, in [indiscernible] that could clearly be the case. So if and then we would address larger indications, potentially, the real target patient population would still qualify as orphan. So let's -- the bridge when we're there. There's plenty of work on the table in this space, which Keith just described.

The next question comes from Douglas Tsao of H.C. Wainwright. Please go ahead.

I'm just curious in terms of the early sort of experience from the trials and, obviously, from the early access program that's been a little challenging. But just in terms of educating physicians about the SRM mechanism, and efgartigimod as a therapy, are there any particular challenges? Or is it in terms of the actual therapy in terms of establishing dosing, monitoring patients? Was it really just about understanding, how the mechanism works in the treatment?

Keith, would you mind taking this question, please?

Yes, happy to, Tim. Actually, when you look at the mechanism of action for efgartigimod and explain what it's actually doing, that it's fairly simplistic to understand and how that effect of the auto antibody at the neuromuscular junction and the fact that we're removing it, which is why you're seeing the clinical efficacy. So that part, I don't view as big of a hurdle. When I talk about the education of health care professionals, it's because of the fact that we cannot speak about the mechanism of action, except when we're in market research or in some type of a congress, we can't go out and speak about it at this time because that would be perceived as pre promotion. So that's why I talk about our overall success in MG I feel very good about. It's the gradual uptake because that's when we can begin the education. I can tell you that when we've done this in advisory boards, we can start at the beginning of the day, and there is an interest to learn about it. And by the end of the day, there's an enthusiasm of what this therapy could mean to MG patients. So it's really a testing these physicians with the right message.

And then I guess, just more broadly, I'm just curious in terms of -- obviously, you between 117 and [indiscernible] launch, you have a really strong franchise in neuromuscular. I'm just curious, are there other mechanisms that you're looking into either for internal development or development programs for potentially through business development to bring into the Company.

Yes. We already disclosed that ARGX-119 is neuromuscular efforts. It fits clearly into the neuromuscular franchise, which we're building. And yes, we are, of course, also looking to the outside world for complementary mechanism of action molecules, which could actually fit very nicely. Although I must say that we're pretty busy developing our own innovation from the IIP program, the Immunology Innovation Program that proves to be a very rich hunting ground for opportunity, but that being said, we are looking holistically at building out a viable long-term neuromuscular franchise.

The last question will come from Rosie Turner of Barclays. Please go ahead.

Yes, just one last for me. So in the presentation and in the release this morning, you mentioned that Zai Labs are going to be [indiscernible] accelerated approval in China. And I just wondered what this actually could mean in terms of timing kind of your base case assumption for launch over in China. So, we've got some pretty and chunky royalties over there. Thank you.

I would like to comment on that question later in the year because, frankly speaking, there are two possible scenarios. So, there would be a practical scenario. But on the back of a BLA approval, you would basically have to do a small PK study in order them to file for approval in China. That is a potential faster path where actually would stick that PK study. And actually, you could go straight into registration. One of the many, many reasons why we did partner with Zai Lab is because of the pool in traffic in navigating the regulatory landscape in China, but I'll leave that to Zai Lab to comment on that. I think we need to navigate it step by step and, we will keep you informed, okay.

This concludes our question-and-answer session and the argenx full year and fourth quarter 2020 financial results conference call. Thank you for attending today's presentation. You may now disconnect.

Goodbye.