Earnings Call Transcript - ARGX Q4 2022

Operator, Operator

Good morning. My name is Rob, and I will be your conference operator today. 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. Thank you. I'd like to introduce Beth DelGiacco, Vice President of Corporate Communications and Investor Relations. You may now begin your conference.

Beth DelGiacco, Vice President of Corporate Communications and Investor Relations

Thank you, operator. A press release was issued earlier today with our full year 2022 financial results and the 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 developments, regulatory timelines, the potential success of our product candidates, financial projections, and upcoming milestones. Actual results may differ materially from those indicated by these statements. argenx is not under any obligation to update statements regarding the future or to conform those statements in relation to actual results unless required by law. I'm joined on the call today by Tim Van Hauwermeiren, Chief Executive Officer; Karl Gubitz, Chief Financial Officer; and Keith Woods, Chief Operating Officer. I will now turn the call over to Tim.

Tim Van Hauwermeiren, CEO

Thank you, Beth, and welcome, everyone. Reflecting on 2022, it was a year of many achievements for argenx as we evolved from an R&D organization into a fully integrated R&D and commercial organization. We launched our first-in-class FcRn blocker VYVGART in the U.S., Japan, and Germany and exceeded our own expectations, generating $401 million in global net product revenue. I'm very proud of the team for the strategy they built and executed, solidifying our reputation with our key stakeholders. With this significant momentum, we start 2023 in a position of strength. We also have our marching orders in hand for multi-dimensional expansion to reach more patients with VYVGART through anticipated regulatory approvals and launches in new regions and by driving usage earlier in the gMG treatment paradigm. This year, we also generated a significant amount of data on our first-in-class FcRn blockers through clinical trial readouts, installation research, and peer-reviewed publications. We reported data from our subcutaneous bridging study in gMG, which demonstrated non-inferiority to the IV, based on IgG lowering, as well as consistency across secondary efficacy endpoints and safety. We have now filed for approval with the FDA, EMA, and PMDA and have a PDUFA target action date in the U.S. of June 20, 2023. We received a communication from the FDA in January notifying a three-month clock extension. Since that time, the FDA's review continues and we are engaging regularly with the agency, being responsive to inquiries as we advance towards an anticipated approval. We reported ITP data from our first registration trial last May and presented these data during a planned session at ASH in December, which triggered significant interest from the hematology community. We are preparing to submit an MAA in Japan in the middle of this year for approval based on the first advanced trial and will await the data readout of advanced subcutaneous in the second half of this year to support filing in the U.S. and Europe. Across all of our efgartigimod studies, we also generated significant data in 2022 to broaden the scope of our safety database, which now includes more than 3,000 commercial patients globally, more than 1,300 clinical subjects, up to 19 cycles of intermittent cyclic dosing, and more than two years of weekly chronic dosing, all with a cumulative exposure of more than 1,000 patient years. Lastly, before we look ahead to 2023, I want to call out a strong sign that continues to serve as a cornerstone of argenx, solidifying our leadership in FcRn as both the first-in-class and likely best-in-class therapy. Our teams are committed to building a deep repertoire of preclinical and translational data, which can serve as an important basis for indication selection or to underscore the clinical or commercial data we are generating. We had several key publications in 2022, including on the long-term remission fee observed in autoimmune diseases and the underlying reduction of autoreactive B-cells, the differentiation of our Fc fragment and its intracellular phase keeping FcRn in its recycling path without interfering with albumin homeostasis, review of the humoral immune response to vaccines during treatment, and multiple publications and presentations on the health economic outcomes front highlighting the value that this drug can bring to gMG patients from a quality of life perspective. We are well on our way to achieving the argenx 2025 vision, which we laid out a couple of years ago. Specifically, we are now reaching patients with VYVGART globally, evaluating efgartigimod in 13 severe autoimmune indications, preparing for the first clinical efficacy data from ARGX-117, our next pipeline product candidate, and we are investing in our ecosystem of innovation. We have an impressive track record for molecules that have emerged from our immunology innovation program, both within our pipeline and those with our partners. Beyond efgartigimod and ARGX-117, some of these include ARGX-119, an agonist to muscle-specific kinase, which we dosed the first subject last month, our third pipeline candidate is now in clinical stage, Cusatuzumab targeting CD70, which led to forming Oncoverity with the University of Colorado last year based on the translational work of Dr. Clayton Smith on the CD27/CD70 pathway, which when combined with our clinical studies provides a robust data set. ARGX-112, targeting IL-22 receptor in development by LEO Pharma and moving forward in development. ARGX-115, targeting GARP development by AbbVie, which is also advancing. We have a very busy year ahead as we make further progress on our path as an integrated immunology company. We continue to expect top line data from the ADHERE trial of efgartigimod in CIDP in the second quarter of 2023. There remains a significant unmet need for CIDP patients for a safe, effective therapy with a manageable dosing schedule and delivery. With ADHERE, we hope to address these needs and demonstrate the potential for efgartigimod to provide patients with a differentiated therapeutic profile across efficacy, safety, and convenience measures. In addition to the advanced subcutaneous readout in the second half of this year, we also expect pivotal data from the ADDRESS trial for pemphigus, where we hope to see efficacy data that builds on the exciting results from Phase II, a fast onset of action driving patients into disease control and ultimately complete remission, with the ability to taper to a minimal dose of steroids. We will have our first group of concept data in post-COVID POTS in the fourth quarter of 2023. This was an indication that was brought to us, particularly with the growing incidence in the wake of COVID. Physicians report that IVIg and other therapies have shown promise, and we know that anti-adrenergic and antinuclear antibodies are involved in disease pathophysiology. All of this is a strong rationale for evaluating efgartigimod in what could be a very sizable indication. Finally, we're also planning for the first clinical efficacy data from ARGX-117 in patients with multifocal motor neuropathy. IVIG is the only treatment option for MMN, and it comprises a significant proportion of that market. With our interim analysis in the middle of this year, we will have data from the first cohort of nine patients. Our main goal is to determine whether to advance to a second larger cohort and at which dose. We continue to produce translational data supporting the pathological role of IgG autoantibodies in MMN and the rationale for a C2 inhibitor as a new treatment modality. Before I turn the call to Karl, I want to spend a few minutes on the leadership transition we announced today with the planned retirement of Keith. We are very excited to welcome Karen Massey to the team as our Chief Operating Officer as of March 13, 2023. She is a very talented and inspirational leader with significant operational and commercial experience. She's joining us from Genentech Roche, where for the last three years, she had a global clinical operations team of over 2,000 people. She has broad commercial experience, including specific experience within the neuroinflammation space, having launched first-in-class medicines that disrupted the treatment paradigm. I was very impressed to hear about her role with Ocrevus launch, taking an already successful launch and accelerating it in a crowded market. Beyond this remarkable achievement, the quality that most caught my attention is her focus on building teams, creating a company culture and community, and designing a nimble, global, innovative organization, all of which will benefit argenx. I would also like to share my gratitude to Keith for his partnership and his friendship. He is a visionary leader with a patient-first mindset. We are so fortunate for the role he has played in our growth over the last five plus years of his distinguished career in biopharma. He joined argenx after the release of promising data when he convinced me that argenx could launch efgartigimod. He saw a vision for argenx commercially not only in the U.S. but also in Japan, Europe, and Canada. I could never have imagined at that time the impact it could have on patients, even in the first year of launch. He was committed throughout our search process to find the right person to fill his role. I knew I could count on him to stay until we all agreed we had the right successor, and we are both very confident we have that in Karen. We are also fortunate he will be staying with the company not only during the transition period, through the SC efgartigimod launch, but also after he retires. He will transition to serve as a Board adviser on our commercial committee and will continue to make a significant impact on our commercial strategy and for our patients. With that, I will turn the call to Karl.

Karl Gubitz, CFO

Thank you, Tim. Our full year 2022 results are detailed in our press release from this morning. So I will keep this section of the call short. On the next slide, you will find global net VYVGART revenues for the fourth quarter and the full year 2022. We generated $401 million in global net product revenues in 2022 and $173 million in the fourth quarter, specifically which was comprised of $159.1 million from the U.S., $8.3 million from Japan, and $6 million from Europe and the other distributor markets. Total revenues for the full year 2022 were $445.3 million, which also includes $10 million in collaboration revenues and $34.5 million in other operating income. Cost of sales for the year were $29.4 million. Our total R&D and SG&A expenses for the full year 2022 were approximately $663 million and $472 million, respectively, and can mainly be attributed to efgartigimod and other pipeline research expenses, as well as marketing and headcount expenses related to our global launch. The research and development expenses include the recognition of a priority review voucher submitted with the BLA filing for SC efgartigimod. We ended the year with $2.2 billion in cash, cash equivalents and current financial assets. Based on your current operating plans and a projected 2023 cash burn of approximately $500 million, we expect our existing cash, cash equivalents and current financial assets, together with anticipated future product revenues to fund the company to profitability. You can find additional details on these numbers in the press release we issued this morning. Before I turn the call over to Keith, I would also like to share my gratitude. Under his leadership, we were ready to launch VYVGART, and it has been a very successful first year, both with our performance and also seeing the team of leaders that Keith has built across the commercial organization. I am confident that Karen is the right person to build on this momentum and lead us to the next stage of our growth as a global company.

Keith Woods, COO

Thank you, Karl, and thank you both for the kind words. While I'm very much looking forward to this next phase, spending more time with my family, and transitioning to an advisory role for argenx, it was still a difficult decision to make. The last five plus years have been the most rewarding of my career. Being able to build a commercial team and launch a truly transformative first-in-class medicine for patients. I am proud of the success we had in the first year and know that this is just the beginning for argenx and for patients, especially with Karen at the helm and the team of impressive leaders behind her. We closed out the first year of our VYVGART launch in a very strong position. We were able to reach more than 3,000 patients in 2022 with our transformative therapy, well beyond the expectations we set for ourselves at the beginning of the year. Our commercial and medical teams have done an outstanding job working hard every day on our path to redefine how autoimmune diseases are treated, and the work has just begun. First, on patients. We continue to see a steady demand from new VYVGART patients, both in new scripts and patients on therapy. We also see positive trends in moving earlier into the treatment paradigm. We still see approximately half the patients coming from IVIg as their most advanced therapy, but the dynamic is shifting in the other half, with more coming from earlier lines than refractory. We still continue to learn about our launch and the trends, but we are going in the direction that we want. We are seeing a similar positive trend with physicians. Increasing numbers of repeat prescribers and the growth in the number of physicians who have written greater than five or even greater than 10 prescriptions. Our field teams have reached more than 90% of their key targets and almost 8,000 healthcare professionals overall across targets and non-targets. Our medical affairs teams have had a significant presence at all major neurology conferences, broadly reaching the prescribing community. They also worked on more targeted engagement through scientific roadshows to reach the typically difficult-to-access institutions. The field teams were nimble throughout the year leaning in on tactics that worked well, which led to an overall successful year of physician engagement. Payer interactions also continue to be an area of strength for this launch. We ended the year with approximately 90% of commercial lives covered and almost 80% of these policies being favorable. The team is still successfully working to switch unfavorable policies to favorable, removing IVIg as a step-through, just as one example. The recertification dynamic does appear to exist as we are switching to a new year. But this is something we are watching closely. For the most part, re-approvals have been smooth, occurring every six to 12 months, which allows the physicians to redose as they see fit. We presented data last month on the time distribution between cycles one and two from over 4,000 VYVGART patients. As we saw in ADAPT and ADAPT+, it is a true distribution with 32% of patients receiving a second cycle less than six weeks after the conclusion of the first. On the other side, we also had 32% of patients receiving a second cycle greater than nine weeks after their last dose of their first cycle, the rest fall in the middle. Based on the data we see and the feedback we hear, individualized dosing is doing what it's supposed to do. Patients asked for this when we were designing our trial, and we're pleased to see that a substantial number of patients are benefiting from that decision. We are now looking ahead to the expected FDA approval of subcutaneous efgartigimod in June. The team is using the extra three months to refine our strategies and expand our opportunity to reach patients, both with IV infusion and subcutaneous administration. We're taking a similar early engagement approach with payers as we did with the IV launch, but we still expect several months where we won't have a published policy in place post-approval. Beyond subcutaneous approval, we also expect to drive VYVGART expansion geographically this year, with anticipated regulatory approvals in China, Canada, and additional launches in Europe as we work through price negotiations. Before I turn the call to Tim, I want to end with one VYVGART patient story from my trip to Japan earlier this year. I heard from a young mother who was really struggling when she learned that she had a chronic disease because she was feeling very socially isolated. She was not able to participate in family activities, play with her children, or pick them up to give them a hug. She had lost her job because she could not use the equipment to perform small manual tasks. VYVGART worked quickly for her, and within a week or two, she had restored more movement than she had in several years. Her gratitude was so rewarding. We shared her story more broadly with our teams to remind them of the impact that we can have. This is the motivation we are taking forward as we build on our momentum from 2022 and apply it to our successful strategies for the year ahead. Back to you, Tim.

Tim Van Hauwermeiren, CEO

Thanks, Keith. 2022 was a historic year for us. I will first see it as a commercial company and we are very happy with the outcomes. We build momentum across our key stakeholders with physician and patient demand and a smooth payer process. We know from precedence that the initial six months of the launch often defines the trajectory, and now we have our trajectory. We are looking forward to the rest of 2023, focusing on multidimensional expansion into new geographies, the anticipated launch of SC efgartigimod, and moving into earlier line gMG patients. We also see the opportunity to transform the treatment paradigm in many other autoimmune indications. As we look ahead to our upcoming data readouts in CIDP, ITP, and PV, and the first efficacy look at ARGX-117 and MMN. Thank you for your time today. I would now like to open the call to your questions.

Operator, Operator

And your first question today comes from Tazeen Ahmad from Bank of America. Your line is open.

Tazeen Ahmad, Analyst

Hi, guys. Good morning. Thanks for taking my questions. Keith, I want to wish you really well. It's been great to get to know you, and you've been an amazing head of commercial, and all companies deserve to have someone as good as you. Maybe my question will be on MMN for the interim read in mid-2023. What level of data should we be expecting to see at the top line? And what would you consider to be clinically meaningful? Thank you.

Tim Van Hauwermeiren, CEO

Thank you, Tazeen, and thank you for joining us in today's call. That's what we think will be the level of disclosure detail for the first nine patients.

Beth DelGiacco, Vice President of Corporate Communications and Investor Relations

Yes. So what we really want to see from those first nine patients is to understand early clinical activity but also what level of dose we want to take forward into that second cohort. We haven't specified what exactly we'll share, but that's really the goal of that first cohort and disclosure will be around that.

Tazeen Ahmad, Analyst

Okay. How many patients will that be again? Sorry, Beth.

Beth DelGiacco, Vice President of Corporate Communications and Investor Relations

Nine patients.

Tim Van Hauwermeiren, CEO

The way to think about it, Tazeen, is that all MMN patients today are on IVIg. So the way that the proof of concept is designed is that we first establish the dependency of these patients. We document their IVIg cycle and then switch either to placebo or ARGX-117 and see whether we can keep the patient stabilized compared to placebo. We think this first dose cohort should give us a very clear idea of whether the drug works and, more importantly, what level of C2 inhibition we need going forward.

Tazeen Ahmad, Analyst

Okay. Thank you, Tim.

Operator, Operator

Your next question comes from the line of Rajan Sharma from Goldman Sachs. Your line is open.

Rajan Sharma, Analyst

Hi. Thanks for the question. So I was just wondering if I could get your thoughts on kind of VYVGART’s trajectory this year. And whether kind of the slight delay to the PDUFA for the subcutaneous formulation has changed your expectations? Thanks.

Tim Van Hauwermeiren, CEO

Thank you for this question. Keith, do you want to run this one?

Keith Woods, COO

Very happy to do so, Tim. So first of all, the delay by three months in the PDUFA date for subcutaneous does change the fact that we were going to have two different opportunities to serve patients with two different formulations for nine months of the year. That only turns into six months of the year. As you know, we haven't given guidance at this time. And so, all I can say is that we believe that the trend that we're currently on will continue to allow for growth, and we believe that subcutaneous will expand the total potential market for patients that would receive VYVGART.

Operator, Operator

Your next question comes from the line of Thomas Smith from SVP Securities. Your line is open.

Thomas Smith, Analyst

Hey, guys. Good morning. Thanks for taking the questions, and let me add my well wishes to Keith on his transition and retirement. Just, I guess, one quick one on the subcutaneous PDUFA. It sounds like the dialogue here is pretty dynamic regarding the application. Can you comment on whether there's been, I guess, any area of particular focus for the FDA in the review? Whether there's been any unanticipated asks for further data?

Tim Van Hauwermeiren, CEO

I would say that the review continues at a good cadence. The way we would describe the ongoing Q&A is rather routine, standard. We get your typical questions in the review of the file. So no specific area to call out. So we believe in the strength of the data in our file, and we see continued good progress in the review of the file. So we're all hopeful for the June 20 PDUFA date.

Thomas Smith, Analyst

Okay, great. Thanks. And if I could just squeeze in one follow-up just on the commercial trajectory. If you could just comment on expectations, I guess, for Q1 relative to Q4? And how to think about combination of seasonality and kind of payer reset there would be very helpful. Thanks.

Tim Van Hauwermeiren, CEO

Keith, would you like to take this question, please?

Karl Gubitz, CFO

It's Karl here. For Q1, the launch is bringing in new patients and showing consistent growth. I want to highlight two aspects for Q1. First, we notice the effects of seasonality. When we lose a selling day due to a holiday or a winter storm, those sales do not get carried over to the next day, meaning we effectively lose those sales. Additionally, we are experiencing re-verification of benefits, which usually occurs in Q1.

Thomas Smith, Analyst

Understood. Thank you, guys.

Operator, Operator

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

Brendan Smith, Analyst

Hi, guys. This is Brendan on for Yaron. Thanks for taking the questions. First, quickly on CIDP. Can you maybe just tell us how many patients you have randomized into Stage B as of today? Is that something you're able to share with us? And then just looking back at the ICE and PAS studies, it looks like there may be some slight difference in the rate of relapse in treatment naive versus IVIg experienced patients. So are you able to give us a little bit of a sense of what the breakdown of patients enrolled in here thus far is looking like, just in terms of background therapy? Thanks.

Tim Van Hauwermeiren, CEO

Yes, Brendan, thanks for the question. So we're not public on the number of patients randomized in Stage B. I think what we said earlier is that we have exceeded the number you would normally need to successfully come to the trials. So all continues to progress well. In terms of representation of patients with the different backgrounds, being newly diagnosed on naive, being on steroids or being on IVIg, I believe the last disclosure we did is that we have about 40 patients in the process. We think there may be a relative increase in IVIg patients. It was the second half of the trial because we had more U.S. sites getting online and involved, but that's my speculation. From a biology point of view, looking at the mode of action of Cusatuzumab, I cannot think of the reason why an IVIg patient or a steroid patient would react differently to VYVGART’s mode of action. So let's wait for the data and see whether we can find any correlations.

Brendan Smith, Analyst

All right. Great. Thanks, guys.

Operator, Operator

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

Yatin Suneja, Analyst

Good morning, everyone. Keith, that's been great working with you. Good luck with your future endeavors. Just following up on a question on the CIDP. Could you provide some detail on the baseline and cap score that you showed or you might be expecting in Stage B? And the reason I ask is because, for the first 40 patients in ADHERE, the baseline was around five, which seems to be a little bit higher than in previous studies. And there seemed to be this inverse correlation between a high cap score and probability of relapsing. So just trying to get a sense of how the placebo might perform? Is there a particular score that you are looking for? And then the second part is like, what about the maximum number of patients that can be enrolled in Stage B? Thanks.

Tim Van Hauwermeiren, CEO

Thank you, Yatin. So on question 1, I need to wait for the answer also until we unblind the study and we look at the data. I have no further information above and beyond what was historically disclosed. It's also very difficult to compare apples with apples between the IV trials and the ADHERE trial. There is probably a difference in placebo response, but it's premature for us to comment on that. Let's wait until we unblind the data. Is there a limit to how many patients we can enroll in Phase B? No, there is no real limit beyond what we highlighted for enrollment. You can see that we basically stopped screening for the study, and we feel that we have a handful of patients that have now made it into the funnel. So, let's wait. This is a Q2 event as far as we can see today. Let's look at the unblinded data together soon. Thank you.

Yatin Suneja, Analyst

Very good. Thank you.

Operator, Operator

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

Myles Minter, Analyst

Hi. Thanks for taking the question. You mentioned you stopped screening the study for ADHERE. Is your screen-out rate during the independent investigator confirmation of the VYVGART score still around the 50% rate you presented at the last meeting? Has that been consistent with the patients you’ve been enrolling beyond the 120 to 130 range? Thanks.

Tim Van Hauwermeiren, CEO

Hi, Myles. Thanks for the question. My information is that the screening failure rate continues to be consistent, around 50%. It's also perfectly in line with earlier published studies looking at the accuracy of the CIDP diagnosis. So we feel it's in sync with the real world and think that it is constant throughout the study. Thank you for the question.

Myles Minter, Analyst

Thanks.

Operator, Operator

Your next question comes from the line of Manos Mastorakis from Deutsche Bank. Your line is open.

Manos Mastorakis, Analyst

Yes, hi. Thanks for taking my question. So I wanted to ask first of all in terms of the priority review voucher and the unwanted scenario of an FDA rejection. What happens to the priority voucher? Do you get it back? And maybe a quick follow-up on whether you have any data on the duration of the second cycle, that is patients going from second to third dose? Thank you.

Tim Van Hauwermeiren, CEO

Keith, would you mind starting with the second to third dose, the relative distribution we see in the real world? And then I will take on that question on the PRV.

Keith Woods, COO

Yes. So the data that I quoted in the prepared remarks are the first to second dose, and it really shows a nice distribution about a third, a third, a third. I want to call out that that interval is after the last dose of the first cycle. So when we have about a third of patients that are going nine weeks and some substantially longer than that just like we saw in the ADAPT trial. We haven't been public with any data on real-world findings between the second and third doses. But as you might recall from the past, we've referenced that from the ADAPT, OLE study, you can typically see that when a patient gets in their individualized cadence, so if they become accustomed to a nine-week interval between the last dose of one cycle and the first dose of the next one, that cadence typically holds standard. Once they get dialed in, it just becomes their regularly scheduled dosing. Although we haven't been public with something between the second and third, right now I'm not expecting a major change except for maybe some of those patients that went with shorter intervals to see if there isn't an opportunity to stretch a little further.

Tim Van Hauwermeiren, CEO

Thank you, Keith. And then on the PRV, we continue to understand our options, but technically speaking, we're still in a priority review, and we've decided to take a forward-looking approach with the FDA and try to collaborate as swiftly and expeditiously as possible toward the PDUFA date. Thank you for the question.

Operator, Operator

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

Alex Nackenoff, Analyst

Hey, guys. This is Alex on for Danielle. Just another one on CIDP. We had a few questions come our way. Just when did you decide to increase the enrollment? And what information, if any, did you have in hand that aided your decision to upsize, or was this just an organic strategic decision? Thanks.

Tim Van Hauwermeiren, CEO

Well, thank you for this question, Alex. There was not a distinct point in time where we decided to increase enrollment. We decided just not to stop enrollment and continue to enroll. The reason is that it would be a pity for those patients who all have an opportunity to come on drug not to do that, because not all of them, of course, are going to make it to the end of Stage B, but all of these patients would then have the opportunity to roll over to the open-label extension and also contribute to the safety database. Remember, in the background, not only do we need to build efficacy data but also strong files of evidence regarding safety. So it was a decision not to stop rather than a large history.

Alex Nackenoff, Analyst

Great. Thanks.

Operator, Operator

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

Allison Bratzel, Analyst

Hi, good morning. Thanks for taking my question. Just another one on ADHERE. It seems like a lot of focus has been placed on the relapse rate in Stage B. I guess, it's our understanding the endpoint is actually time to relapse rather than a percent of patients relapsing at a given time point. So my question is, what is the actual metric we should expect to see from Stage B? Is that going to be communicated as a hazard ratio median time to relapse something else? And just in that case, would you look to the hazard ratio from past as the best comparison? And then just related, will you have actual relapse rate data in time for the top line readout, just given that a bunch of patients may not have made it to the end of Stage B by the time the event has occurred? Thanks.

Tim Van Hauwermeiren, CEO

Thank you, Allison. Maybe Beth, you can take on what we expect in terms of top-level data disclosures. And then I can take the question on the comparison with past trials.

Beth DelGiacco, Vice President of Corporate Communications and Investor Relations

Yes, of course. So the primary endpoint, as you said, in Stage B is time to relapse. During our communication, we're committed to showing the primary endpoint of Part A, the response rate, and the primary endpoint of Part B, of course, with a view of safety. Beyond that, we're not ready to provide too much information on what that top line will look like. I think what you can expect is exactly what you've seen with ADAPT and ADVANCE in terms of transparency in our communication, and we will ensure that we give a complete picture of what we're seeing with those data to make sure that you understand them well.

Tim Van Hauwermeiren, CEO

Thank you, Beth. And you're absolutely correct, Allison. The primary endpoint for Stage B is time to relapse; it’s a typical endpoint in a cancer trial. Indeed, a hazard ratio would be a proper way to look at this data. We're still thinking about how we are going to present the top line data, but you should be able to draw a fair comparison with the prior trial in the way we present the data. So we're still rolling it over. In terms of separation between active and placebo, that continues to be the proper benchmark to match or to beat. Thank you.

Operator, Operator

Your next question comes from the line of Matthew Harrison from Morgan Stanley. Your line is open.

Matthew Harrison, Analyst

Great. Thanks for taking the question. I've asked the flavor of this question before, but I wanted to ask it again in a different way, which is, we're expecting to get some Phase 2 studies from J&J this year, especially some of the larger indications. How should we think about that impacting your view on what you may or may not be willing to invest in the pipeline and sort of how ready you are to potentially pivot quickly to think about investing in maybe a large Phase 3 study for some of these broad indications? Thanks very much.

Tim Van Hauwermeiren, CEO

Thanks, Matthew. Thanks for joining us today. I think overall it's exciting to see some other players in the class venture into other indications than the argenx indications because so far we saw mainly imitation and not too much creativity. So good to see new indications coming up where we feel there's a different proposition from a biological rationale point of view, and we'll actually be very happy to see other people delve into these indications. We have our own list of preferred indications, which we select based on biological rationale, technical feasibility, and then the lead medical lead and commercial opportunity. We're not going to deviate from our own list, which starts from the science and biology. Of course, we are keenly looking at other indications that are turning data cards. Overall, I believe they will show that the opportunity is a real big opportunity warranting multiple players active in the space. Thank you for your question.

Operator, Operator

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

Alex Thompson, Analyst

Hey, great. Thanks for taking my question. I guess, Keith, maybe on your commentary as it relates to real-world observations cycles on VYVGART. How should we think about net price per patient in 2023? Do you expect that to stay pretty constant as to what you have been guiding in 2022? Or how is that going to look moving forward, at least for the IV version? Thanks.

Karl Gubitz, CFO

It's Karl here. So we got it in the beginning of last year at a typical net price of $225,000. If we consider all the data points, the average wait per patient, the number of cycles, the gross to net, and the value-based agreements, we are taking all of those things into account. We think that the $225,000 per patient, those metrics will remain constant for 2023. Thank you for your question.

Operator, Operator

Your next question comes from the line of Will Olds from Evercore. Your line is open.

Will Olds, Analyst

Hey, guys. Congrats on the great quarter. I'm very curious about the technical difficulty.

Tim Van Hauwermeiren, CEO

I could not understand the question. Did anyone else understand it?

Beth DelGiacco, Vice President of Corporate Communications and Investor Relations

Yes, it's about thyroid eye disease and the positioning and the potential trial design.

Tim Van Hauwermeiren, CEO

Okay. So the only thing we have disclosed at the JPMorgan Conference is the choice for this indication. This is one indication where we're not leading; we will not be first to market. I think we've been speaking mainly about the biological rationale but we reserve the right to answer your question until we disclose the trial design, and then we can expand on competitive positioning, but it's a bit premature for us to comment on it right now. So bear with us; that will come later in the year. Thank you.

Operator, Operator

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

Joel Beatty, Analyst

Great. Thanks for taking the question. For the current FDA review of the subcutaneous formulation of Cusatuzumab, is there the potential to add seronegative patients to both subcutaneous and IV labels?

Tim Van Hauwermeiren, CEO

Thank you for this question. In the bridging study, remember, this was a head-to-head comparison of a non-inferiority trial between the IV version of VYVGART and the subcutaneous product presentation of VYVGART. We basically included both seropositive and seronegative patients. VYVGART has shown that it works equally well across the board in a non-inferior manner between subcutaneous and IV. Together with some other data, we collected from the real world and the rollover from the ADAPT trial in the OLE, we brought all this data together and resubmitted them to the FDA, making a case for the seronegative patients. This is a review issue, and this is not in our hands only. We submitted the data, and we look forward to the interaction with the FDA on this topic. Thank you for the question.

Operator, Operator

Your next question comes from the line of Douglas Tsao from H. C. Wainwright. Your line is open.

Douglas Tsao, Analyst

Hi, good morning. Thank you for taking my questions, and first, I want to extend my regards and congratulations to Keith. It's been wonderful to know him. My first question is for Keith. You mentioned insurance resets, and I'm curious about how that is playing out in practice, considering the timing of cycles, re-dosing, and ensuring continuity of treatment.

Keith Woods, COO

Thank you for the comments and the question, Douglas. The main point is that during the insurance reverification process, nearly all of our policies are seeing favorable outcomes, with 90% of covered lives and 80% of those being approved. Most approvals are for durations ranging from six to 12 months, and while we are going through the reverification, we are not facing significant challenges; it’s just a bit more time-consuming. As Karl mentioned, our net projections made before the launch still hold true as we move into 2023. This situation puts us in a strong position with payers, as our pre-launch discussions are materializing as anticipated.

Douglas Tsao, Analyst

Okay, great. That's helpful. And then just as a follow-up, just curious, we're going to start to get data from 117 this year. I'm just curious, should we think about that development program once we get to initial proof of mechanism data, sort of expanding as quickly as what we saw happen with efgartigimod? Or will that development program sort of take place in a more measured pace and organically? Thank you.

Tim Van Hauwermeiren, CEO

Thanks for the 117 question. Look, 117 has its own program and its own plan behind it. We do believe it's a pipeline and a product. If you look at the biology, which is so universal across multiple indications. We're already public on MMN, also in delayed drafting, and there are more indications to come. Whether 117 will ever become as big as efgartigimod is a different question. But we believe there's a significant pipeline of indications where the biology of 117 is really in play. What's similar to efgartigimod is that we invest a lot in the translation of biology and showing the right to succeed with the C2 blocker in these indications. For example, the work we presented on multiple occasions for MMN, but now also at the JPMorgan Conference that that's your transfer model. Think of that type of quality, translation, and biology work that is taking place in all indications we're addressing. That is definitely a similarity between 117 and efgartigimod. Thank you for the question.

Douglas Tsao, Analyst

Just as a quick follow-up, when should we get more indications beyond this first review? Do you have a sense of that?

Tim Van Hauwermeiren, CEO

Well, leave it to the future. There are definitely more indications. If we continue at this pace, we will already be in 20 indications. It also needs to be executable. So let's continue to roll out indications in a thoughtful fashion and in a manner that we can execute. Okay?

Douglas Tsao, Analyst

Okay, great. Thank you so much.

Operator, Operator

Your next question comes from the line of James Gordon from JPMorgan. Your line is open.

James Gordon, Analyst

Hello, James Gordon from JPMorgan. Thanks for taking my question. Question about CIDP. I guess, the question was, is the data I believe it's showing what the ICE trials show in Stage B. If you do that, is that enough, do you think to be a blockbuster indication that we've got in CIDP? The other part just also in CIDP, in terms of what a CIDP launch could look like. If you do show similar data to what IVIg has shown in CIDP, do you think the VYVGART launch is a good proxy for CIDP for the launch like in 2024? How are you thinking, what are the considerations, please?

Tim Van Hauwermeiren, CEO

Thank you, James. It’s a bit premature to talk about how our launch would look in absence of data, but I’ll leave it to Keith in a minute to share some conceptual thinking on how a launch could be different between CIDP and MG. I just repeat what I said before, during our analyst breakfast at the JPMorgan Conference. We believe we are well-equipped to compete if we come out with a roughly speaking, similar response in stages and similar effect size to path in Stage B. We feel equipped to effectively compete in such a position. The launch, of course, in such a well-entrenched market could look quite different. Keith?

Keith Woods, COO

Yes, I mean, certainly, James, I think the first thing we need to do is to see the data to see how we stack up not only in efficacy, but as we believe from the profile of the product, we do think we'll probably have an edge on safety and convenience. With all that being said, it might not be wise to compare it to MG as a likely scenario. This is because the IVIG companies cannot promote IVIG and MG; it’s off-label. However, CIDP is their single largest indication, and this is a satisfied market. I think there is room for improvement and the possibility to disrupt if the data allows, but we're going into a market where physicians and patients are satisfied with IVIG. So I would not use the MG launch as a proxy for the CIDP launch, but let's wait and see those data.

Operator, Operator

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

Joon Lee, Analyst

Hey, thanks for taking our questions. Keith has done a phenomenal job with the VYVGART launch, and conventionalism is that if it didn’t broke, you don't fix it, but I totally understand Keith has personal reasons. Could you elaborate a bit more on what Ms. Karen Massey brings to the table and what aspects of her expertise you think are particularly well-suited to further drive VYVGART uptake? I'm sure you had many qualified candidates to choose from. Thank you.

Tim Van Hauwermeiren, CEO

Thank you for joining us on the call. As you correctly called out, this was a planned transition. Keith is retiring, and his aspiration is to spend more time with family and serving on the board, including continuing to be an adviser to our board as a participant in our commercial committee. I think with Karen, we have the right person at the right time for argenx. She brings global operational experience, and she has successfully led launches in the neuro-inflammation space. Specifically, I referred to the OCREVUS launch, where she accelerated an already successful launch. I think she needs a proven track record of building innovative, nimble teams, which is exactly the type of teams we need to continue being successful on the commercial side. We believe Karen will also be a great cultural fit, and I think the culture of the company is strong. Not only did we hire a great leader from a technical standpoint, but we also think we have an excellent cultural fit. There was indeed choice, and I'm extremely excited about Karen joining us on March 13. Thanks for the question.

Operator, Operator

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

Unidentified Participant, Analyst

Hi, this is asking questions on behalf of Simon Baker. Thanks for taking my questions. Two questions if I may. So the question one is, can you discuss the IP position for VYVGART beyond the March 2036 composition patent expiry, particularly on the subcutaneous formulation? And the question two is, can you give us an update on the European rollout of VYVGART? In which countries do you expect to begin selling in 2023? Thank you.

Tim Van Hauwermeiren, CEO

Could you repeat question one on patent life, please? I couldn't hear it.

Joon Lee, Analyst

Yes. The question one is, can you discuss the IP position for VYVGART beyond March 2036, a composition patent expiry, particularly on the subcutaneous formulation?

Tim Van Hauwermeiren, CEO

Oh, okay. I got it. Keith, I will hand over the question to you on what we expect in the context of European rollout for the drug this year. From a production point of view, what I would like to leave you with conceptually is that, of course, there are multiple layers of IP protection for VYVGART. We have specific limitations which we used and in license actually from other companies, and indeed we have the composition of mega claims, which are on roughly speaking, to 2035. We continue to file additional composition of matter and formulation patents on the back of clinical data. So we have not been public. I would be explicit on the final IP horizon for the molecule, but there is significant IP life in the making above and beyond composition claims you referred to. Keith, you want to comment on the European rollout, please?

Keith Woods, COO

Yes, happy to do so, Tim. As you know, we are currently in the AMNOG process in Germany, and VYVGART is available in Germany, and we're off to a successful launch there. But we will continue to go through that reimbursement process to have final approval in late quarter three of this year. In France, we're in an AP2 program, which makes VYVGART available to patients. It’s not quite as broad as the label at this point, but it does give access to patients that need it while we continue to go through the reimbursement process in France. We've submitted dossies in numerous countries across Europe, including Italy. We've been working with the U.K. and Spain. I want to call out that we have a broad pre-approval access program so that we can begin to serve patients. Basically, this is all going to be based on the timeline of gaining approved reimbursement on a country-by-country basis.

Operator, Operator

And your next question comes from the line of Charles Pitman from Barclays. Your line is open.

Charles Pitman, Analyst

Hi, thank you very much for taking my questions. I apologize if these are any repeats. But just first on OpEx. Could you give us an idea of how this is going to progress over 2023? R&D obviously came in a bit light at Q4. I'm just thinking in terms of you've got a number of pivotal trials set to read out ahead of the earlier-stage trials starting in Q4 2023 and how you're controlling costs? And then second, we have top-line data around the corner for pemphigus. I was wondering if you could just update us on how these trials are proceeding and maybe particularly what you're trying to demonstrate from the trial readouts?

Tim Van Hauwermeiren, CEO

Karl, if you would take the OpEx question, then I will take the pemphigus question. Okay? Thank you.

Karl Gubitz, CFO

Thank you. And thanks, Charles, for the question. If we look at Q4, you will see that the R&D spend is roughly $115 million. It is lighter than Q3, but Q3, of course, included $100 million for the PRV. Going forward, I would expect the Q4 number to either stay flat or increase by inflation for the rest of the year by quarter. For SG&A, if you look at the Q4 number of around $140 million a little bit below, think about what's going to happen in 2023. We're going to have a second launch in the U.S. for subcutaneous, but there will not be material increases with that. There will be marketing spend for the second campaign. Of course, Keith mentioned about the European launches and those investments in those countries are stage-gate. We don't put commercial colleagues in the market until such time, but we do have pricing and reimbursement in place. The point is that the SG&A number will increase quarter by quarter throughout 2023.

Tim Van Hauwermeiren, CEO

Thank you, Karl. I'm very happy with the pemphigus question. Pemphigus is a significant unmet medical need, there are hardly any treatment options out there for these patients. The trial actually has been going very well. This is a global Phase 3 registration trial based on very strong Phase 2 data. The trial enrolled extremely well. From an endpoint's point of view, the primary endpoint is complete remission on the minimum dose of corticosteroids. These patients need to stop information of new lesions, close existing lesions, and taper steroids as fast as possible. The primary endpoint is minimum corticosteroid use. In the second release, we will look at CR off therapy, quality of life, safety, and cumulative use of corticosteroids. These are key secondary endpoints. This data point is expected for the second half of this year.

Operator, Operator

And there are no further questions at this time. This does conclude today's conference call. Thank you for your participation. You may now disconnect.