argenx SE (ARGX) Q1 2022 Earnings Report, Transcript and Summary

Good morning. My name is Adil, and I will be your conference operator today. At this time, I would like to welcome everyone to today's call. [Operator instructions]. Thank you. I'd like to introduce Beth DelGiacco, Vice President of Corporate Communications and Investor Relations. You may now begin your conference

Thank you, operator. Two press releases were issued earlier today, one which summarizes the positive results from our Phase 3 ADVANCE trial and the other which outlines our first quarter 2022 financial results and business updates. These 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; Luc Truyen, Chief Medical Officer; Karl Gubitz, Chief Financial Officer; and Keith Woods, Chief Operating Officer. I will now turn the call over to Tim.

Thank you, Beth. Good morning, everyone, and thank you for joining today's call. Slide 3. I'm thrilled to discuss our strong first quarter results, in particular, we have shared two sets of exciting news this morning. First, we have exceeded expectations for the first quarter of our U.S. VYVGART launch, generating $21.2 million in net product revenues. Keith is going to provide more context on our commercial progress later in the call, but at a high level, this demonstrates both the clear unmet need for new treatments in the GMT community and the tremendous execution of our team to translate their needs into new demands from patients and physicians. Our carefully crafted strategies with regards to pay physicians and patients on paying off today, and I'm more confident than ever that we have the right team in place to bring VYVGART to the GMG community. We're also on track to launch in Japan this month. So we are advancing well on our global launch strategy. Second, we announced positive results from the ADVANCE trial, the first of our two registrational ITP trials. We met a very high bar in achieving these positive results with a difficult primary endpoint and a refractory very heavily pretreated patient group. We also have a robust set of data from secondary endpoints that provide additional context on patent conductivity throughout the study. These data points align closely with how physicians treat ITP patients and will be critical as we look to bring the new treatment option to the ITP community. ITP is now the second serious autoimmune disease in which we've shown a statistically significant treatment benefit. We're starting to see the reality of efgartigimod as a pipeline in a product. I want to spend most of the call on these topics. So I'm going to be brief in talking through the rest of our first quarter progress. We reported positive results from the Phase 3 ADAPT subcu trial and are on track to file by the end of the year. We will build on the positive momentum of our IV launch by bringing additional optionality to patients who may refer a subcu delivering option. We are executing well across all programs and expect by the end of the year to be a clinical development with 10 efgartigimod and two ARGX-117 indications and also to start a Phase 1 trial with ARGX-119. We saw in our press release that we are expanding enrollment in the ADDRESS trial for pemphigus, and therefore, push by the timeline for top line results to the second half of 2023. We decided to take a conservative view on our exposure in Ukraine and Russia because we believe this sets us up for the best chance of success with the trial. Ultimately, we want to reach patients as quickly as we can. Of course, we will update you with any changes as we make progress on enrollments. Moving on to the ADVANCE trial results in ITP. Keith will walk through the data in detail, but I'd like to first spend a few minutes on why we selected ITP as our second indication and what these positive results could mean for ITP patients. ITP, like all our indications, clearly aligned with our multifaceted indication selection strategy. First and foremost, the biology of rationale is evidence. Primary ITP is truly in IgG-mediated serious autoimmune disease in which pathogenic autoantibodies work through four modes of action as depicted on Slide 4. We believe that efgartigimod with its novel mechanism of action could be a differentiated approach by targeting all formats of action simultaneously. This means that we can right-size the balance between enhanced ways of production and reduced patent clearance by targeting the autoantibodies driving both modes of action. Second, we pursue rare disease and auto indications because there is a significant unmet need for new treatment options and ITP is no different. ITP affects more than 70,000 adults in the United States. This is a disease that affects not only the patients' platelet count, but is also associated with bruising, bleeding, fatigue, anxiety and depression, all of which significantly impact the individual's quality of life. The challenge in treating ITP patients is that no defined treatment paradigm exists and physicians have adopted a trial and error approach in which they cycle patients on and off different therapies as one or the other loses effect. As they would care less about the treatment goals for ITP patients, and they share consistent feedback around the need for more options. We are aiming to drive platelets to a safe and sustained platelet level whether its 20,000 or 30,000 platelets while managing bleeding events and to do this without adding known toxicity to the treatment approach. We kept this growth in mind with a selection of, secondary endpoints if we evaluated in advance. We will need to wait for the outcome of the ADVANCE subcu trial before we find our DNA, but believe we have a strong data set from the first trial across our primary and secondary endpoints. This puts us on track to deliver a new treatment option to people living with a serious disease. This is a commitment we make to the ITP community. With that, I will hand the call to Luc to walk through the data in detail.

Thank you, Tim, and good morning, everyone. I'm very excited as we have a positive data readout for my first conference call as Chief Medical Officer of argenx, a role which I assumed on April 1st. Let's start with the trial design on Slide 6. We included patients both on concomitant therapy or a watch-and-wait approach of therapy. 131 patients were randomized 2:1 treatment versus placebo after a two-week screening period. All patients received a fixed weekly infusions for the first four weeks. Between weeks five and 16, if patients have platelet counts of 100,000 or more for three out of four visits, they could transition to every other week dosing. The primary endpoint was measured starting at week 19 and patients were classified as sustained responders if they achieve a platelet counts of 50,000 in four out of the last six visits. This primary endpoint was selected to fulfill regulatory requirements, but we also look at metrics throughout the study that align with real-world treatment objectives. One of these is the International Working Group assessment. Patients who completed ADVANCE could roll over in ADVANCE-Plus to open-label extension. We had 101 patients total rollover, which is 95% of those who completed the trial. On Slide 7 are the patient baseline characteristics. We enrolled primarily chronic ITT patients into ADVANCE, but also had a small number of persistent patients in each arm. We stratified for history of splenectomy and a concomitant therapy. Approximately half of the patient had platelet counts below 15,000 at baseline. The mean time since diagnosis was approximately 10 years and over 50% of patients had received three or more prior ITP therapies. This could be classified as a refractory heavily pretreated patient group. Turning to Slide 8. On the left is the clear correlation of VYVGART infusions and platelet count improvement. The separation of the treated group from placebo is evidenced throughout the trial period. On the right is a primary endpoint analysis. In a treated arm, we had a response rate of 21.8%, or 17 out of 78, compared to 5% in placebo. This was encouraging in such a heavily pretreated population. And even with a tough primary endpoint measure, we met a high regulatory hurdle. On Slide 9, we can see that we also looked at the responders based on criteria from the international working group for ITP. These endpoints were developed by leading ITP physicians as a way to incorporate real-world treatment implications into clinical trial assessments. We include this as a secondary endpoint because these are incorporated in the ENA guidelines for drug development of novel ITP drugs, and we also wanted to capture our response rate along the same access as how physicians think about treatment goals. A response on IWG scale is defined as having platelet counts of at least 30,000 and a two-fold increase from baseline in the absence of bleeding events for at least two separate consecutive visits. A complete response has a higher threshold for platelet counts and is defined as having at least 100,000 platelet counts and absence of bleeding for at least two separate consecutive analysis visits. You can see how this aligns with the treatment goals of physicians the platelets to a safe level in the absence of bleeding events. 51.2% of treated patients achieved an IWG response and 27.9% a complete response, compared to placebo where 20% achieved an IWG response and 4.4% the complete response. On Slide 10, we highlight additional context around the platelet response in VYVGART-treated patients throughout the trial. The fast onset of action is evident, and you can see a clear separation between the VYVGART and placebo arms as early as week one. The durable platelet count increase is observed over the duration of the study with a clear separation between VYVGART and placebo arms at each week. We have 10 VYVGART patients switched to every other week dosing. Patients are eligible to make this switch if they surpass the 100,000 platelet counts at three out of four consecutive visits. Importantly, nine of the 10 patients who switched remained responders. Only one placebo patient was able to switch to every other week dosing and this patient was not a responder. Moving to Slide 11. We look at sustained platelet counts response across many different subtypes. And as you can see on the slide that regardless of the category, there's a high response rate in VYVGART-treated patients. We observed responders in each patient type regardless of age, disease severity, time since diagnosis, prior ITP treatment, use of background medication or history of splenectomy. Next slide, please. You can see on the chart here that we showed statistical significance in our key platelet-derived secondary endpoints, including cumulative number of weeks where platelet counts were at least 50,000 in the chronic ITP population and sustained platelet response in the overall population, including both chronic and persistent ITP patients. The response rate in the overall population was slightly higher than the chronic population alone, which indicates that a small number of persistent patients performed well in the trial. We did not show statistical significance in the number of WHO classified bleeding events. This was not surprising because bleeding events below that baseline, making a delta difficult to achieve. We did see numerically fewer bleeding events categorized as adverse events in treated patients compared to placebo. And we also saw fewer platelet transfusions as a rescue therapy in treated patients compared to placebo. This would indicate that placebo patients required more immediate rescue therapy than VYVGART patients. And finally, with our last key secondary endpoint, we showed a significant difference between VYVGART and placebo patients in durable sustained platelet count response [indiscernible] testing, we could not classify it as having met the endpoint. This is an important data point, though, because the response rate holds up whether you look at four of the last six visits, six of the last eight visits, or even eight of the last 12. This means if you're a responder, you're a durable responder. On Slide 13, we cover safety and tolerability. ADVANCE is our first registrational trial with chronic administration. We are very pleased to confirm the safety and tolerability profile of VYVGART as we move from a cyclical treatment scheduling in ADAPT, with chronic 24-week scheduled in ADVANCE. There were no new meaningful safety findings. To conclude, we are very excited with the totality of the data we're showing today. First, we met the primary endpoint, which was a high bar, especially for a difficult-to-treat patient group. We also gathered important data for physicians that aligns with how they make treatment decisions. We showed a fast onset of action and a durable platelet count with clear separation from placebo throughout the trial. We saw a significant proportion of responder switch to every other week dosing and maintain their response. And we are particularly pleased with the safety profile as we move from cyclical to chronic dosing. With that, I will turn the call over to Karl for the financial update. Karl?

Thank you, Luc. Slide 15. Our first quarter 2022 results are detailed in our press release from this morning, so I will only highlight the key points here. First, on the cash balance. We ended the first quarter with cash, cash equivalents, and current financial assets totaling $2.9 billion, which includes $761 million of net proceeds from a successful financing round in March. Based on current plans, are again expected to utilize approximately $1 billion of available cash in 2022. The spend will support the global VYVGART launches, clinical development of efgartigimod 10 indications and ARGX-117 in two indications; investment in the global supply chain and continued focus on pipeline expansion through our immunology innovation program. We will not be providing any revenue guidance on today's call or any guidance on the expected ramp of product revenue. We expect to be able to provide guidance once we have a few quarters underway and can have a better perspective on the ramp of the launch, competitive market dynamics and how individualized dosing translates to the real-world use. Now on financial results. For the first quarter 2022, our net product revenue from the VYVGART launch in the U.S. were $21.2 million. Inventory in the channel at quarter end was well-managed and reflects less than two weeks [indiscernible]. Total revenues for the quarter were $31.5 million, which also included $2.2 million in collaboration revenue and $8.2 million in other operating income. Cost of sales for the quarter were $1.4 million. Our total R&D and SG&A expenses for the first quarter were approximately $152 million and $100.9 million, respectively. These can be mainly attributed to both research expenses related to efgartigimod and other programs as well as planned marketing and headcount expenses related to the global commercialization of VYVGART. You can find additional details behind these numbers in the press release we issued this morning. I'll now hand the call to Keith for a commercial update.

Thanks, Karl. Next slide, please. To echo Tim's earlier comments, we are excited about the strong start we've had in the first quarter with regard to our commercial efforts. Our progress reflects both the benefit of our strategic preparation and the hard work and dedication of our experienced team. We outlined our launch priorities in our December 2021 approval call around empowering patients to demand better, providing best-in-class patient support, encouraging rapid VYVGART adoption by healthcare professionals and enabling appropriate access. We have been systematically executing on all fronts to deliver results today that exceeded our expectations. First, we continue to make progress on our work with payers. Next slide, please. On our quarter 4 call, we announced that VYVGART-specific policies had been published in plans covering approximately 25% of U.S. commercial lives. We are pleased to share today that, that number has increased to over 60% of covered lives and we remain on track to have broad coverage in place by the end of the second quarter. We are encouraged that policies continue to align to the VYVGART label, both in terms of step-through and prior authorization requirements. We are seeing many favorable policies where patients need to fail mestinon or steroids only to gain access to VYVGART and approvals are typically for six to 12 months of therapy with retreatment at the physician's discretion. We also received confirmation that the J-Code has been approved and will go into effect on July 1, 2022. Second, we've made great strides in our efforts to engage with the physician community. Next slide, please. With a brand-new mechanism of action, we knew it would take time to encourage adoption, and we are pleased with the initial excitement from the community. At the end of the first quarter, we continue to see both breadth and depth of prescribers. We're still in the early stages of our plans for educational programs and peer-to-peer engagement but we're pleased to report that we had 129 speaker programs that have been held since launch with over 600 healthcare providers attending. Key opinion leader physician feedback also continues to be positive. Most KOLs report that they plan to utilize the individual treatment cycles for VYVGART and are comfortable initiating subsequent cycles based on their evaluation. They also report that the safety profile of VYVGART is a positive differentiator. We are pleased to see that the prescriptions being written reach a wide breadth of individuals and closely reflect the population we observed in the Phase 3 ADAPT trial. Half of the patients on VYVGART have previous experience with IVIg and the other half have experienced other available therapies across the treatment paradigm, some with only steroids or ISTs and some with other biologics. Moving on to the next slide. Third and most importantly, we are thrilled to finally be reaching patients in need. And as of the end of the first quarter, we have approximately 380 patients on VYVGART. We are sharing this metric today because we think it's important to show the strong early demand. We will continue to share patient numbers as we were able, but it is possible that patients on therapy will be harder to track going forward with staggered start times for subsequent treatment cycles. We expect to rely mostly on revenue numbers to show growth on a quarter-over-quarter basis. We shared at the time of approval that empowering patients would be a core component of our launch. Next slide, please. We are inspired by the feedback we have received so far which is depicted on this slide and know that we have the right team in place with My VYVGART Path to help them through each step of their treatment journey. Next slide, please. We're still in the very early days of this launch and market dynamics are changing already. This successful first quarter has opened our eyes to the real unmet need for patients but we know that we will need to continue to execute and engage with our key stakeholders to maintain this strong momentum. There are still many unknowns ahead with competition, the contribution of more refractory patients and the reality of how individualized dosing will play out cycle-over-cycle. We're very proud of the effort that our teams have put forward for this quarter, but we also know that we need to see results from the next few quarters before we can understand our real launch trajectory. Before I turn the call back to Tim for concluding remarks, I'll wrap up with a brief update on our global launch strategy. Next slide. In Japan, we will plan to officially launch next week. Our field teams have been engaging with healthcare providers and can start to book sales now that we have aligned on price. The approval decision from the European Medicines Agency is also on track for the second half of 2022. We plan to proceed with a gated approach to building out our commercial organization in Europe on a country-by-country basis. argenx Canada was established in the first quarter and we are in the process of engaging with regulatory bodies on a path forward there. With that, I'll turn the call back to Tim. Tim Van Hauwermeiren Thank you, Keith. Before we open the call to your questions, I would like to conclude with the following on Slide 21. Efgartigimod remains strongly positioned to be not only the first-in-class [indiscernible] blocker, but also the best-in-class. We hope to continue to extend our leadership in the FCRM space with upcoming publications and presentations and investment in our health economics outcomes research in order to demonstrate the broad potential and differentiation of efgartigimod. We are also realizing the potential of efgartigimod to be a true pipeline in a product opportunity with the potential to address a multitude of serious IgG-mediated autoimmune diseases with strong out of the gates on our first commercial launch with a second expected next year with subcu efgartigimod in GMG. We have reported positive Phase 3 data in two indications and proof-of-concept data in four indications and we remain committed to our ambition to be active in 15 indications by 2025. And perhaps most importantly, efgartigimod is just the first of what we hope will be several pipeline product opportunities. In sum, with the support of our strong balance sheet, strategic partners and experienced global team, we are set up to deliver sustainable growth and long-term shareholder value as a fully integrated immunology organization in 2022 and beyond. With that, we can begin the Q&A session. Operator?

Thank you. [Operator instructions] Our first question today comes from Yatin Suneja from Guggenheim Partners. Yatin, your line is open. Please go ahead.

Hey, guys. Congrats on good quarter and positive results. Couple of questions for me. Can you just clarify or quantify what the inventory build was? And then what type of patients you are getting and what the cadence was throughout the quarter? Any pent-up or bolus demand dynamic that we should be thinking about? And then, finally on the ITP side, could you comment on the bleeding rate in the study, I think in Phase 2, there was a slight imbalance. So I just want to get a sense how it was balanced between drug and placebo. Thank you.

Thank you, Yatin. Thank you for being with us today. On the bleeding side, I can be brief. There was a perfect balance between both study arms. The truth is in this study that there was very little bleeding going on at baseline. About 50% of the patients had no bleeding. So it's very difficult to create a real meaningful delta on a crude scale like WHO scale. There is many more data to be unpacked, however. So sophisticated tests would lead into bleeding and we will be reporting on these data at the future clinical conference. Now for the inventory, patients and bolus questions, I'm going to hand over to Keith.

Yes, Yatin. It's Karl. I will quickly take the inventory question. So we're not going to be specific on the number of vials or the dollar amount associated in the channel. But inventory is really well managed at quarter end. It's less than two weeks' worth of inventory and those inventory are under specialty promises.

Yatin, thank you for the question. In regard to the patient types, what we saw is almost half of the patients that are now on VYVGART at a previous experience with IVIg. That's really not a surprise as we thought at the beginning with the new biologics, physicians would turn to patients that were very much in need, having failed several lines. What we believe and what we are seeing is the physicians that get experience with VYVGART then see the benefit that this can provide a wider range of patients. And so the other half of the population that hadn't experienced IVIg come from across the spectrum. Some have just experienced mestinon and steroids. Others have been on broad ISTs. And then we have some that have come from relapsed/refractory biologics. So as far as pent-up demand, we're one quarter in, it's really too early to say. I think just overall, the launch reflects the unmet medical need that exists in MG.

[Operator instructions] The next question is from Matthew Harrison from Morgan Stanley. Matthew, please go ahead. Your line is open.

Great. Good morning. Thanks for taking the question. I was just wondering if you could comment a little bit more on insurance and prior authorizations. I know you gave some commentary in your prepared remarks, but just broadly what you're seeing if you're expecting or how many more plans that you need to see to codify what they may be doing on prior offs or reauthorizations and the frequency there? Any more details would be super helpful. Thank you.

Hey, Matthew. Thank you for the question. So as you heard, even one month into it, we alluded to the fact that we had 25% of covered lives. I credit that to the fact that our market access team, we're already working with payers prior to the PDUFA date. And in fact, looking at contracts in principle that were value-based agreements. We've moved forward with signing those value-based agreements. And now at the end of Quarter 2, we have greater than 60% of covered lives. We expect that number to go up here in Quarter 2. So continued success in market access. For the most part, these plans have been very favorable, many requiring only the utilization of one previous oral therapy, whether that be mestinon, steroid, or an IST. Also, we're seeing approval for six to 12 months right off the bat. This is not being approved on a cycle-by-cycle basis, it's six to 12 months. As far as reapplying, we haven't got to the six to 12 months yet. So we'll cross that bridge when we get there. But overall, very pleased with the work that the team has done with payers. The last thing you heard in the prepared remarks that we will clear the hurdle on July 1st, and we'll have a J-Code in place that's specific for VYVGART to take a month.

The next question is from Tazeen Ahmad from Bank of America. The line is open. Please go ahead.

Hi. Okay. On the subcu, can you just remind us what remains to be done for the application to be submitted? And would you expect an accelerated path because the original filing for the original approval to get a standard review? And then quickly on the J-Code, I know you're not providing sales guidance. But once you do get that, do you expect that that should meaningfully increase your uptake for the rest of the year? Thanks.

Thank you, Tazeen. I'm going to give the J-Code question to Keith in a minute. The path to registration ITP remains, as we said. So the second registrational trial is required before we can submit that is an identically the same study but with a subcu product execution of efgartigimod. We are on track to read out top-line data in Q1 next year. And then I think you can expect further guidance on what we think is a realistic time-line to submission and approval. But you're right, we will require two studies to submit and there's going to be a regular review time-line. Keith, the J-Code?

Yes. Just first, a quick clarification, Tim. Tazeen, were you inquiring on the subcu to MG and what are the hurdles needed?

Yes.

Okay. Thanks. Yes. So quickly, we've already shown the top-line results and we're really pleased with the non-inferior effect that subcu efgartigimod has compared to RD 10 milligram per kilogram. It's really the safety database that we've agreed upon with the FDA that is the time-limiting factor and we've said we'll file BLA before the end of the year. As far as accelerated review, I would say that, that is probably doubtful because there is already product available in the U.S. to treat MG, in particular, VYVGART IV. But remember, we do have a priority review voucher and we will share with you if we plan to use that for subcu MG at the time of filing. Lastly, the J-Code. The J-Code is going to make things go through smoother, faster and easier for offices with less work and less time with rejections and appeal. I don't necessarily think that you're all of a sudden going to see a quarter or three bolus because you have a J-Code in place. And I say this because our team with My VYVGART Path and our field reimbursement managers are working with the offices and with the specialty pharmacies to help patients that want to be on VYVGART today be able to get on it. So we're working through the issues. It's just taking a little longer and the J-Code will make it easier.

The next question comes from Akash Tewari from Jefferies. Akash, please go ahead.

Hey. So congrats on the really strong VYVGART launch. Any color why it's been just so much stronger than Solaris was out of the gate. I think Solaris had 43 patients, you have 380. Do we know what percent of patients have actually switched from IVIg regimens? And specifically, what patients within those 380 were refractory just Solaris amount went out to VYVGART? And then maybe on ITP as well. The data was positive in a pretreated population, but the response rate looks optically similar to what Rigel had. Given consensus peak sales for ITP are now approaching $1 billion in Rigel's products has had a modest launch out of the gate doing about $120 million in sales and they had VYVGART'S price, do you feel like consensus numbers for VYVGART and ITP may have gotten a bit ahead of themselves? Thanks so much.

Thank you, Akash, for the two questions. Let me start with the ITP question, and then I will pass over again to Keith. I think, Akash, it's very difficult to compare between trials and molecules in an ITP space. It's really something to try and do that, but you are looking at different trial designs, different patient populations, different endpoints. And in an ITP space, the benefit risk profile, which we put forward, I think, is very strong. The primary endpoint has made a very stringent bar to satisfy the [indiscernible] requirements, but then I feel we've put forward a very exciting clinical data, relevant clinical data with an exciting another mode of action, which is supporting the positioning which we have in mind which is to break that cycle where people are cycled from 1 TPO to the other one when the first one doesn't work. They just take you to the second one. When the second one no longer works, they take you to third one. It does make sense now to switch to another mode of action, which has proven to be fast, durable and working across all lines of therapy. The safety profile of the molecule, as Luc called out, is exciting. So I feel that with the IWG endpoint, where we have about one in two of these respective patients responding in a clinically meaningful way with such a clean safety profile, that's a very compelling proposition. Keith, I'm handing over to you for the comment on the strong start.

Yes, Akash. Thank you for the question. I guess, first of all, I want to put into context that I think a comparison of the efgartigimod, the VYVGART launch to that of Solaris is really not an accurate comparison because we're looking at two different audiences. Solaris really studied a severe relapsed/refractory population, and therefore, they were targeting a smaller percentage of MG patients. So comparing the numbers is really kind of apples to oranges. What I will say is, we had a team that was built well in advance and we're well prepared. We've hired people from across the industry that have MG experience and have experience in neurology, whether that's coming from previous IVIg companies or coming from other companies that have therapies in neurology. So they had existing relationships with healthcare professionals. You know the work that we did with the payers in advance. I think that that put us in a position to be able to work through some of the payer issues earlier across the treatment paradigm. But really, one of the big things is this has clearly told us from the physicians that there is an unmet medical need in MG, and they love having this new mechanism of action and a new tool in their toolbox. Lastly, I really am pleased with the effort that our team has done in being a patient-focused organization because we have communicated directly to people that are suffering with MG, and they have come in and ask for a different opportunity or a different treatment for their disease.

The next question comes from Yaron Werber from Cowen. Yaron, your line is open.

Great and congrats on the launch. I thought maybe just a couple of really quick questions. The first one, can you give us a little bit of a sense in Japan now that you're underway? How fast do launches typically happen given that it's a fairly concentrated GMG market? And then, secondly, on PV, are you able to use any of the data from the Ukraine or Russia or those 14 sites and all that data are totally out, do you need to essentially accrue 14 new sites? Is that what you mean by expanding the study? Thank you.

Let me maybe start with the pemphigus question and then hand over to Keith for Japan. So what you see on clinicaltrials.gov is indeed a number of clinical sites that doesn't mean this is an equivalent number of patients. So what happens in reality with these patients is some of them, we were able to move them to other clinical sites across the border where they could continue the clinical trial but the bulk of these patients actually are from a conservative risk management point of view, considered by the team to be lost for data collection, data review and inspection afterwards. So yes, we've been taking a conservative approach, Yaron, and we're seeking to replace that number of patients inside in a more secure place of the globe. Back to you, Keith, on expectations for the launch in Japan.

Yes. Thank you for the question. I'm really excited to hop on a plane Saturday morning to head to Japan as we launch next Monday in the country. And then I'll be able to give you a lot more color on next quarter's earnings call. The good news about the launch in Japan is with the approval and with reimbursement established, you have 100% of the people that are insured for MG. So it's going to take that issue off the table. Now the challenge is why you don't see this just all of a sudden take off is in Japan, most infusions, almost all infusions are given in a hospital setting. And just like we have in the U.S., you have to go through the formulary process. So we will be going through the formulary process. The last thing is, the No. 1 thing that I've been saying to you all for about a year that was going to be required is education on this brand new mechanism of action. We have very few number of physicians in Japan that have experienced actually infusing a patient with VYVGART. So it's going to take time for that experience to occur, that comfort to exist, and then we will build up over time.

The next question is from James Gordon from JPMorgan. James, your line is open. Please go ahead.

Hello. James Gordon, JPMorgan. Thanks for taking the question and follow up. The first question was on the ITP data. So it's just subject to the regulatory approval based on the data received this morning. Where is that [indiscernible] VYVGART use? Or do you think it's going to be largely people who are multiple TPO failures or earlier? Any other ways that we should segment the market for trying to build our models? And then could you just provide us, if it was TPO failures, how many TPO failure patients you think there are in the U.S. that we should be using for model purposes? And then the follow-up was VYVGART and MG. So it looks like a really good first quarter. Can you just talk was the build fairly linear through the quarter in terms of number of patients? And have you seen that same trajectory be maintained for April? Or did you accelerate through the quarter in April adding patients even more quickly?

Thank you, James. So let me maybe start with the ITP questions and then hand over back to Keith. So I think the beauty of this study is that we see activity of efgartigimod across the board. So wherever you are in the treatment paradigm, you have the right to respond to this therapy. Splenectomized refractory to steroids, ISTs, TPO receptor agonists, even a fair share of rituximab experienced people in the trial, which is a PT refractory patient population. So that basically allows us to play across the board. How we think about positioning is that TPO receptor agonist, are very well entrenched in this market. And because there is a shortage in different modes of action, patients who are failing a first TPO are typically put on a second one and with the approval of eltrombopag that even put on a third TPO. So it does make sense with this new mechanism of action, this fast onset of action and activity across the board to basically try and position on the heels of a first TPO receptor agonist. Excitingly, a fair amount of patients, which respond on our drug are actually people who stopped responding on a TPO receptor agonist. So the data are supportive of the positioning and that is a pretty exciting opportunity in the market. The way to think about success of the different agents, which are currently approved, James, is that almost one-third of the patients regardless of the type of therapy show long-term response and other people just relapse and need a different type of agents. So whoever you put on a TPO receptor agonist, roughly speaking, only one-third of these patients will give you a long-term response and the two-thirds other patients will need a different therapeutic agents. So I think that should help you from a modeling point of view. Maybe, Keith, you want to comment on the MG question.

Sure, Tim. Happy to do so. So James, basically, what we've seen in patients being prescribed VYVGART has been consistent and gradual growth over the first quarter. Really, the answer is the pull-through time. The conversion from when you're prescribed to when you actually become a VYVGART patient are being treated. I can tell you that, that time has been reducing on a month-over-month basis as we get more policies in place with payers. But really, we're one quarter into it and it's really too early to provide any direction on how this is headed. Thank you.

The next question is from Derek Archila from Wells Fargo. Derek, your line is open.

Hey. Thanks for taking the questions. Good morning and congrats on the progress here. Just two quick ones from us. I guess maybe can you talk about how you expect the gross margin to progress over time? Just want to understand how a normalized out year gross margin might look like? And then just a follow-up, I think, to James' question in terms of how long is it really taking to get MG patients on therapy? And then how do you think this could maybe shorter since -- once the J-Code is in force? Thanks.

It's Karl. I'll take the question on the gross margin. So -- and Derek, our gross margin -- of course, the sales is 1.4%, gross margin of around 6%. We don't expect that number to change materially in the short-term, but we're not going to give any more guidance at this stage.

Derek, it's Keith. Thank you for the question. As far as how long does it take from a patient that's prescribed VYVGART to get on therapy. It varies. It just absolutely depends upon what insurance that they have. We've had some that have been able to be infused within a week after the time that they were prescribed. We've had others where we've had to work on their case for better than four weeks. We've had to go through appeal processes and denies. You have some insurance companies that are going to deny your first claim right off the get-go. So there is no answer. What I can tell you is when I look at the entire group of patients, that time line is coming down on a month-over-month basis. And really, by the time we get to Quarter 3, we should be in a better spot where we have more policies in place, more covered lives and we'll have a specified J-code, which should really shrink that time down to what you see typical for the industry for infusions.

The next question is from Danielle Brill from Raymond James. Danielle, your line is open. Please go ahead.

Hi, guys. Good morning. Congrats on all the progress. And thanks so much for the question. Two quick ones. First, on ITP. What was the antibody status of the enrolled population? And did you see any differences in response rates based on patents of identifiable antibodies? And then on the MG launch, Keith, you have a really solid base. Can you just remind us what you're anticipating in terms of retreatment on a quarterly basis? And how we should be thinking about modeling revenues for these patients moving forward? Thank you.

Thank you, Danielle, and thank you for these two excellent questions. So we did not use antibody status as an enrollment criteria. We believe that true primary ITP is 100% antibody mediated. And there's a bunch of scientific literature supporting that the presence of the oral antibody is basically detectable if your assay is sufficiently sensitive, especially when you go and look at platelet-associated antibodies. So we believe that all three primary ITP patients are antibody mediated. We did collect the data, however, and we will be able to report on that in a post-work analysis. So it's too early to comment on your question. Keith, can I refer to you on the retreatment dynamics?

Sure, Danielle, thank you for the question. The data from the ADAPT study shows that 58% of patients are going to require five cycles per year or less. And right now, that's the only data that we have to go on. We're just one quarter into this. And so we need to really have a close look on individualized dosing in the real-world and what that actually means. Almost all patients that started on VYVGART were only completed one cycle or in their first cycle by the end of Quarter 1. So we're going to have to come back to you later on retreatment. But for the time being, I go with the ADAPT data of 58%, 5 cycles or fewer.

The next question is from Charles Pitman from Redburn. Charles, please go ahead.

Hi. Thank you and congratulations on the positive results today. I've just got one question on the PV trial. You mentioned the 12-month delay is more conservative. I was just wondering if you could give us an update on the enrollment for those other areas you've got to enroll now you're dropping the Ukraine-Russia clinical sites and kind of what's left to complete until you have a more firm expect to read out date? And how this delay has changed your commercial expectations for PV? Thanks.

Thanks, Charles, for the question. So let's not forget that in the background that is something else still playing, which is called COVID. So we still see an impact of COVID on the dynamics of our global clinical trials. But that's not different from what we used to report in the past quarters. So I think we did a good job spreading these global registrational trials geographically, thereby accommodating waves of COVID, which are still occurring. So I think we feel good about our ability to enroll pemphigus patients within a reasonable period of time based on reopening of existing sites, where we know the enrollment dynamics, but also adding a couple of other sites, which simply didn't make it in time to the original enrollment. Commercial expectations. I think what we put forward in our Phase 2 study are very exciting data in pemphigus. I think we show a fast onset of action. We show an ability to push patients into CR on minimum background therapy in a pretty spectacular fashion and then unexpectedly, we see the nice durability of the effects where some of our responders go into long-term remission. And we will be talking about the biology understanding behind the dynamic because I think it's very exciting. So stay tuned on further scientific explanation on that topic but I feel we have a very strong and unique proposition in the pemphigus space, and that's not changing fundamentally because of a few quarters of delay. Thank you for the question.

The next question comes from Joon Lee of Truist Securities. Joon, please go ahead.

Hey. Thanks for taking our questions and congrats on the quarter. Regarding ITP, you mentioned reduced need for platelet transfusions in the drug arm. Can you help us quantify that? And also, if you track by patients on the magnitude of platelet improvement with efgart, do you see a better response in bleeding? And also related to that, what can you tell us about the PK/PD of efgart and ITP? In other words, what's the magnitude of autoantibody reduction that you're able to achieve with the efgart and ITP? Thank you.

Thank you, Joon. Thank you for the question. So before I hand over to Luc on the question regarding the ITP platelets, what I would like to say is that there are no PK/PD data available to the company at this point in time. These are top-line data. But based on everything we have seen across healthy volunteers and the different disease indications. We feel comfortable predicting that the PK/PD profile in ITP patients is going to be very comparable to all other indications and the healthy volunteers. And maybe, Luc, you want to comment on the numerical difference in the use of platelet transfusion as rescue therapy and the potential impact of platelet count at baseline on ability to respond.

Yes. And thanks for the question, and I'll start with the last one first. So the platelet count at baseline is something that was used, of course, in the change from baseline analysis of the primary endpoint. So any differences there were already taken into account in the analysis. And then if you look at it at a categorical like below and above 15, you'll see that the response is the same in the subgroup. So on those both counts, I don't think this had a material impact. The numerical advantage of need for transfusions and IVIg for that matter between placebo and active is for us in a general picture, where we also see on the adverse events and numerical imbalance between placebo and active and we will be looking at that in more detail and roll that in future data presentations.

But it's fair to say, Luc, if I can complete what you started. We see a clear trend in the AE table for less bleeding events in the efgartigimod arm compared to placebo and the need for less acute rescue. So Joon, thank you for these questions. And stay tuned, many more data to be unpacked from this interesting trial. Thank you.

The next question is from Allison Bratzel from Piper Sandler. Alison, your line is open.

Hi. Good morning. Thanks for taking the question. So just on the VYVGART launch, I think, you talked about having good prescriber breadth. Could you maybe talk to the prescriber mix between academic and community physicians and how you expect that to evolve over time once the subcu comes to market? And also just on the site of VYVGART infusions, could you talk about what you're seeing on the split between in-office infusion centers and at home administration volume at this planned launch and how you expect that to evolve as the launch gets further underway and as the COVID situation continues to develop? Thanks.

Yes, Allison. Thank you for the question. Go ahead, Tim.

Keith, go ahead. Man, I was going to hand over to you.

Sorry. Sorry. Thank you. So Allison, thank you for the question. As far as the split between academic and community, we haven't given the specific numbers publicly. We did say that we expected there was more experience in the academic community with VYVGART from the clinical trial. But if we look at the last launch in this segment, the community had the majority of the business. It's only one quarter in, so it's too early to make projections off just where we've seen the initial patients come on therapy. As far as the site of infusion, this is heavily determined by the type of insurance that the patient has. I can tell you that we have patients that are being treated in office in a buy-and-bill situation. We have them being treated in home infusion. We have them being treated in infusion centers and in outpatient hospital. So we're seeing site of care across the board. Again, too early to make predictions or trends of just one quarter worth of data.

The next question comes from Laura Sutcliffe from UBS. Laura, your line is open.

Hello. Thank you. I hear what you say on your J-Code sort of smoothing things for you. But from an inventory perspective, would you expect sort of any extra channel stocking when you get that permanent J-Code in the middle of the year? And then secondly, maybe you could just talk briefly about some of the characteristics of your repeat prescribers. I realize there probably aren't many, but some color there would be helpful. Thank you.

Thank you, Laura. Yes. Go ahead, Karl. My apologies.

Yes. I will take the question on the inventory channel stocking. So we monitor the inventory at our specialty pharmacies where the bulk of our inventory is and contractually, we have to keep it good in certain limits. So I mean, numerically, the amount of valves will increase, of course, but it will be within 2 weeks of sales.

Thank you. Keith?

Yes. Thanks, Karl. As far as repeat prescribers, we do have physicians that have more than one patient on therapy. I said before the launch that I thought the most difficult patient to get on therapy was going to be the first one for each physician. We feel confident in the data that almost 8 out of every 10 patients that are prescribed VYVGART have a clinically meaningful response. And we believe that when physicians see this, they're going to want to use the product more. So I can give you examples, but they're going to be small and anecdotal. This is where we see the example of physicians that first used VYVGART on maybe somebody that was exposed to IVIg, a more relapsed/refractory type patient and had a positive experience and said, I'm going to move this earlier into the treatment paradigm, and that's why we've seen patients treated all the way across the ADAPT population.

The next question comes from Joel Beatty of Baird. Joel, please go ahead. Your line is open.

Hi. Congrats on the progress. Now that you've seen today's trial results from the first Phase 3 ITP trial, what's your confidence in the powering of the second trial? And do you see any potential to make trial design changes to help increase powering? Today's results are clearly statistically significant, but with the p-value of 0.03, that's perhaps somewhat close to 0.05.

Thanks, Joel. That's an excellent question because both studies are running targets, you're spot on. We're trying to identify lessons learned from this trial and see whether it makes sense to basically still tweak the second study. Now from a powering point of view, we feel pretty confident. And the primary endpoint was a very trouble bar. I think we achieved our objective in terms of trying to nail placebo as good as we could. So placebo is as close to zero as we can realistically get. So overall, when it comes to the construction of the trial and the design of the endpoint, we feel sufficiently comfortable but we will do some further work and see where it makes sense to still tweak and tune some of the other details. Thank you for the suggestion.

The next question is from Douglas Tsao from H.C. Wainwright. Douglas, please go ahead.

Hi, good morning. Thanks for taking the question. Just maybe to start, just curious in terms of the people who are writing prescriptions. I'm just curious, what percentage were writers -- or writers for investigators in the ADAPT trial as well as -- and how much penetration are you getting outside of sites that weren't in ADAPT? And then I'm just curious in terms of the customized dosing, I'm just curious how physicians are implementing that. Are they sort of having patients do ADLs on a regular basis? Or are they really sort of starting? And I know it's early days, sort of starting more regular four-week on and off schedule? Or are they sort of starting to push things out on a customized basis based on individual responses? Thank you.

Thanks, Douglas. Again, two excellent questions. So maybe, Keith, you want to comment on the number of ADAPT prescribers and then having reality, people are picking up on individualized dosing, which mechanism they use to do that, please?

Yes. Happy to do so, Tim. So Douglas, I think, first of all, we haven't given information on the number of individual prescribers here in the U.S. But when you look at the total number of study sites that existed in the U.S., which I think is public from the clinicaltrials.gov, you'll note that the number of 380 patients comes from a much broader set than those that participated in the ADAPT Phase 3 study. So we are starting to see good breadth in prescribers outside of just those that participated in the study. As far as the customized dosing, the majority of patients are being started on the individualized dosing. Right now, the question on ADLs, it varies from physician to physician. Some are using the ADL for insurance purposes. Some are using it to track their patients progress on a regular basis, but that's not 100%. Many will tell you, ADLs is only something that I've used in a clinical trial. So it varies on a physician-by-physician basis. Last thing, dosing cadence. We have a few different things that are taking place. We have some folks that are giving me four weeks the one cycle of infusion and then they're monitoring their patient on a regular basis and asking their patients as soon as you feel return to symptoms, you need to notify us and we will retreat. That's one example of what's taking place. We have others that are going with the four-week treatment and then they're waiting and asking the patient to come back in four weeks later for an appointment and then they will begin to stretch their dosing interval out. So you see variability in how this is taking place. But overall, what I can say is, once we get patients to their consistent dose, so those that have been on the ADAPT and the ADAPT, OLE that rolled into commercial product, they're on a very consistent regimen.

This concludes today’s call and thank you very much for joining. You may now disconnect your lines.