argenx SE

switch between treatments. Finally, there is a considerable market opportunity with approximately 16,000 to 17,000 addressable patients in the U.S. alone. We are continuing to enroll patients in the ADVANCE APPEAL, ADHERE, and ADDRESS trials for ITP, CIDP, and PENFIGUS, respectively, which are shown on slide 7, 8, and 9. As we approach enrollment completion, we will be able to provide more granular timing for these results. We recently shared the full results from the Phase II panthicus study in the British Journal of Dermatology. We would encourage you to read this manuscript with data to support our latest understanding of how mCarticumab could fit into the treatment paradigm in panthicus given the observed fast onset of action, favorable tolerability profile and potential to use lower initial doses of corticosteroids and start early steroid tapering. With our newest indications, we are in the final preparation stages to initiate registrational trials. The Bullets-Pentagord trial is on track to start by the end of this year, and myositis is expected to start during the first quarter of 2022, now that we have wrapped up our FDA consultations, and these are depicted on slides 10 and 11. Through our collaboration with Xilab, we are also planning to launch proof-of-concept trials in additional indications. We aren't ready to be public on the plan yet, but in the meantime, XI is preparing to start enrollment of Chinese patients into our ongoing global clinical trials. I'm going to quickly talk about two other important programs in our pipeline, starting with ARGENIX 117, our first-in-class C2 inhibitor. We shared Phase I data from ARGENIX 117 during our R&D day when we explained the reasons why we believe that C2 is the ideal point of intervention within the complement cascade. To name a few, it is upstream of C5, keeps the alternative pathway intact to reduce infection risk, and patients with a genetic deficiency of C2 have a more benign phenotype than that of other complement deficiencies. The Phase I data show the favorable safety profile with both the IV and sub-Q formulations and PKPD profiles that support infrequent dosing. We remain on track to begin the Phase II trial in MMM by the end of this year and look forward to talking about additional indications for this pipeline in a product opportunity next year. Slide 14. We also talked about Argenix 119 for the first time during our R&D day, which is a simple antibody aimed at boosting the neuromuscular junction. This is the latest pipeline product that has emerged from our immunology innovation program. We are excited to share more on this program next year. Before I turn the call to my colleagues, I would like to take a moment to thank our team for their collective efforts as we approach this exciting new stage for Argenix. In particular, I would like to acknowledge Wim Pares. We announced today that Wim will retire after three years with Argenix in March of 2022. In this planned transition, he will become a member of the R&D committee of our board of directors and succession plans are underway for Lutruyen to assume the role in April 2022. We are so grateful to him for his invaluable contributions, the transformation of our R&D organization, and for his humble leadership these past few years. With that, I will turn the call over to Carl to provide a financial update.

Carl? Thanks, Tim. Slide 15 covers our 2021 financial results for the nine-month ended September 30, 2021. I will summarize them here, but they are covered in more detail in today's press release. Total operating income increased to 494.6 million compared to 47.7 million during the same period in 2020. The significant increase was primarily due to the recognition of 315.1 million as a consequence of a termination of a collaboration agreement with Janssen. Additionally, the closing of a strategic collaboration with XyLab resulting in the recognition of $151.9 million in collaboration revenue. R&D expenses increased to $413.3 million compared to $276.4 million in 2020. The increase resulted primarily from higher external research and development expenses. mainly for our FGAR TV mode programs. SG&A expenses totaled $210.2 million for the first nine months for 2021, compared to $113.2 million in 2020. The increase resulted primarily from higher personnel expenses. The change in fair value on non-current financial million so far this year, which is the result of a closing of a Series B financing round of Agomab Therapeutics, in which we have a profit share. Finally, cash, cash equivalents and current financial assets total $2.53 billion as of the end of September, compared to $2 billion on December 31, 2020. I now like to turn the call over to Keith Woods to provide an update on our commercial launch preparation. Keith?

Thanks, Carl. Flight 16, please. We are on track with our preparations for the global launch of F-Guard Tigamod in MG. Based on our December 17th PDUFA date in the U.S., we anticipate an effective launch date in January 2022. In Japan, we anticipate an approval in the first quarter of 2022, followed by a commercial launch three months later once we have price set. In Europe, we expect to have an approval in the second half of 2022, and then we will negotiate price and reimbursement on a country-by-country basis, and this is a process that can take anywhere from 12 to 36 months. Slide 17, please. We are also excited to announce that as of today, our U.S. and Japan field teams are fully on board. We are currently conducting training and account profiling to ensure that we are prepared to reach patients, providers, payers, and other stakeholders upon approval. We have 70 territory business managers in the US and 24 in Japan, but our full field force in the US will be a team of 146 people. In addition to the territory business managers, the team also includes the regional business directors, nurse case managers, case coordinators, medical research liaisons, thought leader liaisons, field reimbursement managers, regional account managers, and national account directors. We continue to be impressed with the level of talent, experience, and enthusiasm the new team members bring, and we see their shared commitment towards the patient. We know that the investments we are making in our team and our other infrastructure now will benefit us for the long term because we will recognize economies of scale as we expand to each commercial franchise across new indications and with new assets. While we feel we have assembled a best in class team that is equipped to handle the challenges associated with this potential launch, we know that there are certain aspects that are outside of our control. Namely, the COVID pandemic continues to create uncertainty for our teams and the communities we hope to serve. We are building a launch plan that incorporates both virtual and in-person components based on feedback from physicians on how to optimize our interactions with a hybrid approach. We also know that it may still be difficult for patients to easily access the facility for treatment. So in addition to building a network of infusion centers, we have also built a home infusion network. In addition to the unique COVID scenarios we are facing, there are additional challenges associated with a first launch of a product. As we've said many times, we will not have a J code at launch. We will apply for one shortly after approval in the first quarter and expect to have a dedicated J-code in place by quarter three of 2022. This may slow things down in the first two quarters with prescribers having to go through a reimbursement appeal process. Second, F-gartigamide will be a first-in-class therapy. Targeting FCRN is a novel mechanism of action that many physicians are not familiar with and do not have hands-on experience. It will take time to get to the physicians, patients, and payers and educate until they are comfortable with this new, innovative class of medicines. Finally, we are limited in the extent of engagement we can have with stakeholders before an actual approval. For these reasons, we continue to believe that we are positioned for a launch with a gradual, steady growth, and it will take time to reach the full potential of EFGAR-Tigamot and MG. With all this in mind, I want to make it clear that our overall outlook on the potential for FGAR-Tigamot and GMG remains unchanged. We know that this community is in need of alternative options and that we have a compelling value proposition based on the strong ADAPT data, the potential for individualized dosing, having both IV and sub-Q formulations, and our growing safety database. Slide 18, please. In summary, We are excited and prepared for the global launch of FGAR-Tigamod and see the significant unmet need that people living with MG still face. We learned from our real-world evidence study that people living with this disease are negatively impacted on multiple levels, physically, mentally, socially, and emotionally. In fact, 92% of survey responders agree that there is a significant need for new treatments. and 96% of responders were hopeful for options with fewer side effects. Participants in the study were most likely to experience problems with double vision, breathing, and eyelid droop severity. We also learned that 42.4% of participants had depression score high enough to meet the threshold for this diagnosis, as well as 52.4% for anxiety. In a separate Argenic-sponsored patient burden survey, 51% of patients stopped working entirely due to their disease. We have been fortunate enough to spend considerable time with the MG community over the last several years. Hearing about these challenges, We are hopeful that F-gartigamide can be a new treatment option for people living with GMG. I'll conclude there and turn the call back over to Tim for final remarks. Tim?

Thank you. I'd first like to echo what Keith said. We are on the precipice of an important moment for Argenix, our first opportunity to bring a new medicine to people living with MG and those suffering from a multitude of other serious autoimmune diseases. This is what motivates us every day. To summarize, we are excited and ready for the global launch of Avgatigamot for the treatment of myasthenia gradus, first in the US, then Japan, then Europe. In order to maximize long-term value, we are efficiently developing multiple indications in parallel and working with partners such as Tsai and Medicine to accelerate and expand the development and reach of this first and potentially best-in-class asset. As we grow into a fully integrated global immunology organization, we have not lost sight of our strong scientific foundation and commitment to translate immunology breakthroughs into groundbreaking treatments for patients in need. This is why we are simultaneously progressing other assets such as Argenix 117 and Argenix 119, and fueling our long-term growth by continually adding new assets to our powerful discovery engine, the Immunology Innovation Program. We believe this will provide long-term, sustainable growth for all stakeholders. With that, I will open up the call now to your questions. Operator? It's so sad.

We will now begin the question and answer session. To ask a question, you may press star then one. If you're using a speakerphone, please pick up your headset before pressing the keys. If at any time your question has been addressed and you would like to withdraw your question, please press star then two. In the interest of answering as many questions as possible, each person in the queue is limited to one question only. At this time, we will pause momentarily to assemble our roster. Our first question comes from Akesh Tolari with Jefferies. Please go ahead. Hey, guys.

Thanks so much. Have any of your sites from Vetter, Landa, or Cardinal been inspected either in person or remotely by the FDA heading into your December PDUFA decision on FGAR-Tetamon? And just if I can think this in, what's the rationale for you initiating trials that are exploring other dosing regimens in GMG? Was that a decision based on doctor feedback or agency feedback? Thanks so much.

Thank you, Akash. Thanks for the question. So first question, the manufacturing sites are currently being inspected by the FDA remotely. And remember, these are sites which are very well known to the FDA. These are sites which have been inspected in the past on numerous occasions, and notable products are being manufactured there, which are FDA-approved. So that is ongoing, and we think we're on track. You see on clinical trials of DOF one of, hopefully, many phase 4 studies, and we'll be continuing to test at Cartesian MOX in some of our indications. So I would say there's nothing more, nothing less to say than this is one of the phase 4 studies which we're going to be rolling out.

Thank you.

Our next question comes from James Gordon with JP Morgan.

Please go ahead. Hello, James Gordon, JP Morgan. Thanks for taking the questions. One question was on ESCA pricing. What is your latest thinking, assuming U.S. approval, about how the product could be priced? Is it a product we should think of being priced, a similar price to what it would cost to give sodium immunoglobulin, so not much more than $100,000? Or could this be more like a $200,000 per patient per year product, depending quite how many doses a patient were to get? And if I could squeeze in a follow-up question, just ESCO ramp, and I noted some of the comments about needing to get a J code and the time taken to get a J code and also to build awareness of a new mode of action that all makes total sense. In light of those comments, I think Bloomberg consensus has revenues of 193 million for next year for the group overall. Could that be a little bit high given just some of the things we need to bear in mind for the ESCO ramp?

Keith, would you mind taking the first question on pricing, please?

Thank you. Happy to do so, Tim. So, James, we've been doing homework for quite a while on pricing, and we've also been looking at IVIG. And if you look at it with the recent price increases that they've taken over the last couple of years, The average cost of chronic IVIT treatment for an MG patient is about $190,000 for a year. And I want to call that the average. Some patients are much more expensive. We believe that we offer a premium value proposition based on our efficacy, our rapid onset of response, and our depth of response over that of IVIG. In addition, we think we provide greater convenience and overall safety and tolerability with our individualized dosing schedule. So that's kind of where we are on this with our pricing thoughts, and this should be the last earnings call before we can actually disclose price.

Maybe Carl, you want to comment on the second question, please?

Thank you, James. So I'm just going to comment on, you said that consensus is 193. When I looked at the consensus, I see for product revenues, it's around 140 million. So that's what I see for consensus for product sales. I think some analysts still have revenue assumptions in there for CUSA, which, of course, has now all been recognized in this year. So I think that's something which analysts will look at as they refine their models. Thank you.

Our next question comes from Danielle Brill with Raymond James. Please go ahead.

Hi, guys. Good morning, and thanks so much for the questions. Tim, I was wondering if you could provide some color on the topics of focus and maybe the types of questions posed by the agency during your late-cycle review meeting. And then also curious, given the proximity to the PDUPA date, if labeling discussions have begun yet. Thank you.

Daniel, thanks for being with us today. So there's not too much, of course, we can publicly discuss about the ongoing dialogue with the FDA, but we can confirm that the late-cycle review meeting is behind us. I would say it was a meeting in line with our expectations, and we believe that based on the short discussion, this company is on track with the review of the file. We got confirmation again on, you know, No need for an advisory panel. We did explicitly ask a question to the FDA, but we are on track from their point of view with the leaving of the file, which is something which they confirmed. And therefore, based on that discussion, we believe we're on track for the due date of December 17. But thank you for the question.

Our next question comes from Yatin Sunja with Guggenheim. Please go ahead.

Hey, guys. Thank you for taking my question. Another question on the launch dynamic. So I understand I think the revenue is likely a function of price and how many cycles a patient can receive. So can you just talk about how should we think about cycles per patient per year? And then You know, maybe just moving away from revenue, if you look at Solaris, I think they added about 750 to 800 patients in the first year of launch. Obviously, you are going after a much bigger term. So just trying to get a sense that is Solaris a good comp or sort of a reasonable base to build a case and then sort of more upside as you expand in other geographies.

Yatin, thanks for being with us today. And these are two great questions. I'm going to give the floor to Keith, who is best placed to address those. Keith?

Yeah. Thank you for the question, Yatin. So when it comes to cycles per patient per year, what we're seeing from the data is a distribution curve. So you're going to have about 50% of patients that are going to be able to take advantages of a substantial period of time off therapy and experience few cycles per year, where we also have part of the population that is going to require closer to chronic dosing. So I think what the... How we are discussing this with the payers is they're taking a look at where on that distribution curve do they feel a typical patient will fall, realizing that with some of their patients, it's going to be relatively low expense for them, and with others, it will be more of a chronic dosing, and therefore, it would be a higher revenue patient for us. As far as the read-through from the Solaris launch, it's really hard to give a read-through because it's not a pure apples-to-apples comparison. They do have a broad label, but they're restricted to acetylcholine receptor positive patients. But the real thing is a lot of the payers have limited them to the severe relapsed refractory. And as you know, we are targeting a broader audience. So it's difficult to use that as a direct read-through.

Just one clarification question. The 20,000 addressable patient that you talk about, that's a U.S. number, correct?

That's correct. That's correct. That is the U.S.

Our next question comes from June Lee with Truist. Please go ahead.

Hi, thanks for the updates and taking our questions. You know, ICER recently published the report giving ecolizumab B plus and F-carcinoma to C plus plus. Also, they concluded that quality adjusted life years was less than half of that of ecolizumab. Obviously, they made several assumptions, including, you know, placeholder for price. and not accounting for the differences in frequency of dosing and other convenience factors. But we'd love to hear your comments on their findings and where you differ from them on the value prop at Garcismo. Thank you.

Thank you for the question. I think the review done by ICER was a great opportunity for us to really take a deep dive into our own data and develop the fullest understanding of our own data. And we continue to be very excited about this data. And I think if you look at the track record and history of ISF, you can see that typically the conclusions they report on are never really aligning well for rare disease drugs from a pricing point of view. So it looks like their models are not really in tune with, you know, modeling a rare disease drug like Partigemol for the treatment of MG. We did agree with some of their relative conclusions, however, in terms of positioning vis-à-vis some of the other medications, including Eculizumab. And one of the things which really surfaced from the data is that if you would look at the subset of patients in the ADAPT study, which would meet the Regain criteria, you would basically see that the data in that Regain-like population was inline and as strong as it was in the overall population. And that also gives me the opportunity to relate back to some of the latest data disclosures which we have given at the EAM conference or which we work with in the upcoming weekends during the scientific session of the MGFA. Very excitingly, you see that in the VET study, the effect of FGAT-TicaMod was as potent regardless of the number of lines of background therapy a given patient was on. So even in the most effective patients, we have an equally strong effect, but also across the different muscle domains. So regardless when you talk about ocular, vulgar, respiratory, or limb and gross motor function, you see that the effect of F-pactigma is consistent and strong across the different subsets of muscles. So I thought it was a great for the data analysis continuing to understand the strength of our data. Thanks for the question.

Thank you. The next question comes from Haseen Ahmed with Bank of America. Please go ahead.

Hi, guys. Good morning or good afternoon to you. Tim, just a quick question. I'm sorry if it's already been asked. I joined it just a tad bit late. But how are discussions with FDA going regarding the application for F-Gard-Teta-Mod and MG, and have labeling discussions started yet?

Thanks for joining us. Yeah, we did cover the topic briefly based on the status of the reality inspections, the review of the file, and how the late cyber review meeting has been going. We think that we are on track vis-a-vis the data of December 17th. From a labeling discussion point of view, we have to refrain from asking those questions. We will talk about labeling discussions, hopefully, on a later occasion. But so far, we think that's a good catch. Ultimately, of course, this remains an FDA decision, and only FDA will decide. Thank you.

Okay. And then just a follow-up on how you think of the market opportunity, just not including the products that are on the market now, but ones that might be coming on for MG in the future. So, for example, I think that Regeneron is working on bringing a product into the clinic for MG. Where do you think the biggest point of differentiation will be for F-Gar-Tigamon versus anything else that you potentially foresee entering the market? Thank you.

Well, two-step answer to the question, which is a great question. If you look beyond the HClN class to, for example, complement inhibitors, I think we now have an understanding of the biology such that we do know that the pathogenic autoantibody is acting upstream of complement. So it's actually having multiple pathogenic modes of action on the junction. complement recruitment is one of them and i think it is fair to see that or to say that you know the adept data show the strength of you know or the power of removing the pathogenic auto antibodies and the power which probably goes above and beyond what a complement blocker can do now within the fcn class i think we've put the bar very high and if you look at the safety profile of our drug where by far we have the biggest and the largest safety data set of all across healthy volunteers and multiple indications, it's fair to say that, you know, the safety profile of Ergatigamot is emerging as a potential differentiator. I think we've also put the bar very high when it comes to the efficacy. I mean, an 80% response rate over the first two cycles, achieving almost a 60% minimization In fact, that is a very tall bar for other people to come and even try too much. And then on the convenience angle, we do continue to believe that the exclusive HeroZone license and the very convenient sub-Q dosing that enables, we're again setting a whole new standard in the space of energy. So in its totality, safety, efficacy, convenience, I think we're really setting a tall bar. Thanks for the question.

OK. Thank you, Tim.

Our next question comes from Rosie Turner with Barclays. Please go ahead.

Hi, good afternoon. Thank you so much for taking my questions. Just two very quick ones for me. In terms of the 15 indications that you're targeting being in by 2025, will those Zylabs indications be in addition to that, or is that including those Zylabs indications? And then just thinking about the at-home infusion network you mentioned, just wondering how that will work. Is that going to be a cost borne by yourself or something that you can pass on to insurers? Just thinking about whether that will have an impact on margins. Thank you.

These are two great questions. Keith, I will hand over question two to you in a minute on the infusion network and how that would work. On the 15 indications, the simple answer is that this includes the strategic alliance with Xylax. So this is the totality of indications we need to claim, pursuing our own indications, but also indications pursued by our partner. Keith?

Yes, thank you. As far as the infusion network goes, we're working with a number of providers across the U.S. And how this is designed is there are certain insurance companies that have preferred home infusion providers, and we will be working with them. We also have targeted the home infusion centers that currently treat a great deal of neurology patients at home. So it is a broad network because our overall concept here, especially in a COVID environment, is as we launch, we want to be able to meet the patient demand where it needs to be met. And what I mean by that is we will offer through specialty pharmacy, we will offer home infusion, we will offer in-office treatment, we will offer infusion centers where patients can go be treated. So the idea is to make it as convenient as possible.

Great. Thank you very much.

Our next question comes from Jason Butler with JMP Securities. Please go ahead. Jason, you might be muted.

Oh, sorry. Thanks for taking the question. Just one on Japan and the reimbursement process there. Can you just talk to us at a high level how you think about price dynamics versus the U.S. and also the reimbursement process relative to any relevant reference in Japan? Thanks.

Thank you, Jason. Thanks for being with us today. Keith, this is a question for you, right?

Yeah, thanks, Jim. And Jason, thanks for the question. So as far as the process for reimbursement in Japan, the first thing that we need to do is negotiate price with Japan. That's an ongoing process that takes some time. Ideally, our pricing strategy is to have as close of a tight pricing ban across the globe, but we will continue to work with Japan. And after we have regulatory approval in Japan, it is typically three months later that you get your NHI price from them. So we will continue through in the negotiation of that process with them. Great.

Thanks for taking the question.

Mm-hmm.

The next question comes from Joel Betty with Citi. Please go ahead.

Thanks for taking the question. For the subcutaneous trials underway, such as in MGE and ITP, what are your expectations for showing comparable data versus opportunities to show some type of benefit compared to the MGE formulation?

Great question. In the MG situation, we believe that the 1,000 mg flat dose of Q has an almost identical PD effect as the 10 mg per kg IV. So we're actually going for non-inferiority, and that will be measured in the primary endpoint based on percentage IVG reduction. and in the secondary endpoints based on improvement of clinical symptoms. We've been expecting equivalent safety and efficacy. Of course, we're aiming for a different public presentation which could be appealing from a convenience point of view to a subset of patients. Again, for ITP, here we need two registration files for submission. We've chosen to do one with the IT product and one with the sub-Q product with, again, identical PD codes. So we expect that the total data sets will be consistent between both studies. Thank you for the question. Thank you.

The next question comes from with Wells Fargo. Please go ahead.

Hi. Thanks for taking my questions. I have two quick ones. Is it reasonable to assume that the antibody negative patient population might be one of the topics of labeling discussion? And also, more broadly, do you contemplate any head-to-head studies with IVIG in some of the indications that you're pursuing where IVIG is approved treatment.

Thanks. Thank you for the question. Do you want to take the seronegative question, please?

Yeah, happy to do so. If we take a look at the seronegative population, I just want to call out that, you know, they were not a part of our Phase II study, but we honored our commitment to the MG patient community by including the seronegatives in our Phase III trial. We did this because of the belief of the impact that F-cortigamide has on specifically IgG4. We did, in the Phase III study, see in the data that there was a treatment benefit in using epiglartigamide. But I want to call out that the response to placebo was nearly equivalent. So the data we saw are not statistically significant. We continue to look at this group even further by not just looking at ADL, but also QMG. We've shared some information on both MGADL and QMG, as well as those who achieved MSC. So we have provided all of this data to the FDA, but ultimately this is going to be a decision by the agencies.

And then on the second question, look, for the current studies, none of these studies are doing head-to-head, of course, against IVIG. As a reminder, in Myasthenia gravis, IVIG is not a approved product in ITP with any chronic setting and not for the acute setting where IVIG is in play. For CRDP and myositis, there was no need or no requirement by the FDA to do such a head-to-head study vis-à-vis IVIG. And again, in PAMFIG, as I said, PAMFIG or IVIG is not really a player. So for the current announced trials, there's no head-to-head comparison required or warranted. And of course, we cannot comment yet on future clinical trials. But thank you for the question.

Got it. Very helpful. Thank you.

Our next question comes from Douglas Tazzo with HCU Wainwright. Please go ahead.

Hi, good morning. Thanks for taking the questions. I'm just curious if you have a sense for providers, are they going to be treated? Since you have so many patients who do treat sort of minimally symptom expression, are they going to be dosing to that level? And then just I'm curious, do you see in the data, patients who achieve MSC, do they achieve the same level of durability of response, or is when they start to, the disease starts to manifest again as a sort of slow progression, or do symptoms come out fairly quickly?

It's a great question. Kiki, if you feel comfortable to ask about, to answer the question, whether we think physicians should observe until MSC?

Sure. Ultimately, we believe not only physicians are going to want to treat their patients to achieve MSE because until there's a cure, there's really nothing more powerful than being able to walk around with no symptoms and not having to deal with adverse events that are associated with many of the current off-label treatments for MG. We've also met with physicians, most recently at AANEM, where we got to meet with them live. And ideally, they want to put their patient into MSC and be able to maintain them there. By the way, payers feel the same way because a patient that is not experiencing symptoms stands a substantially lower opportunity for wind up being hospitalized for MG and therefore incurring higher costs. So ultimately, the ADAPT trial, you did see MSE, but as you know, in the dosing cycles, because of how we needed to learn from the trial, we did allow patients to lift back up out of MSE before redosing. I think real world, you're going to see those patients achieve MSE and then attempt to be maintained there.

We tend to keep the nanodurability of the effects. Of course, now we have data from two open-able extensions or extension studies, you know, taking patients two to three years on study drug. And what we said earlier in the call is that the ICD review was an opportunity for us to really take a deep dive into the totality of our data. And we continue to be excited about the strength of the drug through the data review. The only thing we have publicly said is that in the second treatment cycle, we continue to see an equally strong, if not stronger, NFC effect in our patients. We will be talking about interim data looks in the oral extension studies going forward, but there is data to be expected at conferences most likely next year. Okay?

Great. Thank you.

Thank you. Our next question comes from Charles Pittman with Redburn. Please go ahead.

Hi. Good morning, good afternoon. Thank you very much for taking my questions. I just have two, if I may. Firstly, we've seen a number of delayed BDUFA decisions due to COVID-related manufacturing inspection issues due to regulators' inability to visit manufacturing facilities. I was just wondering if you could talk to whether or not this is a risk for the 17th of December BDUFA date? And then secondly, just on your partnerships, could you give us an indication on the potential approval timelines for ZyLab in China and medicine in Israel? And just to clarify, for the medicine partnership, does this have potential to extend to other indications beyond Mars and Uranus? Thanks.

Thank you, Keith. I wanted to give you the second question on likely approval or approval process for Zy and medicine. And on the first question, what we said publicly is that clinical site inspections have been successfully concluded by the FDA in person. The selected manufacturing sites are being inspected currently remotely. These are facilities which are known to the FDA. They have had numerous FDA inspections before with a good track record. And therefore, there's a good likelihood that the manufacturing site inspection will basically happen completely remotely. So at this moment, I just repeat what I said before in this call, we cannot see any risk associated with manufacturing site inspection when it comes to a potential delay of the due date of December 17. Thank you.

So let's take XI first. So in regard to XI and the timelines, we expect that we will make submission in China that will occur after we have approval here in the U.S. And after we've made that submission, we expect the review timeline to be approximately one year. As for the medicine agreement, the process in Israel can actually start once we have approval in the U.S. And we've done this. Medicine has been selected on the basis of their reputation and their track record. It's part of a business case on whether to partner Israel, and we just believed in their capabilities. We've seen their track record of success there and being able to get patients started. Just to give you some reference, in Israel, from the literature that we can see, there's about 1,500 diagnosed MG patients there. So we expect this to be the first of several distribution agreements that we will be providing throughout the world. It's too early to give definitive regions on whether we will be Argenix by ourselves or with a distributor partnership, but this is just the first example of one.

Brilliant. Thank you very much.

Next call comes from Manos Mastarakis with Deutsche Bank. Please go ahead.

Yes, thanks for taking my question. Essentially, I wanted to ask how important will subcaps be in accelerating MG uptake in 2023? Once it is approved and secondly, what are the expectations for ITP data next year relative to the current standard of care and its likely clinical positioning? Thank you.

Thanks for these two excellent questions. Keith, why don't you go ahead and you talk about how we look at the importance of the sub-Q products relatively compared to the high-D products for penetrating our energy market, and then I will take the second question, okay?

Sure. I'd like to first call out that IV F-cortigamide for MG patients is meeting a substantial unmet medical need. And patients that are experiencing F-cortigamide that I've had the opportunity to meet with are extremely happy with their experience. So I think that because if you think of some of the stats that I quoted in the prepared statements of 51% of people not being able to go to work, you will gladly go sit down and have an IV if you're going to be able to improve your quality of life and overall what you're able to do by taking F-Gar-Tigamot IV. We do believe that when sub-Q is available, that there will be where the market will get slightly bigger, and that is because you do have some patients that just from a convenience point of view or how far they are from a possible infusion site might not go on to therapy while it's IV, whereas with sub-Q, we expect that they are going to be able to self-inject at home. So I think you will see the overall size of the pie grow once we have the sub-Q available for MG. At the end of the day, it's about optionality for the patients. It's about optionality for the healthcare professionals. And even when sub-Q is available, we still expect up to 30% of the patients will remain on IV.

Thank you, Pete. And then with regards to the IPP question, I would like to refer to the Phase 2 results. When we studied the Phase 2 trial, which we published, you can see that we had quite a refractory patient population on study. So refractory to spinaectomy, corticosteroids, TPO's, one or more. And we hit a response rate of 46%. So our expectations for the readout of the Phase D trials, when it comes to the patient population they will be able to enroll, and a likely response rate which we could see our expectations are comparable to the case two. From a product positioning point of view, we're thinking about a positioning right after filling the first TPO instead of then cycling the patient to the next and the next TPO, which will be equally unsuccessful. And it's not unlikely that in such a line you will see an improved efficacy compared to the quite effective patient population you're expecting in the phase two. Thanks for the questions.

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