Good morning. My name is Sarah, and I will serve as your conference call operator. As a reminder, this call is being recorded. Before we begin, I would like to remind everyone that today's conference call will include certain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, for example, statements regarding the potential efficacy and safety of Immunovant's product candidate, expectations regarding the timing, design, and results of its clinical trials, including the timing of future data readouts, the timing of interactions with regulatory agencies, and expectations regarding Immunovant's cash runway. These forward-looking statements are not guarantees of future performance, are subject to various risks and uncertainties and assumptions, known or unknown, which could cause actual results to differ materially from those indicated or anticipated, and speak only as of the date of this call. For more information, investors are encouraged to review Immunovant's most recent quarterly report on Form 10-Q filed with the SEC on August 5th, 2022. Joining me on the call today will be Dr. Pete Salzmann, Chief Executive Officer of Immunovant. Pete, please proceed with your prepared remarks. Thank you, Sarah. Good morning, everyone. I'm very excited to announce our plans to develop batoclimab in chronic inflammatory demyelinating polyneuropathy, or CIDP, and Graves' disease. We believe batoclimab's unique product attributes, namely its ability to deliver deep IgG reductions and its simple subcutaneous route of administration, have the potential to offer differentiated benefit to people with a number of autoimmune diseases. Given this broad opportunity, our team conducted careful diligence before selecting CIDP and Graves' disease as our new target indications. The scientific rationale supporting batoclimab's potential in these indications is strong, and each indication represents an area with significant unmet medical needs. First, CIDP is recognized as an important autoantibody-driven disease within neurology and an exciting opportunity for the anti-FcRn class to improve on the standard of care. Today's discussion will focus on our differentiation strategy, rooted in a careful review of the disease and of completed and initiated studies to date. Our trial design includes some unique features that are intended to optimize the potential effect size we'll observe and the potential for competitive differentiation in the market if successful. Second, with Graves' disease, we are focusing on a serious condition that we believe has lacked meaningful innovation for many years and where the current standard of care is not adequate for many patients. Also, we believe Graves' disease represents a first-in-class opportunity for batoclimab, and our rationally designed phase II study offers an interesting potential synergy with our planned clinical trials in thyroid eye disease. Studying these two new indications now not only offers us an exciting opportunity in terms of meeting patients' needs, but we expect it will also create a steady cadence of data starting in the H2 of calendar year 2023. Before giving a brief overview of batoclimab's mechanism of action for those who are newer to the story, I want to go a bit deeper here on slide seven. Regarding that steady cadence of data I just mentioned. 2022 has been a busy year of indication selection, trial design, regulatory interactions, and trial initiation. As we move to trial execution across the indications, we're expecting more frequent data releases, starting with the initial results from weeks 12 and 24 from the Graves' disease phase II trial in the H2 of 2023, followed by data from the randomized open-label lead-in period of the CIDP trial in the H1 of 2024, followed next by previously announced top-line MG data in the H2 of 2024, and then by previously announced top-line TED data in the H1 of 2025. I will note that all the dates here and throughout the presentation are calendar year dates. Finally, as previously disclosed, our trial design for wAIHA will depend on discussions with regulators later this year. Let's start now with a brief overview of batoclimab's mechanism of action for those newer to this exciting class and asset. On slide eight, batoclimab is shown as a fully human monoclonal antibody designed to inhibit the FcRn-mediated recycling of IgG. Pathogenic IgG plays an important role in a variety of autoimmune conditions. In some cases, pathogenic IgG triggers an immune response after binding to an autoantibody, and in other cases, pathogenic IgG simply stimulates or inhibits a biological function and causes disease in this way. Emerging evidence suggests that clinical disease severity may correlate with the quantity of pathogenic IgG across a range of conditions. Slide nine shows the role of the Fc receptor, which is to prolong the half-life of IgG in circulation. The Fc receptor protects IgG from lysosomal degradation by binding it and returning it to circulation. For this reason, IgG has an unusually long half-life compared to other circulating proteins. In the case of autoimmune diseases characterized by pathogenic IgG, this mechanism also prolongs the half-life of the pathogenic IgG, which is undesired. On slide 10, we see how batoclimab binds to and blocks FcRn activity, thereby reducing the recycling of IgG. By inhibiting IgG recycling, degradation of pathogenic IgG increases, resulting in lower circulating levels of these problematic autoantibodies. Moving now to slide 12 and transitioning to CIDP. We see this as a very exciting opportunity for the anti-FcRn class, with the potential to expand the existing $3 billion IVIG CIDP market. Existing treatments for this disease work for many patients but have meaningful safety, tolerability, and/or convenience limitations. Because there are other anti-FcRn programs underway in CIDP, it's very important that our program can generate differentiated data. The basis of the differentiation we're pursuing is tied not only to batoclimab's unique features but also to certain aspects of the disease. To further highlight key elements of CIDP, I'm now going to transition to a pre-recorded discussion with two experts. Good morning, everyone. Today, I'm joined by Dr. John Katz and Dr. Todd Levine for a discussion on CIDP. Dr. John Katz is a board-certified neurologist specialist currently practicing at Forbes Norris MDA/ALS Research and Treatment Center and is affiliated with California Pacific Medical Center. Dr. Todd Levine is a board-certified neurologist and medical director of the neurology department at HonorHealth in Scottsdale, Arizona. John and Todd, thank you so much for joining me this morning to discuss CIDP. I'd like to begin with a patient journey. Todd, what is the typical path from initial symptoms to diagnosis and treatment for patients with CIDP, in your experience? It's difficult to say that there's a typical path, I think, is the first point. It's a disease that causes predominantly weakness and sensory changes. The challenge, I think, is that it can present relatively sub-acutely and sometimes even chronically, meaning over many weeks or several months. Okay. Well, excellent. We're going to return to the clinical picture and diagnosis and prognosis and treatment. Before we go there, I wanna take a little bit of a dive into the underlying pathophysiology. Todd, what do we know about the cause of CIDP? Surprisingly little. What we believe is that a person's immune system is attacking the myelin in their peripheral nerves. If we think about nerves, there are two main components of a nerve. There is an axon, which is the wire that sends the electrical information, and then there is this insulation around that wire that we call the myelin. The myelin is what allows the nerves to conduct electrical signals quickly. The less myelin around the nerve, the slower that nerve conducts electricity. In large part, because of the response that patients have to immune modulating therapies like prednisone and IVIG and plasmapheresis, we believe that a person's immune system is attacking their nerves. It may be more antibody-driven or what we call humoral driven. It may have a cellular component as well. As long as we can stop that attack on the myelin and preserve the axon, the person's body is very good at repairing that myelin and regrowing it. We believe as you allow that damage to the myelin to occur for longer and longer, so six months, 12 months, two years, eventually those axons start to die. It takes much, much longer, if at all, to regrow the axons, than it does to regrow the myelin. The current answer to the question is, we believe a person's immune system attacks the myelin, and if you attack that myelin long enough, you eventually start to damage the axon. Yeah. Yeah. John, maybe ask you, do you think this is even one disease? Therefore, is there maybe multiple pathophysiologies? Or, what's your thought there? Yeah, it's probably not one disease. You know, we've talked about pathology. We can talk about nerve conduction studies. You're looking at differences in every single case and clinical presentation. We're really clearly in many, many ways looking at different things, both how the nerve is affected, what components of the nerve are, is affected, where in the nerve the nerves is affected, how long the attack on the nerve is gonna go on for. This, to somebody who's an expert in the field, when added on to the fact that we don't have gold standards for diagnosis and we're working off criteria, you could see why this is an area that would take a lot of expertise to understand and manage. One more discussion point with regard to diagnosis. John and Todd, you have developed an algorithm to help aid the diagnosis, which for any condition is important, but certainly for a condition as complicated as this, is really important. Maybe I'll ask both of you to share a little bit your perspective on the value of that algorithm in clinical practice or even in clinical trials. I can start that one. It's a long answer. I'll try to make it short. What we've realized is that in the community, in the neurology community as a whole, there has been a tendency to misdiagnose CIDP, and that may be in both directions. In fact, missing the diagnosis or over-diagnosing it when it doesn't really exist. We began to think, well, what if we just parse out the information into its elements and just have a computer summarize it? The computer turns out to do better than the human. The second thing is, once we write a computer algorithm about the disease and say, "Tell me if this meets the criteria for CIDP," it'll actually perform better than me looking at the same chart. Basically, you're taking my brain. Because what happens when you're looking at a case is it just is really hard to see everything because you're dealing with onsets, how quick something comes on, how long it takes to plateau, what are the nerve conduction features, what are the clinical features? When you put that on a setting of. Maybe the notes aren't that great, or maybe the patient's not that great a historian, or maybe you just don't have all the information. It starts to make sense to say, like, "Let's just lay this bare and see what we think. That's great. It's also great for clinical trials to have access to such a tool, because one of the most important things for clinical trials, both of you know, having been involved in a lot of clinical trials, is to have the disease population as well described as possible. Ideally, as homogeneous as possible, but if it's not a perfectly homogeneous condition, then at least have it well-characterized so that you can stratify your analysis. I guess one more thing that we talked, I think both of you brought up just a little bit, but it plays a role in clinical trials specifically, is kind of the level of disease activity relates a little bit to the temporal nature. If we're gonna test a new therapy for CIDP, you want to enroll patients who have active disease, meaning they need their therapy currently. Their disease course is gonna change if they're not actively treated. What are the ways to identify people with, let's say, it's a spectrum I know, but more active disease versus less active disease, which would be important for clinical trial enrollment? To back up a second, I think your points are really important ones. If you look at some recent CIDP trials and you compare the active arms of the patients getting the drug to the patients getting placebo, and you look at the placebo patients over, let's say, a six-month trial, if 50% of them don't get worse on placebo, it is gonna be very difficult to ever prove that a drug works because the best clinical trial up to this point, about treating CIDP is the ICE trial using IVIG. In that trial, the arm that got IVIG had a 50% response rate. If 50% of your patients don't worsen in the placebo arm, you'll never be able to show a benefit of the drug. It is critical in clinical trials of CIDP to try to find the patients that have active disease and therefore are likely to get worse on placebo. That's really what we're talking about, because that way you can see the difference with the treatment arm. When you have a heterogeneous group of patients in a clinical trial like that, you can immediately see how you would say, in the next trial we do, let's strip off the patients that are less likely to respond to therapy, and we'll have a much higher chance of a drug being able to be proven effective with a smaller number of patients simply because of our patient selection. Excellent. I wanna go off on just a little bit of a tangent, which is important from a trial design perspective and important because clinical trials are global these days. Outside the U.S. and major Western Europe, where IVIG or SCIg or PLEX isn't quite as available, there's a lot of treatment with steroids. Patients who are treated with steroids they may be treated for quite a while. Whereas with IVIG, I think it's true you could just stop it and you would expect the CIDP to return if it's active. You're not expecting that there's gonna be other problems with, quote-unquote, "IVIG withdrawal," since that's not really a concept. With prednisone or steroids, if a person has been on a reasonable dose of steroids for a while, when those steroids are taken away, they're going to have, to some extent, steroid withdrawal, and that's gonna complicate, I believe, teasing out whether their symptoms are returning 'cause they have active CIDP or whether they're having steroid withdrawal. Todd, do you agree with that, and do you see that as an issue for clinical trials where standard of care is steroids? I think it's an important issue. As you said, I think outside of the U.S. and Canada, where IVIG is, you know, maybe thee or four to one compared to steroids, Europe, you know, South America, the rest of the world, steroids are really the mainstay of treatment, with IVIG being second. The issue becomes, depending on the dose of steroids that a person is on chronically, as you said, you can't just stop it. Number one, they have adrenal crisis, so there's a life-threatening issue if you just stop the high dose of prednisone. Number two, we do know that prednisone has lots of nonspecific effects. People feel better, their joints are better, their back is better, and they may have many complaints as you start to lower the prednisone that doesn't necessarily relate directly to their CIDP. It is an important issue to try to figure out how to deal with, particularly in a global study. You know, slower tapers, maybe not getting people off of prednisone entirely, but getting them down to a lower dose, but still trying to use the measure of disease activity as a way of then seeing if your new intervention is going to make a difference. The challenge when you come into a disease state where there are already existing therapies that we believe are effective, like IVIG and prednisone, is it's difficult then to remove the standard of care. We really have to do that because we know many studies in the past where you don't remove the IVIG or prednisone will fail to show a benefit of the new drug because IVIG and prednisone is effective. You need to withdraw the baseline therapy, but with steroids, you have to do it much more carefully. Right. Maybe this is a little bit oversimplified, but if I oversimplify it to make the point. With someone who's on IVIG, you can withdraw it completely. Assuming the new investigational product works, then they're gonna go from untreated active CIDP, and you're gonna be able to see the full effect of the product being studied. With steroids, you're not gonna be able to stop it completely. As you said, that would be dangerous, particularly if they were on a higher dose. You're partially stopping their steroids. Their disease is still partially treated by the steroid because you have to leave a little bit on board, and therefore the investigational product doesn't have the same opportunity to show as big of an effect if it's effective. Is that right? I think that's right. Yeah. I guess maybe come back to the question of new therapies on the horizon. We talked earlier about the subset of patients who respond well to IVIG or PLEX, it's likely that they have a strong humoral component to their underlying pathophysiology. Many of them are doing well, but from an efficacy standpoint. There's limitations to those therapies that would motivate them to want to consider a new therapy, I guess. When you use IVIG in your clinical practice, John, what are some of the challenges? Yeah. You know, it's a treatment where different people are on different doses, so there's a burden of how often somebody has to go to an infusion center if they're getting home infusion, having somebody come over to your house and treating you on a regular basis. They get sort of locked down into this sort of monthly treatment that could take anywhere from one, a few hours on one day to several hours over two or three days on a chronic basis. You know, with something like IVIG or prednisone, those drugs do have a decent amount of side effects. A lot of the times people who get IVIG get headaches, they feel achy for a few days after the treatment. Sometimes that kind of happens randomly, so it's, you know, a treatment here and a treatment there. They need to start thinking about pre-medication or, you know, having a couple of bad days after the therapy. Prednisone obviously has its set of side effects, you know, that are sort of along the lines of things we don't want, like weight gain, changes your skin, can cause diabetes, so on and so forth. They're not perfect therapies, and I think people are sort of looking a little bit and are open to sort of being unshackled from sort of the time and financial burden in the sense you might miss work and that kind of thing. I think as many of the newer immune modulating therapies are coming out in the neuromuscular space, what we're really trying to focus on a lot is quality of life. Prednisone has terrible side effects. We know that, particularly for people that are on it for years. That starts to affect a person's quality of life. Now they're diabetic, now they're hypertensive, now they have osteoporosis, now they have to have surgery for cataracts. These are not rare occurrences with steroids. These are common occurrences with steroids. Even though there's this conception that IVIG is perfectly safe, as John said, we see many patients that get one or two days of IVIG, and then they're just knocked down for two or three days, and then they repeat that every three weeks. You're talking about four or five days that they have to give to their disease, if you will. From your perspective for patients, for both of you, for patients with CIDP, how important is the element of route of administration? The chance of an at-home subcutaneous injection versus an infusion? Yeah. I think that speaks exactly to trying to improve the quality of life of a person. If they don't have to have a nurse in their house for five hours or six hours every three weeks, that's gonna be significantly important. Many patients, because these are chronic diseases, if they're receiving IVIG, they lose their veins over years, and then they have to have a port put in like a cancer patient, and that has its set of complications. Putting the patient in charge of their disease, for me is really an amazing opportunity, for CIDP. If they had at-home subcutaneous injection that they do themselves, very much like, you know, the early days of some of the, multiple sclerosis therapies where patients just did it at home, it puts them in control or lets them feel in control of their disease when many of them have felt that the disease has controlled their life with their previous therapies or with their disease disability. Yeah, I think it would be a big improvement, and I think, you know, they wouldn't be thinking twice, hopefully, about the, you know, method of administration and the side effects. I mean, those two things would be a big improvement on where we are now unto themselves. Thank you, John and Todd, for that really robust discussion on CIDP. We covered a lot of ground. We talked about the clinical manifestations, which are really variable, and we talked about several really important things to consider when designing a trial in CIDP. Then we concluded with some really interesting ideas regarding new innovation for patients who are suffering from CIDP. I wanna really thank you again for joining me this morning. Great. Returning to the live discussion. We're really glad to have had John and Todd join us for that discussion on CIDP. There's a couple of key takeaways. First, we believe CIDP offers a really exciting opportunity for new innovation based on the significant observed limitations of current standard of care, and it's a serious condition within neurology. As you heard from John and Todd, this is a heterogeneous disease, and this heterogeneity contributes to both the difficulty in accurately diagnosing the condition as well as in studying CIDP. Similar to other trials, we are carefully specifying disease criteria required for entry. Then, as part of our CIDP trial, we'll use an algorithm to make sure all these criteria are correctly and consistently evaluated in the final adjudication. Thirdly, we're planning to segment the trial such that only those patients whose standard of care is IVIG, SCIg, or PLEX contribute to the primary endpoint in order to maximize our effect size. More on this in a moment. Finally, John and Todd highlighted the potential benefits of a simple subcutaneous injection for these patients needing regular treatment for a long duration. During their discussion, John and Todd reviewed the underlying pathophysiology of CIDP. In fact, we'll be posting a longer version of the discussion on our website for anyone who wishes to gain an even deeper understanding of each of the primary endpoint in order to maximize our effect size. More on this in a moment. Finally, John and Todd highlighted the potential benefits of a simple subcutaneous injection for these patients needing regular treatment for a long duration. During their discussion, John and Todd reviewed the underlying pathophysiology of CIDP. In fact, we'll be posting a longer version of the discussion on our website for anyone who wishes to gain an even deeper understanding of CIDP. Significant evidence suggests that the disorder is immunologically mediated and that the disorder is an autoantibody-driven disease for many patients. This evidence includes the clinically demonstrated effectiveness of IVIG in treating CIDP, which suggests that pathogenic IgG are involved in causing the disease, even in cases where a specific autoantibody has not been identified. Given the multiple potential root causes of CIDP, we believe that treatment effectiveness will depend on properly segmenting the patient population to identify individuals most likely to benefit from IgG reduction, whether or not a specific autoantibody is present. Our trial is designed to do this with a triple enrichment strategy that I'll review in a moment. With the appropriate patient population identified, the potential benefit of batoclimab in CIDP becomes more straightforward. Ideally, we're looking to enroll patients with active autoantibody-mediated disease that reduction in pathogenic IgG will demonstrate a meaningful benefit. As with other recent CIDP trials, this includes, patients without an identified autoantibody. The inclusion of these patients is enhanced via an enrichment strategy. CIDP trials are somewhat unique within neurology and also across the anti-FcRn trials more broadly. Okay, I want to go into a few important conceptual points here. Why are they different? The reason they're different is that IVIG has been observed to be an effective therapy, as you heard, but it's associated with side effects and logistical limitations that many patients wish to avoid. Often, IVIG can even be used to aid the diagnosis of CIDP, meaning patients with probable CIDP who respond to IVIG are more likely to have definite CIDP. Given all this, the pool of patients, especially in the U.S., who are interested in a new therapy, are in large part already being treated with IVIG. Many fewer patients are not yet on treatment with symptoms. Enrolling treatment-naive patients would be hard in CIDP, and therefore, these trials commonly take the approach, as you heard, of withdrawing standard of care at the beginning of the trial. Now, some trials have immediately randomized such patients to investigational product or placebo without waiting to determine which patients worsened when IVIG was withdrawn or steroids were tapered. The UCB trial took this approach. Such trials go directly from randomization of participants on standard of care to the gray bubble on this slide labeled Period Two. The risk with this approach is that not all patients have active disease and some don't flare, and this can lead to a high placebo response. Therefore, some ongoing trials, such as the efgartigimod trial, have been designed with a double enrichment. First, after standard of care is withdrawn, patients must experience disease worsening in order to progress in the trial. Once disease worsening occurs, patients receive open-label investigational product as a second enrichment step. Patients who respond to open-label retreatment are then randomized to either placebo or investigational product. This is the randomized withdrawal component, and this period of the study generates placebo-controlled efficacy data. Our trial also employs these two enrichment steps noted in light purple. We then introduce a third enrichment step, which we believe is differentiated within the anti-FcRn class, and that is to restrict the primary analysis to IVIG, SCIg, and PLEX. This is shown with the first and last blue bubbles, clarifying that the primary analysis cohort is, represents these patients. Finally, we believe our trial is also unique in studying two doses in Period 1, including our highest dose, 680 mg given weekly by subcutaneous injection. The 680 mg dose of batoclimab has been observed to deliver up to an 80% reduction in IgG, the largest reduction reported with a simple subcutaneous injection. The next slide highlights how washout works in a washout and retreatment trial designed to maximally enrich the study population. In these trials, the standard of care needs to be fully washed out. As I just discussed with Doctors Katz and Levine, steroids often can't be fully washed out. This means patients on steroids often remain partially treated even after washout. When such patients get randomized to the randomized withdrawal portion of the study and are randomized to placebo, they are not likely to decline as much as someone who started on IVIG and is now fully off therapy. The potential treatment effect that can be demonstrated in the controlled portion of the trial could be blunted in patients on steroids. We plan to address this issue by conducting the primary analysis only on the IVIG/SCIg PLEX cohort. This then is the full study schematic with triple enrichment. The primary analysis is done only on the IVIG PLEX cohort, as I mentioned. That's the first enrichment. Patients in the primary analysis cohort must worsen during the washout period. That's the second enrichment. Patients who worsen during the washout then receive open-label batoclimab, to which they must respond in period one in order to progress in the trial, and that's the third enrichment. The third enrichment is further enhanced by studying two doses. Studying two doses in period one has the potential to generate very interesting data on the relationship between IgG reduction and clinical response. The clinical course of CIDP patients treated with IVIG, and in particular, the observation that some patients need higher doses of IVIG than other patients in order to maintain their muscle strength, suggests that deeper IgG lowering will matter for some patients with CIDP. We believe our trial design will enable this relationship to be further characterized, and if some patients need deeper IgG lowering, we believe this will line up well with what batoclimab can deliver with a simple subcutaneous injection. We believe these enhancements and enrichments are designed to give the best likelihood of success in period two and to generate the largest effect size in period two. Because of these enhancements, our trial is smaller than some other ongoing trials. We intend to have about 100 participants in cohort A, the IVIG/SCIg PLEX cohort, enter period one of the trial. Of course, this is an event-driven trial, and so the actual number needed may be a little lower or a little higher. This approach also creates flexibility for our overall CIDP program. Based on the results from competitors' trials and based on the results from period one of our trial, we may start a second trial in parallel with this one, or we may expand the size of this trial. We believe this approach, whether ultimately one or two trials, will yield the strongest and most differentiated registration package. To sum up our approach to studying CIDP, we're using a diagnostic algorithm which is new in CIDP trials. We're using a double enrichment, which two ongoing trials are also using. We are then adding a third enrichment, which is also new in CIDP trials and unique to us. We're using multiple doses in period one. All of these trial features are designed to maximize the probability of success and to maximize the potential effect size. Our development program will begin with a smaller pivotal 2B trial, and we therefore have the flexibility to add a second trial in parallel if that is required or if that makes sense based on emerging data. We have the flexibility to increase the size of this trial if that is the best approach as more data becomes known. Finally, in summary, we've covered a lot on CIDP, but I wanna leave you with three key ideas. First, we believe CIDP is an exciting indication for the anti-FcRn class. Second, our differentiated trial design is intended to improve the probability of success, to optimize study effect size, and will include multiple doses to maximize differentiation. Finally, we believe batoclimab and our trial design create the potential for best-in-class efficacy with a first-to-market, simple subcutaneous route of administration. With that, I'll now transition to the second indication we're announcing today, Graves' disease. Because Graves' disease might be less familiar to those on today's call, I'm going to provide a quick introduction and then transition to a prerecorded discussion with Dr. Kahaly, an expert in this area. Graves' disease is a systemic condition that impacts many organ systems. The reason for this is that thyroid hormones have wide-ranging impact, essentially controlling the metabolic rate throughout the body. We'll hear more about this from Dr. Kahaly. Like many conditions, Graves' disease starts slowly and gains momentum. The incidence of Graves' disease is on the high end of autoantibody conditions at 116,000 per year in the U.S. alone. On the left slide, left side of slide 24, you see that thyroid follicles are naturally stimulated by the thyroid-stimulating hormone or TSH. In Graves patients, anti-TSH receptor autoantibodies, shown here in green, also stimulate the thyroid gland, leading to increased production of T3 and T4, two different thyroid hormones. T4 has four iodine molecules and T3 has three iodine molecules, but they're both thyroid hormones. When too much thyroid hormone is present, the patient experiences hyperthyroidism, affecting many organ systems, shown in the bottom right. We believe there is potential for batoclimab to reduce these pathogenic autoantibodies, thus reducing overstimulation of the thyroid gland and alleviating Graves' symptoms. Moving from left to right, we expect that batoclimab inhibition of FcRn should reduce autoantibodies which are stimulating the thyroid gland and thereby reduce overproduction of thyroid hormones. Medical therapy for Graves' disease consists of antithyroid drugs or ATDs. Importantly, many patients remain symptomatic despite maximally tolerated medical therapy. Given the lack of recent innovation in Graves' disease, well-controlled population studies are lacking. Experts in both the U.S. and Europe recognize this group of patients that need additional efficacy. Discussions with these experts suggest that up to one-third of Graves' patients are not controlled on anti-thyroid drugs, meaning they suffer the impact of insufficiently controlled hyperthyroidism, or elevated T3 and T4, causing myriad symptoms. Based on the annual incidence of 116,000 Graves' patients, we estimate the insufficient responder group to be between 29,000 and 38,000 U.S. patients annually. Additionally, there are patients who have been on anti-thyroid drugs for years, and although their thyroid function is controlled, they're unable to stop their anti-thyroid drug or ATD and are facing the possibility of thyroid ablation via radioactive iodine or surgery. Given the long-term risks of these two therapeutic approaches, we expect that many patients from this group might also choose a targeted medical therapy instead of ablation. I want to note that these patient numbers represent incidence, not prevalence. The potential market opportunity, if successful in Graves', could actually be larger than the opportunity in TED. Slide 27 reviews the options that patients have today. In many cases, patients are not able to achieve full relief of symptoms or become euthyroid with antithyroid drugs like methimazole. That's because of dose-dependent side effects such as rash, gastrointestinal side effects, and even idiosyncratic liver damage. I want to emphasize again that elevated thyroid hormone levels, meaning increased T3 and T4, don't just represent abnormal blood tests. Rather, these hyperthyroid patients are universally symptomatic. When patients can't be controlled with antithyroid drugs, radioactive iodine or surgery can be used, but these have some pretty big limitations as well, and we'll hear more on this from Dr. Kahaly. Overall, we believe there are significant numbers of patients who need efficacious therapy to address their elevated thyroid hormone levels in Graves' disease. Turning now to slide 28. Earlier, I showed the underlying mechanism of Graves' disease, starting with the anti-TSHR antibody. We are excited about Graves' disease not only because it is a classic autoantibody condition with unmet need, but also because we have very interesting data from our TED2b trial. This slide shows some data from our TED2b trial with batoclimab. This TED trial has been informative for our clinical development efforts despite being terminated early. We've previously shown population data from this trial in terms of stimulating autoantibody levels. Here I'm showing three anecdotal cases, three individual patients, one of whom was treated with 340 mg of batoclimab weekly, and two of whom were treated with 680 mg of batoclimab weekly. These three patients all entered the TED2b trial with elevated anti-TSHR autoantibodies and then experienced significant reductions in the autoantibody on batoclimab. Reviewing data like this makes us very excited to study Graves' disease specifically. To further highlight the key elements of Graves' disease, I'm now going to transition to a prerecorded discussion with Dr. Kahaly. I'd now like to introduce Dr. Kahaly. Dr. Kahaly is a professor of medicine, endocrinology, and metabolism, and is chief physician of the Endocrine Outpatient Clinic at the Johannes Gutenberg University Medical Center, located in Mainz, Germany. In addition to leading a large clinical practice and conducting clinical trials across a range of conditions, Dr. Kahaly also leads a lab that specializes in the characterization and analysis of autoantibodies in endocrine disorders. Dr. Kahaly is kind enough to join us to discuss Graves' disease and to bring to life not only the patient experience, but also current concepts in the underlying pathophysiology of this autoantibody-driven condition. George, thank you so much for joining me today. A pleasure, Pete. I'd like to start by drawing on your clinical experience as an expert at a large referral center. You see many patients with Graves' disease whose condition has been hard to manage when they were under the care of a general internist or under the care of an endocrinologist with less focus on Graves' disease. Why does a generalist struggle to manage the more, you know, moderate to severe Graves' patients? Well, this is a very important question because several physician general practitioners have problem accurately treating patients with severe hyperthyroidism. They have problems managing the clinical signs, the clinical symptoms, and more importantly, they have problems with the dose of the anti-thyroid medication. When the patients have problems or are developing complications, these general physicians or practitioners will refer the patients to the specialist, to a referral centers. In those cases, in those actually severe cases, we do see patients coming to us with very bothersome symptoms. These symptoms and signs are really problematic, like arrhythmia or depressive mood or weakness, fatigue, diarrhea. The patients are insecure because they have the feeling that their general practitioner was not experienced enough to help them. That makes a ton of sense. You have a patient whose disease started slowly, but then for the people who come to you, it got pretty severe. It was beyond the capability of their local physician to manage. Now they know there's a lot of things going on with their body, and they're not sure how it all fits together, and they really are seeking someone with expertise to help them understand what's happening and put together a treatment plan. When you see somebody like that, what is your initial diagnostic workup? How do you evaluate somebody like that when you're seeing them for the first time? After seeing them and talking to them, and explaining actually the whole story, I will investigate this patient. I will look, of course, at the whole body, but focusing, of course, on the thyroid, on the neck, and of course, on the eyes, because 50%-60% of the patients will develop eye disorders, orbital disease. I will, of course, subsequently draw blood, and especially I will look at the specific biomarker of the disease, apparently the TSH receptor antibodies, which are 100% specific, disease-specific, telling us actually how active the hyperthyroidism is. TSH receptor antibody are not only specific, they are predictive markers for the further course of the disease and for the systemic development of the disease. That makes a ton of sense. I'm gonna return to the antibody story after in a moment, but I would like, if you don't mind, take a quick tangent to discuss some of the therapies and particularly discuss how they're used, you know, kind of in common practice, not necessarily at a referral center, but you know, most patients who are treated locally. I wanna focus on all these therapies have benefits, but I wanna focus on the limitations of each of these therapies to help understand the potential for new innovation. If we start with antithyroid drugs, what are some of the limitations that local physicians experience when they're using antithyroid drugs? You have actually to be knowledgeable to administer the right dose and the right medication. Point one. Point two, the remission rate of these antithyroid drugs is low, unfortunately low. Even if you treat the patients in a very accurate manner, if you actually want to taper the dose or stop the drug, the remission rate will be approximately 50% to maximum 60% after 12 months. You may continue and treat the patients for 18 months or 24 months. The remission rate will probably increase by 5%- 10%. The side effects, the adverse event, the drug-induced adverse event called side effects, which is dose dependent. Many physicians have problem finding the right balance between the efficacy of the drug and the toxicity of the drug. Either they overdose or they underdose the patients. If you overdose the patients with, let's say, more than 20 mg or 30 mg of methimazole, you will have indeed side effects induced by the high dose of methimazole or PTU. These side effects might be very dangerous or severe or even life-threatening. For example, agranulocytosis or leukopenia or increased liver enzyme. You have to differentiate, of course, between hyperthyroidism-induced increase of liver values and antithyroid drug-induced also the increase of liver value. That's really, really helpful, George. In some ways, methimazole, which was approved in the United States in 1950, by the way, I looked that up over the weekend, is a classic sort of older small molecule innovation. It has idiosyncratic liver toxicity, as you pointed out, and trying to determine whether some small elevation in liver functions is due to just the disease course itself or the beginning of something very serious. That's super tricky. The drug has a very narrow therapeutic window, as you pointed out. It's short half-life. You can underdose it, overdose it. Absolutely sounds tricky to use unless you're one of the lucky patients, I guess, who's milder, and they respond well at a low dose. Even for those patients, you have the long-term lack of remission that you highlighted. That's. I think you really painted a very clear picture there, George. How about radioactive iodine? That's used more commonly in the U.S. and Europe, but it's used around the world, as a way to essentially get rid of the thyroid gland, ablate it in more technical terms. What are some of the issues with radioactive iodine? A very recent report published in the Journal of the American Medical Association in JAMA has been the increased prevalence and incidence risk of cancer, especially of solid tumors, breast cancer in patients having received radioactive iodine for hypothyroidism. Meaning that within 5 years-10 years, patients would have an increased incidence of solid tumors, especially breast cancer, with an increased risk of between 8%-10% in comparison to the normal population who has not received radioactive iodine. This is indeed, well, a severe side effect, a long-term side effect, which will change the treatment paradigm of hypothyroidism. Pete. Thanks, George. That is another very, very rich answer there. I think we can assume safely that the use of radioactive iodine is likely to go down over time, given that information, as well as potentially new therapies. I want to touch on surgery just quickly and use the case of someone who undergoes surgery to talk about how well, in your experience, patients do with long-term thyroid hormone replacement. After the thyroid gland is removed, obviously, they need to have thyroid hormone replaced. That's been done for a long time, so now you probably have decades of experience of people who had surgery 10 years, 20 years ago. How do those people do in the long term on average? Surgical removal of the thyroid gland. When you are talking about surgery, Pete, I mean total thyroidectomy, meaning that the complete thyroid gland is removed by the surgeon. The problem with thyroid surgery or total thyroidectomy is that you need, I would say, a high-volume surgeon is warranted. A survey in more than 10,000 actual hospitals. This has been reported and published, showing you that if a high-volume surgeon is doing thyroid surgery, the complication rate, for example, bleeding or injury of the recurrent nerve, will be, let's say, between 0.5%-1%. Other complications are hypocalcemia due to actual injury of the parathyroid gland. If you go now to a hospital with a thyroid surgeon or where thyroid surgery is being done, let's say, once a week or once a month, the complication rate will average, and I'm not exaggerating, more than between 10%-15%. Surgery will not heal the disease. What also important information is that the quality of life after surgery is often decreasing because the patients have weight, an increase of weight, and they have also. They are not euthyroid. If they are on T4, there is not enough T3 entering the cell and the brain, and this may explain the bad quality of life, the passive mood, and the fatigue. Yeah, that makes a lot of sense. So coming back to the antibodies, I mean, interestingly, of the therapies we just discussed, anti-thyroid medications, radioactive iodine, and surgery, none of them really address the root cause of Graves' disease, which is an autoantibody, as you well know and pointed out already, that binds to and stimulates the TSH receptor. George, your lab has really led the way in characterizing this aspect of Graves' disease. I know this is a really big question, but what have you learned over the years with regard to anti-TSHR antibodies? The most important notion is here to tell the patients what are TSH receptor antibody. To explain to the patients that these TSH receptor antibody are actually causing the disease. That the thyroid gland is normal, but these antibody, which are the specific marker of the disease, are stimulating continuously, in a continuous manner, the thyroid gland. The daily correlation between the clinical judgment, the clinical management of the patients in combination with the present measurement or the present TSH receptor antibody. Having both information is of extremely clinical relevance and utility. This is very important. Also, and last but not least, this is again to emphasize that these TSH receptor antibodies are still present after a definitive treatment of the thyroid. Meaning even if you are performing radioactive iodine treatment and irradiating the thyroid, you will induce an immunological boost, meaning that the TSH receptor antibody titer or concentration will quadruple, will increase 5- 10 fold, and the increase will sustain for years. If you do surgery and remove the whole thyroid gland, the surgeon are telling or informing the patients, "Well, once we remove the thyroid, the antibodies will disappear." Unfortunately not, because the antibodies are produced by the white blood cell or the plasma cells, and the white blood cells are everywhere, are ubiquitous, are circulating in the blood, in this peripheral blood. Even if you remove the thyroid or the eye muscles, you will still have your TSH receptor antibody. Super interesting, George. It's funny, it's a common misconception, even among some physicians who are distant from the day-to-day expertise that you have with regard to Graves' disease and the immunologic basis of it. I often do hear that, well, once the thyroid's gone, the antibodies are gone. Of course, as you pointed out, the antibodies are made by white blood cells, and there's other TSH receptors even outside the thyroid gland for them to bind to. That's a really important point. I guess just in closing, briefly, you know, coming to the potential for new therapeutic options. Earlier in today's call, I shared the mechanism of the batoclimab, with which I know you are very familiar. In fact, you presented data in scientific form showing a dose-dependent decrease in total IgG and in stimulating anti-TSHR antibodies when the batoclimab was administered to patients in the thyroid eye disease trial who had Graves' disease. Anecdotally, we saw some patients in our thyroid eye disease trial who were on methimazole and may have responded to the tocilizumab in terms of their Graves' disease. Of course, this was very anecdotal and just kind of hypothesis generating. Do you recall reviewing that data with us and what's your perspective on that? Yeah. This is a very important question because the batoclimab is indeed a novel and innovative approach, meaning a monoclonal antibody blocking the effect of the FcRn. We know that the FcRn is inhibiting the degradation of pathogenic immunoglobulins. If you block the FcRn to protect actually the degradation of immunoglobulins, you are increasing the degradation of these pathogenic TSH receptor antibody. This is a novel, innovative approach, and this seems to be a specific approach because you are targeting the root cause of Graves' disease. You are markedly decreasing the concentration and the titer of the disease-specific biomarker. Excellent. Well, that's a really wide-ranging discussion we just had, George, covering the clinical presentation, the underlying pathophysiology, some existing therapies, and highlighting limitations in their use, and ending with, you know, I think a lot of enthusiasm for new innovation and, you know, this approach, which has sound mechanistic rationale. Now we're going to do a study to increase our scientific understanding of the effect of tocilizumab in Graves' disease, which I'm really looking forward to. Thanks again, George, for joining me for this discussion. It was really a lot of fun, as always, to speak with you about this condition. You are most welcome, Pete. Thank you so much. Great. Returning to the live discussion and slide 29. As Dr. Kahaly mentioned, the standard of care for Graves' disease leaves a meaningful percentage of patients unable to achieve normal thyroid function, and they remain symptomatic. Graves' disease is, of course, a classic autoantibody condition and a relatively straightforward indication to study, as the biomarkers T3 and T4 are actual thyroid hormones that are not just indicative of disease but are actually causing the symptoms, and in fact, they are the disease. We believe that FcRn inhibition offers a promising and a targeted approach to Graves' disease. Given this, on slide 30, there's a schematic for our newly designed phase II trial, focusing on refractory patients with moderate to severe Graves' disease who are insufficiently controlled on anti-thyroid drugs. These patients will all have positive anti-TSHR stimulating antibodies. The 24-week treatment period will study two doses with the intention of further defining the relationship between lowering anti-TSHR antibodies and normalizing thyroid hormone levels. This dosing approach includes higher IgG suppression in the first 12 weeks of the study and then more typical anti-FcRn-mediated IgG suppression in the second 12 weeks. Anti-thyroid drugs have a short half-life and will be down titrated to prevent hypothyroidism, meaning too little thyroid hormone. This study, which we plan to conduct at a single site with extensive experience in treating Graves' disease, will define the time course and dose response for the batoclimab in Graves' disease and thereby provide the information needed to set up a multicenter pivotal trial in the future, assuming success with the phase II. The primary endpoint is normalization of thyroid hormone levels on a lower dose of anti-thyroid drug or off anti-thyroid drug. Secondary endpoints will include immunologic seroconversion, meaning normalization of the stimulating autoantibody levels. For this target population, Graves' patients who are hyperthyroid despite treatment with anti-thyroid drugs, we would not anticipate spontaneous resolution over 24 weeks. In fact, in the placebo arm of our TED study, anti-TSHR antibodies did not fall. We also anticipate that the target population and endpoints will be the same or very similar in a future pivotal trial should the phase II succeed. Bottom line, we believe the phase II, if successful, will be de-risking for a phase III and provide us the information we need to design the phase III trial. To recap our rationale for studying Graves' disease and our approach to clinical development, we believe there's a high unmet need and promising opportunity to provide efficacy to those without a good option today. Our approach is to leverage the generally easy-to-identify subjects with elevated thyroid hormone levels despite anti-thyroid drugs. We are studying well-validated clinical endpoints that correlate with the disease state. We believe the scientific rationale is strong, in part because of the unique data that we possess from our TED2b trial. Looking forward, we believe the learning from this phase II trial and likely similarities in both study population and trial endpoints for pivotal development represent a compelling de-risked path to phase III in Graves' if successful in phase II. Circling back to where I started today, we are excited to announce today our expanded development program for batoclimab. After a rigorous indication evaluation process, we believe we have selected two new indications for CIDP and Graves' with a high unmet need and a high scientific rationale for success and potential for first-in-class or best-in-class opportunities. These will also complement our other announced programs. Furthermore, we are now planning a regular cadence of data releases approximately every six months, starting in the H2 of 2023 through our previously announced pivotal top line readouts in MG and TED. With that, I'd like to thank you for your time and open up the call to questions. Thank you, Pete. At this time, we'll begin conducting our Q&A session. As a reminder to the audience, you may submit your questions through the Q&A function at the bottom of the webcast player. To our analysts, please raise your hand to indicate you would like to join the queue. With that, I'll take the first question from Mike Kratky at SVB Securities. Hi, everyone. This is Mike on for Tom. Thanks for taking our questions. Two from our end, and the first is, how will you decide whether you'll need a second CIDP study, and at what point will we have clarity there? Secondly, can you just discuss what results we should expect to get from the initial results in Graves' disease in the H2 of 2023? Will the full results be needed to advance this asset into a pivotal study? Thanks, Mike. With regard to our CIDP development program, if you look on ClinicalTrials.gov, the argenx program lists 400 participants, and the Janssen program lists 300 participants. These are event-driven trials, and so the actual final number of participants can vary a little bit, the trial reaching its power when a certain number of events have been achieved. Our trial, as I noted, is smaller, and we're starting out with a plan to randomize 100 patients in Cohort A into Period 1. The decision on whether to expand the size of this trial as it's designed or add a slightly modified second trial in parallel will be based on the published results from the argenx trial as well as information we'll gain from the open-label Period 1 of our trial. There might be other information also that comes, that becomes known over time, but I anticipate that those are probably the two most important pieces of information that will determine whether our best path to a differentiated label is to expand the current trial or add a second trial in parallel. With regard to Graves' disease, what we expect to share in the H2 of 2023 is the experience on a good number of patients. Well, what will be a good number? The trial is designed for enrollment of up to 40 patients who meet those criteria that I mentioned. It could be the case that after 15 or more, we have a good sense of the response rate that we're observing. We'll also be measuring response not only at the 24-week primary endpoint but also at 12 weeks, and we have the two different doses. The results that we'll share in the H2 of 2023 will give a good picture of how well batoclimab is working in Graves' disease to achieve what will be important both for phase II and for phase III, which is to normalize thyroid hormone levels. That information is likely going to be sufficient to allow us to prepare for an end of phase II meeting that we would then execute after the phase II trial was completed in the early part of 2024. Got it. Thanks so much for the clarity there. Yeah. Thanks for the questions, Mike. Thanks for the question, Mike. The next question comes from Yatin Suneja from Guggenheim. Hey, guys. Can you hear me? We can. Oh, perfect. Thank you. Thank you for that presentation. Very, very helpful. Couple questions from me, starting with the CIDP. Can you just talk a little bit about the mechanism? It is our understanding that FcRn has a similar mechanism as IVIG, but a little bit more narrowed or more targeted. Using this mechanism, could we get a similar level of benefit that we get with IVIG? That's first part. The second part is that it is our understanding that there are a couple buckets of CIDP patients, some that have antibodies that are identified, some that where we don't know the defined antibodies. What type of patient do you expect? Do you expect similar benefit across all subtypes of CIDP patients? Thank you. Yeah, two great questions. Some sub-questions there are really important. With regard to CIDP and the potential for anti-FcRn and how to compare potential results with anti-FcRn to those that have been observed with IVIG, I think across a lot of different indications, IVIG has been a pretty good proxy for likely benefit with anti-FcRn because there is mechanistic overlap, as you mentioned. You correctly point out that IVIG has likely effects beyond just reducing IgG. It competitively binds with a person's endogenous IgG, and so inhibits the FcRn receptor by that mechanism, whereas anti-FcRn. It does some other things as well, binding to Fc gamma receptors, et cetera. Whereas anti-FcRn is targeted to just the FcRn receptor. That is narrower, which probably explains why the tolerability of anti-FcRn seems to be much better than IVIG. The other advantage that FcRn has is the targeted binding to the Fc receptor yields greater reductions in endogenous IgG. Certainly for batoclimab, as you know, and I mentioned on this call, we've observed reductions in IgG, meaning the patient's IgG, as great as 80% with a 680 mg dose delivered subcutaneously. It's a little bit harder to measure the reduction in the endogenous IgG when you're giving IVIG, but the estimates are in the 50%-55% reduction range there. To the extent that an autoantibody is important, as we believe it is in CIDP and other conditions, anti-FcRn inhibition with a potent FcRn inhibitor such as batoclimab is likely to reduce autoantibodies even greater than IVIG. Where will that all net out? That's, you know, I think that's what we're gonna see, but we're very optimistic that that's gonna net out in a good way, particularly with the enrichments that we have in the trial. I'll come back to that in a second, but I wanna address your second question, which is the role of autoantibodies and, you know, and a similar question could be, will an FcRn only work where an autoantibody is identified? The answer is probably not. Ironically, some of the variants of CIDP where an autoantibody have been identified are affecting parts of the nerve that are more distal or more likely to have permanent damage. Some of those variants of CIDP with an autoantibody, such as nodopathy, which has actually been carved out of CIDP, don't respond as well to IVIG. The autoantibodies affecting the myelin sheath or patients who have those antibodies, whether you can identify it or not, those are the patients that are most likely most responsive to a therapy like an anti-FcRn because the myelin is more amenable to re-healing once the autoantibody has been removed. You can't rely on the presence of autoantibodies in CIDP to select patients. That's the bottom line. What do you do to ensure that you have the right patients in your trial? Well, I think the experience with non-enriched trials shows that you really need enrichment. If you go directly from withdrawing standard of care right into randomization, there's a high risk that the placebo group doesn't flare and your trial fails because of that. The double enrichment strategy introduced by argenx ensures to a large extent that only those patients who have active disease will move forward. The second part of the enrichment, where they need to respond to open label therapy, is gonna select for those patients who are, again, likely to be amenable to anti-FcRn therapy. We're enhancing this strategy by adding a third enrichment that I discussed during the call today, where our primary endpoint is focused on the IVIG PLEX group, where we believe the effect size will be the largest. Okay. If I may, could I ask one more? Please. Just commercial question on the CIDP? Fast-forward, let's say the FcRn's work. Just talk about the commercial dynamic. Are there sets of patients or a particular group of patient where you think the adoption will be first? And what do you really have to show given IVIG obviously is effective in about 60%-70% of the patients? Right. Maybe take the second question first. What do you need to show? You know, the trials are done by withdrawing standard of care, and then you demonstrate that, the investigational product, in our case, batoclimab, can recapture the worsening of disease that happens when you withdraw the standard of care, so you recapture the health of the patient, and then you maintain it. That's what you need to show, and you need to show that when standard of care is withdrawn, and you go through the enrichment, and eventually people go on to a placebo that then they get worse. You're preventing worsening. What the eventual label will look like, I think, we'll have to see exactly what the indicated population is. I think in terms of actual practice, it may not matter that much. That's because the vast majority of patients with CIDP are already being treated with IVIG in the United States. The pool of patients that are going to be treated with an anti-FcRn is not gonna be the few newly diagnosed CIDP patients each year, but rather people who are doing well on IVIG, but they're really suffering from the logistical burden or and/or the side effects that Doctors Katz and Levine highlighted. They wanna get away from, you know, a couple hour infusion, couple days a month of not feeling well and have a therapy that's just as efficacious but doesn't come with those burdens. Ideally, if it can be administered by a simple sub-Q that they just, you know, do themselves over a, you know, over 5 seconds-10 seconds at home. Thank you. Does that answer your question, Yatin? Yes. Very, very helpful. Thank you. Okay, great. Thanks for the questions, Yatin. The next question comes from Alex Nackenoff at Raymond James. Hey, guys. Thanks for taking the question. This is Alex on for Danielle. Just a quick one. What are the LDL mitigation strategies going to be for these trials? Are they gonna be similar to how you've designed MG and TED? Correct. These are during the 24-week treatment period. LDL and albumin will be measured in the background, but won't be provided to the investigators because that would be unblinding and the short-term excursions in LDL don't require management from our perspective. We have agreement with regulators on that point. During the long-term extension, the investigator would have an opportunity to see those values, and if there were to be a persistent change that they wanted to address, then they can treat them during the long-term extension. Great. Thanks for the color. Yeah. Thanks, Alex. Thanks for the question, Alex. The next question comes from Samuel Slutsky at LifeSci Capital. Hey, good morning, everyone. Thanks for the questions. A few from me. This first, for the phase II Graves' study, what magnitude of efficacy are you hoping to see to justify going into phase III of the program? Yeah, that's a great question, Sam. For the patient population that we're enrolling into the Graves' trial, as I mentioned during the call, we wouldn't expect them to improve over the 24 weeks. You know, these are patients who've been treated for at least 12 weeks with an anti-thyroid drug. They're still hyperthyroid on maximally tolerated dose, and they're symptomatic. They've got, you know, they've got a lot of reason to need a new therapy. During the 24-week period, since we wouldn't expect really any resolution if there were a placebo arm that we'd eventually have in the phase III, and because these patients are so symptomatic and because T3, T4 is essentially the disease itself, an improvement of, you know, getting 30%-35% of those patients euthyroid on a much lower dose of anti-thyroid drug or off anti-thyroid drug, I think would be the minimum bar, you know, for success that would offer a really promising commercial opportunity and a great solution for patients. Got it. Okay. I think I heard you mention that some patients in the prior TED study may have saw some signs of benefit of their Graves' disease. Just anything in particular that you're able to quantify or just provide more color on? Yeah, nothing we're able to quantify. It's all anecdotal. The patients in our TED protocol, and this is the same for our phase IIIs, excludes people who are hyperthyroid. The population that we'll enroll in the Graves' disease is different than the population in the TED. We don't want the TED trial to be complicated by uncontrolled hyperthyroidism. That said, there were some people in the TED trial who were euthyroid, meaning their thyroid hormones had normalized. Most of them were on a lower dose of methimazole. Again, their Graves' wasn't their main problem. TED was their main problem. With all those caveats, some of those patients did have their methimazole titrated down over the course of the treatment period during the TED trial, even though they don't really represent the right population to be studied. There, there's some encouraging anecdotes, but no kind of quantitative summary data that I can provide. That's what the Graves' is for. Got it. Just last one for me on wAIHA. You know, you'd mentioned that you're gonna meet with the FDA in the H2 of this year, but curious on how you're thinking about that indication overall versus the multitude of other indications where FcRn inhibition should work. Should we expect kind of the next study to be wAIHA after these next two launch or just kind of where is it falling priorities? Yeah, absolutely. We're still committed to wAIHA. The sequencing of the trials, you know, as reflected by today's announcement, we're sequencing CIDP and Graves' just a little bit in front of our wAIHA. We'll have a meeting with the heme division later this year to ensure we can have the best trial design. We have some creative ideas there that we think could lead to potentially more efficient path to registration, but we need to have a discussion with the division on those. We wanted to get going with CIDP and Graves, given the therapeutic synergies in neurology and endocrinology between these two conditions and our, you know, our two programs that we're already starting to get up and running in MG and TED. This was a sequencing decision, not a prioritization decision. Got it. Thanks. Thanks for the question, Sam. The next question comes from Douglas Tsao at H.C. Wainwright. Hi. Good morning. Thanks for taking the questions. Just curious, Pete, how you're thinking about sort of adding new indications. Obviously today with Graves as well as CIDP, you're deepening your presence in neurology and endocrinology. Obviously with wAIHA, you have something in hematology. Is that a priority or how do you think about going deeper within an existing TA for the company versus perhaps expanding into a new therapeutic area? Yeah, really great question, Doug. You know, there's a lot of variables to consider, and you've hit on many of the important ones. When considering new indications, which we're still continuing to do because we anticipate having more indications in the future beyond the five that are announced. The two main things that we look at sort of first and foremost are how likely is it that, and we believe an anti-FcRn is likely to work, and how large is the unmet need? What's the sort of patient demand for innovation? They need new efficacious therapy to what extent? Those are sort of the two most important things. There's many indications that kinda make it through that filter with a relatively equally compelling, you know, kind of, score. The next question is, well, are there any synergies therapeutically? Those synergies are really important not only in development, but certainly at the time of launch. Having multiple indications within a particular therapeutic area can be really helpful. The first order of decision is the probability of technical success and the degree of unmet need. wAIHA is in that in the same bucket, I think, as the others on those two dimensions. As you point out, we don't have another announced indication in hematology. As we looked at our current portfolio of five indications, we chose to sequence CIDP and Graves you know to start them now. The wAIHA is just, you know, just right behind there. We have that FDA interaction coming up that I mentioned. Okay, great. Maybe as a follow-up to one of the earlier questions in terms of Graves' disease and the phase II, you're not doing a placebo arm. Do you have sort of benchmarks in terms of what you're thinking about in terms of the response rates you're thinking about? How do you think about, you know, sort of your powering and just sort of getting comfort that you're gonna see the separation needed ultimately in a pivotal study? Right. Exactly. We'll learn a lot from the phase II. In particular, we will learn, you know, the dose response between batoclimab in a larger number of patients studied more carefully and enrolling the target patient, which is a person who's still hyperthyroid in spite of antithyroid drug. How does someone like that, as their stimulating antibodies come down, what happens to the thyroid hormones, both the T3 and T4? What's the time course there? Importantly, what's the pace of titrating down their antithyroid drug? The antithyroid drugs have methimazole, has a very short half-life, so the down titration is gonna be tricky. By doing this at a single site, you know, we can kinda manage that with the expertise of the principal investigator. Going forward to phase III, we're gonna wanna have some specific just kinda protocolized parameters. All that information will then get to your question, which is powering the phase III. We'll be able to estimate, I think with good accuracy what is our likely effect gonna be in the batoclimab arm. Then, you know, we'll have some assumption for a placebo that'll be conservative, but again we wouldn't expect in a short-term trial much change in the placebo arm. Putting all that together, we'll get a, you know, a power calculation for our phase III. I think that'll be a relatively easy process to run once we have the data from the phase II trial. Okay, great. Thank you so much. Yeah. Thanks, Doug. Thanks for the questions, Doug. The next question comes from Robyn Karnauskas at Truist Securities. Hi. Thank you for taking my question. I know you mentioned the standard enrichment step, and I thought maybe you could just, you know, not only IVIG or PLEX, but I think you on one slide said you could be on steroids, just confirm that. Help us understand like what that could do to the outcome of the trial. When we see data from competitors, how do we think about adding that enrichment step and what the impact might have? I guess another way to ask that question is, in a normal study population like this, what percentage of patients would not be on IVIG or PLEX? The second question is, if you think about your cash runway through 2025, if you had to enroll a second study or enlarge the study for CIDP, or even begin more studies in wAIHA, does that cash runway guidance include that? Thanks. Thanks, Robyn. A bunch of really good questions there. First of all, really, really importantly, to clarify who is in cohort A, which is the primary analysis cohort for the CIDP trial. I may have misspoke somewhere along the line, but just to be super clear, there are no patients whose standard of care is steroids in that group. The three types of standard of care that can get you into cohort A would be IVIG, subcutaneously administered IG or subQIG, or PLEX. Most of those people will probably be on IVIG or subQIG, but all three of those, essentially an IgG lowering standard of care gets you into cohort A. If in the other trials, as far as we can tell from what's publicly available, those patients, as well as people who are on steroids for their standard of care, are blended into a blended cohort, you know, it's not a cohort anymore. It's just a population that's blended. What's the percentage on them in those other trials is gonna be highly dependent on a lot of factors that wouldn't really be easy to glean from the outside. It would depend on what countries are running the studies in, whether there's any controls to try and get a certain percentage in one or the other. You know, in some of the IVIG trials that were done with similar types of populations of, you know, treated people with CIDP, there were roughly equal proportions of patients who enrolled who had their standard of care was an IgG lowering or steroids. Why are we doing the third enrichment? The reason we're doing that third enrichment is we expect people who are treated with steroids as their standard of care to not be fully tapered as a general rule. When they go through the washout, and retreatment with open label, they're not gonna fully come off their steroids, so they're gonna enter the randomized placebo-controlled portion of the trial still partially treated, and therefore the total potential effect size available to be demonstrated by the investigational product may not be as large in the steroid group. If you have a blended group of a blended population that has some who have a high effect size and some who have a little bit lower effect size, and that's gonna obviously, you know, give you a more modest average. We're looking to just have the IgG, SCIg or PLEX cohort in our primary analysis, then they're likely to have the largest effect size. That's, I think that may have gotten the questions about the cohort strategy, but maybe I may as well stop there and see if I got all those, Robyn, or if you had any other follow-up question on that specifically. T hat's great. Just the cash would be great. That'd be helpful, thanks. Yeah. The cash runway that we have through into 2025 includes the pivotal trial for CIDP. It includes MG, TED, and two phase IIs and all the various things to run those. There's a lot of uncertainty with the CIDP trial because it's an event-driven trial, and in terms of the rate of enrollment and the rate of events, there's a fair amount of play there. We've left ourselves a fair amount of wiggle room in terms of forecasting there, which enables us, you know, some flexibility. We don't have in our cash runway an entirely equally sized second pivotal trial, but that trial could be increased in size at some point within our cash runway. Great. Thanks for the questions, Robyn. The next question and last question comes from Colin Bristow from UBS. Hey, thanks a lot. Can you guys hear me okay? We can, Colin. Super. Well, congrats on all the progress. A couple on CIDP from me. You know, you mentioned challenges finding patients with active CIDP. What's your level of concern just given others are also pursuing active patients? And what's your sense of the screen out rate you're expecting given the sort of extensive enrichment strategy? And then the second question is, you know, you mentioned this not being a one disease. Can you talk about your confidence and the sort of evidentiary level for the consistency of the pathophysiology here? Thanks. Yeah, some really good questions, there, Colin. In terms of the, you know, the efficiency of the trial and our confidence in finding people with active disease, we're pretty confident. We've got the, you know, the. I think this approach has been refined. I think, the double enrichment strategy that, argenx introduced and it appears Janssen is using as well, together with a really carefully specified set of criteria that, ensure not only that people have active CIDP, but the more treatable CIDP, which is typically more proximal and things like that. You know, that's all good versus a more of an all-comers approach that was employed in the past. We've put some additional enrichment on top of that. The change to the efficiency of a trial by having the third enrichment, which is the IVIG PLEX arm, doesn't really impact negatively. You know, the washout relapse rate or the response rate in the Period 1 open-label. In fact, it should do the opposite. It should actually. You know, our prediction is that those patients are gonna be more likely to relapse 'cause you can totally withdraw their standard of care, and they'll be more likely to respond to an anti-FcRn because IgG is more narrow than steroids. I think you know, we're getting efficiency by making those changes. That's something we'll be you know, monitoring. We'll have to see as the trial unfolds. In terms of the underlying pathophysiology, I think the algorithm, adding the algorithm to the really carefully specified inclusion criteria and adjudication committee just ensures that we're gonna do the scoring correctly. I think the scoring is actually pretty well described now in terms of who are the types of patients that are likely to be both active and responsive. The algorithm adds an extra level of discipline to just make sure that scoring's done really well. Whether a person has an identified autoantibody or not, the double, and for us, triple enrichment, you know, is going to do a really good job on top of that algorithmic strategy to weed out those patients who are not likely to respond to therapy in the context of a clinical trial. That's great. Thank you. Okay. Thanks, Colin. Thanks, Colin. Pete, that wraps up the Q&A session, so I'll hand it back to you for concluding remarks. Thank you, Sarah. We're really excited about the potential of batoclimab in these two new indications, and I very much appreciate everyone's time this morning, and thank you for joining us. That concludes today's call.