... Good day, and thank you for standing by. Welcome to the Immunovant Graves' Disease Data Update Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, we'll open up for questions. To ask a question during the session, you will need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I would now like to hand the call over to your first speaker today, Stephanie Lee. Please go ahead.
Good afternoon, and thanks for joining today's call to review the Immunovant Graves' disease data. I'm Stephanie Lee with Roivant. Presenting today, we have Matt Gline, CEO of Roivant. For those dialing in via conference call, you can find the slides being presented today, as well as the press release announcing these updates on our IR website at www.investor.roivant.com. We'll also be providing the current slide numbers as we present to help you follow along. I would like to remind you that we will be making certain forward-looking statements during today's presentation. We strongly encourage you to review the information that we have filed with the SEC for more information regarding these forward-looking statements and related risks and uncertainties. With that, I'll turn it over to Matt.
Thank you, Stephanie, and thank you, everybody, for dialing in this afternoon on short notice. It's an exciting opportunity to get together today, midday. The American Thyroid Association abstracts went live, and with it, a presentation of our follow-up data for our Graves' disease study went live. There's just some really, really exciting updates in that data set. I wanted to get on the phone with everybody and walk through it. I'm gonna start on slide three with just a little bit of an overview of what I think are the most important messages, and then we'll go through a little bit of disease background and the data in more detail.
Look, in short, so as a reminder, the data that we're presenting today, the data that's being presented today, is data. The main portion of the study, the 24-week treatment, we presented on that data about a year ago. And since then, we have been following the patients in that study for six months of off-therapy follow-ups. These are patients who have not been on batoclimab for six months at the time of this update. And the sort of truly remarkable two things that we've seen during that period are, again, a full 80% of patients who entered the off-treatment follow-up period had a response. They were responders to therapy six months after they had been off therapy.
17 out of the 21 patients who went into the off-treatment follow-up period were still responders after six months of no therapy. So that really speaks to the potential for this as a disease-modifying therapy. We have changed the course of these Graves' patients, all of whom entered the study overall uncontrolled, and now 17 out of 21 of those patients, or seventeen out of the 25 in total, are controlled six months after cessation of therapy. And we've seen very good remission data. Of those 17 responders, nearly half of them, eight of the `17 patients, were off antithyroid drugs while being controlled. So they were not only responders, but they were responders and off antithyroid drugs six months after the cessation of FcRn therapy. So a pretty great outcome.
Two points, the potential for disease modification and a really strong rate of remission that we are very proud of and excited to be presenting today. I want to very briefly just remind everybody on Graves' disease, kind of what it is, why we care, a little bit of the opportunity and the unmet need, and then I'll dig into the study and the data. Starting again, super briefly on the background stuff on slide five. Look, Graves' is an autoimmune disease driven by the presence of autoantibodies that effectively attack the thyroid and lead to an overactive thyroid. In a normal thyroid, there's this sort of regulatory cycle where TSH causes the thyroid to be active, the thyroid produces thyroid hormones, and those hormones impacts your thyroid regulation.
In Graves' disease patients, autoantibodies are attacking the thyroid in a way that leads to increased production of T3 and T4 without the regulatory mechanism kicking in, and so you wind up with a dysregulated, overactive thyroid. On slide six, there are many, many Graves' disease patients. There's a full treatment hierarchy in the back of this presentation, but many, many patients. A good % of them on first-line therapy manage to get controlled with antithyroid drugs or have ablation, either surgical removal of the thyroid or radioactive ablation. The truth, though, is over time, first of all, a significant % of patients simply fail. And second of all, some of them simply can't maintain; they either relapse or they cannot maintain control on antithyroid drugs.
And that's about 25%-30% of the total Graves' population in America wind up with either relapse or they are uncontrolled or intolerant to ATD. So a large %. That comes out to about 330,000, sort of prevalent, sort of circulating in the world, uncontrolled Graves' patients in the U.S.. This is a severe disease on slide seven. People really need to care. There's a whole bunch of risks that are elevated in these patients. The risk of cardiovascular disease is 2.5x higher in the Graves' population than the overall population. Patients are four times more likely to have preeclampsia and seven times more likely to have thyroid cancer. So this is a severe disease with severe comorbidities. Insufficiently treated Graves' populations can go on...
Graves' patients can go on to develop thyroid eye disease. It affects about 40% of patients diagnosed with Graves' disease, including a meaningful % of those patients who experience, like, optic neuropathy. Impairment of visual function can lead to blindness. And then there's some other significant complications, such as a thyroid storm, some % of hospitalized patients with Graves' disease, which can cause mortality, as well as a high risk of recurrent thyroid cancer in Graves' disease who develop thyroid cancer. So a lot of severe comorbidities and severe consequences of having Graves' disease. It's a high unmet need on slide eight.
As I said, 25%-30% of patients are uncontrolled on existing therapies, and there really is no other second-line therapy for these patients other than antithyroid drugs. There are no existing disease-modifying therapies for these uncontrolled patients. So if you're uncontrolled, you're either sick for life or having your thyroid removed. And patients with uncontrolled Graves' disease, as we just went into, experience a range of severe comorbidities. And there are 65,000 incident patients and a very large prevalent pool of patients who are uncontrolled but choose not to undergo thyroid ablation. So okay, getting to the data for today, starting on slide 10.
So just as a reminder of what we're doing, this is a picture of the schema for the Phase II trial that we've now run for batoclimab in Graves' disease. As a reminder, these patients entered the trial with active Graves' disease and uncontrolled hyperthyroid, despite ATD therapy. So these were all patients who were refractory to every available therapeutic treatment option. They went through 24 weeks of treatment. First, 12 weeks on high-dose batoclimab, followed by 12 weeks on low-dose batoclimab, with step-down at week 12, and then they were modified for... Sorry, modified. They were observed or followed up with for 24 weeks after the cessation of therapy.
The data that we presented in 2024 was for the left-hand side of this, before the blue box, was for the 24-week treatment period, and there were 25 patients who entered the trial and were dosed for 25, 24 weeks, and those are the patients who we've already previously reported on. 21 of those patients entered the off-therapy follow-up period, and we have data today that we're presenting for the off-treatment period. And so that's the data that we'll be talking through today. As a reminder, the baseline characteristics of this population on slide 11 was representative of an uncontrolled population despite ATD use. They were sort of normal in age.
This population skews female, the Graves' population skews female, and they had elevated free T3 and free T4 and elevated TRAb levels to a significant degree. Okay, so now for the exciting bit, starting on slide 12 with some of the new data. So some of this is a representation of some of the data we put out last year, but just to sort of walk people through the study. 25 uncontrolled Graves' disease patients entered the study at baseline. First of all, a pretty great treatment effect. 20 out of those 25 patients at the end of week 12 had thyroid hormone levels, T3 and T4, below the upper limit of normal, so normalized thyroid hormone levels for hyperthyroid patients and had ATD doses that were at least at or below their baseline level.
And at week 24, there were still, even though there had been a step-down therapy, 18 patients. So a couple of notes there. One is, and we've talked about this before, a helpful fact for us overall, given that we have the deepest IgG suppression practically of any anti-FcRn antibody, is we saw our best response rates for the high-dose portion, and patients deteriorated somewhat during the step-down portion. And what's not clear from this picture, but is clear from the previously presented data, is that of those 18 out of 25, some of them had to step up ATD dose relative to their efficacy at week 12. So patients got worse when we stepped down therapy. Again, helpful because we believe that IMVT-1402 will have the deepest IgG suppression of any anti-FcRn antibody.
Now, the new data for today, the really sort of remarkable effect, is 18 out of 25 patients were responders at week 24. After 24 weeks of being off drug, so at week 48, these patients had been off drug for six months. Still, 17 out of the 21 patients for whom we had data were responders. So 80% of the patients for whom we had data at week 48 were responders to therapy, which to me, and we'll talk a little bit more about this from a pathophysiology perspective in a moment, this is just clear evidence of disease-modifying potential for this therapy. That patients who were uncontrolled at the beginning of the study were able to be controlled, were responders to therapy, even six months after discontinuing the batoclimab. So that was a great data point.
On slide 13, the other exciting data point here that we're sort of putting out there is of those 17 responders, first of all, nearly half of them were fully in drug-free remission. So 47%, 8 of these 17 patients, were ATD-free at week 48. They were on no antithyroid drugs. These are patients who, despite use of antithyroid drugs, could not be controlled at the start of the study, are controlled and off antithyroid drugs at week 48. Another close to 30%, 29% of these patients, another five patients, are on really the lowest dose of ATDs, two and a half milligrams, and only less than a quarter of them, only another four patients, were on greater than two and a half milligrams of ATDs.
So tremendous remission data for an uncontrolled patient population that shows that not only can we be disease-modifying, but for a significant % of patients, we can get them off antithyroid drugs. There's one other data point that really supports this disease-modifying benefit on slide 14, and it's remarkable in just how clean the picture is. So as you would expect, so this is a chart that shows during the treatment period and after, both IgG levels relative to baseline and TRAb, antithyroid antibody levels, during and after the period. And what you can see is exactly what you would expect for an anti-FcRn antibody. You get rapid suppression of both IgG generally and specifically TRAbs during the high-dose treatment period.
Those numbers come up somewhat during the low-dose treatment period, less control of IgG, some amount of increase in thyroid hormone levels, and then during the off-treatment follow-up period, you see exactly what you'd expect. The only data point in here is the week 48 data point. We haven't filled in any of these curves, but by week 48, all of these patients have basically returned to normal pre-treatment baseline levels of IgG, but the TRAb levels stay low. So these patients have had the course of their Graves' disease changed, whereas previously their TRAb levels were high. My audio has cut out. Am I back now? Great. It sounds like I'm back now. So I'm just gonna repeat slide 14 in case I missed that.
So on slide 14, again, this shows the course of treatment for these patients. It shows IgG levels as well as antithyroid antibody levels during the treatment. It shows that during the high dose portion of the treatment, both IgG levels and TRAb levels were nicely suppressed to a significant degree, but that suppression got slightly worse when we stepped down to lower dose therapy. That IgG levels recovered a little bit, that TRAb levels recovered a little bit, and then notably, these curves diverged during the off-treatment follow. So the only data point here is the 48-week data point, but you can see these patients returned to normal IgG levels at week 48, despite their TRAb levels remaining low.
That is, the course of disease for these patients was altered, and they had sort of normal TRAb levels, which coincides with their overall sort of clinical picture on the previous slides, while they had a meaningful benefit. We think this is a new scientific finding. It's an interesting finding. It merits further investigation, but it may very well be due to the ability of an anti-FcRn antibody to disrupt some of the feedback cycles at play in Graves' patients. Okay, a couple of more points, and then we'll go to Q&A. One is on slide 15, as a reminder, the batoclimab was well tolerated in the trial. There were no new safety signals identified. There was no sort of significant TEAEs, other than what we've previously talked about.
Nothing, nothing new to report from a safety perspective and consistent with what we've seen broadly from anti-FcRn antibodies and from batoclimab. Secondly, a reminder on slide 16. So the Phase III program for IMVT-1402 is underway with two registrational studies, two potentially registrational trials now running, and you can see the schematic on this slide for the batoclimab phase II that we're talking about today, as well as for the first of those two 1402 trials at the bottom, and as a reminder, the batoclimab phase II was certainly underoptimized in terms of how these patients were treated, right? They had to step down to lower dose, which did in fact reduce response rate. You can see the decline of response rate shown at the picture at the top.
Whereas the Phase III program, the Phase IIb , the pivotal program at the bottom, is clear. We are dosing even in the sort of group two patients that are designed to show the same remittive benefit. We're dosing at a high dose of IMVT-1402 for six months, which should give us the potential for a greater treatment effect with a greater number of responders and hopefully a greater remission and post-treatment effect for those patients. So we will find that out with that study. Again, both of the potentially registrational trials, 1402 , are now running. This is the schematic for the first of those studies. We will also have a 52-week treatment arm, where we'll treat 52 weeks of high-dose batoclimab, which should give us the opportunity to see potentially an even greater treatment benefit in patients on chronic therapy.
And in particular, we think there will be some patients for whom, look, remission or sort of a complete response may not be in the cards, and those patients may require chronic therapy. And we expect to show the benefit of long-duration therapy as well in that first study. So, wrapping it up before we go to Q&A, and again, a relatively short presentation today, but wanted to highlight this data. This is the potential, we think this is potentially a first-in-class, disease-modifying therapy in Graves' disease. We've seen a remarkable effect. First, 18 out of 25 patients treated were responders at week 24. Secondly, 17 out of 21 patients with whom we followed up, remained responders six months after the end of treatment.
We observed a close to 50% remission rate in those responders, with eight out of the 17 responders off all medications six months after the cessation of batoclimab. And we think the design for our pivotal program could potentially generate improved efficacy, with continuous 600 mg dosing vs the step down in the phase II, and both of those phase II studies have enrolled patients at this point. They are ongoing, with our data expected in 2027. So we're really looking forward to generating that data. We think this is super helpful in sort of explaining the benefit that we may have in these patients and in helping, we hope, the world see just how excited we are about the use of IMVT-1402 in Graves' disease.
With that, I will conclude my prepared remarks and hand it over to the operator for Q&A. Thank you, everybody.
Thank you. As a reminder, to ask a question, you will need to press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. One moment for our first question. Our first question will come from the line of Sam Slutsky from LifeSci Capital. Your line is open.
Hey, good afternoon, everyone. Thanks for taking the questions and congrats on this update. Just kind of curious how the data looked between that week 24 and week 48 time points, and whether the week 48 data were kind of consistent across that whole time period, or did it bounce around a bit? And then, was there any predictors of those who had the best response at week 48 vs what their response was at week 24? So essentially, was there any correlation of being in remission at week 24 vs week 48, or just kind of any predictors there?
Yeah, thank you. That's a great question. Look, I think the short answer is, that the overall data throughout the time period was consistent. We're not showing the kinetics for competitive reasons. Graves' at this point is a competitive field, but in general, I would say consistent. And in general, I would say, look, for the most part, the responders and the stronger responders at week 24 are the ones who maintain a response through treatment. Thank you. Great question. I appreciate it.
Thank you. One moment for our next question. Our next question comes from the line of Yatin Suneja from Guggenheim. Your line is open.
Hey, guys. Two questions from me. Thank you so much. A very nice presentation. So the first one is on. Maybe if you can elaborate a little bit on this total IgG level and the TRAb levels, what exactly you are seeing from a correlation perspective? I understand that the TRAbs levels are down about 70% and you still are in remission, but the total IgG is still up. So I don't know what the disconnect is, or maybe I'm missing something. So that's one. And second, if you can just elaborate also on how the enrollment is going and what is the exact ATD titration protocol you are using in pivotal study and how that compared to phase II. Thank you.
Great. Thanks. Yeah, perfect. So on the IgG TRAb question, that's a super important question, and thank you. If I wasn't clear on this, I just want to highlight it again. This is on slide 14. So what you see during the first 24 weeks here is approximately exactly what you would expect to see from FcRn therapy. That is, what FcRn therapy does is reduce levels of IgG antibodies, and what you see is a commensurate and correlated reduction in both overall IgG levels as well as specifically TRAb levels. Those reductions are more pronounced during the higher dose period and less pronounced during the lower dose period. The disconnect that you see during the off-treatment period is those patients are no longer being treated with anti-FcRn antibody. So what you would expect to see is that antibody levels recover to pre-baseline levels, right?
They're not being treated, their IgG levels are not suppressed, and so therefore, what you would expect to see is an increase in IgG levels that brings them back to baseline, and that is exactly, in fact, exactly what you're seeing. What you see in many indications is a commensurate increase in autoantibody levels, right? In many indications, the quote, unquote, "only reason" why autoantibody levels are down is because you're suppressing IgG, and when you take away the IgG suppression, you see a more or less immediate and commensurate recovery. We do not see that here, and so instead, what we see is, despite the fact that overall antibody levels are recovering, these patients are effectively no longer producing TRAbs at the same level as they were prior to treatment, and so their TRAb levels remain suppressed.
And that is exactly the disease-modifying benefit that we are excited about, that by interrupting this feedback loop in some way, we are able to see sustained TRAb reductions even though therapy is discontinued. And that is why you see the disconnect or the correlation or the sort of lack of correlation from week 24- week 48. That's on the IgG and TRAb question. In terms of question two, look, on enrollment, I think it's fair to say we are happy with the enrollment overall. We have a lot of excited docs who are participating in the trial. We have a lot of sites active on both studies at this point, and we have patients enrolled in both studies. There's a lot of patient enthusiasm, a lot of physician enthusiasm.
Frankly, we get a lot of questions from docs over time about remission, about durability of response, and I think this data will be helpful in even further supercharging the enrollment on these studies. So we're happy to be putting it out because I think docs will absolutely react favorably, and we're excited to see what kind of reaction this data gets at ATA, when presented by George next week. So that's the first thing on enrollment. On ATD titration, the short answer to that question is the protocol has an aggressive titration of ATD pushed by the protocol. It is not forced to zero, but there's a forced attempt to get it to zero. T3 and T4 are normal, and I think that's about what we've said about the protocol at this point. Thank you.
Those are both good questions, and it's important to clarify that antibody data. Thank you.
One moment for our next question. Our next question will come from the line of Samantha Semenkow from Citi. Your line is open.
Hi, good afternoon. Thanks very much for taking the question. Apologies if this has been asked, but maybe could you talk a little bit about what the potential remission rate could be if we're looking at the patients not stepping down to 340 milligrams? I'm curious if it gets above what you've seen in this proof of concept study. Thanks very much.
Yeah, thank you. It's a great question that has not been asked. Look, I think it's a difficult question to answer mechanically because it's speculation, but I think just based on what we see, even for the difference between the patient sort of outcomes at the end of week 12 vs at week 24, first of all, a higher rate of controlled patient, a higher rate of responders at the end of week 12 than at week 24. And second of all, again, though it's not in this deck, it's in some of the prior materials, more of the patients at the end of week 12 are ATD-free than at week 24, which means there has been a mechanical step up in ATD dose in order to maintain response during the lower treatment, the lower dose treatment period.
I think it sort of very strongly seems that we will get to better control at higher dose, a greater number of responders, a greater number of ATD responders at the end of the treatment period, and that it seems from the data we've generated here, like that should lead to a higher rate of remission. But obviously, that is the thing we are testing in phase III. Remember, there's also an arm that will show 52 weeks of treatment at the high dose, and I would expect to see potentially even higher rates of response at the end of 52 weeks of therapy, and potentially to see even better rates, therefore, of remission for the 52-week cohort on follow-up after that.
But again, the phase III is really designed to look at treatment effect on drug for 52 weeks for the high-dose cohort and then remission benefit for the sort of group two, the cycle after six months. Thanks. It's a great question, and it's obviously an important factor for the phase III.
Very helpful. Thank you.
Thank you.
One moment for our next question. Our next question will come from the line of David Risinger from Leerink Partners. Your line is open.
Yes, thanks very much. And congrats, Matt. It's great to see the results. So could you talk a little bit about, you know, what this data may imply for 1402 in other disease states? That you're testing? And then, specifically with respect to Graves' disease, are you evaluating longer duration off treatment effects? And how are you thinking about this commercially if patients can see such a sustained benefit off drug over the long term? Thanks so much.
Yeah, great. Thanks, Dave. Those are both really, really good questions. Look, I think in terms of the implication for other disease states, obviously, a thing that we were happy with with the Graves' data originally, just the way the study was designed, was that we felt it showed benefit from deeper IgG suppression. And we think we've shown that consistently across several indications at this point with batoclimab, and bluntly, we hope to continue to see that, and we think this data is supportive. I don't know that it implies there will be remission off drug in other indications. And frankly, what you see in many indications is that when you withdraw FcRn treatment, autoantibody levels come right back, which means I don't think in those diseases you'll see remission.
I think what we found here, which makes us really proud of, of our scientific choice in Graves' disease, is that there is something special about Graves' disease, where mechanistically you have these enlarged thyroids, you have the body sort of producing autoantibodies, in part because of the Graves' disease. And once you suppress the antibody levels, you sort of break this sort of nasty feedback cycle, and you get away from, you know, producing the antibodies to begin with. I think that, that appears to be potentially specific to Graves. It opens a question what other indications might be like that, but I think in many FcRn indications, this is not the pattern that you see. Specifically with respect to Graves' disease, you know, are we evaluating longer duration of treatment?
I think the answer to that question is we are planning to continue to follow off-drug effects in all of these studies, and I think it will allow us to generate even longer-term data. You know, commercially, what I think is clear from the data set we've generated here is there's just gonna be a diversity of treatment effects and a diversity of treatment durations. Some patients are gonna be very sick and are gonna need potentially, like, chronic, long, long, long duration of therapy in order to maintain control. Some patients may need a year of therapy, eighteen months of therapy, longer in order to get control, but once they get controlled, potentially have the possibility of remission.
And some patients may get to, you know, ATD-free control during a shorter period of treatment and may be able to get off drug or may be able to take a holiday. And we don't know yet, based on the studies we've run, whether some of those patients will ultimately have flare-ups and recurrence of disease or not. It will ultimately depend on the etiology of their Graves' disease, and because it's such new science, I think we just, like, we won't know that fully until we get a little further along. There are some hints from what you see with methimazole, where some methimazole patients go on methimazole, get their Graves' disease under control, and then never have a relapse. Some Graves' disease patients go on methimazole for a period of time, see improvements, get off methimazole, are in remission, and then have a recurrence.
Some Graves' disease go on methimazole and can never come off it because they simply can't get disease control. So I think- I think we'll likely see something similar in the Graves' population. And thank you. It's a great question, and it's one that's top of mind for us.
Thank you.
One moment for our next question. Our next question comes from the line of Yaron Werber from TD Cowen. Your line is open.
Great. Thanks so much for doing the call and terrific data. Matt, maybe just a question to zoom out and just give us a little bit of a sense of the strategy between the development program. The one study, the one you showed us, the 240 patients, that looked like started December late 2024. It has a host of secondary endpoints, and that's the one that's testing 26 and 52 weeks, right? And then you have a second-
Correct.
Study that you just started about a couple of months ago, right? So that's 210 patients, and that's only dosing for 26 weeks. Two different dose levels. That's the one you're not showing us here. What, how is the second study differ, and why is it only 26 weeks? It sounds like you're not doing the second 26 weeks as part of that protocol. Maybe the strategy behind that.
Yeah, perfect. Thank you. These are great questions. By the way, for anyone's reference, the design of both of the full schemas for both of these studies is shown on slides 22 and 23 in the deck. I didn't walk through them in the presentation today, but they're available for anyone who wants to look. Look, I think a few things here. First of all, the benefit of the 52-week study was, A, to show very long duration treatment in support of chronic therapy for patients who really need it, in support of maximum benefit for patients who really need it.
And B, to have that group two that looked at remission, where we could take a group of patients off therapy after six months, which you know gives us some interesting and useful commercial data, frankly, aligned with the data that we've generated, hopefully today. And so I think that's sort of the point of the longer study. In general, based on the phase II, we're confident in the treatment effect at 26 weeks. Obviously, we need two studies for approval. And so the second study is designed in large part for regulatory support. That is, designed to give us an additional study with appropriate data, including at multiple dose levels. And the FDA has obviously looked at these designs and is overall aligned with our plan here.
And so I think the, you know, the point in aggregate is to get the data we need for regulatory approval, regulatory submission, as well as to generate commercially important data for patients around remission and longer treatment effects in the first study. The reason it went in the order you observed is we started enrolling the longer trial first, so that we had a hope of reading them both out at a relatively comparable time point.
One moment for our next question.
Thank you.
The next question comes from the line of Yasmeen Rahimi from Piper Sandler. Your line is open.
... Thank you so much, Matt. Congrats on the outstanding data. Two quick questions. One is, what % of patients are TRAb negative at the various time points? And then question number two is, did you see a difference? I know IgG levels came up during the off-treatment period, but was there a difference among the patients who remained completely ATD-free vs being on the 2.5 mg dose group based on the IgG response climb, increases up?
Perfect, thanks. So those are both great questions. My answer on the first one is going to be a little bit annoying, which is, this is the first data ever presented for TRAb recovery after a treatment period in a Graves' study of an FcRn or in a Graves' study of an IgG suppressive therapy. There are a couple of other people either thinking about or actively running such studies, and we think we have some real competitive benefit on phase III program design and commercial benefit in that data. So we're not going to share, at this point, you know, specific % of patients that are TRAb negative at more time points than we've got here.
And look, was there a difference in patients who were ATD free vs two and a half milligrams, based on IgG response? Look, I think the short answer to that question is it's not like ATDs are a major driver of IgG.
Mm-hmm.
And so in general, by week 48, these patients have recovered from an IgG perspective. But we don't have sort of a lot of specific data to show here on how that relates patient by patient. But I'd say, I think you can think about sort of across all patients, I think you can think about IgG as having normalized by the end of the trial.
Got it. Thank you so much. Definitely not annoying, Matt.
Thank you.
One moment for our next question. Our next question comes from the line of Leland Gershell from Oppenheimer. Your line is open.
Great. Thanks very much for reporting these terrific data. I wanted to just ask, Matt, with respect to the first registrational trial in Graves', you know, you have group two going to either, you know, going to the placebo, if they are a TRAb responder or not, just staying on drug if they aren't. I just wanted to ask, you know, what the definition of a TRAb responder is, based on the data you've shown us from before and today, it seems like, you know, TRAb is suppressed pretty well. So presumably most of those patients from group two would be going to placebo.
But I guess the reason why I'm asking this question more broadly is, do you think that you will have enough data from this study with remission data in the placebo group, that that will be enough for docs to be convinced of the remission benefits of IMVT-1402 when it comes to market? Thanks.
Yeah, got it. I don't think we've given the exact definition of TRAb responder, but it's, you know, down a lot from where they started, and relatively close to normal is the definition. But I don't think for competitive reasons, we've given the exact number. I do think we will have plenty of data on both how placebo patients progress and how drug patients progress to get comfortable with what the remission rates are and to get docs excited about what this drug can do. Remember that first of all, we have lots of placebo patients out to 52 weeks. And second of all, in the second study, the entire follow-up of that study effectively is patients, many of whom off drug, after six months of therapy.
And so I think there's a lot of other data to point to. But and the short answer to your question is, I think we're going to have plenty of evidence to suggest the effects that we're looking for. But good question.
Thank you.
Thanks.
One moment for our next question. Our next question comes from the line of Douglas Tsao from H.C. Wainwright. Your line is open.
Hi, good afternoon. Thanks for taking the questions. I guess, Matt, when we just think about the sort of remission data and the patients sort of adult sort of having a disease-modifying effect, I'm just curious if, you know, if you've gotten feedback from either KOLs and clinicians as well as payers, just in terms of their sense at that six-month point of sort of remission. Because obviously, you know, with Graves' patients, many do enjoy six months, but they do relapse after, call it nine months or twelve months and so forth. And just, you know, will you need data beyond what is needed from a regulatory standpoint to sort of more conclusively provide evidence that patients are achieving, you know, true long-term remission?
Yeah, thanks. That's a great question. Look, I think the short answer is a few things, but remember, every single patient in this study was uncontrolled on standard of care, and a huge % of them are leaving this controlled at the end of treatment and remaining controlled after six months. So I think docs looking at this data will be excited and will view this as differentiated. I think the potential disease-modifying benefit here, where we're seeing, you know, TRAb stay low, where we're seeing a durable treatment effect, where we're seeing patients controllable on ATDs, even like independent of the remission point, is going to be helpful. Then I think the remission number is going to be compelling.
I think a few things about the time point. First of all, I think based on the way these patients look at the end of six months, my expectation is that many of them will continue to be responders beyond. Obviously, we'll have plenty of follow-up in the phase threes. We'll be able to continue to comment on how durable those responses seem to be. But also, I think docs are going to look at this data out at six months, and I think they're going to be... I hope that they will be convinced that there's a real and durable effect here. And I think the remission, in some ways, is a cherry on top, and that we're able to get these uncontrolled patients controlled. But I think the rates of remission are going to be really exciting to patients and physicians.
And Matt, I mean, I think it's a good point, right? You know, obviously, we have to remember that these were patients who were uncontrolled, right, on high doses for some amount of time. And so this was a very difficult to treat population. I'm just curious, along those lines, I mean, what will the open label extension and how long do you plan to follow patients in the phase III, even beyond the sort of primary data point readout?
Yeah, I don't, I don't know that we've given all of that publicly. We may in the future, but the answer is there's long follow-through on these patients. In fact, it says on the file, 52 weeks, we're following through in the-
No, I mean, after the 52-week point, right, where, you know, beyond that, what is there sort of like a long-term extension for this plan for the study? And how long will that be?
It's another year beyond that. Yeah.
Okay. Thank you.
More than enough for payers and physicians.
Thank you.
In fact, more than a year. Yeah.
All right. One moment for our next question. Our next question will come from the line of Brian Cheng from JP Morgan. Your line is open.
Hey, team. Congrats on the update, and thanks for taking our question. This is Shana for Brian. So following up on the extra-thyroidal benefits we saw last year at ATA, can you elaborate a bit more on whether you're seeing deeper responses and/or prolonged durability in proptosis and the other metrics? And also, just to confirm, were the nine ATD-free patients at week 24, the same patients that remain ATD free by week 48? Thank you.
So, we don't have additional sort of TED or proptosis kind of data to present today. Obviously, we followed these patients for the six months after treatment, so it may get presented in another setting, but we don't have it today. In general, I'd say it looked favorable, and it's something we'll continue to look at and talk about. And then, I think the answer is there was some movement in and out of cohorts, but in general, patients that did well continued to do well over the course of the study. Thank you. Those are both good questions.
Thank you. One moment for our next question. Our next question will come from the line of Dennis Ding from Jefferies. Your line is open.
Hi, this is Georgia on for Dennis. Thank you for taking our question. Could you please talk about how you define remission in the phase III, and if our focus should be on the Group 2 patients respond and then transition to placebo in Period 2? And then, what is the statistical plan for the study, and will you have enough power to detect a statistical difference on remission? Thank you.
Yeah, thanks. Good, good questions. Well, in this data set, in terms of how we presented it today, we defined remission as patients whose T3 and T4 were below the upper limit of normal and who were off ATD. So that's how we analyzed it today. In the phase III, it's patients who are responders and are ATD-free, is the answer to that question in terms of how remission is defined in the phase III. Look, I think there is plenty of power overall in these studies to answer the questions we need to answer. And the truth is, because the endpoints are pretty stringent, I don't think we expect a ton of placebo response for most of these endpoints.
So I think in general, we should get what we need out of the powering of the study. Thanks. It's a good question.
Thank you.
Thank you.
One moment for our next question. Our next question comes from the line of Jason Gerberry from Bank of America Securities. Your line is open.
Hey, guys. Thanks for taking my question. I guess just wanting to come back to slide 14, and you have a really good reduction, durable reduction in TRAb in the off-treatment phase. And I guess, what would you say is the biological hypothesis at this point? That going to the 52 weeks of treatment could generate a better outcome, even if it's just hypothesis. And, you know, one of the things, going back to my note, when the, you know, the public data was published a year ago, there was some commentary about, well, maybe IgG reduction was associated with ATD-free response. And so in those eight subjects, I'm just wondering, you mentioned some diversity of response at the patient level.
Is there something maybe going on at the patient level that maybe explains the confidence in getting a better response in the full year of treatment? Thanks.
Look, I think the short answer to your question on, like, why we believe the data will look even better at 52 weeks than it does at 24 weeks is twofold. One is it looked better at 12 weeks of high dose than it did at 24 weeks of high than low dose. And so you can see that there is, like, the possibility for degradation on removal of therapy at that point. Also, in general, many of these patients were continuing to improve across various measures, continually able to titrate ATDs, continually able to get to better levels over the course of time. And so it, it's like, it didn't look like we had found max treatment benefit either at 12 weeks or at 24 weeks.
You know, I think there's like, in terms of the biological hypothesis, it seems like, and this is true for methimazole as well, some sick thyroids sort of need time to wake up. They need TRAb to be normal. They need to be euthyroid for a long time before getting to the best responses. Many of these thyroids are heavily inflamed, which is part of what may lead to the sort of feedback loop of anti-inflammatory and therefore autoantibody activity. And so, you know, I think you need to, like, get that inflammation down in order for the TRAb levels to stay low. And I'll say, yeah, look, I think it is, it is definitely the case that our conviction in the benefit of long duration treatment is higher because of the patient level data that we've seen. So there is some heterogeneity.
There are obviously some patients who respond quickly and durably, but there's also, like, information embedded in the patient level sort of study or the patient level analysis that gets to, like, what happened to each patient and how those responses were maintained, and for the patients that were responders, you know, what happened to ATD dose over time, and maybe you can make some predictions about what would have happened to ATD dose if they had been on therapy a little bit longer.
Okay. Thank you.
Thank you.
One moment for our next question. Our next question will come from the line of Charles Ndiaye from Stifel. Your line is open.
Hi, this is Charles on for Alex. Maybe one question from me. In terms of the phase III and expectations for placebo, you know, do you think it's possible for patients to achieve spontaneous remission? Thank you.
Well, thank you for the question. Biology is humbling, so anything is possible. But the truth is that uncontrolled Graves' patients who have been uncontrollable on ATDs do not, in general, achieve spontaneous remission. And if you ask these docs, like if you ask Kahaly, who ran this study, it's gonna be a very small % of these patients that spontaneously remit.
Thank you.
Thank you.
One moment for our next question. Our next question comes from the line of Thomas Smith from Leerink Partners. Your line is open.
Hi, this is Matt Tittler on for Tom Smith. We have a couple of questions. First, are there any patients that did not respond during the 24-week treatment period but became a responder during the off-drug follow-up period? And second, it's interesting to see the TRAb levels stay down to week 48. How do TRAb levels correlate to corresponders - sorry, responders or durable remission during the follow-up period?
Yeah, great. Those are both good questions. Look, I in terms of the TRAb levels, we're not giving, like, super specific answers on what this stuff looked like, but I think you can imagine the responders had overall better durability of TRAb response, and the non-responders had lesser durability of TRAb response. So I think that's sort of biology, sort of as you would expect from the biology here. In terms of expectations for... Sorry, yes. So sorry, that's the second question. Sorry, I apologize. I've lost track of the first question, if there was one.
So the first question is whether there are any patients that did not respond during the 24-week treatment period.
Right, right, right. Yeah. So, mechanically, there were-
Off-drug period.
Mechanically, I think one or maybe two patients, like, moved around between the definitions, between the week 24 and week 48 time point, but I think that's mostly a technicality. I think basically the answer is no, that the patients that were responders at week 24 were the patients who were responders at week 48.
Got it. And one question, if I may. So for the one patient who discontinued the treatment but got included in this presentation as a responder, how long was that patient on the batoclimab before treatment discontinuation?
Thanks. It's a good question. I think the answer is seven weeks.
Got it.
So that patient received seven weeks of high-dose to batoclimab and then maintained the response through week 48.
Got it. Thank you so much.
One moment for our next question. Our next question comes from the line of Corinne Jenkins from Goldman Sachs. Your line is open.
Thanks. As you guys look at the mechanisms that are also in development for Graves' disease, you've referenced a couple times it's getting a bit more competitive. I guess, how do you think this remission data could be differentiated over time, both with respect to the data that you've shown and also how you're developing this program?
Yeah, great question. Thank you. Look, I think it's hard to call and the different mechanisms. There's a handful of different mechanisms. There's obviously, you know, there's IgG degradation, where I think it matters which types of IgG you are degrading. Some of them are, for example, IgG3 TRAbs, which would therefore you'd need to degrade those, too. You know, I think as you get to like some of the anti-TSHR mechanisms and so on, I think the answer is, it's all a little bit complicated in terms of like how the... I think the sort of feedback loop mechanisms that are at play here are specific. And, frankly, like it's new, it's new information that you're able to do this, and so I think it's a little bit unclear on exactly how those mechanisms.
I think the fact is, until those mechanisms are able to prove they can generate this kind of data, we just don't know if they're gonna be able. It does seem like if you are able to get the thyroid to reregulate over time, you may be able to drive remission. But how durable that's gonna be, how effective that's gonna be, I think it's gonna be different depending on which mechanism, and the blunt answer is we're years ahead in terms of how much data we have about our mechanism.
Okay. Thank you.
Thank you.
One moment for our next question. Our next question will come from the line of Andy Chen from Wolfe Research. Your line is open.
Hey, Brandon, on for Andy. A quick one from us. At what point in time did those safety issues occur during the phase II study, and is there any concern about safety as we head into phase III with the higher dose over 52 weeks? Thank you.
Yeah, I think the short answer is that the safety and tolerability of FcRns is pretty well characterized at this point. That the safety findings all were as reported in the original 24 weeks. That there was nothing particularly concerning about the time point. Remember that, obviously, the phase III is IMVT-1402 instead of batoclimab, and sort of a number of the sort of observed findings were sort of obviously batoclimab specific, you know, albumin or LDL-related findings. So I think in general, my expectation is that we will not see anything meaningful or interesting from a safety or tolerability perspective that's different from what we've already observed. And I don't think we have much in the way of concerns about longer duration for the therapy. Great.
Thank you.
Thank you.
I'm not showing any further questions at this time. I want to turn it back over to Matt Gline for any closing remarks.
Fantastic. Thank you. Look, thank you all for listening today. We're again, very excited to be able to present this data. We're looking forward to the actual presentation at ATA next week, and we wanna thank, obviously, George Kahaly for, for running this study with us, to the patients who trusted us with their care, to the Immunovant team, who's worked really hard to bring this to fruition, and to the sort of entire team over at Immunovant, who sort of helped come up with this idea and, and have really propelled us to the front of what we think is a really exciting area of biology. So thank you all, and, looking forward to speaking again soon on a variety of topics.
Thank you for your participation in today's conference. This does conclude the program. You may now disconnect. Everyone, have a great day.