Immunovant, Inc. ($IMVT)

Good day, and welcome to the Brepocitinib Program Expansion and Batoclimab update. [Operator Instructions]. Please note, this call is being recorded. I would now like to turn the call over to Stephanie Lee. Please go ahead.

Good morning, and thanks for joining today's call to review Brepocitinib Program Expansion and an update on Batoclimab. I'm Stephanie Lee with Roivant. Presenting today, we have Matt Gline, CEO of Roivant, and Ben Zimmer, CEO of Priovant. 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'd like to remind you that we'll be making certain forward-looking statements during today's presentation. We strongly encourage you to review the information that we filed with the SEC for more information regarding these forward-looking statements and related risks and uncertainties. And with that, I'll turn it over to Matt.

Good morning, and thank you, everybody. Thank you, Steph, thanks for dialing in on short notice, as always, with these things. We have 2 agenda items today. We had originally intended to schedule a call right around now, to take you through our new indication of Priovant like [indiscernible], and we're going to do that and excited about that. I think that's going to be a really great addition. And then just because it happened to lineup timing-wise that we just got the Phase III data in tandem Batoclimab, we put out a press release on that this morning, and we'll cover it for just a few minutes at the end of the call and take questions on both. So I'm going to kick it off on Slide 4, starting with LPP. So look, I think it will come as no surprise to any of you that we are, at this point, super excited about what Brepocitinib could be and frankly, proceeding with urgency around the idea that it's going to be a large opportunity to expand across multiple indications and to build -- I don't love the phrase pipeline and a product generally. I think it's overused, but a pipeline and a product. We -- so far on Slide 4, look, we've set some criteria for ourselves for the things that we really care about in terms of what indications are going to work well. Starting with the sort of orphan immunology space where we're looking at indications that have, call it, mid-tens to very low hundreds of thousands of patients, with a lot of morbidity and sort of severe disease with a lot of unmet need. We're also looking for indications where the pathobiology aligns with our specific unique mechanism hitting both JAK1 and TYK2 and ideally, where there's some proof-of-concept data highlighting the potential benefit of either JAK1s or TYK2s or both, and we have something specifically useful on that here. And finally, we're looking at indications with high unmet need where there's really not much approved right now. So I think everyone is familiar with the sort of first three indications in our portfolio there. Obviously, Dermatomyositis, first of them with the PDUFA date in the third quarter, NIU with Phase III top line data coming in the back half of this year and Cutaneous Sarcoidosis with Phase III study starting in the second half of this year. And I'm pleased to announce that there's another one now Lichen Planopilaris. We'll talk more about the disease in a moment, where we're beginning an effectively direct to registrational combined Phase IIb/III program. In fact, began, I would say, last month. And so that study is now underway and represents a fourth leg to the stool here, that we are really excited about. So LPP on Slide 5, and then I'm going to hand it over to Ben to talk a little bit more about the indication and sort of why we're excited about it. Look, this is a severe and deeply unpleasant disease. It's a highly morbid inflammatory scalp disorder. There's nothing approved for it now. And it localized -- it's really -- it's an inflammatory scalp where the inflammation localizes to the permanent part of the hair follicle, which first of all, leads to generally irreversible hair loss, but it's also scarring can be permanently disfiguring and in many cases, is intensely painful, has a lot of itch, burning, redness, scaling. This is a really, really tough disease for these patients. When you see the sort of polypharmacy and some of the other things we'll talk about later in the call, these patients require a lot of medical care and have bad comorbidities. There are no FDA-approved therapies for LPP, and these patients require chronic aggressive multimodal therapy and are largely poorly responsive to first-line therapy like steroids and ISTs, hence the polypharmacy, hence, the pain management. This is not a well-controlled disease at all. And it's a fairly prevalent disease. It's got sort of a large orphan size. It's, I'd call it DM-like in population size with probably up to 100,000 U.S. patients and the [indiscernible] are indicating the prevalence and diagnosis is increasing over time. So we think this is just right in the center of the bull's eye for us. It's the kind of disease. You'll hear more about our understanding for why our mechanism is good for it, but the kind of disease with high unmet need and a lot of severity that we think Brepocitinib is exactly the right kind of drug for. So with that, I'm going to hand it over to Ben, starting on Slide 6, just to talk through what the experience of these patients is like and a little bit more about why we're excited about it. Ben, take it away.

Great. Thanks, Matt. So as Matt mentioned, an indication with very high patient burden. A lot of that is the direct symptoms and manifestations of the disease, as Matt walked through. Also on Slide 6, you can see LPP is associated with an increased risk of many severe comorbidities, including both skin cancer and other autoimmune diseases. And as Matt mentioned, no FDA-approved therapies given the severity, a lot of different drugs are attempted off-label, but generally with limited efficacy and high rates of discontinuation based on tolerability and efficacy issues. So really an area of very high unmet need, very high sense of urgency to treat quickly and with efficacious therapies, and we think there's really a significant opportunity for a new efficacious drug. And turning to Slide 7, we're optimistic that Brepocitinib can be that drug. Like Cutaneous Sarcoidosis, LPP is a disease-driven primarily by Th1-polarized T-cell aberrant behavior. And this is a category of indication where the biology really aligns with TYK2/JAK1 inhibition, IFN gamma and IL-12 are two of the critical cytokine signaling cytokines within the Th1 pathway and a JAK1/TYK2 inhibitor is distinctively able to suppress signaling of both of those cytokines. And then I bring up Cutaneous Sarcoidosis because through that study and other Phase II studies, we've really seen that play-out in the clinic with excellent data from Brepocitinib in indications with similar biology. And so mechanistically, we really feel this fits into the sweet spot of where brepo can be a potentially highly efficacious treatment. In addition to brepo specifically, there's a large number of case reports and investigator-initiated trials of both JAK1 and TYK2 inhibitors that generally establish clinical validation for this mechanism and gives us the excitement around moving quickly and rapidly into a potentially pivotal program. And turning to Slide 8. One of these is actually in Brepocitinib itself. This was a small investigator-initiated trial conducted at Mount Sinai. Unlike many of the other investigator-initiated trials, this one was placebo-controlled. There was only 3 patients in the placebo arm. It was also using the LPPAI, which is a generally noisy instrument that is actually not that preferred by clinicians. And so in our program, we're using different endpoints. So small study really not to be overread into in terms of the specific data. But big picture, you see the brepo treatment arm clearly getting better over time and really overall amidst the totality of other data furthers our confidence around the POC for this drug and moving quickly into a potentially pivotal program. And before Matt walks through the design of our trial, I would also just note on Slide 9 that although the clinical data with a small study in the LPPAI is, I think, around a somewhat noisy endpoint, that still persuasive. Actually, what I think is probably most powerful about this study result is the biomarker data, which is on Slide 9, where you see a very clear and convincing effect of brepocitinib on multiple markers of Th1-driven disease activity, including both interferon-gamma and IL-12 themselves as well as other important chemokines that are markers of Th1-driven inflammation like CCL-5. So I think all of this together sets the foundation for what we view as a high probability of success study in an indication with very high unmet need, and we're really excited to be moving very quickly into a potentially pivotal program that should hopefully deliver some excellent data. So with that, I'll hand it back to Matt.

Thanks, Ben. Appreciate it. So on Slide 10, you can see the trial design that we're -- that we've initiated for brepo and LPP. And this is really designed to function like a single straight to registrational trial, except -- and this is sort of the -- there are many benefits to pioneering new clinical development areas. One, cost to pioneering new clinical development areas is there's some work you generally have to do from a regulatory perspective. And so this set up effectively as a sort of combined Phase IIb/III, where we have a 72-patient Phase IIb portion of the study. And then immediately at the end of that, we will just go straight into enrolling patients in effectively the same study into a Phase III pivotal Part 2, where we expect the end to be approximately 270, although we'll do a sample size re-estimation after the Phase IIb. And that will allow us to go through sort of proper endpoint validation and to get the data we need once we ultimately do read out the Phase IIb portion to finalize the regulatory work and read out the Phase III. So this should be -- we're not ready to guide today on enrollment. Obviously, we've gotten a lot of enthusiasm from the investigator and patient communities as we've gotten the program up and running. Ben and the team have been engaging super actively with this population of physicians. We're not ready to guide today on time line, but the plan here is for this to function like straight to registrational program, and we're excited for what that means for time lines and what that means for our opportunity to get a new option to patients quickly. So we're looking forward to playing that through. Look, on Slide 11, just to summarize, and I think we hit these points all pretty clearly here. First of all, this is a disease with tremendous high unmet need. I'm confident as the investor community does work on it, talks to physicians, talk to patients, you'll see a disease with a high burden and a lot of unmet need. These patients are very uncomfortable. We have a drug that is distinctly suited mechanistically to LPP. LPP has a Th1-dominant immuno-phenotype. It's really exactly down the fairway of where we've succeeded elsewhere. We think we've got a creative, aggressive development strategy that will get us to market hopefully quite quickly. And we think we've got good synergy from a commercial perspective in the sense, not just in the sort of literal cost perspective, meaning, but we know these docs, we know these centers, we know this community. Priovant has done a phenomenal job and the team of building relationships at tertiary medical derm centers in some of these other indications, and we think we're really going to be able to leverage those relationships. In fact, they were some of the very same relationships that help us sort of key in on LPP as a desired indication to begin with. So really looking forward to that, super appreciative of all the work the Priovant team has done and excited to announce that trial is now up and running. And so I look forward to sharing more updates and answering questions about it today and in the future. Before we go to Q&A, I just want to turn quickly to the next topic, which is the Phase III study results in TED. So as I'm sure many of you saw Immunovant this morning, turn to Slide 13 that our Phase III TED study had failed to meet the primary endpoint for Batoclimab. As a reminder, I think everyone is clear on this, Batoclimab is the first-generation anti-sRNA antibody at Immunovant. The subject of the vast majority of our future -- all of our future development at this point is IMVT-1402. So this was effectively the last study to read out from the first-generation program. And it was not a focus area for us, for that reason, as we've said in other context. Obviously, disappointing to see the study failed to meet the primary endpoint. Batoclimab had succeeded, as you may remember, in an earlier Phase II study in TED. Ultimately, in the long-mark of our future, I suspect the meaning of TED for us is largely going to be that it was what guided us to Graves' disease and got that program up and running, and we'll talk more about some of the data we generated there. But first, just really quickly on what we saw in the study. So as a reminder, this study was actually designed pretty similarly to our Phase II study in Graves. It had a 12-week period of high-dose batoclimab designed to get IgG as low as any FcRn can take it, followed by a 12-week period of lower dose batoclimab, which suppresses IgG in general, more like what we see in some of the other FcRns currently on the market, and we actually have that number later in the deck in terms of what we saw in that period, at least in a subset of patients. The primary endpoint of the study was 2 millimeter -- greater than 2-millimeter proptosis responder rate, and that's the endpoint that we failed to meet. We measured some secondaries as well. What we said in the press release, and I just want to reiterate here, again, not trying to dress up a failed study. This is not a study that supports sort of further progress in TED. But in terms of things that we were looking for, there were probably two key things we were looking for in this study other than success. One was continued evidence that our deeper IgG suppression matters. And I think there's like a few ways to read that in this study. But I'll say, first of all, consistently across everything we looked at in the study, patients did better in the first 12-week period broadly than in the second 12-week period. Again, it was a relatively noisy study in terms of some of the endpoints, but there's a lot of different data points pointing in that direction. We take a lot of signal from that, including, frankly, the fact that at least one other FcRn inhibitor failed on futility in TED, and we would not have failed on futility. We saw separation in a positive direction, in multiple endpoints, and we'll talk more about that in a second. And then the other thing we were looking for is evidence of read-through to Graves' disease and trying to understand as this -- although it was not a study focused hyperthyroidism, in fact, very hyperthyroid patients were not allowed into the study, there were nonetheless a relatively small proportion, but large in the context of studying hyperthyroid patients with FcRns of hyperthyroid patients. So we wanted to continue to confirm our hypothesis there. And I think we've had some good outcomes there, too. On Slide 14, there are a lot of different data points we could have shown in terms of like the benefit in the study. And I think anyone who's familiar with TED will look at these numbers and agree. Numerically in the context of treating TED patients, these are not like super exciting proptosis improvements. But we did see meaningful numerical separation from placebo on, for example, change in proptosis at week-12. In fact, when you pull the two studies together, that was sort of nominally significant in a post-hoc statistical analysis. Again, with that $20, you can buy a sandwich. But I think it is evidence that the drug was, in our view, doing something and that we were seeing a benefit for these patients. Probably most importantly, these numbers all got worse, and I don't have that slide in here, but these numbers all got worse as you went from week 12 to week 24. So as you step down FcRn dose and saw lower IgG, the level -- the amount of proptosis improvement degraded, which I think is an important point. And I think also, as we think about this patient population, this was an active TED patient population that has sort of later stage, more advanced TED, the kind of populations that have been studied in other TED programs, by the way, many of which have, I'd say, underperformed recently as I think the disease landscape of TED has changed a little bit. But there is plenty of evidence in this data set, including the slide you're looking at on Slide 14, that suggests that we will improved proptosis and potentially delay proptosis development in Graves patients. And I think that is important to us as we continue to measure all of those things in the ongoing Graves disease program for 1402. And I think the study does broadly support that we should be able to deliver a benefit of that kind in our Graves program. And then the last thing, which is probably the single most important thing to come out of this data set in terms of readthrough Immunovant prospects here is on Slide 15, which this is on the left-hand side, the pooled results across the 2 studies, and they're pooled simply because the ends are small overall of the hyperthyroid patients in the program. Again, the study didn't allow very hyperthyroid patients. But within the boundaries of what we permitted, there were about 20 hyperthyroid patients between the two active treatment arms of the studies. And what you see here is in those two studies as pooled, there was a 75% mean IgG reduction. So batoclimab did consistently what it has done in all of these studies from an IgG supression perspective. And actually, what we saw was an 80% responder rate using the same responder definition, normal T3 or T4, at least T3, T4 below the upper limit of normal with no increase in ATD doses. And again, the same definition we used in the Phase II. And we said 80% responder rate, which was just bang on the same at the end of week 12, as the responder rate we saw in the more severe Graves population in the Phase II study for batoclimab. And one thing that's comforting is this was a very different patient population, a very different study design. Remember, a very different study sort of structure. The Phase II was a single-site study with no placebo, whereas this was a placebo-controlled study with many patients across many different centers and a different hyperthyroid population. So you see that consistent effect, especially at the high dose is helpful. I also think it's notable, as with the Phase II study, we saw a lower responder rate after the 24-week, after the second 12-week period as we reduced IgG suppression. And in fact, nicely, although I can't claim given the end that it's like a perfect correlation, the IgG suppression wound up a little bit lower in that population and the responder rate wound up a little bit correspondingly lower in that population. And I think that just further underscores that in a disease like Graves' disease, the deeper you can get IgG lowered, the better you're going to do with these patients. So I think that is also, again, a helpful outcome from an otherwise disappointing study. So look, again, there was a lot of debate here about how much to say about this given the outcome, which is disappointing for these patients. I want to say, as I'll say again at the end of this, thank you to the investigators, to the patients to the Immunovant team. These studies are hard to run whether they work or not and everyone trusts us with their care. And I'll say, I think the useful scientific evidence that came out of this, on supporting our thesis around treating Proptosis via Graves and on deeper IgG suppression mattering and being able to Graves patients will certainly help inform our plans. Notably, we're only sharing a relatively small amount of this data now. I think that we've said consistently is that we think there is important and useful information in this study, that informs how we are managing the Graves study super actively. And so I expect we will share more of this over time. But for now, we're being relatively quiet in terms of the breadth of what we're sharing. Happy to take questions broadly, though. Look to wrap up for the day before we open it up to Q&A on Slide 16. Our pipeline to me looks better and more mature every time we get on the phone. I'm really excited about the addition of LPP here. Brepo is really shaping up to be a broad franchise opportunity across multiple indications. And I think there are potentially many more lines to add to this graph as we think about where we're working right now and the Priovant team has done an awesome job of executing thus far on clinical programs and excited to see the outcomes from this study and more. I'm really happy with where the FcRn franchise looks. Obviously, IMVT-1402, firmly the drug to beat there and excited about the data coming later this year, both in D2T RA and in CLE and excited for 2027, which is one of the, if not the most important years, at least in Immunovant's history and potentially Roivant between the breath of launch and the Graves' disease data that's coming. Not to mention, which won't be subject to this call, mostly [indiscernible] with the Phase IIb data in PH-ILD coming in the second half of this year. So a rich catalyst calendar on Slide 17, a bunch of stuff upcoming that we're excited to talk about, just a huge year for us and disappointed about the outcome on TED, but otherwise, just really excited about what we're doing here. So I'm going to stop there. I'm going to open it up for Q&A. Excited to take questions on LPP. Obviously, also happy to take some questions on the TED study as well as I'm sure people have them. And so with that, I'll turn it over to the operator for Q&A.

[Operator Instructions] Our first question comes from David Risinger with Leerink Partners.

So I have two questions. First, for LPP, Slide 8, I don't know if you have these details, but could you talk about background therapy in the 13 brepo patients and the 3 placebo arm patients and whether that might have impacted the results of that study that was shown on Slide 8? And then I know that Graves' disease is actually a comorbidity in a meaningful percentage of LPP patients. which obviously is a positive indicator for potential success of your new program given the Graves' disease results that you've previously disclosed. But could you talk about that and any other comorbidities that we should be aware of with respect to LPP? And then actually, I have one more after that, if that's okay.

Thanks, Dave. I appreciate the questions. So the first one for the tangible answer to that question is that meds were washed out pre-baseline in that IAT. That said, in general, I want to highlight LPP patients are polypharmacy patients who are on a whole host of background meds. And one of the things the Priovant team has thought very carefully about is management of, call it, polypharmacy background and concomitant meds in the Phase IIb/III program simply because these are very sick patients and poorly managed. There are a ton of comorbidities with LPP. These patients are sick in a variety of ways, including with Graves. As a reminder, the Graves study was obviously on the FcRn side and the study is with brepocitinib JAK1/TYK2. So I think the ability to effectively access and treat Graves patients is probably a useful indicator of a sick patient population. But obviously, in terms of the actual pathobiology, probably not as much direct read-through. But nonetheless, look, I think excited about what we're going to be able to do for these patients. And frankly, look, I think brepo is a great drug for patients with a lot of comorbidities because of the broad anti-inflammatory activity. David you said, you have one more question?

Yes. Thank you. So obviously disclosed that the subset of hyperthyroid patients in the TED study showed similar response rates of thyroid hormone normalization to those seen in the batoclimab Phase II in Graves. So how did batoclimab performed in thyroid eye disease in that subgroup relative to the rest of the study participants?

Yes. I think the answer to that question is somewhat better in the hyperthyroid population in general. And we saw the most recent cut-off that I looked at in detail was in only one of the studies. So I don't have the full pool data on the top of my head. But in general, the answer is we did better in hyperthyroid patients than in the general population on proptosis.

Our next question comes from Yasmeen Rahimi with Piper Sandler.

This is Liam on for Yas. So I guess just in regard to the TED study, do you think there's an opportunity to transition any of the TED sites to the ongoing Graves pivotal program? And then if you could just provide an update on how enrollment is progressing across those 2 trials as well?

Yes. So first of all, specifically in the Graves program, we're focused on Graves patients, and we've excluded the more moderate and severe TED patients. And many of the sites in the TED study were more Opto-focused sites and sort of TED-focused sites, whereas obviously, we're focused on endos and the sort of Graves III physicians. That said, I'll say also, we are not particularly thirsty for more sites in Graves right now just because enrollment is generally going well. We're reaching as many docs as we can, and we will certainly increase site numbers over time in studies. But in general, I'd say we're happy with how enrollment is going in Graves and seeing a really enthusiastic reaction from the doc community there. Again, we expect both Graves studies to read out next year.

Our next question comes from Sam Slutsky with LifeSci Capital.

This is Kate on for Sam. Yes, we were curious just regarding the TED study, how much of a difference in proptosis response was there in the first 12 weeks versus the final 12 weeks? And I guess, did you see any similar numerically better trends on the secondary endpoints? And I also have a follow-up.

Yes, great. So -- I'm sorry, I didn't quite follow the first question. I think it was the difference between first and second -- first 12-week and second 12 weeks. I didn't quite catch if you asked on the primary or on the endpoint that we showed in the deck. The answer in either case is there was degradation in both numbers as between the first 12-weeks and the second 12-weeks. The proptosis responder rates, like I think in one of the -- in the blended across 2 studies, the proptosis responder rates in treatment arm were like low to mid-20s, maybe low 20 precent, and the placebo arm was sort of high teens. And so there was some degradation, but the numbers are relatively -- the numbers of responders were relatively small. In general, we saw trends supporting better performance in the first 12-weeks and the second 12-weeks. I think the proptosis -- like the proptosis improvement measure that we showed was something like -- I'm trying to do math at the top of my head, which is always dangerous, but like 20% to 30% better at the end of week-12 than at the end of week-24. But did we get the exact number with a better thing. And the answer is yes, it was consistent across both the primary and multiple secondary endpoints that people perform better at week-12 than at week-24.

Okay. Great. And if you don't mind if I squeeze one more in. For the subset of hyperthyroid patients, any anecdotes of how they're doing off treatment and whether they're remaining in thyroid?

It is a great question. I don't have any anecdotes from that population right now, but it's a good question. And honestly, I hadn't thought to ask in the last couple of days, but we'll take a look.

Our next question comes from Brian Cheng with JPMorgan.

Just catching up on your comments around LPPAI being noisy. How should we think about the correlation of the endpoints that you have mentioned on the slide here and also the primary endpoint that you'll be using for the Phase IIb/III? And then I have a follow-up.

It's a great question. IGA-01 is generally just a much higher bar than LPPAI. But Ben, do you want to talk a little bit about endpoints and where we're at?

Yes. The LPPAI, it's a composite endpoint that includes a bunch of different symptoms. Some are physician assessed like erythema and scale and some are patient reported. The biggest problem with the endpoint in addition to just combining all of those, like all composite endpoints can have noise is that there's no definitions in the LPPAI. Each of the symptoms is rated 0 to 3 with no guidance or definition for the raters on what would be a 0, 1, 2 or 3. So generally, just like a highly noisy measurement. What we've done instead is really try to break it up into much more precise measurements. So our IgA measures erythema and scale with clear definitions consistent with the rigor that goes into an FDA supported supported IgA. And then through different secondary endpoints, we'll be assessing each of the different other burdensome symptoms for patients like pain, itch, et cetera, through, generally speaking, NRS scales. So I think, in our view, a more kind of less noisy and more clinically meaningful to physicians and patients' way to assess benefit.

Great. And maybe just a follow-up on the TED data that you presented today. Can you also give us some color on the proptosis improvement that you saw once you step down to the 340 mg second portion? Particularly was the proptosis impact quick to see deterioration once you pull back on the dose? And how does that proptosis reduction change once the IgG also start to see lowering once you switch to the step-down dosage?

Yes, thanks. Look, I think the answer -- and I don't have the number in front of me. I've seen it in the last couple of days, but the answer is the proptosis improvement that we showed in the deck gets worse at week-24. And I think it's about 20% to 30% worse at the end of week-24 relative to at the end of week-12. So that's that's about what it looked like, specifically on the improvement. So that's -- yes. And I don't have a time scale of like how quickly it degraded. But in general, IgG falls over a period of a couple of weeks to the lower level. And so I think -- and then proptosis obviously lags further. So I think it takes some time to get worse roughly. Yes.

Our next question comes from William Pickering with Bernstein.

So on LPP, can you just confirm that the primary endpoint for the Phase III portion is IGA-01 responder rate? And kind of what are your expectations for effect size there? And then could you talk about how you're going to be handling background therapies in the study?

Yes. Great question. First of all, I'll just say, and I'll hand it over then to Ben. I think, first of all, the primary of the Phase IIb portion is IGA-01. I think part of the reason the study is designed this way is to make sure that we're aligned with the FDA on the Phase III primary. And so I think our hope and expectation is that there'll be identical endpoints in the Phase III. But obviously, until we've finished the Phase IIb and had a conversation with FDA, we probably don't know 100% for sure. And in terms of background meds as well is just to confirm my understanding there and anything else. Ben, do you want to answer those questions?

The general approach is going to be to wash patients out of background meds ahead of the enrollment quite aggressively, which is consistent with how we've approached a number of other trials like Cutaneous Sarcoidosis and things should set it up for success. And yes, I think our base case is that the primary endpoint in the Phase III will be the IGA-01 with 2-point reduction. That's obviously generally the gold standard derm endpoint for inflammatory conditions. But as Matt noted, part of the, point of the -- this is an endpoint that's never been actually used before. So part of the value of the Phase II portion is to get a sense of the behavior of the endpoint, including even just on a blinded pooled basis before we read out the Phase IIb just to confirm that thinking ahead of starting the Phase III.

And if I could just squeeze in a follow-up. What do we know about the efficacy of off-label JAK use in this indication?

Yes. I mean, look, I think -- among the things we know about the efficacy of the use of JAKs and drugs like ours, obviously, is what we showed for the IAT for the use of brepocitinib. There's a lot of case reports as well. I think in general, you'd see across the board, like broad support for mechanisms like these JAK inhibitors, TYK2s and certainly JAK1s and TYK2s combined in improving these patients. I think they're not like -- in my sense, not like super widely used off-label, but they seem to work based on case reports.

Our next question comes from Samantha Semenkow with Citi.

Two for me. Just another on the IGA-01 endpoint. I think, Ben, you mentioned that this was -- this will be the first time you're using this endpoint in LPP. Can you just talk a little bit about some of the powering assumptions in the Phase IIb and what kind of placebo response you're sort of expecting to see or designed maybe around to see? And then, Matt, you outlined in the start of the call some criteria for assessing indications for brepo. Just wondering what your capacity is for nominating even more indications going forward? And is it reasonable to think that you might stick within the rheum derm sort of inflammatory space for those additional indications?

I'll take the second question because I can answer on Ben's behalf and put pressure on Ben, which is, look, I think we are almost endlessly enthusiastic for the breadth of opportunity for brepo. I think there's a lot of value to the relationships we've built in the rheum derm context and frankly, a long list of indications in the rheum derm context that we like. So I think that you will see us do more there. I also think we are excited about indications that go beyond that context, and you may very well see us go kind of outside of that area as well. And I think we want the Priovant team to succeed in everything it's doing. But certainly, this will be the second additional pivotal study we're starting this year in addition to the Cutaneous [ Sarcod-1 ]. So we're looking at now, assuming everything succeeds at least 4 launches over the next couple of years, and I hope we can add to that list. Ben, do you want to take the question on IGA-01 powering?

Yes. So as a general matter, we've looked at the kind of precedents we've used, if you look at kind of how these instruments work in general, the IgAs, particularly those that are developed in partnership with the FDA and used for registrational programs, the placebo rate in general across them tends to be extremely low. We saw that in our own Phase II sarcoid study recently, particularly requiring not just a 2-point reduction, but 2-point reduction, 2.01 tends to be a very high bar for placebo. So our general ingoing assumption is that we would hypothesize the placebo rate would not be high, but we'll have to see what the actual results are. We think that on the basis of looking at effective therapies in other inflammatory skin disorders and kind of how the IgAs there have behaved that this Phase IIb portion should be very well-powered to detect the difference. But again, ultimately, to Matt's point in the opening, from a clinical confidence perspective, I think we would have been happy to just go straight into a Phase III program without doing a Phase II piece. But I think that just given we're pioneering a new indication here, part of the point of the Phase II program is really to learn more and inform the Phase III and ultimately, we'll see the results of the Phase II and use that to repower the Phase III if needed, which is what will ultimately be the portion of the study that we rely on to support potential registration.

Our next question comes from Yaron Werber with TD Cowen.

This is Sarah on for Yaron. Just two quick questions from us. So on the Brepo study, which of the 7 other successful Phase II studies give you conviction in LPP, mainly on the -- beyond IgA-01, which I know you've just discussed a bunch and maybe on the secondary endpoints? And then just a follow-up beyond that.

Yes. Perfect. Look, obviously, alopecia and CS, which we highlighted in this deck are both sort of very much the same phenotype from an inflammatory perspective, they're both sort of really sort of Th1-driven diseases. I'll say personally, I also just take a lot of comfort from the overall breadth of clinical evidence at this point in inflammatory disease across -- you look at the interferon drivers of LPP, et cetera, like I just think like it's pretty clear, and you can see it in the IIT on the sort of biomarker data. It's pretty clear that we sort of hit a lot of the right biology here. And I think that gives us some comfort. And then there's many of the other indications, significant components of these same inflammatory drivers. And so I think almost all of our studies contribute, probably the ones with skin components most of all, but not uniquely, but alopecia and CS are probably the two most important ones.

Got it. That makes a lot of sense. And then on the TED study, are you also taking forward the 680 mg and 340 mg dosing in the Graves study? And maybe just if you could just provide a little bit more color on what read-through that might have on the trial design for the Graves study?

Got it. And as a reminder, so the equivalent doses of -- so the test study we were out here was in batoclimab, which is not the drug we're studying in Graves disease. We're studying 1402 in Graves. The equivalent doses in Graves are 300 milligram and 600 milligram versus 340 milligram 680 milligram. Our Graves programs have both 300 milligram and 600-milligram dosing arms as between the 2 studies, and we're carrying forward both of those. As a reminder, based on our Phase I work, our expectation would be that 300-milligram would have competitor-like suppression of IgG and 600-milligram would have IgG suppression that is similar to what we saw at 680 milligrams in the batoclimab study. And I think all of the data we have is small end, et cetera. But the short answer is that our best expectation is that the Phase III data is heavily informed by what we saw in the Phase II, which is to say the high-dose arm outperforms the low-dose arm and that we see sort of adjusted for differences in endpoints and populations and other things, similar results at the high-dose arm in the Phase III to what we saw here. As a specific reminder, the longer 52-week 2502 study is 600-milligrams only and then the shorter 2503 study, the 24-week study is 600 milligram versus 300 milligram versus placebo. So that's the difference.

Our next question comes from Thomas Smith with Leerink Partners.

First on the TED results, did you comment on what you observed on the [indiscernible] levels in the study over time and how those compared to the Graves' disease data set? And then can you clarify, were the hyperthyroid patients in this study committed to titrate [indiscernible] ATD dose? And if so, did you have any patients that were able to down titrate or discontinue their ATDs entirely either over the course of the 12-weeks or the 24-weeks? And then I have a quick follow-up, if I could.

Yes. So -- on the [indiscernible] levels question, I guess like the first thing I'd say is like the data was just like unsurprising and matched what you would expect from these studies. So I'd say, yes, that's probably the best thing to say about [indiscernible]. On ATDs, the answer to your question is no. In fact, they were not permitted to titrate ATD. So these patients were required to stay on a stable ATD dose for the duration of the TED study. So unfortunately, we don't have evidence of clinical practice around ATD titration here. In fact, not only they were -- they effectively weren't permitted to titrate ATD. So we don't even get a look at what they would have done organically with these patients. Now as a reminder, and I think in some ways, the following is comforting and helpful. These were different hyperthyroid patients than in the Phase II Graves study and the criteria required patients to be relatively close to [indiscernible] thyroid. And so these patients were less sick hyperthyroid patients than the hyperthyroid patients in the Phase II. And I think the fact that they continue to respond at a similar rate is encouraging in so far as it highlights our ability to treat a pretty broad range of Graves patients at this point.

Got it. That makes sense. And then just one quick follow-up, if I could, on -- looking forward to the D2T RA results later this year. Just wondering if you could provide any updated expectations for that readout? And also any clarity on whether you expect to report both the Part A open-label and the Part-B randomized withdrawal portion simultaneously or if you're thinking that will be more of a staggered approach?

I don't have updated guidance to give on either of those questions right now. We're still working through our analysis of the sort of best criteria to run the Phase III. And so I say that work is happening actively, and we'll share our thoughts on it as soon as we're ready. But we're excited about it, too.

Our next question comes from Dennis Ding with Jefferies.

This is Anthea on for Dennis. We have two. First, the investigator study looked at other scarring alopecia like FSA and CCCA. It seems like there were promising signals there, but curious what your interpretation of that data is and why you chose to go into LPP specifically? And then second, on LPP specifically, how does disease activity fluctuate over time? And how are you planning to capture [indiscernible] efficacy within 24-weeks? And if there are any sorts of enrichment that you plan to do?

Yes. Thanks. I appreciate both questions. On the first one in terms of breadth of indication, first of all, both across other like inflamous-related diseases as well as other potential scarring alopecias. There's lots of interesting data available across different studies, et cetera, that suggest opportunity, including in the IIT, as you mentioned. LPP was pretty clearly to us the initial greatest unmet need and a well-circumscribed orphan population that, among other things, the regulators were excited about as well. So it just felt like a nice clean opportunity all around. But if your question is, are there even more indications in which brepo might work based on the IIT and otherwise? You're never going to get an objection to that question from me. And over time, there's a lot of different things we could study. LPP tends to have a fairly steady unremitting course. These patients look, the disease is ultimately irreversible in a lot of the ways it affects people. And so these patients just get worse. And so there's a high desire to treat quickly, which is something that's sort of interesting about the disease, again, because it's sort of -- it's effectively viewed as an emergency. It's an urgent condition, and it tends to be irreversible.

Our next question comes from Corinne Johnson with Goldman Sachs.

This is Eric on for Corinne Johnson. We have one question regarding TED. So how should we think about the implications this clinical failure has on how physicians and payers think about utilizing 1402 in Graves' given the overlap in this indication and that TED is downstream of Graves' disease?

Yes, it's a good question. Look, I think the easy answer for me to give is, overall, I think there's going to be a lot of excitement for Graves. And I think the data that this study showed on improvement in proptosis as well as the data that this study suggests to me we will show on the same in the Graves study, I think will ultimately be encouraging for the use of these drugs in Graves. And as I think the limitations of using FcRns in TED, mostly stemmed from catching the patients too late at a time where FcRn therapy is simply not sufficient to treat the -- at that point, presentation of the disease. But I think there's plenty of evidence in this data to suggest we're going to be able to benefit proptosis in Graves patients and catch it early. Look, obviously, at some level, if this study had been extraordinary, I would be here telling you how great the read-through was to doc enthusiasm for Graves. And so yes, I think it probably would have been even better if this study had shown better proptosis response rates. But I think in terms of our ability to improve proptosis in Graves patients, overall, I would call the evidence from this study net encouraging. And I think in the fullness of time, docs will see it as such.

Our next question comes from Del Makadi with Guggenheim.

So on LPP, you described it as a strategic fit with dermatomyositis given the overlapping prescriber basis. Can you quantify the extent of that overlap between rheumatologists and dermatologists treating DM versus those treating LPP? And how does that inform your commercial infrastructure build-out?

Yes. Great question. Yes. So look, I think the short answer is LPP is mostly treated by derms and especially hair loss and scalp experts. But there's a lot of overlap at the centers. So many of the centers that are sort of big myositis treatment centers are also big centers treating LPP. I'll tell you, and Ben should feel free to add anything to this than he has. Our focus on commercial build-out right now is succeeding in dermatomyositis and making sure that we have enough breadth and enough coverage and enough relationships to succeed there. I don't think we are changing anything about our DM commercial strategy in anticipation of CS or LPP or anything else. I think in the fullness of time, the relationships that we have at these tertiary centers will definitely be helpful with the subsequent build-outs for the other indications treated at overlapping centers. But we're going to take each of these launches as the opportunity that it is to make sure we invest fully in it. Ben, anything you'd add there?

I'd just add on DM specifically, there's a combination of rheum, derms and neuromuscular specialists who all will be potential prescribers, and we're focused on all three of those groups as appropriate. As Matt mentioned, I think there's overlap. Obviously, the clearest overlap is in the derm subset of that DM prescriber base, but also even a lot of the rheums and neuromuscular physicians, not all of them, but many are at tertiary centers of excellence where there's often multidisciplinary myositis clinics and myositis specialists, especially in the rheum derm space, but also involving neuromuscular experts. And so I think there's, in addition to specific prescriber overlap, the overlap in terms of overall institutional engagement and collaboration that is important.

Got it. That's very helpful. And maybe if I may, another question on the -- whats your [indiscernible] on LPP? What's the internal bar for success in Phase IIb to progress to Phase III?

Yes. So the short answer to that question is we are going to enroll patients in the Phase III before we read out the Phase IIb. So we're really not viewing this as a -- like run the Phase IIb, get the answer, run the Phase III. We're really [indiscernible] like a continuous study. And I think the reason for that is, as Ben said, clinically, I think we have plenty of confidence to go directly into a registrational program. We're just making sure we have all the information we need from a regulatory and process perspective as well as to get the right powering assumptions and so on for the Phase III portion of the study.

Our next question comes from Alex Thompson with Stifel.

Appreciate the update. I guess for batoclimab, I think, Matt, you alluded to maybe sharing some more data from the study in the future. I was curious if you could elaborate on to whether we should expect to see more data from MG or CIDP in particular in the future? And then as a follow-up to that, curious about your thinking on whether MG and CIDP data or even some of this TED data could help support ultimate 1402 filings in the future?

Look, I think never say never in terms of publishing MG or CIDP or other data. I mean we have an interesting treasure trove of things there. That said, like the 1402 MG program, for example, reads out next year. And I think at that point, everyone is going to be much more interested in the ins and outs of that data set than anything about what we saw in the Batoclimab study. CIDP, there's a little bit more time between now and when the studies come out, and there might be interesting things to say there. So it's certainly possible. We're obviously principally focused on 1402. I don't think we will need any of the MG or the CIDP data to support the regulatory filings. I think the 1402 data will be sort of sufficient in and of itself. Obviously, the FDA is aware of all these studies, has seen safety data and everything else from these studies. And although I'm not sure the FDA would like publicly declare that they take great comfort in sort of cross-mechanism comparisons of things, obviously, the body of evidence suggesting safety and efficacy for FcRns in those diseases is helpful to us in our interactions with the agency, and I suspect helpful to the agency in making approval decisions. Obviously, the CIDP trial design is different for 1402 than the Phase IIb was. So that's something to take into consideration.

Our next question comes from Douglas Tsao with H.C. Wainwright.

I'm just trying to understand the sequencing on the LPP Phase III study. It sounds like this is going to be sort of continuous enrollment from Phase II to Phase III. I guess I'm just trying to understand at what point you are going to validate the data and engage with the agency just in terms of finalization on the primary endpoint?

Yes. After we've read out the Phase IIb when we have the data to share with them is the answer to that question. Probably along the way as well after we read out the Phase IIb.

Okay. And so there will be patients who, I guess, you'll just be insured or just in terms of making sure you're collecting everything that is necessarily needed to input into some kind of composite endpoint if some kind of change or tweak is needed?

Yes. The short answer to that question is yes. I don't think we are anticipating like major changes to the way the endpoints are structured and things like that. Obviously, there's a fair amount of knowledge about this going in. It's mostly about sort of validating assumptions that we're going in with.

Our next question comes from Dina Ramadan with Bank of America.

First is maybe to clarify an earlier point. Given there's considerable overlap between the TED and Graves populations, and it looks like you guys had a strong responder signal in TED patients with elevated thyroid levels. How do you plan to apply these learnings to your pivotal Graves program? Just curious what your thoughts are on how you're thinking about the inclusion of patients with ocular symptoms and if you think there's still an opportunity in the Graves program to show a benefit on proptosis and maybe a subgroup population? And then just on the subgroup data you presented in TED patients that were hyperthyroid at baseline, could you provide just some additional color on how this patient population compares to the Phase II Graves in terms of kind of disease characteristics that define severity, maybe baseline T3, T4 levels or length of time uncontrolled or hyperthyroid on ATD?

Yes. These are all great questions. Thank you. Look, I think the first answer is, although this comment may read as glib, the quality of the response in hyperthyroid patients in the TED study mostly just validates our view of where we're at in Graves that this is across multiple sites, a broader population in some ways, like continuing to show like very strong performance in treating hyperthyroidism in these patients. But the TED study was designed to exclude severely hyperthyroid patients. And so the reason that only 20 out of the 100-some-odd patients in the overall combined program on drug had sort of hyperthyroidism is because mostly the patients who came in were controlled. Now many of them were controlled on moderate doses of ATDs and things like that. But nonetheless, like these were mostly not hyperthyroid patients at baseline. So I think like from that perspective, they were less sick than the patients in the Phase II study. I think we expect to show benefit in the Graves study on ocular symptoms, and we think it will be incrementally helpful. But it's not obviously the focus of the Graves program. And the Graves program excludes moderate to severe TED patients who've already progressed to more significant ocular symptoms.

And our next question comes from Chi Fong with Bank of America.

I just have a quick follow-up on brepo. So given the integrated trial design and you mentioned parallel enrollment as well earlier in the call, how do you plan to handle the Phase IIb results once you have those on hand? Could you or do you plan to top line or publish the Phase IIb results? Or would the disclosure be more go or no go, or tweak or no tweak? And ultimately, the Phase IIb data would be kept in-house until you have unblinded the Phase III data?

I don't know that we have a super well-formed view on what we'll say publicly about that data. I think our pretty strong expectation -- at some level, the biggest possible version of the impact of that data is like some kind of futility analysis basically, where like, obviously, if we saw something super unexpected, it could cause us to like change our conviction. I think that would be pretty surprising given what we know. And so I think that's sort of the sort of basics, whether we will say something about it once we have it or not, I just -- to be totally honest, I just haven't thought that much about it.

I'm showing no further questions at this time. I'd like to turn the call over to Matt Gline for closing remarks.

Thanks very much. I appreciate it. Thank you, everybody, for dialing-in. Obviously, a lot of good questions on both LPP and on Graves' and TED. I'm sorry if we missed anyone in the queue. Look, I want to say thank you again, first of all, to the Immunovant team to the patients and the investigators in this TED study. Obviously, always disappointing when a study doesn't work out. I hope one of the things you walk away from this call with is we learned a lot from that study that has been helpful. We learned even more that we haven't shared today because it's competitively valuable and will set us up to win in Graves. So we're excited for all of those learnings. And it's just a herculean effort to get these things across the line. And then excited in advance from the same commitment that we're going to get from the LPP community who are deeply in need of new therapies and really excited about -- really excited about the possibility of something new. I have great confidence in the Priovant team to run a good study there and to take advantage of all the relationships we've built and the work that we've done and excited to just continue to add big bricks in the wall that is the brepo opportunity. So looking forward to having a call similar to this one again in the not-too-distant future to talk more about new indications for brepo, at least on that side of it. Thanks, everybody. Thank you for joining this morning, and we'll talk again soon.

Thank you for your participation. You may now disconnect. Everyone, have a great day.