I think we're going to get started here.
Let's do it.
Good to see you, everyone. Thanks so much for joining us for the next Fireside. My name's Derek Archila. I'm one of the Wells Fargo biotech analysts. Next company here, we have Roivant. From the company, we have Matt Gline, CEO. Matt, thanks for joining us today on a great day for some new data. Great times always have good data, is right around a conference, for sure.
That's right, yeah. Thanks for having us. It's great. We put out some data in PH-ILD this morning that was pretty extraordinary, so it's exciting to be here.
Well, let's start there. Very topical. Maybe walk us through kind of the PHocus trial, and ultimately, what we're putting into context some of the data that we saw today.
Yeah. Taking just like a two-second step back first, just in case anyone's not familiar. Roivant now, just under a $30 billion market cap company. At this point, a leg with three stools, such as it were. Brepocitinib is our lead product, just got approved a couple weeks ago in dermatomyositis under the brand name LISRAYA. We have an FcRn that Derek knows extremely well, and I'm sure we'll spend some time talking about today at Immunovant. The third of them, which had been third in line until this morning, is mosliciguat. Mosliciguat is an inhaled sGC activator. This is a mechanism, it's effectively a potent vasodilator, among other things, and it's a mechanism. sGC-targeted therapies have been studied.
In fact, in one case, there's a systemically administered sGC called Adempas that was a Merck-Bayer collaborative project in PAH, so it was about a $2 billion drug at peak. PH-ILD, for those who are unfamiliar with it, is pulmonary hypertension that comes from having lung disease. It's been a tough indication because systemic vasodilation for these patients is dangerous. You wind up all the benefit you get from vasodilating the healthy lung tissue, you give up by vasodilating the unhealthy lung tissue. It's been a tough indication to study. In the last few years, inhaled treprostinils, most notably Tyvaso from United Therapeutics, but also YUTREPIA from Liquidia and coming TPIP from Insmed, all different formulations of treprostinil have been successful at treating these patients. We took mosliciguat, this inhaled sGC activator, into PH-ILD with the hope of replicating that idea.
PHocus was a large, 100 some, 120-ish patient, phase IIb study in PH-ILD that was designed to demonstrate that we could treat these patients, and boy howdy, that was a really nice outcome. We got the deepest ever observed PVR, pulmonary vascular resistance, measured by right-hearted cath, I think in any pulmonary hypertension study ever. We had about a 56% placebo-adjusted improvement in PVR. We were not powered for a p- value on the functional endpoint six-minute walk, but we delivered a p- value on the functional endpoint six-minute walk. Just a really, really good set of data all around. I don't know how familiar people are with PH-ILD. This is a terrible disease. These patients are dying, and so it's phenomenal to be able to deliver this kind of outcome.
What is kind of next steps here, now that you have the data in hand?
Yeah. A few months ago or earlier this year, we were kind of looking at each other and realized that we had pretty good conviction and that we wanted to move fast, and we started the phase III earlier this year. The phase III is enrolling patients now. I think the next step is to finish that study, which should then be sufficient for approval. That is what is ongoing now.
Is there any difference between phase II, phase III in terms of population or study design, or we should think it is pretty replicable?
Basically, no, with one key exception, which is in the phase IIb study, we did not allow for concurrent use of treprostinil of Tyvaso, and in the phase III, we are allowing for some measure of concurrent Tyvaso. We have an open label study that is a combo study that we have not read out yet, but will allow for some concurrent Tyvaso use. It will be stratified, and we will probably cap it at some level. That way, we will not have any label restrictions, which pulmonary hypertension, for those that follow it, is a polypharmacy market where these patients go on every available drug.
Actually, in PH-ILD specifically, because these patients have lung disease, treprostinil is an irritant and it causes cough in these patients, which is lousy for a patient with already a coughing disease. We had less cough on drug than in placebo. We're one inhalation of a DPI once a day. I think we should have a pretty compelling value proposition, but ultimately, these patients are very sick, and I expect they will also wind up on a combination of these drugs over time.
Got you. Where do you kind of see the opportunity here and ultimately, I guess, I don't know, put it into context or frame out the overall kind of peak sales opportunity potentially?
We don't have peak sales guidance to give. The most conservative estimates for PH-ILD is a sort of number of patients in the. We think there's probably about 200,000 PH-ILD patients in the world. United Therapeutics gives a conservative estimate of 30,000 in the U.S. Other companies have bigger estimates. I think there's tens to maybe low hundreds of thousands of PH-ILD patients potentially in the U.S.
Sure.
These patients are really sick. I think with our quality of data and with the fact that we don't have cough and have simple administration, there's no reason to think we couldn't have frontline use or sort of first line of major new therapy use in PH-ILD.
Yeah.
We'll also, I suspect, be used after treprostinil in some cases, and they'll be used after us in some cases. I think the real opportunity here is this is a you-don't-have-to-outrun-the-bear situation, it's just these patients are sick and you got to get out to them.
Got you. We should be feeling very good about the phase III. When will we get data there?
We haven't said that either. We're just getting enrollment up and running now. We just read out the phase IIb today. We'll meet with FDA and confirm things like size and may be able to repower, et c, now that we know the phase IIb data pretty cleanly. I think it should enroll nice and quickly given the quality of the data that we've got here, and the phase IIb enrolled pretty quickly as well, so fingers crossed for a nice timeline. I don't have a timeline to share right now.
Got you. Anything else to highlight there, or any other thoughts on the data today?
I'm not very practiced talking about this data.
Yeah, it's brand new.
This is an hour in, so I don't have the super prepared talking points. Look, this was phenomenal data across PVR and hemodynamics, across six-minute walk and functional endpoints. Again, the lack of cough is really nice and the one inhalation once a day. The only other thing I'll say is I think this opens the door to not just PH-ILD, but to, first of all, any form of pulmonary hypertension is for sure on the table.
Sure.
PAH is an indication that we got asked about a lot before this data set, and my answer at the time was PAH is very competitive. There's a lot of other drugs there. This data is good enough that I suspect it opens the door for even competitive indications, so I think you better believe we're evaluating that. We've been looking at IPF, following up on, United Therapeutics has had some success there with Tyvaso. I think lots of places to go, and I think this really does become a proper third leg to the Roivant stool at this point.
Got it. Okay. Maybe shift gears to LISRAYA and dermatomyositis. Your recent approval. Maybe talk about how you think about this opportunity, and ultimately this is an area where there's really been a dearth of-
Yeah
... options for patients. Just kind of think about ramp and uptake.
Yeah. It's hard to believe that this was just last week, the week before last week. It was very recently that we announced the approval of Brepo and DM. And it felt like we've been working on it for so long that it feels like I said on the approval call, it's the rare marathon that ends with the right to begin another marathon immediately. Now we're out there with LISRAYA on the market. Look, dermatomyositis, again, for those that aren't familiar with it, severe inflammatory disease, terrible skin rash. In fact, many DM patients say the worst thing about it is this very painful disfiguring rash. And then on top of that, it's got these muscle wasting effects that lead to things like can't climb stairs, can't lift objects, can't dress yourself, can't eat. So a really bad disease.
There are basically no modern options approved other than LISRAYA at this point. People are on high-dose steroids, immunosuppressants. IVIG is approved, and the labeled dosing paradigm involves basically four or five consecutive days, full days in the infusion clinic. A lot of patients are on it, which just gives you a sense of how bad the disease is. Brepo's data was really, really strong, and we were able to show not just very good clinical benefit, but steroid-sparing, conjunctional clinical benefit, which we got on label. So I think we have a really nice story to tell, a great value proposition to patients. I think the patient community and the physician community are really excited, obviously, tremendously excited now that it's approved. Drug has launched, prescriptions written, all that. So really looking forward to just getting out there.
We get asked all the time about ramp, and our answer has been consistent. I was talking to an investor this morning who wondered why we hadn't gotten slow and steady printed on headbands yet. I don't look good in headbands, but otherwise, I think it's a good idea. Look, I think it's a new indication. It's not like there's a lot of patterns to point to. There's a lot of physician and patient enthusiasm, and the most important thing is we're out there and I'm excited for what we're going to do. It's obviously just like day six or something. So it's early days.
Okay. Yeah. Well, I guess maybe talk about rheumatologists are generally pretty familiar with JAKs, and Brepo kind of fits right into the bag of tricks for them. I guess, do you think there's going to be much education and learning around the actual mechanism or safety, things like that? Maybe just walk us through how you guys are kind of educating the field force is educating the docs here.
In general, two things. One is, I completely agree that rheumatologists, and even dermatologists, are familiar with the mechanism or at least with part of the mechanism with JAK inhibitors. Are also familiar with TYK2s for that matter. Brepo is a dual inhibitor of JAK1 and TYK2. And I think there's been so little actual successful drug development in myositis that there's like a ton of physician enthusiasm even apart from that. And one of the things you asked about safety, we have a black box warning like JAK inhibitors do. The truth is, dermatomyositis as a disease causes things like JAK inhibitor side effects, malignancies, cardiovascular events. High-dose steroids and methotrexate and immunosuppressants cause the same.
Yeah.
Treating these patients effectively is worth it, and in fact, may even reduce the risk of those things, depending on sort of how you look at it. Certainly in our data in the study, we did not If anything, we saw lower events of these kinds on drug than on placebo because I think you're treating these patients effectively, getting them off immunosuppressants and steroids and so on. So I think there's not going to be a heavy lift on education. And in fact, one of the other things about myositis, it's treated in a pretty concentrated way. About half the U.S. patients are treated at about 200 specialty myositis referral clinics. And those docs are familiar with our study. Many were investigators in our study, excited about the drug. We've been talking to them from a medical education perspective over the course of the past year since the data.
I don't think there's a lot of education to do. In fact, one of the reasons I feel obligated every time I go out in public to say the phrase slow and steady is because if you call these physicians, the physicians are incredibly enthusiastic. In fact, one of the ways a lot of investors have come to us in the last year or so is, you know, argenx has recently read out data in a myositis program. Argenx obviously has an impassioned and enthusiastic group of investors who were calling docs asking about argenx. In many cases, what the docs wanted to talk about, because it was more proximate, was brepocitinib. We got a lot of argenx investors showing up in our office saying, "I keep asking about efgartigimod, and I keep being told, first you should look at Brepo. It's sooner.
That I think there's just a lot of doc enthusiasm for the drug.
Yep. We've heard the same in upwards of maybe 60% utilization for the patients that are candidates for the drug.
Those are large numbers.
Yes.
There are tens of thousands of DM patients.
Yeah.
We certainly do not need 60% penetration in order to have a big and exciting drug.
Well, that is good to know. I guess when you think about the field force that you guys are going to put out there, and you just kind of alluded to it in terms of the concentration of where these patients are, what kind of gets you confident in terms of your ability to launch Brepo?
Oh, gosh. Biotech is not a field that rewards confidence.
Right.
You asked me what my confidence is. Look, I think we have a great team. I think we have great relations with the doc community. I think the level of doc feedback and the early enthusiasm from the prescriber community is certainly encouraging. One of the things I really like about orphan disease launches, I often talk about how we previously launched a drug in psoriasis. These bigger market indications are like a fluid dynamics problem where you can't approach the patients as individuals. You have to think about the shape of the surface, and branding, and marketing, and D2C advertising are all the sort of tools that you have for manipulating and accessing those patient populations. Manipulating is not the right word. We're accessing those patient populations.
Dermatomyositis, it's an orphan disease, and you can approach these patients where they are, one doc at a time, one patient at a time. In many ways, treating these patients in the market is like treating them in a clinical trial. You find them, you get to them, you sort of communicate about the benefit of the drug, and I think that's the way that you build a roster such as it is. I feel confident that our relationship with dermatomyositis physicians are extraordinary.
I feel confident that the Priovant team has done a great job building confidence within that community, and I think that's ultimately what's going to translate to uptake. The other thing that really matters in these fields are access, and we have a great patient support team that's out there making sure that, to the extent possible, these patients have no copay and are able to get on drug quickly and seamlessly.
Got you. How should we be thinking about the KPIs that you guys will share in terms of the launch?
Net sales.
Just sales. Okay.
Net sales, the product. Look, the truth of the matter is, in the long run, that's what matters, is getting out there, getting reimbursed, getting patients on drug. I think there's a lot of desire to find measures early in launches to sort of tell what's going to happen. Look, I think we'll see how the launch goes, but my gut feeling is net sales is going to tell the story.
Got you. Anything else that we should be thinking about in pushes and pulls for the launch? Obviously there's reimbursement and things like that that will come on, but anything else that we should be considering?
Yeah. Look, we're obviously paying attention to how quickly we can get coverage for these patients. That's an important indicator. We're sort of alone in the field right now. As I said, there's not a lot of other novel drugs, so I think that most of it is just getting out there and getting behavior change in these practices. One of the questions I get a lot is, which patients are going to be on drug first? I think the interesting thing is different docs are approaching that question differently, and so there are some docs who use JAK inhibitors off-label and are enthusiastic to switch their off-label patients over to Brepo.
There are some docs who are heavier users of IVIG and are looking to switch those patients. There are some docs who just have a lot of steroids and immunosuppressant patients who have resisted IVIG or off-label therapy, and they want to put those patients on. I think it's very much a meet the docs where they are kind of a launch, and so I think we're trying to figure out what the early patients look like in different settings.
Can you talk to the amount of steroid usage in myositis?
Oh, gosh. Very high.
The doctors think this is a huge-
Yeah.
... benefit to get down to 5 mg or less.
Yep.
Ideally zero.
Yeah. Steroid sparing is a huge benefit here. Funnily enough, when we designed the study, we had a steroid taper in the study, which you do in these trials in part to basically protect the drug effect, right? You want to get patients off steroids so you are not getting placebo patients up titrating on steroids and getting treated actively anyway. You had a steroid taper, and in some sense, we failed at the steroid taper. That is, what happened is we were able to get Brepo patients to a much lower level of steroid use than we were able to get placebo patients because the placebo patients were just sick enough, it was harder for them to titrate.
And that wound up being, ironically, one of the best features of our data, was that discrepancy, which docs look at as a huge benefit to Brepo, that you can get patients on lower dose steroids. Many DM patients are on high dose steroids. You are talking about average steroid burdens of 10 mg or 20 mg for six months out of the year. I do not know if you have been on oral prednisone before, but being on 20 mg of prednisone for six months is a miserable way to live. The docs are incredibly excited about the ability to get these patients to lower steroid doses.
Got you. Maybe shift gears to IMVT-1402 and kind of the FcRn pipeline. I guess one of the questions that always surfaces around increased IgG reduction and conferring better efficacy. I guess just kind of broadly speaking, but MG, CIDP, all these other indications, what gets you confident that you guys have maybe the best reduction and could lead to the best efficacy?
Well, I used to think data would answer that question. I think we've generated the data that answers that question in four or five indications, and still mostly people seem to want to ask it. I don't know what's going to answer that question conclusively for everybody else. We feel like in every indication where we've tested it, first of all, at the individual patient level, patients who have deeper IgG suppression get better clinical benefit than patients who have lesser IgG suppression. That's been true in our MG data, in our CIDP data, in our RA data, in our Graves' data, obviously.
Across the board, every disease where we have been able to measure this effect, we have shown that deeper IgG suppression yields better clinical benefit. I think that's going to translate over time across indications to an attractive clinical profile for our drug. Obviously, in indications like MG, where efgartigimod is a very well-established therapy, whether it's better by enough to win that market is something we'll have to see when we get our phase III data. But I think in indications like Graves', where we're first, in indications like RA, where we're ahead of the field. I think that better clinical profile, in our view, is going to translate to a real leadership position.
Yeah. Maybe let's talk about difficult-to-treat RA. The data, very impressive and maybe surprisingly so for period one. As we look to Period 2, one of the questions is really that withdrawal period being long enough, and I think you set the right expectations in terms of what we should see, but maybe just rehash that and ultimately how does this inform a phase III or the next development in this indication?
Yeah. Perfect. So look, for those that may or may not have been paying attention, we put out data in sort of an interesting trial design. It was a randomized withdrawal design where period one was an open label period where patients were on drug, and then responders were re-randomized either to the high dose, low dose, or placebo. Frankly, the period one data was so good that it has made the Period 2 bar difficult. That is, the endpoint in Period 2 is loss of ACR20 response in that randomized withdrawal period, and of the ACR20 responders who got re-randomized, half were ACR70 responders and two-thirds were ACR50 responders. You're talking about taking an ACR70 responder and trying to get them to lose an ACR20 response in 12 weeks where they're still getting some pharmacodynamic benefit for the beginning of the period.
It's just a high bar. I don't know, frankly, given the quality of the period one data, what's going to happen in Period 2, and I think it's a reasonable thing to be concerned about. That said, the period one data was so good that even if we don't get a p-value in Period 2, it doesn't really matter. We're basically set on running a phase III program here given the quality of the period one data as long as we see clear evidence that there is a drug effect, which I believe that we will given the number of ACR70 responders and so on.
We're looking forward to seeing that data, but also in parallel, we're setting up a discussion with FDA about what a phase III program should look like. Our hope is that we can run a reasonably sized RA study, specifically in this late line population that can get us to a product for, again, these patients. The patient population that we studied, sorry to take a step back, was refractory patients who have failed at least two basically of IL-6s, TNFs, and JAK inhibitors. For patients that have failed multiple lines of advanced therapy for RA, there really aren't options. Our hope is that we can design a study for that patient population and have a real impact.
Yeah. This seemed like almost like a fourth line plus setting-
Exactly.
... for these patients.
Yep.
One of the interesting features here is that, could you get that almost indication carve out for difficult -to- treat RA? What do you think the FDA's receptivity would be, given the fact that you've now produced some really interesting data, very positive data in this population, which is very tough to treat?
I think one of the things that FDA has consistently, quote unquote, worried about in RA is that people are trying to sneak into earlier line therapy, and we are not.
Lead us.
FcRns have a different price point. This does not make sense as an early line medicine. I think we would be enthusiastic, per se, about a label restriction to late line patients. I hope that FDA will be receptive to that for a bunch of reasons. There are, at this point, a couple of examples of people pushing in that direction. There is obviously the T-cell engagers and the CAR -T therapies that will also be multi-mechanism failure patients. I think there is a little bit of FDA is clearly thinking along these lines. We will be the first with a phase III study, I think, in this population. I think we are going to have to have that conversation.
So base case is that you are running another study. Somehow if it hits that sig, would you file on that data for Period 2?
I think it is extremely unlikely that the FDA would accept for approval a randomized withdrawal 170 patient study in RA. Obviously, if we hit a p- value, we are going to take the data to FDA as a part of the overall conversation, but I am not holding my breath for that outcome. But hopefully the phase III program from here can be straightforward. And again, obviously these are patients with a lot of unmet need, so we will see what happens.
Got you. So we should be thinking probably more traditional type of trial, maybe single trial, but more traditional type of RA trial in just that specific population.
Look, I think our hope would be to run a single relatively small for RA phase III study of a relatively conventional design. But there is still a pretty wide range of things on the table. We will talk to FDA. Obviously, if we did hit a p- value here, we could consider rerunning a randomized withdrawal trial. I do not think that is the base case plan here, but it is one of the things that is on the table. If FDA wanted two studies, as long as they were both reasonably sized, this study enrolled really quickly, I am not sure it would be a problem for us. But that said, if this study hit, I am not sure why we would need that. So it just depends on how this looks, and we will have the conversation with FDA.
Got you. In terms of the opportunity, it is fairly small, but again, maybe there is pricing opportunity here because it is such a narrow population and a very sick population. I guess, how do you think about the difficult-to-treat RA opportunity if that is kind of the specific label indication you are able to get?
Would you describe myasthenia gravis as small?
Yeah.
I think it is comparable in size to the other FcRn indications. I think there are 75,000+ patients who are multi-mechanism failure RA patients who would be potentially eligible for an FcRn. I think that is the commercial model of an FcRn that is an incredibly attractive market. I think we have carved out a leadership position, in part because I am really proud of the study we run. I think we really have figured out how to enhance a patient population for FcRn applicability, both through things like ACPA titers and enrolling patients who have high autoantibody levels.
Then I think the very fact that we are looking at, let us say, JAK and TNF failure patients. Why is there a late line RA patient who cannot be treated with all of the potent anti-inflammatories we know of? It is because their disease is caused by something other than inflammation. There is something interesting and causal about the autoantibody selectivity, if you will, of these patients who have failed inflammatory mechanisms. I think that is giving us a super enriched patient population for our needs.
Got you. Is it fairly easy for these docs in clinical practice to measure those titers and get that information to figure out who is best suited for a therapy like this?
Measuring autoantibody levels in RA is an easy thing to do, is the honest answer. I am not worried about that. The truth is, if you are treating multi-mechanism failure RA patients, the willingness to go on a variety of drugs is an answered question. These are docs who are using pharmacotherapy for these patients. These are patients who are willing to try things, and they have just failed so far. I think they should be pretty easy patients to access, and they are sick, and they need help.
Got you. Maybe moving along to CLE. You also have an update coming in terms of more of a proof of concept trial, signal finding trial. Maybe put into context what we should expect from that trial and ultimately what is the path forward there if we start to see an interesting signal.
Yeah, perfect. Look, we've said all along CLE is a bit of a flyer for us. It's an indication that it's high risk. If we are successful there, that'll be an opportunity. We'll be a first in mechanism approval or first in mechanism program. There's sort of two quote unquote issues. One is that lupus in general is a hard space, and the other is it's not just good enough to have a successful study. There's a bunch of mechanisms coming in CLE that have less frequent dosing and other things. I think we've got to look at our data and feel confident that we have a commercial opportunity.
This is a small and inexpensive study, and I think the way that I would prefer people think of it as a true proof of concept, like signal finding. What do we see? If we see great data, I think we'll be excited to carry it forward into phase III, and if we don't, we'll write it off as an experiment and some information. I think that's kind of how I think about the CLE opportunity.
How strong do you think the rationale there is given some of the data that's out there, either for FcRn or just in general?
Reasonably strong. Look, nipocalimab, obviously, I don't know how much detail we have about it, but nipocalimab has succeeded in SLE, which is a related indication and probably a harder one to study clinically. We had a couple of patients' worth of good data in a sort of small program in, I think it was New Zealand. I think there's reasonable rationale. There's clearly an autoantibody role in CLE, forget it, Jake, it's lupus. It's a tough set of indications, but I think the therapeutic sort of mechanistic rationale is reasonable.
Yeah. What is a win for this? What is like, "Oh, this looks good. We are moving forward. We have got a path here," versus middling data?
Unfortunately, my unsatisfying answer to that question, I think it is going to be a little bit of an I-know-it-when-I-see-it outcome, in that there is a bunch of different parameters, and you are going to have to take a step back and look at the data and decide, would a drug of this profile be competitive? That is on top of the fact it is a pretty small study.
Yeah.
But look, I think you can certainly generate commanding data in small studies, and I think if we do, the path forward will be clear.
Yeah. I guess, should we think about, because it is a small study, a lot of variability here, or again, it is going to be kind of noisy.
Yeah. Absolutely. That's why I say, I think it's going to be a totality of the evidence kind of a consideration. It's just hard to say with this number of patients. I think the main thing we're looking for is there real disease activity? And if there is real disease activity, is it the kind of disease activity that we could design a phase III study around to produce a competitive profile?
Got you. Okay. As we think about other Type I interferon and autoantibody driven disease, so we were talking about this with argenx before. But ultimately, we're starting to get a nice proof of concept here across myositis. We're getting Sjögren's and also potentially lupus, JASMINE, your CLE data. I don't know. One, how do you think that impacts potential Sjögren's trial, but also just potential for future indications with that kind of mix of underlying disease pathology?
Look, I think it's difficult to appreciate because we all live it every day in different ways, just how large the potential field of FcRn indications could be. And every time you add a brick to the wall, you put RA in, and then you're like, "Oh, wait. There's a bunch of inflammatory diseases that kind of rhyme with RA that could be interesting." Obviously, if CLE works, there's a bunch of things that rhyme with lupus that could be interesting. As we move into Graves', we haven't talked about at all yet in this conversation. There's a bunch of endocrine diseases. There's a bunch of different places you could imagine going. And I'd say, as I'm sure Karen did the same, everyone keeps their best ideas quiet. But I think there are a lot of interesting places to imagine going with an FcRn from here, and we're working up a bunch of those possibilities in parallel.
Got you. This is one where you guys certainly will be first, for an FcRn, and in general. I guess we're seeing a lot more entrants, more competitive intensity that's coming into the pipeline. I guess when you look at FcRn versus maybe more the TSHr antibody approach, who do you think wins in this market?
Imitation is the finest form of flattery. I'm very proud of the following statement, but also I believe it. I think if we had not pioneered development in Graves' disease, it would not be a thing right now. I think it was not on people's radars. People were focused on TED and other places, and so I feel really great about that. I think ultimately, Graves' patients are going to win from the plurality of options that are coming. MG is a crowded field, and argenx is doing great. I don't think the fact of competition. I think the fact of competition is generally good for first entrants, as we will be in Graves'. To be honest, I'm not worried about it. I'm excited about it.
I think the more people pitching new therapies to endocrinologists in the U.S., the more they will use new options for these patients, the more they will improve the lives of these patients, and the more they'll wind up using IMVT-1402, if our clinical profile is what I hope it will be. We'll see. Specifically to your question about TSHr mAbs. Look, I think the problem per se. First of all, I think all of these things are good approaches, should work. I think anti-TSHr therapies, whether they are antibodies or small molecules or whatever, should produce a good effect in Graves' disease. The nice thing about FcRn is it's a very elegant mechanism for Graves'. Graves' is the cleanest autoantibody driven disease in the book. It is caused by autoantibodies that are stimulatory of the thyroid.
If you can reduce the autoantibodies, they stop stimulating the thyroid, the thyroid stops being overactive. It's not very complicated. The problem with the TSHr mAb is similar to the problem with methimazole and ATDs. Ultimately, what's going to happen with a highly effective down regulator of the TSH receptor is you're going to wind up pushing patients to hypothyroidism. I suspect that most of those programs, the way they will be developed is they will dose to saturation, they will floor the thyroid, and then they will replace with SYNTHROID.
Which is, as a clinical profile, probably not as good as something that can elegantly take away the autoantibodies. Now, the flip side to that is, if you are a patient with 100 times the normal limit of TRAb, even a drug like ours that 80% suppresses TRAb is going to leave you with 20 times the normal limit of TRAb. There will be patients that you cannot treat, even with an FcRn. The TSHr approaches should work. They will effectively shut down the thyroid chemically, and you may be able to get patients regulated that way.
I think there is absolutely an interesting opportunity for a TSHr-directed therapy. I think it will be a likely more complicated, potentially less pleasant patient experience than an FcRn if FcRn works. But I think these things could all happily exist side by side. And there is other cool things. There is specific autoantibody degraders in development, and lots of other neat ideas for treating these patients. And I am sure there will be a plurality of approaches that make sense.
Got you. So one of the things, and I think this has evolved over time in terms of how investors in the community have looked at Graves' as an opportunity. Originally it was like, "Ah, there is really no market. ATDs are great," whatever. And there has just been really little innovation in the space. So I think that narrative has changed. But I guess, how do you guys view the market and the best candidates for therapy as you guys will be emerging as the first new therapy in a long time?
I don't envy your job.
Yeah.
In that the problem with Graves' disease is you are faced with a tough choice. You either need to believe in it, in which case, the numbers that stare back at you on the page are idiotic.
They do.
Difficult to reconcile, or you need to find some reason to be skeptical so that you can write a normal-sized number on the page. Those are the choices. Obviously, it's clear where we are.
Yeah.
It's just a tough problem. The truth is there are hundreds of thousands of poorly controlled Graves' patients in the U.S., and they walk around feeling sick, and some of them develop thyroid cancer, and some of them develop other comorbidities, and it's a tough disease. I think if we're successful, there's a lot of different ways to get into that market, and we are enrolling a variety of different kinds of patients, from patients who have sort of variable waxing and waning disease, to patients who just have an inability to get controlled on antithyroid drugs, to patients who are controllable maybe, but only on pretty high doses of methimazole, where they're unpleasant from the side effects of methimazole. Further complicating things, in the U.S., you could have two patients who are in God's eyes the same.
The underlying Graves' disease is the same, but they are treated at different endocrinologists. One of those patients is treated on low-dose methimazole and is miserable because their thyroid hormones are out of whack. The other patient is on high-dose methimazole and is miserable because of the side effects of the methimazole, and that's its own difficult thing to manage. I think the short answer is, I think these patients are going to come from a variety of different phenotypes, and I think we're going to have to meet them where they are. It's one of the complicated things about getting out into the world.
Understood. Maybe with the last couple of minutes, just we're the FcRn, the mechanism is evolving and obviously long acting and things like that. How do you remain competitive here with IMVT-1402, are there other things that you guys are working on in terms of life cycle extensions and things for your FcRn franchise?
Yeah. Like everybody, we're thinking about novel next generation ideas. We've got some stuff in the works, and we'll talk about it when it's worth talking about. Until then, it's just an idea. I'll say, I think the greatest mark of success is when people are asking you what's next. I think mostly IMVT-1402 is a great drug and it's not yet approved in any indication. I think our first and near term goal is to turn that into a drug that matters for a bunch of patients in a bunch of different indications.
Believe it or not, in addition to Graves', we have a full pivotal registrational program in MG reading out next year, and that could be interesting depending on what that data looks like. I think it'll be hard to unseat argenx as the king in the MG market. We're going to hope that we generate compelling enough data to have a real shot and we'll see where we go.
Got it. And maybe just lastly, maybe walk us through the next 12- 18 months in terms of readouts across the pipeline and other events that is going on for Roivant.
Busy. Today was the PH-ILD data. Later this half we have, probably most notably at this point is the phase II registrational program for brepocitinib in non-infectious uveitis, which will be a second indication for LISRAYA or for Brepo. We have the CLE data, and we will provide an update on the second half of the D2T RA study as well as hopefully on the FDA feedback and the path forward there. That is all coming this six months.
I cannot think of any other major event through now and the end of the year, obviously, other than the continued launch of Brepo and DM. Next year we have the registrational data in Graves', the registrational data in MG, obviously a full year of potential DM commercialization, and a bunch of other stuff coming in different directions, some of which we have and some of which we have not talked about. Next year is going to be really busy.
All right. Action packed. Well, Matt, thank you so much for the discussion.
Thank you.
Really appreciate it.
Really fun.
All right. Cool.
Thanks very much.
Good to see you.
Thanks for sticking.