Roivant Sciences Stock

Good day, and thank you for standing by. Welcome to the Roivant's CLARITY Phase III Study Results Conference Call. [Operator Instructions] Please note that today's conference is being recorded. I will now hand the conference over to your speaker host, Stephanie Lee. Please go ahead.

Good morning, and thanks for joining today's call to review the CLARITY Phase III results. I'm Stephanie Lee with Roivant. Presenting today, we have Matt Gline, CEO of Roivant. For those dialing into your 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 them. I'd like to remind you that we will be making certain forward-looking statements during today's presentation. We strongly encourage you to review the information that we have filed with the SEC for more information regarding these forward-looking statements and related risks and uncertainties. And with that, I'll turn it over to Matt.

Thank you, Steph, and thank you, everybody, for joining this morning on short notice. We really appreciate it. It's obviously an exciting moment to get together. So I'm going to do a little bit of frame up here, and then I'm going to take you through what are some obviously really exciting data that we're putting out this morning. So starting on Slide 3, just as a reminder, and this was from our Investor Day last year. And by the way, we're announcing today that we're doing another Investor Day in December of this year.

So we'll come back to more of that in a moment. But it's obviously -- it's the middle or sort of early innings of a really busy period for us, and we're excited about continuing to add green check marks to this slide, such as it is as we advance multiple among these programs, but just want to highlight lots more to come, including LPP, CS, other brepocitinib indications and well beyond. So just a tremendously exciting moment. As a reminder, on Slide 4, our overall hypothesis around brepo was always that we could find a constellation of diseases where there was a sort of orphan prevalence with a large unmet need with pathobiology specifically aligned to the unique mechanism of brepo and where we thought we could make a big difference.

And I think DM was obviously the first proof point for that, and now LISRAYA is out in the market. By the way, one comment, we're not going to be talking today about the LISRAYA launch. We're excited to do that on our call on November 9 with our quarterly earnings. So today, we're focused on the NIU data.

But now with NIU, we've added another leg to that stool, such as it is another proof point, which hopefully will become a commercial product here that we can deliver this kind of transformative data in these high morbidity indications, there's a lot of need. And on Slide 5, look, NIU is a high morbidity indication. It is the third leading cause of blindness in the U.S.

There's not a lot that works here. The only really sort of approved non-steroid therapy is HUMIRA. And both in the clinical data as well as you look at the claims data, it looks like half of NIU patients on HUMIRA either fail or worsen while they're on the drug. So there's a high unmet need. And you can wind up in addition to blindness, obviously, wind up with pain, with redness, with distorted vision, with floaters, headache, fatigue, just a really tough disease.

It's a fairly prevalent disease as well. Obviously, many of these patients have front of the eye inflammation, but even among sort of patients with back of the eye or sort of all over sort of inflammation, there's somewhere between 70,000 and 190,000 of those patients from a variety of different etiologies. And it's just an indication with a huge amount of unmet need in the world.

One highlight on Slide 6, and we're going to talk much more about the marketplace for NIU, how it is evolving, how we see the patient numbers, et cetera, on our Investor Day in December. But in the meantime, just as a reminder, we are in a moment of evolution for the treatment of NIU across a couple of different axes.

First, over time, more and more of these patients are getting treated by uveitis specialists, often at uveitis referral centers. These are docs with either a specific uveitis fellowship under their belt or they're double boarded or whatever. These are docs who are like really specific to treating these patients and who are highly comfortable with systemic therapy.

Often they have a general medicine training as well and away from the retina docs who are more sort of procedure-based in their approach. And part of that is coming with an increasing understanding that this sort of systemic -- the sort of local saw-tooth flare and treat cycle, which sort of localized therapy and high-dose steroids lends itself to is just not good for patients or their eyes.

And so there's a goal to get much more stable, long-term sort of properly controlled disease. And bluntly, given the quality of data we're putting out today, Roivant couldn't come at a better moment for that transition. So we're excited to talk more about that. And I think as you speak, especially these uveitis specialists in your own research, you will hear something similar reflecting back to you from the field. We're now going to get the data. By the way, Ben Zimmer from Priovant is on the call, too. I'm going to present the data, but he'll be available for Q&A as we get into it. So look, on Slide 8, before we get to the headline, just a reminder, we chose NIU on a pretty directed thesis that it's understood that a number of the key pathogenic cytokines involved in NIU, IL-23, interferon-gamma, IL-12, IL-6, all of these are signaled by either JAK/TYK2, JAK1 rather or TYK2 and the brepo will therefore, get us good inhibition across this whole inflammatory cascade. And so that was the hope.

Obviously, the NEPTUNE Phase II data was highly suggestive, albeit with small n. And I think, look, the headline here, and we'll get into it now on Slide 9, is I feel like largely, we recapitulated the really, really exciting data that we had seen in NEPTUNE in Phase II in much larger N, and we introduced a placebo arm that looks comparable to what the placebo arm in other studies, including the HUMIRA study showed. So just a really, really great outcome. We got the largest efficacy benefit ever seen for a nonsteroidal therapy. Our time to treatment failure which was the primary endpoint here was over 48 weeks. So it was a 48-week study. We'll go to the study design.

More than half of the patients had not yet failed by the end of the study. So the median treatment time was -- median treatment failure was, in some sense, indeterminate or not reached by 48 weeks versus about 12 weeks, 12 weeks in one of the studies and 13 weeks in the other study with obviously a really great p-value. We met the primary endpoint and every secondary endpoint in each study on a separate basis as well as on a pooled basis. We had over 60% of patients got to steroid-free quiescence that is a steroid-free quiet eye at the end of the study, which is really a key treatment goal for physicians.

It's something that docs are really working towards. And it was consistent across all subgroups. We had statistically, clinically meaningful improvement in vision-related endpoints, structural and functional benefits, including on fluorescein angiography, really great resolution of macular edema. We'll talk more about that. Just a phenomenal outcome. And the safety profile, which we'll go into, but which is well tolerated and entirely consistent with everything you'd expect, both from our own prior data and from the JAK inhibitor class and other JAK inhibitors. On Slide 10, as a reminder of the study design here.

So this was an event-based study. It was a 48-week treatment period. CLARITY-1 and CLARITY-2 were identical studies. You can see on the N's on the slide. And the way these studies work is you start out with a very high dose burst of steroids, 60 milligrams starting for 2 weeks and then you taper. And as a reminder, we had, I think, the most aggressive steroid taper certainly in any big NIU study, and we were tapering over 6 weeks as these patients were fully tapered by week 8. And so our data is particularly exciting in the context of having achieved it even against the backdrop of a more aggressive taper than in the other studies for approved drugs.

And that's sort of the design of the study. And then these patients, once they failed treatment along a variety of different axes, they were then taken out of the study and put into an open-label extension. So -- or a long-term extension, I should say. So that is -- that's the design of the trial. This was a representative NIU population on Slide 11, good range of patients, good disease severity. Notably, about 1/3 of the patients across the studies were exposed to prior TNF. So that's really nice to have that data set, and we'll talk more about what it looked like in that group specifically.

Obviously, this is one of the first studies where that specific population could have been evaluated. And so exciting to see that. But overall, a severe sort of high rate of macular edema in the patient population, a good group of patients for the study. We're happy with how that shook out. I won't go into them all here, but on Slide 12, just again, we hit really terrific p-values in both studies on every -- on the primary and on every secondary endpoint, and that's across a variety of both functional patient reported, et cetera, a variety of outcomes.

On Slide 13 -- so we -- most of our trials thus far have not been event-based studies. So we have not had a lot of opportunity to put out Kaplan-Meier curves. These are, from our perspective, just absolutely beautiful curves from a variety of different axes. One, just in absolute terms, you look at these patients, the rates of treatment failure, again, placebo, 12 and 13 weeks depending on which study in both studies, brepo didn't hit 50% treatment failure by the end. But also frankly, it just like the flatness of this curve in the back half of it. Not only are we not hitting 50%, but it really looks like these patients are stable leaving the study, which is a phenomenal outcome given the quality of the treatment effect.

Notably, on Slide 14, on the left-hand side here, you have the pooled Kaplan-Meier curve for both CLARITY-1 and CLARITY-2. On the right-hand side, you have the equivalent curve from the VISUAL 1 from the HUMIRA study. Obviously, a cross-trial comparison with all the appropriate caveats. Obviously, on the right-hand side, VISUAL a less aggressive steroid taper. But overall, just -- I think it highlights in pretty sharp relief that this is field changing, that this is a really different qualitative option for these patients that will, we hope, help a lot of people.

On Slide 15, this is another version of effectively the same cross-trial comparison. I just want to highlight not only did we blow it out of the water in terms of time to treatment failure, but because we did it against a more aggressive steroid taper, the overall time from the end of steroid dosing to the median treatment failure is even more exaggerated to our favor in a way that feels really great.

These patients are getting long durable responses or long durable stability, I should say, without being on background steroids, which is just -- it's just awesome for this patient population. I'll go through a couple of the subgroups and secondaries now, starting on Page 16.

We -- this is a comparison on the left-hand side of the pooled data in the overall population for the treatment failure rate at the end of the study. You can see, again, 33.5% on brepo, 78% on placebo. And then on the right-hand side, we have the data specifically in the subset that had prior TNF experience. This is data that has already been pretty head turning in the community of docs here, and it looks pretty similar, to be honest. We're able to deliver a highly comparable rate of treatment failure on drug for the TNF failure patients as in the overall population, which feels really good.

I mentioned on Slide 17, this like change in paradigm where we're going away from sort of saw-tooth sort of flare cycle treatment to trying to get this like sustained steroid-free quiescence, trying to get these patients to a stable place. You see a quote here from an important doc in the field. And I think that change is particularly good for us in this moment because of what we've been able to show. And on Slide 18, this has been another really well received early with efficacy data point. We're getting very high rates of steroid-free quiescence at the end of the study, up to close to 60% or above 60% in one of the studies versus about 20% on placebo.

A very high proportion of these patients are stable with quiet eye with -- and I think notably, this is quite a strict definition for steroid-free quiescence. If you show this definition to docs who treat these patients. This is a really good bar to hit, and we cleared it very comfortably. I'm not going to go through a lot of great detail about what this is, but docs now manage these -- obviously, treatment failure is a very clinical trial endpoint. It's not something that docs are like thinking about on a day-to-day basis. A lot of these docs use fluorescein angiography as a technique to monitor and manage these patients.

And we have an endpoint in the study, it's on Slide 19 defined where we had a scale using fluorescein angiography to evaluate these patients. And that's notable again because it's a lot of how these patients are managed in the field.

And on Slide 20, you can see as a matter of separation from placebo, this again is in the pooled data, just tremendous separation from placebo on this measure, which again is something that I think docs are going to find really valuable because it fits much more closely with a relatively rigorous benchmark against which how they manage their own patients. A couple of more data points here to share. Again, we're just excited about the totality of it here. So we're putting a lot out there.

One, on Slide 21, macular edema. So we said about 1/3 of the population, I think, came in with macular edema. The exact numbers are in the earlier slide. Of those patients, 40% of them in CLARITY-1 and a little bit more than that in CLARITY-2 saw resolution -- clinically meaningful resolution of their macular edema by the end of the study compared with very low rates on placebo. This is something that generally you don't achieve with systemic therapy in other studies. So the fact that we were able to get quite high rates of resolution of macular edema, again, very exciting here in another way in which brepo has the potential to be important for this patient population.

Lastly, from an efficacy perspective on Slide 22, there's a variety of different ways of measuring efficacy from a functional perspective. And frankly, everything we studied looked good. This is one of the secondaries is a visual function questionnaire. It is a patient-reported outcome with a bunch of subscales include general vision, pain, near activities, distance activities, mental health, difficulty with role, dependency and driving. And we saw starting with week 6, meaningful separation with very good benefit for brepo 45 relative to placebo in both studies.

So again, not only delivering sort of the kind of things that ophthalmologists care about managing the disease, but kind of thing that patients care about and living with the disease, which feels really, really good. The truth on Slides 23 and 24 on safety is not much new to report. Consistently well tolerated and consistent with prior brepo studies and with the JAK class. We lay out the rates of AEs on 23 in a little bit of detail on Slide 24.

I'm happy to take questions that come up, but our overall view of this is it's consistent with the label on LISRAYA already and consistent with what people will expect for the drug. So look, to summarize the data on Slide 25, just a really terrific outcome. We could not be happier here. The steroid-free quiescence sets us up for the sort of present and future of treatment of NIU.

The imaging biomarkers will appeal to docs who use those techniques to manage these patients on a daily basis. We're preserving acuity and function, and we have safety that is consistent with JAKs and certainly, in our view, a good trade-off for benefit for patients with a disease that can lead to very bad morbidity in the eye. And remember, many of these patients are otherwise on quite high doses of background steroids, which are not safe or well tolerated over long periods of time. So against that backdrop, just a really nice finding. The Priovant team is going to get this sNDA in the first half of '27. And hopefully, through everything that will lead to a relatively quick approval. So taking a step back before we head out and open the line for Q&A on 26.

We've said all along that we are just getting started with brepo, and we're starting to sort of climb the hill or build this wall one brick at a time. NIU, obviously now, hopefully, the second registrational indication. We got 2 more already in the pipeline with CS and LPP, both well underway, enrolling patients looking promising from that perspective. We have a ton more we want to do.

I know Ben and Priovant team are raring to go getting additional studies up and running. And we think this just has the potential to be a huge opportunity across lots of diseases where consistently very high unmet need and not a lot of other options for these patients. And as a reminder, on Slide 27, this is just one of multiple among our programs now with [indiscernible] in pivotal studies after the great data we had earlier this fall and obviously, 1402 with a huge year -- huge next year with data coming in MG and Graves and a number of other studies ongoing as well. And still to come this year with further updates on the Period 2 of the difficult-to-treat rheumatoid arthritis study, another really exciting indication for us with a high unmet need.

Lastly, on Slide 28, on December 9, we'll have our Annual Investor Day or Investor Day this year anyway, in New York City. Looking forward to seeing many of you there. One of the things we will definitely do is talk more about the NIU market and get into what we see as the opportunity and the unmet need for patients in clear relief.

Frankly, I think this is an area that has been understudied by our investors over the last, call it, 12 months as people have been more focused on the present commercial launch in DM. And as a reminder, as we get to Q&A, we're not going to take questions on the LISRAYA launch today. We're looking forward to taking them and talking more about how that's going, which we're very excited about on the Q in November. So that's it for the presentation today. Before we head out to Q&A, I just want to say thank you to a bunch of people here, obviously, most importantly, to the investigators and patients who have trusted us. Thank you. We wouldn't have the science without you. And obviously, it's an interesting thing to give yourself over to a clinical trial.

We're happy in this case to have been able to make it worthwhile. Secondly, I want to thank Ben and the Priovant team who did a phenomenal job again with this study. I'm really proud of the quality of clinical execution that Roivant has been putting up here, and this is another example of an indication where I think first pioneered by Roivant by the investments of the governance team by Mayukh, Frank and everybody at the Roivant side and then put it into a Phase II study and then a Phase III study. It's just nice to continue to see this execution. So I want to thank the Priovant team, the Roivant team, just a huge effort. So thank you, everybody. And with that, I want to say thank you all for listening, and I will turn the call over to Q&A.

[Operator Instructions]

Our first question in queue coming from the line of Yaron Werber with TD Cowen.

Congrats on a really fantastic data set. So my question is, the data is so clear pretty much all across the board, whether you look at TNF experience, you look at macular edema, oral, very well tolerated, very fast onset of action and obviously, very good durability. HUMIRA is cheaper. Do you think you'll need to go through a HUMIRA step edit? I assume you'll get a broad label. And is there a chance you can get used before HUMIRA?

Yes. Thanks, Yaron. Look, thank you also for the commercial on our own data. We agree with everything you just said about it. It's really great data. I appreciate the question.

Look, I think -- the truth is we obviously don't know the answer to that question. Our data is really, really strong. And HUMIRA has some real liabilities in this area. So there's certainly a chance that docs will be excited about the data and will want to use it earlier. And I think that opportunity exists. As a reminder, in general, the FDA stance on JAK inhibitors is in a TNF-approved indication. There's some labeling that suggests the use of a TNF first.

And I think your payer point is reasonable, although there are plenty of plans where more expensive therapies are allowed without first stepping through HUMIRA in indications where is approved. So there are certainly examples of earlier line therapy is possible. I think the only thing I'll say is there are -- I think we put out a number for like 37-ish thousand at least NIU patients on TNFs. Even the TNF failure population or the population of people who could be better controlled despite use of a TNF is a large and exciting opportunity and one where there's a lot of unmet need. So I think we certainly have an opportunity to go earlier, but also I think we don't need to.

Our next question coming from the line of Brian Cheng with JPMorgan.

On the data this morning. Maybe just to -- when we look at the treatment failure, I believe that there are 3 criteria that goes into defining treatment failure. So I'm curious how the response you're seeing, how does that break down compared to HUMIRA treatment failure is what we're seeing driven by a specific component?

And then second is, can you frame how we should think about the resolution in macular edema this piece? Do you expect that benefit to be on the label? And just curious how important that is from a commercial perspective?

Yes. Thanks. So on the first question, I can say there are 4 criteria for treatment failure. the new vascular lesions, a change in ACC or VH grade or BCVA worsening. And I'd say like overall, across the population, treatment failure was driven by all of the different components. So there was nothing that like stood out specifically. It was pretty well balanced. Ben, do you want to take the macular edema question short?

Yes, sure. I think we'll -- TBD won't get on the label. I think that it is an exciting add-on and differentiation, particularly from adalimumab or any off-label other TNF inhibitors or biologics that are used.

As Matt mentioned before, it's generally both from clinical trial data and clinical experience of view that these patients are not able to address their macular edema through those therapies. I think what's really exciting about this data overall is the opportunity to combine benefit on macular edema and CST with a therapy that could provide overall sustained disease control around inflammation and uveitis more broadly. And I think that -- I think it will be an exciting point of differentiation in the context of the overall data set, but I think that there's a lot here that is going to be really exciting to doctors.

Our next question in queue coming from the line of Yasmeen Rahimi with Piper Sandler.

Congrats to the outstanding data. Gline, it would be wonderful if you could kind of educate us. I think you did a great job with brepo and DM on kind of helping us understand that these patients are in concentrated centers.

Maybe just talk about sort of the heterogeneity or the -- like where -- is there a cluster of these patients under these community retinal docs? How do you envision that? And maybe to the extent you could talk about how much that would involve expansion of your sales force that would be dedicated to the NIU launch? And I know maybe many of these things may come up at the R&D Day in December, but to the extent you could give us some broad color, we would be very grateful.

Thanks, Yasmeen. I appreciate it. It's a good question. And we will hit a lot of this in more detail on our Investor Day in December. I think, first of all, there's just an increasing trend towards more of these patients being treated at these centers. I think the centers make excellent early relationship points for us here because they are equipped to manage systemic medicine and are already big users of systemic medicine. We'll talk a little bit more about number in the future, but I think they will be among our earliest and most important call points.

There are obviously also retina docs and docs in the community who partner with rheumatologists and so on to use systemic medicine. You can see where they are. They use HUMIRA and so on. So I think we're going to be able to call on a variety of different physicians. I'll say, I think the correct expectation here is this is a different commercial organization than the one largely currently launching in dermatomyositis.

So I think it's not, it's not -- it's going to be a new commercial effort. Obviously, the patient support work, a lot of the other things that are going into making those trial successful will be reusable, but the field personnel will be different. Look, I think the truth is these patients are often going blind.

They're not hard to find, right? They're out there. They're engaged with their docs and the doc tolerance in general for eye disease is poor for eye inflammation is poor. So docs are reaching for the most aggressive things they can find. And so they are -- tens of thousands of these patients are treated in these specialty centers, more and more are getting referred there. And I think the goal is to treat them very aggressively.

Our next question coming from the line of Samantha Semenkow with Citi.

Congratulations on this really great data set. I'm wondering if you could talk a little bit more about your appetite for potentially expanding indications for brepo, specifically within ophthalmology, maybe even for diseases with macular edema given the data this morning relative to the expansion opportunities for other therapeutic areas because I know that there's potentially a long list that you're evaluating.

Yes. It's a great question. Look, I think the short answer to our appetite for expanding indications for brepo is high, and we're doing a lot of work on that. There are ophthalmology indications on our list. There are other indications on our list.

I'm not prepared sitting here today to commit to any particular sequencing or pass of those, but I'll say we're living with this data fresh. We've only had it for a few days. So let us continue to study it and see what avenues it suggests, but lots of great places to go, spoiled for choice and definitely hoping to do more fast.

And our next question coming from the line of Alex Thompson with Stifel.

Congrats as well on the data. I guess one of the other differences versus VISUAL-1 was that you didn't require patients with baseline OCS use. I guess could you comment on sort of how those patients did? And maybe to Yaron's question earlier, sort of what that might mean for how brepo could be positioned within the broader NIU population?

Yes. Thanks. It's a great question. I appreciate it. And Ben, I'll ask you to comment, too. Look, I think in general, first of all, it's a severe patient population. We have similar efficacy regardless of whether baseline OCS were involved or not. Obviously, a unique thing about this patient population is that there are also TNF experienced patients in it.

So there's some pretty sick patients who have gone through a lot of things. So obviously, like, for example, the VISUAL studies obviously couldn't have included TNF refractory patients. So we wanted a broad population. I think that will be helpful in the sense that it opens up the broadest possible opportunity for NIU patients sort of regardless of where they are in the treatment cascade. But again, no sort of significant differences in effect across those subgroups. Ben, anything you'd add to that?

No, I would just say that the VISUAL study was conducted a while ago. I think there are more heterogeneous therapies used today to control patients with active disease, including systemic therapies, obviously, TNF inhibitors, which were not used at that time, being the major other off-label therapies, DMARDs. And so what we really wanted was a population that matched the real-world population. And I think that's what we got, which includes a lot of patients who were on background steroids, some who had been on in the past but weren't at the moment, patients who have been on other therapies.

And yes, that's what the baseline criteria or the baseline demographics, I think, capture well across a variety of ways in terms of percent of patients with macular edema, percent of patients with posterior and panuveitis, percent of patients who had prior TNF therapy, I think, captures this broad-based active population. And I think that's really kind of where we would expect to see the drug used in the real world as well.

Our next question coming from the line of Yatin Suneja with Guggenheim Securities.

Congrats, obviously, on the data and continued amazing execution. Just a question on the payer front. I mean, what sort of feedback you have received or the work that you have done, especially now that we know what the price is going to be. And again, I think it's a similar type of a question that Yaron asked earlier. How should we think about positioning and the acceptability of the price in the context of what is out there for these patients?

Yes. Thanks. Look, it's a great question. Obviously it's early days even in the LISRAYA launch. So I think it's still -- we're happy with how things are going so far, but still learning how to manage that over time. But again, happy with how things are going so far. And also quite early days with this data.

So I think it's like a little bit premature to answer that question. The unmet need is very high. These patients are losing vision. There's very high morbidity from the disease. And we've seen in other markets tolerance for high price points in eye disease, frankly, because the unmet need is high and because the ability to improve morbidity for these diseases really matters.

I'll say, as a reminder, dosing here is 45 milligrams, which is different from the DM dose. So we have some flexibility on price in terms of where we could go. And I think we're -- I'd say every option is open. We haven't made any decisions. Again, we have only had the data for a few days. So looking forward to learning more from exactly the conversations you're suggesting over the next months. And I think we have a lot of flexibility in a disease with very high unmet need.

Our next question in queue coming from the line of Prakhar Agrawal with Cantor Fitzgerald.

As well from my side on the data. Maybe, Matt, you talked about the different subcomponents of the treatment failure. One of the subcomponents, the change in mean BCVA. Could you confirm if that also looked comparable to Phase II and better than that seen with HUMIRA. We've gotten some questions on that. And then one technical clarification. rescue meds seem to be handled as failures.

How were the discontinuations handled in the stat plan and whether this handling is comparable to HUMIRA VISUAL 1? And just lastly, as you think about the sales force expansion, given this is a new physician call point, how should we think about that?

I'll take those in reverse order. They're all good questions. On the field force, I think the answer is we'll provide more color on like the specific sizes of things probably starting on Investor Day and developing from there. So stay tuned. On the

discontinuation handling versus visual, I think the answer -- I'm going to hand it over to Ben for the first of your question, so he can take the other one as well. I think the discontinuation handling was the same as it was handled in the VISUAL program, which is a little bit different than the way the primary endpoint was defined in our own Phase II, although we presented the data both ways.

But the discontinuations were handled consistently here as in VISUAL. On BCVA, my only comment is everything looks strong and consistent across the map. That data is still being analyzed in part. It wasn't -- it wasn't in the hierarchy and stat plan, a little bit of a different handling. But overall, it all looks very good. Ben, anything you'd add on BCVA or any of the other data points?

On BCVA, I would just highlight that we -- all 4 of the components of treatment failure contributed to the results. So we saw differences between drug and placebo across the board. I would also highlight that just the way this disease is managed is the doctors precisely because of what Matt was describing in terms of really today, even in many ways compared to when the visual program was conducted, there's really even less of a tolerance for vision loss.

The doctors really do not want these patients to worsen because they're of the view that they might not fully ever get better. And so I think often, you'll see patients failing for one of the other criteria because doctors are monitoring the biomarkers carefully and then they want to switch therapies before the patient has a 15-letter loss in acuity. And that's very much consistent with clinical practice in a growing way at these uveitis centers as Matt described upfront. That said, there were patients who failed for BCVA. And like I said, all 4 components, including that one contributed to the total result.

And just 2 other points just to close the loop. One is discontinuation handling, just to be clear, didn't matter in the results. And BCVA, which we presented at an academic conference, which was great, also hit stat.

Our next question coming from the line of Douglas Tsao with H.C. Wainwright.

Congrats on the data. Matt, I think at the beginning of the call, you talked about sort of how patients are treated very differently by uveitis specialists versus more sort of general treaters in the community. And I'm just curious if you have a sense of both the split between patients between the 2 and how a patient ultimately ends up being treated by uveitis specialists.

Yes. Thanks, Doug. And again, we'll hit more of this at the Investor Day in December. But including numbers on the split, there are tens of thousands of patients at least treated at uveitis specialty centers, and there is -- there's a little bit of a gray area where there are some community docs that are double boarded or have uveitis fellowships and some centers that are like really concentrated. So it's not exactly a bright line.

But part, by the way, of the reason I say that is what I expect many people are going to do in the coming days given the quality of this data is make doc calls. I think it's important to talk to docs who use systemic therapy to treat these patients because they are the ones who really contextualize this data and the way they're managed in that sense. How do these patients get to these centers?

In part the answer to that question is the way they get -- by community physicians who don't do a lot of systemic therapy management, there's sort of a flare and response cycle. And what winds up happening is these patients come in, they flare and they get treated with something, either a high-dose steroid or something local an injection and then they're better for a little bit and then they flare again. And eventually, frankly, these community docs the retina specialists don't want to keep treating these patients.

It's not their area of expertise. And so the referral is often sort of bidirectional -- that is the doctor themselves would prefer to be in the procedure business in many cases and wants to get out of systemic management. So they're happy to refer. Also, these patients are sick, they're losing sight. So they're aggressively seeking expert therapy and they're eager to find a good place to be themselves. And so it's a combination of different things.

Our next question in queue coming from the line of Jason with Bank of America.

My question is on the filing for brepo, NIU. What are the gating factors to filing as we think about the first half '27 window? And secondarily, brepo has fast track designation for NIU. Do you assume a standard review or priority review for the sNDA?

Thanks. That's a great question. I don't have an answer sitting here right now other than this is great data, and we think it is important to get the drug approved as quickly as possible. We're working along that axis in every way that we can, and we'll provide an update when the sNDA has been accepted and we have a PDUFA date.

Our next question coming from the line of Andy Chen with Wolfe Research.

I just wanted to ask a quick question about the market share pool that you guys have. So what is the pool of untreated NIU patients eligible for brepo versus HUMIRA experienced patients? And within the untreated population, how many actually require systemic therapy? And how should we think about the prevalent patient opportunity at launch versus annual new patient starts?

Yes. Thanks. These are all great questions about the market opportunity, and we do think there's a lot more work to do in the world for people to understand just how many of these patients there are. There are lots of NIU patients. And frankly, there's a variety of reasons why HUMIRA is used, where it's used, many of these patients have comorbidities.

So there's a lot to talk about here, much of which we're going to cover in detail in December. I'll say there's a huge opportunity just concentrated in the sick patient population today that is on best available therapy and not well managed and are often on and off high-dose steroids, in some cases, 20-plus milligrams of steroids being used, like these are sick patients who are losing their sight.

So I think like there's a sort of [indiscernible] easy sort of first call point. But there's 50,000 patients systemically treated today, as we said, potentially upwards of 100,000 or close to 200,000 patients overall, many of whom are poorly managed in this flare and retreat cycle. So lots to do, again, excited to talk more about it in December.

And there are no further questions in the Q&A queue at this time. I will now turn the call back over to Mr. Matthew Gline for any closing comments.

Look, thank you again, everybody, for listening. It's always fun when these things work. It's always fun to put out data like this. I think this is head turning data that's going to matter to physicians. It's going to matter to patients. This is a disease with really bad morbidity.

I always do this, but like you should go on Reddit to the uveitis subreddit and look at how patients talk about their experience with disease. This is a tough diagnosis, a tough situation, and it's just phenomenal to be able to make a difference. So thank you again to the investigators and the patients who entrusted us with their care here. Thank you to the Priovant and Roivant teams too and everybody who ran this study. It's a great outcome, and we couldn't be more excited to be taking this one forward and advancing other indications as well. So thank you all and look forward to catching up again in a couple of weeks with the Q.

Thanks, everybody.

Ladies and gentlemen, that does conclude the conference for today. Thank you for your participation, and you may now disconnect. Goodbye.

Good afternoon. Welcome back from lunch. To introduce myself, my name is Richard Wagner. I work with Jason Gerberry on the U.S. large-cap pharma names. I'm based in London. On behalf of my colleagues, Chi Fong and Dina Ramadane, covering analysts for Roivant and Immunovant, respectively, I'm pleased to welcome Matthew Gline, CEO of Roivant for a 40-minute fireside chat.

Thank you, Richard.

Roivant has achieved several key milestones this year, including positive Phase II readout of your once-daily inhaled sGC mosliciguat in PH-ILD and approval of your TYK2 JAK inhibitor, brepocitinib in dermatomyositis. We still have multiple readouts coming up before year-end. To help level set the discussions, what would be the company's top priorities in the next 12 months?

Yes, perfect. So look, it's been a period of a lot of progress for us. It's been a great 12 months behind. We just, as you mentioned, got brepocitinib, now LISRAYA approved, and we're making some real progress on the SGC front on the pulmonary hypertension franchise. Look, coming up the next 12 months, very busy 12 months ahead. Obviously, one of the most important things for us is with brepocitinib now in the market, we're in the early innings of that launch, but we want to go as well as we possibly can have it. And so there's a lot of work going into making that successful.

We have some major clinical data coming in brepocitinib, including between now and the end of the year in non-infectious uveitis, where we haven't given specific guidance on when, but relatively soon, we'll have data from that Phase III program. If that's successful, we'll then file registration there, and that would be a second potential registered indication for LISRAYA for brepocitinib.

And then after that or in addition to that, we have a bunch of data sort of going on as it work for our FcRn programs at Immunovant, including later this year, updates on both the CLE program as well as probably more importantly, the D2T RA, the late-line rheumatoid arthritis program, where we'll talk about our development plan there and our path forward after putting out some good early data earlier this year. And then next year for Roivant is a huge year with registrational data, less importantly in myasthenia gravis and much more importantly in Graves' disease, major indication for. So those are sort of upcoming data. And then other than that, I'd say major priorities are getting everything else up and running to sort of start new studies for the pulmonary hypertension program and to initiate new indications for all of the other drugs as well.

Thank you. That's a great introduction. So I'd like to start with brepocitinib or brepo, you mentioned 1 month into the launch in dermatomyositis. What can you say about the launch experience? How is it tracking with your internal expectations so far?

Well, our both internal and externally disclosed path there is slow and steady. That's what we said over and over and over again. The truth is we're 3 weeks in. So there's really very little to say that's productive. I'll say what I think most investors know, which is if you talk to treating physicians, at least the KOL community, there's a tonne of enthusiasm and that has certainly translated into our early experience. But what that means in terms of scripts and coverage and everything else, it's just too early to know, but we feel great about what we're doing and optimistic that we're going to have a good outcome there. But slow and steady remains the guidance. Look, first time there has been a novel therapy launched in dermatomyositis in a very long time or ever. And so it's just hard to know the unknown.

You mentioned scripts. So what type of launch metrics can investors expect on the earnings call? Will you present the patient numbers, enrollment forms?

Yes. What we've mostly said about this is that we're focused on the launch itself and focused on net sales is the ultimate judgment. I don't -- we have not given specific guidance on what metrics we're going to provide. I'm sure we won't be able to help ourselves from providing some subset of that stuff. But the honest answer is it feels like companies have mostly not been rewarded for providing a lot of detail and guidance on this. So I think mostly, we're focused on having the launch itself go well, having the patient experience be positive, having the reimbursement piece be positive and letting the sales speak for itself over the medium term.

Good. Do you see any read-through from the evolving competitive landscape for the commercial opportunity for brepo and [indiscernible]?

Mostly no. I guess the sort of most sort of obvious version of that question is argenx put out their myositis data whatever it was late in the summer. I think prior to their receiving that data set, my sense is that their expectations for DM were relatively muted, and they had more hope in IMNM. Indeed, they hit a p-value in the IMNM subset of patients as well as for the study overall and did not get a p-value in the dermatomyositis subset. That said, I think their data in DM probably exceeded their own internal expectations. And it's clear from their body language and their voice would like to see the product approved in DM ultimately.

I think they've been a little bit equivocal on whether -- what that's going to take from a clinical development perspective. But I think a reasonable expectation is they'll have to run a study in dermatomyositis, potentially some sort of small bridging study similar to what they did seronegative MG, but we'll have to see. Our view commercially all along has been, look, this is an orphan indication with very high morbidity, reasonable mortality, a lot of unmet need. I think a rising tide is going to lift all boats here in the sense of like my hope is that they get approved. I think their approval will be good for us. I think brepo remains in DM specifically, the drug in position. But I think it would be good if they got approved as well over time. And I think their data was reasonably impressive for what they clearly view as the secondary indication of myositis.

Okay. Good. So turning to non-infectious uveitis. What outcome would you define as a good outcome for brepocitinib?

Yes. So this is another indication where there hasn't been a lot of medical innovation. And so there's a lot of unmet need. This is the third leading cause of blindness in the U.S. It's a pretty devastating disease and tolerance among the ophthalmology community for occular inflammation is very low because it can lead to blindness and permanent damage. The only sort of approved "novel" next-generation therapy is HUMIRA. And there's about 50,000 -- a little bit less than 50,000 NIU patients currently on TNFs.

Our Phase II data was very, very good on cross-trial comparison. The primary endpoint in these studies is time to treatment failure, which is what it sounds like. And in the HUMIRA studies, placebo was 3 months and change and HUMIRA itself had like, I think, 5.6 months time to treatment failure. In our Phase II study, we didn't have a placebo arm, but our high dose was greater than 12 months on average treatment failure. That was as far as we measured. So a pretty significant difference from HUMIRA experience.

I think that leaves a lot of room. I think even if we do not wind up being in the Phase III program sort of "better than" HUMIRA cross-trial comparisons, it may not matter that much in the sense that HUMIRA has a pretty high treatment failure rate and these patients are generally looking for new options relatively early into treatment. So I think we're going to have -- as long as we're statistically significant, we should have a drug and a good commercial opportunity. And then within that envelope, the better the data, the better we look comparatively, I think the better our chances are of earlier adoption, earlier in the treatment cascade.

Yes, that was my next question. Where would you see it positioned commercially given that the TNF biosimilars are available?

Yes. Look, I think you got to assume that the default expectation here is that we live in a HUMIRA refractory or TNF refractory population, both from an access perspective and frankly, the FDA's general stance on JAK inhibitor and JAK inhibitor-related mechanisms in TNF-approved indications is that a TNF is the right first bet.

I think there's 2 important caveats to that. One is until we've seen the data, it's just impossible to know. And I think because this indication can lead to blindness, because tolerance for inflammation is very low, I think it's possible if our data is good enough that will push aggressively for earlier line use, and that may help both with the FDA ultimately and with payers. And I as a reminder, biosimilar TNFs available, et cetera, in a world where docs feel like they need to get patients through a TNF in order to get them on to an efficacious therapy where data is very good.

I think you could just see TNF use increase as docs are trying to cycle patients on to brepocitinib over time. So I think we'll have to sort of see how that plays out. But I think a reasonable base case expectation is that we live in a sort of TNF refractory world. And again, there's 50,000 NIU patients on TNFs. Many of them have inflammatory comorbidities like an RA or an IBD or something like that. But anyway, if you're on a TNF for any of those indications and you develop by definition, a TNF failure, you switch patients on to something else.

Okay. You mentioned soon having the Phase III soon. Can you narrow it?

We have not given guidance beyond second half is the official guidance on it. We announced that the 52-week study fully enrolled sometime prior to November of last year. So that puts us squarely in the second half -- hope we are in the second half now. I have not seen any data yet.

Okay. No data in-house. So turning to 1402, the FcRn you mentioned, and you set up the different readouts very nicely. So starting with difficult-to-treat RA, expecting the randomized period 2 data in the second half of '26, you've guided to sharing a comprehensive update. Also caution that period 2 may not look as great as the open-label period 1 data. So can you speak about the potential data scenarios if you hit or not in period 2? And what would be the implications for?

So as a reminder, this is sort of an interesting study. So this is a study of our anti-FcRn antibody IMVT-1402 in late-line treatment refractory RA. So these are patients who have failed at least 2 sort of biologics classes in RA, I think IL-6s, TNFs, JAK inhibitors, et cetera. Many of them, I think 60% have failed a JAK inhibitor, for example. So these patients have few other pharmacotherapeutic options and are quite sick. And the study we ran was an open -- was a randomized withdrawal trial, open-label run-in period followed by -- for those who had achieved an ACR20 response in period 1, they were then rerandomized either a lower dose or they either stayed on drug, went to a lower dose or dropped off altogether on placebo. That was sort of a blinded randomized withdrawal period.

Now the period 1 data that we generated, the open-label data was very striking. So of the patients in period 1, about 70% of them achieved an ACR20, about 50% of them achieved an ACR50 and about 35% of them achieved an ACR70. Now if you think about the period 2 population as denominated in that 70% of the ACR20 responders, that means like almost 2/3 of the period 2 patients had an ACR50 or greater response and almost half or about half had an ACR70 response. The primary endpoint in period 2 was loss of ACR20. So you've got all these patients who have achieved an ACR70 or an ACR50 who in order to be primary endpoint responders have to drop down below ACR20. It just feels like a pretty high bar to imagine hitting statistical significance in period 2, given the depth of response in period 1.

So what that means is what we said at the time we put the period 1 data, I think period 2 from like a data perspective is probably less informative than it could be because the period 1 data was so good. Now the good thing is the likelihood that we're even an open-label study, ACR70 spontaneous ACR70 responses don't occur in this RA population very often. So when we look at period 1 and we're like, okay, we have a drug. Like this is very likely some signal here. I think we'd like to see some amount of separation in the period 2 data that the patients who went into placebo lose response ideally faster than the patients who are still on drug.

There is some tail pharmacodynamic effect with the drug in the first few weeks of that period is still working. The randomized withdrawal is only 12 weeks long. So it's hard to know exactly. We'd like to see some separation in order just like make us confident about Phase III. Other than that, I'm not sure we're going to learn that much from the clinical data here given what we saw in period 1. So I think like success here looks like no red flags that would stop us from running a Phase III study. And then the real question mark isn't so much what is the period 2 data. The real question mark is what is the development path forward for the drug in this subset of RA patients?

It's a subset of RA patients which there have been vanishingly few clinical trials run. There's 1 or 2 ongoing now, mostly in like T-cell engager or CAR-T kind of therapies where there's -- or B-cell depleting therapies where the risk profile looks pretty different. I think the question for us, for the agency is, what are you going to try and make us do? What are we going to be comfortable with? And there's a pretty wide envelope from relatively small hundreds of patients, like a few hundred patient studies to the typical thing in RA development will be multiple 1,500-plus patient RA studies.

It would be surprising to me if FDA in this late-line population want us to run something more like that program, but we won't know until we talk to them. And I think the big update later this year is going to be like what have we aligned on with FDA. I think there -- it is imaginable that FDA could dig their heels in, in a way that would make us question the program overall, but the most likely outcome is we get comfortable with some kind of middle ground and we go forward.

Do you think you could file on a single Phase III?

I think that is a question we will have to discuss with FDA. The rheum division is historically relatively conservative on that point. But again, this is a patient population with few options. And the data from the open-label period at least here was impressive enough that it's certainly a conversation worth having. But I'm not sure is the answer.

I do think -- we will see other drugs in this patient population approved with comparatively small and comparatively few studies because some of those drugs will be CAR-Ts and T-cell engagers where there will just be a preference to expose as few patients as possible in the clinical setting without an obvious risk-benefit discussion to that kind of risk. And so I think we have that going for us as we go in front of the agency. We're like they're clearly going to be focused on streamlined studies in this patient population, which I hope we can take advantage of.

There's also the cutaneous lupus or CLE POC headline data at the end of the year. You've described CLE as a commercial hurdle as well as a scientific one. What would 1402 need to demonstrate for the company to commit capital behind the Phase III program?

That's a good question. And we've always described -- and frankly, we described D2T RA the same way as well before we had the data. CLE really is an option bet that is like it was never intended to be a heart of the thesis kind of a thing. It was about the upside skew. And to your point, that's in part because, look, CLE is not just about the state of the field. There's a lot coming. There's the BDCA2 from Biogen, there's TLR7/8, including from [indiscernible], like a bunch of other mechanisms. A lot of those mechanisms have the advantage of being less frequently dosed than an FcRn.

And so I think we have to not just think about what a successful study looks like, but like how do we convince ourselves that we'll be commercially viable and over all those programs are coming. There's a little bit of like we'll know it when we see it on the answer to that question, but I think it's got to be like pretty good data. And bluntly, I think it's not very likely we're going to clear that bar, but that was the point all along. If we clear the bar, we've opened up a new swim lane for FcRn, and that would be really exciting. If we don't clear the bar, we spend very little money on a small study, and it didn't work out, and that's sort of fine. That's part of the portfolio that we're taking forward with FcRn is to have to do those bets.

Yes. You mentioned, I think, clearing a lane was your analogy. So would you see this then as a broader validation of FcRn inhibition across lupus spectrum?

Bluntly, no in the following senses. One is specifically within lupus, look, we know that FcRns can deliver some benefit in lupus now. Nipocalimab, for example, has generated positive data in a properly powered much larger study in SLE. And so I think like there isn't really a need to "validate" the idea in lupus spectrum diseases. And so I think it's more of a specific referendum on CLE. And again, this study is fundamentally underpowered at some level in a way that makes it like hard to treat it as validation in either direction, either affirmatively or negatively. So I think the answer to that question is like it's not that relevant.

The other thing that I'll say is insofar as an important question about FcRns is how do they work more broadly in sort of multifactorial immune complex kind of diseases that involve -- like for example, RA fits in this bucket, Sjögren's fits in this bucket, CLE fits in this bucket, SLE fits in this bucket. I think the amount of data that has now been generated across these diseases is supportive of the idea that FcRns can play a role in their treatment in a way where, again, I think whether this trial has failed or successful, it's not going to like radically alter at least our view of what FcRns can do with those kinds of diseases.

And look, we pick CLE over SLE because SLE is tough and CLE should be slightly less tough, but it's tough. And I think it's like hard to overread from a single small CLE study. Again, I think the main question is just do we see enough signal in this study to want to run what will be itself a relatively risky registrational program just given the nature of lupus.

In 2027, you have the Phase III Graves' disease readout. So what keeps you up at night operationally about the Phase III Graves study?

Biotech is an industry that everything keeps me up at night all the time. I guess where I'm going with that comment. It's just biotech is a wood chipper designed to shred souls. So there's a lot of things that keep me up. With Graves' specifically, if you want to feel comfort about our Graves' study, you would stand back and you'd say, okay, of every indication in which FcRn has ever been studied, none has clearer biology than Graves' disease or more straightforward endpoints than Graves' disease, at least in terms of thyroid hormone levels, right?

Graves' disease is a disease where antithyroid antibodies affect the TSH receptor and lead to an overactive thyroid. It's like a relatively straightforward thing. And the disease is clinically managed on T3/T4 and to some degree, TSH. And so that's sort of the focus of the study. So we want to feel good. The biology is very clear, and our Phase II data was unequivocal. If you want to feel less good, our Phase II data was a single site, roughly open-label study run by one investigator in Germany. And that is plus or minus some TED studies, which aren't really the same patient population, the only modern study of Graves' disease ever conducted.

So we have very little information going into this study about the variability of patients, et cetera. And among the things in the endpoint is an antithyroid drug titration criteria, which rhymes with all of the challenges people have always had in immunology trial, trying to taper people down on steroids and other things. So look, I think there are real and meaningful risks associated with that study. Biologically, the rationale for the Phase II data was quite good. So I'm pretty optimistic, and I think it's a less risky study than something like CLE or the D2T RA was before we got into it. But I think of the major studies we're running, Graves' was definitely the riskiest.

Okay. And where would you see 1402 positioned in the current treatment landscape, assuming success in the Phase III?

Yes. This is the crazy thing about Graves' disease, which I think we have struggled with a little bit, to be honest, is if you sit down and you model Graves' disease as a commercial indication, I mean, there truly are, call it, 350,000 uncontrolled Graves' patients in the U.S. who have exhausted every treatment option available to them. And the truth is for an FcRn, if you can get 5% or 10% share of that kind of market, you have a huge, huge, huge drug. And so I think against that backdrop, these numbers just get like unimaginably large very quickly.

What do I think in terms of where we could be used? I think some of this is like what we're trying to learn in the clinical setting, but I think there are first of all, there's about 20,000 patients here who have their thyroid surgically removed to a lifetime of synthetic thyroid hormones. I think like those are pretty good candidates for therapy. And at least before they have that surgical procedure, they might consider trying something like an FcRn.

But then there's still a lot of patients who are either uncontrolled, meaning even at quite high doses of methimazole or other antithyroid drugs, they can't get thyroid hormone levels controlled or who can get control on methimazole, but who deal with -- but can't get off methimazole and deal with a lot of negative side effects associated with methimazole. I think both of those populations are like reasonable places for us to think about, and we're studying versions of both in Phase III.

When we talk with KOLs, they speak about the threshold of patients focusing on patients who achieved thyroid hormone normalization. And you had mentioned tapering that may not go off of the antithyroid drug. What threshold do you think would be needed to displace methimazole in first line?

I don't think we will displace methimazole in first-line treatment of Graves' disease. First of all, there are millions of patients with Graves' disease, and many of them can get adequately controlled pretty quickly on a low or reasonable dose methimazole. We're not even tracking those patients, not enrolling in the study. We're not focused on them, et cetera. I think the real question is in the 350,000 patients for whom methimazole is just like descriptively not sufficient in one way or another.

And I think the answer is like at that point, the threshold is not "displacing" methimazole, the threshold is just like clinical meaningfulness. The threshold is just like what level of normalization of thyroid hormones is going to be sufficient to get people on drug? And how successfully do we need to get patients off ATDs for them to want to be on another agent. In our Phase II study, I think close to 60% of patients were able to get off ATDs or to reduce their ATD dose meaningfully while getting normalized from thyroid hormone perspective. I think anything like our Phase II data would be a grand slam like that outcome for us.

Are you looking at drug-free remission as a value driver?

We studied in the Phase II, and we're studying it again in the Phase III. There's reasons to believe in Graves' disease, taking a step back that -- well, biologically, part of what happened in Graves is you get these negative feedback loops for the antithyroid hormones. The antithyroid antibodies attack the thyroid. The thyroid becomes enlarged and inflamed. And then that seems to beget a negative cycle of more autoantibodies. And methimazole in many patients can lead to remission because these patients are like not that -- some of them, not all patients, but like some Graves' patients wind up being not that sick with Graves' disease in a way where like you use methimazole, the thyroid reregulates, it shrinks down in size and the body stops producing enough of these autoantibodies have a problem.

It stands to reason then that for sicker patients, okay, you can't treat them successfully with methimazole and get them into remission now. But if you could add on a layer of treatment on top of that, you might be able to actually reregulate. And so I think that's encouraging. In our Phase II study, we were able to get a pretty significant portion of patients under control in an off-drug remission. Remember all of the patients in the Phase II came in uncontrolled and like 17 out of 25 of them, I think, were still controlled months after the end, maybe more than that maybe, were still controlled.

17 of 21.

17 of 21 were still controlled 6 months after discontinuation of therapy. And so it's -- I think we do have a possibility of some durable off-drug remission.

And I assume that there's an open-label extension for you to be able to...

In fact, one of our 2 Phase III trials has a -- it's a 12-month study with a 6-month primary where there is a proper like responder rerandomization to measure remission built into the study. So it's not just an open label. We will generate placebo-adjusted remission data in.

So just a general question about FcRn. As they move into increasingly heterogeneous diseases, what have you learned about which diseases for which deeper IgG lowering actually matters versus where you may be constrained by a ceiling...

We have studied this question ourselves in many indications. And I appreciate that it is convenient for our competitors to talk about the existence of possible ceiling effects because they have limitations as to how deeply [indiscernible]. But to be honest, first of all, FcRn biology is not actually that complicated. You're reducing the level of pathogenic autoantibodies in diseases where pathogenic autoantibodies are some level of disease driver.

I think the burden is on the poser as far as arguing that there should be a threshold effect, and we have not found one anywhere. That is, in every indication we have ever studied, we have found at least at the individual patient level, the patients with deeper IgG suppression had better responses than patients with lesser IgG suppression, which I think is what you would biologically expect. And so my honest view is there will not be a threshold effect. In any disease, deeper IgG suppression will matter. The curve of how much it matters versus other things may vary from indication to indication.

And bluntly, there's a commercial question, which is like, what, take myasthenia gravis. I think our -- I think if you ran a head-to-head study versus VYVGART, we have a reasonable chance of winning just given the depth of IgG suppression. Does that mean we would then win commercially? I'm not sure. Argenx is very well established and VYVGART is a well-loved drug, and it helps control these patients. And if our data is only marginally better, which who knows what our data will be these studies coming out next year, it's just not obvious whether we can sort of take a majority share commercially get some share take majority is hard to know.

But in general, the answer is, I think deeper IgG supression appears to be a little better benefit. You started out this question when talking about the complexity of some of these diseases in terms of being multifactorial like rheumatoid arthritis, for example, is not cleanly an autoantibody-driven disease. I think, a, learning -- one learning of ours that is deeper expression seems to be better all around.

I think a learning specifically from our RA study is that patients who fail anti-inflammatory drugs and have high levels of autoantibodies may be specifically good treatment populations for us and that you've sort of really narrowed it down to patients who are still sick, who cannot be treated with anti-inflammatories, which I think is sort of suggestive that a driver of disease for them is autoantibodies. They're obviously also assessing the antibody level itself. I think that playbook, if it continues to look good in RA, could also apply in some other settings as well.

Any questions from the audience on brepo or 1402? Then transitioning to mosliciguat...

Just on 350,000 patients with Graves' disease which are poorly controlled. Is there any further way that you segment that market as far as where this drug makes more sense, where patients maybe have come up to the trial quicker easier?

So I think the problem with this indication for a lot of people is you start with 350,000 patient number and then you try and build a commercial model and it looks sort of silly, any way you cut it, if you assume the drug is going to be successful. And I think it's just true, right? I think like if you assume whatever, 10% share of 350,000 patient market is 35,000 patients at an FcRn price point is a $12 billion indication. So like you could get big numbers very quickly.

I think in practice, there's a bunch of different ways that cat will wind up getting skinned to be a little worried about it. I think one is I mentioned patients who are having thyroidectomies. I think obviously, for that subset of patients, it was a relatively smaller group, I think about 20,000 a year, you can imagine people wanting to try a final pharmacotherapeutic option before they move to a surgical procedure in a lifetime of Synthroid. But also, I think patients who are intolerant of methimazole or who need to be on such high doses is to be limited by the side effect profile.

I think patients who are living with meaningfully out of whack thyroid hormone levels in a way that leads to real sequelae, I think those are probably like the most obvious first patients versus the patients who are sort of subclinically hyperthyroid or whatever or they are whack on relatively low dose methimazole they're making it. That said, there are absolutely patients who are on chronic 5-milligram dose of methimazole who have been for years and who are incredibly eager to like put that chapter behind them. And I think those patients are absolutely eligible to try something like an FcRn and see where it takes them.

Just a simple question. Looking back, right, historically, you've had a history of finding attractive buyers for your assets. And now you have a fully developed commercial infrastructure in place. So how do you then decide which assets to keep and which to probably sell to others?

Maybe you could repeat the question. There was a problem with the microphone.

The question was, in the past, on a couple of occasions, we have sold drugs that we have developed to third parties. probably most notably, we sold a portfolio of drugs to Sumitomo Pharma back in 2019, and we sold an anti-TL1A antibody to Roche in, I want to say, 2023, 2024. I'll start by saying we are in an incredibly privileged position right now. I would hope most companies feel this way, but I would not trade our pipeline for basically any other pipeline in biotech.

And I think if you drew like a chart of valuation on one axis and I don't know, probability of exceeding $20 billion of sales on another axis, we are at a pretty unique corner there, right? There are other drugs that have some probability of getting there where the companies are less highly valued, but they're just like a tonne of whatever, they're like an obesity company with a tonne of complicated compounded commercial and clinical risks. You have companies like argenx or whatever that have obviously, at some level, a higher probability of those kinds of sales because they're commercial and already doing many billions of dollars of sales, but they're valued much more richly than we are.

I think we're like at a pretty unique opportunity. I think that is a pretty unique spot on that chart. I think it's like a function of the programs that we have. And I can't name any other biotech company where I feel like there's 3 drugs that are as credibly potentially as large as the 3 that we are focused on right now. So I think parting with any of them would be a painful proposition relative to the unique opportunity in front of them. And I think our default case here is let's try and build something big and durable around this pretty unique moment for us.

For those who followed the company, I think you know that Roivant is ruthlessly economic in our decision-making and that everything has a price. And that if someone offered us tens of billions of dollars [indiscernible] tomorrow, we would take the call because it's what we're supposed to do. So I think never say never, but I think our default here is to build something big and durable and not to sell these programs.

Okay. Next topic I wanted to touch on was mosliciguat. And you had mentioned that your culture is ruthlessly economic. You're not capital constrained. How do you balance those dynamics as you build out the development plan for mosliciguat?

One of the things about how we're structured is, in general, once you get to executing a trial, at least each program's resources don't cannibalize the other programs. That is what we can do in pulmonary hypertension is fully distinct from what we can do in orphan inflammatory disease and brepocitinib is fully distinct from what we can do in the FcRn market. So we have -- to the extent that we have resource constraints, and we do -- we can't start 10 studies all in the same day. Those resource constraints are sort of by program. And I think the impetus at this point for all of these programs, including mosli, is to get a new study set up as quickly as we possibly can.

I think the value for us of indication expansion is extraordinary right now, 0 upfront, relatively modest capital out of the door. I think we're pretty good at choosing indications, pretty good at running studies. I think that combination is really potent for what we think we can deliver. So look, with mosli, we made a decision to start the Phase III study at risk about 6 months ago because we wanted to not be sitting around waiting if the data looked good. That decision would have looked dumb if the study failed and now it looks prescient because the study succeeded, and we're all judged in hindsight.

But that means we probably have the capacity to turn our attention relatively quickly here to like the second indication at mosli. And I think we're finalizing our work on that now. I think our view of what is optimal from a path perspective is probably changed given the high quality of the data we saw in the PH-ILD study. And so I think we're just like reassessing that ordering and prioritization.

I think we've definitely -- next year, Graves' and MG will roll off in Immunovant. This year, NIU is rolling off at Priovant. I think as those indications complete, there is absolutely capacity to ramp up new ones and then we continue to hire and grow and build out the clinical team the more we have data that reinforce our view. So I think between those things, we should have the capacity to stand up new indications across all these programs in the coming months.

When would you communicate to investors what the next development phase would be?

We, in general, tend to wait until we've started the study before we communicate the next indication. That's true for a variety of reasons. FcRn is competitive. It would not be surprising to me if argenx wind up running an RA study now we put out the data, we've got in RA, they are running a Graves' study. So I think maintaining the lead is helpful. And then also just there hasn't been much reason to like get out ahead of our skis on this stuff, so we haven't done it.

With the remaining time, just to conclude, what excites you in the early pipeline?

We haven't talked much about anything other than those 3 programs, and I'm probably not going to start doing that now. there's BD stuff that we're excited about that we're close to. And then there's other tricks up our sleeves that we haven't discussed very broadly. And then there's just like I'm personally incredibly focused on and excited about standing up additional indications, starting with brepocitinib but across the whole portfolio because as I said before, if you look at argenx had like $12 billion of market cap on their myositis data. The market is rewarding new indications. I think we're pretty good at choosing indications running clinical trials. And we have 3 programs from which to choose from, all of which have broad enough biological activity to open a bunch of doors. So I think there's just a lot of value to that exercise.

Any last questions? Great. Thank you very much.

Thank you. Appreciate it.

Sam Semenkow, one of the senior biotech analysts here at Citi. And it is my pleasure to be hosting Roivant at Citi's 2026 Biopharma Back to School Summit. I'm joined by Richard Pulik, CFO of Roivant. Richard, welcome, and thank you so much for being here.

Thank you so much. And it's officially, I think, also the first day of school in New York School. So perfect timing with the conference.

Yes, it is. It is, and we will go to school today on Roivant. So why don't we just start off high level, Richard. Obviously, you've made a lot of progress on the pipeline, lots of great data that you shared with us this year. And you've had your first FDA approval for brepocitinib. Maybe just level set all of that and what we can expect throughout the rest of the year, where Roivant stands and where Roivant aims to be in the next several years?

Look, we've had an incredible year so far. As we think about Roivant, look, we're approaching $30 billion market cap here. We have $3.9 billion in cash, which doesn't include the $700 million plus that we received in July on the Moderna settlement. And we have now, I would say, with the [ mosli ] data that read out a couple of days ago, really affirmed the third leg of the stool into a place where that can be another big pillar for the company, adding to brepocitinib, where you mentioned, just had our first approval for LISRAYA is the drug name in dermatomyositis, which, look, I think if you look at the label, it's pretty incredible in terms of the indication statement, no restrictions in concomitant use. And then also covering the skin and muscle manifestations and breadth of the disease of the study that we had in the Phase III data, which was a disease that's been largely ignored and it was the largest DM study that's ever run.

And so to kick off and going into this patient population is ignored for a long time, I think, is a very Roivant move, right? We -- as we formed the company and thought about areas where to go, it was really to think about disease areas where there's high unmet need that have been ignored for a long time that are severe in scope and also where we had a bit of validation, right, where certainly, there was either data that was driven by investigators or that we had seen from other JAKs that worked here. So look, it's a very exciting time for brepo. We certainly have 3 other indications that are late stage there with NIU reading out this year in a Phase III study and then CS and LPP ongoing.

And then the third leg of the stool is really Immunovant-1402, where we also had some exciting data, and I think data that surprised a lot of the investment community, especially in difficult to treat RA. Certainly, [ nipo ] paved the way a little bit with in RA, certainly -- but in a much earlier population, but we saw that FcRns had activity there. And then we, again, thought in the Roivant way, where do we go here? Where is the underserved population. And that was in patients who are very late line where JAKs and TNFs have failed and where we can deliver strong efficacy. So we saw very strong efficacy rates there with ACR70, 50 and 20, and that was period 1 and period 2 is reading out later this year.

And then along with -- we have CLE data, right, which is, again, another Roivant type indication where we could potentially be first. Certainly, I think that's a flyer, right? We're really trying to see if this is an area where we hit a bar that makes sense from a commercial perspective. And I think there's a little bit more competition there. But we had seen a little bit of data in some patients in you see that sort of help validate this, and we'll see what that looks like. And then we have 4 other indications with MG and Graves potential approvable data sets next year and other indications that we can go into, but that's really the third leg of the stool here. Certainly, we're very active as well on BD given our cash balance and the breadth of resources we have.

It's a great overview. Lots to dig into. So maybe we do start with the [ mosli ] data that you shared earlier this week. Excellent data, clear proof of concept. I think it exceeded the expectations you've set for the Street by far and even the expectations I had in like a bull case scenario. So maybe just talk a little bit about that data set, what the reaction has been from KOLs in the few days since you presented it at ERS and just frame the market opportunity for us for PH-ILD.

So maybe to back up a little bit. So we -- [ mosli ] is an sGC activator that we got -- we did this deal with Bayer. We paid, I think, roughly $15 million or so is the upfront. And then there's milestone payments under $300 million and then high single-digit royalties. This is an area where, look, sGC activators have been looked at systemically for quite some time in pulmonary hypertension. And then we showed data about a couple of years ago at ERS that showed the highest PVR reductions we've seen in PAH. PAH was a market that had, what, 6 or 7 therapies, I think, at the time when we showed the data. So lots of breadth of available therapies, mosli was a once-a-day inhaled DPI. And then -- so it doesn't -- and then with a differentiated mechanism with a long half-life and we delivered in PAH.

Then as we were thinking about where do you want to go, going back to what I said before, to a place that doesn't have a lot of addressable and really a lot of scientific development, right? Obviously, we have Tyvaso and we saw the great data, and I would say, innovation there for PH-ILD patients. And so we ran the study. And then what happened and happened a couple of days ago, we saw the highest PVR reductions we've seen in PH-ILD. We surprised people because we -- look, we didn't power for the 6-minute walk test, but we delivered with 35 and then we saw -- this is at week 16, and we saw continued improvement at over 50 placebo adjusted.

So -- and then if you look at across all of the key measures we had, we saw that they continue to improve. So these are very smooth curves where you actually continue to improve after week 16 and as you're dose escalating and then on the safety, right, we had very good safety data, no -- I would say the [ treprostinil ], obviously, of cough is an on-target effect. So again, an easy to use once-a-day molecule that has delivered really the best efficacy markers we've seen so far and even on 6-minute walk, which we were powered for. So I think that's really opened up a lot of excitement for these patients. And then that data was presented at ERS a couple of days ago on short notice, I think the room, as I was told, was very full.

There was a lot of excitement from KOLs. And this is a really severe disease where people really have trouble just walking across the small room. The morbidity is very high with a lot of people dying within a couple of years and have a terrible quality of life. So this is to deliver this kind of data is very exciting for the field.

Yes, absolutely. And you maybe anticipated some of this in some sense because you started the Phase III at risk already. So that is well underway. The only major difference might be just -- and correct me if this is wrong, but background treprostinil is permitted here. And -- but you have a Phase II combo study ongoing. So you're going to learn a little bit more about that in the coming -- going forward. So could you speak to how that data will inform how you're thinking about how much background treprostinil to enroll? And just overall, if you replicate the Phase II data that you have today, would that be more than sufficient for you to take this to FDA and then be quite competitive? I think the answer is probably yes.

So in the Phase III study, that's ongoing. Yes. So look, I think we did take a flyer here, right, moving directly into Phase III. And I think that's another place where we surprised people. Certainly, we obviously didn't really know the breadth of this data and took a little bit of risk on there. But look, I think the other thing that's been at the core of the company is to really to get -- look, we knew the PAH data. We knew how powerful and how unique this drug was and to be able to get this out to patients quickly. That seemed like a risk that we should be taking.

And then in terms of the study, look, I think the titration is a little bit faster. It also allows treprostinil as we're -- we have another study that's ongoing that you mentioned, which is pretty small. That was really driven for safety. So that will kind of help us inform the cap we want to have there on treprostinil use. I think one consideration there's obviously given Tyvaso not approved ex U.S., that certainly is something we need to think through as well as we're thinking about that. But it will help us as we go to the FDA here to help validate the Phase III thinking and then also, look, as you see the data, you see this data on top of other therapies, right? So this was -- this is an indication, just like we've seen in PAH that could be used on top of other therapies. It can be potentially additive. We'll see what that looks like on the combo. And then this could be one of those diseases that's treated multifactorially.

And then we think beyond PH-ILD into expansion opportunities, you mentioned a few of the obvious ones that are on the table for you. But maybe just talk about those and how you're thinking about prioritizing what the next indications for mosli are? How many can you maybe go forward with at once to maximize this opportunity? Or is it more one at a time as you triage through them?

Look, I think certainly, what I said is in our initial thinking, we thought PAH was potentially too competitive. But we now really have proven with this data set that we have really delivered the best PVR reductions we've seen across pulmonary hypertension. And maybe that gets us back to thinking around whether we go there. I also think as we look at these data a little bit more fully, there's certain subtypes of patients here that can help us inform where we want to go. And -- but look, I think it's -- with the data came out a couple of days ago, I think this is really, like I said, created and firmed up the leg of the stool here, and it's really all hands on deck now to think very broadly about developing this just like we did with brepo and with 1402.

And I would say the beauty of our setup is that we really think given demand structure, we can really move quickly here and do this in multiple ways. Of course, right now, the -- we're going to go to FDA. We're going to talk about the PH-ILD data and really push that forward. And I think simultaneously, the team will be doing quite a lot of work to think through where does it make most sense and where can be the biggest impact on patients across some of these other disease areas across pulmonary hypertension.

The great data has created a lot more work for you. So looking forward to hearing more about that in the future. Maybe just switching over to DM then and talking about the approval of LISRAYA. Maybe can you speak to any of the early engagement that you're seeing from physicians since the approval?

So look, I think -- so first of all, this is the biggest DM study that we've seen. These patients are treated on very high dose steroids and then also IVIg. And this is a disease where -- that has muscle and skin involvement. If I think about -- and so we delivered data across all of these different areas, I think that got physicians excited. And then we have, like I said, captured a lot of that data on label. Certainly, we anticipated a black box given it's a JAK. And I think that's -- that was always in our hypothesis here, and it hasn't really stopped much of the broader indications that JAKs are going after either. And so given the area of the disease, I think that's all again very manageable.

But I think the physicians are very excited here. We -- the reality, check, is that we're going into a disease here that's been ignored for a long time. And so to change behavior, look, there's the sort of Ivory tower that we all sit in and then there's the reality of the physicians and changing behavior. And so I think that's the work we have to do now. I think we're well set up with MyCompass. We thought through the dynamics here. And then we have the real -- there's a lot of breadth here for brepo. So it's sort of a long haul to make sure that we're maximizing the value across these other indications as well. But look, I think there's a lot of excitement from patients and also physicians. But certainly, we think this will be a slow and steady launch as we really develop this molecule broadly.

Maybe we can dive a little deeper on the breadth of where brepo can be used. We've heard physicians say they're excited to switch their patients off IVIg if they're not fully controlled. Some physicians are heavily using off-label JAKs, others don't have any. So perhaps there's an off-label JAK switching market or physicians have even said first line to us. So when you think about what that initial addressable population is in DM, like how should we be thinking about that?

I would think all of the -- I mean, you can use it with IVIg. I mean -- so look, I think the reality is these are kind of younger patients who -- if you're on IVIg, you have to go in an infusion center 4, 5 days a week, obviously, in a month. That's a pretty big burden for someone of working age. And -- but look, if they're doing well on that, they can obviously also go on brepo. So I think there is a -- I would not think about this as exclusively across these different segments. I think the data that we certainly delivered was also -- you can think about it as first line in some of the KOL discussions, also some of these patients are on off-label JAKs. So to have actually real data in hand for -- with the breadth we have, I think we're very well positioned, and you can think through it across all of those different segments of the market.

And I think slow and steady has been your guidance for some time now. You reiterated on the approval call. And revenue is really the metric -- main metric you're going to provide to the Street. This is perhaps maybe a little unfair, but as we go to 3Q earnings, you've already had some -- I think you mentioned like some engagement on even day 1 post approval. What is -- how should we be thinking about that? Like is that something that's like a couple of single-digit million? Like any guidance you can really like -- not guidance, any framework you could share?

Look, I just think it's so early that -- and I'm not -- this is not to sort of -- it's what, August 27, if I recall, was when we had the approval. So look, it's super early days. I think like ultimately, you can think about various different -- because of specialty pharmacy, it's going to be hard to sort of see script data, et cetera, right? I mean this is like a typical rare disease launch. And so as a CFO, what matters is net revenue ultimately. And I think that just takes quite a bit of time to build and do well, especially as we focus on making sure we get the medicine to patients. We have the bridge program in place, and we have a good patient and physician experience here.

And then given the breadth of data that we have, the revenues will come, and I'm confident that since given the data set and then even as potential competition comes, that really helps with new approved therapies and awareness for the disease to get these patients on much better drugs.

Got it. And on the side of competition, I think it's picking up in DM. I think people have looked at your success, looked at the market. a lot more interest that we're seeing from a range of companies and a range of mechanisms. How should we think about the longer-term opportunity for LISRAYA as the DM market matures with multiple novel therapeutic options, particularly given this is a polypharmacy market currently?

So I'd just like to remind people, there were many failures in this disease area, 6 or 7 of them with very smart, very large different trials. And we are very uniquely positioned here because it's the TYK2/JAK1. When we looked at the data when we did this deal, we had roughly 1,500 patients of data across and we compared that to different JAKs alone or TYK2s alone and outperformed across all of those different data sets. I mean this is for a much broader disease, right? But that -- there is a unique mechanism here where we're first. And then we also have the data in hand. Look, I think when -- as you're thinking about where you go and as you're thinking about mechanisms, I mean, sGC activator, sGC stimulator, there's sort of stories we say to try to think through, but the data that really matters is the patient data.

And given that this is the largest DM study we've had and the breadth of data and endpoints, I think we're very firmly positioned here and also given our mechanism, and it's a once-a-day oral. So being able to really replace -- most of these patients are really on high steroids. I mean that sort of 70%, I think, of the market. And so switching those patients and getting them off of a pretty bad being on these high steroids is pretty bad, not just from a lifestyle perspective, but also from a side effect profile perspective as we had seen in the DM data. So I think we're very firmly positioned, and it will be great to have other mechanisms come here to help these patients.

Absolutely. Maybe we switch gears a bit and talk about NIU as well because this is the next major data set for you before the end of the year, in terms of like Phase III, although we have some 1402 data to talk about as well. But I mean, the unmet need is clear in NIU, but can you just talk overall how you're thinking about that market opportunity?

So noninfectious uveitis, that's one of the leading causes of mice in the U.S. There is -- again, you have steroids and then you have HUMIRA. We had a Phase II data set fairly small that was not placebo-controlled, where we saw compelling data, not just on sort of this multifactorial time to failure endpoint, but also on edema, resolution of edema and also keeping patients from getting edema and resolving it that was -- we haven't seen really across any of the available therapies. These are also -- if you think about the HUMIRA patient pool, that's probably 50,000 at this point. So delivering a once-a-day oral with such strong data, I think, is very compelling.

The reality is the Phase III placebo controlled. We know in these studies that placebo is always difficult. But as we design the study and thought about the mandatory steroid taper, which, again, we had in the Phase II study, right, where it was much faster than HUMIRA. And then we also think about the endpoint, which is essentially time to treatment failure over quite a long time, that should also ultimately show up on the placebo versus the brepo arms. But look, this is a commercial opportunity that's, I would say, even larger than DM. So it's very exciting for us, and we'll see the data in short order this year.

Looking forward to it. I have a pricing question for you. You set the price for LISRAYA. And as we think about the upcoming Phase III NIU data potentially being positive and pricing in that setting, particularly because the brepocitinib dose that you're testing is higher for NIU. It's about 45 milligrams versus 30, which is on label for LISRAYA. So how should we think about pricing? Is it going to be higher from a WACC perspective? Or how should we think about net pricing to the extent that you can provide some framework there?

Look, I think the first thing is what do you deliver to these patients, right? And so once we see the data and if we can deliver what we saw, then that will help command price. And then certainly, because the DM indication is 30, there's some flexibility there potentially, right, since that would be a 45 mg dose. But we'll -- look, we have -- once the data reads out and if it's positive, we'll have a lot of feedback on the current price, and we can think through those dynamics, but there's certainly flexibility then to do what's right given the data set and where we land. And then, of course, we have the CS and LPP indications as well as we're thinking through that, which are also at 45-milligram dose.

Which is a good segue. Maybe let's talk about those. You're running pivotal trials in both. And I think these get less airtime perhaps because there's not any more data from either of them this year. But maybe just like walk through both diseases, how they fit into your broader dermatology franchise that you're building for brepocitinib and just a little bit on the opportunity for both there.

So look, we delivered very compelling data with CS that I think got a lot of excitement where we quickly were able to enroll and start this Phase III study. That patient population is sort of similar size to roughly 50,000. And then LPP is maybe twice that size. There's really no approved therapies. It can be very disfiguring, particularly drives hair loss and pretty terrible disfiguration on the scalp. So this is a disease area where there really isn't much. And so we have another Phase III there. But look, I think both very exciting in terms of the potential and then the unmet need.

And then, of course, given the data we delivered in CS. I think a lot of excitement there. With LPP, we did have a little bit of data as well that we showed for -- I think it was less than 40 patients roughly that also help validate the Phase III study and that I think has gotten investigators excited. So there's certainly some meat there to go off of as well. But these are -- when we're set and done and assuming all these indications come through, I mean, brepo could be addressing roughly over 250,000 patients in the U.S. for -- in areas where there's really no real treatment options, and there hasn't been a lot innovative treatment options, and there really is an availability of this type of once-a-day oral therapy.

And when you think about your strategy for indication selection for brepocitinib going forward, I mean, should we expect that the dermatology franchise continues to be something that you're considering expanding? Or could we see you branch out into other therapeutic spaces kind of like you've done for NIU? I mean you have a plethora of options here, I imagine.

Yes. Look, I think number one is scientific, right? Where does -- given the uniqueness of the molecule, where can the science go that differentiates? And I think these are multifactor diseases where -- you have cutaneous sarcoidosis, pulmonary sarcoidosis like that you have overlap with a lot of different diseases. So you have skin and muscle manifestations. And so I think you really have to think about this as where is the science and where does that make sense? Where is the patient need? And then where can we make a big difference? And I think there are -- I think given the data we have, I think there's a lot of interesting areas where we can go. So stay tuned. But I wouldn't necessarily think about, oh, well, because we have derm data, we need to stick to derm. I think it's where is the need and where the patients need us to go.

Yes. Fair enough. Maybe we spend a little bit of time on 1402 as well. We're expecting that rheumatoid arthritis period 2 data. And I think you've guided to ideally wanting to share a bit of a more update, which includes the period 2 data and perhaps some regulatory feedback, if possible. What are the potential scenarios we should be considering on the path forward for RA towards the end of the year when we see that data?

So look, I think the data that we had in Period 1 was surprising to people, right, given the ACR70, 50 and 20 response rates we had. In the period 2 portion of the study, the real question is, can you get patients down to -- in a 12-week period, really make a meaningful impact on ACR20 when you've had such success, right? And so I think that will be answered soon. We said that's coming out this year. We'll go to the agency with that. I think what we have answered is that we have found a niche here in rheumatoid arthritis for patients where nothing worked, right, that were on JAKs, TNFs, and we delivered incredible data that really, as you looked at [ nipo ] and some of the other things that are out there, like the reality is IMVT-1402 degrades IgG to the 80% range, right?

All of the other late-stage anti-FcRns in development are in the 60% range. And so we -- this, I think -- this is the first data set, large data set we've had for IMVT-1402 that's really proven out that IgG hypothesis that's carved out a -- these are very sick patients that are pretty desperate. And so we'll see what that looks like on period 2 is I think do we hit it or not? I think it's really -- how do we then incorporate that into a Phase III study and talk to the agency about it and where do we go with it and D to TRA, I think, is the real question.

Yes. Absolutely. So I mean, it's likely then Phase III, you'll need another study. Is that...

Yes. I think that should be the base case assumption here.

And then just quickly on CLE. You alluded to this in your opening remarks that it's a competitive space. You want to make sure that this will be a competitive product. Can you help us frame what that bar looks like for what would be competitive versus just 1402 works from a proof-of-concept perspective?

So look, I think we got -- when the nipo lupus data came out, I think we got quite a few questions, well, does this have a read on CLE. Look, I think that, again, frames that potentially this could work. I think the reality is this is a small -- fairly small study. We need to really look at the data closely and then understand is it making an impact? Like who are these patients? What kind of efficacy are we seeing? And is the impact meaningful enough to invest behind it and also to get investigators and patients excited. So I'm going to disappoint you not throw out a percent number for you. But look, I think there's also other CLE trials reading out, right, around this time or in the next few months. So we'll kind of look at that closely and see what makes most patients for patients.

Fair enough. Okay. Well, we are nearly out of time. So Richard, I just want to turn it back to you for any closing remarks you have to share and just maybe recap -- we've gone through 2026 and the expectations, maybe recap what we can expect next year from you as well.

So look, I think such a fun time for Roivant for our patients. I think it's really validated a lot of key areas of our strategy. I think mostly now has been -- is now a solid pillar of the stool. And then we're really looking forward to the MG and the Graves data. I mean we didn't even cover Graves really. I mean this is an area that, again, there hasn't been innovation for a long time. These patients are very sick. These -- they're not responding to existing therapies. And that will be a very exciting launch for IMVT-1402. And then hopefully, on MG as well, we can deliver better efficacy data as we had seen earlier with bato. So look, we'll see what that looks like. That will give us our first launches, hopefully for 1402. And then we have the other launches behind as we expand on brepo and I think exciting pieces to announce for mosliciguat as we expand the breadth given the incredible data we had and then stay tuned as we look through other business development opportunities.

But I think that it's -- we're in a really unique situation in place. And -- and then from a cash perspective, it's well funded, and we still have the ongoing litigation on the other LNP trial that goes. And so we'll see how that plays out. But we're just in a pretty incredible place here, and we returned a lot of capital to shareholders, right? We had, I think, at this point, returned over $1.7 billion. A lot of that was returned at $10 a share. And so really created a lot of value. And I think we're going to continue to be very disciplined and very thoughtful about capital allocation and making sure we're making the right choices across the portfolio.

Absolutely. You're in a privileged place where you have more going on than we can fit into 35 minutes. So well, thank you, Richard. This has been wonderful. I really appreciate all your insights and the time today. Thank you.

Thank you, Sam.

All right. Good day, everyone. Welcome to Day 1 of Cantor's Global Healthcare Conference. For the next session, we are very excited to host the Roivant team. And representing Roivant, we have CEO, Matt Gline. Matt, coming off the back of a very strong data set. Happy to host you here.

Yes. Great. Thanks for having me. It's always easier to do these after putting out good data. So...

Great. So why don't we start there? Well, first of all, congrats to your clinical operations team. As well as your BD team, who got this asset from Bayer for, what, $15 million?

About that. Yes, a little less.

What's the secret sauce?

I don't know the answer. And if I did, I couldn't tell you.

Anyways, maybe focusing on mosli first, given it's hard off the press. What were some of the more surprising aspects of the data set now that you have had some time to digest?

I had like 36 whole hours. Yes. So look, this -- for those that don't know, so mosli -- mosliciguat is a drug that we had in development. It is an inhaled sGC activator that we are developing in pulmonary hypertension. And it's a drug we got, as you mentioned, from Bayer, a few years ago. And I think what I said about this data set all along was if it worked, it was going to be obvious in hindsight that it was a good idea. And if it failed, it was going to be obvious in hindsight that it was a bad idea. Because the truth is like, we know that inhaled vasodilators are generally effective in pulmonary hypertension and also the only other sGC targeted therapy ever tested in PH-ILD, [ riociguat ] had a death imbalance against the drug and was harmful to patients. And so that was obviously like not a great setup.

But our hope was that by delivering the drug in inhaled format, we were going to have good efficacy. I think what I -- so we put out data yesterday morning, and the data was phenomenal. We had the deepest ever PVR reduction shown in any pulmonary hypertension study. The study was very much not powered to show a placebo-adjusted benefit in 6-minute walk and very much did get a p-value on that endpoint. So -- there's a lot to love in this data set.

And overall, just like the consistency of it, the hemodynamics working so nicely in accordance with the clinical endpoints. Just look at this like this drug was effective in this study. And by the way, I don't know how familiar people are with PH-ILD is an indication. These patients are really, really sick. And so to be able to deliver this kind of benefit, I mean, I think it's going to change the field in many ways. Overall, the data was phenomenal. I'd say like the depth of hemodynamic responses in particular, are probably the thing that has changed the most for me in that they open my mind to a much broader set of indications across pulmonary hypertension, whereas I think if we have seen a narrower benefit PH-ILD is still a phenomenal indication. We were thinking about IPF even before. But I think with data this good, you want to go broad.

Got it. Now the conversation has shifted from the clinical data to what's the size of the market and how big this product be in PH-ILD and maybe other indications as well. But maybe focusing on PH-ILD, like -- what's the current market right now? And how many patients could be addressable with a drug like this?

Yes. So there's a range of estimates for the PH-ILD market. Our competitors have numbers out there that range from probably 30,000 patients in the U.S. on the low end to 100,000 patients on the high end. We probably think the market is on the higher end of that range. And we haven't put out our own research yet. It could even be bigger if you really push me on it. PH-ILD has a lot of patients, they're really sick. And the thing that you see in PAH, which is the much more developed pulmonary hypertension market, people have been treating PAH patients with novel therapeutics for decades, is the more drugs enter the market, the better every drug does. The patients are living longer, they're healthier for longer. They use drugs stacked on top of each other. And so I think the idea that we can be a new class in the PH-ILD market, it should further expand upon the really good work now done by United Therapeutics and Liquidia and others who have got products on the market in PH-ILD.

Okay. And you talked about the indication expansion. Given the strong efficacy here, clean safety. How are you thinking about the indication expansions, PAH, PH-COPD, IPF. How do you prioritize the opportunities where you maximize the value for this asset, aggressively?

Yes. The first -- I'm sure earlier -- I'm sure, later in this conversation, we'll talk about brepocitinib, and we'll talk about our FcRn. I think like a month ago, I would have said, okay, Roivant is a 3-legged stool or 2 legs are bigger than the third. And mosli was kind of coming up from behind. And I think this data catapults mosli into approximately equal standing with the other two programs in terms of what I think it could be long term. And so it makes you want to think broadly, as I said.

IPF was certainly something that we would have been thinking about even prior to this data set, just given what Tyvaso has shown and the nature of that market. I think what we would have said about PAH prior to seeing this data is PAH is competitive, and it's hard to know exactly where we would play. Now that we have seen this data, I think the answer is clear. I think we should be an early line therapy for PAH patients, if we decide to go there. And so I think we're evaluating that. We're evaluating other forms of pulmonary hypertension, PH-COPD, based on our subgroup data, is a little less scary although many drugs have failed in PH-COPD. And then there's Group 2, Group 4 and Group 5 of pulmonary hypertension, which are more or less completely white space therapeutic areas that are now -- we're rapidly working to come up to speed on those areas this week as we try and figure out where else we can go because it's all -- I mean, it's phenomenal to be in this situation, but it's not like we anticipated the data would be this good.

Okay. So what's the constraint? Is it capital? Or is it just resources or...

We're very blessed that it's never really been capital for us. We've just always run with a strong balance sheet, thanks to the deals we've done and so on. At the moment, I think in terms of like getting these trials started, I mean, I don't mean to be -- It takes a lot of manpower to figure out what you want to do and we run a Phase III study. And we have a lot of manpower, but we don't have enough manpower to start 8 studies all at once tomorrow. And so I think that we've got a scale up. We've got to prioritize a little bit just to get things up and running, and we've got to figure out how to get the right people in fast so that we can grow the opportunity quickly. Now the other good thing about mosli is we have IP into the mid-2040s. And so this is the long game, not a short game. But you really want to -- whatever. Once you know you've got something you want to work on, the right day to start is yesterday.

In fact, one of the things that we did, which was going to look stupid in hindsight in a bad data scenario and looks good in hindsight in a good scenario, we started the Phase III study like 6 months ago. And so we're now enrolling patients. That's all up and running. We've got the protocol in place. So like the fact that we are underway there is a huge benefit in part because it means we can probably be faster to start the next study because we're not starting from a standing start already.

Got it. Phase III, 6 months back is...

Well, yes. I'm sorry -- I started with the planning process and getting the protocol -- running. We're really just starting to enroll patients now.

Okay. Got it. Got it. Well, maybe we can move to the next leg of the stool, brepocitinib -- I realize it's...

Lisraya.

Sorry?

Lisraya. I don't know. I'm trying to get you calling by the brand name.

Yes. I'm still getting used to it.

Yes, me too.

So let's stick with brepo. I realize it's only been a few weeks, but any early feedback on the launch from the physician community? And...

We called all our physicians and we asked them what they thought of the launch, and they all said the same thing. They said they thought the launch was going to be slow and steady. That's right. Look, I think it's 2 weeks in. It's much too early to have anything useful to say other than even before the drug was approved, the receptivity from the DM community was extraordinary because of the high level of unmet need here. And so it's just exciting to be able to get out there with the drug after all of this time getting ready. And I do think the DM doc and patient community are prime.

Frankly, one of the reasons we've been so consistent with our slow and steady messaging is the docs are doing a great job of getting everybody else onto a more aggressive message. And we've had to talk to people back to the realities of like, okay, they say that, but they're going to take time to get their patients in the office and they're going to take time to get their patients through the process. And so we just got to -- we've got to work with what we've got, but the doc community is very enthusiastic.

What about access? Like how quickly would you expect access to come in? Because it's a rare disease, high unmet need, nothing is approved.

Yes. Look, at least initially, this is a patient-by-patient process, right? Each patient is sick, each patient has a need, and we have a patient support hub and a co-pay assistance program that are designed together to get patients on drug seamlessly. And initially, I think I don't -- it's too early for me to know like what the normal time line is, but what I know is that we have a team that is committed to helping each patient that wants to be on this drug, get on it in an economical and efficient way. And I think as long as we're working together, we're going to be able to get them on drug quickly, and we're going to be able to get them covered, I hope, quickly as well.

Okay. And are there specific segments of the DM market that may need some more work to get on brepo. For example, some of the feedback that we have got is like some severe phenotypes that have just polypharmacy may be a little bit slower to adopt because it's a JAK, you have to make sure that the safety profile is fine. Like based on your work, any specific subsegments of the DM market that you feel will need some work?

The first thing, and I appreciate this has been a consistently unsatisfying answer is -- in terms of like how different docs tell us they intend to use brepo, there is actually, in a pleasing way, a fair amount of heterogeneity. There are docs who are big users of off-label JAK inhibitors and want to move all of their off-label JAK inhibitor patients over. There are docs who are big IVIG users and their patients don't like the infusion burden of IVIG. There are docs that use neither of those things and have a lot of patients running around on very high dose prednisone and are trying to get their patients to lower doses of steroids, and they really like the steroid-sparing aspect of our data. So I do think it like varies a little bit practice by practice, patient by patient in terms of like who's going to get on drug early.

Look, I think one of the slightly complex dynamics here is some of the sickest patients are also the ones who are like on things already, right? They're on IVIG. They're on an off-label rituximab or something like that. And on the one hand, there are a lot of really good reasons that the docs and the patients have available to them as to why they might want to make a change. But on the other hand, if you're this sick, there's also if ain't broke, don't fix it kind of thing going on. And so you're sort of balancing those two considerations. That's said, I don't think there's like any one patient or group of patients that are going to be particularly hard to get on. Look, obviously, it will be easier to get more severe patients covered versus like a patient who's reasonably well controlled on low-dose prednisone or just methotrexate or whatever, may wish to switch to brepo for better disease control but it may be like a little bit harder to push those patients through from an access perspective. But in general, these patients are sick, and I think we won't have a lot of trouble.

Okay. And one lingering, I think, investor debate in the DM market and maybe some -- relevant for some of the other markets where you are testing brepo is, these docs are already using off-label JAKs. So why wouldn't they continue using off-label JAKs? Some of those are generics right now or will go generic in the future. Why would they prescribe a $400,000 drug?

I think you've got to do two things. First of all, as a reminder, and I think it's like a really important point. Brepocitinib is not a JAK inhibitor. It's a dual inhibitor of JAK1 and TYK2. These are largely interferon-driven diseases, certainly dermatomyositis is. And while TYK2 -- while JAK1 is relevant in signaling interferons, we do think there is likely a meaningful effect that comes from hitting both of these targets. And I think the doc community, by and large, believes that as well. They believe that this drug is as effective as it is in part because of that dual mechanism. And so I think against the backdrop of any JAK inhibitor, off-label tofacitinib that is basically generic or off-label Rinvoq that is definitely not generic. I think there's a general belief that we have a reasonable likelihood of being more effective. And by the way, there is an enormous amount of clinical data now generated by us around the use of brepocitinib, whereas all of those other drugs are just speculating on how well it's going to work. So I think that is a driver of people moving over.

As far as like the practical realities of the world, look, putting a patient on off-label generic tofacitinib isn't very hard in the sense that you can write the script and get it filled. It's not that expensive for the patient to fill it, although there's no co-pay assistance and no sort of support program generally for those patients. Tofacitinib among JAK inhibitors is not like even if you think of brepocitinib is like in the same pantheon, tofacitinib is a very minor deity by comparison. And so I think like you just have to understand that docs are not like, "Oh, I'm so excited to get patient off-label tofa. I'm not looking to consider new options." I think they want to put their patient on the most effective thing.

I think in general, there's a belief that Rinvoq is, again, probably not as good as brepocitinib because of the fact that it's a single inhibitor versus the dual inhibitor of JAK1 and TYK2, but like maybe an effective drug. Getting a patient on off-label Rinvoq is extremely difficult. Payers are not there to like help. In fact, they're like -- it's basically medically challenging for payers to get patients on off-label drugs. And certainly, like they can never like push an off-label drug over an on-label one. And docs and patients want the on-label therapy. They want the therapy that's been properly studied. They want the therapy that's been characterized.

So I think that's why when you talk to some of these physicians and they have patients on off-label drug is they want to switch them over. It's because they like the mechanism writ large, and now they want to help getting their patients on to the most effective version of that mechanism that has been shown to work in this disease, and that's brepocitinib at the moment.

Right. And there's also the medical liabilities of prescribing...

For sure. Yes.

Got it. And so I guess, how big do you think brepo could be in DM? I know you're not going to put out guidance or anything or peak sales numbers, but Street estimates are anywhere from like $2 billion to $4 billion. Do you think they're at a reasonable ballpark compared to how are you thinking about it internally?

Yes. Look, my first comment on this is -- in terms of what I think needs to happen for brepo as a drug to be a big and important franchise, I think there are plenty of numbers even below the lower end of that range, which if you think about the size of the wall and the number of bricks we're trying to put in it, even just like already underway pivotal programs, we have DM, we have the NIU program that's going to read out shortly. We have CS, we have LPP, I want to add a bunch of indications beyond that. And whatever, if we wind up in 7 or 8 indications, and all of them are only $1.5 billion, that's a really big drug. So I think like it's not like -- and it's much more important to my mind that we set up the drug well for the long run that we get all these other indications up and running, that we get the patient support piece [ right ] so that we don't mess up access, that we get the pricing dynamics right, so that we can build the bigger thing as opposed to like over-indexing on DM.

I think DM has the potential to be a very large indication. I think people's enthusiasm is well founded. There are at least tens of thousands and potentially many tens of thousands of DM patients. The unmet need is high. There's been a graveyard of therapeutic development. And even sort of on the come, we're a little ways away from the next entrant at all. So I think there's like a lot of reasons to believe that DM rhymes with some of the other great opportunities that have come to biotech where you can make a big difference for patients and generate a lot of value doing it. I think the upper end of the range that you described, above the upper end of the range you described, all like plausible outcomes. The truth sitting where we are right now is the error bars are wide because you're talking like 2 weeks into the launch, not a single -- whatever, you're like really early. And so it's hard to know. And you could tell me brepo is going to be a $2 billion drug and you're going to be -- in DM and you're going to be thrilled, you could tell me it's going to be a $6 billion drug, and you're going be thrilled, you could tell me it's going to be $1.5 billion drug, but it's going to be a giant drug in LPP, and I'm going to be thrilled. So I think there's like a lot of different good ways for it to go. But I think the upper end of the range and beyond are certainly on the table given the quality of the data and the quality of the opportunity, and the unmet need.

Great. That's a good segue to the other indication for brepo, NIU. you have data coming hopefully soon. That's a big catalyst for Roivant as well. So -- what are you hoping to see there in terms of is just stat sig enough in NIU? And -- yes, maybe we can start there.

I'm knocking on a metal table, which is the wrong thing to knock on. But the truth is that -- that's probably wood, there we go. The data is that -- is coming. Hopefully, it will be good. NIU is another indication. First of all, today has been fun in part because we put out this great PH-ILD data yesterday. And yesterday, it was a different investor conference and most of the questions were about PH-ILD. And then I walked in today and I sat down and like in my first meeting, there were like 12 people in the room and all of them were just grilling me about NIU because it turns out like that's just the way this works, what have you done for me lately. And so that was interesting. I think NIU is a market where, first of all, the commercial potential is likely underappreciated at this point. There are a lot of NIU patients. They are at a high risk of blindness and long-term complications. And the stuff that's out there by and large, doesn't work very well.

HUMIRA is the only really sort of approved modern agent, and it has very high treatment failure rates. In fact, like the time to treatment failure on HUMIRA in the study on average was like 5.6 months, I think, like less than 6 months and these patients are failing off therapy. So there's a huge amount of need. And bluntly, in order for us to succeed in a post HUMIRA setting, I think all we need is simply to be successful. If we get a label for NIU in the post HUMIRA setting, where your choices are like risk blindness or try brepocitinib, even pretty middling data would result in a commercial success.

The better the data is, the faster patients will want to get off other drugs and onto our agent. And if our data is blow it out of the water good, I have no doubt that docs will try and push for earlier line use. So there's like a range of goodness in the outcome. But I think in order to be a commercially interesting drug, we just need to hit a p-value.

Okay. Got it. The third leg of this stool in the interest of time, Immunovant and the FcRn IMVT-1402. Two catalysts that are very important. I'll touch on the first one, the difficult to treat RA part 2. I feel like this readout has been talked about and debated a lot, maybe because in hindsight, part 1 was so good. So most scenarios, in my view, tend to be a positive outcome in part 2. Like what would be a disappointing result in your view in the part 2 of this difficult-to-treat RA?

I'll say what I've said before, which is bluntly, I don't think we're going to learn very much from part 2 of this study at this point. Because the part 1 data was quite good in a way that, to me, suggests we have an effective medicine that's doing something in these patients. And we're going to run another study, and that study is probably going to have a more conventional placebo-controlled design. And we're going to see what it does in that setting and try to get it approved. And we would do that almost regardless of what we see in period 2 of this data. So I'm not exactly sure how we will change the design of our next study, anything about the future of the program based on what happens in the randomized withdrawal period, given the quality of the data in period 1 of the study.

The only thing I can think of that would be like a truly disappointing outcome is if placebo and drug patient degradation of response looked identical in period 2, and you're like, okay, how do I know the drug is actually working, and this wasn't all some weird placebo fever dream. I think that's extremely unlikely because the truth is ACR70s just don't like spontaneously happen. So the depth of responses we saw in period 1, which is what makes it potentially harder to hit stat significance in period 2 is also the kind of thing that makes you feel like, okay, this is like a "real data set."

But I think if we saw just like parallel degradation with no separation of those curves, I would be like, okay, that's like a little bit nerve-racking for the next study. Other than that, if you see some separation, if the inflammatory markers confirm it, if the drug is clearly doing something relative to placebo, then I think like you're going to run the next study. And actually, the major interesting question isn't what happens in period 2 of the study. It's what can we agree on with FDA in terms of the right treatment paradigm in a population for which a registrational study has never been conducted before, which is to say a population specifically restricted to multi-mechanism failure, where you'd want to run a smaller study potentially with a more stringent endpoint, and where the unmet need is high. And so FDA might be comfortable with those sort of things -- we have to have that conversation. There's a pretty wide range of regulatory outcomes. That, to me, in some ways, is like the more "interesting question" than what happens mechanically in period 2 of the study.

Right. And on that regulatory pathway forward, 1 study versus 2 study, does that make a lot of difference, except maybe some capital and some...

Yes. I mean, look, I think the short answer is, all else equal. We'd rather run 1 study than 2 probably, and we'd rather run a medium to small study than a very large study. And there's -- look, there's some if we had like blow it out of the water stats on every endpoint in the randomized withdrawal trial, we'd probably think for 15 minutes about whether to ask FDA, if we could just run another randomized withdrawal trial, given the first one the FDA dislikes randomized withdrawal trial. So I think they probably just say, no. Anyway, that's like a question that someone could ask.

But other than that, I think 1 study versus 2, big study versus small is mostly a question of time and cost. And I think barring something truly extraordinary in those interactions, we'll probably choose to run a study of some kind, regardless with more or less sponsor risk depending on what FDA thinks we should be doing. So we'll see. But I think multi-mechanism failure RA has the potential to be among the largest FcRn indications. I don't know, I'm not going to -- I'm not going to sit here and choose between that and Graves or whatever. But look, I think it's certainly one of the most exciting things we are working on. And I think the opportunity to be there first in a big way for a population, that's probably 75,000 to 100,000 patients with high need and high willingness to try pharmacotherapy is great.

Yes. Yes, I mean we agree it's a big market as well. And you talked about Graves. The readout is coming next year, probably one of the bigger catalysts in the biotech world next year. You're creating a new category with this indication. Maybe one -- first question on the competition. Lilly bought Merida recently for their TSHR. It seems like there's pharma interest in Graves as well. I think the one thing that we have talked about TSHR as a mechanism as we think about FcRn as well, it's more selective, but probably makes you hyperthyroid. But the argument that the TSHR companies would make is, all right, you can take Synthroid. And it's not -- it's probably one of the most widely prescribed medications out there. It's not a big deal. We are way more selective. So what's your take on that?

So first of all, I don't want to pitch for a competitor too hard. Merida is not a TSHR-directed therapy. Merida is a TSHR autoantibody directed therapy. So it's effectively an antibody degrader for TSHR mAbs. And I say that because I think the anti-TSHR, the ones you're referring to, like the kinetics small molecule or I forgot, there's a couple of other companies that have like TSHR-directed mAbs. Look, I think those are going to work, obviously. And to your point, I think the way -- my prediction is the way most of those drugs will be developed is they will be dosed to saturation. They will send people hypo on purpose and then they will replenish with Synthroid. And I think the answer is like, does that have a role to play? Look, if there is a patient who comes into an FcRn study with 100x the upper limit of normal on TRAbs and then we degrade their TRAbs by 80%, they will have 20x the upper limit of normal on TRAbs. They will still be sick with Graves' disease, and we will not be able to cure them.

It is possible that a TSHR mAb could shut down their thyroid, allow it to reregulate and actually like with Synthroid enough dosing, they could potentially get reregulated and maybe even off drug. So I think like for certain patients, the ability to go after it with the TSHR mAb could be helpful. I think right now, we know, most patients would prefer not to be -- they would prefer to be hypothyroid and on Synthroid relative to having the worst forms of hyperthyroidism in Graves' disease. But mostly, they would prefer not to be hyperthyroid and on Synthroid, which is why they choose to suffer through the side effects methimazole and all these other things to avoid having a thyroidectomy and stuff like that.

So I think in general, the TSHR mAbs will find a place, but it's just like the direct targeting of TSH receptor is like a less elegant mechanism than targeting the autoantibodies because it can send the patient hypo. On the autoantibody directed like degraders, like Merida or some of the other approaches, that is also an elegant mechanism. And in theory, if you could selectively degrade 100% of the anti-TSHR autoantibodies, you would be better than us. But I think there's a whole bunch of scientific questions that nobody has answered yet around the heterogeneity of those antibodies, the side effect profile of these drugs. And so look, I think it's like an interesting potential competitor. It's in the pretty distant future. Lilly must have seen something constructive in the data they were allowed to look at to do it. But it's like just hard to know until we've actually seen what these drugs can do.

Right. And maybe coming to the Phase III for Graves. I mean the mechanism makes a ton of sense. Ultimately, you're doing what reducing the autoantibodies that are causing the disease, so should work. But maybe some of the pushbacks on the prior data from investors could be that small sample, a few sites, some of the sustained reduction in the thyroid receptor antibodies, even after bato was discontinued, but your IgG levels comes up. So what's your take on some of these pushbacks?

Yes. Look -- first of all, I'm trying to think if the following statement is true. In Roivant's history, I think we have never run a study that is less biologically complicated than what we're trying to do in Graves' disease. Mechanistically, this is like -- it's like down the fairway. We're reducing autoantibodies and -- disease that is like every disease is more complicated -- than like pretty well understood to be caused by anti-TSHR autoantibody. So great. So I think like the biology is actually pretty straightforward. I think there are reasons to be nervous about Graves, in the same way, there's reasons to be nervous about anything. And I think idiosyncratically in Graves' disease, or whatever, as is so often the case, our greatest strength is also our greatest weakness.

Simply the fact that we are first in this indication, which as an indication that's managed heterogeneously with sort of varying levels of background methimazole other things. And like we just like don't have a lot of data with which to characterize these endpoints, I think like that sort of dearth of information makes Graves scary. And in fact, like if we fail in Graves disease, I suspect the reason will be -- I mean, I hate to say this, but like it's going to be a study design point. It's going to be just like there was something we missed in the characterization and study of these patients that the many people behind us as well as maybe we in a subsequent study would then get right again. We just had to take some bets based on our Phase II data.

I think our studies are going to work for the reason that the biology is very clear, and I think we're running good studies, but that's the scary thing about Graves. I think the fact that we are the first to run a late-stage placebo-controlled study ever in Graves creates a measure of irreducible risk, no matter how well we think we've designed the study.

But you're running 2 studies. So will there be ways to modify one if something goes...

Sure. Yes. Look, we'll get to watch both, and we can make changes potentially, and we can always run more studies. And the first one, the short study will almost certainly read out meaningfully before the second one. So yes, absolutely, we've got choices. I think this is a real risk. I've got myself in trouble previously for pointing out that the biotech is a risky business. But like I think mostly, I feel pretty good about these studies. We have a good track record of successful clinical development. And I think that track record is mostly that we're not cowboys, and we don't take a lot of risk. It's not that -- so I think like for us, the Graves study is a risky study, but I think it's like against the backdrop of most of our studies are in relatively well characterized territory.

Got it. Got it. And the time line is till 2027, should investors expect that you'll narrow down the time line at some point in the future?

Once these studies are fully enrolled, and we're ready to announce that, we'll announce that they're fully enrolled. And I think at that point, the time lines will become clearer.

Okay. Got it. And -- go ahead.

[indiscernible]

Maybe I can repeat the question for the audience. So as Immunovant continues to mature, how do you think about stand-alone versus maybe consolidating some of that?

Do you ask Sanofi that question about Regeneron? Regeneron is a big company. They're successful. They have a partnership with Sanofi. They've made it work. They've built a big business. I think the answer is like if the drug works and it's commercially successful, lots of strange arrangements have persisted in biopharma for a long time on the basis of good medicine. So I think like one answer to your question is like, if this stuff works and it produces a successful outcome, then I think like a lot will be forgiven and it is what it is.

If I had a time machine and could go back and tell 2018 Matt to not take Immunovant public and instead to own the whole thing, I'd also tell him them about the complicated roller-coaster journey we have along the way, but I'd probably make that decision. And if there were a way for us to own all of Immunovant efficiently tomorrow in a way that made sense, look, we'd love the story, so that's something we would always be thinking about at some level. But practically, the status quo is working well for us right now. And most importantly, I think it's working well for the drug right now. That is like 1402 is being well developed. It is properly capitalized. We have the ability to capitalize it together with outside market participants. And I think the most important thing right now is to maximize the value of 1402 by running the right studies, running them well and generating the best possible data.

Maybe if I can ask a follow-up on that. What would be the, I guess, obvious attributes to consolidate? I mean there are synergies in terms of the markets that you both are competing in with even like DM and IM, where FcRns have values?

I think those are all mechanically solvable problems if we need to solve them mechanically. And the truth is like from Roivant's perspective, you talk about myositis. We own 75% of Priovant, Pfizer owns the other 25%. We own like 60% of Immunovant, the public markets own the other 40%. These things are different, but they're not so different that from Roivant, like the trading as between them is like a big economic delta that drives our incentives. Our incentive is to make the pie bigger, to make both of these programs as important as we can. And that is, I think, how we will act in every instance.

Look, I -- Hindsight's 2020, we should have bought Immunovant when it was a $5 stock. And if Immunovant were ever a $5 stock while Roivant was a $42 stock, I think it was like a pretty easy decision from a concentration perspective. The gosh darn problem is that Immunovant is now also a $40 stock, and so the values are sort of moving up in parallel, and that means that every time we just have to keep making that decision in a value-oriented way.

It's a good problem to have...

It is a good problem to have. And by the way, they're both cheap. So...

All right. That's all the time we have today.

Subject to all of the appropriate securities disclaimers that I'm supposed to make when I say that.

Thanks, Matt, as always. Really appreciate the time. We couldn't get through all of these, all of the different pipeline indications as well, but there's a lot going on at Roivant right now. So maybe in the future. Thank you so much.

Thank you so much. That was fun.

I think we're going to get started here. Good to see everyone. Thanks so much for joining us for the next fireside. My name is Derek Archila. I'm one of the Wells Fargo biotech analysts. So next company here, we have Roivant. From the company, we have Matthew Gline, CEO.

Matt, thanks for joining us today on a great day for some new data, not -- great times to always good data right around the conference.

That's right. No, 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. So maybe walk us through kind of the PHocus trial and ultimately, what -- putting into context some of the data that we saw today.

Yes. Taking just like a 2-second step back first, just in case anyone is not familiar. So Roivant now just under $30 billion market cap company. At this point, a leg with 3 stools such as it were, brepocitinib is our "lead product," just got approved a couple of 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 in Immunovant.

And then the third of them, which had been third in line until this morning is mosliciguat. Mosliciguat is an inhaled sGC activator. So this is a mechanism. It's effectively a potent vasodilator, among other things. And it's a mechanism -- SGC-targeted therapies have been studied. And in fact, in one case, there's a systemically administered SGC called Adempas that was a Merck-Bayer collaborative project in PAH that was about a $2 billion drug at peak.

Anyway, PH-ILD, for those who are unfamiliar with it, is pulmonary hypertension that comes from having lung disease. And it's been a tough indication because systemic vasodilation for these patients is dangerous. You wind up -- all of the benefit you get from vasodilating the healthy lung tissue, you give up by vasodilating the unhealthy lung tissue. And so it's been a tough indication to study. And in the last few years, inhaled treprostinil, 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.

And so we took mosliciguat, this inhaled SGC activator into PH-ILD with -- replicating that idea. PHocus was a large 100-some-odd -- 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. So we got the deepest ever observed PVR, pulmonary vascular resistance measured by right heart 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 6-minute walk, but we delivered a p-value on the functional endpoint 6-minute walk. So just a really, really good set of data all around. And I don't know how familiar people are 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.

So what's kind of next steps here now that you have got the data in hand?

Yes. So we -- a few months ago or earlier this year, we're kind of looking at each other and realized that we had pretty good conviction and that we wanted to move fast. And so we actually have already -- we started the Phase III earlier this year. And so the Phase III is enrolling patients now. And so I think the next step is to finish that study, which should then be sufficient for approval. So that's what's ongoing now.

Is there any difference between Phase II, Phase III in terms of population or study design? Or we should think it's pretty replicable?

Basically, no, with one key exception, which is in the Phase IIb study, we did not allow for concurrent use of treprostinil Tyvaso. And in Phase III, we are allowing for some measure of concurrent Tyvaso. We have an open-label study that's a combo study that we haven't read out yet, but we will allow for some concurrent Tyvaso use. We'll probably -- it will be stratified, we'll probably cap it at some level. But that way, we won't have any label restrictions, which is -- 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 an already like a coughing disease. And so we had less cough on drug than in placebo, 1 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. So where do you kind of see like the opportunity here? And ultimately, I guess I don't put in the 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 as 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 United States. 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. 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 first line of major new therapy use in PH-ILD. We'll also, I suspect, be used after treprostinil in some cases, and they'll be used after us in some cases. And I think the real opportunity here is this is -- 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. So we should be feeling very good about the Phase III. When would we get data there?

We haven't said that either. We're just getting enrollment up and running now. We just read out the the Phase IIb today. We'll meet with FDA and confirm things like size and maybe able to repower, et cetera, now that we know the Phase IIb data pretty cleanly. But 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 time line. But I don't have a time line to share right now.

Got you. I mean anything else to highlight there? Any other thoughts on the data today?

I'm not very practiced talking about this data. We're an hour in, so I don't have like super prepared talking points. Look, this was phenomenal data across PVR and hemodynamics, across 6-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. PAH is an indication that we got asked about a lot before this dataset, 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. So 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. So maybe shift gears to LISRAYA and dermatomyositis. So your recent approval -- so maybe talk about how you think of this opportunity. And ultimately, this is an area where there's really been a dearth of options for patients. So yes, just kind of thinking about ramp and uptake.

Yes. So 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 in DM. And it felt like we've been working on it for so long. It feels like -- I said on the approval call, it's the rare marathon that ends with the right to begin another marathon immediately. And so now we're out there with LISRAYA on the market.

Look, dermatomyositis, again, for those that aren't familiar with it, it's severe inflammatory disease. Terrible skin rash. In fact, many DM patients say the worst thing about it is this like 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 label dosing paradigm involves basically 4 or 5 consecutive days, full days in the infusion clinic. So -- and a lot of patients are on it, which 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 conjunction 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 and 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, which I don't look good in head bands, 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 6 or something. So...

Well, I guess maybe talk about like rheumatologists are generally pretty familiar with JAKs and brepo kind of fits right into the bag of tricks for them. So I guess, do you think there's going to be much education and learning around like 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 part of mechanism JAK and also familiar with TYK2s for that matter, brepo is a dual inhibitor of JAK1 and TYK2. And I think there has been so little actual successful drug development in myositis, but 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. 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 of drugs than on placebo because I think you're treating these patients effectively, getting them off immunosuppressants and steroids and so on.

So I think it is -- 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 of 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.

So 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 well, Argenx has recently read out data in the myositis program. Argenx obviously has an impassioned and enthusiastic group of investors who were calling docs asking about argenx. And in many cases, what the docs wanted to talk about because it was more proximate was brepocitinib.

So we got a lot of Argenx investors showing up in our office saying, I keep asking you about efgartigimod, and I keep being told, first, you should look at brepo, it's sooner. so that I think there's just a lot of doc enthusiasm for the drug.

Yes, I mean we've heard the same and upwards of maybe 60% utilization for the patients that are candidates for the drug.

Those are large numbers. There are tens of thousands of DM patients. We certainly do not need 60% penetration in order to have a big and exciting drug.

Yes. Well, that's good to know. So 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. So 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.

And one of the things I really like about orphan disease launches, I often talk about how -- like we previously launched a drug in psoriasis. These bigger market indications are like a fluid dynamics problem where you can't approach the patients with individuals. You have to think about the shape of the surface and branding and marketing and DTC advertising are all like the sort of tools that you have for manipulating and accessing those patient population -- manipulating is right word, but 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. And 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 like 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. And then 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 co-pay and are able to get on drug quickly and seamlessly.

Got you. So in the quarters, how should we be thinking about the KPIs that you guys will share in terms of the launch?

Net sales. Net sales to 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. And I think there's like 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 kind of thinking about? Pushes and pulls for the launch? I mean, obviously, there's reimbursement and things like that, that will come on. But anything else that we should be considering?

Yes. 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. And so I think that's -- most of it is just getting out there and getting behavior change in these practices.

One of the questions I get a lot is like which patients are going to be on drug first. I think the interesting thing is it's pretty -- 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 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 like the amount of steroid usage in myositis? And obviously, the doctors, this is a huge benefit to get down to 5 milligrams or less, ideally 0.

Yes. Steroid sparing is a huge benefit here. It's 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're not getting like placebo patients up-titrating on steroids and getting treated actively anyway. So you got a steroid taper. And in some sense, we failed 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 placebo 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. You can get patients on lower dose steroids. Many, many DM patients on high-dose steroids. You're talking about like average steroid burdens of 10 or 20 milligrams for 6 months out of the year. I don't know if you've been on oral prednisone before, but being on 20 milligrams of prednisone for 6 months is a miserable way to live. And so the docs are incredibly excited about the ability to get these patients to lower steroid doses.

Got you. So maybe shift gears to Immunovant 1402 and kind of the FcRn pipeline. So I guess one of the questions that always surfaces around kind of increased IgG reduction and conferring better efficacy. So 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. And now I think we've generated the data that answers that question in like 4 or 5 indications and still mostly people seem to want to ask it. So I don't know what's going to answer that conclusively for everybody else. We feel like in every indication where we've tested it, first of all, at the individual patient level, every patient for whom we have -- not every patient, 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, sort of 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.

And 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 this 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.

Yes. Maybe let's talk about difficult-to-treat RA. So the data, very impressive and maybe surprisingly so for period 1. As we look to period 2, I guess 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 kind of a Phase III or the next development in this indication?

Yes, perfect. So look, for those that may or may not been paying attention, we put out data in sort of an interesting trial design. It was a randomized withdrawal design where period 1 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. And frankly, the period 1 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, like half were ACR70 responders and 2/3 were ACR50 responders. And so 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.

So I don't know, frankly, given the quality of period 1 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 1 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 1 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.

So 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. And 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 -- again, these patients -- the patient population that we studied, sorry, to take a step back, was refractory patients who have failed at least 2 basically of IL-6s, TNFs and JAK inhibitors. And for patients that have failed multiple lines of advanced therapy for RA, there really aren't options. And so our hope is that we can design a study for that patient population and have a real impact.

Yes. I mean this seems like almost like a fourth line plus setting for these patients. So I mean one of the interesting features here is that could you get kind of that most indication carve-out for difficult-to-treat RA. Like what do you think the FDA's receptivity would be and 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 is consistently "worried" about in RA is that people are trying to sneak into earlier line therapy, and we are not, right? CRNs have a different price point. It -- this does not make sense as an early line medicine. And so I think like we would be enthusiastic per se about a label restriction to late-line patients. And 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's obviously the T cell engagers in the CAR-T therapies that will also be multi-mechanism failure patients. And so I think there's like a little bit of -- FDA is clearly thinking along these lines, but we will be the first with a Phase III study, I think, in this population. And so I think we're going to have to have that conversation.

So base case is that you're running another study, somehow if it hits that sig, would you file on that data like period 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're going to take the data to FDA as a part of the overall conversation. But I'm 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'll 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 for just that specific population.

Probably that's -- look, I think our hope and our hope would be to run a single relatively small for RA Phase III study of a relatively conventional design. But there's still a pretty wide range of things on the table. We're talking to FDA. Obviously, if we did hit the p-value here, we could consider rerunning a randomized withdrawal trial. I don't think that's the base case plan here, but it's one of the things that's on the table. If FDA wanted 2 studies, as long as they were both reasonably sized, this study enrolled really quickly, I'm sure be a problem for us. But that's it. If this study hit, I'm not sure why we would need that. So it just depends on how this looks, and we'll have the conversation with FDA.

Got you. In terms of the opportunity, so it's fairly small, but again, maybe there's pricing opportunity here because it's such a narrow population and a very sick population. So I guess how do you think about the difficult-to-treat RA opportunity if that's kind of the specific label indication you're able to get?

Would you describe myasthenia gravis as small? I think it's comparable in size to the other FcRn indications. I think there's 75,000-plus patients who are multi-mechanism failure RA patients who would be potentially eligible for an FcRn. And I think that is -- the commercial model of an FcRn, that's an incredibly attractive market. And I think we've carved out a leadership position in part because I'm really proud of the study we run. I think we really have figured out how to enhance the patient population for FcRn applicability, both through things like ACPA titers and enrolling patients who have high autoantibody levels.

And then I think the very fact that we are looking at, let's 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's because their disease is caused by something other than inflammation. Like there's something interesting and causal about the autoantibody selectivity, if you will, of these patients who have failed inflammatory mechanisms. And I think that is giving us a super enriched patient population for our needs.

Got you. And is it fairly easy for these docs in kind of clinical practice to measure those titers and get that information to figure out who's best suited for a therapy like this?

Measuring autoantibody levels in RA is an easy thing to do is the honest answer. So I'm not worried about that. And the truth is if you're 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've just failed so far. So I think they should be pretty easy patients to access and they're sick and they need help.

Got you. So maybe moving along to the CLE. So you also have an update coming in terms of kind of more of a proof-of-concept trial, signal finding trial. So maybe put into context what we should expect from that trial? And ultimately, what's kind of the path forward there if we start to see an interesting signal?

Yes, perfect. Look, we said all along CLE is a bit of a flier for us. It's an indication that's high risk. If we are successful there, that will be an opportunity, we will be a first in mechanism approval or first mechanism program. But there's sort of 2 "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.

So I think we've got to look at our data and feel confident that we have a commercial opportunity. It's 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. So 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. I mean, look, nipo, obviously -- I don't know how much detail we have about it, but nipo 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, and I think it was New Zealand. And so I think there's reasonable rationale. There's clearly an autoantibody role in CLE. Forget Jaccoud's lupus. It's like a tough set of indications, but I think the therapeutic sort of mechanistic rationale is reasonable.

Yes. What's the win like for this? Like what's like, oh, this looks good. We're moving forward. We've got a path here versus like middling data?

Unfortunately, my unsatisfying answer that question, I think it's going to be a little bit of I know when I see an outcome in that there's like a bunch of different parameters and you're going to have to take a step back and look at the data and decide would a drug of this profile be competitive? And that's on top of the fact it's a pretty small study. So -- 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.

Yes. I guess should we think about -- because it's a small study, a lot of variability here? Or like again...

Absolutely. That's why I say like I think it's going to be a totality of the evidence kind of a consideration. It's just like hard to say with this number of patients. I think the main thing we're looking for is like, is there a 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. And as we think about kind of other type 1 interferon and autoantibody-driven disease, so we were talking about this with Argenx before. But ultimately, we're starting to get a nice kind of like proof of concept here across myositis. We're getting Sjogren's and also potentially lupus, JASMINE, your CLE data. I don't know, does that kind of like -- one, how do you think that impacts potential Sjogren'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 like how large the potential field of FcRn indications could be. And every time you get a brick to wall, you put RA in, I mean, 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 kind of rhyme with lupus that could be interesting. As we move into Graves, we haven't talked about it all yet in this conversation. There's like a bunch of endocrine diseases. There's like 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 on a bunch of those possibilities in parallel.

Got you. So yes, maybe a good segue to Graves. So this is one where you guys certainly will be first for an FcRn and in general, but I guess we're seeing a lot more entrants, more competitive intensity that's kind of coming into the pipeline. So I guess would you kind of look at FcRn versus maybe more of the TSHR antibody approach. I guess, 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 like it was not on people's radars. People were sort of focused on TED and other places. And so I feel really great about that. And 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 that competition is generally good for first entrants as we will be in Graves. And so I'm not like -- to be honest, like 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 1402 if our clinical profile is what I hope it will be. So we'll see.

Specifically to your question about TSHR mAbs, look, I think the problem per se -- first of all, I think all these things are good approaches should work. I think anti-TSHR therapies, whether they are antibodies or small molecules or whatever, like should produce a good effect in Graves' disease. The nice thing about FcRn is it's a very elegant mechanism for Graves that is Graves is the cleanest autoantibody-driven disease in the book. It is caused by autoantibodies that are stimulatory of the thyroid. And 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 like methimazole and ATDs. Ultimately, what's going to happen with a highly effective downregulator of the TSH receptor is you're going to wind up pushing patients into hyperthyroidism. So 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 autoantibody.

Now the flip side to that is if you are a patient with 100x the normal limit of TRAbs, even a drug like ours that 80% suppresses TRAbs is going to leave you with 20x the normal limit of TRAbs. There will be patients that you cannot treat even with an FcRn and the TSHR approaches should work, right? They will effectively shut down the thyroid chemically, and you may be able to get patients reregulated that way.

So I think there's absolutely interesting opportunity for TSHR-directed therapy. I think it will be likely more complicated, potentially less pleasant patient experience than an FcRn, and FcRn works. But I think these things could all happily exist side by side. And there's other cool things, right? There's like specific autoantibody degraders in development and lots of other like neat ideas for treating these patients. And I'm 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. So originally, it was like, oh, there's really no market, ATDs are great, like 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 kind of emerging as the first new therapy in a long time?

I don't envy your job in that the problem with Graves' disease is you are faced with a whatever, with like 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 and 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 like the choices. Obviously, it's clear, we are. But it's just like 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.

And 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 like only on pretty high doses of methimazole, where -- the unpleasant side effects of methimazole.

And further complicating things in the U.S. You could have 2 patients who are, in God's eyes, the same. The underlying Graves' disease is the same, but they are treated at different endocrinologists. And one of those patients is treated on low-dose methimazole and is miserable because the thyroid hormones are out of whack and the other patient is on high-dose methimazole and is miserable because of the side effects of methimazole, and that's like its own difficult thing to manage.

So I think the short answer is I think these patients are going to come from a variety of different phenotypes. I think we're going to have to meet them where they are. And it's one of the complicated things about getting out into the world.

Understood. And maybe in the last couple of minutes, just kind of like where kind of the FcRn the mechanism is evolving and obviously, long-acting and things like that. How do you kind of remain competitive here with 1402? And are there other things that you guys are working on in terms of life cycle extensions and things for your FcRn franchise?

Like everybody, we're thinking about novel next-generation ideas, and we've got some stuff in the works, and we'll talk about it when it's worth talking about. And until then, it's just an idea.

I'll say like I think the greatest mark of success is when people are asking what's next. I think mostly 1402 is a great drug, and it's not yet approved in any indication. And so 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 will be hard to unseat Argenx as the king in the MG market, but 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, just maybe walk us through the next 12 to 18 months in terms of readouts across the pipeline and other events that's going on for Roivant.

Busy. So today was PH-ILD data. Later this half, we have probably most notably at this point is the Phase III registrational program for brepocitinib in noninfectious uveitis, which will be a second indication for LISRAYA for brepo. We also have -- we have the CLE data, and we will provide an update on the second half of the Graves -- of the D2T RA study as well as hopefully on the FDA feedback and the path forward there. That's all coming this 6 months. I can't think of any other major event for now and the end of the year, obviously, other than the continued launch of brepo in 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 haven't talked about. So next year is going to be really busy.

All right. Action-packed. Well, Matt, thank you so much for the discussion. Really appreciate it.

Thank you. Really fun. Thank you so much.

Good day, and thank you for standing by. Welcome to the Mosliciguat in PH-ILD PHocus Study Top Line Results Conference Call. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Stephanie Lee, please go ahead.

Good morning, and thanks for joining today's call to review the results from the PHocus study of Mosliciguat in PH-ILD. I'm Stephanie Lee with Roivant. Presenting today, we have Matt Gline CEO of Roivant. For those dialing in via conference call, you can find the slides being presented today as well as the press release announcing these updates on our IR website at www.investor.roivant.com. We'll also be providing the current slide numbers as we present to help you follow along.

I'd like to remind you that we will be making certain forward-looking statements during today's presentation. We strongly encourage you to review the information that we 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.

Thank you, Steph, and thank you, everyone, for joining this morning. These are always the fun ones -- great data is always good to report on. So I appreciate everyone making time for us, and I'm looking forward to taking you through the results from the PHocus study in PH-ILD. So I'll just -- I'm going to do a little bit of frame up, and then I'll get to the data, starting on Slide 3. This is a slide that we've been showing, I think, since our Investor Day late last year, laying out that we have a busy couple of years ahead. And I'm happy to report we continue to add checkmarks to this slide as we move forward.

And obviously, this one is particularly great. First of all, coming so closely on the heels of the approval of what's now LISRAYA in DM, but also, I think, properly standing mosli up as a third leg of the stool, which feels really awesome. So I'm looking forward to talking more about it. I'm not going to spend time on Slide 4 because I'm going to go through the data in great detail in just a moment once I get through some background. But the one thing I will say is, look, this is a great day. This is a phenomenal data set. It is robust across both the primary endpoint, PVR, functional endpoints like 6-minute walk, exploratory prespecified analysis out to 24 weeks, showing improvements even beyond what was possible at the primary 16.

We were not powered for a p-value at 6-minute walk, but we got a really nice one. Just a great data set all along. It's supported by hemodynamic measures and overall, consistent with the disease state, obviously, but a picture on safety and tolerability that feels really good. So this is a great data set. Obviously, and I'll do this again at the end, there's a bunch of people who need to be thanked here, including the Roivant team, the Pulmovant team for running a great study and always, most importantly, the investigators and the patients who trusted us with their care. That's actually a pretty good segue to -- again, I think many folks on this call are likely familiar with pulmonary hypertension and with PH-ILD. But I just want to spend 2 seconds on background.

This is, in short, a terrible disease. These patients, I'm on Slide 5 here, are very sick. They -- PH-ILD, these are patients with pulmonary hypertension that comes from lung disease. They often have lung function issues as the underlying lung disease and then also issues with blood flow to the lung from the pulmonary hypertension. They have a horrible shortness of breath on exertion. So really great difficulty in activity of daily life and then lots of negative sequelae, including, frankly, just a ton of mortality. These patients are really sick, lots of comorbidities -- things like pulmonary circulation disease, congestive heart failure, vascular disease of other kinds, just a really, really tough prognosis [indiscernible] options, right?

Within the last few years, there has been the introduction of inhaled treprostinil, which has been a big step forward for the field here, but we feel strongly that another option is a real benefit and one that delivers this kind of efficacy as well as the tolerability and safety that we've shown here is something we think could make a big difference for these patients. So we're truly thrilled here. PH-ILD on Slide 6, I talked a little bit about this just a moment ago. But again, a really bad disease, [indiscernible] survival despite best available standard of care treatment, which, as I said, includes inhaled treprostinil.

We said in other settings about 200,000 patients between the U.S. and Europe. It's a big patient population with a lot of people with high need. And again, other than sort of the really old stuff, really nothing other than treprostinil approved for this patient population. So a lot of opportunity to deliver some value. Mosli, which we've talked about at length on some earlier calls, is -- we thought from a sort of mechanistic rationale perspective, a really great fit for the disease, especially in the format we've got here, which is on an inhaled basis. We're delivered directly to the lungs to activate impaired sGC.

We think this could be the first non-treprostinil treatment option. sGC is a key enzyme in the pathway here, essential for vascular homeostasis. And we activate both impaired as well as native sGC and restore cGMP production. In short, we're an inhaled vasodilator, and we think that has some real benefits, and then we have potential reduction of fibrosis and inflammation as well. So we think a really good mechanism and again, obviously borne out with the data.

The study here on Slide 8 was a large double-blinded multicenter global trial, 135 patients in PH-ILD across close to 90 sites in 20 countries. Primary endpoint was PVR at week 16 with key secondaries, including 6-minute walk and NT-proBNP and then some prespecified 24-week exploratory endpoints, 6-minute walk, NT-proBNP and TTCW at week 24 as well or [ TTCW ]. So a robust study, and I'll talk more about the data in a second, but obviously set up for hopefully this kind of outcome. We had talked a little bit earlier in June about the blended baseline characteristics.

We show them by arm on Slide 9. In short, pretty well balanced across the arms in most respects, and I think a fair test of the drug. Not too much else to say about it other than it was a pretty sick patient population in the study, which I think speaks to the quality of the data that we've been able to generate here.

So I don't want to spend too much time on preamble. I really just want to get to the highlights. And by the way, this data was also just presented at ERS in Europe this morning as well. So excited to get it out to the academic community. And I think it hopefully will have made a splash there. My understanding is there were a lot of docs in the room.

So on Slide 11, in short, this is the primary endpoint data. I believe this is the largest reduction in PVR from baseline ever observed in any pulmonary hypertension study regardless of which type of pulmonary hypertension. It's in the box on the upper right-hand corner here, but 100% of patients on drug saw a reduction in their PVR.

We had a placebo-adjusted change in PVR with 56.3% reduction with obviously quite low p-value. So this is on an objective endpoint, a commanding outcome and one that we think speaks to the potency of the drug and the effect that we're having in these patients. So a great, obviously, primary.

This is on Slide 12, I just said this, but this is the -- we think the deepest or among the deepest PVR reductions ever seen in pulmonary hypertension. It's a very deep reduction, and it speaks to the breadth of outcomes that we're going to talk about today, including on hemodynamic measures and otherwise that we're able to deliver this kind of reduction in PVR. And I think it hangs in harmony with the rest of the data that we're going to share.

On Slide 13, this is actually an analysis that I just -- I found really interesting, and I think it speaks to the breadth of what we're going to be able to do with mosli from here. We saw a huge benefit relative to placebo in every prespecified subgroup. There were a whole bunch of them ranging from age and sex subgroups to patients with and without emphysema, patients on or not on antifibrotic therapy, patients with different levels of pulmonary fibrosis, patients with different levels of baseline PVR, baseline 6-minute walk, different forms of PH-ILD. And again, across the board, we saw really, really big benefits. Some of these are relatively small subgroups, but really big benefits in PVR. And I think this is helpful for a bunch of reasons.

One is it really underscores the robustness of the data for this patient population. And the other is it opens the door to all kinds of other potential forms of pulmonary hypertension, et cetera, for [ mosli ]. So we think there's a whole lot of opportunity here. And obviously, the robustness of this data across subgroups feels really good.

So on Slide 14, one of the sort of greatest bits of intrigue going into this data set is we had said a bunch of times, this was not a study that was powered to deliver in 6-minute walk. 6-minute walk is a finicky endpoint, and you just never know what you're going to see with that kind of variability. We had a really great outcome in 6-minute walk. We showed a 35-meter change from baseline delta to placebo at week 16. And you can see that on Slide 14 that this is -- I think it's the highest 6-minute walk change from baseline seen in a large placebo-controlled study in PH-ILD, certainly among them.

And so we feel really good about that data as well, and it gets to the crux of the matter here. By the way, one just note, often in the treprostinil studies, there's a discussion of trough PVR, and we don't have the trough data shared, this was measured at "peak". But one of the things about mosli that's interesting is it's got this sort of long deposition in the lung. We talked about a 40-hour half-life before. And actually, our peak and trough measures are nearly identical, very similar to one another. And so I think, again, it just speaks to the unique profile of the drug.

One of the things that I was most excited to see on Slide 15 is that obviously, 6-minute walk at week 16 was a key secondary endpoint, but we measured it all the way out to week 24. And this is a really sort of nice looking chart. It just shows that the placebo-adjusted benefit on 6-minute walk continues to grow over time. We obviously don't know what would have happened beyond week 24, but these are patients who are continuing to improve against the backdrop of placebo patients who are continuing to deteriorate. This is, again, just underscores the big impact that mosli could potentially have for these patients. And ultimately, at week 24 was over 50 meters with, again, a very low p-value separation from placebo.

So this is this is a great outcome. I'm going to move to some of the "more objective measures relative to PVR, starting with NT-proBNP on Slide 16. Again, an equally attractive picture through week 24 with continued improvement through the duration of the study, very low p-values, early separation of NT-proBNP. These are patients who are definitely getting better on drug, and we get up to greater than 75% improvement by week 24.

On Slide 17, one of the other sort of interesting things here is this data is just like fully hang together. This is not just a pulmonary arterial pressure benefit. There's also increased cardiac output for these patients. And obviously, that those components add up together to a significant portion of the PVR number.

So you sort of figured it had to look like this, but seeing it across both of these sort of fundamental hemodynamic measures, again, just gives you confidence that this is really sort of working to improve the overall health of these patients in an exciting way. And again, it gets to the robustness of the data set, again, really low p-values with significant benefits on both pulmonary arterial pressure and cardiac output.

We also did on Slide 18, an exploratory prespecified analysis on time to clinical worsening. We had a relative risk reduction of 37%, not quite a p-value here but 0.09 is still not bad. And again, a significant improvement in time to clinical worsening, which is an important endpoint and something that we would think about as mattering potentially in the Phase III as well.

And then one other point on Slide 19, one of the "issues" with current standard of care, which is these inhaled treprostinils that are good drugs that are important to these patients is treprostinil has a generally on-target effect of inflaming the airway and causing cough, which again, these are patients who already have a high level of cough because of their underlying lung disease. And it's one of the sort of common issues associated with use of treprostinil. And you can see our cough levels, and this sort of makes sense for the mechanism, right?

There's no on-target cough effect from sGC activation. And in fact, mosli patients had less cough than placebo patients on drug. And by the way, I haven't said this, I think, yet on this call, but one notable thing, this is a single puff on a DPI once a day. So these are one puff once-a-day therapy here. So -- and with less cough than placebo and obviously, significantly less cough than what you see on the treprostinils given the nature of those drugs.

Otherwise, on safety and tolerability on Slide 20. Overall, a clean picture. Again, these are sick patients and the overall rates of AEs here are consistent with the sick patient population. These are -- they look different generally than what you see in like a PAH study, for example, but fully consistent with what we've seen generally in other studies in PH-ILD. And overall, the kinds of things you might have worried about given some of the history of sGC and the mechanism, no significant AEs on hypotension that were meaningfully different from placebo.

We don't have data on oxygenation to share in detail today, but I can say, overall, like supplemental oxygen use both at rest and with [indiscernible] basically exactly the same between placebo and drug. Oxygenation at rest or oxygen saturation at rest look good on both placebo and drugs. So I'd say like overall, a data set that's encouraging relative to some of the questions we might have gotten going in.

And certainly, we think with an attractive risk benefit profile relative to the level of clinical benefit we've been able to show with the data set. It's always hard to do cross-trial comparisons on Slide 21, but we're really proud of this data set. We think it matters a lot to patients. And we think across the board, these are measures that stand out from the competitor profile across a bunch of different measures from obviously, PVR and the 24-week 6-minute walk number, which is really exciting to NT-proBNP to the difference in cough profile and the fact that we're 1 puff once a day. This is a phenomenal robust data set.

And again, I couldn't be more excited for what this is going to mean for the PH-ILD community, what it's going to mean for patients, which gets me to the last thing I want to cover today, which is we obviously didn't know what this data set was going to look like, but we were sort of thinking about it earlier this year and decided to accelerate the path to Phase III. And so we put some dollars and some time and effort at risk. And long story short, the Phase III PHrontier study is now underway. It is actively screening and enrolling patients. So the Phase III program is already up and running. It's currently set up as a 375-patient PH-ILD study.

Obviously, one of the things that we're going to do now is take this Phase IIb data to FDA and have a conversation with them about the design of PHrontier, any changes that need to be made, we can make on our end and so on based on powering based on what we now know. But this is -- it's down the fairway, large placebo-controlled, double-blinded multicenter study in PH-ILD with a primary endpoint at week 24 of 6-minute walk with key secondaries, TTCW, PVR, NT-proBNP, et cetera. And we're really just trying to look to replicate what we've been able to see in the PHocus study. As a reminder, we also have an ongoing combo study with Tyvaso -- that's an open-label study.

We will allow some amount of background treprostinil use in PHrontier. And obviously, we'll use the data that we get from the ongoing combo study to titrate a little bit some of the parameters of that. But overall, again, as a reminder, treprostinils are not approved outside the U.S. anyway. So there will be some mix of patients in that study, and we'll know more about how that looks as the combo study comes together. But really excited that, that study is ongoing. On Slide 24, just to sort of wrap up overall sort of the picture here. Obviously, PH-ILD has been a big and growing market for Tyvaso. And now with Yutrepia on the market as well, it's been a really exciting commercial opportunity, again, speaking to the unmet need. And with this data set, we think we're going to be able to play a really big role for these patients.

The other thing I'll say on Slide 25, I'll just reiterate, I'm sure we'll get questions around line of use. I'm sure we'll get questions around how we play versus the others. And one thing I'll just say that I think is an important point, PAH is a polypharmacy market. These patients are on multiple classes of drugs. They are really sick. They want to use everything that they can. And one of the most amazing things as a story for the biopharma industry is that over time, as you look at the history of treatment of PAH, each time a new class was introduced, life expectancy for these patients materially increased.

And I hope, obviously, we can't say anything about that from this data today, but I hope that the same thing is true in PH-ILD that as new options come to market, as new classes come to market, we can materially improve outcomes for these patients. And I fully expect that we are going to be used alongside treprostinil and hopefully, that will make the lives of pulmonary hypertension patients better over time. And it's the reason we're obviously allowing some amount of inhaled treprostinil use in the Phase III study as well.

I won't hammer this too hard again on Slide 26. I think a lot of this data speaks for itself, but we're just -- we couldn't be more pleased with the outcome here across all the endpoints across safety, across tolerability and obviously thrilled to have the Phase III program already underway and excited to talk to the agency about where to go from here. So really, really pleased.

This, as a reminder, although I think most people are aware of this on Slide 27, is only one of our programs. LISRAYA is now on the market in DM, and we've got more data to come in near future on NIU as well as a number of important late-stage data sets, Phase III data sets coming for brepo, a whole bunch of data coming starting later this year and then next year for 1402 on the FcRn side and excited to talk about both more about PH-ILD as well as indications beyond PH-ILD for mosli in the relatively near future as we get everything going.

So a phenomenal outcome, always a great way to get in front of people with data like this on the Tuesday after Labor Day. So excited to take some questions. I just want to say, again, and I'll say it one more time at the end of the call, a big thank you to everybody involved in this program from the Roivant team who brought it in and stewarded it to Drew and the clinical team at Pulmovant who ran this great study. And again, obviously, to the investigators and patients, really sick patients in many cases, who entrusted us with their care here as we tested out a new medicine. We're glad to have been able to show something for it.

So with that, I will wrap up, and I will pass it back to the operator for some Q&A. Thank you, everybody.

[Operator Instructions] Our first question will come from the line of Yaron Werber of TD Cowen.

Great. Really amazing, amazing outcome. I have a couple of questions, Matt, I think you kind of touched on them. The first one is the 6-minute walk distance gets better as you dose longer and the Phase III is looking at 24 weeks and you're on top of inhaled treprostinil. What do you expect? Do you expect any synergy with the drugs or no difference in terms of better efficacy on the background? And what percent of patients would have inhaled treprostinil in the study? And I assume it's going to be stratified.

Thanks, Yaron. Yes, it will be stratified in inhaled treprostinil. I don't have an answer right now to what percentage of patients will be on. Obviously, it's only going to be U.S. patients who are on inhaled treprostinil some proportion of the patients. We may very well cap enrollment for inhaled treprostinil patients depending on what we find out in the combo study. So we'll see more about that. Look, I think mechanistically, I think you would expect some synergistic benefit between the drugs. But what that means on the combined outcome, I think we'll just have to wait and see what the combo data show, and that study is open label and ongoing. But look, generally, what we've seen in PAH and what I would expect here is that highly active agents are additive. And so I would hope to see the same here.

Our next question will be coming from the line of Brian Cheng of JPMorgan on the data.

Matt, can you give us a sense of the dose escalation, the titration up to the optimal dose here? How are patients experiencing dose escalation? And can you talk about the titration up to the optimal dose in the Phase III? Is that the same also as the Phase II? And I have a quick follow-up.

Look, great questions. Appreciate it. In the Phase IIb, the short answer is the vast majority of patients were able to get to the highest dose and to tolerate it which is obviously a great outcome. It's obviously we were hoping to see. And certainly, the outcome speaks for itself in terms of both efficacy and safety and tolerability. I think in general, the Phase III is similar, slightly quicker titration to the high dose in the Phase III, but I don't think it -- the details are not even that important here. I think the point is that we're going to -- we hope to be able to replicate that a high proportion of the patients are going to get to the high dose. And we saw pretty good outcomes there in the Phase IIb.

Okay. And then a quick one on the potential beyond PH-ILD. It seems like you're waiting for feedback with the regulator to get a sense of the next step for mosli. Can you give us a sneak peek there? How many indications are you thinking of? And how should we think about the steps beyond PH-ILD?

I think many people would shoot me if I gave a number of indications. But look, it's a great question. I think the short answer is, first of all, I would say we're not waiting for the regulator per se on indication expansion. Obviously, we're going to meet with FDA to make sure we've got the cleanest, fastest path forward, specifically in PH-ILD, but we've also got lots of other ideas that we're working out right now. And with data this good, especially across all the different subgroups, I think you got to believe every [indiscernible] on the table for consideration. Obviously, even before this, we had looked very closely at the TETON data and we're thinking a lot about IPF.

And frankly, I think as you want with a data set like this, our imaginations are running a little wider as we think about all the possibilities. So I think -- like I said, I think this becomes a real leg for us. I think there is more for us [indiscernible] do we have -- we have IP into the 2040s and the ATMOS data in Phase Ib, which was in PAH patients in part was really good and also showed a compelling PVR reduction, and that was with a single dose. So I think there's a lot of opportunity in that case as well. I think going in, our commentary on PAH had reflected the competitive dynamic in PAH. I think with data this good, we may very well find a role to play in indications that are more competitive. So stay tuned, but I think there's a lot of opportunity from here.

And our next question will come from the line of Prakhar Agrawal of Cantor.

Congratulations on the excellent data. Maybe on the 6-minute walk test, any differences you noticed across the subgroups? I saw that you had a chart on PVR, but I was wondering if something similar on the 6-minute walk test, specifically looking for patients who had CTD-ILD. Did they have any difference versus other subgroups? And then for patients who were on background PDE5, how did they perform given there is some overlapping hemodynamic mechanisms with mosli here? And then finally, given these strong data sets, how quickly can you enroll Phase III given that it took some time for some of the inhaled treprostinil trials in Phase III and the timing of readouts?

Yes, perfect. Great question. And as a reminder, in the deck on Slide 13, we talk a bunch about different subgroups, including with and without PDE5s. So you can see we saw pretty similar effect regardless of PDE5 therapy, which is great, exactly what you'd want. On 6-minute walk, as you're asking your question with no shade on the question, I was thinking about this sort of what have you done for me lately and that we came in with a study that was not powered for a p-value on 6-minute walk, and now we're being asked about subgroup on 6-minute walk. But look, I think 6-minute walk is a noisy endpoint.

But I think given what we saw in PVR just well as given the data set overall, I think the general view here is that there was no -- nothing stood out to us around subgroups in terms of performance here. This drug seems to work just across the board consistently. And again, obviously not powered for comparative analysis on 6-minute walk, but feel really good about the breadth of it. In terms of enrollment on the Phase III, I mean, look, stay tuned and I don't have guidance to give -- but I think the fact that we're presenting this data at ERS is helpful, and I expect it will make an impact in the doc community. And I think these are sick patients. And frankly, we were pretty happy with [indiscernible] that level as well. So we move pretty quickly from here. Thanks for the question.

And our next question will be coming from the line of David Risinger of Leerink Partners.

Congrats, Matt and team, on the spectacular results. So my questions are related to the future potential of the drug. So could you just talk a little bit about the design of Phase III in some more detail, specifically, what percentage of patients you expect to enroll ex U.S. where treprostinil is not typically used? And then do you see an opportunity to be more than just an add-on therapy to treprostinil in the U.S. in the future, i.e., be an alternative to treprostinil?

Yes. Thanks, Dave. Those are both good questions. On the second one first because that's the easy one. Look, I think with data this good, you got to expect that we have lots of opportunity to occupy lots of different lines of therapy in PH-ILD, including frontline therapy. So I think overall, I think we absolutely have an opportunity to be there. I think if we get used first, we will be used with treprostinil on top of us eventually. If treprostinil is used first or patients were already on treprostinil, we will be used on top of treprostinil. But I think we absolutely have a shot here at frontline therapy. It's convenient. It's got 1 puff once a day with significantly lower cost than you see with the inhaled treprostinil.

So I think we have an opportunity to exist on top of existing therapies before existing therapies on top of new therapies that will come in the future, et cetera. I think that everything is on the table here. On the first question on the Phase III design, without getting into too much detail, I think we aren't expecting any differences between the Phase III and the Phase II in terms of the impact on results. I think overall, the Phase III at this point is being designed with that in mind. And I think we are hopeful we're going to be able to replicate that. And like I said, I think we have an eye on the concurrent treprostinil, which is the only meaningful change in a way that we expect to allow the Phase II to fully translate to the Phase III.

And our next question will be coming from the line of Samantha Semenkow of Citi.

Congratulations on the great data as well. And I have 2 hopefully quick questions. I'm wondering, Matt, if you have any immediate feedback from KOLs following the ERS presentation that is worth sharing with us? And then also, just another question on capital allocation. With this great data as your expansion opportunities have just expanded, but you also have really great brepo data and lots of indications there and 1402 has a similar problem. Just how do you think about allocating your capital across these 3 pillars of your business?

Thanks. Both good questions. On the KOL question, we -- as you may know, Drew, who's been on some of these calls in the past, is not on this call because he and I are doing a little bit of a divide and conquer here. He is working in the room at ERS and talking to the docs, and I'm sitting in the Encore in Boston at a conference. So I don't have the direct KOL feedback myself. But what I'm told is that the ERS room was packed to the gills despite being quite a large room. And I know that the KOLs that we managed to speak to, the docs we managed to speak to about the data before today were incredibly enthusiastic, as you would expect, for this kind of data set.

And I know the professor who presented it was thrilled to be able to present it. So I think that the doc feedback so far has been very positive, and I expect we'll know a lot more by later today, but that's what I would expect to hear. On the capital allocation question, I'll say, first of all, we have been fortunate up until now and continue to be fortunate not to have to make the toughest of those decisions. We are spoiled for choice and I think expect to sprint at indication expansion here while continuing to sprint an indication expansion for brepo and to continue to sprint an indication expansion for 1402 in the FcRn world.

So I think we have great opportunities. And we have capital left aside even after all of that for in-licensing opportunities for BD. I feel like a broken record on this point and we've said the same thing for a while now, but there's some opportunities on our racket that we are really excited about that I hope we're going to be able to complete and talk about in the relatively near future. And we can hopefully -- there's nothing to say that a stool can only have 3 legs. So I'm excited to see where we go from here as well.

And our next question will be coming from the line of Yasmeen Rahimi of Piper Sandler.

Congrats for the outstanding data. Looking at the baseline population, it seems like a pretty sick group of patients, right, with baseline 6-minute walk test of like 260 to 285 and PVRs of 580 -- makes me think about as you're designing a Phase III study or the study -- Phase III is up and running, what is the requirement of the minimum 6-minute walk test and PVR that they need to have to be eligible for the study?

Yes, perfect. Great question. And look, it is a sick patient population, not sick. PH-ILD in general is a sick patient population. So this is representative of the PH-ILD patient community generally. And I think the only thing that we've said so far about enrollment criteria in the Phase III is PVR of greater than equal to 4 Wood units. So I think that gives you a sense. But I think in general, as like I said, this is a representative patient population of what the PH-ILD patient experience is like. And my hope and expectation is that the Phase III population will be similarly representative.

Our next question comes from Dennis Ding of Jefferies.

I have 2, if I may. So for the [ Phase II ] to 6-minute walk, it's really impressive that the delta continues to get better from week 16 to 24, but you guys didn't break out how drug versus placebo did at 24 weeks. So can you comment on the shape of the curves between mosli and placebo at 24 weeks basically with the bigger delta driven by mosli doing better and placebo doing worse sort of consistent as to what you saw at week 16?

Or maybe was it from placebo doing much worse? And then Question number two, on time to clinical worsening, can you give a little bit more color on why it mostly did a little bit worse early on? Maybe it's just small numbers, but just talk a little bit more about that and how important is this endpoint from a regulatory perspective in Phase III from the FDA as well as the EMA.

Thanks, Dennis. Those are both really good questions. On the first one on 6-minute walk, I'll say 3 things. One is we had to leave something for future academic conferences. So I'm sure more of that data will come out. The second thing is, and this is not our fault, the way the field works on 6-minute walk in pulmonary hypertension is the sort of interpolation models are complicated in a way that makes this question like slightly complicated to answer. But the short answer is it's clear from our data that both drug effect is consistent and increasing over time through week 24 and the placebo patients are getting worse. And so it's not just one or the other.

And the magnitude of -- in fact, in the academic presentation this morning out to week 16, this was showed. So you can clearly see just like a consistently improving drug effect as well as a consistently worsening placebo, and that was sort of smooth in both directions. And that continued out through week 24. So smooth worsening of drug and -- sorry, smooth improvement on drug and a smooth worsening of placebo patients all the way out to week 24 across the board. So I think anyway, short answer to your question on that is both the drug effect keeps getting better and the patients getting worse. On to TTCW, I'll say, increase for Tyvaso also had a similar early crossover effect. I don't have a clear answer sitting here right now as to why that seems to be the way it works in these studies.

But obviously, by week 8, mosli ahead and it continues to do better and better from there. As far as the regulatory significance of TTCW, obviously, 6-minute walk is a regulatory approval endpoint in pulmonary hypertension and has been used repeatedly in pulmonary hypertension studies. TTCW is looked at, especially in some other geographies. I think both are helpful measures. And obviously, we're measuring both in the Phase III. And in a properly powered study, I think they're both going to be useful outcomes measures that we should be able to deliver on.

Our next question will be coming from the line of Andy Chen of Wolfe Research.

This is Jason taking in for Andy. I just wanted to ask really quickly about the TEAE-related discontinuation rate. Was there any concerns about that? And what maybe drove it to be a little higher? And also, was there any concerning effects on oxygenation, oxygen requirement and blood pressure or hypotension?

Yes. I'll take the second question first because I'm going to pull up some data on this situation while I'm talking. But the short answer is no. We don't have -- I know there's like a lot of data we will eventually have on oxygen saturation and stuff like that. We just like don't have it all clean for now. So I can't speak to the full detailed data set. But we took a look in anticipation of getting this question. And the short answer is we have some oxygen saturation at rest data that was basically consistent between drug and placebo.

We have supplemental oxygen data both at rest and with exertion that are basically the same on drug and placebo. There's not any significant imbalance of hypotension as an AE between the arms. So I think overall, that looks good. Look, on discontinuation, I think the short answer is we're not particularly concerned. The slightly longer answer is this is just what PH-ILD studies look like. And so our TEAE discontinuation rates look like quite similar to what we've seen in the other programs that have been run here.

Obviously, they are generally higher in PH-ILD studies than they are in PAH studies. And I think that's reflective of a sicker patient population in some ways and just different set of situations. But I think overall, as we look across the board, I think our discontinuation rate is like a little bit lower than what we've seen overall on INCREASE, similar just overall like in the same general bucket as what you see in other PH-ILD studies. So we feel relatively unconcerned. And obviously, the fact that so many of the patients made at the high dose is a useful fact for us.

And our next question will come from the line of Chi Fong of Bank of America.

Matt, in the past, you have talked about taking a look at the FVC data in the subset of patients with IPF, granted it's a very small number. I think it's about 25 patients on drug and 15 on placebo. But is there any learning that you can talk about today? And I have a follow-up after that.

Yes, thanks. Look, the first thing I'll say is, like I said, we have to save some things for academic conferences. We have just started to peak at the FVC data and at the IPF subset. It's early days. Look, I think overall, given the magnitude of the effect, given the sort of breadth of the effect across different subgroups, I think we continue to have the belief that anything anybody else can do, we can also do with this drug.

And we're obviously well aware of the IPF data that's been generated by treprostinil, so -- by Tyvaso. So I think we're excited to continue to think about and explore that as an opportunity. And I think our data points to points in a similar direction. But in terms of the specifics on FVC or on the IPF subset, give us a minute, and we'll definitely be back with more presentations on that topic as we lay out our future plans.

And my follow-up question, if I may, is regarding your Phase III population, do you have any thoughts of exploring mosli in milder pulmonary hypertension more specifically between the 2 to 3 Wood units. I understand that the Phase II data and the Phase III enrollment is focused on the above 4, which is in line with the treatment recommendation. But if we were to go by the diagnostic criteria from the World Symposium of PH, there's quite a bit of patients in the 2 to 3 units. So I'm curious if you have any sort of like thoughts about pursuing mostly in those milder patients, maybe perhaps in a separate Phase III or subsequent study?

Yes. Look, I think I'll say 2 things. One is, obviously, our top priority right now in PH-ILD is to get this drug approved as quickly as we can and to run a study that's going to replicate the data that we've seen here as closely as we can. So I think in PHrontier, we're focused on what we're doing. Again, the data is new, and so we're still pressing it, but I would be surprised if we made major changes to that kind of inclusion criteria. That said, I'll reiterate what I said earlier, which is with data that's good. I think every form and severity of pulmonary hypertension is on the table in terms of things we would consider. And I absolutely think we will think about earlier line studies, studies in other forms of pulmonary hypertension, et cetera. So I think all of that is absolutely on the table.

Our next question will come from the line of Yatin Suneja of Guggenheim.

Let me add my congratulations as well. Not very often that you see practice-changing data gets replicated in Phase III. So congrats to the team. Two quick questions for me. The first one is on the PH-ILD population in the U.S. Could you maybe provide a little bit more color in terms of -- I know you mentioned 200,000 patient total, but just in the U.S., what numbers do you come at? Like what is the eligible number? And then -- and then just one quick one on the study, on the Phase III study. Could you talk about -- or are you able to share what magnitude of 6-minute walking distance effect you are powering it to? I mean, obviously, pretty strong result in Phase III. How should we think about modification there, if at all?

Yes. Thanks. Look, great question. On the second one, the study is 375 patients as currently set up, but we'll reevaluate size and powering now that we have the Phase IIb data in hand, and it could change modestly from there. So in terms of powering, stay tuned. But I think certainly, given that the Phase IIb saw such a robust p-value, the Phase III is healthily powered for 6-minute walk. On the market size in the U.S. There are a variety of estimates in the world ranging from mid-tens of thousands to very low 6 figures is probably the current range out there.

Diagnosis is increasing over time now that there are more therapies on the market. And our view is that trend will continue. And so look, PH-ILD is -- in short, it's a big patient population with a lot of really sick patients. And we'll see also -- look, I think duration of therapy will increase over time as mortality comes down and as patients are on multiple things that keep them healthier longer. So I think there's a whole bunch of reasons to expect this -- whatever always feel strange to call a patient population in the market, but to expect this patient population to grow over time. So it feels good to be here at this moment.

I would now like to turn the call back to Matt for closing remarks.

Thank you very much. Look, I'll just say again, thank you, everybody, for joining this morning. This is a tremendous outcome for patients, for the investigators. There's a ton of people it takes to make this happen. The clinical team of Pulmovant ran hard at this study to get it enrolled quickly and run well. Drew, obviously overseeing it all, the Roivant team across the board from the investment team who brought the asset into the government team who oversees it. And then thanks to our partner, [ Bayer ], who got this program off the ground. And I'm happy to take the torque from them and continue to run with it, and it's really great to be here. Look, I'm excited to get back together over the balance of this year. We have a lot more coming. And hopefully, great things to say. I'm excited to talk much more about PH-ILD and [indiscernible] all the around great talking this morning, and we'll speak really soon.

And this concludes today's conference call. Thank you for participating. You may now disconnect.

Good day, and thank you for standing by. Welcome to the LISRAYA approval call. [Operator Instructions ] Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Stephanie Lee. Please go ahead.

Good morning, and thanks for joining today's call to review the FDA approval of LISRAYA. 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 have 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.

Thank you, Steph, and thank you, everyone, for dialing in this morning. Obviously, an exciting update from us, so we're really happy to be here. I've reflected to a few people over the last couple of days the thought that I've had, which is that deeply unsatisfying marathon when the price for winning if you get to start running another marathon immediately. And that's the moment that we're at now where we finally, as you all know, have gotten LISRAYA to the point of approval, and now we got to get it out to patients, and there's a ton of work associated with that.

So we're talking a little bit today about what this means about why we're excited about it. Ben is going to talk a little bit about the label and the process from here. We'll do a quick review of the clinical data we have for the drug because we think it's worth remembering. And then we'll leave much time at the end for Q&A.

So I'm going to start just on Slide 3 of the deck with the headline, which is that LISRAYA is now approved. This is -- it's a huge day. It is the first modern therapy approved for dermatomyositis patients. The first oral targeted therapy approved for dermatomyositis patients. And just in general, there are so few options that a new option is a great thing here. And then also, there's just a bunch of other first associated with what this drug means.

We're super excited about the opportunity to get it out to patients. We're super excited to get to deliver this kind of potential benefit to them. So it's a big opportunity. It will be available at a list price of $35,000 for a 30-day supply, but -- and Ben will talk a lot about this. Access is obviously a huge, huge focus for us. And we're incredibly -- we're working incredibly hard to make sure that every patient who needs has access to it at a reasonable out-of-pocket price. I know that was a question on people's mind.

On Slide 4, it's -- FDA put out a press release on the approval of LISRAYA yesterday. Obviously, we put out on too. But we didn't prompt anything in the FDA press release. And actually, I thought they did a really, really nice job summing up just how exciting this moment is. And so I've just included on Slide 4, the quote from the Director of the Office of Immunology and Inflammation at CDER.

And I think it just sums up what we feel, too, which is that it's been far too long where patients with dermatomyositis have had a significant unmet need. And today is really the first time that there's something targeted approved oral study specifically in dermatomyositis to help them manage what is a really difficult disease.

I hit some of the points on Slide 5 earlier, but this is the first-ever targeted therapy approved for DM. The first once daily oral therapy ever approved for DM. It is the first therapy ever approved specifically for a steroid-sparing benefit in DM alongside, obviously, a disease improvement. It's the first therapy ever approved for DM to show statistical significance in a 52-week DM specific trial and the first ever TYK2/JAK1 inhibitor approved for any indication in a novel first-in-class approval for what we think is a unique mechanism that has a lot of potential from here.

And we've mentioned this, but I'll say it again on Slide 6. That's not for lack of trying. There have been a lot of attempts in history to bring some of the greatest drugs in immunology, Rituximab, Remicade, Enbrel, many others, across the finish line in dermatomyositis, and none of those have been successful in DM-specific studies, and we've continued to see challenges in getting p-value and DM studies until even more recently than that. So it's just really exciting that we've been able to deliver this kind of opportunity.

And I think the DM patient and physician community have been waiting for a moment like this. So we'll do a couple of things to review the data set here. Before I do that, I just want to hand it over to Ben, by the way, and I'll say this at the end as well. One of the things about these approval calls is they're an important moment to thank a ton of people who are involved in bringing these drugs forward.

Obviously, among the most important, they are the patients and investigators who trusted us in the execution of the clinical trial that trusted us with their care, and we're forever indebted. This approval is forever indebted to them. There's also just an enormous number of people at Roivant and Priovant. And I want to give a special note of thanks to Ben and the Priovant team before handing it over to him for the speed, rigor, quality of execution and patient focus of this program.

And although this morning, I was doing what I suspect many of people do every morning, which is talking to ChatGPT. In this case, about the timelines here, because the truth is I looked through the drugs that came to my mind and with the exception of drugs that have benefited from the new CNPV program, vanishingly few drugs have gone as quickly as we were able to go here, from the necessary Phase III data package to an approval. We got together to talk about the data for brepocitinib in dermatomyositis, less than a year ago, in mid-September of 2025, and it's just a huge privilege to be here now with this speed.

And I think Ben and his team deserve a ton of credit for a lot of things. But one of the things they deserve credit for is that they acted with urgency for a population that need it.

So thank you, Ben. I'll hand it over to you to take over on Slide 7.

Obviously, very exciting and meaningful day for me and all of us at Priovant and many others who have been working on the program for a number of years. And exciting starting on Slide 7, actually, not only because today marks the -- or yesterday marks the approval of LISRAYA, but yesterday also marked the commercial launch of LISRAYA. About a month ahead of when we had initially planned, again, speaking to the urgency that Matt spoke about in terms of our enthusiasm to make this drug available to patients and bring it to market for them.

Ultimately, that's really what drives us and drives the sense of urgency, DM patients deserve better treatment options. We're excited to finally have one for them, and we want them to be able to access it as quickly as possible prescribing is open as of yesterday. We actually have already received our first prescriptions for LISRAYA.

And importantly, we also have our first patients consented into the MyCompass support program. This is a critical service that we're offering to patients. Among many other things that will be provided through that is access to insurance assistance and financial assistance programs from Priovant. And we are -- believe that many patients on this drug will have actually $0 out-of-pocket costs.

So very excited and committed to ensure that patients are able to get access to this therapy, and we're really excited to have the launch underway. As Matt said, we celebrated the completion of the first marathon very quickly, and we've started charging ahead with mile 1 of the next one.

Turning now to Slide 8. I want to talk a bit about the label which generally speaking, we're extremely pleased with how that turned out, and I'll just spend a few minutes walking through in a little bit of detail on my own personal perspective on it. I think the first thing I would say that in my view, the most important part of the label is the indication statement and restrictions of use. And we're really quite pleased with how that turned out. Broad indication statement for adults with dermatomyositis with no restrictions based on clinical presentation, disease severity or prior treatment history.

And also no restrictions on concomitant use with steroids, conventional DMARDs or IVIg, which are the therapies that the vast majority of DM patients are on today. And importantly, that gives physicians a lot of flexibility to use LISRAYA in a lot of different ways and different combinations. It can be used as an alternative therapy to what patients are managed on today or in many cases, as an add-on therapy.

And we think that's going to be very important, combined with the broad indication statement, because we feel really that the vast majority of DM patients are good fit to be considered for therapy and really quite pleased with the fact that the label supports and enables that.

Turning next to the efficacy section. I would say that for many drug launches, this is obviously where the heart of the label is, and we couldn't be more thrilled with this. But I would also say, this is the point that I mentioned few times before we do what the final label is going to be if the only thing we could say about LISRAYA is that it is an oral once-daily therapy specifically approved by FDA for dermatomyositis that specifically targets the underlying disease biology. That would be enough.

We could have massive commercial success if that was the only claim we can make because this is a disease where the patients are really sick and they're managed on non-targeted therapies that are just kind of not really consistent with modern therapeutics. And it's important to understand LISRAYA coming to market in that context. But I'm thrilled to say that notwithstanding that fact, we kind of got the icing on the cake too, and got a lot of icing.

I think really the efficacy section of the label provides an extremely deep and robust set of support claims and really brings to life the breadth and depth of the benefit of the therapy for DM patients we have claims to support improvements in skin disease, muscle strength and physical function as well as overall disease burden, which is important in a heterogeneous disease like dermatomyositis where different patients experience the disease in different ways and we are able to call out both many of the specific symptoms on which we've shown benefit as well as benefit on the TIS, which measures whatever aspects of the disease are most burdensome to an individual patient.

So in a rare heterogeneous condition. TIS is actually a quite important and meaningful commercial endpoint, not just a regulatory one, in terms of bringing to life how the drug can help a wide variety of patients. And importantly, we have on the label, both physician reported and patient-reported outcomes. The latter, we think, is very important for our patient-focused promotional efforts. Patients really resonates with them to have proof points from how patients felt and function, not just how clinicians perceive their disease.

And then perhaps most importantly of all, is the steroid sparing benefit that is included on the label and actually two aspects of steroid sparing benefit, both absolute reductions in steroid use compared to placebo that those were quite dramatic in the trial as those familiar with the VALOR data already knew. And then also the endpoints that measure the ability to simultaneously improve disease while reducing or eliminating steroid dependency and I think Matt talked about the set of first that this approval represents.

I think one of the ones that I'm most excited about is to have the first and only medicine for DM that can deliver both benefit on disease activity as well as steroid sparing benefit simultaneously. And then lastly, in terms of the safety information. In many ways, this is really the most predictable part of the label. We've known since we in-licensed brepocitinib in 2021 that we were going to have the JAK-class safety warnings we did not make an effort to not have those warnings and they came in really as expected and consistent with other approved JAK inhibitors.

This is a safety profile that physicians understand and are very comfortable with. The therapies are now very widely used, including in diseases where there's many more alternatives treatment options and there are in DM. And we're very confident that LISRAYA presents a compelling benefit risk profile in this condition for HCPs and patients.

And I would also note that the VALOR trial specific data really reinforced this benefit risk profile both with the efficacy data that we saw in that trial, but also with the safety data in that trial.

And particularly notable, this is actually cited in the FDA's press release is the treatment discontinuation due to adverse events occurred at nearly twice the rate on placebo as compared to LISRAYA in that trial. So very low discontinuation rate due to AEs for LISRAYA very higher in placebo. And I think really nothing speaks better to the benefit risk than that in terms of the patients voting with their feet as it were.

Turning lastly to Slide 9. I just want to kind of bring to life with specific, some of the efficacy data that we were discussing before. And again, really hammer home, I think two specific points. First, starting on the left is the combination of the breadth and depth of response on the TIS. Nearly 70% of patients achieving moderate response nearly 50%, achieving a major response, which is a very high and difficult bar to achieve in a DM study.

And again, I would emphasize the TIS is obviously a cost end point serves regulatory purpose, but I think is very resonant to patients because it captures things like the patient's global assessment, the physician's global assessment, things that kind of overall capture whatever matters most to a particular patient about their disease.

And in a condition like DM where you have skin disease, you have muscle disease, you have in some patient's pulmonary disease or other various manifestations, the TIS is really a great way to kind of capture overall, whether patients are benefiting, and we see really the vast majority of patients who are in this trial achieving meaningful improvement.

And then finally, on the right side of the slide, really just repeating what I already said on the previous slide, the fact that we're able to achieve both very significant clinical improvement on disease activity and very meaningful steroid sparing. This is unprecedented and dermatomyositis and I think is a really compelling part of the LISRAYA value proposition. More than half of patients on LISRAYA are able to simultaneously achieve a TIS 40 improvement and bring their steroids down to minimal or no burden by the end of the study.

As you can see on the right, this is for patients who started on 7.5 milligrams per day or more nearly 2/3 of them getting to 2.5 milligrams or less, and nearly half coming off steroids altogether. So again, very meaningful clinical and disease benefit, very meaningful steroid sparing benefit and we're really excited to bring LISRAYA to market. We're off to the races already, as I said before, and look forward to sharing updates as we charge ahead with the commercial launch.

So thanks, and back you, Matt.

Thank you, Ben. Appreciate it. And look, I'm sure, as you can hear from Ben's enthusiasm, we really feel like we got we've got everything we could possibly need on this label to help patients and physicians understand the benefit of LISRAYA and and the team are chopping it the bit excited to be out there of finally sharing that message appropriate way.

All the data Ben just described on Slide 9 is consistent with the FDA-approved prescribing information for LISRAYA. I think just like a great reminder of just how much we've been able to get on to this label to share with the community. I just say a few words, just as a reminder about the overall clinical data package for LISRAYA beyond just what specifically on the label.

So starting with -- on Slide 10, just a reminder, this VALOR was the largest Phase III placebo-controlled study ever conducted in dermatomyositis. We have had tremendous success owing to the quality of that study and the quality of the data and getting it disseminated in medical community, including with the publication this spring in the New England Journal of Medicine in the publication just this week, I think, in JAMA Dermatology of the skin-specific secondary endpoint, more to come there, but just an enormous wealth of new data in dermatomyositis owing to the side-scale study.

A little bit more in here on Slide 11, 12 and 13. I'll maybe just point out on Slide 12, as we've said before, this was a study that hit on the primary and every ranked secondary endpoint. This is the data as it was reported in the New England Journal publication. And it just gets to the breadth of what brepocitinib was able to do in this trial that it hit on skin and muscle activity that it hit -- across the board on these endpoints. One that I keep coming back to is HAQ-DI questionnaire.

The focus is on the actual disease burden in the daily lives of these patients, things like can you walk up 5 steps can you dress yourself, can you feed yourself and we delivered a meaningful, statistically significant improvement on that questionnaire. So just a tremendous and broad benefit to patients from the study.

We've also reproduced on Slide 13 the safety data from specifically within the VALOR study as presented in NEJM, again a table that highlights some of the risk benefit associated with the drug like brepocitinib in a disease where things like malignancies and thrombotic events are both the feature of the disease itself, the underlying inflammation as well as the things like high dose steroids that these patients are using. So excited overall with what the study was able to show and obviously tremendously excited as Ben highlighted with the data that's on label that's available now for use in this practice.

On Slide 14, we won't go through this again today. But just a reminder that while there's some breadth to this, this is a large indication affecting many people, and we are, again, excited that LISRAYA is now going to be an option for a variety of these patients and looking forward to getting out there.

On Slide 15, and then a fair amount of LISRAYA already. But again, this is just -- this is a tough disease. And I think that's a point that Ben has been mentioning on a day like today. These patients, 60% are more unable to climb a flight of stairs, half unable to walk more than a mile, a good percentage, 50% unable to bend, kneel or stoop. They rely on mobility aids. They are heavily treated with polypharmacy, including very high dose corticosteroids, if you've ever been on something like high-dose corticosteroids.

If you've ever been on something like high-dose prednisone, you can imagine the burden of being on that chronically is challenging. They are unhappy with existing options. They frequently switch. They have continued symptoms, flares, a lot of pain despite treatment.

And these outcomes are compounded by the toxicities of, for example, high-dose chronic steroids, which we've shown we can reduce that burden with brepocitinib. We are -- and you heard this from Ben, fully ready here from a commercial perspective. We are out and about -- patients are at the center of this launch.

Ben mentioned MyCompass Support, which is the patient assistance program with a dedicated patient access liaison on helping each patient through the -- navigating the complicated U.S. health insurance system and eligible patients will pay as little as $0 a month via the co-pay support program. We have a limited network of specialty pharmacies that are offering the kind of white glove high-touch support that rare disease patients have come to benefit from across other launches, and we're just excited to see all of that play forward.

On Slide 17, look, I'll just say we're ready here. All of this is in place. And as Ben said, prescriptions are already coming in. So excited to see that play forward. I mentioned earlier, again, the list price will be $35,000 for a 30-day supply. It's complicated and there's a lot of judgment in translating that to actual meaning in the end. But I think it's reasonable with compliance and other assumptions, and we're not prepared to break them out specifically yet. I think the net value to us or net price to us associated with the patient on a full year of therapy is probably in the low to mid- $300,000.

But again, there's a lot that goes into that estimate. And frankly, because no one's ever launched a novel therapy in this disease before, we'll know much more about that as we get into it. The other thing I'll say is I know Ben used the phrase massive commercial success in his presentation.

I'll just remind everybody that what we've said about this launch is that our expectation is that it will be slow and steady. This is the first time anyone's gotten a novel therapy out to these patients and that we are excited to do that, but obviously also know that there will be barriers and challenges that we'll have to clear through to be successful, and we're going to have to get behavior to change in an area that's been stagnant from a therapeutic development perspective for a very long time.

So looking forward to doing all of that, looking forward to coming back with further updates. I will move to Q&A in just a moment here. But before I do that, I'd be remiss on Slide 18 if I didn't say, for LISRAYA, this is really just the beginning. This is the first brick in what we hope is going to be a large wall of patient benefit that we're able to build or yes, a large wall of patient benefit that we're able to build across indications.

Obviously, DM with tens of thousands of patients now approved, but coming up very soon in the windshield is the non-infectious uveitis data, which, if successful, we'll add another indication here and then with ongoing registrational programs in each of cutaneous sarcoidosis and planopilaris coming in the near future. So just tremendously excited about what we've already built and are working on, tremendously excited about what's coming soon.

And as it says here on the slide, we couldn't be more excited to add even more indications for LISRAYA, think there's a lot of opportunity to do so given what we found so far in clinical practice. And then as a final reminder on Slide 19, brepocitinib LISRAYA is just the beginning. We have data coming in the near term in our PH-ILD program as well in the second half of this year in CLE for 1402.

We have further updates to our RA program all before the end of this year. And 2027 is an incredibly impactful year across the board, including specifically at Immunovant with 1402 reading out in Graves and myasthenia gravis, both. So gosh, we're just -- we're spoiled and privileged with the amount of clinical data and the opportunity we have for reaching patients in the coming couple of years here and looking forward to hopefully many positive updates, and I'm sure some negative ones, too, coming in the next months and years.

So with that, I just want to say again, a tremendous debt of gratitude to everyone who has supported this journey from Ben and the Priovant team to Frank and the other members of the Roivant management team and the entire team at Roivant who has worked tirelessly to make this successful.

And then really, first and foremost, to the investigators and the patients involved in the VALOR study who without the patients and the investigators in clinical trials, we wouldn't have new medicines. And today is really forward about them as much as about anything else. So I just want to say thank you to all of them.

I'll stop there. I will open the line up to Q&A, and I'll pass it back to the operator. Thank you, everybody, for listening this morning.

[Operator Instructions] Our first question comes from the line of Dave Risinger with Leerink Partners.

So congrats to Matt and the team. I've got a number of questions. Is it okay if I go one by one?

Sure. Thank you.

Great. So I guess let me start with the first one, which is we spoke with a leading KOL last year who said that they would convert all of their off-label JAK patients to brepocitinib after approval. So I'm wondering if you could discuss the opportunity to convert off-label JAK users more broadly to LISRAYA given its dual JAK TYK2 mechanism.

Thanks, David. It's a great question. Look, I think the short answer, unless Ben has more to say is I think we believe a very broad set of dermatomyositis patients are potentially eligible, including patients on a variety of other therapies on and off-label. And certainly, we have heard also from KOLs about the possibility that off-label JAK inhibitor patients could benefit from switching to brepocitinib from a variety of different angles, and we may very well see some of that behavior.

Ben, anything you'd add to that?

Yes. I would add that I think many of those patients will switch. But I think also the ultimate eligible population goes well beyond that. I would also add, I think physicians do really understand and appreciate the distinctive value of TYK2/JAK1 inhibition. TYK2 contributes in real way to suppressing the cytokine signaling that drives dermatomyositis.

And I think people understand that. They understand the way that this drug is different from other -- from the approved JAK inhibitors used off-label, the previously approved JAK inhibitors used off-label. This drug has different pharmacodynamic effects that derived from TYK2/JAK1 inhibition, and that has implications for DM patients.

Not to mention there is the most massive DM data set ever generated for a therapeutic behind it. So I think that, that's certainly an area where we would see a lot of receptivity.

Excellent. And then could you comment on anticipated payer access, including the pace of achieving reimbursed prescriptions over the next several months?

Thanks, Dave. It's a good question. I'm sure it's on other people's minds, too. I'll just say, look, I think in general, one of the great things about this moment is that we've been able to follow and learn from many other launches in large orphan indications around access, around helping patients and physicians navigate that dynamic to the greatest extent possible.

I think we're following all of those best practices. And I think we will be there to help patients in every way that we're able. I expect that we will be able to get patients on drug and benefiting from the therapy quickly and that we'll be able to navigate the system. It may take some time to get to full coverage and reimbursement across the board, but I'm confident we have the right systems in place.

Excellent. And then could you tell us the WAC price? And then I'll pass it on to the next person to ask questions.

Yes. Thanks, Dave. Again, I think I mentioned this on the call, but the WACC price for the drug is $35,000 for a 30-day supply. And what I said is my -- look, it's hard to translate that into practice without sort of knowing what the real-world use is going to look like. But for a patient on a year of drug adjusting for compliance and with a pretty wide range of possibilities around GTN and other things, I think that probably translates after adjustments to somewhere in the low to mid- $300,000 on a net basis, but we'll see.

Our next question comes from the line of Samantha Semenkow with Citi.

This is Ben on for Sam. Given the lack of approved targeted competitors, do you anticipate prior auths primarily focused on diagnosis confirmation or step edit requirements? And then I have a follow-up, too, please.

Yes. I'll -- look, obviously, to the extent that we're able, we've had conversations, Ben and the team have had conversations with the payer community. We've had lots of conversations with the physician community. I think it's hard to say specifically how this plays out in terms of like which specific things need to happen.

The thing that I'm most confident of is that we -- as I mentioned in the prior answer, just have all the systems in place to manage and work through prior auths, medical exceptions to help people understand what's needed. And my belief is that the level of enthusiasm and the level of unmet medical need is going to carry the day there sort of regardless of what that looks like.

And I also think that will just evolve over time as the physician community, the patient community and payers get used to brepocitinib and LISRAYA and get used to using it in practice.

And then a follow-up, if I may. You highlighted no restrictions based on disease severity presentation or prior therapy. Based on your physician interactions, where do you expect uptake to occur earliest?

I think I know how I'll answer that question, but I'm going to hand it over to Ben to answer that question.

I think that varies by doctor is the short answer. I think what's exciting to me is that as I was saying, there's a wide variety of patients who are eligible for this medicine and a lot of different ways that doctors can use it. And ultimately, I think each of them will kind of decide individually how they want to approach that.

That is exactly what I expect you to answer.

Our next question comes from the line of Yaron Werber with TD Cowen.

Yes. Terrific. Congrats. Really, really great to see. A couple of questions. One is we've -- I know many people have been talking to a lot of KOLs and running surveys. We're hearing, number one, that some practices are already warehousing patients and have a high degree of potentially switching from other JAK1s. The key is going to be, can they get reimbursement?

And does that make sense to do? What are your thoughts on that? And then maybe secondly, a question that we get a lot from investors. We think the market is huge. And from our service, it's pretty clear that VYVGART, if approved, would probably be positioned more as an IVIg switch and LISRAYA could really get used in everybody. Sort of what are you anticipating in terms of segmentation.

On the first question and mindful of payers appropriately watchful eye. I'll just remind people that our expectation for the launch here is slow and steady. Look, we obviously also talk to the physician community. We know there's a lot of enthusiasm out there.

We are confident in the tools and supports we have in place to help patients navigate access. But how physician practice evolves in the coming weeks and months is something we're just going to have to wait and see, and we're here for the long run and here to build something big in the dermatomyositis community, not. It's about where we are at Mile 20, not where we are at Mile 1 is, I guess, what I'd say. But we'll see. And again, we hear some of the same messages that you do, obviously, from talking to physicians.

On VYVGART Look, obviously, we watched the data set earlier this month with interest and thought it was impressive, especially in IMNM, where there's a tremendous amount of unmet need and where we're excited to see a therapy. In DM, it was a small study. I think it will be interesting to see. They've expressed enthusiasm for getting regulatory approval in DM, and we're watching that.

Most of all, I'll say, there's an enormous amount, as you highlighted, of unmet need in dermatomyositis. And I have said repeatedly that if argenx or anyone else joins us in the space, I think it's a net positive for us in terms of increasing the level of attention paid to these physicians and the level of enthusiasm in the community for new therapies, as I think you've seen in indications like myasthenia gravis, where the more therapies come to market, the bigger that opportunity appears to be.

And I think as argenx has benefited from being the first sort of significant novel approved therapy in myasthenia gravis in terms of physician enthusiasm, I think we have the same benefit in terms of being first in dermatomyositis. And so I think we will reap the same benefit that they have as more people come up.

In terms of like how specifically VYVGART get used, I think the answer to that question depends enormously on the path they take from here from a regulatory perspective and what the data ultimately looks like. And so it's just hard to it's hard to say, but I think brepocitinib has a super attractive profile. And you mentioned some important dynamics, including being on the market first, probably being comparatively attractively priced and being a once-daily oral. Thanks, Yaron.

Our next question comes from the line of Brian Chen with JPMorgan.

Congrats on the approval here this morning. well, yesterday. First, it seems that some doctors are using JAK off-label more among patients with skin manifestation first. Do you expect the initial wave of LISRAYA usage to be driven more from that segment first? And then we have a quick follow-up.

Yes. I'll reiterate what Ben says and see if he has anything he wants to add to it. But I think the practical truth is that the early brepocitinib use is going to come from a variety of different sources and a variety of different sort of patient phenotypes. And I think one of the things that's so exciting to us is that there's a lot of different patients potentially eligible for brepocitinib and a lot of different use cases.

And I think we are keen to support the doc community in figuring out what works best for them and what works best for these patients. I think we'll see a lot of different kinds of experimentation in the early innings and support it.

Ben, anything you'd add to that?

No.

Great. And what kind of metrics could we get during the launch for LISRAYA? And will we be able to track the launch curve using some of the script service like IQVIA or Symphony?

Yes. Look, the truth is that the way these orphan disease launches work for reasons that have nothing to do with investor management, it can be relatively difficult to see that data. And so I think we will be roughly consistent with that. I think quarterly net sales will be a useful metric ultimately on which to judge us. And we'll see what else we're able to provide as we get further into it.

Our next question comes from the line of Prakhar Agrawal with Cantor.

Congratulations on the approval. Maybe just one clarification on the label. It seems like there were a few new cases of thrombosis, MACE and malignancy during the OLE period. So if you can provide more details about this, whether the open-label extension period had flexibility on management of their background treatment? And what are the commercial implications there?

And second question, fully realizing that you don't want to raise expectations here and expect a slow and steady ramp, but are there any specific barriers in DM that we should be aware of on why shouldn't this be the most rapid rare drug disease launch ever given the unmet need and the strong efficacy data for brepo?

Thanks. I'll take the second question first and then hand it over to Ben for the first one. On the second question, I will respectfully reiterate what we have said, which is that our expectation is slow and steady. Look, I think actually, it's important to note on the one hand, at some level, faster is better. But mostly, I think what we are optimizing for is getting this drug out to patients and making it a sustainable, valuable option for patients and physicians with dermatomyositis and changing treatment paradigm takes time, and it will here as it has in other orphan diseases.

So I don't have any -- I don't think there's any sort of magic specific to DM thing that affects the pace of this. But I think the truth is it's just hard to know in a novel disease state in a novel setting exactly what the future is going to look like. So that's why we're sort of thinking about slow and steady as the base case.

The other thing I'll just say is as a reminder, dermatomyositis is just the beginning for brepocitinib, and we want to set up a franchise that is not just sustainable to grow over time within DM, but is able to support all the other indications that are coming, and we're excited to see that play forward as well.

I'll turn it over to Ben, do you want to take the question on the OLE period and overall on safety?

Yes, sure. Yes, I think we will share the full efficacy and safety data from the OLE at a later point. I don't want to fully preempt that. I think your hypothesis is not entirely correct as worded. The one thing I would flag that is correct and is seen on the label is that there were MACE events in the OLE. This is to be expected.

Dermatomyositis patients are very sick. They're at higher risk of are higher risk of these types of events due to underlying inflammation due to steroid burden, which contributes significantly to cardiovascular risk. And then also, certainly, these warnings are on JAK labels for a reason. And all of these events have been seen across the brepocitinib development program, but consistent with other JAK inhibitors, they have occurred at rates that are rare and are uncommon.

And again, ultimately, as we've said before, it's a safety profile that physicians have become extremely comfortable with using JAK inhibitors very widely for patient populations with probably less need for aggressive therapy and more alternative modern options than we have in dermatomyositis.

Great. Thanks, Ben. And I'll just say one additional case of thrombosis in the OLE and no malignancies on treatment in the OLE. So also not a material change in the risk profile and just entirely consistent with the labeling and sort of considerations around the JAK class generally. And as Ben said, I think overall, given the background risks for these patients and the therapies that they're on otherwise, this is -- it's a relative nonissue in dermatomyositis.

Our next question comes from the line of Dennis Ding with Jefferies.

This is Anthea on for Dennis. Congrats on the approval. Just two questions from us. Matt, you kind of mentioned quarterly net sales as a potential metric for the launch. I'm curious how long you expect the lag to be between a patient being prescribed LISRAYA and that demand showing up in reported net sales and how that should evolve over the next 6 to 12 months?

And if we should expect any other launch metrics, disclosures around patient start forms, new patient enrollments, payer coverage, et cetera?

And then second, how should we think about conversion of patients who participated in the VALOR program in terms of how many patients remain on brepo through the extension and what proportion you expect to convert on to commercial drug over the coming quarters?

Yes. Thanks, Anthea. That's a helpful question. I -- on the first question about launch metrics and timing and everything else, look, I think I could give -- we could give best estimates on any of these things, but they would just be guesses on our part at the moment. I think we're just going to have to wait and see in the first months of launch, how this process plays forward. And so I think we'll be able to provide a little more clarity on this as we have it.

But right now, I don't have much to guess in terms of the timing. And I think on launch metrics, I think let's get a little bit further into it. I think in general, our view is we're playing for the long haul and sort of intrigue about the early numbers is less interesting than where we can get to over time. But we're going to sort of look a little bit at how things go in the first innings, and then we'll get back to you.

On the second question of conversions of patients from VALOR to commercial, actually, I don't -- I personally know the answer to that question. Ben, I don't know if you have an easy answer in terms of those conversions or if it's something we're working through.

Yes, I think many patients from the VALOR trial are excited to get on LISRAYA. It's not something we're singularly focused on. We're focused on all the patients who could benefit from the medicine, which includes, but is not limited to those.

Our next question comes from the line of Yasmeen Rahimi with Piper Sandler.

Congrats on your first approval and many more to come. So congrats. A few questions. Maybe just some easy ones in terms of like now with the launch under go, what is the size of the sales force that you've already put into place? And how do you envision sort of growing that over the next 12 months? And then second one is, what do you think the time it takes from writing the script to being reimbursed now that everything is ready to go?

And then also, how do you envision that 3 months from now, 6 months from now, a year from now? And at what point during this launch will you feel really comfortable to kind of give a little bit more color around the metrics and how things are going. Obviously, today is day 1, but like what are the things that you need to see where you could come back? And just -- because you guys are very numbers-driven, data-driven and do such a great job on guiding us.

So at what point do you feel like you could kind of provide some of these more granular metrics? I know that you can't do that right now. But what do you need to learn to do that? Sorry, 3-part questions, I guess.

Perfect. Thank you, Yes. Those are great questions. I feel pride bound to make one small correction to your question, which you said it was our first approval. It's actually the ninth approval to come out of the Roivant apparatus, obviously, including one of the drugs that we commercialized ourselves for a while. But it's potentially the one that's most impactful for us, and we're obviously super excited about it. And it's the first for Priovant, which will hopefully be the first of many for brepocitinib.

On sort of field force in general, I'll say we have a phenomenal team in place. Ben has been laser-focused, Ben and his team have been laser-focused on getting the right people into these seats and there are people who are going to do a great job engaging with the medical community, and we're really excited to see that play forward. We've said before, this is a relatively concentrated field.

I think one of the things we said before is about half of these patients are treated at 200 specialty referral centers. And so I think from that perspective, we feel confident. We will probably continue to grow our field force over time. But for the moment, I think we're in a really great spot in terms of how many people we've got and what we're doing. I think overall, as far as this is a part of cost question, the guidance that we've given historically on cost structure is approximately the same as we give now. No significant change there from what we said.

On the next question, which is what do we need to see to come back with more metrics. Look, I think it's just too early now to say exactly. But my honest view is -- and I don't mean to be glib. I just think in the end, the commercial performance of the drug is what's going to eat everything else that's being used to make predictions. And so I think mostly, we're just going to be focused on maximizing the breadth of usage and making sure that we're out there doing everything we can to make the lives of patients getting on drug easy and to help physicians understand what they can do here. Thank you.

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

Congratulations. Matt, maybe if you could just talk a little bit about what the considerations were in terms of the list price that we set. Obviously, DM is an orphan indication and you're largely pursuing other ones. But how do you see that playing out? And how much do you consider the addition of other indications on label? And if you had sort of used any other sort of commercial analogs that might be helpful that sort of informed your thinking.

Yes. Thanks, Doug. It's a great question. And obviously, there's a lot of judgment and debate and thought that goes into how you do this in the U.S. health care system in 2026. So it's a complicated question. Obviously, we have a number of analogs out there that are in various ways, launched in orphan diseases. And I think we've learned a lot from how those launches have gone and from our conversations with payers and other stakeholders.

Obviously, the commercial cost and value of IVIg is one consideration that was relevant to us as we were thinking about where it made sense to price the product. And I think overall, we are confident in the decision we've made in terms of getting maximum access and the overall value proposition for the drug to patients, clinicians and payers, including the long-term benefits from reduced steroid burden, which we think will be significant.

In terms of the list of other indications and the sort of relevance there, look, obviously, that's something we think about all the time in terms of what brepocitinib could become across a variety of indications. I think given the differences in dose and other things, we still have some flexibility to think creatively about that as the clinical profile of the molecule in these other indications and the breadth of indications becomes clear.

But I think the price point here supports and is homologous with or in harmony with everything else that we're planning on doing for brepo. And I think we feel really great about delivering on the full value proposition of brepo in orphan inflammatory.

And Matt, if I have a follow-up, and I appreciate your point that brepo offers a lot of versatility and could be relevant for a wide range of DM patients. I'm just curious if you have in mind sort of an initial group of patients that you're going to have the field force really sort of hone in on in terms of the messaging with clinicians in terms of who you want to sort of get on to drug to sort of have the real-world effect match what we saw in VALOR.

Thanks, Doug. It's a great question. I'm tempted because we've gotten this question in a few different forms to say something like, well, we're really focused on Fred, Joan and Amy. But look, obviously, the short answer to this question is to repeat what I've said, which is that we think there's a pretty wide range of patients who could benefit from brepocitinib.

And in talking to the physician community, I think it's clear that enthusiastic physicians have a variety of different sort of early use cases in mind for their patients and that we really do want to support all of those use cases.

And what I think in practice is there will be some docs for whom their early use case is converting JAK inhibitor patients and some docs for whom their early use case is patients on high steroid burden who are ineligible or don't want to use IVIg for various reasons and some docs who have been struggling with other off-label therapies are struggling with the side effects of steroid immunosuppressants.

So I think our view is wherever these physicians want to go, we want to be there to support it. So I think we have been specifically focused on not narrowing to a specific subset of patients, but rather helping the community meet us or helping meet the community wherever they want to be.

And if I can, one final one. You said that you expected -- Matt?

Go ahead.

Just one. You said that you expected like sort of low to mid-300s in terms of net to the company. In addition to rebates and sort of free drug, I think you mentioned some compliance. If you could just give us what that sort of -- everything that's going into that, just so we can -- so is it sort of like net pricing? Or were you just talking about net revenue to Roivant?

Yes, Perfect. I think -- the short answer is I think part of the reason we gave a range and part of the reason we caveated it as a rough estimate is there's a lot that goes into these assumptions around compliance, around GTN, around other things. And I think it's fair to say, while we obviously have some sense of how each of those components shake out, the error bars are sufficiently wide and the compounding across those different factors is sufficient, but like it's hard to say specifically, and there's even error bars around that range. So I don't have a ton more to add to that. I will...

Do you have a target for coverage sort of number of percentage of lives and so forth?

Our hope and goal is that every patient who would benefit from brepocitinib will have access to it. And hopefully, we'll have access to it in a way that works in terms of coverage and out-of-pocket expense and so on. So that's really where we're focused. Sorry, Ben, I want to hand it back to you just to answer. I think I missed one of Doug's questions about the VALOR trial specifically.

Yes. I just wanted to add, in terms of your question around kind of patients where we would see the results of the VALOR trial may be replicated in the real world. I just -- I thought that was a thoughtful question and just wanted to say, I think one of the things that's exciting about the VALOR trial and I think exciting to physicians about it is really the breadth of patients who are enrolled.

It enrolled a wide real-world population, including patients with mild, moderate and severe disease, patients on a wide variety of different background therapies, patients where skin disease was driving a lot of the disease burden, patients where muscle disease was driving a lot of disease burden. 20% of the patients had ILD. And across this heterogeneous population, we saw very strong efficacy on both the total improvement score and as we've discussed, other disease measurements across skin disease, muscle disease, physical functioning and steroid sparing. And I think that is what supported the broad label we have received.

And I think as a result, gives us the confidence that kind of broad set of patients being evaluated for care in the real world will allow the benefit risk of the drug to shine through in that setting similarly.

Our next question comes from the line of Andy Chen with Wolfe Research.

This is Brandon on for Andy. Matt, so you mentioned barriers and challenges that you need to get through on the launch. What specifically there were you referring to? I think we're curious to know like why this launch wouldn't be blasting out of the gates. And then second question, on your internal assumptions, what are the key factors that would push net price to the lower end or the higher end of that low to mid $300,000 annual expectation? Is there something within GTN? Or is it compliance that would be the bigger swing factor?

Yes. Thanks. On challenges. And again, I want to be clear, it's not that we're like nervous about facing anything specific to dermatomyositis that is unusual relative to other orphan launches, just that orphan launches are hard. But I'll give it to Ben to answer some of the specific things that we're working on preparing for.

Yes. Look, I would say I think it goes back a bit to the last question. I think the same thing that is the opportunity for this drug in the long term is what makes the early launch challenging in some ways, which is there has been no innovation here in decades and prescribers have been treating patients in certain ways for decades because there hasn't been innovation.

And obviously, they need to change that behavior. And behavioral change takes time for human beings even when there's a lot of intellectual enthusiasm around it. And I think there's as we've discussed, not like, okay, this is the singular group of patients who are going to get on drug initially at launch because in an area where you don't really have moderate approved therapies, every doctor manages their patients differently.

There's a lot of heterogeneity in terms of how patients are cared for today. So our approach is really to think about the medium- to long-term outcome of, as Matt described before, meeting doctors where they are and presenting the breadth of our label and the breadth of data from the VALOR study for them to really consider all adult DM patients who could be a good fit for the drug and consistent with the label for therapy. And we think that over time, that's going to come through. But exactly how fast that adoption is going to vary a lot by prescriber and it's pretty hard to predict with any degree of confidence.

And then I would say a similar approach applies to the reimbursement. We've been engaging with payers a lot. I'm very confident that they appreciate the unmet need. They appreciate how sick these patients are. But obviously, until we get into it, we won't know a lot about the exact way that, that's going. And again, very confident that over time, we will be able to have access to patients, and we have a lot of support in place to ensure they're able to get that access.

And we're committed as Priovant to providing that to patients 100%. But what it means in terms of our commercial results and exactly how quickly those are achieved, we'll have to see.

Thanks, I want to take a moment to unify the community of everyone listening to this call, and we will all silently in our heads, but with the knowledge that everybody else is doing at the same time, chance my other comment about this, which is that our expectation about the launch is that it will be altogether now slow and steady. So however many hundreds of people are now repeating that in their heads.

On the other question that you asked about the band of net price. Look, I think there's a lot of moving parts. You mentioned a few of them. I think the short answer is it will come into sharper relief relatively early in the overall picture here, and we'll be able to talk more about GTN, disclose it and so on when the time comes.

Our next question comes from the line of Yatin Suneja with Guggenheim Securities.

This is Min on behalf of Yatin Suneja. Congrats on the approval. You described slightly earlier, but if you can add a little more about the step edit expectation, the early adopter who can be? And how should we think about the launch cadence?

Look, thanks for the question. I don't actually feel like I have a ton to add on this question. I think from a physician perspective, the early adopters -- look, there's a lot of enthusiasm in the physician community for a novel therapy in an indication where there's not been a lot of innovation. And I think we have a lot of discussion with physicians who are excited to use the product.

Obviously, Ben and the team did a great job running a clinical trial and therefore, we have a lot of those relationships. I suspect some of the docs who are most familiar are probably also some of the practices from where the early scripts are coming. And on the patient side, I think we've answered already the question of what we think sort of "segmentation" looks like here, which is that we have a broad view of who the early patients are going to be.

And then on launch cadence, we get to say it one more time, which is we get to say, look, our expectation for the launch will be slow and steady and that we're building something big and important. And it's not about where we are in a month or 2 months or 6 months. It's about where we are in a year and 2 years and 6 years. And that's how we're thinking about the long-term proposition here, both in dermatomyositis and beyond dermatomyositis.

I think we've had -- look, I think we have a unique opportunity as really and maybe this is a good place to wrap this up to build a durable company that is benefiting patients across a variety of indications. I think the quality of the data in dermatomyositis speaks to what we're trying to do. And I think we're hoping to replicate that in a bunch of places and to build something that matters.

And I hope we can continue to share data in the near future that supports that mission as well as continuing to get this drug starting and now focusing on getting this drug out to dermatomyositis physicians and patients. Thank you very much.

And that concludes the question-and-answer session. I'd like to hand it back over to Matthew Gline for any further closing remarks.

Great. Thank you. Look, thank you, everybody, for listening this morning. It is a privilege to be able to take a drug like this, generate data like this and get it out to patients. It's something we have the honor and responsibility of doing at this point, and I know that Ben and the team are super focused on it. You've heard a fair amount of commentary on this call about our long-term enthusiasm and about our focus on doing this the right way.

And I'm hopeful and confident that we're going to be able to do that. So I want to say thank you again to the enormous number of people who it takes to get to a milestone like this one and in advance to the enormous number of people who it's going to take to carry the baton through the next race here. There's a ton of work coming to the Roivant team, to Ben and the Priovant team who executed tirelessly on this program and will execute tirelessly on what's to come.

And again, to the patients and investigators, it's hard to overstate the extent to which this carries, meaning for some of them who have been suffering from this disease for a long time. So look, thank you again, everybody. We look forward to getting back in touch in the near future on a pretty exciting 6 and then 12 months ahead. And I'm sure we'll have lots of opportunity to stay slow and steady on future calls as well.

Thank you. This concludes today's conference. Thank you for your participation. You may now disconnect.

Good day, and thank you for standing by. Welcome to Roivant First Quarter 2026 Earnings Conference Call. [Operator Instructions]

Please be advised that today's call is being recorded. I would now like to hand the conference over to your first speaker today, Stephanie Lee. Thank you. Please go ahead.

Good morning, and thanks for joining today's call to review Roivant's financial results for the first quarter ended June 30, 2026. I'm Stephanie Lee with Roivant. Presenting today, we have Matt Gline, CEO of Roivant. For those dialing in via conference call, you can find the slides being presented today as well as the press release announcing these updates on our IR website at www.investor.roivant.com.

We'll also be providing the current slide numbers as we present to help you follow along. I'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 have 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.

Thank you, Steph, and good morning, everybody, and thank you for joining. This is a little bit of a calm before the storm moment for us. And so a pretty quiet quarter and maybe not the most interesting of our earnings calls in recent memory. But nonetheless, a lot of great progress in the business. And certainly, we're expecting a jam-packed second half, as I'll get to in a moment.

So I'll be relatively brief in my remarks, and then we'll go to Q&A. I want to start on Slide 4. This is a slide we took from our own prior deck. This is from the Investor Day that we did in December of last year, and this was a list of our priorities for the year. And we're sitting here a little bit more than halfway through the year. So I just wanted to highlight that it's gone well for us, that we feel really good about the setup.

And so on Slide 5, looking across the list here, we've got brepocitinib expected to launch by the end of September. Obviously, we got priority review and our PDUFA date, as we said, is this quarter. We have great data from 1402 in the D2T RA study that we presented on our last quarterly call. Probably the most notable update for today on the top center of this slide is that we've now enrolled patients in the Phase III study in cutaneous sarcoidosis for brepocitinib, which follows on the positive results that we had in our Phase II data, which I think we announced on our first quarterly call of this year, earlier in the calendar year.

We've now received the initial payment from Moderna in the settlement and that -- the sort of second part of that, the 1498 part of that case is progressing, and we filed international proceedings against Pfizer and BioNTech in that case. And finally, earlier this year, we added LPP as a fourth brepocitinib indication. And as I'll remind people later today, that study is continuing to enroll really well.

As I mentioned at the top of the call here on Slide 6, I'll just say this is a quiet quarter, and this is a quiet day. I don't know exactly how the following statement could be true, but I think it is. The next 6 to 12 months are, in many ways, busier than the prior 6 to 12 months for us. And so we just have an enormous amount coming up, starting, as I mentioned, with the upcoming potential brepocitinib launch in DM, which should happen imminently assuming everything goes as we hope and expect it will with FDA.

We've got top line data in brepo from the NIU study, an indication that could easily be as large as dermatomyositis. That data is coming in the second half of this year. We also have top line data coming shortly in the second half from mosli, the Phase II study in PH-ILD. I know that's being closely watched, and we're looking forward to getting that data and presenting it. We will provide updates -- further updates on the D2T RA program at Immunovant in the second half of this year, including hopefully a download on a conversation we hope to have with FDA about that program as well as the results of the second part of the study and a little bit more about our plans going forward.

And then finally, probably the smallest of these, we're expecting top line data from the POC study in CLE also in the second half of this year and looking forward to finding out what we've got there when that comes in as well. So just a jam-packed second half and even more coming in 2027 with the Graves data and beyond. So just a lot in here. I'll just hit a couple of highlights in terms of the pipeline updates in a little more detail here before, again, before we go to Q&A.

Starting on Slide 8 with a reminder because it's been a few months since we've talked about it. The initiation of the cutaneous sarcoidosis Phase III study is a pretty exciting event. It's a little bit ahead of schedule in terms of what we've been able to do here. And this is a disease that we're just privileged to be able to work in here. It's a high morbidity, very difficult disease with a high urgency to treat. You can see on Slide 8, some of the photos we've shared before, but these are patients who are really sick and have very few treatment options.

On Slide 9, as a reminder of the data that we generated in our Phase II study, we had set for ourselves a goal of a sort of 5-point benefit on the CSAMI scale for clinical meaningfulness. And in the study on the top left of this chart, we showed a greater than 20-point benefit compared to roughly nothing on placebo. So just a huge benefit to those patients in the Phase II study and really excited to carry that forward into the pivotal program.

As a reminder, on Slide 10, we think this is a pretty decent sized indication, again, with high unmet need, probably about 40,000 patients in the U.S. and reasonable overlap with some other organ systems, including ocular sarcoidosis or GI sarcoidosis, where that overlaps with NIU that is one of the types of NIU that we're studying as well as pulmonary sarcoidosis, which is a big potential indication as well and where we hope to be able to treat some of those patients via either their ocular sarcoidosis or CS.

The Phase III study that we've now begun, the design is laid out on Slide 11. I know there were some questions after the Phase II about what exactly this study would look like. It is designed to take all of the learnings from the Phase II study that was successful. It is a 16-week study with the primary endpoint of CSAMI greater than or equal to 50% response rate.

It's a 140-patient study across about 70 sites, 3 to 2 randomized with patients either on 45 milligrams of brepocitinib or placebo, and with a mandatory -- sorry, a mandatory steroid taper going from week 2 to week 8 down to 0, which is consistent with -- roughly consistent with what we did in the Phase II and generally consistent with what we think is appropriate for patients in this indication.

So that study, as I said, has already begun enrolling patients, and we expect top line data in 2028, which just adds to the list of registrational -- potentially registrational indications for brepocitinib coming up. I'll reiterate on Slide 12, the other ongoing registrational program is the brepocitinib study in lichen planopilaris, or LPP, that we announced earlier this year. That study is enrolling, I would say, extremely well. There's a lot of enthusiasm from physicians and patients for that, speaks to the high unmet need in the indication, speaks to the quality of the work being done by Ben and the Priovant team and looking forward to sharing more about that as soon as we've got it. So that's also moving along nicely.

Look, finally, and I'm sure there will be questions about this in Q&A and lots of opportunity to talk about it, hopefully, with a potential approval and beyond. Obviously, one of the major events in the near term here is the launch -- potential launch of brepocitinib in dermatomyositis. Obviously, I think we're in a phenomenal position here in terms of what we've got in terms of what we hope to be able to do, starting with the quality of our clinical data, which, as you know, from the multiple times we've talked about it from the publications, including in the New England Journal and so on, just phenomenal data, stat sig across all 10 endpoints big clinical benefit, a lot of enthusiasm from the doc community.

This is a really tough disease, a large addressable population, most of them on sort of polypharmacy, trying a lot of different things. And frankly, most of them still dissatisfied with the available treatments. So we feel like we have an opportunity to do something big and different for this patient population. Our team has been out spending a lot of time with the physician and the patient communities on overall education. And I think the enthusiasm for a new therapy is coming out loud and clear, including with all the academic presentations that have been done and so on. Commercial launches, there's not much to say today other than that it's on track. We're ready to launch on time, having received priority review. The sort of commercial and patient support teams are built out, trained, ready to deploy.

We feel really great about the hires we've made there, really great about the organizations we've built there. We think we're doing this in a way that is both capitalizing on all the learnings from successful launches at other companies in recent years and doing it in a Roivant-Priovant way. There's nobody in the world that will be more excited to see -- oversee this than the team we've got at Priovant with Ben and Daniel and others. And I think we're going to be fully ready. Everything is on schedule. So we'll have much more to say about that with the potential approval and after, but looking forward to it.

I'll say one more thing about the commercial franchise overall at brepocitinib on Slide 14. We get a lot of enthusiastic questions from investors around pace of launch. And we've been pretty consistent that our answer to that question is sort of slow and steady is what we're looking to build there. And I think there's a bunch of reasons for that. Obviously, some of them are DM is a new indication and no one's launched a novel therapy basically ever or at least a targeted therapy basically ever. And so it's just hard to know exactly what work will need to be done to get everyone comfortable and excited on drug, although I think we're fully prepared.

But also, to me, it's because brepocitinib is a lot more than just dermatomyositis. And to me, what we're really doing here is not just trying to make that launch as fast as possible, we're trying to lay the groundwork for the overall opportunity, which goes beyond DM into first NIU and then CS and LPP with the data coming thereafter.

And I think as you think about that layering, to me, it's much less about what week 1 or month 1 or quarter 1 looks like and much more about making sure that the foundation around access, the foundation around patient support, the foundation around the institutional activities, the foundation around our communication with the scientific and physician community and our communication with patients are all set up to deliver the maximum opportunity for brepocitinib across all of these indications. And so I think slow and steady isn't just about sort of guidance.

Slow and steady is about the approach that we're taking with the program to make sure we have maximum reach across everything that we're doing there, including indications that we're excited about beyond the ones we've already announced. So a lot to come, as I said, on track for that launch. You all hear the same thing we do, which is a ton of enthusiasm from the patients and physician community for new options in all of these indications and looking forward to sharing more when we know about it.

But our guidance is going to continue to be slow and steady because that's what we think we're building. Final business update here is we got the upfront payment in the settlement with Moderna. That $950 million has come in, $770-ish million of it to Genevant and the rest to Arbutus. So that's done. there will be progress in terms of return of capital, et cetera, of that and so on. The 1498 sort of appellate ruling is that that process is ongoing in the Federal Circuit. That would be another $1.3 billion if we got a favorable outcome there.

And then we continue to advance our litigation against Pfizer and BioNTech. We filed 3 international lawsuits, notably in Canada and the UPC in July, so just last month and continue to progress that case as fast as we can. Obviously, not all of it in our control, but equally enthusiastic about the potential there in terms of what we could get.

I'll wrap up just with our usual financial update on Slide 17. Look, I think overall, most importantly, we are spending in areas that we're excited to be spending. We're excited about all of our R&D programs, about $200 million of R&D expense for the quarter, of just under $100 million of non-GAAP adjusted G&A or $166 million of GAAP G&A expense and cash just under $4 billion, and that's before the receipt of the $772 million. Notably, pretty significant share repurchase activity, about $200 million in the quarter, a bit more than that when you include March.

Obviously, what we did there was we accelerated our share repurchase program upon the announcement of the Moderna settlement so that we could get those shares in. And the shares that -- and remember, the shares that we bought back kind of the first round of this, the $1.5 billion that we have bought back sort of up through mid last year, we bought back at around $10 a share. I think the average price at which we've been able to buy back stock since we kicked off the second round of this in earnest in March has been in the high 20s. So feeling good overall about retiring those shares and getting that capital back to shareholders. I'm going to continue doing that according to our authorizations for now.

And all of it ahead of on Slide 19, a really rich catalyst calendar ahead with a lot coming. So looking forward to all of that, with just an incredibly busy stretch ahead. On Slide 20, again, a little bit incredulous for the people around Roivant who are doing all of this work or incredible people to do this work. But by the end of calendar 2028, we'll have had hopefully 3 or more commercial launches, 9 or more pivotal study readouts, 4-plus NDA or BLA filings and a number of proof-of-concept studies, just a ton coming up in the near term. So with that, I'm going to wrap up my prepared remarks for the day, and I will hand it back over to the operator for Q&A in just a moment. Thank you again for listening this morning and looking forward to taking your questions.

Operator, over to you.

[Operator Instructions] Our first question comes from the line of Brian Chen of JPMorgan.

Maybe just thinking through the DM launch, Matt, can you give us a quick sense of what metrics we could be receiving right out of the gate to help us better track the initial launch? And then secondly, on PH-ILD, as we think about the baseline characteristics here in PHocus, it seems that more patients are on nintedanib.

We are curious if there's any implication in terms of the fibrosis versus emphysema ratio in the population? And then further down the line, whether there's any implication towards the bar for success for both 6-minute walk and also PVR?

Yes. Perfect. Thanks. I appreciate both questions. Look, on a thing I've gotten fond of saying as I've watched other companies with commercial launches is that you all don't deserve our guidance, which isn't quite fair. But look, I think other than sort of a slow and steady launch and obviously, the sort of top line metrics will be clearly visible in our financials each quarter.

I don't know that we're going to provide a ton of detail in the early days. I think it's important for us mostly to spend our time focused on understanding those dynamics ourselves, getting out, talking to patients, talking to physicians, doing the work we need to do. We'll give a little more color on what that's going to look like on a call with potential approvals, and then we'll start to flesh out the package that we share with each successive quarter.

But I don't have a lot to say right now about metrics. I'll say, I think typical with these launches, I'm not sure a ton is going to be visible in the early days, just given how the commercial apparatus is set up for practical purposes, but we'll provide more guidance on that as it gets closer and is here. On PH-ILD, I guess, first of all, we've obviously been watching, for example, the treprostinil data in IPF and trying to understand a little bit better what's been going on with these PH-ILD patients in treatment of PH-ILD for fibrosis and for lung disease. It's been a view of ours for a while that one of the things to look out for in treatment of PH-ILD with vasodilators is emphysema.

And so the study was designed with care around the amount of emphysema allowed in the study overall, and that was an important part of the guiding philosophy of the study to make sure that we could serve the patient population broadly, but also we're maximizing the potential benefit of the therapy. So that was considered from the beginning. So those are, I think, things we're keeping an eye on. I know there is a vocal cohort that believes that treprostinil has antifibrotic benefit.

Look, I think our view is if you treat PH-ILD patients well for their pulmonary hypertension, you may well deliver a benefit overall on their lung disease. And I think our view is probably that vasodilation is driving a lot of the activity there. But we also have some evidence from nonclinical models of antifibrotic activity for it. Overall, on 6-minute walk and PVR, and I'm sure I'll get versions of this question more today.

Look, I think it's consistent with what we said before. We're hoping to see a clear signal on PVR. We expect if the drug is all active, we will. We don't expect to see very much with clarity on 6-minute walk. The study is not powered for 6-minute walk. It would be nice to see some separation, but I don't think that's essential for our sort of go/no-go decision from here. And we'll just -- we'll know what we've got once we get a closer look at it, including the full balance of that data.

Next question comes from the line of Dave Risinger from Leerink Partners.

So I have three questions, but rather than rattling them all off right now, maybe if it's okay, I'll go one by one. So first, on mosli, you commented just now on 6-minute walk distance. But if you were to run a large trial, what type of 6-minute walk distance would you be hoping for, i.e., what would be relevant to the clinicians and to the patients? So that's my first question.

Yes. Thanks, Dave. Look, I think, obviously, we'll have a slightly better answer to these questions overall once we have a sense of what we saw in Phase II. The truth is the PH-ILD patients are really sick. There are not a lot of options for these patients. And as we saw in Group 1 in PAH, when you have more treatment options, first of all, patients go on multiple options, multiple lines of therapy.

And second of all, most importantly, like the actual -- not from a clinical trial perspective, but from like a real-world evidence perspective, like survival and mortality rates go down as new classes of drugs are introduced in PAH over time. And I think it's like less about a number on 6-minute walk and more about having an approvable therapy. Remember, these are patients that are trying to walk to the car.

They're trying to walk to the bathroom. They're trying to like live their daily lives. So I don't know that I think it's like correct scientifically to describe a specific numerical bar that matters versus just being able to get a new therapy. And some of that's, frankly, because 6-minute walk in clinical settings is an art that is complicated and noisy and like a little bit difficult to translate into daily lives, whereas if these drugs really effectively vasodilate and improve lung function and improve PVR, I think you wind up seeing a lot of benefit for these patients.

So I don't know that we're going to articulate or have a specific numerical bar versus a successful study. Obviously, we will be judged, especially by the investor community based on competitor data, but I don't think we even need to be per se better than any other mechanism in order to have a big benefit to patients.

Great. That's very helpful. And then regarding the forthcoming brepo DM launch, could you discuss the cadence of formulary reviews for rare disease drugs? I ask because for mass market drugs, P&T committees often wait until 6 months after launch before putting drugs on formulary.

Yes. Thanks. Look, I don't have a ton to say about that right now other than we're having all of the normal engagement with the payer community that you'd expect us to have at this stage. And also -- and I think this is a critical point about all of these launches. We are super focused on making sure that patients -- the physicians who want to write this drug and patients who want to get on this drug are going to have access. I think that's going to be really important for our engagement with the community for access generally.

I think in terms of like literal formulary, it's probably like not so different. It's not like there's a separate committee for different kinds of diseases, but there's lots of medical exception procedures and other things that you can do to get patients covered. And we have a whole team of people built out at Priovant that's dedicated to making sure whether the formulary -- the formulary work has happened yet, whether the P&T committee has happened yet is not something that our patients and physicians have to spend a lot of time thinking about as they're deciding how to use the drug.

Excellent. That's really helpful context. And then finally, beyond the list of programs on Slide 19, could you remind us about pipeline and product opportunities for your portfolio, including specific products that you could announce initiation of new studies for over the next year or so?

I think every single one of the programs that the world is aware of in our pipeline as well as potentially ones that the world is not yet aware of in our pipeline. In all of those cases, we could announce new trials, new indications in the next year. I think it's every one of those are eligible and all of our molecules could be put into indications beyond the ones we've talked about.

And I think it's fair to say in each case, we have specific ideas of indications we're excited about. We've done active work and are, in fact, like preparing to initiate programs to varying degrees depending on how busy those teams are today versus next month or the month after, but real progress. So I think the answer is we are actively working on that, that all of our products are, as you call them, pipeline of products and that we're excited to share more indications as we start those studies.

The next question comes from the line of Samantha Semenkow from Citi.

I also have 2, one on mosli, one on brepo. For mosli, I'm wondering if you could just talk about the translatability of PVR reductions in patients with PAH to those with the PH-ILD population that you enrolled in PHocus. Are there any aspects of either disease that could influence the magnitude of PVR that you could see in the mosli data? And I have a follow-up.

Yes. So look, I think -- thanks for the question. I appreciate it. I think the translation from PAH to PH-ILD is the fundamental question being answered by our study. And so the first unfortunate answer to that question is we're just going to have to see what we see. And it is the it is the risk of the program at some level that we find something -- again, the Phase I data, including in PAH patients look very good on a PVR basis.

So one of the main "risks" of this program is that there's something, I would call it, unexpected in the PH-ILD translation. Obviously, I use the word unexpected because I think scientifically, it seems relatively straightforward that inhaled vasodilation is an effective mechanism in PH-ILD, but we'll find out. Obviously, the lungs of PH-ILD patients are different than the lungs of PAH patients.

And so you might expect some difference in sort of the pharmacodynamics of the drug in those patients. But overall, it seems pretty clear that when you take an inhaled vasodilator in PH-ILD patient, you get drug to the healthy lung tissue and it matters. So that's what I'd say.

Got it. That's very helpful. And then just on brepo and DM, in your conversations that you've been having with physicians for education, I'm wondering if you could just talk about the reception to brepo given the JAK class safety concerns. Obviously, the safety profile on VALOR was quite favorable. But from a class perspective, it would just be helpful to hear how the physicians are thinking about safety, particularly since DM patients already tend to have a higher underlying risk for cancer.

Yes. We've said a few times that when we first in-licensed brepocitinib, we didn't exactly know what the reception to JAK inhibitors was going to be following the addition of black box warnings. And our whole view is to choose indications where the safety profile of JAKs was going to be much less of a focus. I think dermatomyositis is a poster child for this in that while JAK inhibitors are at this point, extremely widely used in diseases with much less morbidity, many more alternative therapies in dermatomyositis, there's really no other options available. And I don't think physicians, therefore, are going to be particularly focused on this question.

Remember, these patients are often -- first of all, I think you sort of alluded to the profile in the trial. Dermatomyositis patients are inherently at risk of many of these concerns, malignancies, cardiometabolic events and treating them well makes them healthier and reduces those risks. And then on top of that, the therapies that they are currently on for dermatomyositis are things like high-dose steroids, which themselves add meaningfully, in fact, in many cases, much less severe disease.

As a reminder, we fully expect that our label is going to look like the labels for other JAK inhibitors that's going to have the black box warnings that's going to talk about experience with JAK inhibitors and other indications. And like I said, I think docs expect that. And I think are not going to be too concerned about it because these patients are, a, very sick; and b on other drugs with, in many cases, significantly worse safety concerns.

Our next questions will come from the line of Prakhar Agarwal from Cantor Fitzgerald.

Congrats on the continued execution. So maybe a couple of questions from my side as well. Firstly, on brepo and DM, could you remind us what percentage of DM patients are on off-label JAKs based on your latest primary or secondary research? And would you expect rapid switches from these patients who are on off-label JAKs to brepo? If not, why is that the case? And secondly, for brepo and NIU trial, what do you see as the biggest risk for Phase III, given the Phase II was really strong?

And is this geographic variation, which has been a key risk for this trial, which could drive some of the baseline variability -- this has been flagged as one of the risk factors by some of the KOL checks that we have done.

Great. Thank you. So I -- in terms of your first question on brepo and DM around who's on off-label JAKs and what does that look like? Look, I think, first of all, there's just like variability in physician practice and some physicians use more JAKs and some physicians use less JAKs. And that has more to do, I think, with the docs in many cases than with any specific subcategory of patients.

I think what we've said publicly is a low single-digit percentage or mid-single-digit percentage of dermatomyositis patients have experience with these things. Some of the docs who are involved who do use -- and some of that -- some docs don't use off-label drugs full stop. I think some of the docs who use off-label JAKs have said they expect to switch patients over, and I hope they do. And obviously, we'll be working to help them where that's appropriate, facilitate those switches.

I think it's just going to be down to the preference and practice of each individual doc. I think one of the things that our team is finding in talking to physicians is that different patients have -- different docs have different sort of ideals in mind for who their sort of first patients might be. And I think it just varies based on the patient experience, the physician. And so obviously, we'll be able to have much more of these conversations pending a potential approval.

But I think medically, we'll see a wide variety of different phenotypes. On what is the biggest risk in Phase III, it feels funny to call placebo risk in these trials and that's not quite exactly what I mean, but I think the variability in placebo response rates in immunology trials is significant. And if you're asking me what keeps me up at night, it's that we don't know exactly what placebo response rates will be in that study.

And that just makes it hard to know exactly what the trial is going to look like on outcome. Obviously, the Phase II data was quite compelling and the level of drug activity seems good. And so I'm pretty optimistic about the study, but there's certainly -- this is biotech, you can lose sleep over anything. Is geography a risk?

I think there may be geographic variation just as there is in many other indications and some of that's literally driven by geography and some of it's driven by physician practice and some of it's just noise. I don't know that it's a risk in the sense that it's like unanticipated or whatever. It's just a feature of running immunology studies. But overall, I think the team is doing a great job with the study, and I hope it's going to come out well.

Our next question comes from the line of Andy Chen of Wolfe Research.

I don't think this has been talked about yet. But for the brepo launch, can you maybe talk about a few launch analogs that you're assessing right now, either patient curve or market share curve? What are the historical products with the most resemblance to brepo and DM?

Well, thanks. It's a good question. The truth is there has never been a launch of a targeted therapy in dermatomyositis before. And so there is no good "analog" in the sense that you can point to lots of other launches of lots of other kinds and some have been faster and some have been slower and some have been slow and steady and some have been -- it's like different versions of different things.

And I think it's hard to say, and there have been successful products with all kinds of different launch phases. So I think the short answer is I don't have a specific analog for another drug that we're watching as like evidence of our own penetration. I think what we're really focused on here is the dermatomyositis opportunity itself, these docs, these patients and the benefit and the cost of being a pioneer in an indication is that you don't get to look at others, you have to try your own course. I don't have an analog to point to.

Our next question comes from Yatin Suneja from Guggenheim.

Just a quick one on difficult-to-treat RA. Could you maybe talk about the strategy there? Would you need one more study, 2 more studies? How are you thinking about that? What should be our expectations for the randomized withdrawal phase that we're going to get data on?

Yes. Thanks. Great question. Look, on study design, so we're going to come back later this year with a full update on that program, and that includes -- we don't yet have the randomized withdrawal period data yet, so I can't speak to what's in it or how it will or will not inform strategy from here. And I think at some level, the results of that study may inform whether it is usable or not as one of our pivotal studies, et cetera. I think we designed it to serve potentially as 1 of 2.

But obviously, it's got to hit for that to work. And as we said, when we announced the data, the quality of the response rates in the open-label period have set a somewhat higher bar for hitting a p-value on the randomized withdrawal section. So I think we've got to sort of see all that taken in aggregate, look at the patient level data, understand what's going on. And we are planning for an FDA conversation this fall that will inform both the exact design of that study as well as help us answer those questions.

I don't have a specific guidance to give on exactly what those studies are going to look like now because we don't know, but I'll say the team is working on it hard. The data was obviously exciting. It has gotten noticed. We've got a lot of enthusiastic reception, including from the doctor community on it. And we're excited to finalize those plans and bring them back to you later this year.

Our next question comes from Yaron Werber from TD Cowen.

Great. I have a couple of questions. The first one with mosli, once you release the data this year, would you release both the mono and the combo data at the same time? And then secondly, for CS, the trial design is super interesting. It makes obviously a lot of sense. The primary endpoint is CSAMI more than a 50% response -- can you maybe translate the Phase II data into the same context? Because I think the Phase II looked at CSAMI over 10 points and the change from baseline. So I'm just trying to get a sense of apples-to-apples kind of what to expect.

Great. So on mosli, I think the short answer to your question is we will not release the monotherapy data and the combo data at the same time because the combo study started much later and is enrolling now, whereas the monotherapy study, obviously will read out pretty soon in the second half.

So I think the answer is they won't come out at the same time, and we'll put out the combo data when we've got it. The combo study, remember, it's an open-label study. It was designed -- the truth is, I think a lot of the information that we could want will come out of the monotherapy study anyway, so the combo study like won't provide that much incremental. I think it was designed in part to give us really good safety experience in the combination as well as like a little bit of information about incremental efficacy just so that we could get a sense for like inclusion criteria and management in the Phase III.

But I'm not sure it's going to be like a super, super informative outcome. Yes. So that's what I'll say on mosli. I think data are going to come at separate times. On CS, I don't have to give right now the exact delta, but I'll say we saw meaningfully higher rates of greater than 50% CSAMI in the treatment arm than in the placebo.

So the delta was wide. And I think in the press release that may have gone out around the initiation of the CS study, it will have said well north of 50% of the patients in the treatment arm of the Phase II had a CSAMI response rate greater than 50%, I think it was 0 on placebo. So it should be a good bar to set for us in terms of the endpoint. I don't know that we're going to replicate exactly what we saw in the Phase II, but I think the point is it's well powered for probability success given what we saw in the Phase II.

Great. And if I can maybe just sneak in the Phase III NIU, do you have a sense, is the percent Humira experience going to be the same as the Phase II, given that the data looked pretty good overall. So it must have been pretty good in that segment, too.

I don't think we've said -- thank you. What's the percentage of patients in the Phase III have HUMIRA experience. I don't have that number on the top of my head, so I'll have to check into it. But I think the answer is there's no reason to expect it to be very different than what we've seen. There are a meaningful number of HUMIRA experienced patients in the Phase III, which matters in terms of ability to go into all of those patients. But I think the short answer to your question is I wouldn't expect it to be a major driver, and I wouldn't expect anything markedly different about the patient population from the Phase II.

Our next question comes from Thomas Smith from Leerink Partners.

On the 1402 difficult-to-treat RA program, I just wanted to clarify how you're approaching the disclosure in the second half of the year. Should we expect to see the Part 2 randomized withdrawal data prior to your meeting with FDA? Are you planning to share the data and the regulatory feedback and next steps simultaneously? And then on Graves, I just wanted to get your thoughts on the competitive landscape.

Obviously, you're the first advanced therapy there with really stellar Phase II data, and you'll have the first pivotal readout next year with 1402. But there are a number of different approaches targeting various segments of the Graves patient population. Just wondering if you could comment on the competitive landscape. And as you see some of the approaches some of these competitors are taking with respect to the patient population, wondering how you're thinking about potential future studies for 1402 and Graves.

Yes, perfect. Those are both really great questions. On the first one, I think what we said we put the data out still holds. I think my dream, our dream for the second half of this year is that we can come back with everything tied as nicely into a bow as possible, which is to say the period 2 data, the FDA conversation, maybe some further analysis of patient experience through both periods in the RA study, all shared at the same time.

Obviously, until we have the Part 2 data in hand, we can't sort of specifically know whether there's anything in there that requires earlier disclosure. But in general, I think the answer is our hope and expectation would be to give a fulsome update later this year on everything all at once for D2T RA. On Graves, look, I think, first of all, I cannot say enough times that discussion of competition in Graves' disease among therapeutic categories is just misplaced in the sense that you've got so many patients with unmet need that have had no -- the last time a novel therapy was developed in Graves disease was like the 1950s or 1960s.

There's so many patients who have need of novel therapy that it's not about outrunning the bear. It's not about beating some specific competitor. It's about changing doc behavior in an indication that badly needs new options. 1402 will have been studied in lots of patients. It's a safe and well-tolerated drug. Graves is going to have room for lots of mechanisms and lots of products.

Among the other mechanisms, some will have specific either safety liabilities or they'll mimic a thyroidectomy and they'll require treatment with Synthroid or there's just like lots of different approaches and those patients may be appropriate for -- those drugs may be appropriate for later-line patients or a different subset of the patient population. And over time, I'm sure that segmenting will occur.

But first of all, we're going to be first out in the marketplace there long before anybody else. And so we're going to get to have some influence over the treatment paradigms and also just get an option out to patients and physicians before some of those other choices are available. And second of all, I think it's mostly about building the market, not about any specific alternative and so on. So look, we're tremendously excited to be in our position in Graves to be first to be able to offer hopefully a new option here. The only other thing I will say is -- you learn a lot running these studies.

You learn a lot engaging with this physician community. And I do think there is nuance to the patient population. I think there is nuance to the prescriber behavior. I think there's a lot of heterogeneity in terms of how these patients are managed around the world and around the U.S. And I think one of the things that we're going to be able to do is to take advantage of those learnings in future studies, in these studies, in commercial prep. And I think that will be a big benefit to us in being in the first place here.

Our next question comes from Yasmeen Rahimi of Piper Sandler.

This is Shannon on for Yas Rahimi. Congrats on the great quarter. Maybe just one more from us about clarity with the readout in second half '26. Could you give us just maybe what you might be thinking about narrowing guidance if you expect to do that? And then sort of how you're thinking about the bar for success? And then timing post data, would you expect to file an sNDA and sort of what would be the cadence on that?

Thanks. Look, I think I doubt that we're going to provide more specific timing guidance at this point than we have. We announced, I think, when the study was fully enrolled. I think we're just going to read the study out when it's done and we have the data clean. The truth is NIU is another one of these diseases where there's a lot of unmet need. HUMIRA leaves a lot of room on the table.

And frankly, a lot of patients aren't even getting it. And so I think the truth is that the bar for success is successful studies that would support registration. And I think if we get that, we will have a big opportunity to help lots of patients who need it. So I don't think there's like a numerical bar. Obviously, better data is better. And the more we mirror our Phase II, the happier I'll be about that.

Our Phase II was really, really great data. But overall, I think as long as we have a successful clinical trial, a successful outcome, we're going to get what we need and we have a lot of patients we can reach. And I don't want to put Ben on the spot right now on exactly when that sNDA goes in, but we got the DM1 in nice and quickly. And I know the team is enthusiastic for indication. So if that study is positive, you got to believe that team is going to be working really quickly to get that sNDA in as fast as possible. Thank you.

Our next question comes from Douglas Tsao from H.C. Wainwright. The next question comes from Sam Slutsky from LifeSci Capital.

Two quick ones for me. I guess for the proof-of-concept readout in CLE, there's a few parts to that study. So just remind me what we'll be getting in that initial release this year. And then for the initial launch in dermatomyositis, remind me how many clinics you're targeting and the concentration of patients at those clinics?

Yes. On CLE, and again, I think we've said this before in other settings, as I was mentioning, I think CLE is an interesting indication. This is a small study. It's really a fact-finding proof-of-concept study. We've been watching the competitive landscape in CLE closely. There's a lot of other exciting therapies in development as well. Our early data from a couple of patients that we have dosed was encouraging.

We're really sort of overall just looking to understand what our treatment benefit looks like, how we could conceptually stack up in the future treatment landscape. And I think that will all be super informative to what we do from here and whether we go forward. I think the primary, as a reminder, is 12 weeks, 600 versus placebo. And then in period 2, all patients collapse 600 at 52 weeks. The thing that we'll be reporting first is that 12 weeks for 600 versus placebo. So that's what we'll see. And then obviously, a bunch of other data beyond just the specific primary endpoint.

On the DM launch, I'm not going to share today exactly what our sort of targeting strategy is. But as a reminder, there's about 200 myositis referral centers that treat approximately half of the U.S. patient population. And so obviously, those clinics are -- those docs, those centers are an important part of the overall picture, but there are other important physicians as well.

And I think Ben and the team have done a really great job overall engaging with the physician community. So I'm excited about what we've done there, excited about the sort of medical publication strategy. Obviously, New England Journal publication was a great outcome. So feeling good overall about that plan. And we're going to talk to as many docs and get out there as much as we can, pending potential approval. So thank you. Great questions.

We will now take the last question from Alex Thompson of Stifel.

Maybe two more on 1402. Going back to the questions around placebo responses, how are you thinking about managing placebo response in the Graves studies, particularly in the backdrop of ATD down titration and the potential for waxing and waning of disease in that context over longer periods of time? And then secondly, what's your current thinking on sort of where 1402 could fit within MG and CIDP as that landscape continues to evolve?

Yes. Thank you. Great questions. I appreciate it. Look, on Graves, I think the short answer to this question is if you set the bar high enough on the endpoints, these are just not patients who are spontaneously remitting. And so if you're looking at patients who are getting to proper thyroid hormone levels and off ATDs, I think the simple truth is placebo should be pretty manageable here without saying much more about exactly how the ATD titration works and so on and different of the studies being run by different companies are taking slightly different approaches there.

So I'm not going to say too much about exactly what we're up to. But overall, I think this is something that is likely manageable. And then I think as far as MG and CIDP are concerned, and I'll say first of all, it's pretty rare that you have a great drug where you can run a clinical trial and be just like very confident that the trial is going to work. FcRns have been studied many times in MG at this point.

1402 really should work in MG. The data that we generated in bato, although I know there was plenty of debate over the deeper is better question, we think showed a real treatment benefit, especially on things like MSE and sort of clinical remission that other FcRns in our view, have not been quite as compelling on. So I think we have an opportunity to deliver really great data, and I think that data will translate to adoption.

I'll say two other things. One is that the MG market has just shown itself to be extremely large. There's room for lots of different classes. There's room for multiple FcRns. There's a little bit of cycling going on. There's differences in dosing paradigm and so on. So I think like no matter what share we take, even a relatively modest share of a market that size is a big opportunity. I think argenx has done a really great job establishing that market, establishing themselves in that market, becoming the drug of choice that people reach to for a next-generation therapy.

I think they may very well remain the class leader there. And I think we will find lots of operating room around them with hopefully incremental meaningful benefit to patients beyond what they can deliver and just with another option with different route of administration and so on. So I think in MG, we'll be out there. I think we'll have a big opportunity just given the size of the overall market and then exactly what our share is and where we fit in will depend on the clinical data that we generate in the study.

CIDP, my one comment is, I think there is -- I think the -- the end on other indications. I think in CIDP, class leadership has been less concretely established at this point. It's a more recent launch. And I think there's probably a little bit more room for improvement on treatment paradigm.

And so I think what we showed with bato in the CIDP study was pretty encouraging, and I hope we're able to do something similar with 1402. And I think there will be a lot of enthusiasm if we can, for our role there. So I think we have an opportunity to be a major driver in that market. Overall, I think the level of success that argenx has had with things like MG and CIDP make me tremendously excited about Graves and about D2T RA and the other indications where we are first in that the first-mover advantage that argenx has been able to develop in their indications are significant, and I expect to build a similar moat for ourselves.

Look, I think ultimately, these docs are going to be sensitive to clinical data, focused on clinical data. And I think if our data is phenomenal, we'll be able to lead in every indication where we have that kind of data. Big docs are going to follow the quality of the evidence.

With that, I'd like to hand the call back to management for closing.

Great. Okay. Well, look, thank you, everybody, again. Thank you for the thoughtful questions. I appreciate how much work it is to come up with good questions in a quiet quarter. I promise there'll be lots coming in the coming weeks and months to give you more substrate in the future. But in the meantime, we appreciate it. We appreciate everyone for listening. As always, I'm super appreciative of everybody who works for Roivant and the Vants who are working just super hard on all of these programs to move them forward.

I've been very proud of our execution and pleased with the quality progress we made. And I want to thank the physicians and investigators and patients in our studies who trust us with their care. And I couldn't be more excited for the 12 months ahead. This is the last -- one way or another, this is the last boring quarter we're going to have for a while. So looking forward to the more exciting ones ahead and losing sleep over them until we get there. Thank you, everybody. Have a good day.

That does conclude today's conference call. Thank you for your participation. You may now disconnect your lines.

Great. Thank you guys for joining us, and good morning. I guess we're still morning at the Goldman Sachs Global Healthcare Conference. I was thrilled to be joined on stage today with the Chief Executive Officer for Roivant, Matthew Gline.

And so maybe first, Matt, I just wanted to ask you maybe a little bit of a higher level question, which is, the company was originally developed on the basis of this Vant model. You had distributed and uncorrelated development programs across subsidiaries. But how are you thinking now about kind of the core competencies of the Roivant business model across programs? And how has that model evolved over time?

Yes, thanks, and thanks for having us at the conference. It's great to be here. I can see that you think we're a worse and worse client by the fact that our room keeps getting smaller and smaller. It's all good. No, it's -- look, it's been a fun year.

I think there are things we've always been good at. And then there are things I think we've like more recently gotten better at, which I think is sort of worth the model. The truth of the Vant model, which for those of you who don't know, so we are a $20-ish billion biotech company principally focused on developing and soon to be commercializing a portfolio of late-stage drugs. We're really excited about. In that sense, we look like basically every other company. But if you sort of look beneath the surface, we're organized in this weird portfolio model as opposed to a single sort of R&D structure is what you're referring to the Vant model, where each sort of program lives within its own company which I think makes us a real devil to model.

The truth of the model -- the truth of why we're set up that way is because every time we deviate from that model, we get worse from an execution perspective. And so it's just having tested everything else that is how we run our programs best. And I don't think we have any sort of near-term plans to change that. It's just been what's working for us. In terms of what I think we're good at, I think we've always been good at asset selection, going out to the world and finding programs we're excited to work on.

I think we've generally been pretty good at like indication selection. I think we've gotten better and better at that over time as we've learned more and more actually how we want to do it. And then I think recently, we've built some real capabilities in actual -- just like clinical development and execution that have gotten. Again, it's something we've gotten much better at over the last 5 or 6 years that served us well. And those things, I think, together form the core of what Roivant is, is being able to like choose programs, choose smart places hope, smart places to develop those programs, and then hopefully run those programs while we're developing them. And I hope is over the next 12 to 18 months, we'll show that we can also now launch a product in one of those indications as well.

That is an excellent segue into my first question, which was on the commercialization front. Brepocitinib is your most advanced asset on that front, and you've got a PDUFA set now for September 2026. Maybe you could just refresh us on the highlights of the data in that indication and how you think that could translate into a label?

Sure. So brepocitinib -- again, I think everyone is familiar with this, but it's a dual inhibitor of JAK1 and TYK2. It's a drug we've had since about 2021, where we in-licensed it at a time where JAK inhibitors were at sort of meter of their own development. And our view was we know exactly what's going to happen in the class. It turns out the class has done just fine. But what we do know is there's an opportunity to develop these drugs in orphan inflammatory disease that nobody else is taking. And so that's how we built our franchise.

The first indication that we chose, the one that we're now sharing our initial PDUFA date for is dermatomyositis, which is an orphan inflammatory disease. It affects probably 70-ish thousand people in the U.S., of whom 40,000 show open claims database right now is actively treated terrible disease. There's really very little for these patients. Most of them are sort of living on high-dose steroids and immunosuppressants -- some of them go on IVIG, where the treatment paradigm is 5 days a month in an infusion center, 8 hours a day or on a variety of off-label things, most of which has failed studies in dermatomyositis. So that's kind of what the setup is.

Now our data Look, our data is great. In a field where very few people have succeeded. Great is a complicated bar, but we've shown really nice separation on the endpoint in dermatomyositis which is thing called total improvement score. It's one of these composite scores in immunology not only that, we got responses quickly, and we were able to maintain those responses against the backdrop of a pretty significant steroid taper. So these patients were both getting a lot better and also reducing their background steroid dose, which is important because these patients come in often on quite high doses of oral prednisone .

And as you think about what will kind of show up on the label or what you'd like to see show up on the label, what are you framing as kind of like a base or best case scenario on that front?

Yes. The truth is we haven't had labeling discussions with FDA yet. So I don't really know what's going to be on the label. I don't know that I'm that worried about how the label reads. We're really the first targeted therapy that hopefully will be approved in dermatomyositis. I think there's a lot of flexibility. I think the FDA is excited about the drug in the sense they're having good constructive conversations with us, but we'll see what they think in terms of labeling when we get there, that's really a discussion to have with them.

I think mostly what we need is -- look, I think ideally, we get a broad dermatomyositis label, lets us approach all of the patients. Even if there were some restrictions on that, I think it would be fine. It would be nice to get some of the data on label around steroid use in the trial. Certainly, one of the secondaries involved benefit well on low steroid doses, but also some of the clinical conduct stuff around steroids. It would be nice to have in there. I think docs are mostly at this point getting familiar with the data and the way the trial was run, the way that makes the label a little bit less important. It's pretty academic field of physicians. But regardless, I think that's all coming.

We will have, in all likelihood, JAK class labeling, there will be a black box on a label for the things that exist on JAK class black boxes mortality, et cetera, but nothing that we're particularly concerned about being unusual or mattering much in this patient population.

Okay. You just mentioned that it's a pretty academic kind of group of physician's. I guess, how is that -- how are you thinking about the size of the commercial sales force you need to build? And where are you in terms of hiring that out?

Yes. So we're making great progress. So there's -- about half of the U.S. patient population or a little more than half is treated at 200 referral centers, most of which are academic. It's things like Johns Hopkins and Mayo Rochester and stuff like that at Cleveland Clinic. And they -- about half the population is treated at those 200 centers. We will cover all of those centers and then into the tail of community derms and rooms. We will have a field force numbered in the 10s, exactly where in the 10s, we haven't said, and we've made tremendous progress at hiring those in general, a pretty experienced capable sort of medical personnel with a myositis KOL herself before leaving clinical practice to work with us. It's a field force that knows in many cases, this community. A lot of the people who are taking into the field from a medical perspective, worked on the clinical trial and have now moved over into the medical field force for this sort of launch. And so they already had the relationships from clinical trial sites coming in. I think it's been a great process for us.

And how are you thinking about pricing strategy, particularly given you have a sort of other indications coming behind DM?

Yes. Look, I think all of the indications that we were studying with brepo have in common that they are between, call it, 20,000 and 150,000 patient orphan inflammatory diseases without a lot of other options, they should all sustain or support pretty similar pricing bands. So I'm not -- I think whatever we do here is going to work within the envelope of the flexibility we have going forward, it's going to work just fine.

All we said publicly about price is that IVIG on the low end is a $200,000 a year-ish therapy. And if efgartigimod is successful in myositis, it will be a call it $500,000 or $600,000 net price therapy maybe. And so those are reasonable bookends. I think anywhere within that range is still on the table. To be honest, given the size of the patient population, if everyone just models the bottom, then everyone can be pleasantly surprised.

Under promised, over delivered. So in terms of the you have just mentioned -- sorry, I lost my train of thought. But in terms of the patient population, how are you thinking about like what the right peak penetration is? And how do you think about like the path to peak, given this is a rare disease? And what would you point to as analog in that market?

Yes. I don't -- the truth is with 40,000 patients at the price points I just articulated, you don't need very deep penetration to be a great foundational indication. Remember brepo is in development in three other indications, a lot of other places to go. We will certainly add indications beyond these four. So I don't think we need very high penetration [Audio Gap] incredibly enthusiastic [Audio Gap] 30%, to much higher than 30% of their patients. any of those numbers would be just fine from a penetration perspective.

I think I don't have analogs on launch trajectory. I think every rare disease is its own thing, and I think slow and steady is the right way to think about the launch in any new indication until you have a better sense of how the payer and physician dynamics are going to play out.

I'll say in terms of like market size, first of all, DM does feel like a market where the total patient number could grow once there's novel therapies in the market, it's somewhat -- despite the already relatively high number of diagnosed patients, it's somewhat difficult to diagnose and you get patients with lupus diagnosis or you get patients with other myositis. So I think there is an opportunity for the patient population to grow. And without intending to give any guidance on trajectory, I'll just say in terms of like analogs to the patient population. There are not a whole lot of things you would have said about the myasthenia gravis market in 2019 that you wouldn't say about DM today, right?

Before the introduction of efgartigimod, there were about 40,000 MG patients in claims data sets. About 20% of them were on sort of novel therapies, much of which was IVIG like a relatively similar composition. And obviously, that market over time has shown itself enthusiastic for a new option. I hope and expect we'll see something similar in DM.

Great. You mentioned there's three other indications in development. Maybe could you speak to what each of those are and how they match the indication selection strategy you've already outlined?

The other three indications are cutaneous sarcoidosis -- let me go in order. The first next indication is noninfectious uveitis, which is a noninfectious inflammation of the eye. We're focused on back of the eye inflammation that will read out a registrational data set in the second half of this year, which would then be a second approved indication if all that is successful. That is 70,000 to 180,000 patients, depending on how you count it. It's a very messy claims landscape or a very messy diagnostic landscape. So a little bit hard to know the precise number. But a severe disease third leading cause of blindness in the United States, low tolerance for optical inflammation. So if our drug works, and we have a really good Phase II study there. I think that will be an exciting market and pretty similar in size or maybe even a little bit bigger than DM.

The next indication is cutaneous sarcoidosis, where we are beginning a pivotal study this year. We had a Phase II data set readout earlier this year. That's a slightly smaller indication, maybe 20,000 to 40,000 patients, but still quite severe, no approved options, really sick patients with a really bad set of inflammatory and potentially permanently disfiguring skin symptoms. So that pivotal program will be ongoing shortly.

And then the most recently announced indication is Lichen Planopilaris, which is sort of form of lichen planus that involves scale scarring of the scalp and can involve permanent hair loss, very painful, high concurrent use of opioid pain medications. It's like really tough disease for the people that have it and basically nothing approved so far. We're, I think, the leading and potentially only mechanism or only program in late-stage development at this point. So an exciting addition and that's in sort of a continuous Phase II/III study that will start -- has started is enrolling nicely already.

Could you speak to the conviction you have in the Phase III NIU study that's coming based on the data you've presented to date and if there's any sort of like commercially relevant, secondary endpoints or bar that you think matter here?

I feel pretty good about the Phase III study. I lose sleep over it because it's biotech and you have to lose sleep over everything all the time. It's just the rule. But we had quite good Phase II data, which left quite a lot of margin. So the challenge of the Phase II data is a relatively small end study and didn't have a placebo. And placebo in all these conditions are variable and have been trending up over time.

HUMIRA in their Phase III study in NIU, the primary endpoint is something called time-to-treatment failure, which is what it sounds like it's how long these patients take to fail treatment. Placebo patients failed in 3 months and change in the HUMIRA study and the drug delivered just under 6 months of sort of total benefit, so 2 or 3 extra months over placebo. In our Phase II study, it was greater than 12 months. That was as far out as the study went -- and so I think a lot of cushion.

Frankly, I don't even think we have to be better than HUMIRA to be commercially successful, HUMIRA fails in a lot of patients. And the HUMIRA there's about 40,000 TNF patients with NIU now. So even in the half of those patients who eventually fail, that's a pretty big market, but I expect it would grow over time. But I think based on the Phase II data, there's certainly a possibility for better than HUMIRA across time treatment failure across treatment failure rate itself. Docs look a lot at indocyanine fluoroscopy and some of these other measures. So I think those things will matter commercially as well.

So recognizing this is somewhat early and you haven't provided guidance, how do you think about like the total sales opportunity for this product across the indications that you guys have outlined?

Across all of the indications. Look, I think it goes beyond those indications, too. Again, I think if it is inflammatory and has between [ 20,000 and 150,000 ] patients, it ought to be an eligible indication for us. I think over time, we could be in quite a large number of diseases. We have IP as it stands out to 2039.

If each indication we're in is a low blockbuster indication, you can just start adding things up and finding a $5 billion to $10 billion drug pretty easily. And so I think as we continue to add indications and continue to find success indication by indication, the opportunity here is very large.

All right. Let's switch gears to Immunovant program, IMVT-1402. And again, let's start at a high level. As you think about the FcRn cost and your development strategy there, like where do you see unmet need? And how did you map the development strategy to that?

Yes. It's interesting. So we had a couple of ideas in mind with our FcRn franchise. One was just that we thought we could build a best-in-class agent, right? We have a better administration than the other drugs. We have a simple subcu injection, low-volume, sort of normal similar to DUPIXENT and other very successful subcu medications. And One of the key things in FcRn is the way these drugs work is by suppressing levels of IgG and there for autoantibodies, our view has been consistently and our clinical data has shown consistently the deeper you suppress IgG, the better you treat these patients.

So the world sort of split into a few different categories. There are indications where others in the FcRn space, especially Argenx sort of the leader in the space, have carved a path forward, myasthenia gravis CIDP. I think in those indications, our goal is optimistically to deliver better clinical data and to take share that way to win share in route of administration. Those are really big markets, and the studies should work. And so it's like an opportunity to have sort of a base level of just even relatively modest penetration of those indications would matter.

Then there are two other categories of indications, The indications I am most excited about are places where we have carved out a path either where we were first or where we are now first by end of the way that we've developed the drug. This includes things like Graves' disease, which is probably what I would call our lead indication, which is a truly massive opportunity, hundreds of thousands of poorly controlled patients where I would say there had been -- despite the fact that there are hundreds of thousands of patients who have failed every therapeutic option available to them. No modern clinical development had been done in Graves' disease prior to the introduction of our studies. And it feels like we have just a great opportunity to provide a new option to a ton of patients.

We're now mutations of finest form of flattery. We're now the leader of a large number of companies doing different things in Graves' disease. And I think that will also help the market and help us in the long term. But now we've also added to that this sort of late-line multi-mechanism failure, D2T RA, rheumatoid arthritis, where these patients have failed multiple lines of therapy. We are not the first FcRn to be studied there, but I think we have found in our view, the right patient population is borne out with our clinical data for a real opportunity in FcRn. I think in both of those, we are now kind of the pole position FcRn.

And then there's a third category of indications like Sjogren's disease, where we're not first, but we're much closer to first than an MG and where we think between the time line gap being shorter and the quality of our agent, we have a chance of being sort of a class leader or at least close to the front of the pack.

Great. You just mentioned the RA data from period 1, which came in earlier than we expected, and it was definitely pretty impressive. Maybe you could walk through the highlights of that data with an emphasis on contextualizing those results in the context of this patient population.

Yes. So this is a study that we ran. It is bluntly a weird study in the design of it. We had watched J&J begin development of nipocalimab in RA. And the thesis behind an FcRn and RA is RA is principally inflammatory disease, and most of the approved drugs are anti-inflammatory drugs, but at least in some subset of RA patients, there is an autoantibody component that is it seems like some of these patients have elevated levels of certain autoantibodies that are causal.

That was the idea behind development of FcRns in general. And J&J showed something. They showed that if you suppress IgG, you can deliver at least modest benefit. And what they also showed is that benefit was significantly higher in patients who were positive on autoantibody titers than patients who weren't. And because it is orthogonal to the anti-inflammatory mechanisms, early evidence from the J&J data suggested that the benefit might be preserved even in patients that have failed anti-inflammatories.

So we designed a study on that basis that looked at truly refractory patients who have failed at least 2 of the 3 late-line classes, JAKs, TNFs and IL-6 is about 60% of the patients we ran up setting had failed both TNF and JAKs, which is that's like basically the sickest of the patients or at least the most refractory of the patients. And what we showed in those patients and contextually, this is in the open-label lead-in portion to a randomized withdrawal study, we showed ACR20 response rates very high in the 70s. We showed ACR50 response rates above 50%, and we showed ACR70 response rates in the mid-30s, which even in an open-label study, you just don't see a lot of placebo response in ACR70. And so it's clear that there is real activity there. We selected for a high baseline antibody -- autoantibody titer of ACPA, the specific autoantibody that we think is most likely to be causal in the disease.

I think in practice, in a multi-mechanism failure population, the data could be much worse than this and still see use because these patients don't have a lot of options. And this data is just pretty exciting data.

Okay. Broad brush strokes, knowing that you're still working on it. But what does the things I kind of have to look like here with respect to trial size? And how quickly can you start moving towards that?

That is mostly a question for FDA to answer. And I think there's a pretty wide range of possible answers. We would like to see, given that we are happy to accept restrictions in terms of being late line, et cetera. Smaller study, the typical RA study is 1,500 patients or 2,000 patients and FDA has historically been concerned that everyone in RA is trying to move into earlier treatment and so they want to make sure for the size of the RA population early line therapy that the drugs are sort of safe and efficacious.

Our view is, if you're looking at that later line market, you should be comfortable from a scientific perspective with smaller studies, hopefully hundreds of patients. And that's certainly the conversation we intend to have with FDA.

I think the most likely thing is that we would run a placebo-controlled study of a normal sort of head-to-head versus placebo design, but there's a lot of possibilities, including attempting to replicate the existing Phase IIb randomized withdrawal trial. That's just all a conversation for us to have with FDA. It's a conversation that we will have with FDA in the second half of this year and come back hopefully with everything kind of packaged in the bow in terms of what our plan is.

One thing I'll say is I think we will be among the first companies to have a discussion with FDA about late-line RA studies, but it's coming, right? There's CAR-T studies, there's NK-targeted studies. There's T cell engagers there's people doing work. And by dint FcRn being quite a safe mechanism, I think like we're in an interesting position where all of those other mechanisms that I mentioned are not going to run 1,500 patient studies. You couldn't possibly. And so I think we get to approach FDA as kind of the first in this category, with a willingness to do more than I suspect others in the sort of general indication space are going to be able to do, and we can use that flexibility to hopefully have a constructive discussion.

You mentioned it already but Graves' disease is definitely the lead indication for the development program for 1402. Maybe you can refresh us on the clinical data to date and how it answers for the unmet need you see in that patient population?

Yes. So there are -- so Graves' disease is a disease where you have [Audio Gap] a way that causes the thyroid to become overactive. There are [Audio Gap] most of them are effectively treatable with the course of an antithyroid drug of some kind. And in fact, many of them eventually, if they're treated on relatively low doses of methimazole can get under control and then get off antithyroid drugs. For about 350,000 of these patients, 330,000 of these patients, their journey just can't end there. That is either they can never get off methimazole or methimazole is insufficient to control their Graves' disease and they continue to relapse and have issues. And those patients they're sort of stuck at that point.

About 20,000 of them a year wind up having their thyroid removed, either surgically via radiation or radioactive ablation. And other than that, they just live sick. They live either on high-dose methimazole that's miserable or they live with symptoms of Graves' disease or both.

Our clinical data suggests that for that patient population, we can get a very high proportion of them controlled. In our Phase II study at our high dose, over 70% ultimately got controlled and somewhere between 30% and 50% depending on how you count it got off ATDs and controlled. And in fact, of the people who were controlled and off ATDs, not that, but we were able to drive remitted benefit where even after some period of time, they could get them off our drug and remain off ATDs and control. Remember, these are patients who weren't controllable on ATDs before. So this is a pretty remarkable outcome for the data. Again, paves the way for a real clinical benefit, let's call it, 350,000 patients who otherwise didn't have a path.

Great. And you have Phase III data next year. I guess, what do you need to see there for clinical and also commercial success? And could you talk about the design of the two Phase IIIs you have relative to that?

So we're running two studies. One is a relatively straightforward 6-month study. The other is a 12-month study, where the primary endpoint is at approximately 6 months, 26 weeks. And the study is designed to allow us to show a remitted benefit in the second period. So responders in the first period are then taken off drug on a randomized basis and looked at for remission. So that study will read out effectively after 52 weeks. The other study will read out after 26 weeks.

In terms of what we need clinically, again, first modern therapy ever in Graves' disease, a p-value we will do it. We think that will lead to an approvable drug, knock wood. That's really all we need, I think, also for commercial success, to be honest. Again, the size of that commercial success and how the competitive field plays out will depend on what we show. If we show anything that looks even remotely like our Phase II data, it will be transformative for tens of thousands or more of these patients. I think it's a huge commercial opportunity. But even with more modest data than that, I think we can have a big effect on the second of these patients.

You mentioned the size of the number of patients you have need here. I guess, how are you thinking strategically about pricing for this lead indication relative to a broader development path across indications?

We haven't given an answer to that question. But I think in general, our mind is on pricing comparably to in the same range as other FcRns and this is a refractory population that has no other therapeutic options. And so there are definitely large subsets of that population for which I think that price point could be sustained.

How do you think about the role of remission in the patient population? And what is your expectation in terms of how long patients -- like that the impact on duration of therapy?

Yes. Look, I think on the second question, based on what we know, there will be some patients who -- probably some patients who can't even get controlled on our drug. So they're better controlled on our drug, but not fully control in our drug. I suspect there are some patients who can get fully controlled in our drug potentially in perpetuity, but will need to be on our drug in perpetuity. And some of those patients will continue to require methimazole and our drug to be controlled and some will not require methimazole at all, but will require our drug to be controlled.

And then I think there are patients who will go into remission. I think that whole spectrum will exist. And so from a duration of therapy perspective, obviously, the patients who can get into remission will be shorter duration therapy, but there will be some patients for whom this is unfortunately just going to be a chronic condition, whatever.

Overly simplistically, I think 1402 suppresses IgG by about 80%. If you think the equivalent is roughly -- impact is roughly equivalent on TRAb, so if you're coming in at 5x the upper limit of normal antithyroid antibodies, then we will get you to within the normal range. If you're coming in at 20x the upper limit, we won't get you to it within the normal range. And I think that's sort of a rough heuristic for like how you might think this will evolve over time.

Okay. And how are you thinking about the emerging competitive clinical landscape? Obviously, there's other FcRns coming. There's also degraders that have entered the Graves' disease market? And how do you think about those agents?

Yes. As I said earlier, imitation is the finest form of flattery. I think this is a very much -- you don't have to outrun the bay indication. And what I mean by that is first of all, we're first, but even more importantly than that, it will be years before novel agents have saturated in Graves' disease. There are hundreds of thousands of patients treated in a variety of settings. I think the main question for everybody approaching Graves' disease is just like how do we build awareness of novel therapies? How do we get out there? How do we get patients out of the uneasy existing paradigm and into a space where there are actual treatment options.

Practically speaking -- so that's the first answer. I think a rising tide lift all boats. I think this field is about to be transformed, and I don't think it's about sort of jockeying for position versus other competitors and won't be for many, many, many years.

Of the stuff in development, I think general IgG approaches, other FcRn, the broad IgG degraders, et cetera, are going to look pretty similar conceptually to one another. And what we can do, they can do and probably vice versa. The degraders, I'd say like the one asterisk there is obviously like they haven't been tested in large-scale clinical trials at this point. So we'll learn more about how that actually plays out in Graves' disease and generally after we see that data, and there could be some issues. But mostly, if I had to guess, they'll all be sort of fine and pretty similar.

Then there are two other approaches that people are taking. One is not autoantibody driven at all. There's just people working on therapies that either directly affect the TSH receptor in one or another. There's either small molecules or antibodies. Those approaches may very well treat patients even sicker than the ones we can treat, but they will send patients from hyperthyroid to hypothyroid and so they'll either need to be carefully titrated or you'll need to concurrently dose synthetic thyroid hormone. So my guess is they will be reserved in many cases for the sicker patients who can't be treated with a more elegant autoantibody-driven mechanism.

And then there are a couple of companies now that are working on autoantibody specific degradation, meaning like TRAb degraders or whatever, I think that's a really interesting idea. It is the kind of mechanism that in the fullness of time could deliver even better data than we could, but it's just early to know how possible that's going to be. And how varied the antibodies are in Graves' disease is not something we have a very clear answer to scientifically yet.

I want to switch gears again to mosliciguat. And maybe you could just remind us the Phase II results that we should expect in the second half of this year and where you get conviction in, potentially a positive outcome?

Sure. So mosliciguat is our third late-stage drug. This is an inhaled sGC activator, which we're developing in pulmonary hypertension for lung disease patients. This is a mechanism that is a cousin to sGC stimulation, which was the basis of the drug called the mechanism of the drug called Adempas, that was a collaboration between Merck and Bayer that was quite commercially successful in Group 1 pulmonary hypertension.

We are developing drug in PH-ILD as an inhaled formulation. Our Phase IIb data comes later this year. PH-ILD is an indication that has risen in prominence and relevance with the commercial success of Tyvaso and with Liquidia now coming into that market as well and Insmed eventually, all with different formulations of treprostinil.

It's worth noting that Adempas, the drug I mentioned before, which was a systemic sGC stimulator failed in PH-ILD and had some pretty significant safety issues. Our expectations -- first of all, what do we know? We know that mostly in Group 1 pulmonary arterial hypertension patients, healthy volunteers is a very good local vasodilator that improves cardiac output and lung function, saw very deep reductions in PVR. We know that other systemic vasodilators in PH-ILD, the treprostinil, for example, don't work. We know that other locally administered inhaled vasodilator, treprostinil for example, do work. The end of those mechanisms is small, but that is where we get our conviction. Our drug is good as an inhaled as a dilator in Group 1 patients. The other drugs that have been good as inhaled vasodilator, Group 1 patients have worked in Group 3, and that other drugs have mechanisms that have failed systemically in Group 3 when administered from a local perspective, administered on an inhaled basis have worked.

That's basically what gives us comfort, there's a lot of uncertainty there, and we won't know if it works until it works. I'll say we have the benefit and the challenge that if the drug works in hindsight, everyone will say, obviously, it worked, it was just as you described, inhaled vasodilators work in Group 3 and local and systemic vasodilators don't. [Audio Gap] everyone will say, obviously, it failed. Adempas failed, why did you think an sGC [Audio Gap]. Either way, we will look like with obvious in hindsight. But in fact on an end basis, who knows.

There's the reason we play the game, right?

That's right.

Yes. So in terms of investing further behind this program, what do you need to see from the Phase IIb coming to kind of move into pivotal?

The reason, I guess, you're implying is fear or gambling addiction or something, I'm with the hope of helping patients. Sorry, what do we need to see here? Look, I think if you can improve cardiac output in these patients in a properly sized Phase III study, it will benefit them clinically on measures like 6-minute walk. This study is not powered for 6-minute walk. I don't expect to see a p-value on 6-minute walk. I don't even know what kind of delta we're going to be able to put up in 6 minute walk. It would be nice to see some kind of trend. But the truth is if we see significant benefits in PVR and cardiac output, the rest will follow. And so as long as we see that and a safe agent in Phase IIb, we will run a Phase III study. It would be nice to see something a 6-minute walk. We're not looking for p-value. I'm not expecting a p-value to say that 1 million times in public settings so that the [ goofy Bloomberg chats ] about this will at least have me to contend with. So mostly, I think we're looking for good safety, the kind of thing that would support a registrational program and a strong benefit on PVR.

Okay. Great. And how are you thinking about positioning of this agent relative to the other things that are in development? You kind of mentioned a bunch of them in PH-ILD?

PH-ILD -- pulmonary PH, Group 1 pulmonary hypertension is a polypharmacy market. Basically, every patient in the fullness of time ends up going on every mechanism or at least many, many patients do. Right now, only treprostinil approved in PH-ILD. I think PH-ILD will evolve the same way. These are really sick patients if multiple mechanisms are approved, patient will try all of them. So this isn't really an us versus them. This is -- if we present a good compelling option, people will use it.

I think given the PVR reductions we saw, given we are a once-daily puff of a DPI, which makes us nice from a form factor perspective relative to the treprostinil that are currently on the market or even coming. And given that treprostinil causes cough as it's an irritant. It causes cough as an on-target side effect, and we shouldn't. I think we have a chance of early first-line use in PH-ILD, but that's not really important. What's really important alongside these other agents.

Significant capital on your balance sheet and you have an upcoming launch. Can you walk us through the path to profitability from here?

Well, I think if our launches are successful, they will be high-margin launches and will become profitable. We have not given specific guidance on timing, but I think we've got plenty of cash to get there and shouldn't need any more money to do it. We've been buying back stock pretty consistently, and we'll continue to do so.

Okay. Speaking of that could you speak to the capital allocation priorities you have between returning cash to shareholders, business development and investing in the existing pipeline?

Yes. So last year, ending the middle of last year, we bought back about $1.5 billion of stock at about $10 a share, which has proven a good investment in hindsight. We are now doing further buybacks, we've sort of ramped them up after we settled with Moderna back in March and continue to buy back stock here.

That's sort of on the premise that we've articulated for years that if we can't make it with $4 billion, we probably can't make it with $6 billion. And so we feel like we've got some flexibility. And then the $4 billion, we've said consistently is more than enough to fund both all of our existing programs to profitability as well as new stuff. The new stuff is new indications as you even announced for FcRn and brepo and mostly new stuff is business development, which we're continue to be focused on. And one of these days, we'll get a deal done and even we'll be excited about it. I hope.

In terms of the business development, we have 1 minute left. So what kind of criteria are you guys using as? Have you consider these potential opportunities?

In general, we like what we like, which is late-stage programs with relatively open competitive fields with a clinical development strategy that we think is interesting and differentiated. So that's most of what we're looking for. It's most of what we brought in historically. And we continue to see lots of opportunity approximately meeting that description.

All right. I think that does it for us today. Thank you so much, Matt, for joining us. And thanks to everyone, who joined us here and online.

Thank you. Appreciate it. Thank you.

Welcome to the Jefferies Healthcare Conference. My name is Dennis Ding, Biotech Research Analyst here at Jefferies. I have the great pleasure of having Matt Gline here, CEO of Roivant. Welcome.

Thanks for having me. It's great to be here.

Before we kind of get into Q&A, and there is certainly lots to talk about, I'd love to hand it over to you to just kind of give an overview. I mean it's been incredibly -- I mean, Roivant is a $20 billion market cap company now.

It's true. It's a while -- look, it's been a really great 12 months for us. Look, I think many of you know a little bit about our story, but we are roughly out there trying to do the same thing everybody else is, which is to develop medicines that matter. And we've been very fortunate to have now 3 drugs in our late-stage pipeline and brepocitinib, IMVT-1402, our FcRn and mosliciguat, all of which appear to be drugs that matter.

We have our first sort of major commercial launch, certainly our first next commercial launch in brepocitinib in dermatomyositis, which should be by the end of September, assuming everything goes along as expected with FDA, a bunch more data coming later this year and all that building on top of positive data in DM, in cutaneous sarcoidosis, in D2T RA at Immunovant, all sort of in the recent history. So just a ton going on, a ton we're excited about and a really great year for us.

Yes. I mean I think going back several years, one of the big narratives around Roivant is that you guys are really good at identifying assets going outside of the cookie cutter, right, and finding unique opportunities that you guys could capitalize on under Roivant. Has that changed at all? Or are you guys more focused right now on developing mosliciguat or 1402 and launching DM? And has that focus shifted?

I'm smiling in part because I thought you were going to end that sentence. But you guys haven't found an asset in a few years. So now you must be known for something else. Well, look, I think the other side of the finding a good asset coin is how do you know it's good? Well, you know it's good when you've successfully developed it in indications, you've generated good clinical data, like that's actually when the -- when you know the answer, right? Every new program is a question being begged. And until you've run the study, you don't know what the outcome is.

And I think one of the things that I'm probably most proud of is I feel like at this point, I believe one of the things that we ought to be known for is creative aggressive clinical development. We found great indications. We've run good studies. We've generated a lot of data that has created a lot of value. And I think that's something we are excited to continue doing with each of our late-stage programs, all of which have opportunities for expansion. That said, look, we were built on DNA of thoughtful asset hunting and creative development. And I think we will continue to be who we've always been. We're excited about deals in the market, excited about things we're looking at. And despite appearances, we've been super active on the BD side and have been at the one yard line multiple times in the last couple of years. And when the right thing crosses the finish line, everyone will know about it.

Is there a sense of urgency in terms of finding the next big asset? Or are you fairly content and excited about what you have right now?

We're definitely excited about what we have now. I would say constitutionally, content isn't our thing. So we're never like fully content. I think one of the things that has served us well is restraint that is I think we've been pretty disciplined allocators of capital. We've been pretty disciplined about chasing the right opportunity. We haven't sort of built a portfolio for the sake of building a portfolio.

And by the way, that's in part because we, at various times in our history, did more of that, and I think we regretted it after. And so I think as a consequence, we've been pretty choosy, and I think we'll continue to be pretty choosy. One of the things that's great about where we're at now is, obviously, thinking about the 10- and 20-year future, we replenish our pipeline, we need to keep bringing things in, we need to keep building on what we've got. But I think for the immediate term, we don't need anything else to build a big company. We have all of the ingredients in-house. We just need to nail the execution. And so that's where a lot of our immediate focus is.

Yes. So maybe let's talk about DM because that's going to be approved soon and knock on wood. And I guess, how are you thinking about that launch? What sort of commercial readiness initiatives that you guys are doing ahead of the PDUFA?

Yes, perfect. So dermatomyositis for those who are not familiar with it, is an orphan inflammatory disease. There's about 40,000 treated patients and claims data sets now. There's probably 70,000 patients on an epidemiological basis. And it's one of these diseases where that population could easily grow as more people get diagnosed as more treatments are available. The data we generated last year was really great. This is the first effectively modern targeted therapy ever to succeed in the Phase III study in dermatomyositis. There's IVIG. But other than that, there's really been nothing out there.

And one of the things that I feel very privileged is the Priovant team has done a phenomenal job working closely with the doc community in DM. And I think the community of physicians and patients is excited about the fact that there's a new opportunity coming. So I think, look, one of the main things -- well, so anyway, so I think we've got all the right ingredients in front of us on the table. I think one of the great things about dermatomyositis is it rhymes in severity and scale in existing treatment landscape with a bunch of the other indications like myasthenia gravis, like TED, where commercial launches from biotech companies have been successful. And so I think the first thing we're doing is just making sure that we've learned all of those lessons as well as we possibly can.

We studied those launches, Ben and the Priovant team have studied those launches. And certain patterns emerge on pricing, on rebating strategy, but also just on like how you structure the organization that you have medicalized field forces that talk to these docs where they are, that build good relationships with them on a scientific basis, that you focus on the broad community of docs, including community docs, but especially on the referral centers where a lot of these patients are treated and that you build these patient support organizations that are designed to help manage the coverage and payer process.

And I think we've been both like trying to learn as much as we can from other institutions that have done this successfully and in many cases, hiring people from those institutions who have been successful because I think at this point, I hope someday we are thought of as commercial innovators. But before we get that opportunity, I'd like to be thought of as people who successfully replicated the commercial model that's working for other companies now, and that's a lot of what we're after.

What are some of the learnings on price? Because historically, you've given a fairly broad range in terms of what to sort of expect for this sort of prevalent population in DM?

One of my learnings on every sort of number is not to provide guidance because it doesn't benefit anybody else who's ever done it. So I don't have a new narrow or benchmark to give on price. Look, I think the truth is what we've said about price before without giving any guidance around price is that IVIG is about $200,000 in dermatomyositis and if efgartigimod is successful in myositis, it will be a $500,000, $600,000 plus drug. And that sets some bookends, and there's a lot of good territory between those bookends in which we can develop a commercial strategy.

I think access is important. I think talking about learning from other launches, I think the work that Argenx has done in moving into earlier and earlier line therapy in myasthenia gravis has been powerful. And I think it's not an accident that Tim made a good decision that they made a good decision to price lower in that indication. So I think -- but then also, they've been very successful in indications like CIDP at higher price points. So I think there are good arguments for living anywhere in that band, and I think we will make a choice on that basis. What I've been saying lately, which I think works well for us is everyone should assume we're going to be at the low end of that range, and we're pleasantly surprised if we price higher because there's just plenty of patients here such that it's really just about the commercial model working the way we want it to.

How do you think about the phases of uptake in year 1, year 3, year 10 in terms of, I guess, the low-hanging fruit perhaps would be off-label JAKs and you switch those patients over. Do you agree with that? Or just any kind of color there?

I'll say, first of all, I think the truth is in any indication where nothing novel has launched for a good time -- for a good long time, there's like very wide error bars around the early launch. We've been saying slow and steady. I believe slow and steady is the right way to think about this. It's just like it's just really hard to know who the early patients will be, how the payer process will work, and it could take a long time to dial all that in. And so in some weird perverse way, it's easier to have confidence around the peak number and the size of that opportunity than it is to have confidence around year 1 or year 2 or year 3 or whatever.

And I think there's pretty wide error bars around the early launch. And I don't think it -- in the long term, I think it may not matter that much in the sense that if we launch slow and enroll to a big opportunity, I think that could be the best outcome. I don't know that I agree that like off-label JAK use is the lowest hanging fruit. I think the truth is the DM population is littered with poorly controlled patients. And some of them are poorly controlled patients because they're on off-label therapies like an existing JAK inhibitor or rituximab or something like that, that doesn't -- or Remicade, that doesn't work very well. Some of them are poorly controlled in the sense that they're on IVIG and maybe their disease is okay, but they're spending 5 days a month, 8 hours a day in an infusion clinic and want to try something different.

And then that -- together, all of the sort of "Advanced therapies," IVIG and off-label stuff accounts for about 25% of the treated patients. And 75% of these patients are just on high-dose steroids and immunosuppressants. And in many cases, like very high-dose steroids, like more than 6 months a year at over 10 or even over 20 milligrams of prednisone. I don't know if you've been on oral prednisone before. Being on 20 milligrams of oral prednisone is miserable for a weekend. Imagine doing it for 6 months. It's terrible. And so those patients are like -- and it's probably not doing a particularly good job of controlling DM in the long run. So these patients are like sick, miserable, unhappy and are ideal candidates even though they're not in any of the treated population. So I think it's going to come down to each physician is going to approach the early patients differently, and we're going to meet everybody where they are and just like find the right patients to get started with and build from there.

Yes. I think you guys are somewhat steroid sparing as well, right?

That's right. Look, we -- in what I best describe as an accident of history, we ran very intentionally in our Phase III study, a steroid taper, which was designed as with most steroid tapers to ensure or protect separation from placebo in the study by making sure that the placebo patients were not sort of just increasing steroid dose over time because they were getting worse as the disease progressed.

And what happened in practice is these patients were sick enough, it was like relatively difficult to guarantee a full taper. And we wound up with a pretty significant difference between the steroid dose on drug versus steroid dose off drug, which wasn't the goal. But it turns out I wouldn't change a thing in hindsight because I think one of the things that docs are most excited about is that we've demonstrated that we can get patients with a clinical benefit also on significantly reduced steroid burden, and that's something that these patients think a lot about.

Okay. One of your competitors, Argenx is going to have Phase III data in the third quarter also in DM. So I'm curious how you're thinking about the market, assuming their data is positive. Now we obviously have to see if -- what the magnitude of this is in the clinical trial. But do you have any thoughts on that?

Yes. Look, I -- the first thing I'll say is efgart is a great drug. Argenx is a great company. They've done a phenomenal job. I think, in general, the lesson from Argenx' experience in diseases like MG is that these are markets where more new drugs actually benefit everybody. I think efgart has done better in MG because of the complement inhibitors. I think we will do better in DM if efgart is approved because there will be more awareness of novel therapies, more docs trying to figure out which drug to use for their patients.

And frankly, we get to play in DM, the role that Argenx got to play in MG that is we are coming in as the [indiscernible] drug, the docs are excited about as other things enter the market, they will find new patients, they will get new docs excited, and I think that will continue to accrue to our benefit. So I genuinely believe Argenx' success will be our success. That's thing one. Thing two is, look, I think biologically, there's reason to believe that IMNM is probably a better myositis for an FcRn and DM is a better myositis for an anti-inflammatory like brepocitinib. And so I think like my hope and to some degree, expectation is that we have a better agent for this patient population. I think indeed, Argenx' body language around their trial suggests that their heads in a similar place.

And so I think that's all potentially helpful. And I think if you look at the Argenx data, as of -- I think they cover some more today that I can talk more about a second, but even as of the earlier data, we had a significantly faster path to a moderate TIS response, and we saw at least a comparable TIS benefit while they didn't have a steroid taper in their induction study. And so I think all of those suggest to me that we have a good setup here from a data perspective. That's -- and I think this is both a liability and a blessing.

Argenx' study is very different than ours. It's not a DM study. It's a study across 3 different myositis subtypes, IM, DM -- sorry, IMNM, DM and polymyositis. And in each myositis subtype, it's about 25 patients on drug and 25 placebo patients. So first of all, DM treating physicians are obviously aware of that and are, I think, deeply appreciative that we ran a proper sized study with lots of patients, specifically in DM. And second of all, look, it does mean they could just get lucky, right? Like if 25 patients, TIS is a noisy endpoint, we're going to have to contend with whatever that study shows. Again, I'm not that worried about it long run, but I think that's sort of the rub.

Sure. Okay. Even outside of DM, you guys have NIU data coming up. I guess like a big part of the brepocitinib thesis is way bigger than just DM, right?

I totally agree.

I call it RINVOQ for rare disease...

Yes, I think...

Multiple indications.

I appreciate that nomenclature. Anything to draft off RINVOQ.

So for NIU, I guess, characterize how that -- the size of that opportunity relative to DM.

Yes, perfect. And by the way, I think in some ways, NIU is among the more underappreciated of our commercial opportunities in that it is devilishly hard to isolate in claims data sets. So it's like hard to isolate -- even for us, and we're out there in the field with these docs all the time in the trial, like hard to isolate the size of the patient population. But I think it could be, frankly -- so first of all, NIU overall non-infectious uveitis and eye inflammatory disease. These are patients who have eye inflammation and it's the third leading cause of blindness in the U.S.

So high morbidity, docs want to treat it aggressively because it can lead to blindness. Of the 400,000 NIU patients in the U.S., the vast -- significant majority of them have mostly front of eye inflammation and get treated with steroid eye drops, and those are not our patients. We are treating patients with back of the eye or whole eye inflammation. And I think like there are somewhere between 70,000 and call it, 150,000, 160,000 those patients, which is wide error bars because there's a lot of diagnostic slop. But I think it just gets to the -- the answer is probably there are more such patients than dermatomyositis patients. HUMIRA is approved in NIU. It doesn't work spectacularly well and certainly left some room in our Phase II data for what it's worth was obviously meaningfully different than what HUMIRA had seen in NIU. But if we're successful, I think there's a huge opportunity in NIU to be a big market.

Yes. How would you approach pricing, I guess, for DM? And like how much do you consider some of these pipeline opportunities?

Yes. I think we are absolutely thinking about a collection of indications that can support the same commercial model, the same price point, the same orphan setup, the same patient support structure. And I think we certainly have some levers to pull. We could decide to do different prices for different doses. DM is a 30-milligram dose, NIU is probably 45. But overall, I think the answer is like these are comparably morbid, comparably sized populations. Like I think these are both really bad disease -- they're all really bad diseases.

And I think they will all support the kind of price point to commercial model that we have in mind. And the one thing I'll say is like, look, I think it's very tempting you're at this stage in the game to think of brepo as a dermatomyositis drug. To your point, that's not how I think of it at all. Like I think dermatomyositis is a base layer on which to build a really big setup across a whole bunch of different indications. And while DM is certainly large and you can underwrite, in my view, like a very big peak sales market opportunity for it. By the time it's close to peak, there will be -- we've got 3 other indications in active late-stage development and more to come. So we have a lot more work to do to build this into what it could be.

For NIU, remind me what do you view as like a clinically meaningful improvement on treatment failure?

Well, HUMIRA, as I recall, in visual had like 3.5 or 4 months placebo time to treatment failure, around 6 months of drug time to treatment failure. And in our Phase II, we were greater than 12, meaning the median patient had not failed by the end of 52 weeks when we finished the study or 48 weeks or whatever it was. So look, I think the answer is HUMIRA is viewed as not a perfect agent in NIU, but clinically meaningful. And so I think like certainly anything in the same ballpark as HUMIRA is going to matter to patients. And the more better than that, that we can do, the more people will be excited about the data. But there's room for a lot of degradation from the Phase II.

Your Phase III, does it enroll pre or post HUMIRA or it does not specify?

It doesn't specify. We have both.

Okay. Okay. Well, that's a readout, the Phase III readout in the second half.

Yes. Absolutely.

Very interesting. It could be, in our views, $2 billion to $3 billion peak sales depending on price. I mean, let's see on price. But another catalyst that's super interesting to us is PH-ILD, right? This was a small asset that you got from Bayer several years ago, very under the radar, but here we are Phase II data coming up in the second half. So maybe talk about the opportunity in PH-ILD and what gave you the conviction to go away from PAH, which is where the Phase Ib data or trial was run in and into PH-ILD?

What gives us conviction is a question that investors ask often, and I think it presumes that I sleep better than I do. Look, so this is a drug we in-licensed it from Bayer. It is an sGC activator. That's a related mechanism to sGC stimulation, which is a mechanism of a systemic drug called Adempas that was commercially quite successful in PAH and failed a clinical trial in PH-ILD in our indication. What we think we know from the field, and this is principally paths paved by prostacyclins by Tyvaso and other treprostinils is systemic vasodilation works in PAH, does not particularly work in PH-ILD. And the ostensible reason is you vasodilate a lung with diseased tissue and as much benefit as you get from vasodilating the healthy tissue and improving lung function on healthy tissue, you give up a lot of that benefit in the disease tissue.

And so you get this like VQ mismatch basically. The solution for PH-ILD in prostacyclins and treprostinil world has been inhaled prostacyclin. Tyvaso is approved and doing very well in PH-ILD. YUTREPIA is on a path to doing well in PH-ILD is another formulation of treprostinil. There's clearly like a lot of enthusiasm for that idea. The thing that we've done is neither more simple nor more complicated than simply try to replicate that with sGCs. That is we know that systemic treprostinil does not particularly work in PH-ILD.

We know that systemic sGC modulators did not work in PH-ILD, but we have an elegant formulation of an inhaled sGC activator. And in Group 1 patients, it demonstrated extraordinary some of the best PVR reductions ever seen. And so we believe strongly that it is an effective locally administered vasodilator, inhaled vasodilator of this mechanism. And the hope is that we replicate this idea that taking an inhaled potent vasodilator into PH-ILD can yield benefit for these patients. That's the bet. That's the risk, that's the setup.

Okay. So then on PVR in PH-ILD, right? I think PAH is fairly standard to assume that anything north of 20% will -- is clinically meaningful, and there's a good shot that 6-minute walk will be positive. But what about PH-ILD?

Look, again, the end of studies run in PH-ILD is small. So I don't have like some giant body of evidence to point to. I think we do a lot of translational thinking from PAH. And I think our general view is north of 20% on PVR is likely to -- the math or the mechanism of translation from cardiac output or PVR to 6-minute walk is pretty similar in PH-ILD. There's probably some differences related to the other causes of morbidity associated with PH-ILD.

But like in general, I'd say, if we see north of 20% on PVR, I think we're going to be pretty happy with that. And I think ideally, we would see some directional signal on 6-minute walk. We're not powered for 6-minute walk. I don't expect a p-value on 6-minute walk. And to be honest, if we see a high enough PVR, we could see literally nothing on 6-minute walk and still go ahead with the Phase III because I think you'd have to -- if we saw good safety and a deep PVR reduction, you would have to really contort our current understanding of these patients to not think we could generate a 6-minute walk benefit in a properly sized study.

When you say it's not powered for 6-minute walk and there's no p-value, are you saying that's not even being tested or that is just vastly underpowered?

We will mechanically run stats on 6-minute walk, but I expect to not get a p-value on 6-minute walk.

Okay. Okay. When you think about the mechanism of action, right, and you guys have -- you guys and Bayer have done a lot of studies across Phase I and studies, right, in healthy volunteers.

170 subjects. Yes.

It seems like from what's disclosed, I believe the MOA acts specifically to improve PAP, mean PAP. But then for PVR, there's obviously that cardiac output component to it, right? So in your Phase Ib, it was interesting to me that I believe only the 4-milligram dose had an improvement -- or sorry, improvement in cardiac output, but not the others.

We ran a bunch of Phase I studies. And in general, I'd say the picture was consistent, and we measure different things in different studies. Like, for example, we see elevated cGMP production for 48 hours after a single dose of drug at different dose levels. So I'd say, in general, I'm pretty confident looking at the totality of the evidence that this drug will deliver a cardiac output benefit.

And I think that's just what we've consistently observed. That said -- so the way the Phase IIb works is a dose titration paradigm where you start at a low dose and you get up to 4 milligrams pretty quickly. And one of the things that gives me comfort, especially from a safety perspective or tolerability perspective is that 95% of these patients are getting to 4 milligrams and staying there. And that's obviously a sign that people are, a, tolerating the high dose; and b, not having sort of massive safety issues.

Yes, this is a once-daily inhaler.

Once daily, puff of -- once daily, one puff of a DPI.

That's right. Okay. And one of the key reasons that's able to do that is that there's a lot of deposition in the lungs.

That's right. We really -- we do well at getting into lung and we do well at staying in the lung.

Yes. Okay. Perfect. So you guys are -- the Phase II is for PH-ILD, but I'm also curious like how you're thinking about opportunities beyond PH-ILD.

Look, PH-ILD is obviously a great market, and we're excited to be there, and we're going to learn a lot from this study, including one of the things that we're going to measure in this study is things like FVC and other measures of like underlying lung function. Obviously, one of the things we've watched closely is the TETON data around IPF. Certainly, once we've seen this data, I think IPF is a natural place for us to be thinking about. But also we think about PH-COPD, we think about PAH, we think about other indications of impaired lung function or other subgroups of pulmonary hypertension. So I think there's a lot of places to go. Obviously, first and foremost, this is a don't screw it up opportunity in PH-ILD, but it's the kind of mechanism that should work more broadly as well.

Yes. I mean, depending on the Phase II data, like how would you approach the development of mostly across many of these indications?

Well, I think we would run more studies if the -- if the Phase II data was suggested...

Like one at a time and look at PH-ILD and see how that goes? Or would you take a [indiscernible] can go broad.

Look, it's not -- we haven't like perfectly clearly articulated the regulatory path that we intend to follow from here to approval in PH-ILD. But I think insofar as that path cuts through another Phase III study that we're probably going to start relatively soon in PH-ILD, I think we would start other indications in parallel with that study. We're not going to -- at this point, after we generate this Phase II data, are going to wait to go broader.

Maybe briefly, how big do you think is PH-COPD? I'm just curious because Merck has a 5475 product that's availed, that's supposed to read out this year. So if that data were positive, like...

Yes, that would be informative. Look, the scary thing about PH-COPD for clinical development of inhaled therapy is the -- is like the lung tissue is a little bit more complicated to work with. And so I think that's on the list of like things that would give us some consideration there. But obviously, if Merck succeeded there, that would be super informative. That Merck drug, if I'm remembering the study correctly, is a once-daily study of a drug with less deposition in the lung, which is one of the issues they've had with that drug in PAH.

So even if that study doesn't work there, if we see evidence of good safety and the possibility of really efficacy, I think that could be informative as well. I think PH-COPD is a big market. Look, one facile explanation for why there are a lot of theories as to why treprostinil works in IPF. I think there's like a series of religious devotees who think it has to do with this like preclinical fibrotic -- anti-fibrotic effect of treprostinil.

I think there are people who are just of the opinion that you get vascular remodeling when you improve lung function in pulmonary hypertension patients with lung disease. And then I think there's like another possibility, which is just a lot of IPF patients have undiagnosed pulmonary hypertension. And when you get out there and you treat their pulmonary hypertension, they get better. And so I think like across a variety of different explanations, I think a lot of those explanations potentially hang true for us.

Yes. Okay. That is very helpful. So in the last few minutes, we'd love to talk a little bit about Immunovant.

Sure.

Just remind us, you guys did have some RA data recently. And it seems like still kind of TBD and we'll get some more updates in the second half, but just remind us of where you are?

Now I've been caution not to answer questions on Immunovant because you're hold rated on it. But I'll do it anyway just because we're here. Look, so the D2T RA data was -- it honestly better data than we expected in D2T RA, and it showed meaningful -- whatever, it's an open-label run-in to a randomized withdrawal study. And so it's like hard to interpret, especially in this patient population. But we have pretty high ACR70s and ACR50s, which are not the sorts of things that happen that often spontaneously. And so it feels like there's a real effect here, and we're excited about it. As we said when we announced the data, so this is a randomized withdrawal study, there's an open-label run-in followed by a randomized withdrawal period.

And the truth is because the data was as good as it was, a lot of these patients had ACR50 and ACR70 responses, the primary endpoint of period 2 of the study is loss of ACR20. If you are an ACR70 responder, are you definitely going to lose an ACR20 in 12 weeks? I'm not sure. You've got some extended pharmacodynamic benefit from the drug and then you're trying to get a lot worse fast on placebo. So I don't know exactly what our likelihood of "Hitting in period 2 is." So what we said is we're going to look at period 2, obviously, but equally informative is like a lot of patient level work we want to do on inflammatory markers, dimensioning autoantibodies and trying to understand like which patients are responding and why and looking to make sure there's like coherent narratives that support the drug activity. So we want to do that analysis.

And then bluntly, there's like a pretty important regulatory question here in that historically, basically every approved RA therapy has gone down the broad indication, like large, in some cases, thousands of patients, large study. And so we're trying to understand what a regulatory path looks like for an agent willing to restrict itself to late multi-mechanism failure D2T patients who have like, for example, failed like a JAK and a TNF, where the needs are different. And I think what that pathway looks like affects a little bit whether and how we run the second Phase II.

One thing that benefits us is there's a whole class of -- between the CAR-Ts and the T-cell engagers, there's a bunch of stuff coming in late line RA where they obviously won't run 2,000 patient CAR-T studies, and so there's going to be answers to these questions but we're kind of out in front of that. Anyway, what I'm hoping is that by the end of this year, we can package period 2 with the patient level analysis I just described and with that regulatory feedback and present it as a coherent whole with a plan forward, and that's what the next update will really look like.

Got it. Perfect. Well, I will just limit it to one Immunovant question. But thank you so much, Matt, for being here. It's great to hang out with you. Have a great conference.

Thank you. Thanks, everybody.

All right. Welcome, and good morning. Thank you all for joining us. My name is Will Pickering. I cover U.S. biotech at Bernstein. I have the privilege of sharing the stage with Matt Gline, CEO of Roivant. The company has had a remarkable run over the past year, certainly with brepo as the standout, but far from the only value driver. We'll dig into that and the other assets over the next 50 minutes conference, I would also like to spend some time on bigger picture questions, the Roivant business model and Matt, your view as an asset hunter about the overall health of the biotech ecosystem today.

For those in the audience, please submit your questions through the Pigeonhole app so we can make this as relevant for you as possible.

So with that as a preamble, Matt, how would you describe the evolution of Roivant over the past a few years into the company than it is today?

Yes, thanks, and thanks for having me. It's nice to be here. I appreciate the invitation. Thanks for all the work you guys have done on us. It's been a fun early run here. So look, it's always funny when I'm at a more generous event or just like ask to talk about Roivant because I feel like there's so much complexity in our history in that we got our start as sort of a -- whatever these words are all overused, sort of a Maverick outsider biotech company doing things our own way, walking our own path. We're built in kind of a funny way that I'm sure we'll talk a little bit about with this Vant model.

And I think we do bring a pretty different philosophical lens to the industry and that we are a mixture of experienced industry insider drug developers, but also a lot of outsiders like myself. I was a physicist, I was an investment banker. A lot of my leadership team had been public markets biotech investors before joining Roivant or private markets biotech investors before joining Roivant. And so you take all that history and you hold it and it sort of creates opinions, attitudes, a feeling of not fitting in as it were.

And then the moment that we're at in the business actually is, in some ways, it's the most normal moment in biotech. It's the moment where finally, we've invested for years. We've wandered through the desert. We've reached the other side. We have a portfolio of programs that I think can convert us into, for lack of a better phrase, a real business, right? We're at this precipice of launching one and then multiple drugs and one and then multiple indications that I think stand us a real chance of building one of the next large-cap biopharma companies. And that's just a tremendously exciting moment to be in.

That's great. And BD has been a huge part of your approach historically, but the current pipeline is very full. So I think 10 indications across brepo, mostly, Immunovant, if I'm counting roughly right.

I trust that you have.

How much of a focus is further BD for the company today?

Yes. So I'll say for those who don't know the company, look, I think if you're thinking about biotech from the outside, I think people take a relatively reductionist view on what sort of "science" is and I've used like mental image of science as like a thing that happens in the lab at the bench for the white lab code on. And in fact, there's like many different kinds of science that happen within biotech. And bluntly, I make that maybe defensive sounding case because we've never been that good at the white lab code version of the activity.

But we have been, I think, increasingly, and I'm super proud of this, very good at the kind of science that takes place in the clinic in doctors' offices around the world, in clinical trial design and indication selection and understanding patients and diseases and figuring out the right way to develop a drug ideally in a disease where the patients have high unmet need and where not a lot of novel science has been done. And if you're good at that latter kind of science, but don't fancy yourself that good at the former kind of science, you're sort of stuck, right? Because it turns out every drug must be discovered in some kind of lab before it is studied in the clinic. And so we have, as Will has alluded to, built basically our entire pipeline via collaboration, via BD, via acquiring programs.

And in fact, another thing that I'm proud of that I think we're pretty good at in addition to sort of asset hunting, spotting things in the world that are attractive, is most of our partnerships have come from big pharma companies. And I think we have built a pretty good understanding of and some very good relationships with some of the largest pharma companies in the world. And they all have a problem, which is that they do all kinds of science. And sometimes the first kind of science that happens in the lab and the second kind of science that happens in the clinic and third kind of science that happens when you're trying to build a commercial business don't all align in a nice train that makes you want to start on the same projects that you want to end on.

And so big pharma companies often have really great things that fall by the wayside, not because they're not great, but because they don't fit with the strategic commitments the companies have made. And I think what we've built a lot of our portfolio around is bringing in those programs. It is profoundly a part of our DNA to be on the hunt. And frankly, biopharma is a treading water industry. It's like whatever the -- I'm not sure it's actually scientifically accurate, but they say that if shark stop swimming, they die. If pharma companies stop replenishing their pipeline, they die because our drugs are all wasting assets. From the minute you invent a drug, it has a fixed life before the patent runs out.

And so we are always on the hunt. And I think that still serves us well in developing the drugs we have now. But absolutely, we continue to look for programs, and we'll continue to bring more in. That said, I completely agree with the comment that you made. Our pipeline is rich and exciting, and there's plenty to do just within the context of the late-stage clinical programs that we're bringing to market.

And as you look at the biotech landscape today, both from an innovation perspective, but also looking at valuation, how attractive is that for an asset hunter?

I mean, very -- look, I think the last really 25 years in biotech have been pretty remarkable in that we went from an industry in the early 2000s where 99.5% of drugs were small molecule pills of the same general sort that has been around a long time. And the big story in the previous 25 years have been the invention of modern synthetic medicinal chemistry that lets us do some version of designing those drugs intentionally to now we have mRNA vaccines and monoclonal antibodies are used left, right and center, and people are injecting themselves with unapproved peptides manufactured by small Chinese CDMOs. Like the world is crazy in terms of like the kinds of things that people are working on.

And while our understanding of human biology remains what I'll call nascent across the industry, it's gotten better. And I think that has made for an explosion of ideas. And look, I think anyone living in the world knows that we are still far behind in terms of our fight versus disease illness and aging. And so with the explosion of ideas and a lot of territory left to cover, it's a good time to be an asset hunter. There's a lot out there that could be valuable.

And then there's all kinds of more localized shifts, right? There's geopolitical things going on. There's the incredible pace and quality of antibody discovery, especially in China. There's the pace with which you can run early clinical trials in places like Australia and New Zealand and China. And there's a series of global and U.S. political factors buffeting big pharma that creates a need for shift in their portfolios. And I think all of that also benefits us.

Excellent. Well, why don't we dig into parts of the pipeline, I'll start with brepo. You're approaching your first commercial launch in dermatomyositis. Could you start by framing the opportunity and then talk through the key priorities for your commercial team to drive that launch?

Yes, perfect. I get ever so slightly defensive, although maybe it's not serving me well when people call it our first commercial launch because, in fact, we have had now 6 or 7 FDA approvals come effectively through our business. Many of them have been commercialized externally, a number of them through Sumitomo, a company we partnered with a few years ago on the first generation of our pipeline. And then we did, in fact, launch a drug called VTAMA in psoriasis. I'm not sure it benefits me to bring it up in a setting like this because it didn't go spectacularly well, but it went fine.

And then we sold it to Organon a couple of years after we launched it because it just didn't fit with the quality of the pipeline that we had in-house. But we learned an enormous amount about what it takes to launch a drug and what we think will make us successful, including enormous amount that makes us more and more excited about launching brepocitinib. So I think that's kind of where we're at now.

What would you say are like the top priorities for your commercial team to really get that launch?

One of the cool things about the current moment is if we were at this stage, if we were about to launch a drug like brepocitinib and it were 2019, I think there'd be a lot of healthy skepticism would be a sort of a short launch story. But you look out over the past 5 or 6 years and probably first Horizon with TEPEZZA, but Horizon, argenx, obviously, Insmed now, Madrigal, Verona, BridgeBio, there have been a number of very successful commercial launches from and out of biotech. And in fact, I suspect that at least some of those drugs have been launched better in the hands of companies like argenx than they might have been in the hands of big pharma companies that argenx' creativity in crafting a modern commercial strategy has been really transformative.

And so the first thing that we're trying to do is, look, I hope eventually people describe us in the same terms that they describe companies like argenx as a commercial innovator. But before that, I hope they simply say they learned the lessons that argenx taught us. And so we are trying to do everything that argenx and Horizon and others have done. And that includes -- look, the world has had some structural shifts on access, for example, where rebating at least in orphan disease is less a part of the landscape and where patient support has been an enormously important part of access. And so for example, we hired this woman Lee Liberator who built TEPEZZA's patient support organization, and she is building our patient support organization.

I think one of the things about launching an orphan disease that's become increasingly true is these patients, and this is true in DM, are treated at a more and more concentrated set of referral centers. And a, we've built excellent relationships with those referral centers. They were the people who ran our clinical trial in many cases, and they are where we are spending a lot of our commercial time and medical education time now. And then b, I think you build a field force, therefore, that is the right people not necessarily to call on a community dermatologist, but to call on an expert in the field who spent their entire career treating dermatomyositis patients.

And that means we have recruited some of the -- one of our field force personnel, one of our sales reps is a career-long myositis KOL who left clinical practice because she was so excited about what dermatomyositis might do that she thought she'd take a hand to like help them make it a success. And I think that is -- she's not really a sales rep therefore, she's a medical care professional. She's jack of all trades, but I think that's the sort of thing that is a really high priority for us and making sure we're making the launch success.

The point that you made about short the launch not being as successful of an investment strategy today as it was maybe a few years ago. I mean, part of that is these companies have done a good job. Part of it, I think, is also that I think expectations have been a little bit more well grounded. How are you thinking about what that means for communication with investors about the early launch, about KPIs, what you're planning to share for brepo?

I -- this is a subject of healthy debate at Roivant and other places historically. And bluntly, I think we've learned a few things from recent launches and from the investor trajectory of recently launched companies. The first is I have a great deal of confidence in the ultimate commercial potential of brepocitinib as a drug, specifically in dermatomyositis and across indications. These are -- there's a lot of these patients. We can talk more about it. They have high unmet need. It's not a very competitively intense field right now in terms of people who are offering them options.

And look, at some level, this isn't rocket science. The only other approved therapy in dermatomyositis requires on label that you spend 8 hours a day, 5 days a month consecutively in an infusion center receiving an IV infusion, and we are a once-daily oral that provides probably better clinical benefit. This is not the most uphill battle in terms of convincing people that it's an attractive alternative. So I think all of that pulls together to a high set of expectations. That said, no one has launched a novel targeted therapy in dermatomyositis ever. And so the pace of the launch, how quickly we'll be able to get doctors changing clinical practice, how quickly we'll be able to work with payers in this specific population and do the education work. I just think it's basically impossible to know. And we've certainly seen launches rocket out of the gate, and we've seen more slow and steady ramps.

My general view is I expect -- I think everyone should expect slow and steady. And also there is 0 benefit to providing guidance. Just standing up there and giving people a sense of what I think is we're going to have to wait and see, and we're going to do our level best to make it a long-term success. And along the way, I'm sure we'll have fits and starts, but I'm excited for where it heads. And frankly, I think the companies that have attempted to provide guidance have not been rewarded for providing that guidance anyway. And so I'm not sure -- that's also a lesson learned from the Darwinian process.

Yes. Other indicators like new start forms? Have you thought about whether you'll be sharing that information?

Yes. So the honest answer is most of our decisions on that basis are going to be rooted in commercial and competitive dynamics. We will be, as all orphan launches do now, using tailored quite narrow focused, limited distribution. And in general, for a variety of commercial reasons, when you do that, you pretty rarely wind up sharing scripts. And so our scripts will probably not be widely available on a regular basis just because of our commercial distribution plans. And so that's just how that's going to play out.

Got it. Got it. What are you hearing from docs on the likely mix of patients in terms of prior therapy? And one of the questions that we get a lot is the pace of JAK switching.

Yes. Look, I think -- so taking a tiny step back, in claims data sets today, there are about 40,000 patients actively treated for dermatomyositis. That is a portion of the total dermatomyositis population. I think epidemiology suggests maybe that number is 70 plus. It's also a relatively difficult to diagnose condition. And so there's probably more patients out there who have either not received the diagnosis at all or have received a lupus diagnosis or whatever, who like may very well have dermatomyositis show up later once we arrive.

And anyway, of those 40,000 patients, about 75% of them are on steroids and immunosuppressants, prednisone, methotrexate. And many of those patients are poorly controlled. And the way we know they're poorly controlled is they're on quite high doses of steroids, in many cases, more than 6 months a year on greater than 10 or even greater than 20 milligrams of prednisone. If you've ever had like an allergic reaction, you've spent time on 20-plus milligrams of prednisone, it's a miserable existence for 3 days. I cannot imagine doing it for 6 months.

And so you know those patients are poorly controlled because they're making that choice. That is absolutely one of the early groups of patients that we are most enthusiastic about. Those patients are not on other therapies for a variety of reasons. They can't spend 5 days a month in an infusion center. They don't want to take an unapproved B-cell depleting drug like rituximab or whatever that has failed clinical trials in dermatomyositis. And so they're sort of stuck with steroids and DMARDs and dealing with the unsuccessful treatment that comes with it. You can imagine an IVIg patient spending all this time in an IVIg infusion center, thinking that maybe a 1 pill regimen sounds good.

So that's like -- that's another place where I think we will get early patients. There are -- so about 25% of the patient population is on something other than steroids and DMARDs. That's like about half of those patients are on IVIg and the other half are on a collection of off-label stuff. The vast majority of the off-label stuff are literally drugs that have failed dermatomyositis trials, but that probably provide some benefit in inflammatory disease. And so docs are trying it because they don't have anything else to do. Some small low to mid-single-digit percentage of those patients are on off-label JAK inhibitors.

The truth of the off-label JAK inhibitor population, when you actually do the math, low single-digit percentage of a 40,000 patient number, it's hundreds of patients basically, maybe a couple of thousand patients in total. It's actually a pretty concentrated group. For example, I think at another bank's KOL call, Julie Paik of Johns Hopkins said she had 70 patients on off-label tofacitinib. What she said she -- that's like a relatively significant percentage of the total patients off-label JAK inhibitors. What she said she would do is switch those patients as soon as she could basically.

So I think like what will wind up happening is prescriber by prescriber. Some docs will be eager to switch. Some docs will say, look, at least the off-label JAK patients are like kind of on something that works for them. I'm going to go with my high-dose steroid patients. I think some of that will come down to access and how easy we make it to get patients on drug. I think some of it will come down to how the docs that were on our trial and have a lot of familiarity with brepocitinib, may be faster to use it. The docs that were not in our trial and are still coming to speed with it, may do a little more experimentation. So I think it will be a mixture.

Yes. In terms of competition, VYVGART, they got the Phase III IM later this year. Assuming that works, like how much of a swing factor are the actual results really in terms of brepo's future market share, do you think?

Yes. I mean, look, they're 18 months behind us probably. And so we're not that far. Right now, we do have to outrun the Bayer as it were. That is it's not about the competitors. It's just about the disease. Later, we only have to outrun them or something. Look, I -- first of all, I think DM is one of these diseases where the unmet need is so large and there are so many patients that more share of voice by the industry, more new therapies, more options for doctors is mostly going to be a rising tide. And I think VYVGART in MG has benefited from the existence of the complement pathway programs. I think we will benefit from the existence of VYVGART.

And I think I would much rather be VYVGART in MG than a complement company. I would much rather be brepocitinib in DM than VYVGART because we're first because I think -- look, we're getting a lot of inbound calls now from investors and the path they're taking to get to us is they are argenx shareholders, and they're focused on DM. And so for the first time, they're doing KOL calls in DM and they pick the phone and they call DM docs and they like what do you think of VYVGART and the docs are like, "Hey, have you heard of brepocitinib? And so they're calling us because they're sort of coming at this from the side, and that's an enormously rewarding thing in the sense that it helps bring people to our story. I think it just underscores the lead that we've got.

Practically speaking, I think there are reasons to believe that dermatomyositis is not going to be the strongest setting for VYVGART among the myositis. The trial of VYVGART is running is across multiple different myositis. It's running in IMNM and in DM and in polymyositis. I think IMNM is more biologically on point for an FcRn. And I think their efficacy will probably be better in IMNM than it is in DM. I think that based on biological rationale, I think that because argenx' public statements to me suggest that they generally believe that, too. And I think if you compare our Phase III data to the Phase II data generated across the myositis, they didn't break it out by subtype in their Phase II study.

We were faster to achieve a moderate TIS response and achieved our responses against the backdrop of an aggressive steroid taper and still did comparably or better than VYVGART did. So I think we will have a competitive profile. The truth is, ultimately, you're only as good as your label. And if VYVGART gets lucky and blows out of the park in this study, it will be more of a competitive factor than if they don't, and we'll just have to see what their data looks like when it comes.

All right. NIU, next most mature indication, you've got the Phase III later this year. Phase II, highly compelling small cohort. But I mean, frankly, I've not heard a real strong bear case for this trial. I'm not going to sit here and ask you to articulate one, but...

You can if you want.

Maybe what were some of the risks that you sought to mitigate when you designed the Phase III?

Yes. Look, I think -- so NIU, noninfectious uveitis is a basket diagnosis for inflammations of the eye that are not caused by an infection. It's a heterogeneous patient population. It has not been an area of very active clinical development and has stymied a lot of others who have tried to develop there. It's a bad disease. And ophthalmologists tolerance for eye inflammation is very low because it's actually -- NIU is the third leading cause of blindness in the United States right now. It's like a bad disease and patients really don't want to go blind. And so they're willing to get treatment.

Against that backdrop, the only other sort of approved modern "therapy" for NIU is HUMIRA, which bluntly doesn't work that well, somewhere between 50% and 80% of patients or 50% and 75% of patients fail HUMIRA depending on how you count it, et cetera. And they fail pretty quickly, right? The time treatment failure in the HUMIRA study was like 6 months median. So it's a disease with a lot of unmet need. We ran a study, it was a Phase II study. It was blinded and dose ranging, but it did not have a placebo. And I said HUMIRA's time treatment failing in their Phase III was a little under 6 months. We went over 12 months as median time treatment failure. So with a lot of cushion versus the field, but no placebo.

The blunt level truth in immunology is the placebo response rates have crept up in every indication in history, and we didn't have placebo in our Phase II. And so you asked me what the risks in the trial are. The biggest risk in the trial is whatever, the bear in this clinical trial is placebo, and we have to outrun it. And so I think that's a challenge that we're cognizant of.

How do you do that? First of all, the heterogeneity of the patient population is always an obstacle. I think we've done a very good job with some creative and aggressive strategies to make sure we have the patients we need in the trial, that they are sick in the right way, that they are sick NIU patients. We have specific adjudication criteria for making sure the right patients get into the trial. We have a very aggressive steroid taper.

One of the things we did in the Phase II, the way these trials all work because tolerance for eye inflammation is poor is you can't just bring a patient in and put them on your drug. You have to bring them in, put them on a very high dose of systemic steroids to get the inflammation under control and then taper the steroids and see if you can maintain a response on your drug. And the HUMIRA study used a 12- to 16-week taper, I think, we used a much more aggressive taper than that. And we used in the Phase II in partnership with no placebo, and we want to give ourselves a hard test, but it worked. And so we're using a similarly aggressive taper in the Phase III. I think that will help control placebo response as well.

How much of a headwind do you think the availability of biosimilar HUMIRA is in this market?

Look, 2 things. One is there's about 40,000 patients on TNFs with NIU. And as I said, the treatment failure rate is 50-plus percent, and they tend to fail within 6 months in the clinical trials. Even if at the price points that we have in mind for brepocitinib, we live entirely in a HUMIRA refractory population, it's a blockbuster indication for us. And because ophthalmologists tolerance for eye inflammation is low, if our data are good, I think there will be a strong desire to use us aggressively in early line settings.

And so that will be a question of label. It will be a question of payer dynamics. But mostly, I think there will be a lot of people fighting for early access if our data supports it. And I think we will work with those people to get these patients on drug so they don't go blind.

I had intended to spend a little bit more time on CS and LPP, but maybe let me just ask a broader question of what is your indication selection strategy for brepo? And maybe just hit some of the highlights on CS and LPP.

I could launch into an, I think, interesting thematic history of JAK inhibitors here. But in the interest of parsimony, I won't. Look, I think in 2019, if you had said, by 2026, there will be a large, successful important JAK inhibitor franchise targeting orphan disease, everyone around you would have said, duh. It's obvious, right? In 2019, JAK inhibitors were everywhere. They were going to be the future. And then the black box warning thing happened and everyone kind of backed away.

If in 2019, you said, "Oh, who is going to own that large franchise of JAK inhibitors in orphan disease", everyone would have just looked at you and said, obviously, it's going to be Eli Lilly. It's going to be Sanofi. It's going to be AbbVie. It's going to be any of the companies that like had a place in JAK inhibitors and a place in orphan disease and a right to win there. The fact that approximately random mid-cap biotech company owns that franchise is a combination of cleverness on our part that I'm proud of and random accidents of history that I'm glad to have benefited from.

But as a consequence, we own right now the category of JAK inhibitors in orphan inflammation, and there are many orphan inflammatory diseases. I mean, literally almost any inflammatory disease with, call it, 30,000 to 130,000 patients is a good swim lane for us. And we are looking -- obviously, we're focusing on the diseases where we know the physicians. We're focusing on Th1-mediated disease, the places where JAK1 and TYK2 had benefit for a variety of reasons. But we're looking across that space, and there are quite a lot of indications to go after. And I think even more than DM being an exciting indication, though it is or NIU being an exciting indication, though it is, the breadth of what brepocitinib could do is actually pretty staggering in terms of the number of diseases we could help.

Switching over to mosli, maybe would you like to start with just an overview of the drug and why you're excited about PH-ILD and then we can shift over into expectations for the trial.

And I talked at the beginning of this, you asked about BD around how we bring our drugs in. I didn't mention, we paid $14 million upfront to Pfizer for brepocitinib. We also paid $14 million upfront to Bayer for mosliciguat. Mosli is a drug. It's an inhaled vasodilator, mechanism of this thing called sGC activation. We got it from Bayer a few years ago.

And basically, what happened here was Bayer had a history in this chemistry. They sort of originated the development of drugs in sGC. They were partnered with Merck on respiratory disease around a drug called Adempas that was a commercially successful drug, $2 billion or $3 billion in peak sales, a big drug. And then Bayer and Merck had kind of a messy divorce at the end of that process or at least they split foot ways and each went on down their separate path of developing a successor drug to Adempas. Both of them developed inhaled sGC drugs. Bayer's, in our view, was the better drug. And then Bayer went and did some M&A in the agrochemical space that was complicated. And they had to make difficult choices around their pharma portfolio because Roundup allegedly causes cancer. And so they got out of respiratory disease.

And this was a while ago, and they no longer had a real footprint there, and they weren't sort of doing active research in respiratory disease. And meanwhile, United Therapeutics, one of the forefathers of pulmonary hypertension development and a phenomenal company, sort of whatever, struck gold for a second time. They found pulmonary hypertension from lung disease, PH-ILD as an indication. They got Tyvaso approved there. They launched it commercially, and it has been an enormous commercial success that has engendered an entire field of literal follow-on molecules of other treprostinil similar to Tyvaso from Liquidia, from Insmed that I think are also really exciting drugs.

We went to Bayer at that moment in time, realizing that mosli, which had been developed principally in the more competitive Group 1 pulmonary arterial hypertension should also, in theory, work as an inhaled vasodilator in PH-ILD. And Bayer was not at all really paying attention to the field and certainly wasn't going to run a novel development strategy in lung disease. And so we in-licensed it from them and set on retraining the program towards PH-ILD. And now we are reading out a Phase IIb study later this year, the first basically in a non-treprostinil mechanism of a late-stage study for PH-ILD.

What does the successful Phase II look like for you?

Yes. So in PH-ILD, as with all pulmonary hypertension, the approvable Phase III endpoints are things like 6-minute walk, which, again, because it's a generalist conference, 6-minute walk, first of all, is a widely hated indication widely hated endpoint in biotech. And the reason is because roughly speaking, what happens is you're standing in a doctor's office, picture your doctor's office and the doctor says, how far can you walk in 6 minutes? I'm going to set a stop watch and get out a tape measure and you're going to go.

It turns out conditions vary widely. Are you walking in a hallway? Are you walking in a waiting room? Are you walking in circles on a tile floor? Are you walking on a carpeted floor? And this leads also like did you eat your Wheaties when you woke up in the morning, did you drink a cup of coffee? There's just like a lot of things that make this a variable endpoint. It turns out that it is a relatively well-behaved endpoint in pulmonary hypertension, but it's quite variable. And so in Phase II studies in pulmonary hypertension, including in PH-ILD, the primary endpoint tends to be something called PVR, which is right hearted blood pressure. It is a literal measure of disease activity in that you are measuring the flow of blood through the right ventricle.

The way you measure it is under general anesthesia on an operating table with a catheter. And so it's not something that you can do regularly in very large studies, but it is the primary endpoint of our study. And again, a measure of how sick these patients are as they subject themselves to a clinical trial that requires regular general anesthesia catheterization. So that's the primary endpoint. There has not been across pulmonary hypertension, a mechanism that doesn't -- that delivers 20-plus percent reductions in PVR and has not gone on not just to be clinically successful on 6-minute walk, but to be a multibillion-dollar class.

And so our view is if we can deliver 20-plus benefit on PVR, nothing else really matters. That is almost certainly a good enough indicator that we will be able to deliver clinical benefit in a subsequent Phase III study that we will run the subsequent Phase III study. That said, we are measuring 6-minute walk in the trial. We are measuring other clinical endpoints. And while the study is not powered to deliver p-value statistical significance on those endpoints, it would certainly be helpful to understand the magnitude of effect in those endpoints as well.

With Tyvaso, I think that they had a pretty big gap between peak and trough 6-minute walk. which I think kind of underscores that your daily dosing could be a clinical advantage and not just a convenience advantage. Are you collecting 6-minute walk at different time points post inhalation, either in this or in a future Phase III?

Yes. We are measuring a bunch of different time points. One of the great things about our drug is it is quite stable in the lung. And in fact, in Phase I studies, we have like elevated cardiac output, cGMP production out 48 hours after a single dose. And so I think we do actually get quite a lot of benefit from the time course because it's 48 hours, we will get meaningful stacking over multiple days over multiple dosing. And I think all of those things should contribute to better clinical benefit. And I think we will measure at different time points so that we can begin to sort of dimension out that effect.

How do you envision the commercial opportunity for mosli either as monotherapy or combination? And what kind of evidence would you need to generate to support that?

So this is another thing where we can learn from history. So in PAH, pulmonary arterial hypertension, which is a, I think, $10-plus billion category now, one of the -- what was this first to the pulmonary hypertension is a word to be treated. What happened was actually treprostinils were the first modern drugs approved at prostacyclins. And then a series of successive classes, including systemic sGC stimulators were approved.

And each time a new class entered 2 things happened. One is actually life expectancy for these patients increased by, in some cases, as much as 2 to 3 years. And the other is patients just went on multiple categories of drugs. This is a polypharmacy market. Pulmonary hypertension ultimately often kills you. It's a very bad disease. These patients go on everything they can get. They cycle drugs, they add them on top of each other. And so I think that is exactly what will happen in PH-ILD as well. It will be a polypharmacy market, and we will be used before Tyvaso, after Tyvaso, on top of Tyvaso in every combination and with other mechanisms, hopefully, as well.

Practically, that means from a clinical benefit perspective, worse than Tyvaso, better than Tyvaso, similar to Tyvaso, it doesn't matter that much in the end because most patients will wind up on most drugs. Obviously, the better we are than Tyvaso, the earlier will potentially be used. We have some other advantages where one inhalation once a day versus more for the others, one from the dry powder inhaler once a day. In fact, we don't likely cause cough as an on-target effect with prostacyclin do. There's a variety of reasons why we could be use in an earlier line setting. But mostly, the answer is this is going to be a polypharmacy market, and everyone is going to be on top of everything.

To answer your question about evidence generation, in our Phase III study -- we -- sorry, in a Phase IIb study, we do not allow concurrent Tyvaso use. Tyvaso is only approved in the U.S. It's a global study. It's like slightly complicated. In the Phase III study, we will allow some patients on concurrent Tyvaso precisely because it's important that the label allow for concurrent use. However, it's important, therefore, to know a little bit about what we do together with Tyvaso, especially from a safety perspective, but also to get some sense of efficacy. So we are currently, in addition to the main Phase IIb running an open-label combo study with Tyvaso that has just started. So we don't have any data from it right now, but that will help inform things like stratification in the Phase III.

Question on the iPad. What other indications in PH could you look at? And like when would you consider starting those?

Yes. Perfect. So look, I think the history of this is helpful, too. Most -- locally administered vasodilators are effective in pulmonary hypertension. We probably work in PAH. We have good Phase I data there. It's competitive, but we could go there eventually. I think PH-COPD is an interesting indication, although local vasodilation in lung disease patients with emphysema is a more complicated proposition, and there's more emphysema in the PH-COPD population. So that, for that reason, requires some more careful thought.

Recently, though, we've also seen the prostacyclin and treprostinil Tyvaso specifically be successful, for example, in IPF. And that is absolutely high on our list of things that we are excited to think about. Ultimately, we're going to learn a fair amount about all of that from this Phase IIb later this year. We're measuring FVC in IPF patients. We'll have a sense for how we did there, albeit in a small subset. I think all of that will inform next steps. PH-ILD is a huge indication, and we wanted to make sure we nailed it, but I think we will be initiating new indications if the Phase IIb data supports it pretty quickly after we get this data.

Switching to Immunovant. Could you start with how 1402 is differentiated from the other FcRns in terms of either product profile or the indications that you're in?

Perfect. So again, I'm sure many people in this room are familiar with FcRns as a mechanism because argenx has been so enormously successful in creating that category. This is sort of a -- whatever, it's like a big moment in immunology in that this is sort of the HUMIRA moment for a new kind of immunology. It's the first time we've had a drug approved that can treat what I'll call B-cell disease, autoantibody-driven disease, much of which isn't even inflammatory. Graves disease isn't really an inflammatory disease at some level. And so it opens up an entire set of new indications, and argenx has done a phenomenal job in MG and in CIDP and other places, creating those markets and showing real benefit for those patients.

VYVGART has some limits. Nipocalimab, the J&J drug has some limits. Among them, as each of them is currently studied practically and in VYVGART's case, probably just like due to biological limitations, they don't suppress IgG more than, call it, 60% or 70%, whereas I believe we will suppress IgG by 80-plus percent with 1402. So I think we can get better efficacy. We are formulated as a simple standard DUPIXENT style auto-injector, which is something that VYVGART is not. VYVGART is a Hytrulo long push with dire injection site reactions and things like that or Halozyme, sorry, or an IV drug. So I think those are all advantages that we have.

And then I think although not as important as being a better molecule, almost as important as being a better molecule, I think we just carved out some really great white space indications for ourselves. We have pioneered modern drug development in Graves' disease where we have an ongoing pair of registrational studies that we hope will be successful and will create the first approved novel therapy in Graves' disease since the 1950s. So that's an indication with millions of total patients, hundreds of thousands of poorly controlled patients. Imitation is the finest form of flattery. We have created a cottage industry of other companies now developing Graves' disease, but they're all years behind us.

And I think we have really built out some expertise and positioning there that's exciting. Just last week, we showed some data in a subsetting of rheumatoid arthritis that was, frankly, more compelling data than we expected it to be and showed a potential role for FcRns in late-line multi-mechanism failure rheumatoid arthritis that I am excited to explore from here. So I think those are both indications where we're way out in front and kind of alone right now, and there's many others that we're pursuing, some of them like MG more competitive and some of them like CLE, less competitive.

That's where I was going to go next was RA. If you want to share some of the highlights of that data and why you think you're able to achieve such higher ACR responses versus nipo?

Yes. So RA, obviously not an orphan disease, many, many patients with RA. It is a disease that is more complicated than Graves' disease and that it is not just an autoantibody disease. It's an inflammatory disease. It's an autoantibody disease in some patients. It's a -- there's different etiologies. It comes from different places. It's a complicated disease. The idea that FcRns could work in RA is not an idea of our own invention. And we know that some of the disease is autoantibody driven.

In fact, one of the exciting things about FcRns there is unlike all of the other drugs basically in RA, it's not an anti-inflammatory. And so it might work differently on a different axis and therefore, work in combo or in later line settings where antiinflammatories failed. This was the idea with which they had been studied historically. J&J has run 2 studies in RA. One was effectively a monotherapy study across a variety of lines of therapy across a variety of different patients. And they showed fine responses. Nothing -- they showed clear benefit, but nothing that was like getting people out of bed.

The 2 exciting sort of indicators in the data that were interesting. One, almost all of their responses came from the subset of patients that tested positive for autoantibodies. And so that was like a clear way to enrich on a biomarker. And then two, their efficacy appeared to be preserved irrespective of line of therapy. And so you look at that and you're like, okay, maybe there's something here in late line. And in fact, even though their efficacy was kind of middling in late-line multi-mechanism failure patients, it was potentially good enough to have a commercial plan.

So then we and J&J after seeing that monotherapy data, each then plowed on with different strategies. J&J said, okay, we're going to run a combo study in early line patients combo with a TNF and that was a study they ran. And we were like, we're going to focus on the late-line multi-mechanism failure population and run the study that we ran, which was in patients who effectively failed everything they can. They failed at least 2 of TNF, IL-6 and JAKs. A majority of them, as we now said, have failed TNFs and JAKs. These are like late-line patients without other options.

The confusing thing is J&J's combo therapy pretty spectacularly didn't work. They basically didn't separate from the TNF. That was always a hard study to run. You're putting patients on a TNF for the first time. They're going to benefit significantly from the TNF. And so you have to kind of demonstrate benefit on top of something that's already helping them. But still, the level of separation was disconcertingly poor. And so I think like that confused us when we saw it.

Then our study read out, and it showed something sort of surprising in the opposite direction, meaningfully better responses than either of the other 2 studies. The data that we've produced so far is data from an open-label run-in period to a randomized withdrawal trial. It is nuanced data across multiple axes. And certainly, one of the reasons it looks as good as it did. We showed ACR 70s in the high 30s, which is as good as anyone ever shows basically. It's close to JAK-like in its efficacy, which in a JAK failure population is extraordinary, especially for mechanism that's pretty safe like an FcRn.

Part of the quality of that data has to be due to the fact that it's an open-label setting. There's some rising tide effect here, but you just don't spontaneously have an ACR70 response. Those are pretty big improvements in sick patients who have failed a lot of other drugs. So I think there's like -- our belief is there's clearly something real happening. The other 2 things, I think, that are relevant. One is we did a pretty good job selecting for an autoantibody positive population. The J&J combo study with Cimzia was autoantibody selected, but not they allowed rheumatoid factor patients, for example, is not as rigorously specifically focused on ACPA as ours. I think we generated some benefit there.

And then I sort of have to believe, although I don't yet have the evidence to back this up, but the other thing that happened for us is it turns out that when you filter out patients who have failed, remember, failed is an important word here, JAK inhibitors and TNFs, that those patients have tried anti-inflammatory mechanisms that are very effective for treating their RA and have not succeeded that it must, at some level be that we are enriching for a population whose disease is causally driven by autoantibodies in a way that even we didn't totally anticipate. But ultimately, we'll find out.

Period 2 of this study is going to be harder now because we have to generate meaningful reversion in patients that have benefited a lot clinically from being on drug. And so we might not even a p-value in period 2. We're going to really study the patient level data here and try and understand what's happening and then work with FDA on a trial design for a subsequent study that I hope will be tractable and lead to a lot of benefit for these patients.

Getting some more questions on the iPad, and this is more of a big picture thing, but the cash balance, you've got $4 billion, you'll be getting more from Moderna. What are your plans for that considering that you have not spent that -- you've not spent a lot of money on transactions historically?

Yes. Look, I think one of the things about Roivant is we are sort of culturally built to be good stewards of capital. It's just sort of part of who we were to begin with. And it's led to some puzzling decisions over time. Look, I think like biotech companies historically haven't bought back stock. That's changed a little bit, but like we bought back $1.5 billion of stock at $10 a share because we had too much cash. That turned out to be a good investment over time. We continue to buy back stock now as we're bringing more money from Moderna.

What we said lost in history at this point is that we bought a drug from Pfizer a while ago and then sold it to Roche for a lot of money. And so we had a lot of cash on our balance sheet. That's -- that plus the Sumitomo deal is how we wound up sort of highly capitalized. And I think what we said all along is if we can't do it with $4 billion, we probably can't do it with $6 billion. That is like there's an amount of money beyond which it just like isn't required to build the kind of business we're building. And frankly, the kind of BD that we've done historically has been pretty capital efficient on the upfront, expensive clinical development, pretty capital efficient on the upfront.

So look, I think as cash comes in above and beyond current levels, we will continue to be pretty aggressive about returning it to shareholders just because I think balance sheet leanness is something we believe in. But we have still a lot of cash even absent that, and we'll spend a fair amount of it on breadth of development for the existing pipeline. We will add indications for brepo. We will add indications for FcRn. We will add indications for mosli, and we'll be active on the BD side. And I really hope we bring programs in with expensive Phase III trials. Those tend to be big indications. The tend to be exciting. They tend to be the kinds of things we can make a difference at. So I hope we spend a fair amount of our money on that.

AI has been a big theme for this conference. What are your expectations for how that impacts drug development and over time? And what is Roivant doing today?

At the current moment at a generalist conference, I think what I'm supposed to say here is we're an AI-native AI-first company building data centers in space. We're not building data centers in space. I don't know how. But I think that's what we're supposed to say. Look, I am -- there is a lot of talk about AI in biopharma. And a lot of that talk centers on novel uses of AI in drug discovery, on medicinal chemistry, on biology. And I think that stuff is super interesting. We have invested in it. We have built a company that is successfully using AI to model protein-protein interactions that we have a big stake in that I think could be.

Look, I think it could be a company that invents designed molecular glues in a way that wasn't possible for AI. There's like cool things that are going to happen here. That said, those are the apples at the very top of the tree. Those are the hardest of the hard problems to improve with AI in biopharma. And while we and others will work on them, I don't know how quickly we're going to revolutionize drug discovery. If quickly, that will be great for us. There will be many more drugs to put into clinical development, and we are very good clinical developers. If slowly, that's okay, too.

That said, in clinical development, what is clinical development really in addition to a science problem. It is a massive logistical coordination exercise where you're reading hundreds or thousands of patients' medical charts coming through them literally as human beings, like trying to figure out which of these patients are good for your trial. You're trying to turn around legal documents like site agreements and IRBs and better B agreements and protocols quickly there all similar to each other, but different in little ways. These are all things that like the AI of today, the Claude that is on all of our desks is really good at.

And so like our ability to prosecute large trials at scale is dramatically better than it was a year ago, and we are coming to terms with that. And I'll say like, look, I think we made a concerted effort to get these tools out and available to everybody, and we are building tools every day to make ourselves better at this. But again, if I were to try and defend ourselves as like an AI-first company, those are things I would talk about. But also, it's just been this incredible Darwinian process. You put cloud on the desk of a smart person running a clinical trial, and they're like, "Oh, my life is easier now. Here are the 7 ways my life is easier now. So I think a lot of what we're doing is just putting the right people in the right seats with the right tools, and it turns out that's making us better.

One more question to close this out. If we fast forward 2 to 3 years, what has to be true for Roivant to be a $50 billion market cap company?

Look, I think some of our launches have to go well. I think that's true. I don't think DM has to be an $8 billion indication. I think DM has to be a $1.5 billion indication in people's minds. NIU -- look, if DM is a $1 billion or $1.5 billion indication, NIU is a $1.5 billion indication in CS and LPP are $1 billion or $1.5 billion indications and FcRn in total is $3 billion or $4 billion, we're there easily, right? We're on our path to being -- I don't mean that literally in 3 or 4 years. People have to believe those things in 3 or 4 years or 2 or 3 years for us to achieve that kind of scale.

So I think we have to do reasonably well commercially somewhere, and we have to keep stacking indications. And to be honest, I think that's about it there. I think if you asked me how we become a $150 billion company. There's a lot we have to do between here and there. But I think the path to $40 billion or $50 billion or $60 billion is good execution on what we've got now.

Great. Let's leave it there. Thank you, Matt.

If you take nothing away from this conference, just remember, we are an AI-first company building data centers in space.

Ladies and gentlemen, thank you for standing by. Welcome to the Roivant Fourth Quarter 2025 Earnings Call. [Operator Instructions] Please be advised that today's conference is being recorded.

I would like now to turn the conference over to Stephanie Lee. Please go ahead.

Good morning, and thanks for joining today's call to review business updates from Roivant's fourth quarter and fiscal year ended March 31, 2026. I'm Stephanie Lee with Roivant. Presenting today, we have Matt Gline, CEO of Roivant; and Drew Fromkin, CEO of Pulmovant.

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 have 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.

Thanks, Stephanie. Thank you, everyone, for dialing in this morning. I'm glad we're talking. We had an unexpectedly busy agenda with a bunch of topics. I'm looking forward to going through all of it, including, obviously, what we announced this morning, which is the preliminary open-label period data from the 1402 study in D2T RA as well as a planned spotlight we've been planning to do for a while on mosliciguat getting into that data, which Drew will take us through and some smaller updates on the brepocitinib program, although exciting. So a lot to cover.

I want to -- before I get into all that, there's one small bit of executive privilege and wish my father, Jerry, a happy 75th birthday. Today is his 75th birthday. So happy birthday dad. He sometimes listen in on these calls. I don't know if he's listening in now. If not, he'll catch it on the replay.

Okay. Into the important topics now, starting on important business topics now. Starting on Slide 5. Look, this has been a pretty wild 12 months for Roivant, and we continue to see just tremendous execution momentum across our development portfolio. An update that will get drowned in some of the other things for today, but it's actually pretty great is that brepocitinib was awarded breakthrough designation and break therapy designation for cutaneous sarcoidosis, which just underscores indication selection and development there in terms of what that could mean for those patients.

Obviously, also in this quarter, we announced LPP as an indication for brepo, and that study is already enrolling, and we're excited about how that's going. And then a ton of work ongoing in commercial prep for the launch in DM, which assuming FDA goes as we expect it to, we'll launch by the end of September.

Obviously, the biggest data update for today in the FcRn franchise is what I mentioned earlier, which is that 1402 showed, we think, clinically meaningful, pretty exciting ACR response rates across ACR 20, 50 and 70 in D2T RA study in the open-label portion, we'll talk more about that, but that's obviously encouraging data that we're looking forward to spending some time on.

We're also fully enrolled on CLE, with top line data expected in that study in the second half. And earlier in this quarter, we announced the failure of the batoclimab studies in TED, but also the hyperthyroid patients showed normalization, which was supportive of our Graves studies, which are ongoing and continue to enroll well also.

And then finally, hard to believe it was this quarter, but earlier this quarter, we also announced our $2.25 billion settlement with Moderna, and we expect to receive the first portion of that payment, the $950 million upfront in July. So just an incredibly busy quarter of execution for us and an incredibly busy fiscal year for us. It's really hard to believe how much has changed in year for Roivant.

None of that, though, is to say on Slide 6 that we're done. And the next 12 months are also incredibly exciting. Obviously, one of the most important things going on, we will hopefully be launching brepocitinib in dermatomyositis by the end of September. The Phase III study in cutaneous sarcoidosis, we expect to begin this year as well, and we expect the NIU Phase III top line data in the back half of this year. So a transformative year for brepo as all of that comes around. We'll spend time on this today, but the mosliciguat PH-ILD Phase IIb top line data is expected in the second half. That also will potentially underscore that as a really important program. And hopefully, look forward to that data and just talk more about it.

Obviously, D2T RA, some of the data is around today, but we're looking forward to providing a pretty significant update later this year with a little bit more data as well as detailed analysis we're doing at a patient level and hopefully, with some feedback from FDA on a go-forward plan given what we've now seen. And then obviously, we'll get the CLE PoC top line data as well. And then next year is a huge year with 1402 data in Graves and MG coming in. So a ton to look forward to and frankly, as much in the windshield as in the rearview mirror. I think I've got the car analogy right there.

Great. Okay. I'm going to go in now without spending more time on the preamble and talk a little bit about this D2T RA data, which I would call surprisingly good. We were pretty excited to see what we saw here is slowly been a little bit hard to process just how exciting this data is. And so we're still doing a lot of work on it.

As a reminder on Slide 8 of what we're talking about today, this was a unique study designed in a few ways. First of all, as I think everyone is aware, this was a study in heavily refractory patients. Every patient in this study in addition to failing steroids and DMARDs, also had to fail at least 2 advanced lines of therapy. So most commonly, that's 2 of, for example, TNFs, JAKs and IL-6s. And we'll talk a little bit about that. There's obviously some other things that could be in that bucket as well.

The study also had a pretty strict entry criteria on autoantibody positivity. We had a criteria on ACPA positive above a certain level, and that was also specific to the study and design. And then the other way, which the study was unique because it was a randomized withdrawal study with 2 periods. First, an open-label active treatment period of 16 weeks of high-dose 1402, 600 milligrams, followed by a period 2, 12-week rerandomization where ACR 20 responders at week 14 and 16, both are rerandomized into a 12-week randomized withdrawal period, where some of them stay at 600, some go down to 300 and some go down to placebo.

What we have to share today is preliminary data. We're still actually cleaning and finalizing it all, but it shouldn't move very much from here. On the top line treatment effect from period 1. Period 2 is still ongoing with more than half of patients still being dosed in the study, but we don't have any data or information about period 2 to share today. And then even for period 1, there's a whole bunch of data like IgG, for example, that we haven't analyzed fully and are not ready to share. So nothing to say about it other than that we're going to be sharing a pretty limited subset of this data today.

On Slide 9, you can see baseline characteristics for the patients in the study. We got over 165 evaluable patients. I'm not going to go through all of this in detail other than to say this is quite a sick patient population. Obviously, by design, it's refractory, and we'll talk more about that in a second. But for example, if you look at the DAS28 CRP score of 6.1, that's quite high for a study like this. There's a bunch of measures on here that suggest a quite sick population, which was the goal, right? This is the population that we set out to enroll. And so we feel good about who's in the study.

On prior lines of therapy, specifically on 10, so you can see on the right-hand side, we succeeded with our entry criteria that is basically all of these patients have failed more than 2 advanced therapy mechanisms. And that's very different than either the NIPO study or really any of the later line RA studies that have been run. And actually, one thing that we're highlighting today which I think is interesting, 65% of these patients roughly have failed specifically JAK inhibitors. And notably, we'll highlight this elsewhere as well. Basically, every single one of the patients who failed a JAK inhibitor also failed a TNF. So this is a TNF and JAK refractory patient population that we're focused on.

So look, Slide 11 is the headline here. And the headline is with all of the appropriate caveats for an open-label study, these numbers are high. We saw 73% of patients roughly with ACR 20 responses. And not just that, but we saw quite deep responses. We saw over half of patients with an ACR 50 and over 1/3 of patients with an ACR 70. And notably, once you get onto the deeper end of that with ACR 50s and ACR 70s, you just don't see a lot of placebo response in that level of responder analysis. And so it feels to us like looking at this data, there's something going on that's meaningful and interesting with this drug and something that merits enthusiasm and a lot of further investigation, and we're certainly doing all that work now as we get ready to take the program forward.

I'll highlight on Slide 12, the one other bit of interesting data from the study that we're able to present today, which is we pulled out the subset of patients who are JAK experienced. Remember, those patients, 107 of them are both JAK and TNF experienced all of them. Some of them have also failed something else as well. And one of the things that I think is maybe most exciting about this data is it's basically fully preserved in that subset.

And so as you think about that opportunity where these patients have really failed all of the most advanced options available to them, we're able to deliver in an open-label setting, pretty exciting response rates for those patients, which I think bodes well for the exact biological thesis with which we ran the study to begin with that autoantibody positivity is an orthogonal mechanism, some of the other anti-inflammatory options. And then for ACPA positive patients, this could be an effective treatment option.

So look, I think on Slide 13, just to reiterate what we're showing here, look, these are sick patients, a difficult-to-treat patient population who have failed a lot or all of the available options and come in with highly active disease. We showed really great response rates in the data that we're excited to see how they evolve through the rest of the study and on deeper patient-level analysis. And also notably, this is the largest patient population dosed with IMVT-1402 to date. It was safe and well tolerated in the study, nothing new drug-related from a safety signal perspective identified. So a clean data set overall and further underscoring what we think we've got with 1402.

Path forward from here, obviously, you look at this data and you feel pretty good about what this could be, significant potential benefit, a differentiated mechanism, a difficult-to-treat population with not a lot of options. So we're actively working right now to get ready to talk to FDA about this data and plan a path forward. The data is encouraging. I'll make one comment about it, which is the depth of responses is exactly what's exciting about the data set. It's exactly what makes us believe there is something beyond placebo happening in the data set.

But as you'll recall, the randomized withdrawal period, the primary endpoint of period 2 is do patients taken off drug lose their ACR 20 response in 12 weeks, which was a relatively short period to begin with and almost certainly would have been fine if we had seen more marginal benefit on ACR 20. But the truth is once you're looking at ACR 50 and 70 responders, I think the bar has actually gotten a fair amount higher for period 2. And so paradoxically, I think we still have a good shot of success there. But in some ways, period 2 is less meaningful than it might otherwise have been. And I think there are plenty of scenarios where we don't see a p-value in period 2 and continue forward with the drug given the overall quality of this data.

And conversely, depending on FDA's feedback, potentially situations where we do see a p-value in period 2 and just need to make sure we're comfortable with the plan forward. So I think much more interesting than the period 2 data at this point is more patient level analysis as well as a result of those FDA discussions, and we expect to share all of that in the second half of this year. We're working on it right now. And my hope, given the quality of the data that we'll be coming back to you with an enthusiastic update about next steps here that lay the groundwork for just a really big opportunity.

Remember, we presented some data at our Investor Day suggesting this is at least a 70,000 patient population and some more specific revised commercial analysis that Immunovant has now done that looks like that number could be 85,000 or higher. It's a big patient population in need. And I think underscoring that the speed with which this trial enrolled, the enthusiasm that physicians have for putting patients on study is just further evidence that there's really something interesting here.

And with that, actually, I just want to also just give a shout out to the Immunovant team who have continued to execute really well. Obviously, the data itself is strong, but also the speed of enrollment, the speed with which we're moving through the study, the full enrollment on CLE. And I think that spans all of our programs. I think we're excited about what -- obviously, what Priovant has been able to do with brepocitinib from a clinical enrollment perspective. We're excited about the speed of enrollment for mosliciguat. Obviously, the quality of that data we'll find out soon. But look, we're really excited about what we've been able to do across the portfolio of clinical execution. So much appreciation for the enormous number of people who are working towards those goals.

Cool. I'm going to pivot now to mosliciguat and do a little bit of a data preview there because the next time we get together, that data could potentially be very close in front of us. And so we wanted to get out ahead of that and give people a chance to just ground themselves in what's coming as we did last year around this time or a little later for brepo in dermatomyositis.

Look, I'll do a little bit of an introduction here. And then you all heard from Drew back at Investor Day in December. He's in the room with me and he's going to talk through a little bit more about the program. Look, intense unmet medical need. These patients, in the extreme, a significant proportion of them die. They're very sick. There's currently only one approved mechanism with 2 therapies, and we think there's probably 200,000 patients across the U.S. and Europe. And that one mechanism for treprostinil is underscoring multiple really great launches at this point. So we're excited to see the commercial enthusiasm and excited to see these patients have access to something that provides real benefit already, and we're hoping to add to that.

Mosliciguat has a completely differentiated mechanism of action for the disease. It's an sGC activator. It's an inhaled sGC activator. It's potentially the first non-treprostinil that could be available for these patients. We expect this to be a polypharmacy combination therapy market as PAH has been. And we think mosliciguat has a chance to be -- first line has a chance to be a major part of the treatment paradigm, and we're just looking forward to getting this data moving forward there.

In our Phase I data across healthy volunteers of pulmonary hypertension patients, and Drew will remind us of this data specifically, we saw among the best PVR reductions to date. And one thing we're going to remind people of today is that although we saw a 38% PVR reduction in some of those patients, that basically anything that has ever showed 20-plus percent PVR reductions has been able to deliver clinically meaningful benefit. I think it's true that there has not been any class of drug showing a 20-plus percent PVR reduction that has not gone on to be a commercially successful class of drugs. And then finally, as a reminder, unsurprisingly, the top line data from that study is on track, and we expect to get it in the second half of 2026. It's a 135-patient study.

So with that, I'm going to hand it over to Drew, who's going to take you through the next handful of slides here on the program, and then I'll come back for a little summary at the end and the rest of the presentation. Drew?

That's great. Thanks a million, Matt. And I can tell you there's a lot of excitement about mosliciguat. Mosli is an inhaled sGC activator that's delivered directly to the lungs to activate sGC and restore impaired sGC function. sGC is a key enzyme in the NO-sGC-cGMP pathway. And in oxidative stress environments like PH-ILD, nitric oxide may be reduced and the sGC binding site can become impaired, leading to sGC dysfunction.

Now typically, sGC is activated when nitric oxide engages sGC in the presence of heme and cGMP is then produced. Unlike cGMP sGC stimulators, that requires nitric oxide and heme to activate the sGC. Inhaled mosliciguat binds to the heme pocket independent of the need for NO and heme, producing cGMP, which results in vasodilation of pulmonary arteries and potential reduction of fibrosis and inflammation of the lung tissue.

Next slide. So we know many pulmonary diseases are heterogeneous in nature, and that fact can make patient treatment complex. To start, there's disease of the pulmonary vasculature and disease of the lung parenchyma. The combination of these 2 disorders is embodied in pulmonary hypertension with interstitial lung disease, which is the first indication we're exploring in our Phase II FOCUS study. We believe mosli has the potential to address both the pulmonary vascular and the lung parenchymal diseases experienced with patients with PH-ILD.

Mosli, next slide. I want to make sure that...

Let me just call out the slide numbers for everyone...

Okay. Thank you very much. I appreciate that.

I just want to make sure we're advancing.

Mosli's preclinical properties led Bayer to take mosliciguat into Phase I trials in a total of 170 patients, including healthy volunteers and patients with group 1 PAH and Group 4 CTEPH. In the Phase I study, Bayer studied mosliciguat in 132 healthy volunteers and 38 PAH patients. The healthy volunteers underwent studies with single and multiple dose formats and mosli proved to be well tolerated, active and have an extended half-life of approximately 40 hours. And in the Phase Ib ATMOS study, 38 patients with PH were dosed in a single ascending dose format and mosli again proved to be very active, producing deep PVR reductions and was very well tolerated.

On to Slide 20. So given mosliciguat's mechanism of action and inhaled route of administration, one would expect to see notable reductions in pulmonary vascular resistance associated with hemodynamic changes. And with one dose of mosli in PH patients, that's exactly what we saw. A single dose of mosliciguat reduced PVR in these patients early and sustained through the 3-hour observation period with a mean PVR reduction of greater than 30% and a mean peak PVR reduction of approximately 38%. This places mosli's PVR reductions amongst the highest reductions seen in single and multi-dose trials in PAH treatment space.

With one dose of mosliciguat, we also saw cGMP levels rise as measured in plasma with no associated clinically meaningful systemic side effects, including systemic blood pressure and heart rate. We also observed the desired impact on other hemodynamic measures, including mean reduction in mPAP of up to 20% and mean increase in cardiac output of up to 25%.

Slide 21. Mosliciguat was also well tolerated in Phase I patients in healthy volunteers and patients with PAH, with treatment-emergent adverse events being mild to moderate in intensity across both groups. And all doses were well tolerated, and we did not see significant cough, which is often exacerbated by inhaled treprostinils, and we did not see clinically relevant systemic side effects, which we believe in great part was due to the inhaled direct delivery of mosli to the lungs and the limited bioavailability of mosli in circulation.

Slide 22. So with mosli's Phase I tolerability and clinical profile, we look to take mosli into Phase II development, an indication where there exists a major unmet medical need. And we felt that PH-ILD was an exciting opportunity for development. Given the primary site of PH-ILD, it's in the lungs involving the pulmonary vasculature and the lung parenchyma and the currently approved treprostinil treatments have high treatment burden as well as tolerability challenges with highly variable efficacy. And so mosli lines up really nicely in this moment. Since it was delivered directly to the lungs as a once-daily dosing, that's been very well tolerated and produced limited incremental cough and systemic side effects in Phase I and has the potential to address both the pulmonary vascular and lung parenchymal diseases.

Slide 23. So to go a little deeper into PH-ILD patient populations and the opportunity, PH-ILD represents a large and underserved market where new drugs are sorely needed for these patients. There are up to approximately 200,000 patients in the U.S. and Europe, likely underdiagnosed given the lack of treatment options in particular. And this is a sick population and severe subgroup of PH, less than a 5-year median survival and the combination of PH and ILD represents an increasingly poor prognosis compared to each alone. And I mentioned previously the lack of treatment as there are currently only 2 approved FDA treprostinil drugs, leaving room for significant improvement.

Slide 24. Now the core field of drugs in development for the treatment of PH-ILD is rather sparse. There are 3 companies, all with treprostinil treatments in different formulations and all of these treprostinil treatments continue to have a range of challenges. Seralutinib with its different mechanism has also run into recent challenges as Gossamer's Phase III PROSERA trial in PAH did not meet its primary endpoints, coming off challenges in Phase II as well. And the result of the recent PROSERA trial outcome, Gossamer has paused its planned studies in PH-ILD.

So mosli, on the other hand, with its first-in-class opportunity as an inhaled sGC activator has once-daily dosing, positive tolerability and positive activity in its profile from Phase I studies, and this really positions mosli to be a leader in the treatment of patients with PH-ILD upon its approval.

I also wanted to share about -- and this is Slide 25. I also wanted to share our thoughts about how we see PH-ILD and the market and how it's going to develop. We actually think the PAH market provides a likely road map for that development. In the early days, supportive care was the only option for patients with PAH. And this is what we currently see, and that's the reality of PH-ILD patients in most regions outside of the U.S. where there are limited treatment options.

Over time, drugs with newer mechanisms were approved and combination therapy involving multiple mechanisms of action became more common as the median survival of these PAH patients has also steadily increased as time went on from 2.5 years to where they are today at 12 to 15 years and treatment guidelines evolved alongside the data, which reinforce the evolution of the treatment paradigm.

Today, revenue in the PAH market has really reached a stellar level at $100 billion in aggregate sales and a robust $7 billion per year with 15 drugs approved, and there remains a good pricing environment and commercial opportunity for these newer therapies because this is driven by the complex nature of PAH.

And finally, a key takeaway is that today, over 40% of patients with PAH initiate their treatment with dual therapy and 15% of these patients will add a third therapy by the end of the year. This combo therapy, as Matt said, is really the norm. And so we are currently deep into our Phase II study exploring mosliciguat in our blinded Phase II placebo-controlled and randomized study in adults in PH-ILD. The study is a multicenter study across the globe. We're targeting 120 patients. We ended enrollment with 135 patients.

During the screening period, the investigators look hard to find patients to confirm ILD, elevated baseline PVR indicative of PH and limits on the level of fibrosis and emphysema as determined by CAT scan. If eligible for the study, the patients then randomized 2:1 placebo -- drug to placebo and then they go through a rapid up titration, and that moves from 1 milligram to 2 milligrams to 4 milligrams. And Matt may have spoken about it, but we've seen really great progress there with the vast majority, over 95% of our patients achieving that 4-milligram dose and sustaining on well through the week 16 period. So that's been very attractive and positive.

And at week 16, the primary endpoint is change from baseline PVR, and that's determined at 16 weeks alongside the secondary endpoint of change from baseline of 6-minute walk and change from baseline NT-proBNP. And then the patient moved on to week 24, secondary and exploratory endpoints, and then they all go on drug if they weren't on drug into the long-term extension.

Slide 27. So very importantly, and as we get closer to data in the second half of this year, we focused very heavily in designing our Phase II study and defining our patient population. And we carefully designed around the Seventh World Symposium on Pulmonary Hypertension, and these guidelines are crucial for PH-ILD patient selection. We targeted patients with worsening symptoms of PH, mild-to-moderate impaired lung function based on pulmonary functional testing, elevated PVR and mean pulmonary arterial pressures were crucial. And also, we excluded severe emphysema to ensure a cleaner ILD population. The result is that the study population closely mirrors the recommended guidelines and more severe patients.

And on Slide 28, as you can see, this effort is reflected in our baseline data in FOCUS. Our mean PVR came in at 7.1 wood units, so very elevated. Mean pulmonary arterial pressures of 39.3, consistent with our desired thresholds and confirming we enrolled patients with significant hemodynamic involvement.

The lung disease mix also looks well balanced, and we protected for emphysema, both in number of patients and level of severity as determined by the CAT scan. And this was very important from all of those learnings. And we also explored background therapy, including exploring PDE5s on background, and this is also consistent with real-world practice. So this careful patient selection and enrichment gives us confidence we've enrolled the right population to detect meaningful treatment effect and are very much looking forward to our Phase II data in the second half of this year.

Matt, back to you.

Awesome. Thank you. Thanks, Drew. So look, a lot to be excited about on the program here. I just want to -- a couple of quick reminders and a summary on Slide 22 and 23 here -- on Slide 22. So Drew talked about this in detail, but just as a reminder, the primary endpoint of this study is PVR. That is the same as the primary endpoint for the Phase II programs across a variety of other PH-ILD studies or mechanisms or drugs. And so we're doing the same thing following a well-trodden path there.

We will then, in Phase III, move to 6-minute walk and other clinically relevant endpoints as the way that the trial is measured. I want to remind everybody, this study is not powered to achieve a p-value on 6-minute walk. We may or may not achieve a p-value. And what we're really looking for is affirmation of dosing, affirmation of safety, affirmation of PVR in this patient population. And we will obviously look for interesting trends and patient level data on 6-minute walk. But I want to make sure we've been clear ahead of time. This is not a study designed to achieve a p-value on 6-minute walk, and that's not what we're looking for as our own criteria to go from here. That's the point I wanted to highlight. I want to highlight it now while having not seen any of that data so that I can't possibly be telegraphing anything about the study other than how it was designed.

On Slide 23, just to recap what Drew has said here. First of all, again, with appreciation of the Pulmovant team. This study enrolled very quickly with all the patients enrolled within 12 months of the first patient being dosed. Early discontinuation rates compare favorably to what we've seen in previous PH-ILD studies. Look, with this and $20, you can buy 2 pizzas at Domino's, but our investigators are enthusiastic about the program. They're excited. The feedback is good. I think we're feeling great about how the study is being run.

And then -- and this is a great thing for safety. It's a great thing for the opportunity. As Drew said, 95% of the participants reached the maximum dose during their titration and all of the blinded safety reviews and the ongoing assessments by the DMC have continued to affirm the safety of the program and allow people to run the study. Obviously, there's lots of things that don't get revealed until the data is unblinded, but it certainly gives us comfort that the patients are achieving a high dose and the things are moving as they should be. So again, thank you to Drew. Happy to provide this update now ahead of that data. I'm really looking forward to seeing the outcome from this program in just a few short months at this point. So looking forward to it.

Lastly, in terms of the pipeline updates today, I'm just going to give a brief recap of where we are on brepo. Brepo has been the focus of so much of our conversation for the past 10 months. It's less of a focus today as we're in execution mode there. But just as a reminder, on Slide 25 here -- sorry, that's -- I'm looking at the wrong slide numbers. As a reminder on the next slide, on the first slide of the brepo section, it's Slide 32, sorry. Look, this is a huge opportunity for us. There's possibly close to 300,000 patients addressable by the existing indications and just a ton of data coming over the next 12 to 24 months between the potential approval, obviously, in dermatomyositis, but also the NIU data, the potential for the NIU launch, the ongoing program that we'll start enrolling soon in cutaneous sarcoid, the currently enrolling study at LPP and potentially more indications to come. So just a lot of great stuff coming for brepo and a really exciting moment from here.

On Slide 33, we've put this up a few times, but just to remind people, first of all, these are sick patients. And there are really very few options for them in dermatomyositis. As a reminder, 75% of these patients are on principally steroids and in many cases, on very high doses of steroids, over 10 milligrams a day for a good portion of the year. And beyond that, it's a combination of IVIG, which, as a reminder, the sort of established treatment paradigm for IVIG in dermatomyositis is somewhere between 4 and 5 days a month consecutive in an infusion center. So a really arduous path. And then other than that, it's off-label stuff, much of what has not been successful in studies, but is used because there's no other options. So we feel really great looking forward here to our ability to bring a new option to these patients.

And on Slide 34, further underscoring -- and again, this is not new. We presented this before, further underscoring the need here. These patients are treated -- as with PAH for that matter, with polypharmacy on multiple lines of therapy, they're bouncing around. They have accumulated organ damage with high systemic corticosteroid exposures. It's just a tough experience for these patients, and we think a new option is going to go far.

We're not saying a lot on Slide 35 about our commercial progress. First of all, it is and will become a more competitive field. And second of all, where mosli just head down in execution mode. But I'll just say, suffice to say, we're doing all the things that you would expect us to be doing at this stage. We're in the thick of payer engagement. We're working with the physician community. We're partnering with specialty pharmacies to make sure distribution is effective for these patients.

We've built a strong commercial team that we're really excited about, and we continue to do unbranded patient engagement. We talked about dermatomyositis.com when we got together in December. And I'm super pleased with the work that team is doing. I think they are executing on the commercial side with the same vigor that they executed on the clinical side, and I'm excited to see what we're able to do there later this year and beyond.

We have also been moving along on the scientific and medical side. As you look at Slide 36, this is a small subset of the presentations that have been made of this data, but this data has been presented all over at this point and continues to be presented all over, both at the major medical meetings as well as at a whole host of regional myositis meetings and rheumatology meetings. And notably, in March, the Phase III data was published in NEJM, which is a testament to how exciting the data is, a testament to the importance of the study, the quality of the study, and we couldn't be more excited for that publication as well.

Finally, just a super quick recap on LPP, which we announced just about 1.5 months ago. A fourth indication for brepocitinib. It's a highly morbid disorder with no FDA-approved therapies. These patients are miserable. They are in a ton of pain. It's a really tough disease that in addition to pain causes itch, burning, redness, scaling, generally irreversible hair loss. There's probably 100,000 or so such patients in the U.S. It's been growing in prevalence over time, and there's nothing approved. So we have an opportunity to do something really interesting for these patients.

Our trial design on Slide 38, we talked about when we first unveiled the program is a sort of continuous enrolling Phase IIb/III pivotal that's designed to give us endpoint validation and is going to get us into hopefully registration there. So we're really looking forward to that.

And there's just a ton of reasons to be excited about the program on Slide 39, the high unmet need in LPP, the mechanistic rationale for brepo is strong. It's a Th1-dominant disease, where dual JAK1/TYK2 inhibition should work specifically well. We think we've got the right trial design, and there's obviously some overlapping prescriber base and KOL community with our existing indications. So it all sort of fits together, and we're excited to see how that program continues from here.

Great. Okay. I'm going to wrap up quickly with the financial update, and then we'll get to Q&A. So I'm not going to spend a ton of time on this. Financial quarter was relatively straightforward. We continue to be in a strong position from a cash perspective, $4.3 billion in cash and cash equivalents as of 3/31 before the Moderna settlement, no debt. We continue to retire shares, repurchased a fair amount in this quarter. We continue to have an active program. And spend continues to be sort of as it has been. Over time, R&D has grown a bit and the scope of the programs have increased, but that's all for the good and looking forward to the future.

There is a couple of slides in here that I'm not going to talk to now, but we've gotten a few questions on accounting treatment as the launch gets closer. And so there's some good reference material in here on Slides 44 and 45 if you're trying to build models and understand our financial statements in the future. And look, I've talked about this a fair amount already, but on Slide 46 and 47, we just have a great run ahead of us here. We've got a lot to do. Obviously, we've been fortunate and have had high-quality execution so far with the quality of our data. It sets a high bar for the stuff coming next, which I couldn't be more excited for. So a lot of really great data coming in our existing programs and new programs and looking forward to sharing all of it in the period to come as well as obviously getting back on the commercial arena and watching all of that play through.

So with that, I'm going to say thank you again. I'm going to say thank you to, obviously, all of you for listening. Thank you to all of our teams, Pulmovant, Priovant and Immunovant for continuing to run high-quality studies, executing well, generating quality data, couldn't ask more of these drugs, couldn't ask more of these teams. And obviously, a great thank you to the investigators and the patients who work with us and make this happen. So thank you to everybody who makes this work. And I'm going to pass it over to the operator for Q&A so that we can get to it.

[Operator Instructions] And our first question is going to come from Corinne Johnson with Goldman Sachs.

Happy birthday to Papa Gline as well. Maybe you could just contextualize the ACR responses you saw here at 16 weeks first. I think more kind of typical in later-stage studies, there's a 24-week reporting time line. And how would you expect those responses to trend with more time on therapy with kind of implications then towards the randomized withdrawal phase?

Yes. Perfect. Appreciate it. Look, I think the first answer to that question is we don't know. This is the first time patients have been treated with this drug and the first time this patient population has been studied this way in detail. Sicker people tend to need more time to get better in general, and that's why I made the comments I made about the Phase II sort of randomized withdrawal period. But in terms of week 16 versus week 24, I don't know. I'll say I don't think there was anything specific about the data leading into week 16 that suggested we were done. And I think there's certainly a possibility for continued improvement with therapy over time. But we'll find out as we look at that part of the patient population. Thanks, Corinne, I appreciate the question.

And the next question is going to come from Yasmeen Rahimi with Piper Sandler.

Congrats team and congrats to Papa Gline for also achieving a major milestone of 75 years. So happy birthday to him as well. Quick question on mosli. Congrats, we're very much looking forward to the data. You've been very granular on sort of the baseline as well as what you're seeing of up titration and safety. Have you been able to look at whether your assumptions for standard deviation in PVR and 6-minute are sort of tracking in alignment with what you're seeing? And I'll jump back in the queue?

Yes. Thanks. I appreciate it. So look, I think the short answer to that question is we are largely blinded to all of that data and we don't have a lot of information about it. So it's hard to say. But I think given the patient population we enrolled, we feel pretty good about where the study is headed. And we think we've got an efficacious drug. But we don't have a lot of information about sort of ongoing distributions because the way the study has been blinded. Thank you.

And the next question will come from Andy Chen with Wolfe Research.

So Matt, I'm aware that you said with Immunovant, you haven't analyzed IgG reduction, but that's still my biggest question. So other FcRn drugs, they don't seem to be able to achieve this level of efficacy in RA and people blame it on fab glycosylation. Do you somehow have ACPA antibody reduction data? Or will we see that data before you unblind the period 2 data? And do you expect ACPA reduction to be less than IgG reduction?

Look, I don't have that data now, as I said, so I can't answer the question. We know from our Phase I studies that IMVT-1402 suppresses IgG quite deeply relative to other drugs. And given the quality of the clinical data we've seen on ACR, I think it's certainly a thing to speculate on that the overall profile of 1402 is part of what's contributing to our ability to deliver this data. Obviously, it's also a different patient population that has been studied, and it could also be partially patient selection. And I think that could certainly be playing a role here. So I think those are both important.

Look, I think we will continue to analyze this data. I don't know at this stage exactly when we're going to present what data. So I don't have a good answer to like what you're going to see before or after the period 2 is unblinded. I think we will provide more information about what we've seen, about what our analysis looks like when we're sort of prepared to talk about the full future of the program. I'll say, I think mosli, this has been a blessing but also its curse. We've been -- wonder if this data is going to also establish a leadership role for us along the lines of which others may follow. So I do think we're going to be a little bit conservative on what exactly we say from a competitive perspective. But overall, I think the data are starting to speak for themselves here in terms of the quality of what we're able to do, and I hope we are continuing to able to see that as the data mature. Thank you, Andy.

And our next question will come from David Risinger with Leerink Partners.

So congrats on the phenomenal data this morning. My question is on mosli. So if the Phase II FOCUS study surprisingly shows a statistically significant benefit on 6-minute walk, could it represent a pivotal study? And what would the requirements be in that scenario for a future NDA filing? And then just one other on mosli. Is the company considering development of mosli in any additional indications?

Thanks, Dave. On stat sig of 6-minute walk, I think it's impossible to say exactly what we would do until we saw the data. And so if the data look good enough to support a productive conversation with FDA, I think we would have a conversation with FDA and the FDA has been aggressive lately on conversations about single pivotal designs. So never say never is the answer. I want to be clear, it's not the base case expectation and the study is not powered to show a benefit on 6-minute walk. So we'll see what we see. But look, I think given where we're at, we'll certainly take that as we go.

And in other indications, I'll say, every sign around mosli is pointing to an effective exciting agent with a lot of things we could do with it as we watch the field around us. Others are showing us good ideas all the time in terms of how these mechanisms might work. And we have some of our own that others haven't shown us yet. And so I think there are absolutely opportunities for indication expansion. Although I remember we got this question about 40 times when we first unveiled mosli and our comment then, which is still our comment now is, man, PH-ILD is an area with a lot of unmet need. And even if it were the only thing we ever did with mosli, it's a big opportunity with a lot of value to deliver to patients. So I think there's a lot of different ways to go there.

And our next question will come from Yaron Werber with TD Cowen.

Great. And also congrats on the difficult to treat RA study. So a question actually about that. Is there any chance you can amend that protocol and essentially run period 1 and then sort of get new patients completely into period 2. So you're not going to have that step-down issue? And then secondly, based on our analysis, we think that about 75% of patients are ACPA positive. Is that still kind of what you think the data shows?

Yes. Thanks, Yaron. Look, I think on your first question, there's a lot of things you could imagine doing. I think the truth is between this data and detailed patient level analysis of this data plus the period 2 data, we're going to have a pretty good sense for what we've got and a pretty good sense for what we need to do going forward. And so I don't know that we would gain that much from dragging this study out given the quality of the data we're seeing here. So I think we're going to do that analysis in detail. I think we're going to have the conversation with FDA, and I think we're going to plot a course forward. But I think we'll have a pretty clear sense. And then look, we've done some commercial analysis of the market in various settings. There's an updated version of analysis actually in Immunovant's 10-K that was filed today. I think your number is within the range of what we have seen in the literature for ACPA-positive patients generally. Thank you, Yaron.

And our next question comes from Brian Cheng with JPMorgan.

In this RA EXPLORE trial, since there's no washout period between period 1 and 2, I'm curious if you have some thought around the tail of the efficacy from dose going from drug to placebo. You said that period 2 might be less meaningful. Are you saying that 12 week may not be enough to fully drive the separation?

Yes. I appreciate the question, Brian. And just to reiterate, I just like -- look, I think, first of all, it's hard to know exactly what the tail will be at the end of dosing at the end of week 16. So that's like one piece of this. Obviously, period 2 is blinded, so we don't know now anything about what's in there. So that's all sort of a part of that.

Look, I'll say the other thing is, and just to reiterate what I said earlier, I think given that the period 2 primary endpoint is losing an ACR 20 response, if you imagine a patient who has achieved an ACR 50 or an ACR 70 response, even if they start worsening on the first day of period 2, it just takes some time to give up that level of response. And so that's where I'd say like the quality of the data in period 2 is -- the quality of the data in period 1 is it's always counting against period 2, irrespective of the pharmacokinetic effects of withdrawal of the drug. So I think it's -- remember, every ACR 70 responder is an ACR 50 responder is an ACR 20 responder. So it just takes time to come off that hill. We have people who've achieved a lot of benefit. So that's that. Thank you.

And our next question will come from Dennis Ding with Jefferies.

For PH-ILD, I'm curious what are your thoughts around the Phase Ib data and the interpretability of that data in the small number of patients. Specifically, why did the 4-milligram cohort outperform so much relative to the 2-milligram dose on cGMP and also cardiac output?

And I wonder if you're expecting -- if you should expect a big increase in cardiac output since mosliciguat is locally delivered to the lungs and it's not really a systemic.

Thanks, Dennis. I appreciate the question. Look, I think -- the first answer is 4 is twice 2. So there's just a lot more drug being delivered. The second point I'll make is, remember, there are 170 patients across the Healthy Volunteers program. And so while the specific study that you're referring to may have had a smaller patients, we have a large body of evidence at this point across mosliciguat being administered in a lot of different settings.

And I'd say the dose-dependent improvements in cGMP were broadly consistent across all of that data. The dose-dependent improvements in PVR were broadly consistent across all of that data. So I think we like generally think we know what we've got.

I think with a single dose, you saw a real robust growth and immediately right away in cGMP. I think the thing that was exciting for us is it demonstrated that the inhaled approach was really buffering us from a systemic result. and that was really important for us. And I think we'll see that as we go forward.

This inhaled approach is so important because you can get the drug to the well-ventilated parts of the lung without worrying about those systemic effects. And so I think that's the biggest takeaway was we saw cardiac output, we saw mPAP reductions. These are the things you want to see, but these were single-dose studies. So now we'll see them much more robust fashion in our Phase II.