Roivant Sciences Ltd. (ROIV) Q4 2025 Earnings Report, Transcript and Summary

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 [indiscernible], CEO of [indiscernible]. 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 to be talking. We have 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 DTRA as well as a planned spotlight, we've been planning to do for a while on mostly getting into that data, which we 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 involved that is 1 small bit of executive privilege and wish my father Jerry, a happy 75th birthday, today it's his 75th birthday. So happy birthday dad. He sometimes listen in on these calls. I don't know if it's listening in. Now if now he will be 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 drawn on some of the other things for today, but it's actually pretty great is that brepocitinib was awarded breakthrough designation -- breakthrough therapy designation or continue 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. We're excited about how it'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 basically on response rates across ACR20, 50 and 70 in the TTR 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 on that study in the second half. and Earlier in this quarter, we announced the failure of the bitokamab studies in TED, but also the hyperthyroid patients show normalization, which is supportive of our grade studies, which are ongoing and continue to enroll well also. And then finally, partially, 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 a 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 we're going on, we will hopefully be launching brepocitinib [indiscernible] 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 mostly [indiscernible] Phase IIb top line data is expected in the second half. That also will potentially underscore that as a really important program, and hopefully [indiscernible] going forward to that data, I just talk more about it. Obviously, DDTRA, some of the data is around today, but we're 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, there's 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 and a ton to look forward to, and frankly, as in the -- as much in the windshield in the rearview mirror. I think I've got the car analogy right there. Great. Okay. I want to go in now without spending more time with the [indiscernible] and talk a little bit about this DTRA data, which I would call surprisingly good. We were pretty excited to see what we saw here. It is been only 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. So this was a unique study design 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 to, for example, TNS 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 auto antibody positivity. We had a criteria on [indiscernible] positive above a certain level. and that was also specific to the study the design. And then the other way I was just selling was unique is it was a randomized withdrawal study with 2 periods: first, an open-label active treatment period of 16 weeks at high dose 1402, 600 milligrams, followed by a Period 2 12-week rerandomization where ACR20 responders at week 14 and 16 both are rerandomized into a 12-week randomized withdrawal period where some of them stay at 600 and some go down to 300 and some of the nonplacebo. 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. So we've not any data or information about Period 2 to share today. And then even for period 1, there's whole 1 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 we're going to be sharing a pretty limited subset of this data today. On Slide 9, you can see based on characteristics for the patients in the study, [indiscernible] 165 evaluable patients, I'm not going to go through all of this in detail, I would 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 DSAH28 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 [indiscernible] study or really any of the later line RA studies that have been run. And actually, one thing that we're highlighting a particularly interesting, 65% of these patients roughly have failed specifically JAK inhibitors. And notably, and we'll highlight this elsewhere as well, basically every single one of the patients who fail the JAK inhibitor also failed the 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 the appropriate caveats for an open-label study, these numbers are high. We saw 73% of patients roughly with ACR20 responses, and not just that, but we saw quite deep responses. We saw over half of patients with the ACR50 and over 1/3 of patients with an ACR70. And notably, once you get on to the deeper end of that with ACR50 and ACR70, 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 experience, remember those patients, 107 of them on 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 positivities and orthogonal mechanisms, some of the other anti-inflammatory options and then for [indiscernible] positive patients, this could be an effective treatment option. So like, 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 [indiscernible] today, were safe and well tolerated in the study, nothing new regulated 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, if 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 randomize withdrawal period, the primary endpoint of period 2 is do patients taken off drug lose their ACR20 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 ACR20. But the truth is, once you're looking at ACR50 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 was 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 diversely depending on FDA feedback, potentially situations where we do see a p-value 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 the results 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 state is that will be kind of a 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, but 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 just want to also just give a shout out to the minima team who have continued to execute really well. Obviously, the data itself is strong, but also the speed of enrollment, the [indiscernible] removing study, the full enrollment on CLE. And I think that spans all of our programs. I think we're exciting about what -- obviously, what [indiscernible] has been able to do with brepocitinib from a clinical enrollment perspective. We're excited about the speed of enrollment 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 on [indiscernible] execution, so much appreciation for the enormous number of people who are working toward those goals. Cool. I'm going to pivot now to mostly [indiscernible] and do a little bit of a data preview their 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 interaction here. And then you all heard from Drew back at Investor Day in December, he's in the room with me and is going to talk through a little bit more about the program. Look intense unmet medical need. These patients in the extreme significant proportion of them die. They're very sick. There is currently only 1 approved mechanism with 2 therapies, and we think there's probably 200,000 patients for rest of the U.S. and Europe. And that one mechanism for [indiscernible] 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 some of the [indiscernible] benefit already, and we're hoping to add to that. Mostly has a completely differentiated mechanism of action for the disease. It's an STC activator. It's an inhaled STC activator is potentially the first nonpropropanil that could be available for these patients. We expect this to be a polypharmacy combination therapy market as PAH has been. And we think mosli 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 potential patients and Drew will remind us of the state specifically, we saw among the best PVR reductions to date and 1 thing we're going to run people up today is that although we saw a 38% PVR reduction in some of those patients, that basically anything that has ever shown 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 PPR 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 with a little summary at the end and the rest of the presentation.

Thanks, Matt. And I can tell you there's a lot of excitement about most So mosli is an inhaled SGC activator that's delivered directly to the lungs to activate SEC and restore impaired SGC function. SGC is a key enzyme in the NOCCGMP pathway and in attentive stressed 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 [indiscernible] binds to the heme pocket independent of the need for NO and heme, producing CGMP, which results in vasodilation of the pulmonary arteries and potential reduction of fibroprosis 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. Everyone has got...

Okay. Okay. [indiscernible] slide numbers, you call thme. I just want to make sure we are davancing. Both of these preclinical properties led Bayer to take mosli into Phase I trials in a total of 170 patients, including healthy volunteers and patients group 1 PAH and Group 4 CCAP. In the Phase I study, BIR study most in 132 healthy volunteers and 38 PH 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 mosli [indiscernible] 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 1 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 PBR reductions amongst the highest reduction seen in single and multi-dose trials in PH treatment space. With 1 dose 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 NPAT 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 PH. With treatment-emergent adverse events being mild to moderate intensity across both groups, and all doses were well tolerated, and we did not see significant cough, which is often exacerbated by inhaled [indiscernible], 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 of these Phase I tolerability and clinical profile, we look to take mosli into Phase II development in 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 a 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. They're 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 [indiscernible] 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 PERSERA trial in PAH did not meet its primary end points, coming off challenges in Phase 2 as well. And the result of the recent PRERSERA trial outcome [indiscernible] 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 being 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 their are limited treatment options. Over time, drugs with newer mechanisms were approved, the combination therapy involving multiple mechanisms of action, became more common. As a median survival of these PH 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 evolve alongside the data, which reinforced 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 emphysema as determined by CAT scan. If eligible for the study to patients that are randomized 2 to 1 drug placebo and then they go through a rapid 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 changed 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've focused very heavily in designing our Phase II study and defining our patient population. And we carefully designed around the Seventh World Symposium of 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 [indiscernible] 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 TVR 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 from 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 a meaningful treatment effect. We're 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 the 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 traveled path there. We will then, in Phase III, move to a 6-minute walk and other clinically relevant endpoints is 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 have a p-value. 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 in 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 design 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 home on that 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 in $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 reach the maximum dose during their titration and all of the blinded safety reviews and the ongoing assessments by the DMC continues to affirm the safety of the program and have people to run the study. Obviously, there's lot of things that don't get revealed till the data is unblinded, but it certainly gives us comfort that the patients are achieving high dose and the things are are moving as they show basis. 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 months at this point. So looking forward to it. Lastly, in term of the pipeline updates today, I'm just going to give a brief recap of where we are in brepo. Brepo has been the focus of so much of our conversation for the past 10 months. It's less of the 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 line of the breo 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 the random [indiscernible], but also the NIU data, the potential for the NIU launch, the ongoing program that will start rolling soon and [indiscernible] currently enrolling study in LPP and potentially more indications to come. So just a lot of great great, great, 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 etin4and 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 it's used because there's no other option. 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 we age 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 a -- and will become a more competitive field. And second of all, we're mostly 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 are in the thick of payer engagement. We are 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 am 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've also been moving along on the scientific and medical side. If you look at Slide 36, this is a small subset of the presentations that [indiscernible] 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 myocytes meetings and otology meetings and notably in March the Phase III data was published in NEJM, which is a testament to how exciting the data is the custom of the importance of the study, the quality of the study, and we can'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 [indiscernible] hair loss. There's probably 100,000 or so such patients in the U.S. that'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 [indiscernible] 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 JAK innovation 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 intent to see how that program continues from here. Great. Okay. I'm going to wrap up quickly with a financial update and then we'll get to Q&A. So Max spent 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 [ 03/31 ] before the Moderna settlement, no debt. We continue to retire shares we purchased 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 at 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 or 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 that 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 assay thank you to, obviously, all of you for listening. Thank you to all of our teams, [indiscernible] and [indiscernible] for doing to run high-quality studies, executing well, generating quality data. I couldn't ask more of these drugs, could mess where 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] So our first question is going to come from Corinne Johnson with Goldman Sachs.

Maybe you could just contextualize the ACR responses you saw here at 16 weeks as first I think, more kind of typical and later stage in a 24-week reporting time line? And how would you expect those responses to trend with more time on therapy with kind of implications set towards the randomized withdrawal phase?

Yes. Perfect. I 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 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 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, Corrine, I appreciate the question.

And the next question is going to come from Yasmeen Rahimi with Piper Sandler.

Quick question on [indiscernible]. 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 in 6 minutes or 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 strike. But we don't have a we don't have a lot of information about sort of ongoing distributions because the late study has been blinded.

And the next question will come from Andy Chan 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 fat 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.

I don't have that data now, as I said, so I can't answer the question. We know from our Phase I study 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 like certainly a thing to speculate on that the 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 know a good answer like what you're going to see before or after the Period 2 was unwinded. I think we will provide more information about what we've seen, about what our analysis looks like when we're prepared to talk about the full future of the program. I'll say, I think mostly this has been a blessing but also its curse. We've been a [indiscernible] wondered 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 able to see that as the data mature.

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 that take a 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 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 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 on different ways to go there.

And our next question will come from Yaron Werber with TD Cowen.

Great. And also congrats on difficult to treat or study. So a question actually about that. Is there any chance you can amend that protocol and essentially 1 -- 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. 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 as an update on version analysis actually in [indiscernible] 10-K that was filed today. I think your number is within the range of what we have seen in the literature for [indiscernible] patients generally.

And our next question comes from Brian Cheng with JPMorgan.

And this area EXPLORER trial, since there's no washout period between Tier 1 and 2. I'm curious if you have some thought around the tail of the efficacy from those going from drug to placebo? You said that Tier 2 might be less meaningful. Are you saying that 12 weeks may not be enough to fully drive the separation?

Yes. I appreciate the question, Brian. And just to reiterate, I guess like, Look, 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 1 piece of this. Obviously, Period 2 is blinded, so we don't know now anything about what's in there. So that's all 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 ACR20 response, if you imagine a patient who has achieved an ACR50 or an ACR70 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 to 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 ACR70 responder is an ACR50 responder as an ACR20 responder. So it just takes time to come off that hill. We have people who we've achieved a lot of benefit. Just so that's that.

And our next question will come from Dennis Ding with Jefferies.

For will be curious where your thoughts around Phase Ib data and the interpretability of that data in the small number of patients Specifically, why did the 4-milligram cover outperformed 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 in mosli 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 to, 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 be a smaller pace, we have a large body of evidence at this point across mosli 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 will probably consistent across all that data. So I think we like generally think we know what we've gotten.

I think a single dose you saw 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. At 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 NPAP reductions these are the things you want to see, but these were single-dose studies. So now we'll see the much more robust fashion in our Phase II.

Thanks, Drew. Yes. The other thing I'll say, just because the Drew was answering that question is, look, I think one of the things that makes PH-ILD exciting as a commercial opportunity is it really requires inhaled therapy precisely because of this effect. And so the competitive landscape will be thinner and the ability to develop drugs for this market will be more challenging because you need to sort of thread the needle on systemic vasodilation. And so we feel that gives us an advantage as well and frankly increases the level of need for the patients. So look, I think it's all all setting up in that way.

[Operator Instructions] Our next question comes from Derek Archila with Wells Fargo.

This is Jacob on for Derik. Congrats on the 202 data. So real quick on safety. I just want to clarify firm, there were no LDL changes or other events of interest observed, right? And then Secondly, on the -- given the strong activity in Period 1, how does this inform your trial design strategy in the future? I know you mentioned and this is likely 1 of a couple of registrational trials, but do you think this data changes that?

Thanks, Derek. Great questions, both, although I'll remind you politely for the other analysts, we're trying to keep to 1 given the number in the queue, but I appreciate both questions, and I'll take both of them. First of all, on safety, in fact, what I can say here is not just in this study, but across now hundreds of patients dosed across 1402 studies, the DMC has been watching that issue, and we have seen no impact on [indiscernible] LDL across the hundreds of patients dosed with 1402. So while I don't have the very specific data to share for this study numerically. I think the answer is we've seen literally nothing [indiscernible] from 1402. And then, look, given the level of activity in Period 1 on trial design, I think the answer is, we're going to have to take this data when we get it. We're going to have to look closely at it, and we're going to have to have a conversation with FDA about where we stand and what we need to do. Obviously, the stronger the data from the first study or from this study overall, the more compelling that conversation is. And so I think we're excited about this data. Our belief is that we should be able to run a lean program from here given the patient population we're focused on given the level of need in this patient population, but that's a conversation we're going to have to have together with FDA in the months to come.

And our next question comes from Samantha Semenkow with Citi.

Congratulations on the data this morning and all the progress. Now that you have this first data in RA for 1402, I'm wondering also how we should be thinking about the CLE data coming up in the second half? Will that readout include the entire 52-week study? Or will that just be the 12-week randomized portion? And what magnitude of treatment effect do you think would be meaningful here?

On the first question -- thank you, I appreciate the questions. On the data, that will just be the 12-week period. And that's what we'll have by that. So that's what we'll be able to share. And in terms of what treatment effective meaningful, look, I'll say 2 things. One is we will have an opportunity to continue to talk about what we expect to see from that study over time, and we'll probably do a little preview of that data before it comes. Secondly, CLE is a little bit different than some of these other indications. I mean it is commercially more competitive and there's other mechanisms coming. And so I think the bar for us is not just sort of per se clinical meaningful. I think the bar is like do we think our data is good enough to support a program in the face of where the landscape is headed. And so we're going to look closely at that data. We're going to look at what we see, and we're going to make a decision based on the totality of the data. But I think the bar there is pretty high, and I think we knew that going in.

And our next question is going to come from Thomas Smith with Leering Partners.

Congrats on the really stellar RA data here for 1402. Just wanted to ask one, if I could, on the pivotal Graves' program. Any updates you can share with respect to patient enrollment? I think you were initially kind of gating some of the scale-up activities and trying to get a sense for how the early enrollment trends were going. But just wondering if there's anything that you could share there in terms of pace cadence and maybe patients being enrolled, anything different from initial expectations?

It's a good question. Look, I think the short answer is we have a pretty high bar for ourselves when we started the study, and we didn't exactly know because there hadn't been a lot of development in Graves' disease. I think we can now say enrollment is going great. We're on track. We'll have the data in 2017, as we previously discussed, and a lot of enthusiasm and a growing amount of enthusiasm as we continue to add sites, as docs continue to get comfortable with the study. So I think overall, really happy with how that program has evolved. And I'll again take the opportunity to say, I think all of our main teams at this point are executing at a really high level from clinic enrollment perspective. And I think that's been a real driver of value for us.

And our next question is going to come from Alex Thompson with Stifel.

This is Patrick Colton on for Alex. I guess, just kind of building on the path forward here in RA, looking at period 2, I guess if you were 300-milligram ROm performs just as well as 600-milligram, how are you guys thinking about your dosing strategy going forward in Phase III?

I -- it's fun to sit here and think about like what has in the Phase II study, we see as good -- first of all, it's a randomized withdrawal study, so I was like trying to figure out exactly what it would look like for the 300 and 600 to perform equivalently. But look, I think overall, it's just too early to say. We've got to look at the data. This is a patient population with extremely significant unmet need. And without -- I mean, to say without a lot in development is an understatement. I think like basically, we are following a new course for this patient population. So I think we've really got to look at that at that data and get an outcome from it. I think the inclusion of 300 and 600 in the study was important because FDA, especially in new indications, especially in new indication s like RA is likely to want some dose-ranging information. But I think we're going to have some flexibility and we're going to get to see. Historically, there has been a separation in IgG reduction, obviously, between 300 and 600. So we'll see how that translates in this population. But I think we have options here.

And the next question comes from Prakhar Agrawal with Cantor Fitzgerald.

Congrats on this impressive data. So maybe on the RA front, given the sample size is quite large, but ultimately, this trial was open-label and some of the ACR responses can be susceptible to open-label nature of the trial. So maybe just if you can expand if you have any data on some of these secondary endpoints, which might be less susceptible to open-label design of the trial? And what gives -- how much efficacy degradation would you assume as you move from an open label to more of a placebo-controlled trial in a registration trial?

Yes, thanks. This is -- it's a great question. It's obviously what was on our mind from the day we first saw the data, I think it is certainly helpful that we're talking about ACR50 -- ACR50 and ACR70 response and ACR20 responses, I think once you get to that level, sort of spontaneous placebo style like [indiscernible] and those kinds are less frequent. We don't have any of the secondaries or additional markers to share. We've been looking at that data hard, and we feel excited about the data based on what we've seen in terms of everything hanging together, but that's about all we're able to say at this point because it's about all we know at this point. One other thing is, we have -- the way the study is designed, the people doing the joint assessments are blinded so they are doing the assessments without knowing anything about the study, what patients are on, where the study they are or whether they're under placebo. That's obviously only one component of the total here, but it is one way for us to get a little bit of a little bit of objectivity into a study that is otherwise at this stage open label, and that is helpful and pretty objective.

And our next question comes from William Pickering with Bernstein.

Congrats on the update. On mosli, you also have a Phase II open label with patients on background to [indiscernible]. What are you hoping to see in that study? And then how are you thinking about broader evidence generation strategy to support reimbursement and mosli in combination with [indiscernible]?

Yes. So I think in the combo study, we have patients on background trospenol. Obviously, in the main Phase IIb, we don't have patients on background [indiscernible]. And the reason we set this up this way is because we know that polypharmacy is going to be a part of the landscape. And so in the phase -- in the subsequent study that we run, we're likely to have some proportion of patients on background [indiscernible] as well. And it felt like going into that state study with no experience treating patients on both drugs was, for a variety of pretty obvious reasons, a liability. And so I think the combo study is, in part, really a safety study. It's just designed to make sure these things can be administered safely together. We will learn from it, the information that will help us designing the stratification rules, help us understand better who's going to be on what in the subsequent study. But I think beyond that, it's hard to say at this point. And that's -- the [indiscernible] still in pretty early days, so we don't have much to to say about it. Drew, anything to add to that?

I think that's exactly the case. We decided not to go on top of [indiscernible] in the first FOCUS study, but we were initially looking at our drug in single agent activity in PH-ILD, and we wanted to have some time to understand that population, understand mosli. Also, as you know, treprostinils do have a sticky issue with cough. And we wanted to make sure that our drug would have a clear path to be able to demonstrate its tolerability profile, which I think has been relatively impressive. So with that, in the later days, we decided with the team to go a little deeper and look at mosli on top of inhaled treprostinil given the confidence we had in mosli after seeing it in our FOCUS study, of course, in an aggregated setting. So with that as a backdrop, as Matt said, we're only in the days, but we actually don't expect there to be much of an issue there, but we definitely want to understand that from a dosing and safety perspective.

And the next question is going to come from Douglas Tsao with H.C. Wainright.

[indiscernible] at progress, Matt, I'm just curious in terms of the RA data, if you've had a chance to sort of talk with some of the KOL physicians on the data. I'm just curious what their sort of feedback is. And they were more focused on yet the response that you saw the breadth of the stock. And obviously, you've got that both so you necessarily have to choose, but if there's anything that would strike for the initial days then?

Thanks, Doug. So we have obviously a bunch of [indiscernible] involved with the study, therefore, we have those conversations continuously and with some of the important ones for the field who have been on multiple of these studies as well. I think in general, the answer is they're super impressed. I think 1 KOL our team roughly as a quote you can't fake ACR70s like this. That the opinion of 1 physician. I think it's true at sublevel, but ultimately, we'll have to see what the rest of the studies show. But look, I think docs are excited. They're excited about the depth of responses. They're excited about what this could mean. And look, I think the most important thing is these are physicians who they're treating these patients. They have no options. Many of these patients are very uncomfortable with a lot of pain. I think they see a new option for this population. And they were hoping for something that worked even a little. And obviously, this is beating that for handling. So I think there's a lot of enthusiasm.

And our next question will come from Dina Ramadane with Bank of America Securities.

Congrats on the data this morning. Just a quick 1 from us. On the nonresponders, could you provide maybe more color on these nonresponders in Period 1? Was there anything you can maybe point to such as prior [indiscernible] therapy or baseline characteristics, such as maybe antibody levels that were the reason for not responding to 1402?

Yes. So we're looking at that in detail now just to try and get some further comfort and understanding about what's going on. I don't have anything to say about it now, but that's exactly the kind of analysis that we're running. And you said nonresponders, just a reminder, 72% or 73% were ACR20 responders. So we're also looking at some of who got to the 20, but not 50, just like trying to get a better sense of what happened there.

Our next question will come from Maresca with Guggenheim.

This is Iris on Seating. Congratulations on the data. My question is on not. Are there any more colors on what proportion of patients were refractory to rituximab and maybe anti-IL-6s amid are relevant enteroplasty patients. So [indiscernible] that with you.

Yes. Thanks. I don't have that in front of me. It's a good question. We have cleaned some of that data. We had a bunch of IL-6 about 6 refractory patients for rituximab, I don't know. And so look, overall, we don't have that share right now. But I think the answer is that the population is consistent with a heavily pretreated population. They've been on multiple lines of therapy. Many of them have failed things in addition to JAK and TNF. So all of those different mechanisms are in. We may eventually share more data on sort of what those different subsets look like, but I think we're particularly enthusiastic about the JAK and TNF combined failures. Remember that over 10% of these patients have failed more than 3 lines of these advanced therapies.

And our next question will come from Sam Slutsky with LifeSci Capital.

This is Kate on for Sam. So I know the strength of Period 1 data has made period to all the more challenging, particularly on ACR20. But looking to period 2, is there a delta versus placebo potentially on other endpoints that would [indiscernible] commercially?

I don't think Phase 2 was really about commercial value at this point. I think Phase 2 is about better understanding the characteristics of the patients seeing erosion of efficacy, starting to understand to separate out drug effect from other things. So I think it's not so much that we're looking for some commercial bar in Phase II. I think the quality of this headline data is such that even if it degrades we're happy with it. And I think even in subsequent studies, I don't know if we're like shooting for this bar per se. This is just a great foundation from which to build something pretty exciting in RA.

And that will conclude today's Q&A session, and I will now turn the call back over to Matthew Gline for closing remarks.

Great. Look, thank you, everybody, again. Appreciate it. There were a lot of questions there. So I appreciate everyone's forbearance and helping us get through it all and then limiting a number of questions, which is a great favor to the people lower in the queue. We need to come up with questions if this has already been asked. So thank you again to everybody for playing along with that. An exciting day for us and exciting data to be able to put out. So thank you again to everybody who makes that happen from the [indiscernible] Roivant team for the patients and investigators. It takes a [indiscernible], and it's a great outcome. It's something that we can really go firm from here. And once again, happy birthday to my dad. Thank you, everyone, for listening, and we'll talk again soon. Have a good day.

This concludes the conference call. Thank you for participating, and you may now disconnect.