Q4 2025 Roivant Sciences Ltd Earnings Call

May 20, 2026

Operator 2: Ladies and gentlemen, thank you for standing by. Welcome to the Roivant Q4 2025 Earnings Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 1 on your telephone. You will then hear an automated message advising your hand is raised. We ask that you please limit to 1 question. To withdraw your question, please press star 1 1 again. 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.

Operator: Ladies and gentlemen, thank you for standing by. Welcome to the Roivant Q4 2025 earnings call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. We ask that you please limit to one question. To withdraw your question, please press star one one again. 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.

Speaker #1: After the speaker's presentation, there will be a question-and-answer session. And to ask a question during the session, you will need to press star 11 on your telephone; you will then hear an automatic message advising your hand is raised.

Speaker #1: We ask that you please limit to one question. And to withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded.

Speaker #1: I would like now to turn the conference over to Stephanie Lee. Please go ahead.

Speaker #2: Good morning, and thanks for joining today's call to review business updates from Roivant's Fourth Quarter and Fiscal Year ended March 31st, 2026. I'm Stephanie Lee with Roivant.

Stephanie Lee: Good morning. Thanks for joining today's call to review business updates from Roivant's Q4 and fiscal year ended 31 March 2026. I'm Stephanie Lee with Roivant. Presenting today, we have Matt Gline, CEO of Roivant, and Drew Fromkin, CEO of Comagine. 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. With that, I'll turn it over to Matt.

Stephanie Lee: Good morning. Thanks for joining today's call to review business updates from Roivant's Q4 and fiscal year ended 31 March 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. With that, I'll turn it over to Matt.

Speaker #2: Presenting today, we have Matt Gline, CEO of Roivant, and Drew Fromkin, CEO of Palmolive. For those dialing in via conference call, you can find the slides being presented today, as well as a press release announcing these updates, on our IR website at www.investor.roivant.com.

Speaker #2: 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.

Speaker #2: 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.

Speaker #2: And with that, I'll turn it over to Matt.

Speaker #3: 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, so I'm looking forward to going through all of it.

Matt Gline: 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, so 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 IMVT-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. A lot to cover. Before I get into all that, use one small bit of executive privilege and wish my father, Jerry, a happy 75th birthday. Today is his 75th birthday. Happy birthday, Dad. He sometimes listens in on these calls. I don't know if he's listening in now.

Speaker #3: Including, obviously, what we announced this morning, which is the preliminary open label period data from the 1402 study in DGTRA, as well as a planned spotlight we've been planning to do for a while on Mosley getting into that data, which Drew will take us through, and some smaller updates on the Representative Program, although exciting.

Speaker #3: So a lot to cover. I want to, before I get into all of that, use one small bit of executive privilege and wish my father, Jerry, a happy 75th birthday.

Speaker #3: Today is his 75th birthday. So, happy birthday, Dad. He sometimes listens in on these calls. I don't know if he's listening in now. If not, he'll catch it on the replay.

Matt Gline: Into the important topics now. Important business topics now. Starting on slide 5. Well, look, this has been a pretty wild 12 months for Roivant. We continue to see just tremendous execution momentum across our development portfolio. Update that will get drowned in some of the other things for today, but is actually pretty great, is that brepocitinib was awarded breakthrough designation and a rare therapy designation for cutaneous sarcoidosis, which just underscores indication selection and development there in terms of what that could mean for those patients. 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.

Speaker #3: Okay. Into the important topics now. Starting on important business topics now. Starting on slide five, look, this has been a pretty wild 12 months for Roivant.

Speaker #3: And we continue to see just tremendous execution momentum across our development portfolio. An update that we'll get drowned in some of the other things for today, but is actually pretty great, is that Representative was awarded Breakthrough Designation and a Breakthrough Designation for continuous sarcoidosis, which just underscores indications selection and development there in terms of what that could mean for those patients.

Speaker #3: Obviously, also, when 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.

Speaker #3: And then a ton of work ongoing in commercial prep for the launch in DM, which, assuming FDA goes as we expect it to, will launch by the end of September.

Matt Gline: A ton of work ongoing in commercial prep for the launch in DM, which assuming FDA goes as we expect it to, will 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 IMVT-1402 showed, we think, clinically meaningful, pretty exciting ACR response rates across ACR20, ACR50, and ACR70 in the D2T RA study in the open-label portion. We'll talk more about 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 H2. Earlier in this quarter, we announced the failure of the batoclimab studies in TED, but also that the hyperthyroid patients showed normalization, which was supportive of our Graves' disease studies, which are ongoing and continue to enroll well also.

Speaker #3: 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 2050 and 70 in the DGTRA study.

Speaker #3: 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.

Speaker #3: And earlier in this quarter, we announced the failure of the botulinum studies in TED, but also that the hyperthyroid patients showed normalization, which was supportive of our GRAVE studies, which are ongoing and continue to enroll well.

Speaker #3: Also, and then finally, hard to believe it was this quarter, but earlier this quarter, we also announced our two and a quarter billion dollar settlement with Moderna, and we expect to receive the first portion of that payment, the $950 million upfront in July.

Matt Gline: 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. 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. 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. We expect the NIU phase III top-line data in the back half of this year.

Speaker #3: 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.

Speaker #3: None of that, though, is to say on slide six, 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 Representative prior to hopefully launching Representative in dermatomyositis by the end of September.

Speaker #3: The phase three study in continuous sarcoidosis, we expect to begin this year as well. And we expect the NIU phase three top-line data in the back half of this year, so a transformative year for BREPO.

Matt Gline: A transformative year for brepocitinib as all of that comes around. We'll spend time on this today, the mosliciguat PH-ILD phase II-B top-line data is expected in H2. That also will potentially underscore that as a really important program, hopefully looking forward to that data and just talking more about it. D2T RA. Some of the data is around today, 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. We'll get the CLE POC top-line data as well. Next year is a huge year with IMVT-1402 data in Graves' disease and MG coming in.

Speaker #3: As all of that comes around, we'll spend time on this today, but the Mosley PHLD phase two B top-line data is expected in the second half.

Speaker #3: That also will potentially underscore that as a really important program and hopefully. Looking forward to that data and to talk more about it. Obviously, DGTRA 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 in a patient level and hopefully with some feedback from FDA on a go-forward plan given what we've now seen.

Speaker #3: 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.

Matt Gline: A ton to look forward to, and frankly, as much in the windshield as in the rear view mirror. I think I've got the car analogy right there. Great. Okay. I'm going to go in now without spending any 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. It has only 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's aware, this was a study in heavily refractory patients.

Speaker #3: 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.

Speaker #3: Great. Okay. I'm going to go in now without spending any more time on the preamble and talk a little bit about this DGTRA data, which I would call a surprisingly good.

Speaker #3: We were pretty excited to see what we saw here is bluntly been a little bit hard to process just how exciting this data is.

Speaker #3: And so we're still doing a lot of work on it. As a reminder on slide eight of what we're talking about today, so this was a unique study designed in a few ways.

Speaker #3: First of all, as I think everyone's 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 two advanced lines of therapy.

Matt Gline: Every patient in this study, in addition to failing steroids and DMARDs, also had to fail at least two advanced lines of therapy. Most commonly, that's two of, for example, TNFs, JAKs, and IL-6s. 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 the design. The other way in which the study was unique is it was a randomized withdrawal study with two periods.

Speaker #3: So, most commonly, that's two 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.

Speaker #3: The study also had a pretty strict entry criteria on autoantibody positivity. We had a criteria on ACPO positive above a certain level. And that was also specific to the study and the design.

Speaker #3: And then the other way, which the study was unique is it was a randomized withdrawal study, with two periods, first an open label active treatment period of 16 weeks at high dose 1402.

Matt Gline: First, an open label active treatment period of 16 weeks at high dose IMVT-1402, 600 milligrams, followed by a period 2 12-week re-randomization where ACR20 responders at week 14 and 16 both are re-randomized into a 12-week randomized withdrawal period, where some of them stay on 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. We don't have any data or information about period 2 to share today. 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.

Speaker #3: 600 milligrams. Followed by a period two, 12-week re-randomization where ACR 20 responders at week 14 and 16 both are re-randomized into a 12-week randomized withdrawal period where some of them stay on 600 and some go down to 300 and some go down to placebo.

Speaker #3: 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.

Speaker #3: On the top line treatment effect from period one, period two is still ongoing with more than half of patients still being dosed in the study.

Speaker #3: So we're not any data or information about period two to share today. And then even for period one, there's a whole bunch of data like IgG, for example, that we haven't analyzed fully and are not ready to share.

Speaker #3: 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 nine, you can see baseline characteristics for the patients in the study.

Matt Gline: 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. A run of 165 valuable patients. I'm not going to go through all of this in detail other than say, this is quite a sick patient population. Obviously, by design, it's refractory, and we'll talk more about that in a second. 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 slide 10.

Speaker #3: We went up with 165 valuable patients. I'm not going to go through all of this in detail other than say this is quite a sick patient population.

Speaker #3: 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.

Speaker #3: 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.

Speaker #3: And so we feel good about who's in the study. On prior lines of therapy, specifically on 10, you can see on the right-hand side, we succeeded with our entry criteria.

Matt Gline: 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. That's very different than either the NIPPON study or really any of the later line RA studies that have been run. Actually, one thing that we're highlighting today, which I think is particularly interesting, 65% of these patients roughly have failed, specifically JAK inhibitors. Notably, and we'll highlight this elsewhere as well, basically every single one of the patients who fail a JAK inhibitor also fail the TNF. This is a TNF and JAK refractory patient population that we're focused on. Look, slide 11 is the headline here. 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.

Speaker #3: That is basically all of these patients have failed more than two 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.

Speaker #3: And actually, one thing that we're highlighting today is 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 failed a JAK inhibitor also failed a TNF.

Speaker #3: So this is a TNF and JAK refractory patient population. There were 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.

Speaker #3: 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 a third of patients with an ACR 70.

Matt Gline: Not just that, but we saw quite deep responses. We saw over half of patients with an ACR50 and over a third of patients with an ACR70. Notably, once you get onto the deeper end of that with ACR50s and ACR70s, you just don't see a lot of placebo response in that level of responder analysis. 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.

Speaker #3: 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.

Speaker #3: 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.

Speaker #3: 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.

Speaker #3: 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.

Matt Gline: 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. One of the things that I think is maybe most exciting about this data is it's basically fully preserved in that subset. 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 to some of the other anti-inflammatory options. For ACPA-positive patients, this could be an effective treatment option. Look, I think on slide 13, just to reiterate what we're showing here.

Speaker #3: 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.

Speaker #3: 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.

Speaker #3: 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 to some of the other anti-inflammatory options.

Speaker #3: And that for ACPO 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 that difficult to treat patient.

Matt Gline: 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 this study and on deeper patient-level analysis. 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. A clean data set overall and further underscoring what we think we've got with 1402. Fast-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.

Speaker #3: 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 this study and on deeper patient-level analysis.

Speaker #3: And also, notably, this is the largest patient population dosed with IMPT1402 to date. It was safe and well tolerated in the study. Nothing new, drug-related from a safety signal perspective identified.

Speaker #3: So a clean dataset 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.

Speaker #3: 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.

Matt Gline: 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. As you'll recall, the randomized 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've been fine if we had seen more marginal benefit on ACR20. The truth is, once you're looking at ACR50 and ACR70 responders, I think the bar has actually gotten a fair amount higher for period 2.

Speaker #3: The data is encouraging. I'll make one comment about it, which is: the depth of responses is exactly what's exciting about the dataset. It's exactly what makes us believe there is something beyond placebo happening in the dataset.

Speaker #3: But as you'll recall, the randomized withdrawal period, the primary endpoint of period two, is do patients taken off drug lose their ACR 20 response in 12 weeks?

Speaker #3: 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.

Speaker #3: 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 two.

Speaker #3: And so paradoxically, I think we still have a good shot of success there. But in some ways, period two was less meaningful than it might otherwise have been.

Matt Gline: Paradoxically, I think we still have a good shot of success there. In some ways, period 2 is less meaningful than it might otherwise have been. 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. 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. 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 H2 of this year. We're working on it right now.

Speaker #3: And I think there are plenty of scenarios where we don't see a p-value in period two and continue forward with the drug given the overall quality of this data.

Speaker #3: And conversely, depending on FDA's feedback, potentially situations where we do see a p-value in period two. And just need to make sure we're comfortable with the plan forward.

Speaker #3: So I think much more interesting than the period two data at this point is more patient-level analysis. As well as the results of those FDA discussions.

Speaker #3: 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 this data, is 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.

Matt Gline: My hope, given the quality of this data, is 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 that 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. 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. With that, I actually just want to also just give a shout-out to the Immunovant team who have continued to execute really well.

Speaker #3: 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 Immunovent has now done that looks like that number could be 85,000 or higher.

Speaker #3: It's a big patient population in need. And I think underscoring that the speed with which this trial was rolled, the enthusiasm that physicians have for putting patients on study is just further evidence that there's really something interesting here.

Speaker #3: And with that, actually, I just want to also just give a shout-out to the Immunovent team who have continued to execute really well. Obviously, the data itself is strong, but also the speed of enrollment, the speed of which we're moving through these studies, the full enrollment on CLE.

Matt Gline: Obviously, the data itself is strong, also the speed of enrollment, the speed with which we're moving through these studies, the full enrollment on CLE, I think that spans all of our programs. I think we're excited about obviously what Priovant's 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. Look, we're really excited about what we've been able to do across the portfolio on clinical execution, so much appreciation for the enormous number of people who are working toward 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.

Speaker #3: And I think that spans all of our programs. I think we're excited about what obviously what Privance has been able to do with Brexit and different clinical enrollment perspective.

Speaker #3: We're excited about the speed of enrollment for Mosley. Obviously, the quality of that data we'll find out soon. But look, really excited about what we've been able to do across the portfolio in clinical execution.

Speaker #3: So much appreciation for the enormous number of people who are working toward those goals. Cool. I'm going to pivot now to Mosley Sigawatt 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.

Speaker #3: 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.

Matt Gline: 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 brepocitinib 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 is going to talk through a little bit more about the program. Look, intense unmet medical need. These patients, an extreme significant proportion of them die. They're very sick. There's currently only 1 approved mechanism with 2 therapies, and we think there's probably 200,000 patients across the US and Europe. That 1 mechanism for treprostinil is underscoring multiple really great launches at this point.

Speaker #3: Around this time, or a little later for BREPO, the independent myositis. Look, I'll do a little bit of an introduction here and then you all heard from Drew back at investor day in December.

Speaker #3: He's in the room with me and is going to talk through a little bit more about the program. Look. Intense on that medical need.

Speaker #3: These patients in the extreme significant proportion of them die. They're very sick. There's currently only one approved mechanism with two therapies. And we think there's probably 200,000 patients across the US and Europe.

Speaker #3: And that one mechanism to Profenol 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.

Matt Gline: 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 is potentially the first non-furosemide that could be available for these patients. We expect this to be a polypharmacy combination therapy market, as PAH has been. We think mosliciguat has a chance to be first line, has a chance to be a major part of the treatment paradigm. We're just looking forward to getting this data and moving forward there. In our phase I data across healthy volunteers and pulmonary hypertension patients, and Drew will remind us of this data specifically, we saw among the best PVR reductions to date.

Speaker #3: And we're hoping to add to that. Mosley has a completely differentiated mechanism of action for the disease. It's an SGC activator. It's an inhaled SGC activator.

Speaker #3: It is potentially the first non-for-Profenol that could be available for these patients. We expect this to be a polypharmacy combination therapy market as PAH has been.

Speaker #3: And we think Mosley 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 and moving forward there.

Speaker #3: In our phase one data across healthy volunteers and pulmonary hypertension patients, and Drew will remind us of this data specifically, we saw among the best PVR reductions to date.

Matt Gline: One of the things 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 shown 20%-plus 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 PVR reduction that has not gone on to be a commercially successful class of drugs. Finally, as a reminder, unsurprisingly, the top-line data from that study is on track, and we expect to get it in H2 2026. It's a 135-patient study.

Speaker #3: And one of the things 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.

Speaker #3: 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.

Speaker #3: 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, as 135 patients were studied.

Speaker #3: 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.

Matt Gline: 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, go ahead.

Speaker #3: And then I'll come back to a little summary at the end, and the rest of the presentation. Drew, that's great. Thank you. Thanks, Emilio. Matt.

Drew Fromkin: That's great.

Matt Gline: Thank you.

Drew Fromkin: Thanks a million, Matt. I can tell you there's a lot of excitement about mosliciguat. Mosliciguat 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 PHILD, nitric oxide may be reduced and the sGC binding site can become impaired, leading to sGC dysfunction. Typically, sGC is activated when nitric oxide engages sGC in the presence of heme, and cGMP is then produced. Unlike 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 the pulmonary arteries and potential reduction of fibrosis and inflammation of the lung tissue. Next slide.

Speaker #3: And I can tell you there's a lot of excitement about Mosley Sigawatt. So Mosley is an inhaled SGC activator that's delivered directly to the lungs to activate SGC.

Speaker #3: And restore impaired SGC function. SGC is a key enzyme in the NO–sGC–cGMP pathway. And in oxidative stress environments, like PHILD, nitric oxide may be reduced and the SGC binding site can become impaired, leading to SGC dysfunction.

Speaker #3: Now, typically, SGC is activated when nitric oxide engages SGC in the presence of heme, and cGMP is then produced. Unlike cGMP, SGC stimulators require nitric oxide and heme to activate the SGC.

Speaker #3: Inhaled Mosley Sigawatt binds to the heme pocket independent of the need for NO and heme. Producing CGMP. Which results in vasodilation of the pulmonary arteries.

Speaker #3: 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.

Drew Fromkin: 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 two 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 mosliciguat has the potential to address both the pulmonary vascular and the lung parenchymal diseases experienced with patients with PH-ILD. Next slide.

Speaker #3: To start, there's disease of the pulmonary vasculature. And disease of the lung parenchyma. The combination of these two disorders is embodied in pulmonary hypertension with interstitial lung disease.

Speaker #3: Which is the first indication we're exploring in our Phase 2 focus study. We believe Mosley has the potential to address both the pulmonary vascular and the lung parenchymal diseases.

Speaker #3: Experience with patients with PHILD. Mosley, next slide. I want to make sure that what I'm going to do is call out the slide numbers.

Matt Gline: What I'm going to do is call out the slide numbers. Everyone's got them.

Speaker #3: Everyone's got them. Okay. Okay. I'll call out let me pull out the slide numbers. You just call mine. Okay. Thank you very much. I appreciate that.

Drew Fromkin: Okay. You'll call out the slide numbers for me.

Matt Gline: You can call them out.

Drew Fromkin: Okay. Thank you very much. I appreciate that. I want to make sure we're advancing. Okay. mosliciguat'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 PH patients. The healthy volunteers underwent studies with single and multiple dose formats, and mosliciguat proved to be well-tolerated, active, and have an extended half-life of approximately 40 hours. In the phase I-B ATMOS study, 38 patients with PH were dosed in a single ascending dose format, and mosliciguat again proved to be very active, producing deep PVR reductions, and was very well-tolerated. On to slide 20.

Speaker #3: I want to make sure we're advancing. Okay. Mosley's preclinical properties let buyer to take Mosley Sigawatt into phase one trials in a total of 170 patients, including healthy volunteers and patients who group one PAH and group four CPAP.

Speaker #3: In the phase one study, buyer studied Mosley Sigawatt in 132 healthy volunteers and 38 PAH H patients. The healthy volunteers underwent studies with single and multiple dose formats.

Speaker #3: And Mosley proved to be well tolerated, active, and have an extended half-life of approximately 40 hours. And in the phase one B ATMOS study, 38 single ascending dose format and Mosley again proved to be very active, producing deep PVR reductions and was very well tolerated.

Speaker #3: On to slide 20. So given Mosley Sigawatt's mechanism of action in inhaled route of administration, one would expect to see notable reductions in pulmonary vascular resistance associated with hemodynamic changes.

Drew Fromkin: 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. With 1 dose of mosliciguat 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 mosliciguat's PVR reductions amongst the highest reductions seen in single and multi-dose trials in PH treatment space. With 1 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.

Speaker #3: And with one dose of Mosley in PAH patients, that's exactly what we saw. A single dose of Mosley Sigawatt reduced PVR in these patients early and sustained through the three-hour observation period with a mean PVR reduction of greater than 30% and a mean peak PVR reduction of approximately 38%.

Speaker #3: This places Mosley's PVR reductions amongst the highest reductions seen in single and monthly dose trials in the PAH treatment space. With one dose of Mosley Sigawatt, 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.

Speaker #3: We also observed the desired impact on other hemodynamic measures, including a mean reduction in mPAP of up to 20% and a mean increase in cardiac output of up to 25%.

Drew Fromkin: 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 PH, with treatment-emergent adverse events being mild to moderate in intensity across both groups. All doses were well-tolerated, and we did not see significant cough, which is often exacerbated by inhaled treprostinils. We did not see clinically relevant systemic side effects, which we believe in great part was due to the inhaled direct delivery of mosliciguat to the lungs and the limited bioavailability of mosliciguat in circulation. Slide 22. With mosliciguat's phase I tolerability and clinical profile, we look to take mosliciguat into phase II development, an indication where there exists a major unmet medical need.

Speaker #3: Slide 21. Mosley Sigawatt was also well tolerated in Phase 1 patients, in healthy volunteers and patients with PAH, with treatment-emergent adverse events being mild to moderate in intensity across both groups.

Speaker #3: And all doses were well tolerated. And we did not see significant cough. Which is often exacerbated by inhaled propranolols. And we did not see clinically relevant systemic side effects which we believe in great part was due to the inhaled direct delivery of Mosley to the lungs.

Speaker #3: And the limited bioavailability of Mosley in circulation. Slide 22. So, with Mosley's phase one tolerability and clinical profile, we looked to take Mosley into phase two development in an indication where there exists a major unmet medical need.

Speaker #3: And we felt that PHILD was an exciting opportunity for development. Given the primary site of PHILD, it's in the lungs. Involving the pulmonary vasculature and the lung parenchyma.

Drew Fromkin: 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, the currently approved treprostinil treatments have high treatment burden as well as tolerability challenges with highly variable efficacy. Mosliciguat lines up really nicely in this moment. Since it was delivered directly to the lungs, it has a once-daily dosing that's been very well-tolerated and produced limited incremental cough and systemic side effects in phase I, has the potential to address both the pulmonary vascular and lung parenchymal diseases. Slide 23. 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.

Speaker #3: And it currently approved propranolol treatments have high treatment burden. As well as tolerability challenges with highly variable efficacy. And so Mosley lines up really nicely in this moment.

Speaker #3: Since it was delivered directly to the lungs, it has a once daily dosing that's been very well tolerated and produced limited incremental cough and systemic side effects in phase one.

Speaker #3: And has the potential to address both the pulmonary vascular and lung parenchymal diseases. Slide 23. So to go a little deeper into PHILD patient population and the opportunity, PHILD represents a large and underserved market where new drugs are sorely needed for these patients.

Drew Fromkin: There are up to approximately 200,000 patients in the US and Europe, likely underdiagnosed given the lack of treatment options in particular. This is a sick population and severe subgroup of PH, less than a five-year median survival, and the combination of PH and ILD represents an increasingly poor prognosis compared to each alone. 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.

Speaker #3: There are up to approximately 200,000 patients in the US and Europe likely under diagnosed given the lack of treatment options in particular. And this is a sick population and severe subgroup of PAH less than a five-year median survival and the combination of PAH and ILD represents an increasingly poor prognosis compared to each alone.

Speaker #3: And I mentioned previously the lack of treatment. As there are currently only two approved FDA propranolol drugs, leaving room for significant improvement. Slide 24.

Speaker #3: Now the core field of drugs in development for the treatment of PHILD is rather sparse. There are three companies all with propranolol treatments in different formulations and all of these propranolol treatments continue to have a range of challenges.

Drew Fromkin: Sotatercept, 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. The result of the recent PROSERA trial outcome, Gossamer has paused its planned studies in PH-ILD. mosliciguat, 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 mosliciguat 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 roadmap for that development.

Speaker #3: Serolutinib with its different mechanism has also run into recent challenges as Gossemer's phase three PRESERA trial in PAH did not meet its primary endpoints.

Speaker #3: Coming off challenges in phase two as well. And as a result of the recent PRESERA trial outcome, Gossamer has paused its planned studies in PHILD.

Speaker #3: So Mosley 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 one studies and this really positions Mosley to be a leader in the treatment of patients with PHILD upon its approval.

Speaker #3: I also wanted to share about—and this is slide 25—I also wanted to share our thoughts about how we see PHILD and the market, and how it's going to develop.

Speaker #3: We actually think the PAH market provides a likely roadmap for that development. In the early days, supportive care was the only option for patients with PAH.

Drew Fromkin: In the early days, supportive care was the only option for patients with PAH. This is what we currently see, and that's the reality of PH-ILD patients in most regions outside of the US, where there are limited treatment options. Over time, drugs with newer mechanisms were approved. The combination therapy involving multiple mechanisms of action became more common. As the median survival of these PH patients has also steadily increased as time went on from two and a half years to where they are today at 12 to 15 years, the treatment guidelines evolved 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 at a robust $7 billion per year, with 15 drugs approved.

Speaker #3: And this is what we currently see, and that's the reality of PHILD patients in most regions outside of the US, where there are limited treatment options.

Speaker #3: Over time, drugs with newer mechanisms were approved, and combination therapy involving multiple mechanisms of action became more common. As a result, the median survival of these PAH patients has also steadily increased as time went on, from two and a half years to where they are today, at 12 to 15 years. Treatment guidelines evolved alongside the data, which reinforce the evolution of the treatment paradigm.

Speaker #3: 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.

Drew Fromkin: There remains a good pricing environment and commercial opportunity for these newer therapies because this is driven by the complex nature of PAH. Finally, 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. 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 multi-center study across the globe. We're targeting 120 patients. We ended enrollment with 135 patients. During the screening period, the investigators looked 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.

Speaker #3: And finally, 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.

Speaker #3: This combo therapy as Matt said is really the norm. And so we are currently deep into our phase two study exploring Mosley Sigawatt in our blinded phase two placebo-controlled and randomized study in adults in PHILD.

Speaker #3: 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 looked hard to find patients to confirm ILD.

Speaker #3: Elevated baseline PVR indicative of PAH and limits on the level of fibrosis and emphysema as determined by CAT scan if eligible for the study to patients in a randomized two to one placebo drug to placebo and then they go through a rapid up titration.

Drew Fromkin: If eligible for the study, the patients randomized 2 to 1, placebo to drug to placebo. They go through a rapid uptitration. That moves from 1 mg to 2 mg to 4 mg. 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 mg dose and sustaining well through the week 16 period. That's been very attractive and positive. 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 six-minute walk and change from baseline NT-proBNP. The patient moved on to week 24, secondary and exploratory endpoints. They all go on drug if they weren't on drug into the long-term extension. Slide 27.

Speaker #3: And that moves from one milligram to two milligrams to four milligrams. And Matt may have spoken about it but we've seen really great progress there with the vast majority over 90% 5% of our patients achieving that four milligram dose and sustaining on well through the week 16 period.

Speaker #3: 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 six-minute walk and change from baseline NT-proBNP.

Speaker #3: 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.

Speaker #3: Slide 27. So, very importantly, and as we get closer to data in the second half of this year, we've focused very heavily on designing our Phase Two study and defining our patient population.

Drew Fromkin: Very importantly, and as we get closer to data in the H2 of this year, we've focused very heavily in designing our phase II study and defining our patient population. 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 in more severe patients. 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.

Speaker #3: And we carefully designed around the seventh world symposium on pulmonary hypertension and these guidelines are crucial for PHILD patient selection. We targeted patients with worsening symptoms of PAH 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.

Speaker #3: The result is that the study population closely mirrors the recommended guidelines and includes more severe patients. And, on slide 28, as you can see, this effort is reflected in our baseline data in focus.

Speaker #3: Our mean PVR came in at 7.1 woods 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.

Drew Fromkin: 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. We protected for emphysema both in number of patients and level of severity as determined by the CAT scan. This was very important from all of those learnings. We also explored background therapy, including exploring PDE5s on background, and this is also consistent with real-world practice. 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 H2 of this year. Matt, back to you.

Speaker #3: 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.

Speaker #3: 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.

Speaker #3: So, this careful patient selection and enrichment gives us confidence we've enrolled the right population to detect meaningful treatment effect. They're very much looking forward to our Phase 2 data in the second half of this year.

Speaker #3: Matt, back to you.

Matt Gline: Awesome. Thank you.

Speaker #1: Awesome. Thank you. Thanks, Drew. So look a lot to be excited about on the program here. I just want to a couple quick reminders and a summary on slide 22 and 23 here.

Drew Fromkin: Yeah.

Matt Gline: Thanks, Drew. Look, a lot to be excited about on the program here. Just a couple quick reminders and a summary on slide 22 and 23 here. On slide 22, 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. Just so we're doing the same thing following a well-trodden path there. We will then, in phase III, move to a 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.

Speaker #1: 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 two programs across a variety of other PHILD studies or mechanisms or drugs.

Speaker #1: And so we're doing the same thing, following a well-trodden path there. We will then, in phase three, move to a six-minute walk and other clinically relevant endpoints as the way that the trial is measured.

Speaker #1: I want to remind everybody this study is not powered to achieve a P-value on six-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.

Matt Gline: 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. We will obviously look for interesting trends in patient-level data on 6-minute walk. 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 wanted 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.

Speaker #1: And we will obviously look for interesting trends in patient-level data on six-minute walk. But I want to make sure we've been clear ahead of time.

Speaker #1: This is not a study designed to achieve a P-value on six-minute walk and that's not what we're looking for as our own criteria to go from here.

Speaker #1: That's the point I wanted to highlight. I wanted 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.

Speaker #1: On slide 23, yeah, just to recap what Drew has said here. First of all, again, with appreciation of the pulmonary team, this study enrolled very quickly, with all the patients enrolled within 12 months of the first patient being dosed.

Matt Gline: First of all, again, with appreciation to the Roivant 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. Our investigators are enthusiastic about the program. They're excited. The feedback's good. I think we're feeling great about how the study is being run. 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 allowed people to run the study.

Speaker #1: Early discontinuation rates compare favorably to what we've seen in previous PHILD studies. Look with this and 20 bucks you can buy two pizzas at Domino but Domino's but our investors our investigators are enthusiastic about the program.

Speaker #1: They're excited. The feedback's good. I think we're feeling great about how the study is being run. And then and this is a great thing for safety.

Speaker #1: 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 have continued to affirm the safety of the program and allowed people to run to run the study.

Speaker #1: Obviously there's lots of things that don't get revealed until the data's unblinded but it certainly gives us comfort that the patients are achieving high dose and that things are moving as they should be.

Matt Gline: Obviously, there's lots of things that don't get revealed until the data's unblinded, but it certainly gives us comfort that the patients are achieving high dose and that things are moving as they should be. 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. 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 Breppo. Breppo 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. Just as a reminder on slide 25 here. Sorry, I'm looking at the wrong slide numbers.

Speaker #1: 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.

Speaker #1: 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 BREFO.

Speaker #1: BREFO 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.

Speaker #1: 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 BREFO section it's slide 32 sorry.

Matt Gline: As a reminder on the next slide, on the first slide of the Breppo section, it is slide 32, sorry. Look, this is a huge opportunity for us. There is 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 will start enrolling soon in cutaneous sarcoid, the currently enrolling study at LPP, and potentially more indications to come. Just a lot of great stuff coming for Breppo and a really exciting moment from here. On slide 33, we have 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.

Speaker #1: 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 and dermatomyositis but also the NIU data the potential for the NIU launch.

Speaker #1: The ongoing program that we'll start enrolling soon in case sarcoid. The currently enrolling study at LPP. And potentially more indications to come. So just a lot of a lot of great great great stuff coming for BREFO and I'm really exciting moment from here.

Speaker #1: You know on slide 33 we've put this up a few times. We're just to remind people. First of all these are sick patients. And there are really very few options for them in dermatomyositis.

Speaker #1: As a reminder, you know 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.

Matt Gline: As a reminder, 75% of these patients are on principally steroids, in many cases, on very high doses of steroids, over 10 milligrams a day for a good portion of the year. 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. A really arduous path. Other than that, it's off-label stuff, much of which has not been successful in studies, but is used because there's no other option. We feel really great looking forward here to our ability to bring a new option to these patients. On slide 34, further underscoring, and again, this is not new, we've presented this before, further underscoring the need here.

Speaker #1: 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 four and five days a month, consecutive, in an infusion center.

Speaker #1: So, a really arduous path. And then, other than that, it's off-label stuff, much of which has not been successful in studies, but is used because there's no other option.

Speaker #1: 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.

Speaker #1: We've presented here these patients are treated as with PH for that matter with polypharmacy on multiple lines of therapy. They're bouncing around. They have accumulated organ damage with high systemic corticosteroid exposures.

Matt Gline: 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 steroid 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. 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.

Speaker #1: It's just a tough experience for these patients and we think a new option's going to go far. We're not saying a lot on slide 35 about our commercial progress.

Speaker #1: 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.

Speaker #1: But I'll just say suffice to suffice to say we're doing all the things that you would expect us to be doing at this stage.

Speaker #1: 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.

Speaker #1: 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.

Matt Gline: We've built a strong commercial team that we're really excited about. We continue to do unbranded patient engagement. We talked about dermatomyositis.com when we got together in December. 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'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 have been made of this data, but the data's 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.

Speaker #1: 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.

Speaker #1: 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.

Speaker #1: As you look at slide 36 this is a small subset of the presentations that have been made of this data. But the data's 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.

Matt Gline: 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 a month and a half 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, and generally irreversible hair loss. There's probably 100,000 or so such patients in the US. It's been growing in prevalence over time. There's nothing approved, so we have an opportunity to do something really interesting for these patients.

Speaker #1: And notably, in March, the Phase 3 data was published in NEJM, which is a testament to how exciting the data is—a testament to the importance of the study.

Speaker #1: The quality of the study. And you know, we couldn't be more excited for that publication as well. Finally, just a super quick recap on LPP, which we announced just about a month and a half ago.

Speaker #1: A fourth indication for Repositinib. It's a highly morbid disorder with no FDA-approved therapies. These patients are miserable. They are in a ton of pain.

Speaker #1: It's a really tough disease that, in addition to pain, causes itch, burning, redness, scaling, and generally irreversible hair loss. There are probably 100,000 or so such patients in the US.

Speaker #1: It's been growing in prevalence over time. And there's nothing approved to so we have an opportunity to do something really interesting for these patients.

Speaker #1: Our trial design on slide 38 we talked about when we first unveiled the program is a sort of continuous enrolling phase two B3 pivotal that's designed to give us endpoint validation and is going to get us into hopefully registration there.

Matt Gline: Our trial design on slide 38, we talked about when we first unveiled the program, is a sort of continuous enrolling phase II-B/III pivotal that's designed to give us endpoint validation and is going to get us into, hopefully, registration there. We're really looking forward to that. 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 brepocitinib is strong. It's a Th1-dominant disease where dual JAK1/JAK2 inhibition should work specifically well. We think we've got the right trial design, and there's obviously some overlapping prescriber base in KOL community with our existing indications. 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.

Speaker #1: 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.

Speaker #1: The mechanistic rationale for BREFO is strong. It's a TH1 dominant disease. We're dual JAK1/TEK2 innovation should work specifically well. We think we've got the right trial design.

Speaker #1: And there's obviously some overlapping prescriber-based 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.

Speaker #1: Great. Okay. I'm going to wrap up quickly with the financial update, and then we'll get to the Q&A. So I'm not going to spend a ton of time on this.

Matt Gline: 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 equivalents as of 31 March 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. Spend continues to be sort of as it has been. Over time, R&D has grown a bit as the scope of the programs have increased, but that's all for the good, and looking forward to the future.

Speaker #1: Financial quarter was relatively straightforward. We continue to be in a strong position from a cash perspective. 4.3 billion in cash-to-cash equivalents as of 3/31.

Speaker #1: Before the Moderna settlement, no debt. We continue to retire shares. We purchased a fair amount in this quarter and continue to have an active program.

Speaker #1: And you know spend continues to be sort of as it has been. Over time R&D has grown a bit as the scope of the programs have increased.

Speaker #1: 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.

Matt Gline: 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. 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. 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 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.

Speaker #1: 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.

Speaker #1: 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.

Speaker #1: We 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.

Speaker #1: Which I couldn't be 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.

Matt Gline: 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. 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. Obviously a great thank you to the investigators and the patients who work with us and make this happen. Thank you to everybody who makes this work. I'm going to pass it over to the operator for Q&A so that we can get to it.

Speaker #1: 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—Pullman, Private, and Univan—for continuing to run high-quality studies and executing well.

Speaker #1: Generating high quality data couldn't ask more of these drugs. Couldn't ask more of these investigators and the patients who work with us and make this happen.

Speaker #1: 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 2: As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. We do ask that you please limit to 1 question. Our first question is going to come from Corinne Johnson with Goldman Sachs. Your line is open.

Speaker #2: As a reminder, to ask a question, please press *11 on your telephone and wait for your name to be announced. To withdraw your question, please press *11 again.

Operator: As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. We do ask that you please limit to 1 question. Our first question is going to come from Corinne Johnson with Goldman Sachs. Your line is open.

Speaker #2: Please press star 11 again. And we do ask that you please limit to one question. And our first question is going to come from Corinne Johnson with Goldman Sachs.

Speaker #2: Your line is open.

Corinne Johnson: Good morning. Happy birthday to Matt 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 timeline. How would you expect those responses to trend with more time on therapy with kind of implications then towards the randomized withdrawal phase? Thank you.

Speaker #3: Good morning, and happy birthday to Papa Kline as well. Maybe you could just contextualize the ACR responses you saw here at 16 weeks first.

Speaker #3: I think more kind of typical in later-stage studies of the 24-week reporting timeline. And how would you expect those responses to trend with more time on therapy, with kind of implications then towards the randomized withdrawal phase?

Speaker #3: Thank you.

Speaker #4: Yeah. 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.

Matt Gline: Yeah, 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 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. 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. I think there's certainly a possibility for continued improvement with therapy over time. We'll find out as we look at that part of the patient population. Thanks, Corinne. I appreciate the question.

Speaker #4: And it's 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.

Speaker #4: And that's why I made the comments I made about the phase two to randomized withdrawal period. But in terms of week 16 versus week 24 I don't know.

Speaker #4: 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.

Speaker #4: Over time. But you know, we'll find out as we look at that part of the patient population. Thanks, Corinne. Appreciate the question.

Speaker #3: Thanks.

Corinne Johnson: Thanks.

Operator 2: Thank you. The next question is going to come from Yasmin Rahimi with Piper Sandler. Your line's open.

Operator: Thank you. The next question is going to come from Yasmin Rahimi with Piper Sandler. Your line's open.

Speaker #2: Thank you. And the next question is going to come from Yasmine Rahimi with Piper Sandler. Your line's open.

Yasmin Rahimi: Congrats team, and congrats to Papa Gline for also achieving a major milestone of 75 years. Happy birthday to him as well. Quick question on mosliciguat. 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? I'll jump back in the queue.

Yasmeen Rahimi: Congrats team, and congrats to Papa Gline for also achieving a major milestone of 75 years. Happy birthday to him as well. Quick question on mosliciguat. 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? I'll jump back in the queue.

Speaker #5: Congrats, team, and congrats to Papa Kline for also achieving a major milestone of 75 years. So, happy birthday to him as well. Quick question on—mostly congrats.

Speaker #5: 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 with up-titration and safety.

Speaker #5: Have you been able to look at whether your assumptions for standard deviation in PVR in six-minute or sort of tracking and alignment with what you're seeing?

Speaker #5: And I'll jump back in the queue.

Speaker #4: Yeah. 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 don't have a lot of information about it.

Matt Gline: Yeah, thanks. I appreciate it. Look, I think the short answer to that question is we are largely blinded to all of that data and don't have a lot of information about it, so it's hard to say. I think given the patient population we enrolled, we feel pretty good about where the study's headed, and we think we've got an efficacious drug. We don't have a lot of information about sort of ongoing distributions because the way the study has been blinded. Thank you.

Speaker #4: So, it's hard to say. But I think given the patient population we enrolled, we feel pretty good about where the study's headed. And, you know, we think we've got an efficacious drug.

Speaker #4: But we don't have a—we don't have a lot of information about sort of ongoing distributions because of the way the study has been blinded.

Speaker #4: Thank you.

Operator 2: Thank you. The next question will come from Andy Chin with Wolfe Research. Your line's open.

Operator: Thank you. The next question will come from Andy Chin with Wolfe Research. Your line's open.

Speaker #2: Thank you. And the next question will come from Andy Chen with Wolf Research. Your line's open.

Andy Chin: Hey, thank you for taking the question. Matt, I am aware that you said with Immunovant, you haven't analyzed IgG reduction, but that is still my biggest question. Other FcRn drugs, they do not 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? Do you expect ACPA reduction to be less than IgG reduction? Thank you.

Andy Chen: Hey, thank you for taking the question. Matt, I am aware that you said with Immunovant, you haven't analyzed IgG reduction, but that is still my biggest question. Other FcRn drugs, they do not 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? Do you expect ACPA reduction to be less than IgG reduction? Thank you.

Speaker #6: Hey. Thank you for taking the question. So Matt I'm aware that you said with Immunovent you have an analyzed IgG reduction. But that's still my biggest question.

Speaker #6: 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.

Speaker #6: Do you somehow have ACPA antibody reduction data or will we see that data before you unblind the period two data? And do you expect ACPA reduction to be less than IgG reduction?

Speaker #6: Thank you.

Matt Gline: Look, 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. 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. I think those are both important. Look, I think we will continue to analyze this data.

Speaker #4: Look I don't have that data now as I said. So I can't answer the question. We know from our phase one studies that IMVT-1402 suppresses IgG quite deeply relative to other drugs.

Speaker #4: And given the quality of the clinical data we've seen non-ACR I think it's like 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.

Speaker #4: 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.

Speaker #4: 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.

Matt Gline: I don't know at this stage exactly when we're going to present what data. I don't have a good answer to what you're going to see before or after the phase II 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 mostly this has been a blessing, but also its curse. We've been a leader wondered if this data is going to also establish a leadership role for us along the lines of which others may follow.

Speaker #4: So I don't have a good answer to, like, what you're going to see before or after the period two was 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.

Speaker #4: I'll say I think mostly this has been a blessing. But also it's a curse. We've been a leader. Wondered if this data is going to also establish a leadership role for us along the lines of which others may follow.

Speaker #4: 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.

Matt Gline: I do think we're going to be a little bit conservative on what exactly we say from a competitive perspective. 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 continued able to see that as the data mature. Thanks, Andy.

Speaker #4: And I hope we are continued able to see that as the data mature. Thanks Andy.

Operator 2: Thank you. Our next question will come from David Risinger with Leerink Partners. Your line is open.

Operator: Thank you. Our next question will come from David Risinger with Leerink Partners. Your line is open.

Speaker #2: Thank you. And our next question will come from David Reisinger with Lyric Partners. Your line is open.

Speaker #7: Yes, thanks very much. So, congrats on the phenomenal data this morning. My question is on Mosley. If the Phase 2 FOCUS study surprisingly shows a statistically significant benefit on six-minute walk, could it represent a pivotal study?

David Risinger: Yes. Thanks very much. Congrats on the phenomenal data this morning. My question is on mosliciguat. If the phase II FOCUS study surprisingly shows a statistically significant benefit on six-minute walk, could it represent a pivotal study, and what would the requirements be in that scenario for a future NDA filing? Just one other on mosliciguat, is the company considering development of mosliciguat in any additional indications? Thanks so much.

Speaker #7: And what would the requirements be in that scenario for a future NDA filing? And then just one other on Mosley. Is the company considering development of Mosley in any additional indications?

Speaker #7: Thanks so much.

Speaker #4: Thanks Dave. I'm static at six minute walk. I think it's impossible to say exactly what we would do until we saw the data. And so if the data looked good enough to support a productive conversation with FDA I think we would have a conversation with FDA.

Matt Gline: Thanks, Dave. On statistic at six-minute walk, I think it's impossible to say exactly what we would do until we saw the data. If the data looked good enough to support a productive conversation with FDA, I think we would have a conversation with FDA. The FDA has been aggressive lately on conversations about single pivotal designs. Never say never is the answer. I want to be clear, it's not the base case expectation. The study is not powered to show a benefit on six-minute walk, we'll see what we see. Look, I think given where we're at, we'll certainly take that as we go. On other indications, I'll say every sign around mosliciguat is pointing to an effective, exciting agent with a lot of things we could do with it.

Speaker #4: 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.

Speaker #4: And the study is not powered to show a benefit on six 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.

Speaker #4: And another indication I'll say—every sign around Mosley is pointing to an effective, exciting agent with a lot of things we could do with it.

Speaker #4: 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 our own that others haven't shown us yet.

Matt Gline: As we watch the field around us, others are showing us good ideas all the time in terms of how these mechanisms might work. We have some of our own that others haven't shown us yet. I think there are absolutely opportunities for indication expansion. Although, I remember we got this question about 40 times when we first unveiled mosliciguat, and our comment then, which is still our comment now, is man PHILD is an area with a lot of unmet need. Even if it were the only thing we ever did with mosliciguat, it's a big opportunity with a lot of value to deliver to patients. I think there's a lot of different ways to go there. Thanks, Dave.

Speaker #4: 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 Mosley.

Speaker #4: And our comment then which is still our comment now is man PHILD is an area with a lot of unmet need. And even if it were the only thing we ever did with Mosley it's a big opportunity with a lot of value to deliver to patients.

Speaker #4: So, I think there are a lot of different ways to go there. Thanks, Dave.

Operator 2: Thank you. Our next question will come from Yaron Werber with TD Cowen. Your line's open.

Operator: Thank you. Our next question will come from Yaron Werber with TD Cowen. Your line's open.

Speaker #2: Thank you. And our next question will come from Yoron Werber with TD Cowen. And your line's open.

Speaker #8: Great. Thanks so much. And also congrats on the difficult to treat RA study. So question actually about that. Is there any chance you can amend that protocol?

Yaron Werber: Great. Thanks so much, and also congrats on that difficult-to-treat RA study. Question actually about that, is there any chance you can amend that protocol and essentially run period one and then sort of get new patients completely into period two, so you're not going to have that step-down issue? 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? Thank you.

Speaker #8: And essentially run period one and then sort of get new patients completely into period two? So you're not going to have that step down issue.

Speaker #8: And then secondly based on our analysis we think that about 75 percent of patients are ACPA positive. Is that still kind of what you think the data shows?

Speaker #8: Thank you.

Speaker #4: Yeah. Thanks Yoron. 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 two data we're going to have a pretty good sense for what we've got.

Matt Gline: Yeah. 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. 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. 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. I think we'll have a pretty clear sense. Look, we've done some commercial analysis of the market in various settings.

Speaker #4: 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.

Speaker #4: So, I think we're going to do that analysis in detail. I think we're going to have the conversation with the FDA. I think we're going to plot a course forward.

Speaker #4: 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 the analysis actually in Immunovance 10K that was filed today.

Matt Gline: There's an updated version of analysis actually in Immunovant 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.

Speaker #4: I think your number is within the range of what we have seen in the literature for ACPA positive patients generally. Thanks Yoron.

Operator 2: Thank you.

Operator: Thank you.

Matt Gline: Thanks, Yaron.

Operator 2: Our next question comes from Brian Chang with JPMorgan. Your line's open.

Speaker #2: And our next question comes from Brian Cheng with JPMorgan. Your line's open.

Operator: Our next question comes from Brian Chang with JPMorgan. Your line's open.

Speaker #5: Hey guys. Thanks for taking our question. In this RA Explorer trial since there's no washout period between period one and two I'm curious if you have some thought around the tail of the efficacy from those going from drug to placebo.

Brian Chang: Hey, guys. Thanks for taking our question.

Brian Cheng: Hey, guys. Thanks for taking our question.

Matt Gline: Yeah.

Brian Chang: In this RA EXPLORER trial, since there is no washout period between period 1 and 2, I am curious if you have some thought around the tail of the efficacy from those 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? Thank you.

Brian Cheng: In this RA EXPLORER trial, since there is no washout period between period 1 and 2, I am curious if you have some thought around the tail of the efficacy from those 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? Thank you.

Speaker #5: You said that period two might be less meaningful. Are you saying that 12 week may not be enough to fully drive the separation? Thank you.

Speaker #4: Yeah, thanks. I appreciate the question, Brian. And just to reiterate, I guess, 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.

Matt Gline: Yeah. Thanks. I appreciate the question, Brian. Just to reiterate, 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. That's one piece of this. Obviously, period two is blinded, so we don't know now anything about what's in there. 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 two 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 two, it just takes some time to give up that level of response.

Speaker #4: So that's, like, one— that's like one piece of this. Obviously, period two is blinded, so we don't know now anything about what's in there.

Speaker #4: 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 two 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 two, it just takes some time to give up that level of response.

Speaker #4: And so that's where I'd say, like, the quality of the data in period two is—the quality of the data in period one is in some ways counting against period two.

Matt Gline: That's where I'd say the quality of the data in period one is in some ways counting against period two, irrespective of the pharmacokinetic effects of withdrawal of the drug. I think, remember, every ACR70 responder is an ACR50 responder, is an ACR20 responder. It just takes time to come off that hill. We have people who've achieved a lot of benefit. That's that. Thank you.

Speaker #4: 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.

Speaker #4: 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.

Operator 2: Thank you. Our next question will come from Dennis Ding with Jefferies. Your line's open.

Operator: Thank you. Our next question will come from Dennis Ding with Jefferies. Your line's open.

Speaker #2: Thank you. And our next question will come from Dennis Ding with Jefferies. Your line's open.

Speaker #8: Hi. Good morning. Thanks for taking our questions. For PHILD, I'm curious where your thoughts are around the Phase 1b data and the interpretability of that data in the small number of patients.

Dennis Ding: Hi. Good morning. Thanks for taking our questions. For PH-ILD, I'm curious what are your thoughts around the phase I-B 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?

Speaker #8: Specifically why did the four milligram cooler outperform so much relative to the two milligram dose on CGMP? And also cardiac output? And I wonder if you're expecting a if you should expect a big increase in cardiac output since Mosley is locally delivered to the lungs and it's not really a systemic.

Dennis Ding: Also cardiac output. I wonder if you should expect a big increase in cardiac output since mosliciguat is locally delivered to the lungs and is not really a systemic. Thanks so much.

Speaker #8: Thanks so much.

Speaker #4: Thanks Dennis. I appreciate the question. Look I think the first answer is four is twice two. So there's just a lot more drug being delivered.

Matt Gline: Thanks, Dennis Ding. 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. While the specific study that you're referring to may have had a smaller patient, we have a large body of evidence at this point across mosliciguat being administered in a lot of different settings. 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 that data. I think we generally think we know what we've got.

Speaker #4: 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 small number of patients we have a large body of evidence at this point across Mosley being administered in a lot of different settings.

Speaker #4: 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 that data.

Speaker #4: So, I think we've generally—think we know what we've got.

Drew Fromkin: Yeah. I think with 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, that was really important for us. 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. I think that's the biggest takeaway was we saw cardiac output, we saw mPAP reductions. These are the things you want to see, these were single-dose studies. Now we'll see them much more robust fashion in our phase II.

Speaker #8: 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.

Speaker #8: 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.

Speaker #8: 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.

Speaker #8: But these were single dose studies. So now we'll see them much more robust fashion in our phase two.

Speaker #4: Thanks Drew. Yeah. The other thing I'll say just because it occurred to me as Drew was answering that question is look I think one of the things that makes PHILD exciting as a commercial opportunity is it really requires inhaled therapy precisely because of this effect.

Matt Gline: Thanks, Drew. Yeah, the other thing I'll say, it just previously occurred to me as Drew was answering that question is, look, I think one of the things that makes PHILD exciting as a commercial opportunity is it really requires inhaled therapy precisely because of this effect.

Drew Fromkin: Yeah.

Matt Gline: 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. We feel that gives us an advantage as well and frankly increases the level of need for the patients. Look, I think it's all setting up in that way. Thanks, Dennis. Appreciate the question.

Speaker #4: 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.

Speaker #4: 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 setting up in that way.

Speaker #4: Thanks Dennis. Appreciate the question.

Speaker #8: Perfect. Thank you.

Dennis Ding: Perfect. Thank you.

Operator 2: Thank you. As a reminder, please limit to 1 question. Our next question comes from Derek Archila with Wells Fargo. Your line's open.

Operator: Thank you. As a reminder, please limit to 1 question. Our next question comes from Derek Archila with Wells Fargo. Your line's open.

Speaker #2: Thank you. And as a reminder please limit to one question. Our next question comes from Derek Archilla with Wells Fargo. Your line's open.

Speaker #8: Good morning. This is Jacob Monfort Derek. Thanks for taking our question and congrats on the fortunate two data. So, real quick on safety, just want to clarify and confirm there were no LDL changes or other events of interest observed, right?

[Analyst] (Wells Fargo): Good morning. This is Jacob on for Derek. Thanks for taking our question and congrats on the 1402 data. Real quick on safety, just want to clarify, confirm there were no LDL changes or other events of interest observed, right? Secondly, given the strong activity in period 1, how is this informing your trial design strategy in the future? I know you mentioned that this is likely one of a couple registrational trials, but do you think this data changes that?

Speaker #8: And then secondly on the given the strong activity in period one how does this inform your trial design strategy in the future? I know you mentioned that this is likely one of a couple registrational trials but do you think this data changes that?

Speaker #4: Thanks, Derek. Great questions—both of them. Although, I'll remind the other analysts politely that we're trying to keep it to one question each, given the number in the queue.

Matt Gline: Thanks, Derek. Great questions both. I'll remind politely for the other analysts, we're trying to keep to one given the number in the queue, 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 albumin or LDL across the hundreds of patients dosed with 1402. 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 on albumin or LDL from 1402. Look, given the level of activity in period one on trial design, I think the answer is we're going to have to take this data when we get it.

Speaker #4: 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.

Speaker #4: And we have seen no impact on albumin or 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 on albumin or LDL from 1402.

Speaker #4: And then, look, given the level of activity in period one on trial design, I think the answer is we're going to have to take this data when we get it.

Speaker #4: We're going to have to look closely at it. And we're going to 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.

Matt Gline: 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. 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. That's a conversation we're going to have to have together with FDA in the months to come. Thanks for the question.

Speaker #4: 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.

Speaker #4: Thanks for the question.

Speaker #8: Awesome. Thank you.

[Analyst] (Wells Fargo): Awesome. Thank you.

Matt Gline: Cool. Thanks.

Operator 2: Thank you. Our next question comes from Samantha Simenko with Citi. Your line's open.

Operator: Thank you. Our next question comes from Samantha Simenko with Citi. Your line's open.

Speaker #2: Thank you. And our next question comes from Samantha Simincoh with Citi. Your line is open.

Speaker #5: Hi. Good morning. Thanks for taking the question. And congratulations on the day 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.

Samantha Simenko: Hi, good morning. Thanks for taking the question and 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 H2. Will that readout include the entire 52-week study, or will that just be the 12-week randomized portion? What magnitude of treatment effect do you think would be meaningful here? Thanks very much.

Samantha Semenkow: Hi, good morning. Thanks for taking the question and 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 H2. Will that readout include the entire 52-week study, or will that just be the 12-week randomized portion? What magnitude of treatment effect do you think would be meaningful here? Thanks very much.

Speaker #5: 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?

Speaker #5: Thanks very much.

Matt Gline: On the first question. Thank you. Appreciate the questions. On the data, that will just be the 12-week period. That's what we'll have by then. That's what we'll be able to share. In terms of what treatment effect would be meaningful, look, I'll say two 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 in that it is commercially more competitive, and there's other mechanisms coming. I think the bar for us is not just sort of per se clinical meaningful. I think the bar is, do we think our data is good enough to support a program in the face of where the landscape is headed?

Speaker #4: On the first question, thank you. Appreciate the questions. On the data, that will just be the 12-week period. That's what we'll have by then.

Speaker #4: So that's what we'll be able to share. And in terms of what treatment effect will be meaningful look I'll say two things. One is we will have an opportunity to continue to talk about what we expect to see from that study over time.

Speaker #4: 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 in that it is commercially more competitive.

Speaker #4: 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 do we think our data is good enough to support a program in the face of where the landscape is headed?

Speaker #4: 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 an we're going to make a decision based on the totality of the data.

Matt Gline: 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. I think the bar there is pretty high, and I think we knew that going in. Thanks for the question.

Speaker #4: But I think the bar there is pretty high, and I think we knew that going in. Thanks for the question.

Speaker #2: Thank you. And our next question is going to come from Thomas Smith with Laring Partners. Your line's open.

Operator 2: Thank you. Our next question is going to come from Thomas Smith with Leerink Partners. Your line's open.

Operator: Thank you. Our next question is going to come from Thomas Smith with Leerink Partners. Your line's open.

Speaker #6: Hey guys. Good morning. Congrats on the really stellar RA data here for 1402. Just wanted to ask one if I could on the pivotal GRAVES program.

Thomas Smith: Hey, guys. Good morning. 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. Just wondering if there's anything that you could share there.

Speaker #6: 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.

Speaker #6: But just wondering if there's anything that you could share there in terms of pace, cadence, and maybe patients being enrolled. Anything differing from initial expectations?

Thomas Smith: pace, cadence, and maybe patients being enrolled, anything differing from initial expectations? Thanks so much.

Speaker #6: Thanks so much.

Speaker #4: Thank you. Yeah, it's a great question. Look, I think the short answer is we had a pretty high bar for ourselves when we started the study.

Matt Gline: Thank you. Yeah, it's a great question. I think the short answer is we had a pretty high bar for ourselves when we started the study and we didn't exactly know it because there hadn't been a lot of development in Graves' disease. I think we can now say enrollment's going great. We're on track. We'll have the data in 2027, 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. I think overall, really happy with how that program is evolving. I'll just, again, take the opportunity to say, I think all of our main teams at this point are executing at a really high level from a clinical enrollment perspective, and I think that's been a real driver of value for us. Thank you.

Speaker #4: 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's going great.

Speaker #4: We're on track. We'll have the data in 27 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.

Speaker #4: So I think overall really happy with how that program is evolving. And I'll just again take the opportunity to say I think all of our VAT teams at this point are executing at a really high level from a clinical enrollment perspective.

Speaker #4: And I think that's been a real driver of value for us. Thank you.

Operator 2: Thank you. Our next question is going to come from Alex Thompson with Stifel. Your line's open.

Operator: Thank you. Our next question is going to come from Alex Thompson with Stifel. Your line's open.

Speaker #2: Thank you. And our next question is going to come from Alex Thompson with Stifel. Your line's open.

Speaker #7: Hi, guys. Congrats on the data. This is Patrick Colleton on for Alex. I guess just kind of building on the path forward here in RA, looking at period two—I guess if your 300 milligram arm performed just as well as the 600 milligram, how are you guys thinking about your dosing strategy going forward in phase three?

Patrick Colston: Hi, guys. Congrats on the data. This is Patrick Colston on for Alex. I guess just building on the path forward here in RA. Looking at period two, I guess if your 300 milligram arm performs just as well as 600 milligram, how are you guys thinking about your dosing strategy going forward in phase III?

Patrick Krause: Hi, guys. Congrats on the data. This is Patrick Colston on for Alex. I guess just building on the path forward here in RA. Looking at period two, I guess if your 300 milligram arm performs just as well as 600 milligram, how are you guys thinking about your dosing strategy going forward in phase III?

Matt Gline: It's fun to sit here and think about what happens if in the phase II study we see. First of all, it's a randomized withdrawal study, so I was trying to figure out exactly what it would look like for the 300 and 600 to perform equivalently. 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 to say without a lot in development is an understatement. I think basically we are plowing a new course with this patient population, so I think we've really got to look 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 indications like RA, is likely to want some dose-ranging information.

Speaker #4: I it's fun to sit here and think about what happens in the phase two study. We see as good first of all it's a randomized withdrawal study.

Speaker #4: So we're just 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.

Speaker #4: 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.

Speaker #4: I think, basically, we are plowing a new course with this patient population. So I think we've really got to look at that data and get an outcome from it.

Speaker #4: I think the inclusion of 300 and 600 in the study was important because FDA especially in new indications especially in an indication like RA is likely to want some dose-ranging information.

Speaker #4: But I think we're going to have some flexibility and we're going to get to see. Historically there has been separation in IgG reduction obviously between 300 and 600.

Matt Gline: I think we're going to have some flexibility, and we're going to get to see. Historically, there has been separation in IgG reduction, obviously between 300 and 600. We'll see how that translates in this population, but I think we got a lot of options here. Thanks for the question. I appreciate it.

Speaker #4: So we'll see how that translates in this population. But I think we got a lot of we got a lot of options here. Thanks for the question.

Speaker #4: I appreciate it.

Speaker #7: Thanks.

Patrick Colston: Thanks.

Patrick Krause: Thanks.

Operator 2: Thank you. The next question comes from Prakhar Agarwal with Cantor Fitzgerald. Your line's open.

Operator: Thank you. The next question comes from Prakhar Agarwal with Cantor Fitzgerald. Your line's open.

Speaker #2: Thank you. And the next question comes from Prakhar Agrawal with Cantor Fitzgerald. Your line's open.

Speaker #8: Hi. Thanks for taking my questions. And congrats on these 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.

Prakhar Agarwal: Hi. Thanks for taking my questions, and congrats on these impressive data. 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. Maybe just if you can expand, if you have any data on some of the secondary endpoints which might be less susceptible to open label design of the trial, and 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? Thank you.

Prakhar Agrawal: Hi. Thanks for taking my questions, and congrats on these impressive data. 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. Maybe just if you can expand, if you have any data on some of the secondary endpoints which might be less susceptible to open label design of the trial, and 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? Thank you.

Speaker #8: So maybe, just if you can expand if you have any data on some of these secondary endpoints, which might be less susceptible to the open-label design of the trial.

Speaker #8: And what give 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?

Speaker #8: Thank you.

Speaker #4: Yeah, thanks. This is—look, it's a great question. It's obviously what was on our mind from the day we first saw the data.

Matt Gline: Yeah, thanks. Look, 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 ACR 50 and ACR 70 responses than just ACR 20 responses. I think once you get to that level, it's sort of spontaneous placebo-style remissions of both 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. That's about all we're able to say at this point because that's about all we know at this point. One other thing is the way the study is designed, the people doing the joint assessments are blinded.

Speaker #4: I think it is certainly helpful that we're talking about ACR in 50 ACR 50 and ACR 70 responses and just ACR 20 responses. I think once you get to that level sort of spontaneous placebo-style remissions of those kinds are less frequent.

Speaker #4: 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.

Speaker #4: But that's about all we're able to say at this point. I mean, that'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.

Speaker #4: So they are doing the assessments without knowing anything about the study, what patients are on, or where in the study they are, whether they're on drug or placebo.

Matt Gline: They are doing the assessments without knowing anything about the study, what patients are on, where in the study they are, whether they're on drug or placebo. That's obviously only one component of the total here, but it is one way for us to get a little bit of objectivity into a study that is otherwise, at this stage, open label, and that is helpful and pretty objective. Thank you.

Speaker #4: 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.

Speaker #4: And that is helpful and pretty objective. Thank you.

Operator 2: Thank you. Our next question comes from William Pickering with Bernstein. Your line's open.

Operator: Thank you. Our next question comes from William Pickering with Bernstein. Your line's open.

Speaker #2: Thank you. And our next question comes from William Pickering with Bernstein. Your line's open.

William Pickering: Hi. Congrats on the updates, and thanks for the question. On mosliciguat, you also have a phase II open label with patients on background treprostinil. What are you hoping to see in that study? How are you thinking about broader evidence generation strategy to support reimbursement of mosliciguat in combination with treprostinil? Thanks.

Speaker #8: Hi. Congrats on the updates and thanks for the question. On Mosley you also have a phase two open label with patients prostinal. What are you hoping to see in that study?

Speaker #8: And then, how are you thinking about broader evidence generation strategy to support reimbursement, mostly in combination with Prostinal? Thanks.

Matt Gline: Yes. I think in the combo study, we have patients on background treprostinil.

Speaker #4: Yes. So I think in the combo study we have patients on background to prostinil. Obviously, in the main phase 2b, we don't have patients on background to prostinil.

Drew Fromkin: Right.

Matt Gline: Obviously in the main phase II-B, we don't have patients on background treprostinil. The reason we set this up this way is because we know that polypharmacy is going to be a part of the landscape. In the subsequent study that we run, we're likely to have some proportion of patients on background treprostinil as well. 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. 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 design the stratification rules, help us understand better who's going to be on what in the subsequent study.

Speaker #4: And the reason we set this up this way is because we know that polypharmacy is going to be, is going to be a part of the landscape.

Speaker #4: And so, in the phase in the subsequent study that we run, we're likely to have some proportion of patients on background Tyvaso or Prostinil as well.

Speaker #4: 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.

Speaker #4: 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.

Speaker #4: We will learn from it, but information that will help us design the stratification rules will help us understand better who's going to be on what in the subsequent study.

Speaker #4: But I think, beyond that, it's hard to say at this point. And that's—the combo study is still in pretty early days.

Matt Gline: I think beyond that, it's hard to say at this point, and the combo study is still in pretty early days, so we don't have much to say about it. Drew, anything to add to that?

Speaker #4: So we don't have much to say about it. True. I think you'd add to that. I think that's exactly the case. We decided not to go on top of inhaled propostanil.

Drew Fromkin: I think that's exactly the case. We decided not to go on top of inhaled treprostinil in the first FOCUS study. 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 mosliciguat. Also, as you know, treprostinil do have a sticky issue with cough.

Speaker #4: In the first focus study we were initially looking at our drug in single-agent activity in PHILD. And we wanted to have some time to understand that population, understand Mosley.

Speaker #4: Also as you know propostanils 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.

Drew Fromkin: 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. With that, in the later days, we decided with the team to go a little deeper and look at mosliciguat on top of inhaled treprostinil, given the confidence we had in mosliciguat after seeing it in our FOCUS study, of course, in an aggregated setting. 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. We definitely want to understand that from a dosing and safety perspective.

Speaker #4: So with that, in the later days we decided with the team to go a little deeper and look at Mosley on top of inhaled propostanil, given the confidence we had in Mosley after seeing it in our focus study.

Speaker #4: Of course, in an aggregated setting. So with that as a backdrop, as Matt said, we’re only in the early days, but we actually don’t expect there to be much of an issue there.

Speaker #4: But we definitely want to understand that from a dosing and safety perspective.

Speaker #5: Thanks all.

Matt Gline: Thanks, Will.

Speaker #2: Thank you. And the next question's going to come from Douglaso with Dacey Wainwright. Your line's open.

Operator 2: Thank you. The next question's going to come from Douglas Tsao with H.C. Wainwright & Co. Your line's open.

Operator: Thank you. The next question's going to come from Douglas Tsao with H.C. Wainwright & Co. Your line's open.

Douglas Tsao: Hi. Good morning. Thanks for taking the questions and congrats on the data 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 key KOLs, physicians on the data. I'm just curious what their sort of feedback is, and if they were more focused on the depth of response that you saw or the breadth of response. Obviously you've kind of had both, so you don't necessarily have to choose. If there's anything that was striking to them from the initial data set. Thank you.

Speaker #6: Hi. Good morning. Thanks for the data and the progress. And 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 key KOLs and clinicians on the data, and I'm just curious what their sort of feedback is, and if they were more focused on the depth of response than you saw or the breadth of response, and obviously you've kind of had both.

Speaker #6: So if you didn't necessarily have to choose. But if there's anything that would strike me to that I would put in the initial dataset.

Speaker #6: Thank you.

Speaker #4: Thanks Doug. So look we have obviously a bunch of KOLs 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.

Matt Gline: Thanks, Doug. Look, we have obviously a bunch of KOLs 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 one KOL told our team, roughly as a quote, you can't fake ACR70s like this. That's the opinion of one physician. I think it's true at some level. Ultimately, we'll have to see what the rest of the studies show. Look, I think docs are excited. They're excited about the depth of responses. They're excited about what this could mean. 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 and in a lot of pain.

Speaker #4: I think in general the answer is they're super impressed. I think one KOL told our team, roughly as a quote, 'You can't fake ACR70s like this.'

Speaker #4: That's the opinion of one physician. I think it's true at some level. But ultimately we'll have to see what the rest of the studies show.

Speaker #4: 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.

Speaker #4: They have no options. Many of these patients are very uncomfortable. And in a lot of pain. I think they see a new option hoping for something that worked even a little.

Matt Gline: 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 bar handily. I think there's a lot of enthusiasm. Thanks, Doug.

Speaker #4: And obviously, this is beating that bar handily. So I think there's a lot of enthusiasm. Thanks, Doug.

Speaker #6: Very great. Thank you.

Douglas Tsao: Great. Thank you.

Operator 2: Thank you. Our next question will come from Dina Ramadane with Bank of America Securities. Your line's open.

Operator: Thank you. Our next question will come from Dina Ramadane with Bank of America Securities. Your line's open.

Speaker #2: Thank you. And our next question will come from Dina Ramadane with Bank of America Securities. Your line's open.

Speaker #9: Good morning. Congrats on the data this morning. And thanks for taking our question. Just a quick one from us. On the non-responders could you provide maybe some more color on these non-responders in period one?

Dina Ramadane: Good morning. Congrats on the data this morning, and thanks for taking our question. Just a quick one from us. On the non-responders, could you provide maybe some more color on these non-responders in period one? Was there anything you can maybe point to, such as prior lines of failed therapy or baseline characteristics such as maybe antibody levels, that were the reason for not responding to 1402? Thank you.

Speaker #9: Was there anything you can maybe point to such as prior lines of failed therapy or baseline characteristics such as maybe antibody levels that were the reason for not responding to 14.02?

Speaker #9: Thank you.

Speaker #4: Yeah, 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.

Matt Gline: Yeah. 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. You said non-responders. Just a reminder, 72% or 73% were ACR20 responders. We're also looking at some of whom got to 20 but not 50 and just trying to get a better sense of what happened there. Thank you.

Speaker #4: But that's exactly the kind of analysis that we're running. And you said non-responders. Just a reminder 72 or 73 percent were ACR 20 responders.

Speaker #4: So we're also looking at some of the people who've got to 20 but not 50, and just trying to get a better sense of what happened there.

Speaker #4: Thank you.

Operator 2: Thank you. Our next question will come from Iris Gao with Guggenheim. Your line is open.

Operator: Thank you. Our next question will come from Iris Gao with Guggenheim. Your line is open.

Speaker #2: Thank you. And our next question will come from Iris Gow with Guggenheim. Your line is open.

Iris Gao: Good morning. This is Iris on for Yatin. Thank you for taking my question. Congratulations on the data and happy birthday to Matt's father. My question is also on 1402. Are there any more colors on what proportion of patients were refractory to rituximab and maybe anti-IL-6 in these MOAs are relevant in seropositive patients? Would like to check with you. Thank you.

Speaker #10: Good morning. This is Iris Santillate. Thank you for taking my question. Congratulations on the data and happy birthday to Matt's father. My question is also on 14.02.

Speaker #10: Are there any more colors on what proportion of patients were refractory to rituximab? And maybe on NTL-6 and these MOAs are relevant in seropositive patients.

Speaker #10: So let's get back with you. Thank you.

Matt Gline: Yeah, 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 refractory patients, but rituximab, I don't know. Look, overall, we don't have that to 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. All of those different mechanisms are in. We may eventually share more data on sort of what those different subsets look like. I think we're particularly enthusiastic about the JAK and TNF combined failures. Remember that over 10% of these patients had failed more than 3 lines of these advanced therapies. Thank you.

Speaker #4: Yeah, 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 or IL-6 refractory patients.

Speaker #4: But we're talking about—I don't know. And so, look, overall, we don't have that to share right now. But I think the answer is the population is consistent with heavily pretreated populations.

Speaker #4: They've been on multiple lines of therapy. Many of them have failed things in addition to JAKs and TNFs. So all of those different mechanisms are in.

Speaker #4: 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 the TNF the JAK and TNF combined failures.

Speaker #4: Remember that over 10 percent of these patients had failed more than three lines of these advanced therapies. Thank you.

Speaker #10: Thank you very much.

Iris Gao: Okay, thanks.

Operator 2: Thank you. Our next question will come from Sam Slutsky with LifeSci Capital. Your line's open.

Operator: Thank you. Our next question will come from Sam Slutsky with LifeSci Capital. Your line's open.

Speaker #2: Thank you. And our next question will come from Sam Slutsky with LifeSac Capital. Your line's open.

[Analyst] (LifeSci Capital): Hi. Good morning. This is Kate on for Sam. I appreciate you taking the question. I know the strength of period 1 data has made period 2 all the more challenging, particularly on ACR20. Looking to period 2, is there a delta versus placebo potentially on other endpoints that would excite you commercially?

Kate Dellorusso: Hi. Good morning. This is Kate on for Sam. I appreciate you taking the question. I know the strength of period 1 data has made period 2 all the more challenging, particularly on ACR20. Looking to period 2, is there a delta versus placebo potentially on other endpoints that would excite you commercially?

Speaker #11: Hi. Good morning. This is Kate on for Sam. I appreciate you taking the question. So I know the strength of period one data has made period two all the more challenging.

Speaker #11: Particularly on ACR 20. But looking to period two is there a delta versus placebo potentially on other endpoints that would excite you commercially?

Speaker #4: I don't think phase two is really about commercial value at this point. I think phase two is about better understanding the characteristics of the patients.

Matt Gline: I don't think phase II is really about commercial value at this point. I think phase II is about better understanding the characteristics of the patients, seeing erosion of efficacy, starting to understand, to separate out drug effects from other things. 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. I think even in subsequent studies, I don't know that we're shooting for this bar per se. This is just a great foundation from which to build something pretty exciting in RA.

Speaker #4: Seeing erosion of efficacy. Starting to understand to separate out drug effect from other things. So I think I think it's not so much that we're looking for some commercial bar in phase two.

Speaker #4: 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 that we're shooting for this bar per se.

Speaker #4: This is just a great foundation from which to build something pretty exciting in RA.

[Analyst] (LifeSci Capital): Makes sense. Thank you.

Kate Dellorusso: Makes sense. Thank you.

Speaker #11: Makes sense. Thank you.

Operator 2: Thank you. That will conclude today's Q&A session, and I will now turn the call back over to Matthew Gline for closing remarks.

Operator: Thank you. That will conclude today's Q&A session, and I will now turn the call back over to Matthew Gline for closing remarks.

Speaker #2: Thank you. And that will conclude today's Q&A session. I will now turn the call back over to Matthew Gline for closing remarks.

Matt Gline: Great. Look, thank you everybody again. Appreciate it. There were a lot of questions there. I appreciate everyone's forbearance in helping us get through it all. In limiting the number of questions, which is a great favor to the people lower in the queue who need to come up with questions if theirs has already been asked. Thank you again to everybody for playing along with that. An exciting day for us, and exciting data to be able to put out. Thank you again to everybody who made that happen, from the Vants and Roivant teams to the patients and investigators. It takes a village and it's a great outcome and something that we can really build from from here. Once again, happy birthday to my dad. Thank you everyone for listening, and we'll talk again soon. Have a great day.

Speaker #4: Great. Look thank you everybody again. Appreciate it. There were a lot of questions there. So I appreciate everyone's forbearance in helping us get through it all.

Speaker #4: And in limiting a number of questions which is a great favor to the people lower in the queue who need to come up with questions if theirs has already been asked.

Speaker #4: 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.

Speaker #4: So thank you again to everybody who makes that happen from the Vanton Roivant teams to the patients and investigators it takes a village. And it's a great outcome.

Speaker #4: It's something that we can really build from here. And once again happy birthday to my dad. Thank you everyone for listening. And we'll talk again soon.

Speaker #4: Have a great day.

Operator 2: This concludes the conference call. Thank you for participating, and you may now disconnect.

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

Speaker #2: This concludes the conference call. Thank you for participating. And you may now disconnect.

Douglas Tsao: Goodbye.