Brepocitinib in NIU: CLARITY Phase 3 Study Results - ROIVANT SCIENCES LTD

Good day and thank you for standing by. Welcome to the Revan's Clarity Phase 3 Study Results Conference Call. At this time, all participants are in the 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. Please note that today's conference is being recorded. I will now hand the conference over to your speaker host, Stephanie Lee. Please go ahead. Good morning, and thanks for joining today's call to review the clarity phase three results. I'm Stephanie Labus-Roygans. Presenting today, we have Matt Lyon, CEO of Roygans, 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.roygans dot com. We'll also be providing the current slide numbers as we present them as we follow along. I'd like to remind you that we will be making certain forward-looking statements during today's presentation. We strongly encourage you to review the information that we have filed with the FCC for more information regarding these forward-looking statements and related risks and uncertainties. And with that, I'll turn it over to Matt. Thank you, Steph, and thank you everybody for joining this morning on short notice. We really appreciate it. It's obviously an exciting moment to get together. So I'm going to do a little bit of frame-up here, and then I'm gonna take you through what are some obviously really exciting data that we're putting out this morning. So starting on slide three, just as a reminder, and this was from our investor day last year, By the way, we're announcing today that we're doing another investor day in December of this year, so we'll come back to more of that in a moment. But it's obviously the middle or early innings of a really busy period for us, and we're excited about continuing to add green tech marks to this slide, such as it is as we advance multiple among these programs. but just wanted to highlight lots more to come, including LPP, ECS, other representative indications, and more beyond. So just a tremendously exciting moment. As a reminder on slide four, our overall hypothesis around BREPO was always that we could find a constellation of diseases where there was an orphan prevalence with a large unmet need with pathobiology specifically aligned to the unique mechanism of of brepo and where we thought we could make a big difference and i think you know dm was obviously the first proof point for that and now let's raya is out in the market by the way one comment we're not going to be talking today about the list raya launch we're excited to do that uh on our queue on november 9th uh with our quarterly earnings so today we're focused on the on the uh niu data but uh you know now with niu we've added another linked VAT stool such as it is, another proof point, which hopefully will become a commercial product here, that we can deliver this kind of transformative data. And these high morbidity indications is a lot of need. And on slide five, look, NIU is a high morbidity indication. It is the third leading cause of blindness in the US. There's not a lot that works here. The only really sort of approved non-steroid therapy is Humira. And both in the clinical data as well, if you look at the claims data, it looks like, you know, half of NIU patients on Humira, you Know, either fail or worsen while they're on the drug. So, there's a high unmet need and, you can wind up, in addition to blindness, obviously wind up with pain, with redness, with distorted vision, with floaters, headache, fatigue, just a really tough disease. It's a fairly prevalent disease as well. You know, obviously many of these patients have, you know, front of the eye inflammation, but even among sort of patients with back of the eyes or are all over sort of inflammation. There's somewhere between 70,000 and 190,000 of those patients from a variety of different ideologies. And, you know, it's just an indication with a huge amount of unmet need in the world. One highlight on slide six, and we're going to talk much more about the marketplace for NIU, how it is evolving, how we see the patient numbers, et cetera, on our investor day in December. But in the meantime, just as a reminder, we are in a moment of evolution for the treatment of NIU across a couple of different axes. First, over time, more and more of these patients are getting treated by uveitis specialists, often at uveitus referral centers. These are docs with either a specific uveritis fellowship under their belt or they're sort of double-boarded or whatever. These their docs were like really specific to treating these patients and who are highly comfortable with systemic therapy. Often they have a general medicine training as well, and away from these community-run docs who were more sort of procedure-based in their approach. And part of that's coming with an increasing understanding that this sort of systemic, this sort of local sawtooth flare and treat cycle, which the sort of localized therapy and high-dose steroids lends itself to is just not good for patients or their eyes. And so there's a goal to get much more stable, long-term, sort of properly controlled disease. And bluntly, given the quality of data we're putting out today, REPL couldn't have come at a better moment for that transition. So we're excited to talk more about that. And I think as you speak, especially these UVA specialists in your own research, you will hear something similar reflected back to you from the field. With that, I'm going to give the data. By the way, Ben Zimmer from Priyavent is on the call too. I'm gonna present the data, but he'll be available for Q&A as we get into it. So, look, on slide eight, before we get to the headline, just a reminder, we chose NIU on a pretty directed thesis that it's understood that a number of the key pathogenic cytokines involved in NIU, IL-23, interferon gamma, IL12, IL6, all of these are signaled by either JAK1 or TIK2, and the BREP will therefore get us good inhibition across this whole inflammatory cascade. And so that was the hope. Obviously, the Neptune phase two data was highly suggestive, albeit with small n. And I think, look, the headline here, and we'll get into it now on slide nine, is I feel like largely we recapitulated the really, really exciting data that we had seen in Neptune in phase two in much larger n, and reintroduced a placebo arm that looked comparable to what the placebo arm in other studies, including the Kivira study, showed. So just a really, really great outcome. You know, we got the largest efficacy benefit ever seen for a non-steroidal therapy. Our time to treatment failure was the primary endpoint here, was over 48 weeks. So it was a 48-week study. We'll go into the study design. More than half of the patients had not yet failed by the end of the study. So the median treatment time was, median time for treatment failure, was in some sense indeterminate or not reached. by 48 weeks versus about 12 weeks. 12 weeks in one of the studies and 13 weeks in the other study with obviously a really great p-value. We met the primary endpoint and every secondary endpoint in each study on a separate basis as well as on a pooled basis. We had over 60% of patients got to steroid-free quiescence. That is a steroid free quiet eye at the end of the study, which is really a key treatment goal for physicians. It's something that docs are really working towards. And it was consistent across all subgroups. We have statistically and clinically meaningful improvement in vision-related endpoints, structural and functional benefits, including on fluorescein and geography, really great resolution of macular edema. We'll talk more about that. Just a phenomenal outcome and a safety profile, which we'll go into, but which is well-tolerated and entirely consistent with everything you'd expect, both from our own prior data and from the JAK inhibitor class and other JAK intimidors. On slide 10, as a reminder of the study design here, so this was an event-based study. it was a 48-week treatment period. Clarity 1 and Clarity 2 were identical studies. You can see all the ends on the slide. And the way these studies work is you start out with a very high-dose burst of steroids, 60 milligrams starting for two weeks, and then you taper. And as a reminder, we had, I think, the most aggressive steroid taper certainly in any big NIU study, and we were tapering over six weeks as these patients were fully tapered by week eight. And so our data is particularly exciting in the context of having achieved it, even against the backdrop of a more aggressive taper than in the other studies for approved drugs. And that's sort of the design of the study. And then these patients, once they failed treatment along a variety of different axes, they were then taken out of the studies and put into an open-label extension or a long-term extension, I should say. So that's the design of the trial. This was a representative NIU population on slide 11. Good range of patients, good disease severity. Notably, about a third of the patients across the studies were exposed to prior TNF, so that's really nice to have that data set, and we'll talk more about what it looked like in that group specifically. Obviously, this is one of the first studies where that specific population could have been evaluated, and so exciting to see that. But overall, a severe sort of high rate of macular edema in the patient population, a good group of patients for the study. We were happy with how that shook out. I won't go into them all here, but on slide 12, just again, we had really terrific p-values in both studies on every, on the primary and on every secondary endpoint, and that's across a variety of, you know, both, you know, functional, patient-reported, etc., a variety of outcomes. On slide 13, so, you know, we are, most of our trials thus far have not been event-based studies, so we have not had a lot of opportunity to put out Kaplan-Meier curves. These are, you know, from our perspective, just absolutely beautiful curves from a variety of different axes. One, just in absolute terms, you look at these patients, the rates of treatment failure, you know, again, placebo 12 and 13 weeks, depending on which study. In both studies, BREPO didn't hit 50% treatment failure by the end. But also, frankly, just like the flatness of this curve in the back half of it, not only are we not hitting 50%, but it really looks like these patients are stable leaving the study, which is a phenomenal outcome given the quality of treatment effect. Notably, on slide 14, on the left-hand side here, you have the pooled Kaplan-Meier curve for both Clarity 1 and Clarity 2. On the right-hand side, you have the equivalent curve from the visual one from the Humira study. Obviously, a cross-trial comparison with all the appropriate caveats. Obviously on the right- hand side, in visual, a less aggressive steroid taper. But overall, just, you know, I think it highlights in pretty sharp relief that this is field-changing, that this a really different qualitative option for these patients that will, we hope, help a lot of people. On slide 15, this is another version of effectively the same crush-off comparison. I just want to highlight, not only did we blow it out of the water in terms of time treatment failure, but because we did it against a more aggressive steroid taper, the overall time from the end of steroid dosing to the median treatment failure is even more exaggerated to our favor in a way that feels really great. These patients are getting long durable responses or long durable stability, I should say, without being on background steroids, which is just, it's just awesome for this patient population. Then go through a couple of the subgroups and secondaries now, starting on page 16. You know, we, this is a comparison on the left-hand side of the pool of data in the overall population for the treatment failure rate at the end of the study. You can see, again, 33.5% on brepo, 78% on placebo, and then on the right-hand side, we have the data specifically in the subset that had prior TNF experience. This is data that has already been pretty head-turning in the community of docs here, and it looks pretty similar, to be honest. We're able to deliver a highly comparable rate of treatment failure on drug for the TNFC failure patients as in the overall population, which feels really good. I mentioned on slide 17 this, like, change in paradigm where we're going away from sort of sawtooth sort of flare cycle treatment to trying to get this, like, sustained steroid-free quiescence, trying to get these patients to a stable place. You can see a quote here from an important doc in the field. And I think, you know, that change is particularly good for us in this moment because of what we've been able to show. And on slide 18, this has been another really well-received early with activity data point. We're getting very high rates of steroid-free quiescence at the end of the study, up to close to 60% or above 60% in one of the studies versus about 20% on placebo. A very high proportion of these patients are stable with quiet eye. And I think notably, this is quite a strict definition for steroid free quiesence. If you show this definition to doctor-treat these patients, this was a really good bar to hit. and we cleared it very comfortably. I'm not going to go into a lot of great detail about what this is, but docs now manage these. Obviously, treatment failure is a very clinical trial endpoint. It's not something that docs are thinking about on a day-to-day basis. A lot of these docs use fluorescein angiography as a technique to monitor and manage these patients, and we have an endpoint in the study. It is on slide 19 defined where we had a scale using fluoresceин angiology to evaluate these patients. That is notable, again, because it's a lot of how these patients are managed in the field, and on slide 20, you can see as a matter of separation from placebo, this again is in the pool of data, just tremendous separation from a placebo on this measure, which again is something I think docs are going to find really valuable because it foots much more closely with a relatively rigorous benchmark against which how they manage their own patients. A couple more data points here to share. Again, we're just excited about the totality of it here, so we're putting a lot out there. One, on slide 21, macular edema. So we said about a third of the population, I think, came in with macular edema, the exact numbers are in the earlier slide. Of those patients, 40% of them in clarity one and a little bit more than that in clarity two saw resolution, clinically meaningful resolution of their macularedema by the end of the study compared with very low rates on placebo. This is something that generally you don't achieve with systemic therapy and other studies. So the fact that we were able to get quite high rates of resolution of macular edema. Again, very exciting here in another way in which BREPO has the potential to be important for this patient population. Lastly, from an efficacy perspective on slide 22, there's a variety of different ways of measuring efficacy from a functional perspective, and frankly, everything we studied looked good. This is one of the secondaries is a visual function questionnaire. This is a patient-reported outcome with a bunch of subscales that include general vision, pain, near activities, distance activities, mental health, difficulty with role, dependency in driving, And we saw, you know, starting with week six, meaningful separation with very good benefit for BRPA45 relative to placebo in both studies. So, again, not only delivering some of the kinds of things that ophthalmologists care about managing the disease, but the kind of thing that patients care about in living with the disease which feels really, really good. The truth on slides 23 and 24 on safety is not much new to report. You know, consistently well-tolerated and consistent with prior BRPA studies and with the JAK class. We lay out the rates of AEs on 23 in a little bit of detail on slide 24. You know, I have to take questions as they come up, but our overall view of this is it's consistent with the label on Lysri already and consistent with what people will expect for the drug. So, look, to summarize the data on slide 25, just a really terrific outcome. We could not be happier here. The steroid-free quiescence sets us up for the sort of present and future of treatment of NIU. the imaging biomarkers will appeal to docs who use those techniques to manage these patients on a daily basis. You know, we're preserving acuity and function, and we have safety that is, you know, consistent with Jax, and certainly, in our view, a good trade-off for benefit for patients with a disease that can lead to very bad morbidity in the eye. And remember, many of these patients are otherwise on quite high doses of background steroids, which are not safe or well-tolerated over long periods of time. So, you know, against that backdrop, just a really nice finding. The private team is going to get this S&DA into the first half of 27. And, you Know, hopefully between everything, that'll lead to a relatively quick approval. So, You Know, taking a step back before we head out and open the line for Q&A on 26, we've said all along that we are just getting started with repo and we're starting to climb this hill or build this wall one brick at a time. NIU, obviously, now hopefully the second registrational indication. We got two more already in the pipeline with CS and LPP, both well underway, enrolling patients, looking promising from that perspective. We have a ton more we want to do. I know Ben and the private team are raring to go getting additional studies up and running, and we think this just has the potential to be a huge opportunity across lots of diseases where consistently very high unmet need and not a lot of other options for these patients. And as a reminder on slide 27, this is just one of multiple among our programs now with Moseley-Sigawatt in pivotal studies after the great data we had earlier this fall and obviously 1402 with a huge year next year with data coming in MG and Graves and a number of other studies ongoing as well. And still to come this year, further updates on the period two of the Difficult to Treat Rheumatoid Arthritis Study, another really exciting indication for us with a high unmet need. And lastly, on slide 28, on December 9th, we'll have our annual investor day, or our investor day this year anyway, in New York City. Looking forward to seeing many of you there. One of the things we will definitely do is talk more about the NIU market and, you know, get into what we see as the opportunity and the unmet need for patients in clear relief. Frankly, I think this is an area that has been understudied by our investors over the last, call it, 12 months, as people have been more focused on the, you Know, present commercial launch in DM. And as a reminder, as we get to Q&A, we're not going to take questions on the list that I launched today. We're looking forward to taking them and talking more about how that's going, which we're very excited about, on the queue in November. So that's it for the presentation today. Before we head out to QAnon, I just want to say thank you to a bunch of people here. Obviously, most importantly, to the investigators and patients who have trusted us, thank you. We wouldn't have this science without you. And obviously, it's an interesting thing to give yourself over to a clinical trial. We're happy, in this case, to have been able to make it worthwhile. Secondly, you know, I want to thank Ben and the Privant team who did a phenomenal job, again, with this study. I'm really proud of the quality of the code of execution that Roivant's been putting up here. And this is another example of an indication where, you Know, I think first pioneered by Roivand on the investments of the governance team, by you, Frank, and everybody at the Roivans side. And then, you Now, put into a phase two study, then a phase three study. It's just nice to continue to see this execution. So I want to thank the private team, the relevant team, just a huge effort. So thank you, everybody. And with that, I want say thank you all for listening, and I will turn the call over to Q&A. Thank you. Ladies and gentlemen, to ask a question at this time, you will need to press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, simply press star 11 again. As a reminder, in the consideration of time, please limit yourself to one question and one follow-up. one moment for our first question now first question in queue coming from the line of iran weber with td kawa new line is now open uh good morning congrats team and uh congrats on a really fantastic data set so my question is the data is so clear pretty much all across the board whether you look at tnf experience. You look at macular edema, oral, very well tolerated, very fast onset of action, and obviously very good durability. Humira is cheaper. Do you think you'll need to go through a Humira step at it? I assume you'll get a broad label. Is there a chance you can get used before Humira? Thank you. Yeah, thanks, Jeroen. Look, thank you also for the commercial on our own data. We agree with everything you just said about it. It's really great data. I appreciate the question. Look, I think the truth is we obviously don't know the answer to that question. Our data is really, really strong, and Humira has some real liabilities in this area. So there's certainly a chance that docs will be excited about the data and will want to use it earlier. And I think that opportunity exists. As a reminder, in general, the FDA stance on JAK inhibitors is in a TNF-approved indication. There's some labeling that suggests the use of a TANF first. And I think your pair of points are reasonable, although there are plenty of plans where more expensive therapies are allowed without first stepping through Humira in indications where Humira is approved. So there are certainly examples where earlier line therapy is possible. I think the only thing I'll say is there are, I think we put out number for like 37-ish thousand at least NIU patients on TNFs. Even the TNV failure population or the population of people who could be better controlled despite use of a TNR is a large and exciting opportunity and one where there's a lot of unmet need. So I think we certainly have an opportunity to go earlier, but also I think that we don't need to. Thanks, Jeroen. Thank you. Our next question coming from the lineup, Brian Cheng with JP Morgan. Your line Ms. Malikun. Hey, guys. Thanks for taking our questions and congrats on the data this morning. Maybe just to, you know, when we look at the treatment failure, I believe that there are three criteria that goes into defining treatment failure. So, I'm curious how the response you're seeing, how does that break down compared to, um, you don't want to do that? Um, you know, Humira treatment failure is what we're seeing driven by specific components. And then second is, you know, can you frame how we should think about the resolution in macular edema, this piece? Do you expect that benefit to be on the label? And just curious how important that is from a commercial perspective. Thanks, guys. Yeah, thanks. So on the first question, I can say there are four criteria for treatment failure. There are new vascular lesions, a change in ACC or VH grade or BCVA worsening. And I feel like overall across the population, treatment failure was driven by all of the different components. So there was nothing that like stood out specifically. It was pretty well balanced. You know, Ben, do you want to take the macular edema question short? Yeah, sure. I think, you know, TBD won't get on the label. I think that it is an exciting add-on and, you know, differentiation, particularly from adalimumab or any off-label other TNF inhibitors or biologics that are used. As Matt mentioned before, it's generally, you Know, both from clinical trial data and clinical experience, the view that these patients are not able to address their macular edema through those therapies. I think what's really exciting about this data overall is the opportunity to combine benefit on macular edema and CST with a therapy that can provide overall sustained disease control around inflammation and uveitis more broadly. And I think that, I think it will be an exciting, you know, point of differentiation in the context of the overall data set. But I think that there's a lot here that is going to be really exciting to doctors. Thanks, Brian. Thank you. Our next question in queue coming from the line up, Yasmin Rahimi with Piper Sandler. Yolanda, it's now open. Team, congrats to the outstanding data. Team, it would be wonderful if you could kind of educate us. I think you did a great job with Repo and DM on kind of helping us understand that these patients are in concentrated centers. Maybe just talk about sort of, you know, the heterogeneity or is there a cluster of these patients under these community retinal docs? How do you envision that? And maybe to the extent you could talk about how much that would involve expansion of your sales force that would be dedicated to the NIU launch? And I know maybe many of these things may come up at R&D day in December, but to the extent you could give us some broad color, we would be very grateful. Great. Thanks, Yasmeen. I appreciate it. It's a good question. And we will hit a lot of this in more detail on our investor day in September. You know, I think, first of all, there's just an increasing trend towards more of these patients being treated at these centers. I think the centers make excellent early relationship points for us here because they are equipped to manage systemic medicine and are already big users of systemic medicine. We'll talk a little more about number in the future, but I think they will be among our earliest and most important call points. There are obviously also retina docs and docs in the community who partner with rheumatologists and so on to use systemic medicine, and you can see where they are. They use Humira and so on, so I think we're going to be able to call on a variety of different physicians. I'll say I think the correct expectation here is this is a different commercial organization than the one largely currently launching in dermatomyositis. So I think it's going to be a new commercial effort. Obviously, the patient support work, a lot of the other things that are going into making the Lyserio launch successful will be reusable, but the field personnel will be different. Look, I think – the truth is these patients are often going blind. They're not hard to find, right? they're out there, they're engaged with their docs, and the doc tolerance in general for eye disease is poor, for eye inflammation is poor. So, docs are reaching for the most aggressive things they can find. And so, they are, you know, tens of thousands of these patients are treated in these specialty centers. More and more are getting referred there. And I think the goal is to treat them very aggressively. Thanks, Yasmin. Thank you. Thank Thank you. Our next question coming from the line of Samantha Semienko, Wood City. Your line is now open. Hi. Good morning. Thanks very much for taking the question, and congratulations on this really great data set. I'm wondering if you could talk a little bit more about your appetite for potentially expanding indications for BREPO specifically within ophthalmology, maybe even for diseases with macular edema, given the data this morning, relative to the expansion opportunities for other therapeutic areas? Because I know that there's potentially a long list that you're evaluating. Thanks very much. Yeah, thanks. It's a great question. Look, I think the short answer to our appetite for expanding indications for BREPO is high. We're doing a lot of work on that. There are ophthalmology indications on our list. There are other indications on OurList. I'm not prepared sitting here today to commit to any particular sequencing or path of those, but I'll say we're living with this data fresh. We've only had it for a few days, so let us continue to study it and see what avenues it suggests, but lots of great places to go, spoiled for choice, and definitely hoping to do more fast. Thanks, Sam. Thank you. Our next question coming from the lineup, Alex Thompson with Stiefel. Yolanda is now open. Hey, great. Thanks for taking our question, and congrats as well on the data. I guess one of the other differences versus visual one was that you didn't require patients with baseline OCS use. I guess, could you comment on sort of how those patients did and maybe to Yaron's question earlier, sort of what that might mean for how REPO could be positioned within the broader NIU population? Thank you. Yeah, thanks. It's a great question. I appreciate it. And Ben, I'll ask you to comment too. Look, I think in general, you know, first of all, it's a severe patient population. We had similar efficacy regardless of whether baseline OCS were involved or not. Obviously, a unique thing about this patient population is that there are also TNF-experienced patients in it. And so there's, you know, there's some pretty sick patients who have gone through a lot of things. So obviously, like, for example, the visual studies obviously couldn't have included TNFR refractory patients, and we wanted a broad population. I think that will be helpful in the sense that it opens up the broadest possible opportunity for NIU patients sort of regardless of where they are in the treatment cascade. but again, no sort of significant differences in effect across those subgroups. Ben, anything you'd add to that? No, I would just say that the visual study was conducted a while ago. I think there are more heterogeneous therapies used today to control patients with active disease, including systemic therapies, obviously TNF inhibitors, which were not used at that time, being the major other off-label therapies, DMARD. And so what we really wanted was a population that matched the real world population. And I think that's what we got, which includes a lot of patients who were on background steroids, some who had been on in the past, but weren't at the moment, patients who've been on other therapies. And yeah, that's the baseline criteria or the baseline demographics, I think, capture well across a variety of ways in terms of percent of patients with macular edema, percent of patients where asteria and panubiitis, percent of patients who had prior TNF therapy, I think, captures this broad-based active population. And I think that's really kind of where we would expect to see, you know, expect to see the drug used in the real world as well. Thanks, Alex. Thank you. Our next question coming from the line of Yatin Suneja with Guggenheim Securities. Your line is now open. Hey, guys. Thank you for taking my question, and congrats, obviously, on the data and continued amazing execution. Just a question on the payer front. I mean, what sort of feedback you have received or the work that you have done, especially now that we know what the price is going to be? And again, I think it's a similar type of a question that Yaron asked earlier. How should we think about positioning and the acceptability of the price in the context of what is out there for these patients? Thank you. Yeah, thanks. Look, it's, it'S a great question. Obviously it's early days, even in the Lysrila launch. So I think, you know, itS still, we're happy with how things are going so far, but still learning, you Know, how to manage that over time, but again, happy with things are going so far, and also quite early days with this data. So I think it's like a little bit premature to answer that question. The unmet need is very high. Here, these patients are losing vision. There's very high morbidity from the disease. And we've seen in other markets tolerance for high price points in eye disease, frankly, because the unmet needs is high and because the ability to improve morbidity for these diseases really matters. I'll say, as a reminder, are dosing here is 45 milligrams, which is different from the DM dose. So we have some flexibility on price in terms of where we could go. And I think, you know, we're, I'd say every option is open. We haven't made any decisions. Again, we have only had the data for a few days. So looking forward to learning more from exactly the conversations you're suggesting over the next month. And, uh, I think we've got a lot of flexibility in a disease with very high unmet need. Thank you. Thank you. Our next question in queue coming from the line of Raghav Agrawal with Cancer Fitzgerald. Your line is now open. Hi. Thank you for taking my questions, and congrats as well from my side on the data. Maybe, Matt, you talked about the different subcomponents of the treatment failure. One of the subcomponent, the change in mean BCVA, could you confirm if that also looked comparable to phase two and better than that seen with Hemiret. We've gotten some questions on that. And then one technical clarification, rescue meds seem to be handled as failures. How were the discontinuations handled in the start plan and whether this handling is comparable to Hemire's visual one? And just lastly, as you think about the Salesforce expansion given this as a new physician call point, how should we think about that? Thank you so much. I'll take those in reverse order. They're all good questions. On the field force, I think the answer is we'll provide more color on the specific sizes of things, probably starting on Investor Day and developing from there. So stay tuned. On the discontinuation handling versus visual, I'm going to hand it over to Ben for the first of your questions, so he can take the other one as well. I think discontinuation handing was the same as it was handled in the visual program, which is a little bit different than the way the primary input was defined in our own phase two, although we presented the data both ways. But the distributions were handled consistently here as in visual. You know, on BCVA, my only comment is everything looked strong and consistent across the map. That data is still being analyzed in part. It wasn't in the hierarchy of stats plans. It was a little different handling. But overall, it all looks very good. Ben, anything you'd add on BC VA or any of the other data points? On BCVA, I would just highlight that we, you know, all four of the components of treatment failure contributed to the results. So, we saw differences between drug and placebo across the board. I would also highlight that just the way this disease is managed is that, you know, the doctors, precisely because of what Matt was describing in terms of, you know, really today, even in many ways compared to when the visual program was conducted, there's really even less of a tolerance for vision loss. The doctors really do not want these patients to worsen because they're of the view that, you know, that they might not fully ever get better. And so, you Know, I think often you'll see patients failing for one of the other criteria because doctors are monitoring the biomarkers carefully, and then they want to switch therapies before the patient has a 15-letter loss in acuity, and that's very much consistent with clinical practice in a growing way at these uveitis centers, as Matt described up front. That said, there were patients who failed for BCBA, and like I said, all four components, including that one, contributed to the total result. Thanks, Ben. And just two other points just to close the loop. One is, discontinuity of handling, just to be clear, didn't matter in the results. And BCVA, which we presented at an academic conference and which was great, also hits that stage. Thanks, Prakhar. Thank you. Our next question, coming from the line of Douglas Tull with HC Wrenright, your line is now open. Hi. Good morning. taking the questions, and congrats on the data. You know, Matt, I think at the beginning of the call, you talked about sort of how patients are treated very differently by uveitis specialists versus more sort of general treaters in the community. And I'm just curious, you know, if you have a sense of both the split between patients between the two and how a patient ultimately ends up being treated by a uveitus specialist. Thank you. yeah thanks doug and again we'll hit uh more of this uh at the investor day in december uh but you know including numbers on the split there are tens of thousands of patients at least treated these uva especially centers and there is a there's a little bit of a gray area where there are some community docs that are double boarded or have uva fellowships and some centers that are like really concentrated so it's not it's Not exactly a bright line but part by the way of the reason I say that is what I expect many people are going to do in the coming days given the quality of this data is make doc calls. I think it's important to talk to docs who use systemic therapy to treat these patients because they are the ones who really contextualize this data and the way they're managed in that sense. How do these patients get to these centers? In part, the answer to that question is by community physicians who don't do a lot of systemic therapy management, there's sort of a flare and response cycle. What winds up happening these patients come in, they flare, they get treated with something, either a high-nose steroid or something local, an injection, and then they're better for a little bit, and then I flare again. And eventually, frankly, these community docs, the retina specials don't want to keep treating these patients. It's not their area of expertise. And so the referral is often sort of bidirectional. That is, the doc themselves would prefer to be in the procedure business in many cases and wants to get out of systemic management so that they're happy to refer. Also, these patients are sick, they're losing sight, so they're aggressively seeking expert therapy, and they're eager to find a good place to be themselves, so it's a combination of different things. Thanks, Doug. Thank you. Our next question in queue, coming from the line up, Jingfeng with Bank of America. Your line is now open. Hey, guys. Good morning. Thanks for taking my question. My question is on the filing for Bradford NIU. What are the gating factors to filing as we think about the first HOP27 window? And secondarily, Brad Pohl has fast-track vaccination for NIU. Do you assume a standard review or priority review for the SMDA? Thanks so much. Thanks. That's a great question. I don't have an answer sitting here right now other than this is great data, and we think it is important to get the drug approved as quickly as possible, and working along that access in every way that we can, and we'll provide an update when the S&DA has been accepted and we have a Biduva date. Thanks, Jackie. Thank you. Our next question coming from the lineup, Andy Chen with Wolf Research, Yolanda Salvin. Hi, guys. Thank you so much. We just wanted to ask a quick question about the market share poll that you guys have. So, what is the pull-up untreated NIU patient eligible for BREPO versus HUMAR experienced patients? And within the untreated population, how many actually require systemic therapy, and how should we think about the prevalent patient opportunity at launch versus annual new patient starts? Thank you. Yeah, thanks. These are all great questions about the market opportunity, and we do think there's a lot more work to do in the world for people to understand just how many of these patients there are. you patients. And frankly, there's a variety of reasons why Humira is used, where it's used. Many of these patients have comorbidities. I think there's like a lot to talk about here, much of which we're going to cover in detail in December. I'll say there's huge opportunity just concentrated in the sick patient population today that is on best available therapy and not well-managed, that are often on and off high-dose steroids. In some cases, 20 plus milligrams of steroids being used, like these are sick patients who are losing their sight. So I think like there's a sort of quote-unquote easy sort of first call point. But, you know, there's 50,000 patients systemically treated today, you Know, as we said, potentially upwards of 100 or close to 200,000 patients overall, many of whom are poorly managed in this flare and retreat cycle. So lots to do. Again, exciting to talk more about it in December. Great. Thank you. Thank you. And there are no further questions in the Q&A queue at this time. I will now turn the call back over to Mr. Matigline for any closing comments. Great. Look, thank you again, everybody, for listening. It's always fun when these things work. It's fun to put out data like this. I think this is head-turning data that's going to matter to physicians, it's going to matter for patients. This is a disease with really bad morbidity. I always do this, but you should go on Reddit, to the UVA to subreddit, and look at how patients talk about their experience with disease. This is a tough diagnosis, a tough situation, and it's just phenomenal to be able to make a difference. So thank you again to the investigators and the patients who entrusted us with their care here. Thank you to the Privant and Roivant teams, to Ben and everybody who ran this study. It's a great outcome, and we couldn't be more excited to be taking this one forward and advancing other indications as well. So thank you all, and looking forward to catching up again in a couple weeks with the Q. Thanks, everybody. Ladies and gentlemen, that's the conference for today. Thank you for your participation, and you may now disconnect.