Conference Transcript - ROIV 2026-09-08

Derek Archila, Analyst — Wells Fargo

Good to see everyone. Thanks so much for joining us for the next fireside. My name is Derek Archilla. I'm one of the Wells Fargo biotech analysts. So next company here, we have Roy Vant from the company. We have Matt Glein, CEO. Matt, thanks for joining us today on a great day for some new data. Great times to always have good data is right around a conference.

Matt Gline, CEO

That's right. Yeah. No, thanks for having us. It's great. We put out some data in PHLG this morning that was pretty extraordinary. So it's exciting to be here.

Derek Archila, Analyst — Wells Fargo

Well, let's start there, you know, very topical. So maybe walk us through kind of the focus trial and ultimately, you know, what we're putting into context, some of the data that we saw today.

Matt Gline, CEO

Yeah, taking just like a two-second step back first, just in case anyone's not familiar. So we're even now just under a $30 billion market cap company. At this point, a leg with three stools, such as it were. You know, brepacitinib is our quote-unquote lead product. Just got approved a couple weeks ago in dermatomyositis under the brand name Lysraya. We have an FCRN that Derek knows extremely well, and I'm sure we'll spend some time talking about today, and Immunivant. And then the third of them, which had been third in line until this morning, is Mosley-Seguat. Mosley-Seguat is an inhaled SGC activator. So this is a mechanism. It's effectively a potent vasodilator, among other things. And it's a mechanism. SGC-targeted therapies have been studied. In fact, in one case, there's a systemically administered SGC called Adempis that was a Merck-Bayer collaborative project in PAH. It was about a $2 billion drug at peak. Anyway, PHLD, for those who are unfamiliar with it, is pulmonary hypertension that comes from having lung disease, and it's been a tough indication because systemic vasodilation for these patients is dangerous. You wind up, all the benefit you get from vasodilating the healthy lung tissue, you give up by vasodilating the unhealthy lung tissue, and so it's been a tough indication to study. And in the last few years, inhaled treprosinols, most notably Tivaso from United Therapeutics, but also Eutrepia from Liquidia and coming TPIP from InnsMed, all different formulations of teprostanol have been successful at treating these patients. And so we took Mosley Sigawatt, this inhaled SDC activator, into PHILD with the hope of replicating that idea. FOCUS was a large 100-some-odd, 120-ish patient phase 2B study in PHILD that was designed to demonstrate that we could treat these patients. And boy, howdy, that was a really nice outcome. So we got the deepest ever observed PVR, pulmonary vascular resistance, measured by right-hearted I think in any pulmonary hypertension study ever, we had about a 56% placebo-adjusted improvement in PVR. We were not powered for a p-value on the functional 1.6-minute walk, but we delivered a p-value on the functional 1.6-minute walk. So just a really, really good set of data all around. And I don't know how familiar people are with PHLD. This is a terrible disease. These patients are dying. And so it's phenomenal to be able to deliver this kind of outcome.

Derek Archila, Analyst — Wells Fargo

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

Matt Gline, CEO

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

Derek Archila, Analyst — Wells Fargo

Is there any difference between phase two, phase three in terms of population or study design, or we should think it's pretty reputable?

Matt Gline, CEO

Basically, no, with one key exception, which is in the phase two B study, we did not allow for concurrent use of deprostanol of Tyveso, and in phase three, we are allowing for some measure of concurrent Tyveso. We have an open-label study that's a combo study that we haven't read out yet, but we'll allow for some concurrent Tyveso use. We'll probably, it'll be stratified. We'll probably cap it at some level, but that way, you know, we won't have any label restrictions which pulmonary hypertension for those that follow it is a polypharmacy market where these patients go on uh every available drug actually in phld specifically because these patients have lung disease troposinol is an irritant and it causes cough in these patients which is lousy for a patient with an already like a coughing disease and so we had less cough on drugs than in placebo where one inhalation of a dpi once a day i think we should have a pretty compelling value proposition but ultimately these patients are very sick and i expect they will also wind up on a combination of these drugs over time gotcha so where do you kind of see like the opportunity here and ultimately, I guess, I don't know, put it into context or frame out the overall peak sales opportunity potentially? We don't have peak sales guidance to give. The most conservative estimates for PHLD is a sort of number of patients in the, we think there's probably about 200,000 PHLD patients in the world. United Therapeutics gives a conservative estimate of 30,000 in the United States. Other companies have bigger estimates. I think there's tens to maybe low hundreds of thousands of PHLD patients potentially in the U.S. these patients are really sick I think with our quality of data and with the fact that we don't have cough and have simple administration there's no reason to think we couldn't have front line use or first line of major new therapy use in PHLD will also I suspect be used after deprosanol in some cases and they'll be used after us in some cases and I think the real opportunity here is you don't have to outrun the bear situation these patients are sick and you've got to get out to them so we should be feeling very good about the phase 3 when will we get data there? We haven't said that either. We're just getting enrollment up and running now. We just read out the Phase 2B today. We'll meet with FDA and confirm things like size and maybe be able to repower, et cetera, now that we know the Phase 2B data pretty cleanly. But, you know, I think it should enroll nice and quickly given the quality of the data that we've got here and the Phase 2B enrolled pretty quickly as well. So, fingers crossed for a nice timeline. But I don't have a timeline to share right now.

Derek Archila, Analyst — Wells Fargo

Gotcha. I mean, anything else to highlight there or any other thoughts on the data today?

Matt Gline, CEO

I'm not very practiced talking about this data. This is an hour in, so I don't have super prepared talking points. Look, this was phenomenal data across PVR and hemodynamics, across six-minute walk and functional endpoints. Again, the lack of cough is really nice, and the one inhalation once a day. The only other thing I'll say is I think this opens the door to not just PHLD, but to, first of all, any form of pulmonary hypertension is for sure on the table. You know, PAH is an indication that we got asked about a lot before this data set, My answer at the time was PAH is very competitive. There's a lot of other drugs there. This data is good enough that I suspect it opens the door for even competitive indications. So I think you better believe we're evaluating that. We've been looking at IPF following up on United Therapeutics has had some success there with Tavaso. So I think lots of places to go. And I think this really does become a proper third leg to the Reuven stool at this point.

Derek Archila, Analyst — Wells Fargo

So maybe shift gears to Lysriah and dermatomyositis. So your recent approval. So maybe talk about, you know, how you think of this opportunity, you know, and ultimately this is an area where there's really been a dearth of, you know, options for patients. So, yeah, just kind of think about ramp and uptake.

Matt Gline, CEO

So it's hard to believe that this was just last week, the week before last week. It was very recently that we announced the approval of Repo and DM. And it felt like, you know, we've been working on it for so long that it feels like, I said on the approval call, it's the rare marathon that ends with the right to begin another marathon immediately. And so now we're out there with this rye on the market. Look, dematomyositis, again, for those that aren't familiar with it, severe inflammatory disease, terrible skin rash. In fact, many DM patients say the worst thing about it is this, like, very painful, disfiguring rash. And then on top of that, it's got these muscle-wasting effects that lead to things like, you know, can't climb stairs, can't lift objects, can't dress yourself, can't eat. So a really bad disease. There are basically no modern options approved other than Lysriah at this point. People are on high-dose steroids, immunosuppressants. IVIG is approved, and the labeled dosing paradigm involves basically four or five consecutive days, full days in the infusion clinic. And a lot of patients are on it, which gives you a sense of how bad the disease is. Brepo's data was really, really strong, and we were able to show not just very good clinical benefit but steroid-sparing conjunction clinical benefit, which we got on label. So I think we have a really nice story to tell, a great value proposition to patients. I think the patient community and the physician community are really excited, obviously tremendously excited now that it's approved. Drug has launched, prescriptions written, all that. So really looking forward to just getting out there. You know, we get asked all the time about RAMP, and our answer has been consistent. I was talking to an investor this morning who wondered why we hadn't gotten slow and steady printed on headbands yet, which I don't look good in headbands, but otherwise I think it's a good idea. Look, I think it's a new indication. It's not like there's a lot of patterns to point to. There's a lot of physician and patient enthusiasm, and the most important thing is we're out there, and I'm excited for what we're going to do. It's obviously just like day six or something, so it's really good.

Derek Archila, Analyst — Wells Fargo

Well, I guess maybe talk about, like, you know, rheumatologists are generally pretty familiar with Jax, And, you know, BREPO kind of fits right into, you know, the bag of tricks for them. So, I guess, do you think there's going to be much education and learning around, like, you know, the actual mechanism or, you know, safety, things like that? Maybe just walk us through how you guys are kind of educating the field forces, educating the docs here.

Matt Gline, CEO

In general, two things. One is I completely agree that rheumatologists and even dermatologists are familiar with the mechanism or at least with part of the mechanism with JAK. And we're also familiar with TIC-2s, for that matter. Brevo's a dual inhibitor of JAK1 and TIK2. And I think there's been so little actual successful drug development in myositis that there's like a ton of physician enthusiasm even apart from that. And one of the things, you know, you asked about safety. We have a black box warning like JAK inhibitors do. The truth is, dermatomyositis as a disease causes things like JAK inhibitor side effects, malignancies, cardiovascular events, high-dose steroids and methotrexate and immunosuppressants cause the same. Treating these patients effectively is worth it, and in fact may even reduce the risk of those things, depending on sort of how you look at it. Certainly in our data in the study, we did not, if anything, we saw lower events of these kinds on drugs than on placebo, because I think you're treating these patients effectively, getting them off immunosuppressants and steroids and so on. So I think there's not going to be a heavy lift on education. And in fact, one of the other things about myositis, it's treated in a pretty concentrated way about half the US patients are treated about 200 specialty myositis referral clinics and those docs are familiar with our study many more investigators in our study excited about the drug we've been talking them for a medical education perspective over the course of the past year since the data so I don't think there's a lot of education to in fact one of the reasons I feel obligated every time I go out in public to say the phrase slow and steady because if you call these physicians the physicians are incredibly enthusiastic in fact one of the ways a lot of investors have come to us in the last year or so is you know well our Gen X has recently read out data in a myositis program with Argenix obviously has a impassioned and enthusiastic group of investors who were calling Docs asking about Argenix and in many cases what the Docs wanted to talk about because it was more proximate was brepacitinib and so we got a lot of Argenix investors in our office saying I keep asking you about F cartigamide and I keep being told first you should look at brepo it sooner and so that you know I think there's just a lot of Doc enthusiasm for the drug yeah I mean we've heard the same and you know upwards of maybe 60% you know utilization for the patients that are candidates for the drug but those are large numbers. Yes. There are tens of thousands of DM patients. We certainly do not need 60% penetration in order to have a big and exciting drug.

Derek Archila, Analyst — Wells Fargo

Yeah, well that's good to know. So I guess when you think about the field force that you guys are going to put out there, and you just kind of alluded to it in terms of the concentration of where these patients are, you know, what kind of gets you confident in terms of your ability to launch, you know, Brepo?

Matt Gline, CEO

Oh gosh, you know, biotech is not a field that rewards confidence. So you asked me what my confidence is. Look, I think we have a great team. I think we have great relations with the doc community. I think the level of doc feedback and the early enthusiasm from the prescriber community is certainly encouraging. And one of the things I really like about orphan disease launches, I often talk about how, look, we previously launched a drug in psoriasis. These bigger market indications are like a fluid dynamics problem where you can't approach the patient as individuals. You have to think about the shape of the surface and branding and marketing and dtc advertising are all like the sort of tools that you have for manipulating and and accessing those patient populations manipulating is another right we're accessing those patient populations um you know dermatomyositis it's an orphan disease and you can approach these patients where they are one doc at a time one patient at a time and in many ways treating these patients in the in the market is like treating them in a clinical trial you find them you get to them you sort of communicate about the benefit of the drug and i that's like the way the way that you build a roster such as it is I feel confident that our relationship with dermatomyositis physicians are extraordinary I feel confident that the private team has done a great job building confidence within that community and I think that's ultimately what's going to translate to uptake and then the other thing that really matters in these fields are access and we have a great patient support team that's out there making sure that to the extent possible these patients have no copay and are able to get on drug quickly and seamlessly gosh so in the quarters how How should we be thinking about the KPIs that you guys will share, you know, in terms of the launch? Net sales.

Derek Archila, Analyst — Wells Fargo

Net sales, okay. Net sales, the product.

Matt Gline, CEO

Look, the truth of the matter is in the long run, that's what matters, is getting out there, getting reimbursed, getting patients on drug. And I think there's like a lot of desire to find measures early in launches to sort of tell what's going to happen. Look, I think we'll see how the launch goes, but my gut feeling is net sales is going to tell the story. anything else that we should be kind of thinking about pushes the polls for the launch I mean obviously there's reimbursement and things like that that will come on but do anything else that we should be considering yeah look we're obviously paying attention to how quickly we can get coverage for these patients that's an important indicator we're sort of alone in the field right now there's as I said there's not a lot of other novel drugs and so I think that's you know that most of it is just getting out there and and getting behavior change in these practices you know that one of the questions I get a lot is like which patients are going to be on drug first I think the interesting thing is it's a pretty different docs are approaching that question differently and so there are some docs who use jack inhibitors off-label and are enthusiastic to switch their off-label patients over to brepo there are some docs who are heavier users of ivig you know switch those patients there are some docs who just have a lot of steroids and immunosuppressant patients who have resisted ivig or off-label therapy and they want to put those patients on i think it's very much a meet the docs where they are kind of a launch and so i think we're trying to figure out what the early patients look like in different settings can you talk to like the amount of steroid usage in myositis and obviously the doctors see this is a huge benefit to get down to five milligrams or less.

Derek Archila, Analyst — Wells Fargo

Ideally zero.

Matt Gline, CEO

Yeah, steroid sparing is a huge benefit here. Funnily enough, when we designed the study, we had a steroid taper in the study, which you do in these trials in part to basically protect the drug effect, right? You want to get patients off steroids so you're not getting like placebo patients up titrating on steroids and getting treated actively anyway. So you had a steroid taper and in some sense we failed at the steroid taper that is what happened is we were able to get brepo patients to a much lower level of steroid use than we were able to get placebo patients because the placebo patients were just sick enough it was harder for them to titrate and that wound up being ironically one of the best features of our data was that discrepancy which docs look at as a huge benefit to brepo you can get patients on lower dose steroids many many dm patients are on high dose steroids you're talking about like average steroid burdens of 10 or 20 milligrams for six months out of the year i don't know if you've been on oral prednisone before but being on 20 milligrams of prednisone for six months is a miserable way to live. And so the docs are incredibly excited about the ability to get these patients to lower steroid doses.

Derek Archila, Analyst — Wells Fargo

So maybe shift gears to, you know, Immunivant 14.02 and kind of the FCRN pipeline. So, you know, I guess, you know, one of the questions that is always surfaces around, you know, kind of increased IgG reduction and conferring better efficacy. So I guess just kind of broadly speaking, but, you know, MG, CIDP, all these other indications, what gets you confident that, you know, you guys have maybe the best reduction and could lead to the best efficacy?

Matt Gline, CEO

Well, I used to think data would answer that question, and now I think we've generated the data that answers that question in like four or five indications, and still mostly people seem to want to ask it. So I don't know what's going to answer that question conclusively for everybody else. We feel like in every indication where we've tested it, first of all, at the individual patient level, every patient for whom we have, not every patient, patients who have deeper IgG suppression get better clinical benefit than patients who have lesser IgG suppression and that's been true in our MG data in our CIDP data in our RA data in our in our grave data obviously sort of across the board every every disease where we have been able to measure this effect we have shown that deeper IgG suppression yields better clinical benefit and I think that's going to translate over time across indications to an attractive clinical profile for our drug. Obviously, in indications like MG, where F-cortigimod is a very well-established therapy, whether it's better by enough to win that market is something we'll have to see when we get our phase three data. But I think in indications like Graves, where we're first, indications like RA, where we're ahead of the field, I think that better clinical profile, in our view, is going to translate to a real leadership position.

Derek Archila, Analyst — Wells Fargo

Yeah. Maybe let's talk about difficulty, RA. So the data, you know, very impressive and maybe, you know surprisingly so for period one you know as we look to period two I guess one of the questions is really that withdrawal period being long enough and I think you set the right expectations in terms of what we should see but maybe just rehash that and ultimately how does this inform you know kind of a phase three or the next development in this indication yeah perfect so look for those that may or may not have been paying attention we put out data in sort of an interesting trial design it was a randomized withdrawal design where period one was an open label period where patients were on drug, and then responders were re-randomized either to the high dose, low dose, or placebo.

Matt Gline, CEO

And frankly, the period one data was so good that it has made the period two bar difficult. That is, the endpoint in period two is loss of ACR 20 response in that randomized withdrawal period. And, you know, of the ACR 20 responders who got re-randomized, like half were ACR 70 responders and two-thirds were ACR 50 responders and so you're talking about taking an ACR 70 responder and trying to get them to lose an ACR 20 response in 12 weeks where they're still getting some form of a dynamic benefit for the beginning of the period it's just a high bar so I don't know frankly given the quality of the period one data what's gonna happen in period two and I think it's a reasonable thing to be concerned about that said the period one data was so good that even if we don't get a p-value in period two it doesn't really matter we're basically set on running a phase three program here given the quality period one day as long as we see clear evidence that there is a drug effect which I believe that we will give the number of ACR 70 responders and so on so we're looking forward to seeing that data but also in parallel we're setting up a discussion with FDA about what a phase three program should look like and you know our hope is that we can run a reasonably sized RA study specifically in this late line population that can can get us to a product for pay again these patients the patient population that we studied sorry to take a step back, was refractory patients who have failed at least two, basically, of IL-6s, TNFs, and JAK inhibitors. And for patients that have failed multiple lines of advanced therapy for RA, there really aren't options. And so our hope is that we can design a study for that patient population and have a real impact.

Derek Archila, Analyst — Wells Fargo

Yeah, I mean, this seemed like almost like a fourth line plus setting, you know, for these patients. So, I mean, you know, one of the interesting features here is that, you know, could you get kind of that most indication carve out for difficult to treat RA? What do you think the FDA's receptivity would be, given the fact that you've now produced some really interesting data, very positive data in this population, which is very tough to treat?

Matt Gline, CEO

I think one of the things that FDA is consistently, quote-unquote, worried about in RA is that people are trying to sneak into earlier line therapy, and we are not, right? SCRNs have a different price point. This does not make sense as an early line medicine, and so I think we would be enthusiastic, per se, about a label restriction to late line patients, and I hope that FDA will be receptive to that for a bunch of reasons there are at this point a couple of examples of people pushing in that direction there's obviously the t-cell engagers in the CAR T therapies that will also be multi-mechanism failure patients and so you know I think there's like a little bit of FDA is clearly thinking along these lines but we will be the first with a phase three study I think in this population and so you know I think we're gonna have to have that conversation so base cases that you're running another study, somehow if it hits that SIG, would you file on that data period for period two? I think it is extremely unlikely that the FDA would accept for approval a randomized withdrawal 170 patient study in RA. Obviously, if we hit a p-value, we're going to take the data to FDA as a part of the overall conversation, but I'm not holding my breath for that outcome. But hopefully, the phase three program from here can be straightforward. And again, obviously, these are patients with a lot of unmet need, so we'll see what happens.

Derek Archila, Analyst — Wells Fargo

Gotcha. So we should be thinking probably more traditional type of trial, maybe single trial, but more traditional type of RA trial in just that specific population.

Matt Gline, CEO

Probably that's – look, I think our hope would be to run a single relatively small for RA phase three study of a relatively conventional design. But there's still a pretty wide range of things on the table. We're talking to FDA. Obviously, if we did hit a p-value here, we could consider rerunning a randomized withdrawal trial. I don't think that's the base case plan here, but it's one of the things that's on the table. You know, if FDA wanted two studies, as long as they were both reasonably sized, this study rolled really quickly, I'm not sure it would be a problem for us. If this study hit, I'm not sure why we would need that.

Derek Archila, Analyst — Wells Fargo

So, you know, it just depends on how this looks, and we'll have the conversation with In terms of the opportunity, so, you know, it's fairly small, but again, maybe there's pricing opportunity here because it's such a narrow population and a very sick population.

Matt Gline, CEO

So I guess, how do you think about the difficult to treat RA opportunity, if that's kind of the specific label indication you're able to get? would you describe myasthenia gravis as small i think it's comparable in size to the other uh fcrn indications i think there's 75 000 plus patients who are multi-mechanism failure ra patients who would be potentially eligible for an fcrn and i think that is a at the commercial model model of an fcrn that's an incredibly attractive market and i think we've carved out a leadership position in part because i'm really proud of the study we run i think we really have figured out how to enhance a patient population for FCR inapplicability, both through things like acpetitors and enrolling patients who have high autoantibody levels. And then I think the very fact that we are looking at, let's say, JAK and TNF failure patients, why is there a late-line RA patient who cannot be treated with all of the potent anti-inflammatories we know of? It's because their disease is caused by something other than inflammation. Like, there is something interesting and causal about the autoantibody selectivity, if you will of these patients who have failed inflammatory mechanisms and I think that is giving us a super enriched patient population for our needs.

Derek Archila, Analyst — Wells Fargo

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

Matt Gline, CEO

Measuring auto-anybody levels in RA is an easy thing to do, is the answer. So I'm not worried about that. And the truth is, if you're treating multi-mechanism failure RA patients, the willingness to go on a variety of drugs is an answered question. These are docs who are using pharmacotherapy for these patients. These are patients who are willing to try things, and they've just failed so far. So I think these should be pretty easy patients to access, and they're sick, and they need help.

Derek Archila, Analyst — Wells Fargo

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

Matt Gline, CEO

Yeah, perfect. Look, we've said all along CLE is a bit of a flyer for us. It's an indication that it's high risk. If we are successful there, that'll be, you know, an opportunity will be a first in mechanism approval or first in mechanism program. But there's sort of two quote unquote issues. One is that lupus in general is a hard space and the other is it's not just good enough to have a successful study. There's a bunch of mechanisms coming in CLE that have less frequent dosing and other things. So I think we've got to look at our data and feel confident that we have a commercial opportunity. This is a small and inexpensive study. And I think the way that I would prefer people think of it as a true proof of concept, like signal finding, what do we see? If we see great data, I think we'll be excited to carry it forward into phase three. And if we don't, we'll write it off as an experiment and some information. So I think that's kind of how I think about CLE opportunity.

Derek Archila, Analyst — Wells Fargo

How strong do you think the rationale there is, given some of the data that's out there, either for FCRN or just in general?

Matt Gline, CEO

Reasonably strong. I mean, look, NIPO, obviously, I don't know how much detail we have about it, but NIPO has succeeded in SLE, which is a related indication and probably a harder one to study clinically. We had a couple of patients' worth of good data in a sort of small program in, I think it was New Zealand. And so, you know, I think there's reasonable rationale. There's clearly not an antibody role in CLE. You know, forget it, Jake, it's lupus. It's like a tough set of indications, but I think the therapeutic sort of mechanistic rationale is reasonable yeah what's a win like for this like what what's like oh this looks good we're moving forward we've got a path here versus like middling data unfortunately my unsatisfying answer that question i think it's going to be a little bit of an i know it when i see it outcome in that in that there's like a bunch of different parameters and you know you're going to have to take a step back and look at the data and decide would a drug of this profile be competitive and that's on top of the fact it's a pretty small study so yeah but look i think uh you can certainly generate commanding data in small studies. And I think if we do, the path forward will be clear.

Derek Archila, Analyst — Wells Fargo

Yeah, I guess, you know, should we think about, you know, because it's a small study, a lot of variability here or like, you know, again, yeah, absolutely.

Matt Gline, CEO

That's why I say, like, I think it's going to be a totality of the evidence kind of a consideration. It's just like hard to say with this number of patients. I think the main thing we're looking for is like, is there real disease activity?

Derek Archila, Analyst — Wells Fargo

And, you know, if there is real disease activity, is it the kind of disease activity that we could design a phase three study around to produce a competitive profile gotcha okay and as we think about kind of other type 1 interferon and autoantibody driven disease so we were talking about this with our genetics before but you know ultimately we're starting to get a nice kind of like proof of concept here across the myositis we're getting like Sjogren's and also potentially lupus jasmine your CLE data I don't know does that kind of like one how do you think that impacts potential Sjogren's trial but also just potential for future indications you know with that kind of mix of, you know, underlying disease pathology.

Matt Gline, CEO

Yeah, look, I think it's difficult to appreciate because we all live it every day in different ways, just how, like, how large the potential field of FCR and indications could be. And every time you had a brick to the wall, you put RA in, and then you're like, oh, wait, there's a bunch of inflammatory diseases that kind of rhyme with RA that could be interesting. You know, obviously, if CLE works, there's a bunch of things that kind of rhyme with lupus that could be interesting. You know, as we move into graves, we haven't talked about it all yet in this conversation. There's like a bunch of endocrine diseases, There's a bunch of different places you could imagine going, and I'd say, as I'm sure Karen did the same, everyone keeps their best ideas quiet, but I think there are a lot of interesting places to imagine going with an FCRN from here, and we're working up a bunch of those possibilities in parallel. Gotcha.

Derek Archila, Analyst — Wells Fargo

So yeah, maybe a good segue to Graves. So this is one where you guys certainly will be first for an FCRN in general. But I guess we're seeing a lot more entrance, more competitive intensity that's kind of coming into the pipeline. So I guess when you kind of look at FCRN versus maybe more the THHR antibody approach, who do you think wins in this market?

Matt Gline, CEO

Imitation is the finest form of flattery. I'm very proud of the following statement, but also I believe it. I think if we had not pioneered development in Graves' disease, it would not be a thing right now. I think it was not on people's radars. People were sort of focused on TED and other places, and so I feel really great about that, and I think ultimately Graves' patients are going to win from the plurality of options that are coming. MG is a crowded field, and Argenix is doing great. I don't think the fact of competition... I think the fact of competition is generally good for first entrants, as we will be in Graves, and so I'm not like... And to be honest, I'm not worried about it. I'm excited about it. I think the more people pitching new therapies to endocrinologists in the U.S., the more they will use new options for these patients, the more they will improve the lives of these patients, and the more they'll wind up using 1402, if our clinical profile is what I hope it will be. So we'll see. Specifically to your question about TSHR mabs, look, I think the problem per se, first of all, I think all of these things are good approaches, should work. I think anti-TSHR therapies, whether they are antibodies or small molecules or whatever, should produce a good effect in Graves' disease. The nice thing about FCRN is it's a very elegant mechanism for Graves. That is, Graves is the cleanest autoantibody-driven disease in the book. It is caused by autoantibodies that are stimulatory of the thyroid. And if you can reduce the autoantibodies, they stop stimulating the thyroid. The thyroid stops being overactive. It's not very complicated. The problem with the TSHRMAB is similar to the problem with, like, methimazole and ATDs. Ultimately, what's going to happen with a highly effective down regulator of the TSH receptor is you're going to wind up pushing patients to hypothyroidism. So I suspect that most of those programs, the way they will be developed is they will dose to saturation, they will floor the thyroid, and then they will replace with Synthroid, which is, as a clinical profile, probably not as good as something that can elegantly take away the autoantibodies. Now, the flip side to that is if you are a patient with 100 times the normal limit of T-Rabs, even a drug like ours that 80% suppresses T-Rabs is going to leave you with 20 times the normal limit of T-Rabs. There will be patients that you cannot treat even with an FCRN, and the TSHR approaches should work, right? They will effectively shut down the thyroid chemically, and you may be able to get patients re-regulated that way. So I think there's absolutely an interesting opportunity for a TSHR-directed therapy. I think it will be a likely more complicated, potentially less pleasant patient experience than an FCR and FCR and works. But I think these things could all happily exist side by side. And there's other cool things, right? There's like specific auto-antibody degraders in development and lots of other like neat ideas for treating these patients. And I'm sure there will be a plurality of approaches that make sense.

Derek Archila, Analyst — Wells Fargo

So, you know, one of the things, and I think this has evolved over time in terms of how, you know, investors in the community have looked at Graves as an opportunity so originally it was like ah there's really no market you know ATDs are great like whatever and there has just been really little innovation in the space so I think that narrative has changed but I guess how do you guys view the market and the best candidates for therapy as you guys will be kind of emerging as the first you know new therapy in a long time I don't envy your job in that the problem with Graves disease is you are faced with a whatever with like a tough choice you either need to believe in it in which case the numbers that stare back at you on the page are idiotic and like difficult to reconcile or you need to find some reason to be skeptical so that you can write a normal size

Matt Gline, CEO

number on the page those are like the choices um obviously it's clear we are but uh but it's just like a tough problem the truth is there are hundreds of thousands of poorly controlled Graves patients in the U.S., and they walk around feeling sick, and some of them develop thyroid cancer, and some of them develop other comorbidities, and it's a tough disease. And I think if we're successful, there's a lot of different ways to get into that market, and we are enrolling a variety of different kinds of patients, from patients who have sort of variable waxing and waning disease, to patients who just have an inability to get controlled on antithyroid drugs, to patients who are controllable maybe, but like only on pretty high doses of methimazole, where they're unpleasant from the side effects of methimazole. And further complicating things in the U.S., you could have two patients who are in God's eyes the same. The underlying Graves' disease is the same, but they are treated at different endocrinologists. And one of those patients is treated on low-dose methimazole and is miserable because their thyroid hormones are out of whack. And the other patient is on high-dose methimazole and is miserable because of the side effects of the methimazole. And that's its own difficult thing to manage. So I think the short answer is, I think these patients are going to come from a variety of different phenotypes. And I think we're going to have to meet them where they are. And it's one of the complicated things about getting out into the world understood and maybe with the last couple of minutes just kind of like we're kind of the fcrn um you know the mechanism is evolving and you know obviously long acting and things like that how do you kind of remain competitive here with 1402 and you know are there other things that you guys are working on in terms of life cycle extensions and things for um your fcrn franchise yeah like everybody we're thinking about novel next generation ideas and we've got some stuff in the works and we'll talk about it when it's worth talking about and until then it's just an idea i'll say like i think the greatest mark of success is when people are asking me what's next i think mostly 1402 is a great drug and it's not yet approved in any indication and so i think our first and near-term goal is to turn that into a drug that matters for a bunch of patients a bunch of different indications believe it or not in addition to graves we have a full pivotal registrational program in mg reading out next year and that could be interesting depending on what that data looks like i think it'll be hard to unseat argenics as the king in the MG market, but we're going to hope that we generate compelling enough data to have a real shot, and, you know, we'll see where we go.

Derek Archila, Analyst — Wells Fargo

And maybe just lastly, maybe walk us through the next 12, 18 months in terms of readouts across the pipeline and other events that's going on for Roy Vant. Busy.

Matt Gline, CEO

So today was the PHLD data. Later this half, we have, probably most notably at this point, is the face-to-regradational program for breposidinib and non-infectious uveitis, which would be a second indication for Lysriah or for Brepo. We also have the CLE data, and we will provide an update on the second half of the DGTRA study as well as hopefully on the FDA feedback and the path forward there. That's all coming this six months. I can't think of any other major event through now and the end of the year, obviously, other than the continued launch of BREPO and DM. Next year, we have the registrational data in Graves, the registrational data in MG, obviously a full year of potential DM commercialization. and a bunch of other stuff coming in different directions, some of which we have and some of which we haven't talked about. So next year is going to be really busy.

Derek Archila, Analyst — Wells Fargo

All right, action-packed. Well, Matt, thank you so much for the discussion. Thanks very much.