All right. Well, good morning, everybody. Thank you once again for joining us for the 46th Annual TD Cowen Healthcare Conference. I'm Yaron Werber from the Biotech team. It's a great pleasure to moderate the next fireside chat with Roivant, with the CEO, really needs no introduction, Matt Gline. Good to see you. Really appreciate you being here.
Thanks for having me. I still don't think it's true that I need no introduction. I appreciate it.
I think it's safe to say that everybody in this room and in the industry knows who you are.
Well, they came to the room, so.
You announced today, Kayar and I were going back and forth this morning now that you've announced that, there's a PDUFA date, I basically said, I think we know what month it's gonna be, I'm just gonna ask you, is the PDUFA August 1st ? Second question, is the PDUFA August 2nd?
The PDUFA date is in the Q3 .
It's in the Q3 . You filed... We think you filed late December. I'm not good at math, and you just corrected my math. Eight months is probably late August, is the way we're thinking about it. I think you said you'll launch in September.
The PDUFA date's in the Q3 , and we said we're gonna launch by the end of September.
By the end of September. Okay. That's terrific, and congrats on that.
Yeah. Thanks. Look, I think embedded in all of that, we got priority review from FDA, which we thought all along, we absolutely deserve for this therapy given the quality of data, but it wasn't certain. That, that was obviously a vote of confidence in what we hope the drug's gonna be able to do, it gets us to patients sooner, which is obviously important. Look, I think with ordinary course review, this could easily have been a 2027 launch, and now it's very much not.
you know, I think Ben and the Priovant team, and kudos to them for everything to get us to this point, including the quality of the data, including the priority review itself, I think are waking up to the exciting but cold reality that they have a lot of work to do, most of which they, to be clear, they've been working on already.
Yeah. You know, we've been doing a lot of physician checks with many people and including a survey that we'll show here at the dermatology panel as well and then publish it afterwards. There's a lot of excitements among physicians. They're expecting sort of 30% share. It's been very consistent, and to be honest, these surveys I think have been fairly accurate historically. I think that's kind of been encouraging as well in terms of calling how drugs are gonna do. When you're thinking about the label breadth and then the potential for including a steroid tapering provision in the clinical section, what do you what can we expect or what are you asking for?
Yes. Look, obviously labeling is subject to FDA discussion. I have no idea at this point in the process what's gonna show up on the label. What I can say is I think our hope and expectation would be a label that says. Well, the study was designed in the patient population we would like to serve. I think this is a drug that could benefit any patient with dermatomyositis. I think the hope is the indication statement is dermatomyositis, that there's no sort of restriction to some subset of the population. Obviously, in the study, we focused on patients who had both skin and sort of non-skin muscle activation. I think the hope is that we get to as many of these patients as we can. Obviously, all of that is a discussion to have with FDA. In terms of steroid data, first of all, at least one of the secondary endpoints covered efficacy and steroid taper at once. At a minimum, you would expect, given that we hit on that secondary, that we get to talk about that in the clinical data section.
The study conduct included a taper. I think we are thinking about all kinds of ways to get as much information out there about how to taper steroids and how to reduce steroid burden for patients who are on drug. That includes, to the extent that we're allowed to talk about it in the study conduct piece of the label, great. It also includes things like publications in academic settings and other places to talk about sort of how we manage steroids, what happened to patients as they reduce steroids, 'cause I think it's really important that the docs, you know, have as much information as they can about what we were able to do there. I think the... One of the pieces of consistent feedback we've gotten as we've worked with the doc community is just how excited physicians are about a drug that can reduce steroid burden for these patients.
Where do you think it's ultimately gonna fit into the treatment paradigm? I mean, the patients are typically starting with steroids, DMARDs, you know, hydroxychloroquine, and then IVIG. JAKs have been kind of third line, in some cases fourth line. depends. In some cases, they try to move it out for skin. where do you think this is really gonna fit in?
Yeah. The way the treatment landscape currently looks is of the 40,000-ish patients who we track in claims datasets, 75% of them today are managed to varying degrees of success or failure on some combination of DMARDs and oral steroids, and then about 25% are on stuff. The only on-label stuff is IVIG, and that's about half the 25%. Then the other half is a long tail of off-label JAKs, off-label Remicade and rituximab, off-label other sort of immunosuppressive agents, and that's what the world looks like now. I'll say two things. One is, if you had produced an analysis in 2019 of the world of MG patients, it would have looked, we literally were just looking at this data last week, almost identical.
That is 75% of these patients were on old generation, mostly oral meds. Some were on IVIG, and some were on other immunosuppressive stuff. So I think we are looking at a landscape that is, like, frankly pretty similar to what you saw in myasthenia gravis beforehand, and I think that is among the good recent analogs for how this works. What I think in practice is, we'll get some patients who are on IVIG but don't like the burden of the routine administrations. It's many hours a month to be on IVIG.
We'll get patients who are on off-label things who are either uncomfortable being on off-label things or just, like, tired of fighting with payers over it. Then you get a whole lot of patients from that 75% bucket who have high steroid burden, are on DMARDs, are very unhappy about it, are nonetheless not well managed, but weren't willing or able, for whatever reason, to either go on an off-label immunosuppressant or weren't willing to take on the burden of IVIG. I think it really is there will be patients from a lot of different buckets. Obviously, as you talk to individual docs, they have different use cases in mind. For example, I remember... I don't think it was your call, but someone did a call with a KOL, and she had, I think it was 70 patients on off-label tofacitinib, and her comment was, "I will move every off-label tofacitinib patient to brepo as soon as brepo is approved." People have, like, different ideas for how they'll use the drug. I think in general, you look at this and it looks a lot like the kind of underdeveloped landscape that we've seen successful launches in elsewhere.
Do you think it's gonna get equal use in skin and muscle, or is it gonna be a little bit kind of more popular in skin?
Our data showed really good efficacy on both skin and muscle and on the combination of the two. I think the answer is it will get a lot of use in both settings. Obviously, dermatologists know JAK inhibition as a mechanism. We know that it works well in skin disease, so I think there'll be some familiarity from that perspective. That said, muscle disease is a really devastating part of the DM burden. Sometimes these patients can't walk upstairs and they can't do basic activities of living around their house. I think those patients are desperate for new options. One of the really nice things about JAK inhibitors generally, about TYK2/JAK1 inhibitors and about brepocitinib, is we saw quite fast onset in the dataset. I think about 60 days on average to a moderate TIS response. You know, I think you look at that and you're like, "These patients need relief, and they're gonna go on drug and they're gonna feel it quickly, and they're gonna feel it across the burden of symptoms from skin to muscle.
Okay. By the way, if anybody has any questions at any point, just raise your hand. Happy to take them. Maybe a quick question on non-infectious uveitis. The NEPTUNE study showed really nice data in phase II. Just for the audience, it had a 29% relapse at the 45 milligram dose, a higher relapse, 44% at 15. Both were much better than Humira. Humira did 62%. Placebo did 82%, by the way, in those studies. Both of them were much better than the current standard. There's two studies, CLARITY-1 and 2, both They're identical. Read out data in the second half of the year. You know, we get a lot of questions whether there's some subtle differences between CLARITY, the phase III, to NEPTUNE, the phase II, in trial design. Can you maybe just remind us the NEPTUNE had the steroid taper, between NEPTUNE and CLARITY, how that works? [crosstalk].
Identical is the answer on the steroid taper.
Identical at six weeks [crosstalk].
At six weeks. Yep, identical and more aggressive than in the Humira visual study. Which to be honest, we did that in the phase II because the phase II was a blinded randomized trial but had no placebo arm. It was just high dose and low dose brepocitinib, and we wanted to give ourselves a hard. We did that because historically it's been very hard to enroll in NIU studies, and we wanted to make sure we enrolled. Now, it's clear that that has changed, at least for us, and enrollment has been great in all of these studies. Anyway, we put the hard steroid taper in place for us because we wanted to give ourself a tough test in an otherwise not placebo-controlled study. Obviously with the quality of the data, it was good enough that we just To the spirit underlying the are the trials different question, we just ported it right over.
In terms of baseline criteria, I think in NEPTUNE about 30% of patients were stable on immunosuppressants at baseline. Does CLARITY have the same sort of population?
I, to be totally honest with you, have not recently looked at the baseline characteristics of the, of the CLARITY population. I'll tell you that the idea behind the trial design was to get a population that was basically the same as the NEPTUNE population.
You know, in the study, you don't mandate for a patient to be biologic experienced, so they could be naive as well [crosstalk].
There will be patients in both of those categories in the study. That's right.
The goal is to have a broad label.
That's right.
How important is macular [crosstalk].
That's right. Having said that, certainly we're gonna treat a patient population with a broad label. That would support a broad label. I mean, just to acknowledge the reality of FDA on JAK inhibition, I think, in general, in indications where TNF is approved, the FDA stance has been that you exist in a post-TNF setting. Humira, as you've pointed out, has some limitations in terms of efficacy in NIU. Physician tolerance for inflammation in eye disease is very low, right? These patients go blind if they have bad disease, the physicians are looking to hit hard. If there is an indication in which that FDA guidance might be addressable, it certainly feels like NIU is the kind of disease where it might be. just to be clear, that's in all of the other indications currently where there is both a TNF and a JAK approved, that's the way the FDA has handled it.
In those studies, did they enroll, TNF naive patients as well?
It varies based on which indication you're talking about, but there definitely are studies, for example, of JAK inhibitors in rheumatoid arthritis that include both TNF naive and TNF exposed patients.
In RA, that's exactly historically what JAKs highlighted their talks.
Absolutely.
We've not seen that since then in Crohn's or [crosstalk].
Yep. No, I totally agree. I'll say that if you study closely the evolution of class labeling for things with JAK signaling, even in Crohn's, for example, there has been some softening and change in that language to reflect the fact that, bluntly, with the current generation of therapies for Crohn's disease, there's a strong desire by a lot of physicians to use something not a TNF in those patients. The label is less prescriptive on sort of how to manage patients from a standard of care perspective, given that not everyone's gonna cycle through a TNF in Crohn's these days.
Okay. How important is macular thickness and macular edema? There was a change of 0.1% change in macular thickness and 43% resolution on brepo. How did that compare to Humira?
I don't remember the exact numbers versus Humira there. I think the truth is that fluorescein angiography is actually like an increasingly important way that eye docs are managing the disease. I think they are looking at that data closely and care a lot about it. In some look, the primary endpoint in the NIU studies across the world is time to treatment failure, which I don't wanna call it a dumb endpoint. It's not a dumb endpoint. No endpoint is dumb. It's not like it's like this. It's an endpoint that exists in the context of a clinical trial sort of definitionally, right? It's a time to measure that measures a relapse rate.
It's good that it measures a relapse rate, like that's a real thing that people care about. It's not like NIU patients are running around thinking, "Oh, I know my time to treatment failure. It's three months." That's just like not the way the world works. They go to the doctor, and their symptoms are managed on an ongoing basis. You know, docs know the treatment failure data in the studies because it's the primary endpoint. Actually, the docs are in general looking at things like. They're looking at macular degeneration, they're looking at fluorescein angiography, they're looking at the things that reflect the way they treat these patients. I think all of that data, in some sense, is gonna matter commercially because it's how these patients and these physicians think about their disease.
The BEACON study, that data was really unprecedented to see CSAMI improvement of 22 points, against placebo on both doses. This is a 31 patient study, and you're gonna start the phase III in the second-
Yeah
Half of the year. The minimal clinically important difference is five points. The 22 is really a nice bandwidth.
Yeah
To carry into phase III. Is the phase III design gonna be just identical to BEACON with randomization against placebo, or is there gonna be some nuances to it, and do you need one study or two?
Yeah, it's a fair question because it has been a full two weeks since we put that data out, so we've probably answered all of these questions by now. Look, first of all, we were tremendously happy with that data. It was really exciting. It was much greater than what we think the physician bar for clinical meaningfulness was. It was unambiguous in a population that is pretty sick, as evidenced by the fact that placebos saw no improvement at all. So, you know, I think great data. I like your use of the word unprecedented. One of the best ways to generate unprecedented data is to study in indications where basically nobody has ever studied before, 'cause then all data is unprecedented.
But it was, it was, it was phenomenal data, and we are thrilled with it, and we're excited to be developing in cutaneous sarcoidosis, and it has our gears turning on all of the other things we might be able to do based on that data set. I think our goal for the phase three, given how good this data was, will be to do things as similar to the phase two as we possibly can. There are topics for discussion with FDA, duration of study, what the dosing will look like in the phase three study. These are all topics that we have had discussions with FDA before the phase two data set and will continue to have discussions with FDA to finalize, and I'll say we won't have a final trial design until that's all been worked through. I think the first principle for us is, if it ain't broke, and so, you know, I think given the quality of that data set, we're looking to match it.
Yeah. In NIU, you're testing 45. In DM, you're testing 30 and 45, right?
In DM, we tested 30 and 45. Sorry, no, in DM, we tested 15 and 30. 15 didn't hit a P value, which was... Look, the reason we tested 15 and 30 in DM was because we hadn't run a dose-finding phase II study in DM, so we needed to establish minimally efficacious dose, and I think we're expecting to launch DM in 30. NIU, we tested 45. In CS, we tested 30 and 45.
Mm-hmm.
No, we tested 15 and 45. Yeah. I think the question is whether we will include a low dose in the phase III in addition to the high dose. I think the answer to that question, to be clear, is we will do whatever maximizes the likelihood of an approval and a useful label and all that good stuff because enrollment won't be a problem. The data in the phase II study was really good. We're alone in the indication, and the incremental cost and time of putting in a low dose arm is.
Yeah
Not significant. I think the answer is we're gonna discuss with FDA, and we're gonna do whatever ultimately is right for the outcome for the program.
Do you need two studies, 'cause it's gonna be a first approval and a first indication, or you're gonna have so much data from other safety that at this point is unquestionable, so just one study sufficient?
I forget what we've guided to, but obviously, this is the kind of indication where even prior to FDA guidance changes, a single study seemed like a plausible path, and FDA certainly seems like their general posture on those things is shifting in that direction over time. That said, I think that question is also largely irrelevant to the path forward and that like CLARITY, for example, is technically two studies, but it doesn't really matter. We enrolled them fast, and it's all good.
Okay. Let's move to mosliciguat. I need to learn how to say that faster.
I just say mosli, so.
Mosli. We actually did a PH-ILD panel yesterday. We've been doing a lot of checks. It continues to get very high marks by virtue of the SVR data that you showed with a single dose was essentially unprecedented, almost reaching 2%-38% peripheral vascular resistant reduction in that.
Yeah
phase Ib ATMOS study. The phase IIb PHocus study will read out data second half this year. Actually, you just started a combo study with TEV-574, which we'll come back to in a few minutes. In terms of getting to phase III readiness, what do you wanna see on PVR and six-minute walk as well?
Yes. Look, that phase I data, which remember, was in a different patient population. That phase I data was in group 1 PAH patients, we're studying in phase IIb in group 3 PH-ILD patients. That's a different patient population. The study's primary is PVR. Gosh, if we don't hit on PVR, it'll be embarrassing at this point. We'll find out. I mean, like I said, the translation from PAH to PH-ILD is really the whole question of the study. Historically, 20 points of PVR reduction has been a good sort of clinically meaningful bar that has translated to six-minute walk into other clinically meaningful endpoints. I think that's a threshold level that's probably reasonable to watch. In terms of six-minute walk-
Mm-hmm.
First of all, in general, you saw this in the TEV-574 studies, the variability of six-minute walk in PH-ILD patients is pretty wide. The study is not powered to produce a delta on six-minute walk. It's powered to give us information about trends and how we're doing. I think what we're looking for is, yeah, a large PVR benefit, 20-plus, and we're looking to see evidence of trends and everything else on six-minute walk and time to clinical worsening and the other sorta patient-driven endpoints such that we're confident in a phase III program we'd get what we needed.
What's the baseline six-minute walk that you typically see in, you know, in other indications, typically 30 meters is usually considered clinically meaningful.
Yeah. the answer is it's variable, and there isn't really a typical in PH-ILD-
Mm-hmm.
'Cause there's only been a handful of studies in PH-ILD. I don't have like a baseline number to throw out there. you know, TEV-574 worked on six-minute walk. Like, you definitely see benefit in these patients when you improve vascular. When you dilate in the lungs.
I think, United was mentioning recently in their last call that they're gonna try to move away from a nebulizer, which is almost 20 times a day, to something that I believe is four to six one per day, and it's a few puffs. soft mist, yeah.
Yeah. Teva has that as an approved format. They have a DPI as an approved format already. I think they may be trying to move to a soft mist inhaler from the DPI. Basically in PH-ILD, these patients aren't using the nebulizer. They're using a DPI already, and it's, you know, four puffs four times a day or something like that. I think they are trying to move to an even better format than that. I think they're trying to move to that format for a few reasons. One is that treprostinil is in general, prostacyclins probably, but certainly treprostinil, and this is true for the other treprostinils that'll come to market in PH-ILD.
Cough is an on-target effect for the mechanism, these patients who have lung disease and are coughing all the time anyway are coughing more on these drugs, and obviously part of a contributor to that could be the form factor. I think their view is any benefit they can take on that is good. I think the other thing that Uther is likely dealing with in the treprostinil world is their competitors, TPIP at Insmed, the Liquidia program, are all less frequent administration, or shooting for less frequent administration. I think that is, you know, something that Uther is probably, like, well aware of in terms of their in-class competitors. We are a single puff of a DPI once a day. That's the format of mosli.
We're already at the sort of best end of that, and we don't in... In none of our existing studies do we see cough as a tolerability issue associated with the drug. I wouldn't expect to see it. Again, biology's humbling, but I'd see no reason to expect it in PH-ILD as an issue associated with mosli. I think we're already better than competitive on administration and tolerability sort of by right in PH-ILD. Obviously, we'll see on the tolerability side once we get the data. That having been said, that was a long preamble to a point that you were getting to maybe with the TEV-574 combo study as well. PAH is a polypharmacy market. These patients are on everything, and the bar for us is definitely not like we have to beat treprostinil, we have to get ahead of them.
Our data could be awesome, and we could be a first-line therapy, and that'd be great. It doesn't really matter is the point. These patients are really sick. In other pulmonary hypertension indications, they go on multiple mechanisms, and whether they start on treprostinil and add an sGC after, or whether they start on an sGC and add a treprostinil after, that's the way these markets evolve, and that's definitely what we expect in PH-ILD. I believe we will be the first non-treprostinil approved in PH-ILD if everything goes well, that polypharmacy will be a result of our market entry.
Yeah. Okay. You did answer my next question, was whether you think patients ultimately are gonna switch, change MOA, or just do an add-on.
I mean, I think "yes, and" is the answer to that question. Patients who don't like the cough might try something different. New patients coming in might start on our drug or start on treprostinil, I think lots of patients who are not fully treated will go on both.
Okay. I'm gonna switch over to 1402, the FcRn program, data from FORWARD-1 and FORWARD-2 for Graves are expected next year. You're testing both 300 and 600. Just remind us, Have you commented a little bit more whether it's gonna be first half or second half next year?
We have not.
Okay. The studies are still enrolling?
The studies are still enrolling. That's right. Although, remember, the second study there is a six-month study, so it could be enrolling until midyear and still be early 2027.
Yeah.
Um [crosstalk].
FORWARD-1 is 12 months.
FORWARD-1 is a 12-month study with a 26-week primary, we'll need to run the full 52 weeks to get the data. FORWARD-2 is a 26-week study. Sorry, I think I have that right, I think of them as 25 oh 2 and 25 oh 3, I just need to make sure I'm using the correct public names of those studies.
Yeah. It's positioning sort of as potential replacement for ATD and obviously avoidance of ablative therapy and looking at potentially time off therapy as well. What do you think is a win in that data?
There has not been a novel therapy developed in Graves' disease in 70 years. So much so that it's one of these indications where when we first started developing in it, docs were like, "Why do we need a drug? We can just take out people's thyroids." Which is the kind of thing that you hear in markets that have had no new therapeutic agents for a long time. We get that answer less and less now, and I think that's thanks to us, and I think it's thanks to the fact that there's others in the area as well. Frankly, there are hundreds of thousands of Graves' patients in the world who are uncontrollable on ATDs, and they feel sick, and they're uncomfortable, and they cycle on and off ATDs or are perpetually on high-dose ATDs.
They contemplate surgical excision to the thyroid, they contemplate radioiodine. I think a win is delivering clinical benefit in that refractory patient population, and I think there's a pretty wide range of what good looks like. If you take our phase II data, in the phase II setting, we were able to get refractory patients controlled, which even if that was all you could do, even if it was just as an add-on on top of ATDs, you took sick patients and got them to a place where their thyroid hormone levels were controlled, that is a big opportunity that patients would be excited about. We were able, in the phase II setting, to get a meaningful proportion of those patients not just controlled, but controlled off ATDs, which is an even bigger benefit.
First of all, ATDs have safety and tolerability issues of their own. Second of all, patients don't wanna be on them. If you can get them switched over to a drug. If they go from uncontrolled on one line of therapy to controlled on a monotherapy after, that's great. The third opportunity for us is to show that for some of those patients, they won't even need to be on our therapy chronically, that once they get re-regulated, they'll be able to get off drug and maintain control. I think all of those three things are different levels of win. What I think is we're gonna show all of them, that is, there are some patients who are gonna come in with severe enough Graves' disease that we probably won't be able to get them even off ATDs, let alone in remission. There are some patients who will be in a broad middle ground, where we are able to get them off ATDs, but they may require some level of FCR in therapy. There will be a meaningful proportion of patients who are able to re-regulate and get off all drug.
Mm-hmm.
What those proportions are we won't really know until we've seen the data. My guess is that the proportion will increase over time, who are able to get into each bucket, that the 52-week data will look better than the 26-week data as well.
I think we have maybe a minute and a half. Moderna, the trial expected to start March 9th.
Yeah.
How long do you normally expect a trial to run? How long does it take for the jury to decide?
Yeah, what we said before about the trial is a couple weeks, plus a relatively short deliberation period thereafter.
Okay. the good news is, the, on the section relating to the government involvement, 99% of the liability, so to speak, rests with Moderna. under doctrine of equivalence, there it's gonna have to be frank infringement, literal infringement.
Yeah
Is it really gonna come down to a half a percent of LNP? Is that sort of what it's really gonna come down to?
Yeah, look, I think the short answer to this is we're a week out from trial. We feel good about our positioning overall there, as we've made public in other cases. I think at this point, we just gotta wait and see where we go.
In the discovery, then we get questions about whether it's gonna be a chance for, you know, frank infringement with treble damages. In the discovery of Moderna, did you find any evidence to suggest that there was a premeditated effort to try to circumvent the IP?
Yeah. So there's a bunch of documents that are public that highlight various parts of that question, and so I can point to those documents. Some of them went under docket in September. The main thing I'll say though, again, is like, first of all, these processes, this is just, like, as a useful fact to remember. The trial is not the end. These processes go through lengthy appeals and, like, on the 1498 issue, for example, I'm sure Moderna will want to appeal there, regardless of how this goes. I don't think any of these issues are sort of settled until they're settled, such as it were. Look, it's... Like I said, at this point, we're in the final innings here, I think it's probably best to-
Yeah
Best to see how things go.
Okay. Excellent, Matt.