Roivant Sciences Ltd. ($ROIV)

Hi, everybody. So my name is Dave Risinger. On behalf of Leerink Partners. I just wanted to thank you for joining our conference. It's very much my pleasure to introduce Matt Gline, the CEO of Roivant. He's just putting a little sugar in his coffee and then we'll get started. But really appreciate you being here and his team members Richard and Keyur are in the audience as well. So I thought it would be great for you to just maybe kick off, Matt, with some opening comments on the business prospects. You've had a tremendous run of good news and hoping for good -- for more good news ahead, but I would love you to start with some opening comments.

Yes. Thanks, Dave. Thanks for having us. It's obviously it's a great venue for a conference. I think the best in Miami at present. So thanks, Dave. Thanks for having us. Look, it's been -- I don't know it's hard looking out over the room to know exactly who's got what level of familiarity, but it's been a really transformative period for us. And I think in some ways, we've been built for a long time to find drugs that matter, develop them in creative ways. I think we've done a phenomenal job in indication selection and sort of building a pipeline. And at this point, I feel like the fruits of that labor have like finally come together. And so as many of you may know, mid last year, we got data in a registrational program in dermatomyositis that sets us up now, our NDA was just accepted last week with priority review. So we'll now be, knock wood, launching that product in this year, by the end of September. And that sets us up for this incredible period ahead with the stacked series of data and commercial launches, starting with dermatomyositis launch, but also with data coming in multiple other registrational programs in NIU later this year in Graves' disease for our FcRn next year. On top of that, we have Phase IIb data from mosliciguat in PH-ILD. I'm sure we'll talk about all these different programs. But just -- it's a period of true business transformation for us where we're standing at the cusp of becoming as daunting as it sounds, a real company, the kind of business that has to generate sales and make quarters and be profitable and all that good stuff. And so I think it's an exciting moment to stand at the doorstep of that, and I'm excited to talk more about everything that's going on.

Phenomenal. So before we go into the details, maybe you could step back. Obviously, you had an analyst meeting in December in New York, but just highlight sort of your vision and where you want to take the company?

Yes. Look, I think it's sort of funny in biotech where -- so when I first got started, I had all these friends in tech, and I was like new to biotech and someone I cannot remember who gave me this piece of advice. And they said, "Oh, the difference between tech and biotech is that in tech, all the ideas sound stupid and some of them turn out to be really good. And in biotech, every idea sounds amazing and most of them don't work." And just like I thought a lot about that as our business has matured. But one thing about it is like you say, what do you want to be? And the answer is like I want to be what everybody else wants to be. I want to be a successful therapeutics company that deliver drugs that matter to patients that need them. And that's sort of -- like from a vision perspective, it's not more complicated at some level than that. I think what I think we are really good at, in particular, obviously, is we don't do a lot of basic bent science. So most of our pipeline is in-licensed partnered, et cetera. And we're good at finding real value in the world and in particular, in seeing creative ways to build partnerships around drug development, indication selection, good clinical execution. And I hope that as we become a commercial pharma company, first of all, we can bring some of that energy to launching a dermatomyositis, our orphan JAK/TYK franchise that I think should be a really important franchise. And then into the FcRn programs, we can bring some of that energy to the commercial field. But also, I hope that it serves us well in -- I think the next -- I think whatever -- one of the things about biotech is every marathon ends with another marathon. And I think our next marathon is both about commercial success, but also, I mean, how many quarters into our launch are you going to turn to me and ask me what's next? It's not going to be very many. And I think one of the great things about the business we're building is I hope that we're capable of continuing to deliver on an R&D base layer that allows us to stack and compound. And I think that is a big part of what we're building from here.

Yes. Well, you've certainly demonstrated to date that the ROI in your business model with your leadership team and the structure of the company is extremely high. But just provide a little bit more color on that. So what makes Roivant so special?

Yes. I mean, look, I think there's a few things. One is we've just always been of the belief that bringing people together of different backgrounds and phenotypes can make a difference in how drugs are developed in the industry. And so we have a leadership team that comprises career drug developers, but also, frankly, a lot of former buy-side people who think about the world like investors do. And I think that's just been a very potent combination for us in designing an R&D portfolio and thinking about ROI and thinking about the ways of investing to generate maximum value from the next data set. I think sometimes we've made decisions that have initially because I think they don't necessarily rhyme with the decisions of other biotech companies been a little bit head scratchers. And I think it's always been in service of sort of ruthlessly economic thinking about R&D that is like how do you drive value by making every dollar and every inch count in a clinical trial. And I'm proud of where we are right now on the back of that, but it wasn't always easy.

Yes. Excellent. So why don't we turn to brepocitinib with the launch plan for the end of the third quarter. How do you expect brepocitinib to be taken up? Could you just kind of contextualize the opportunity and describe your launch plans?

My handlers are in the room, and I'm talking through a sell-side analyst. So the answer is slow and steady, Dave, slow and steady. Look, I -- the truth is there has not been a modern therapy developed in dermatomyositis basically ever. I mean, IVIg is approved, but has been used off-label for a long time. And it's a physician and patient community that on the one hand, is desperate for new options. These are very sick patients. And if you talk to the doc community, I think you'll find a lot of enthusiasm for our drug. But on the other hand, it's steep and unknowns. It's very hard to tell exactly how early adoption will work. It's very hard to tell exactly which patients will come. We have theories about all of these things, and I'm excited about the work that we're doing to identify these patients ahead of time to work with the referral centers that treat a lot of them to make sure the docs are familiar with our data and how to think about what our drug might be capable of. But ultimately, we won't know about what the next step looks like until we reach the next step. So we're doing all the prep work that we can. We're building our patient support org so that we're going to be able to get patients on drug and covered. We're building a field force of incredibly qualified sort of high degree of medical expertise, a lot of advanced degrees to make sure that -- again, it's a pretty academic treating physician community, so to make sure we're sort of steeped in that community and working with all the right people. But ultimately, it's going to come down to execution, and we're going to have to see when we see.

Excellent. Well, the KOLs with whom we've spoken are obviously quite excited about brepocitinib given the oral administration and the efficacy and safety profile you detailed, particularly relative to IVIg for those patients that are not in a crisis at this very moment. But could you just talk about the 40,000 U.S. patient opportunity, including what percentage have both skin and muscle involvement?

So taking a tiny step back, dermatomyositis is -- and the whole of the idea behind our development plan for brepocitinib is to take the most potent anti-inflammatory mechanisms we've ever developed in JAK and TYK inhibition, especially JAK1 and TYK2 inhibition and turn them on orphan inflammatory disease with high unmet need. And so brepocitinib is like a perfect sort of center of the bull's eye indication for us. These are very sick patients. It's in part an interferon-driven disease. We know the signaling pathways we hit should matter. And there's a lot of need. So you talked about the number of 40,000. There's probably about epidemiologically, some of our competitors have found sort of 70,000 patients in literature search in terms of total U.S. population. We think about it in terms of treating patients now. And in claims data set, there's about 40,000 patients who show up as an active therapy for dermatomyositis. And it looks very similar to some of the other great orphan indications that people have launched into like myasthenia gravis. Today, the vast majority of those patients, about 75% of them are on what I would call sort of "first-line therapy," right, older meds, steroids, immunosuppressants, methotrexate, DMARDs, things like that. And then about 25% of the patient population is on later-line meds. About half of that 25% are on IVIg and the other half are on sort of zoology of other anti-inflammatory stuff Remicade and rituximab and off-label JAK inhibitors. And basically, everything in that bucket has failed dermatomyositis studies, but these patients are desperate and they're antinflammatory medicines and so people are trying them. And so that's kind of what the treatment landscape looks like today. Notably, you mentioned the oral administration. Those 75% of patients that are on corticosteroids that are on methotrexate, obviously, those patients are all on oral regimens now. And so you have someone coming in and offering for that patient population, the sort of uncontrolled patients on, in many cases, like very difficult like regimens, right? Being on high-dose oral prednisone is terrible and yet these patients are consistently on high-dose prednisone because nothing else is really working for them, being able to offer them something that is going to be a real alternative with an improvement in efficacy, being able to reduce that steroid burden, I think it's going to be a really exciting opportunity.

Excellent. And what is the process to be able to garner access? So obviously, these are pretty desperate patients. So payers should allow access quickly. But how do you think about that?

Yes. I mean it's a good question. One of the beautiful things about the current moment in the biotech industry is we would like to be commercial innovators along certain dimensions, but we don't really have to be commercial innovators. That is Horizon and argenx and BridgeBio and Insmed and Madrigal and Verona and a number of other companies have demonstrated what a biotech company can do in a modern commercial launch, especially in sort of orphan-ish indications. And so I think the first thing is we've learned a lot from that playbook. And part of what's been shown is if you have a patient community, if you have high unmet need and an important medicine that you can get patients and docs to work with payers and you can get patients on drug. And so you wind up building these patient support hubs where the patients and the physicians agree in exchange for a bridge program to really work with you to convince the payers that it's the right thing. And again, in recent memory, that's worked pretty well for biotech companies. And so we're working on that endeavor, and we're building the team out of people who have done that on some of the very same launches I just mentioned.

That's great. So then let's transition to CSU. So congrats on those recent compelling results. How quickly can you get Phase III up and running? And how long will it take to generate Phase III results?

Yes, perfect. So Dave is talking about -- we had another indication for brepocitinib. We were running a small but interesting proof-of-concept study in disease called cutaneous sarcoidosis or CS, which is another devastating orphan inflammatory disease. It's a subcomponent of sarcoidosis generally, which affects multiple organs. Actually, one other form of it is ocular sarcoidosis, which is a subset of non-infectious uveitis, yet another brepocitinib indication. Anyway, you asked about key sarcoidosis. It's a devastating inflammatory skin disease. It can be permanently disfiguring if left untreated. There's a high desire to treat the symptoms, and it's very uncomfortable. We ran a Phase II study that demonstrated -- so our assessment of the bar for -- the endpoint, the scale of disease activity is called CSAMI. It's one of these skin scales like CDASI and dermatomyositis or EASI in psoriasis or -- sorry, PASI in psoriasis or EASI in atopic dermatitis. And our view was a 5-point improvement in CSAMI was clinically meaningful. In the study we ran, placebo patients were flat to slightly worse and drug patients on brepocitinib improved by about 20 points. So just blew our own bar for clinical meaningfulness out of the water. To give you a sense, the baseline CSAMI scores were in the 30s, and we were delivering a 20-point improvement. So just a huge benefit to these patients in the Phase II. So there's a lot of excitement for the pivotal program that we're now about to begin. We said we're going to start the study this year. Basically, the only significant gating item is a discussion with FDA about the Phase II data. And you can imagine we put that data out a few weeks ago. We've been preparing for and lining up for that conversation as quickly as possible. I think once we're done with that, and we've answered a couple of relatively minor in the grand scheme of things questions about how the protocol should be set up for the Phase III, we should be off to the races. And I think this trial will be pretty easy to enroll because the Phase II data was very good, and there's not a lot of other options for these patients. So I think we're excited to see that through. I think it's -- it will be -- we haven't given specific guidance on the time line is the short answer, but a couple of years.

Okay. Great. And before we go on, I just thought it would be helpful for those that aren't familiar for you to just briefly touch on why this is such a safe drug, i.e., and how it will be perceived to be safe in the wake of JAK adoption, particularly RINVOQ despite its label warnings.

Yes. I hate to undercut my own truth, but want to cut my own messaging. Look, brepocitinib is a JAK inhibitor. It hits JAK1 and it hits TYK2, and it will have. It has had in its clinical data, the kinds of safety issues that people talk about with JAK inhibitors, slightly elevated risk of infections, slightly elevated risk of MACE events, et cetera. And that's just a fact of life for these drugs. Now we in-licensed brepvocitinib from Pfizer in 2021, right around the time that black box warnings were known to be becoming a thing for the class. And at the time, RINVOQ was a $3 billion drug in inflammatory bowel disease and some skin conditions. And I think like the presupposition was that in sort of "mass market indications in places like psoriasis and AD and then in inflammatory bowel disease" that docs would go elsewhere because of these safety concerns. And our view at the time was, okay, we're going to go after severe orphan disease with high unmet need where the cost-benefit trade-off is just different, where people would more comfortably tolerate the kinds of things that JAK inhibitors introduced. And for example, in dermatomyositis, first of all, dermatomyositis causes elevated risk of MACE events, it causes malignancies. Steroids and methotrexate cause elevated risks of these things. Getting patients properly treated and off steroids is going to provide benefit along the exact same axis that people otherwise worried about with JAK inhibitors. So it felt like the kind of thing where we wouldn't face the same cost risk trade-offs as people might be wondering about in something like IBD. Now fast forward to 2026, the truth is docs don't seem all that worried about these things in IBD relative to the benefit of a RINVOQ and very few other drugs, if any, have come close to RINVOQ-like benefit in these inflammatory markets. And so RINVOQ is probably going to be a $15-plus billion drug and rheumatologists and other sort of immunologists are very happy to prescribe it. So I do think that the specific concern that we were engineering around may wind up being a little bit different. But anyway, in these inflammatory diseases, the orphan diseases that we're going after, the feedback we get from physicians is an option that works is going to be incredibly important and people will look past for the most part with education, any of the JAK class sort of safety liabilities that these drugs will have. And I think brepo is a very good JAK inhibitor. It's very sort of specific to JAK1 and TYK2. And I think overall, its safety and tolerability looks to be kind of on the benign end of what you see for the class. But make no mistake, we will have the kinds of things that people see with JAK inhibition.

All right. Very good. That's very helpful context. So let's transition to NIU. Can you talk about those results and the timing for the Phase III readout?

Yes. So this is our next pivotal indication. CS will just start a pivotal program, but dermatomyositis will launch by the end of September. And then in the second half of this year, we will get data for our pivotal program in non-infectious uveitis. So this is a sort of umbrella diagnosis for inflammation of the eye, and in particular, in our case, inflammation of the sort of back or -- back of the eye structures, where these patients generally can't be treated with locally administered steroids, which is the sort of first-line therapy for front of the eye inflammation. And so standard of care is a combination of high-dose anti-inflammatory drugs, steroids, DMARDs. HUMIRA is approved in the indication, although it doesn't -- it leaves room for improvement from an efficacy perspective. And so we ran a Phase II that read out a couple of years ago at this point that showed really sort of transformatively better data for NIU patients, right? The HUMIRA data, for example, the clinical endpoint is time to treatment failure. And in the HUMIRA study, it was what, about 3.5 months on placebo and just a hair shy of 6 months on drug. Our Phase II study at the high dose was greater than 12 months. We stopped evaluating patients after a year basically or at least the study concluded at 12 months. And so the median time to treatment failure, most of the patients were still appropriately treated at 12 months. So really, really great data. That then kicked off a pair of pivotal studies that are reading out later this year and an indication that is frankly similar in size and scope to dermatomyositis, but 70,000 to even more potentially patients in claims data sets with non-anterior uveitis who could be good candidates for a good systemic drug and about 47,000-ish uveitis patients on TNF inhibition, many of whom, just given the data I just shared, will fail in a later line option.

Phenomenal. That's great. So let's then turn to potential other indications for brepo.

Yes. Lots of great ideas, some indications that will be proof of concept, some indications that may be straight to pivotal, some of those studies ready to start in the relatively near future and looking forward to talk about them as they get up and running. But look, our view at this point is, look, we're in the sort of pinch-me position. We have one of the best sort of JAK class drugs ever developed, which is itself one of the best classes ever so far discovered for anti-inflammatory use. And we have carved out with a significant lead orphan inflammatory disease as a swim lane for us. It's an amazing position of privilege to be in. And there are many, many places you could imagine going, right? There's a whole host of inflammatory skin conditions that are orphan and quite severe. Now that we have good data in cutaneous sarcoidosis and [ orphan ] ocular sarcoidosis, you can imagine thought going into pulmonary sarcoidosis. We get a lot of investor ideas that are good ideas. People suggest systemic sclerosis and things like that. There's a lot of good places to imagine taking the drug. And I think at the moment, we're focused on expanding indication opportunity, doing a good job with it and making sure that we're focused on the right number of things such that we can win and continue to grow the franchise without diluting our efforts. And I think there's -- we're spoiled for choice.

Excellent. So then is there a way for you to contextualize those incremental opportunities for brepo relative to the indications that are currently modeled by -- The Street, whether they're modeled right or wrong, right? When you think about the size of the first 3 potential indications. And then you consider those incremental opportunities that you're going to start to disclose this year. Any way to contextualize that? Are we talking about 50% greater potential, double the potential, 25% more?

Well, I think of the 3 indications that we've now talked about, I think NIU and DM are roughly similar in size. You can imagine puts and takes as the market evolves in terms of which one winds up being bigger than the other, but they're both about the same size. And cutaneous sarcoid is very large. There's about 30,000 or 40,000 patients in cutaneous sarcoid as well. It's probably like a little smaller than a DM or an NIU, but maybe only a little, to be honest. I think the other indications that we're looking at range in size from sort of CS-ish on the small end to bigger than DM and NIU on the big end by at least a bit. So I think we're looking at indications that are right in the same range. And add legs to the stool that are every bit as large as the other ones that are currently in place.

Excellent. That's great. We look forward to those updates. So let's turn to mosli. Would love to hear you talk about how translatable you think the proof-of-concept data from Group 1 PAH will be to -- and also Group 4 PAH to the Group 3 PH-ILD setting.

Yes. So mosli, again, for those not familiar, it's a drug we in-licensed from Bayer. It is an inhaled activator of sGC. That's a target that's been used successfully in pulmonary hypertension before as a systemic therapy. It's a drug called Adempus, that was -- Adempas that was a Merck Bayer collaboration that did about $2 billion, close to $2 billion in sales in pulmonary arterial hypertension. But in general, systemic vasodilation, which was partly the name of the game in PAH has not been efficacious or safe in PH-ILD, because of this VQ mismatch tissue, basically because if you have a lung that is healthy in parts and disease and other parts that when you systemically vasodilate, as much oxygenation benefit as you get in the healthy lung tissue, you give it right back again in the disease lung tissue. And so the way the field has gone, obviously, the leaders here have been United Therapeutics with Tyvaso is you administer inhaled vasodilators that sort of only activate the healthy part of the lung, and so you get a more sort of targeted approach. In general, I'll first make broad statements that make the risk seem low. In general, the translatability of inhaled vasodilation has been good from PAH to PH-ILD. And the things that have worked well in PAH and have demonstrated good, for example, PVR reductions, and we have basically the best PVR reductions ever seen in Group 1 have translated to good clinical benefit in PH-ILD. Now the words in general are doing a lot of work in that comment and that we're talking about a very small end of clinical trials, almost all of them with prostacyclins. And so that's sort of the unknown unknowns here is we know that SGC works and pattern matches really well to what has happened with the prostacyclins with Treprostinil as between Group 1 and Group 3. And I think we have good reason to believe that SGC as a mechanism should be sort of active in Group 3 and PH-ILD. But the risk that we're taking is the unknown unknowns as we see that through. And there's Phase IIb data, as you know, coming second half of this year that, look, I think if successful, PH-ILD is a market that looks every bit as exciting from an unmet need and opportunity perspective as Group 1 pulmonary arterial hypertension. Tyvaso has been on a rocket ship. And one of the great things about pulmonary hypertension -- great -- one of the terrible things about pulmonary hypertension is a very bad disease. And so these patients wind up using in Group 1, for example, ultimately every option they can get their hands on. It's a polypharmacy market. And so the goal is not even to like beat Tyvaso. The goal is to deliver another therapeutic option for these patients so that they can get used earlier and the patients that like our profile better later and patients that like Tyvaso better, but sort of used in every combination with all the different prostacyclins and Treprostinil and other things that will come. And I think we should be the first knock wood non-Treprostinil mechanism if we're successful.

Excellent. Okay. That's great. So then could you talk about the primary endpoint and how you'd characterize your base case PVR efficacy expectations?

Yes. So the primary endpoint is PVR is a right hearted blood pressure. It's measured under anesthesia on an operating table with a catheterization. So it's not an easy thing to measure. But again, these are quite sick patients. In our Phase I studies, both in healthies and in PAH patients, for example, we saw, I think, a peak around a 38-point PVR reduction, 38%. I think what it generally seems to take in these indications to deliver a clinical benefit is sort of 20-plus percent PVR reductions. So I think that's kind of the bar for the primary, which is this PVR. In the study, we'll also be measuring 6-minute walk and other sort of clinical endpoints, which will ultimately be the registrational endpoints of the Phase III program. And I think it's hard to power for those things for those that have followed this field for a long time, 6-minute walk is a notoriously frustrating endpoint. But I think what we're looking for is this, like I said, 20-point PVR benefit and evidence of separation and progress on things like 6-minute walk that help us contextualize for a Phase III.

Excellent. All right. That's great. And then just touch on safety and tolerability for mosli, expectations there.

Yes. In the Phase I program, it was a very well-tolerated drug. Not a lot to speak of mostly sort of on-target related to vasodilation is the kind of stuff you see. And all of that is the same as any vasodilate PD5s or Treprostinils or whatever. One of the nice things about mosli is it's a very well-formulated drug. It's a single puff of a DPI once a day is the formulation we're testing. It's got very long activity. So we have Phase I data that shows enhanced cGMP production out like 2 days from a single administration. So we've got nice long sort of half-life, if you want to call it that, which is super encouraging. And in general, I think we expect it to be a well-tolerated agent. One of the challenges with these patients is inhaled drugs can cause cough. We don't see a lot of that. And in particular, cough is an on-target, we believe, effect of Treprostinil, and it shouldn't be an on-target effect of sGC activators. So we're hoping not to see significant cough and cough is a meaningful safety side effect in these patients because you're an IPF patient, you already have quite a bad cough and adding on top of it is something we're generally trying to avoid. So I'm hopeful that that's going to be good. The way the study is designed, it's a dose escalation study where patients start out on a low dose and then are escalated relatively quickly to the highest dose they can tolerate. And from what we've seen so far, and obviously, we don't know who's on drug, who's on placebo. We don't know really anything about the performance of the drug. But what we do know is that a lot of patients have been able to get to the high doses, which is encouraging in terms of tolerability.

Excellent. So any opportunities to go beyond PH-ILD?

Absolutely. Look, I think you could imagine other pulmonary hypertension indications, PAH -- PHP and COPD is like a little bit complicated because emphysematous lung has not generally been great for these mechanisms, but it's something we've thought about, and it's something that Merck has explored with similar related drug I was in the middle of a study for. Obviously, we've watched with interest the TETON data that showed that Treprostinil works in IPF. And that's definitely an area that we are actively focused on. But PH-ILD is such a big opportunity. We've been pretty head down there until we've gotten to this moment with the Phase IIb and getting ready for the Phase III. But there's a lot of places you can imagine going beyond PH-ILD, and I'm confident we will in time go broader.

Excellent. And what's the patent life?

I was literally answering the question I was just answering and I was like Dave is going to ask me the patent life for this drug. Sorry -- 2042. 2042. And I was like, I don't remember sitting here right now, and I felt like I was caught not having quite studied enough for the test. 2042.

Well, you have all the other answers.

Only to the questions you've asked so far.

All right. So why don't we -- we're running out of time here, but it'd be great for you to talk about the Immunovant readouts we should focus on this year. And then would love to hear about the Graves' disease opportunity for next year.

In a minute, 19 seconds, we'll talk about those things. Look, so Immunovant is developing our franchise of FcRn inhibitors, which are a class that is, at this point, needs no introduction. Argenx has done an amazing job with it. We have 2 data sets coming this year, a small proof-of-concept study in cutaneous lupus where, look, I think we have good evidence of disease activity there. And obviously, J&J's nipocalimab studies have been successful in an encouraging way. The bar there is to make sure we're able to outpace competitive programs that are also looking good in CLE. So we'll have a good look at that data when it comes later this year. And then the other readout coming this year is in treatment-refractory difficult rheumatoid arthritis where, look, the opportunity is huge. These patients are in bad need. We're looking at patients that have failed some combination of TNF, IL-6 and JAK inhibitors. These are pretty sick patients and not a lot of options. That study has enrolled really nicely. Obviously, there's some data from nipocalimab there as well with mixed results, and we think we've done a nice job on patient selection. We're only looking at autoantibody positive late-line patients. And so we'll know later this year what that looks like, but looking forward to that data as well. And then you alluded to Graves disease. That reads out next year and is what I would call the lead indication for us. It's an enormous market of patients who are undertreated at present, no good options beyond very old antithyroid drugs. And I feel very proud. I feel like we have pioneered modern Graves disease drug development, which is an indication that, yes, I think there's 330,000 fully treatment refractory Graves patients in America. And if we can get to even a small percentage of those patients with a new option, we have a lot of opportunity ahead. So that registrational program reads out next year and would be probably the first indication commercially for 1402.

Phenomenal. Well, this has been great. We covered a lot of ground. Thank you so much for being here with us.

Thank you, Dave. Really fun.