Standing by. Welcome to Roivant Investor Call this morning. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I would like now to turn the conference over to Stephanie Lee with Roivant. Please go ahead.
Good morning, and thanks for joining today's call to review Roivant's unveil of its new pipeline program, Mosliciguat . I'm Stephanie Lee with Roivant. Presenting today, we have Matt Gline, CEO of Roivant, and Mayukh Sukhatme, President and Chief Investment Officer of Roivant. For those dialing in via conference call, you can find the slides being presented today, as well as the press release announcing these updates on our IR website at www.investor.roivant.com. We'll also be providing the current slide numbers as we present to help you follow along. I'd like to remind you that we'll be making certain forward-looking statements during today's presentation. We strongly encourage you to review the information that we filed with the SEC for more information regarding these forward-looking statements and related risks and uncertainties. And with that, I will turn it over to Matt.
Great. Thank you, Steph, and thank you everybody for joining this morning. For those closely following the Roivant story, this may very well be your second call in two days, so we appreciate your time and attention. It's an exciting day for us. I'm gonna do a little bit of framing here and then hand it over to Mayukh to introduce the new program. I'm just gonna, on slide four, kind of situate this within a year. Look, it's been a busy week, and one of the things that's exciting is to be able to sort of put these two bookends out there, namely important supportive data, Immunovant and Graves' disease, which I'll remind people of towards the end of the call today.
And then clinical data in a phase I-B study in this new program with Pulmivant, which we think makes a really compelling addition to our pipeline. Obviously, a lot going on this year between continued development and Immunovant, continuing the possibility for additional BD transactions to bring even more programs into the pipeline, and working through capital strategy. And then on slide five, I'll just remind everybody, this new program really adds to a growth story that we are very proud of, with the addition of a new therapy area on top of what we think is a $10 billion-plus annualized pipeline, especially between the FcRn franchise and Brepocitinib.
We think, and you'll hear all about it from Mayukh in just a minute, we think this program has certainly got multi-blockbuster potential in an indication with very high unmet patient need and not a lot of other options. So it's exactly the kind of partnership we like working on for exactly the kind of program and patient population we are excited about. So, with that, not too much additional framing, I'm going to hand it over now to Mayukh Sukhatme, our President and Chief Investment Officer, to introduce Pulmivant.
Thanks, Matt. Please, turn to slide seven. So, I'm very excited to have the opportunity to unveil this new program in the Roivant pipeline, Mosliciguat . It's a soluble guanylate cyclase activator with the potential to transform pulmonary hypertension. Mosliciguat, or Mosley, as I'll call it going forward, since it's a bit of a mouthful, was in-licensed from Bayer, the leading experts on sGC modulation. Mosley was designed from the start to be the ideal therapy for pulmonary hypertension. Direct delivery to the lungs minimizes side effects and the risk of V/Q mismatch seen with systemic agents and something that is particularly relevant as a risk in PH-ILD. sGC modulation has a wide range of beneficial effects, extending beyond simple vasodilation to anti-inflammatory and anti-fibrotic benefits. Bayer also did a lot of hard design work to make Mosley even better.
Unlike sGC stimulators, as an activator, Mosley will retain full functionality even in highly oxidative environments, common in many forms of PH. We've created a new entity called Pulmivant, which is wholly owned by Roivant to develop Mosley. Pulmivant will be developing Mosley initially in PH-ILD, which is a large population with significant unmet need and very limited treatment options. Pulmivant will be initiating a robust global phase II study in PH-ILD imminently. To date, Mosley has shown some of the highest reductions in pulmonary vascular resistance ever seen, with a favorable safety profile and a robust safety database of 170 subjects dosed. Results from Mosley's phase I-B ATMOS study were presented earlier today at the European Respiratory Society annual meeting.
Now, typically, if we see a drug with a chance to win on both efficacy and safety in a large market with a high unmet need, that's a slam dunk. But with Mosley, there's more. All inhaled therapies for pulmonary hypertension require multiple puffs multiple times per day. It's cumbersome for patients and often runs into compliance issues and therefore efficacy reductions in the real world. Mosley's extended half-life allows for convenient one puff per day dosing regimen with a dry powder inhaler formulation, much preferred to more cumbersome nebulizers or frequent DPI use. Lastly, this collaboration with Bayer has attractive economics for us, with $14 million up front, back-end milestones on success, and a tiered royalty in the high single digits. There's no equity or other consideration. This is a wholly owned program.
Mosley is granted and pending IP protection through 2042, with additional extension that would take us into the twenty to the mid-2040s. Please turn to slide eight. Pulmonary hypertension is classified into one of five groups based on what is actually causing the disease. Group 1 PAH is the most well-known, that's also known as pulmonary arterial hypertension or PAH, Group III PH, which is PH associated with lung disease, is an emerging area of focus and attention, reminiscent of where PAH was some twenty years ago. Group III consists of multiple distinct disease states, including PH-ILD, or pulmonary hypertension associated with interstitial lung disease, which is our key initial area of focus for Mosley. Please turn to slide nine. PH-ILD is quite common and unfortunately, an extremely serious disease for patients.
Median survival is less than five years, with significantly reduced functional capacity and quality of life during that time. Elevations in PVR are associated with worse mortality in PH-ILD patients, which points to PVR reduction as a key leading indicator for clinical benefit in this population. TYVASO's 2021 approval for PH-ILD in the U.S. was the first, and to date, only approval in PH-ILD. Yet there remains significant room for improvement, particularly given the cumbersome dosing, limited efficacy, and tolerability issues like cough in patients whose lungs are already compromised. Despite this need, the development space remains quite sparse, with TYVASO's success representing an outlier for Group I drugs that have tried to cross over into Group III, for reasons we'll discuss more later.
From our perspective, TYVASO's success in its phase III study provides a roadmap of how to successfully develop a drug in this indication, and also underscores the importance of using inhaled route of administration for any mechanism that works principally by vasodilation. Please turn to slide 10. This slide helps illustrate why we at Roivant are so excited about entering PH-ILD. The trailblazer in this indication, United Therapeutics, a company with a long history in PAH, has talked about how PH-ILD is PAH reborn. I think that sums things up beautifully, and we could not agree more. PH-ILD is an incredibly attractive market with extremely high unmet need for patients, as you saw in the previous slide. Prevalence is likely meaningfully higher than PAH, with more most people listening know is a massive market.
For many of us who've been around a while, the PAH story is a fascinating one. With effective options, we've seen the market grow to a more than $6 billion commercial market, with major clinical benefits to patients, sustaining more than 15 therapies, multiple blockbusters, and five different approved drug classes. Companies continue to develop new PAH therapies today. In much the same way, we believe that with the right treatment options, PH-ILD is primed for a similar journey, one for which PAH should be seen more as a floor. TYVASO is already approved, approaching $1 billion in sales in PH-ILD alone, just three years into its launch. While we'll be among the earliest entries into PH-ILD, we expect there will be much less competition in PH-ILD than there has been in PAH.
We'll get into this more later, but in sum, we believe that because of the nature of the disease, systemic vasodilators won't work. That eliminates whole classes of potential entrants. Inhaled prostacyclins, such as TYVASO, will be meaningful, but have a lot of limitations. As such, with better options such as ours, we believe that the prostacyclins will be relegated to a niche portion of the market, just as we've seen within PAH. Please turn to slide eleven. So what would the right treatment option look like exactly for PH-ILD? Honestly, it looks a lot like Mosley, a trifecta of big gun efficacy combined with highly differentiated convenience and great safety and tolerability. We know from PAH that PVR is a predictor of success.
Drugs that meaningfully reduce PVR, typically by about 20%-30%, are almost uniformly highly successful, while those that don't meaningfully reduce PVR are not. TYVASO's phase III INCREASE study confirmed that this basic principle also holds in PH-ILD. In INCREASE, clinical benefit, for example, six-minute walk distance, was driven entirely by patients with elevated PVR at baseline. A single dose of Mosley was not only able to reduce PVR more than any other product to date in the single dose setting, but also surpasses what many products were able to do even with repeat dosing. Given its efficacy and extended half-life, Mosley is also able to differentiate on convenience. Just one puff once per day, compare this to any other approved therapy, inhaled therapy in PAH, regardless of group, which all require [audio distortion] well tolerated.
Compared to inhaled prostacyclins, which are often relegated to later line use, as I've mentioned before, their class, effect AEs preclude-
Please stand by for one moment. We are experiencing a technical difficulty, so please stand by for one moment.
Sorry, can we be heard?
Yes, you are. I can now hear you.
Okay. Mayukh, why don't you go back to the beginning of the slide? Yeah. Can you hear me all right?
Sorry for the technical difficulty. So we're now... I'm gonna just start at the top of slide 11. So what would the right treatment option look like exactly for PH-ILD? So it looks a lot like Mosley, with a trifecta of big gun efficacy combined with highly differentiated convenience and great safety and tolerability. Now, we know that PH, from PAH, that PVR is a predictor of success. Drugs that meaningfully reduce PVR, typically by about 20%-30%, are almost uniformly highly successful, while those that don't meaningfully reduce PVR are not. TYVASO's phase III INCREASE study confirms that this basic principle holds in PH-ILD as well. An INCREASE clinical benefit, for example, six-minute walk distance, was driven entirely by patients with elevated PVR at baseline.
A single dose of Mosley was not only able to reduce PVR more than any product to date in the single dose setting, but also surpassed what many PAH products were able to do even with repeat dosing. Given its extended efficacy and extended half-life, Mosley is also able to differentiate on convenience. Just one puff once per day, compared to other approved inhaled therapies in pulmonary hypertension, regardless of group, which all require between one and twelve breaths, four separate times per day. Lastly, the third leg of the stool. So Mosley's been shown to date to be remarkably safe and well-tolerated. Compared to inhaled prostacyclins, which are often relegated to later line use in PAH, given their class effect AEs, which precludes many patients from reaching maximally effective doses and lead to significant rates of discontinuation.
We believe a key to success here will be our inhaled dosing strategy as well. Systemically administered agents in PH-ILD have been shown not to be successful, likely due to risk of worsening oxygenation status or so-called V/Q mismatch, in addition to other adverse events. This feature creates for us a significant moat for Mosley in PH-ILD, which again, is given by a simple-to-use DPI. So put everything together, we see in Mosley a perfect drug for PH-ILD, one that has the potential to meaningfully differentiate versus competition and be the first-line agent of choice. TYVASO already gives us a clue as to what an agent might be worth.
I think despite its limitations, TYVASO is already on track for doing close to $1 billion now, and consensus about $1.5-$2 billion in sales in PH-ILD alone at peak. Please turn to slide 12. Mosley's been extensively characterized in a robust set of phase I and phase I-B studies. SAD and MAD studies in healthy volunteers showed dose-dependent increases in cGMP, which is a key biomarker to assess in healthy volunteers. Mosley has been well-tolerated through 14 days and is delivered effectively via inhaled formulation. In total, as I've noted previously, earlier, 170 subjects have been dosed to date, including 38 in the phase I-B ATMOS study. That's the data set we'll get into a little bit more and results of which have just been presented at ERS.
In addition, product work, tox work is complete in two species with a high margin of safety and no dose-limiting tox, so there's no constraints on duration of exposure in patients going forward. Please turn to slide thirteen. How does Mosley actually work, and what explains its high efficacy? I'll go through a little bit of the biology here. Soluble guanylate cyclase, or sGC, is a key enzyme in the nitric oxide and cGMP signaling pathway, responsible for the conversion of GTP to cGMP. cGMP is a key messenger molecule responsible for a wide variety of desirable outcomes, not just vasodilation, but also inhibition of inflammation, platelet aggregation, and various anti-apoptotic, anti-proliferative, and anti-fibrotic effects. For sGC to work effectively, both reduced heme and nitric oxide are required.
PH-ILD is associated with particularly high oxidative stress, and when that happens, heme gets oxidized and NO levels are depleted. And as a result, sGC activity is impaired and cGMP levels drop. sGC modulation gets at the problem directly by restoring impaired sGC activity and consequently recovering cGMP levels. Please turn to slide 14. So Mosley is an sGC activator, which is distinct from existing sGC modulators. We are, again, I think, the first-in-class inhaled sGC activator, and we're pursuing this indication. So this distinction is actually quite fundamental. This is not a me-too or a look-alike of an sGC stimulator. Stimulators act by stabilizing binding of reduced heme to sGC, and therefore require both reduced heme and nitric oxide to work optimally. Activators, as you see on the bottom, on the other hand, work independently of heme and NO. So what does that mean in practice?
It means an oxidized environment, such as what you see in PH-ILD. We would expect stimulators to lose efficacy, while activators retain efficacy. In summary, we believe sGC modulation is uniquely suited for PH, and that Mosley as an activator will be the go-to sGC modulator in PH-ILD. We're the only sGC activator in active development today and expect to continue to have meaningful first-mover advantage. Please turn to slide fifteen. I made reference multiple times to Mosley's high efficacy. For those who haven't had a chance yet to see the ATMOS data, let me show you what I mean. So shown here are PVR reductions for a representative set of approved pulmonary hypertension therapies, spanning all key classes, the ERAs, the PDE5s, prostacyclins, and so forth.
These reductions are either in a single dose setting on the left, or in the repeat dose setting on the right. Where PVR reductions are not reported on the label, we're using ranges showing ranges based on phase II or phase III, or academic studies. This slide, of course, is a cross-study comparison, but we tried to show the single-dose PVR data whenever available, and if we didn't have that, we showed the latest phase of data for which we did have PVR data for the drugs in the repeat dosing slide. Note, most products squarely perform in the 20-30% range I referenced before, which appears to represent a threshold for generating meaningful clinical outcomes.
In fact, we have not found a program that generated a PVR reduction in the 20-30% range that went on to fail in an industry-sponsored phase III and not get approved. Finally, in PAH, the leading drug of each class went on to be a blockbuster, is expected to be a blockbuster, with the exception of PDE5, because, of course, those drugs were available at a totally different price point for erectile dysfunction for years before their efficacy in PAH became apparent. Please turn to slide 16. Mosley's data, which you see in blue on the left, in ATMOS, sits well above this bar. We showed an eye-popping mean max PVR reduction in the mid- to high 30s%, which is head and shoulders above what we'd expect from TYVASO, Adempas, or Ventavis.
Just a single dose of Mosley appears to drive greater PVR reductions than even repeat doses with Revatio, Opsumit, Uptravi, or Winrevair. As one might expect, PD data suggests even greater efficacy is likely with repeat dosing of Mosley. In addition, Mosley's improvements in PVR were due to robust improvements in both pulmonary artery pressures as well as in cardiac output. Before I move on, I do wanna draw attention again to the relative convenience of Mosley's dosing regimen versus the others. Just one puff per day has the potential to deliver this magnitude of efficacy. Please turn to slide seventeen. So why is this so important, and why, how is Mosley able to do this? So we'll actually go right to left on this slide. So on the right, you can see the time course of PVR reductions with inhaled treprostinil.
Note that TYVASO was studied up to the 72 microgram dose in its PH-ILD phase III, which is in between the blue and green curves shown here. PVR reductions with treprostinil max out 30 to 60 minutes before starting to return to baseline. By a little over two hours, the effect is gone. This explains why TYVASO needs to be dosed four times per day, that you can do the math here and see that even with that frequency, you spend most of the day with suboptimal PVR reduction. Certainly, if you're not waking up in the middle of the night to dose. Ultimately, the translation to clinical endpoints like Six-Minute Walk Test and time to clinical worsening are a function of max PVR, but also the amount of time with that sort of suppressed or reduced PVR.
So then turning to the left, you can see the time course of PVR reductions from Mosley's Phase I-B ATMOS study. So while TYVASO peaked and then long returned to baseline by three hours, Mosley at three hours is generating greater than 30% PVR reductions with a slope that you can pretty clearly see here is pointing downwards. Again, this is a testimony to Bayer's deep expertise designing sGC modulators. Mosley's extended 40-plus hour half-life, combined with excellent PD, allow for potentially game-changing efficacy with just one puff per day. Please turn to slide 18. We've now discussed how Mosley is differentiated on efficacy and convenience. The third leg of this stool is safety and tolerability. In ATMOS, we saw a clean safety and tolerability profile. Most treatment emergent events were mild.
Continuous dosing in the rest of the clinical experience to date, from seven to 14 days, revealed no relevant additional events. We've seen no clinically significant changes to blood pressure or heart rate, and all doses have been well tolerated without significant AEs. We don't expect to see an increase in AEs beyond what you expect to see as part of underlying disease in PH-ILD patients. This stands in stark contrast to inhaled prostacyclins, for which class effect AEs include high rates of cough, throat irritation, oropharyngeal pain, and headache, among others. Now, these are, in fact, class effects and would be expected regardless of dosing frequency or formulation. These side effects are not inconsequential.
TYVASO's INCREASE study in PH-ILD, which led to its approval, showed that 45% of patients receiving drug had cough, and less than half of patients were able to reach the top dose level. In the INCREASE open label extension, 22% of patients discontinued the drug due to AEs. Please turn to slide 19. So here's a list of relevant drugs in the competitive landscape. I think in sum, Mosley's differentiation on efficacy, safety, and tolerability, and convenience, positions it as a potential best-in-category therapy. So among approved or relevant development-stage competitors, Mosley is unique in its ability to deliver a greater than 30% PVR reductions with just one inhalation per day, an extended half-life, enabling sustained duration of effect, and in its ability to do those things with a clean safety and tolerability profile.
These other drugs are, or might prove to be important drugs, and we think that they might be, but we also think that they have significant limitations. TYVASO, as noted previously, is an inhaled prostacyclin. It's about to reach blockbuster status in PH-ILD within just three years of launch. Consensus forecast peak sales at $1.5-$2 billion in PH-ILD alone, and that's in a product that requires multiple breaths from a DPI or nebulizer four times a day to get to less than 30% PVR reductions, with a tolerability profile that leaves much to be desired. Mosley's profile is a meaningful improvement across the board.
Seralutinib, while also inhaled, does not act principally by vasodilation, and so the benefit of targeted lung delivery is perhaps an open question, although it may help them avoid systemic tox based on its mechanism of action. In addition, impact on PVR is modest, even through week 24, which was somewhere around 10%, much smaller than you see with Mosley or TYVASO. It, too, needs to be dosed multiple times per day, although it may have better short-term tolerability than the prostacyclin. Lastly, even though Merck is not studying MK-5475 in PH-ILD, they're studying it in a different indication, PH-COPD.
Recall, however, that stimulators like MK-5475 are highly likely to leave a lot on the table compared to activators like Mosley, especially in oxidative environments like those that are typical with Group Three disease and in PH-ILD specifically. Whether due to the specific molecule, the mechanism or both, PVR reductions seen to date with MK-5475 aren't close to what we've seen with Mosley. There's also an open question whether once daily dosing profile continues for that program into phase III. The short half-life and data to date suggests suboptimal coverage over a twenty-four-hour period. We think Merck will most likely need to decide whether to sacrifice efficacy or convenience going forward. Please turn to slide twenty. Here's a schematic of the phase II study that is beginning immediately.
And with this phase II study, we really look forward to seeing the full extent of what Mosley can do. The FOCUS study will enroll roughly 120 PH-ILD patients, and the overall design is straightforward. So two-to-one randomization of drug to placebo, so a 24-week placebo-controlled, blinded treatment period, where patients are rapidly uptitrated to a maximum dose. The primary endpoint is PVR at week 16, as assessed by right heart catheterization. There's then an open-label extension period, where active patients remain on drug, and placebo patients are switched to drug and uptitrated to a maximum dose. A sort of very key and important secondary and exploratory endpoints are also gonna be collected, some of which are listed on the right.
What's special and important to note is that to avoid some of the pitfalls from prior studies, we'll be focusing on patients for whom a vasodilatory therapy is expected to show benefit, namely those with high PVR at baseline, fibrosis above a certain threshold, and importantly, emphysema below a certain threshold, as assessed by high-resolution CT. Lastly, development in PH-ILD is highly efficient. I think, following positive data, we expect a single registrational trial will be sufficient for approval, which is fully consistent with precedent in the pulmonary hypertension space. And with that, I'll end. Thank you all for your time. I think I also want to thank Bayer for their outstanding work and for being an excellent partner throughout this process.
I also wanna thank the Pulmivant team, who have been working tirelessly on the transition and subsequent preparation for phase II, and of course, the investigators, sites, and most importantly, all of the patients, and with that, I'll turn it back over to Matt.
Thanks, Mayukh. And again, thanks, everybody, for listening. We're as you can surely hear in Mayukh's messaging, we're very excited about the program. Sorry for the little technical difficulty in there, but obviously, we'll have a lot of opportunities to talk about this. Look, I think for us, it really comes down to three things here. It's a proven market in an indication where TYVASO is already doing quite well and where there's clearly a lot of unmet need. Where we think we have potential best-in-class tolerability and once-day dosing, which is unusual, and where PVR data suggests early efficacy with this novel s GC activator mechanism.
So we feel, we feel really good about where we are here, and we feel really good about adding this as a pillar and a component of our pipeline. So before we go to Q&A, and we'll spend the vast majority of that, I'm sure, on this new program, I just wanna reiterate a couple of the messages from yesterday's Immunovant update. So I'll do that very quickly and then open the line for questions. Look, I think there are really three points I wanted to hit in here. One, on slide twenty-two, is just...
I'm sure there will be a lot of healthy discussion around this topic, but every time we scratch the surface and go deeper on Graves, we find ourselves more and more excited about the size of the opportunity here. There's just a lot of patients, hundreds of thousands of prevalent market patients, who have relapsed on ATD, ATD relapse patients who are not pursuing ablation, not pursuing radioiodine, but who are clearly uncontrolled on background therapy, and for whom we think an FcRn can make a really big difference. You know, frankly, it is an opportunity that is so large that when you do the basic multiplication, you get an almost unfathomable number.
And we are just really excited to continue to sort of understand the shape of that opportunity and figure out how best to get an FcRn out to patients who will benefit from it. You know, the second thing, which I've got a few of the different efficacy slides in here, but I'll just jump to slide 26, is just as a reminder, this data surpasses. I know we signaled good things about it starting earlier this year, but it surpasses, I think, even our own expectations, bluntly, for what we thought we might see in this study. With you know, over 50%, 56% of patients after only 12 weeks of 600 milligram dosing, getting completely off ATDs while having normal thyroid hormone levels.
It's just a pretty remarkable data set from that perspective. Then, look, the last point here, which has really only a little bit to do with Graves' disease, is this study was never designed to underscore the more is better case. It was built at a time when 1402 was not as big a part of the pipeline, and we were trying to set up for the best possible case for, for rituximab. But it does a nice job of highlighting what happens here, which is we have patients dosed for 12 weeks at our high dose, a dose that we think only really batoclimab and 1402 are able to consistently deliver from an IgG suppression perspective, and we see these really exciting response rates.
And then the minute we swap in that low dose and get to the second twelve weeks of the study at three forty, where we get to IgG suppression, that is much more in line with our competitor programs. You still see a lot of patients well controlled. You still see a reasonable number of patients off ATDs, but the numbers get significantly worse quickly, and that's despite residual benefit associated with the period of being dosed at six eighty, and it is despite the benefit of those patients being allowed to up titrate ATDs to compensate. So, you know, we think there's also some really good evidence embedded in this data set that underscores more is data, sorry, more is better, and sets us up well for, you know, the next leg of our journey here as we expect more data to come.
And then, you know, I won't review it, but on slide 27, we've got the trial design here. Suffice to say, we are very excited about progressing 1402 in Graves' disease and think we're gonna be able to answer some really important questions in these upcoming Graves' studies. So, enough said on that, today is really about Mosley. So with that, I'll echo all of Mayukh's thanks for everybody who worked on this program, from all of the team at Bayer to the Roivant and Pulmivant teams who have been working really hard getting this study off the ground, to the investigators and the patients. So thank you to everybody. And with that, I will turn the line back over to the operator for some Q&A.
Thank you. As a reminder to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster, and our first question comes from David Risinger with Leerink Partners. Your line is now open.
Thanks very much, and congrats on the update, and thank you, Mayukh, for the very detailed presentation. So I have a couple questions. I'm gonna ask mainly high-level questions. The presentation was quite comprehensive and helpful. So Matt, I know that you've been excited to share this news for a long time. Can you just step back and review, you know, how you decided to keep this drug confidential over the past year and developments in recent months, and just what activities you've been engaged in? You know, obviously, that's included designing the phase II, but additional color would be helpful.
Yeah, sure. So I'll take a crack at that, and then, Mayukh, if you have anything to add. Look, in terms of the decision to keep it confidential, you know, I think, PAH, the different groups of pulmonary hypertension are a relatively competitive area, and there's different people doing different things. And we felt like we had an opportunity to get ourselves set up for a best-in-class program, positioned correctly with investigators, positioned correctly, you know, in the world, if we did it on our own time, and we did it quietly.
So, you know, during the time that we kept the program quiet, we designed the phase II study, we met with FDA, we got ourselves organized around the indication, and we are now imminently starting this study with data expected, you know, by the second half of 2026 or maybe even a little bit ahead of that. And so we're, you know, we're sort of in pole position, ready to go with the study, which is something that took a fair amount of time to get going. So you look, I think it was about the competitive dynamic, about keeping the lead, and about positioning the program correctly for success. Mayukh, anything to add to that?
Yeah, it was, I mean, it was really kind of a strategic decision, I think, to maintain the kind of first-mover advantage that I think we talked about in the prepared comments.
Thanks, Dave.
Great. And then, are you studying a single dose in phase II?
So the design of the phase II study involves... Yeah, go ahead, Mayukh.
Yeah. So basically, there's kind of a rapid up titration. So we'll have patients, you know, potentially in sort of may settle at slightly different doses, sort of across the board, but really, we're expecting most all the patients to get to the top dose and sort of view it as a group, so it's a group comparison versus placebo and versus baseline.
Yeah, and given the tolerability, I'll just reiterate, we expect most of the patients to get to the top dose and to be there for the vast majority of the duration of the study.
Great. And then, with respect to the trial design, I mean, obviously, you're moving very rapidly, and it's only a 120-patient study, which is great. But could you have considered conducting an adaptive phase II/III study to go even faster into phase III, given the unmet need and the profile of the drug? Or is that just not possible? You have to run the phase II, complete it, have an end of phase II meeting, and then start phase III separately.
Mayukh?
Yeah, I mean, we've So Dave, it's a great question. I think you should assume that we've thought a lot about different approaches for this program overall. I think that the major objective from, you know, for us, 'cause I think we could have done sort of a shorter phase II. I think we feel really, really confident about, you know, about PVR as an endpoint. It's kind of a no-brainer, candidly, based on the data that we've seen before and then sort of the translation. But we want to get a sense of that translation. And I think, you know, while a sort of seamless design, I think often sounds appealing, I think as a practical matter, it oftentimes does kind of slow down the start of the phase II on the front end.
And so I think kind of blending all those considerations together, I think this sets us up well, you know, a really robust phase II study, maximum conviction coming out of that into phase III, and then the fastest time to market.
Excellent. And then one final one. Could you comment on your consideration of potential development in PHCOPD?
Go ahead. I'll just say, look, I think, obviously, with PVR data this good and with a unique and novel mechanism, there are a number of places you could imagine going with the mechanism from here. That said, I think right now, as far as these conversations are concerned, we really want people to focus in on that PH-ILD indication because we see it as having, very significant unmet need and being a, really great place to get started.
Yeah.
Excellent.
I think you, you've got it. I mean, the other thing just to add is, look, I think one of the beautiful things in the setup for us in PH-ILD is that I think we have the benefit of, you know, TYVASO really kind of showing the roadmap of how to, how to be successful, how to run a successful clinical trial at PH-ILD. I think that is still a map that's being drawn in PH-COPD. And so I think for us, the setup is really particularly appealing in PH-ILD, but we'll see how the data across the space emerges.
Great. Thanks, Dave.
Great. Thank you.
Really appreciate it.
The next question comes from Allison Bratzel with Piper Sandler. Your line is open.
Hey, good morning. Congrats on the update, and thank you for taking the questions. Maybe just two quick ones from me. First, could you just clarify for us the timelines and catalyst flow we should be looking for with respect to Mosley in PH-ILD? You know, given the phase III-B data we've seen, I would think you'd see pretty rapid enrollment and FOCUS and an eventual phase 3. So just thought there would be helpful. And then maybe building on that last question, you know, I know you're initially focusing on Group 3 and PH-ILD for Mosley. I guess, you know, at what point do you explore other PH expansion opportunities? You know, is FOCUS data a gating factor, or what's gating there?
You know, just maybe kind of bigger picture plans for the asset would be helpful. Thank you.
Yeah, great. Thanks, Allie. On the timeline of the catalyst question, so this study will start imminently, is the word we've chosen to use, and we mean imminently. So we should see patients enrolling soon. And, you know, I think I just said earlier, our expectation is that we will get data from this study in the second half of 2026. We are hearing a lot of enthusiasm from the investigator community. And so I think there's some upside potential to that, but let us get a little bit into enrollment here, and then see. I think the dynamics here are good. So we'll see what we get to.
And then on the expansion opportunities, similar to what we said to Dave. Look, I think it's great biology. The early PVR data is encouraging. PH-ILD is a nice place to start because of the clean path paved by FDA already or with FDA already. But I see. We see other places to go as well, and I don't think there's any reason to believe that the FOCUS study is per se gauging on expansion beyond PH-ILD. We'll just take it as it comes.
Yeah, the only thing I'd add to that, Allie, is that you sort of said bigger picture, and I guess what hopefully we're able to convey here is PH-ILD is a really big picture already. And so, we're excited about kind of the market opportunity there, but it's obviously not long-term constraint to PH-ILD alone, but PH-ILD is pretty meaty.
Thank you.
The next question comes from Dennis Ding with Jefferies. Your line is open.
Hi, good morning. Thanks for taking the question. Maybe a question around the phase 2 design. Can you talk about your target enrollment criteria, your, I'd say, elevated baseline PVR, but is there a specific cutoff? And maybe you can comment on, you know, the number of background therapies and other things like mix of high vaso, naive or experienced, that'd be helpful. Thank you.
Sure, go ahead.
Yes, sure. So we are, I think one of the, sort of, to go along with the roadmap, I think, it is important to verify that the patients in the study do have an elevated PVR at baseline, so we've got criteria of greater than four Wood units, enrollment eligibility in the study. We do allow concomitant PDE5, which are used occasionally in off-label. We are not in this study allowing background TYVASO. You can have been on TYVASO in the past, and so we are expecting that there may be some patients who have, you know, who have been on TYVASO and maybe refractory TYVASO. Again, as a reminder, TYVASO is only approved in the U.S. This is a global study, and so we'll kind of get that experience.
Got it. Thank you.
Thank you, Dennis. Appreciate the question.
And the next question comes from Yaron Werber with TD Cowen. Your line is open.
Great. Thanks so much, and congrats on this program. Excuse me. Couple of questions. Number one, just kind of, systemically, are you seeing any exposure at all and any, systemic vasodilation? And then secondly, our understanding is that Merck's program in PAH didn't have great data. I don't know if you have any insights on that. And then maybe just finally, give us a little bit of a sense, when is the composition of matter expiring? I see that the overall patent status until 2042. Thank you.
Yes, thanks. Those are all good questions. First, on the systemic exposure and the vasodilation question, this is incredibly important in PH-ILD, and the answer is we see very minimal systemic exposure, and we don't see sort of systemic vasodilation, which is actually, which is really important here, and one of the reasons we like the inhaled therapy. You know, as far as Merck is concerned, I think that data, some of that data is being presented today. We have not seen all of it. Our sense is it was all right. That program is not the same mechanism as our drug. It is a stimulator, not an activator, and so we think it is, you know, interesting in so far as it's sGC targeted, but obviously, there's other data there.
And then most notably, that Merck program has a two-hour half-life compared to a forty-hour half-life of ours. So it's just a very different profile in terms of the way it's gonna affect the patient. And then it's gonna require, even if it were successful, many inhalations per day compared to our just one, given the half-life. That's what I have on sort of those two questions. But, Mayukh, anything you can add in there, and also if you have composition of matter handy.
Oh, yeah, composition of matter. So with extensions, composition of matter is through, I think, 2038. And then I said there's a lot of other sort of IP that we're expecting, you know, as an operative matter, to get into the mid-2040s. Just to add maybe a little bit to the sort of systemic exposure question. So, you know, evidence of things that we're not seeing that would be evidence of sort of systemic would be, you know, impact on heart rate and blood pressure, which we're not seeing. We sort of looked at a number of different things.
Our, you know, I think it really, you know, in comparison to, for example, riociguat, we're seeing that our cGMP production is higher, but our Cmax exposures are 30- to 60-fold less than a systemic activator or systemic stimulator. So we're getting, you know, I think, really great benefit from that targeted lung delivery based on everything that we've seen and without any of the attendant systemic effects.
Thanks, Vihang.
Yeah, thanks. It's a great question.
The next question comes from Louise Chen with Cantor Fitzgerald. Your line is now open.
Hi. Congratulations on the progress this week. It's only Tuesday, and you've announced a lot. And thanks for taking my questions here. So first question I had for you was, Roivant has always been very good at spotting trends early, and what really piqued your interest in this opportunity, and what do you think the Street hasn't caught on to yet? And then secondly, any physician feedback you can offer from your ERS presentation? Thank you.
I will let Mayukh take those two, but I'll just ask if you've got your calendar cleared for the rest of the week. No, I think no calls currently planned for beyond today. Mayukh, on both those questions. Great, great questions. Go ahead.
Yeah, look, I think as you guys, as everyone, I think, hopefully has come to learn about us, I think we like to look at everything. We have sort of very much an asset-focused or program-focused approach, but we'll look at any therapeutic area and, you know, any state of development.
I think here, what we saw is, I think, you know, a really, really good program with a lot of great attributes to it, and then I think this kind of product market fit to PH-ILD specifically, at a time where, you know, I think when we first started talking to Bayer, and it's now become, I think, more clear with the commercial success of TYVASO, that PH-ILD is, a really attractive market with a lot of unmet needs, but a huge amount of commercial potential.
You know, look, I, I agree with all that. Look, I think, it's hard to take credit for spotting trends early, precisely, for obvious reasons. But look, I think, like, our hope is this looks like a number of other indications where, early in the first launch of the first product, you can start to tell that there's a real unmet need, and then we can bring a product that frankly has a pretty great profile into that population. And so we're looking forward to it.
Sorry, we didn't hit the sort of what we're hearing at ERS. I think we're hearing all the things you want to hear at this point, which is great. I think great enthusiasm on the part of KOLs and, you know, study sites to the ATMOS data. I think an appreciation of really kind of the lack of of a lot of other options for patients and candidly, even in clinical development, which I think as you've heard already, we're hoping we can't yet pledge to it, but we're hoping ought to portend well for enrollment and for data read out.
Yeah. I've been sent a photograph of a bunch of people sort of clustered around our poster at ERS. So if that's any indication, there's good enthusiasm. Thank you very much.
The next question comes from Brian Cheng with J.P. Morgan. Your line is open.
Hey, guys. Thanks for taking our question this morning. Just a couple from us. Can you give us a sense of the duration of the titration period in the phase II? Y ou know, what are the doses that you'll be testing going into this titration period? Are those the same doses that we have seen in the phase I? And any trigger that you can discuss, you know, you can disclose on, you know, what you would need to see to further escalate the dose? And I have a follow-up. Thank you.
Yeah. I think the answer on dose titration is we expect these patients to reach sort of terminal dose within a matter of a few weeks, so it should be, it should be pretty quick, and we're testing a dose range that is pretty similar to the phase II, but we're not saying exactly which doses we're testing at this point.
Yeah, it's within sort of the envelope of doses already tested, and it's a two-week dose titration.
Okay.
It's rapid escalation.
Okay. When we look at your ERS presentation, you know, it seems like you already got decent PVR reduction in patients with high 400s and, you know, low 700s PVR at baseline. You know, Mayukh, I don't know if you can discuss a little bit about how you envision success, you know, when it comes to PVR change from baseline, which is your primary endpoint in your phase II.
Yeah, look, I think the way, the way we're looking at it is kind of, you know, in line with what I talked about in the prepared comments, which is we really ought to see PVR reductions at least in that 20-30% range. I think kind of once you're over that threshold, you know you've got a drug. I think we're feeling really good about that. So that's kind of where I'd like to kind of have the bar set or hopefully cleared, and then I think beyond that, what we're hoping to get out of the phase II is, you know, early signs of translation.
You know, I would say that it's kind of early signs, so this is sort of in the you know, trends that are helpful here, rather than sort of a definitive statistics around it. But trends that sort of support that bridge from PVR, which is, of course, just a hemodynamic marker, to the clinical outcomes that everybody's used to seeing, such as six-minute walk test, time to clinical worsening, and so forth.
Great. Thank you.
And the next question comes from Andy Chen with Wolfe Research. Your line is open.
Hey, good morning. Thank you for taking the question. So, activators have been around for a while, even though some of them may have been terminated. Why is it that they haven't entered PH-ILD? And then, on a related note, because you've been hiding the assets, if your competition should enter PH-ILD with an activator, are there certain pharmacological or molecular properties that make Mosliciguat better than other activators? The only thing I see on the slide is half-life and convenience. Curious if there are other advantages. The reason I'm asking is because if your competition also pursues PH-ILD, will they be immediately at a molecular disadvantage? Thank you.
Yes. So the first and easiest comment is, we have no competitors with an inhaled activator. So right now, nobody has a program that we're aware of. You know, I think in terms of why this program and others didn't go into PH-ILD earlier, remember that TYVASO has really paved the way from a trial design and from a market perspective. And so I think we're still in very early days of the indication. And I don't think we have a lot of clear competitors. There are some oral activators in other unrelated indications, but none of those are inhaled. You know, in terms of like, if somebody were to come up with an inhaled activator tomorrow, I think the bar would be high, given the properties that Mosley has, right? The half-life is important.
It contributes to our ability to dose once daily. The potency is important. It allows us to be in a single puff. The convenience is important, which is a function and part of that potency and a part of formulation advantages and other things. But I think all told, the bar would be high for another activator showing up in this indication.
Yeah, Andy, just to add to that, this is Mayukh here. I do think it is important just to kind of as a reinforcement of points that I made kind of during the prepared comments, which is in PH-ILD, specifically, there is a lot of damaged lung. And what you don't want is you don't want to have vasodilation in areas that are damaged, because that can lead to worse oxygenation status. And so we don't actually think that a systemic vasodilator will work in PH-ILD. And so actually having it inhaled is a meaningful differentiation, and we're the first in class in this indication.
And to reiterate another point, look, Bayer is really good at this chemistry and this biology. They have been a leader for a very long time in sGC, and it took them a while to discover this drug. And so I think the other moat we have to be one is I think it will be hard for others to come up with as good an agent as they were able to.
Thanks, Andy.
Thank you.
And the next question comes from Corinne Johnson with Goldman Sachs. Your line is open.
Good morning, and thanks, guys. Maybe a couple questions for me. Maybe first, I mean, you just mentioned Bayer is sort of an expert in the space. So what's your understanding for why they'd be willing to sort of part with this drug and let you take over the development there? And then, you mentioned, I think, that you'd be willing to talk about expansion opportunities, albeit you see the group three PH-ILD here as compelling o n its own. But would you run those proof-of-concept type studies kind of in parallel to a phase II? And when would you aim to have, like, more clarity on a broader development strategy for this program? Thanks.
Thanks, Corinne. Those are all good questions. Maybe I'll hand it to Mayukh to take the,
Yeah, so on your question about what, why did Bayer give it up? Well, look, I guess I would say I look forward to the day that we don't get the question when we do a deal, that people wonder why, you know, another company made a decision. But I think that we think that they didn't give it up. I think this is a way they were getting out of respiratory as a therapeutic area, and this is a way for their great work to make it and to have a great impact on patients. So we really view this as a win-win partnership, as we do with all of our deals.
Remember, Rio goes generic shortly, so they had to figure out a thing to do with their franchise, and the thing they chose to do was deprioritize it. On the expansion opportunity question, love the collective enthusiasm for additional indications. We share it, but at the moment, we're trying to keep focus on PH-ILD, which we think is a great opportunity with high unmet need and some very sick patients. So look, I think as soon as we get this study up and running, we'll think more about and talk more about plans beyond it. But for now, this is a big opportunity, and we wanna make sure we get it right.
Thanks.
Thank you.
And the next question comes from Yatin Suneja with Guggenheim. Your line is open.
Hey, guys. Thank you for taking my question. Just maybe two for me. With regard to the dose response, could you maybe articulate for us, what did you see in preclinical model? Are you seeing a similar effect, where you're seeing a plateauing open effect around two milligram? So that's one. And then the second question is around, you know, this, activator versus stimulator. So the question is, how variable are the levels of NO and heme in PH-ILD? In other words, are there patients that might respond to stimulator better versus an activator? Thank you.
Yeah, Mayukh, why don't you take that? But I think the answer on the latter question, just to be clear, is that sGC exists at all times in multiple different configurations, some of them with bound NO and heme and some without. And so it's not a question of like variable, quote, unquote, "levels of NO and heme," so much as it is a question of what the sort of balance of those different states of sGC is and how oxidized the environment is. But Mayukh, why don't you go ahead?
Yeah, that's right. So, maybe at the risk of maybe oversimplifying, but I think you've actually captured the underlying sort of biology. And so there's basically different, I guess I'd say, states or species of sGC, as Matt mentioned, going from sort of the, you know, the reduced heme and NO bound to the oxidized heme bound without NO, to the heme-free sGC. But the thing that's interesting is that we are actually seeing with Mosley outperformance, really, regardless of sort of disease groups.
So, again, in a cross-study comparison, we're seeing, for example, not just this great data, you know, that we've seen already in group one and group four, but we also see that Mosley outperforms riociguat, a stimulator in healthy volunteers as well. So that's obviously not a, you know, a state where you would view it as a highly oxidized environment, and yet Mosley outperforms riociguat there, too.
Yeah. And then in terms of dose response, obviously, the data being shown today was specifically from the ATMOS study. But I think you don't need to go back to preclinical models to answer any of these questions, since this has been dosed in 170 subjects across a range of phase I studies. And so we've seen a robust dose response across all of those studies that continue to support the range of doses we're testing, the clarity of the dose response from here. And, you know, I think in general, we feel good about our dosing, and we feel good about the dose response of the program, and it's supported by both clinical and preclinical evidence.
Thank you.
Thank you.
Our next question comes from Douglas Tsao with H.C. Wainwright. Your line is open. Douglas, your line is now open. If you are on mute, please unmute. At this time, I show no further questions, so I would like to turn the call back over to Matt for closing remarks.
Thank you, everybody. Sorry, Doug, we weren't able to get you there, but we'll chat when we can. Thank you, everybody, for listening today. Again, second day in a row, and once again, we're just excited for the new additions of the company and excited for an opportunity to bring a meaningful therapy to patients who really need it. So looking forward to providing continued updates here and to this becoming a part of what we chat about on a regular basis. So thank you again. Have a great day, and we'll talk to many of you soon.
This concludes today's conference call. Thank you for participating. You may now disconnect.