Insmed Incorporated (INSM) Earnings Call Transcript & Summary

Okay. Good afternoon, everyone, and welcome to the 2:10 session on day 2 of the Goldman Sachs Global Healthcare Conference. My name is Graig Suvannavejh. I cover U.S. and U.S. -- European, excuse me, biopharma names here at the firm. It's my great pleasure to be hosting Insmed today on a fireside chat or in a fireside chat. And with that, let me welcome the company's CEO, Will Lewis. Will, it's great to see you again, and thanks for joining us.

Thanks for having me, Graig. Really appreciate it.

Okay. Great. Maybe just to -- from a high-level perspective, let's why don't we start pretty simply and this could be a situation where it's new for investors in terms of getting to know who Insmed is or maybe it's for those who are just taking a look at the name again, but could you provide for us just very high-level summary of Insmed and where your key areas of focus are and perhaps what you would consider your core areas of expertise, so that would be great?

Sure. So let's start with the core area of expertise. We are a rare disease company. We have set ourselves on a mission to address patients who suffer from serious and rare diseases. And we do that by bringing forward impactful products. We'll talk about what we mean by that. That allow these patients to have a material change in the outcome of their clinical circumstance. So these are not the fifth or tenth program that's coming forward. These are ones that are going to step forward and either be first in disease or they're going to have a material impact on the patient's underlying clinical profile. And when we think about that, and we talk about where we are as a company, we've just come off our most transformative year in our history. And we now sit with 4 different, what we call, pillars, that we are bringing forward, and we are extremely well resourced to do that. I'm sure we'll cover all of that. But the 4 pillars, just for everyone's reference are our approved product, ARIKAYCE for the treatment of refractory NTM disease. It's a lung infection. It's now approved in the U.S., Europe and Japan. The second program is brensocatib. That's our DPP-1 inhibitor. We in-licensed from AstraZeneca with global rights, and that is in a Phase III trial globally for the treatment of bronchiectasis. The third is our TPIP program, treprostinil palmitil inhalation powder. And TPIP is a product that's joining a crowded space in the PAH arena, but has the potential to really alter the way that prostanoids impacts patients. And so that's why we're excited about that. And it has some additional indications that it can go after. And then fourth and finally, our translational medicine or research department's efforts, which increasingly, over the next 12 months, you're going to hear more about. And here, it's worth linking back to that notion of being a rare disease company because that pillar is going to be increasingly demonstrating the breadth of its capability and the novelty of the science that it pursues. This is not simply the kinds of programs you've seen from us in the past, but it's going to include some new and very exciting technologies.

So well, just let me pick up on that. This fourth pillar of this translational medicine aspect is this seems to signal kind of a new emphasis on that side. Can you give us a sense of what that cadence of information coming out of those efforts are going to be like? Is it this year? Is it next year?

Yes. I will just put very simply, I'm expecting in the next 12 months, some exciting advances there. I think research is always hard to predict, but that certainly is our ambition. And I would cast that in the following history, right? When we brought forward TPIP, we wanted that drug to have been tested extensively prior to its announcement to the world so that we could define what we thought the drug was, what we thought its potential clinical benefit would be and also laid the groundwork for its immediate transition into a Phase I study. And that's the kind of framework that we want to bring forward if we have something that clears our hurdle for approval in terms of our research stage-gate approach.

Now if we look back over the past year, certainly was challenging for many -- for many obvious reasons. I think for Insmed, it was also challenging just given heavy emphasis by investors on your commercialized product ARIKAYCE. Certainly, the ability to engage with patients and physicians was dramatically impacted. As a CEO, how did you manage that in terms of the challenges that were presented and how did that really impact your ability to execute from a commercial and R&D perspective?

Yes. I'm unbelievably proud of the way the commercial team responded to the challenges of the COVID-19 era. I mean if you think about what we managed to accomplish over the course of the last year, quarter-over-quarter, we had a steady performance. Now it was not the growth trajectory we had enjoyed prior to COVID, but I was actually really happy with the outcome of the performance over the last year. Because it could have been a much more significant set of challenges in the sense that we were offering a respiratory product for patients and the respiratory physician community, the pulmonologists, the infectious disease specialists, they were 100% focused on COVID at periods of time. So to be able to continue to support them and ultimately, the patients was really quite an accomplishment. We had to work to remote support. We did telemedicine. We did all kinds of creative ways to reach and provide needed information. And our patient support services went into overdrive in terms of making sure that patients that adopted into that program continue to receive support, access to medicine, et cetera. We even went to virtual training for new patients that were starting. So we did a whole host of things, some of which will take forward into the future to be able to access patients that perhaps are more remote in certain territories. But overall, I would just say, it really is a case study of how we were able to pivot and engage and in my opinion, succeed in one of the most challenging environments that we would ever expect to face. And as we look at the second half of this year, we're already seeing the green shoots now, the return. We see offices open. We see patients that are fully vaccinated. And we know that our therapeutic specialists are back out in the field with the arrival of the vaccine to enable the ability to reach out to these physicians who want them back in their offices. So this is not an era where this heralds the end of the therapeutic specialist, quite the contrary, in the rare disease world, I think now they're needed more than ever, particularly in the respiratory arena. And to that, I would say we've added Europe approval, Japan approval, and that was done during the COVID epidemic in a remote way. So I can tell you, it's hard enough to go to Europe, where you have all the countries together at the EMA and securing approval, try doing it by a Zoom with everybody dialing in from around the world. It's -- it was an extraordinary accomplishment. And with those approvals, we've launched in Europe at the end of last year. Now we launched into a very challenging market. Germany was in lockdown, and that's the first country we launched into. Certainly, we brought over the lessons of the launch success in the U.S. and the adjustments we did there. And we're bringing those to Japan, which we expect we'll launch in the next month. But overall, I'm just incredibly proud of what the team has been able to do. And I would just put one highlight on that overall accomplishment. Probably, the most dramatic thing that matters to investors is that we managed to secure a price that is equal in the U.S., Europe and Japan. So the list price across those 3 territories is now the same, and that is an extraordinary outcome.

New list price in Japan. That's relatively recent, correct?

Yes, very . This week and point of fact. And I think what's interesting about that is it really punctuates what we've heard is very positive interest in our drug. It has potential to play a role in that part of the world and really the excellence of the team over there. We have just absolutely top shelf people in that part of the world that have built great relationships and have taken the data that was in Japanese patients and been able to bring it forward to the KOL community and to the regulatory world and secure this outcome.

I know that the past year has seen the portfolio of the company expand. Obviously, you discussed brensocatib and the data you showed, I think it was February of 2020 and then you've got the TPIP that has emerged recently. I do want to stay on ARIKAYCE because it just seems that investors still are very much focused on ARIKAYCE. And so with that, let's talk about picking up on those green shoots that you're seeing. Obviously, we're here in June, but should we really be thinking about any sort of inflection in the ARIKAYCE trajectory really being more skewed towards the back end of the year? And would it be even perhaps fourth quarter versus third quarter. I'm getting a sense from many of the companies who are commercial stage that second quarter is really not a great quarter to be trying to look for an inflection?

Yes. I think what I would say to that is, while we haven't provided guidance, as you know, and I appreciate that that's frustrating for people. One needs to understand the degree of variability across the country in terms of return to normal and what that looks like. And maybe I can just dig into that a little bit. Our Head of North America, who just came back from a sort of a tour across United States, captured the following metric for me, which I thought was very illustrative. He went to 3 different KOLs and in those centers, one was 93% of pre-COVID levels, open for business, ready to go. The second center of excellence was at about 60% of pre-COVID levels, but on a trajectory back to normalcy, which I think will fall in the next month or so. And that's their prediction, they see things coming back. The third was still virtual. And so you see the complete range across the country. And depending on where you are, it's going to have a major impact because one of the major drivers of our ability to return to revenue growth in the kind of levels we saw prior to COVID was the fact that the physician's offices are open. They're seeing patients. Those patients are vaccinated and able to go to the office and feel comfortable doing so. And then finally, there are therapeutic specialists who are able to go back into the field in-person because those elements all collectively are needed for us to return to that pre-COVID kind of trajectory. I do think we're returning to the U.S. with growth on the U.S. on a stand-alone basis. Obviously, this year, we will add to that Europe and Japan. And those may be a little bit muted because I think Europe and Japan are about a quarter or 2 behind the U.S. in terms of their return to normalcy. But the good news is those offices that I just described, some of them are already opened fully, most are on their way back to that position. And this is no longer an ambition. We're seeing it playing out now. We're on the front lines. This is the pulmonology community, the infectious disease community. They are going back into business in a broad range of diseases. They've done that to the best of their ability in COVID, but it's just a different world now. And I think you will see measures of that, but -- and the question is really what is the slope from here? That's really hard to predict, which is why the forecast is just not within our grasp, given the variability I just described.

An interesting, I think, theme that I'm also hearing from my commercial stage companies is, one, where even though company has done a great job in terms of staying in front of physicians, in terms of perhaps more of a digital strategy, a virtual strategy, there's still nothing like being in front of a doc. And so that pull-through, so to speak, in terms of, okay, I might have been able to hit a certain percentage of my physician target demographic, but it doesn't necessarily translate into sales. For ARIKAYCE, what does that dynamic look like? What does that pull-through kind of look like?

Yes. I think, look, this is a promotion-sensitive program. Because I think what we're really doing with that so-called promotion is describing the patient profile that is suitable, and we have now in our back pocket, the new international guidelines, which strongly recommend our drug for use in the treatment of refractory patients. The physicians don't struggle with the decision so much, at least in my opinion, as they do with the proper identification of the patient. And that's where the guidelines, I think, can be helpful. And of course, they don't even have the ability to reflect on that or consider it. It's not front of mind if there isn't someone there to help them on that journey because these are patients who are fairly rare. And so unless you're a center of excellence, this isn't your daily patient. This is a refractory patient who has a severe condition. And the data that just came out at ATS, if you're a COPD patient with NTM, your mortality is 40% greater. So these patients need to be treated. And that awareness, those data, that medical education is going to be extremely helpful, I think, as physicians turn their attention back to their patients and try to figure out who needs to receive treatment and who will benefit from it. And so I think that pull-through will accelerate as we get more in person. I think that's a fair comment. I also think that the awareness of disease right now, the index of suspicion is as high in respiratory disease as it's ever going to be because of COVID, right? And we have also this new sNDA data, which shows that if you use our drug, you can achieve a durable conversion. So what does that all mean? It means that we're back in person. We're talking about international guidelines, strongly recommending our medicine. And we have data now in our label that shows that you can achieve a durable culture conversion if you use it. That's a very powerful message.

Okay. Thanks so much for that. Again, momentum, I believe we're talking about ARIKAYCE overall. In terms of a return to normal in the U.S., you are launching in Europe and you soon will be launching, I believe, maybe by the end of the month in Japan. Maybe for those who don't know the product closely in terms of how to think about the ex-U.S. dynamics, whether it be Europe and/or Japan. I know that you have prioritized Japan perhaps more than you have Europe, and there are certainly reasons behind them, but if you can just briefly mention kind of the ex-U.S. opportunity?

Sure. And I mean, I guess the way I would say it is we prioritize both territories equally. The opportunity is certainly more self-evident in Japan, and let me dig into that a little bit. We have an absolute top shelf team across Europe. They've been there for years. So the medical education has been ongoing. The networks and relationships with the center of excellence have been developed. I think what Europe always represents when a launch of a new drug comes along is a stepwise advance, right? And why is that? Because you get approved at the EMA level, but then what happens is you have to go country-by-country to secure reimbursement. And that's negotiated one country at a time. So Germany allows for immediate launch with a free pricing environment that then gets scrutinized a year later. The Netherlands had an accelerated program for specialized medicines, we're only the second medicine to go through that program. And so that got us approval and reimbursement in the Netherlands early. We have the ATU program up and running in France. And that's a temporary authorization for use, which unusually, the French government has extended during the time that we're in negotiations for the final approved price. So we'll see modest revenue contribution from that specialized program and from the Netherlands and Germany. Germany is in lockdown right now. So it's not exactly the ideal time to be going after a pulmonary launch, but the team has done remarkably good work in accomplishing what they can in that environment. To that, we will add the United Kingdom, Ireland, Italy and ultimately, France. And those countries and those contributions will slowly add up over time, so that we will see Europe really beginning to contribute next year. But you'll see numbers coming from Europe this year, obviously. And by then, I would expect them to be pulling completely out of COVID as well. When we talk about Japan, Japan will launch in July. The work -- the groundwork for that has been laid with the 20 sales reps that we've had in the field since December of last year. I think we're in as good a position there as we could hope to be. But we're talking about a country that, in the last month, probably had a 2% vaccination rate overall. So there's a long way to go to get that country past the COVID headwind. Having said that, I think that our team has done an excellent job. We've done 40% of our calls to date in person, which is remarkable. We just came off the Japanese Respiratory Society meeting, where there was literally, you can imagine, this sounds almost unthinkable, a standing room only meeting of respiratory experts, talking about NTM. They're all in person standing next to one another. So I find that to be quite a strong statement about their interest in the disease and the drug's potential to have impact on their patients. There are perhaps 15,000 to 18,000 refractory MAC patients in Japan, that's the diagnosed level. In the U.S., it's probably 12,000 to 15,000. So more in Japan than the U.S. And right now, the literature would suggest it's only about 1,400 across Europe. So we see a more modest opportunity that's diagnosed there. However, I think that's going to evolve into a larger number as awareness grows and the availability of the medicines there.

Okay. Great. And before we switch to the pipeline with brensocatib and TPIP, which are important, I do want to touch upon your interests in advancing ARIKAYCE. The first-line setting, you've got the ARISE and ENCORE studies as a very important. In terms of the PRO that you're developing, can you help investors, again, put into context the importance of that PRO and how that may help to improve the probability of success in your larger study?

Sure. So this PRO is really the primary endpoint only for the U.S. setting. Europe and Japan both won bacterial culture conversion as the primary endpoint. So we'll be measuring both in these studies. The 2-study design is intended to really optimize the quality of life bronchiectasis PRO questionnaire that we're using and accompanying fatigue instrument. So the simple way to think about this is for full approval in frontline indication and refractory, we have to have the ENCORE study deliver on the primary endpoint of either PRO or culture conversion depending on the territory of the world. So that PRO becomes very important. To make sure that, that PRO is going to work as intended, we're doing a smaller dry run study called the ARISE study which will test the PRO in the exact same patient population. We'll see if the PRO is doing as it's expected to, this is sort of a page from the global blood book in terms of learning from precedents. And we're going to see if that works. And if it does, we're good, we don't have to touch the ENCORE study in any way. If we learn something that perhaps the expectoration domain or the cough domain is more sensitive and more responsive, we can adjust our statistical analysis plan in the ENCORE study and take that into account because that study is still blinded. And the FDA has agreed to that. So we feel like we're in a very good spot with regard to the probability of success. And that's very important because that increases the addressable market, some fivefold from where it is for refractory. So I talked about 12,000 to 15,000 refractory patients in the U.S. It's perhaps 85,000 that are frontline MAC. This would then become effectively the standard of care for the treatment of these patients. So it's a big step-up. It's a huge opportunity for us, and it's obviously one we know well, being the first and only approved therapy for this disease at the moment. And that just gives us a command position. And we'll do the same thing in Europe and Japan.

And just a quick reminder on time lines for ARISE and ENCORE?

Yes. So we haven't given specific guidance yet for the same reasons, we're uncomfortable giving guidance on revenue. We want to see how the global picture unfolds with COVID because these are global clinical trials. I mean, just to punctuate the point, in Japan, for example, that's a population that perhaps is 145,000 frontline MAC patients. So we think there are a lot of patients over there that would benefit from this drug. We want to obviously enroll the trial appropriately. But to do that in the middle of COVID, it makes it very challenging to know how long that will take.

Okay. I appreciate it. Let's quickly switch to brensocatib. We've got really encouraging data that you shared early last year. And now I feel that the asset has potential in many different areas. There's a lot going on in terms of where that product is being investigated. We've got to stop COVID-19 trial. Bronchiectasis is clearly where you have the original data, but there also a relationship that you have with AstraZeneca, and you've got your own thoughts around where else you can take the products. Maybe I'll turn it to you to kind of distill quickly kind of how we should be processing everything that's going on with brensocatib right now?

Yes, sure. And I think the simple takeaway for everyone on this Zoom call is the value creation from the success of the ASPEN study is expected to be quite substantial. Securing the first ever approved therapy in the treatment of bronchiectasis will be a material change, an asymmetric return to the profile that this company has enjoyed at this point. And I sort of liken it to sort of the success that Vertex has enjoyed with their CFTR modulators, they're addressing a population of 70,000 patients. Think about Alexion and how they went after their rare disease and what that created for that company. Celgene with its first cancer program. When we look at brensocatib, we see a program that addresses bronchiectasis, a global disease that numbers in the diagnosed category right now in excess of 1 million, and indeed, may include a significant portion of undiagnosed COPD patients who are, in fact, bronchiectatic. That means they would be on label for the treatment of our drug, and that number is estimated to be in the millions. So we're talking about a very substantial addressable market for which there is nothing approved around the globe. And right now, we have the most advanced compound with a novel mechanism of action that is a once-a-day pill. It was referred to by the ATS as the holy grail of pulmonary medicine. And that's why it got published in the New England Journal. That's why it's gotten prime designation, breakthrough designation, and we're well underway with the ASPEN study. That is the key to unlocking this value. Everything else you mentioned, the ability to go into CF and other diseases. The ability to read through information from the investigator-initiated study by James Chalmers. And ultimately, the interest of AstraZeneca in getting this compound back to potentially explore it in COPD or asthma. Those are all very real, but bronchiectasis is the one for which we have the Phase II data that's definitive. We hit statistical significance on the primary endpoint, and we are well positioned to replicate that in Phase III. So it's all about getting that drug through that program and getting the other side of that.

And where are we in terms of when you start firing up that Phase III?

So that Phase III started in December of last year. It is a global trial. We are targeting over 480 clinical sites around the world in 40 different countries. And obviously, those numbers may change a little bit, but that's the scope of what we're trying to take on. We want to be able to bring this drug around the world to those who will benefit from it. And it represents a step change in terms of what we can bring to bear. Understand the background here, which is somewhat extraordinary. We have ARIKAYCE for NTM. That's a first in disease product. For a company to have that is a rare thing. We also have brensocatib potentially for bronchiectasis. That's a second first-in-disease product, and these 2 diseases overlap. So the infrastructure we have invested in and built and the capabilities we've developed are directly relevant for the frontline setting and the bronchiectasis setting. It's the same call point. And that is incredibly important to understand. And one of the reasons why the investments we're making now will be a benefit to investors in the near future with the revelation of that -- those data.

With brensocatib, I almost feel on some level, there's almost too much going on or that it's almost has a dilutive effect to kind of remember to keep your eye on the prize on what it could represent. So I appreciate kind of that perspective on the opportunity in bronchiectasis alone. So I know that you mentioned that the trial started in December. When I think about how to compare, contrast the Phase III clinical trial design versus the Phase II besides larger patients, where are the sensitive spots that investors should keep in mind?

Yes. So the first thing that investors should understand is my philosophy on Phase III trial design. You saw it on display with ARIKAYCE. What worked in Phase II gets replicated in Phase III. Our Phase III ARIKAYCE readout was a p-value of less than 0.0001. When we look to replicate in the ASPEN study, what we did in WILLOW, which was a statistically significant outcome, we start by saying change as little as possible. Phase III is not the time to answer interesting scientific questions. It is the time to replicate the success of your Phase II study. The key to that and making that work is ensuring that what you study in Phase II is actually what you need to see in Phase III. And this is where most companies have made very candidly, a mistake. Oftentimes, in Phase II, they study a biomarker or some related indication, not the primary endpoint that needs to be proven in Phase III. Why? Because nobody wants to show up with a failed Phase II program. We were perfectly prepared to do that with bronchiectasis because we knew it was a heterogeneous population and this was a novel mechanism of action. So we had a sizable Phase II study that studied that primary endpoint we would look at in Phase III, but also had a lot of other examinations built into the data set. And what we found quite importantly was that almost regardless of the background of the patient, they responded to the drug. And that was the real revelation that caused New England Journal of Medicine to publish for the first time in almost 20 years a finding from a bronchiectasis study. So this puts us on track for Phase III with a lot of confidence that if we just replicate Phase II, we'll win. So how do we improve those chances? We keep the definition of an exacerbation the same. And we have that definition linked to a physician's judgment and a change of treatment. So it's not just enough for a person to say I felt I had an exacerbation, it has to be a clinical judgment made and the change in treatment. So it's a higher threshold. That's the same one we used in Phase II. We look at the event rate that patients experienced. In Phase II, we had an event rate of 1.37 events per patient per year. Phase III, we are estimating it to be 1.2. So it's a more conservative look and how many events we'll see. And therefore, that enhances the ability of us to show an impact by assuming there'll be lower events to demonstrate the effect in. When we look at powering, we were 80% powered in Phase II to show a 40% reduction in exacerbation. In Phase III, we are 90% powered to show a 30% reduction. So again, a more conservative posture. We have 2 doses, a 10 and 25 versus placebo. So about 500 patients, a little more in each arm, 1-1-1. And in our judgment, if we can secure a win in either 10 or 25, that's what matters. We don't need both doses to work. We love for them too. People sometimes say, well, you're Phase II, maybe there was a dose plateau in the Phase II study. I think we made the clear arguments for why that isn't the case. But even if there is, if either 10 or 25 works again, we all win, most importantly, the patients.

Thanks so much for that. Let's switch over to TPIP. And I think -- I think investors have started to begun doing their work around TPIP. With that in mind, I think it's still one where perhaps people like myself can do some additional work, but certainly, you did set the stage for an opportunity that could be large. But again, it is also a competitive landscape. And so can you just remind us how we should think about TPIP and its positioning within PAH, and then I also want to bring up the fact that you are looking at indications outside of PAH as well.

Yes. So I think what is TPIP? TPIP is a once-a-day dry powder formulation of treprostinil. That is designed specifically to change the PK/PD profile of the drug with the consequence that it should change the clinical impact of the drug in the way it's used. Let me give you an example of what I mean by that. When you think about Tyvaso, which is inhaled treprostinil nebulized, that product has a half-life of around 45 minutes in reality. And it probably -- in the German study paper that was published, I think, in 2005 showed a comparison among 3 different doses and a duration of effect of about 90 minutes. So 1.5 hours, you get pulmonary vascular resistance reduction with Tyvaso. What we're hoping to show is with once-a-day dry powder dosing, which is incredibly convenient, obviously, we would be able to cover 24 hours of PVR reduction and extension. So that means that all of the benefit that is promised by prostanoid therapy would be unlocked constantly by one dose in comparison to Tyvaso, which is taken 4 to 7x a day and obviously, not at night, and so you don't get nighttime coverage. The goal of this is obviously to vasodilate or create relief in the vasculature of a PAH patient. Because what causes them to succumb is right heart failure. Right heart hypertrophy, which is caused by them having to press -- the heart to have to work harder to pump blood through the vasculature. Vasodilation relaxes that and all of the benefits that flow from that are well understood. The problem is, no one's been able to find a way to do that over an extended period of time. This drug has the potential to provide that. And in our animal studies, where we compared it to all these other approved drugs, I think we had half a dozen of them, we saw a superior profile. So now we have to replicate that in humans. We'll first do that with a IIa study, which is open and enrolling now. And that study will demonstrate, we hope in PAH patients, the pulmonary vascular resistance profile of a single administration of a dose of our drug. Success in that study would be showing that reduction in PVR over an extended period of time, 8, 10, 15, 24 hours. If we can deliver that, this is, we believe, a game-changing drug. Because it will allow physicians to use it as the cornerstone of therapy in PAH. And all those other competitive drugs, certainly all the forms of prostanoids, I think, would be inferior in that setting. And any of the newer technologies that are coming out could be complementary to it.

So just, I just want to double-click on that point. So you believe that if you're able to show the profile that aspirationally, if they exist with TPIP, it could be a cornerstone for all PAH therapy? In other words, it's not just within the trepostinil segment of the market that you could perhaps become a leading product within that, but perhaps way beyond?

What we've heard from KOLs is that they think this would change the way they would use prostanoid therapy. So the short answer to your question is, yes.

Okay. We know that Tyvaso has been able to expand to additional indications and ILD, in particular, PH-ILD. We -- on the Goldman Sach side, we do have other analysts that cover companies that have presence in the PAH space. And I think just very recently, our team came out with a report on just kind of initial thoughts on the ILD landscape. And with that said, one interesting piece of feedback that we heard was that there is a little bit of pushback related to Tyvaso and ILD just based on price. So how are you thinking about the TPIP opportunity where there's obviously the potential in PAH, but then there's the orphan ILD opportunity. How do you weigh out all those considerations when it comes to pricing?

Yes. So to be clear, we're going to be starting a Phase IIb study in both PAH and separately in PH-ILD by the end of this year or early part of next year. 16-week study is designed to show the impact of our drug in those 2 separate disease settings. I'm actually equally excited about our ability to impact both and to be a potential cornerstone of therapy in both PH-ILD, I think, because there's only one other drug that's now Tyvaso, that is approved to treat that. I think that will enroll faster. I think there are probably, I mean, based on their numbers, 30,000 patients that are eligible for treatment. And if nothing else is there, except Tyvaso, we've shown superiority in animal models to Tyvaso. And certainly, we've heard from physicians based on our target product profile that if we produce that sustained vasodilation from our formulation, that would be their go-to choice. So I think it is very promising for both. We're also looking at idiopathic pulmonary fibrosis. I think that one is a higher hurdle to clear. IPF is a very difficult disease to treat. But one of the reasons I'm excited about the PAH ILD study is because if we can show benefit there in the same way that we think we can in PAH, we're talking about potential for disease modification. So that's why this drug is exciting. It's not just that it's once-a-day or it's a dry powder or it's a different formulation of treprostinil. It's that the PK/PD profile will cause a clinical output that could result in histologic change, disease modification for those suffering from these conditions. And that, to me, is where the real value in this drug lies and why the animal data, which, by the way, is still on our website, is so exciting because it shows that histologic change compared to the other drugs that are already approved.

Thank you very much for that. We've got probably about 3 minutes left with our fireside chat, I feel like we've covered quite a lot. Would love to perhaps look at how you're financing the company. Clearly, you're commercializing ARIKAYCE. You've got lots of clinical trials ongoing across your entire portfolio. There certainly is a large capital commitment that's needed. Maybe you recently raised funds. First of all, could you just remind us where the company stands with respect to cash? And what the current runway looks like and whether that's pro forma, your recent financing or not? Any color would be great there.

Yes. So with the byproduct of our recent financing, we have about $1 billion on the balance sheet in terms of cash we can deploy behind programs. The purpose of this financing was to fully fund the 4 pillars that I described at the outset and to bring them to fruition. So that we can see the value creation that is going to be associated with potentially having 3 or more distinct programs, each of which has either a first-in-disease profile or a profile that would allow it to become the new cornerstone of therapy in an existing disease. Each and in their own way, as we've talked about today, has been derisked to a degree. And so the capital is behind these programs, I think, in an appropriate way to unlock value, I think that's going to be quite dramatic. We obviously need to have the trials be successful, but we got a lot of confidence in our programs.

And with that in mind, could you remind us in terms of how you think about, from a corporate perspective, capital allocation, whether it's -- where do you put the incremental dollar? Given that you are a commercial stage company, these are tough decisions, every dollar accounts. So your thoughts there?

Yes, absolutely. And I think one of the great things transformations that took place. We talked about a lot of transformation at Insmed. One of them was the arrival of Sara Bonstein as our Chief Financial Officer. And you can see her fingerprints all over the flat year-over-year selling, general and administrative line. We were basically flat 1 year to the next when we announced our end of year numbers. And I think that's a sign of cost control and careful deployment of capital to come. And I think you can expect more of that. It will be very purposeful for value creation. But each of these pillars warrants additional investments that's why we access the capital. We'll do it in a prudent way. But I believe investors have the right to expect us to deploy that capital for the purpose of turning over these important cards, which I think are going to represent some really exciting data sets.

And BD strategy. Given where the company is right now, is there an appetite? Is there a bandwidth to think about bringing things externally from the outside in terms of assets? Or is that BD strategy really one more about partnership, which is another important element?

Partnership is not something that I think is a good way for us to develop drugs that we have validated and have brought to clinical proof. I think we have the commercialization chops, I think we've proven that. I think we need to add to that infrastructure additional compounds. That's what this strategy is all about. You will see more coming out of our translational medicine research efforts. That will be not necessarily in the pulmonary area, but will certainly be in rare disease, in diseases where our approach can have a big impact. And I'm excited about the -- what those present as well. I don't think partnership is the right way to go. I think it dilutes shareholders' return potential. I think the company develops products, it learns them, it brings them forward. And if it has the capability to commercialize and we do, then it should do so. And that's why we built the infrastructure in the U.S., Europe and Japan. I'm incredibly confident in our commercial leadership and our ability to replicate this with the other programs that are coming, and you can expect to see more about that in the not-too-distant future.

Great. Maybe if I could ask just to summarize for our audience over the next 6, 12 months, what they should look out to in terms of potential value-creating events? And I'll ask one last big picture question.

Sure. Return to growth on the revenue profile with ARIKAYCE, the addition of the launches of Europe and Japan. That's going to be happening and I think that will be exciting. Clinical data, Phase IIa from TPIP. If we see PVR reduction, pulmonary vascular resistance reduction and it is extended over a long time, significantly longer than what you see with Tyvaso, that's a win, and that's a big derisking event for that portfolio. And then, of course, updates on where we are with enrollment in these studies that are so important.

Okay. Great. And then my last question for you as I've asked other companies that I've hosted fireside chats with is in 5 years from now, where would you think or where would you hope for? Where do you see ARIKAYCE? And if we were doing this fireside chat live in Southern California in 2026, what would ARIKAYCE look like? I mean, what would Insmed look like?

Well, Insmed will have 3 different commercial programs. This is -- I have to put all the caveats about forward-looking statements in here. But you're asking me where we would be, where I'd like to see us in 5 years. ARIKAYCE's frontline approval, ARIKAYCE's refractory approval and used effectively as the standard of care around the world for the treatment of NTM. Brensocatib is approved and is commercially working in bronchiectasis patients and potentially cystic fibrosis patients and potentially additional indications beyond that. TPIP is in PAH and PH-ILD, and we'll have the question answered about whether it belongs an IPF or not. So I'll leave that at that. But I think all 3 of these represent our step 2, what is our ultimate vision, which is a sustainable global biotech company that can really make a difference in the lives of patients.

That's fantastic. Well, very promising picture for Insmed in the 2026 time frame. And with that, I want to thank you for your participation in this fireside chat, and I want to thank the audience for joining us. Have a great rest of the conference, and have a great rest of your day.

Thanks very much.