Insmed Incorporated (INSM) Earnings Call Transcript & Summary

Perfect. Thanks, everyone, for joining us. Andrea Tan, biotech analyst at Goldman Sachs. She we're pleased to have Will Lewis, CEO of Insmed with us. Thanks again, Will, for joining us.

Glad to be here.

Maybe if we can start big picture. Insmed, 4 pillars, very, very active. Maybe walk us through a high-level overview of each of those pillars, the progress you're making there and then the expectations for these key data reads that are coming from each one.

Sure. I think the next 12 months is probably the most exciting time in the history of the company, and I've been at the company now coming up on 11 years. We've really spent the last several years constructing each of these in such a way that they will read out their material data in this next time frame. So that's a pretty exciting time for the company at this moment. The first pillar is ARIKAYCE. That's our approved product, conditionally approved in the U.S., fully approved in Europe and Japan for the treatment of refractory NTM. That has been on the market now for about 5 years. Our global forecast for the year is $285 million to $300 million. We feel good about where we are with that. What's exciting about that product is that it is about to read out the so-called ARISE study, and that will be in the third quarter of this year. And that will be the first insight both into our patient reported outcome and our culture conversion primary endpoints for the possibility of this drug to be used in all MAC NTM. So that will be a dramatic increase in addressable market of about 3- to 5-fold from where we are today. So we're excited about that data readout. And that ARISE study is really a canarian coal mine. It's a practice study, if you will, for the full approval study called the ENCORE study, which were enrolled in parallel. But the ARISE study will inform whether or not the PRO is operating as we expected, what our culture conversion rates look like, et cetera, so we can adjust ENCORE to ensure success in the best possible way. The second product is our DPP1 inhibitor called brensocatib. That one is a real monster because it has the potential to address several very significant indications where there is currently nothing approved to treat these indications. The first of these is bronchiectasis. This is a first in mechanism treatment, and that means that unlocking this mechanism of action, potentially affords the opportunity to go after other diseases that are impacted in the same way. This is so-called neutrophil-mediated diseases. Bronchiectasis is such a disease. There is 1 million diagnosed patients in the markets where we operate right now. And this Phase III study is 90% powered to show a 30% treatment benefit. Our Phase II study, which was published in the New England Journal of Medicine was 80% powered to show a 40% benefit, and it was statistically significant. So we feel really good about that study. We're super excited for it to read out, and that will happen in Q2 of next year. Beyond that, we're going to be kicking off a study in CRS without nasal polyps. Again, a neutrophil-mediated disease for which there is no approved therapy. In the U.S. alone, there are 26 million people that suffer from this condition. We will be going after the most severe end of that spectrum. But like bronchiectasis, it's a very sizable addressable population with nothing approved to treat it. And this once-a-day small molecule pill has the potential to be just such a treatment. So very exciting stuff. And that, as I said at our most recent public event, those 2 alone, I think, if they are successful as we expect, we anticipate peak sales between the 2 of these alone at in excess of $5 billion. So we can let that one hang in the air for a second because it's a big bold statement, but I think it tells you how enormous the market opportunity is for these and how excited we are to bring that data forward. As we move to our third pillar, it's TPIP, that is a treatment for pulmonary hypertension, both Group I and Group III patients. Those Phase II studies are running now. I view this as the hidden gem within Insmed. This is a drug that is underappreciated in terms of both its potential efficacy and safety and its impact on this disease state. It was recently mentioned by someone that this drug could be a category killer, by which they meant dominate in the PAH space. We like to always think about some of the other drugs that are out there like sotatercept, which was a compound that on the heels of Phase II data was purchased for $13 billion. So the potential for intrinsic value creation by Phase II data readout here, we think, is pretty underappreciated by the market. And finally, our fourth pillar, which I won't go into in great detail other than to say it represents a collection of different cutting-edge technologies that have been assembled over the last 2 years. Very exciting stuff, very impactful. Our first indication is a gene therapy treatment for Duchenne muscular dystrophy. We should have patient data from that first study, biopsy data in at least 1 patient before the readout of the ASPEN study. So the simple way to think about Insmed is it has a lot going on, but all of it will read out in the next 12 months, culminating with the readout of the ASPEN study in Q2 of next year.

Perfect. Well, that was a great overview. Maybe I can ask you very quickly before we jump into these upcoming data reads, for your commercial ARIKAYCE business in refractory NTM, that guide of 285 to 300, maybe help us understand those underlying assumptions there? And what are the pushes and pulls that can move that number as you move through the year?

Yes. I think we're looking at a wonderful year because we're back toward normalcy. as a general rule. The U.S. market is performing as expected. Europe has never been a significant part of our forecast or our expectation, and it really is struggling, not with our product, but just generally because it not just of geopolitics, but because of the general pressures on drug pricing and reimbursement in that environment. Europe is a tough market right now for anybody. Japan is a very exciting market for us and one where we've had really good success. It represents more than 20% of our revenue coming out of its first year of launch. The challenge there is COVID is still very much upon them. They lifted their COVID restrictions in May, so a couple of weeks ago, give you some idea of how bad it has been over there. But consequently, we think the second half of this year will see the same thing that we saw in the U.S., which is a return to that growth, and that should continue to help support ARIKAYCE.

Great. Maybe moving to arise, which is the first data read that's coming in the third quarter here for ARIKAYCE. Maybe help frame some expectations as we look towards the first patient-report outcomes tool to be developed in NTM.

Yes. So the exciting thing about the ARISE study, as I mentioned earlier, is that it's really a test for us to see how our PROs are working. And I suddenly mentioned PROs because we really have two. We have the promise fatigue score, which is for fatigue, and that is on PRO. And then we have the bronchiectasis quality of life respiratory domain score. And those 2 are separate. If either one of them works, we have a PRO that will be sufficient to secure, we believe frontline approval in the U.S. It's important to understand that these PROs are only for the U.S. They're not needed for approval in Japan or anywhere else. And indeed, in the U.S., market access, physicians and patients are all focused on culture conversion, not the PRO. I think the PRO as a bit of a curiosity for folks. And I think it will give us very valuable information, but it's really intended and designed to address the request of the FDA for that broader opportunity. So those 2 PROs will read out, and we'll see whether or not the use of our drug with background therapy is better for patient-reported outcomes and for culture conversion than the baseline comparison.

Let's dig into the PROs there. So 16 total questions across the 2 PROs. Maybe help us understand your level of confidence that these questions will be able to detect a meaningful benefit from ARIKAYCE. .

So these PROs are not purpose-built for NTM. They've been purpose adjusted for NTM. And what I mean by that is they're used successfully and validated in bronchiectasis and other disease states, but because they've never been validated in NTM, that's a part of what ARISE is going to accomplish. It's going to validate that these PROs are sensitive to changes in patient symptoms and that those symptom changes are associated with patients feeling better. So an example would be cough. You might cough less. But importantly, it's not only that you cough less, it's that you feel better as a result of that. So we have to establish that in this trial. Once we've done that, then we can use it as an appropriate tool for the evaluation of patients. We mentioned all 16 questions, but really, it's 2 separate PROs, and we'll be thinking of it that way. While we will certainly examine all of them, if either one works, as I mentioned before, we should be successful. When we develop these, we are doing it on the basis of 5 years of launch experience in the commercial setting. So we know how patients respond to our drug. We know the benefits that they reap from using it once they're on the drug for a period of time. So we feel like we've got really good insight into how these patients are going to respond and what these PROs are going to capture, and that's why our confidence is high.

And you've spoken in the past about some blinded data that may be suggestive of a treatment effect happening or being patients responding to drug in a way that you're hoping for. Maybe just explain that to us, and is there an analog on the fatigue score that you could also point to?

Yes. What I can tell you is that when you look at blinded blended data, obviously, caution is the watchword, but we are seeing significant changes in the PRO scores such that there are 2 groupings, if you will. There's a group of patients who have had very good response and improvements in their PROs. And then there's a group that has responded less well. And those 2 plot clusters of blended blinded patients, it's a necessary but not sufficient insight into how the study is performing. It means that there are patients who are showing responsivity, which is what we want. Now we just need to see if they're in the right treatment arm. And if they are, then we win. And if we do, then that's a big deal. It's important to understand that ARISE is really an exploratory study. It's not powered for statistical significance, but it will be clear directionally. And I think that's all we need in order to feel confident that ENCORE will work.

And then any analogs for the fatigue?

We don't really have analogs for the fatigue score, its use -- the PRO or its use, but we do know from our experience with patients in the marketplace and from our relationships with KOLs how patients respond and improve over time, and that's what really informed a lot of our work. I am aware that there have been some sort of one-off studies using different PROs, but those aren't well controlled. Nonetheless, we want to weave that understanding into our design.

Got it. And if you do need to make any changes to the PRO for Encore, how does that process work with the FDA? And how will that be communicated to the Street?

So the first and simple answer is we're going to communicate to the Street, whether or not the PRO won? And if it did in what way? So this will not be an opaque announcement in Q3. It will be very clear that the PRO performed or it didn't. And what we learned from the world where it doesn't perform as expected, is where we would have that exploration of what might we do to enhance the probability of success. And the way we would do that is to select questions for either greater weighting and consideration or we might remove a question that didn't seem to be responsive to the patient need or outcome. And in that case, we want to be sure to talk to FDA about that. So I would anticipate a clear press release and conference call to discuss results in Q3 at some point on the basis of ARISE and then a dialogue with FDA that would clarify what we would agree to with them, if any changes were to be made, and we would communicate after that. I wouldn't expect that before the end of the year.

Perfect. And then if you think to culture conversion, which you're also studying in the ARISE trial, how important is it to show correlation between the PRO outcomes and culture conversion as you think about the stakeholders?

So the only stakeholder where the PRO is important, as we mentioned before, is the FDA. And FDA has been explicit that it is not necessary to show a correlation between the PRO and culture conversion. Culture conversion is a point of interest for all the stakeholders for sure. And there, I think we know from our experience that we should be in a good shape to hopefully show better results.

Do you have a sense with these baseline antibiotics, what level of conversion there, maybe they're able to achieve? And then where will ARIKAYCE come in on top of that?

So the data on that is mixed because people haven't -- other than the work that Insmed has done, no one's really ever done a controlled experiment looking in NTM with the standard of care. It was the sort of best advised standard of care. It wasn't developed by clinical trial work. So in our case, what we've done is talk to centers that have done individual studies or best available data sets. It usually seems to come in around 50%, although there can be quite a bit of variability around that in terms of conversion rates for frontline or all -- in all new coming MAC patients. But we'll see. The study will be the first time that, that really gets elucidated and then we'll see how we perform relative to that. I think it's important to remember it's not just overall conversion, but also things like time to conversion, durability of conversion. Those are all important considerations as we examine the data.

Perfect. Let's jump to brenso. Obviously, a key focus for investors as they head into the second quarter of next year. we've talked about your -- you've referenced the positive Phase II WILLOW study, but what gives you the confidence that you'll be able to see that similar result in the upcoming ASPEN trial?

So we recently announced the baseline characteristics for the ASPEN study, and it was important to note that they almost perfectly mirrored what was in WILLOW. So that tells you we're looking at the same kind of patients in both studies. When we think about WILLOW, that was roughly 250 patients, as I mentioned before, 80% powered to show a 40% reduction, and we were stat sig. In this study, we are enrolling -- we have enrolled over 1,700 patients. This is a massive study, more than 75% larger than any other Phase III study that has ever been done in this space. We intend to win. The study is designed to win based on the success of Phase II. And the way you do that, in my experience, is you change as little as possible going from Phase II to Phase III. So we have kept the definition of an exacerbation the same. We have assumed a conservative level of underlying exacerbations in the patient population. For example, we saw 1.37 events per patient per year in Phase II that's consistent with what other studies have shown, but we're assuming 1.2 in this study. That provides actually extra power statistically for outcomes. So there's a lot of aspects about this study that are almost identical to Phase II, but just scaled up. And since we know we have the same kind of patients, there's every reason to believe that this study will be very successful.

Given the baseline number of exacerbations is such an important factor. Remind us how you're defining exacerbations as patients come on to the study.

Yes. In contrast to some other studies, we wanted to sort of go that extra mile. And so we have both -- the patient has to identify the experience of having an exacerbation, but then the physician has to not only diagnose it as such, and they have to introduce a change in their treatment regimen, either put them on antibiotics, put them in the hospital. So it's a higher threshold. You need a medical professionals judgment and action to validate that, that exacerbation has taken place. That makes it harder to identify an exacerbation, but it also means that if one occurs, you can rely on it, and that should help us in our Phase III study just as it did in Phase II.

Maybe in that context then, how meaningful is the 1.12 to 1.15 blended rate of exacerbations that you've disclosed to date?

So similar to what we saw in WILLOW and that's why we disclosed it. I think every touch point we can give the investment community because of the importance of this trial is helpful. And so this is exactly the range -- kind of range we saw in WILLOW that resulted in success. So we're seeing a blended rate here that is similar and that should be comforting. Obviously, it isn't controlling, but it's comforting. And I think every time we can come across that kind of validation we want to share it. This is over 1 million patients with nothing approved to treat them. And this is a chronic medication that is a once-a-day pill. It was referred to by the American Thoracic Society as the holy grail of pulmonary medicine. And within a year of now, we will have the Phase III trial that should empower the filing and approval of this medicine, which should result in an absolute blockbuster first indication. For us as a company, what makes this really exciting, we already have the commercial infrastructure for this. The call point for ARIKAYCE is the same as the call point for brensocatib. All we're going to do is scale it up.

And you touched a little bit on the powering assumptions, 90% powered to show the 30% reduction. But remind us maybe at what level could you be stocked say here? And there's been some talk around if you kind of hit between 0.01 and 0.05, did it still be -- this becomes a review issue. But maybe talk us through that.

Yes. So into the low 20s, we will still be statistically significant. We could still be statistically significant in terms of the percent reduction. And that's appropriate because the FDA and most thought leaders would tell you around 50% or 20% at the upper end is the minimum kind of threshold they would want to see for clinical relevance. So to be able to reach that with stat sig is what's important and why we chose that architecture. When we talk about what does it mean to be stat sig, it's a single Phase III trial. So we have to be less than 0.01 on the p-value. But our Phase II study, which studied a primary endpoint that is consistent with Phase III was already stat sig. So if we are between 0.01 and 0.05, which is the traditional threshold for statistical significance in a Phase III trial, that would become a review issue because we would include WILLOW and ASPEN as studies that represent 2 well-controlled studies and could easily give us a path to approval. So that was a very encouraging piece of information from FDA that they would want to -- that would be a review issue. They want to look at that. It isn't an outright no. And that opens the door to a path to approval even in a world where we don't hit stat sig on the Phase III study.

And how is alpha being allocated here given you are setting 2 different doses? Do you only need 1 dose to have a successful outcome? Do you need both?

If we have success with either dose, we obviously have a win. And so the methodology we're using to get into the weeds is truncated Hochberg. And that means that you can go if one study dose works and the other study dose does not hit stat sig, you still can preserve to go to the primary endpoint of the dose that worked. So that gives you the opportunity to really validate behind the dose selection that seems to be successful. In my mind, I think both will be successful. So this will be irrelevant. But in the rare circumstance where only one works, and we want to validate the secondary endpoint behind the primary, we'll be able to do that using this approach.

Perfect. And you've talked a little bit about expanding beyond bronchiectasis. You've come out, you've disclosed some indications, but how are you thinking about that in the context of IRA? Is it possible that you explore other DPP1 candidates? Help us understand that. .

Yes. So right now, what we're doing is sort of both. We're going to be going after bronchiectasis, as I mentioned, and also CRS without nasal polyps. Both of these are indications where there is nothing approved to treat. They're neutrophil driven. There's every reason to believe the drug will be successful in both indications. So the Phase II study for CRS without nasal polyps starts at the end of this year. And we look forward to updating you more on the outcome of that. We could go after additional indications. We think the best thing to do is to wait to see the readout of ASPEN first and then the sort of way where we are with respect to our forecast as it relates to IRA and so on and so forth. It's important to realize that we will not be considered by IRA for a very long time, well into the 2030s. And by the end of this decade, we would expect to be a multibillion-dollar product. However, the mechanism and the animal models we've been running suggest that this may well have efficacy in other diseases like rheumatoid arthritis, lupus nephritis, some other very compelling indications. The way we think we want to approach that is by bringing forward a separate DPP1, slightly altered from the one we have. So we've been doing a lot of chemistry work and we've got a good cadre of DPP1 candidates, one or more of which we may select and bring forward or choose to out-license or sell. So there's a lot of different ways to create value for shareholders, having validated the DPP1 mechanism using both the existing one that's coming through Phase III by adding indications or by bringing others forward, partnering with others or selling.

Can you remind us what the competitive landscape looks like for DPP1 inhibitors?

So it's fascinating. Everyone knows DUPIXENT, and that's a big monster drug. That is focused on eosinophilic-driven disease as is Fasenra, which is AstraZeneca's drug for eosinophilic asthma. There isn't anybody else in neutrophil-driven diseases other than BI. Beringer Ingelheim kicked off their DPP1 program after our Phase II was so successful. They brought it back to life. And so they have been trying to enroll a Phase II study in bronchiectasis with their DPP1 inhibitor. The design of that study is identical to our WILLOW study. We've seen Fasenra and DUPIXENT both drop out of bronchiectasis and drop out their clinical study in CRS without nasal polyps. So we have these 2 ourselves other than BI, which is a really daunting prospect because they are so massive.

And then remind us on the partnership with Astra here, and the potential to go after COPD patients?

Yes. So AstraZeneca, we in-licensed this molecule from AstraZeneca in 2016. And part of that agreement gave them the right subject to our approval to go back after asthma or COPD. While we've had discussions with them and they've activated some of those options to consider that, we don't see a path where that's going to make sense, because, frankly, there were patients who were comorbid with asthma and COPD in the bronchiectasis study that responded to the drug. So there's no real need or purpose for getting a separate indication in asthma or COPD since any patient that has the comorbidity would be on label for the use of our drug under our direction. It sounds a little audacious and I have a great deal of respect for AstraZeneca, but it's -- they don't bring a lot to this equation for us in this moment. What I do think is interesting is that many of the patients who have COPD have never had a CT scan. There's no reason to give them a CT scan if you diagnose them with COPD. However, in many cases, it may be that they're actually bronchiectatic. And so the literature right now is quite varied, but it suggests that between 4% and 54% of COPD patients are actually bronchiectatic. There are 20 million patients in the U.S. with COPD. So if you take the low end of that, it means that this market is actually significantly larger than the 1 million patients we've already identified. And that's where this product gets really, really interesting.

Maybe moving to TPIP, which really gets ignored in the context of ARIKAYCE and brenso. But remind us what you've seen either preclinically Phase I, what makes you so excited and what makes the physician community so excited about this asset?

It's funny, we just came from the American Thoracic Society. And at that one society meeting, there were KOLs addressing pulmonary arterial hypertension, bronchiectasis, CRS without nasal polyps and NTM. So it was a very efficient way to talk to the physicians that matter. The physicians that matter around PAH who are aware of TPIP are unbelievably excited about its potential. And I hesitate to put words in their mouth, but I will tell you that they are believers that this could be a category killer, meaning it will be the dominant medicine in pulmonary arterial hypertension as a prostanoid, better than anything else that is out there. Now we have to prove that out with data, and we're excited to produce our Phase II data to put support behind that level of excitement, but it is there. The KOLs see the mechanism. They see what this drug can do. And their enthusiasm comes from the fact that in preclinical animal models, we saw disease-altering outcomes. And as we went into Phase I, we were able to titrate to very high levels using this drug. This is the hidden gem inside Insmed. There is a lot of value in this drug, and people are not paying attention to it. And we have a lot going on. So that, in a sense, is understandable. But as we put forward our first data beginning with titration data at the end of this year, it's going to really unlock the door to understand why there is real value here. The TPIP profile, this is a 16 carbon chain appended to treprostinil with an ester bond in dry powder format. You breathe it in, the ester bond gets cleaved by esterases in the lung and you get a slow release profile of treprostinil. Why does that matter? Because it means your peak is lower and your trough is longer. Your AUC delivered to the patient is above the therapeutic dose over a 24-hour time frame. Up to 640 micrograms we've gone to. The label indication for DPI Tyvaso is 64. So we are getting to much, much higher levels of this drug into patients and distributing it to them slowly over a 24-hour time frame. For the first time, it's once a day. For the first time they're getting nighttime coverage. And what we are anxious to look at are things like the pulmonary vascular resistance impact, 6-minute walk, those kinds of things, and we'll have some of that data at the beginning of next year. But for now, what I would draw your attention to is the level that we can titrate to because it follows that if we can get higher dose levels, then we know that the efficacy will be greater based on historic studies. And that's what's got everybody so excited. The ability to go that much higher. So we expect to share with everyone by the end of this year what level we're able to get patients to titrate to. And if that is high, then you can begin to bet on this study, in my opinion.

How much can you take from the one patient that was treated in the Phase II PAH study that you had last year?

Not a lot because it's 1 patient and because the difficulty of doing a right heart cath for 24 hours, it turns out that's quite an intervention for a very sick patient. And so we have sort of stepped away from going into that and extrapolating that out. What I'd tell you is that we were very happy with what we saw. We feel very good about what is going on with these studies. We can't wait for the data to come out. But I think what distinguishes this is we're not talking about an unknown mechanism of action. And when we think about sotatercept getting a 35% reduction in pulmonary vascular resistance in their Phase II data, that's what we have our eye on. We want that as our benchmark. We want to understand how we stand up against other drugs that had impact on these measures and what that means for potential value, because we think if this animal experience and the human Phase I study work out, we should be able to have a pretty significant impact on these patients. I mean the ranges are anywhere from 12% to 35%. So anywhere in there, we're comparable. The question is, can we do better?

Perfect. Maybe on the last and the fourth vertical here in the final 5 minutes that we have, obviously, you had a whole day dedicated to this. We can be brief. But for your first lead program, targeting DMD, maybe walk us through the thought process behind going after this indication. And how 1201 will differentiate itself from potentially other assets that are on the market?

So the first and most important thing to understand is that the team we have assembled is the best in the world as far as I'm concerned. They are the group that built Zolgensma, the most successful clinical and commercial product in gene therapy history. And it's the exact same clinical and regulatory team. It's not the business development side. It's the people that did the real work. And they have been working at Insmed for 2 years. So very quietly in the background, we have developed this capability. We've already brought our manufacturing up to 1,000 liter scale. We have already brought ourselves to a place where the assays can quantify the degree to which we're delivering certain vector genomes per nucleus. What using Digital Droplet PCR, we are quantifying what our empty capsid rate is, and it's radically lower than everyone else that's out there. So our data is really good before we begin the clinical trial work. In addition, we're using a novel method of delivery, which is intrathecal delivery. We have unbelievably compelling transduction data showing that we're not only getting to muscles of all kinds, but also to the heart, to the diaphragm, areas that are critically underserved in existing DMD gene therapy approaches. And you can see that in the data from our Research Day, which is still on our website. It's a very exciting program. It is but the first step. We have assembled a number of other technologies that we think will allow us to go to mid- and full-length dystrophin delivery. So this is going to take DMD from an incremental gene therapy improvement program to something that could radically alter the outcome. And I'll tell you what I shared with Brian Kaspar when he first joined the company. I said, Brian, we got to get these kids so that they never have to go into a wheelchair. And that's what we're after. And with RNA and joining technology that we've assembled, we should -- we feel we've got a shot at that. So we're not going to match what's out there. We're going to beat it. We want to be the best DMD gene therapy there is. This is our first generation. The first data will be out in the first quarter -- first second quarter of next year, human biopsy data from the use of this intrathecal approach to gene therapy in DMD, and we have several other INDs behind that.

Maybe in the context of Sarepta's asset potentially being approved later this year, how do you think about 1201 fitting in? And what is the commercial opportunity that's really at play here for that asset?

Yes. So to be conservative, the easiest way to model this is to assume we're only going after incidence population. We still see that as a $1 billion market opportunity. And we think that our profile will be comparable for purposes of conservative modeling, our planning is that it will be superior. Our first generation will be better than Sarepta's in our estimation based on the data that we've seen and what we're trying to develop. Hold me to that when we first see the data, but that's what we're targeting. And the reason for that is the intrathecal delivery, coupled with a lot of the other technical stuff I talked about in terms of CMC. I think Sarepta is doing great work. The enemy here is the disease. Let's be crystal clear about that, but we want to give these patients the best chance at improving their lives. And we think our approach will be able to do materially better and that, that will be the beginning of what will hopefully be an ultimate journey toward radically altering this disease the same way Brian and his team did for spinal muscular atrophy.

Maybe let's put some numbers to that, if you can. When the data come next year, what is the profile or the target profile you would be looking for to convince you, yes, we're better than Sarepta and this is worth moving forward.

Yes. And I want to be really clear, we have a number in mind on the NSA score for improvement. We know what Sarepta is. We know what ours is. I can tell you that ours is not incrementally more, it's materially higher. And that is the threshold that we'll be using to judge whether or not this program should go forward and investor capital should continue to support it, or we redeploy that capital elsewhere into, for example, a second-generation program that is doing mid or full-length dystrophin as a part of the plan. Hold us to that. If we are not developing a program that is materially better then it needs to be -- that capital needs to be redeployed elsewhere.

And then just in terms of timing, has that IND been submitted?

So we haven't updated on the actual timing of the IND. As you know, we wanted to get the benefit of what Sarepta's ADCOM, and there was a lot to learn from that. I would tell you that we're very focused on producing our first human data in advance of ASPEN next year, and that's the benchmark I would invite you to look for.

And maybe in the final minute, a lot other -- a lot of other things in the sports vertical, but any that you would like to highlight?

Well, there's a lot going on there, and I think it's very exciting. You'll see upwards of 6 IND filings between now and the end 2025. This is the answer to the question of what's next inside the company. Insmed has everything it needs to be one of the next great biotech companies. And we are building deliberately for that outcome. So if it seems like there's a lot going on at different stages within the company, that's very deliberate. But if our first 3 pillars work the way we think they're going to, we'll have all the cash flow we need to support this. This is not going to be a perpetual research company needing financing forever. This is going to be a journey to cash flow positivity that will support new impactful medicines for patients with serious rare diseases.

Perfect. Well, with that, thank you so much, Bill, for joining us. Thank you, everyone.

You bet. Thank you.