All right. Thanks, everyone, for joining us. I'm Thiago Fauci, biotech analyst here at Wells Fargo. We're joined today by Insmed for a fireside chat. We have Sara here. Thanks so much for joining us. Yeah, thanks for having us. Really appreciate it. I'd like to just open up with some broad intro remarks. We have a lot of detailed questions that we usually get from investors that we want to walk through. Overall, it's a very different setup for the company. A lot of moving parts. Perhaps, what is the current state of affairs? Then we'll dive in. Yeah, sure. I'd be happy to provide a brief overview. Again, thanks for having Insmed here at this conference. One takeaway that I'd ask everyone to kind of walk away from today's discussion is, while we have been able to show tremendous growth from a value perspective, as well as hope for patients over the last 12 months, 18 months or so, the potential that we have from here, we think, could be just as great, if not greater, than what we've been able to show. Let's kind of walk through why I have conviction in saying that. We have three programs that are in clinical/commercial stage. Actually, we have four, but we'll focus on three right now. ARIKAYCE. ARIKAYCE is kind of our diesel engine that has been our commercial product for now 7+ years. In each of these programs, you'll see this unique opportunity where we have the current indication or area of focus, but we also have the ability to grow that. ARIKAYCE, while it's continued to be successful year- over- year, double-digit growth, we have the potential to have that label expansion. That data will read out first half of next year. We can kind of dive into that and have the ability to be a billion-dollar-plus program. As you think about brensocatib, now you can call BRINSUPRI on a commerical basis, obviously showed tremendous success in both the WILLOW and ASPEN programs, both of those being published in The New England Journal of Medicine, and now most recently having FDA approval for brensocatib, now under the commercial name of BRINSUPRI. This is a first-in-class, first-in-disease drug. Non-CFB or bronchiectasis patients now have the opportunity to go into their physician's office, get this diagnosis, and actually have something available to treat them. That's absolutely tremendous. We've said $5 billion peak sales opportunity for in CFB. What I think is just as exciting is the opportunity that we have in some of the other indications, like chronic rhinosinusitis without nasal polyps and HS. Those data readouts will be forthcoming and we believe can be very significant value inflection points from a company perspective and obviously potential huge impacts on patients assuming success. Our third program, Treprostinil Palmitil Inhalation Powder, again, a program we developed in our own research lab similar to ARIKAYCE. We put out positive PAH-ILD data last year. Most recently, back in June, we put out positive phase II data in PAH. That gives us a ton of conviction in that program. That's what we call our sort of three for three: the successful ARISE data in ARIKAYCE, the successful ASPEN data in brensocatib, and the successful data in ILD and PAH. We have the ability to be three for three, unlike many in this industry. We are humbled by that, that we've been able to produce that, but then also have the ability to multiplex across various indications and continue that value creation to hopefully be able to come out to you guys all in the coming quarters with additional inflection points. Happy to dig into any of that. Thank you. We do have a lot of cash. Also, I wouldn't be a CFO unless I mentioned it. Thank you to all of you that have supported us through this journey to allow us to have about $1.9 billion in cash as of last reported to help fund our business. Perfect. I know there's a lot of focus on the BRINSUPRI launch, but perhaps since we had news that are relevant to you guys this week, let's start with TPIP. Sure. Earlier this week, you had United reporting positive T10 data in IPF. That could unlock another large commercial opportunity. Can you just recap how you guys are framing peak opportunity for TPIP previously and what has changed since, I guess? You had a couple of data sets. You had your competitor with a positive data set in a large indication. What's the current state of affairs? Yeah, yeah. TPIP, we're obviously really excited about this program. We believe, and what you hear from the medical community, that this could be the [prosperity] of choice, obviously assuming success in our phase III programs that will be up and running very shortly. Let's take each in turn. What we've said previously is we believe TPIP, this was before obviously the data that we put out most recently with PAH in June and before the United readout. What we said in PAH and PAH-ILD, we believe that could be a $2 billion peak sales opportunity. As you reflect on the strength of the PAH data, 35% PVR, 35 m, six-minute walk, those were sort of unprecedented type results. We obviously know we owe you sort of a refresh on those numbers. That did not include the potential for IPF. With now having the first of the Teton data, what we have committed to is we would look to move quickly into a phase III program. Again, that $2 billion peak sales number does not include IPF and does include, I would say, a little bit of a different TPP for PAH. More conservative product profile. Yeah, yeah. Some free options in that number for sure. Got it. Thinking about next steps and gating steps, everyone's super excited. How quickly can you actually get into clinic? I know it's not that easy as an operator. For the three indications, again, IPF, you just flipped the data card. I'm assuming you guys are already on the drawing board. What about for PAH-ILD and PAH? Any upcoming regulatory interactions that need to happen? Is it more about just finalizing trial design? Yeah. Regulatory, like what's the lineup here? Yeah. Let's go through each. There's a lot of indications there. We'll start with ILD. What we've committed to is to start that phase III program by the end of the year. I'm happy to say we remain on track to start that program by the end of the year. Excited to kick that off and provide more options for patients in that clinical setting. For PAH, we've shared that we have our FDA meeting as planned, as you normally do, after a phase II data readout in October. We'll share more data and feedback once we have that interaction. Our expectation is we look to start that study in 2026. For IPF, we obviously wanted to see the Teton data. We have been thinking internally what that could look like. We'll be putting that in gear, in motion, and going through all the operational steps. I won't be here committing to a specific timeline on IPF from a phase III perspective. We would look to move directly into phase III and do that as soon as possible. Got it. We get some pushback just in terms of enrollment dynamics, especially for PAH, where polypharmacy is kind of standard of care. There are a lot more moving parts, I guess. You guys had success with an uptick in enrollment on the PAH trial post-publishing or at least disclosing blinded data, right? Are there any concerns from a feasibility perspective across any of these indications? The standard of care is slightly different. The current penetration for therapeutics is different. What are some considerations from an execution perspective? Yeah, yeah. It's absolutely fair. We were not known as a PAH company, right? We have very strong and established relationships in the NTM market, as well as the bronchiectasis market with the pulmonologists and ID docs. We have spent a lot of time over the last handful of years establishing those relationships. Part of the reason that we put out the blended blinded data, which I know everybody loves, last year was to arm conversations with the medical community. What you saw in the uptick last year in enrollment, once we put out that blended blinded data, was a significant uptick in enrollment in the PAH program. Now with the strong PAH phase IIb data in hand, we believe that we are becoming part of the conversation and a very important part of the conversation on the medical side of potential opportunity for patients. What physicians say is the more drug they can get into the patient, the better. If you look at the sheet models and all the past data and the prodrug formulation of TPIP, we believe provides that opportunity for patients. We're eager to get those phase III started. Got it. Perfect. Let's move on to BRINSUPRI. Great. Again, what is the number one question that you guys are getting right now as you're heading into the launch, right? I'm assuming we're not going to be able to talk about any metrics. For us, it has been mostly around access, right? You guys have been very proactively outlining your strategy. What are some of the steps that you guys have taken to ensure that seamless launch and broad access, I guess? Yeah. We did invest early in this potential launch, which has now turned into a launch. Thank you to the investment community for giving us that latitude to be able to invest early. We invested early on a couple of fronts. One, as you think about the medical affairs strategy, we invested early in our Medical Science Liaisons and our Medical Outcome Liaisons to help with that disease state awareness. We felt that that was critical, knowing it was a first-in-class and first-in-disease drug, to get that education out there. We also invested early in our field force expansion. We had an existing field force that called on pulmonologists and ID docs for ARIKAYCE in the NTM space. We expanded that back in October of last year. They were in field almost 10 months before launch. We added about 120 reps. That gave us the ability to call on every pulmonologist in the United States, as well as the appropriate ID docs and some other specialties to cover this patient population, to establish those relationships, to do the appropriate and compliant disease state awareness. That investment, we think, was absolutely critical for when we got that approval on August 12th from FDA. Third, and I think gets to the heart of your question, on that market access side. We can have the best trial results and have approval from FDA and have a clean label. If you don't have access for patient, you're not going to be able to have the impact on patient, which is why we do what we do at Insmed, to have impact on patient. We invested very early in some in-house expertise on market access and building out that team. We also invested in our two field-facing market access functions, field access managers and case managers. Those are the folks that help on the white-glove, " service" for the patient side, as well as the support on the back office side to help through the medical exception process, which we know very, very well from ARIKAYCE, and help that paper process. On the payer side, the conversations that we had were on this frictionless launch. How can we make it as straightforward for the treating physician from an administrative perspective? The conversations that we had were, what is the appropriate targeted rebating strategy that we could put into place to allow for this frictionless launch, which would mean physician attestation versus getting sort of bogged down with tons of paperwork and medical records and all those good things? We felt like having access on day one on the initial script, as well as the reauthorization—this is a chronic therapy that they will take potentially for the rest of their lives—having that sort of all work through was going to be most impactful for patient, for access. That would then result in the most positive uptick from a revenue and value creation perspective. Yeah. If you were to break down payer mix and, again, some of those considerations, it seems like at least the paperwork is not going to be as cumbersome. It may not require a CT scan. It may not require this super extensive medical history. I guess what are some of the gating steps then for a large uptake? You hear on both extremes, you hear, hey, this could be huge. There is definitely an unmet need. I've heard from physicians that there's a lot of excitement. What are the gating steps on why this actually could have, again, a super strong INI launch? I've heard some fairly bullish near-term metrics. Is it more about capacity, physician education, the more community center? Again, we usually talk to specialists. There's a bias there. Yeah. What are some of those pushes and pulls? A couple of things there, a couple of pushes and pulls to kind of call out. If you think about how many appointments there are at a pulmonologist's office, right? A pulmonologist sees bronchiectasis patients, as well as folks with a lot of other similar type of conditions, asthma, COPD, so on and so forth. There are only so many appointments in a day. I would anticipate a patient will need to see their pulmonologist for the majority of scripts that are written. That is one sort of getting through the funnel. Obviously, once the script is written, it needs to go to the insurance provider. It needs to kind of go through the channel. We have tried to make that as seamless as possible. I will just take this opportunity to comment on some of the information we've shared previously on third quarter. Obviously, approval on August 12th from FDA. If you look at ARIKAYCE as an analog, it took about four weeks to get through the channel. We were ready on day one with our reps in- field promoting on drug, as similarly as we were with BRINSUPRI. It does take time for a specialty drug to get through the channel. That is something just to be very mindful of. I won't speak specifically on the nuances that obviously have occurred since August 12th. What we have said previously is you could expect a handful of weeks of revenue in Q3. Just be mindful of that. Q4 will really be the first full quarter of being able to see revenue and performance from this product. The other just some shining lights that I'll kind of share is we did have a disease state awareness website. We had about a million unique sort of hits on that site. We had about close to 70,000 self-identified individuals that said, I am a patient that has bronchiectasis. You can see an active community, an active patient population. Again, it takes time to get patients funneled through their pulmonologists and scripts in hand, drugs sent to their house, all that good stuff. Got it. Q3 results, we're going to hear on the earnings call late October, early November. You generally pre-announce revenues. I think, is it fair to assume, as the last several years, in January at a conference, we might hear about it? Yeah. A couple of things. What we've committed to from a metrics perspective is during this launch period, before we provide formal guidance, we would provide a number of new patient starts and cumulative number of prescribers on a quarterly basis for BRINSUPRI. I think if you look at our past practice, not committing to anything, but if you looked at our past practice, we have historically pre-announced revenue for ARIKAYCE at a health care conference that happens in January. If you sort of follow that cadence, you can assume that the first real kind of meaningful quarter of revenue for could come at that point. We will provide those specific metrics that we talked about, cumulative number of prescribers and new patient starts through the launch period, once we provide full-year revenue guidance, which I would not anticipate in 2026. Not committing to when we would provide it, but would not anticipate that to happen in 2026. Once we do provide that, then we let the revenue numbers kind of stand for themselves. Got it. Just to follow up on the access side of things, because a lot of investors are really honed in on the two exacerbations or more. How does that actually impact that initial $250,000 patients that everyone estimates that would fit that criteria? Again, how formulaic has it been when you talk to payers about the specifics around exacerbations and documentation? You mentioned mostly physician attestation. Could you actually see potentially broader adoption than originally the street is modeling? I'm just trying to think about some of the puts and takes on the access side. It does not feel like it's an overly burdensome process to actually get this reimbursed. Yeah, yeah. A couple of thoughts. If you look at the claims data, there was already an ICD-10 code established for this disease indication, which was really helpful because then there was claims data. There's about 500,000 diagnosed patients in the U.S. with NCFB. Based on the data, we believe, and based on some published literature, we believe about half of them have had two or more exacerbations in the prior 12 months. To be clear, the label that was provided by FDA is a very broad label. The label allows physicians to choose physician discretion on which dose. [crosstalk] 10 and 25. The medical community was very happy with the broad label. It does not preclude that it needs to be two or more, anything like that. It is a broad label. In the clinical section, it references the inclusion/exclusion criteria from our phase III program, which was two or more exacerbations in the prior 12 months. The conversations with payers are really around, this is what you studied in a clinical setting. This is what we will support from a reimbursement perspective. The importance of that physician attestation is really critical. The disease state awareness and Speak Up Early and Often campaign that we did throughout the pre-launch period was also very critical. Physicians had a better line of sight to when their patients were exacerbating. The typical patient demographic here is elderly population, typically more female. They're typically the people that like to take care of everyone else and not need to be taken care of themselves. They aren't always the ones that speak up and say, hey, there's something going on. They kind of brush it under the rug. That is why some of that pre-disease state awareness work was very, very important. We're making a physician attestation. That's up to the physician and the patient as to that process. I will just note the safety profile, obviously, here is attractive. It is a small molecule. It is not overly onerous from a patient perspective. That actually segues into my next question, which is related to peak sales opportunity and, again, long-term compliance and adherence to therapy, right? Questions that we get are related to, again, if the sell side is modeling this to be a $5 billion- $6 billion opportunity in bronchiectasis, that is one of the most successful single indications INI launches ever. A few folks are skeptical around that, given that a lot of drugs that launch in INI markets usually do hit blockbuster potential, but perhaps not as high as the street is currently modeling for BRINSUPRI and bronchiectasis. Competition, I think, is the biggest factor in trying to reconcile those two ideas. What are some factors that make actually that special and those lofty metrics achievable? Yeah. We put out some metrics, some launch metrics on what really, really great launches look like. You saw those. It's obviously not formal guidance. I know folks have studied what really good INI- type launches look like. A couple, I think, unique factors with, there is nothing available for these patients today. Today, when patients go into their doctor's office, they explain their symptoms. The doctor may or may not even give them a CT scan. A CT scan is a definitive way to diagnose for this condition. They may not even give them a CT scan because they're not going to be able to treat them until August 12th any differently because there was nothing approved. I think that goes to another sort of layer here on that undiagnosed or misdiagnosed patient population. Let's focus on the diagnosed patient population for right now. If you think about from a patient perspective, they were told, I have this condition, but I can't do anything for it. Continue with your airway clearances. You're going to have to go on antibiotics. You might have to get hospitalized. Now patients have the first and only available medicine that can reduce exacerbations. The other, I think, really important piece that you saw in the data is, depending on the dose and the statistical powering and all that kind of stuff, some quality of life. Patients feel better when they're on this. A patient that has bronchiectasis and exacerbates, they sort of put their life on hold. They don't go to family events. They don't plan things. Their exacerbation can last. It's not just an hour. It can last days. It can last weeks. It really is life-altering for these patients. Between the way of administration, nothing else available, the quality of life, they feel better, reducing exacerbations. Exacerbations create permanent lung damage for these patients. That kind of comes into this vicious sort of cycle of they had permanent lung damage. They're more susceptible to having a future exacerbation. If they could stop that or they can halt that or alter that course, they're going to want to do that. Fair enough. Let's move on to some of the additional indications you guys are pursuing there. Chronic rhinosinusitis without nasal polyps, data by year end, right? Mechanistic, there's some rationale there. There are very few comps, I guess, tons of failures in that space. Why did you guys decide to pursue that? What does success look like? Let's kind of unpack that over time. Yeah, yeah. We're CRS without nasal polyps. This is one of the things I'm most excited about. There's a lot to be excited about. It's one that I'm super excited about. Let's take a step back and kind of walk through the trial, the design, what we're trying to do there. If you think about chronic rhinosinusitis without nasal polyps, from a non-scientist, obviously, you can view it very similar to bronchiectasis in the lung. This is very similar, but in the nasal capacity. What we're studying here, it's a thorough, very WILLOW-like kind of phase II. It was designed for 270 patients. We over-enrolled at 288 patients. It's a three-arm study, one-to-one-to-one, randomized placebo, 10 mg and 40 mg. We studied a higher dose. It's 24 weeks in duration. What we're looking here for is change in total sinus symptom score. What is that? What does that mean? There's three components of the total sinus symptom score. There's pain or pressure in your face, there's nasal congestion, and there's discharge. Those are the three components that you're studying. Each of the individual components are on a scale from 0- 3, so it's a total scale of 0 - 9. Patients have to have a five or greater coming into the trial. They get put on a course of steroids to make sure they're kind of stable on steroids. They check them again, make sure they're still at a five. These are more the severe end of patient. What we're looking for for success would be a one-point placebo-adjusted change is what we would look for. The way we measure that is the last 28 days of the study, every day, they give us their score. We average it, and then we see, do we have what is the change? We would look for a greater than one change placebo-adjusted or one or greater. In the past, you guys have said that you are seeing, at least on a blended- blinded basis, something that is exceeding that one point, right? What's the latest in terms of the blended- blinded data that you can share? Perhaps, how do you actually assess that, right? For PAH and the blended-b linded data, you had a lot of comps, not as many comps on this indication. We were able to find only two, three studies that could be relevant here. How should we interpret the data that you know so far and how that's trending? Yeah, yeah. A couple of things there. We look at blended- blinded data internally because if you don't see any change on a blended- blinded basis, that should be a red flag, right? We look to see, are we seeing something? We don't know where that's coming from. We don't know if that's coming from placebo patient, drug patient. We need to see some level of change. Last time that we've spoken about this, we've said we've seen a north of a two-point change. Again, that's not determining to say that those are drug patients. We are seeing a north of two-point change. That gives us encouragement that we are seeing change. Now we obviously need to unblind it and see, is that change coming from those that are on drug? The other piece I would just comment on is there is an approved nasal steroid. They saw, I want to say, about 0.7- 0.9, depending on which dose change, placebo-adjusted change. That helps to hopefully put it in frame of reference. This is a significant patient population. If you look just again in the U.S., CRS without nasal polyps, there's almost 30 million patients. I think it's 29 million patients in the U.S. that have CRS without nasal polyps. About 3 million of those are steroid non-responders. 200,000 patients in the U.S. alone each year get surgery from this condition. It's definitely an underserved patient population. We're just as eager as you all are to turn over that data. We remain confident that we'll be able to have that data in-house before end of the year. Got it. Pivoting to hidradenitis suppurativa, again, a lot more investor skepticism there, understandably so, given the checkered history in the indication. You built in an interim analysis on your trial. Can you talk about next steps? We know it's neutrophil driven. There's definitely a neutrophilia component to the disease. Hard to know exactly how the biology is going to play out. What is the setup there? Yeah, yeah. We were slightly more cautious on this indication while we believe in it. As you said, obviously neutrophil driven. We don't have a lot of good animal models, so we wanted to be very thoughtful as we designed the program, both from a patient perspective as well as a resource allocation perspective. This is a little bit of a smaller study than the BIRT study that we just spoke about for CRS. This study we call CEDAR. It's about 200 patients, 204 patients, similar in design, one-to-one-to-one randomized, placebo, 10 and 40. It is a 16-week study. We sized it and powered it at 0.1 because we wanted to be able to have it be a little bit smaller and get information a little bit sooner. We also built in a futility analysis at week 16. While patients will go on for a total of 52 weeks, at week 16, there is a cut of data. After 100 patients get to week 16, there will be an independent board that will unblind the data. We will not see it. It will be an independent board that unblinds the data, and they will determine, should we proceed or not proceed. There will be no p-value. It will just be a signal of efficacy, so they will just tell us yes or no. That's all we will get, to be fully, fully clear. We'll look to share that information first quarter of next year. Once we share that information, then we'll provide guidance, assuming that is a go to move forward on the timing for the full 204 patient study. Eager to see that. That one is the one I'm a little more still excited about, but cautiously optimistic as we enter that. I think that's fair. In terms of patient numbers, both for CRS, you guys have mentioned in the past this could be bronchiectasis-like to an extent. I think even for HS, most folks think that a new therapeutic could get substantial revenue. What is the revenue opportunity across some of these indications? Yeah. Because it's starting to add up. Yeah, yeah. It's starting to add up for sure. Yeah. All we've committed to externally is the $5 billion peak sales for NCFB. What we have said is for CRS without nasal polyps, we believe that could be just as large, if not larger, from a revenue opportunity perspective. More to come on that. We know we owe you some education on the TAM and the market opportunity there. That could be very, very significant. HS on its own is also significant, hundreds of thousands of patients in the U.S. alone for HS. Not willing to commit to a peak sales number for either of those today. They are very significant. As you sort of stack up ARIKAYCE, the label expansion, brensocatib, TPIP, some of the early stage research, get into some big numbers. Fair enough. You have been talking about TPP1 inhibition as kind of a new class, right? We're starting to get some more questions on the follow-on molecules. Some of that is a life cycle management of brenso, but also, you've alluded to maybe exploring much larger indications. What is the rationale there? What is the product profile? When should we start to see some progress towards that? What are some of the gating steps? Yeah, yeah. That's like CRS, the follow-on work that our research team has done is also something that really excites me and not something we've talked about as much externally because of everything else that we have going on. Hold on for 2026. You'll hear more about that. What I can say is on the heels of the WILLOW data that we put out in very, very early February of 2020, it was actually my first day in the office. It was a really cool first day. On the heels of putting out that WILLOW data, we doubled down on the mechanism. We really believed in and still believe in the TPP1 mechanism. Our research lab has done a ton of work. Big shout out and kudos to all of our great scientists back in New Jersey and around the globe that have done this work. We've developed over 800 different follow-on molecules, and we'll look to move forward the first of those into IND candidate very soon. You'll hear more about that in 2026 and more significant market opportunities, potentially, maybe something like an RA, and those types of and all follow-on TPP1s would be fully owned by us. Perfect. ARIKAYCE, again, I feel bad because now it's always the last item on the list, right? Again, at least what we hear from physicians we talk to, on the low end, they think their revenues could double. On the high end, we hear even as much as 5x the refractory revenue opportunity. Yeah, can you just talk about that frontline expansion, expectations for that? We have data upcoming. There was a lot of skepticism you'd be able to show a clear benefit in PRO. I think that's kind of gone, right? Yeah. The data has been pretty compelling so far. I know it doesn't get as much airtime. Yeah, no. Again, not an immaterial part of the business. Yeah, yes. I appreciate you calling that out because it has been really our mainstay. It has helped us have a lot of the success along with the support from the investment community that we've had with the other programs. Encore, that readout will be first half of next year. That's not something to overlook. What we were able to show in the ARISE program, which was the first of the two label expansion programs, is we were able to show a meaningful difference on both the patient-reported outcome tool. This is an eight-question utilizing the quality of life bronchiectasis questionnaire, eight questions. We are powered for Encore to show a four-point difference between groups. We showed north of that in the ARISE program. Also, if you think about culture conversion, FDA cares about PRO, field function survive. We're also looking at culture conversion. The Japanese regulatory authorities are focused there, as well as the patients and payers and physicians in the U.S. What we were able to show in ARISE was north of a 16% change there. Really excited to be able to unblind and see the data in Encore first half of next year. You'll get both the PRO data. You'll get the culture conversion data. From a patient number perspective, 12,000 - 17,000 patients in the U.S. alone with refractory NTM, that's about 100,000 all of NTM. We've set a billion-dollar peak sales opportunity for ARIKAYCE. We obviously are a mainstay in that community, the only approved product and the only with a high recommendation for use in the international treatment guidelines for refractory. More to come there. Fantastic. I know we only have about a minute left. The fourth pillar. Yeah. We have to talk that much about it. Again, news flow is probably going to be a little slower than some of these other programs. Overall, what are some of the next steps for the fourth pillar? Yeah. We did announce that we dosed our first patient in DMD. That was, again, a humbling experience. Really eager to see what that program could potentially do for those boys and those families. We will also look to move forward additional programs in our gene therapy. ALS would be the next one that would move forward. We obviously have the follow-on TPP1. You'll hear a lot more next year on the early stage sort of fourth pillar, yet another value inflection creation point for this story. In 2026, hold on to your hats, because 2024 and 2025 are really big important years. 2026 is going to be a great one as well. Awesome. Fantastic. Thank you. Thank you so much, Sara. Thank you all. Appreciate it. Yep.