Good morning, everyone. Thanks for joining the session with Insmed. My name is Clara Dong, one of the biotech analysts here. Sitting next to me is the Chief Executive Officer of Insmed, Will Lewis. Welcome. Thank you very much. Appreciate you having us here. Great. It has really been a landmark year for Insmed, I have to say, first in disease FDA approval and a very strong launch and impressive data in PAH. There is really more to come. I will pass it to you to give an audience of what is going on at Insmed and what have kept you busy for the past year. Yeah, it's been an interesting last 18 months, for sure. As we like to point out, we're facing an even more eventful next 18 months because we've just had the ASPEN trial readout, which was successful, obviously, and then the approval of brensocatib for the treatment of bronchiectasis. Beyond that, we have the TPIP data that came out, and then others data, which validated TPIP, its potential in IPF and PPF. We are now looking at three programs at the company, ARIKAYCE, which is approved for refractory MAC lung disease conditionally in the U.S. and full approvals in Europe and Japan. That is going to enjoy the ENCORE trial readout, which should expand that market opportunity from 30,000 patients to over 250,000. That's a big expansion should that data read out as we expect it to. The second program we have is brensocatib, the DPP-1 inhibitor that, as you just pointed out, is approved in bronchiectasis. This is a disease that has been around since 1819 and never had anything approved to treat it. We are very proud of the fact that this medicine has cleared that hurdle and is now available for patients. The launch early days, it is just a handful of weeks, but certainly was going well. I think we want to be cautious about where it goes next. We are going to be learning more with this first full quarter. We have said publicly we think this medicine could clear $5 billion in peak sales just in that indication. We are very excited about that and are resourcing that effort. It has the potential to be used in other diseases as well. Anywhere there's a neutrophil component to the disease, we think it may have applicability. So we're studying it in CRS and HS to other diseases. The CRS data will read out by the end of the year. We'll make that public shortly thereafter, probably in early January. HS will read out in the first half of next year. While that's a longer shot, as we like to describe it, both are really interesting opportunities and very substantial. We've said CRS could be bigger than bronchiectasis. Another major readout here in the near term. As we look out beyond that, we think of next generation DPP-1s that we have in our library. They're going to be entering the clinic next year for sizable market indications like rheumatoid arthritis, IBD, and others, COPD, asthma. There's a lot more to come with DPP-1, assuming that it is working as effectively in these other diseases as it has in bronchiectasis. Finally, TPIP, which is going to be kicking off phase three trials in PAH, PH-ILD, IPF, and PPF. If you take a snapshot of where we're going to be in the next 18 months, all of those things kicking off, all of the data reading out, plus the commercial launch update in the U.S., the addition of Europe and Japan, the Salesforce we use for Arikayce is the same one we're using for bronchiectasis. This is territory we know very well. That just gives us an awful lot to talk about over the next 18 months. Next year, for example, we could be kicking off as many as close to a dozen phase three programs. Before we talk about brensocatib launching in bronchiectasis, I mean, I also just want to talk about your vision here. You're kind of moving into a multi-franchise commercial company. You have a lot of R&D going on as well. How are you thinking about the prioritization between your commercial execution for Arikayce and brensocatib and your R&D efforts? This is the byproduct of rational design. We are hitting our stride here just as we intended to and try to create a kind of news flywheel, if you will, where in the next 18 months, these data readouts will give us additional momentum in addition to the performance of the commercial launch of the drug. Beyond that, we have close to 30 programs in preclinical development right now that span a range of diseases and technologies and therapeutic areas. Several of those are in the clinic right now. Gene therapy for DMD, for ALS, and Stargardt will all be in the clinic next year. Beyond that, we have programs using our deimmunized therapeutic technology for proteins. It's driven by AI, which is kind of interesting. It's obviously a buzzword right now, but we've been doing this for several years, and we think we may have successfully deimmunized a version of ARIKAYCE. That'll be entering the clinic probably in 2027. That's a pretty exciting program for us and would be a landmark achievement if we were to be able to successfully bring that all the way through. We also have efforts for novel mechanisms of action that are complementary to DPP-1, which are being developed in our New Jersey research labs. Finally, we have a program using a technology called Synthetic Rescue, which is looking at CNS disorders out of Cambridge, England. That's a few years away from the clinic, but exciting nonetheless. I mention all this stuff because we've always referred to that as our fourth pillar. There has always been a little bit of discomfort with, why are you investing in that? Now it becomes apparent why. Because with these three main commercial programs we were just describing and these 30 programs internally, we really do not need to do anything else in order to continue to build value for the company and this franchise. We just need to execute on what we have. We will be selectively engaging in business development as well, but we will be looking at a very high hurdle to bring those programs in. We are going to be targeting low upfronts for asymmetric returns in these novel MOAs. One of the lessons of our industry is that if you get a novel mechanism of action like DPP-1, the upside potential of that is almost unlimited, whether it is CFTR modulation in Vertex, the franchise they built, or PD-1 at Merck. That's a $30 billion franchise. We all know GLP-1 and where that could go. That is what we're focused on, novel MOAs that are first in disease or best in class for these various diseases. We have got a lot in-house that we're executing on right now. Thanks to the excellent work of our Chief Financial Officer, we are well capitalized to be able to pursue all of that. I think your question really goes to how are we going to prioritize. Right now, the pedal is down, and we are full on on development because of all the positive readouts we've had, and we're going to continue to do so. I think even in that circumstance, we're very fortunate because the revenue generation potential of Brinsupri will outstrip the expenses related to these development programs. We're on what we like to think of as an almost inevitable journey to cash flow positivity. We haven't timed that yet for the market, but it's coming. Great. Let's maybe dive deeper a little bit to Brinsupri launch. It has been a lot of recent focus in the first partial quarter, fresh out of the gate. It has been really strong. How does the initial performance kind of compare to your initial launch expectations and what has been the key drivers contributed to this early traction? It was a partial quarter, and we obviously posted $28 million in revenue, which was very encouraging. I think we want to urge a little bit of caution around that because some of that is inventory build on the part of the pharmacies. It is still too soon to know what this launch curve is going to look like. We really need a few quarters under our belt. Certainly out of the gate, this is positive. I think the greatest positive that we see in the launch so far is the breadth of prescribing. We are very encouraged that we have seen script writing not just in the centers of excellence. We believe over time the centers of excellence will get there and write high volume for their patients. What we're really trying to make sure is that we also get the community level physicians to be writing early and then focus on creating depth of prescribing behavior there. We are just now beginning to turn on some of the additional elements that can drive a launch's success, things like speaker programs, advertising. There is a lot of awareness of this disease among the patient community, and we're seeing a lot of proactive outreach by them to their physicians. I think all of these are positives directionally, but it's still very early, and we need to see where things go before we know what the true demand is versus things like inventory build. Market access is going to be a huge driver. So far, that's gone very well, but we do not know what the final program decisions will be from the different plans. That will obviously potentially put a brake on some of the uptake. We'll just have to see. We'll know much more with the fourth quarter and the first quarter of next year. In terms of the market access criteria, you mentioned some of them are being finalized. How should we think about the timeline for those criteria to be finalized and what's your expectation? We're going to see some of those plans finalize their decisions between now, really, and the first quarter of next year. That will give us a clearer picture on what we can expect for uptake. What we're trying to do with a little bit of outreach and some modest discounting is ensure both frictionless uptake and then also a frictionless reauthorization process, which we think is important for this because it's a chronic medication that's going to be used for life. We want to make that as easy as possible for patients, and we'll see how that goes. You also have other regions following on their way. What kind of tell us what are the key milestones for Arikayce launches and how do you plan to set the pricing? I think you mentioned in Europe you're going to set the pricing in parallel. Yeah, Europe has already come out with a recommendation to approve the medicine. We expect that will happen sort of between now and the end of the year. That puts us in a very positive position, obviously, with the European launch next year. We already have all the infrastructure in place to execute that launch because of Arikayce, which has been on the market in the U.S. for almost eight years now. Europe, similarly, has been on the market for several years. Japan is right behind it. I'll remind you that our Japanese colleagues have just done fantastic work in terms of driving volumes for Arikayce's use. I expect that will lay the groundwork for a very successful launch of Brinsupri. When we think about pricing in a world of MFN, we obviously want to be sensitive to this. I'll remind everyone that we priced Arikayce at list price parity between the U.S., Europe, and Japan. There is discounting that goes on. Some of that is visible. That may change with the MFN pressures that are being brought to bear, particularly in Europe. It is something we're watching carefully. Our ambition is obviously to bring the medicine wherever patients will benefit. If the systems that provide that final pricing structure are constructive, then we'll bring the medicine there. If they're not, we frankly won't. We have to see how that unfolds. We don't have a lot of leverage over the country of, say, Germany to dictate that they're going to accept a particular price. It's up to them what they'll ultimately offer to pay. We have to make the difficult decision about whether or not we can support bringing the medicine forward. List price parity is the way we're going to approach all of these markets. How are you thinking about the long-term opportunity maybe in COPD patients as well? If we just talk about bronchiectasis as a target market, we've said that there are in the U.S. 500,000 patients that are diagnosed today with the disease, and about half of those have two or more exacerbations. Beyond that, we know there are patients with COPD, some 20 million of them in the United States, and some portion of them experience exacerbations, which are probably indicating that the underlying disease may also include a diagnosis of bronchiectasis if examined. We're encouraging that examination to take place. I think in the medium term, not upfront, but in the medium term, that may fill the top of the funnel with more patients. The literature right now suggests somewhere between 4%-60% of COPD patients are also bronchiectatic. You can see behind that 250,000 initial patient target group that we're going after in the U.S., which are two or more exacerbations in the last 12 months, are all these COPD and asthmatic patients who may be comorbid. That could number in the millions. There is a lot further for us to go. That's why we are comfortable with the guidance that we think this could be a $5 billion-plus peak sales drug in this indication. I also want to talk about another disease that Brinsupri is being studied for, and you have the data, upcoming data in early next year, that CRS without nasal polyps. For those who might be less familiar with the disease, can you just maybe talk a little bit about what are the unmet needs for this disease and how do you see Brinsupri might potentially address them? CRS comes in sort of two forms, with nasal polyps and without nasal polyps. With nasal polyps, there are surgical options to treat it. There are also a lot of the biologics available, approved, like Dupixent and Humira are available to treat that population. CRS without nasal polyps, which is what we're targeting, has nothing approved to treat it except for a generic steroid. There is a clear unmet medical need. There are more than 30 million patients in the U.S. that have this condition. We're going to be targeting those who are at the severe end of the spectrum. Indeed, the entry criteria for this study are patients who have a score on what's called a total symptom score, or TSS, above 5 on a scale of 1 to 9. These are highly symptomatic patients. They come in with that score. They then are randomized. They are placed on the generic steroid for 30 days. That is to ensure that the best available treatments have already been, they've already been exposed to. They still have to have a score of 5 or greater at the end of that 30-day run-in period. They are randomized in the trial. That should, we hope, mute the placebo effect that is sometimes seen in the treatment of these patients. We are targeting in this trial a 0.7 improvement. If we see 0.7 or greater, we will move forward into phase three. We set that number based on the fact that that is what Opdenose, the only approved generic steroid in this indication, achieved, and they secured approval. On the basis of that, we think that is the right target. If we get above that, obviously, that would be a home run, but 0.7 is the threshold we're looking for. It probably won't be statistically significant just to set everyone's expectations. The trial is not designed or powered that way. If we get the directional benefit, or indeed if we see a subpopulation of patients that are responders, we would go forward with them because this market is so substantial. Are you going to show any secondary endpoints as well? Maybe SNOT-22 and what's the significance of that secondary endpoint? Yes, it's unfortunate that someone with a sense of humor named the symptom score the SNOT-22 score, but that is actually the benchmark that is used in clinical practice. The TSS, or total symptom score, which is the primary endpoint of our study, is what the FDA looks at. We are studying both, and we'll have the data from both of those. As we've commented publicly, we do see directionally in the blended blinded data improvement on both measures. It's always dangerous to look at blended blinded data, so buyer beware. We like to look at that because if the drug is having an effect, you should see something in the blended blinded data. Indeed, we do. We see a two-point move in the totality of the data. That could lay the groundwork for a success. We just won't know until we unblind. That'll be by the end of the year, and then we'll probably report at the early part of January. Maybe just when we are thinking about the bronchiectasis and CRS without nasal polyps, how should we think about when we extrapolate the efficacy we've seen in bronchiectasis to CRS? Maybe talk about the overlap of patient populations between these two diseases as well. There's quite a bit of overlap between those populations and also with NTM. Indeed, the COPD Foundation has gone about qualifying centers of excellence in the United States to treat both NTM and bronchiectasis. That will lay the groundwork for additional patients coming into the funnel. What's interesting about CRS without nasal polyps and bronchiectasis is that they are part of this thing called the integrated airway, where it's believed that anything that starts out of the nose essentially ends up in the lungs. It may be that bronchiectasis is a downstream manifestation of people who get CRS with or without nasal polyps, and it results in bronchiectasis down the road. This could be a really important aspect of the treatment paradigm for these patients. Of note, we talked about subpopulations in CRS without nasal polyps that we may be able to treat. One of the things we looked at was eosinophil count. Patients above and below 750, down to 300, and then below 300 that we stratified the statistical analysis plan initially for CRS without nasal polyps for that particular subpopulation. Having looked now at the Aspen data, we can see that we are able to treat patients successfully regardless of eosinophil count. That puts us in a very strong position. It means we may be able to go after CRS with nasal polyps as well. There is a lot more room for this to run if this trial reads out successfully. I would say the biggest point of intrinsic value creation for this company in the next six months is the readout of CRS. Because if CRS works and we move into phase three, we probably have unlocked what we like to call a skeleton key of medicine, which means that this should be applicable in multiple diseases. You start to adjust the probability of success for things like rheumatoid arthritis, irritable bowel disease, COPD, asthma. These are massive market opportunities that we'll be bringing DPP-1s into. That just gives us an awful lot of room to run as a company. Maybe just talk about how large exactly is this opportunity for CRS, if you have to put a number? We can say that the bronchiectatic patient population we're targeting with two or more exacerbations right now in the U.S. is 250,000. As I mentioned before, there are more than 30 million that have CRS without nasal polyps. Even if we're going after the most severe end of the spectrum, this is a massive prevalence population and a significant incidence population every year exceeding the size of the bronchiectatic population. If we talk about being $5 billion in peak sales just for bronchiectasis and we are successful in CRS, you can see where this can go. This could be a very substantial additional opportunity for us. We'll know that answer in a couple of months. I also want to, for the rest of the time, talk about TPIP as well. Maybe can you talk about the trials you are running or the pivotal opportunities for TPIP in multiple indications? TPIP has advantages because it is once a day. It is a dry powder. It is able to show benefit 24 hours after administration. You are getting benefit in these patients not only during the daytime, but while they sleep. With those data that came out showing the best available pulmonary vascular resistance reduction, we had a 35.5% reduction. That is better than catetersept had. This is a very significant finding. It opens the door to the use of this drug in PAH, PH-ILD, IPF, and PPF. We are going to be running four different phase three programs with this medicine. We have advantages not only of the kind I have described, but also because we can titrate up to much higher doses. We went up to 640 micrograms in these studies. We're going to be able to go up as high as 1280 in the next set of studies. We're also going to be measuring three hours after administration as opposed to 24 hours after administration in the phase three trial. That parallels what's been studied by companies like United Therapeutics. Our ambition here is to simply put forward the best-in-class medicine. We have seen such positive results to date that we are really bullish on where this could go for all four of these indications. If you think about where the company is, we have Arikayce. It's about to get an expanded opportunity. We have bronchiectasis. We're looking at CRS and HS, and then IBD, RA, COPD, and asthma. We look at TPIP going into PAH, PH-ILD, IPF, and PPF. That's just the first three medicines which have been largely de-risked. This company has had a very good run in the last 18 months. From our point of view, because of all of these programs and their probability of success, we have a lot further to go. I think what you're looking at is the creation of the company we had in our vision, which is the next biotechnology company on par with the likes of Vertex and others. What kind of regulatory feedback have you received on the TPIP clinical development strategy so far? We have talked to them only about PAH and ILD. What is encouraging is that we are only going to have to run a single phase three study. That lowers the cost and hopefully the timeline to accomplish this. We always say that the order is quality first, speed second, and budget third in terms of our prioritization. That has served us well to date. I think just given the promise of the data we have seen, we will be powering these studies conservatively to make sure that we show a treatment effect. If we see something like 35.5% PBR reduction in the PAH phase two study, and we can replicate that in phase three, we will be clearly not only best in class, but best in disease with that kind of performance. Right now, there are some that model treprostinil just in PAH at $7 billion in peak sales. Even if you take a discount to that, we're going after PAH, ILD, IPF, and PPF. This is a very substantial program. For the last two minutes, I also want to touch on your first product, Arikayce. I mean, you do have clinical readout in the front line disease coming up. What is your expectation for that data readout and what is the opportunity for that? Right now, we're going to be we've got guidance of $425 million-$435 million, $440 million. What is it? $420 million-$430 million. I never remember. That's because we just raised it. It's been a very successful year despite the launch of Brinsupri. Shout out to Sara Bonstein, our Chief Financial Officer, for knowing things I should know. What's really interesting about this is we're about to expand that. If ENCORE works as well as ARISE did in terms of phase 3 readout, which will be in the first half of next year, we're going to go from an addressable patient population between the U.S., Europe, and Japan of 30,000 to 250,000. It's a very substantial expansion. Every other company that has come along and tried to create a medicine for NTM has failed. This is a very, very difficult disease to treat. The success we've had to date should be able to put us in a strong position to target the broader market opportunity as well. Japan, just as an example, is now responsible for more than 20%, almost 30% of our revenue. It is a very exciting time to think that they could expand as well because it's going to drive our revenue into 2026 and beyond without competition. I also want to quickly touch on the gene therapy you mentioned earlier. I think it's pretty under the radar. Maybe talk about what's the next milestone we should expect from your gene therapy? This is part of our fourth pillar, gene therapy. We have programs in Duchenne muscular dystrophy. We're using an intrathecal delivery approach, which lowers the amount of virus you have to deliver and should improve the safety profile while also ensuring good transduction in both skeletal muscle tissue and cardiac tissue, which is what we've seen in our work to date. We've already completed the first cohort of treatment without any issue. We're excited about that and progressing into others. We're going to be bringing forward treatment for ALS. We're looking at both SOD1 patients and sporadic patients. There is a very substantial opportunity if ALS works. It's a terrible disease, and the ability to have an impact there would be a capstone in a career as far as I'm concerned. The possibility that we could actually treat sporadic patients makes that a blockbuster drug if it works. We are hopeful that it will. Beyond that, we also have a treatment for Stargardt. There are three gene therapy programs in the clinic next year. We are excited about what those will yield. There is a lot more in our pipeline. We do not tend to talk about it, as you say, but that is because we want the data to speak for itself. Perfect. That brings to the end of our discussion. Thank you all for joining us here. Thank you for all the audience joining us in person and online. Thank you. Enjoy the rest of the conference.